PROCEEDINGS

of the 36th National

Continuing Medical Education
Programme in Surgery

Surgery Update 2018

Compiled by

Prof Rajdeep Singh

&
Dr Anurag Mishra

Department of Surgery
Maulana Azad Medical College
New Delhi
NOTE: The Organizing Committee of SURGERY UPDATE 2018 takes no responsibility for
the contents of the lectures which are the sole responsibility of the concerned
authors. None of the lectures has been edited in part or in whole. A part or whole
of the lecture may be reproduced with the prior permission of the concerned
author.

Liposuction
Dr. Rajat Gupta
Consultant, Cosmetic Surgery,
RG Aesthetics/Pentamed,
Skinnovation, Delhi
Approach to lower GI Bleed
Dr. Sundeep Saluja
Professor of Gastrointestinal
Surgery, Govind Ballabh Pant
Hospital, New Delhi
Advances in the management
of rectal prolapse
Dr. Rajesh Bhojwani
Consultant & Head of GI
Surgery, Santokba Durlabhji
Memorial Hospital, Jaipur
Current concepts and
medical management of
urinary stones
Dr. Rishi Nayyar
Assistant Professor, Dept. of
Urology, All India Institute Of
Medical Sciences, New Delhi
Germ Cell tumour of testis
Dr. Kim Mammen
Professor & Head of Urology,
Christian Medical College &
Hospital, Ludhiana, Punjab
Lymphoedema
Dr.Trilok Chand
Assistant Professor of Surgery,
Maulana Azad Medical College
and assoc. Lok Nayak Hospital,
New Delhi
Pathology of breast cancer-
current concepts
Dr. Nita Khurana
Dir Professor & Head of
Pathology, Maulana Azad
Medical College & associated
Lok Nayak Hospital, New Delhi
Contributors list
Mandibular tumours
Dr. PS Bhandari
Consultant & Head, Dept. of
Plastic Surgery, Lok Nayak
Hospital, New Delhi
Intestinal Polyposis
syndromes
Dr. Manoj Andley
Professor of Surgery, Lady
Hardinge Medical College &
Smt. Sucheta Kriplani Hospital,
New Delhi
Damage Control Surgery
Dr. Anurag Mishra
Associate Professor of Surgery,
Maulana Azad Medical College
& Lok Nayak Hospital, New
Delhi
Surgical Management of
Urinary stones
Dr. Sanjay Gupta
Dir. Professor & Head, Dept. of
Surgery, University College of
Medical Sciences and Guru Teg
Bahadur Hospital, Delhi
Imaging in Urology
Dr. Anjali Prakash
Dir. Professor of
Radiodiagnosis, Maulana Azad
Medical College & Lok Nayak
Hospital, New Delhi
Critical Limb Ischemia
Dr. Rajiv Parakh
Chairman, Division of
Peripheral Vascular and
Endovascular Sciences,
Medanta, Gurgaon, Haryana
Adjuvant therapy in breast
cancer
Dr. Shaji Thomas
Director Professor of Surgery,
Lady Hardinge Medical College
and assoc. Smt. Sucheta
Kriplani Hospital, New Delhi
Surgical Flaps
Dr. Karoon Agrawal
Director Professor and former
Head of Dept of Burns, Plastic
and Maxillofacial Surgery,
VMMC & Safdarjung Hospital,
Delhi
Management of colon cancer
Dr. PK Mishra
Head Gastrointestinal Surgical
Oncology and Senior
Consultant Gastrointestinal
Surgery, Max Super speciality
Hospital, Patparganj, New Delhi
Surgical Site infection
Dr. VK Malik
Professor & Sr Consultant, Dept
of Surgery, Sir Ganga Ram
Hospital, Delhi
Carcinoma Penis
Dr. Gagan Gautam
Head of Urologic Oncology &
Robotic Surgery, Max Institute
of Cancer Care, Saket, New
Delhi
Surgical Nutrition
Dr. Nikhil Talwar
Associate Professor of Surgery,
Lady Hardinge Medical College
and assoc. Smt. Sucheta
Kriplani Hospital, New Delhi
Risk factors, assessment
models and tumour markers
in breast cancer
Dr. Geeta Kadayaprath
Consultant Surgeon & Head of
Breast Oncology Max Hospital
Patparganj New Delhi
Approach to a patient with
breast lump
Dr. PN Agarwal
Former Dir. Professor of
Surgery & Head, Maulana Azad
Medical College and assoc. Lok
Nayak Hospital, New Delhi
Abdominal tuberculosis
Dr. Lovekesh Kumar
Assistant Professor of Surgery,
Maulana Azad Medical College
& Lok Nayak Hospital, New
Delhi
Enhanced recovery after
Upper GI Surgery
Dr. Vikram Kate
Professor & Head, Dept of
Surgery, JIPMER, Puducherry
Well differentiated thyroid
cancer
Dr. Amit Agarwal
Professor of Endocrine Surgery,
Sanjay Gandhi Post Graduate
Institute of Medical Sciences
(SGPGIMS), Lucknow
Approach to a patient with
parotid swelling
Dr. Jainendra Arora
Professor of Surgery,
Vardhman Mahavir Medical
College & Safdarjung Hospital,
New Delhi
Laparoscopic IPOM for
ventral hernia
Dr. Anubhav Vindal
Professor of Surgery, Maulana
Azad Medical College & Lok
Nayak Hospital, New Delhi
Laparoscopic Anterior
Resection
Dr. Deep Goel
Director of Minimal Access
Surgery, BL Kapoor hospital,
New Delhi
Surgery in gall bladder
cancer
Dr. Vikas Gupta
Professor of GI Surgery,
Postgraduate Institute of
Medical Education & Research,
Chandigarh
Upper Limb Ischemia
Dr. Robbie George
Head of Department and Senior
Consultant, Department of
Vascular & Endovascular
Surgery, Narayana Hrudayalaya
Hospital, Bengaluru
Approach to a patient with
ascites
Dr. Lalit Agarwal
Professor of Surgery, Lady
Hardinge Medical College &
Smt. Sucheta Kriplani Hospital,
New Delhi
Hyperthyroidism
Dr. Chandrabhushan Singh
Professor of Surgery, Maulana
Azad Medical College & Lok
Nayak Hospital, New Delhi
Medullary Thyroid Cancer
Dr. Sunil Chumber
Professor of Surgery, AIIMS,
Delhi
Safety in Laparoscopic
Cholecystectomy
Dr. Nitin Agarwal
Associate Professor of Surgery,
Dr Ram Manohar Lohia
Hospital, New Delhi
Current status of
Fundoplication
Dr. Pawanindra Lal
Dir. Professor of Surgery,
Maulana Azad Medical College
and assoc. Lok Nayak Hospital,
New Delhi
Pancreatic Necrosis
Dr. Sushanto Neogi
Professor of Surgery, Maulana
Azad Medical College and
assoc. Lok Nayak Hospital,
New Delhi
Current concepts in
component separation
Dr. Pramod Shinde
Consultant Laparoscopic GI,
Onco, Bariatric & Hernia
Surgeon, Kaushalya Hospital &
Research Centre, Nashik, India
Aberrations of Normal
Development & Involution
Dr. Anurag Srivastava
Professor and Head of
Department of Surgery, All India
Institute Of Medical Sciences,
New Delhi
Abdominal compartment
syndrome
Dr. Lovenish Bains
Assistant Professor of Surgery,
Maulana Azad Medical College
& Lok Nayak Hospital, New
Delhi
Thyroiditis
Dr. Tarun Sekhri
Scientist 'G' & Additional
Director, Senior Consultant &
Head, Division of
Endocrinology & Thyroid
Research, INMAS, Timarpur,
New Delhi
Cystic neck swellings
Dr. Amit Gupta
Additional Professor of Surgery
All India Institute of Medical
Sciences, Rishikesh
Laparoscopic
Appendicectomy
Dr. Naveen Sharma
Professor of Surgery, University
College of Medical Sciences
and Guru Teg Bahadur
Hospital, Delhi
Laparoscopic Splenectomy
Dr. Deborshi Sharma
Professor of Surgery Lady
Hardinge Medical College &
RML Hospital, New Delhi
Hydatid disease
Dr. RS Mohil
Consultant & Professor,
Vardhman Mahavir Medical
College & Safdarjung Hospital,
New Delhi
Radiology for PG exam
Dr. Nikhil Gupta
Associate Professor of Surgery,
RML Hospital, New Delhi
Chronic Venous Ulcers (PPT)
Dr. Mohd Aslam
Chairman, Department of
Surgery, JN Medical College,
Aligarh Muslim University,
Aligarh, (UP)
Sr Title Page
No Author No
1. Liposuction 1
Dr. Rajat Gupta, Dr Priya Bansal
2. Mandibular tumours 4
Dr. PS Bhandari
3. Surgical Flaps 7
Dr. Karoon Agrawal, Dr Anmol Chugh
4. Approach to lower GI Bleed 11
Dr. Sundeep Saluja, Dr Shashi Kiran
5. Intestinal Polyposis syndromes 19
Dr. Manoj Andley
6. Management of colon cancer 31
Dr. PK Mishra, Dr Raghav Bansal
7. Advances in the management of rectal prolapse 37
Dr. Rajesh Bhojwani, Dr Deepak Bajaj
8. Damage Control Surgery 42
Dr. Anurag Mishra
9. Surgical Site infection 48
Dr. VK Malik, Dr Ashish Dey, Dr Sarrah Idrees
10. Current concepts and medical management of urinary stones 55
Dr. Rishi Nayyar, Dr Kulbhushan Sharma
11. Surgical Management of Urinary stones 64
Dr. Sanjay Gupta
12. Carcinoma Penis 66
Dr. Gagan Gautam, Dr Sunny Khanna, Dr Saurabh Patil, Dr Puneet Ahluwalia
13. Germ Cell tumour of testis 74
Dr. Kim Mammen, Dr Shradha Engles, Dr Uma Kant Dutt
14. Imaging in Urology 82
Dr. Anjali Prakash
15. Surgical Nutrition 92
Dr. Nikhil Talwar
16. Lymphoedema 96
Dr.Trilok Chand
17. Critical Limb Ischemia 102
Dr. Rajiv Parakh
18. Risk factors, assessment models and tumour markers in breast cancer 104
Dr. Geeta Kadayaprath, Dr Neerja Gupta
19. Pathology of breast cancer-current concepts 108
Dr. Nita Khurana, Dr Nishant Sagar
20. Adjuvant therapy in breast cancer 114
Dr. Shaji Thomas
21 Approach to a patient with breast lump 120
Dr. PN Agarwal, Dr Anurag Mishra
22. Abdominal tuberculosis 126
Dr. Lovekesh Kumar, Dr Naveen Kumar Solanki
23. Approach to a patient with ascites 134
Dr. Lalit Agarwal
24. Abdominal compartment syndrome 142
Dr. Lovenish Bains, Dr Pawan Lal
25. Enhanced recovery after Upper GI Surgery 150
Dr. Vikram Kate, Dr Archana Elangovan, Dr R Kalayarasan, Dr Mohsina Subair
26. Hyperthyroidism 159
Dr. Chandrabhushan Singh
27. Thyroiditis 169
Dr. Tarun Sekhri
28. Well differentiated thyroid cancer 174
Dr. Amit Agarwal, Dr Suneel Mattoo, Dr Rashid Mohd
29. Medullary Thyroid Cancer 180
Dr. Sunil Chumber, Dr Dhritman Maitra
30. Cystic neck swellings 182
Dr. Amit Gupta
31. Approach to a patient with parotid swelling 187
Dr. Jainendra Arora, Dr Swapnil Kushwaha
32. Safety in Laparoscopic Cholecystectomy 197
Dr. Nitin Agarwal, Dr Sunil Satihal
33. Laparoscopic Appendicectomy 203
Dr. Naveen Sharma
34. Laparoscopic IPOM for ventral hernia 204
Dr. Anubhav Vindal, Dr Rushil Jain
35. Current status of Fundoplication 210
Dr. Pawanindra Lal, Dr Anubhav Vindal
36. Laparoscopic Splenectomy 222
Dr. Deborshi Sharma, Dr Saurabh Sekhar
37. Laparoscopic Anterior Resection 227
Dr. Deep Goel, Dr Sarabjit Singh, Dr VP Bhalla
38. Pancreatic Necrosis 235
Dr. Sushanto Neogi
39. Hydatid disease 239
Dr. RS Mohil, Dr Sandhya
40. Surgery in gall bladder cancer 244
Dr. Vikas Gupta, Dr Irrinki Santosh, Dr Yashwant Raj Sakaray
41. Current concepts in component separation 249
Dr. Pramod Shinde
42. Radiology for PG exam 261
Dr. Nikhil Gupta
43. Energy sources in laparoscopic surgery 267
Dr. Pawanindra Lal
44. Upper Limb Ischemia 277
Dr. Robbie George, Dr Prasenjit Sutradhar
45. Aberrations of Normal Development & Involution 284
Dr. Anurag Srivastava
46. Chronic Venous Ulcers (PPT) 286
Dr. Mohd Aslam
47. Fluid & Electrolytes in surgery (PPT) 297
Dr. Pawanindra Lal
 LIPOSUCTION
Rajat Gupta, Priya Bansal

Introduction
Liposuction is the surgical aspiration of fat which helps achieve desirable shape and contour of the body by the
removal of unwanted pockets of fat deposits beneath the skin. Although it is one of the most popular cosmetic
procedures performed by plastic surgeons worldwide, its application is not limited to cosmetic surgeries alone and it
is also indicated for pathologies like cellulite, lipoma, sweat gland disorder like hyperhidrosis, lymphedema etc.
Each one of us is born with a predetermined number of fat cells which increase in size as we grow and gain weight.
Liposuction causes permanent removal of fat cells thereby decreasing their number for life.

History
Techniques in liposuction have evolved considerably from the curetting technique used by Dujarrier in 1921 to the
present use of third generation ultrasound assisted liposuction. The development of modern liposuction is credited to
father and son gynaecologists, Arpad and Giorgio Fischer, who in 1974 invented the cannula, but the tip was sharp.
French doctors Illouz and Fournier further improvised the procedure around 1978 by introducing the use of blunt
cannula, use of wet technique and the concept of compression. By 1980, liposuction became very popular.
In 1985, Dr. Jeffrey A. Klein, a dermatologist based out of California, created the tumescent strategy for liposuction,
which enabled patients to have liposuction performed under local anaesthesia utilizing significantly smaller
cannulas. Patients could now have liposuction surgery without the dread of massive blood draining and unfortunate
skin issues.
With the change in surgical techniques, newer devices were devised in an attempt to improve the ease and safety
profile of liposuction. Power assisted liposuction (PAL) was developed by Rebelo. Ultrasound assisted liposuction
(UAL) was developed by Michael Zocchi in 1992. Since first being introduced in 1998 by Columbian surgeons Drs.
Rodrigo and Clara Neira, laser liposuction has drawn a great deal of attention. The most recent addition has been
water‑jet assisted liposuction; which was devised by Taufig in 2000.

Anatomic Considerations
For the purposes of liposuction, subcutaneous fat is arbitrarily divided into three layers: superficial, intermediate,
and deep. The relative consistency and thickness of each of these separate layers varies for different anatomic areas.
The most common areas treated are the intermediate and deep layer which allows uniform reduction. The
importance of superficial layer lies in Hi-definition liposuction. This layer needs to be treated with utmost caution,
else there may be vascular compromise and/or contour irregularities.
Anatomic “zones of adherence,” are important to identify and mark during the preoperative consultation. These are
areas of relative dense fibrous attachments to underlying deep fascia, which help define the natural shape and curve
of the body. These are high-risk areas for contour irregularities, however, these are not areas to avoid in all cases.

Wetting Solutions
In an effort to reduce blood loss, the practice of infiltrating wetting solutions was first developed by Illouz, later
popularized by Klien. This provides hydro-dissection, improves hemostasis, and potentially provides some
perioperative analgesia.
There are four different terms used to describe the types of wetting solution based on the volume of infiltrate as a
ratio of the volume suctioned:
Dry -no infiltrate
Wet-200-300 ml/area
Superwet- 1 ml infiltrate:1 ml aspirate
Tumescent- infiltrate to skin turgor
Different authors have popularized different variations of these solutions, but all formulations include some variant
of fluid (NS/LR), epinephrine, and lidocaine. Most commonly used is Klien’s formula. We have devised our own
modification….

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 Klien’s solution Our solution

Normal saline 1000 ml 1000 ml

1% lidocaine/ 2%lidocaine 50 ml/ 25 ml 20 ml/ 10 ml

1:1000 epinephrine 1 ml 1 ml
8.4% sodium bicarbonate 12.5 ml Not used

Techniques of Liposuction
Many techniques and technologies have evolved. Selecting the appropriate modalities requires a knowledge
of and familiarity with it and no single technology is complete in itself. We are the only team in entire North
India, to possess each of these technologies in our armamentarium!

Suction-assisted liposuction (SAL)

It is the classical form of liposuction that removes the pockets of fat cells using a vacuum. In this traditional
form of liposuction, cannulas are placed in the fat pockets through tiny incisions and the site is infiltrated
with wetting solution. The surgeon then moves the cannula in a push/pull motion to penetrate the fat that
loosens the fat cells which are then suctioned out of the body, using vacuum. The disadvantages include
being more difficult to use in fibrous areas, more physical work involved and more trauma to tissues.

Power Assisted Liposuction (PAL)/Microaire

This uses an externally powered cannula, which is variable in size and flex, and oscillates in reciprocating
motion at rates of 4000–6000 cycles/ min. Because the PAL cannula breaks up fibrous fat much more readily,
the procedure is significantly faster and less labor intensive. Suction is still a major component of PAL, and
both the power source, and the suction are attached to the proximal end of the handpiece. With this technique,
the tissues, vessels and nerves do not get damaged or tear apart making the recovery less painful and faster.

Ultrasound Assisted Liposuction/VASER

Ultrasound-assisted liposuction utilizes ultrasonic energy to break down fat and facilitate suction-assisted
removal. Its mechanism of action is primarily mechanical and cavitation and some thermal effects which
provides skin retraction owing to “stimulation” of the dermis of the treated areas. With this technique, fat is
emulsified, which is then suctioned out with traditional cannulas.
Advantages of UAL include less surgeon fatigue, as well as improved results in fibrous areas and in
secondary procedures, more uniform treatment of fat layers and improved contour with less revision.
Disadvantages include slightly larger incisions, longer operative times, and the possibility of thermal injury
to skin.
VASER (Vibration Amplification of Sound Energy at Resonance) is a third generation ultrasound assisted
device for body contouring. It works on the concepts of pulsed delivery of ultrasonic energy utilising small-
diameter solid probes.

Laser Assisted Liposuction

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The treatment involves insertion of a laser fiber via a small skin incision. The laser fiber purportedly acts to
disrupt fat cell membranes and emulsify fat Once the fat is liquefied due to the heat of the laser, it is drained
from the body by gentle suction. Due to its heating properties, it also results in good skin retraction. This
procedure is very gentle, as it only targets the fat cells, protecting the vessels and nerve tissues. This also
means, less pain and bruising and faster healing process.

Complications
Although viewed by many people as a simple and benign procedure, liposuction, especially large volume
liposuction, can be associated with significant morbidity.

Early postoperative complications can include fluid overload and pulmonary edema- most often due to poor
fluid management; venous thromboembolism in <1%; wound infection, and skin necrosis.

Late complications of liposuction include delayed seroma formation- which can be prevented with the use of
compression garments, edema and ecchymosis, paresthesias- which is reversible and resolves in about 10
weeks, hyperpigmentation, and contour irregularities- the most dreaded but preventable complication for
aesthetic surgeons.

Recent Advances

Hi-Definition Body Sculpting

Hi Definition Liposculpting involves the use of advanced techniques, extensive contouring, superficial fat
removal and creation of sculpted irregularities. The human body can be sculpted like a work of art, working
in all planes, by adding and subtracting fat with delicate instruments and refined techniques. This procedure
is highly suited for patients of normal body weight who wish to reduce bulges and define features in exercise
and diet resistant areas. Common requests in female patients include toned arms, flat abdomen, reduced
bulges in inner thighs, improved curves, and an overall athletic appearance. In men, six-pack abdominal wall
definition, sculpted pectorals, muscular arms and removal of superfluous fat in the flanks are the most
common concerns.

SAFE Technique of Liposuction

SAFE Liposuction, as described by Simeon Wall Jr, is a multi-step process of comprehensive fat management
that adheres to the principles of minimizing tissue injury and fulfilling aesthetic ideals. It combines elements
of liposuction, fat shifting, and fat grafting:

Separation: This is the first step, in which infiltration of tumescent fluid and simultaneous separation and
emulsification of fat cells is carried out either by the traditional method or power assisted method. During
this step, both superficial and deep fat is separated through continuous passing of the cannula while no
suctioning is performed. As there is no suction, minimal injury occurs to the dermis, vascular network,
nerves, and fascia while the fat is being separated.

Aspiration: The next step involves use of cannulas to aspirate this low-resistance, separated fat. As the blood
vessels were spared during the separation process, there is little to no blood present in the aspirated fat.

Fat Equalization: This is the final step in which the surgeon evens out the layer of fat that was left behind
accomplished by further emulsification of the remaining fat bed, evening out the inevitable thicker and
thinner areas that exist. This helps achieve smooth and natural-looking results and avoids contour
irregularities.

Conclusion
Liposuction/liposculpture is as much an art as science The procedure has evolved consistently and is now the
most popular and most common cosmetic procedures performed across the globe. Innumerable technologies
have been devised, yet no single technology suits all needs and often a combination is required. Although
touted as a relatively simple procedure and performed unethically by almost all specialities, the procedure
requires much expertise to achieve safe and aesthetically pleasing results.

3
 MANDIBULAR TUMOURS
P.S. Bhandari

To understand the mandibular tumours , it essential to understand the tooth development.In 37 days embryo ,a U
shaped band of thickened epithelium develops in each jaw. It forms series of ingrowths in the underlying
ectomesenchyme. Epithelial ingrowth represents dental lamina . It divides in to tooth bud to form enamel organ
which is composed of inner and outer enamel epithelium. Cells of inner enamel differentiate in to ameloblasts
which secrete enamel.
Underlying condensed ectomesenchyme is dental papilla which forms dentin and pulp. Odontoblasts develop in
dental papilla which forms dentin that results in tooth root.
Eectomesenchyme surrounding dental papilla and dental lamina differentiate in to dental follicle . It develops in
to cementoblast which secrete cementum on root surface.
An epithelial structure , Hertwigs root sheath surrounds the tooth with in the periodontal ligament.
Epithelial structure ultimately disintegrates leaving islands of epithelial structures: the rests of malassez. The dental
lamina also disintegrates leaving epithelial rests Serres and the dental lamina rests in the gingival tissues and dental
follicles.
Classification. Mandibular tumours can be classified in to
 Odontogenic - Lesions arising from cells involved in tooth development
 Nonodontogenic- Lesions arising from tissue not intended for tooth formation
They can be further classified in to Cysts and solid tumours

Cysts of jaws
They can be classified in to
 Odontogenic cysts -arising from odontogenic epithelium
 Fissural cysts – arising from oral epithelium
 Non epithelial cysts - includes traumatic and aneurysmal bone cysts

 Odontogenic Mandibular Cysts : they can be further divided in to

o Inflammatory cysts include Periapical cyst (Radicular cyst), residual cyst, Lateral periodontal
and paradental cyst.
o Developmental cysts include Gingival cyst, lateral periodomtal cysts, Dentigerous cyst,
Odontogenic keratocyst and calcifying odontogenic cyst.
o Fissural custs includes Nasopaltine Duct cysts, Median maxillary Palatal cysts,
Globulomaxillary cysts snd Medial mandibular cysts.
 Solid Tumours : Solid lesions can be classified in to
o Odontogenic Benign tumours- It includes ameloblastoma,odontoma, odontogenic
myxoma ,calcifying epithelial odontogenic tumour (or Pindborg tumour), cementoblastoma,
ameloblastic fibroma and adenomatoid odontogenic tumour
o Odontogenic Malignant tumours include odontogenic carcinoma (e.g. ameloblastic carcinoma),
odontogenic sarcoma and odontogenic carcinosarcoma
o Non-dontogenic Benign tumours It includes cemento-ossifying fibroma, juvenile ossifying
fibroma,exostosis (or torus mandibularis),osteoma,fibrous dysplasia,Paget's disease,central giant
cell granuloma (giant cell reparative cyst),eosinophilic granuloma,neurofibroma,schwannoma
o Non-dontogenic Malignant tumours: It include squamous cell carcinoma of mandible,
osteosarcoma, Ewing sarcoma, chondrosarcoma
o Metastastatic tomours -multiple myeloma/plasmacytoma, lymphoma/leukemia, fibrosarcoma
and leiomyosarcoma

Periapical cyst (radicular cyst )

It is the most common odontogenic cyst. These cysts are thought to arise from epithelial rests of Malassez in the
periodental ligament It is also known as radicular cysts and is the most frequent cystic lesion related to teeth . It
makes around 54-74% of all jaw cysts.it starts with infection of the tooth, spreads to the apex and adjacent bone and
results in apical periodontitis resulting a periapical granuloma. This granuloma/epithelium undergoes necrosis
caused by a lack of blood supply- leading to cyst formation .These cysts are therefore on the apex of the tooth.
These are small lesions are usuallyless than 1 cm. The associated tooth usually has a large carious lesion. They are
usually asymptomatic and are diagnosed on routine dental radiographs . At radiography, most radicular cysts appear
as round or pear-shaped unilocular and radiolucent lesions in the periapical region . Microscopically it is stratified
squamous epithelium without keratin formation. Inflammatory changes in turn, may lead to epithelial changes (eg,
ulceration, atrophy, hyperplasia).

4
Treatment- Several options exist for such cysts. Many cysts resolve with endodontic therapy of the involved
tooth.Lesions that fail to resolve with such therapy should be surgically removed. Although these cysts arise from a
mature resting epithelium, they have a relatively low growth potential.A squamous cell carcinoma occasionally may
arise de novo in a radicular cyst,thus all removed tissues should be subjected for histopathologic examination

Residual cyst
These are actually retained periapical cysts from teeth that have been removed. The histology is stratified squamous
epithelium. The treatment is excision.

Dentigerous cyst
It is second most common odontogenic cyst and constitutes around of 18% of all jaw cysts. It develops within the
normal dental follicle that surrounds an unerupted tooth . Commonly they are relatively small. Most are
asymptomatic. Their discovery is usually an incidental finding on radiography. If infected, they present as painful
swelling. If largwill present as facial swelling .Size is usually 2-10 cm . If large, there can be resorption of
adjacent tooth and tooth is mobile . Common age is 20-50 years. In decreasing order of frequency the involvement
mandibular third molar is 60% followed by maxillary third molars and maxillary canines. Radiologically it appears
as well-demarcated radiolucent lesion associated with an unerupted tooth. The margins of the cyst is thin regular
sclerotic . In CT relationship to the unerupted tooth can often be better appreciated .Histologically dentigerous cyst
is lined with a stratified squamous nonkeratinizing epithelium.As it develops from follicular epithelium it has
greater potential for growth. Occasionally ominous lesions arise within the walls of the dentigerous cyst. It can give
rise to epidermoid carcinoma , ameloblastoma (17%) and squamous cell carcinoma . Treatment requires removal of
the entire cyst and the associated unerupted tooth. In patients with very large lesion or who are unfit medically-
marsupialisaiton is an option. Recurrence is uncommon, but may occur if parts of the cyst lining are left in situ
.Complications. If the lesion is large , it can cause pathological jaw fracture.

Odontogenic keratocyst (keratocystic odontogenic tumor)

This is the third most common odontogenic cysts. It constitutes approximately 9% of all jaw cysts. It Develops
from two sources Dental lamina rests and Basal cell hemartoma The diagnosis is confirmed histologically . These
lesions are different from other cysts. They are aggressive . They can grow quite rapidly. They can be difficult to
remove and the recurrences are frequent. OKCs is one of the lesion in the differential diagnoses of any
radiolucency of the jaws. 40% of OKCs appear in a dentigerous relationship. 9% of dentigerous cysts are OKCs
when the histology is examined. Histologically it is a stratified squamous epithelium that produces orthokeratin
(10%), parakeratin (83%) or both types of keratin (7%). It grow in a multilocular bosselated fashion with daughter
cysts that extend into the surrounding bone. Because of this relationship, the tendency for recurrence is high
particularly if the original surgical treatment does not result in complete removal of the lesion. Treatment -
enucleations with peripheral ostectomy . Cryosurgery is another option.As the recurrence is high - Long term
(lifetime) follow-up radiography is imperative.

LATERAL PERIODENTAL CYST

Usually they are asymptomatic and constitute approximately approximately 2% of jaw cysts .It probably arise from
dental lamina rests. They are most commonly associated with the mandibular premolar area and are occasionally
found in the maxillary anterior. Radiographly appear as ovoid radiolucency with sharp defined margins lateral to
tooth, tratment is excision.

Primordial cyst
By definition, the primordial cyst develops instead of a tooth. Presumably, the dental follicle forms and
subsequently undergoes cystic degeneration without ever completing odontogenesis. treatment-excision

Ameloblastoma
Ameloblastoma is the most common epithelial odontogenic tumor. It may originate from one of the several
structures. Including dental lamina rests, the enamel organ , basal cell of oral mucosa or epithelial linning of of
dental follicles/dentigerous cysts. It usually occur in 20-40 years . It occurs in both the maxilla and mandible, but
the posterior mandible is the most common location. Ameloblastomas are often associated with the presence of
unerupted teeth . It is equally commoc between males and females. Although generally it is not classified as a
malignant lesion (a rare malignant variant exists), it is extremely aggressive and infiltrative. It expands the bony
cortices. As it grows slowly- this allows time for periosteum to develop thin shell of bone ahead of the expanding
lesion. This thin shell of bone cracks on palpation. This phenomenon is referred to as "Egg Shell Cracking" or
crepitus,is an important diagnostic feature.
It is tentatively diagnosed through radiographic examination .radiolucency in the area of the lower third molar. It is
diagnosed by its typical expansile multilocular "soap bubble" appearance. These lesions may be unilocular when
small, and they often resorb the teeth they contact. These lesions are never radiopaque.It must be confirmed by
histological examination (e.g., biopsy )

5
Treatment is surgical excision with wide free margins. Appropriate reconstruction may be performed at the same
time. All patients with ameloblastoma, must be monitored radiographically throughout their lifetime. If excision is
inadequate, recurrence is common. All patients with ameloblastoma, must be monitored radiographically
throughout their lifetime

Adenomatoid odontogenic tumour

One of common solid lesions mandible . it is common in 2nd decade of life. It is thought of a 'tooth hamartomas'
with the lesion consisting of various tooth components (dentin, cementum, pulpal tissue and enamel).They are
divided histologically into: complex odontoma: irregular calcified lesions with no distinct tooth compoents and
compound odontoma: identifiable tooth components. Initially the tumour is lucent, but with time it develops small
calcifications which eventually coalesce to form a radiodense lesion with a lucent rim.Complications. Epithelial
components may occasionally give rise to a dentigerous cyst.Treatment and prognosis Surgical resection is the
treatment of choice and there is no recurrence.

Odontoma
They can be complex or compound In Complex –dental tissues are found but in disorderly pattern. Compoun
tumours ar more more organized . Commonest age is usually 20-40 years . Mostly found posterior mandible and
anterior maxilla. Patient usually presents with pain due to expansion of buccal plate with absence of corresponding
teeth. Radiologically it is radiopaque, The treatment is enucleation

Fibrous dysplasia
It is not strictly a neoplasm but behaves like one. There is developmental derangement of bone from an abnormal
proliferation of undifferentiated mesenchymal bone forming cells It may be diffuse or localized. accordingly it is
called Monostotic or Polyostotic. There is diffuse enlargement of bone. It may be associated with endocrine
abnormalities or precocious puberty. V is one of the causative factors besides endocrine disturbances Monostotic
Polyostotic. Treatment If localized excision of lesion. If diffuse, shaving of bone to give shape.

Osteosarcoma
Osteosarcomas are malignant neoplasms of the bone which commonly affect the long bones.Mandibular and
maxillary osteosarcomas account for 6% to 9% of all the osteosarcomas. It is commonly found in adolescents and
young persons. It start with small painful swelling with associated parasthesia . Large lesions there may present as
facial swelling. The may present as oral mucous ulceration . Radiologically they are radiolucent and poorly
delineated. Some time they appear as dense radio-opaque mass. Wide radical resection is the treatment of choice for
osteosarcoma of jaws with clearance margins of 1.5–2 cm. Adjuvant chemotherapy and radiotherapy is also
indicated.

Embryonal rhabdomyosarcoma
It is a rare histological form of cancer of connective tissue . The mesenchymally-derived malignant cells resemble
the primitive developing skeletal muscle of the embryo.. It is the most common soft tissue sarcoma occurring in
children. It responds well to surgery and chemotherapy.

6
 SURGICAL FLAPS IN PLASTIC SURGERY
Karoon Agrawal, Anmol Chugh

Introduction
A flap is a unit of tissue that maintains its own blood supply while being transferred from a donor to a recipient site.
In contrast, grafts are transferred unattached to a vascular source and rely on the blood supply at the recipient site for
their survival. Flaps range from simple movement of skin and subcutaneous tissue to composite tissues that may
contain any combination of skin, muscle, bone, fat, or fascia. They are used for reconstructive, aesthetic and
functional purposes. The anatomical basis of flap is the blood supply of the tissue to be transferred.

Difference Between Graft And Flap

Flap Graft
Blood supply Blood supply is maintained throughout the No blood supply
transfer
Take Maintains blood supply from donor area and Has phases of nutritional development
the vascularity develops from recipient at recipient site:
region Plasmadic imbibitions
Inosculation
Neovascularisation
Nourishment Initially from the donor area From the recipient area
Tissue volume Large amount of tissue can be transferred Limited amount of tissue is transferred
Technical difficulty level Technically difficult Relatively easier
Tissues which can be All the tissues could be transferred as flap There is limitation
transferred
Tissue combinations Any combination is possible There is limitation
Reliablity Highly reliable Not so reliable

Blood Supply of Skin

Every tissue in the human body can be transferred as flap. However skin is important component of any flap. Hence
understanding of vascularity of skin is relevant for the topic. Skin is supplied by named vessels and some of them
are unnamed. The skin flaps are named on the choice of its blood supply:
Axial pattern flaps are the flaps based on named vessels eg Radial Artery Forearm flap
Random pattern flaps are supplied by unnamed vessels eg local advancement flap or tube flap
For past few decades the understanding of blood supply of tissues specially skin has improved significantly and
hence newer flaps have been designed.

Cormack and Lamberty classified skin flaps as direct cutaneous, fasciocutaneous or musculocutaneous based on
their vascular anatomy rather than their tissue components.

Perforators: Three types of perforators were identified supplying the skin:

1. Direct Septocutaneous perforators are the blood supply to the skin from major named vessel to skin directly
and they travers through the fascial septa.
2. Indirect septocutaneous perforators
3. Indirect Musculocutaneous vessles are the perforators coming out of muscles and supplying th skin. These
are the cutaneous branches of muscular vessels from deep vessels.

These perforators reach the subcutaneous tissues and form different plexuses which are key to survival of flaps:
1. Subfascial plexus: present on undersurface of deep fascia.
2. Prefascial plexus: presnt superficial to the deep fascia. This is predominantly supplied by
septocutaneus vessels.
3. Subcutaneous plexus: present at the level of superficial fascia and supplied mainly by muculocutaneus
vessels.
4. Dermal-subdermal plexus: is present at the undersurface of dermis and is predominant blood supply to
skin.

Reconstructive Ladder
Sequence begins with primary closure, proceeding to skin grafts, local flaps, regional flaps, distant flaps and finally
microvascular free flaps is adaptable for use in any reconstructive procedure. (Fig.1) Using the technically simplest
option first leaves open for the opportunity to perform more difficult procedure if previous one fails. There are
however exceptions to this rule e.g. local flaps for nasal defects may be preferable to grafts because of better
aesthetic results. Some of the surgeons call it reconstructive elevator.

7
 Fig 1. Reconstructive Ladder

GOALS AND PRINCIPLES OF FLAP SURGERY:

Any flap surgery is performed with a specific purpose to achieve goal which are as follows:
1. For resurfacing of a defect
2. Reconstruction of the deformed or lost organ
3. Improving blood supply to the region
4. Reconstruction should be performed with aesthetic considerations.

Principles:
1. Use like to like tissue in reconstruction
2. Should be able to fill the cavity to the desired extent
3. Bring more blood supply for better healing of wound and bone
4. Should reconstruct the cavity wall in minimum two layers.
5. There should be anatomical reconstruction
6. Should be able to perform function for which it is intended to
7. Aesthetically it should be acceptable.
8. Minimal scarring and good colour match are intended.

Classification of Flaps
There are various classifications of surgical flaps. These are classified based on vascular supply, anatomical design
of the flap, anatomical components, regions and movements..
A. Based on component tissues: The nomenclature of the flap will be based on the constituent tissues in the
flap. Eg. Skin flap, fasciocutaneous flap, muscle flap, myocutaneous flap, osteomyocutaneous flap etc.
B. Based on the region of its movement:
a. Local,
b. regional,
c. distant,
C. Based on the blood supply:
a. Random pattern,
b. axial pattern,
c. Perforator based flap,
d. Extracorporeal
e. free microvascular flap
D. Based on the movement of the flap:
a. Advancement,
b. rotation,
c. transposition,
d. interpolation,
e. Propellar
f. turnover flap
g. caterpillar
h. sommersault
i. waltzing

E. Based on the shape and design of the flap:

a. Peninsular

8
 b. Island flap
c. Rectangular flap,
d. Rhomboid flap
e. Triangular flap,
f. Circular flap.

F. Based on the incision and movement of tissue:

a. Z-plasty,
b. V-Y,
c. Y-V procedures.

CHOOSING AND PLANNING A FLAP

Choosing and planning of a flap are two most important components of flap surgery. There are many factors to
consider while choosing a flap for any reconstruction. These considerations are:
1. The tissue components of the flap should characterize the anatomical and functional defect
2. It should restitute the structure and function
3. Movement of the flap should be vascularity friendly
4. Should not compromise the anatomy, function and aesthetics of donor site.
5. Local is preferred over distant
6. Aesthetically the reconstruction should be as normal as possible
7. Choose technically least demanding technique
8. Should cause minimum morbidity to the patient as a whole- functionally as well as psychologically.

Planning of the flap is the most intricate part of flap surgery. The planning of flap requires experience and
innovation. This is true specially in pedicle flaps. The planning becomes easier in free flap as the designing in free
flap is based on the dimensions of the defect.
One should plan the flap considering all the features mentioned as above. While planning the flap one needs to
consider that the vascular supply of the flap should not be compromised during transfer. Also the flap should cover
the defect comfortably without any tension. The tension on the flap may compromise the venous return and may
cause ischemia.
Pedicle flaps are best planned by ‘planning in reverse’. The lint piece or rubber sheet is used for planning. In this
planning method, the flap is considered as if it is on the donor site. The pedicle should be extended to the anticipated
base of the flap. Keeping the base fixed, the flap planner is transferred to the donor area. The placement of the flap
planner in recipient region decides the design and territory of the flap.

SPECIAL FLAPS:
Z-plasty is a useful technique with many applications in plastic surgery such as revising and redirecting existing
scars and lengthening scars in the setting of scar contracture by recruiting lateral tissue. The technique is a variation
of the transposition flap in which two triangular flaps are reversed. The technique involves three limbs of equal
length – two parallel lateral limbs, joined obliquely by a central limb – with equal angles between each of the lateral
limbs and the central limb.

Figure- Z plasty

These angles can vary from 30° to 90° depending on the increase in length required; however, 60° is the classic
angle and provides a theoretical 75% increase in length in the direction of the central limb.
Multiple small Z-plasties can be designed in series to release a contracture or to break up the appearance of a
straight line. Other applications for Z-plasty include the correction of congenital skin webs, improvement of U-
shaped (‘trapdoor’) scars and lengthening of circumferential scars, especially constricting scars.

Fasciocutaneus flaps

9
Fasciocutaneous flaps include skin, subcutaneous tissue and the underlying fascia. Vessels supplying these flaps
arise at the flap base from musculocutaneous perforators or from the branches of major arteries. Perforating vessels
pass along fibrous septa between muscle bellies or compartments. They then spread out and form plexuses at the
level of the deep fascia, and branches from this point supply the skin.

Cormack and Lamberty created a classification for fasciocutaneous flaps based on their vascular patterns:
Type A – Flaps supplied by multiple fasciocutaneous perforators, entering at the base of the flap and extending
longitudinally throughout the length.
Type B – Flaps with a single fasciocutaneous perforator of moderate size which is consistently present in the
same location.
Type C – Flaps based on multiple small perforators which run between muscles along a fascial septum. The flap
includes the supplying deep artery.
Type D – Osteomusculofasciocutaneous flap, which includes portions of adjacent muscle and bone.

Muscle and Musculocutaneus flaps

Muscle flaps are advantageous because they fill the dead space with vascularised tissue, which increases resistance
to infection. Musculocutaneous flaps are composites of skin, subcutaneous tissue, and the underlying muscle and
fascia supplied by a dominant vascular pedicle. Increased blood flow through musculocutaneous flaps and reduced
bacterial concentration in the first 24 hours after flap elevation suggest greater resistance to infection and better
ingrowth into inoculated tissue compared with fasciocutaneous flaps. The disadvantages of muscle and
musculocutaneous flaps are flap bulk, donor site morbidity, and risk of functional deficit. Mathes and Nahai
classified muscles as five types based on pattern of their vascular supply.
Type I Single vascular pedicle -Tensor fascia lata
Type II Dominant pedicles and minor pedicles- Gracilis
Type III Two dominant pedicles - Gluteus maximus
Type IV Segmental vascular pedicles - Sartorius
Type V Single dominant pedicle and secondary segmental pedicles- Latissimus dorsi

Perforator flaps
Perforators were defined by Hallock as any vessel that enters the suprafascial plane through a fenestration in the
deep fascia, regardless of its origin. Flaps supplied by isolated perforator(s) are known as perforator flaps. All skin
flaps receive their vascular supply from perforating vessels to the fasciocutaneous plexus.
Perforator flaps are typically composed of skin and subcutaneous tissue supplied by a deep fascial perforating
vessel. Perforator flaps enable reconstruction with the tissue types that are most frequently missing: skin and
subcutaneous fat. Perforators pass from their vessel of origin to the flap tissue either through or between deep
tissues, predominantly muscle.
Advantages of perforator flaps include:
a. Minimal donor site deformity
b. Muscle sparing hence no functional deficit
c. Ability to design flaps of different sizes, shapes and thickness
There is a learning curve to perforator based flap surgery. It requires meticulous dissection and may be time
consuming. The perforators may vary in position and size.

Conclusion
Knowledge and application of flaps empowers the surgeon with a plethora of tools to aid the management of defects
and the restoration of form and function. Understanding of anatomical, physiological and surgical principles enables
to provide good and reliable coverage.

Further reading:
1. Agrawal K. Principles and Advances in Plastic Surgery. New Delhi : Thieme;2016
2. Cormack GC, Lamberty BGH. The Arterial Anatomy of Skin Flaps. London:Churchill Livingstone;1986:8-
9.
3. Mathes SJ, Nahai F. Reconstructive Surgery : Principles, Anatomy and Technique. New York:Churchill
Livingstone;1997:30.
4. Taylor GI ,Rozen WM, Whitaker IS. Establishing a perforator flap nomenclature based on anatomical
principles. PlastReconstrSurg 2012;129(5):877e-879e.
5. Wei FC, Mardini S. Free- style flaps. PlasReconstrSurg 2004;114(4):910-916.

10
 Approach to Lower GI Bleed
Sundeep Singh Saluja, Shashi Kiran
Introduction
Lower gastrointestinal (GI) bleeding is defined as bleeding that occurs from a source distal to the ligament of Treitz.
It accounts for about 20% of major gastrointestinal bleeding and is less common and generally less severe than
upper GI bleeding. Nearly 80% of lower GI bleeding stops spontaneously, similar to upper GI bleeding. The
incidence of rebleed is around 25% while in 10% cases source of bleed cannot be identified. The overall mortality
rate of lower GI bleeding is 2% to 4%.1

Epidemiology
LGIB is a frequent condition, resulting in the hospitalization of 21 per 100,000 individuals each year and carries a
significant risk of recurrence.1 Data from west is different from Indian data in term of both age of presentation and
etiology. The experience from AIIMS shows that mean age of patients presenting to tertiary care in India is 41 years
as compared 70 years in US.

Etiology
Various causes reported in western series remain similar to those reported in past. They include Diverticulosis (30-
33.5%), Anorectal disease incluing haemorrhoids & fissures (14-20%), Ischemia (12%) Inflammatory bowel
diseases including Crohns disease & UC (9%), Malignancy (6%), AV malformations including angiodysplasias (3-
5%), radiation proctitis, colonscopic procedure related postpolypectomy bleed and infectious colitis.
While Indian series from AIIMS & Army show causes as Non specific colitis (32.5%), Enteric ulcers (13.5%),
tubercular (3-7.1%), vascular (10.8%), IBD (5.4%), Malignancy and polyps (4-10%) and Diverticulosis (3-5%) in
the descending order. In children juvenile polyps (77%) followed by non specific colitis & ulcer (23%) are common
causes of LGIH.

Presentation
LGIH has wide spectrum of presentation ranging from a) streaking the side of well formed stool, b) splattering on
the pan after passasge of hard stool, c) bloody diarrhoea, d) malena, e) passage of maroon stools f) large amount of
fresh blood haematochezia. These presentation vary according to amount, source and etiology of bleed.
Hematochezia is defined as bright red blood per rectum and usually implies a left colonic source, although it can be
caused by a more brisk, proximal source of bleeding. Maroon stools are maroon-colored blood mixed with stool that
is often associated with a right colonic source of bleeding; however, it can also result from a more brisk, proximal
source of bleeding. Melena refers to black, tarry, foul smelling stool that results from the bacterial degradation of
hemoglobin over a period of at least 14 hours. It usually implies an upper GI source of bleeding, although it may be
associated with right colonic bleeding in cases of slow motility. Ingestion of iron, bismuth, charcoal, and licorice
should be excluded as they all can turn stool black.

Various classification are proposed for ease of understanding and management of LGIH
Acute overt lower gastrointestinal bleeding (LGIB) accounts for approximately 20% of all cases of GI bleeding,
usually leads to hospital admission with invasive diagnostic evaluations, and consumes significant medical
resources. Around 80-85% of bleeds originate from large bowel, while 0.7-9 % arise from small bowel.
Approximately 15% of patients with presumed LGIB are ultimately found to have an upper GI source for their
bleeding.
An individual with acute overt LGIB classically presents with the sudden onset of hematochezia (maroon or red
blood passed per rectum). However, in rare cases, patients with bleeding from the cecum/right colon can present
with melena (black, tarry stools).2 In addition, hematochezia can be seen in patients with brisk upper gastrointestinal
bleeding (UGIB).

Occult Lower Gastrointestinal bleed: Occult blood refers to the presence of small quantities of blood in the stool
that does not change its color and can only be detected by performing a stool guaiac card test. Blood loss of at least
5–10 mL per day can be detected by stool guaiac card tests. The gastrointestinal tract normally loses about 0.5–1.5
mL of blood per day, which is not usually detected by guaiac tests. They usually present as microcytic hypochromic
anemia.

LGIH is also classified as four overlapping categories based on nature and severity bleed
a) Minor self limiting: Most commonly secondary to anorectal disorders. 75-90% of these bleeding are minor
and respond to conservative therapy.
b) Chronic Intermittent bleed usually are elusive in nature and require extensive investigation.
c) Massive Intermittent type is one in which patient has episodes of severe bleeding with haemodyamic
stability in between.

11
 d) Massive ongoing bleeding is one which patients passes maroon or bright red stools with haemodyamic
instability (BP< 90 mm of Hg or Pulse rate >100/min) or Hb < 6 g/dl or patient requiring > 4-6 units of
blood transfusion in 24 hrs. It usually occurs in elderly induvidual with comorbidity. Diverticulosis and
angiodysplasia are common causes in west and non specific colitis & ulcer in India.

Clinical features
Salient features on history which may point towards particular etiology are useful in evaluation and management of
these patients.
a. Pain abdomen with frequent stool mixed with blood and mucus point towards IBD.
b. Fever, crampy pain abdomen and haemtochezia in young adult suggest Infectious or non-specfic colitis
c. Similar features in older patients with cardiac comorbidity may point towards Ischemic colitis
d. Painless bleeding as haematochezia in older patients hint diverticulosis or angiodysplasia as etiology
e. H/o peptic ulcer disease, liver disease or h/o NSAIDS intake with massive haemorrhage may suggest
UGIH as cause of bleed
f. h/o of drug intake such anticougulant, aspirin should be documented.
g. h/o radiation, intervention should be asked.

Examination
After vital examination in GPE one should look for rashes, purpuric spots and hemangiomata. Oral cavity may be
looked for melanic spots. Complete abdominal, pelvic and perineum examination including per rectal and
proctoscopic assessment should be performed.

Components of management
1) Initial assessment 2) localization of bleeding site 3) Intervention to control the bleeding

Initial assessment

Evaluation and risk stratification

A focused history, physical examination, and laboratory evaluation should be obtained at the time of patient
presentation to assess the severity of bleeding and its possible location and etiology. Initial patient assessment and
hemodynamic resuscitation should be performed simultaneously.

Hemodynamic resuscitation
 Two large IV line are placed along with a cardiopulmonary monitor and O2 supplementation
 Patients with hemodynamic instability and/or suspected ongoing bleeding should receive intravenous fluid
resuscitation with the goal of normalization of blood pressure and heart rate prior to endoscopic
evaluation/intervention.
 Packed red blood cells should be transfused to maintain the hemoglobin above 7g/dl. A threshold of 9g/dl
should be considered in patients with massive bleeding and those with significant comorbid illness.
 Platelet transfusion should be considered to maintain a platelet count of 50 × 10/L in patients with severe
bleeding and those requiring endoscopic hemostasis.
 Platelet and plasma transfusions should be considered in patients who receive massive red blood cell
transfusions.
 A nasogastric aspirate/lavage may be used to assess a possible upper GI source if suspicion of UGIB is
moderate since 15% patients Hematochezia associated with hemodynamic instability can have UGI Bleed
as a source. Presence of bile in ryle tube aspirate rule out UGI bleed. However aspiration of clear gastric
aspirate does not exclude UGIH completely. and an upper endoscopy should be performed.
 Endoscopy may performed before colonoscopy in unstable patient especially when UGIH suspected and
patient is unstable.
 Labortaory work up including Haemogram, KFT, LFT, coagulation profile and lactate level should be sent
 Management of anticoagulant medications require a multidisciplinary approach in order to avoid risk of
thromboembolic event vs risk of bleeding. Reversal agents should be considered prior to endoscopy in
patients with an INR > 2.5. Endoscopic hemostasis may be considered in patients with an INR of 1.5 – 2.5
prior to or concomitant with the administration of reversal agents.

Risk assessment and stratification is performed to help divide patients at high and low-risk category to triage
patients including timing of colonoscopy and level of care.

Bleed Criteria is useful for risk stratification of patients with both UGIB/LGIH.
They include: -

12
  Ongoing Bleeding: Red bloody emesis/NG aspirate or spontaneous passage of red/maroon blood (not
counting formed stool). coffee ground emesis/nasogastric aspirate is not considered active/ongoing
bleeding. Formed maroon or black stool is not considered to represent active bleeding.
 Low Systolic Blood Pressure: Less than 100 mmHg not counting orthostatic readings
 Elevated Prothrombin Time: Greater than 1.2 times normal
 Erratic Mental Status: Any altered level of consciousness from any cause.
 Unstable Comorbid Disease: Another disease process that would warrant intensive care unit (ICU)
admission without the presence of a GI bleed

Presence any one risk factor is considered as High-Risk condition.

Increased severity of lower GI bleeding is associated with the following risk factors (RF):
 heart rate greater than 100 beats per minute
 systolic blood pressure less than 115 mm Hg
 syncope
 non-tender abdomen
 rectal bleeding within four hours of presentation
 aspirin use
 more than two comorbidities

Zero RFs equates to a low incidence (6%) of severe bleeding.

One to three RFs equates to a moderate incidence (43%) of severe bleeding.
More than three risk factors equates to a high risk (79%) of severe bleeding

Localization of bleeding Site

Colonoscopy is the initial diagnostic procedure for nearly all patients presenting with acute LGIB except in patients
with massive LGIH with haemodynamic instability. The colonic mucosa should be carefully inspected during both
colonoscope insertion and withdrawal, with aggressive attempts made to wash residual stool and blood in order to
identify the bleeding site. The endoscopist should also intubate the terminal ileum to rule out proximal blood
suggestive of a small bowel lesion. Colonoscopy can diagnose the site of bleeding from 74-83% cases.
Bowel preparation
Once the patient is hemodynamically stable, colonoscopy should be performed after adequate colon cleansing.
Four to six liters of a polyethylene glycol (PEG) based solution or the equivalent should be administered over 3–4
hours until the rectal effluent is clear of blood and stool. It is associated with higher chance of localization of lesion
with a lesser risk of perforation. RCT shows the requirement of repeat colonscopy is < 8% in prepared bowel. AGA
guidelines recommend that unprepared colonoscopy / sigmoidoscopy should not be done Another study showed
colonscopy in unprepared bowel was associated with lower rate caecal intubation (69.2%) and localization of source
of bleed (38.5%). A nasogastric tube can be considered to facilitate colon preparation in high-risk patients with
ongoing bleeding who are intolerant to oral intake and are at low risk of aspiration. Factors predicting poor
preparation include presence of cirrhosis, High BMI, patients taking medication such as narcotic or antidepressant,
old age, presence of complex medical history

Timing of colonoscopy: Early colonoscopy within 24 hrs preferably (6-8hrs) versus delayed colonoscopy (>24 hrs)
is an issue of debate. The rationale being early diagnosis and control of source of bleeding. The metanalysis shows
early colonoscopy is associated higher detection of bleeding lesions, stigmata of recent haemorrhage and/ or
therapeautic interventions but that does not translates into decreased hospital stay, transfusion requirement,
decreased need for surgical intervention and lower mortality rate.
AGA guidelines recommend colonoscopy to be performed within 24 hours of patient presentation after adequate
colon preparation to potentially improve diagnostic and therapeutic yield in patients with high-risk clinical features
and signs or symptoms of ongoing bleeding following hemodynamic resuscitation. Colonoscopy should be
performed next available slot after a colon purge in patients without high-risk clinical features or serious comorbid
disease or those with high-risk clinical features without signs or symptoms of ongoing bleeding.

Radiologic studies
Tagged red blood cell radionuclide scan
Indication as screening modality to determine which patients will benefit from mesenteric angiography.
99 Tc pertechnate RBC scan is a sensitive investigation in patients with active gastrointestinal (GI) bleeding, with a
ability to identify bleeding that is occurring at rates as low as 0.1 mL/min.3 In addition, this study may be performed
several times over the course of a day if there is difficulty identifying the etiology of an intermittent bleed.3
Radionuclide scans, however, are a blunt diagnostic tool and can only suggest the general region of a bleed, which
limits its utility. Ng et al found that if blush is seen within 2 min after starting the scan then it had a 75% positive

13
predictive value on angiography while if the blush was seen after 2 min then it had a 93% negative predictive value
on angiography.

MDCT abdomen and pelvis along CT angiography

Indication
Next line investigation when routine colonoscopy fail to localize bleeding.
Triple phase study should be performed. It has a sensitivity of 100% for site localization whereas 88.2% for
etiology. Sensitivity is reported around 85-90% while specificity 79-96.6%. It is usually considered before
conventional angiography (CA) as pre CA screening modality.
The indicator of bleed on CT are a) enhancing bowel wall b) spontaneous hyperdensity of peri-bowel fat c)
extravasation of contrast in lumen d) presence of tumour, polyp or vascular ectasia e) pooling of contrast.
Macari et al found that CT is useful in differentiating intestinal ischemia from intramural bleed. The intestinal
ischemia involves long segment of bowel with wall thickening < 1cm whereas intramural bleed usually involves
shorter segment of bowel with wall thickness > 1cm on CT imaging.

Mesenteric angiography
Indication
When colonoscopy fail to localize bleeding
When bleeding is too brisk that colonoscopy cannot be performed such as patient received 4 unit blood in 2hr after
admission with a BP < 100mm Hg.
If a diagnostic test is desired for localization of the bleeding site prior to angiography, CT angiography should be
considered.
Conventional Angiography (CA) can detect bleeding at rates greater than 0.5 mL/min and allows therapeutic
intervention with catheter-guided embolization or injection of vasoactive substances at the same siting.3 The
disadvantages of CA include risk of colonic infarction with therapy & contrast-induced nephropathy. Since the
origin of bleeding is more common from right side therefore SMA is first investigated. Bleeding site could be
located in 72% cases using CA.

Small Bowel visualization studies including video capsule endoscopy (VCE), push enteroscopy, double balloon
enteroscopy can be used in case distal small bowel is the source of bleeding.

Intervention to Control the bleeding

Endoscopic hemostasis therapy
Endoscopic therapy should be provided to patients with high-risk endoscopic stigmata of bleeding: active bleeding
(spurting, oozing), non-bleeding visible vessel, or adherent clot. The various modalities available to control bleeding
are epinephrine/adrenaline injection, thermal contact, argon plasma coagulation (APC), clipping or band ligation.
10-40% patients require endoscopic treatment. Outcomes of colonoscopic haemostatic therapy are best when patient
is haemodynamically stable and bleeding slowly or bleeding has stopped. It is contraindicated in patients who are
haemodymaically unstable.

o Diverticular bleeding—Through the scope endoscopic clips are recommended since clips may be safer
in the colon than contact thermal therapy, and are generally easier to perform than band ligation
particularly for right-sided colon lesions.
o Angioectasia bleeding—Non-contact thermal therapy using argon plasma coagulation (APC) is
recommended.
o Post-polypectomy bleeding—Mechanical (clip) or contact thermal endotherapy, with or without the
combined use of dilute epinephrine injection, is recommended in such cases. Epinephrine injection
therapy (1:10,000 or 1:20,000 dilution with saline) can be used to gain initial control of an active
bleeding lesion and improve visualization, but should be used in combination with a second hemostasis
modality including mechanical or contact thermal therapy to achieve definitive hemostasis
Role of repeat colonoscopy in the setting of early recurrent bleeding
Repeat colonoscopy, with endoscopic hemostasis if indicated, should be considered for patients with evidence of
recurrent bleeding

Non-colonoscopy interventions
Mesenteric angiography
Radiographic interventions should be considered in patients with high-risk clinical features and ongoing bleeding
who have a negative upper endoscopy and do not respond adequately to hemodynamic resuscitation efforts, and are
therefore unlikely to tolerate bowel preparation and urgent colonoscopy. They should undergo angiography for
bleed localization and then control simultaneously.
Also performed as second line therapeutic option where colonoscopic methods fail to control the bleeding.

14
Transcatheter superselective embolization can control bleeding in around 63-92% cases. The bleed tend to recur in
around 11-50% more commonly in small bowel sources. The incidence of colonic necrosis reported in up to 20%
cases. However serious necrosis occur in 3% cases.
Transarterial instillation of vasopressin is reported to have 90% success but has recurrence of bleed in 22-71%
cases.

Surgery
A surgical consultation should be taken in patients with high-risk clinical features and ongoing bleeding. Surgery for
acute LGIB should be considered after other therapeutic options have failed, and should take into consideration the
extent and success of prior bleeding control measures, severity and source of bleeding and level of comorbid
disease. It is important to localize the source of bleeding whenever possible prior to surgical resection to avoid
continued or recurrent bleeding from an unresected culprit lesion. Morbidity and mortality associated with surgery is
reported around 60% and 10% respectively. Therefore it is considered as second line treatment. It is usually required
in 10-25% cases.

Indications for surgery are

Persistent hemodynamically instability with active bleeding.
Patient requiring > 4 unit PCV transfusion in 24 hrs with active or recurrent bleed
Persistent or recurrent bleed.
Surgical Options depend upon if the site is identified preoperatively

If bleeding site is not identified

Use of non crushing clamps to identify the bleeding site intra-operatively is no more used.
Intra-operative enteroscopy can be performed
Blind right hemicolectomy and subtotal colectomy can be performed in these sub group of patients.
Blind right hemicolectomy is still useful in India in patient where left side colonoscopy is negative as most causes in
our studies are right sided.
Subtotal colectomy is treatment of choice in patients with acive bleeding where site could not be localized in West.
The decision to perform primary anastomosis depend upon
a) haemodynamic instability
b) whether site of bleeding could be localized or not
If patient is unstable or if site is not localized ileostomy & mucous fistula should be performed as it is safe and helps
to localize whether bleed is originating from small bowel or large bowel.
The outcomes of data from AIIMS reveal that 44% patients underwent right hemicolectomy, 35% underwent
segmental resection whereas 9% underwent subtotal colectomy for LGIH. Bleed recurred in 8% patients while 30
day morlality was 15.5 %

Prevention of recurrent lower gastrointestinal bleeding

Predisposing factors of rebleed include the modality used to achieve primary hemostasis5; the use of antiplatelet
agents, nonsteroidal anti-inflammatory drugs (NSAIDs), and anticoagulants; the presence of end-stage renal disease
or cirrhosis; and the etiology of the initial bleed.4 It is not well established what the proportionate impact of these
individual characteristics have on the incidence of recurrent bleeding.5
Non-aspirin NSAID use should be avoided in patients with a history of acute LGIB particularly if secondary to
diverticulosis or angioectasia. In patients with established high-risk cardiovascular disease and a history of LGIB,
aspirin used for secondary prevention should not be discontinued. Aspirin for primary prevention of cardiovascular
events should be avoided in most patients with LGIB. In patients on dual antiplatelet therapy or mono-therapy with
non-aspirin antiplatelet agents (thienopyridine), non-aspirin antiplatelet therapy should be resumed as soon as
possible and at least within 7 days based on multidisciplinary assessment of cardiovascular and GI risk and the
adequacy of endoscopic therapy (as above, aspirin use should not be discontinued). However, dual antiplatelet
therapy should not be discontinued in patients with an acute coronary syndrome within the past 90 days or coronary
stenting within the past 30 days

Salient features of individual causes

Diverticulosis: It has been reported as most common cause of LGIH in west. The incidence is less in India but
under reported. Either stercoral trauma or repeated contraction and relaxation of muscularis propria leads to thinning
of media. The bleeding is most commonly from the dome of diverticulum or at its anti-mesenteric margin. 20%
diverticula bleed. Four-fifth (80%) stops on its own, 25% rebleed while 5% present as massive bleed. Sixty percent
bleed are from diverticula located in right colon. The evidence of bleed include visualization of bleed, presence of
adherent clot or non bleeding vessel are associated with higher risk of rebleed and therefore indication for
endotherapy. Rebleeding usually occur from same diverticula in 90% cases.

15
Only 5-40% bleed are localized on colonoscopy. The use of bowel preparation with colonoscopy performed within
24 hrs increases the chances of identifying culprit diverticulum. Among various options available clip application is
most commonly used to control bleeding as it has low risk of perforation. The culprit diverticulum should be stained
with India Ink or marked with clip for identification in future in case of rebleed. Strate reported 92-100% success in
cessation of bleeding after clip application. Thermal coagulation has a similar success but is associated with a little
higher risk of perforation. EBL used by Tokyo group to control the bleeding has been reported to have a success rate
similar to clip or heater probe. EBL has a potential risk of developing full thickness colonic necrosis although it has
not yet reported in that study. Rebleed after colonoscopic control of bleed is reported around 10%.

Angiodysplasia are ectatic vessels in the mucosa and submucosa of the GI tract. They appear as red flat lesions
measuring 2-10 mm in diameter with a sharp/indistinct margins, most commonly found in caecum and ascending
colon. It commonly occurs in older age group especially with patients having co-morbidity such as aortic stenosis,
CRF, COPD, cirrhosis. Majority of them have occult bleed which resolves spontaneously. Unlike deverticular bleed
80% patients with angiodysplasia rebleed. Symptomatic angiodyaplasia both occult and overt require treatment.
Asymptomatic lesions can be left alone. Many patients respond to Iron supplementation along transfusion and
correction of coagulopathies.

Endoscopic therapy in form of Argon plasma coagulation is useful in controlling bleeding in most cases (85%) but
these lesions are associated with high incidence of rebleed (up to 50%). Rebleed can occur at a different location
also. Other options for controlling bleed include heater probe & monopolar thermal coagulation. Heater probe has a
similar efficacy to APC but has a higher risk of perforation. Clip application may used in only select cases such as
large size lesions. A retrospective review of 62 pts comparing conservative management vs conservative plus APC
found a rebleed rate of 44% vs 21% (p=0.06). respectively. The risk factors identified were multiple prior bleed,
over anticoagulation and more than one site of lesions. Medical therapy such as hormonal therapy, octreotide and
thalidomide not advocated because of limited success and higher incidence of side effects. reserved for high burden
disease with failed endotherapy.

IBD usually causes mild to moderate bleed. In UC around 5% patient experience massive LGIH. Patients are started
on medical management. Those who do not respond to medical management undergo emergency surgery with
subtotal colectomy, ileostomy and Hartmann depending upon the friability of distal colonic end. Rarely protectomy
is required in emergency for ongoing bleed. Crohn's disease usually cause occult bleeding with anemia as common
presentation.

Ischemic colitis account for 3-5% causes of LGIH. It usually occur in elderly patients with cardiac comorbidity.
Bleed is usually mild to moderate. Patients present as bloody diarrhoea and pain. The most commonly affected area
are watershed region of splenic flexure and rectosigmoid junction.

Anorectal disease: blood streaked stools with painful defecation is diagnostic of Anal fissure. Haemorrhoids present
as painless spurts of fresh blood usually after stool. Anorectal disorders usually causes minor self limiting bleed.
More important is to remember that presence of anorectal cause without telltale signs of bleed does not exclude a
proximal source of bleeding. One should investigate proximal source of bleed with a detailed history and
sigmoidoscopy to exclude another cause. Medical management remain mainstay of treatment for fissures while
banding for haemorrhoids,

Colorectal carcinoma: usually present as mild to moderate bleed from ulcerated growth. Management is done
according to stage of the tumor.

Post polypectomy bleed: The incidence vary 0.6%-1.2% after polypectomy to 2.4-9.2% after Endoscopic mucosal
resection for > 2cm polyp. The risk factors for bleed include right sided polyps, large size polyp and use of low
wattage coagulation therapy. The bleeding is usually controlled by endoscopic clip placement.
Role of prophalytic clipping after polypectomy to prevent delayed post polypectomy Hge remain to be proven.
Studies suggest no role except in patients undergoing EMR for a large polyp >2 cm, sessile or flat nature. The
antiplatelets and anticoagulants should be preferably stopped for 1 week. Presently it is suggested that prophylactic
clip placement can be done for covering significant mucosal defect particularly in right colon and for those patient
who are being started on antiplatelet or anticoagulant post procedure. Post EMR scar clip artefact can be mistaken as
adenoma on follow up imaging.

Radiation induced proctitis & colitis: The incidence varies from 5-30% after radiotherapy and is on a decrease with
more precise administration of RT. It can be either acute (onset within 6 months of cessation of RT) or chronic
variety. Radiation therapy induces telengectasia and inflammatory changes in tissue thereby making it prone to
bleeding.

16
The incidence of bleeding varies from 6-8%. Massive bleeding more often occurs in chronic radiation proctitis. It
can occur months after radiation therapy. The rectal symptoms related chronic proctitis include rectal discomfort,
haemotochezia, stricture formation, loss of stool control and rarely perforation & fistula formation. The risk factor
for radiation injury include high dose of radiation, presence of co-morbidities such as diabetes, vasculitis, stage of
tumour, type of RT and other treatment received. Sigmodoscopy in these patients shows pale mucosa which easily
bleed on touch and presence of telengectasia. Biopsy if required should be taken from less radiated area as these
tissue have an increased risk for fistula formation. Many bleeds stops spontaneously with supportive treatment
alone.

Medical therapy is first line treatment if conservative management fails. Oral/ topical aminosalisylic acid,
oral/topical steroids, sucralfate enemas, metronidazole, vitamin A, formalin and hyperbaric oxygen therapy are
among various options for medical management. Best evidence exist for oral metronidazole, sucralfate enemas and
hyperbaric oxygen. Sucralfate act as physical barrier and promote vascular growth and healing. Kochhar et al
reported a success of 88.5% in 4 months treatment with 20 ml suspension of 10% sucralfate applied twice daily in
patient with moderate to severe haemochezia secondary to radiation proctitis. 20% patient developed a rebleeding
after sucralfate enemas.

20 ml of 4% or buffered 10% formalin soaked in guaze or cotton administered through proctoscopy followed by
thorough irrigation with saline is used for controlling severe bleeding. It works by inducing chemical burn. Side
effects associated with this therapy include perianal inflammation and discomfort, delayed rectal strictures,
rectovaginal fistula and necrosis. RCT from India compared Formalin vs Sucralfate steroid retention enema given
for 7-10 days in post radiation proctitis in cervical cancer patients. They reported success of 90% with formalin vs
74.5% with sucralfate-steroid enema. At 6-months follow up no major adverse effect were reported. In this study
patients with severe endoscopic disease such deep ulcers, strictures and fistulae were excluded.

ALGORITHM FOR MANAGEMENT OF LOWER GI BLEED

Endoscopic therapy in form of APC, heater probe and bipolar coagulation are reported to have equal efficacy for
controlling bleed. APC penetrates up to 3 mm tissue from surface. In APC 40-50 watt current is used with flow rate
1-1.5l/min. It control bleeding in 80-90% cases with 12-15% recurrence rete.

17
Surgery is rarely indicated in patients with radiation proctitis. Diverting stoma is most commonly performed. It
helps in healing and thus controlling bleed. Proctectomy is rarely performed as it is associated with high morbidity
(upto 80%) in form of leak, stricture and fistula and mortality (10%).

Non specific ulcers and colitis are most common cause of massive LGIH in India. These patients usually present
with history of fever and pain abdomen followed by hematochezia. Colonoscopy is the initial investigation of
choice. Bleed stop spontaneously in 80% cases. Surgical treatment is required in 10-20% as per the indication
mentioned above. Use of NSIADs and anticoaugulants should be noted as they are predictor of rebleed.

Drug induced LGIH is common in elderly patient with cardiovascular disorders on indiscriminate use of low dose
NSAIDS.

References
1. Strate LL, Naumann CR. The role of colonoscopy and radiologic procedures in the management of acute lower intestinal
bleeding. Clin Gastroenterol Hepatol 2010;8:333–43.
2. Case records of the Massachusetts General Hospital . Weekly clinicopathological exercises. Case 20-1985. A 39-year-old
man with melena and a radiologic abnormality of the cecum . N Engl J Med 1985 ; 312 : 1311 – 8 .
3. Alexander J. Nonvariceal gastrointestinal tract bleeding. In: Hauser SC, editor. Mayo clinic gastroenterology and hepatology
board review. 5th edition. New York: Oxford University Press; 2015. p. 123–4.
4. Strate LL, Gralnek IM. Management of patients with acute lower gastrointestinal bleeding. Am J Gastroenterol
2016;111(4):459–74.
5. Anthony T, Penta P, Todd RD, et al. Rebleeding and survival after acute lower gastrointestinal bleeding. Am J Surg
2004;188(5):485–90.
6. Beck KR, Shergill AK. Colonoscopy in Acute Lower Gastrointestinal Bleeding: Diagnosis, Timing, and Bowel Preparation.
Gastrointest Endosc Clin N Am. 2018 Jul;28(3):379-390. doi: 10.1016/j.giec.2018.02.009. Review. PubMed
PMID:29933782.
7. Gupta S, Greenwald DA. Prevention of Recurrent Lower Gastrointestinal Hemorrhage. Gastrointest Endosc Clin N Am.
2018 Jul;28(3):409-424. doi: 10.1016/j.giec.2018.02.011. Epub 2018 Apr 17. Review. PubMed PMID: 29933784.
8. Feinman M, Haut ER. Lower gastrointestinal bleeding. Surg Clin North Am. 2014 Feb;94(1):55-63. doi:
10.1016/j.suc.2013.10.005. Review. PubMed PMID: 24267497.
9. Sengupta N, Cifu AS. Management of Patients With Acute Lower Gastrointestinal Tract Bleeding. JAMA. 2018 Jul
3;320(1):86-87. doi: 10.1001/jama.2018.5684. PubMed PMID: 29971385.

18
 Intestinal Polyposis Syndromes
Manoj Andley
Introduction
Intestinal polyposis syndromes are relatively rare, however awareness of the existing health risks is important for patients and
their families affected by these disorders. Intestinal polyposis syndromes can be classified based on histology, into the broad
categories of familial adenomatous polyposis (FAP), hamartomatous polyposis syndromes, and other rare polyposis
syndromes, such as hereditary-mixed polyposis syndrome (HMPS) and serrated polyposis syndrome (SPS).

Several genetic disorders may present with GI polyps. FAP is the most common inherited polyposis syndrome, including
multiple phenotypes. These phenotypes range from a mild phenotype in attenuated polyposis syndrome to specific clinical
syndromes recognized many decades prior to the discovery of the adenomatous polyposis (APC) gene.

Several specified variants of FAP, namely Gardner syndrome, Turcot syndrome, and MYH-variant, have been identified.
Individuals with Gardner syndrome develop adenomatous polyps throughout the GI tract, accompanied by extracolonic
manifestations, including periampullary adenomas, papillary carcinoma of the thyroid, hepatoblastoma, osteomas of the
mandible and skull, epidermal cysts, and desmoid tumors. Gardner syndrome, which has autosomal dominant inheritance, is a
term used to refer to patients in whom these extraintestinal features are unusually prominent.

Turcot syndrome another variant of FAP, is a rare autosomal recessive disorder that can present with brain tumors
(glioblastoma multiforme, medulloblastoma) and colonic adenomas that frequently become malignant in those younger than 30
years.

MYH-associated polyposis, or MutYH - associated polyposis (MAP), occurs in a small number of patients with FAP and
results from a mutation in the human MutY homolog gene instead of the APC gene. Unlike FAP, MAP is autosomal recessive,
with complete penetrance by age 60 years.[1]

The broad category of hamartomatous polyposis syndromes includes several syndromes, mainly Peutz-Jeghers Syndrome
(PJS), PTEN -associated hamartomatous syndromes (including Cowden syndrome and Bannayan-Riley- Ruvalcaba syndrome
[BRR]), familial juvenile polyposis, and Cronkhite-Canada syndrome.

In PJS , an autosomal dominant disease, polyps can occur anywhere within the digestive tract (consistently within the jejunum)
and are accompanied by characteristic melanin spots on the lips and digits. Scattered studies have reported malignant
degeneration within GI polyps and development of extraintestinal malignancies, including pancreatic, testicular, and
gynecologic malignancies. Development of gynecomastia commonly preceded the development of gynecologic or testicular
malignancy.

Cowden disease is classified as a multiple hamartomatous syndrome with autosomal dominant inheritance.[2] . Individuals
with Cowden disease present at age 10-30 years with hyperplastic hamartomatous polyps throughout the GI tract (including the
esophagus), glycogenic acanthosis of the esophagus, orocutaneous hamartomas of the face, pulmonary hamartomas, and
neoplasia (breast, thyroid, adenocarcinoma of the colon [rare) In BRR syndrome hamartomatous polyps of the colon and
tongue are present along with macrocephaly, lipomas, and hemangiomata. Recent studies have supported the argument that
they are the same disease with variable expression and age-related penetrance.[3] The PTEN- associated hamartomatous
syndromes can also include Proteus syndrome and Proteus-like syndrome.

FJP, also described in the literature as juvenile polyposis, is characterized by multiple inflammatory polyps throughout the
colon that are associated with painless rectal bleeding (rare serious hemorrhage), rectal prolapse, and failure to thrive. This
entity is different than solitary juvenile polyps, which are common in children and do not have the lifetime risk of malignancy.

Cronkhite-Canada syndrome presents at an average age of 59 years, exhibit multiple intestinal polyps and ectoderm
abnormalities, including hyperpigmentation of the skin, alopecia, and onychoheterotopia. Cronkhite-Canada syndrome is
acquired rather than inherited and is associated with a high mortality rate.

HMPS is extremely rare. It is characterized by familial presentation of colorectal polyps that have mixed histologic elements
with both adenomatous and hyperplastic features.[4] Gorlin syndrome (GS), also termed nevoid basal cell carcinoma
syndrome, is associated with medulloblastoma . GS commonly presents with hamartomatous gastric polyps, palmar pits,
short metacarpals, odontogenic keratocysts, intracranial calcifications, skeletal malformations, and neoplasia (basal cell
carcinoma, ovarian carcinoma, medulloblastoma).

SPS is characterized by multiple, large serrated polyps within the colon leading to a high risk of colorectal cancer. Although its
inheritance is unclear, hereditary and sporadic cases have been described in the literature.[5]
Pathophysiology

19
With the exception of Cronkhite-Canada Syndrome, all of the intestinal polyposis syndromes have been associated with
genetic mutations. Mutations within the loci of tumor suppressor genes result in the myriad of clinical manifestations of
disease.

EPIDEMIOLOGY

Frequency
The frequency depends on the specific syndrome and does not vary drastically between the United States and other countries.
FAP is inherited in an autosomal dominant fashion and is the most common intestinal polyposis syndrome with an estimated
frequency of 1:13,000 births.[6]
Some overlap between kindreds with Gardner syndrome and kindreds with Turcot syndrome may be observed, but these
variants of FAP are much rarer than FAP itself. PJS has an estimated prevalence of between 1:120,000 and 1:200,000 births.
The estimated incidence of Cowden syndrome is 1:200,000 but is likely higher than that due to its penchant for being
underdiagnosed.[7] BRR syndrome is extremely rare despite its autosomal dominant inheritance.
FJP is thought to have an incidence of 1:100,000, making it the most common hamartomatous polyposis syndrome. [8]
Cronkhite-Canada Syndrome is considered to be a rare, sporadic, and acquired syndrome.[4] To date, barely over 500 cases
have been reported worldwide. Estimated incidence is 1:1,000,000. Disease presents later in age, with a mean age of diagnosis
of 59 years.[9]
Farndon et al have conservatively estimated the prevalence of GS at 1:57,000 births.[10] In individuals who develop basal cell
carcinoma before age 19 years, the incidence of GS rises markedly to 1:5.
Initial studies estimated the prevalence of SPS at 1:3,000 patients who were screened. However, the true prevalence is most
likely closer to less than 0.09%. If screened after a positive fecal occult blood test result, the prevalence increases to 0.34% to
0.66%.[11]

Mortality/Morbidity
Morbidity and mortality in intestinal polyposis syndromes are largely due to complications from polyps or development of
associated malignancies. Complications from the polyps include bleeding and intussusception.

The development of associated malignancies differs based on the specific intestinal polyposis syndrome. Individuals with FAP
have a 100% lifetime risk of colorectal cancer if they do not undergo colectomy. Cancer usually develops at age 20-40
years.[12] In addition, a 5-10% lifetime risk of duodenal adenocarcinoma and/or periampullary adenocarcinoma is also noted.
The lifetime risk of thyroid cancer and gastric adenocarcinoma is less than 1%. Other malignancies, including desmoid tumors
(especially after surgery), hepatoblastoma, adrenal cortical carcinoma, thyroid carcinoma, sarcoma, glioblastoma, and
medulloblastoma have been associated with Gardner syndrome.

Morbidity and mortality in Turcot syndrome arises from complications of CNS tumors (eg, medulloblastoma, astrocytoma,
gliomas, glioblastoma multiforme, gliomas), GI neoplasia (eg, colonic adenocarcinomas, gastric carcinomas), and basal cell
carcinomas of the scalp. Van Meir reported mean survival rates of 5.6 years from diagnosis for patients with medulloblastoma
and colonic adenomas and 27.5 months from diagnosis for patients with glioblastoma and adenomas.[13]
Morbidity and mortality in PJS arises from complications of polyps such as intussusception and bleeding and the development
of malignancies of the stomach, pancreas, and lung. An increased risk for breast, ovarian, uterine and cervical cancer is noted
in young women along with Sertoli cell tumors in young men; 93% of patients with PJS develop cancer by age 65 years, with a
mean age of 42 years.[12] GI cancer develops in 70% of patients with PJS. [8]

Individuals with PTEN- hamartomatous syndromes, such as Cowden syndrome and BRR syndrome, are at risk from non-GI
malignancies such as breast, uterine, cerebellum, thyroid, kidney, and skin; complications from lipomas and arteriovenous
malformations; and thyroid disease. Female breast cancer has an 85% lifetime risk.[14]

Similar to PJS, in FJP, polyps may bleed or cause obstruction. Sporadic reports detail gastric, small bowel, and pancreatic
cancers, but a more substantial increased risk of colon cancer is seen in these individuals, with cumulative lifetime risk of
50%.[15]

Cronkhite-Canada syndrome has an extremely unfavorable prognosis, with a 5-year mortality rate of 55%, secondary to life-
threatening GI bleeding, intussusception, infection, malnutrition, heart failure, and protein-losing enteropathy leading to
electrolyte disturbances.[4]

White individuals who have GS develop basal cell carcinomas when younger than 20 years. Patients with GS are at increased
risk for ovarian carcinoma and medulloblastoma. Children who are younger than 5 years and have medulloblastoma should be
tested for GS before initiation of radiation therapy to diminish the risk for early development of basal cell carcinoma.
Patients diagnosed with SPS have between a 25-75% risk of colorectal cancer, which increases as the number of polyps and
serrated adenomas increase.[5]

20
Race
FAP, PJS, the PTEN- hamartomatous syndromes, FJP, and Cronkhite-Canada syndrome have no reported race predilection.
Patients who have Gorlin syndrome and are of Mediterranean or African descent have diminished risk for developing basal cell
carcinomas secondary to skin pigmentation. Kimonis noted that basal cell carcinomas develop in 80% of white patients
compared with 38% of black patients.[16]

Sex
The inheritance for Gardner syndrome is autosomal dominant, with nearly 100% penetrance of the APC mutation by age 40
years. Women with Gardner syndrome have an increased risk for the development of thyroid cancer and desmoid tumors.
Klemmer et al found an increased incidence of desmoid tumors among females (8% of male vs 13% of females).[17] Bell and
Mazzaferri reported that 94% of patients with Gardner syndrome who had thyroid carcinoma were women.[18]
The inheritance of Turcot syndrome is autosomal recessive. No differences in symptom manifestations between the sexes has
been reported. The inheritance for PJS is autosomal dominant. The life expectancy for women with PJS may be decreased by
development of gynecologic malignancies. Males with PJS are at increased risk for development of testicular cancer.
The PTEN- hamartomatous syndromes are considered to be autosomal dominant. In a 1993 series by Hanssen et al, an excess
of affected female patients was reported in Cowden disease.[19] In that survey of 87 patients, 70% (61) of the patients were
female. Female patients with Cowden syndrome are predisposed to the development of breast neoplasia and neoplasia of the
urogenital system.
Cronkhite-Canada syndrome exhibits a slight male predominance at a ratio of 3:2.[9] GS is inherited in an autosomal dominant
pattern, without reported differences in disease manifestation by gender. FJP is also autosomal dominant. SPS has no
documented sex predominance.

Age
Patients with FAP generally present in late adolescence with symptoms of polyposis (GI bleeding). Some patients have
reported GI bleeding in early childhood, and case reports have noted colon cancer presenting in children aged 5 years old and
younger.[20] Children with Gardner syndrome and Turcot syndrome can present with extraintestinal manifestations before
symptoms of polyposis arise, including medulloblastoma, hepatoblastoma, osteomas, or retinal pigment epithelium
hypertrophy. Patients in the Turcot syndrome subgroup develop glioblastomas; colonic adenomas develop somewhat later
(mean age 18 y; range 4-70 y).[21]
Children with PJS have presented in the neonatal period with complications of GI polyposis.[22] The average age of diagnosis
of PJS is 24.3 years.
Patients with PTEN- hamartomatous syndrome can often be diagnosed in childhood, with congenital findings of macrocephaly
and mild or moderate developmental delay. During later childhood, trichilemmomas within the nasolabial folds, palmar pits,
subcutaneous lipomas, and hemangiomas manifest.[23]
Patients with Cronkhite-Canada syndrome present in middle to late adulthood; mean age of presentation is 59 years. The rare
reported pediatric cases have features similar to infantile juvenile polyposis.[9] Patients with FJP present in childhood and
adolescence, most commonly with isolated rectal bleeding.[24]
Neonates with GS present with lung cysts, rib and vertebral anomalies, palmar pits, hydrocephalus, and cleft palate. Symptoms
of medulloblastoma in GS manifest in patients younger than 2 years. Basal cell carcinomas generally appear in patients with
GS who are in their early twenties but may present in patients younger than 10 years.[16]

PRESENTATION

History
Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) presents with multiple adenomatous polyps, anywhere from 100s to 1000s, throughout
the colon . The colonic mucosa is studded with innumerable sessile and small pedunculated polyps, which involve the entire
length of the specimen.
Eighty percent of these polyps present in the left colon. Patients with FAP are at risk for upper GI tract malignancies as well as
for hepatoblastoma, which has an increased incidence in children with a family history of FAP.
In variants of FAP, manifestations can affect the entire body. Talbot classifies the manifestations of Gardner syndrome via
tissue distribution.[25]
In most individuals, symptoms of polyposis manifest as sessile tubular adenomas in late adolescence; however, some
individuals have developed polyps in early childhood. Fundic gland polyps rarely develop into gastric cancer.
Mesodermal sites associated with Gardner syndrome include fibrous tissue (desmoid tumors), bone (osteomas, dental
anomalies), and liver (hepatoblastoma).
Ectodermal tissues include the eyes (congenital hypertrophy of the retinal pigment [CHRPE]), skin (cysts), CNS
(medulloblastoma), and endocrine system (thyroid carcinoma, multiple endocrine neoplasia 2B).
Van Meir classified the presentation of patients with Turcot syndrome into 2 categories, stratified by the presence or absence
of colorectal phenotype.[13] Patients with medulloblastoma who expressed the colorectal phenotype were older than 17 years
at disease onset, whereas patients with medulloblastoma in the absence of the colorectal phenotype were younger than 10 years
at disease onset. These patients also have manifested ocular fundus lesions, epidermal inclusion cysts, and osteosclerotic jaw

21
lesions consistent with Gardner syndrome.

Peutz-Jeghers Syndrome
Patients with Peutz-Jeghers syndrome (PJS) generally have with multiple pedunculated GI hamartomatous polyps, with lesions
distributed through the small intestine (78%), colon (42%), stomach (38%), and rectum (28%).[26] They tend to present with
the following symptoms:
GI bleeding
Intussusception
Rectal prolapse
Nasal polyposis (chronic sinusitis) Pigmented macules on the lips and digits
Gynecomastia. The diagnosis of PJS should be made with 2 or more histologically confirmed polyps, polyps associated with
characteristic pigmentation, or polyps in setting of family history. The development of gynecomastia in a child with suspected
PJS should prompt investigation for underlying testicular or gynecologic malignancy.

PTEN-hamartomatous syndromes
Cowden disease, which is thought to be the same entity as BRR syndrome, manifests with variable penetrance at a later age
and is typically associated with the following features:

Developmental delay Macrocephaly (38%), Cerebellar dysfunction, Scoliosis ,Cutaneous hamartomas,
Thyroid disease
(>50%) such as Hashimoto thyroiditis ,Chronic diarrhea

Malignancies: Neoplasia of the breast develops in 75% of females with Cowden disease. Other malignancies that have
been reported in patients with Cowden disease include dysplastic gangliocytomas of the cerebellum, ovarian tumors,
thyroid tumors, renal cell adenocarcinoma, and Merkel cell carcinomas

Visceral arteriovenous malformations: These malformations have been reported in a family diagnosed with Cowden
syndrome and, based on genetic testing findings, were found to have a frameshift mutation in the PTEN gene.[27] This
association has been attributed to hypothesized function of the PTEN gene in the suppression of angiogenesis.

Bannayan-Riley-Ruvalcaba (BRR) syndrome: Features commonly associated with the entity that is known as BRR
syndrome include increased weight and length at birth. Growth velocity generally tapers by the time the patient is aged 7
years. Children often present with developmental delay, mild mental retardation, excessive drooling and hypotonia.
Cutaneous features frequently include freckling of the glans penis (85% of male patients), lipomas (70% of patients),
myopathy (60% of patients), hamartomatous GI polyps (45% of patients), hemangiomata (10% of patients), and
telangiectasias. Typical dermatologic findings include vascular malformations, lipomatosis, speckled lentiginosis of the
penis or vulva, facial verrucae–like or acanthosis nigricans–like lesions, and multiple acrochordons of the neck, axilla,
and groin. Other reported features include testicular enlargement, cryptorchidism, Hashimoto thyroiditis, and congenital
heart disease (ventricular septal defect).

Familial juvenile polyposis

Usually, polyps vary in number, with variation in size and location. They can present with rectal bleeding, abdominal pain, and
diarrhea. Patients with familial juvenile polyposis (FJP) are diagnosed when the following criteria are met: 5 (some sources say
10) juvenile polyps in the colon
Juvenile polyps throughout the GI tract
Any number of juvenile polyps with a family
history of juvenile polyposis[28]. Associated congenital extracolonic anomalies are described in as many as 20% of these
patients, ranging from neurologic (macrocephaly), thoracic (congenital heart disease), and urogenital, to GI(malrotation).[4]
Congenital findings are more common in sporadic cases than the familial form of FJP.

Cronkhite-Canada syndrome
Cronkhite-Canada syndrome is a clinical syndrome with high mortality that presents with the following: Generalized GI
polyposis (sparing the esophagus),
dermal pigmentation and atrophy of the nail beds, alopecia. Other characteristics may
include anosmia, cataracts, thrombosis, cardiac failure, peripheral neuropathy, psychiatric issues, and acute pancreatitis,Severe
protein-losing enteropathy, leading to malabsorption with electrolyte disturbances [4]

Gorlin syndrome
Patients with Gorlin syndrome (GS) may present in infancy with congenital hydrocephalus, cleft lip and palate, lung cysts, rib
and vertebral anomalies, and palmar pits. A case report by Genevieve et al described a child with GS who presented prenatally
with a chylothorax.[29] Enamel hypoplasia has also been described in the dental literature and attributed to lyonization.
Children at risk for inheritance of the gene should undergo a detailed examination at birth to look for palmar pits and other
physical features, as well as radiologic evaluation of the rib, skull, and spine. Children with GS may present with symptoms of
medulloblastoma when younger than 5 years. Dental anomalies and basal cell carcinoma can appear in adolescents.
Serrated polyposis syndrome
Serrated polyposis syndrome (SPS) is characterized by progression from hyperplastic polyps to serrated carcinoma and require
the following criteria for diagnosis as per WHO guidelines:
At least 5 serrated polyps proximal to the sigmoid colon, 2 of which are greater than 10 mm in diameter Any number of
serrated polyps occurring proximal to sigmoid colon in individual with first degree relative already diagnosed with SPS More

22
than 20 serrated polyps of any size throughout the colon.Patients with SPS can have conventional adenomas in addition to
serrated polyps.

PHYSICAL EXAMINATION

Familial adenomatous polyposis

Physical examination findings of FAP include the following:
Ocular: Congenital hypertrophy of the retinal pigment epithelium (characteristic pigmented fundus lesions) occur in roughly
70-80% of patients with FAP.[1]
GI: Multiple gastric polyps, multiple duodenal polyps, multiple colonic polyps, and mesenteric fibromas (desmoids) are noted.
Oncologic: Malignant transformation of polyps, gastric carcinoma, periampullary carcinoma, hepatoblastoma, biliary ductal
carcinoma, osteosarcoma, adrenal carcinoma (Cushing syndrome), and thyroid carcinoma are noted.

Gardner syndrome
Physical features commonly associated with Gardner syndrome, addition to those listed above for FAP, include the following:
Skin - Epidermal cysts (commonly on the back), sebaceous cysts (commonly on the back)
Craniofacial - Osteomas (including the mandible), skin fibromas, dental anomalies (supernumerary teeth, impacted teeth,
missing teeth, root anomalies)[30]
Endocrine - Cushing syndrome (adrenal carcinoma), multiple endocrine neoplasia 2B

Turcot syndrome
Attributes of Turcot syndrome include the following:
Skin - Café au lait spots, multiple lipomas, basal cell carcinoma of the
scalp
GI - Colonic polyps (including adenomatous), hepatic focal nodular hyperplasia, adenocarcinoma of the colon, gastric
carcinoma
CNS - Glioma, glioblastoma multiforme, astrocytoma

Peutz-Jeghers Syndrome
The following findings are common in PJS:Skin - Melanin spots on the lips, digits, and oral mucosa GI - Multiple GI polyps
(especially jejunal), intussusception, GI bleeding, rectal prolapse Genitourinary (GU) - Polyps within ureter, bladder, and renal
pelvis Pulmonary - Nasal and bronchial polyps
Thorax - Gynecomastia (testis, ovarian tumors)

PTEN hamartomatous syndromes

Manifestations of Cowden disease include the following:
 Skin - Multiple hamartomas of skin and mucus membranes, verrucous lesions, acral keratoses, papules of gingival
and buccal mucosa, facial trichilemmomas (benign tumors of the lower outer root sheath epithelium of a hair follicle)
Cerebrospinal, head - Craniomegaly, adenoid facies, ataxia, increased intracranial pressure, cerebellar degeneration,
mental retardation, tremors, tonsillar herniation, seizures
 Endocrine - Thyroid hamartomas and nonmedullary carcinoma
 Chest - Breast hamartomas and carcinomas, pectus excavatum
 GI - Scrotal tongue, intestinal polyps (hamartomatous)
 Oncology - Dysplastic cerebellar gangliocytoma, breast carcinoma, ovarian carcinomas, Merkel cell skin carcinomas,
renal cell adenocarcinomas, thyroid carcinomas
 Spine – Scoliosis Common findings associated with BRR syndrome include the following:
 General - Increased weight and length at birth, macrocephaly, scaphocephaly, broad thumb, and hallux CNS -
Hypotonia and myopathy, developmental delay, mild mental retardation Cardiovascular - Arteriovenous
malformation, congenital heart disease (eg, ventricular septal defect) Pulmonary - Pectus excavatum
 GI - High palate, hamartomatous intestinal polyps (colon, tongue) GU - Enlarged penis, spotted pigment of glans
penis, testicular enlargement Ocular - Pseudopapilledema, exotropia

Familial juvenile polyposis

Common findings with FJP include the following:
GI - Numerous hamartomatous polyps throughout the GI tract that may cause bleeding or obstruction, malrotation,
Meckel diverticulum
Cardiac - Congenital heart disease (eg, tetralogy of Fallot, atrial septal defect, coarctation of the aorta, patent ductus
arteriosus, subvalvular aortic stenosis)
CNS - Macrocephaly, hydrocephalus, spina bifida
GI - Undescended testes, bifid uterus and vagina, abnormal UPJ
insertion, unilateral renal agenesis Skeletal - Osteoma , abnormal facies, cleft lip/palate

Cronkhite-Canada syndrome

23
This syndrome typically presents with complications from generalized polyposis associated with typical hyperpigmented skin
findings.[31]

Gorlin syndrome
Physical characteristics associated with GS include the following:
Skin - Basal cell nevi and carcinoma
Craniofacial - Broad facies, including nasal root, bossing of frontal and parietal bones,
cleft lip and palate, mandibular prognathism, dental anomalies (odontogenic keratocysts)
Ocular - Strabismus, hypertelorism,
colobomas, subconjunctival epithelial cysts, glaucoma
Cardiac - Cardiac fibromas
Pulmonary - Congenital lung cyst, rib
anomalies
GI - Hamartomatous gastric polyps, lymphomesenteric cysts
GU - Ovarian fibromas and carcinomas CNS -
Congenital hydrocephalus, mental retardation, medulloblastoma Skeletal - Scoliosis, kyphoscoliosis, cervical anomalies, rib
anomalies, brachydactyly, short fourth metacarpal and thumb

Differential Diagnoses
Colitis,Inflammatory Bowel Disease,Malignancy,Pediatric Intussusception ,Pediatric Meckel Diverticulum,
Pediatric Rectal
Prolapse,Pediatric Anal Fissure, Congenital Arterial, Venous, and Lymphatic Anomalies.

Investigations
The following studies are indicated in patients with intestinal polyposis syndromes:CBC count with differential and
platelets,
Stools for occult blood,
Prothrombin time/activated partial thromboplastin time (if significant bleeding is present)
Serum albumin levels (if weight loss is present) Genetic testing, including band 5q21-22 for Gardner syndrome (ie, familial
adenomatous polyposis [FAP]), band 7p22, 5q21-22, and 3p21.3 for Turcot syndrome, band 19q13.3-13.4 for Peutz-Jeghers
syndrome (PJS), band 10q23.3 for Bannayan-Riley-Ruvalcaba syndrome (BRR) and Cowden disease, band 9q22.3-q31 for
Gorlin syndrome (GS).Fecal alpha1-antitrypsin or fecal calprotectin (if albumin is low and weight loss is present; to evaluate
for protein-losing enteropathy). Levothyroxine (T4), triiodothyronine (T3), thyroid-stimulating hormone (TSH), thyroid
antimicrosomal or thyroid peroxidase antibody to exclude Hashimoto thyroiditis in individuals with symptomatic BRR
syndrome. Liver function tests and alpha-fetoprotein level to screen for hepatoblastoma in patients with suspected Gardner
syndrome and an abdominal mass; electrolytes, plasma or urine cortisol, and adrenocorticotropic hormone (ACTH) in patients
with suspected Gardner syndrome if Cushing syndrome is present

Imaging Studies
The role of imaging studies in favor of endoscopic examination has not been well established for individuals with intestinal
polyposis syndromes.[32]
For those individuals with small bowel polyposis, double balloon enteroscopy (DBE), both radiation exposure. Thus, video
capsule endoscopy is an emerging modality used to evaluate for small bowel polyps that spares radiation for the patient.[34,35]
It has been shown to be better than UGI with SBFT for polyp detection rate, comfort, and patient preference.[36]

Air-contrast barium enema (BE) can be used to evaluate for colonic polyps in patients who are not candidates for colonoscopic
examination. Magnetic resonance enterography can be used for small bowel surveillance of polyps as well and serves as a
complementary study to video capsule endoscopy, especially because the capsule can overestimate polyps secondary to
retrograde flow.[36] Air-contrast barium enema (BE) can be used to evaluate for colonic polyps in patients who are not
candidates for colonoscopic examination. Contrast-enhanced ultrasonography is emerging as a noninvasive technique to
characterize vascular patterns of polyps with the aim of recognizing neoangiogenic traits of colorectal adenomas and
carcinomas. This imaging modality may help differentiate hamartomatous polyps from adenomatous polyps, which may have
malignant potential, especially in PJS.[37] Additional imaging studies in patients with Gardner syndrome may include the
following:
Radiographs of the skull, teeth, and mandible to screen for osteomas and plan management of dental anomalies, CT scanning,
ultrasonography, or MRI of the abdomen to evaluate abdominal masses (hepatoblastoma, adrenal carcinoma, mesenteric
fibromas/desmoids).In patients with Turcot syndrome, CNS imaging, GI imaging, and other imaging modalities are indicated if
Gardner syndrome is suspected, as clinically warranted. For patients with known PJS, perform routine screening,
mammogram, and breast ultrasound for early detection of occult neoplasms. Perform ultrasonography or CT scanning of the
pelvis or testicles to screen for possible malignancies in patients with conditions such as gynecomastia and precocious puberty.
For patients with known PTEN- hamartomatous syndrome imaging studies include the following:
Routine breast imaging to
screen for neoplasia (Seventy five percent of females develop breast neoplasia.) Imaging of the thyroid, if suggestive of
malignancy
Imaging of the ovaries, if suggestive of malignancy
MRI of the head, if symptomatic
Radiography of the
spine to monitor for scoliosis. For patients with known GS, perform radiography of the mandible, ribs, and spine to diagnose
and treat anomalies. Perform CNS imaging to exclude hydrocephalus and medulloblastoma if warranted by clinical evaluation.
Perform imaging of the ovaries to exclude pathologic conditions of the ovaries in women with suggestive symptoms. Patients
with GS should not require SBFT or BE for detection of polyps (only gastric polyps have been reported). In a series of 105
patients with GS, Kimonis et al reported the following radiologic findings:[16] Calcification of the falx cerebri
(65%)
Bridged sella (68%)
Flame-shaped lucencies in the phalanges, carpals, and metacarpals (30%) Bifid ribs
(26%)
Calcification of the tentorium cerebri (20%)
Hemivertebrae (15%)
Fused vertebral bodies (10%)

24
Procedures
All patients with polyposis syndromes require serial endoscopy and colonoscopy to evaluate for the degree of polyposis and
survey for malignant transformation. In patients who have PJS and chronic sinusitis, endoscopic evaluation for possible nasal
polyposis may be required. In patients with Cowden disease, biopsies of suspicious lesions seen on the mammogram are
warranted to exclude neoplasia, and biopsies of other suspicious areas are indicated to exclude malignancy. In patients with
GS, skin biopsies may be required to exclude basal cell carcinomas.

Treatment Medical Care

In several of the polyposis syndromes, medical care encompasses screening and intervention for malignant transformation.
Particularly in the case of familial adenomatous polyposis (FAP), in which an inevitable progression to colorectal cancer
occurs by age 35-40 years,[6] screening of patients and family members has led to an improvement in cumulative survival and
a 55% reduction in colorectal cancer at diagnosis of FAP.[38] Approximately 50% of patients with familial juvenile polyposis
(FJP) develop GI cancer.[39]

Familial adenomatous polyposis

Unless a family history of early and aggressive disease is noted, children at risk for FAP should be screened twice yearly
starting at age 10-12 years. Flexible sigmoidoscopy is sufficient because the adenomas are distributed throughout the colon.
The American Gastroenterological Association recommends an annual sigmoidoscopy or colonoscopy for patients with a
genetic diagnosis of FAP or for at-risk family members who have not undergone genetic testing.[40] Narrow-band imaging can
identify higher numbers of duodenal adenomas, but it did not lead to a clinically relevant upgrade in stage when compared with
high-resolution endoscopy.[41]
If the patient undergoes prophylactic colectomy, the ileal pouch is at risk for developing adenomatous carcinoma and should be
screened with endoscopy on a yearly basis. Gastric and duodenal lesions occur in 45% of patients with the APC mutation, and
upper endoscopy should begin when colonic adenomas are identified or at age 20-25 years. A study of pediatric patients with
APC mutations suggests that upper endoscopy should begin even earlier.[42]
The risk of developing malignancy in these lesions is lower than the risk from colonic lesions but is still approximately 12%.
Depending on the polyp burden, front and/or side-viewing endoscopies of the stomach, duodenum, and periampullary region
should occur every 6 months to 4 years. The risk of periampullary tumors is increased in these patients. The tumors are best
viewed with both side-viewing and end-viewing instruments.[43] Current options for management include endoscopy,
chemoprevention, duodenectomy, the Whipple procedure, and ampullectomy, none of which have been especially successful.
Patients with the APC gene mutation at codon 1309 are at risk for a more aggressive phenotype, and early screening and
colectomy is advocated for in children with this mutation.[42]
Postcolectomy, mesenteric or abdominal wall desmoids can develop and may cause fatal complications from sepsis or
hemorrhage. They are more common in females and can cause obstruction of the mesenteric blood supply, intestines, or
urinary tract.[1]

Gardner syndrome
In addition to the above recommendations for FAP, patients with Gardner syndrome require medical care and management of
cutaneous cysts, osteomas, fibromas, polyposis, and diligent surveillance for neoplasia. Carcinoma may develop at any age,
from late childhood through senior years. Young children with gene mutations related to Gardner syndrome have an increased
risk for development of hepatoblastoma. Hughes and Michels noted Gardner syndrome in 2 of 470 children who had parents
with Gardner syndrome versus an incidence of 1 per 100,000 general population.[44] Patients with Gardner syndrome are
predisposed to the development of polyposis throughout the GI tract and to carcinomas of the stomach, periampullary region,
biliary tract, and colon. Women with Gardner syndrome have an increased risk of desmoid tumors and thyroid carcinoma.
Development of thyroid carcinoma is 100 times more likely among patients with Gardner syndrome. Osteosarcomas and
adrenal carcinomas (with Cushing syndrome) have been previously reported in patients with Gardner syndrome.

Turcot syndrome
As with Gardner syndrome, in addition to the above recommendations for FAP, patients with Turcot syndrome require
management of basal cell carcinomas and treatment of CNS malignancies, including astrocytoma, glioblastoma, and
medulloblastoma.
Patients with Turcot syndrome are predisposed to the development of hepatic focal nodular hyperplasia.

Peutz-Jeghers syndrome
Patients require medical management for problems attributed to polyposis and for detection of malignancy. Patients with
Peutz-Jeghers syndrome (PJS) may develop significant GI bleeding, intussusception, and rectal prolapse, requiring diagnosis
and treatment, including endoscopy and surgical resection. Nasal endoscopy may be necessary in the presence of chronic
sinusitis to exclude the presence of significant nasal polyps. Long-term surveillance strategies to monitor for GI malignancies,
including bowel, pancreatic, and periampullary malignancies. Colonoscopy is recommended every 3 years starting when
symptoms occur or in the early teenage years in asymptomatic patients. At age 10 years, twice yearly upper endoscopies and
barium imaging of the upper GI tract are recommended.[43] Long-term surveillance to monitor for extraintestinal malignancies
(eg, breast, gynecologic, testicular) is indicated. The use of the potassium titanyl phosphate (KTP) laser to treat mucocutaneous

25
melanosis of the lips and hands in a patient with PJS has been reported in the United Kingdom.

PTEN-hamartomatous syndromes
If a patient remains asymptomatic, a first colonoscopy is recommended between the ages of 35-40 years, with follow- up
determined by number and type of polyps found on screening.[45] Patients require medical therapy for CNS abnormalities,
complications of lipomas and arteriovenous malformations, treatment of Hashimoto thyroiditis, and surveillance for
malignancy.
Children may exhibit hypotonia, developmental delay, and mild mental retardation that requires coordinated speech and
occupational and physical therapies to maximize potential. Development of pediatric nonmedullary thyroid cancer should raise
clinical suspicion for PHTS.[45] Significant lipomatous or vascular lesions (hemangiomas, arteriovenous malformations) have
resulted in CNS complications (eg, seizures), amputations, and premature death. Patients appear to have an increased risk for
CNS tumors.
Increased incidence of Hashimoto thyroiditis, along with abnormalities of the PTEN gene (tumor suppressor
gene), enhance the likelihood for development of neoplasia, especially thyroid and breast. Patients require careful monitoring
for the development of malignancies within the cerebellum, breast, skin (Merkel cell), and kidneys (renal cell adenocarcinoma)
with scheduled screening of mammograms, dermatological examinations, and appropriate imaging.

Familial juvenile polyposis

Esophagogastroduodenoscopy (EGD) and colonoscopy should be performed at age of onset of symptoms or at age 15 years in
asymptomatic patients at risk. If no polyps are present, this should be repeated every 3 years. If polyps are seen, they should be
removed and EGD and colonoscopy should be performed yearly until no polyps are seen.[46]

Cronkhite-Canada syndrome
Patients should be regularly screened for colorectal and gastric cancer because they are at higher risk of developing
malignancy in these areas.

Gorlin syndrome
Patients may require medical attention for craniofacial, vertebral, dental, and ophthalmologic abnormalities, in addition to
diagnosis and treatment of potential neoplasia. Bale reported that 3% of patients with Gorlin syndrome (GS) presented with
cleft lip and palate at birth.[59] Scoliosis is commonly associated with GS. Jaw cysts are noted in more than 50% of patients,
accompanied by symptoms of optic nerve compression, abnormalities of taste, and facial paresthesias. Fibrosarcomas of the
jaw have been encountered in patients with GS.
Glaucoma and cataracts have been described in patients with GS. Patients with GS are predisposed to the development of
neoplasia of the CNS, skin, and reproductive organs.
In childhood, medulloblastomas have been reported in 5% of patients with GS. Basal cell carcinomas may present in patients
younger than 10 years, especially with prior history of exposure to ionizing radiation. Nearly all patients with GS develop basal
cell carcinomas by the fourth decade of life. Individuals with GS may present with abdominal symptoms that arise from
abnormalities of the GI (lymphatic, mesenteric cysts) and gynecologic systems. Young girls with GS may develop ovarian
fibromas (predisposed to torsion) and fibrosarcomas. Khalifa et al reported endometrial adenocarcinoma in a 37-year-old
woman with GS.

Serrated polyposis syndrome

Patients with serrated polyposis syndrome (SPS) require regular screening colonoscopies to remove premalignant lesions that
could lead to colorectal cancer. First-degree relatives of patients with SPS should begin screening 10 years prior to the index
case. Screening should occur every 1-2 years with removal of all visualized polyps.[5]

Surgical Care
Familial adenomatous polyposis

The inevitable course is the development of colorectal cancer. To prevent this, surgical intervention is required, in the form of
total proctocolectomy with ileoanal anastomosis, subtotal colectomy with ileorectal anastomosis, or total proctocolectomy with
permanent ileostomy.
In patients who have subtotal colectomy with ileorectal anastomosis, the remaining rectal stump must be monitored for polyp
recurrence. Timing of prophylactic colectomy or proctocolectomy has not been standardized, with most authors recommending
that once polyposis is confirmed, severely affected patients should have prophylactic surgery as soon as possible. Mildly
affected patients are recommended to have surgery within the year.[47]

Patients with Gardner syndrome require surgical treatment of the following:

Cutaneous cysts
Symptomatic dental anomalies and osteomas
Biopsy and resection for malignancies, including hepatoblastoma, thyroid carcinoma, osteocarcinoma, gastric carcinoma,
periampullary carcinoma, and biliary tract carcinoma
Liver transplantation may be required in patients with hepatoblastoma

Patients with Turcot syndrome require surgical intervention for diagnosis and management of CNS lesions, gastric lesions and
hepatic lesions.

26
Peutz-Jeghers syndrome
Patients may require surgical intervention for symptomatic GI lesions and biopsy of suspicious areas to exclude the possibility
of malignancy. Some patients with PJS develop manifestations of short-bowel syndrome secondary to long-term resections for
potential malignancies (ie, antrectomy, duodenectomy).

PTEN-hamartomatous syndromes
Patients may require surgical intervention for management of serious lipomatous, vascular lesions, and undescended testicles
and biopsy of suggestive areas to exclude the possibility of occult malignancy. Later in age, these patients may require surgical
intervention for management of symptomatic polyposis, scoliosis, and increased intracranial pressure
Biopsy and resection of lesions within the cerebellum (dysplastic gangliocytomas), breast, and kidneys (renal cell
adenocarcinoma) may be required. Consideration of prophylactic mastectomy is recommended for women

Familial juvenile polyposis

With the cumulative risk of malignancy greater than 50%, no guidelines have been established; however, some authors are
recommending subtotal colectomy with ileorectal anastomosis in children with anemia, hypoproteinemia, and failure to
thrive.[48] Prophylactic colectomy with ileorectal anastomosis is recommended for children who have severe or repeated
bleeding and adults with FJP.[49]

Gorlin syndrome
Patients with GS may require surgical management for the following:
Craniofacial lesions (cleft lip and palate, jaw cysts, other mandibular lesions)
Abdominal masses (mesenteric cysts, lymphatic cysts, ovarian fibromas)
Diagnostic and therapeutic interventions for potential neoplasia within the CNS (medulloblastoma), skin (basal cell
carcinoma), jaw (fibrosarcoma), ovaries (fibrosarcoma), and endometrium (adenocarcinoma)

Serrated polyposis syndrome

Prophylactic colectomy with ileorectal anastomosis is recommended for those with detection of cancer, inability of
colonoscopy to control polyps, or patient preference.[50]

Diet
The benefits of low-fat/high-fiber diets and supplementation with either calcium or antioxidants, including ascorbic acid and
alpha-tocopherol, is controversial in patients with FAP. Several controlled trials in adults have studied dietary interventions,
including wheat bran, vitamin intake, and fiber on the rate of development of adenomatous polyps.[51] Yang et al noted a
decrease in colonic epithelial proliferation activity via increasing calcium intake to 1200 mg with low- fat dairy foods;[52]
however, the Toronto polyp prevention trial found no difference in the incidence of polyp recurrence between a low-fat/high-
fiber diet and a typical Western diet with placebo fiber.[53] Fuchs et al also noted no protective effect of dietary fiber against
colorectal adenomas and carcinoma in women.[54] No studies are currently available regarding dietary modification in patients
with PJS. Development of short-bowel syndrome from repetitive intestinal resections requires special nutritional interventions,
including vitamin and nutrient supplementation, continuous enteral feedings, or parenteral nutrition. No studies are currently
available regarding dietary modification in patients with PTEN -hamartomatous syndromes or GS. Nutritional support is the
mainstay of treatment of Cronkhite-Canada syndrome, especially in light of protein-losing enteropathy.

Medication Summary
Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, have been consistently associated with diminished risk of
colorectal cancer. Sulindac has been reported to cause regression of adenomas in patients with Gardner syndrome. NSAIDs
suppress cyclooxygenase-2 (COX-2), which affects epithelial proliferation and apoptosis.
Studies by Watanabe et al suggest an important role of antagonistic agents for the prostaglandin EP1 receptor for
chemoprotection against the development of colon cancer.[25] Many future therapies will target the actual signaling pathways
disrupted by the affected genes in polyposis syndromes. For example, a trial studying rapamycin use in Cowden syndrome has
been conducted.[7] In additional to nutritional support, steroids have also been shown to be the mainstay of medical treatment
that can lead to remission in Cronkhite-Canada syndrome. Azathioprine is also used as a steroid-sparing agent.[55]

Nonsteroidal anti-inflammatory drugs (NSAIDs) Class Summary

Growing evidence suggests a protective role for NSAIDs against the development of colorectal cancer. In addition, a
significant effect in reversing adenoma growth has been illustrated with the use of sulindac and celecoxib in patients with FAP.
Aspirin may also be useful to reduce the recurrence of polyps or cancer, but because of the potential for these drugs to cause
damage to the upper gastrointestinal tract, they are not routinely recommended for this purpose.
Studies have shown that APC inactivation and EGFR signaling increase COX2 expression, which may lead to intestinal
neoplasia. The mechanism of NSAID-induced polyp regression is not completely known, but it thought that it is at least in part
due to inhibition of cyclooxygenase 2 (COX2) and the resultant decrease in prostaglandin synthesis although a non-COX
mechanism may also contribute. The mechanism of NSAID-induced polyp regression is not known, but it thought that it is at

27
least in part due to inhibition of cyclooxygenase 2 (COX2) and the resultant decrease in prostaglandin synthesis although non-
COX mechanism may also contribute.

Sulindac
Has been reported to cause regression of adenomas in patients with Gardner syndrome (ie, FAP). (56)

Cyclooxygenase-2 (COX-2) inhibitors Class Summary

These agents inhibit COX-2, thus suppress production of prostaglandin E2 at inflammation sites.

Celecoxib
Recently was approved by the FDA for treatment of Gardner syndrome as an adjunct to endoscopy and surgery.

Prevention Familial adenomatous polyposis

Well-established guidelines published by the American Gastroenterological Association for surveillance in individuals with
FAP, and are discussed above in medical management.[40]
A study of patients who have had an early colectomy (younger than 14 y) showed that 43% reported daytime or nighttime
incontinence, which was associated with lower levels of psychosocial functioning.[57]
Patients with Gardner syndrome require routine surveillance for GI malignancy via guaiac cards in the asymptomatic patient
and serial upper and lower endoscopies and small bowel evaluation.
Patients with Turcot syndrome require surveillance for malignant transformation within gastric and colonic polyps, cutaneous
surveillance for basal cell carcinomas, and possible CNS malignancies.

Peutz-Jeghers syndrome
In patients with PJS, establishment of surveillance programs for occult malignancies may permit early detection. Specifics of
surveillance are detailed in medical management.
The development of gynecomastia of precocious puberty in a child with PJS merits further diagnostic investigation to exclude
underlying testicular or gynecologic malignancy.

PTEN-hamartomatous syndromes
The Cleveland Clinic PTEN Risk Calculation tool calculates a patient’s risk for PTEN mutation risk, which can allow for
earlier recognition of the syndrome, initiation of a cancer genetics consultation, and early screening practices for the
syndrome’s sequelae.[45]
Patients have an increased risk for development of breast cancer. Early institution of screening programs and consideration of
prophylactic mastectomy should be considered.
In addition, these patients are predisposed to the development of thyroid disease; complications from hamartomatous GI
polyps; and cerebellar, skin, and renal malignancies.

Gorlin syndrome
Patients with GS should minimize exposure to ultraviolet light and ionizing radiation to deter the development of basal cell
carcinomas.
Establishment of skin self-examination programs may facilitate early detection of basal cell carcinomas. Patients with GS
should have ophthalmologic screening for glaucoma and cataracts.
Patients should have routine dental follow-up care if cysts
are present within the jaw.
Women should undergo routine gynecologic examinations.

Serrated polyposis syndrome

Patients with SPS should undergo regular screening colonoscopies for polyp removal and detection of colorectal cancer.

Prognosis
Patients with FAP and its variants have an increased incidence of malignancies, including gastric carcinoma, colonic
carcinoma, periampullary carcinoma, biliary tract carcinoma, thyroid carcinoma, osteosarcomas, and adrenal carcinoma.
Patients with Turcot syndrome have an increased incidence of gastric and colonic carcinomas, basal cell carcinomas, and CNS
malignancies. Patients with PJS have increased morbidity and mortality rates that arise from the complications of GI polyps
and potential development of malignancies. Patients with PTEN -hamartomatous syndromes have increased morbidity and
mortality rates because of complications of cutaneous lesions (eg, lipomas, arteriovenous malformations), increased incidence
of CNS abnormalities, as well as malignancies within the cerebellum, breast, skin, and kidneys. Patients with GS have an
increased incidence of malignancies, which include basal cell carcinoma, sarcomas, ovarian carcinomas, medulloblastoma, and
astrocytoma. Patients with SPS have increased risk of colorectal cancer.

Patient Education
Patients with FAP and its variants should undergo routine medical examinations and endoscopic and radiologic evaluations for
surveillance of potential malignancies. In particular, patients with Turcot syndrome should be routinely screened for basal cell
carcinomas, GI cancer and breast cancer. Routine screening of stools for occult blood and early institution screening for the

28
detection of breast cancer (self- examination, mammography) may improve life expectancy in patients with PJS. The presence
of gynecomastia or precious puberty in the patient with suspected PJS should prompt careful evaluation to exclude testicular or
gynecologic malignancy. Early institution of screening for the detection of breast cancer (self-examination, mammography)
and awareness of the increased risk for development of malignancy may improve the life expectancy of patients with PTEN -
hamartomatous syndromes.
Minimizing exposure to ultraviolet light and ionizing radiation in patients with GS may diminish the potential for development
of basal cell carcinomas. Establishment of skin self-detection programs may permit early detection of basal cell carcinomas.
Patients should undergo routine ophthalmologic, dental, gynecologic, and medical examinations.

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27. Tan WH, Baris HN, Burrows PE, Robson CD, Alomari AI, Mulliken JB. The spectrum of vascular anomalies in patients with
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polyps in hamartomatous polyposis syndromes. J Gastroenterol Hepatol. 2013 Feb. 28 (2):268-73. 

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42. Attard TM, Cuffari C, Tajouri T, Stoner JA, Eisenberg MT, Yardley JH. Multicenter experience with upper gastrointestinal polyps
in pediatric patients with familial adenomatous polyposis. Am J Gastroenterol. 2004 Apr. 99(4):681-6. 

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45. Mester J, Eng C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol. 2015
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46. Burt RW. Colon cancer screening. Gastroenterology. 2000 Sep. 119(3):837-53.
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cancer?. Dis Colon Rectum. 2002 Jul. 45(7):887-9. 

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280(5366):1086-8. 

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Med. 1999 Jan 25. 106(1A):38S-42S. 

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30
 MANAGEMENT OF COLON CANCER
P K Mishra, Raghav Bansal

Epidemiology
Colorectal cancer (CRC) has maximal incidence in west and lowest in south central asia 1.
3rd MC cancer in men and the 2nd MC cancer in women worldwide2
3rd MC site of new cancer cases in US and 3rd MC cause of cancer related death worldwide3
Incidence of Colorectal cancer has reduced in recent times due to intensive screening programs

Etiology And Risk Factors

CRC can occur in sporadic, hereditary or familial forms
Sporadic – MC, occurs in absence of family history, elderly (>60yrs) and usually an isolated lesion
Hereditary – Younger age group, positive family history – HNPCC and FAP
Familial – Increased incidence in families with index case being young (<50years) and relation is close (1 st degree).
Risk rises as the number of members with cancer rises – Genetic polymorphism, gene modifiers and defects in
tyrosine kinase

Risk factors - Modifiable and non-modifiable

Non-modifiable: Age – bimodal distribution – juvenile and adult forms - juvenile more aggressive and mainly
mucinous variety; IBD, family history
Modifiable: Dietary habits – Dietary fat, fiber deficient diets, alcohol intake, smoking, sedentary lifestyle, obesity

Screening4
 Average Risk – Age 50 years or older, those with hyperplastic polyps less than 1 cm in size and a negative
family history for CRC, no history of adenoma, CRC, or inflammatory bowel disease (IBD)
 Increased Risk - Personal history of adenomatous polyps or sessile serrated polyps (SSPs), CRC, or IBD
(ie ulcerative colitis rohn’s disease) and those with a positive family history of R or advanced
adenomatous polyps

Screening modalities that detect adenomatous polyps and cancer:

- Colonoscopy every 10 years
- Flexible sigmoidoscopy every 5–10 years
- CT Colonography every 5 years

Screening modalities that primarily detect cancer :- Stool-based screening

- High-sensitivity guaiac-based testing annually
- Immunochemical-based testing annually
- Stool DNA test - high-sensitivity FIT(Fecal Immunochemical Test) every 3 years.

Genetics

1. Tumour Suppressor genes (Gatekeeper genes):

They produce proteins that inhibit tumour formation by regulating mitotic activity and inhibitory cell cycle control.
Loss of function mutations renders the cells autonomous resulting in unregulated growth.
APC gene- MC, 5q21 – product forms a complex with β-catenin and axin. β-catenin activates
transcription of genes that regulate cellular growth and proliferation in nucleus. APC regulates intra-
cytoplasmic pool of β-catenin. Germline truncation mutations result in FAP with about 30% being de novo
mutations ie without family history
Classic FAP – Truncation mutation from codon 1250 – 1464, > 100 adenomatous colorectal polyps, 100%
risk of developing cancer
Attenuated FAP – utations close to 5’ end of the gene – produces a short truncated protein - <100polyps
with rectal sparing
Variable extra-intestinal manifestations - Gardeners syndrome, Turcot syndrome
p 53 gene- chr 17p – Guardian of genome – Induces apoptosis in response to cellular damage or causes G1
cycle arrest - preserved p53 has survival benefits

2. Mismatch repair genes (Caretaker genes)

Involved in base-excision repair hence they police the integrity of genome. Loss of function mutation results in
accelerating tumour progression due to accumulating mismatched base pairs. Mutations in MMR genes (hMLH1,
hMSH2, hSMH3, hPMS1, hPMS2 and hMSH6) lead to microsatellite instability resulting in errors in S phase. MSI
exists in 10-15% sporadic tumours and in 95% patients of HNPCC.

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3. Oncogenes
Proto-oncogenes produce proteins that promote cell growth and proliferation. Gain of function mutation makes it an
oncogene and produce – growth factors, growth factor receptors, signal transducers and transcription factors. e.g.
RAS proto-oncogene – chr 12 – aberrant crypt formation and adenomatous polyps

There are multiple signaling pathways that regulate cell growth. Consequently, there are multiple possible pathways
for tumorigenesis which makes CRCs heterogeneous genetically and clinically.

CLASSIC CHROMOSOMAL INSTABILITY

Fearon-Vogelstein adenoma-carcinoma sequence
The first step in the CIN pathway is inactivation of the WNT signaling pathway, followed by activating mutations in
key growth-stimulating genes, such as KRAS, CDC4, PIK3CA, and others, followed
by disruption of the negative growth regulatory network of transforming growth factor (TGF)-β signalling (typically
through inactivation of one or more of the SMAD genes), and then conversion of benign to malignant behaviour by
mutations and allelic losses of the p53 (TP53) gene, which abrogates the G1/S cell cycle checkpoint and permits the
accumulation of chromosomal rearrangement and aneuploidy. More than half of all CRCs develop through this
pathway. There is considerable heterogeneity in the evolution of this pathway, and only three of these, APC, KRAS
and p53, are mutated in greater than 11% of all CRCs. The initial genetic alteration in the classic pathway is
inactivation of the WNT signalling pathway, which is a key to familial adenomatous polyposis (FAP).

Earliest implicated gene is APC

Earliest phenotypic change – aberrant crypt formation

Unregulated growth leads to accumulation of epithelial cells – polyp formation and persistent occurrence of
mutations leads to adenoma formation which progresses through early, intermediate and late adenoma eventually
leading to intraepithelial neoplasm and carcinoma6. The polypoidal lesions harbouring carcinoma are classified by
Haggit’s classification5 into 5 levels (Level 0-4) which stratifies risk of Lymph nodal involvement and recurrence.

Haggitt classification
Level 0—Carcinoma in situ or intra-mucosal carcinoma; non-invasive.
Level 1—Carcinoma invades muscularis mucosa to submucosa; limited to head of polyp.
Level 2—Carcinoma invades neck of polyps.
Level 3—Carcinoma invades any part of the stalk.
Level 4—Carcinoma invades submucosa of bowel wall, below polyp stalk but above muscularis propria.
As sessile polyps are not described in detail other classification systems such as Kudo’s or Kikuchi’s are used.

CPG ISLAND METHYLATOR PHENOTYPE

The second CRC pathway involves the inactivation of tumour suppressor genes through hyper-methylation of gene
promoters, accelerated normal physiologic process for silencing genes. This is the CpG island methylator
phenotype, or CIMP. This occurs as a predominant epigenetic lesion in about 32% of CRCs. CIMP often occurs in
association with mutation in the BRAF gene (V600E), and this is associated with more aggressive, lethal CRCs.
Tumours in the CIMP pathway are thought to begin as sessile serrated adenomas (SSAs) rather than as typical
adenomatous polyps; consequently, this has been called the serrated carcinoma pathway. Both SSAs and CIMP
CRCs occur predominantly in the proximal colon. The genes that commonly undergo promoter methylation in
CIMP include p16, CDKN2A,THBS1, HPP1, and MLH1.

MICROSATELLITE INSTABILITY
The third pathway for colorectal carcinogenesis is a secondary consequence of either CIN (in the setting of Lynch
syndrome) or I and is called “microsatellite instability”or SI. DNA mismatch repair ( R) system
identifies DNA copying errors and removes the faulty sequences. In the absence of DNA MMR activity, there is
greater than 100-fold increase in synthetic errors in microsatellite sequences. CRCs with MSI can occur in three
circumstances. First, approximately 12% of all CRCs begin as CIMP tumours, but when methylation occurs at both
alleles of one of the DNA MMR genes (MLH1), MSI ensues and overwhelms the CIMP background, as the
accumulation of mutations occurs rapidly. Second, about 3% of CRCs occur in the setting of Lynch syndrome
(previously referred to as hereditary nonpolyposis CRC [HNPCC]), of which most have MSI. Neoplasms in Lynch
syndrome arise initially as otherwise ordinary adenomatous polyps, and then develop MSI when there is loss of the
wild-type allele of the DNA R gene responsible for the Lynch syndrome. hird “Lynch-like syndrome” in
which CRCs begin in the CIN pathway, and develop biallelic mutations at one of the DNA MMR genes, after which
MSI ensues, which rapidly overtakes the prior phenotype.

32
PATHOLOGY
Macroscopically, the tumour may take one of four forms – Annular, tubular, ulcer and cauliflower.
Annular variety tends to present with obstructive symptoms whereas other varieties present more often with
bleeding. Microscopically, the neoplasm can be adenocarcinoma, sarcoma, neuroendocrine tumour, melanoma etc.

CLINICAL FEATURES
Depend on various factors:
1. Anatomical location
Right colon – proliferative with ulceration of mucosa leading to occult blood loss and anaemia, less obstructive
symptoms due to capacious bowel and soft faecal matter.
Left colon – Constricting nature – subacute obstruction or recent alteration of bowel habits, hematochezia or
blood mixed with stool
2. Involvement of adjacent structures
Retroperitoneal structures such as ureters – hydroureteronephrosis
Duodenum by hepatic flexure growth – duodenal obstruction
Urinary bladder by caecal or sigmoid growth – colo-vesical fistula

3. Metastasis – cachexia, ascites and features of peritoneal dissemination

DIAGNOSIS

COLONOSCOPY – Gold standard; Direct visualisation and biopsy of growth, look for synchronous malignancy or
polyp and tattooing of lesions for surgery
DOUBLE CONTRAST BARIUM ENEMA –Subsequent coloscopy required
CECT – Assess relation and extent of adjacent organ involvement and metastasis
VIRTUAL COLONOSCOPY/ CT COLONOGRAPHY – Especially when colonoscopy cannot be done
MRI –Evaluation of Liver metastasis, endorectal coils for carcinoma rectum
PET – Equivocal finding of CT/MRI, potentially curable M1 disease surgically

STAGING AJCC 8th

Primary tumour (pT)
TX: primary tumour cannot be assessed
T0: no evidence of primary tumour
Tis: carcinoma in situ, intra-mucosal carcinoma (involvement of lamina propria with no extension through
muscularis mucosae)
T1: tumor invades submucosa (through the muscularis mucosa but not into the muscularis propria)
T2: tumor invades muscularis propria
T3: tumor invades through the muscularis propria into the peri-colorectal tissues
T4a: tumor invades through the visceral peritoneum (including gross perforation of the bowel through
tumor and continuous invasion of tumor through areas of inflammation to the surface of the visceral
peritoneum)
T4b: tumor directly invades or adheres to other adjacent organs or structures

Regional lymph nodes (pN)

NX: regional lymph nodes cannot be assessed
N0: no regional lymph node metastasis
N1: metastasis in 1 - 3 regional lymph nodes
N1a: metastasis in 1 regional lymph node
N1b: metastasis in 2 - 3 regional lymph nodes
N1c: no regional lymph nodes are positive but there are tumor deposits in the subserosa,
mesentery or non peritonealized pericolic or perirectal / mesorectal tissues
N2: metastasis in 4 or more regional lymph nodes
N2a: metastasis in 4 - 6 regional lymph nodes
N2b: metastasis in 7 or more regional lymph nodes

Distant metastasis (pM)

M0: no distant metastasis by imaging; no evidence of tumor in other sites or organs
M1: distant metastasis
M1a: metastasis confined to 1 organ or site without peritoneal metastasis
M1b: metastasis to 2 or more sites or organs is identified without peritoneal metastasis
M1c: metastasis to the peritoneal surface is identified alone or with other site or organ metastases

33
CRC involving colonic wall and contiguous adjacent organs – Stage I and II, regional lymphnodal involvement –
Stage III and presence of distant metastasis – Stage IV.

TREATMENT7
Management of the Malignant Polyp
A malignant polyp is defined as one with cancer invading the submucosa (pT1). Conversely, polyps classified as
carcinoma in situ (pTis) have not penetrated the submucosa and are therefore not
considered capable of regional nodal metastasis.

Indications of surgery after endoscopic polypectomy:

 Polyp specimen is fragmented and the margins cannot be assessed
 Specimen shows unfavourable histopathology - grade 3 or 4, angiolymphatic invasion, or a positive margin
of resection (presence of tumor within 1 to 2 mm of the transected margin or the presence of tumor cells
within the diathermy of the transected margin)

Management of Invasive Nonmetastatic Colon Cancer

SURGERY: Surgery is the mainstay of treatment.

Principles of surgery:-
Extent of colectomy:
The extent of colonic resections depends on vascular supply and lymphatic drainage of involved segment.
Lymphatic drainage from colon is in centripetal fashion – Epicolic(wall of colon), Paracolic (along marginal artery),
Intermediate (Vascular pedicles in mesocolon) and Principle nodes (route of SMA and IMA).Intramural spread
occurs upto 2cm thus forming the basis minimum 5cm resection margin. But actual resection length depends on
vascular pedicle division needed for lymph node clearance. In colon cancer, the radial margin (or circumferential
resection margin, CRM) represents the adventitial soft tissue closest to the deepest penetration of the tumor. It is
created surgically by dissection of the retroperitoneal aspect, and it corresponds to any aspect of the colon that is not
covered by serosa. The radial margins should be assessed in all colonic segments with non-peritonealized surfaces.
In segments of the colon that are completely encased by peritoneum, such as the transverse colon, the mesenteric
resection margin is the only relevant radial margin.

Outline of surgical resections for colonic malignancy:

Location of tumour Surgery Vessels ligated Length of bowel

Caecum and Right Ileocolic, Right Colic Terminal 6 inches of ileum, right
Ascending colon Hemicolectomy and Right branch of colon and proximal tranverse
Middle colic colon
Hepatic flexure Extended Right Ileocolic, Right Colic Terminal 6 inches of ileum, right
Hemicolectomy and Middle colic colon and proximal 2/3rd tranverse
colon
Splenic flexure Extended Left Left colic and Left Mid transverse and descending
Hemicolectomy branch of Middle colic colon
Descending colon Left Hemicolectomy Left colic and sigmoid Distal 1/3rd of transverse and
vessels descending colon
Sigmoid colon Sigmoidectomy Inferior mesenteric after Sigmoid colon
origin of Left colic

Lymphadenectomy
Lymph nodes at the origin of feeding vessel(s) should be identified for pathologic exam. Clinically positive lymph
nodes outside the field of resection that are considered suspicious should be biopsied or removed, if possible.
Positive nodes left behind indicate an incomplete (R2) resection.
A minimum of 12 lymph nodes to be examined to establish N stage.

Complete mesocolic excision (CME) with central vascular ligation results in greater mesentery and lymph node
yields resulting in better DFS.

Minimally Invasive approach

May be considered based on the following:
Experienced surgeon
No locally advanced disease.
Not indicated for acute bowel obstruction or perforation from cancer.
Thorough abdominal exploration is required.

34
Consider preoperative marking of lesion(s).

Obstructing Colon Cancers

Left colonic lesions are usually at risk of causing bowel obstruction. Treatment requires emergency surgery with
resection of appropriate colonic segment with or without primary anastomosis. Primary anastomosis is usually not
preferred so proximal end is brought out as end colostomy and distal end is either closed(Hartmann procedure) or
brought out as mucus fistula. Primary anastomosis can be considered after ontable lavage through appendix or ileum
in patients who are hemodynamically stable and have pliable, nonedematous, well-vascularised bowel. Recently
SEMS have been used as a bridge to surgery by relieving the obstruction and thus allowing elective surgery with
primary anastomosis.

ADJUVANT THERAPY
Stage I disease and patients with MSI-high [MSI-H] - do not require any adjuvant therapy

Low-risk stage II disease – can be enrolled in a clinical trial, observed without adjuvant therapy, or considered for
capecitabine or 5-FU/leucovorin (LV)

High-risk stage II disease[with poor prognostic features, including T4 tumors (stage IIB/IIC);poorly differentiated
histology (exclusive of those cancers that are MSI-H); LVI;PNI; bowel obstruction; lesions with localized
perforation or close, indeterminate, or positive margins; or inadequately sampled nodes (<12 lymph nodes)] -
adjuvant chemotherapy with 5-FU/LV, capecitabine, FOLFOX, capecitabine/oxaliplatin (CapeOx), or bolus 5-
FU/LV/oxaliplatin(FLOX)

Stage III disease – 6 months of adjuvant chemotherapy after primary surgical treatment – FOLFOX or CapeOx(both
category 1 and preferred); FLOX (category 1) or single-agent capecitabine or 5-FU/LV in patients for whom
oxaliplatin therapy is believed to be inappropriate

Timing of Adjuvant Therapy - adjuvant therapy should be administered as soon as the patient is fit as each 4-week
delay in chemotherapy results in a 14% decrease in OS.

Perioperative Chemoradiation - Neoadjuvant or adjuvant radiation therapy delivered concurrently with 5-FU–based
chemotherapy - considered for very select patients with disease characterized as T4 tumors penetrating to a fixed
structure or for patients with recurrent disease. Radiation therapy fields includes the tumor bed as defined by
preoperative radiologic imaging and/or surgical clips. Intraoperative radiation therapy (IORT), if available, used as
an additional boost. Chemoradiation can also be given to patients with locally unresectable disease or who are
medically inoperable.

Management of Metastatic Disease

Approximately 50% to 60% of patients diagnosed with colorectal cancer develop metastasis with liver being the
most common site of involvement followed by lung. 20% to 34% of patients with colorectal cancer present with
synchronous liver metastases.

The standard of care for patients with resectable metastatic disease is surgical resection. If resection is not feasible,
image-guided ablation or stereotactic body radiation therapy (SBRT) can be done. Other options include hepatic
arterial infusion (HAI), radioembolization, transcatheter arterial chemoembolization (TACE) and tumour ablative
techniques like radiofrequency ablation (RFA), microwave ablation, cryoablation, percutaneous ethanol injection,
and electro-coagulation.

Resection or ablation (either alone or in combination with resection) is done only for patients completely amenable
to local therapy with adequate margins for all known sites.

Conversion to Resectability - Chemotherapy is used in selected cases of liver-limited unresectable disease due to
involvement of critical structures. Surgical re-evaluation is done every 2 months to look for resectability.

Neoadjuvant and Adjuvant Therapy for Resectable Metastatic Disease - Active systemic therapy
is administered for a total period of approximately 6months. The choice of chemotherapy regimen depends on
several factors such as chemotherapy history, synchronous or metachronous disease, and the response rates and
toxicity profiles of various regimes. Biologics are not recommended in the peri-operative period.

Peritoneal Carcinomatosis - Approximately 17% of patients with metastatic colorectal cancer have peritoneal
carcinomatosis, and in 2% the only site of metastasis. Treatment is mainly with palliative intent rather than curative.
Role of cytoreductive surgery + HIPEC is debatable.

35
Systemic Therapy for Advanced or Metastatic Disease
The current management of disseminated metastatic colon cancer involves various active drugs, either in
combination or as single agents: 5-FU/LV, capecitabine, irinotecan, oxaliplatin, bevacizumab, cetuximab,
panitumumab, ziv-aflibercept, ramucirumab, regorafenib, trifluridine-tipiracil, pembrolizumab, and nivolumab

ROLE OF BIOLOGICS – Metastatic CRC

 Bevacizumab - humanized monoclonal antibody inhibits the activity of VEGF(tumor angiogenesis)
 Cetuximab and panitumumab - monoclonal antibodies directed against EGFR that inhibit its downstream
signaling pathways.
 Panitumumab is a fully human monoclonal antibody, whereas cetuximab is a chimeric monoclonal
antibody – Used in patients with RAS wild-type.

GENETIC TESTING:
KRAS, NRAS,and BRAF Status - Genotyping of tumor tissue (either primary tumor or metastasis) in all patients at
diagnosis of stage IV disease. They are used to decide regarding usage of biologics and prognostication.

Microsatellite Instability (MSI) or Mismatch Repair (MMR) Testing - Recommended in all patients with a personal
history of colon or rectal cancer. The presence of a BRAF V600E mutation in the setting of MLH1 absence would
preclude the diagnosis of Lynch syndrome. Stage II MSI-H patients may have a good prognosis and do not benefit
from 5-FU adjuvant therapy.

SURVEILLANCE:
Stage I disease
Colonoscopy at 1 year. Repeat colonoscopy is recommended at 3 years, and then every 5 years thereafter, if
advanced adenoma (villous polyp, polyp >1 cm, or high-grade dysplasia) found - 1year.

Stage II/III disease

History and physical examination every 3 to 6 months for 2 years,and then every 6 months for a total of 5years.

CEA at baseline and every 3 to 6 months for 2 years then every 6 months for a total of 5 years.

Colonoscopy at approximately 1 year after resection (or at 3–6 months postresection if not performed preoperatively
because of an obstructing lesion). Repeat colonoscopy at 3years, and then every 5 years thereafter. More frequent
colonoscopies in patients < 50years of age.

Chest, abdominal, and pelvic CT scan are recommended every 6 to 12 months for upto 5years
Routine CEA monitoring and CT scanning are not recommended beyond 5 years.

Stage IV
Contrast-enhanced CT scan of the chest, abdomen, and pelvis every 3 to 6 months in the first 2years after adjuvant
treatment (frequency <6 months) and then every 6 to 12 months for up to a total of 5 years. CEA every 3 to 6
months for the first 2 years and then every 6months for a total of 5 years

References
1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in
2008: GLOBOCAN 2008. Int J Cancer. 2010; 127:2893–2917.
2. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA
Cancer J Clin. 2015;65(2):87–108. doi: 10.3322/caac.21262.
3. Shibuya K, Mathers CD, Boschi-Pinto C, Lopez AD, Murray CJ. Global and regional estimates of cancer
mortality and incidence by site: II.Results for the global burden of disease 2000. BMC Cancer. 2002;2:37
4. Colorectal Cancer Screening, Version 1.2018- March 26,2018 Issued by NCCN Clinical Practice
Guidelines in Oncology. NCCN.org
5. Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinomas arising in
adenomas: implications for lesions removed by endoscopic polypectomy. Gastroenterol. 1985;89:328–36
6. Kumar A, Puri P. Colorectal Cancer : An overview. Mishra, P K. (2016). Textbook of surgical
gastroenterology. 1st ed.Delhi.Jaypee Brothers Medical P, pp.1118-27.
7. Colon Cancer, Version 2.2018- March 14,2018 Issued by NCCN Clinical Practice Guidelines in
Oncology. NCCN.org

36
 ADVANCES IN THE MANAGEMENT OF RECTAL PROLAPSE
Rajesh Bhojwani, Deepak Bajaj

Definition
Complete rectal prolapse: Circumferential protrusion of all layers (full thickness) of rectum through anal canal is
called complete or full thickness rectal prolapse.
Incomplete rectal prolapse: only mucosa prolapses out of the anal canal.

Classification of full thickness rectal prolapse

Grade I: inner recto-rectal intussusception of the rectum proximal to the anal canal;
Grade II: inner recto-anal intussusception into the anal canal;
Grade III: external prolapse of the rectum beyond the anus.1

Evaluation
History- bowel habits, pelvic symptoms, urinary symptoms, obstetric history, history of previous pelvic surgery.
Sigmoidoscopy and colonoscopy: to rule out haemorrhoids, SRUS or a neoplasm

Radiological imaging

Barium enema: to assess the redundancy of sigmoid colon, if any and to rule out other diseases (redundancy of
sigmoid may have a bearing on the surgical procedure).

Defaecography: Useful in patients in whom prolapse is suspected but not seen during physical examination. It
reveals associated anterior pelvic floor support defects, such as cystocele, enterocele and vaginal vault prolapse.
It demonstrates a correlation between improvement in clinical symptoms and quality of life with the improved
prolapse grade after resection rectopexy. It can be useful when symptoms and QOL show no improvement
postoperatively.2

FLUOROSCOPIC MRI Defecography

Natural (upright position during evacuation Supine

More widely available Less widely available

Low cost High cost

Radiation exposure No radiation exposure

 PNTL(pudendal nerve terminal motor latency)

 Ano rectal manometry

TREATMENT

Surgery is the only available option for cure.

Goals of surgery include:
1) to cure the prolapse and to restore normal anatomy,
2) to correct functional abnormalities
3) to avoid the creation of new bowel dysfunction.
T
here are two approaches for repair: trans-abdominal and perineal

ABDOMINAL PERINEAL

Considered the preferred approach for young and fit individuals For elderly, frail and unfit patients

Done under general anaesthesia Done under regional anaesthesia

Less recurrence rate Higher recurrence rate

37
  Perineal Procedures
o Delorme’s uscosectomy - resects redundant rectal mucosa
o Thiersh.s encirclement
o Altemeier’s rectosigmoidectomy (full-thickness resection) be performed with or without
levatorplasty
 Abdominal Procedures
o Suture Rectopexy
o Mesh Rectopexy
 Posterior (Well / lvalon)
 Anterior (Ripstein)
 Lateral (Orr-Loygue)
 Ventral
o Resection Rectopexy (Frykman and Goldberg)
o Anterior Resection
o Abdominal approach:
 Open
 Minimal invasive- Laparoscopic
 Robotic

TRENDS IN TREATMENT
Rogers et al in a population-based study found that majority of patients of rectal prolapse had undergone a perineal
resection (47 %) followed by abdominal rectopexy with or without resection (45 %). The use of laparoscopic
approach has significantly increased over time. The mortality rate was found to be 0.2%.
Despite the popularization of ventral mesh rectopexy over the study period (2005 to 2015), perineal resection
Delorme’s procedure remains the most common procedure. 3 Overall, recurrence was found in app16% patients.
Complications occurred in 13 % of patients. A high incidence of recurrence with low complication rate and
satisfactory improvement in the incontinence was seen after the perineal approach. 4

Components of Rectopexy:
 Posterior dissection upto the levator muscles
 Lateral dissection upto the beginning of Lateral ligaments. Lateral ligaments are not divided to avoid
autonomic nerve injury.
 Obliteration of the deep Pouch of Douglas., involves 1-2cm dissection anteriorly.
 Preventing intussusception and consequent rectal prolapse
 Treating the rectocele.
 Treating obstructed defaecation syndrome and solitary rectal ulcer syndrome.

Open vs Laparoscopic Abdominal Rectopexy

Laparoscopic surgery has similar functional outcome, recurrence with advantages of being cosmetically better and
resulting in a shorter length of stay.5

Laparoscopic Posterior Rectopexy

Arguments in favour of posterior rectopexy include a collagen rich thicker fascia propria of rectum (more thick
posteriorly than anteriorly) that tends to hold sutures better and provides stronger fixation. Thick posterior wall also
reduces chances of rectal wall perforation. Also, the mesh is not placed in rectovaginal septum, thereby avoiding the
related problems.
Autonomic nerve injury due to division of lateral ligaments is one of the causes for post-operative constipation.

Resection Rectopexy
Resection of redundant sigmoid colon combined with rectopexy is known as Frykman-Goldberg procedure. In this
procedure, rectum is completely mobilized upto the levator complex while the lateral ligaments are left intact.
Rectum is elevated with suture fixation to the presacral fascia just below the promontory. Cul-de-sac is obliterated
by suturing of the endopelvic fascia anteriorly to the rectum and redundant sigmoid colon is resected with an end-to-
end anastomosis.7

Laparoscopic ventral mesh rectopexy (LVMR)

LVMR is a common procedure and the components include :

TECHNIQUE
As described by Hoore et al. an inverted J-shaped peritoneal incision is given on right side of sacral promontary
along the rectum and over the deepest part of the pouch of Douglas. Right hypogastric nerve is preserved.

38
Denonvillier’s fascia is incised and the rectovaginal septum is
opened. Rectal mobilization or lateral dissection is not
performed. The mesh is sutured with non-absorbable sutures to
the ventral aspect of the distal rectum and then fixed to the lateral
seromuscular borders of the rectum proximal and distal to the
incised pouch of Douglas. The mesh is fixed on the sacral
promontory. The posterior vaginal fornix is sutured to the
anterior aspect of the mesh. Thus rectovaginal septum is closed
and vaginal vault prolapse is corrected, if present. The incised
peritoneum is then closed over the mesh. This elevates the new
pouch of Douglas.8

Complications
Many complications (infection, mesh erosion, fistula formation,
and dyspareunia) have been reported in the literature with the use
of synthetic mesh. In a study of ventral rectopexy (laparoscopic
and robotic) using biological mesh, conducted by Brunner et al.
found that overall complication rate was 14% with 2% major
complications. There was no mesh related complication.
Functional outcome was excellent with short term follow up. 12

In a systematic review of literature by Balla et al., mesh related

erosions are more common with the use of synthetic mesh then biological mesh, with LVMR . 13 In the largest
reported series(n=224) of LVMR using biological mesh (PERMACOLTM) showed the recurrence rate 10.7% at 5
years and at 19.4% at 8 years. Stress urinary incontinence, urge incontinence and dyspareunia improved
significantly. The constipation and faecal incontinence improved significantly. Overall complication rate is low
10.7% (early 4.9% and late 5.8%), while biologic mesh-related complications were 0.45%.14 Synthetic mesh-related
morbidity after LVMR has been reported as 1.1% (polypropylene), 3.3% (polyester), and 4.6% (Marlex or
polypropylene).

Mesh Rectopexy In Pre Menopausal Women

In general, mesh rectopexy in a pre-menopausal woman is avoided owing to the concerns related to pelvic adhesions
and consequent infertility, mesh migration due to pressure by gravid uterus leading to the recurrence and mesh
infection caused by obstetric trauma. But a recent retrospective study by Hogan et al. showed delivery of six patients
by LSCS and of two patients by spontaneous vaginal delivery without any adverse event. Also, the pelvic floor
symptoms did not change post-delivery. This study provides the option of laparoscopic mesh rectopexy in pre-
menopausal women when conservative treatment fails.16

Old Age
In general, perineal procedures are preferred over the abdominal procedures in elderly patients. In the current era,
however, laparoscopic rectopexy seems to be the preferred option. In a study by Dyrberg DL, median age of patients
undergoing laparoscopic posterior rectopexy was 73years. Patients had 5.3% Minor and 14.8% major complications.
The 30-day mortality rate was 1.2%. Recurrence rate was 11.1%. 17

Learning Curve of Laparoscopic Rectopexy.

The estimated learning curve of laparoscopic abdominal rectopexy is 25-30 cases.18

Robotic Rectopexy
Surgical robots were introduced in 1990s and are being increasingly used for rectopexy across the countries.
Improved dexterity, seven degrees of freedom, elimination of fulcrum effect and physiological tremors, tele surgery
and ergonomic position are the advantages which make it an attractive option.
In a retrospective observational study by Iersel et al. it is found that, out of 258 patients who underwent robot
assisted ventral mesh rectopexy, there was no conversion to open. Only 5 had intraoperative complications, 1.3%
had mesh related complications and 0.4% mortality.19

Current Status
There is no clear evidence-based recommendation regarding the most suitable surgical procedure for rectal prolapse,
as there is no significant difference in the QOL after different kinds of procedures. Also, a weak and heterogeneous
methodology has resulted in a lack of high quality of evidence to compare results of different techniques. The
therapeutic decisions must therefore be individualised considering patient’s functional status co-morbidities and
surgeon preference.22,23.

39
Evaluation and Treatment Algorithm

EVALUATION AND TREATMENT ALGORITHM 24

Recurrent Rectal Prolapse

Recurrence after Rectopexy can be multifactorial. Circumferential rectal mobilization, during rectopexy was
associated with a decreased long-term recurrence rate, and the type of rectal fixation and the surgical access did not
influence recurrence.25Eldely patients, having poor baseline continence, and with prolonged pudendal nerve terminal
motor latency are at higher risk of recurrence. 26

Summary and Guidelines

The initial evaluation of a patient with rectal prolapse should include a complete history and physical examination
with focus on the prolapse, on anal sphincter structure and function, and on concomitant symptoms and underlying
conditions.

Additional testing, such as a fluoroscopy or MRI defecography, colonoscopy, barium enema, and urodynamics, may
be used selectively to refine the diagnosis and identify other important coexisting pathology.

Anal physiologic testing may be considered to assess and treat coexisting functional disorders associated with rectal
prolapse, such as constipation or fecal incontinence. Multicompartment prolapse must be ruled out before offering
surgery for rectal prolapse

Rectal prolapse cannot be corrected nonoperatively, although some of the symptoms associated with this condition,
such as fecal incontinence, pain, and constipation, can be palliated medically.
In patients with acceptable risk, the procedure of choice for the treatment of rectal prolapse should typically
incorporate transabdominal rectal fixation.
There is insufficient evidence to argue that posterior rectal prolapse repairs, such as suture rectopexy or resection
with suture rectopexy, are better or worse than anterior rectal prolapse repairs, such as ventral mesh rectopexy.
Posterior rectal mobilization without a rectopexy (with or without a concomitant anterior resection) is associated
with higher recurrence rates and complications and is typically not recommended.
Rectopexy is a key component in the abdominal approach to rectal prolapse.
Sigmoid resection may be added to posterior suture rectopexy in patients with prolapse and preoperative
constipation.
Division of the lateral stalks during posterior rectal dissection may worsen postoperative constipation but is
associated with decreased recurrence rates.
Posterior mobilization of rectum with mesh fixation of the anterior rectal wall to the sacral promontory may be used
for treatment of rectal prolapse but is associated with higher morbidity.

40
A modified Wells procedure using a variety of foreign materials for posterior fixation of the rectum may be used for
treatment of rectal prolapse.
Ventral mesh rectopexy offers an alternative approach to the repair of rectal prolapse with acceptable short- and
long-term complication rates.
A minimally invasive approach to rectal prolapse by experienced surgeons is associated with improved morbidity
and comparable recurrences compared with open surgery and should be considered when technically feasible.
Patients with a short segment of full-thickness rectal prolapse can be treated with mucosal sleeve resection.
Rectal prolapse may be treated with a perineal rectosigmoidectomy.

References
1. Rickert A, Kienle P. Laparoscopic surgery for rectal prolapse and pelvic floor disorders. World J Gastrointest Endosc
2015;7:1045-1054.
2. Otto S, Dizer AM, Kreis ME, Gröne J. Radiological Changes After Resection Rectopexy in Patients with Rectal Prolapse—
Influence on Clinical Symptoms and Quality of Life. J Gastrointest Surg2017
3. Rogers AC, McCawley N, Hanly AM, Deasy J, McNamara DA, Burke JP. Trends in the treatment of rectal prolapse: a
population analysis. Int J Colorectal Dis. (2018)
4. Emile SH, Elfeki H, Shalaby M, Sakr A, Sileri P, Wexner SD. Perineal resectional procedures for the treatment of complete
rectal prolapse: A systematic review of the literature, International Journal of Surgery (2017)
5. Kariv Y, Delaney CP, Casillas S, Hammel J, Nocero J, Bast J. Long-term outcome after laparoscopic and open surgery for
rectal prolapse. A case–control study. Surg Endosc (2006)
6. Hyun K, Yang SJ, Lim KY, Lee JK, Yoon SG. Laparoscopic Posterolateral Rectopexy for the Treatment of Patients With a
Full Thickness Rectal Prolapse: Experience With 63 Patients and Short-term Outcomes. Ann Coloproctol 2018.
7. Hori T, Yasukawa D, Machimoto T, Kadokawa Y, Hata T, Tatsuo Ito, Kato S, Aisu Y, Kimura Y, Takamatsu Y, Kitano T,
Yoshimura T. Surgical options for full-thickness rectal prolapse: current status and institutional choice. Annals of
Gastroenterology (2018)
8. D’Hoore A adoni R and enninckx F. Long-term outcome of laparoscopic ventral rectopexy for total rectal prolapse.
British Journal of Surgery 2004.
9. Lundby L, Lene H Iversen, Buntzen S, Wara P, Høyer K, Laurberg S. Bowel function after laparoscopic posterior sutured
rectopexy versus ventral mesh rectopexy for rectal prolapse:a double-blind, randomised single-centre study.
www.thelancet.com/gastrohep.2016
10. Madbouly KM and Mohamed Youssef. Laparoscopic Ventral Rectopexy Versus Laparoscopic Wells Rectopexy for
Complete Rectal Prolapse: Long-Term Results. Journal Of Laparoendoscopic & Advanced Surgical Techniques. 2017
11. Zaidi H, Gupta A, Khetan N, Habib K. Knot free technique for Laparoscopic Ventral Mesh Rectopexy. Annals of Medicine
and Surgery 19 (2017) 51-54
12. Brunner M, Roth H, Günther K, Grützmann R, Matzel KE. Ventral rectopexy with biological mesh: short-term functional
results. International Journal of Colorectal Disease 2018.
13. Balla A, Quaresima S, Smolarek S, Shalaby M, Missori G, Sileri P. Synthetic Versus Biological Mesh-Related Erosion
After Laparoscopic Ventral Mesh Rectopexy: A Systematic Review. Ann coloproctol 2017
14. Short- and long-term clinical and patient-reported outcomes following laparoscopic ventral mesh rectopexy using biological
mesh for pelvic organ prolapse: a prospective cohort study of 224 consecutive patients. doi: 10.1111/codi.13996
15. Evans, C., Stevenson, A. R. L., Sileri, P., Mercer-Jones, M. A., Dixon, A. R., Cunningham, C., and Lindsey, I. (2015), A
Multicenter Collaboration to Assess the Safety of Laparoscopic Ventral Rectopexy. Diseases of the Colon and Rectum, 58:
8, 799–807. doi:10.1097/DCR.0000000000000402
16. Hogan AM, Tejedor P, Lindsey I, Jones O, Hompes R, Gorissen KJ, Cunningham C. Pregnancy after Laparoscopic Ventral
Mesh Rectopexy: Implications and Outcomes. doi: 10.1111/codi.13818
17. Laparoscopic posterior mesh rectopexy for rectal prolapse is a safe procedure in older patients:A prospective follow-up
study. Dyrberg DL, Nordentoft T, Rosenstock S. Scandinavian Journal of Surgery 2015.
18. Pucher PH, Mayo D, Dixon AR, Clarke A, Lamparell MJ Learning curves and surgical outcomes for proctored adoption of
laparoscopic ventral mesh rectopexy: cumulative sum curve analysis. Surg Endosc 2016
19. Iersel JJV, Jonkers HAF, Paulides TJC, Verheijen PM, Draaisma WA, Consten ECJ, Broeders IAMJ. Robot-Assisted
Ventral Mesh Rectopexy for Rectal Prolapse: A 5-Year Experience at a Tertiary Referral Center. Diseases Of The Colon &
Rectum Volume 60: 11 (2017)
20. Swain SK, Kollu SH, Patooru VK, Munikrishnan V. Robotic ventral rectopexy: Initial experience in an Indian tertiary
health‑care centre and review of literature. Journal of Minimal Access Surgery 2017.
21. Trilling B, Sage PY, Reche F, Barbois S, Waroquet PA, Faucheron JL Early experience with ambulatory robotic ventral
rectopexy. Journal of Visceral Surgery (2018
22. Tou S, Brown SR, Nelson RL. Surgery for complete (full-thickness) rectal prolapse in adults. Cochrane Database Syst Rev
2015;(11):CD001758
23. Schiedeck TH. Complications after rectal prolapse surgery. Chirurg 2015;86:747-751.
24. Varma MG. Expert Commentary on Rectal Prolapse. Diseases Of The Colon & Rectum Volume 60: 11 (2017)
25. Bishawi M, Foppa C, Tou S, MinInSu M, Bergamaschi R. Recurrence of rectal prolapse following rectopexy: A pooled
analysis of 532 patients. 2015.
26. Fu CWP, Stevenson ARL. Risk Factors for Recurrence After Laparoscopic Ventral Rectopexy. Diseases of the Colon &
Rectum Volume 60: 2 (2017)

41
 Damage Control Surgery
Anurag Mishra
Introduction
As the health facilities including pre-hospital care improves, surgeons are faced with an increasing number of
seriously injured patients surviving their initial accident and arriving in hospital. These injured patients often
exhausted their physiological reserve. Other than trauma, hospital not very infrequently receive patients in sepsis
where patients might not be fit for surgery. The “Lethal riad” of acidosis, hypothermia, and coagulopathy
precludes definitive surgery as primary treatment in such patients. Management of such cases has seen a drastic
change in the last decade with the emergence of a new paradigm termed damage control surgery (DCS).

DCS is a treatment strategy of temporization; prioritizing physiological recovery over anatomical repair. A
relatively recent concept, but it has revolutionised the way critically injured/ ill patients are treated in surgical wards
these days. The approach involves identifying those patients who cannot tolerate extensive surgery and manage
them by methodological resuscitation, an abbreviated initial laparotomy to control bleeding/ contamination,
followed by recovery in the intensive care unit (ICU) before taking them for definitive surgery.

History
While some reference of similar abbreviated laparotomy can be found back in days of American Civil War and
World Wars, it was generally dismissed as poor surgical care. It was maybe due to very high infection rates
associated with such attempts.
 It was not until the 1980’s with H Harlan Stone demonstrating improved survival with abdominal packing
for coagulopathic bleeding and Burch with hepatic injuries, that a more rigorous evaluation of this
approach was begun.1,2
 he term “Damage ontrol Surgery” was introduced in 1993 with Rotondo and Schwab’s landmark paper
showing a seven- fold improvement (11% to 77%) in mortality in patients with combined visceral and
major vascular injury using the damage control approach. 3
 Over the following decades, refinements were made to the basic steps to produce the current model in use
today. 4, 5, 6, 7
 DCS was originally described by Rotondo and colleagues in 1993 as a three phase technique. This was
later modified by Johnson and Schwab7 to include a fourth, pre-theatre phase.
 Closure of the abdominal wound has further been separated in the sequence; a change brought about by an
emerging understanding of abdominal compartment syndrome..

Indication
Therefore, the primary determinant in the need for damage control surgery should be the patient’s own physiology
(Table 1).
Table 1: Indications for Damage Control Surgery
Critical  Hypothermia- temperature < 35° C
Physiological  Acidosis- pH < 7.2 or base deficit > 8
Factors  Coagulopathy- nonmechanical bleeding, increase in prothrombin (PT) and/or
partial thromboplastin time (PTT), thrombocytopenia, hypofibrinoginemia, or
massive transfusion requires (> 10 units packed red blood cells [pRBC] or body
volume replacement)
 Prohibitive operative time needed for definitive repair (> 90 minutes)
 Hemodynamic instability or profound hypoperfusion
Injury Complexes  High energy blunt torso trauma
Associated with  Multiple penetrating torso injuries
Loss of  Combined visceral injury with major vascular trauma
Physiologic  Injuries across body cavities, especially those with competing treatment priorities,
Reserve such as closed head injury, major vascular injury and pelvic trauma
Other  Injuries better treated with nonsurgical adjunct, such as angiographic embolization
Considerations in of hepatic or pelvic injuries
Trauma Patients  Variation in physiologic reserve (elderly, multiple comorbidities, young, athletes)
Traditional Damage Control Sequence (Fig 1)

Part Zero (Prehospital and Initial Evaluation)

This is the earliest phase of the damage control protocol. It occurs in the prehospital setting and continues into the
emergency department. The aim of this phase is to recognise injury pattern and to identify patients who are likely
candidates for damage control protocol.

42
Following are key constituents of Part Zeros of DCS.
 In prehospital setting:
o Rapid response with minimal time at site of injury ('scoop and run' rather than 'stay and play')
o Early notification of the receiving hospital trauma team are the priorities;
o Rapid sequence induction (RSI) of anaesthesia and intubation can minimise time to surgery
o Early rewarming
o Expedient transport
o Blood products and tranexamic acid (TXA) if available

 Once in hospital:
o Rapid assessment of the trauma patient is the goal.
o Gaining large bore i.v. access,
o RSI (if not performed already),
o chest drainage if indicated,
o prevention of hypothermia,
o DCR (Damage Control Resuscitation)
o expedient transport to the operating theatre
o Broad spectrum i.v. antibiotics and tetanus prophylaxis where appropriate
o theatres should be placed on standby

Damage Control Resuscitation

In recent past delayed fluid resuscitation8 or
permissive hypotension9 have started gaining
popularity due to established deleterious effects of
Part Prehospital/initial evaluation
excessive fluid resuscitation on haemostasis. Zero stage
Another important factor which is gaining Part 1 Abbreviated Laparotomy
importance is presence of coagulopathy in a large
proportion of severely injured trauma patients on
arrival in hospital. This known as 'acute traumatic Part 2 ICU Resuscitation
coagulopathy' is present in the most severely
injured patients and is associated with poor Part 3 Definitive Repair
outcomes. Modern resuscitation after major
haemorrhage therefore incorporates permissive Part 4 Definitive Abdominal Wall Closure
hypotension and early treatment of anticipated
coagulopathy with blood products.

Figure 1
The main elements of DCR are:
 <C>ABC resuscitation- ATLS protocol
 Permissive hypotension (goal of SBP 90mmHg or palpable radial pulse)
 Limitation of crystalloid with early use of blood and blood products
 Early use of (Tranexamic Acid- TXA)
 DCS (DC I)
There is emerging evidence that using DCR might result in more favourable perioperative physiology and lessen the
need for DCS.9, 10, 11

Early use of Blood and Blood Products

Most of new recommendations are advising on making available an initial pack of uncross-matched blood for
immediate use in the unstable patient. Once bloods for crossmatch have been taken, further group specific or fully
matched components are provided. In addition to using blood earlier in the resuscitation effort, attention is given in
DCR to the ratio of blood components that are used in transfusion, to directly target coagulopathy. A higher ratio of
1:1:1 (pRBC:FFP:platelets) has been associated with survival benefit in trauma patients. 12

The initial resuscitation period is altered somewhat in septic patients. Resuscitation has to be more thorough as
sepsis still gives us few hours, as opposed to minutes with the bleeding trauma patient. Once adequate preload and
systemic pressure are established, the patient may proceed to operative intervention to obtain source control.
Furthermore, correction of hypothermia, acidosis, and coagulopathy should be started. Vasoactive medication like
nor-epinephrine and epinephrine is often needed in these patients, along with aggressive volume replacement.

Imaging
Under DCS protocol, rapid workup of unstable patient using minimal diagnostic tests is stressed upon.

43
  A chest Xray is an important tool to confirm tube placement and to identify haemo, pneumothorax, or both.
If patient is too unstable trauma team should rely on clinical signs and consider placement of chest tubes
bilaterally.
 Plain films may also be useful to confirm the presence or absence of residual foreign bodies.
 Rarely spinal/ pelvic xrays will be needed as protocol already treats them presuming them to be unstable.
 Pre-OT CT can be considered if the patients can be stabilized sufficiently in the emergency department to
survive their trip through the CT scanner
 In the unstable patient, however, any delay to the operating theatre may be detrimental and CT may have to
be bypassed.

Part 1 (Initial Laparotomy)

The primary objectives of the initial laparotomy are
 Haemorrhage control,
 Limitation of contamination (and subsequent secondary inflammatory response), and
 Temporary abdominal wall closure.
Speed is the key factor and priority is given to restoring physiology over anatomical reconstruction.
Preparation
The operating theatre should be ready when the patient of major trauma arrives. Suction equipment, instrument trays
consisting of a standard laparotomy set, vascular, and chest instruments (including a sternal saw) should all be
immediately available. A large supply of laparotomy pads must also be available for the initial packing. It is useful
to have a trolley stocked with damage control equipment available in or immediately adjacent to theatre, reducing
the time need to spend fetching equipment.
The patient is placed on the table supine with upper extremities abducted on arm boards. Whole of abdomen and
chest should be prepared in anticipation of the need for a median sternotomy, resuscitative left thoracotomy, or
bilateral tube thoracostomy, no leads or tubing should be present on the anterior or lateral chest wall. A urinary
catheter and nasogastric/orogastric tube are inserted at this stage if not done already. Surgery should not be delayed
for the insertion of arterial or central venous lines in the unstable patient. These can be placed during the procedure.

Incision
A vertical midline incision extending from the xiphoid process to the pubic symphysis is arguably The best incision
to explore abdomen. In cases of a suspected severe pelvic fracture, the incision can stop short of pubic symphysis,
allowing for continued tamponade of a pelvic haematoma.

Haemorrhage Control
 Once the peritoneum is entered, the first step is haemorrhage control. Large clots should be removed
manually and then all four quadrants of abdomen are packed using laparotomy pads and retractors. The cell
salvage suction if available can help in maximizing autologous blood capture and return.
 Abdomen is quickly assessed for the degree and location of the most significant injuries.
 History of nature and mechanism of injury may aid in assessing potential sites of major bleeding or organ
injury.
 Adequate packing generally provides a good degree of haemorrhage control for most cases.
 Manual occlusion of the aorta at the diaphragmatic hiatus can be performed quickly to control abdominal
exsanguination if the patient continues to lose blood. It gives body time to recover with volume
replacement and also has been shown to augment cerebral and myocardial perfusion. Once clamped, the
time should be noted to ensure timely removal of clamp and prevent visceral ischaemia. By this the
majority of significant bleeding should be controlled.
 Once exsanguinating haemorrhage has been stopped, packs are removed in a sequential fashion, from site
least likely to bleed.
 For major vascular injuries, damage control options are either vessel ligation or placement of temporary
13, 14
intravascular shunts in critical arteries. It should be remembered however, that ligation of almost any
15
major vein is usually a survivable procedure if required. Definitive reconstruction of complex arterial
injuries should be avoided in unstable patients. If limb circulation has been compromised for a significant
period of time, fasciotomy is often necessary once haemorrhage is controlled.
 Prolonged repair of solid organ injuries must also be avoided in unstable patients. Splenic, renal, and
pancreatic tail injuries are managed best with total or partial resection or just packing. Pringle manoeuvre
(temporary hepatic vascular inflow occlusion by compression of the porta hepatis within the lateral edge of
the gastrohepatic ligament) can provide a good mechanism to control bleeding and helps identifying source
of bleed.
 Use of topical haemostatic agents (like microfibrillar collagen, or fibrin glue) on the liver injury itself may
16
provide additional haemostatic support.

44
  Angioembolization is another useful technique for the treatment of bleeding vessels deep within the liver
parenchyma and in other viscera. This technique can also be used in case of continued bleeding in post
operative period.

Contamination Control
 The second priority in a damage control laparotomy is to control the spillage of intestinal contents or urine
from hollow viscus injuries.
 Simple bowel perforations, may be primarily repaired using a single layer continuous suture.
 More extensively injured bowel segments can be resected using a linear stapler.
 Any reconstruction, stoma creation, and feeding tube placement are avoided at this stage and the intestine
is left in discontinuity.
 In high energy injuries and otherwise, the extent of bowel wall injury is generally not apparent at the initial
operation, thus bowel viability will be assessed during definitive surgery.
 Biliary and pancreatic ductal injuries can be managed initially by simple drainage to form controlled
fistulae. Definitive repair or resection is delayed until physiological restoration is achieved
 Most injuries to the bladder may be suture repaired primarily and then drained with a Foley catheter.
 Ureteric injuries can be repaired primarily over a stent but in an unstable patient can simply be drained to
the abdominal wall (with a paediatric feeding tube into the proximal lumen) or even tied off.
 In the septic abdomen, this part focusses on identifying and managing the source of sepsis along with wide
drainage. Additionally, abdominal compartment syndrome is much more common in these patients.
 Once all vascular and viscus injuries have been controlled, intraabdominal packing is performed. Packing
should be sufficient to provide adequate tamponade without impeding venous return or arterial blood
supply.

Abdominal Closure
The main principles to be followed here are to ensure quick cover in order prevent visceral prolapse, allowing
drainage of oedema fluid thus preventing Abdominal Compartment Syndrome, and facilitating secondary closure.
 Fascial closure is not recommended at the initial laparotomy.
 Several methods of temporary abdominal closure have been described, like the simple homemade solutions
(e.g. the Bogota bag, OpsiteTM sandwich) to custom made commercial devices, mostly using Vaccum
assisted technology. (Table 2)
Table 2 - Characteristics of the Optimal Temporary Abdominal Closure.
 Control the abdominal viscera
 Prevent additional contamination of the peritoneal cavity
 Prevent injury to the abdominal viscera
 Control and quantify the effluent
 Preserve skin and soft tissue integrity
 Avoid radiographic artifacts that could complicate other diagnostic and therapeutic modalities
 Avoid tension that could lead to abdominal compartment syndrome
 Prevent fusion of the visceral block to the abdominal wall
 Promote medialization of the fascial edges
 Preserve fascial integrity for later definitive native tissue closure
 Ease of placement
 Not costly

Part 2 (ICU Resuscitation)

In the second phase, the goal is to correct the sequelae the severe injury/ sepsis. Such management is often labour
intensive and require the collaborative inter-disciplinary efforts of multiple critical care physicians, surgeons,
nurses, and ancillary staff.
 Establishing adequate oxygen delivery to body tissues is topmost priority during the ICU resuscitation.
Invasive monitoring devices are generally used to guide fluid administration and normalize haemodynamics. No
consensus is reached regarding the exact hemodynamic endpoints that patients must attain after severe injury.
Recent studies are advocating use of serum lactate clearance as marker of effective resuscitation. Ability to
clear lactate to normal levels within 24 h has shown improved patient survival. 17
 Hypothermia should be avoided by aggressive core rewarming as it can lead to poor outcomes inspite of
aggressive resuscitation otherwise. Maintaining body temperatures improves perfusion and helps reverse
coagulopathy.18 All fluids and blood products should be warmed before administration.
 Correction of coagulopathy is achieved by maintaining body temperature and administration of FFP until
coagulation profile is normal. Platelet levels and fibrinogen levels also should be followed and corrected
accordingly.

45
 Proper settings of ventilators should be used to minimise chances of Ventilator associated ARDS
 Monitoring of intraabdominal pressure is mandatory in order to identify and timely treat intra-abdominal
hypertension,. This can be easily done by measuring intra vesical pressure urinary catheter as described by Kron
and colleagues.19
 A thorough complete physical examination or 'tertiary survey' of the patient should be done at this stage
including relevant imaging studies like CT scan to detect occult injuries whenever stable enough. In cases of
blunt trauma, completion of the spinal survey is imperative. Peripheral wounds are addressed and vascular
integrity of all injured limbs is assessed frequently.
 Planning for all definitive repairs should also start in this phase, deciding on both the extent and priority of
repairs.

The exact end point of part 2 is variable and may require upto 24–36 h. It is imperative that if a patient does not
normalize haemodynamically or lactic acid or base deficit fail to improve, he should be taken back for reexploration.
This can happen in following situations:
 Patients who have ongoing surgical bleeding manifested by continuous transfusion requirements or persistent
acidosis despite normalized clotting and core temperature. Re-exploration is done to control bleeding failing
which this can cause to be fatal.
 Patients who developed abdominal compartment syndrome ACS.
 to salvage an ischaemic limb because of shunt occlusion
 for managing closed loop obstruction in bowel that has been interrupted at several sites

Part 3 (Subsequent Laparotomy/Definitive Repair)

Timing of definitive surgery is critical and the team should ensure that adequate resuscitation and physiological
optimization has been achieved. Patients should be normothermic, have normal coagulation studies and also a
normal pH and lactate.

Operative Game Plan

Ideally the definitive surgery should be performed by same surgeon who perform the original DC I laparotomy. If
that is not possible, surgeon should have a thorough discussion and go through patient records.
All packs are irrigated copiously and removed carefully to avoid clot disruption or further visceral damage. If
bleeding restarts and is not controllable, immediate repacking is the safest course of action.
After successful pack removal, a complete reexamination of the abdominal contents should be done performing
definitive repairs of vessels, intestine etc. (Table 3)

Part 4 (Abdominal Wall Closure)

 As a final step it can be very challenging as only about in 40 % cases tension free primary closure will be
possible. A standard fascial closure should be done as far as possible.
 However, if there is increased risk of ACS, as suggested by increase in peak airway pressure by >10 cm H 2O
during temporary fascial approximation, then the fascia should be left open and the temporary abdominal
closure device applied (Table 4).
 Delayed Primary closure will be possible in majority of cases within 1 week, especially if there is no sign of
intraabdominal infection.
 If fascial closure is not achieved after 7 days, it heals by secondary intension and surgeon should plan a formal
ventral hernia repair at a later date.

Outcomes
In large series, damage control surgery has shown a survival rate of approximately 60%, compared to the 11%
survival rate of conventionally treated patients in Rotondo and Schwab’s initial study3. In lower energy mechanisms
like stabbings, rates as high as 90% have been reported. Moreover, Duchesne has recently reported improved
outcomes with the addition of damage control resuscitation to damage control surgery (74% vs. 55%)21. However,
damage control surgery is not without its own complications.
 Abdominal compartment syndrome can be commonplace in both traumatic injury and the septic abdomen
patient given the aggressive resuscitations both receive.
 Enterocutaneous fistulae are more common with damage control surgery, due to increased manipulation of the
viscera. Up to 15% of trauma patients may experience this complication, with higher rates reported in septic
abdomen patients.22 Additionally, these fistulae tend to be the more aggressive entero-atmospheric type, which
have lower spontaneous closure rates and more difficult wound contamination control issues.
 Intraabdominal abscess (IAA) is another common complication arising out of DCS with occurance rate of 10
to 70%. While more frequent washouts of the peritoneal cavity may decrease IAA rates, but it increases the
enterocutaneous fistula rates. Luckily, most of these can be managed by interventional radiology. 23, 24

46
 Table 3 - Sequence of Definitive Repair Table 4 - Closure Options of Open Abdominal
Wounds.
 Careful removal of packs Immediate  Skin closure only
 Inspection/identification of all injuries term  Silo placement (Bogota bag)
 Control of remaining errant bleeding points  Vacuum assisted abdominal
 Definitive gastrointestinal repair dressing
 Thorough abdominal washout Intermediate  Sequential skin or fascial
 Avoid stomas and tube enterostomies, if possible term closure
 Nasoenteric feeding tube placement  Interpositional mesh
 Closed suction drainage, if needed placement
 Temporary versus definitive abdominal wound closure  Vacuum assisted abdominal
 Tracheostomy, if needed dressing
 Radiographic evaluation for retained packing Long term  Planned Ventral Hernia

Conclusions
Damage control strategies prioritize physiological and biochemical stabilization over the full anatomical repair of all
injuries.
 Damage control strategies are useful for a subset of trauma patients and are not appropriate in all cases.
 Selection criteria for damage control management include the mechanism of injury and the degree of
physiological derangement.
 The recent advances like permissive hypotension and damage control resuscitation along with new
technologies such as new ventilator modes, hemostatic agents, and temperature regulation devices have
allowed for better survival rates.
Damage control surgery is the mainstay treatment modality for patients with life threatening conditions incapable of
tolerating traditional methods. It is for DCS that majority of trauma patients reaching hospital can hope to survive
what was once considered fatal.
REFERENCES
1. Burch JM, Ortiz VB, Richardson RJ, et al. Abbreviated laparotomy and planned reoperation for critically injured patients. Ann Surg. 1992;
215: p. 476-83; discussion 483-4.
2. Stone HH, Strom PR, Mullins RJ. Management of the major coagulopathy with onset during laparotomy. Ann Surg. 1983; 197: p. 532-5.
3. Rotondo F Schwab W cGonigal D et al. ‘Damage control’: an approach for improved survival in exsanguinating penetrating
abdominal injury. J Trauma. 1993; 35: p. 375-82; discussion 382-3.
4. Rotondo MF, Zonies DH. The damage control sequence and underlying logic. Surg Clin North Am. 1997; 77: p. 761-77.
5. Shapiro MB, Jenkins DH, Schwab CW, et al. Damage control: collective review. J Trauma. 2000; 49: p. 969-78.
6. Hoey BA, Schwab CW. Damage control surgery. Scand J Surg. 2002; 91: p. 92-103.
7. Johnson JW, Gracias VH, Schwab CW, et al. Evolution in damage control for exsanguinating penetrating abdominal injury. J Trauma.
2001; 51: p. 261-9; discussion 269-71.
8. Bickell WH, Wall MJ, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.
N Engl J Med 1994;331:1105–9.
9. Dutton RP. Lowpressure resuscitation from hemorrhagic shock. Int Anesthesiol Clin 2002;40:19–30.
10. Cotton BA, Reddy N, Hatch QM, et al. Damage control resuscitation is associated with a reduction in resuscitation volumes and
improvement in survival in 390 damage control laparotomy patients. Ann Surg 2011;254:598–605.
11. Fox CJ, Gillespie DL, Cox ED, et al. Damage control resuscitation for vascular surgery in a combat support hospital. J Trauma 2008;65:1–
9.
12. Dua A, Patel B, Kragh JF, Holcomb JB, Fox CJ. Longterm followup and amputationfree survival in 497 casualties with combatrelated
vascular injuries and damagecontrol resuscitation. J Trauma Acute Care Surg 2012;73:1517–24.
13. Borgman MA, Spinella PC, Perkins JG, et al. The ratio of blood products transfused affects mortality in patients receiving massive
transfusions at a combat support hospital. J Trauma 2007;63:805–13.
14. Subramanian A, Vercruysse G, Dente C, Wyrzykowski A, King E, Feliciano DV. A decade's experience with temporary intravascular
shunts at a civilian level 1 trauma center. J Trauma 2008;65:316–24.
15. Chao A, Chen K, Trask S, et al. Time to failure of arterial shunts in a pig hemorrhagic shock model. Am Surg 2012;78:1045–8.
16. Hirshberg A, Mattox KA. Top Knife: The Art and Craft of Trauma Surgery. Shrewsbury: TFM Publishing; 2005.
17. Shen GK, Rappaport W. Control of nonhepatic intraabdominal hemorrhage with temporary packing. Surg Gynecol Obstet 1992;174:411–3.
18. Abramson D, Scalea TM, Hitchcock R, Trooskin SZ, Henry SM, Greenspan J. Lactate clearance and survival following injury. J Trauma
1993;35:584–8.
19. Kron IL, Harman PK, Nolan SP. The measurement of intraabdominal pressure as a criterion for abdominal reexploration. Ann Surg
1984;199:28–30.
20. Gentilello LM. Practical approaches to hypothermia. Adv Trauma Crit Care 1994;9:39–79.
21. Duchesne JC, Kimonis K, Marr AB, et al. Damage control resuscitation in combination with damage control laparotomy: a survival
advantage. J Trauma. 2010; 69: p. 46-52.
22. Anderson O, Putnis A, Bhardwaj R, et al. Short- and long-term outcome of laparostomy following intra-abdominal sepsis. Colorectal
Disease. 2011; 13: p. e20-32.
23. Buijk SE, Bruining HA. Future directions in the management of tertiary peritonitis. Intensive Care Med. 2002; 28: p. 1024-9.
24. Evans HL, Raymond DP, Pelletier SJ, et al. Diagnosis of intra- abdominal infection in the critically ill patient. Curr Opin Crit Care. 2001; 7:
p. 117-21.

47
 Prevention of Surgical Site Infections
Vinod K Malik, Ashish Dey, Sarrah Idrees
The principles of antisepsis by Joseph Lister and asteur’s germ cell theory in the 19th century have led to a better
understanding in the etiopathogenesis of post-operative wound infection. Despite improvements in operating room
practices, instrument sterilization methods and better surgical technique, surgical site infections (SSIs) remain a
major cause of post-operative morbidity and delay in discharge from the hospital.
SSI are the most commonly reported nosocomial infections accounting for 38 per cent of all nosocomial infections
among hospital inpatients. They are also the most frequent cause (20%) of unplanned readmissions after
surgery. Organisms associated with SSIs vary with the anatomic location of the operation and the procedure
performed. The most common organisms isolated from SSIs are Staphylococcus aureus (coagulase negative
staphylococci), enterococcus species and Escherichia coli for most SSIs, the source of the pathogen(s) are
endogenous and comes from the patient’s skin, mucous membranes or bowel. Exogenous SSI pathogens are
occasionally responsible and include aerobic staphylococci and streptococci. These organisms mostly come from
members of the surgical team (e.g., hands, nose or other body parts), contaminated surfaces in the operating room,
even the air; and contaminated instruments, surgical gloves or other items used in surgery.

At the end of surgery bacteria and other microorganisms contaminate all surgical wounds, but only a small number
of patients actually develop a clinical infection. Whether an infection actually occurs depends on the number of
bacteria entering the wound, type and virulence of the bacteria and the host defense mechanisms. In a study done to
find the incidence of SSIs in clean and clean contaminated surgeries it was found that the risk also increases in cases
where a drain was put as compared to cases without drainage.

Other factors affecting rates of SSIs include emergency surgery, remote infection, obesity, malnutrition, associated
comorbidities and immunocompromised states (Malignancy, Diabetes mellitus, steroid consumption).
A system of classification for operative wounds that is based on the degree of microbial contamination was
developed by the US National Research Council group in 1964. The system described four wound classes with an
increasing risk of SSIs: clean, clean-contaminated, contaminated and dirty. The simplicity of this system of
classification has resulted in it being widely used to predict the rate of infection after surgery. The surgical wound
classification system can be divided into the following four categories:

Class I—Clean. Uninfected operative wound with no inflammation and in which the respiratory, gastrointestinal,
genital and urinary tracts were not entered. Clean wounds are closed at surgery and, if necessary, drained with
closed drainage.
Class II—Clean-contaminated. Wound in which the respiratory, GI, genital or urinary tract(s) were entered under
controlled conditions but without unusual contamination or spillage of contents (e.g. Operations involving the
biliary tract, appendix, vagina and oropharynx, provided no evidence of infection or major break in technique in
encountered).
Class III—Contaminated. Open, fresh accidental wound or an operation with a major break(s) in aseptic technique
(e.g., open cardiac massage) or gross spillage from the GI tract. Also included are incisions in which acute, non-
purulent inflammation is found.
Class IV—Dirty or infected. Old wounds with dead tissue and those that involve existing clinical infection or a
perforated bowel, suggesting that the pathogens causing the postoperative infection were present in the wound
before the surgery.

DEFINITION OF SSIs
Surgical site infections- Either an incisional or organ/space infection occurring within 30 days after an operation or
within 1 year if an implant is present, and at least one of the following (Day 1 is the procedure date):
• Purulent drainage, with or without laboratory confirmation, from the superficial incision.
• Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision.
• At least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or
heat and superficial incision is deliberately opened by surgeon, unless incision is culture-negative.
• Diagnosis of superficial incisional SSI by the surgeon or attending physician
Incisional SSIs are further divided into superficial incisional (that only involves skin and subcutaneous tissue) and
deep incisional (those involving deeper soft tissue, including fascia and muscle layers).

Organ/ Space SSI are those infections occurs within 30 days after the operation if no implant is left in place or
within one year if implant is in place and the infection appears to be related to the operation and infection involves
any part of the anatomy (e.g. organs or spaces), other than the incision. Table 1 shows the classification of SSI as
per the CDC guidelines.

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Reducing the Risk of Surgical Site Infections
Changes in definition of surgical site infection have focused attention on the factors associated with SSIs and are
now being studied with a view to limiting the risk of infection. Host-related factors that lead to an increased risk of
SSI include: -
• Extremes of age.
• Morbid obesity.
• Other co-morbid illness.
• Increased glucose levels (>200 mg/dL) in the immediate post-operative period (48- hours) were
• associated with increased SSI risk.
• Smoking delays primary wound healing and may increase the risk of SSI.
• Patients who are receiving steroids or other immuno-suppressive drugs pre-operatively may be predisposed to
developing SSI.
• Malnutrition
• Prolonged pre-operative hospital stay.
• Perioperative transfusion.
• Poor bowel preparation before colon surgery increases SSI rates.

Research has shown that surgical techniques, skin preparation and the timing and method of wound closure are
significant factors that can influence the incidence of subsequent infection. Antibiotic prophylaxis has also had a
positive impact after certain types of surgery. Many other factors have been identified as having an effect on the
potential for infection and healthcare professionals should consider these before, during and after surgery. In 1999,
CDC issued a number of guidelines for reducing the risk of SSIs. They can be grouped into 3 categories as follows:
I. Preoperative Measures
a. Method of hair removal- In a Cochrane review that included Eleven RCTs that compared hair removal (using
either depilatory cream or razors) with no hair removal showed no statistically significant difference between
the groups in terms of surgical site infections. It also showed that there were statistically significantly more SSIs
when people were shaved rather than clipped. There were also no difference in SSIs when patients are shaved
or clipped one day before surgery or on the day of surgery. The recommendations therefore are: -
• Hair should not be removed preoperatively unless the hair at or around the incision site interferes with the
operation.
• If hair is removed, it should be removed immediately before the operation, preferably with electric clippers
or depilatory agents BUT NOT RAZORS.
• Razors cause gross skin cuts, clippers cause less injury than razors, depilatory agents cause no injury to the
skin.
b. Hand/forearm antisepsis for surgical team members-All members in the team must practice hand hygiene
including anesthesiologists.
 Nails should be kept short.
 A preoperative surgical scrub should be performed for at least 2 to 5 minutes using an appropriate
antiseptic. The hands and forearms should be scrubbed up to the elbows. Aqueous alcoholic solution is an
effective as traditional hand scrubbing and also requires shorter duration of scrubbing
 Wearing of hand or arm jewellery should be discouraged (watches or rings).
c. Surgical attire–Includes scrubs, gloves and barrier devices (masks, caps, gowns, drapes, shoe covers)
d. Asepsis and surgical technique
The American college of surgeons’ guidelines for surgical attire is as follows:
 For clean and clean contaminated surgery preoperative skin cleansing with chlorhexidine based
preparations are superior to povidone based preparation because the former is not inactivated by blood or
serum. Table II shows the various antiseptic solutions available and their spectrum of activity.
 Principles of asepsis when placing intravascular devices (e.g., central venous catheters), spinal or epidural
anesthesia catheters, or when dispensing and administering intravenous drugs should be adhered to.
 Good surgical technique is indispensable as it minimizes tissue trauma, controls bleeding, eliminates dead
space, removes dead tissue and foreign bodies, uses minimal suture and maintains adequate blood supply
and oxygenation. Specifically, it is important to handle soft tissue gently to avoid crushing that can result in
tissue necrosis. Electrocautery should be sparingly to control bleeding because it leaves behind dead tissue
that is more likely to become infected.
 Absorbable suture should be used whenever possible because permanent suture, especially silk suture,
reduces the number of bacteria necessary to cause infection
 Closed suction drains that exit through a separate stab wound helps prevent accumulation of tissue fluid in
the dependent portion of the wound. Preventing this is especially important in obese patients and may
reduce SSIs. Passive drains, such a Penrose drain, exiting through the bottom of the incision should not be
used.
e. Antimicrobial prophylaxis: Experimental studies published during the early 1960s helped to achieve a more
scientifically accurate approach to antimicrobial prophylaxis. Most important was the report by Burke which

49
 demonstrated the crucial relationship between timing of antibiotic administration and its prophylactic efficacy.
His experimental studies showed that to greatly reduce experimental skin infection produced by penicillin-
sensitive S. aureus, the penicillin had to be in the skin shortly before or at the time of bacterial exposure. This
important change in strategy helped correct the common error of first administering the prophylactic antibiotic
in the recovery room. Table III lists the commonly used antimicrobials for SSI.

Goal: Prevent SSI by reducing the burden of micro-organism at surgical site during the operative procedure.
Antimicrobial prophylaxis is justified for most clean contaminated procedures. In dirty procedures they are given as
treatment of presumed infection not prophylaxis.
A prophylactic antimicrobial agent should be used only when indicated, and selected based on its efficacy against
the most common pathogens causing SSI for a specific operation and published recommendations.
 The initial dose of prophylactic antimicrobial agent should be administered by the intravenous route, timed
such that a bactericidal concentration of the drug is established in serum and tissues when the incision is
made. Therapeutic levels of the agent in serum and tissues should be maintained throughout the operation
and until a few hours after the incision is closed
 The use of antibiotics preoperatively can reduce the rate of infection, particularly wound infections, after
certain operations. For most procedures, an inexpensive, first- or second-generation cephalosporin, which
has a moderately long half-life and is active against staphylococci and streptococci, has been effective
when given intravenously (IV) 30 minutes before surgery.
 Also, third- and fourth-generation cephalosporins should not be used for routine surgical prophylaxis
because they are expensive, their spectrum of activity includes organisms rarely encountered in elective
surgery and their widespread use may promote the emergence of resistance.
 Repeat dosing if duration of procedure exceeds two half-lives of the drug and if there is excessive loss of
blood (>1500 ml), in extensive burns, renal dysfunction or in special circumstances such as gross
contamination secondary to a ruptured viscus or severe trauma.
 Recommendations of a single preoperative dose of antibiotic is as effective as a full 5-day course of
therapy assuming an uncomplicated procedure.
 Complicated, contaminated, or dirty procedures should receive additional postoperative coverage.
 Before giving antibiotic, prophylaxis consider the timing and pharmacokinetics (for example, the serum,
half-life) and necessary infusion time of the antibiotic.

Antibiotic Prophylaxis before Elective Colon Resection

The human colon and distal small intestine contain an enormous reservoir of facultative and anaerobic bacteria,
separated from the rest of the body by the mucous membrane. A reliable method of sterilizing the colonic contents
has been a goal of surgeons throughout this century. In the past 25years, clinical trials have demonstrated that to
substantially reduce septic complications after elective colon surgery, antibiotics must have activity against both
colonic aerobes (e.g., Escherichia coli) and anaerobes (e.g., Bacteroides fragilis). Today, approaches to mechanical
cleansing differ widely.

Modern approaches include standard outpatient mechanical cleansing with dietary restriction, cathartics, and enemas
for a 2-day period, or whole-gut lavage with an electrolyte solution of 10%mannitol, Fleet's phospho-soda, or
polyethylene glycol, done the day before the operation.

Most surgeons use both antibiotics and mechanical cleansing for preoperative preparation before elective colon
resection. The most popular regimen in the United States has been the neomycin erythromycin base preparation,
which was introduced in 1972. The use of outpatient bowel preparation is increasing; however, patient selection is
critical, and education is needed to reduce the rate of complications.

In spite of the use of prophylactic antibiotics, SSIs are still a real risk of surgery and represent a substantial burden
of disease for both patients and healthcare services in terms of morbidity, mortality and economic cost. Factors like
Prolonged preoperative hospitalization exposes patients unduly to hospital flora including multidrug-resistant
organisms. Prompt postoperative discharge reduces the risk of infection, provided patients are able to take care of
themselves at home. A combined effort between the health care providers including hospital staff and nursing
personnel can go a long way in preventing surgical site infections and reducing the burden of health care costs to a
great extent.

Antibiotic Prophylaxis for Appendectomy

The pathologic state of the appendix is the most important determinant of postoperative infection. Wound infection
after appendectomy for perforated or gangrenous appendicitis is four to five times higher than for early disease.
Because the pathologic state of the appendix often cannot be determined before or during operation, a parenteral
antibiotic agent is recommended as prophylaxis in all patients. Regimens with activity against both facultative gram-
negative bacilli and anaerobes are more effective than those active only against aerobes.

50
Antibiotic prophylaxis in Urogenital surgeries.
Antibiotic prophylaxis is recommended in transrectal prostate biopsy, in ESWL, in PCNL, endoscopic ureteric stone
removal and highly recommended in TURP. This is to prevent bacteriuria, urinary tract infection and subsequent
urosepsis. Gram (-) bacilli and Enterococcus are the predominant organisms. Cefazolin is the recommended drug
and Ciprofloxacin the alternative antibiotic.

Antibiotic prophylaxis in Upper G I surgery

Antibiotic prophylaxis is recommended in gastric surgeries including gastric bypass and small intestinal surgery.
Predominant organisms include Enteric Gram (-) bacilli and Gram (+) cocci. Preferred antibiotic for prophylaxis is
Cefuroxime and Clindamycin + Aminoglycoside being the alternative regimen.

Antibiotic prophylaxis in Biliary tract surgery

Antibiotic prophylaxis is recommended is recommended in biliary surgery, pancreatic surgery, liver surgery and in
high risk patients for gall bladder surgery. However, for patients undergoing routine laparoscopic gall bladder
surgery in general risk patients, antibiotic prophylaxis is not recommended. Predominant organisms again include
Enteric Gram (-) bacilli and Gram (+) cocci. Preferred antibiotic for prophylaxis is Cefuroxime and Clindamycin +
Aminoglycoside being the alternative regimen.

Preventive Antibiotic Use in Traumatic Chest Injuries-

Cefuroxime, Ampicillin Sulbactam.
Recently published studies have shown the value of parenteral antibiotic prophylaxis in the prevention of pneumonia
or empyema after the placement of a chest tube to correct the hemo-pneumothorax associated with chest trauma. In
both studies patients receiving antibiotics had substantially lower infection rates than those receiving placebos.

Preventive Antibiotic Use in Cardiac Surgery- 1st and 2nd generation cephalosporins.

Preventive Antibiotic Use in Neurosurgery- Cefuroxime, Clindamycin or vancomycin

DOSING OF ANTIBIOTICS: Cefuroxime: A new semi-synthetic cephalosporin that has an unusually broad
antibacterial spectrum and improved stability to β-lactamase degradation from Gram-negative aerobic bacteria as
well as some activity against non-β-lactamase-producing strains of Bacteroides fragilis.

Dosage in Clean-contaminated or potentially contaminated surgical procedures:

 Preoperative: 1.5 g IV 30 to 60 minutes before the initial incision
 Intraoperative (for prolonged procedures): 750 mg IV or IM every 8 hours
 Open heart surgery: 1.5 g IV at induction of anesthesia and every 12 hours thereafter. The maximum dose
which can be administered is 6 g.
 Prophylaxis usually unnecessary postoperatively and should be stopped within 24 hours; in most surgeries,
continued prophylaxis does not reduce incidence of subsequent infections but increases likelihood of side
effects and bacterial resistance developing.
 Peri operative use during open heart surgery has been effective in surgical patients for whom infection at
the operative site would present serious risk; for such patients, this drug should be continued for at least 48
hours after the end of surgery. If signs of infection observed, specimens for culture and susceptibility
testing should be obtained to isolate and identify infecting organisms in order to start appropriate therapy.
 Redosing interval (from start of preoperative dose): 4 hours
 Redosing may be needed if drug half-life is shortened (e.g., extensive burns) or if prolonged/excessive
bleeding during surgery; redosing may not be needed if drug half-life is prolonged (e.g., renal dysfunction).
 Co-administration with other agents may be recommended, depending on type of procedure.

II: PERIOPERATIVE MEASURES

 Maintain normothermia – hypothermia causes increased risk for surgical site infection by triggering
vasoconstriction and reducing subcutaneous oxygen tension.
 Limit traffic in operating room – Number of people in OR and number of door openings are related to the
number of airborne particulates. Microorganisms causing SSI after implant infections can be recovered
from ambient air during surgical procedures.
 Use of air barrier systems – designed to filter ambient air through highly effective filters, significantly
reduce the risk of SSI.
 Supplemental oxygen – High inspired supplemental O2 is associated with decreased rates of SSI
 Minimize red cell transfusion intraoperatively
 Glucose control.

51
III Operating Room Measures: Although all guidelines regarding Intraoperative Operating Room ventilation may
not be financially possible they should be adhered to as much as possible.
a. Ventilation
 Positive-pressure ventilation in the operating room with respect to the corridors and adjacent areas should
be maintained.
 A minimum of 15 air changes per hour, of which at least 3 should be fresh air should be ensured.
 Air should be introduced at the ceiling, and exhaust near the floor.
 Operating room doors should be kept closed except as needed for passage of equipment, personnel and the
patient.
 The number of personnel entering the operating room should be limited to necessary personnel.
b. Cleaning and disinfection of environmental surfaces
When visible soiling or contamination with blood or other body fluids of surfaces or equipment occurs
during an operation, a disinfectant should be used to clean the affected areas before the next operation.
c. Sterilization of surgical instruments
 All surgical instruments should be sterilized according to published guidelines.
 Flash sterilization should be performed only for patient care items that will be used immediately (e.g., to
reprocess an inadvertently dropped instrument). It should not be used for reasons of convenience, as an
alternative to purchasing additional instrument sets, or to save time.

In 2016, the World Health Organization (WHO) published the following guidelines regarding SSI :
 It is good clinical practice for patients to bathe or shower prior to surgery. Either plain soap or an
antimicrobial soap may be used for this purpose.
 Patients undergoing cardiothoracic and orthopedic surgery with known nasal carriage of S. aureus should
receive perioperative intranasal applications of mupirocin 2% ointment with or without a combination of
chlorhexidine gluconate (CHG) body wash.
 Surgical antibiotic prophylaxis (SAP) should be administered prior to the surgical incision when indicated
(depending on the type of operation). The panel recommends the administration of SAP within 120 min
before incision, while considering the half-life of the antibiotic.
 Preoperative oral antibiotics should be combined with mechanical bowel preparation to reduce the risk of
SSI in adult patients undergoing elective colorectal surgery. Mechanical bowel preparation alone (without
administration of oral antibiotics) should not be used for the purpose of reducing SSI in adult patients
undergoing elective colorectal surgery.
 In patients undergoing any surgical procedure, hair should either not be removed or, if absolutely
necessary, should be removed only with a clipper. Shaving is strongly discouraged at all times, whether
preoperatively or in the OR.
 Alcohol-based antiseptic solutions are recommended based on CHG for surgical site skin preparation in
patients undergoing surgical procedures.
 Antimicrobial sealants should not be used after surgical site skin preparation for the purpose of reducing
SSI.
 Surgical hand preparation should be performed by scrubbing with either a suitable antimicrobial soap and
water or using a suitable alcohol-based handrub before donning sterile gloves.
 Consider the administration of oral or enteral multiple nutrient-enhanced nutritional formulas for the
purpose of preventing SSI in underweight patients who undergo major surgical operations.
 Do not discontinue immunosuppressive medication prior to surgery for the purpose of preventing SSI.
 Adult patients undergoing general anesthesia with endotracheal intubation for surgical procedures should
receive an 80% fraction of inspired oxygen intraoperatively and, if feasible, in the immediate postoperative
period for 2-6 hr to reduce the risk of SSI.
 Use triclosan-coated sutures for the purpose of reducing the risk of SSI, independent of the type of surgery.
 Preoperative antibiotic prophylaxis should not be continued in the presence of a wound drain for the
purpose of preventing SSI.

To summarize, prevention of Surgical site infection results in reduction of morbidity and translates into reduced
hospital costs. Prevention of SSI starts from prophylaxis preoperatively, includes the period of inhospital admissions
discharge of the patient from the hospital postoperative follow up to ensure favorable outcomes. Guidelines and
recommendations based on high level clinical evidence goes a long way in guiding clinicians towards optimal use of
antibiotics.

52
 WHO Guidelines on Surgical Site Infection
Table I: Source: SSI: surgical site infection; NHSN: National Health Safety Network; CDC: Centers for Disease
Control.
Extent of tissue
Time to event Clinical features Criteria for diagnosis
involvement
At least one clinical feature AND at least
one of the following:
• Peri-incisional pain • Purulent drainage from the superficial
or tenderness incision
Within 30 days Skin and • Localized peri- • Organisms are identified by culture (or
Superficial
of NHSN subcutaneous incisional swelling non-culture-based microbiologic testing
incisional SSI
procedure tissue • Peri-incisional method) performed for clinical diagnosis
erythema or heat or treatment (eg, not surveillance)
• Incision opened by the surgeon (or other
designated clinician) because of concern
for superficial SSI
• Purulent drainage from the deep incision
• Deep incision that spontaneously
dehisces or is opened by the surgeon (or
other designated clinician) because of
Deep soft tissues
Within 30 or 90 • Fever (>38°C) concern for deep SSI ANDorganisms
Deep incisional of the incision
days of NHSN • Localized pain or are identified by culture (or non-culture-
SSI such as the fascia
procedure tenderness based microbiologic testing method)
and muscle layers
performed for clinical diagnosis or
treatment (eg, not surveillance).
Presence of at least one clinical feature,
in absence of microbiologic testing
Clinical features for
specific organ/space can Appropriate clinical features specific to the
be found at the CDC organ/space AND at least one of the
website following:
Any part of the As an example, for • Purulent drainage from a drain placed
body deeper than intra-abdominal into the organ/space
Within 30 or 90 the fascia/muscle infection, at least two of • Organisms identified from culture of
Organ/space days of NHSN layers that was the following: fluid or tissue obtained from a
SSI procedure opened or • Fever (>38°C) superficial incision
manipulated • Hypotension • Abscess or other evidence of infection
during the • Nausea, vomiting involving the organ/space detected on
procedure • Abdominal pain or gross anatomical exam or
tenderness histopathologic exam
• Elevated • Radiographic imaging findings
transaminases suggestive of infection
• Jaundice

Table II: Characteristics of Antiseptic Solutions and suggested application

Mechanism of Antimicrobial
Antiseptic Onset Duration Application
Action Coverage
Excellent for gram +ve
Free iodine −
bacteria, good for gram 2-step scrub and
Aqueous-iodophor protein, DNA Intermediate 2 hours
−ve, fungi, virus, paint
damage
mycobacteria
Excellent for gram +ve,
Aqueous-
Disrupts good for gram –ve and 2-step scrub and dry,
chlorhexidine Intermediate 6 hours
membranes virus, fair for fungus, repeat
gluconate(CHG)
poor for mycobacteria
Denatures 1-step paint Dry
protein, free Improved gram –ve time, minimum of 3
Alcohol-iodophor Rapid 48 hours
iodine − protein, ,mycobacteria activity min on hairless
DNA damage surface
Dry site: 30-sec
Alcohol- Denatures Moist site: 2-min
Improved gram −ve,
chlorhexidine protein, disrupts Rapid 48 hours Dry time, minimum
Mtb, fungal activity
gluconate (CHG) membranes of 3 min on hairless
surface

53
Table III: Details of commonly used antibiotics in practice for prevention of surgical site infections
Bacteri Bactericida Intracellular Administr
Name Class Half-Life
ostatic l Penetration ation
Amoxicillin +
Penicillin yes good O
Clavulnate
Azithromycin Macrolide yes Very good 2-4 days O. IV
Cefuroxime Cephalosporin 2 yes good 1 hour O, IM, IV
Clarithromycin Macrolide yes yes for G+ good 3-7 hours O
Clindamycin Macrolide O
Doxycycline Tetracycline yes 16-20 hrs O, IV
Gentamicin Aminoglycoside yes O, IV
Imipenem Beta-lactam IV
Levofloxacin Fluoroquinolone yes O, IV
Meropenem
Metronidazole Nitroimidazole good O
Ofloxacin
Penicillin G Penicillin yes good 14 days IM
Piperacillin Penicillin yes good
Tinidazole Nitroimidazole 12-14 hrs O
Vancomycin Glycopeptide yes

Suggested reading
 Berríos-Torres SI, Umscheid CA, Bratzler DW et al. Healthcare Infection Control Practices Advisory
Committee. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site
Infection, 2017. JAMA Surg. 2017 Aug 1;152(8):784-791.
 Micah L Hemani, Herbert Lepor, Skin Preparation for the Prevention of Surgical Site Infection: Which
Agent Is Best?, Rev Urol. 2009;11:190–195.
 A J Mangram et al, Guideline for Prevention of Surgical Site Infection, 1999 (Infection Control and
Hospital Epidemiology 20 (April 1999) 250-280.
 Lilani SP, Jangale N, Chowdhary A, Daver GB, Surgical site infection in clean and clean-contaminated
cases. Indian J Med Microbiol2005;23:249-52.
 Ronald Lee Nichols, Preventing Surgical Site Infections: A Surgeon's Perspective, emerging infectious
diseases, Vol. 7, No. 2 Mar–Apr 2001.

54
Current concepts of Urinary stones formation and their medical management
Rishi Nayyar, Kulbhushan Sharma

INTRODUCTION
Renal stone disease is the most common disease of urinary tract affecting mankind. It has been described since
antiquity and still remains one of the most common afflictions of modern society. With westernization of global
culture, however, the site of stone formation has migrated from the lower to the upper urinary tract. The lifetime
prevalence of kidney stone disease is estimated at 1% to 15%, varying according to age, gender, race, and
geographic location. Increased incidence and prevalence seen worldwide can be attributed to a rise in the detection
of asymptomatic calculi through increased utilization of radiographic imaging, particularly computed tomography.
In the absence of metaphylaxis (medical management), the relapse rate is estimated to be 50 % in 5-10 years and
i
75% in 20 years.

EPIDEMIOLOGY
Globally, kidney stone disease prevalence and recurrence rates are increasing, with limited options of effective
ii
drugs . Historically, stone disease affected adult men more commonly than women. However, recent evidence
suggests that the difference in incidence between men and women is narrowing. NHANES (National Health and
Nutrition Examination Survey of Center for disease control, USA) data, reported a slight decrease in the male-to-
female ratio of stone disease, from 1.75 to 1.54. The prevalence and incident risk of stone disease were directly
correlated with weight and body mass index (BMI) in both sexes, although the magnitude of the association was
greater in women than in men. Stone occurrence is relatively uncommon before age 20 and gradually peaks in
incidence in the fourth to sixth decades of life. Highest prevalence of stone disease is seen in whites, followed by
Hispanics, Asians, and African-Americans. A higher prevalence of stone disease is found in hot, arid, or dry
climates such as the mountains, desert, or tropical areas. Heat exposure and dehydration constitute occupational risk
factors for stone disease. Obesity, diabetes and metabolic syndrome, have also been linked to an increased risk for
kidney stones.

PATHOPHYSIOLOGY
Mechanism of renal stone formation
Renal stone formation is a biological process that involves physicochemical changes and super saturation of urine
(Figure 1). Supersaturated solution refers to a solution that contains more of dissolved material than could be
dissolved by the solvent under normal circumstances (Figure 2). As a result of super saturation, solutes precipitate in
urine leading to nucleation and then crystal concretions. This process is influenced by pH and specific
concentrations of stone-forming constituents like calcium, phosphorus, uric acid, oxalate, cystine. Crystallization
process depends on the thermodynamics (that leads to nucleation) and kinetics (which comprises the rates of
nucleation or crystal growth) of a supersaturated solution.

Crystal Nucleation - First step in the formation of kidney stone begins with formation of nucleus (termed as nidus)
from supersaturated urine retained inside the kidneys4. Once a nucleus is created, crystallization can occur at lower
chemical concentration than required for the formation of the initial nucleus (homogenous nucleation). Existing
epithelial cells, urinary casts, RBCs, and other crystals in urine can act as nucleating centers in the process of nuclei
formation termed as heterogeneous nucleation5.

Crystal Growth - Crystals in urine stick together to form a small hard mass of stone referred as crystal growth. Stone
growth is accomplished through aggregation of preformed crystals or secondary nucleation of crystal on the matrix
coated surface6.

Crystal Aggregation - Process whereby a small hard mass of a crystal in solution sticks together to form a larger
stone is called aggregation. Crystal aggregation is considered to be the most critical step in stone formation5.

Crystal-Cell Interaction - The attachment of grown crystals with the renal tubule lining of epithelial cells is termed
as crystal retention or crystal-cell interaction5. In individuals with hyperoxaluria, renal tubular epithelial cells have
been shown to be injured due to exposure to high oxalate concentrations or sharp calcium oxalate monohydrate
(COM) crystals7. Crystal-cell interaction results in the movement of crystals from basolateral side of cells to the
basement membrane7. Injured cells release substances like renal prothrombin, fragment-1 or other anionic proteins
which induce COM crystal agglomeration. Reactive oxygen species is thought to be one of the factors involved in
renal cell injury8.

55
 Endocytosis of CaOx Crystals - Endocytosis of crystals
by renal tubular cells is the earliest process in the
formation of kidney stones. Studies on tissue culture
crystal-cell interactions indicated that COM crystals
rapidly adhere to microvilli on the cell surface and
subsequently internalized. Polyanion molecules present
in tubular fluid/urine such as glycosaminoglycans,
glycoproteins, and citrate may coat crystals and inhibit
the binding of COM crystals to cell membrane5.

Cell Injury and Apoptosis - Exposure to high levels of

oxalate crystals induces epithelial cellular injury, which
is a predisposing factor to subsequent stone formation.
CaOx crystal depositions in the kidneys upregulate the
expression and synthesis of macromolecules that can
promote inflammation. Crystals may be endocytosed by
cells or transported to the interstitium. It has been
suggested that injured cells develop a nidus which
promotes the retention of particles on the renal papillary
surface. Apoptosis at the level of renal tubular cells may
lead to stone formation through cellular demise and
post-apoptotic necrosis which could promote calcium
crystal aggregation and growth9.

Randall’s Plaques - Randall’s plaques appear to be the

precursor’s origin of urinary stone development
although it is unclear. Pathogenesis of Randall’s plaque
itself is not clearly known6. The majority of CaOx
stones are found to be attached with renal papillae at the
sites of Randall’s plaque10. It is located at the interstitial
basement membrane in loop of Henle. Due to renal cell
injury, plaque is exposed to supersaturated urine. Renal
epithelial cell damage (degradation) products promote
heterogeneous nucleation and promotes crystal
adherence in renal cells. Randall plaque calcification is
triggered by oxidative stress. Renal epithelial cells of the
loop of Henle or collecting ducts produce membrane
Figure 1. Pathophysiological events of kidney stone vesicles at the basal side which leads to plaque
iii
formation . formation. Apatite crystal deposits have been proposed
to act as nidus for CaOx stone formation by attachment
on further matrix molecules10

Role of metabolite excretion in renal stone disease

Hypercalciuria
The association between increased urinary calcium excretion and calcium oxalate renal stones has been reported and
about 30-60% of patients with calcium oxalate stones have increased urinary calcium excretion in the absence of
raised serum calcium levels11. Urinary calcium excretion depends on dietary calcium intake, which varies between
400-2000 mg/day. Thus, the diagnosis of hypercalciuria requires a strict definition:
- Excretion of >200 mg of calcium/24 hrs after one week adherence to a 400 mg of calcium and 100 mg of sodium
diet. 12
- Excretion of greater than 4 mg of calcium/kg body weight or greater than 7 mmol in men and 6 mmol in women. 13
- Excretion of urinary calcium of greater than 0.11 mg/100 ml of glomerular filtrate. 14

For the purpose of diagnosis and management hypercalciuria is divided into three types:
1. Absorptive hypercalciuria - Where the primary abnormality involves the increased intestinal absorption of
calcium. This is further divided into three types:
Type 1 - the intestinal hyperabsorption of calcium exists irrespective of calcium restricted diet.
Type 2 - a variant where the patients exhibit increased urinary calcium excretion while on their normal diet
but normal calcium excretion on a low calcium, low sodium diet.
Type 3 - a variant with renal phosphate leak causing hypophosphatemia which leads to increased renal
synthesis of 1, 25 (OH)2 D resulting in hyperabsorption of calcium and the syndrome of hypercalciuria.

56
2. Renal hypercalciuria - This involves primary renal
wasting of calcium with consequent reduction in serum
calcium stimulating parathyroid production. The
increased parathyroid results in hydroxylation of 25
hydroxy Vit D to 1,25 dihydroxy Vit D3 increasing
intestinal calcium absorption. These effects restore the
serum calcium to normal at the expense of increased
parathormone and 1,25 dihydroxy Vit D3.
Two factors which differentiate renal hypercalciuria
from absorptive type hypercalciuria are elevated fasting
urinary calcium and stimulated parathyroid function.
There is a more generalized disturbance is renal tubular
function with renal hypercalciuria as shown by an exag- Figure 2. Physical chemistry of stone formation.
gerated natriuretic response to thiazide15 and (Adapted from Urologic Clinics of North America,
exaggerated calciuric response to carbohydrate load. 2007)

3. Resorptive hypercalciuria - Hypercalciuria results from excess PTH dependent bone resorption as well as
enhanced intestinal absorption of calcium caused by PTH itself or by a PTH dependent synthesis of 1,25 OH2 Vit
D316. Although PTH causes increased tubular absorption of calcium, the increase in the filtered load of calcium
overwhelms this and results in excessive urinary calcium excretion.

Hyperoxaluria
Hyperoxaluria is related to calcium oxalate nephrolithiasis and is of three types.
1. Increased oxalate production
1. Primary hyperoxaluria: It is of two types-
Type 1 - an autosomal recessive inborn error of metabolism characterized by nephrolithiasis, tissue deposi-
tion of oxalate and death from renal failure before the age of 20 in untreated patients17. There is increased
excretion of oxalic, glycolic and glyoxalic acids due to the defect of enzyme alanine glyoxalic acid
aminotransferase (AGT) in the liver.
Type 2 - a rare variant occurs due to the deficiency of hepatic enzyme D-glycerate dehydrogenase and
glyoxylate reductase, which leads to increase in urinary oxalate and glycerate excretion18.
2. Increased hepatic conversion: It occurs due to the pyridoxine deficiency, ethylene glycol ingestion and
methoxyflurane anesthesia.
3. Increased oxalate absorption: Conditions causing increased oxalate absorption leading to hyperoxaluria are
malabsorption occurring from bowel resection, intrinsic disease or jejunoileal bypass, which leads to increased
colonic permeability of oxalate as a result of exposure of the colonic epithelium to bile salts; further the
unabsorbed fats bind with the calcium making the dietary oxalate free for absorption.
4. Mild Metabolic Hyperoxaluria: Increased urinary oxalate excretion is seen in 0.3-0.5% of patients with calcium
stones. Increased dietary protein intake and altered renal excretion of oxalate have been predicted as an
important cause for increased oxalate excretion19.

Hyperuricosuria
Patients with gout or hyperuricosuria form calcium oxalate stones apart from the uric acid stones. The most
important cause for hyperuricosuria is excessive purine intake. Apart from this some patients have tendency to
excrete more uric acid in the urine than do the normal subjects even on purine-free diet due to the increased uric acid
production from endogenous purine metabolism20.
Factors leading to uric acid lithiasis in these patients are:
i. Excessive excretion of acid urine at relatively fixed low urinary pH;
ii. Absorb, produce and excrete more uric acid than patients without gout to uric acid stones
iii. Diminished urine volumes

All these factors serve as an ideal mechanism for the crystallization of uric acid in the urine. Uric acid further
promotes calcium oxalate crystallization by facilitating the formation of nuclei. Addition of crystal of uric acid to
the supersaturated calcium oxalate solution induces the deposition of well-oriented crystals of calcium oxalate over
the uric acid. Sodium acid urate also nullifies the effectiveness of naturally occurring inhibitors of calcium oxalate
crystal growth.

Hyperuricosuria may be seen in patients with specific enzyme defects such as increased activity of 5 phosphoribosyl
1-pyrophosphate synthetase, the enzyme that initiates purine metabolism and Lesh-Nyhan syndrome, with
deficiency or complete lack of hypoxanthine guanine phosphoribosyl transferase resulting in shunting of hypox-
anthine to xanthine/uric acid pathway leading to hyperuricosuria and hyperuricimea. Myeloproliferative disorders
such as acute leukemia are important causes in childhood.

57
Hypomagnesuria
Decreased magnesium excretion is also a known fact for increased stone formation. The most common cause of
overt hypomagnesuria is inflammatory bowel disease associated with malabsorption. Patients with hypomagnesuria
also have hypocitraturia21. The loss of inhibitory or complexing activity of magnesium or citrate is responsible for
calcium oxalate crystallization.

Ammonium Acid Urate Stones

The stones are commonly found in children of developing countries and females with a history of laxative abuse.
Conditions giving rise to these stones are22
 low fluid intake;
 urealytic infection in the presence of excessive uric acid excretion;
 urinary phosphate deficiency.

Cystinuria
It is an autosomal recessive disorder of transmembrane cystine transport manifested as disease in absorption in the
intestine and reabsorption in the proximal tubule23. The cystine excreted in the urine is poorly soluble within the
range of normal pH and thus crystallizes to form the stone.

Hypocitraturia
Hypocitraturia has been reported in 19-63% of patients with nephrolithiasis. There is wide range of variation for the
normal level of citrate in urine. According to Dallas the low normal limit of citrate in urine is 320 mg/day for both
men and women, irrespective of age and this limit provides a good empirical definition of hypocitraturia, since
patients with urinary citrate below this level often show a clinical response to potassium citrate therapy superior to
those whose citrate exceeds 320 mg/day24.
Hypocitraturia results from acidosis owing to a variety of disturbances, including distal renal tubular acidosis
(complete and incomplete), acidosis of chronic diarrhoea) state and potassium loss occurring from thiazide therapy.
In some patients, the exact cause of hypocitraturia is not known. In these patients, it is usually related to the
consumption of a diet rich in animal proteins consisting of sulphur-containing amino acids (producing acid
load), strenuous physical exercise24 and high sodium intake in the setting of low potassium intake (resulting in
intracellular acidosis). Hypocitraturia is also encountered in patients with active urinary tract infection, presumably
from the degradation of citrate by bacterial enzymes.

Pathogenic Role of Citrate in Calcium Nephrolithiasis

Citrate retards the crystallization of stone forming calcium salts by two mechanisms:
1. The principal action is the complexation of calcium causing a reduction in ionic calcium concentration and in
the urinary saturation of stone-forming calcium salts25.
2. Citrate directly inhibits the crystallization of calcium oxalate and calcium phosphate by agglomeration of
calcium oxalate. It has a modest inhibitory role on the growth of calcium oxalate crystal. Citrate acts as a potent
inhibitor of crystal growth of calcium phosphate. In addition citrate has the ability to impair urate induced
crystallization of calcium oxalate26.

When expressed relative to molecular weight, the inhibitory activity is much less than that of other inhibitors such as
pyrophosphate, glycosaminoglycans, glycoproteins or Tamm-Horsfall protein but the amount of citrate normally
present in the urine is many times that of other inhibitors.Due to this inhibition by citrate, the urinary environment
of patients with hypocitraturic nephrolithiasis is characterized by an increased propensity for the crystallization of
calcium salts.

MEDICAL MANAGEMENT

General Dietary Modifications

All patients of stone disease are advised to follow the dietary modification irrespective of their normal investi-
gations.
High fluid intake
Patients are informed to measure urine output once a week and then adjust the fluid intake to maintain urine output
more than two litres per day. They are also advised to take maximum intake of fluid within three hours after taking
the meals, during periods of physical exercises, bedtime and once at midnight. Plain water is good enough but
potassium rich citrus fruit juices such as orange, grape fruit and cranberry are preferable to low potassium citrus
fruits such as lime and lemon. Orange juice, for example, represents a natural form of potassium citrate and pos-
sesses alkalinizing and citraturic action33. Lime juice, on the other hand, is composed largely of citric acid, and does
not affect acid base balance appreciably, so it does not alter urinary pH and only modestly increases urinary
citrate. Increasing fluid intake actually has been demonstrated to have positive effect on two urinary inhibitors,

58
citrate and Tamm-Horsfall protein. Hydration augments urinary citrate excretion, which is thought to result from an
increased fluid flux in the proximal tubule resulting in the delivery of more bicarbonate to the cells of this portion of
the nephron34. Urinary dilution has been found to increase the inhibitory activity of Tamm-Horsfall protein on the
calcium oxalate monohydrate crystal aggregation in the urine of the stone formers35.

Restriction of animal proteins

Patient is informed to avoid nonvegetarian diet and the recommendation is of 8 oz or less of dry meat per day.
Animal proteins are rich in sulphur-containing amino acids such as cystine and methionine, which on oxidation
produces sulphate which forms a soluble complex with calcium in the nephron and limits the reabsorption of this
cation. Bone serves as a buffer and the resultant osseous dissolution provides more calcium to be
excreted36. Chronic metabolic acidosis decreases calcium reabsorption within the nephron, which further augments
excretion of this mineral. Increased protein consumption also augments glomerular filtration, thus delivering more
calcium to the nephron, which promotes its excretion. 37 Animal protein has a high purine content, which leads to
increase in uric acid excretion. The associated acidosis results in a decrease in urinary pH that could potentiate uric
acid urolithiasis. Acidosis also enhances citrate reasbsorption in the proximal tubule, thus decreasing the excretion
of citrate in the urine.

Sodium restriction
Patient is asked to avoid high sodium-containing food with restriction of salt in the diet and salty shakers. Increased
sodium intake may promote a variety of metabolic changes that may be detrimental to stone formers, including
increase in the urinary pH, calcium and cystine excretion and a decrease in citrate excretion.

Oxalate restriction
Avoidance of nuts, spinachs, dark roughage, chocolate, tea, and vitamin C coupled with the advice to maintain
recommended daily intake of calcium and to ensure that calcium consumption accompanies the ingestion of oxalate
rich foods to prevent the absorption of oxalate.

Restriction of calcium
Moderate restriction of calcium is recommended and about 250ml of milk or milk products can be taken daily. In
patients who are advised for long-term restriction of calcium intake, measurement of bone density, particularly in
the spine is recommended.

Treatment of Individual Abnormal Stone Risk Factors

Hypercalciuria
The management of hypercalciuria depends on its type.

Absorptive hypercalciuria
Type I - Cellulose phosphate in the dose of 10-15g orally in three divided dosages is to be taken with meals. It is an
effective non absorbable exchange resin, which binds the calcium in the gut and prevents bowel absorption. It has
no impact on the calcium transport mechanism and the urinary calcium excretion returns to normal values with
therapy. This therapy is contraindicated in postmenopausal women and in children during the period of active
growth. Hydrochlorothiazide is an alternative treatment but the effect on calcium excretion is temporary. It causes a
decrease in the renal excretion of calcium. The increased absorbed calcium is deposited in the bone. Gradually the
bone reservoir reaches its capacity and the drug becomes ineffective. Hydrochlorothiazide may be alternated with
cellulose phosphate for an effective treatment regimen.

Type II - Since this is dietary dependent reduction of the calcium intake to 400-600 mg/day reduces calcium
excretion to normal.

Type III - Orthophosphate is administered in the dosage of 250 - 2000 mg 3-4 times/day preferably after meals and
before bedtime. It inhibits vitamin D synthesis, which finally decreases absorption of the calcium.

Renal Hypercalciuria
Thiazide diuretics like trichlorthiazide are recommended. They have effect on the proximal and the distal tubules.
Acting as a diuretic, it decreases the circulating blood volume and subsequently stimulates proximal tubular
absorption of calcium.

Resorptive hypercalciuria
The underlying cause of hyperparathyroidism needs to be corrected.

59
Hyperoxaluria
Patients suffering from mild hyperoxaluria (<60 mg/ day) are easily managed on the dietary restriction of oxalate
rich foods such as spinach, dark roughage, tea, chocolate and nuts. Vitamin C supplementation should not increase
more than 500 mg/day in such patients. Patients suffering from absorptive hypercalciuria maintained on calcium re-
striction could have mild hyperoxaluria due to insufficient amount of calcium left in the bowel to bind oxalate.

In patients with moderate to severe hyperoxaluria commonly seen in patients suffering from intestinal malabsorption
of fat, inflammatory disease or resection of the small bowel, patients with aborptive hypercalciuria taking cellulouse
phosphate, a rigid restriction of dietary oxalate is critical. Solublized calcium may further help to lower urinary
oxalate by binding oxalate.

In the absence of bowel disease or absorptive hypercalciuria in the patients suffering from moderate to severe
hyperoxaluria, mild metabolic hyperoxaluria or primary hyperoxaluria must be suspected and pyridoxine in the
dosage of 100 to 200 mg/day is required for suppression of oxalate synthesis in vivo.

Hyperuricosuria
In patients with normouricemia, hyperuricosuria is caused by dietary excess of animal proteins. The general
recommendation in these patients is a balanced diet with a reduced intake of animal proteins and increased intake of
vegetables and fruits, although the long-term compliance in patients with dietary modification is very poor.
Allopurinol (300 mg/day) is indicated in such patients if hyperuricosuria is more than 800 mg/day.

In patients with hyperuricemia e.g., gouty diathesis, allopurinol (300 mg/day) is indicated to reduce serum uric acid.
Potassium citrate is also added to alkalinize the urine.

Cystinuria
The main goal of therapy is to lower cystine concentration in the urine below 200 mg/L. Dietary restriction is the
primary therapy with the avoidance of diet containing essential amino acid methionine such as meat, poultry, fish,
and dairy products. Increasing urine output on 3 L/day allows dissolution of existing stones and prevents new stone
formation. The pH of the urine is kept high (>7.5) to allow dissolution of the stone. Sodabicarbonate (15-25 gm/
day) and potassium citrate (15-20 mmol two to three times per day) are commonly used to alkalinize the urine.
Acetazolamide 250 mg three times a day augments the alkalinization achieved by the citrate and bicarbonate.
Glutamine 2 g/day can further reduce the excretion of the cystine especially if the intake of sodium is very high.

If hydration and alkalinisation is ineffective in reducing the excretion of cystine or cystine formation then
complexing agents such as penicillamine or alfa mercaptopurine can be used. These agents bind cystine, forming a
complex solution that is soluble in the urine. Captopril has also been used to lower cystine excretion by forming a
captopril-cystine disulfide complex.

Hypocitraturia
Citrate is an important inhibitor of crystallization of stone-forming salts and hypocitraturia being common among
patients with calcium nephrolithiasis. It is apparent that maneuvers that maintain urinary pH between 6&7 and that
raise urinary citrate levels to the normal would be desirable in preventing the formation of calcium oxalate stones.

Potassium citrate taken orally is absorbed mostly under normal circumstances. The citrate after absorption is me-
tabolized to bicarbonate. In absence of a deficit of bicarbonate in plasma, the bicarbonate ions are excreted in urine
that is rendered alkaline.

The small amount of absorbed citrate that escapes oxidation in the urine contributes in a minor way to the citraturic
action of potassium citrate38. In the presence of hypokalemia, the potassium ion augments citrate excretion by
correcting intracellular acidosis.

During long-term treatment, potassium citrate has been shown to cause a sustained rise in urinary citrate and pH. In
patients with mild to moderate hypocitraturia (100-320 mg/day), potassium citrate (60 meq/day) increases urinary
citrate by about 400 mg/day. The urinary pH rises by about 0.5 units and can be maintained at about 6.5. The
citraturic action is less prominent in those cases with severe hypocitraturia (e.g., complete renal tubular acidosis and
severe chronic diarrhoeal syndrome). The total rise in urinary pH is less marked in renal tubular acidosis in which
urinary pH is usually high.

Potassium citrate has a hypocalciuric effect because of enhanced renal calcium absorption and is usually tran-
sient39. In patients with renal tubular acidosis the hypocalciuric effect is sustained. This is in contrast to sodium
citrate where calcium excretion is unaffected since alkali mediated hypocalciuric effect is offset by sodium linked

60
calciuresis40.

Physiochemical effects of potassium citrate are associated to its citraturic and alkalinizing action resulting in
 Inhibition of the crystallization of calcium salts in the urine.
 Rise in pH contributes to the retardation of the crystallization of calcium salts and inhibits uric acid
crystallization.
 At a high pH more phosphate and citrate ions become dissociated further augmenting the complexation of
calcium.
 Dissociation of citrate, pyrophosphate and other macromolecules may accentuate their inhibitor activity
against crystallization of calcium salts.
 The rise in urinary pH increases the dissociation of uric acid, reducing the concentration of undissociated
uric acid and the propensity for the uric acid lithiasis.

Distal Renal Tubular Acidosis Type 1

Potassium citrate therapy is capable of correcting both metabolic acidosis and hypokalemia. In severe acidosis, large
doses (up to 120 mEq/day) may be required to restore normal urinary citrate level. Urinary calcium declines with
the correction of acidosis. The overall rise in urinary pH is generally below 7.5 during treatment unless there is a
complication by a urinary tract infection.

If there is a substantial renal sodium leak, alkali must be provided as a mixed sodium potassium salt, although renal
sodium wasting is not prominent in most patients with renal tubular acidosis who present with stones.
Potassium citrate is contraindicated in patients with moderate to severe renal disease (endogenous creatinine
clearance of <40 ml/mt). If it were to be used in those with moderate renal disease, it should be begun at a lower
dosage and the serum potassium levels should be carefully monitored.

Chronic Diarrhoeal Syndrome 41,42

In patients with mild to moderate severity of intestinal fluid loss and in whom hypocitraturia is not severe (100-320
mg/day), potassium citrate (40-60 mEq/day in 3-4 divided doses, is effective in restoring normal urinary citrate.

A liquid preparation is usually preferred in such cases rather than a slow release tablet because some of these
patients have intestinal adhesion and may be prone to obstruction from a tablet preparation. Furthermore, a slow
release medication may be poorly absorbed due to rapid intestinal transit. A frequent dose schedule (3-4 times/day)
is advisable for the liquid preparation because of relatively short duration of biological action. Other drugs may be
necessary for the treatment of additional disturbances.

If hypomagnesuria is present, magnesium citrate (10 mEq two to four times/day) may raise urinary magnesium and
increase urinary citrate and pH.

When hyperoxaluria coexists, dietary oxalate restriction is a must. In patients of hyperoxaluria with hypocalciuria,
calcium citrate is useful which lowers renal excretion of oxalate by binding it in the intestinal tract, raises urinary
citrate, corrects malabsorption of calcium and averts potential developments of bone disease.

Thiazide Induced Hypocitraturia 43

Hypokalemia resulting from thiazide leads to hypocitraturia, which may attenuate the beneficial hypocalciuric
effects of therapy in urolithiasis. Use of potassium citrate with thiazide raises urinary pH and citrate. It is recom-
mended that potassium citrate (15-20 mEq twice a day) be given to all patients being treated with thiazide for
hypercalciuric nephrolithiasis.

Idiopathic Hypocitraturic Calcium Nephrolithiasis 43

This includes hypocitraturia occurring alone with calcium stones and hypocitraturia occurring in conjunction with
absorptive and renal hypercalciuria and hyperuricosuric calcium oxalate nephrolithiasis. In these patients the stones
are predominantly calcium oxalate.
Potassium citrate (15-30 mEq twice a day) produces a sustained increase in urinary citrate excretion, maintains pH
between 6.5-7.0 and decreases the urinary saturation of calcium oxalate to normal limits.

Uric Acid Nephrolithiasis

Potassium Citrate is recommended in patients with hyperuricosuric (gouty diasthesis) for prevention of both calcium
oxalate and uric acid stone formation.

Potassium citrate creates an environment less conducive to the crystallization of uric acid by increasing urinary pH
and reducing the amount of undissociated uric acid. It inhibits urinary crystallization of calcium oxalate by reducing
urinary saturation and augmenting the inhibitor activity owing to the rise in urinary citrate and pH.

61
Advantages of Potassium Citrate Compared with other Alkali44
 Potassium citrate is a better substitute than potassium bicarbonate because of more prolonged rise in
urinary citrate and pH. The increment in urinary citrate is more pronounced with potassium citrate due to
the renal excretion of small amount of absorbed citrate that has excaped oxidation.
 When compared with sodium citrate, potassium citrate reduces calcium excretion by augmenting the renal
tubular absorption of calcium. Urinary sodium remains unaltered with potassium citrate but increases
during sodium citrate therapy. In patients with hypokalemia, potassium citrate causes a more pronounced
rise in citrate excretion than sodium citrate.

Post Extra Corporeal Shock Wave Lithotripsy Fragments

The natural history of residual stone fragments after ESWL shows growth and persistence of the calculus. In
patients with residual fragments <5 mm or clinically insignificant residual fragments (CISF) with calcium oxalate
and/or infection stones use of potassium citrate (6-8 gm in 2-3 divided doses) has significantly ameliorated the
outcome of these residual fragments by decreasing growth or agglomeration, allowing spontaneous passage and fi-
nally improving the clearance rate.

Medical Expulsive Therapy (MET)

For patients presenting with renal colic due to ureteral stone, the most important factors predicting spontaneous
stone passage are stone size and location. A meta-analysis demonstrated spontaneous passage rates of 68 and 47%
for ureteral stones less than 5 mm and 5 to 10 mm, respectively. The probability of passage was also related to the
location in the ureter with 12, 22, and 45% of stones passing depending on whether they were in the proximal,
middle, or distal ureter.

The most common medications used for MET are α-1 blockers and calcium channel blockers. The α-1D receptor
has been shown to be the most common α-adrenergic receptor in the ureter and it is most heavily expressed in the
distal ureter. Alpha-1 blockers decrease the force and frequency of ureteral contraction. Nifedipine, a calcium
channel blocker, has been shown to relax ureteral smooth muscle in vitro and its effect is predominantly seen in the
distal ureter as well

The guidelines suggest that for patients with a ureteral stone <10 mm and well-controlled symptoms, a period of
observation along with MET is an option for initial treatment, and recommend α-1 blockers as the preferred agents
for MET. Side effects of α-1 blocker therapy include dizziness, nasal congestion, ejaculatory disturbances, and
hypotension. In patients undergoing cataract surgery, intraoperative floppy iris syndrome has been associated with
α-1 blocker therapy

Use of corticosteroids has been attempted to reduce both edema and inflammation in order to facilitate stone
passage.

Nonsteroidal anti-inflammatory drugs (NSAIDs) provide excellent analgesia in renal colic through inhibition of
prostaglandin synthesis, which reduces glomerular filtration and renal pelvic pressure, ureteric peristalsis and
ureteric edema. They are highly effective in reducing the number of new colic episodes and hospital readmission [1-
3]. However, NSAIDs do not appear to have any effect on the time to stone passage or the likelihood of stone
passage in renal colic.

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2. Knoll T. Epidemiology, pathogenesis and pathophysiology of urolithiasis. Eur Urol Suppl. 2010;12:802-6.
3. Alelign T, Petros B. Kidney Stone Disease: An Update on Current Concepts. Adv Urol. 2018 Feb 4;2018:3068365.
4. S. B. N. Kumar K. G. Kumar V. Srinivasa and S. Bilal “A review on urolithiasis ” International Journal of Universal
Pharmacy and Life Sciences, vol. 2, no. 2, pp. 269–280, 2012.
5. K. . Aggarwal S. Narula . Kakkar and . andon “Nephrolithiasis: molecular mechanism of renal stone formation and
the critical role played by modulators ” Bio ed Research International vol. 2013 Article ID 292953 21 pages 2013.
6. V. N. Ratkalkar and J. G. Kleinman “ echanisms of stone formation ” linical Reviews in Bone and ineral etabolism
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7. M. Courbebaisse, C. Prot-Bertoye J. Bertocchio et al. “Nephrolithiasis of adult: from mechanisms to preventive medical
treatment ” Revue edicale Internationale vol. 38 no. 1 pp. 44–52, 2017.
8. S. R. Khan . A. Glenton R. Backov and D. R. alham “ resence of lipids in urine, crystals and stones: Implications for
the formation of kidney stones ” Kidney International vol. 62 no. 6 pp. 2062–2072, 2002.
9. N. Hsieh . H. Shih and H. Y. hen “ ffects of amm- Horsfall protein on the protection of MCDK cells from oxalate
induced free radical in ury ” Urological Research vol. 31 pp. 10–16, 2003.
10. A. . van “ hysiopathology and tiology of stone formation in the kidney and the urinary tract ” ediatric Nephrology
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62
11. Albright F, Suby H, Sulcowitch HE. In Albright F, Refienstein EC, (eds). The parathyroid glands and metabolic bone
diseases. Balti¬more, Williams and Wilkins 1948
12. Pak CYC. Renal stone disease. Boston, Martirus, Nijhoff Publish¬ing 1987
13. Parks JH, Coe FL. A urinary calcium citrate index for the evalua¬tion of nephrolithiasis. Kidney Int 1986; (3) 85-90.
14. Broadus AE, Domoingres M, Bartter FC. Pathophysiological stud¬ies in idiopathic Hypercalciuria : Use of an oral calcium
tolerance test to characterize distinctive Hypercalciuria subgroups. J Clinic Endocrinol Metab 1978; 47: 751-760.
15. Sakahee K, Nicar MJ, Brater DC, Pak CYC. Exaggerated natriu¬retic and calciuric response to hydrochlorothiazide in renal
hypercalciuria but not in absorptive hypercalciuria : J Clin Endo Metab 1985: 61: 825.
16. Pak CYC, Petus P, Hurt G, Kadesky M. Fine M, Reisman D, Splan F, Caramela C, Freena A, Britton F, Sakahee K, Breslar
NA. Is selective therapy of recurrent nephrolithiasis possible ? Amer J Med 1981;71:615.
17. Williams HE. Smith LH. L-glyceric aciduria : A new genetic vari¬ant of primary hyperoxaluria. N Engl J Med 1978; 278:
233-328
18. Williams HE, Smith LH. Disorders of oxalate metabolism. Am J Med 1968; 45: 715-735.
19. Pinto B. Crespi G, Sole BF, Barcelo P. Patterns of oxalate metabo¬lism in recurrent oxalate stone formers. Kidney Int 1974:
5: 285-¬329.
20. Coe FL, Kavalach AG. Hypercalciuria and hyperuricosuria in pa¬tients with calcium nephrolithiasis. New En-1 J Med
1974; 291: 1344.
21. Preminger GM, Baker S, Peterson R. Hypomagnesuric hypocitra¬turia: An apparent new entity for calcium nephrolithiasis.
J Lith¬stone Dis 1989; 1: 22-25
22. Hsu TG. Ammonium acid urate lithiasis, experimental observations. J Urol 1966; 96: 88-94.
23. Their SO, Segal S. Cystinuria. In Stanbury JB, Wyngaarden JB, Fredrickson DS. (eds). The Metabolic Basis of Inherited
Diseases, New York, McGraw Hill 1972; 504-519
24. Sakahee K, Nigam S, Snell P et al. Assessment of the pathogenic role of exercise in renal stone formation. J Clinic Endocrin
Metab 1987; 65: 974-979
25. Pak CYC. Nicar MJ, Northcutt C. The definition of the mechanism of hypercalciuria is necessary for the treatment of
recurrent renal stone for men. Contrib Nephrol 1982; 33: 136-151
26. Pak CYC, Paterson R. Successful treatment of hyperuricosuric cal¬cium oxalate nephrolithiasis with potassium citrate. Arch
Intern Med 1986:146:863
27. Sherman CC. Mendel LB, Smith AH. The metabolism of orally administered citric acid. J Biol Chem 1936; 113: 265-271.
28. Fourman P, Robinson JR. Diminished urinary excretion of citrate during deficiencies of potassium in man. Lancet 1953; 2:
656-657.
29. Baruch SB. Burch RL, Eun CK, King VF. Renal metabolism of citrate. Med Clinic North Am 1975; 59: 569-582.
30. Down WH. Sachrin RN, Shasseud LF et al. Renal and bone uptake of tartaric acid in rats: Comparison of L(+) and DL-
forms. Toxi¬cology 1977: 8: 333-346
31. Shorn E, Bernhiem AR, Tassuky H. The relation of urinary citric acid excretion to the menstrual cycle and the steroidal
reproductive hormones. Science 1942; 95: 607.
32. Costello LC, Stacey R. Franklin R. Parathyroid hormone effects on soft tissue citrate levels. Horm Metab Res 1976; 2: 242-
245.
33. Wabner CL, Pak CYC. Effect of orange juice consumption on uri¬nary stone risk factors. J Urol 1993; 149: 1405-1408
34. Hess B, Michel R, Takkinen R et al. Risk factors for low urinary citrate in calcium nephrolithiasis : Low vegetable fiber
intake and low urinary volume to be added to the list. Nephrol Dial Transplant 1994;9:642.
35. Jaeger P, Hess B, Takkinen R et al. Nutritional determinants of ne¬phrolithiasis. Adv Nephrol 1995; 24: 217.
36. Lemann J, Adams ND, Gray RW. Urinary calcium excretion in hu¬man beings. N Engl J Med 1979; 301: 535.
37. Schuette SA. Zemel MB, Linkswiler HM. Studies on the mecha¬nism of protein induced hypercalciuria in older men and
women. J Nutr 1980; 110; 305.
38. Sakahee K, Pak CYC. Contrasting effects of various potassium salts on acid-base status, urinary citrate excretion and renal
citrate clear¬ance. Abstracts from Urologic Research : VI International Sympo¬sium on Urolithiasis and Related Clinical
Research. Vancouver, British Columbia; 197.
39. Pak CYC. Physichemical action and extrarenal manifestations of alkali therapy. Presented at Urologic Research : VI
International Symposium on Urolithiasis and Related Clinical Research. Van¬couver, British Columbia 1988; July 24-29
40. Sakahee K, Nicar M. Hill K, Pak CYC. Contrasting effects of potas¬sium citrate and sodium citrate therapies on urinary
chemistries and crystallization of stone forming salts. Kidney Int 1983; 24: 348-352.
41. Pak CYC. Citrate and renal calculi. Miner. Electrolyte Metab 1987; 13: 257-266.
42. Pak CYC. Fuller C, Sakahee K. Preminger GM, Britton F. Long term treatment of calcium nephrolithiasis with potassium
citrate. J Urol 1985; 134: 11-19.
43. Pak CYC, Fuller C. Idiopathic hypocitraturic calcium nephrolithi¬asis successfully treated with potassium citrate. An Int
Med 1986; 104: 33-37.
44. Resnick MI, Pak CYC. Urolithiasis - A medical and Surgical Reference. WB Saunders 1990; 91.

63
 Surgical management of urinary stones
Sanjay Gupta

Urolithiasis is a very commonly encountered disease in the surgical practice in North India, both in emergency and
non-emergency situations. Of all the cases of urolithiasis, majority remain asymptomatic and the small stones/
crystals pass out spontaneously in the urine without any problem experienced by the individual. Of the remaining
patients, stones may become symptomatic and need active management in the form of medical expulsive therapy or
surgical intervention.

Surgical modalities for management of urolithiasis

Various options for active surgical management of urolithiasis include:
Uretero-renoscopy [URS] Percutaneous nephrolithotomy [PCNL]
 Semirigid URS  Standard PCNL
 Flexible URS  Mini Perc
 Retrograde intra-renal surgery [RIRS]  Ultra-mini PCNL
Non-endoscopic surgery  Micro PCNL
Open surgery Endoscopic combined intra-renal surgery [Mini-
Laparoscopic surgery ECIRS].
Robotic surgery Shock wave lithotripsy [SWL]

A comparison of these surgical options is given in the Table 1.

Table 1: Surgical options for treatment of urinary stones
Technique Advantages
Semirigid Durable, larger working
URS channel for larger instruments urethra/ureter, limited access
(e.g., laser fibers, baskets),
better visibility related to
increased irrigating ability.
Flexible Can reach every part of the
URS urinary tract (including lower
pole).
Some models have “double
deflection” allowing easier
access to all calyces in the
kidney
Retrograde Can manage stones with
intra-renal unfavorable calyceal anatomy/ ureteral perforation/ avulsion.
surgery radiolucent stones/ bleeding
[RIRS] disorders/ patients’ choice.
Standard Able to remove large stone
PCNL fragments.
Increased stone-free rates.
Can treat large/ staghorn
stones.
Mini Reduced blood loss.
PCNL Can retrieve smaller stone
fragments.
Ultra-mini Single step dilatation.
PCNL Reduced blood loss.
Micro Smallest caliber access.
PCNL Insignificant blood loss/
bleeding complications.
Potentially safe for multiple
punctures.
Mini- Can help managing stones in
ECIRS multiple calyces without
creating multiple renal tracts.
Disadvantages
May be more traumatic to the
within the ureter
Flexible fiberoptic require
frequent repairs, which are
costly; smaller working
channels have lower flow rates;
the image is not as sharp as with
semirigid endoscopes because
of the smaller fiberoptic bundles
Risk of complications including
Larger access caliber.
Increased bleeding/
complication rates.
Less suitable for multiple
punctures.
Difficult to treat large/ staghorn
stones.
Stone removal by water-jet
effect only, no active retrieval.
No ability to remove stone
fragments.
Potentially lower stone-free
rates.
Increased cost of disposables &
laser fiber.
Complications of both PCNL
and RIRS may occur.
Remarks
Typically for stones below the
iliac vessels
Typically used for stones
above the iliac vessels and in
the kidney
For renal stones up to 20 mm
which are unsuitable for SWL.
PCNL has been the gold
standard treatment for larger
kidney stones (>2 cm) and
staghorn calculi
Similar to Standard PCNL
using a 15-20 Fr. Metallic
sheath and 12 Fr nephroscope.
For small and residual stones
done using 9.5 Fr – 12 Fr
metallic sheath and 7.5 Fr
nephroscope.
Done using a metallic sheath
of 4.8–4.85 Fr and a micro-
optical system.
Mini PCNL simultaneously
assisted by RIRS to improve
stone-free rates.

64
SWL For suitable stones the stone-
free rates are comparable to
other techniques with lower
incidence of complications.
Open/ Lap/ Can correct those associated
Robotic anatomical anomalies/
surgery obstruction which cannot be
managed endoscopically.
Not suitable in pregnancy/
bleeding disorders.
May need multiple sessions/
adjunctive procedures.
Greater morbidity/ time to
recovery in comparison to
minimally invasive procedures.
Best for stones which are <20
mm, not in lower pole, radio-
opaque and not extremely
hard.
Necessary component to
complete management of
urolithiasis.

Factors which influence the choice of technique for stone management

Renal stones Ureteral stones
Size of the stone Stone size
Location of stone Stone location
Stone composition [if known] Presence and duration of obstruction
Anatomy of the urinary system Presence of sepsis
Availability of instrumentation/ experience Response to previous treatment
Associated medical conditions Advisability of radiation exposure
Age of the patient
atients’ choice

Current guidelines for the choice of treatment for urolithiasis

Several urological societies around the world have issued guidelines for the surgical management of urinary stones.
The most commonly cited guidelines are from European Association of Urology [EAU] and American Urology
Association [AUA]. These guidelines give multiple options for treating urinary stones, based on different
parameters, and leave the choice to the surgeon. The treatment options for managing urinary stones, based on the
EUA guidelines, are summarized in Table 2.

Table 2: EAU Guidelines for the interventional treatment of urolithiasis

Location Size Other parameters Recommended modality
1. PCNL
> 20 mm
Renal stone [all except 2. RIRS or SWL
lower pole stone 10 – 20 10 – 20 mm SWL/ PCNL/ RIRS
mm] 1. SWL/ RIRS
< 10 mm
2. PCNL
10 – 20 mm No unfavorable factors for SWL SWL/ PCNL/ RIRS
Lower pole renal stone 1. PCNL/ RIRS
Unfavorable factors for SWL +
2. SWL
1. URS
> 10 mm
Ureteral stone proximal to 2. SWL
iliac vessel crossing 1. SWL
< 10 mm
2. URS
1. URS
Ureteral stone distal to > 10 mm
2. SWL
iliac vessel crossing
< 10 mm SWL/ URS

Conclusion
While the available guidelines broadly agree on the treatment of choice for urinary stones, differences exist in the
management of proximal ureteral and lower polar kidney stones. These differences are due to lack of clear evidence,
as well as difference in the urological practices in the countries where these guidelines have evolved.

Bibliography
1. Zumstein V, Betschart P, Abt D, Schmid HP, Panje CM, Putora PM. Surgical management of urolithiasis–a systematic
analysis of available guidelines. BMC urology. 2018 Dec;18(1):25.
2. Ludwig WW, Matlaga BR. Urinary Stone Disease: Diagnosis, Medical Therapy, and Surgical Management. Medical
Clinics of North America. 2017 Dec 9.
3. Agrawal MS, Agarwal K, Jindal T, Sharma M. Ultra-mini-percutaneous nephrolithotomy: A minimally-invasive option for
percutaneous stone removal. Indian journal of urology: IJU: journal of the Urological Society of India. 2016
Apr;32(2):132.
4. ürk etřík A Sarica K Seitz Skolarikos A Straub Knoll . AU guidelines on interventional treatment for
urolithiasis. European urology. 2016 Mar 1;69(3):475-82.
5. Inoue T, Okada S, Hamamoto S, Yoshida T, Matsuda T. Current trends and pitfalls in endoscopic treatment of urolithiasis.
International Journal of Urology. 2018 Feb;25(2):121-33.

65
 CARCINOMA PENIS
Gagan Gautam, Sunny Khanna, Saurabh Patil, Puneet Ahluwalia

INTRODUCTION
Penile cancer constitutes a major health problem in many countries in Asia, Africa, and South America, where it
may comprise up to 10% of all malignancies.Penile cancer is rare in developed countries and varies worldwide with
age, circumcision, and hygiene practices.The incidence of penile cancer increases with age . The peak age is during
the sixth decade of life, though the disease does occur in younger men less than 40 yrs age.

SITES
Penile tumors may arise anywhere on the penis but occur most commonly on the glans (48%) and prepuce (21%).
Other tumors involve the glans and prepuce (9%), the coronal sulcus(6%), or the shaft (<2%).

ANATOMY OF PENIS

RECOGNISED AETIOLOGICAL AND EPIDEMIOLOGICAL RISK FACTORS FOR PENILE CANCER:

Evidence now indicates that penile cancer has two primary etiologies:
Approximately half are related to HPV infection, with the other half related to inflammatory conditions such as
phimosis, chronic balanitis, and lichen sclerosis
1. HPV infection: 45-80 % of penile cancer are related to HPV infection(NCCN 2018). There is strong correlation
with type 16 and 18.The risk increases in patients with HIV infection because of high incidence of HPV
infection among HIV patients.But vaccination of younger men against HPV is still not recommended.

2. PHIMOSIS: Phimosis and poor local hygiene are associated with increased risk as it hinders capability to
properly inspect areas of higher incidence of carcinoma.Desquamated epithelial cells (smegma) when acted
upon by bacterial action produce carcinogenic byproducts,which leads to cancer: The neonatal circumcision
reduces risk of penile cancer due to elimination of other risk factor like removal of phimosis and lower
incidence and duration of HPV infection.Neonatal circumcision reduces the risk by 5 times,but it does not
protect against carcinoma in situ.
3. BALANITIS XEROTICA OBLITERANS (LICHEN SCEROSUS):It is associated with 5-10 % increase
risk of carcinoma penis .It is an inflammatory condition of the glans and prepuce of unknown cause. Recently
Borrelia burgdorferi (spirochete) is identified as causative agent.
4. TOBACCO USE: The use of tobacco products is an independent risk factor and increases risk by 3-4.5
times.(NCCN)
5. PSORALEN AND PUVA THERAPY FOR DERMATOLOGICAL CONDITIONS:There is 286
times(NCCN+DEVITA) increased risk than general population.Hence penile area must be shielded during
treatment.
6. LOW SOCIO ECONOMIC STATUS,POOR HYGIENE
7. MULTIPLE SEXUAL PARTNERS.
8. PENILE TRAUMA

PREMALIGNANT LESIONS (TAKEN FROM CAMPBELL UROLOGY)

Cutaneous Horn: It is a rare lesion. It usually develops over a preexisting skin lesion (wart, nevus, traumatic
abrasion, or malignant neoplasm). It is characterized by overgrowth and cornification of the epithelium, which
forms a solid protuberance. On microscopic examination, extreme hyperkeratosis, dyskeratosis, and acanthosis are

66
noted. It is associated with HPV type 16. Treatment consists of surgical excision with a margin of normal tissue
about the base of the horn. These lesions may recur and may demonstrate malignant change on subsequent biopsy.

Leukoplakia: Leukoplakia is characterized by the presence of solitary or multiple whitish plaques involving the
glans or prepuce in the setting of chronic or recurrent balanoposthitis. Surgical excision in the form of circumcision
or local wedge resection is usually curative.

Balanitis Xerotica Obliterans:Balanitis xerotica obliterans (BXO) is an inflammatory condition of the glans and
prepuce of unknown cause, however, a recent study identified Borrelia burgdorferi infection in affected tissues in
the early course of the disease.; it is a form of lichen sclerosis isolated to the penis. BXO is a scaly, indurated,
whitish plaque that produces significant phimosis and meatal stenosis.Treatment remains controversial and consists
of topical steroids clobetasol propionate cream for 2 to 3 months and surgical excision. Meatoplasty may be
required, with early circumcision the most effective treatment for BXO. Reconstruction for urethral stricture may be
needed.

Condylomata acuminata: It is a soft, papillomatous growths typically considered to be benign.In the male,
condylomata occur most commonly on the glans, the penile shaft, and the prepuce. The meatus should be carefully
inspected. Lesions recur frequently, both in new and in previously treated sites.Treatment of these lesions
with podophyllin may induce histologic changes suggestive of carcinoma Consequently, preliminary biopsy of large
lesions that appear to be condylomata acuminata should precede any treatment with topical podophyllin.
Subclinical disease may be detected by the application of 5% acetic acid solution to the penis, followed by
inspection with a magnifying glass.Imiquimod cream (5%) has become the topical treatment of choice for
condyloma. Imiquimod is an immune modulator that enhances natural killer cell activity.Intraurethral lesions may
be extremely difficult to treat.
5-Fluorouracil cream applied weekly for 3 weeks has been successful in eliminating urethral lesions. Interferons has
also been used .

Carcinoma in situ (Bowenoid Papulosis,erythroplasia of queyrat):First description by Queyrat.It manifests as

multiple papules on the penile skin , usually during the second or third decade of life. The lesions are usually
pigmented and range from 0.2 to 3.0 cm in diameter.Diagnosis is confirmed by biopsy.DNA sequences suggestive
of HPV-16 have been found in specimens of bowenoid papulosis, and a causative role for HPV is
suspected.Whereas histologically this condition is a carcinoma in situ, the clinical course of bowenoid papulosis is
invariably benign . Treatment has included electrodesiccation, cryotherapy, laser fulguration, topical 5-fluorouracil
cream, and excision with skin grafting.Progression to invasive carcinoma may occur in 5% to 33% of patients if it is
not treated. Metastasis has rarely occurred.

Buschke-Lowenstein Tumor (Verrucous Carcinoma,Giant Condyloma Acuminatum): The Buschke-

Lowenstein tumor differs from condyloma acuminatum in that condylomata, regardless of size, always remain
superficial and never invade adjacent tissue. Buschke-Lowenstein tumor displaces, invades, and destroys adjacent
structures by compression. Aside from this unrestrained local growth, it demonstrates no signs of malignant change
on histologic examination and does not metastasize. DNA from HPV types 6 and 11 has been identified in these
tumors.Lymph node metastases are rare with verrucous carcinoma and their presence probably reflects malignant
degeneration in the primary lesion. Either excisional biopsy or multiple deep biopsies are required to distinguish the
lesion from true penile carcinoma. Treatment consists of excision, sparing as much of the penis as possible. Large
lesions may necessitate total penectomy. Recurrence is common,and close follow-up is essential.Radiation therapy
is ineffective for verrucous carcinoma.

HISTOPATHOLOGICAL VARIETY(Cubilla classification):

1- Usual type - 60% (Superficial spreading)
2- Papillary - 15%
3- Basaloid - 10%(Aggressive)
4- Warty – 10%
5- Verrucus – 10%
6- Sarcomatous- 03%(Aggressive)
Metastasis to penis(usually comes from prostatic and colorectal origin)

NATURAL HISTORY OF DISEASE

Carcinoma usually begins as small lesion in glans or peputial area and then gradually enlarges to involve entire
glans,shaft,corpora. Bucks fascia acts as temporary natural barrier to local disease progression.penetration into
bucks fascia and tunica albugenia leads to involvement of corporal bodies and vascular dissemination.

67
REGIONAL LYMPH NODES:The earliest route of dissemination from penile carcinoma is metastasis to the
regional femoral and iliac nodes.
 Superficial and deep ingunal-seperated by fascia lata (Dressler group of Lymph nodes-central around
saphenofemoral jn,supero lateral arond superficial circumflex vein,infero lateral around lateral femoral
cutaneous vein,supero medial around superficial epigastric, inferomedial around great saphenous vein)
 Pelvic nodes-external iliac, internal iliac (hypogastric), obturator

LYMPHATIC DRAINGE OF PENIS

Prepucial skin + shaft skin superficial ing L.N.
Glans Corporal Bodies lymphatic collar at the Base of penis superficial ing L.N.
From superficial inguinal Lymph Node. Deep Inguinal LN Pelvic Nodes (External iliac LN, Internal iliac LN,
Obturator LN).

DISTANT METASTASIS: Distant metastases occur late in the history of the disease and usually not seen without
regional metastasis.
Sites are: retroperitoneal lymph nodes above true pelvis,lungs,liver,bone,cutaneous nodule at distant site.

CAUSE OF DEATH IN CARCINAOMA PENIS:

1. Cachexia
2. Sepsis
3. Chronic Infection.
4. Femoral vessel erosion

SYMPTOMS:
1. Pain does not develop in proportion to the extent of the local destructive process and usually is not a presenting
complaint.
2. Weakness,weight loss, fatigue, and systemic malaise occur secondary to chronic suppuration. -B symptoms
3. On occasion, significant blood loss from the penile lesion, the nodal lesion, or both may occur.

SIGNS:
1. The presentation ranges from a relatively subtle induration or small excrescence to a small papule,pustule,
warty growth, or more luxuriant exophytic lesion.
2. Phimosis may obscure a lesion and allow a tumor to progress silently.
3. Rarely, a mass, ulceration, suppuration, or hemorrhage in the inguinal area may be caused by nodal metastases
from a lesion concealed within a phimotic foreskin.
4. Urinary retention or urethral fistula from local corporeal involvement is a rare presenting sign.

EXAMINATION
1. At presentation most lesions are confined to the penis . The penile lesion is assessed with regard to size,
location, fixation, and involvement of the corporeal bodies.
2. Inspection of the base of the penis and scrotum is necessary to rule out extension into these areas.
3. Rectal and bimanual examination provides information about perineal
4. body involvement and presence of a pelvic mass.
5. Careful bilateral palpation of the inguinal area for adenopathy is extremely important.

STAGING AND CLASSIFICATION: AJCC 8TH EDITION

CHANGES FROM 7TH EDITION

A) GRADE: Any proportion of anaplastic cells - categorise tumor as grade 3
B) T STAGING: Ta now broadened to include non invasive localised SCC
T1a and T1b have been seperated by perineural invasion.
T2 disease includes corpora spongiosum involvement.
T3 disease includes corpora cavernosa involvement.
C) NODAL STAGING:
pN1 is defined as less than equal to 2 unilateral ingunal metastasis no extranodal extension
pN2 is defined as more tha equal to 3 unilateral metastasis or bilateral metastasis

DIAGNOSIS:
Penile biopsy: Biopsy is important for tissue diagnosis and determining lymphovascular invasion, grading, depth of
invasion, histopathological type. Although a punch biopsy may be sufficient for superficial lesions, an excisional
biopsy is preferred as it should be deep enough to properly assess the degree of invasion and stage. A dorsal slit is

68
frequently necessary to gain adequate exposure of the lesion for satisfactory biopsy. FNAC,incisional,true cut core
and brush biopsy can be done. Shaving biopsy should be avoided.

IMAGING OF PRIMARY LESION: Ultrasound and MRI both can be used.Although Ultrasound (US) can give
information about infiltration of the corpora, Magnetic resonance imaging (MRI) with an artificially induced
erection with intracavernosal prostaglandin E1 can help to exclude tumour invasion of the corpora cavernosa if
preservation of the penis is planned.MRI is more accurate to predict deep involvement.

IMAGING FOR REGIONAL LYMPH NODES:

Non-palpable inguinal nodes: Imaging studies are not helpful in staging clinically normal inguinal regions, though
imaging may be helpful in obese patients in whom palpation is unreliable or impossible:
• Inguinal US can reveal abnormal nodes with some enlargement. The longitudinal/transverse diameter ratio
and absence of the lymph node hilum are findings with relatively high specificity.
• Conventional computed tomography (CT) or MRI scans cannot detect micrometastases reliably .
• Imaging with 18FDG-positron emission tomography (PET)/CT does not detect lymph node metastases <10
mm

Palpable inguinal nodes: highly indicative of lymph node metastases. Physical examination should note the
number of palpable nodes on each side and whether these are fixed or mobile. Additional inguinal imaging does not
alter management and is usually not required.
A pelvic CT scan can be used to assess the pelvic lymph nodes. Imaging with 18FDG-PET/CT has shown a high
sensitivity of 88-100%, with a specificity of 98-100%, for confirming metastatic nodes in patients with palpable
inguinal lymph nodes.

Distant metastases: An assessment of distant metastases should be performed in patients with positive inguinal
nodes . Computed tomography of the abdomen and pelvis and a chest X-ray are recommended. Thoracic CT is more

69
sensitive than chest X-ray. Positron emission tomography/computed tomography is an option for identifying pelvic
nodal and distant metastases in patients with positive inguinal nodes .

TUMOR MARKER: SCC ANTIGEN.although not an established marker.

TREATMENT:
Treatment of the primary penile cancer lesion aims to remove the tumour completely, while preserving as much of
the penis as possible without compromising radicality.Penile preservation appears to be superior in functional and
cosmetic outcome and negative margin of 5 to 10mm is needed to be oncologically safe while 10-20mm provides
adequate control.

Penile preservation approach includes topical therapy (5FU is first line and imiquimod as second line therapy),laser
therapy(Nd:YAG and CO2 are most commonly used,Nd:YAG has deeper pentration of 3-4mm while CO2 has
0.1mm penetration),wide local excision,glansectomy and Mohs surgery (for small supeficial lesion on proximal
shaft to avoid penectomy).

Tis or Ta lesions: 5% 5FU cream can be applied twice daily for 2 to 6 weeks for topical therapy. 5% imiquimod
cream application at night 3 times per week for 4 to 16 weeks can also be used.Laser therapy along with 3-5%
application of acetic acid can be done ,acetic acid helps in identification of suspected HPV infected skin.

T1G1-2 lesions: Penile preservation should be considered if patient is reliable in terms of compliance and follow
up.options are
1. wide local excision
2. Glansectomy and mohs surgery in selected cases.
3. Laser therapy
4. Brachytherapy with interstitial implant(preffered) or EBRT(external beam radiotherapy).Circumcision must be
done before radiotherapy.

T1 G3-4, T>/=2: Depending on depth of invasion of tumor and characterstics of tumor extensive surgery in form of
partial or total penectomy to be considered.Intraoperative frozen section will help in achieving negative margins.
• T2 tumor confined to glans: wide local excision with reconstruction,glansectomy with
reconstruction,brachytherapy or EBRT for lesion less than 4 cm and laser with circumcision may be
considered.
• T2 with corporal invasion:partial penectomy with reconstruction or EBRT ,brachytherapy for lesion less
than 4 cm.
• T3 with urethrae invasion:patial or total penectomy with perineal urethrostomy.
• T4 with adjacent organ involvement: neoadjuvant chemotherapy followed by surgery in responders or
palliative external beam radiotherapy.

GUIDELINES FOR TREATMENT STRATEGIES FOR NODAL METASTASES (NCCN): Presence of

lymph node metastasis is identified as single most important prognostic indicator for long term survival.the
involvement can be clinically palpable or non palpable.clinical examination should evaluate number,unilateral or
bilateral localisation,mobility or fixation of node and involvement of skin.MRI is the best to asess the lymph
nodes.25% of patient with non palpable nodes carries occult metastasis hence according to european guidelines
patients are divided into low,intermediate and high risk patients.low risk is defined as Tis,Ta,or T1a,intermediate
group as T1b with lymphovascular invasion and high risk group as T2 or G3/G4 disease.

NON PALPABLE LYMPH NODES: Most low risk patients(Tis,Ta,T1a) are followed with surviellance.If
positive LN are identified on DSNB then ILND(inguinal lymph node dissection) is recommended.
For intermediate or high risk tumor modified or radical inguinal lymphadenectomy is strongly recommended
.Propylactic EBRT(external beam radiation therapy) for patient not fit for or not willing for surgery.DSNB can also
be considered.

KROONS ALGORITHM- For non palpable lymph nodes step 1-do USG groin,step 2-usg guided FNAC,Step 3-do
lymphoscintigraphy with SLNB

There are two invasive diagnostic procedures, whose efficacy is evidence-based: modified inguinal
lymphadenectomy (mILND) or catalona operation and dynamic sentinel-node biopsy (DSNB). Both are standard
approaches for invasive diagnosis of inguinal lymph nodes in clinically node-negative patients.

Modified ILND is the standard surgical approach. Both the superficial inguinal lymph nodes from atleast the central
and both superior Daseler’s zones are removed bilaterally , leaving behind the greater saphenous vein. Lateral limit

70
of dissection is femoral artery and caudally fossa ovalis and eliminate the need for sartorius cover.Nodes are sent for
frozen section and if positive full template lymphadenectomy is to be considered.

Dynamic sentinel node biopsy (DSNB) is based on the assumption that primary lymphatic drainage from a penile
cancer initially goes to one or only a few inguinal sentinel nodes on each side before further dissemination to more
inguinal nodes. Technetium-99m (99mTc) nanocolloid is injected around the penile cancer site on the day before
surgery; patent blue can be injected as well before surgery. A gamma-ray detection probe is used intra-operatively to
detect the sentinel node in 97% of cases.

Data suggest that in clinically negative groin men undergoing immediate ILND has better survival outcome than
men undergoing delayed ILND when clinially nodes become positive.Hence men with high risk tumor and clinically
node negative should be subjected to immediate ILND.

In patient with high risk tumor without inguinal lymphadenopathy should undergo bilateral lymph node dissection
because it is not possible to predict laterality of inguinal node based on tumor location on penis.
Again patient with palpable nodes has 30% chance of contralateral metastasis.Hence bilateral lymphadenectomy to
be considered for patient with high risk tumor undergoing immediate ILND and palpable inguinal
lymphadenopathy.

UNILATERAL PALPABLE NODE <4cm: Palpable node at the time of diagnosis does not warrant an
immediateILND. 30-50% patients have reactive lymphadenopathy.Traditionally differentiation between reactive and
metastatic disease was made with 6 weeks of antibiotics but percutaneous biopsy is now more acceptable approach.
Patient who don’t have risk features such as T1 tumor,high grade or lymphovascular invasion and poor
differentiation in more than half of tumor cells in primary tumor percutaneous lymph node biopsy is done and if
above features are present then lymphadenectomy should be done.
If lymph node biopsy is negative it should be confirmed with excision biopsy .if excision biopsy is positive then
immediate ILND should be done .

UNILATERAL PALPABLE NODE>/=4cm:Percutaneous biopsy must be done.If negative excision biopsy must
be done.If negative again then close follow up must be done.Patient with confirmed positive nodes recieves
neoadjuvant chemotherapy followed by ILND .
No furthur treatment is indicated if no residual disease is present in any dissected node after ILND.If 2 nodes are
positive or extranodal extension present then pelvic LN dissection and adjuvant radiation therapy if pelvic nodes are
also positive. Bilateral pelvic lymphadenectomy is done if 4 or more nodes are positive after ILND.

UNILATERAL FIXED NODES OR BILATERAL PALPABLE NODES:Percutaneous biopsy confirmed with

excision biopsy if reported negative.If excision biopsy is negative patient is closely followed.If biopsy is positive
neoadjuvant chemotherapy followed by ILND and PLND if response to chemotherapy is present.If 4 or more
inguinal nodes are positive then bilateral PLND to be considered and if 3 or fewer ingunal lymph nodes are positive
unilaeral PLND to be considerd.if no respone to chemotherapy then treat as metastatic disease.

ENLARGED PELVIC LYMPH NODES:Patient should undergo percutaneous biopsy.If positive resectibility
should be decided.Patient with resectable disease recieves neoadjuvant systemic chemotherapy and undergo B/L
ILND AND B/L PLND.Post operative chemoradiotherapy to be considered.Non resectable candidates recieves
chemoradiotherapy.Lateral limit is genitofemoral nerve,upper limit is bifurcation of common iliacs,from obturator
fossa anterior to obturator nerve and all nodes medial to external iliacs and hypogastric vessels.

RADICAL ILIO INGUINAL LN DISSECTION- Boundaries(Daseler’squadrilateral)-superiorly line joining

ASIS to pubic tubercle(inguinal ligament),laterally drop 20cm from ASIS(along sartorius),medially drop 15cm from
pubic tubercle(along adductor longus),inferiorly join lower ends of medial and lateral lines(inferior limit is fossa
ovalis).Cover femoral vessel with sartorius slide flap.

MANAGEMENT OF LYMPH NODES ACCORDING TO CAMPBELL

Management of high risk patients

71
Management of low risk patient

GUIDELINES FOR CHEMOTHERAPY IN PENILE CANCER PATIENTS(EAU GUIDELINES):

• Treat patients with pN2-3 tumours with adjuvant chemotherapy (three-four cycles of cisplatin,5-
fluorouracil, paclitaxel or docetaxel).
• Treat patients with non-resectable or recurrent lymph node metastases with neoadjuvant chemotherapy (4
cycles of a cisplatin and taxane-based regimen) followed by radical surgery.
• Treat patients with systemic disease and a limited metastatic load with chemotherapy.

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FOLLOW UP:(EAU GUIDELINES)

Recurrence
1. If after initial organ preserving approach invasion in corpora cavernosa is detected then partial or total
penectomy is to be considered.
2. If primary tumor recurs without corpora cavernosa involvement then repeat peile preservation approach must be
considered.
3. Recurrence in inguinal region carries poor prognosis.if prior lymphadenectomy or radiotherapy was not done
then primary treatment for ingunal nodes as stated above to be considered.if inguinal lymph node dissection or
radiotherapy was done then chemotherapy followed by ILND,ILND alone or chemoradiotherapy to be
considered.

Metastasis: Systemic chemotherapy ,radiotherapy or chemoradiotherapy may be considered for systemic

disease.cisplatin base regimen to be used.If patient responds to systemic therapy ILND can be considered with
curative or palliative intent.However if there is no response then surgical consideration can only be done for local
symptoms control.Preoperative radiation therapy for ln more than 4 cm without skin fixation to improve outcome.
Targeted drugs have been used as second-line treatment and they could be considered as single-agent treatment in
refractory cases.Anti-EGFR monoclonal antibodies,panitumumab and cetuximab has been used.Pembrolizumab can
be used in mismatch repair deficient penile cancer.

REFERENCES
1) Recent NCCN guidelines for carcinoma penis 2018.
2) Campbell Walsh text book of Urology 11th edition.
3) Eau guidelines for carcinoma penis 2017.

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 Germ Cell Tumors of Testes
Kim Mammen, Shradha Engles, Uma Kant Dutt

Introduction
Germ cell tumors (GCTs) of testis are the most frequent malignancies in young men between the age of 20 and 40.
Less than 10% of all GCTs arise in extragonadal sites (e.g. mediastinum), however their management follows that of
testicular GCTs (1)
Primary GCTs of testis constitute 95% of all testicular tumors. Of the extranodal sites predominant site id
mediastinum.
TGCTs consist of two histologically distinct subtypes: seminomas (40%) and nonseminomas (60%). Nonseminomas
are further divided into embryonal carcinoma (EC), teratoma, yolk sac tumor and choriocarcinoma (2)
TGCTs are thought to arise from transformation of primordial germ cells and pluripotent EC represents the stem cell
component of nonseminoma and can differentiate into mature nonseminoma subtypes (3)

Epidemiology
GCTs is most commonly seen in the age group of 15to 35 yrs. Most common tumors in males in this age group.
Contributes to 10% of all cancer deaths. Familial clustering has been observed, particularly among siblings.

Risk factors
 Cryptorchidism
 Klinefelters Syndrome
 Familial predisposition – relative risk of development of these tumors in fathers and sons of patients with
GCTs of testis is 4 times higher than normal and is 8 to 10 times higher between brothers.
 Trauma
 Hormones
 Atrophy

Classification
 Seminomatous – seminoma
 Spermatocytic seminoma

 Non-seminomatous – Embryonal carcinoma

 Yolk sac tumor
 Choriocarcinoma
 Teratoma – mature
 Immature
 With malignant transformation

1. Seminoma – accounts for approximately 50% of GCTs. 4 th decade of life. Types include typical or classic,
atypical, spermatocytic.
 Typical – 50% of all germ cell tumors. Consists of large cell sheets with abundant cytoplasm, and
round, hyperchromatic nuclei with prominent nucleoli. It is frequently associated with a
lymphocytic infiltrate.
 Atypical – lymphocytic infiltration is absent. Necrosis is more common in the tumor mass. It has
higher nucleocytoplasmic ratio.
 Spermatocytic – 2% of all germ cell tumors rare variant. Seen in older men. Not associated with
ITGCN. Has minimal metastatic potential.

2. Embryonal Carcinoma – pure embryonal carcinoma makes up about 3% of all germ cell tumors.
Aggressive tumor with high rates of metastasis. Most undifferentiated type of NSGCT. Necrosis and
hemorrhage are frequently observed in the tumor. Histologically contains epithelioid cells arranged in the
form of nests or tubule-glandular structures or as sheets.

3. Choriocarcinoma – Rare and aggressive tumors. Consists of both syncytiotrophoblasts and

cytotrophoblasts. Shows high levels of HCG. Associated with widespread hematogenous metastasis.
Hemorrhage or infarction can occur at metastatic site leading to severe complications.

4. Yolk sac tumor –Pure yolk sac component is uncommon in adults, < 2%. Can occur as mixed NSGCTs.
Produce alpha fetoprotein. Histology contains hyaline globules and schiller aduval Bodies. Has low rate of
relapse.

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 5. Teratoma – rarest type, < 0.05%. Composed of somatic cell types from two or more germ layers
(ectoderm, mesoderm, or endoderm), with a predominance of ectodermal component, derived from
totipotential, malignant precursor (embryonal carcinoma or yolk sac tumor). Usually are solid or cystic.
Referred to as dermoid cyst if unilocular. Ectodermal component: skin, hair, sweat gland, sebaceous
glands, teeth may be present. Mesodermal component: fat, smooth muscle, bone, cartilage may be present.
Ectodermal component: respiratory and intestinal epithelium may be present. Can be immature with partial
somatic differentiation of ectodermal, mesodermal, endodermal components as seen in fetus or can be
mature. Both mature and immature teratomas are histologically benign. Teratoma with malignant
transformation is a form of teratoma in which an immature or mature component histologically resembles a
non-GCT somatic cancer (leukemias, sarcomas, and carcinoma).

6. Mixed germ cell tumors – 50% of germ cell tumors. Any of the germ cell tumor types are present in
combination.

Tumor model for GCT

Normal spermatocyte

Totipotent germ cell seminoma

Embryonal carcinoma
( Totipotent tumor cell)

Extraembryonic differentiation Intraembroyonic differentiation

Choriocarcinoma Yolk sac tumor Teratoma

( Trophblastic pathways) (Yolk sac pathway)

Serum tumor marker

- Alpha feto protein
- HCC
- LDH (first serum marker showing rising trend, but less specific)

Risk Stratification

- Seminoma
Good risk - Any hCG, any LDH, non-pulmonary visceral metastases absent
Intermediate risk - Any hCG, any LDH, non-pulmonary visceral metastases present
Poor risk – not defined

- NSGCT
Good risk – AFP < 1000
hCG < 5000
LDH < 1.5 ULN
Non pulmonary visceral metastases absent
Gonadal or retroperitoneal primary tumor
Intermediate risk - AFP 1000 - 10000
hCG 5000 - 50000
LDH 1.5 – 10 ULN
Non pulmonary visceral metastases absent
Gonadal or retroperitoneal primary tumor
Poor risk – primary site mediastinal
Extra pulmonary visceral Mets present like brain, liver
AFP >10000
hCG >50000
LDH >10 ULN

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TNM Staging

PRIMARY TUMOUR
 Primary Tumor (T)*
 pTx Primary tumor cannot be assessed
 pT0 No evidence of primary tumor (e.g., histologic scar in testis)
 pTis Intratubular germ cell neoplasia (carcinoma in situ)
 pT1 Tumor limited to the testis and epididymis without vascular/lymphatic invasion; tumor
may invade into the tunica albuginea but not the tunica vaginalis
 pT2 Tumor limited to the testis and epididymis with vascular/lymphatic invasion, or tumor
extending through the tunica albuginea with involvement of the tunica vaginalis
 pT3 Tumor invades the spermatic cord with or without vascular/lymphatic invasion
 pT4 Tumor invades the scrotum with or without vascular/lymphatic invasion

Regional Lymph Nodes (N)

CLINICAL (as determined by noninvasive staging)
 NX Regional lymph nodes cannot be assessed
 N0 No regional lymph node metastasis
 N1 Metastasis with a lymph node mass 2 cm or less in greatest dimension; or
multiple lymph nodes, none more than 2 cm in greatest dimension
 N2 Metastasis with a lymph node mass, more than 2 cm, but not more than 5 cm in greatest
dimension; or multiple lymph nodes, any one mass greater than 2 cm but not more than 5 cm in
greatest dimension
 N3 Metastasis with a lymph node mass more than 5 cm in greatest dimension

PATHOLOGIC (pN) (as determined by pathologic findings of RPLND without prior chemotherapy or
radiotherapy)
 pNX Regional lymph nodes cannot be assessed
 pN0 No regional lymph node metastasis
 pN1 Metastasis with a lymph node mass 2 cm or less in greatest dimension and
less than or equal to five nodes positive, none more than 2 cm in greatest
dimension
 pN2 Metastasis with a lymph node mass more than 2 cm but not more than 5 cm
in greatest dimension; or more than 5 nodes positive, none more than 5 cm;
or evidence of extranodal extension of tumor
 pN3 Metastasis with a lymph node mass more than 5 cm in greatest dimension

Distant Metastasis (M)

 MX Distant metastasis cannot be assessed
 M0 No distant metastasis
 M1 Distant metastasis
 M1a Nonregional nodal or pulmonary metastasis
 M1b Distant metastasis at site other than nonregional lymph nodes or lung

Serum Tumor Markers (S)

 SX Marker studies not available or not performed
 S0 Marker study levels within normal limits
 S1 LDH < 1.5 × N and hCG (MIU/mL) <5000 and AFP
(ng/mL) <1000
 S2 LDH 1.5-10 × N or hCG (MIU/mL) 5000-50,000 or AFP
(ng/mL) 1000-10,000
 S3 LDH >10 × N or hcG (MIU/mL) >50,000 or AFP
(ng/mL) >10,000

STAGING

 Staging A or I Tumour confined to testis.

 Staging B or II Spread to Regional nodes.
 IIA Nodes <2 cm in size or < 6 Positive Nodes
 IIB 2 to 5 cm in size or > 6 Positive Nodes
 IIC Large, Bulky, abd.mass usually > 5 to 10 cm
 Staging C or III Spread beyond retroperitoneal Nodes or Above Diaphragm or visceral disease

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Anatomical consideration in staging

Lymphatic spread to RPLNs – seminomas

Hematogeneous route – non seminomas

The primary landing Zones

Lymphatic crossover
Ipsilateral distribution
Inguinal node involvement
Cephalad spread

1. Paracaval
2. Precaval
3. Interaortocaval
4. Preaortic
5. Para-aortic
6. Right suprahilar
7. Left suprahilar
8. Right iliac
9. Left iliac
10. Interiliac
11. Right gonadal vein
12. Left gonadal vein

Diagnosis

History
- Painless unilateral mass
- Dull scrotal ache, or acute pain (due to hemorrhage) in 10% patients
- Patients with RPLN metastasis or disseminated disease may present with backache, lethargy and other
systemic features.
- Approximately 10% of patients present with symptoms related to metastatic disease.
 Back pain (retroperitoneal metastases involving nerve roots) is the most common symptom.
 Cough or dyspnea (pulmonary metastases)
 Anorexia, nausea, or vomiting (retroduodenal metastases)
 Bone pain (skeletal metastases)
 Lower extremity swelling (vena caval obstruction).

Examination
- Complete examination of external genitalia.
- A testicular mass or diffuse enlargement is found in most cases. The mass is typically firm and nontender
- Always look for an abdominal mass (RPLNs)

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 - Some patients may have palpable supraclavicular lymph nodes
- Gynecomastia (altered hormonal balance) is present in 5% of all germ cell tumors and in 30–50% of Sertoli
and Leydig cell tumors.
- Secondary hydrocele and inguinal lymphadenopathy
- Hemoptysis may be seen in advanced pulmonary disease.

Imaging
To confirm and assess the extent of disease
Ultrasound, CT, MRI, PET
USG scrotum
- Seminoma : well defined, homogenous, hypoechoic testis as compared to the surrounding parenchyma
- Embryonal cell tumor: less homogenous and well defined in comparison with seminoma
- Teratoma: Characteristically of mixed echogenicity; more likely to contain cystic spaces and calcifications.
Ultrasound can assess RPLN but not reliable as compared to CT or MRI
CT
- Staging of GCT
- Assess metastatic disease in thorax, abdomen and pelvis
- Unable to detect small volume lymph nodes
- Post chemo and RT difficult to assess due to fibrosis
- Unable to identify small volume disease in normal sized lymph nodes
- False negative as upper limit of lymph node size is yet to be defined
MRI
- Better view of soft tissue
- Better in defining RPLNs
- Detects CNS, musculoskeletal and hepatic Mets
- Demonstration of IVC tumor invasion
- Demonstration of vascular anatomy prior to RPLN surgery
- As an alternate in patients who cannot be given iv contrast
- In patients who have equivocal findings on CT
- Less accurate in demonstrating lung Mets

PET
- Main modality used in the management of GCTs
- Defines the tumor and Mets anatomically
- For surveillance
- Can detect tumor cells in normal sized lymph nodes
- Cannot identify mature teratomas.
- Evaluation of treatment response

Tumor markers

- Alpha feto protein

- HCC pre orchiectomy levels are important
- LDH
- PLAP

Management

Principles of treatment
- Radical inguinal orchiectomy is standard first line of therapy
- Treatment should be aimed at one stage above the clinical stage
- Seminomas - radio-sensitive. Treat with radiotherapy.
- Non-seminomas are radio-resistant and best treated by surgery
- Advanced disease or metastasis - responds well to chemotherapy
- Lymphatic spread initially goes to retro-peritoneal nodes
- Early hematogenous spread rare
- Bulky retroperitoneal tumours or metastatic tumors initially “down-staged” with chemotherapy

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Every patient is initially subjected to inguinal exploration and orchiectomy with division of the cord at the level of
the internal inguinal ring. Only in life-threatening conditions may up front chemotherapy be started and orchiectomy
delayed for later.
Sperm preservation is offered to all patients prior to orchiectomy.

Seminoma
1. Surveillance
2. Adjuvant chemotherapy
3. Adjuvant radiotherapy

Stage 2a, 2b (T1-3 N1-2, M0)

- Radiation - abdominal and pelvic.

o (ipsilateral external iliac, bilateral
common iliac, the paracaval, para-
aortic nodes including the cisterna
chyli)
- 150 cGy/day, 5 days per week.

Approach to Seminoma: Stage IIc & III (N3 / M1-2)

- Cisplatin based chemotherapy:
o A major breakthrough in treatment of
testicular tumor
3 or 4 cycles depending on response BEP, VIP, VEIP

Residual retroperitoneal mass after chemotherapy in Seminoma

• Diffuse desmoplastic plaque < 3 cm & no hot spot on PET scan: observation
• Discrete mass > 3 cm: surgical resection – Histology-necrosis/ fibrosis-No further Tt
-germ cell tumor -CT- VIP : 2-3 cycles

NSGCTs
1. Surveillance
2. RPLND
3. Chemotherapy
4. Radiotherapy

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 Treatment of Non-Seminoma GCT- Stage 1 (T1-3, N0, M0, S0-1)
 Modified RPLND - Node < 2cm – Observation
- Node > 2cm - adjuvant CT – BEPx 3 cycles.
Or
 Primary chemotherapy - BEP 3 cycles
 Persistent tumor markers - BEP 3 cycles

Therapy of NSGCT Stage IIa, IIb (T1-3, N1-2, M0, S0-1)

 Bilateral nerve sparing RPLND
And/or
 Primary CT- BEP 3 cycles
Therapy of NSGCT Stage IIc, III (N3 / M1-2)
Resolution -
observation

Residual B/L RPLND &

retroperitoneal
disease Tumorectomy
Good risk – BEP x
3 cycles
Residual visceral
Surgical excision
mets

Persistent
elevation of Salvage CT- VIP
tumor markers

Approach to a patient with advanced stage IIB and III non seminomatous germ cell tumor

Treatment after RPLND or Residual mass resection

 After Primary modified RPLND for N0 disease :
 Node <2 cm - observation
 Node >2 cm - Adjuvant CT(BEPx3)
 After Primary B/L nerve sparing RPLND for N1-2 :
 No further Tt, FU with TM & CT
 Post-Chemo residual mass resection :
 If RM show only Fibrosis/Necrosis - no further Tt
 If RM shows Viable tumor cells - further CT needed:
 If RMS was after 1st line CT : BEP x 2
 If RMS was after 2nd line CT : VEIP x2 - Increased survival

NSGCT: therapeutics
 Surgery Sensitive Tumor: RPLND used as
 1) Prophylactic / Elective RPLND : for N0 (stage 1) disease
If high risk (pT2 & LVI) + 2 x BEP also after RPLND
 2) Therapeutic RPLND: for < 5 cm LNs (stage 2a& 2b)

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  3) Desperation Surgery : in chemo resistant resectable disease

NSGCT: therapeutics
Highly Chemosensitive Tumor: used as
1) Prophylactic CT:
For stage 1 (no LN) disease – 1 or 2 cycles
2) Therapeutic CT: for > 5 cm LNs
3) Salvage CT:
If HPE of Residual masses if +ve
As second line CT if first line CT fails

CT Refractory Testicular tumor

- If TM still high after 3 ( low & intermediate risk disease) to 4 ( high risk disease) cycles ---- go
to 2nd line CT : VIP X 4 cycles ----- if TMs still high ----- go for:
- ABMT + High dose CT
Or
- Desperation Surgery

Desperation Surgery
- Sometimes TMs may not respond at all /poorly respond even after 2nd line CT ; then assess the
resectability of whole residual disease in abdominal, mediastinal & supraclavicular region and
lung lesions ( if <2 sites & completely resectable) and remove them
- if TMs become normal: give 2 cycle of CT & FU
- If TMs still high – poor prognosis , uncontrollable disease – very rare situation

Follow up
- 3 monthly x 2 years – then
- 6 monthly x 5 years – then
- Yearly

Prognosis
Seminoma Nonseminoma
Stage I 99% 95% to 99%
Stage II 70% to 92% 90%
Stage III 80% to 85% 70% to 80%

Reference
1. Bosl GJ, Motzer RJ. Testicular germ-cell cancer. N Engl J Med1997; 337:242-53.
2. Houldsworth J, Korkola, JE, Bosl, GJ, Chaganti RS. Biology and genetics of adult human male germ cell tumors. J
Clin Oncol. 2006; 24:5512–5518.
3. Kristensen DM, Sonne SB, Ottesen AM, Perrett RM, Nielsen JE, Almstrup K, Skakkebaek NE, Leffers H, Rajpert-De
Meyts E. Origin of pluripotent germ cell tumors: the role of microenvironment during embryonic development. Mol
Cell Endocrinol. 2008; 288:111–118.

81
 Imaging in Urology
Anjali Prakash

Imaging plays an integral role in urologic diagnosis. Radiographic evaluation can be as simple as an abdominal
plain film or as complex as a triphasic CT study. Imaging data can provide static anatomic information or functional
data such as that obtained by excretory urography (IVP). Uro-radiology is a discipline that utilizes all imaging
techniques to provide answers to specific clinical questions. The required information can be obtained most rapidly
and efficiently by using the correct test or tests performed in the correct order

Imaging modalities
 Plain X-Ray
 Intravenous Pyelogram
 Retrograde Pyelogram
 Antegrade pyelogram
 Nephrostogram
 Micturating Cystourethrography (MCU)
 Retrograde urethrogram
 Ultrasound
 CT Scan
 MRI
 Renal Scintigraphy

ABDOMINAL PLAIN RADIOGRAPHY

 An abdominal plain radiograph is most often referred to as a KUB (kidneys, ureters, and bladder).
 An anteroposterior radiograph of the abdomen may also be referred to as a scout film before the
administration of IV contrast material for an IV urogram.
Indications for x-ray KUB-
(1) Renal or ureteric colic/to assess calculus disease before and after treatment
(2) Hematuria
(3) Burning micturition
(4) As a scout film before any contrast procedure.
(5) To assess position of drains and stents

INTRAVENOUS PYELOGRAPHY/ UROGRAPHY /EXCREATORY UROGRAPHY(IVP/IVU/EU)

IVP allows visualization of the entire urinary tract. The study provides demarcation of the renal
parenchyma, the pelvicalyceal system, ureters, and bladder, providing both anatomic and functional
information.
Indication:
• Demonstrate the renal collecting systems and ureter
• Evaluation of patients with suspected or known ureteral obstruction
• Demonstrate renal function during emergent evaluation of unstable trauma patients
• Assessment of the integrity of the urinary tract following therapeutic interventions especially when cross-
sectional imaging is unavailable or inappropriate.
• Assessment of the urinary tract for suspected congenital anomaly.
• Follow-up of patients with recurrent renal/ureteral calculi.

PROCEDURE
Scout film
 It to check technical quality of the examination, positioning and exposure.
 To detect calcification or calcific densities that could be urinary tract calculi.
 To determine if bowel preparation is adequate or not.
Filming sequences:
 After viewing the scout film, compression device is placed over the abdomen and contrast media is injected
rapidly.
 Compression is applied to achieve partial ureteric obstruction resulting in more complete distension of
collecting system, improved calyceal details.
Dose of contrast media-
 Minimal dose in adult of average size and normal renal function is 50 ml.
 Small children- <4yrs-1.5-2.5ml/kg of body wt
Following contrast media injection and compression suggested filming sequences is:

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 1) 1 minute 10x12 renal area to demonstrate nephrogram. In practice, this radiograph is omitted as the renal
outline as usually visualized on 5min radiograph.
2) 5 minute film- 10x12 renal area, shows renal outline and pelvicalyceal system.
3) 10 minute film- 14x17 supine immediately after release of compression. It demonstrates entire urinary tract.
4) 15 minute film 14x17 prone, this view demonstrates contrast in lower ureters.

Contraindications to compression are:

 After recent abdominal surgery
 After renal trauma
 If there is a large abdominal mass or aortic aneurysm.
 If 5 min film shows dilated calyces or if calyces and pelvis are not adequately opacified, obstruction exists
and compression band should not be applied.

Complications of IVU:
 Adverse reaction to contrast media usually develops within 20min of contrast administration.
 Spontaneous rupture of collecting system in acute calculus obstructions.
 Contrast medium induced nephropathy

RETROGRADE PYELOGRAPHY
 Retrograde pyelography (RP) is the opacification of the ureter and pelvicalyceal system by the retrograde
injection of contrast media through a ureteral catheter inserted under cystoscopic guidance.The procedure
must be performed under sterile conditions
 It is contraindicated in a patient with infected urine because of the risk of introducing bacteria into the
upper collecting system or blood stream.
Indications:
• Usually follows an IVU and is indicated when there is persistent uncertainty about the diagnosis
particularly if there is hematuria and/or suspicious cytology.
• To confirm the presence of one or more filling defects within the collecting system.
• To demonstrate ureteric stricture or fistula/evaluation of ureteral obstruction
• In the evaluation of traumatic or iatrogenic injury to the ureter or collecting system
• In conjunction with ureteroscopy or stent placement

Technique:
 Catheter is placed in renal pelvis cystoscopically.
 A scout film is obtained prior to contrast administration to check position of catheter and to look for
signs of urinary tract pathology.
 Contrast used is fairly dilute 15-45% so that small filing defects such as non-opaque calculi are not
obscured.
 Approximately 10 ml contrast is sufficient to delineate a non dilated PCS.
 AP and bilateral oblique views are taken.
 The catheter is slowly withdrawn from the ureter until the entire ureter is delineated and the catheter
tip lies in distal ureter just proximal to spot radiograph with or without splitting of images is obtained.
 Delayed films with patient sitting or standing for 5-15 minutes can help to determine presence of
ureteral obstruction.

Complications:
 Traumatic injury to the ureter and renal pelvis.
 Urinary tract infection
 Backflow, it results from excessive injection pressure. (e.g pylotubular, and pylointerstitial back flow).

ANTEGRADE PYELOGRAPHY
 It is direct percutaneous injection of contrast medium in to the dilated pelvicalyceal system.
 Unlike RGP, it doesn’t require General Anaesthesia and has lower incidence of UTI.
Indication:
 Urinary tract obstruction when information from IVP is inadequate and RGP has failed or is
contraindicated because of greater risk of introducing infection.
 Prior to insertion of nephrostomy tube.
 Prior to interventional urinary tract procedure.
 To define a ureteric fistula.
 Can be performed when RGP is difficult or impossible.

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Contraindication:
Following are relative C/I:-
 Single functioning kidney
 Uncontrolled hypertension
 Bleeding diathesis
Technique:
 It is done under local anesthesia.
 Chiba needle is placed vertically towards the calyx rather than pelvis because the renal parenchyma
provides a better seal around the needle tract, than the thin walled renal pelvis.
 Urine is aspirated to confirm the position. If clear urine is aspirated contrast is injected through the needle
and appropriate films are taken.
Complications:
 Loin pain
 Hematuria and hemorrhage
 Septicemia
 Urinoma, pneumothorax and damage to other viscera.

NEPHROSTOGRAM
A nephrostomy tube is positioned for therapeutic purpose but while it remains in position a nephrostogram can be
performed.
Indications
It is indicated to assess the obstructing lesions and evaluate its status
Relative contraindications of nephrostomy
• Uncorrectable bleeding disorder
• Severe electrolyte imbalance causing tachypnoea
• Solitary kidney without prior retrograde attempt to relieve obstruction

Technique:
 After a scout film, water soluble ionic contrast is injected in to the collecting system, after clamping the
nephrostogram tube and
 Spot films taken of ureter down to the level of the obstruction.

Complications:
 UTI
 Contrast intravasation
 sepsis

STATIC CYSTOGRAM
Cystogram is done primarily to evaluate the structural integrity of the bladder. The shape and contour of the bladder
give a clue for the presence of bladder obstruction or there being a neurogenic cause of bladder related symptoms.

Technique
Patient is placed supine. After a check X ray, bladder is filled with 200-400 ml of dilute iodinated contrast
depending on bladder capacity and patient comfort. It is important to completely fill the bladder. Oblique films are
also obtained to visualise posterior wall.

Indications
1. Evaluation of intravesical pathology
2. Evaluation of bladder diverticula
3. Demonstrate colovesical or vesico vaginal fistla
4 .Evaluation of bladder or anastamotic integrity after surgical procedure
5. Blunt or penetrating trauma to bladder (CT cystogram is now preferred for this indication)

Micturating Cystourethrography /Voiding Cystourethrogram (MCU/VCUG)

Micturating Cystourethrography (MCU) is a widely applied radiographic technique for the evaluation of the bladder
and urethra in children and adults. MCU allows evaluation of the bladder and urethra during the physiologic act of
micturition, providing visualization of the posterior urethra.

Indication:
In children
 To look for VUR as a cause of recurrent UTI
 Suspected anatomical abnormality of bladder or urethra (posterior urethral valves)

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In adults
 Functional disorder of bladder and urethra
 Suspected vesicovaginal or vesicocolic fistula.
 Suspected bladder trauma.

Contraindication:
 Acute UTI
 Hypersensitivity to contrast medium.
Technique:
 Bladder is catheterized by appropriate gauge catheter using strict aseptic no touch technique.
 Following scout view conventional ionic tri iodinated contrast (around 30% diluted) is delivered through
Foley’s catheter.
 A spot radiography is obtained in a child during early bladder filling as this is best for ureterocele.
 Full film spot for VUR is taken.
 The bladder is filled until there is urge to micturate.
 X-ray is taken in PA and oblique projections to demonstrate the bladder and associated abnormality.
 Lateral view is required in case of fistula.
 The study is finished after taking a post micturating film to diagnose a VUR not seen previously and
amount of residual urine.

Complications-
 UTI
 Complications of catheterization, e.g. urethral trauma.
 Complications of contrast media, e.g. cystitis.

RETROGRADE URETHROGRAPHY
 Retrograde Urethrography (RGU) provides excellent visualization of the anterior urethra in the male.
 The study involves retrograde filling of the anterior urethra with a 30% to 60% solution of water-soluble
contrast material. The contrast medium is retrogradely injected with the urethral orifice occluded to prevent
reflux. Urethral occlusion is usually achieved with either a Foley catheter with the balloon inflated in the
fossa navicularis or a catheter attached to a clamping device onto the glans penis
The primary indications for RGU
1. Evaluation of ureteral stricture disease
2. Evaluation of penile or uretheral penetrating trauma
3. Evaluation of traumatic gross haematuria.

The urethra is better assessed dynamically under fluoroscopy. The male urethra is best seen in the oblique position
and the female urethra in the lateral or anteroposterior position. VCUG demonstrates the prostatic urethra to best
advantage, as this portion is better distended than the membranous and anterior urethra. This approach is preferred
when assessing for abnormalities of the prostatic urethra such as valves, strictures, fistulas, and changes in the
bladder neck. RGU, on the other hand, better depicts the membranous and anterior urethra, and is the preferred
approach for assessing inflammatory lesions and diverticula, which commonly occur in these regions. Some patients
are assessed with both techniques, with the RGU usually being performed first, followed by the VCUG.

ULTRASOUND
Ultrasonography is an indispensable modality for morphological evaluation of the urogenital tract. It is accurate,
safe, does not require exposure to ionizing radiation or normal renal function for image production. Ultrasound has
its disadvantages-of being limited in the field of view,operator dependent and also dependent on the body habitus of
the patient,performing poorly in the obese population.
Common indications are:
 Evaluation of collecting system obstruction.
 Evaluation of suspected or known nephrolithiasis
 Evaluation of cystic renal diseases.
 Detection of renal or perirenal mass lesion.
 Characterization of renal mass lesion
 Guidance for diagnostic and therapeutic interventional procedures.
 Estimation of residual urine in the bladder of patients with outflow obstructive symptoms. (Slow flow with
a large bladder residue, may indicate a decompensated bladder due to outflow obstruction).

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Doppler evaluation
Indications:-
 Renovascular hypertension
 Renal artery embolus/aneurysm
 Characterization of mass lesions
 Evaluation of transplant kidney
 Renal vein thrombosis
 Trauma

COMPUTED TOMOGRAPHY CT
Computed tomography (CT) has become the preferred investigation for acute loin pain, renal mass, renal
vasculature and the urothelium (CT urography) .Multidetector CT systems allow thin slices to be acquired for large
body areas in a single breath hold.

Non contrast CT
Indications for non-contrast examination include:
 Urolithiasis
 Suspected hemorrhage

Multidetector CT
 These CT scanners with reduced gantry rotation times allow 2 to 25 times faster scan times than helical CT
with the same or better image quality.
 The faster scan result in decreased breath hold times with reduced motion artifact and more diagnostic
images.
 MDCT allows images to be obtained in multiple phases of renal parenchymal enhancement and excretion
in the collecting system after administration of a single bolus of IV contrast material.

Technique and imaging protocol of multiphasic helical CT

The different phases noticed after the administration of IV contrast in dedicated renal MDCT are:
I. Corticomedullary phase: seen after 25-80 sec after contrast injection
The enhanced renal cortex is distinctly differentiated from unenhanced medulla.
Advantages:
 Better differentiation of normal variants of renal parenchyma from renal masses.
 Visualization of tumor vascularity helps in characterization of solid renal masses.
II. Nephrographic phase or tubular nephrogram phase: starts 90-120 sec after contrast injection.
 It includes passage of contrast through renal tubule system.
 During this the Corticomedullary differentiation disappears and the renal parenchyma enhances
homogenously.
Advantages: optimal phase for detection and characterization of renal masses especially those <3 cm.
Lesion enhancement of >20 HU is sufficient for diagnosing malignant masses which may not be visualized
in other phases.
III. Excretory phase: seen after 3-5 min of contrast injections.
This begins when contrast material excreted into the collecting system and opacify calyces, renal pelvis,
ureters.
Advantage: opacification of collecting system allows depiction of intraluminal pathology.

MDCT urography -MDCTU:

MDCTU is defined as the examination of the urinary tract by MDCT in the excretory phase following IV contrast
administration. Reconstructed 3D images can be used to produce IVU-like images in different projections.

Indication:
 Calculi
 Renal tumors
 Urothelial tumors
 PUJ obstruction
 Ureteric leaks and fistulae
 Evaluation of living renal donors (comprehensive single test evaluation for the presence of stones or renal
masses, assessment of the urothelium, renal parenchyma, renal arterial and venous configurations, and the
anatomy of the ureters)
 Congenital anomalies

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MDCTU Protocol
Three phase protocol:-
1. Non contrast phase (initial scan)
2. Nephrographic phase ( 90-100 seconds after contrast administration )
3. Pyelographic phase ( 12-15 min after contrast administration)
Dose of contrast: - 100-150 ml of 300 mg I/ml, rate 2-4 ml/sec.

SPLIT BOLUS MDCT Urography

Two phase protocol:-
 Noncontrast scan
 Nephro-pyelographic phase
The examination is performed with the patient supine in two distinct phases as follows:

Pre Contrast:
 Digital scout view abdomen/pelvis.
 Scan abdomen/pelvis
Post contrast:
 30 cc non ionic contrast (300 mg I/ml) at 2cc/sec
 10-15min delay
 100cc non ionic contrast (300mg I/ml) at 2cc/sec
 100 sec delay
 Scan abdomen
 The split bolus technique has a potential to reduce both radiation dose and the number of images generated
by MDCT urography.

CT CYSTOGRAPHY:
Typically done in cases of emergency settings in cases of bladder trauma.Accurate classification of injury in the
clinical setting is critical for proper treatment.
Intraperitoneal bladder ruptures (type 2) and combined intraperitoneal and extraperitoneal ruptures (type 5) require
laparotomy with surgical repair of the bladder defect and diverting vesicostomy whereas contusions (type 1) and
interstitial injuries (type 3) are managed conservatively with Foley catheterization. Most extraperitoneal ruptures
(type 2) may be treated with catheter drainage if the urine clears of blood, the catheter functions well, and the
bladder neck is not injured; otherwise, formal surgical repair is necessary.

Procedure:
 300-500 ml of 5-8% diluted non-ionic contrast (350mgI/ml of iohexol) is injected into the urinary
bladder through the foley’s.
 scan is acquired from dome of diaphragm to the perineum.
 The normal CT cystogram will demonstrate a well-distended urinary bladder with thin walls. The
adjacent fat planes will be distinct, with no evidence of extravasated contrast material.

MAGNETIC RESONANCE IMAGING: MRI

Is a technique which uses radio frequency pulses along with a magnetic field to image the human body. It does not
use ionising radiation. With major refinement in hardware and software MRI is gaining a wider role in abdominal
imaging and urological imaging.the major drawback is high cost,poor availability and certain contraindications like
presence of pacemakers,aneurismal clips and claustrophobia.

Indications
1. In evaluation of renal mass-in complicated cystic lesion,to see enhancement in a partially calcified or
haemorrhagic lesion
2. MR urography-shows obstruction of the urinary system.Calculi, however are not well appreciated on MRI
as they produce no signal
3. Prostate-multiparametric MRI is now the imaging method of choice for prostate cancer
4. Bladder malignancy-to determine muscle invasive or noninvasive bladder carcinoma

CONVENTIONAL ANGIOGRAPHY:
 The use of diagnostic x-ray angiography has been declining as cross sectional imaging techniques have
become more refined and CT and MR angiography have been more widely used.

Conventional catheter angiography is still useful in:-

 Evaluation of kidneys- renal arteries (number, caliber, and course) of renal donors.

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  As an initial step in performing angioplasty and therapeutic embolization.
.
CLINICAL SITUATIONS AND IMAGING MODALITY TO BE USED

Hematuria is one of the most common presentations of patients with urinary tract diseases and of patients referred
for urinary imaging. Hematuria can originate from any site in the urinary tract and be due to a wide range of causes,
which can be roughly divided into renal, urothelial, or prostatic causes

The initial decision to be made is whether all patients with any degree of hematuria need imaging evaluation.
The definition of microscopic hematuria is three or more red blood cells per high-power field on microscopic
evaluation of urinary sediment from two of three properly collected urinalysis specimens The low prevalence of
clinically detectable disease in some groups of patients with asymptomatic microscopic hematuria has led some
investigators to suggest that minimal microhematuria in an asymptomatic young adult needs no evaluation. There
may be specific circumstances in which complete radiologic workup of microscopic hematuria is necessary.

Patients with haematuria can be divided into low risk and high risk groups. Urinary tract infection as a cause must
be excluded prior to imaging. Low risk patients are patients who have microscopic or macroscopic haematuria in
patients less than 40 years of age or patients with microscopic haematuria more than 40 years of age. These patients
should be assessed by ultrasound for medical renal parenchymal disease, especially in patients<40 years of age. Non
contrast CT should be done in patients with macroscopic haematuria aged <40 years or microscopic haematuria in
those more than 40 years of age as renal calculus is the most common cause of haematuria in this subset of patients.
High risk patients are patients more than 40 years of age and who present with macroscopic haematuria. Patients in
the high risk group should be imaged with CT Urography. This triage can lead to optimal selection for CTU.

Imaging Evaluation
Young women with a clinical picture of simple cystitis, and other patients whose hematuria completely and
permanently resolves after successful therapy, are unlikely to benefit from any imaging .Patients who have a known
medical renal parenchymal disease (which include glomerulonephritis, glomerulonephropathy, acute tubular
necrosis, and acute kidney injury) also may not require imaging except renal ultrasound (US) to evaluate the kidneys
for coexistent morphologic abnormalities. In patients with recent history of infection or viral illness, vigorous
exercise, or urological procedures such as catheterization, initial imaging workup is also not beneficial.
Imaging evaluation is recommended for all other adult patients with hematuria to detect urologic malignancies as
well as the other possible causes of hematuria

Computed Tomography
Until the mid-1990’s excretory urography (IVU) was the imaging study used in evaluating hematuria
But the development of multidetector CT and the excretory phase CT urogram, also known as CTU, have
supplanted IVU over the past few years.
Compared to CT and US, IVU has low sensitivity for detecting renal masses <2–3 cm in size, and even if a mass is
visualized, further cross sectional studies such as US, CT, or magnetic resonance imaging (MRI) are then necessary
to characterize the mass.
In one prospective study that compared CT and IVU in the same patients with microhematuria , sensitivity and
accuracy of CT were 100% and 98.3% compared to 60.5% and 80.9% for IVU. Another prospective study that
compared CT and IVU in different patients with hematuria found that CTU had higher sensitivity than IVU for
detecting upper tract pathology (94.1% versus 50%), but both imaging modalities had low sensitivities (40% or less)
for detecting lower tract lesions.

Ultrasound
US still has a role in the initial workup of hematuria to search for bleeding urinary tract lesions .it is easily
available,is portable and completely non invasive. Being a non radiation modality, it is especially useful in, children
and pregnant or child-bearing age women, to detect renal calculi and renal masses. US is used as an initial
screening tool and can triage patients who need further cross-sectional urography.
In patients in whom glomerular disease is the cause of hematuria, US can examine the renal parenchyma and follow
disease progression. US can evaluate length, quantitative echogenicity, cortical thickness, and parenchymal
thickness.
In a prospective study, US had higher sensitivity (96% versus 25%) and negative predictive value (98% versus 91%)
than IVU in detecting abnormalities of the upper urinary tract in patients presenting with hematuria.

Intravenous Urography and Retrograde Pyelography

The detection of urothelial lesions in the upper tracts was traditionally performed with IVU and/or ureteroscopy
along with cystoscopy .CTU has largely supplanted IVU for imaging the upper urinary tract.

88
In a meta-analysis, CTU proved to be a very sensitive and specific method for the detection of urothelial malignancy
with pooled sensitivity of 96% and pooled specificity of 99%, and was superior in direct comparison to IVU in
terms of sensitivity and specificity .
Retrograde pyelography does not rely on renal excretion of intravascular contrast. In patients with impaired renal
function, or contraindications to CTU or MRU, or suboptimal CTU or MRU, a retrograde pyelography may be used
in addition to cystoscopy in patients with suspected upper tract lesions .

Magnetic Resonance Urography

MRU can be performed with or without contrast. MRU without contrast is an excellent technique to demonstrate the
cause and level of urinary obstruction, particularly if it is not due to calculus disease. The sensitivity of MRU in
detecting urothelial lesions is remains under investigation, and at present it is not believed to be the equivalent of
either IVU or CTU .However, in patients who cannot receive iodinated contrast material or are radiation sensitive,
MRU can be useful

MRI and CT have shown comparable accuracy in detection and characterization of most renal lesions.
However,with indeterminate renal lesions on CT or complicated cysts, MRI can be useful for better characterization

Other Imaging Studies

1.Plain radiography of the abdomen and pelvis (KUB) is not used as first line image modalities for initial
evaluation of hematuria. KUB may be useful in patients with history of kidney stones for evaluation of stone size
and position and for assessment of stone passage.

2.Catheter angiography may be useful for diagnosis and for therapeutic interventions in vascular disorders such
as aneurysms, arterio-venous malformations or obstruction of a calyx from overlying artery (Fraley’ssyndrome)
which may result in hematuria.

For the majority of patients with hematuria, multidetector CTU remains

the best overall imaging modality due to its widespread availability, ability to detect a range of possible
causes including small renal masses, calcifications and stones and ability to image the upper tract collecting
system.

UROLITHIASIS
It is a common problem and a cause of significant patient morbidity. Imaging plays an important role in the
diagnosis; pretreatment planning and post treatment follow up of patients with urinary tract calculi.
CT-Non contrast CT or the Stone protocol CT is the gold standard for imaging of urolithiasis.it allows
imaging of all parts of the urinary tract with superior spatial and contrast resolution without the need of iv contrast
media, CT has the added benefit of providing an alternate diagnosis like appendicitis or tubo ovarian abscess in
patients presenting with acute flank pain.
The only drawback of CT is the radiation dose to the patient, with technical advancements; low dose CT protocols
are now available which decrease the radiation dose to the patient.

ULTRASOUND
Ultrasound is an easily available technique which is cheap and has no risk of radiation.it is an excellent technique
for the evaluation of renal collecting system,renal parenchyma and the urinary bladder but there is poor visualisation
of the ureters,particularly in obese patients or with a large amount of bowel gas.
Ultrasound is less sensitive than CT for the detection of intrarenal calculi but is highly sensitive for the
detection of ureteral obstruction in the clinical setting of acute flank pain. Ultrasound has been found to be up to
100% sensitive and 90% specific for the diagnosis of ureteral obstruction in patients presenting with acute
flank pain. US findings of obstructive uropathy include hydronephrosis, ureterectasis, and perinephric fluid.
However, within the first 2 hours of presentation, these findings are less sensitive because, hydronephrosis may not
have had time to develop. However, the sensitivity of US as compared to NCCT for detecting stones overall can be
quite low, ranging from 24%–57%, and is especially poor for small stones. Ultrasound overestimates stone size, is
less sensitive to small stones and for ureteric calculi.
Doppler can aid in the evaluation of nephrolithiasis with the sonographic twinkling artefact seen in cases of calculi.

PLAIN XRAY KUB

Plain radiograph is in our country is the initial imaging modality for the detection of calculi. It has poor
sensitivity to radiolucent calculi and radiopaque calculi can also be obscured by bowel content. XRAY KUB should
be done after bowel preparation. The sensitivity of the KUB for ureterolithiasis varies depending on a number of
factors, including stone composition, location, and size, as well as patient body habitus and overlying bowel
contents.

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Role OF Xray KUB in Urinary calculi
1 In the follow up of ureteral calculi where medical therapy has been done and where calculi were initially visible
on the CT scout film
2 In treatment planning –ESWL
3 In the evaluation of ureteral stents

Intravenous Urography
The IVU was the previous standard study for ureterolithiasis. It provides information regarding site and degree of
obstruction, stone size, and effect of obstruction on renal excretion. IVU has a number of relative contraindications,
including renal insufficiency, dehydration, past reaction to iodinated contrast agents, and pregnancy.

Magnetic Resonance Imaging

MRI can be considered as an alternative to low-dose NCCT in certain patient populations, such as pregnant women
(noncontrast MRI), young individuals, and individuals who have undergone multiple prior CT examinations .In
general, MRI is highly accurate for the diagnosis of hydronephrosis and perinephric edema but is less accurate in
directly visualizing stones as compared to NCCT.

WHAT IMAGING TO BE DONE FOR URINARY CALCULI?

Combined imaging using ultrasound to determine obstruction of the urinary system with Xray KUB to detect calculi
is a common imaging strategy in the setting of loin pain. This has less sensitivity than the stone protocol/CTU.
These 2 modalities are accurate enough in the detection of clinically significant stones and KUB/US can be an
acceptable alternative to NCCT for some patients. In one prospective study of 66 patients, the KUB/US combination
had a sensitivity of 79% (versus 93% for NCCT) for detecting stones.

WHAT IS TO BE SEEN ON IMAGING OF CALCULUS DISEASE??

1. Stone size-is an important factor in deciding the management. Expectant management is often performed for
small asymptomatic stones. Larger asymptomatic stones may be considered for treatment given the likelihood of
enlargement and progression into ureter.Symptomatic intrarenal calculi <1 cm may undergo ESWL or ureteroscopy.
stones 1-2 cm will have ESWL,URS or percutaneous nephrolithotomy(PCNL),stones larger than 2cm will require
PCNL or rarely laproscopic or open surgical intervention. Because urologic management is based on maximal stone
diameter, stone measurements should be provided in the coronal and axial plane.

2.Stone location-this will determine calcyeal access.lower calcyeal stones are less responsive to ESWL,especially
in the setting of unfavourable lower lobe morphology(long lower pole calyces and narrow infundibuli).success of
ESWL is inversely proportional to the stone size and skin stone distance.

3. Stone composition-imaging may help to detect the stone composition to aid treatment. Uric acid stones and
struvite stones are radiolucent at plain radiography. Calcium phosphate and oxalate stones are seen on radiography.
Pure protein matrix and indinavir stones have soft tissue attenuation and can be difficult to visualise on CT.Uric acid
stones have a lower CT numbers (200-450 HU) than most calcium stones (1200-2800 HU). Dual energy CT is a
new technique which is able to distinguish pure uric acid stones from non uric acid stones with a high degree of
certainty

URINARY BLADDER MALIGNANCY

The diagnosis of bladder cancer is clinical and requires cystoscopy with biopsy. While the diagnosis can be made on
an IV urogram or cystogram, a small tumour, especially one of the infiltrative type, can remain undetected.
Furthermore, a dense concentration of contrast material may obscure the intraluminal part of the tumour US has
proved valuable in identifying bladder tumours. The detection rates are as high as 100% have been reported for
lesions greater than 0.5 cm, but difficulties related to tumour size (< 5 mm) or location (near the vesicle neck) often
limit the value of US. Bladder tumour detection rates for CT and MRI are higher than those for US or conventional
radiographic studies.

CT virtual cystoscopy—3D imaging of the intraluminal surface of the bladder—has been compared to conventional
fibreoptic cystoscopy in the detection of bladder tumours. The advantages of CT virtual cystoscopy (noninvasive, no
general anaesthetic required) make it a potentially useful tool for post-treatment surveillance.
CT in carcinoma of the bladder is to stage rather than to detect the primary neoplasm. The staging accuracy of CT
increases with more advanced disease CT cannot differentiate between the various layers of the bladder wall and
cannot, therefore, distinguish lesions limited to the lamina propria (T1) from those invading the superficial (T2) and
deep (T3a) muscle.CT is clinically useful for detecting invasion into the perivesical fat (T3b) ,involvement of
adjacent viscera and pelvic lymph nodes (category N) and distant metastases (category M)
.

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MRI is slightly better than CT for the evaluation of tumours at the bladder base or dome, for differentiation between
deep muscular (T3a) and perivesical (T3b) tumour invasion and for the demonstration of stage T4 disease. MR
imaging has been shown to better depict intramural tumor invasion as well as extravesical extension and allows
differentiation between muscle-invasive and non-muscle-invasive disease.In addition, MR imaging has the
advantage of involving no ionizing radiation

PROSTATE
The bladder neck can be imaged by transrectal (TRUS) and a urodynamic assessment of the bladder may include
ultrasound studies to show an open or closed bladder neck. Zonal anatomy is routinely seen on TRUS .The
peripheral zone is imaged with homogeneous medium echogenicity. The transition zone is imaged with lower
echogenicity and often has a heterogeneous echo pattern. Dense echogenic foci at the margin between the peripheral
and transition zones can be seen; these represent corpora amylacea. The normal prostatic urethra is only rarely
visualized, but the position of the urethra can be assessed by inserting a Foley catheter, and a dilated prostatic
urethra after TURP is easily demonstrated. Prostate size can be evaluated on ultrasound and post void residual urine
can be measured
On TRUS, the demonstration of acute prostatitis is nonspecific. Differentiation on US between an inflammatory and
malignant process is not possible.CT can be helpful in establishing the diagnosis of prostatic abscess in several
clinical situations:
1 patients who have an enlarged indurated prostate without fluctuation on rectal examination
2 patients with unexplained continued infection of the urinary tract
3 Complicated or unresponsive cases of urinary tract infection.

Transrectal ultrasound of the prostate, combined with transrectal biopsy, is widely applied in the detection of early
carcinoma of the prostate
Multiparametric MRI -Which includes T2 Weighted imaging and advanced applications like diffusion weighted
imaging and dynamic contrast enhanced MRI ,MR spectroscopyis now the imaging method of choice in patients
suspected to have carcinoma prostate. It allows diagnosis ,localisation,stratification and staging of clinically
significant cancerThe major role of MRI in prostatic carcinoma is in the local staging of the disease.A recent study
found that MRI performed significantly better than DRE in detecting cancer in the apex, mid-gland and base, and
significantly better than TRUS-guided biopsy in the mid-gland and base. Unlike DRE, MRI was capable of
detecting tumour in the anterior prostate

TRAUMA
CT is the primary diagnostic tool for the rapid and accurate assessment of acute traumatic genitourinary injuries, as
well as for the diagnosis of related complications. In selected situations, other techniques—including intravenous
and retrograde urography, ultrasound, renal nuclear scintigraphy, renal angiography and renal MRI—are required.
For suspected bladder injury, CT cystogram has to be done. However, in the acute phase of post-traumatic imaging,
CT is the most efficient and information-intensive study to ascertain the entire spectrum of injury. Interventional
radiology is used to manage vascular renal injury and complications of urinary tract injury, such as infected urinoma
or partial ureteral tear.

Radiation Issues
When requisitioning for a radiological investigation, one must always keep in mind the fact that x ray, IVP, CT &
CT urography are modalities that use radiation. The effective radiation dose from a single abdominal radiograph is
approximately 0.8 mSv as compared to 10–12 mSv for conventional NCCT of the abdomen and pelvis and 3–4 mSv
for low-dose NCCT of the abdomen and pelvis. However, multiple radiographs can reach an exposure range similar
to a low-dose CT. For example, a KUB with bilateral oblique views results in an effect radiation dose of
approximately 2.4–2.7 mSv

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 Surgical Nutrition
Nikhil Talwar

INTRODUCTION
Perioperative nutrition is a vital yet often overlooked aspect of surgical care. The association between poor
nutritional status and surgical outcomes has been clearly and repeatedly demonstrated for decades. Malnutrition may
be defined as “a disorder of body composition in which macronutrient and/or micronutrient deficiencies occur when
nutrient intake is less than required.” For all hospitalized patients, the reported prevalence of malnutrition is as high
as 50%. A malnourished patient is more likely to have infectious morbidity, a prolonged hospital stay and increased
mortality.

1. SURGICAL STRESS RESPONSE

The response to surgical stress involves endocrine and inflammatory responses. Injury stimulates the hypothalamic-
pituitary-adrenal (HPA) axis that ultimately results in increased secretion of growth hormone, cortisol, epinephrine,
glucagon, aldosterone and antidiuretic hormone. On the other hand, the inflammatory response is largely mediated
via numerous cytokines including tumor necrosis factor-alpha, interleukin-1 (IL-1), and IL-6. Cytokines also
stimulate the HPA axis, thus creating interplay between the endocrine and inflammatory responses.

These mediators create a catabolic state (hypermetabolic response) designed to meet the increased energy demands
of stressed patients. Glucose, fatty acids, and protein are all readily available substrates. Glycogen stores are rapidly
depleted and skeletal muscle is then used for hepatic gluconeogenesis.

2. NUTRITION THERAPY
Nutrition therapy (Synonym: nutritional support) is defined according to the European Society for Clinical Nutrition
and Metabolism (ESPEN): Nutrition therapy is the provision of nutrition or nutrients either orally (regular diet,
therapeutic diet, e.g. fortified food, oral nutritional supplements) or via enteral nutrition (EN) or parenteral nutrition
(PN) to prevent or treat malnutrition. “Medical nutrition therapy is a term that encompasses oral nutritional
supplements, enteral tube feeding (enteral nutrition) and parenteral nutrition”

2.1 NUTRITIONAL ASSESSMENT

A systematic nutritional screening should be done in all patients on hospital admission. The goal of screening is to
identify and optimize or “prehabilitate” patients at nutritional risk for the stress of surgery. Potential causes of
preoperative malnutrition include malignancy, inability to swallow, a lack of access to nutrition, or gastrointestinal
tract dysfunction.

Nutritional care protocols for surgical patient must include:

- A detailed nutritional and medical history including history of nausea, vomiting, abdominal distension,
constipation and oral intake
- Complete clinical examination, BMI calculation,
- A nutrition intervention plan for nutrient intake from enteral/parenteral route, fluid balance
- Resistance exercise whenever possible
- Assessment of nutritional and clinical outcome
Biomarkers like Serum albumin, C-reactive protein, and glycated hemoglobin (HbA1C) may be used for a
comprehensive assessment. Preoperative serum albumin is a prognostic factor for complications after surgery. A
serum albumen <3gm/l (in absence of hepatic or renal dysfunction) has been considered as a severe nutritional risk
in some studies.

2.2 INDICATIONS FOR NUTRITIONAL SUPPORT

In the surgical patient, the indications for nutritional therapy are prevention and treatment of catabolism and
malnutrition. This affects mainly the perioperative maintenance of nutritional state in order to prevent postoperative
complications. Therapy should start as a nutritional risk becomes apparent.
Patients who require nutritional support include:
- Declining or low recent oral intake
- Patient will be unable to eat for more than five days perioperatively
- BMI < 18.5 kg/m2
- Actual body weight of less than 90% of the ideal body weight
- Weight loss > 5% within 1 month, >7.5% in 3 months, and > 10% in 6 months

2.3 DAILY REQUIREMENTS

The basal daily caloric requirement is 20 to 25 kcal per kg of ideal body weight per day.

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The protein requirement is 0.75 to 1 gm/kg/day. 40-50% energy requirement should be met from lipids, 25-45%
from carbohydrates and 15% from proteins.
Rule of nines similar to the one used for fluid resuscitation in burns patients. A 9% increase is done for one major
fracture, 1% increase for every burn. For peritonitis, 18 % increase (similar to the allocation of abdomen in burns)
from the basal requirement is done and 9% increment is done for every 1-degree centigrade rise of temperature.

3. ROUTE OF DELIVERY: Enteral vs Parenteral

The enteral and parenteral routes of delivery are available for supplementation in surgical patients. Substantial
evidence indicates that early enteral nutrition is associated with significant reductions in morbidity and mortality.

3.1 ENTERAL NUTRITION

Enteral nutrition (EN) is currently recommended over parenteral nutrition by all major nutrition and critical care
organizations. Enteral feeding is cheaper, easier and physiological. The immune function of the gut is maintained by
EN.

Gut-associated lymphoid tissue (GALT), a form of mucosa-associated lymphoid tissue is responsible for 60-70% of
total immunity. The gut also provides a physical barrier to infection through the production of mucin and the
presence of tight junctions. Gut starvation and/or critical illness induce changes to the immune function of the
gastrointestinal tract. Lack of enteral feeding causes villous blunting and increased mucosal permeability potentially
allowing bacterial translocation and bacteremia. Additionally, gut starvation decreases hepatic and peritoneal
immune function. Enteral nutrition attenuates these deleterious effects and multiple studies have shown improved
outcomes with early initiation of enteral feeding.
In the absence of a definite contraindication, enteral nutrition should be initiated in all patients, preferably within 24
hours of surgery.

Contraindications to enteral nutrition include:

- Intestinal obstruction or ileus,
- Intestinal ischemia,
- Peritonitis,
- High output fistulas
- Severe shock
- Severe malabsorption
- Severe intestinal hemorrhage

3.1.1 Routes of enteral nutrition

Oral feeding may not be possible due to a variety of reasons. The various routes available include placement of a
nasogastric tube, a small-bore nasojejunal feeding tube into the postpyloric position, an percutaneous endoscopic
gastrostomy (PEG) or a needle catheter jejunostomy placed surgically.
Indications for tube feeding: With special regard to malnourished patients, placement of a nasojejunal tube (NJ) or
needle catheter jejunostomy (NCJ) should be considered for all candidates for tube feeding undergoing major upper
gastrointestinal and pancreatic surgery. Surgically placed tubes are reserved for patients undergoing concomitant
abdominal surgery.
If long term TF (>4 weeks) is necessary, e.g. in severe head injury, placement of a percutaneous tube (e.g.
percutaneous endoscopic gastrostomy i.e. PEG) is recommended.
Timing: If tube feeding is indicated, it shall be initiated within 24 h after surgery.
Formulae for feeding: In most patients, a standard whole protein formula is appropriate. For technical reasons with
tube clogging and the risk of infection the use of kitchen-made (blenderized) diets for tube feeding is not
recommended in general.

3.2 PARENTERAL NUTRITION

Total parenteral nutrition (TPN) was invented by Dr. Stanley Dudrick and revolutionized perioperative care. Normal
osmolarity of plasma is 290 +10 mmol/L. The osmolarity of a TPN solution can be as high as 1200 mmol/L if the
volume is to be limited to usual fluid requirement. Such a hypertonic infusion would case sclerosis of peripheral
veins. The only way this can be done safely is through a central venous catheter in in internal jugular vein or in
subclavian vein. Parenteral nutrition is undoubtedly capable of providing excellent nutrition; however, there are
significant risks with TPN. Risks associated with TPN include complications due to central venous access,
hyperglycemia (as carbohydrates by pass the liver), changes in the immune functions of the gastrointestinal tract due
to disuse and deficiency of various micronutrients. TPN is also costlier and requires close monitoring of electrolytes
and micronutrients.

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3.2.1 Indications of TPN
Parenteral nutrition should be considered as an adjunct for patients unable to meet their full nutrition requirements
with enteral nutrition or as a primary modality in patients with a contraindication to enteral feeding. Also, If the
energy and nutrient requirements cannot be met by oral and enteral intake alone (< 50% of caloric requirement) for
more than seven days, a combination of enteral and parenteral nutrition is recommended.

3.2.2 Timing of TPN

Parenteral nutrition shall be administered as soon as possible if nutrition therapy is indicated and there is a
contraindication for enteral nutrition, such as in intestinal obstruction.
Combined nutrition (EN+TPN) is not necessary if the expected time period of TPN is <4 days. If the expected TPN
period is expected to last between 4 and 7 days, nutrition can be hypocaloric with 2 g carbohydrate and 1 g amino
acids/kg body weight administered via a peripheral catheter, and if it is likely to last more than 7-10 days, it is
recommended that a central venous catheter should be inserted.

3.2.3 Administration
For administration of parenteral nutrition an all-in-one (three-chamber bag or pharmacy prepared) should be
preferred instead of multibottle system.

3.2.4 Hyperglycaemia
In order to avoid hyperglycaemia, intensive insulin therapy is recommended for critically ill patients. Due to an
incalculable risk of hypoglycaemia, intensive insulin therapy is not appropriate in postsurgical patients on the
general ward with less staffing. Therefore, the amount of glucose-based calories in PN should be reduced in case of
blood sugar levels exceeding 180mg/dl. For patients with very unstable and high glucose levels ICU care is to be
preferred.

4. PRE-OPERATIVE NUTRITION
For patients at high risk, preoperative conditioning is required to optimize the patient’s status before major elective
surgery. In cases of severe metabolic risk, 10-14 days of nutritional therapy is indicated. For mildly malnourished
patients, short term (7-10 days) nutritional conditioning has to be considered. Nutritional support should be
combined with resistance exercise.
Preoperative parenteral nutrition should be administered only in patients with malnutrition or severe nutritional risk
where energy requirement cannot be adequately met by EN. A period of 7 to 14 days is recommended.
In the truly infected patient immediately dealing with the focus of sepsis (“source control”) should have priority and
no major surgery should be performed (risky anastomoses, extensive dissections etc.). Definitive surgery should be
performed at a later stage when sepsis has been treated adequately. In such cases, at least 6 weeks and sometime
longer may be required to restore a metabolic and nutritional state allowing a successful reoperation.

4.1 PRE-OPERATIVE FASTING

Preoperative fasting from midnight is unnecessary in most patients. European Society for Clinical Nutrition and
Metabolism (ESPEN) guidelines recommend that patients undergoing surgery, who are considered to have no
specific risk of aspiration, should be allowed to drink clear fluids until two hours before anaesthesia. Solids should
be allowed until six hours before anaesthesia. There is no evidence that patients given clear fluids up to two hours
before elective operations are at any greater risk of aspiration or regurgitation than those fasted for the traditional 12
h or longer, since clear fluids empties the stomach within 60 to 90 minutes. Exceptions to this recommendation are
patients “at special risk” undergoing emergency surgery, and those with known delayed gastric emptying for any
reason or gastro-oesophageal reflux. Since the implementation of these guidelines, there has been no report of a
dramatic rise in the incidence of aspiration, regurgitation, or associated morbidity or mortality.

5. POST-OPERATIVE NUTRITION
ESPEN Guidelines recommend that “In general, oral nutritional intake shall be continued after surgery without
interruption” in the post-operative period. It is recommended to adapt oral intake according to individual tolerance
and to the type of surgery carried out with special caution to elderly patients. Oral intake, including clear liquids,
should be initiated within few hours after surgery in most patients.
Patients undergoing bowel surgery should be administered fluids judiciously and pain control should be adequate.
Preventing fluid overload decreases bowel wall edema, and adequate analgesia facilitates early ambulation.

Oral nutrition can be initiated, in most cases, immediately after cholecystectomy or colorectal resection. In
comparison with conventional open surgery, early oral intake is tolerated even better after laparoscopic colonic
resection, due to earlier return of peristalsis and bowel function with laparoscopy.
It must be emphasized, that good evidence is available for early oral intake only for patients undergoing colorectal
surgery. With special regard to the elderly the benefits are less clear in patients undergoing upper gastrointestinal
and pancreatic surgery.

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5.1 Early postoperative tube feeding
Early tube feeding (within 24 h) should be initiated in patients in whom early oral nutrition cannot be started, and in
whom oral intake will be inadequate (<50%) for more than 7 days.
These include:
• Patients undergoing major head and neck or gastrointestinal surgery for cancer
• Patients with severe trauma including brain injury
• Patients with obvious malnutrition at the time of surgery
Early enteral feeding via a jejunustomy tube is associated with improved outcomes in proximal gastrointestinal
cancer resections.

6. NUTRITION IN ORGAN TRANSPLANTATION

• alnutrition is a ma or factor influencing outcome after transplantation so monitoring of the nutritional
status is recommended. Undernutrition is likely to lead to a faster progression of the underlying disease.
• In malnutrition, additional oral nutritional supplements or even tube feeding is advised.
• Regular assessment of nutritional status and qualified dietary counselling shall be required while
monitoring patients on the waiting list before transplantation.
• Recommendations for the living donor and recipient are not different from those for patients undergoing
major abdominal surgery.
• After heart, lung, liver, pancreas, and kidney transplantation, early intake of normal food or enteral
nutrition is recommended within 24 h.
• Even after transplantation of the small intestine, enteral nutrition can be initiated early, but should be
increased very carefully within the first week.

7. NUTRITIONAL THERAPY IN BARIATRIC SURGERY

• Early oral intake can be recommended after bariatric surgery. Parenteral nutrition is not required in
uncomplicated bariatric surgery.
• In case of a major complication with relaparotomy the use of a nasojejunal tube/needle catheter
jejunostomy is indicated. Even in case of major complications after bariatric procedures EN has
proven advantages with regard to mortality and higher cost-effectiveness
• Further recommendations are not different from those for patients
• undergoing major abdominal surgery

8. IMMUNONUTRITION
Immunonutrition is a relatively new aspect of perioperative care and refers to the supplementation of specific
nutrients, including arginine, omega-3 fatty acids, nucleotides, and/or glutamine. These nutrients are hypothesized to
influence the immune and inflammatory response to surgical stress.
There is no convincing evidence to recommend the use of oral or parenteral glutamine and arginine. Postoperative
parenteral nutrition including omega-3-fatty acids should be considered only in patients who cannot be adequately
fed enterally, and, therefore require TPN.

References
1. Cederholm T, Barrazoni R, Austin P, Ballmer P, Biolo G, Bischoff SC et al. ESPEN guidelines on definitions and
terminology of clinical nutrition. Clin Nutr. 2017; 36(1): 49–64
2. Weimann A, Braga M, Carli F, Higashiguchi T, Hübner M, Klek S, Laviano A et al. ESPEN guideline: Clinical
nutrition in surgery. Clin Nutr. 2017; 36(3): 623-650
3. Codner PA. Enteral nutrition in the critically ill patient. Surg Clin North Am. 2012; 92(6): 1485-501.
4. Phillips MS, Ponsky JL. Overview of enteral and parenteral feeding access techniques: principles and practice. Surg
Clin North Am. 2011; 91(4): 897-911

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 LYMPHEDEMA
Trilok Chand
Introduction:
Lymphoedema is abnormal limb swelling caused by the accumulation of increased amounts of high protein,
interstitial fluid secondary to defective lymphatic drainage in the presence of normal net capillary filtration. The
incidence of lymphedema at birth is one in 6000 but the overall prevalence is about 0.13-2.0 %. The
classification of lymphedema is defined by the origin of the condition, i.e. primary or secondary.

Primary Lymphedema: Lymphedema due to developmental defect in lymphatic system is called Primary
lymphedema 1-3. Primary lymphedema with onset before the first year of life is called congenital. The familial
version of congenital lymphedema is known as Milroy disease and is inherited as a dominant trait. primary
lymphedema with onset between the ages of 1 and 35 years is called lymphedema Praecox. The primary
lymphedemas are relatively uncommon, occurring in one of every 10,000 individuals. The most common form
of primary lymphedema is praecox, which accounts for approximately 80% of the patients. The familial version
of lymphedema Praecox is known as Meige disease. Primary lymphedema with onset after the age of 35 years is
called lymphedema Tarda.

Secondary Lymphedema: Secondary lymphedema can result from many external factors that alter, both
anatomically and functionally, an otherwise normal lymph-conducting system.4 The common causes of
secondary lymphedema are trauma, malignancy, venous disease, infection, inflammation, immobility, parasites,
and factitious conditions. there is no cure for an already damaged lymphatic system. All lymphedemas should be
considered secondary until proven otherwise 5-6. Table is showing the causes of secondary lymphedema.
Classification of causes of secondary lymphoedema.
Classification Examples
1. Trauma and tissue damage Lymph node excision, Radiotherapy
Burns, Varicose vein surgery/harvesting
Large/circumferential wounds, Scarring
2. Malignant disease Lymph node metastases, Infiltrative carcinoma,
Lymphoma
Pressure from large tumours
3. Venous disease Chronic venous insufficiency, Venous ulceration,
Post-thrombotic syndrome
Intravenous drug use
4. Infection Filariasis, Cellulitis/erysipelas
Lymphadenitis, Tuberculosis
5. Inflammation Rheumatoid arthritis, Dermatitis
Psoriasis, Sarcoidosis
Dermatosis with epidermal Involvement
6. Endocrine disease Pretibial myxoedema
7. Immobility and dependency Dependency oedema
Paralysis

Filariasis is the most common cause of secondary lymphoedema worldwide, affecting up to 100 million
individuals. It is particularly prevalent in Africa, India and South America where 5–10% of the population may
be affected. The viviparous nematode Wucheria bancrofti, whose only host is man, is responsible for 90% of
cases and is spread by the mosquito. The parasite enters lymphatics from the blood and lodges in lymph nodes,
where it causes fibrosis and obstruction, due partly to direct physical damage and partly to the immune response
of the host. Proximal lymphatics oedema is often massive, in which case it is termed elephantiasis. Immature
parasites (microfilariae) enter the blood at night and can be identified on a blood smear, in a centrifuged
specimen of urine or in lymph itself. Complement fixation test is positive in present or past infection.
Eosinophilia is usually present.

Lymphadenectomy, or surgical excision of the inguinal, iliac, or auxiliary lymph nodes, the most common non-
infectious cause worldwide, especially following breast cancer treatment. The incidence of upper extremity
lymphedema varies from 2% to 40% in women with breast cancer who have been treated with surgery, radiation,
or both. Overall prevalence of clinically significant lymphedema was 33.5% and severe lymphedema was
observed in 17.2% of patients. The prevalence of lymphedema was 13.4% in patients treated with surgery only
whereas the prevalence was 41.1% in patients treated with surgery and radiotherapy7. Nonsurgical trauma, e.g.
radiation therapy to lymph node groups, may cause chronic unilateral swelling. Surgery of the prostate, uterus, or
cervix may cause bilateral swelling. Recurrent and metastatic malignancy. Hodgkin and non-Hodgkin

96
lymphoma. Reconstructive arterial surgery, e.g. saphenous vein harvesting for coronary artery bypass are the
other causes of secondary lymphedema.

Mechanisms of lymph transport: Initial lymphatics drain into terminal (collecting) lymphatics that possess
bicuspid valves and endothelial cells rich in the contractile protein actin. Larger collecting lymphatics are
surrounded by smooth muscle. Valves partition the lymphatics into segments (lymphangions) that contract
sequentially to propel lymph into the lymph trunks. Lymph trunks Terminal lymphatics lead to lymph trunks,
which have a single layer of endothelial cells, lying on a basement membrane overlying a media comprising
smooth muscle cells that are innervated with sympathetic, parasympathetic and sensory nerve endings. About
10% of lymph arising from a limb is transported in deep lymphatic trunks that accompany the main
neurovascular bundles. The majority, however, is conducted against venous flow from deep to superficial in
epifascial lymph trunks. Superficial trunks form lymph bundles of various sizes, which are located within strips
of adipose tissue, and tend to follow the course of the major superficial veins

Resting ISF pressure is negative (-2 to -6 mmH2O), whereas lymphatic pressures are positive, lymph flows
against a small pressure gradient. prograde lymphatic flow depends upon three mechanisms:
1. Transient increases in interstitial pressure secondary to muscular contraction and external compression;
2 The sequential contraction and relaxation of lymphangions
3 The prevention of reflux because of valves.

Pressures of up to 30–50 mmHg have been recorded in normal lymph trunks and up to 200 mmHg in severe
lymphoedema. Lymphatics may also modulate their own contractility through the production of nitric oxide and
other local mediators. Lymphangions are believed to respond to increased lymph flow in much the same way as
the heart responds to increased venous return, in that they increase their contractility and stroke volume.

In the normal condition the volume of interstitial fluid compartment is about 50% of wet weight of skin and
subcutaneous tissue. In a 70 kg man it will be about 10-12 L and it contains 20-30g/l protein. For clinically
visible oedema the volume of ISF should increase just double. About 8 litres of lymph is produced each day with
protein concertation similar to ISF (20-30g/l) and travels in afferent lymphatics to lymph nodes. There, the
volume is halved and the protein concentration doubled, resulting in 4 litres of lymph re-entering the venous
circulation each day via efferent lymphatics. Any blockage or destruction of lymphatics leads to lymphedema.

Diagnosis: In most patients, the diagnosis of lymphedema can be readily determined from the clinical history
and physical examination confounding conditions such as morbid obesity, lipohyperdystrophy, endocrine
dysfunction, venous insufficiency, unrecognized trauma, and repeated infection may complicate the clinical
picture. The basis of unilateral extremity lymphedema, especially in adults, solid organ tumours (primary and/or
metastatic), lymphomas, and soft tissue sarcomas which may obstruct or invade more proximal lymphatics need
to be considered. Thorough medical evaluation is indispensable before embarking on lymphedema treatment.

Differential Diagnosis: Patients with second- or third-stage lymphedema, the characteristic findings on physical
examination can usually establish the diagnosis. The oedematous limb has a firm and hardened consistency.
There is loss of the normal peri malleolar shape, resulting in a “tree trunk” pattern. The dorsum of the foot is
characteristically swollen, resulting in the appearance of the “buffalo hump,” and the toes become thick and
squared. In advanced lymphedema, the skin undergoes characteristic changes, such as lichenification,
development of peau d’orange and hyperkeratosis Patients with isolated lymphedema usually do not have the
hyperpigmentation or ulceration one typically sees in patients with chronic venous insufficiency. Lymphedema
does not respond significantly to overnight elevation, whereas oedema secondary to central organ failure or
venous insufficiency does.

INVESTIGATION OF LYMPHEDEMA

Routine Test
These include a full blood count, liver function test, kidney function test, thyroid function test, total protein and
albumin, fasting glucose, C-reactive protein, urine dipstick including observation for microfilariae, chest
radiograph.

Ultrasonography
Ultrasound and duplex-Doppler studies can provide useful information about venous function including Deep
Vein Thrombosis and venous abnormalities.

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Lymphoscintigraphy (or isotope lymphography) LAS
LAS is the test of choice in patients with suspected lymphedema. It cannot differentiate between primary and
secondary lymphedemas. It has sensitivity of 70% to 90% and specificity of nearly 100% in differentiating
lymphedema from other causes of limb swelling. The test assesses lymphatic function by quantitating the rate of
clearance of a radiolabelled macromolecular tracer.

This technique is simple, safe, and reproducible, with small exposure to radioactivity (approximately 5 mCi).
injection of a small amount of radio iodinated human albumin or technetium Tc 99m–labelled sulphur colloid
into the first interdigital space of the foot or hand. Migration of the radiotracer within the skin and subcutaneous
lymphatics is monitored with a whole-body gamma camera, thus producing clear images of the major lymphatic
channels in the leg as well as measuring the amount of radioactivity at the inguinal nodes 30 and 60 minutes
after injection of the radiolabelled substance in the feet.

An uptake value that is less than 0.3% of the total injected dose at 30 minutes is diagnostic of lymphedema. The
normal range of uptake is between 0.6% and 1.6%. In patients with edema secondary to venous disease, isotope
clearance is usually abnormally rapid, resulting in more than 2% ilioinguinal uptake. Importantly, variation in
the degree of oedema involving the lower extremity does not appear to significantly change the rate of clearance
of the isotope.

Fig-2.In the (A) sagittal view and (B) axial view of the
Fig-1.9 Lymphedema in her left leg is confirmed by the lower extremities, an MRI shows an extensive
lymphoscintigram, which shows marked dermal backflow honeycombed pattern in the soft tissue, a hallmark of
chronic lymphedema not found in other oedemas.

Computed tomography (CT): A single, axial CT slice through the mid-calf has been proposed as a useful
diagnostic test for lymphoedema it shows coarse, non-enhancing, reticular ‘honeycomb ’pattern in an enlarged
subcutaneous compartment.
Venous oedema (increased volume of the muscular compartment) and lipoedema (increased subcutaneous fat).
CT can also be used to exclude pelvic or abdominal mass lesions. It can also be used to monitor response to
treatment through serial measurements of cross-sectional area and tissue density.

Magnetic resonance imaging (MRI): Non-contrast MRI is useful in identifying the classical circumferential
reticular pattern (honeycomb) within the epifascial compartment. Involvement of the sub fascial compartment is
more suggestive of venous disease.

Pathological examination:
In cases in which malignancy is suspected, samples of lymph nodes may be obtained by fine-needle aspiration,
needle core biopsy or surgical excision. Skin biopsy will confirm the diagnosis of lymphangiosarcoma.

STAGING
Staging is based on clinical manifestations according international society of lymphology (ISL) consensus 2016
it divided into 4 stage10.
Stage 0 (or Ia) It is a latent or subclinical condition where swelling is not yet evident despite impaired lymph
transport. Assessment of early fluid changes can be accomplished using bioimpedance spectroscopy.
Stage I represents an early accumulation of fluid relatively high in protein content (e.g., in comparison with
“venous” oedema) which subsides with limb elevation. Pitting may occur. An increase in various types of
proliferating cells may also be seen.
Stage II signifies that limb elevation alone rarely reduces the tissue swelling and pitting is manifest. Later in
Stage II, the limb may not pit as excess subcutaneous fat and fibrosis develops.

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Stage III encompasses lymphostatic elephantiasis where pitting can be absent and trophic skin changes such as
acanthosis, alterations in skin character and thickness, further deposition of fat and fibrosis, and warty
overgrowths have developed.

Staging on the basis of difference in limb size-

Mild: less than 3 cm differential between affected and unaffected limbs
Moderate: 3 to 5 cm differential between affected and unaffected limbs
Severe: more than 5 cm differential between limbs.

MANAGEMENT OF LYMPHEDEMA
Problem with disease
1. Patient choose not to seek medical advice because of embarrassment and a belief that nothing can be
done.
2. Lymphoedema is often misdiagnosed and mistreated.
3. Early diagnosis is important because relatively simple measures can be highly effective at this stage and
will prevent development disabling late stage disease.
4. It is also an opportunity for patients to contact patient support groups.
5. failure to control lymphedema may lead to repeated infections (cellulitis/lymphangitis),
6. progressive elephantine trophic changes in the skin, sometimes crippling invalidism and on rare
occasions, the development of a highly lethal lymphangiosarcoma (Stewart-Treves syndrome).

The treatment is a team approach, in patients with establish oedema three goals of treatment are
1. To relieve pain,
2. Reduce swelling,
3. Prevent the development of complications.

Prevention/Early Identification and Treatment

The concepts of “primary” and “secondary” prevention (including risk reduction) are receiving increased
attention. Intraoperative imaging techniques to lessen lymphatic system impact by identifying lymphatic vessels
to avoid during procedures as well as performing prophylactic lymphaticvenous shunts in high-risk patients.
A. Non-operative Treatment
1. Physical therapy and adjuvants
Complex Decongestive Therapy (CDT) or Combined Physical Therapy (CPT) it has two stage
treatment Programme:

Phase I: Intensive Treatment

Manual lymph drainage (MLD)
Skin care (including wound care if indicated)
Bandaging (specialized)(MLLB)
Exercise (in bandages)
Compression garment (if appropriate)

Manual Lymphatic Massage (MLB) is done by trained health care professionals. It is based on
physiologic principles that regulate the flow of lymph. MLB has many effects on the lymph system by:
increasing lymph transport capacity, thereby increasing the volume of lymph fluid transported
proximally increasing the frequency of lymph vessel contractions increasing pressure in the lymph
collector vessels redirecting natural flow patterns toward collateral vessels, anastomoses, and
uninvolved lymph node regions increasing arteriolar blood flow.

Multilayer lymphoedema bandaging (MLLB) are Elastic bandages provide compression, produce a
sustained high resting pressure and ‘follow in’ as limb swelling reduces and exercises and sometimes
deeper techniques. The pressure exerted must be graduated (100% ankle/foot, 70% knee, 50% mid-
thigh, 40% groin). the ankle–brachial pressure index (ABPI) using a hand-held Doppler ultrasound
device is usually necessary prior to commencing any form of compression therapy. Standard MLLB
and compression is used in patients with ABPI ≥0.8 and modified techniques with lower pressures in
those with moderate arterial disease (ABPI 0.5– 0.8). MLLB is highly skilled and to be effective and
safe it needs to be applied by a specially trained therapist.
Effects of multilayer lymphoedema bandaging are
• Reduces oedema
• Restores shape to the affected area
• Reduces skin changes (hyperkeratosis, papillomatosis)
• Eliminates lymphorrhoea

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 • Supports inelastic skin
• Softens subcutaneous tissues

The second phase addresses the continuing needs of the patient through self-management the
components of the 2-phase treatment method are:
Phase II: Self-management
Skin care
Manual lymphatic drainage (as needed)
Daytime compression garment, night time bandaging
Exercise (in bandages or garment)
Support groups
Meticulous skin care is an essential component of both treatment phases. The goal of careful and
thorough skin care is to avoid or eliminate fungal and bacterial infections such as cutaneous cellulitis,
erysipelas, or lymphangitis. Patients with lymphedema experience skin changes and are highly
susceptible to infections.

Drug therapy:
Benzopyrones: The benzopyrones are a group of several thousand naturally occurring substances, of which the
flavonoids have received the most attention. Oral benzopyrones, which have been reported to hydrolysed tissue
proteins and facilitate their absorption while has some role but not well proven stimulating lymphatic collectors.
Diuretic agents are of limited use during the initial treatment phase of CDT
Filariasis: To eliminate microfilariae from the bloodstream in patients with lymphatic filariasis, the drugs
diethylcarbamazine, albendazole, or ivermectin are recommended
Exercise: Anaerobic and isometric, will tend to exacerbate lymphoedema and patients should be advised to
avoid prolonged static activities, for example prolonged standing. Slow, rhythmic isotonic movements (e.g.
swimming) and massage will increase venous and lymphatic return through the production of movement
between skin and underlying tissue.
Psychosocial rehabilitation: The magnitude of the relationships between negative psychological and
psychosocial factors and lymphedema has been documented as a cause of non-adherence to self-management as
well as diminution in quality of life. Psychosocial support, quality of life assessment improvement program, and
a patient self-efficacy assessment are integral components of any lymphedema treatment.

B. Operative Treatment
Operations designed to alleviate peripheral lymphedema by enhancing lymph return have gained increased
acceptance worldwide but in advanced stages usually require long-term combined physiotherapy. The following
procedure are in practice but have limited role:
1. Bypass Procedure
2. Liposuction
3. Reduction Procedure

A number of methods have been described, including the omental pedicle, the skin bridge (Gillies),
anastomosing lymph nodes to veins (Neilubowicz) and the ileal mucosal patch (Kinmonth).

Lymphaticovenular Anastomosis (LVA)

More recently, direct lymphaticovenular anastomosis (LVA) has been carried out on vessels of 0.3–0.8 mm
diameter using super-microsurgical techniques. This operative approach is designed to augment the rate of return
of lymph to the blood circulation. The surgeon should be well-schooled in both microsurgery and lymphology
and utilize appropriate imaging tools to document efficacy.

Vascularized Lymph Node Transplantation: Transplantation of superficial lymph nodes from an uninvolved
area together with the vascular supply (VLNT) to the site of lymphadenectomy for cancer has been proposed
both as a preventive and therapeutic. Long-term follow up data on risk and efficacy is scant along with the
influence of adjunctive physical methods. Vascularized lymph node transfer (VLNT) has recently demonstrated
potentially promising outcomes for patients with lymphedema.11-14 These transferred lymph nodes have been
shown to function based on radiotracer uptake on postoperative lymphoscintigraphy.15–17 There have been
several reports of lymphedema developing in the donor area.17 While imaging has demonstrated blood flow to
the transplanted nodes, sparse data have been published on lymph flow through the transplanted nodes. Fig. A is
showing Preoperative lymphoscintigraphy and B after the VLNT. The arrow shows the lymphatic drainage in
axilla.
Liposuction
Liposuction has been used in the treatment of chronic lymphoedema. It is usually reserved for patients who have
progressed to non-pitting oedema. Case series reported thus far have shown promising results with more than

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100% reduction in limb oedema volume, which can be maintained by ongoing use of compression hosiery for at
least 1 year. While liposuction appears to be safe, results of long-term efficacy and effects on the incidence of
future lymphoedema complications (e.g. infection) are awaited.

Fig-3: Lymphoscintigraphy. (A)Preoperative. (B)Postoperative showing new radiotracer uptake in the left axilla
(open arrow) after simultaneous breast reconstruction and vascularized lymph node transfer.

Early Debulking Operations:

Excisional procedures have been described by Charles in 1912, Sistrunk in 1918, Homans in 1936, and
Thompson in 1962.
Charles recommended a radical operation for reducing the size of a massively swollen calf or foot. The entire
skin and subcutaneous fat of the lower leg is removed circumferentially to the muscular fascia. Split-thickness
skin grafts are applied over the denuded areas. The excision includes major veins and nerves of the saphenous
system in addition to the lymphoedematous tissues. The foot can be selectively treated in a similar manner.
Sistrunk described a noncircumferential debulking procedure. It removes a wedge of skin and subcutaneous fat
to the muscular fascia. Skin grafting is not required in as much as the adjacent flaps, created by the excision, are
approximated and sutured.
Homans extended Sistrunk’s operation. He first excised a medial wedge of lymphoedematous calf tissue then
undermined the flaps to extend the area of tissue removal. disease progression during a year of vigorous
nonsurgical treatment is a major criterion for selection for surgical treatment.
Treatment results are based on findings of subjective and objective clinical improvement: pain, fluid leakage,
infection, and reduction of lesion size or swelling. Both clinical and laboratory assessment may be necessary.

References
1. Browse NL, Stewart G. Lymphoedema: pathophysiology and classification. J Cardiovasc Surg. 1985;26(2):91-106.
2. Olszewski WL, Lymph Stasis: Pathophysiology, Diagnosis,and Treatment. Boston: CRC Press; 1991.
3. Cluzan RV, Pecking AP, Lokiec FM. Progress in LymphologyXIII.Amsterdam: Excerpta Medica, Elsevier
Science;International Congress Series; 1992:716–17.
4. Kinmonth JB, Taylor GW, Tracy GD, Marsh JD.Primary lymphoedema. Br J Surg. 1957;45(189):1–9.
5. Dreyer G, Addiss D, Dreyer P. Basic Lymphoedema Management, Treatment and Prevention of Problems Associated
with Lymphatic Filariasis. Hollis, NH: Hollis Publishing; 2002.
6. Olszewski WL, Jamal S. Recurrent dermato lymphangioadenitis (DLA) is responsible for progression of lymphedema.
Progress in Lymphology XV. Lymphology. 1996; 29:331–34.
7. Pillai PR, Sharma S, Ahmed SZ, Vijaykumar DK. Study of Incidence of Lymphedema in Indian Patients Undergoing
Axillary Dissection for Breast Cancer Indian J Surg Oncol. 2010; 1(3): 263–69.
8. Weissleder H, Weissleder R. Lymphedema:evaluation of qualitative and quantitative lymphangioscintigraphy in 238
patients. Radiol.1988;167(3):729–735.
9. Simon J. Simonian, Cheryl L. Morgan, Lawrence L. Differential Diagnosis of Lymphedema.in: Lawrence L. Tretbar.ed.
Diagnosis and Treatment of Lymphedema Springer-Verlag London Limited 2008.p18.
10. The Diagnosis and Treatment of Peripheral Lymphedema: 2016 Consensus Document of the International Society of
Lymphology. Lymphology 49, (2016) 170-84.
11. Becker C, Assouad J, Riquet M, Hidden G. Postmastectomy lymphedema: long-term results following microsurgical
lymph node transplantation. Ann Surg. 2006; 243:313–5.
12. Lin CH, Ali R, Chen SC, et al. Vascularized groin lymph node transfer using the wrist as a recipient site for
management of postmastectomy upper extremity lymphedema. Plast Reconst Surg. 2009; 123:1265–75.
13. Cheng MH, Huang JJ, Wu CW. The mechanism of vascularized lymph node transfer for lymphedema: natural
lymphaticovenous drainage. Plast Reconstr Surg. 2014;133: 192e 8e.
14. Honkonen KM, Visuri MT, Tervala TV. Lymph node transfer and perinodal lymphatic growth factor treatment for
lymphedema. Ann Surg. 2013; 257:961–7.
15. Saaristo AM, Niemi TS, Viitanen TP, Tervala TV, Hartiala P, Suominen EA. Microvascular breast reconstruction and
lymph node transfer for postmastectomy lymphedema patients. Ann Surg. 2012; 255:468–73.
16. Becker C, Vasile JV, Levine JL.Micro lymphatic surgery for the treatment of iatrogenic lymphedema. Clin Plast Surg.
2012; 39:385–98.
17. Pons G, Masia J, Loschi P, Nardulli ML, Duch J. A case of donor-site lymphoedema after lymph node-superficial
circumflex iliac artery perforator flap transfer. J Plast Reconstr Aesthet Surg.2014; 67:119–23.

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 Critical limb ischemia (CLI)
Rajiv Parakh

Description
Critical limb ischemia (CLI) is a severe blockage in the arteries of the lower extremities, which markedly
reduces blood-flow. It is a serious form of peripheral arterial disease, or PAD, but less common
than claudication. PAD is caused by atherosclerosis, the hardening and narrowing of the arteries over time due to
the buildup of fatty deposits called plaque.
CLI is a chronic condition that results in severe pain in the feet or toes, even while resting. Complications of
poor circulation can include sores and wounds that won't heal in the legs and feet. Left untreated, the
complications of CLI will result in amputation of the affected limb.

Symptoms
The most prominent features of critical limb ischemia (CLI) are called ischemic rest pain — severe pain in the
legs and feet while a person is not moving, or non-healing sores on the feet or legs.
 Pain or numbness in the feet
 Shiny, smooth, dry skin of the legs or feet
 Thickening of the toenails
 Absent or diminished pulse in the legs or feet
 Open sores, skin infections or ulcers that will not heal
 Dry gangrene (dry, black skin) of the legs or feet

Risk factors
Risk factors for chronic limb ischemia are the same as those for atherosclerosis, hardening and narrowing of the
arteries due to the build up of fatty deposits, called plaque.
 Age
 Smoking
 Diabetes
 Overweight or obesity
 Sedentary lifestyle
 High cholesterol
 High blood pressure
 Family history of atherosclerosis or claudication

Diagnosis
Your doctor may identify and locate the cause of blockages associated with critical limb ischemia (CLI) using
one or more of the following methods:
 Auscultation: The presence of a bruit, or "whooshing" sound, in the arteries of the legs is confirmed
using a stethoscope.
 Ankle-brachial index (ABI): The systolic blood pressure in the arm is divided by the systolic pressure
at the ankle.
 Doppler Ultrasound: This form of ultrasound can measure the direction and velocity of blood-flow
through the vessels.
 CT angiography: An advanced X-ray procedure that uses a computer to generate three-dimensional
images.
 Magnetic resonance angiography (MR angiography): The patient is exposed to radiofrequency
waves in a strong magnetic field. The energy that is released is measured by a computer and used to
construct two- and three-dimensional images of the blood vessels.
 Angiogram: An X-ray study of the blood vessels is taken using contrast dyes.

Treatment
Critical limb ischemia is a serious condition that requires immediate treatment to re-establish blood-flow to the
affected area. The number one priority is to preserve the limb.

Endovascular treatments
Minimally invasive endovascular therapy is often an option in the care of CLI. The Vascular Center has the full
complement of endovascular treatments available. The treatment recommended depends on the location and
severity of the blockages. Most patients with CLI have multiple arterial blockages, including blockages of the
arteries below the knee. In general, puncture of the groin, under local anesthesia, with insertion of a catheter into

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the artery in the groin will allow access to the diseased portion of the artery. Some of the endovascular
procedures used to treat CLI include:
 Angioplasty: A tiny balloon is inserted through a puncture in the groin. The balloon is inflated one or
more times, using a saline solution, to open the artery.
o Cutting balloon: A balloon imbedded with micro-blades is used to dilate the diseased area.
The blades cut the surface of the plaque, reducing the force necessary to dilate the vessel.
o Cold balloon (CryoPlasty): Instead of using saline, the balloon is inflated using nitrous oxide.
The gas freezes the plaque. The procedure is easier on the artery; the growth of the plaque is
halted; and little scar tissue is generated.

 Stents: Metal mesh tubes that provide scaffolding are left in place after an artery has been opened using
a balloon angioplasty.
o Balloon-expanded: A balloon is use to expand the stent. These stents are stronger but less
flexible.
o Self-expanding: Compressed stents are delivered to the diseased site. They expand upon
release. These stents are more flexible.

 Laser atherectomy: Small bits of plaque are vaporized by the tip of a laser probe.

 Directional atherectomy: A catheter with a rotating cutting blade is use to physically remove plaque
from the artery, opening the flow channel.

Recovery from these procedures usually takes one or two days, and most of these procedures are done on an
outpatient basis. Treatment includes management of the risk factors of atherosclerosis (see reducing risk factors).

Surgical treatments
Treatment of wounds or ulcers may require additional surgical procedures or other follow-up care. If the arterial
blockages are not favorable for endovascular therapy, surgical treatment is often recommended. This typically
involves bypass around the diseased segment with either a vein from the patient or a synthetic graft.
Hospitalization after a bypass operation varies from a few days to more than a week. Recovery from surgery
may take several weeks.

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 Risk Factors, Assessment Models and Markers in Breast Cancer
Geeta Kadayaprath, Neerja Gupta
Breast cancer is the most common cause of cancer amongst women. There are many recognized risk factors
associated with breast cancer and with the rising incidence of breast cancer nearing 1 in 30 women in India and 1
in 8 women in U.K, a number of models have been developed for assessing these risks with varying degrees of
validation.
RISK FACTORS
 Age at onset of breast cancer. The risk for breast cancer increases with age; most breast cancers are
diagnosed after age 50.
 Multiple cases in the family (particularly on one side). Inherited changes (mutations) to certain genes,
such as BRCA1 and BRCA2. Women who have inherited these genetic changes are at higher risk of
breast and ovarian cancer.
 History of ovarian malignancy in personal or family history, other tumours for example meningioma,
sarcoma, prostate, pancreatic cancer.
 Family history of breast cancer in relatives
 Hormonal and reproductive factors have long been recognised to be important in the development of
breast cancer. Taking OCP s or HRT for more than five years raises the risk for breast cancer by 1.5
times. The hormones that have been shown to increase risk are a combination of
estrogen and progestin preparations.
 Obesity, diet and exercise are interlinked. Women who are not physically active have a higher risk of
getting breast cancer.Older women who are overweight or obese have a higher risk of getting breast
cancer than those at a normal weight.
 Physical activity in adolescents and adults decreases risk of breast cancer in women upto 40 years. In a
Norwegian study- 25624 women FU 13.7 years - A 37% decreased risk of breast cancer among women
who exercised regularly.
 Greatest benefit - <45y who exercised regularly over a period of 3-5 years.
 One drink per day increases risk slightly. 2 to 5 drinks per day increases risk about 1.5 times.
 Previous treatment using radiation therapy. Women who had radiation therapy to the chest or breasts
(like for treatment of Hodgkin’s lymphoma) before age 30 have a higher risk of getting breast cancer
later in life.

RISK ASSESSMENT MODELS

Gail model—This is -a risk-assessment model that focuses primarily on non-genetic risk factors, with limited
information on family history. The model is an interactive tool designed by scientists at the NCI and at the
NSABP to estimate a woman's risk of developing invasive breast cancer. The calculations take competing risks
and the interval of risk into account. The data depend on having periodic breast examinations. The Gail model
was originally designed to determine eligibility for the Breast Cancer Prevention Trial, and has since been
modified (in part to adjust for race) and made available on the National Cancer Institute website now . The
model works best in general assessment clinics, where family history is not the main reason for referral. The
major limitation of the Gail model is the inclusion of only first-degree relatives, which results in underestimating
risk in the 50% of families with cancer in the paternal lineage and also takes no account of the age of onset of
breast cancer.

Claus Model-Claus and colleagues developed a risk model for familial risk of breast cancer in a large
population-based, case–control study conducted by the Centers for Disease Control. The data were based on
4,730 breast cancer cases aged 20–54 years and on 4,688 controls who were matched on the basis of both
geographic region and age. Family histories were obtained through interviews. However, Claus computer model
showed that it underestimated risks in the family history clinic when computer model was used. Manual use of
the Claus tables, however, provided accurate risk estimation.

For a woman of average risk-A women having no family history can be assessed for her lifetime risk using
modified Gail or Claus model. The model is available online and uses seven risk factors - age at menarche, age
at first live birth, number of previous breast biopsies, and number of first-degree relatives with breast cancer,
race-Hispanic or Asian. Gail and colleagues described a model that focuses primarily on non-genetic risk factors,
with limited information on family history, which was designed by scientists at the NCI and NSABP to estimate
a woman's risk of developing invasive breast cancer.

BRCAPRO model- An output that calculates breast cancer risk using the likelihood of BRCA1/2 can be utilised
. None of the nonhereditary risk factors can yet be incorporated into the model. BRCAPRO was developed in the
United Sates and uses Bayesian theory and family history information. Parmigiani and colleagues developed a
Bayesian model that incorporated published BRCA1 and BRCA2 mutation frequencies, cancer penetrance in

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mutation carriers, cancer status (affected, unaffected, or unknown), and age of the consultee's first-degree and
second-degree relatives. An advantage of this model is that it includes information on both affected and
unaffected relatives. In addition, it provides estimates for the likelihood of finding either a BRCA1 mutation or
a BRCA2 mutation in a family. The major drawback from the breast cancer risk-assessment aspect is that no
other 'genetic' element is allowed for. As such, this model will underestimate risk in breast-cancer-only
families. The model predicted only 49% of the breast cancers that actually occurred in the screened group of
1,900 women. Of note, however, despite the establishment of ductal carcinoma in situ (DCIS) as part of the
BRCA1/2 tumor spectrum (56), at present, the program does not count DCIS as breast cancer (i.e., it factors in
cases of invasive breast cancer only); therefore, carrier probability may be underestimated. Users may therefore
wish to enter DCIS cases as invasive.

BOADICEA- - Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm.The
BOADICEA Web Application (BWA) is a research tool and it is not licensed to support clinical or diagnostic
decisions. The BWA enables you to run risk calculations on the Web. . Pedigrees built online can extend beyond
2nd degree and can include up to 275 family members. The Web pages have been designed so that they respond
intelligently to user inputs and check that the input data are valid and internally consistent. Like BRCAPRO,
BRCA1/2 test results are considered; however, oophorectomy status and breast pathology is not included and the
model was not developed with in situ cancers in mind. BOADICEA also can be used to predict mutation carrier
probabilities as well as cancer risks. This model is widely used in the United Kingdom, and is one of the models
suggested for use by the NICE guidelines

Different sections of BOIDACEA ONLINE TOOL include-

• The family member web page used to capture details of individual family members when building pedigrees
online .
• Clinical history section used to capture details of the individual’s sex, vital status, age (or age at death), year
of birth, cancer diagnoses and genetic test results.
• Breast cancer section used to capture pathology data from the individual’s first breast cancer.

Cuzick–Tyrer model -The Cuzick–Tyrer model, based partly on a dataset acquired from the International
Breast Intervention Study and other epidemiological data, has now done this. The major advantage over the
Claus model and the BRCAPRO model is that the Cuzick–Tyrer model allows for the presence of multiple genes
of differing penetrance and allows for a lower penetrance of BRCAX.The model addresses many of the pitfalls of
the previous models; significantly, the combination of extensive family history, endogenous oestrogen exposure
and benign breast disease (atypical hyperplasia). In our validation process, the Cuzick–Tyrer model performed
by far the best at breast cancer risk estimation

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Pros and Cons of the various models
The Gail, Claus and BRCAPRO models all underestimated risk, particularly in women with a single first-degree
relative affected with breast cancer. The Cuzick–Tyrer model and the manual model were both accurate in this
subgroup. The Cuzick–Tyrer model was the most consistently accurate model for prediction of breast cancer. All
the models accurately predicted risk in women with multiple relatives affected by breast cancer (that is, two first-
degree relatives and one first-degree relative plus two other relatives). This means that the effect of a single
affected first-degree relative is higher than may have been thought of earlier. The BRCAPRO, Cuzick–Tyrer and
manual models were the only models to accurately predict risk in women with a family history of ovarian cancer
as these were the only models to take account of ovarian cancer in their risk-assessment algorithm. The Gail,
Claus and BRCAPRO models significantly underestimated risk in nulliparous women or whose first live birth
occurred after the age of 30 years. Moreover, the Gail model appeared to increase risk with pregnancy at age <
30 years in the familial setting. It is not clear why such a modification to the effects of age at first birth should be
made because it does not reflect any association with BRCA mutation. The Gail model, however, has determined
an apparent increase in risk with early first pregnancy. Furthermore, the Gail, Claus and BRCAPRO models also
underestimated risk in women whose menarche occurred after the age of 12. The Cuzick–Tyrer and manual
models accurately predicted risk in these subgroups. These results suggest that age at first live birth has also an
important effect on breast cancer risk, while age at menarche perhaps has a lesser effect. The effect of pregnancy
at age < 30 years appeared to reduce risk by 40–50% compared with an older first pregnancy or late-age
nulliparities, whereas at the extremes of menarche there was only a 12–14% effect.

On whom to run the model?-- Probabilities of risk vary based on which person is chosen for the analysis, so
for some patients it might be more appropriate to run the model on the person most likely to harbor a mutation
based on family history.
There are a number of models available to assess both breast cancer risk and the chances of identifying
a BRCA1/2 mutation. Some models perform both tasks, but none are yet totally discriminatory as to which
family has a mutation and who will develop breast cancer.

Pitfalls of these models-Many of the known nonfamily-history risk factors are not included in risk models
(Table 1). In particular, perhaps the greatest factor apart from age:the mammographic density which is
considered to be an independent factor is not yet included.

Validation-The goodness of accuracy of the above four models was assessed using data from 1,933 women
attending the Family History Evaluation and Screening Programme in Manchester, UK, of which 52 developed
cancer. All models were applied to these women over a mean follow-up of 5.27 years to estimate the risk of
breast cancer.

Markers in breast cancer

1) Serum tumor markers
2) Tumor tissue markers

Serum markers-Many serum-based tumor markers have been described for breast cancer, such as CA 15-3, BR
27.29 (CA27.29), carcinoembryonic antigen (CEA), tissue polypeptide antigen, tissue polypeptide specific
antigen, and HER-2, , tissue polypeptide specific antigen, p53, cathepsin D, cyclin E, nestin. Out of these, the
most widely used are CA 15-3 and CEA. CA 15-3 belongs to the MUC1 family. There is a documented lack of
sensitivity for early and low volume disease and lack of specificity and none of the available markers is of value
for the detection of early breast cancer.

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CA 15-3 –It is one of the first circulating prognostic factors for breast cancer. Preoperative concentrations thus
might be combined with other prognostic factors to predict outcome in patients with newly diagnosed breast
cancer. At present, the most important clinical application is in monitoring therapy in patients with advanced
breast cancer that is not assessable by existing clinical or radiologic procedures. Serum markers are the only
validated approach for monitoring treatment in patients when conventional criteria cannot be used for evaluation.
CA 15-3 is a carbohydrate-containing protein antigen called mucin (MUC). It belongs to the MUC1 family.
Although the MUC1 gene is found in several tissues, the variation in the extent of glycosylation (carbohydrate
content) is the distinguishing feature between different tissue sources. In breast tissue, the carbohydrate content
is approximately 50%.

CEA--Carcinoembryonic antigen (CEA), which belongs to a family of related cell surface glycoproteins, it is a
glycoprotein that contains 45–50% carbohydrates. It is a single polypeptide chain consisting of 641 aminoacids,
with lysine at its N-terminal position. As steadily rising CEA may be the first sign of cancer recurrence after
treatment, the lead time from CEA elevation to clinical recurrence is about 5 months. Also, patients with
advanced cancer or metastatic cancer may have higher CEA levels rather than in patients with localized diseases.
Because CEA lacks disease sensitivity and specificity, it cannot be used for screening the general asymptomatic
population, a subpopulation with a high risk for malignancies, or for independently diagnosing cancer.
Circulating levels of CEA in breast cancer patients are directly dependable on the size of both primary and
metastatic tumor. For breast cancer, CEA is being replaced by other more specific markers, such as CA 15-3.
Sławicki et al. reported that CEA alone is non-specific for diagnosis of breast cancer.

It is suggested that there should be an association between CEA, CA 15-3 and the clinicopathological parameters
for proper diagnosis in patients with metastatic breast cancer(Geng et al).Lumachi et al. suggested that CEA and
CA 15-3 should be considered complementary in detecting recurrence of breast cancer but their sensitivity is low
and independent of the majority of the prognostic parameters that may be considered before relapse.

The American Society of Clinical Oncology (ASCO) has updated its recommendations for use of tumor markers
in prevention, screening, treatment and surveillance of breast cancer. The tumor markers (serum and tissue)that
showed evidence of clinical utility and were recommended for use in practice include CA 15-3, CA 27.29,
Carcinoembryonic antigen (CEA), Estrogen receptor (ER), Progesterone receptor (PR), Human epidermal
growth factor receptor 2 (HER2), Urokinase plasminogen activator (uPA), Plasminogen activator inhibitor 1
(PAI-1) and multiparameter assays for gene expression. They demonstrated insufficient evidence supporting
routine use of markers including P53, cathepsin D, cyclin E and nestin.
In a study of 60 patients of breast cancer by Lumachi F ,sensitivity of CEA, CA 15-3, and CEA + CA 15-3
together was 40.3%, 41.9% and 59.7%, respectively. No correlation (p = NS) was found between tumor markers
sensitivity and type of recurrence, surgical procedure, histologic subtypes and hormone receptors rate. CEA
significantly (p < 0.01) correlated with the size of the tumor and axillary node status and CA 15-3 with the age
of the patients. In conclusion, CEA and CA 15-3 should be considered complementary in detecting BC
recurrences but their sensitivity is low and independent of the majority of the prognostic parameters that may be
considered before relapse.

CA27.29 –This can also be found in patients with other malignancies or with benign disorders of the breast,
liver, and kidney, and in patients with ovarian cysts. Therefore, elevation of this marker is not organ specific. It
is a carbohydrate-containing protein. Gion et al. reported that CA27.29 seems to be more sensitive than CA15.3
to limited variations of tumor extension. However, it cannot help clinicians in distinguishing stage I patients
from stage II patients.

TISSUE MARKERS
Estrogen receptor (ER)-ER has a role in cellular growth, proliferation and differentiation. In addition to
prognostic value, it is the most important biologic marker of response to treatment in breast cancer. It is a
member of the family of nuclear steroid receptors and functions as a transcriptional regulator, which is
controlled by the hormone 17p-estradiol estrogen . In both pre- and postmenopausal patients, steroid hormone
status should be used to identify patients most likely to benefit from endocrine therapy such as tamoxifen, and
raloxifene in both the early and metastatic disease. False-positive results of ER assays (ER-positive tumors but
no response to endocrine therapy) are more common than false negative results. The most frequent explanation
is heterogeneity of tumor with biopsy of a site that is not representative of the other tumor deposits. In addition
to this problem, there exists an evidence that some tumor cells have functional receptor defects distal to the
initial binding steps (e.g., variant cells are able to bind steroids in the cytoplasm but will not transport the
receptor to the nucleus)

Progesterone receptors (PR)-It is a member of the family of nuclear hormone receptors that specifically binds
to progesterone. PR is encoded by single gene PGR presenting on chromosome 1 Iq22. PR should be analyzed in

107
every invasive breast cancer as well as metastatic lesions if the results would influence treatment plan. In both
pre- and postmenopausal patients, steroid hormone status should be used to identify patients most likely to
benefit from endocrine therapy in both early breast cancer and metastatic disease. It was recognized that
transcription of the progesterone receptor (PR) gene was regulated by estrogen in breast and reproductive tissues
and that estrogen receptor-positive (ER+) breast tumors that lacked PR expression were less responsive to
endocrine therapy than those that express high levels of PR. During tamoxifen therapy, levels of both PR and ER
decrease but PR levels decrease more dramatically than ER levels, with up to half of the tumors completely
losing PR expression as they develop tamoxifen resistance. In patients with such tumors, the loss of PR
translates into a more aggressive disease and worse overall survival, suggesting that other alterations in the
molecular changes occur at the same time. Loss of PR in ER+ tumors may be a marker of aberrant growth factor
signaling that could contribute to the tamoxifen resistance found in the tumors leading to a poorer survival in
women treated with tamoxifen.

Human epidermal growth factor receptor (HER)-The HER-2 neu gene is localized to a chromosome that
encodes a transmembrane tyrosine kinase receptor protein. HER-2neu gene is normally expressed on the
epithelial cells of numerous organs, including lung, bladder, pancreas, breast, and prostate, and has been found to
be over expressed in cancer cells. Circulating HER-2neu receptor protein levels have predicted the presence and
progression of HER-2neu-positive cells. In breast cancer, circulating HER-2neu receptor protein levels appear to
be useful as prognostic indicator of .High levels of expression of HER2neu receptor protein are associated with
significantly decreased survival rate in patients with breast cancer(Cao et al). Reix et al. reported that HER-2neu
receptor protein appears to be a helpful biomarker for early diagnosis of relapses and to predict the outcomes in
metastastatic breast cancer. HER-2 neu is amplified and overexpressed in 15%-30% diagnosed breast cancer and
is associated with a more aggressive biologic behavior. clinical applications have been proposed in prognostic
estimation in untreated patients, prediction of resistance to endocrine therapy or of selective resistance to
tamoxifen, prediction of relative resistance to certain cytotoxic agents, such as cyclophosphamide, methtrexate,
and fluorouracil regimens and prediction of benefit from athracycline and anti-HER 2 therapies such as the use
of trastuzuamb Reports focusing on the response of HER2-overexpressing breast cancers to either hormonal
therapy or chemotherapy are conflicting, some studies suggesting that these tumors have a decreased response to
tamoxifen and an increased response to anthracycline containing chemotherapy. However, these results have not
been uniformly observed in all studies. Breast cancers without HER2 over-expression usually metastasize to
bone, whereas HER2- overexpressing breast cancers usually spread to visceral organs, such as lung, liver and
brain.

PAI-1 and uPA are recently validated as prognostic factors for lymph node-negative breast cancer patients and
may be used for selecting those patients who may not need to receive adjuvant chemotherapy. Other markers for
breast cancer such as HE4, p53, cathepsin D, cyclin E and nestin need further studies before their clinical utility
is well established.

Suggested Reading
1. B.W. Park, J.W. Oh, J.H. Kim, S.H. Park, K.S. Kim, J.H. Kim, et al. Preoperative CA 15-3 and CEA serum levels as predictor for
breast cancer outcomes. Ann Oncol, 19 (4) (2008), pp. 675-681
2. S. Sławicki B. roczko . SzmitkowskiTumor markers of breast cancer Postep Hig Med Dosw Online, 58 (2004), pp. 292-300
3. B. Geng, M.-M. Liang, X.-B. Ye, W.-Y. ZhaoAssociation of CA 15-3 and CEA with clinicopathological parameters in patients with
metastatic breast cancer,Mol Clin Oncol, 3 (1) (2015), pp. 232-236
4. Y. Shao, X. Sun, Y. He, C. Liu, H. LiuElevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for
different molecular subtypes of breast cancer
5. F. Guadagni, P. Ferroni, S. Carlini, et al.A re-evaluation of carcinoembryonic antigen (CEA) as a serum marker for breast cancer: a
prospective longitudinal study. Clin Cancer Res, 7 (8) (2001), pp. 2357-2362
6. S.G. Wu, Z.Y. He, J. Zhou, et al.Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese
breast cancer Breast, 23 (1) (2014), pp. 88-93
7. B.W. Park, J.W. Oh, J.H. Kim, S.H. Park, K.S. Kim, J.H. Kim, et al. Preoperative CA 15-3 and CEA serum levels as predictor for
breast cancer outcomes. Ann Oncol, 19 (4) (2008), pp. 675-681
8. S. Sławicki B. roczko . Szmitkowski.Tumor markers of breast cancer Postep Hig Med Dosw Online, 58 (2004), pp. 292-300
9. B. Geng, M.-M. Liang, X.-B. Ye, W.-Y. ZhaoAssociation of CA 15-3 and CEA with clinicopathological parameters in patients with
metastatic breast cancer. Mol Clin Oncol, 3 (1) (2015), pp. 232-236
10. E. Manuali, A. De Giuseppe, F. Feliziani, et al.CA 15–3 cell lines and tissue expression in canine mammary cancer and the correlation
between serum levels and tumor histological grade. BMC Veterinary Res, 8 (2012), p. 86
11. F. Lumachi, A.A. Branded, M. Ermani, G. Bruno, P. BoccagniSensitivity of serum tumor markers CEA and CA 15-3 in breast cancer
recurrences and correlation with different prognostic factors.Anticancer Res, 20 (6C) (2000), pp. 4751-4755
12. A. Darlix, P.J. Lamy, E. Lopez-Crapez, et al.Serum HER2 extra-cellular domain, S100ß and CA 15-3 levels are independent
prognostic factors in metastatic breast cancer patients.BMC Cancer, 16 (2016), p. 428
13. B. Rack, C. Schindlbeck, J. Jückstock, et al.Prevalence of CA 27.29 in primary breast cancer patients before the start of systemic
treatment Anticancer Res, 30 (5) (2010), pp. 1837-1841
14. Amir E, Evans DG, Shenton A, Lalloo F, Moran A, Boggis C, Wilson M, and Howell A. Evaluation of breast cancer risk
assessment packages in the Family History Evaluation and Screening Programme. J MeGenet. 2003;40:807–814. Doi
10.1136/jmg.40.11.807. [PMC free article] [PubMed][Cross Ref]
15. Claus EB, Risch N, Thompson WD. Genetic analysis of breast cancer in the cancer and steroid hormone study. Am J Hum
Genet. 1991;48:232–242. [PMC free article] [PubMed]

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 Pathology of carcinoma breast: recent concepts
Nishant Sagar, Nita Khurana
Invasive carcinoma breast is the most common cancer found in women and accounts for 23% of all cancers
globally. Rising incidence is seen with age with highest risk found amongst population of Australia, Europe and
North America.
The diagnosis of breast carcinoma is made on histology. Ancillary tests are done to support diagnosis, classify
the tumour and to prognosticate and predict response to therapy. Non molecular tests are part of standard of care
at the time of diagnosis. Traditional prognostic indicators include distant metastasis, lymph node status, tumour
size, histologic type (invasive tubular, mucinous, medullary ),histologic grade ,surgical margin status. Other
prognostic indictors include mitotic index, lympho-vascular invasion, nerve infiltration, skin and nipple
involvement, adipocytic infiltration, infiltrating margins, extensive necrosis, fibrotic focus, tumour angiogenesis,
tumour infiltrating lymphocytes, perinodal extension and bone marrow micro-metastasis

IDC- recent concepts

The terminology as recommended in the 2012 WHO classification of breast for invasive ductal carcinoma
(IDC) has been changed from ‘not otherwise specified’ (NOS) to invasive carcinoma of ‘no special type’ (NST)
which better indicates the non-specific histologic pattern of the tumour. Use of the term “ductal” continues
which is the traditional terminology but is an incorrect concept that indicates that the ductal tumours arise from
mammary ductal epithelium as compared to lobular carcinomas which were thought to arise within lobules. It
has been shown that the terminal duct lobular unit (TDLU) should be regarded as a single entity which is the site
of origin of most ductal and lobular breast carcinomas.[1]

Medullary carcinoma; recent concepts

Classical criteria for histologic diagnosis of medullary carcinoma(MC) included cells arranged in synctitium in
more than 75% of tumour mass with pushing margins, lack of tubular differentiation, prominent
lymphoplasmacytic infiltrate and pleomorphic high-grade vesicular nuclei containing one or several nucleoli,
multiple mitoses and atypical giant cells.[2,3] The terms “atypical medullary carcinoma” and “carcinoma with
medullary features” were used for tumours that do not fulfil these criteria. As these diagnostic criteria were
difficult to apply, resulting in poor inter-observer reproducibility so now classic MC, atypical MC and invasive
carcinoma NST with medullary features are grouped together as “ carcinomas with medullary features”. [1] and
the practice is to treat MC, like basal-like triple-negative carcinomas, with aggressive therapy. [4]

Invasive papillary carcinoma

Invasive adenocarcinoma with >90% papillary morphology in the invasive component. If the invasive
component is nonpapillary (even if associated with encapsulated papillary carcinoma )and solid it not termed as
invasive papillary carcinoma, but categorized according to the individual invasive component. As a
consequence, true invasive papillary carcinomas are rare. [1]

Flat epithelial atypia

The native epithelial cells of the TDLUs are replaced by one to several layers of cells that lack polarity with
nuclei morphologically similar to low-grade ductal carcinoma in situ (DCIS) [5,6] . The cells may be cuboidal
to columnar with apical snouts. Occasional cellular tufts or mounds may be seen, but well-developed arcades,
bridges( features of DCIS) and micropapillary formations are absent (hence their designation as “flat”). FEA is
considered as a part of spectrum of columnar cell lesions of breast and a preneoplastic lesion, with a strong
association with the co-existence of lobular neoplasia (lobular carcinoma in situ and atypical lobular hyperplasia
[ALH]), atypical ductal hyperplasia (ADH), low grade DCIS and low-grade invasive carcinomas including
tubular carcinoma [7,8,9]. The cells of FEA are strongly and diffusely positive for estrogen receptor and do not
overexpress HER2..

Microinvasive carcinoma
This is characterized by one or more clearly separate microscopic foci of infiltration of tumour cells into the
mammary stroma (less than or equal to 1 mm) in a background of high-grade ductal carcinoma in situ (DCIS).
Historically, there has been wide variation in the definition of microinvasive carcinoma with some advocating
that the definition of microinvasive carcinoma requires extension of the invasive cells beyond the specialized
lobular stroma. As this is difficult to ascertain due to stromal changes in malignancy, the above criteria being
objective is used.

Molecular classification of carcinoma breast

Intrinsic subtypes recapitulate differentiation of breast ductal cells from Progenitors, Intermediate, mature
luminal cells or normal breast like.Invasive breast carcinoma (IBC) was classified based on molecular profile
with gene expression profiling (GEP) by Perou and Sorlie et al into five categories as luminal A, luminal B ,

109
normal breast like, Her2 rich and basal like. [10,11]. Since then various other categories have come up including
Claudin low subtype (CLBC) , Molecular apocrine subtype (MABC) and, a novel luminal-like subtype.

CLBC is characterised by low to absent luminal markers with expression of epithelial to mesenchymal transition
markers. These are triple negative tumours with poor prognosis and histologically include metaplastic
carcinoma and carcinoma with medullary features [12,13]. MABC include tumours with apocrine histology
which lack ER, express androgen receptor and have interferon regulated genes e.g. STAT1 These tumors may be
triple negative and show early recurrence 14,15,16].
• Gene Expression Profiling or Multianalyte assays with algorithmic analysis(MAAA) is the technique
used for molecular analysis. These are in-vitro diagnostic test which measure mRNA levels for selected
genes. Measurement is integrated using a specific proprietary algorithm and result is clinically
validated. Mammaprint (Agenelia, California, 70 genes) Oncotype DX (Genomic Health, California,21
genes) Prosigna, PAM 50 (50 genes), Rotteram signature (76 genes) however it is complex, expensive
and not universally available. Hence in 2013 St Gallen guidelines recommended the use of
immunohistochemical surrogate markers for molecular classification [17].

Molecular classification based on IHC

ER-Positive BC
Most breast cancers showing ER positivity fall into luminal A or luminal B category, however one recent study
has shown that there can be as many as 6 distinct type of ER positive IBC.

Luminal A type are 30% to 40% of all cases. They strongly express Era gene GATA-binding protein 3
(GATA3) which is associated with better prognosis, X-box–binding protein 1, trefoil factor 3, hepatocyte
nuclear factor 3, and estrogen-regulated LIV-1. 13% cases show p53 mutation and 45% cases show PIK3CA
mutation [10,11]. They are negative for Her2neu. Morphologically heterogenous these cases may be well
differentiated carcinoma NST, tubular, mucinous, neuroendocrine carcinoma or classical lobular carcinoma .
The surrogate IHC markers for luminal type A includes ER positive, PR in 20% or more, Her2neu negative and
Ki67 < 14%. [18].

Luminal B type are morphologically less differentiated NST and micropapillary variants . Compared to
luminal A type p53 mutation is more frequent while PIK3CA mutations is less often seen[10,11]. There is low
to moderate expression of ER cluster but not Her2Neu.
On IHC, ER is low with low (<20%) or negative PR and high Ki67(>14%) . Loss of PR is associated with high
chance of recurrence on Oncotype Dx, high chances of metastasis and low response to therapy. [17,18].

HER2-Positive are heterogenous group; 12 to 20% of all cases and categorised as either luminal HER2 subtype
(ER and/or PR positive/HER2 positive) and HER2-enriched subtype (ER and/or PR negative/HER2 positive).
One large study showed that tumors from luminal HER2 subtype have more frequent locoregional recurrence
compared with hormone receptor–negative, HER2-enriched subtype (9.8% vs 3.8%) [19-22].

Luminal HER2 (Luminal B, HER2-Positive) Subtype- express ER at a lower level compared to Her2neu
negative tumors. They show frequentGATA3 mutation as well as BCL2 and ESR1 [23,24]; are generally grade
2/ 3 and more likely to show nodal metastasis, early relapse and lower response to endocrine therapy [25,26].
Based on expression of PR, Luminal Her2neu subtype can be divided as ER+,PR+, Her2+ and ER+PR-,Her2+ as
both have distinct properties. Studies have shown that ER+,PR+, Her2+ cases have a better survival compared to
ER+PR-,Her2+ cases [27].

HER2-Enriched Subtype- On GEP, this subtype shows low to absent ER gene expression , high expression
of several genes in the ERBB2 amplicon at 17q22.24. About 71% show p53 mutation and activation of receptor
tyrosine kinase pathways, such as FGFR4, EGFR, and HER2 while 39% tumors have a PIK3CA mutation.
Morphologically, besides invasive ductal carcinoma NST, apocrine carcinoma and pleomorphic invasive lobular
carcinomas, also belong to this subtype. The IHC surrogates for HER2 enriched subtype are ER-, PR-, HER2+
[18].

Triple-Negative Breast Cancer is defined by the lack of expression for ER, PR, and HER2 on
immunohistochemistry. These show significant overlap with basal like breast cancer. These patients present at a
younger age as high grade tumors and with higher risk of distant recurrence and mortality .Most are ductal
carcinoma NST. Others may be adenoid cystic carcinoma, secretory carcinoma, metaplastic carcinoma, and
carcinoma with medullary features, each with a distinctive morphology and clinical behaviour [28-31]. Lehmann
et al further divided TNBC cancer into 6 different subgroups based on a detailed GEP study, namely: basal-like
1 and 2 subtypes; immunomodulatory subtype; mesenchymal and mesenchymal stem–like subtypes; and luminal
androgen receptor subtype. [32].They respond differently to neoadjuvant chemotherapy , with basal like 1 with

110
highest complete pathologic response rate (52%) and basal-like 2 and luminal androgen receptor tumors having
the lowest complete pathologic response rates (0% and 10%, respectively) [33].

Basal Like subtype comprise of 15% of all cases and show diversity in histological features, survival, chance of
metastasis, response to therapy and mutational status. On GEP genes characteristic of basal breast epithelium
such as CK5, CK17 are seen with frequent p53 mutation. The surrogate markers for these cases are ER, PR,
HER2, CK5, and EGFR. These cases present as large mass and are generally high grade with pushing borders,
dense lymphocytic infiltrate, poor Nottingham Prognostic Index, and frequent local recurrence and distant
metastasis. A small group of low grade BLBCs which have good prognosis include adenoid cystic carcinoma
and secretory carcinoma [18].

Recurrence score vs Histologic type, grade and immunohistochemical surrogate markers

Investigators have attempted to correlate morphology with Recurrence Score .In a study of 536 patients
comprised of invasive ductal and lobular carcinomas and their variants, there was only 1 ER discrepancy
between IHC (3+ 80%) and Oncotype Dx; up to 8% of PR+ cases (mean % positivity = 50%, median = 20%)
and 2% of HER2neu+ cases were undervalued by Oncotype Dx while other studies report 93–100% concordance
with ER and 86–94.2% PR concordance rates. Oncotype Dx results often undervalue ER and PR receptors when
compared to IHC [34]. The discordance may be due to interference by cellular stroma, inflammatory cells, or a
biopsy cavity. [35,36]. Park et al. discuss scenarios where the Oncotype Dx results were favored over the IHC,
resulting in falsely omitting adjuvant therapy. In addition, cases that were HER2neu negative or equivocal by
Oncotype Dx were found to be Her2-FISH amplified indicating discordance between techniques [37]. Dabbs et
al. discussed five patients who also did not receive trastuzumab due to discordant results [38]. Studies have
shown that PR negativity has an inverse relationship with RS, independent of Nottingham score. Auerbach et al.
showed that a mitotic count greater than 1 combined with a negative PR result could serve as a marker for an
intermediate or high RS [39]. Similarly, Allison et al. found an inverse relation between Nottingham grade
combined with PR expression and RS [40]. Studies have shown that PR negative compared with PR positive
breast tumors have higher hazard ratios for relapse free survival and subsequently poorer prognosis. The absence
of PR in ER+ tumors may be a surrogate marker for increased growth factor signaling and could be the cause of
tamoxifen resistance[41]. In the ATAC trial, patients with ER+ R− breast cancers given either Arimidex,
tamoxifen, or a combination treatment saw a greater benefit in time to recurrence than the ER+ PR+ group [42]..
PR expression indicates an intact pathway for ER to perform its role as a nuclear transcription factor and hence
can be targeted via ER modulators. R− cancers are characterized by increased growth factor signaling,
activation of ER signaling, and poorer outcome. As RS is hormone dependent this suggests that ER+ R−
cancers maybe a distinct subtype of luminal breast cancers that may need more aggressive treatment [43].

The recurrence scores helps guide the use of adjuvant therapy in patients with early stage ER+ LN− tumors. As
node positive patients are generally offered both chemotherapy and adjuvant endocrine therapy, there is little
need to use a predictor such as Oncotype Dx to assess the need for chemotherapy in these patients;few studies in
this subgroup indicate that ER+ LN+ patients also had RS predictive of the benefit of anthracycline based
chemotherapy, particularly in postmenopausal women. A recent study results showed that patients with isolated
tumor cells and micrometastases predominated (86%) in the low and intermediate RS scores. The study showed
that cases with high PR score (> 250) and mitotic grade of 1 had low Oncotype Dx RS category and cases with
low PR score( < 150) and mitotic grade of 3 were exclusive to high Oncotype Dx RS category. [34].

Using standard pathologic parameters, one can predict that grades 1 and 2 carcinomas were associated with low
to intermediate RS whereas grade 3 carcinomas had intermediate to high RS. In addition, certain morphologies
such as lobular and tubulolobular are most likely to be associated with low to intermediate RS, whereas other
variants such as mucinous and micropapillary lack such an association and in fact distributed evenly in each of
the three RS. Additionally R− carcinomas associated with high mitotic rates were more likely to be poorly
differentiated and have high RS. This illustrates that, within the family of varied breast cancer grades and
morphologies, there may be heterogeneity even amongst the subsets as seen by the spectrum of RS within each
subset [34]. This emphasizes that morphology and biomarkers should be assessed along with the RS to
determine the use of adjuvant therapy particularly in the intermediate RS.

Lips etal in their study concluded that Histological grade, ER, PR, and HER2 were the best predictive factors for
chemotherapy response in breast cancer and propose to continue the conventional use of these markers.44 Emad
A rakha etal in their review article concluded that the Nottingham Grading System is a validated alternative to
molecular tests in parts of the world where access to new molecular technology is not currently available or
likely to become available in the near future.45

111
How to subtype if molecular methods not available: Use IHC approximations
• Luminal A : ER+/PR +; Her2 -; low Ki67(<14%)
• Luminal B : ER+/PR+ and Her 2 +
• : ER+/PR+ , Her2 Neg, high Ki67(>14%)
• Her 2 enriched : ER- ; PR -; Her2 +
• Basal like : ER- , PR -, Her2 -, CK 5/6 + / EGFR +

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37. . . ark J. J. bel W. Zhao and D. L. Zynger “ R and R immunohistochemistry and H R2 FISH versus
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41. K. H. Allison . L. Kandalaft . . Sitlani S. . Dintzis and A. . Gown “Routine pathologic parameters can
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 ADJUVANT THERAPY IN BREAST CANCER
Shaji Thomas

Agents used in adjuvant breast cancer systemic therapy include the following:
 Taxanes: Among the most active and commonly used chemotherapeutic agents for the treatment of early
stage breast cancer.
 Anthracyclines: Used in the treatment of early stage breast cancer for decades, although concerns regarding
anthracycline-associated cardiotoxicity or leukemogenic potential remain.
 Pertuzumab: Use in combination with trastuzumab and chemotherapy as adjuvant treatment of patients with
HER2-positive early breast cancer at high risk of recurrence.
 Trastuzumab: Used in the (neo)adjuvant treatment in patients with HER2-positive breast cancer.
 amoxifen: Used in the treatment of estrogen receptor ( R) positive breast cancer; decreases estrogen's
ability to stimulate existing micrometastases or dormant cancer cells.
 Aromatase inhibitors (AIs): Inhibit aromatase, the enzyme responsible for converting other steroid
hormones into estrogen.

Combination regimens
Combination chemotherapy regimens are standard recommendations in the adjuvant setting. Major Cancer and
Leukemia Group B (CALGB) chemotherapy clinical trials have consistently shown that chemotherapy produces
significantly better disease-free and overall survival, particularly in patients with ER-negative disease.

Neoadjuvant chemotherapy
The best candidates for neoadjuvant chemotherapy are patients with ER-negative and/or HER2-positive
expressing tumors whose pathologically complete response (pCR) rates can approach 65% and predict long-term
survival. Patients with ER-positive, HER2-negative locally advanced breast cancer (LABC) are unlikely to
achieve a pCR from currently available chemotherapy.

Targeted chemotherapy in early stage breast cancer

Research has been performed on targeted chemotherapy agents, including the following:
 Cyclin-dependent kinase (CDK) inhibitors
 Small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)
 Blockade by antiangiogenic agents
 PI3K/Akt/mammalian target of rapamycin (mTor) inhibitors
 oly(adenosine diphosphate AD ribose) polymerase (PARP) inhibitors]

Overview
Adjuvant treatment of breast cancer is designed to treat micrometastatic disease, or breast cancer cells that have
escaped the breast and regional lymph nodes but have not yet had an established identifiable metastasis.
Depending on the model of risk reduction, adjuvant therapy has been estimated to be responsible for 35-72% of
the reduction in mortality rate.

However, results from a study conducted by the Microarray in Node-Negative and 1 to 3 Positive Lymph Node
Disease May Avoid Chemotherapy (MINDACT) investigators found that among 1550 women with early-stage
breast cancer who were at high clinical risk and low genomic risk for recurrence who received no chemotherapy,
the 5-year rate of survival without distant metastasis (94.7% [95% confidence interval, 92.5 to 96.2]) was 1.5
percentage points lower than the 5-year rate in women at high clinical and genomic risk who did receive
chemotherapy. The researchers concluded that approximately 46% of women with breast cancer who are at high
clinical risk might not require chemotherapy.

Guidelines
In 2016 the American Society for Clinical Oncology (ASCO) published guidelines, based on the Cancer Care
Ontario Clinical Practice Guideline, for the selection of optimal adjuvant chemotherapy regimens for HER2-
negative and HER2-positive breast cancers. Treatment recommendations should be guided by the following:
 Risk of recurrence
 Potential toxicities
 Comorbidities
 Overall likelihood of benefit

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Guideline recommendations included the following:
 For patients at high risk of recurrence, treatment with an anthracycline and a taxane is preferred
 For patients not felt to be candidates for anthracyclines, docetaxel/cyclophosphamide or
cyclophosphamide/methotrexate/5-fluorouracil are acceptable alternative regimens
 On the basis of recent negative trials, gemcitabine and capecitabine are not recommended in the adjuvant
setttings
 For patients with node-negative Her2Neu-positive cancer with tumors > 1 cm, trastuzumab should be
offered for 12 months. It can also be considered in patients with tumors ≤ 1 cm. When given in this setting
trastuzumab should be given concurrently with non-anthracycline chemotherapy.

Combination Regimens for Breast Cancer

Combination chemotherapy regimens are standard recommendations in the adjuvant setting. The most
commonly used regimens are shown below.

Adjuvant Chemotherapy Regimens for Breast Cancer

TAC
Docetaxel 75 mg/m² IV day 1, +Doxorubicin 50 mg/m² IV day 1, +Cyclophosphamide 500 mg/m² IV day 1
Cycle repeated every 21 days. For 6 cycles.
AC ⇒Taxol (T) (conventional regimen)
Doxorubicin 60 mg/m² IV day 1, +Cyclophosphamide 600 mg/m² IV day 1. Cycle repeated every 21 days for 4
cycles.
Followed by Paclitaxel 175 mg/m² IV day 1, Cycle repeated every 21 days for 4 cycles.

Dose-dense
Doxorubicin 60 mg/m² IV day 1, +Cyclophosphamide 600 mg/m² IV day 1. Cycle repeated every 14 days. For 4
cycles.
Followed by Paclitaxel 175 mg/m² IV day 1. Cycle repeated every 14 days. For 4 cycles.
Metronomic regimen
Doxorubicin 20 mg/m² IV day 1, Every week. + Cyclophosphamide 50 mg/m² PO, Every day. For 12 weeks.
Followed by Paclitaxel 80 mg/m² IV day 1, Every week. For 12 weeks.

AC ⇒T + H (trastuzumab)
Trastuzumab dosage: 4 mg/kg IV load, then 2 mg/kg weekly with paclitaxel, then give 6 mg/kg IV every 3
weeks for 40 weeks
NOTE: Trastuzumab to be added to a weekly paclitaxel regimen in HER2-positive breast cancer patients

FEC100
5-Fluorouracil (5-FU) 500 mg/m² IV day 1, + Epirubicin 100 mg/m² IV day 1, + Cyclophosphamide 500 mg/m²
IV day 1. Cycle repeated every 21 days. For 6 cycles.

FAC
5-FU 600 mg/m² IV day 1, + Doxorubicin 60 mg/m² IV day 1, + Cyclophosphamide 600 mg/m² IV day 1. Cycle
repeated after every 21 days. For 4 cycles.
5-FU 500 mg/m² IV days 1 and 8, +Doxorubicin 30 mg/m² IV days 1 and 8, + Cyclophosphamide 100 mg/m²
PO days 1-14. Cycle repeated every 28 days. 6 cycles.

CMF (Bonadonna regimen)

Cyclophosphamide 100 mg/m² PO days 1-14, + Methotrexate 40 mg/m² IV days 1 and 8, +5-FU 600 mg/m² IV
days 1 and 8. Cycle repeated every 28 days. For 6 cycles.
Metronomic regimen
Cyclophosphamide 50 mg/m² PO days 1-7, + Methotrexate 15 mg/m² IV, +5-FU 300 mg/m² IV. Weekly. For 24
cycles.

TC
Taxotere (Docetaxel) 75 mg/m² IV day 1, + Cyclophosphamide 600 mg/m² IV day 1. Every 21 days. For 4
cycles.

Major chemotherapy clinical trials by the Cancer and Leukemia Group B (CALGB) have consistently shown
that chemotherapy produces significantly better disease-free and overall survival in patients with estrogen
receptor (ER)–negative disease. They demonstrated a remarkable 63% improvement in disease-free survival
and a 59% improvement in overall survival in patients with ER-negative disease, compared with 32%

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improvement in disease-free survival and 18% improvement in overall survival in patients with ER-positive
disease. Overall, the advantages of chemotherapy, particularly in ER-negative disease, were observed across all
the trials, irrespective of the chemotherapy regimen used.

In the phase III AZURE trial, the addition of zoledronic acid to standard adjuvant therapy in women with
stage II/III breast cancer did not affect disease-free survival. However, zoledronic acid did reduce the
development of bone metastases (hazard ratio [HR], 0.78). In women who had entered menopause more than 5
years before trial entry, zoledronic acid improved invasive disease–free survival (HR, 0.77).

Taxanes
Taxanes are among the most active and commonly used chemotherapeutic agents for the treatment of early-stage
breast cancer. Although they are generally better tolerated than the anthracyclines, they can have considerable
toxicity: peripheral neuropathy, myelosuppression, myalgias, and the risk of infusions reactions.

A Cochrane meta-analysis showed a statistically significant overall survival and disease-free survival for the
taxane-containing regimens compared with the nontaxane regimens.

The Cancer and Leukemia Group B (CALGB) 9344 study demonstrated a survival benefit for the sequential use
of paclitaxel following Adriamycin (doxorubicin) and cyclophosphamide (AC) chemotherapy. In a retrospective
analysis of CALGB 9344, HER2 positivity irrespective of estrogen receptor status predicted a significant
benefit from paclitaxel in terms of reduced disease recurrence. Patients with ER-positive, HER2-negative,
node-positive breast cancer did not seem to benefit from the addition of a taxane.

However, the National Cancer Institute of Canada MA.21 and UK TACT trials, did not demonstrate a benefit in
using taxanes.

The Eastern Coast Oncology Group (ECOG) 1199 study demonstrated that paclitaxel weekly and docetaxel
every 3 weeks were superior to two other regimens in terms of disease-free survival after a median follow-up of
64 months.

Similarly, the TAX 311 trial, performed by the US Oncology Group in patients with advanced breast cancer that
had progressed after an anthracycline-containing chemotherapy regimen, showed that every-3-week docetaxel at
100 mg/m2improved time to progression (TTP) and overall survival when compared with paclitaxel at 175
mg/m2 given every 3 weeks.

Thus, taxane-based regimens still have use in the treatment of early-stage breast cancer and should be considered
in treating women, especially those with HER2-positive disease, using either the weekly paclitaxel or every-3-
week docetaxel dosing schedules.

Anthracyclines
Anthracycline-containing adjuvant chemotherapy regimens have been used in the treatment of early-stage breast
cancer for decades, although concerns regarding anthracycline-associated cardiotoxicity or leukemogenic
potential remain. The question of long-term cardiac safety remains, particularly for older women with
early-stage breast cancer.

The US Oncology 9735 trial established TC (docetaxel/cyclophosphamide) as a viable option for treating women
with early-stage breast cancer, especially those at high risk of cardiotoxicity or requiring only 12 weeks of
therapy. This study randomized 1016 women with operable breast cancer (stages I-III) to 4 cycles of TC versus
4 cycles of standard dose AC (Adriamycin/cyclophosphamide). After a median of 7 years’ follow-up, both
disease-free survival (81% vs 75%) and overall survival (87% vs 82%) were superior in the TC arm.

Additionally, a meta-analysis of 8 trials, comprising 6564 women with early-stage breast cancer, of
anthracycline-based versus nonanthracycline-based regimens, suggested a benefit with anthracycline
administration only in patients with HER2-positive disease.

The original trials demonstrating superiority of anthracycline-based regimens over CMF (cyclophosphamide,
methotrexate, fluorouracil) did not include HER2 testing.

An anthracycline followed by or concurrent with a taxane is the optimal therapy for "triple-negative" breast
cancer patients with no medical contraindications. However, it remains unclear what the optimal combination
chemotherapy regimen is for ER-positive, HER2-negative tumors. Currently, CMF, TC, or an anthracycline-
based regimen may all be reasonable options.

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Adjuvant Hormone Therapy
In estrogen receptor (ER)–positive early-stage breast cancer, hormone therapy plays a main role in adjuvant
treatment, either alone or in combination with chemotherapy. Hormone treatments function to decrease
estrogen's ability to stimulate existing micrometastases or dormant cancer cells.
Adjuvant hormone therapy can reduce the relative risk of distant, ipsilateral, and contralateral breast cancer
recurrence by up to 50% in tumors with high ER expression. FDA-approved endocrine therapies for adjuvant
treatment of breast cancer include tamoxifen and the aromatase inhibitors (anastrozole, letrozole, exemestane ).

Tamoxifen is a selective estrogen receptor modulator (SERM) that binds to and inhibits estrogen receptor
signaling in the breast. As a receptor antagonist, it is effective in both premenopausal and postmenopausal
women. Tamoxifen has ER-stimulating effects in other tissues, which has both beneficial and adverse
consequences: in bone, the stimulation results in preservation of bone density; in endometrium, it leads to a 2- to
4-fold increased risk of endometrial cancer.

In an analysis of 55 trials evaluating tamoxifen versus placebo in the adjuvant treatment of breast cancer, 5 years
of tamoxifen therapy resulted in a 47% reduction in recurrence and a 22% reduction in mortality.
In 2014, the American Society of Clinical Oncology (ASCO) issued an updated clinical practice guideline on
adjuvant endocrine therapy for women with hormone receptor–positive breast cancer. The guideline includes the
recommendation that women with stage I to III disease consider taking tamoxifen for 10 years.

For pre- or perimenopausal patients, ASCO recommends offering adjuvant endocrine therapy with tamoxifen for
5 years, after which the patient should receive additional therapy based on her menopausal status. If the patient is
premenopausal, she should be offered continued tamoxifen for a total duration of 10 years. If the patient is
postmenopausal, she should be offered continued tamoxifen for a total duration of 10 years or an aromatase
inhibitor for a total duration of up to 10 years of adjuvant endocrine therapy.

Postmenopausal patients should be offered adjuvant endocrine therapy with one of the following regimens:
 Tamoxifen for 10 years
 An aromatase inhibitor for 5 years
 Tamoxifen for 5 years, then switching to an aromatase inhibitor for up to 5 years
 Tamoxifen for 2-3 years, then switching to an aromatase inhibitor for up to 5 years

The 2000 Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis demonstrated that the
risk reduction from adjuvant tamoxifen is similar in older and younger women (or even superior in older
women).

Aromatase Inhibitors
Aromatase inhibitors (AIs) function by inhibiting aromatase, the enzyme (found in body fat, adrenal glands, and
breast tissue, as well as tumor cells) responsible for converting other steroid hormones into estrogen. Aromatase
is the sole source of estrogen in postmenopausal women and likely the underlying reason that obesity (larger
volume of body fat produces more estrogen) has been associated with a higher risk of breast cancer in
postmenopausal patients.
As the AIs have no effect on ovarian estrogen production, these agents are effective only in postmenopausal
women. Common side effects of AIs include hot flashes (12-36%), arthralgia/arthritis (17%), headache (9-13%),
vaginal dryness (2%), and mood changes (19%).

Several large randomized trials, including the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and the
Breast International Group (BIG) 1-98 trials, have shown AIs to be superior to tamoxifen with regard to
disease-free survival in postmenopausal women with early-stage breast cancer.

Significant benefit was also seen in time-to-recurrence of contralateral breast cancer. However, none of the
head-to-head comparison trials has yielded an improvement in overall survival compared with tamoxifen.
Early switching trials in which AIs are initiated after 2-3 years of tamoxifen have also shown improved disease-
free survival. However, in contrast to the upfront trials, an improved overall survival is observed when ER-
negative patients are excluded and randomization occurs at the time of switching.

The Canadian-led MA.17 trial randomized patients to an additional 5 years of AI therapy with letrozole after
completion of 5 years of tamoxifen therapy and resulted in improved disease-free survival in all patients
randomized, as well as improved overall survival in the higher-risk lymph node–positive subset of patients. This
study was the first to suggest that prolonged hormone therapy may be more effective than 5 years of
therapy.

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The optimal duration and sequence for the use of AIs has not been defined clearly, but their benefits in terms of
breast cancer recurrence and survival clearly support their use in all postmenopausal women. Ongoing trials are
now comparing 5 and 10 years of AI therapy.

The BIG 1-98 Collaborative Group found that disease-free survival was not significantly better between 2
sequential treatment groups with letrozole and letrozole monotherapy and that overall survival was not
statistically different between monotherapy with letrozole and monotherapy with tamoxifen (when combined
with previous trial data comparing efficacy in 4922 postmenopausal patients with endocrine-responsive breast
cancer for letrozole).

A meta-analysis by the Early Breast Cancer Trialists' Collaborative Group (EBCTCG) of randomized trials in
early breast cancer found that early recurrence rates favored AIs over tamoxifen in a variety of regimens. The
10-year breast cancer mortality rates were approximately 15% lower in patients who received 5 years of an
aromatase inhibitor than in those treated with 5 years of tamoxifen.

Neoadjuvant Chemotherapy
In inflammatory breast cancer (IBC), the early program of 4 cycles of FAC, then surgery followed by an
additional 4 cycles of FAC, then irradiation, led to a median survival of about 2 years and 5-year survival of
about 30% of patients, which are dramatic improvements over historical outcome with local therapy alone (5-
year survival of < 5%).

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial proved that preoperative
chemotherapy with 4 cycles of standard-dose AC was equivalent to 4 cycles of postoperative standard-dose AC.
This trial also found that pathologically complete response (pCR) in the primary tumor predicts excellent overall
survival and is an excellent surrogate for long-term disease-free survival and overall survival.

In the NSABP B-27 trial, the addition of 4 cycles of docetaxel to standard AC increased pCR from 14% to 26%;
in addition, sandwiching surgery in between the chemotherapy regimens was less effective than administering all
chemotherapy up front.

To date, no cooperative group trial has attempted to improve upon the results of neoadjuvant chemotherapy,
given as induction, with administration of alternative treatment after surgery when the surgical result was
suboptimal. A final important observation made by the MD Anderson group, from a randomized design, was that
12 cycles of weekly docetaxel followed by FAC was superior to paclitaxel given every 3 weeks for 4 cycles,
followed by the same FAC program, resulting in a doubling of the pCR rate for locally advanced breast cancer
from 14% to 28%.

The Southwest Oncology Group (SWOG) confirmed the results of several other neoadjuvant trials in that ER-
negative tumors have a higher pCR compared with ER-positive tumors and that infiltrating ductal histologies
have a higher pCR rate compared with infiltrating lobular histologies.

The continuous or "metronomic" schedule required administration of granulocyte colony-stimulating factor

(GCSF) as growth factor support. All patients on the trial, after completing AC, went on to receive weekly
paclitaxel. The pCR rate was higher on the "continuous" arm, and this effect was most marked in patients with
IBC, as well as triple negative (ER-negative, PR-negative, HER2-negative) patients with LABC.
A study by Fitzal et al determined that breast conserving therapy is oncologically safe after tumor downsizing
via neoadjuvant chemotherapy in patients primarily scheduled for mastectomy. However, the authors of that
study advise that patients should not receive breast conserving therapy without a demonstrated response after
neoadjuvant therapy.

The NSABP B-18 trial found no significant difference in overall survival or disease-free survival between
patients with operable breast cancer randomized to neoadjuvant chemotherapy and patients treated with surgery
first and then followed by chemotherapy. However, survival advantage was significant for the 36% of patients
who experienced a pCR.

Trastuzumab
For patients with HER2 overexpression, the value of adding trastuzumab in the adjuvant setting led to its
incorporation into neoadjuvant therapies for patients with the HER2-positive phenotype. This results in higher
rates of pCR for operable patients—as high as 65% initially reported by the MD Anderson group—when
trastuzumab was given concurrently with an epirubicin -containing program. One preliminary report from a
randomized trial in Europe indicates an improvement in pCR rate from 13% to 48% when trastuzumab was
added to standard neoadjuvant chemotherapy.

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A study by Slamon et al found that adding 1 year of adjuvant trastuzumab therapy significantly improved both
disease-free and overall survival among women who had HER2-positive breast cancer.

Pertuzumab
Pertuzumab, a humanized monoclonal antibody that blocks the activation of the HER2 receptor by hindering
dimerization, was approved by the FDA in June 2012 in combination with trastuzumab and docetaxel for
adjuvant treatment of metastatic HER2-positive breast cancer.
Pertuzumab elicits action at a different ligand binding site from trastuzumab to prevent HER2 dimerization. The
combination of both HER2 receptor antibodies (pertuzumab plus trastuzumab) is superior to either agent alone.

In September 2013, pertuzumab became the first medicine approved by the FDA for the neoadjuvant treatment
of breast cancer. The FDA approved pertuzumab for neoadjuvant treatment in combination with trastuzumab and
docetaxel for patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either
greater than 2 cm in diameter or node positive).

Approval was based on a randomized trial that compared a number of regimens with and without pertuzumab in
women with HER2-positive breast cancer. In the trial, 39.3% of patients treated with pertuzumab, trastuzumab,
and docetaxel (n = 107) achieved a pathologic complete response (pCR) compared with 21.5% of patients
treated with trastuzumab and docetaxel (n = 107) at the time of surgery.

Neoadjuvant hormone therapy

The best candidates for neoadjuvant chemotherapy are ER-negative or HER2-positive expressing tumors in
which pCR rates are generally above 20% and predict long-term survival. Patients with ER-positive, HER2-
negative LABC are unlikely to achieve a pCR from currently available chemotherapy, and the best approach for
these patients is likely to involve building on a backbone of hormone therapy, either alone or in combination
with targeted agents.
Neoadjuvant hormone therapies appear to be very effective in shrinking tumor size to enable breast-conserving
surgery, but pCR is rare.

Advances in Targeted Therapy

Dual blockade by antiangiogenic/HER2 agents

HER2-targeted therapies have been investigated in combination with angiogenesis inhibitors, with promising
results. HER2 overexpression is associated with an increase in VEGF levels in primary breast cancers.
Combination therapy targeting HER2, EGFR, and VEGF pathways produces greater inhibition of human breast
cancer cell lines than inhibition of any single or dual pathway.

In July 2017, the US Food and Drug Administration (FDA) approved neratinib for extended adjuvant therapy
for early-stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy.

PI3K/AKT/mammalian target of rapamycin (mTor) inhibitors

In a study by Baselga et al, the addition of the selective mTor inhibitor everolimus (10 mg/d) significantly
increased letrozole (2.5 mg/d) efficacy (antiproliferative response defined by reduction of Ki67 expression) as
compared with letrozole and placebo. The study included 270 postmenopausal women with operable ER-
positive breast cancer.

In July 2010, the FDA approved everolimus in combination with exemestane to treat postmenopausal
women with metastatic hormone receptor-positive, HER2-negative breast cancer. The drug combination is
intended to be used in women with recurrent or progressive breast cancer after failure of treatment with either
letrozole or anastrozole. Approval was based on another trial by Baselga of everolimus 10 mg/d plus exemestane
25 mg/d (n=485) vs placebo plus exemestane (n=239). Median progression-free survival was 11.0 months in the
everolimus plus exemestane group compared with 4.1 months in the placebo plus exemestane group (P
<0.0001).<ref>57</ref>

PARP inhibitors
Poly(adenosine diphosphate [ADP] – ribose) polymerase (PARP) inhibitors were initially developed to
investigate the role of PARP-1, a nuclear enzyme involved in DNA repair. BRCA1- and BRCA2-deficient cell
lines are defective in homologous recombination, thus relying on PARP-1 for DNA repair. BRCA-deficient cells
treated with PARP inhibitors demonstrate an increase in DNA fragmentation and cell death.

In January 2018, the FDA expanded approval of olaparib, which had been approved for treatment of BRCA-
mutated ovarian cancer, to include treatment of BRCA-mutated, HER2-negative metastatic breast cancer in

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patients who have been previously treated with chemotherapy. Olaparib is the first PARP inhibitor approved
to treat breast cancer, and the first drug of any kind approved to treat certain patients with BRCA-mutated
metastatic breast cancer.

CDK4/6 inhibitors
In estrogen-receptor positive breast cancer, CDK4 seems to heavily influence cell proliferation, and so this has
become a useful target for drug development. In March 2017, the FDA approved both palbociclib and ribociclib
for the treatment of hormone receptor (HR) positive, HER2-negative advanced or metastatic breast cancer in
combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women.

Most recently, the FDA approved abemaciclib in combination with fulvestrant for women with HR-positive,
HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and
as monotherapy for women and men with HR-positive, HER2-negative advanced or metastatic breast cancer
with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.
References
1. DeVita, Hellman, and Rosenberg's Cancer: Principles & Practice of Oncology. Author(s): Vincent T. DeVita Jr. MD,
Theodore S. Lawrence PhD, MD, Steven A. Rosenberg MD, PhD. 10th edition. 2014.
2. Adjuvant Therapy for Breast Cancer: Practice Essentials, Overview . https://emedicine.medscape.com/article/1946040-
overview

APPROACH TO A PATIENT WITH BREAST LUMP

P N Agarwal, Anurag Mishra

A new breast mass/lump is the most common presentation of breast disease for which patients seek medical
attention, other presentation being an abnormal mammogram, pain and tenderness without a mass, nipple
discharge, or skin changes. Such are best evaluated by using what is known as Triple assessment which takes
into account:
1. Clinical Evaluation
2. Imaging
3. Histological assessment

Clinical Evaluation
A thorough history and physical examination are essential components of the diagnostic evaluation of a breast
abnormality.
 History:
o Key features of the history include details about the presenting symptom, history of previous breast
disease, and risk factors for breast cancer including a menstrual history and other contributing past
medical history.
o Patient history should include questions regarding the duration of the symptoms or mass, change in size,
associated pain or skin changes, relationship to pregnancy or the menstrual cycle, and previous trauma.
Nipple discharge should be characterized according to its color and whether it is spontaneous, unilateral,
or emanating from a single duct. Any skin changes in the nipple or areola should be noted.
o The hormonal history includes age of menarche, date of last menstrual period, regularity of menstrual
cycle, number of pregnancies, age at first-term pregnancy, lactational history, and age at menopause or
surgical menopause (note if oophorectomy performed).
o A history of previous breast biopsies, breast cancer, or cyst aspiration should be ascertained, including
any known pathology results and treatment regimens. A history of previous oral contraceptive use and
hormonal replacement therapy should be elicited. The patient should provide dates of previous
mammograms and location of the films. A detailed family history of breast and gynecologic cancer
should be recorded, including the age at diagnosis and the location. This history should include at least
two generations as well as any associated cancers, such as ovary, colon, or prostate (in men).
o Assessment of breast cancer risk: Breast cancer is the most common malignancy among women
worldwide (Int J Cancer 1999;80:827). Hormonal exposure, or pathologic factors or genetics may be
correlated to a risk for breast cancer.
 Hormonal: Factors that increase a patient's risk by 1.5- to 4.0-fold include increased exposure to
estrogen or progesterone due to early menarche (before age 12 years) and late menopause (age >55
years), high body-mass index after menopause, presence of hyperplastic breast tissue with atypia,
and exposure to ionizing radiation. A late age at first full-term pregnancy is an important
determinant of breast cancer risk. Women with a first birth after age 30 years were shown to have

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 twice the risk of those with a first birth before age 18 years. Breast-feeding may exert a protective
effect against the development of breast cancer. Lifetime and 5-year breast cancer risk can be
estimated using the Gail model, which is based on age, onset of menses, onset of menopause, age at
first birth, and prior breast biopsies. This model is used for entering women in chemopreventive
trials.
 Pathology: Certain pathologic features observed on breast biopsy are associated with increased
breast cancer risk. No increased risk is associated with adenosis, cysts, duct ectasia, or apocrine
metaplasia. There is a slightly increased risk with moderate or florid hyperplasia, papillomatosis,
and complex fibroadenomas. Atypical ductal or lobular hyperplasia carries a 4- to 5-fold increased
risk of developing cancer; the risk increases to 10-fold if there is a positive family history. Patients
with increased risk should be counseled appropriately. Those with atypia or lobular carcinoma in
situ (LCIS) should be followed with semiannual physical examinations and yearly mammograms.
 Genetics: A family history of breast cancer in a first-degree relative is associated with an
approximate doubling of risk. If two first-degree relatives have a history of breast cancer (e.g., a
mother and a sister have had breast cancer), the risk is even higher. These familial effects are
enhanced if the relative had either early-onset cancer or bilateral disease.
 BRCA. BRCA1 and BRCA2 are breast cancer susceptibility genes associated with 80% of
hereditary breast cancers, and they account for approximately 5% to 10% of all breast cancers.
Women with BRCA1 mutations have an estimated risk of 85% for breast cancer by age 70 years, a
50% chance of developing a second primary breast cancer, and a 20% chance of developing ovarian
cancer. BRCA2 mutations carry a lower risk for breast cancer and account for 4% to 6% of all male
breast cancers. Surveillance should include a monthly breast self-examination, semiannual clinical
examination, and annual mammography beginning at age 25 to 35 years. Screening for BRCA1 and
BRCA2 gene mutations should be reserved for women who have a strong family history and have
undergone a multidisciplinary evaluation, including genetic counseling. Prophylactic bilateral
mastectomy provides a cancer risk reduction of 90% to 100% and is an option for some patients.
 ErbB2 (Her2/neu) oncogene overexpression is seen in approximately 30% of breast
adenocarcinomas, and its presence in a tumor specimen is a negative prognostic factor. Current
research is investigating methods of targeting this oncogene for future therapies.

Table 1: Risk Factors for Breast Cancer

Female Gender
Increasing age
Genetic risk factors
BRCA1 or 2
Ataxia-telangiectasia
Li-Fraumeni
Cowden syndrome
Family history of breast cancer
Personal history of breast cancer
Previous breast biopsy
Proliferative breast disease without atypia
Atypical hyperplasia
Lobular carcinoma in situ
Previous thoracic radiation
Endocrine risk factors
Early menarche
Late menopause
Late parity
Nulliparity
Long-term hormone replacement with estrogen and progesterone
Lifestyle factors
Alcohol
Obesity

 Physical examination
o The physical examination should be performed with respect for patient privacy and comfort without
compromising the complete evaluation.
o Inspect the breasts with the patient in the upright position, initially with the arms and pectoral muscles
relaxed. Look for symmetry; deformity; skin changes, such as erythema or edema; and prior biopsy
scars. The nipples are inspected for retraction, discoloration, inversion, ulceration, and eczematous

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 changes. The patient is then asked to lift her arms for a more careful inspection of the lower half of the
breasts. This maneuver also highlights any subtle retraction/ dimpling that is not readily visible with the
arms relaxed.
o The regional nodes should be palpated with the patient in the upright position, pectoral muscles relaxed.
Axillary and supraclavicular nodal regions are evaluated. Size, number, and fixation of nodes should be
noted.
o The patient's breasts should be palpated in the upright and supine positions. In the supine position, the
patient's breast is examined with the ipsilateral arm raised above and behind the head. The flat surface of
the examiner's fingers should be used to palpate the entire breast systematically. The examination should
extend to the clavicle, sternum, lower rib cage, and midaxillary line. If a dominant mass (defined as
being three-dimensional, distinct from surrounding tissues, and asymmetric relative to the other breast) is
palpated, its size, shape, texture, tenderness, fixation to skin or deep tissues, location, and relationship to
the areola should be noted. A diagram in the chart noting these features is helpful. If uncertainty remains
regarding the significance of an area of nodularity in the absence of a dominant mass in a premenopausal
woman, a repeat examination at a different point in the menstrual cycle may clarify the issue.
o In patients who present with nipple discharge, the nipple discharge is often elicited during palpation of
the breast. The character, color, and location of the discharging duct or ducts should be documented.

Breast imaging
 Mammography
o A screening mammogram is performed in the asymptomatic patient and consists of two standard views,
mediolateral and cranio-caudal. Studies have shown that screening mammography reduces mortality by
24% to 44%, depending on the age group. The current recommendation from the National Cancer
Institute and American College of Surgeons is annual screening mammography for women aged 40 years
and older. In the presence of hereditary breast cancer with known BRCA mutations, annual
mammograms should begin at age 25 to 30 years, along with semiannual physical examinations. In
patients with a strong family history of undocumented genetic mutation, annual mammograms and
semiannual physical examinations should begin 10 years earlier than the age of the youngest affected
relative and no later than age 40 years.
o Diagnostic mammograms are performed in the symptomatic patient or to follow up on an abnormality
noted on a screening mammogram. Additional views, such as spot-compression views or magnification
views, are performed to further characterize any lesions noted. Spot compression may be used to
differentiate an area of summated breast tissue from an abnormal lesion. Magnification views may be
used to more clearly evaluate microcalcifications. A normal mammogram in the presence of a palpable
mass does not exclude malignancy, and either further workup with a different imaging modality
(ultrasound) or a biopsy should be performed. Mammography is not generally performed in lactating
women or patients younger than age 30 years unless the degree of clinical suspicion is high. In the
augmented breast, displacement views should be ordered to maximize the amount of parenchyma that
can be visualized.
o These views demonstrate the fibroglandular breast tissue. Right and left views are examined side by side
so that asymmetries can be observed. The images are also examined for areas of microcalcifications.
o Most mammographically visible cancers present as masses, calcifications, or architectural distortion, or a
combination of the three. A mass is a space-occupying lesion that can be detected in two projections. If a
finding is only seen on one projection, it is referred to as a density. A density may or may not prove to be
a real finding after directed diagnostic imaging. Masses are characterized by their shape, margin, density,
and associated microcalcifications to determine the probability of malignancy. The shape of a mass can
be described as round, oval, lobulated, or irregular. Round or oval masses are usually benign. Masses
that are irregular imply a greater probability of malignancy. Lobulated masses suggest an infiltrative
growth pattern that may be suggestive of malignancy. Similarly, margin assessment is important because
of the infiltrative nature of most breast cancers. Margins can be described as circumscribed,
microlobulated, obscured, indistinct, or spiculated. A circumscribed margin that sharply delineates a
mass from the surrounding tissue is commonly a benign finding, such as a fibroadenoma or a cyst. A
mass with spiculated or stellate margins is suspicious for malignancy
o Calcifications are a common mammographic finding. Most calcifications are not associated with
malignancy. When found, the shape or morphology, location, number, and distribution of the
calcifications should be noted. Malignant-appearing calcifications are usually less than 0.5 mm,
pleomorphic or heterogeneous, and grouped. They can also be fine, linear, and branching, indicating an
intraductal process

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 Fig. 1. Masses. Shape: (A) round; (B) oval; (C) lobular; (D) irregular. Margin: (E) circumscribed; (F)
obscured; (G) microlobulated; (H) indistinct; (I) spiculated.
(Reproduced from Baker RJ, Fischer JE. Mastery of surgery: diagnostic approach to breast problems,
4th ed. Philadelphia: Lippincott Williams & Wilkins, 2001.)

o After analyzing the mammographic images, radiologists classify findings into a final assessment
category. The Breast Imaging Reporting and Data System (BIRADS) final assessment classification was
developed by the American College of Radiology to standardize mammographic reporting. The BIRADS
classification is listed in Table 2.

Table 2: Breast Imaging Reporting and Data System Classification

Assessment Category Recommendation
0 Need additional imaging evaluation Add views or ultrasound
1 Negative Annual mammography
2 Benign finding Annual mammography
3 Probably benign finding- short interval Unilateral mammography 6 mo follow-up suggested
follow-up suggested and bilateral examinations 12 and 24 mo after initial
examination

4 Suspicious abnormality Biopsy should be considered

5 Highly suggestive of malignancy- Biopsy
appropriate action should be taken
6 Known carcinoma

 Digital mammography- Recent evidence indicates that digital mammography is more sensitive than film
mammography in screening women who have dense breasts and women who are younger than 50 years or
are premenopausal or perimenopausal. Potential advantages of DM include the use of computer-aided
detection (algorithm-based computer programs that alert the radiologist to possible abnormalities on the
mammogram), and allowing centralized film reading.

 Ultrasonography
o Ultrasonography is used to further characterize a lesion identified by either physical examination or
mammography. Ultrasound can be used to determine whether a lesion is solid or cystic or to better define
its size, contour, or internal texture. Although not a useful screening modality by itself due to significant
false-positive and false-negative rates, when used as an adjunct with mammography, ultrasonography
may improve diagnostic sensitivity of benign findings to >90%, especially among younger patients, for
whom mammographic sensitivity is lower. Solid masses may have benign or malignant features.
Malignant features of a solid mass on ultrasound are irregular margins, hypoechoic to the surrounding
tissue, with posterior acoustical shadowing. Malignant-appearing masses usually have a vertical growth
appearance (taller than wider). Benign features include ellipsoid shape, hyperechogenicity or
hypoechogenicity, and smooth, well-circumscribed margins.

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 Magnetic Resonance Imaging
Magnetic Resonance Imaging (MRI) is being used with increasing frequency for the screening and diagnosis
of breast cancer. MRI has several advantages. There is no ionizing radiation to the patient with MRI. MRI is
not limited by breast density and is an excellent tool for the screening of young women with increased risk
for inherited breast cancer. In patients with indeterminate mammographic or ultrasonographic findings, MRI
may be used for clarifying the imaging but should not replace biopsy for clinically suspicious lesions.
Disadvantages of MRI are cost, limited availability, and decreased sensitivity for premalignant lesions.
Images are obtained before and after the administration of gadolinium, an MRI contrast agent. The images
are then evaluated for areas of enhancement and the morphology of the enhancement curve is noted. Lesions
suspicious for cancer will display postcontrast enhancement with malignant morphologic features. MRI may
be useful in patients who have axiliary or other adenopathy and no obvious primary tumor and in evaluation
of the integrity of the breast prosthesis.

 PET scanning –Although positron imaging is very useful in identifying recurrent metastatic disease, its use
for diagnosis of primary breast tumor is not recommended. The tumor size and cell type are factors that
affect PET scan accuracy. Accuracy in detecting tumors larger than 2 cm is high, PET may miss
approximately one third of the invasive cancers smaller than 1 cm. PET and combined PET/CT scanners are
also being used to direct radiation therapy in patients who have localized metastatic disease in areas such as
the chest wall or in bone.

Breast biopsy for palpable masses

 Fine-needle aspiration biopsy (FNAB) is a reliable and accurate office technique with sensitivity greater
than 90%. A 22- to 25-gauge needle on a 10-mL syringe is advanced into the mass, and suction is applied.
The needle is moved back and forth within the tumor with quick short strokes in nearly the same line as the
original puncture. Cells are collected in the hub of the needle. The suction is released and the needle
withdrawn. The contents of the needle are expelled onto a glass slide. A second glass slide is inverted over
the first, and the two are pulled apart. One slide is fixed immediately, and the second is allowed to air dry.
Two to three passes are performed for a total of four to six slides. False-negative findings are caused by
inadequate sampling or improper specimen processing. FNAB results should be concordant with clinical
impression and mammographic findings of the lesion (triple assessment). Fine-needle aspiration diagnoses
the presence of malignant cells; however, it does not give information on tumor grade or the presence of
invasion. Fewer than 5% of malignant masses are comprised of ductal carcinoma in situ (DCIS).
Nondiagnostic or indeterminate aspirates do not exclude malignancy and require a surgical biopsy (Am J
Surg 1997;174:372).
 Core biopsy, with either a Tru-Cut device, can be used to obtain more tissue. The skin is infiltrated with
lidocaine and a nick made in the skin. The needle is inserted into the mass and fired. Three to five cores are
taken and placed in formalin. Invasion, grade, and receptor status can be determined. For indeterminate
specimens, an open surgical biopsy is necessary.
 Excisional biopsy is performed in the operating room using local anesthesia and intravenous sedation.
Incisions should be oriented along Langer lines for optimal cosmesis (curvilinear, parallel to the areola). All
incisions should be planned so that they can be incorporated into a mastectomy incision. Masses should be
excised as a single specimen, the specimen should be oriented so that a short suture is placed superiorly and
a long suture laterally, and the margins should be inked. Improper specimen handling may obscure margin
status.
 Incisional biopsy removes a wedge of tissue from a fungating/ ulcerated breast mass. It is indicated for the
evaluation of a large breast mass suspicious for malignancy but for which a definitive diagnosis cannot be
made by FNAB or core biopsy.
 Punch Biopsy: While the diagnosis of inflammatory breast cancer is made largely clinically, histologic
confirmation of cancer cells within the dermal lymphatics is pathognomonic for inflammatory breast cancer.
In patients who present with skin changes, including erythema and/or peau d'orange, a 3- to 5-mm punch
biopsy can be performed in the office using local anesthesia. The biopsy should be full thickness through the
most suspicious area. Most inflammatory breast cancers do not present with a palpable mass, but if present,
a core biopsy can then be obtained through the punch biopsy site to provide more tissue for receptor assays.

Nonpalpable lesions
 Stereotactic core biopsy is a minimally invasive method of obtaining core samples of nonpalpable,
mammographically suspicious lesions under radiographic control. This technique is ideally suited to
establish tissue diagnoses of several foci in disparate quadrants of the breast. Using a computer-driven
stereotactic unit, two mammographic images, each at a 15-degree angle from the center, are taken to
triangulate the position of the site to be biopsied in three-dimensional space. A computer determines the
depth of the lesion and the alignment of the needle, which can be positioned within 1 mm of the intended

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 target. Biopsies are taken, and postfire images are obtained of the breast and specimen. Contraindications
include lesions close to the chest wall or in the axillary tail and thin or ptotic breasts that would allow needle
strike-through. For indeterminate specimens, an open surgical biopsy is necessary. Nondiagnostic and
insufficient specimens should also undergo NLB.
 Vacuum-assisted biopsy has been developed as a response to the difficulties that FNAB and core biopsy
have with evaluating microcalcifications and DCIS. The Mammotome uses an 11-gauge biopsy probe to
contiguously acquire tissue, which is pulled into the probe by vacuum suction. The advantage of this tool is
that it can pull back several larger volume samples of tissue into the probe while the device remains in the
breast. This technique allows removal of all of the tissue around a cluster of calcifications during a single
insertion of the probe. This device also has the ability to place a marking clip through the probe to allow for
future identification of the biopsy site.
 Needle localization biopsy is performed by placing a needle and hookwire into the patient's breast adjacent
to the lesion under mammographic guidance. The patient is then brought to the operating room. With the
localization mammograms as a map, an excisional biopsy is performed, encompassing the tissue around the
wire and lesion. The specimen is oriented and a radiograph obtained to confirm the presence of the lesion in
the specimen. It is not necessary to remove skin around the needle insertion site.
 Emerging techniques. Iodine-125 seed localization biopsy is a new technique that avoids needle placement
for localization and allows for greater flexibility in operative planning. A titanium seed containing 0.05 to
0.3 mCi125I is inserted into the breast lesion or area of microcalcifications by the nuclear medicine
radiologist under radiographic guidance, and a skin marker is placed. The titanium seed is localized by
dissection with the aid of a handheld gamma detector, and the tissue around the seed is excised. The
remaining cavity can be probed for residual activity to ensure adequate circumferential dissection, and the
biopsy specimen is examined radiographically to confirm removal of the seed and the lesion. Seeds can be
inserted the day before a scheduled biopsy to allow for more flexibility in operative planning.

Suggested Reading
 American College of Radiology (ACR). ACR BIRADS mammography. In: ACR breast imaging reporting and data
system, breast imaging atlas, 4th ed. Reston, VA: American College of Radiology.
 Bassett L, Winchester DP, Caplan RB, et al. Stereotactic core-needle biopsy of the breast: a report of the Joint Task
Force of the American College of Radiology, American College of Surgeons, and College of American
Pathologists. CA Cancer J Clin 1997;47(3):171.
 Bland KI, Copeland EM. The breast: comprehensive management of benign and malignant disorders of the breast,
3rd ed. Philadelphia: WB Saunders, 2004.
 Fine RE, Staren ED. Updates in breast ultrasound. Surg Clin North Am 2004;84(4):1001, v.
 Harness JK, Wisher DB. Ultrasound in clinical practice: basic principles and clinical practice. New York: Wiley-
Liss, 2001.
 Hughes LE, Mansel RE, Webster DJT. Benign disorders and diseases of the breast: concepts and clinical
management. Philadelphia: WB Saunders, 2000.
 Jackson VP. Diagnostic mammography. Radiol Clin North Am 2004;42(5):853, vi.
 Lee CH. Problem solving MR imaging of the breast. Radiol Clin North Am 2004;42(5):919, vi.
 Liberman L. Percutaneous image-guided core breast biopsy. Radiol Clin North Am 2002;40(3):483, vi.
 National Comprehensive Cancer Network. The complete library of NCCN clinical practice guidelines in oncology.
Jenkintown, PA: National Comprehensive Cancer Network, 2004.

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 ABDOMINAL TUBERCULOSIS
Lovekesh Kumar, Naveen Kumar Solanki

Tuberculosis (TB) is a life-threatening disease which can virtually affect any organ system. To end the global TB
epidemic, WHO has proposed End TB Strategy, for the period 2016–2035, which targets 90% reduction in TB
deaths and 80% reduction in TB incidence (new cases per year) by 2030, compared with 2015. Tuberculosis is
ninth leading cause of death worldwide, leading cause from a single infectious agent, ranking above HIV/AIDS.
The five countries viz. India, Indonesia, China, the Philippines and Pakistan; comprise 56% burden of global TB.
India accounts for 26% of TB deaths worldwide. The burden of EPTB is high, ranging from 15– 20% of all TB
cases in HIV-negative patients, while in HIV-positive people it accounts for 40–50% of new TB cases.
Abdominal TB is the 6th most common type of EPTB after lymph node TB, genitourinary, bone and joint,
miliary, and meningeal; comprising 5 percent of all cases of TB. TB is declared as notifiable disease by Indian
Government on May 9th 2012.

Etiopathogenesis
Occurrence of abdominal TB is common in persons who have had previous tubercular infection elsewhere, have
comorbidities such as renal failure, diabetes, HIV infection, silicosis, undergoing hemodialysis, IV drug abuser,
or on immunosuppressive therapy. It is more common in smokers and in patients with malnutrition. Incidence of
abdominal TB increases in patients who have undergone gastrectomy or jejunoileal bypass surgery.

Abdominal tuberculosis can occur either as a primary disease as after ingestion of food contaminated with TB
bacilli or due to spread from a tubercular foci elsewhere in body which is termed secondary disease. Mode of
spread can be direct spread from ruptured lymph node, hematogenous, via lymphatics or a retrograde spread to
abdomen via fallopian tubes.

It is caused by Mycobacterium tuberculosis, Acid-fast, weakly Gram-positive bacilli, which causes pathognomic
tubercular granuloma that is composed of activated macrophages (epithelioid cells), fibroblasts, lymphocytes,
histiocytes, Langhans giant cells with central caseating necrosis. TB organisms when ingested seed to mucosal
lymphoid aggregates of the small and large bowel ( eyer’s patches) and sets up granulomatous inflammation
that leads to ulceration of mucosa. Inflammatory process in submucosa penetrates to serosa that results in
formation of tubercles on serosal surface. Bacilli reach lymphatics and cause lymphatic obstruction of mesentery
and bowel forming thick fixed mass and then it can spread to peritoneum. There can be regional lymph nodes
hyperplasia, caseating necrosis, calcification. Immunocompromised people do not form the characteristic
granulomas.

Hematogenous spread causes involvement of solid organs, kidney, lymph nodes and peritoneum. Rarely bacilli
can enter into portal circulation or onto hepatic artery to involve solid organs like liver, pancreas, spleen.

Clinical Presentation
Abdominal TB causes a variety of presentations. Constitutional symptoms i.e. low-grade fever, malaise, night
sweats, anemia, wt loss occur in 30% of patients.

Intestinal Tuberculosis
The ileo-caecal region is the site most commonly involved, possibly because of increased physiological stasis,
increased rate of fluid and electrolytes absorption, abundant eyer’s patches, alkaline media, minimal digestive
activity and abundance of eyer’s patches. Three types of intestinal lesions are seen- Ulcerative (most common),
Hyperplastic and stricturous or constrictive.

Ulcerative type of lesions occur in presence of poor body resistance and virulent organism. There occur multiple
circumferential transverse ulcers (Girdle ulcers). Hyperplastic Type of lesions occur when there is good body
resistance and less virulent organism. Chronic granulomatous lesions with fibroblastic activity in submucosa and
subserosa causes thickening of bowel wall with lymph node enlargement. It is commonly seen in young well
nourshied people drinking infected unpasteurised milk. Cicatricial healing of ulcerative lesions results in
stricture formation. Occlusive arterial changes may produce ischemia and can also result in stricture formation.
Small intestinal lesions are usually ulcerative or strictures while large intestinal lesions are ulcero-hyperplastic.
Patients present with recurrent intestinal colic, partial or complete intestinal obstruction, chronic diarrhoea,
unexplained weight loss, palpable mass in lower abdomen, lower GI bleeding.

Peritoneal tuberculosis
It can occur either as a result of direct spread from adjacent organ, lymph node, or from distant foci via
hematogenous spread. Patients usually have abdominal distension, abdominal pain and fever. It may present as

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acute abdomen with features of peritonitis due to bowel perforation or rupture of mesenteric tuberculous lymph
node. Peritoneal TB can present as ascitic, fibrotic and plastic subtypes.

Ascitic or wet type is common form of peritoneal TB, associated with large amount of free or loculated fluid in
abdomen, which are usually straw-colored inflammatory exudates.

Fibrotic type is characterized by involvement of mesentery and omentum along with matted bowel loops.
Dry or plastic type is characterized by fibrous peritoneal reaction, peritoneal nodules, adhesions and frequently
presents as abdominal Cocoon. Purulent peritoneal tuberculosis occurs as direct spread from TB salpingitis or
genitourinary TB and contains pus in abdominal cavity.

Tuberculous lymphadenitis
Abdominal lymphadenopathy is common manifestation of abdominal TB. Commonly involved lymph nodes are
mesenteric nodes, omental nodes, nodes at porta hepatis, along celiac axis and peripancreatic location. There are
multiple matted enlarged lymph nodes with caseous necrosis. Some LN can get calcified and are not infective.
Acute mesenteric lymphadenits occurs in children and may mimic acute appendicitis. It presents as tender mass
of lymph node palpapble in RIF which are matted and non-mobile. Sometime caseating material collect in
between the layers of mesentery and forms cold abscess, mimicking a mesenteric cyst are termed as Pseudo-
mesenteric cyst. Chronic tubercular Lyphadenitis is suspected in children with vague abdominal pain who fail to
thrive, have protuberant abdomen and emaciation.

Esophageal TB
Extremely rare (0.2%-1% of gastrointestinal TB) but it is more commonly seen in AIDS patients. The symptoms
are usually retrosternal pain, dysphagia, odynophagia and hematemesis. In esophagus, TB usually occurs in the
middle third and manifests as ulcerative lesion or a tumor like lesion. The esophageal involvement is usually
secondary to a contiguous tubercular mediastinal nodal involvement (extrinsic TB). Middle third of esophagus is
most commonly involved.

Gastric TB
Primary involvement of the stomach is rare (0.4%-2%) because of the bactericidal property of the gastric acid,
scarcity of lymphoid tissue in gastric wall and thick intact gastric mucosa. It can present as gastric outlet
obstruction, upper GI bleeding.

Duodenal TB
It is 2%-2.5% of all gastrointestinal TB cases. The most common site of primary involvement is the third part of
duodenum. It can be intrinsic, extrinsic or both. Extrinsic form, which is more common, is usually secondary to
the lymphadenopathy in the C-loop of the duodenum. Band like narrowing of third part of duodenum may mimic
superior mesenteric artery syndrome. It can present as peptic ulcer with or without gastric outlet obstruction or
perforation.

Hepatobiliary and spleen

Hepatosplenomegaly is usually a part and parcel of disseminated tuberculosis. Microscopic involvement shows
granulomatous hepatitis. It can present as fever of unknown origin, hepatomegaly with or without space
occupying lesions, abnormal LFTs (especially elevated alkaline phosphatase), abnormal imaging (abscess, space
occupying lesions), jaundice.

Pancreatic TB
It presents with abdominal pain, obstructive jaundice, dilated pancreatic or bile ducts with evidence of peri-
pancreatic mass or cyst.

Perianal TB
Anorectal Stricture or fistula-in-ano which is typically multiple with undermined edges, painful , nonindurated
and watery discharge. These are usually complex perianal fistulae, have history of recurrence after multiple
surgical excisions. Hematochezia and constipation are common symptoms.

Presumptive abdominal TB
Newly introduced terminology used for any patient with abdominal pain, distension, fever, unexplained weight
loss, chronic diarrhoea or an abdominal mass.

Investigations
There is usually normal or low total leucocyte counts with relative lymphocytosis along with raised ESR.

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AFB smear microscopy- The Ziehl–Neelsen staining, also known as the acid-fast staining is a quick test. It
takes 1 day to perform.

Mycobacterial culture- It is gold standard microbiologic test for the diagnosis of TB disease. Performing both
liquid and solid cultures likely improves the sensitivity of mycobacterial cultures, while the liquid cultures
provide a more rapid answer and the solid cultures serve as a safeguard against contamination.

Tuberculin Skin Testing –TST

Intradermal injection of 0.1 mL of PPD (5 TU) is given into the volar surface of the forearm (Mantoux method)
to produce a transient wheal. A reaction of 5 mm or greater is considered positive for close contacts of
tuberculosis cases; immunosuppressed persons (HIV infection); individuals with clinical or radiographic
evidence of current or prior TB. A reaction of ≥10 mm is considered positive for other persons at increased risk
of latent tubercular infection (eg, persons born in high TB incidence countries and those with at risk of
occupational exposure to TB). A reaction of 15 mm or greater is considered positive for all other persons.
Though sensitivity of TST is high (95%–98%), false-positive TST reactions occur in Indian scenario because of
BCG vaccination coverage. False-negative reactions occur more frequently in infants and young children, early
(<6–8 weeks) infection, in persons who have recently received viral vaccination, in disseminated tuberculosis,
after recent viral (eg,HIV infection) and bacterial infections and treatment with immunosuppressive drugs (eg,
high-dose corticosteroids, TNF inhibitors).Test specificity of the TST is decreased (false-positive) among
persons with prior BCG vaccination& infection with nontuberculous mycobacteria.

Adenosine Deaminase –ADA

The production of the enzyme adenosine deaminase suggests the presence of activated T lymphocytes and
monocytes. ADA activity is also increased in- liver disease, tuberculosis, typhoid, infective mononucleosis,
certain malignancies, especially those of haematopoietic origin. The threshold used to define an elevated ADA
level ranged from 36 U/L to 40 U/L. Bhargave DK et al in their study reported that Levels above 36 u/l in
ascitic fluid and above 54 u/l in the serum suggest tuberculosis. The ascitic fluid/serum ADA ratio of more than
0.984 was suggestive of tuberculosis. Riquelme et al concluded that elevated ADA in peritoneal fluid showed
high sensitivity (100%) and specificity (97%). They suggested that ADA in ascetic fluid can be used for
diagnosing peritoneal TB with an optimal cut-off value of 39 IU/L. The sensitivity and specificity of ADA were
≥79% and ≥83% respectively, for detecting TB in cerebrospinal fluid, pleural fluid, peritoneal fluid, and
pericardial fluid, so ADA measurements are recommended in these fluids.

Interferon Gamma Release Assay-IGRA

It is in vitro stimulation of peripheral blood T-cells specific for the M. tb-specific antigens- early secretory
antigenic target (ESAT)-6 and culture filtrate protein (CFP)-10. The presence of reactive T-cells is assessed by
the induction of interferon (IFN). There are two commercialized systems available for this purpose. Quantiferon-
TB1 Gold in-tube assay (QFT-G-IT; also including a third antigen TB7.7) - measures IFN-γ using an ELISA and
TSPOT. TB1 assay - counts cells releasing IFN-γ with the enzyme-linked immunospot (ELISPOT) technique.
The threshold used to define an elevated IFN-γ level ranged from 0.35 U/L to 9 U/L. The pooled sensitivity of T-
SPOT is 83% (70% - 91%) and the pooled specificity is 58% (42% - 73%). (8 studies) QFT-GIT has a pooled
sensitivity of 73% (61% -82%) and pooled specificity of 49% (40% - 58%). (11 studies). Among HIV-infected
patients, pooled sensitivity was between 60% (QFT-GIT) and 76% (T-SPOT). Pooled specificity was low for
both IGRA platforms (T-SPOT, 61%; QFT-GIT, 52%) in HIV infected.
IGRA is more specific than the TST. There is less cross-reactivity due to BCG vaccination and sensitization by
nontuberculous mycobacteria. Up to now the accuracy of IGRA for the diagnosis of TB in compartments other
than blood has not been established. It is strongly recommended that these commercial tests not be used for the
diagnosis of pulmonary and extra-pulmonary TB.
Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease
(tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). While
both IGRA and TST testing provide evidence for infection with Mtb, they cannot distinguish active from latent
tuberculosis. Therefore, the diagnosis of active TB must be excluded prior to embarking on treatment for LTBI.
This is typically done by determining whether or not symptoms suggestive of TB disease are present, performing
a chest radiograph and, if radiographic signs of active tuberculosis (eg, airspace opacities, pleural effusions,
cavities, or changes on serial radiographs) are seen, then sampling is performed and the patient managed
accordingly.

Nucleic Acid Amplification Test-NAAT

Xpert MTB uses PCR to test specimens for genetic material specific to Mtb, and simultaneously detects a gene
which confers resistance to rifampicin, rpoB (Blakemore, 2010). Fully automated test using the GeneXpertR
platform is used now a days, in which the specimen is loaded into a cartridge and all steps fully automated and
contained in unit. These tests are termed CBNAAT- cartridge based NAAT. NAAT was originally designed to

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test sputum samples, (Steingart, 2014). But later WHO has endorsed standard operating procedures for the use
of Xpert MTB/RIF for non-respiratory specimens. A positive NAAT gives presumptive evidence of TB disease,
while Negative NAAT cannot be used to exclude TB.

NAAT can detect nucleic acids from dead and live organisms. Smear positive specimens from untreated patients
with high suspicion for TB. It has high sensitivity=95% and high Specificity=98%. In smear negative specimens
from untreated patients with high suspicion for TB, sensitivity is 66% and specificity is 98%. If there is smear
Positive for TB but NAAT is negative; infection with nontuberculous mycobacterium (NTM) is suspected.
NAAT for urine sample has high specificity 91% and high sensitivity 87 %.

Xpert MTB/RIF should be used as an additional test to conventional smear microscopy, culture and cytology in
fine-needle aspiration cytology (FNAC) specimens in Lymph node TB. It should not be routinely used to
diagnose pleural TB.

Ascitic fluid Sampling

Ascitic fluid Cytology, albumin/ protein, adenosine deaminase (ADA), microscopy for AFB and culture for Mtb
and other organisms should be done. A serum albumib: ascitic fluid albumin ratio (SAAG) of <1.1 with a high
protein (>2.5 g/mL) is suggestive of an exudative process, in keeping with abdominal TB. ADA >39 IU/mL,
TLC >500 cells, lymphocytic predominant and LDH >400 SU is suggestive of abdominal TB. (Riquelme A,
2006).

Xray chest and Abdomen

Approximately 17% of cases are associated with active pulmonary disease. Air fluid levels and free gas under
diaphragm can be seen in abdominal x-ray in cases of intestinal obstruction and bowel perforation respectively.

Ultrasound Abdomen
Intraabdominal fluid which may be free or loculated, can be seen. Localized fluid in between bowel loops gives
rise to typical ‘club sandwich’ or sliced bread sign. Ceacum in subhepatic position (pseudokidney sign).
Mesenteric lymphadenopathy, with central caseation and peripheral enhancement can be well visualized in
ultrasound. Both caseation and calcification are highly suggestive of TB. The LN echotexture is mixed
Heterogenous, in contrast to the homogenously hypo echoic nodes of lymphoma. Tuberculosis involves
predominantly the omental, mesenteric and upper para-aortic lymph nodes; while lower para-aortic lymph nodes
are commonly involved in Hodgkin’s and Non-Hodgkin’s lymphoma. Peritoneal / omental /bowel wall
thickening with tubercles can also be seen.

CECT Abdomen
Intestinal strictures and concentric ileocaecal wall thickening is visualized.The thickening is uniform and
concentric as opposed to the eccentric thickening at the mesenteric border found in rohn’s disease and the
variegated appearance of malignancy. Smooth peritoneum with minimal thickening and marked enhancement on
CECT suggest tuberculosis while nodular and irregular thickening of peritoneum suggest peritoneal malignancy
Abdominal lymphadenopathy is the commonest manifestation of tuberculosis on CT. There are multiple
enlarged mesenteric or retroperitoneal Lymph Nodes. CECT abdomen can be helpful in diagnosing all other
types of abdominal TB such as visceral- liver, spleen and peritoneal TB.

Colonoscopy with visualisation of IC junction

During colonoscopy, the most common finding of colorectal TB is presence of ulcers, which are linear/fissured,
transverse or circumferential and are covered with dull white or yellow exudates. Tubercular ulcers are shallow
with extensive irregular “geographic”borders usually not larger than 1-2 cm. These ulcers can be differentiated
from those of rohn’s disease by presence of abnormal mucosa surrounding these ulcers which show features
like erythema, edema, mucosal irregularity and nodularity. In contrast, the ulcers in the CD are usually
surrounded by normal appearing mucosa. The parameters like anorectal lesions, longitudinal ulcers, aphthous
ulcers and cobblestone appearance are significantly more common in patients with CD than in those with TB.
Strictures, deformed ileocaecal valve, mucosal oedema, pseudopolyps and diffuse colitis are other findings in
TB. Mucosal nodules & ulcers in a discrete segment with normal or hyperemic intervening mucosa are
pathognomic of TB.Various conditions like CD, amebic colitis, pseudomembranous and ischemic colitis, and
malignancy form the differential diagnosis of TB colitis.

Barium Studies
Accelerated transit time & flocculation i.e. breaking of barium suspension is the earliest sign in tuberculosis.
Mucosal ulceration, hypersegmentation (“chicken intestine”) of the barium column, localised areas of irregular
thickened folds are other finding. Luminal stenosis with smooth but stiff contours (“hourglass stenosis”)
multiple strictures with segmental dilatation and fixity with matting of bowel loops can be seen.

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Enteroclysis, in which a mixture of barium and methylcellulose is infused by a rate-controlled pump into the
small intestine with fluoroscopic examination followed by a barium enema, may be the best protocol for
evaluation of intestinal tuberculosis. There are various signs described on barium studies. “Fleischner” or
“inverted umbrella” sign, in which there is thickening of the lips of the ileocecal valve and/or wide gaping of the
valve with narrowing of the terminal ileum. The “Goose neck deformity” signifies loss of normal ileocaecal
angle(obtuse) and dilated terminal ileum, appearing suspended from a retracted, fibrosed cecum. The “ urse
string stenosis” signifies localized stenosis opposite the ileocecal valve with a rounded off smooth cecum and a
dilated terminal ileum. The two other signs are “Stierlin sign” and “string sign.” The “Stierlin sign” is a
manifestation of acute inflammation superimposed on a chronically involved segment and is characterized by
lack of barium retention in the inflamed segments the “String sign” shows persistent narrow stream of barium
indicating stenosis. Both Stierlin and String signs can also be seen in CD and hence are not specific for TB.

Laparoscopy
On laparoscopy thickened peritoneum with or without tubercles can be seen. Multiple, yellowish white, uniform
sized (about 4–5mm) tubercles are present diffusely on the parietal peritoneum. Peritoneum is thickened,
hyperaemic, lacks usual shiny lustre. Omentum, liver and spleen can be studded with tubercles. In cases of fibro-
adhesive peritonitis multiple thick adhesions are seen. The gross appearance of the peritoneal cavity is similar to
that of peritoneal carcinomatosis, sarcoidosis, and rohn’s disease, thus reiterating the importance of biopsy.

Treatment
Internationally, most guidelines recommend treating all types of abdominal TB with the same regimen as for
pulmonary TB – RNTCP Daily dose regimen is recommended.
For newly diagnosed Tb case- (2m) HRZE in IP; (4m) HRE in CP. For previously treated Tb case- (2m) HRZES
+ (1m) HRZE in IP; (5) HRE in CP.

Six months ATT standard first-line regimen is recommended for abdominal TB., extended at the discretion of
the treating clinician. Patient is followed up and assessed response to treatment at 3 months and 6 months.
Patients are more likely to complete shorter regimens. Also, there is less exposure to the adverse effects of ATT
in shorter regimens. Theoretically, risk of relapse is higher with shorter regimens, but existing evidence does not
support this.

For all new patients who are drug sensitive or DST unknown/ awaited status; treatment regimen for new case is
started. Previously treated patients with drug sensitive or DST unknown/ awaited status; regimen for previously
treated case is started. New or previously treated patient with drug resistance; regimen based on DST pattern is
started.

Changes in guidelines
It has changed from intermittent dose regimen to daily dose regimen. Fixed dose combinations as per weight
band were introduced. Previously only laboratory follow up were considered while in newer guidelines follow
up is based on both clinical and laboratory investigations. Now long term follow up upto 2 yrs. is recommended.
Recommended dosage-
Drug Daily Dose
Isoniazid 5 mg/kg, max 300 mg
Rifampin 10 mg/kg, max 600 mg
Pyrazinamide 25 mg/kg, max 2 g
Ethambutol 15 mg/kg

Drug Dosage for Adult

Weight Number of tablets (FDCs)
Category IP CP
HRZE HRE Inj Streptomycin
75/150/400/275 75/150/275 gm
25-39 kg 2 2 .5
40-54 kg 3 3 .75
55-69 kg 4 4 1
>= 70 kg 5 5 1

Some patients have lasting T.B. sequelae, cause symptoms mimicking relapse or failed treatment. It is important
to differentiate these patients, who have peritoneal adhesions or luminal strictures from patients with active TB
disease. Giving continued ATT in these patients is not required and could be harmful.

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Some patients with LNTB have residual lymphadenopathy at the end of treatment. This is not usually due to
continued active TB infection where the largest node is less than 1 cm in size. Some patients have residual nodes
more than 1 cm in size, and these patients are classified as partial responders. There is uncertainty about whether
continued ATT in these patients is beneficial. The expert group suggested these patients should receive an
additional 3 months of RHE, followed by a biopsy sent for histology and TB culture in patients who fail to
respond to that. While some evidence suggests that these patients may not require further ATT, the data is
insufficient at this stage

One should consider possible treatment failure in patients who have worsened or deteriorated after initial
improvement – this requires diagnostic investigation and possibly a change of treatment. Deterioration in the
first 3 months may be due to paradoxical reaction – this does not require repeat diagnostic tests or change of
treatment.

Drug Senstivity test (DST) is recommended. Rapid molecular DST is an adjunct and not a replacement for
culture-based DST because it only evaluates susceptibility to rifampin and occasionally isoniazid.

Multidrug resistance -MDR TB

It is resistant to both Isoniazid and Rifampicin.
IP- 6-9 months – Kanamycin, levofloxacin, Ethionamide, cycloserine, pyrazinamide, ethambutol.
CP- 18 months - levofloxacin, Ethionamide, cycloserine, ethambutol.

Extensive drug resistance-XDR TB

It has additional resistance to a fluoroquinolones – ofloxacin / levofloxacin / moxifloxacin; and a second line
injectable anti TB drug- Kanamycin /amikacin / capreomycin.
Type of TB Case Treatment regimen in IP Treatment regimen in CP
XDR (6-12) Cm, PAS, Mfx, high dose- H, Cfz, (18) PAS, Mfx, High dose-H, Cfz, Lzd,
Lzd, Amx/Clv Amx/Clv

Side effects of ATT

• Isoniazid – peripheral neuropathy, skin rash, hepatitis, sleeping and lethargy. Rarely causes
convulsions, psychosis, arthralgia, anemia
• Rifampicin- Abdominal pain, nausea, vomiting, Hepatitis, Generalised cutaneous reactions,
Thrombocytopenic purpura. Rarely causes- osteomalacia, pseudomembranous colitis, pseudoadrenal
crisis, acute renal failure, hemolytic anemia.
• Pyrazinamide – arthralgia, hepatitis. Rarely Cutaneous reactions, sideroblastic anemia.
Ethambutol- Retrobulbar neuritis. Rarely causes generalized cutaneous reactions, arthralgia, peripheral
neuropathy.
ATT induced hepatotoxicity is commonly encountered problem leading to change in regimen. LFT monitoring is
required. Acute viral hepatitis should be ruled out. In established cases of ATT induced hepatitis and drug injury,
hepatotoxic drugs- HRZ should be stopped. One aminoglycoside, one oral fluroquinolone and ethambutol are
started and continued till liver enzymes return to near normal. After return of normal liver function all first line
drugs in full dose should be started gradually in order as rifampicin, isoniazid and pyrazinamide in last, with
one-week gap in between each drug to assess which drug is causing hepatotoxicity.

Introduction of new ATD under RNTCP

Bedaquiline (BDQ): New class of drug, diarylquinoline that targets mycobacterial ATP synthase, and enzyme
essential for supply of energy to mycobacterium TB. Strong bactericidal and sterilizing activities against MTB.
It has no cross-resistance with first- and second-line ATD. Significant benefit is in improving the time to culture
conversion in MDR TB patients. RNTCP is introducing BDQ at six sites in the country initially. Basic criterion
– Adult aged ≥18 years having pulmonary MDR TB. Female should not be pregnant. The drug is being used in 6
sites to establish safety profile due to concerned cardiotoxicity.

Delamanid
It is a recently approved drug for treatment of TB conditional use under programmatic settings only. It is to be
used for Pulmonary MDR-TB in adult patients when effective treatment cannot started because of resistance or
tolerability.

Paradoxical reactions and IRIS in EPTB

Paradoxical reaction refers to the phenomenon of clinical (or radiological) deterioration of TB lesions, or the
development of new lesions in a patient with TB who has initially improved on ATT occurring in the early phase
of treatment (during the first 3 months). The predominant theory is that it occurs as a result of an excessive

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immune response to Mtb antigens in patients on effective ATT, involving dysregulation in innate and acquired
immune pathways.

Immune reconstitution inflammatory syndrome (IRIS) refers to a clinical syndrome observed in HIV-positive
people after starting antiretroviral therapy (ART) caused by an inflammatory response to an antigen, thought to
be due to the reconstitution of the immune response to that antigen.

IRIS can manifest in two principal ways: paradoxical TB-IRIS, where an inflammatory exacerbation of TB
symptoms occurs after commencing ATT in patients being treated for TB; and unmasking TB-IRIS, where
active TB presents in a patient who has commenced ART.

Treatment of HIV Co-existent Tuberculosis

• The treatment of TB should precede the treatment of HIV infection, i.e. HAART.
• Patients already on HAART, should continue the same treatment with appropriate modifications in
HAART and ATT.
• Patients who are not receiving HAART, the need and time of initiation of HAART have to be decided
on individual basis after assessing the CD4 count and type of TB.

Surgical management
The surgical principles and options in the elective patient are very similar to those for rohn’s disease, where
resections should be kept as conservative when the disease is no longer active (as evidenced by return to normal
inflammatory markers, weight gain, negative sputum culture).

Intestinal Obstruction: It is the most common complication of abdominal TB. It occurs due to hyperplastic
intestinal lesions, strictures, adhesion and adjacent lymph node involvement. It is managed with adhesiolysis.

Perforation:TB abdomen is 2nd commonest cause of small intestinal perforation, first being typhoid fever.
These are usually single & proximal to a stricture. It is managed with resection and anastomosis or an Ileostomy.
Ileocecal mass is managed with limited Ileocaecal resection.

Management of stricture is done with stricturoplasty. Pujari BD in his study recommended stricturoplasty in
those strictures which cause more than 50% luminal compromise. When there are multiple strictures, resection
and anastomosis should be done.

Intraabdominal/ perianal abscesses are managed with drainage. Perianal TB cases with complex fistula may
require surgical intervention.

Oesophageal and gastroduodenal TB patients rarely require surgery; ATT alone is usually adequate. Duodenal
strictures may be treated with balloon dilatation. Bypass surgery may be required if this is not successful.

OFFICIAL ATS/ IDSA/CDC & PREVENTION CLINICAL PRACTICE GUIDELINES- DIAGNOSIS

OF TUBERCULOSIS IN ADULTS AND CHILDREN. 2017

Testing for Latent Tuberculosis Infection using IGRA instead of a TST is advised. Perform second diagnostic
test if initial test is positive. The person is considered infected only if both tests are positive. Both IGRA and
TST- provide evidence for infection with Mtb; cannot distinguish active from latent TB. The diagnosis of active

TB must be excluded by symptoms suggestive of TB disease.

Testing for TB disease

Rapid molecular drug susceptibility testing should be done for rifampin, in patients who have history of
exposure to TB. Cell counts, chemistries, ADA, Free IFN- γ AFB smear microscopy, Mycobacterial cultures,
NAAT and histological examination on body fluid from sites of suspected extrapulmonary TB. One culture
isolate from each mycobacterial culture-positive patient be submitted to a regional genotyping laboratory for
genotyping.

These clinical practice guidelines were prepared by a task force supported by the American Thoracic Society,
Centers for Disease Control and Prevention, and Infectious Diseases Society of America (IDSA) with Fellows of
the American Academy of Pediatrics. These guidelines target clinicians in high-resource countries with a low
incidence of TB disease and LTBI, such as the United States. The recommendations may be less applicable to
medium- and high-TB incidence countries. For such countries, guidance documents published by the World
Health Organization (WHO) may be more suitable.

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INDEX-TB GUIDELINES - GUIDELINES ON EXTRA-PULMONARY TUBERCULOSIS FOR INDIA –
2016
Patients with presumptive abdominal TB
All patients presenting with symptoms consistent with TB should have a chest X-ray and offered integrated
counselling and testing- HIV testing.

Patients with presumptive peritoneal TB

Ascitic fluid Sampling with cytology, albumin and protein, ADA , microscopy for AFB and culture for Mtb
should be done in all patients. PCR-based methods for identifying Mtb in ascitic fluid are not recommended.
Ultrasound of Abdomen should be done in all patients. US guided FNAC or core biopsy of mesenteric or
retroperitoneal lymph nodes, omentum or peritoneum should be done in selected patients and specimens sent for
histology, microscopy for AFB and culture for Mtb. Use of CT or MR scan of Abdomen and laparoscopy with
targeted diagnostic sampling should be done in selected patients and not routinely suggested.

Patients with presumptive GI TB

Ileo-colonoscopy with examination of the ileum by retrograde ileoscopy with biopsy should be done in all
patients. PCR based methods for Mtb in biopsy is not recommended. CT, MR enterography, enteroclysis and
upper GI endoscopy is advised in selected patients. Barium studies are indicated where endoscopy is not
available or not possible, or where small bowel stricture is suspected.

Diagnosis of other forms of abdominal TB

Specialist imaging and image guided diagnostic sampling techniques are advised in cases of suspected biliary
and pancreatic TB. Perianal TB is relatively uncommon and careful assessment by specialists is advised to rule
out other differential diagnosis.

References-
1. Datta PK, Lal P, Bakshi SD. .Surgery in Tropics. In: Williams NS, Bulstrode CJK, O'Connell PR. Bailey & Love's
Short Practice of Surgery.London:HodderArnold:2008.p.49-70.
2. Sharma SK, Mohan A. Extrapulmonary tuberculosis. Ind J Med Res 2004;124:316-53.
3. Raviglione O’brien RJ. uberculosis. In: Longo DL Fauci AS Kasper DL Hauser SL et al editor. Harrison’s
principles of internal of internal medicine, 18th ed. USA: McGraw-Hill ;2012.p.1340-9.
4. Kumar V, Robbins SL. Infectious disease. In: Kumar V, Robbins SL,editor. Robbins basic pathology, 8th ed.
Philadelphia: Saunders-Elsevier; 2007.p.369-91.
5. Bhargava DK, Gupta M, Nijhawan S, Dasarathy S et al. Adenosine deaminase (ADA) in peritoneal tuberculosis:
diagnostic value in ascitic fluid and serum. Tubercle. 1990;71(2):121-6
6. Riquelme A, Calvo M, Salech F, Valderrama S et al. Value of adenosine deaminase (ADA) in ascitic fluid for the
diagnosis of tuberculous peritonitis: a meta-analysis.J Clin Gastroenterol. 2006 Sep;40(8):705-10.
7. Jiang J, Shi HZ, Liang QL, Qin SM, Qin XJ. Diagnostic value of interferon- gamma in tuberculous pleurisy: a
metaanalysis. Chest. 2007;131:1133–41.
8. M. Sester, G. Sotgiu, C. Lange, C. Giehl. Interferon-c release assays for the diagnosis of active tuberculosis:a
systematic review and meta-analysis. Eur Respir J. 2011;37:100–11.
9. Horsburgh and Rubin, Clinical practice: latent tuberculosis infection in the United States. N Engl J Med.
2011;364:1441–8.
10. Robert Blakemore, Elizabeth Story, Danica Helb1, JoAnn Kop et al. Evaluation of the Analytical Performance of
the Xpert MTB/RIF Assay. J. Clin. Microbiol. 2010:48(7):2495-501.
11. Karen R Steingart,Ian Schiller,,David J Horne, Madhukar Pai et al. Xpert® Mtb/Rif assay for pulmonary
tuberculosis and rifampicin resistance in adults. Cochrane Database Syst Rev. 2014;(1):1–166.
12. Makharia GK, Ghoshal UC, Ramakrishna BS, Agnihotri A et al. Intermittent directly observed therapy for
abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months of therapy.
Clin Infect Dis. 2015;61(5):750–7.
13. Jullien S, Jain S, Ryan H, Ahuja V. Six-month therapy for abdominal tuberculosis. Cochrane Database of
Systematic Reviews. 2016;11:CD012163. DOI: 10.1002/14651858.CD012163.pub2.
14. Chaudhari AD. Recent changes in technical and operational guidelines for tuberculosis control programme in india
– 2016: A paradigm shift in tuberculosis control. J Assoc Chest Physicians. 2017;5:1-9.
15. Pujari D. Modified surgical procedures in intestinal tuberculosis. Br J Surg. 1979(66):180-1.
16. akharia GK Srivastava S Das et al linical ndoscopic and Histological Differentiations Between rohn’s
Disease and Intestinal Tuberculosis. Am J Gastroenterol. 2010; 105:642–51.
17. Lewinsohn DM, Leonard MK, LoBue PA, Cohn DL et al. Official American Thoracic Society/Infectious Diseases
Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: diagnosis of
tuberculosis in adults and children. Clin Infect Dis. 2017;64:e1–33.
18. Surendra K Sharma, H Ryan, Sunil Khaparde, KS Sachdeva et al. Index-TB guidelines: Guidelines on
extrapulmonary tuberculosis for India. Indian J Med Res. 2017;145( 4):448-63

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 APPROACH TO A PATIENT WITH ASCITES
Lalit Agarwal

Ascites is a pathological accumulation of fluid in the peritoneal cavity. It is a symptom of numerous medical
conditions and has a broad differential diagnosis (table 1). Ascites can be classified by the underlying
pathophysiological mechanism: portal hypertension, peritoneal disease, hypoalbuminaemia and miscellaneous
disorders. Liver cirrhosis (75%) is the most common cause in adults in the Western world, followed by
malignancy (10%), heart failure (3%), tuberculosis (2%), and pancreatitis (1%).1 An adequate diagnosis is
necessary for successful treatment.Ascites can be classified as: mild ascites only detectable by ultrasound (grade
1), moderate ascites evident by moderate symmetrical distension of the abdomen (grade 2), and large or gross
ascites with marked abdominal distension (grade 3).
Table 1.
Causes of ascites
Increased portal venous pressure
 Pre-hepatic: portal vein compression or thrombosis; schistosomiasis
 Hepatic: cirrhosis; acute hepatic necrosis; viral hepatitis
 Post-hepatic: Budd—Chiari syndrome, myeloproliferative disorders, constrictive pericarditis; right heart
failure, hypercoagulable states
Hypoproteinaemia
 Renal-disease—causing severe proteinuria
 Malnutrition and malabsorption
 Protein-losing enteropathy
 Acute or chronic liver disease
 Severe acute or chronic illness
Chronic peritoneal inflammation and infection
 Chronic infection: tuberculosis; fungal infection
 Secondary malignant infiltration (carcinomatosis peritonei)
 Post-irradiation
Leakage of lymphatic fluid (chylous ascites)
 Congenital
 Surgical trauma
 Primary and secondary lymphatic malignancy
Other fluids
 Pancreatic ascites
 Bilious ascites
 Urinary ascites
Staging
Ascites may be semi-quantified using the following system:
 Stage 1+ is detectable only after careful examination.
 Stage 2+ is easily detectable but of relatively small volume.
 Stage 3+ is obvious, but not tense, ascites.
 Stage 4+ is tense ascites.

DIAGNOSIS
History
Patients with ascites should be questioned about the pattern of body weight gain, change in abdominal girth, and
ankle oedema. Information about the medical history, medication use, lifestyle, risk factors for liver disease, and
infectious disease risk (e.g. migration) are relevant to discover the underlying aetiology.

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Physical examination

A screening physical exam should be carried out in every patient, with awareness of signs of liver disease
(erythema palmare, spider naevi, splenomegaly), heart failure (peripheral oedema, jugular venous distension,
third heart sound, pulmonary rales) and malignancy (lymphadenopathy).2The abdomen should be inspected for
the presence of bulging flanks and percussion can reveal flank dullness.

Flank dullness is found when approximately 1500 ml of ascites is present. These combined findings have a
sensitivity of 75% and a specificity of 57%. Shifting dullness, determined by a 3 cm flank dullness shift when
the patient changes from a supine to a lateral decubitus position has a sensitivity of 69% and a specificity of
69%. Detection of a fluid wave or puddle sign is less reliable3,4.Complications accompanying ascites such as
umbilical, inguinal and other hernias and pleural fluid (hepatic hydrothorax) are particularly common in cirrhotic
patients.

Blood tests
It is recommended to assess serum levels of creatinine, urea, electrolytes, prothrombin time and liver function
tests and to order a complete blood cell count5.

Abdominal ultrasound

(A) Ultrasound showing fluid (black) around the liver. (B) CT scan showing ascitic fluid, anterior abdominal distension and there is contrast
in the loops of the bowel.

Abdominal ultrasound is the first-line imaging method to confirm the presence and quantity of ascites.5-
7
Additionally, ultrasound can provide crucial information about the cause of ascites, detect signs of portal
hypertension (splenomegaly and portosystemic collaterals), and offer guidance during paracentesis.

Abdominal paracentesis
Abdominal paracentesis is the most important step in the diagnostic work-up. It is indicated in every patient with
new-onset ascites, patients with known ascites and clinical deterioration or a new presentation to an emergency
department. Paracentesis is usually performed in the left lower quadrant, 3 cm cranially and 3 cm medially from
the anterior superior iliac spine. Other sites include the right lower quadrant and the midline linea alba between
the umbilicus and the pubic bone. Paracentesis should be performed under sterile conditions. Complications
occur infrequently and include abdominal wall haematoma (1%), haemoperitoneum (< 0.1%), bowel perforation
(< 0.1%), and infection (< 0.1%).7,8

Ascitic fluid analysis

Visual inspection
Visual inspection of the ascitic fluid can show a milky, cloudy, bloody, straw coloured or clear appearance
(figure 1). Milky ascites suggests the presence of chylomicrons, containing predominantly triglycerides, and is
therefore called chylous ascites. Chylous ascites can result from malignancy, trauma, liver cirrhosis, infection,
pancreatitis, congenital disease and more uncommon causes.9 Cloudy ascites, also known as pseudochylous
ascites, may indicateperitonitis, pancreatitis or a perforated bowel. Bloody ascites is often associated with
malignancies or results from traumatic paracentesis, whereas straw coloured or clear ascites is common in liver
cirrhosis10. The first impression of the appearance of ascites is non-specific, but can steer the direction of
diagnosis.

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Biochemical testing
Serum-ascites albumin gradient
The serum-ascites albumin gradient (SAAG) is the most sensitive marker to distinguish between ascites due to
portal hypertension/hepatic congestion and other causes, with an accuracy of 97%.11 The SAAG is obtained by
subtracting the level of albumin in the ascitic fluid from that in the serum, both measured at the same time. A
value ≥ 1.1 g/dl (or 11 g/l) indicates underlying portal hypertension or hepatic congestion; a value < 1.1 g/dl
indicates aetiologies not due to portal hypertension, such as malignancy, pancreatitis or infection.

Total protein
Current international guidelines still recommend measuring the total protein concentration in
ascites.Traditionally, this was thought to indicate the aetiology of ascites according to the transudate-exudate
concept, but this approach is now generally considered inferior. The total protein concentration does have
prognostic value as concentrations lower than 15 g/l are associated with an increased risk for spontaneous
bacterial peritonitis (SBP) in cirrhotic patients.

Amylase
The amylase concentration in ascitic fluid should be measured in particular when pancreatic disease is
considered. Pancreatic ascites can be caused by leakage from pancreatic pseudocysts or due to pancreatic duct
rupture. An amylase ascitic fluid/blood serum concentration ratio of 6.0 is indicative for pancreatic disease,
considering that a ratio of 0.4 is normal in non-pancreatic ascites.12 However, high levels of amylase have also
been detected in patients with malignancy and other conditions making it a rather non-specific finding. Still it
can be of significant value in patients with comorbidities such as alcoholic cirrhosis and pancreatitis13.

Triglycerides
A concentration of triglycerides in the ascitic fluid that exceeds the blood serum level (2.2 mmol/l) indicates
chylous ascites. Previous abdominal surgery, pancreatitis, trauma and retro-peritoneal lymphoma are among the
main causes. Malignancy is diagnosed in 80% of patients with chylous ascites; however, it must be noted that
ascites

Adenosine deaminase activity

The activity of adenosine deaminase (ADA), an enzyme of purine metabolism, is a reliable marker to
differentiate tuberculous ascites from other aetiologies. An ADA cut-off value between 36 to 40 IU/l has a high
sensitivity (100%) and specificity (97%) for diagnosing abdominal tuberculosis15. In the Netherlands, the ADA
activity assay is available in a limited number of centres.

Glucose and lactate dehydrogenase

Traditionally, determining glucose and lactate dehydrogenase concentrations in ascites constituted part of the
diagnostic work-up. A lower glucose concentration in ascitic fluid than in blood serum can indicate the presence
of bacteria, white blood cells or cancer cells16,17. A low level of lactate dehydrogenase is associated with non-
malignant ascites, high levels suggest a malignant aetiology18.Unfortunately both measurements are influenced
by the SAAG, are non-specific and are no longer recommended19.

Urea and creatinine

A very uncommon cause of ascites is urinary leakage into the peritoneal cavity. Urinary ascites is associated
with pathological bladder changes and outlet obstruction20-21. Normally the ascites/plasma creatinine ratio is
approximately one, whereas a ratio of five is reported in case of urinary ascites. Importantly, urinary ascites can
be accompanied by pseudo-renal failure due to peritoneal absorption of urea.

Non-biochemical testing
Polymorphonuclear leukocyte count
A polymorphonuclear neutrophil (PMN) count should be performed in the ascitic fluid of all patients with ascites
admitted to the hospital or showing clinical signs suggestive of SBP. A PMN count ≥ 250 cells/mm3 (0.25 x109
cells/l) confirms the diagnosis of SBP in the absence of an evident intra-abdominal source of infection22. A PMN
count repeated after 48 hours of antibiotic administration can distinguish between SBP and secondary bacterial
peritonitis, a decrease suggests SBP and a sustained increase secondary bacterial peritonitis. A repeated PMN
count 48 hours after starting antibiotic therapy is recommended to document the efficacy of antibiotic therapy for
SBP. Although SBP is mainly a complication of ascites due to portal hypertension, it may also develop in
patients with ascites of other aetiologies.

Bacterial cultures
Ascitic fluid should be cultured if SBP is clinically suspected. Bedside inoculation of 10 ml under sterile
conditions using blood culture bottles, containing aerobic and anaerobic media, leads to identification of an

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organism up to 6% of cirrhotic patients has a chylous character.14in ~80% of patients with SBP7,23,24. Ascitic
fluid cultures should be carried out before antibiotic treatment is initiated.

PCR
Bacterial DNA of Mycobacterium tuberculosis in ascitic fluid can be detected using polymerase chain reaction
(PCR) and can be performed when tuberculous ascites is suspected. This method has a high sensitivity (94%)
compared with microscopic acid-fast bacilli smears (~0%) and mycobacterial culture (~50%)25,26. Alongside a
higher diagnostic accuracy, PCR offers a timesaving method in contrast to current Mycobacterium culture
techniques. PCR is a widely available biomolecular technique, however, PCR specific for the genus of
Mycobacterium may not be available in all centres. Furthermore, culturing Mycobacterium from ascitic fluid or
peritoneal biopsy remains the gold standard test according to national and international guidelines, also allowing
antibiotic susceptibility testing.

Cytology
Ascitic fluid cytology should be performed in case of suspicion of malignant ascites or when the underlying
aetiology is in doubt (e.g. no decrease in PMN count after 48 hours of antibiotic treatment). Clearly, positive
cytology is highly indicative for peritoneal carcinomatosis. The sensitivity of cytology is 83%, but can be as high
as97% if three samples from separate paracenteses are analysed27. Crucial factors are avoiding any time delay
between obtaining the ascitic fluid and cytology processing as well as obtaining at least 50 ml ascitic fluid, or
even 1000 ml if the first test was negative. The sensitivity of cytology in patients with hepatocellular carcinoma
and ascites is low (~27%)28.

Diagnostic laparoscopy
If the conventional work-up fails to disclose the cause of ascites, laparoscopy should be considered. Laparoscopy
offers the advantages of visual inspection of the peritoneal cavity in combination with the ability to obtain
targeted biopsies for histological and microbiological studies. The procedure may be particularly helpful to
diagnose peritoneal carcinomatosis, tuberculous peritonitis and other peritoneal or omental diseases such as
mesothelioma and sclerosing peritonitis29,30.

DIAGNOSTIC DEVELOPMENTS
Novel markers in ascitic fluid analysis have been proposed for the initial differential diagnosis as well as for
predicting prognosis in specific diseases. Most discoveries eithertarget on simplifying, accelerating or reducing
the costs of the diagnostic process or they result from advancing biochemical laboratory techniques.

Leucocyte esterase reagent strips

Leukocyte esterase reagent strips are widely used for urinary analysis with the advantages of a simple,
inexpensive and rapid bedside test. Several studies have examined the usefulness of this method for diagnosing
SBP and found this test had a sensitivity and specificity ranging from 80-93% and 93-98%, respectively31. The
negative predictive value is remarkably high ranging from 97-99%, which makes it an ideal tool to rule out
SBP.31Together with the other advantages, the reagent strip could gain a place in routine practice. Recently, an
asciticspecific reagent strip with a cut-off value of 250 cells/mm3 was introduced, which could further improve
diagnostic accuracy32.

Viscosity
A few studies have reported the potential usefulness of viscosity measurement of ascitic fluid. Measuring
viscosity was found to be able to discriminate between portal hypertension and non-portal hypertension related
aetiology and showed a high correlation with the SAAG33.These preliminary results await confirmation by
additional studies.

Vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is a protein which is fundamental in the process of vasculogenesis
and angiogenesis. High concentrations of vascular endothelial growth have been associated with malignant
ascites34.Additional research is necessary to define the diagnostic value of this test.

Bacterial DNA, cytokines and other proteins

Bacterial DNA was studied in two series of 30 patients with ascites due to liver cirrhosis. The presence of
bacterial DNA in ascites was regularly found documenting bacterial translocation, which could indicate a worse
clinical prognosis in this patient group, without implicating a diagnosis of SBP. Markers, such as endotoxin and
peptidoglycan/β-glucan, could predict a poor clinical outcome35,36. Another study, including 52 patients with
SBP and 27 control patients with cirrhotic ascites, found that blood serum concentrations of procalcitonin and an
ascitic fluid concentration of calprotectin were significantly higher in SBP patients. Both serum and ascitic levels

137
of TNF-αand IL-6 were significantly higher in SBP patients than in non-SBP patients37. These findings need to
be confirmedin larger series of patients.

Platelet indices
Increased platelet indices, e.g. mean platelet volume and platelet distribution width, have been reported in the
blood of cirrhotic patients with SBP. The diagnostic accuracy was not sufficient in this study, however, these
indices can be considered as a potential diagnostic tool38.

Tumour markers
Several studies have addressed the diagnostic value of tumour markers in ascitic fluid including α-fetoprotein,
des-gamma-carboxy prothrombin, carcinoembryonic antigen, cancer antigen 19-9 and cancer antigen 125.
Increased concentrations have been associated with underlying malignancies but are also found in medical
conditions such as gastritis, diverticulitis, cirrhosis and pancreatitis.

Medical Care
Sodium restriction (20-30 mEq/d) and diuretic therapy constitute the standard medical management for ascites
and are effective in approximately 95% of patients. Note the following:
 Water restriction is used only if persistent hyponatremia is present (see Diet, below).
 More recent research has focused on the treatment of refractory ascites with aquaretics—vasopressin V2-
receptor antagonists that promote excretion of electrolyte-free water and thus might be beneficial in
patients with ascites and hyponatremia. Although study results have been promising, aquaretics still await
approval by the Food and Drug Administration (FDA).
 In a multicenter study that assessed the safety and efficacy of an automated pump system for the treatment
of refractory ascites in 40 patients at 9 centers, Bellot et al reported the automated pump was an
efficacious tool to remove ascites from the peritoneal cavity to the bladder. During the 6-month follow-up
period, 90% of the ascites was removed with the pump system; there was also a significant reduction in
the monthly median number of large volume paracentesis as well as a reduction in the number of
cirrhosis-related adverse events.
 Therapeutic paracentesis may be performed in patients who require rapid symptomatic relief for refractory
or tense ascites. When small volumes of ascitic fluid are removed, saline alone is an effective plasma
expander. The removal of 5 L of fluid or more is considered large-volume paracentesis. Total
paracentesis, that is, removal of all ascites (even >20 L), can usually be performed safely.
 Supplementing 5 g of albumin per each liter over 5 L of ascitic fluid removed decreases complications of
paracentesis, such as electrolyte imbalances and increases in serum creatinine levels secondary to large
shifts of intravascular volume. Note: The AASLD indicates that postparacentesis albumin infusion may
not be necessary for a single paracentesis of less than 4 to 5 L ((class I, level C recommendation);
however, for large-volume paracenteses, an albumin infusion of 6-8 g per liter of fluid removed appears to
improve survival and is recommended (class IIa, level C recommendation).
 To avoid exposing patients to blood products, the use of terlipressin (eg, 1 mg every 4 hours for 48 hours)
rather than albumin has been proposed for prevention of circulatory dysfunction after large-volume
paracentesis. Initial studies suggest that terlipressin is as effective as albumin for this purpose.
 Repeated therapeutic paracentesis can be used to treat refractory ascites (class I, level C
recommendation). For palliative care in patients with advanced cancer, an alternative to serial
paracenteses is placement of an indwelling peritoneal catheter; ascitic fluid can then be removed by
continuous drainage or intermittent drainage with a proprietary system utilizing vacuum bottles, which
can be performed in the patient’s home. [16] Preservation of good nutrition status is important.
 The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional radiologic technique that
reduces portal pressure and may be the most effective treatment for patients with diuretic-resistant ascites.
In the procedure, which is performed with the patient under conscious sedation or general anesthesia, an
interventional radiologist places a stent percutaneously from the right jugular vein into the hepatic vein,
thereby creating a connection between the portal and systemic circulations. TIPS is gradually becoming
the standard of care in patients with diuretic-refractory ascites.

In a systematic review and meta-analysis of 10 trials comprising 462 patients with cirrhotic ascites, Guo et al
reported that midodrine, a vasopressor, used as a novel threapy for the ascites caused by cirrhosis did not
improve survival but potentially improved response rates and reduced plasma renin activity. However, when
midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for those
receiving midodrine than for those receiving albumin;midodrine and albumin had a similar association with the
development paracentesis-induced circulatory dysfunction.

Conservative management appears to be the treatment of choice for patients with chylous ascites.

138
Patients can actually be maintained free of ascites if sodium intake is limited to 10 mmol/d. However, this is not
practical outside a metabolic ward.

Twenty-four–hour urinary sodium measurements are useful in patients with ascites related to portal hypertension
in order to assess the degree of sodium avidity, monitor the response to diuretics, and assess compliance with
diet.

For grade 3 or 4 ascites, therapeutic paracentesis may be necessary intermittently.

Role of surgical therapy in management of intractable ascites

Almost 10% of patients with cirrhosis and ascites develop intractable ascites. When large-volume paracentesis
fails to relieve ascites, patients may be submitted to one of the three following surgical options: portosystemic
shunting, peritoneovenous shunting, or liver transplantation. Portosystemic shunting is efficient in
clearing ascites, but it is associated with a high rate of encephalopathy and liver failure. The indications for
portosystemic shunting are therefore limited for treatment of intractable ascites and should be performed only in
patients with good liver function in whom all other treatments failed. Peritoneovenous shunting has been
associated with a high rate of early complications and valve obstruction. Improvements in perioperative care and
in the material used have greatly reduced the operative risks and increased the patency rate. Mortality remains
high in patients with severe liver failure or with a history of spontaneous bacterial peritonitis or variceal
bleeding. Peritoneovenous shunting should not be done when these risk factors are present. In the absence of
such risk factors, peritoneovenous shunting is a good procedure and may provide definitive relief of ascites and
long-term survival in more than 50% of the operated patients. In patients with poor risk factors liver
transplantation may be preferable, and the onset of intractable ascites in a patient with a severely compromised
liver should trigger the indication of liver replacement.

Transjugular intrahepatic portosystemic shunts

A shunt is placed between the portal and systemic circulations in the liver
using the transjugular route for venous access. It may stabilise the patient
while consideration is being given to liver transplantation. The shunts have a
fairly high rate of blockage or stenosis (up to 75% after 6–12 months) and the
shunt may induce hepatic encephalopathy.

Portosystemic shunts
If ascites is due to portal hypertension, portosystemic shunting may be
performed in selected patients to reduce portal venous pressure. This may be
using transjugular intrahepatic portosystemic shunts (TIPS) or by making a formal anastomosis between the
splenic and renal veins (lienorenal shunt) or portal vein and inferior vena cava (portocaval shunt). These shunts
do not adress the problem of the underlying liver disease, nor the accompanying oesophageal varices. Shunt
surgery may be complicated by hepatic encephalopathy and hepatorenal syndrome. The presence of ascites in
patients undergoing shunt surgery for portal hypertension is a poor prognostic sign.
The peritoneovenous shunt is an alternative for patients with medically intractable ascites (see image below).
This is a megalymphatic shunt that returns the ascitic fluid to the central venous system. Beneficial effects of
these shunts include increased cardiac output, renal blood flow, glomerular filtration rate, urinary volume, and
sodium excretion and decreased plasma renin activity and plasma aldosterone concentration. Although it has
largely been supplanted by TIPS, peritoneovenous shunting has been shown to improve short-term survival
(compared with paracentesis) in cancer patients with refractory malignant ascites. The AASLD suggests
considering peritoneovenous shunting for patients with refractory ascites who are not candidates for
paracentesis, transplant, or TIPS (class I, level A recommendation).
The AASLD recommends that patients with cirrhosis and ascites be considered for liver transplantation (class I,
level B recommendation).

Peritoneovenous shunts
Symptomatic relief by draining ascitic fluid from the peritoneal cavity into the systemic venous system can be
achieved by way of a peritoneovenous shunt (PVS). A PVS (Denver shunt, LeVeen shunt) consists of a silastic
tube, with multiple side holes at each end and a oneway valve situated in the middle.

The PVS is placed entirely subcutaneously, with one end inserted into the peritoneal cavity and the other into the
superior vena cava (SVC) via a jugular or subclavian vein, so that the valve allows flow of ascites from the
peritoneal cavity to the venous system. A PVS is indicated when medical therapy has failed to control ascites in
patients with (i) intractable ascites in the presence of reasonably good liver function, or (ii) rapidly accumulating
ascites secondary to abdominal carcinomatosis. Concern about infusing ascitic fluid laden with malignant cells

139
into the circulation is theoretical because these patients have widely disseminated malignant disease before
insertion of the PVS.

The post-operative mortality of PVS is 10–20%, reflecting the serious underlying disorder of patients requiring
the procedure. However, most patients obtain useful palliation. A minor coagulopathy is common
postoperatively but can be partly prevented by completely aspirating the ascites and replacing it with warmed
normal saline or Hartmann's solution when inserting the PVS. Long-term complications include occlusion of the
PVS (particularly with bloody or highly proteinacious or mucoid ascites), SVC thrombosis, bacteraemia and
shunt infection, which may lead to subacute bacterial endocarditis.

SPECIAL SITUATIONS
Malignant ascites is defined as an accumulation of excessfluid in the peritoneal cavity secondary to a
disseminated malignancy . Apart from being a poor prognostic indicator italso adversely affects the patient’s
quality of life . Accordingto an estimate, it affects around 3.6-6% of patients admitted inthe palliative care unit.
Malignant ascites is an ominous signwith an average survival of around 20 weeks from its diagnosis. Around
95% of patients have metastatic disease involving peritoneum, liver, bone and lungs. Ovarian malignancy is the
most common cause (37%) followed by pancreatobiliary (21%)and gastric malignancy (18%). Around 20%
patients have unknown primary malignancy.

DISCUSSION

Pathophysiology
Pathophysiology of malignant ascites is multifactorial.It originates from an imbalance between fluid secretion
andabsorption by peritoneum. This is secondary to increasedfluid production by tumor cells lining peritoneal
cavity in cases of peritoneal carcinomatosis (PC), alteration in vascular permeability, release of inflammatory
cytokines and decreased lymphatic drainage due to tumor involvement and increased portal pressure due to
tumor metastasis. Obstruction of lymphatics is believed to be the main pathogenic mechanism for malignant
ascites. It has also been demonstrated that there is an abnormal accumulation of various osmotic macromolecules
in the peritoneal cavity of subjects with malignant ascites. Alteration in the vascular permeability allows larger
molecules to accumulate in the peritoneal cavity, leading to the shift of fluid balance towards net filtration which
overwhelms the drainage capacity of the peritoneal membrane. The combined effect of lymphatic obstruction
and abnormal macromolecule concentration in the peritoneal cavity is thought to produce refractory ascites in
cases of PC. Role of matrix metalloproteinase-9 has also been implicated in the pathophysiology of malignant
ascites.

Presentation
Symptoms are non-specific and may range from abdominal distension, early satiety to dyspnea, orthopnea and
peripheral edema. Diagnosis is made by clinical examination, ultrasonography (USG) or Computed Tomography
(CT) scan. Ascitic fluid analysis is considered the gold standard investigation. Tumor markers are not diagnostic
for malignancy but may help in identifying primary malignancy. Low glucose levels (<100mg/dl) and high fluid
to serum lactate dehydrogenase (LDH) levels (>1) are suggestive of peritoneal carcinomatosis (PC).
Laparoscopy and tissue sampling may be utilized to confirm the diagnosis.

Prognosis
It is associated with a strong negative prognostic value. Survival is poor when ascites is secondary to GI
malignancy as compared to ovarian malignancy. Other prognostic factors include low serum albumin, liver
metastases and elevated serum bilirubin levels. High level of Vascular endothelial growth factor (VEGF) have
been found to be independent poor prognostic factor for overall survival.

Management
The aim of management is to provide symptomatic relief and specific treatment of the primary pathology.
Management options may be classified into conventional methods and newer modalities.

a) Conventional management: General management includes low salt diet and diuretic therapy. Response is
better with diuretic therapy in patients with increased renin values, massive liver metastases and elevated serum
ascites albumin gradient (SAAG). Therapeutic paracentesis can be used for rapid symptom control. Large
volume paracentesis (upto 5 litre) can be done without undue complications. However, it may lead to secondary
peritonitis and pulmonary embolism. Tunnelled catheters like permanent peritoneal catheter drainage system
have been tried. They are placed subcutaneously under local anesthesia. Process involves attaching vacuum
bottle to catheter and draining fluid. Advantages include greater flexibility, frequent episodes can be done,
reduced infections and reducedresource usage. However, they are not widely available.

140
Peritoneovenous shunts have been utilized for malignant ascites. They are recommended if life expectancy is
more than 3 months. Symptom palliation is seen in 70% of patients. Complications include shunt occlusion,
fever, cardiopulmonary compromise, disseminated intravascular coagulation (DIC). Contraindications are
fulminant hepatic failure, ascites with positive malignant cytology, hemorrhagic or chylous ascites and life
expectancy less than one month.

b) Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

As PC is one of the most important cause of malignant ascites, specific treatment may yield better survival
results. Systemic chemotherapy is rarely effective and more toxic in PC due to poor blood supply. CRS with
intraperitoneal chemotherapy has been effectively utilized for GI malignancies associated with PC. Rationale
behind this procedure includes cytoreduction with prolonged contact on tumor nodules, selective cytotoxicity
due to protein denaturation, impaired DNA repair due to hyperthermia and hyperthermia induced vasodilatation
with improvement in tumor oxygenation. Improved survival has been achieved with this technique as compared
to systemic chemotherapy.

Combination with intravenous chemotherapy has been triedalong with HIPEC. Due to high morbidity rates with
CRS and HIPEC, laparoscopic HIPEC has been tried in patients not fit to undergo cytoreductive surgery.
Intraperitoneal chemotherapy is administered via infusion trocar and table is tilted for effective contact. It has
been found to be a safe and effective modality for palliation of malignant ascites.

c) Newer modalities
Newer drugs have been tried for malignant ascites. OK-432 is a preparation from Streptococcus pyogenes.
Intraperitoneal instillation reduces ascites in 60% of patients. Mechanism of action is not clear. Improved mean
survival has been reported with this therapy. Metalloproteinase inhibitors like Batimastat have been studied in
early phase trials with good results. However, larger trials are needed to conclusively define their benefits. Anti
VEGF therapies like Bevacizumab have been shown to inhibit ascites formation in animal models and human
trials are ongoing.

Various cytokines like Interferon alpha, Interleukin 2 and Tumor Necrosis factor have been reported with
variable effectiveness in small pilot studies. Antibodies against cellular adhesions molecules like Epilthelial cell
adhesion molecule (EpCAM) like Catumaxomab after therapeutic paracentesis are associated with prolonged
paracentesis-free survival, improved quality of life and prolonged overall survival. Mechanism of action includes
decreased proliferation, migration and invasion of cancer cells. Photosensitisers have also been tried. They act by
stimulating antitumor response and selective destruction of cancerous tissues. However, further studies are
needed toconclusively recommend the therapy.

Leakage of lymph from the lymphatic ducts causes chylothorax (CT) or chylous ascitis (CA). This may happen
for unknown reasons during fetal life or after birth and may also be caused by trauma after thoracic surgery or by
other conditions. Fetal CT and CA may be lethal particularly in cases with fetal hydrops that sometimes benefit
of intra-uterine instrumentation. After birth, symptoms are related to the amount of accumulated fluid.
Sometimes, severe cardio-respiratory compromise prompts active therapy. Most patients with CT or CA benefit
from observation, rest, and supportive measures alone. Drainage of the fluid may be necessary, but then loss of
protein, fat, and lymphoid cells introduce new risks and require careful replacement. Low-fat diets with MCT
and parenteral nutrition decrease fluid production while allowing adequate nutritional input. If lymph leakage
does not stop, secretion inhibitors like somatostatin or octreotide are prescribed, although there is only weak
evidence of their benefits. Imaging of the lymphatic system is indicated when the leaks persist, but this is
technically demanding in children. Shunting of the lymph from one body space to another by means of valved
catheters, embolization of the thoracic duct, and/or ligation of the major lymphatics may occasionally be
indicated in cases refractory to all other treatments.

Postoperative ascites is a very rare complication of laparoscopic surgery. Significant iatrogenic injuries to the
bowel, the urinary tract, and the lymphatic system should be excluded promptly to avoid devastating results for
the patient. In some cases, in spite of investigating patients extensively, no definitive causative factor for the
accumulation of fluid can be identified. In such cases, idiopathic allergic or inflammatory reaction of the
peritoneum may be responsible for the development of ascites.

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 ABDOMINAL COMPARTMENT SYNDROME
Lovenish Bains, Pawan Lal

Background
The abdominal compartment syndrome (ACS) has tremendous relevance in the practice of surgery and the care
of critically ill patients, because of the effects of elevated pressure within the confined space of the abdomen on
multiple organ systems. Intra-abdominal hypertension has a prevalence of at least 50% in the critically ill
population and has been identified as an independent risk factor for death. Yet, many of the members of the
critical care team do not assess for intra-abdominal hypertension and are unaware of the consequences of
untreated intra-abdominal hypertension. These consequences can be abdominal compartment syndrome,
multisystem organ failure, and death. The problem of ACS goes well beyond the care of surgical patients,
encompassing many diverse disease states and clinical scenarios. Therefore, the ACS should be viewed as the
end-result of a progressive, unchecked rise in IAP from a myriad of disorders that eventually leads to multiple-
organ dysfunction.

Incidence/prevalence
IAH was estimated to occur in 32.1% of ICU patients, and ACS has been reported in up to 4.2% of patients
requiring critical care (2005). Malbrain et al conducted a prevalence study in 13 intensive care units (ICUs) and
assessed 97 patients. The overall prevalence of IAH was 58.8% (IAP >12 mm Hg). Prevalence was 65% in
surgical patients and 54.4% in medical patients. Vidal et al studied the incidence of IAP in 83 critically ill
patients in a single ICU. A total of 31% of the patients had IAH at the time of admission to the unit, and the
condition developed in another 33% after admission. Compared with patients without IAH, patients with IAH
were sicker and had a higher mortality rate (53% vs 27%; P = .02). Reintam et al performed a study to identify
the differences in incidence, course, and outcome of primary and secondary IAH and to determine if IAH is an
independent risk factor for death. He concluded that development of IAH is an independent risk factor for death.
They further concluded that compared with primary IAH, secondary IAH does not occur as often, has a different
development course, and has worse outcomes. These studies indicate that IAH occurs frequently and may
worsen patients’ outcome.

Historical Perspectives
The effects of elevated IAP have been known since the late 19th century when Marey and Burt highlighted the
respiratory effects of elevated IAP. In 1890, Heinricius demonstrated that elevation of IAP to 27 and 46 cmH2O
led to death in feline and porcine models. In 1913, Wendt first described the association of IAH and renal
dysfunction and others corroborated his findings. Basic science and clinical observations have since confirmed
the effects of elevated IAP on multiple organ systems. The term ACS was first used by Kron et al. in the early
1980's to describe the pathophysiology resulting from IAH secondary to aortic aneurysm surgery.
The concept of IAH was proposed in the late 1800s, forgotten after World War I, and rediscovered near the end
of the 20th century. In 2004, a group of international physicians and surgeons formed the World Society of the
Abdominal Compartment Syndrome (WSACS). The goal of this new organization was to develop a cohesive
approach to the management of IAH and ACS, foster education and research, and develop consensus statements
and definitions. WSACS has developed evidence-based definitions, guidelines, and treatment algorithms and has
identified evidence based devices and methods to measure intra-abdominal pressure (IAP).

Definitions (WSACS)
Intra-abdominal Hypertension= IAH is a sustained or repeated pathological elevation of IAP of 12 mm Hg or
greater. IAH is graded as follows
Grade I, IAP 12–15 mmHg
Grade II, IAP 16–20 mmHg
Grade III, IAP 21–25 mmHg
Grade IV, IAP > 25 mmHg
Abdominal Perfusion Pressure = Abdominal perfusion pressure (APP) is a measure of the relative adequacy of
abdominal blood flow. APP is calculated by subtracting the IAP from the mean arterial pressure (MAP): MAP-
IAP=APP.
Abdominal Compartment Syndrome= ACS is a sustained IAP greater than 20 mm Hg (with or without an APP
<60 mm Hg) associated with new organ dysfunction or failure.

Retained definitions from the original 2006 consensus statements (WSACS- 2013)
 IAP is the steady-state pressure concealed within the abdominal cavity
 The reference standard for intermittent IAP measurements is via the bladder with a maximal instillation
volume of 25 mL of sterile saline

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  IAP should be expressed in mmHg and measured at end expiration in the supine position after ensuring
that abdominal muscle contractions are absent and with the transducer zeroed at the level of the
midaxillary line
 IAP is approximately 5–7 mmHg in critically ill adults
 IAH is defined by a sustained or repeated pathological elevation in IAP C 12 mmHg
 ACS is defined as a sustained IAP [20 mmHg (with or without an APP\60 mmHg) that is associated
with new organ dysfunction/failure.
 Primary IAH or ACS is a condition associated with injury or disease in the abdominopelvic region that
frequently requires early surgical or interventional radiological intervention
 Secondary IAH or ACS refers to conditions that do not originate from the abdominopelvic region
 Recurrent IAH or ACS refers to the condition in which IAH or ACS redevelops following previous
surgical or medical treatment of primary or secondary IAH or ACS
 APP = MAP – IAP
 Abdominal compliance is a measure of the ease of abdominal expansion, which is determined by the
elasticity of the abdominal wall and diaphragm. It should be expressed as the change in intra-abdominal
volume per change in IAP
Causes of elevated intra-abdominal pressure
Acute:
Retroperitoneal pancreatitis. pelvic or retroperitoneal bleeding, contained abdominal aortic aneurysm
Origin rupture, aortic surgery, abscess, visceral edema
Intraperioneal inraperitoneal bleeding, free abdominal aortic aneurysm rupture, acute gastric dilatation,
Origin bowel obstruction, ileus, mesenteric venous obstruction, pneumoperitoneum, abdominal
packing, abscess, visceral edema
Abdominal Wall burn eschar, repair of gastroschisis or omphalocele, reduction of large hernias, military anti-
shock garments, laparotomy closure under extreme tension
Chronic: central obesity, ascites, large abdominal tumors, chronic ambulatory peritoneal dialysis,
pregnancy

Pathological effect on organs

The abdomen can be considered a compartment with the spine, pelvis and costal arch as its inflexible edges and
the diaphragm and abdominal wall as its more pliable edges. The internal contents of this compartment consist of
the stomach, large and small intestine, omentum, liver, spleen, pancreas, gall bladder, kidneys, adrenal glands,
ureters, bladder, and, in females, the uterus. Major blood vessels also course through this compartment. The
abdominal aorta, with its branches of the celiac axis and the superior and inferior mesenteric arteries, perfuses
the gut and the accessory organs. All the venous blood from the gut drains into the portal vein to the liver and
leaves the liver via the hepatic vein to be drained into the inferior vena cava. The abdominal compartment
contains solid organs, hollow organs, fluid, gas, solids, and adipose tissue. When a condition arises that
persistently increases pressure in the abdominal cavity to 12 mm Hg or greater, not only the gut but all major
body systems can be affected, and the effects can lead to multisystem organ failure and death.
Salient aadverse effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on
organ systems:

Gastrointestinal function
• Increased intra- abdominal pressure results in an increase in vascular resistance and decreased cardiac
output.
• Results in a decrease in gut perfusion.
• Ultimately tissue ischemia.
 Patients with IAH are also at high risk for stress ulcers because of the loss of the mucosal barrier.8
 An IAP of up to 20 mm Hg can decrease mesenteric perfusion by 40%, and pressures up to 40 mm Hg
can decrease mesenteric perfusion by 70%.12
 The correction of IAH can lead to ischemia reperfusion injury and send inflammatory cytokines to other
organs, setting the ground work for multisystem organ failure.12
 Distention of the abdominal wall by IAH leads to decreased compliance of the wall, further
compounding the IAH.
 The vascular liver is extremely susceptible to IAH.

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Cardiac function
• An increase in IAP causes increased pressure on the inferior vena cava, intra-abdominal circulation and
perfusion.
• Venous return is impaired, preload is decreased with resultant decrease in cardiac output
• Increased systemic vascular resistance.
• Increased pulmonary artery wedge pressures as the myocardium is placed under an increasing
workload.

Respiratory function
• An increased in IAP forces the diaphragm up decreasing intra-thoracic space and restricts respiration.
• Compression atelectasis
• Increases peak inspiratory pressure
• Result in an increase in intra thoracic pressure particularly with mechanically ventilated patients.
• Left uncorrected will result in a decrease in lung compliance, functional residual capacity a VQ
mismatch and hypoxia.

Renal function
• Defined as oliguria and anuria despite aggressive fluid resuscitation.
• The renal impairment, as indicated by an elevated serum level of creatinine, may not appear until 2 to 3
days after the incident of IAH.
• Increase in abdominal pressure decreases renal blood flow coupled with a reduction in cardiac output
leading to decreased perfusion.
• The rennin angiotensin system is activated further adding to intra- abdominal pressure and cardiac
workload.

Cerebral
• An Increase in IAP forces the diaphragm up decreasing intra-thoracic space, increasing the intra-
thoracic pressure.
• Jugular venous pressure elevates.
• Venous return decreases.
• Intra cerebral pressure will increase.
• Cerebral blood flow decreases.

Peripheral perfusion
• Increased intra- abdominal pressure is said to increase femoral venous pressure increase peripheral
vascular resistance and reduce femoral artery blood flow by up to 60%.
• Increased likelihood of DVT.

In summary, IAH can affect almost all body systems. IAH has been proposed as the initial fall of the dominoes
on the pathway of multisystem organ failure.

Clinical Examination
The history varies depending on the cause of abdominal compartment syndrome, but abdominal pain is
commonly present. Compartment syndrome in the abdomen is usually suggested by an increased abdominal
girth. If this change is acute, the abdomen is tense and tender. Physical examination was found to be neither
sensitive nor specific for the diagnosis of IAH/ACS with a sensitivity of 56%, specificity of 87%, positive
predictive value of 35%, negative predictive value of 94% and accuracy of 84%.
Radiological Examination
Imaging studies such as chest X-ray, ultrasound abdomen and CT scan are not useful to diagnose IAH/ACS
efficiently but can give some clue to the possibility, such as elevated diaphragm, basal atelectasis, inferior venae
caval compression, tense infiltration of the retro peritoneum that is out of proportion to peritoneal disease,
massive abdominal distension, direct renal compression or displacement, bowel wall thickening or bilateral
inguinal herniation. Ultrasound (point of care ultrasound) was comparable to abdominal X-ray, but shown to be
superior in determining the gastric content (fluid vs. solid). Furthermore, POCUS allowed faster determination
of correct NGT positioning in the stomach (antrum), avoiding bedside radiation exposure. It has the potential to
be used in both diagnosis and treatment during the course of IAH.
Measurement of IAP
WSACS has standardized intra-vesical (urinary bladder) pressure measurement as the gold standard for
measurement of IAH/ACS. This method uses an indwelling urinary catheter, a pressure transducer, and a syringe
or similar device, capable of infusing fluid. Advantages of this technique are its reliability, relative
noninvasiveness, and elementary process. This was done through puncturing the aspiration port of Foley’s
catheter or attaching a three-way stopcock and connecting it to a manometer, but nowadays a closed system has

145
been developed which avoids the puncturing and ensures sterility. The pressure is measured at end-expiration in
the supine position after ensuring that abdominal muscle contractions are absent. The transducer should be
zeroed at the level of the mid-axillary line. WSACS has also standardized the amount of saline to be instilled as
up to 25 ml. The manometer technique is similar to the method of measuring CVP with a fluid column. The
patient should have a urinary catheter in place; the only equipment needed is a centimeter ruler. This technique is
called the U-tube technique and is a modification of a technique first developed by an emergency department
nurse. The clinical validation with the U-tube technique is poor, and the method is recommended primarily for
screening. Commercial kits include the AbViser AutoValve, Bard intra-abdominal pressure monitoring device,
FoleyManometer (Holtech device) etc.

Physiological factors impacting on intra-abdominal pressure (IAH)

Related to diminished
abdominal wall compliance
• High BMI
• Pregnancy
• Mechanical ventilation
• The use of PEEP or when
auto PEEP is present
• Basal pneumonia
• Pneumoperitoneum
• Abdominal surgery
particularly with tight
abdominal closures
• Pneumatic anti shock
garments
• Prone positioning
• Abdominal wall bleeding or
abdominal hematoma
• Burns with abdominal
eschars
Related to increased
intraabdominal contents
• Gastro paresis
• Gastric distension
• Ileus
• Volvulus
• Bowel pseudo obstruction
• Abdominal hematoma
•Intra-abdominal or
retroperitoneal hematoma
• Damage control laparotomy
• Liver dysfunction with ascites
• Abdominal infection
(peritonitis, pancreatitis)
• Hemoperitoneum
• Pneumoperitoneum
• Major trauma
• Excessive inflation during
laparoscopy
• Peritoneal dialysis
Related to capillary leak and fluid
resuscitation
• Acidosis (pH below 7.2)
• Hypothermia (core temp below 33°
• Coagulopathy
• Multiple transfusions/trauma (>10
units in 24 hours)
• Sepsis, severe sepsis or bacteremia
• Septic shock
• Massive fluid resuscitation (>5 L
colloid or > L crystalloid in 24 hours in
the presence of capillary leak and a
positive fluid balance)
• Major burns

Monitoring Guidelines
Patients who are identified at-risk can be monitored by bladder pressure measurements according to the
following schedule:
(a) On arrival to the SICU.
(b) Every 2 hours for the first 8 hours.
(c) Every 4 hours for the next 8 hours.
(d) Every 8 hours for the next 24 hours.
The surgical/critical care team shall be notified of all bladder pressure measurements >12mmHg and abdominal
perfusion pressures < 60mmHg.

Management
Surgical decompression is the definitive management of IAH/ACS but supportive medical therapy should be
attempted before resorting to this. WSACS has provided algorithm for management of IAH/ACS (Algorithms 1
and 2). Nowadays, the trend is more towards less invasive management such as abdominal wall escharotomy in
burns or percutaneous drainage of intra-abdominal collections.

Principles of supportive care are as follows:

1. Evacuate intra-luminal contents: nasogastric and rectal drainage.
2. Drain extra-luminal collections: evacuate hemoperitoneum, ascites, intra-abdominal abscess and
retroperitoneal hematoma.
3. Improve abdominal wall compliance: supine position, adequate analgesia, sedation and sometimes muscle
paralysis.

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Many of IAH/ACS patients will need ventilator support and should have a lung protective strategy like low tidal
volume, pressure limitation, permissive hypercapnia, use of positive end expiratory pressure (PEEP) and use of
muscle relaxants in indicated patients. Aggressive fluid resuscitation is one of the risk factors for the
development of ACS. As these patients are hemodynamically unstable initially, they receive large amounts of
crystalloids with resultant bowel edema and development or aggravation of ACS. Liberal use of colloids has not
yet proved to prevent this.

Algorithm 1. IAP/ACS Medical management (WSACS)

A systematic review and meta-analysis on effect of decompressive laparotomy on organ function in patients with
abdominal compartment syndrome was done recently. The literature was reviewed for studies reporting on the
effect of decompressive laparotomy in patients with ACS published between 1995 and September 2017. 28 full-
text articles reviewed and ultimately, 15 articles were included in the analysis. Overall, 286 patients with 292
ACS episodes were included in the analysis. The baseline mean IAP was 31.7 mmHg and ranged from 23 mmHg
to 43.4 mmHg. Following decompression, the IAP decreased to an average of 13.5 mmHg, varying between 11
and 17 mmHg. The mortality rate was reported in 11 of 12 studies and ranged from 22.2% to 71.4% in the
individual studies; overall mortality was 49.7% (123 of 247 patients died). Multiple organ failure was the main
cause of death, followed by intestinal ischemia or necrosis. There was a trend toward a statistically significant
correlation between time to decompression and mortality (grades III and IV p = 0.01, F = 30.75, R2 = 1)

Recent insights
• Procalcitonin (PCT) and C-reactive protein: The correlation of PCT values with IAH grades is quite
significant while the CRP results remain high in IAH but without significant difference between the
different grades of IAH.
• Mitochondrial Ca2+uptake 1 (MICU1)-related oxidation/antioxidation disequilibrium is strongly
involved in IAH-induced damage to intestinal barriers.

147
• Melanocortin 4 (MC4 receptor) agonist counteracts the intestinal inflammatory response, ameliorating
intestinal injury in experimental secondary IAH by MC4 receptor-triggered activation of the cholinergic
anti-inflammatory pathway. This may represent a promising strategy for the treatment of IAH in the
future.
• New medical treatment options that are still experimental include tissue plasminogen activator (tPa),
theophylline and octreotide.
o tPa was evaluated for retroperitoneal hematoma. The mean IAP was 23.5 mmHg before
decompression (range 12−35) and when t a was given IA dropped to a mean of 16 mmHg
(range 10−28.5) after 24 h of administration.
o Theophylline improved renal function, splanchnic perfusion, and cardiac contractility possibly
by counteracting adenosine binding to adenosine receptors.
o Octreotide, a synthetic somatostatin analogue, by decreasing myeloperoxidase (MPO) activity
and malondialdehyde levels and thereby increasing levels of glutathione if given before
decompression of IAP has been shown to improve the reperfusion-induced oxidative damage
in rats with ACS.

Algorithm 2. IAP/ACS management (WSACS)

148
All the novel medical options for management of IAH/ACS apart from standard medical management-like
evacuation of intra and extra luminal contents, improvement of abdominal wall compliance, are still in
experimental stage and not recommended for routine use.

To summarize
IAH/ACS is not a problem limited to the abdomen but rather a systemic problem affecting various body systems
adversely with deleterious consequences. Addressing this important pathology in a timely manner is crucial for
the better outcome of critically ill patients. Mainstay of the management in IAH/ACS is still surgical
decompression but medical options are equally important interventions. Better patient selection and optimized
timing of the intervention may result in better clinical outcomes in the future. More studies are needed are
needed for insights into management.

Resources:
1. Rosemary Koehl Lee, Intra-abdominal Hypertension and Abdominal Compartment Syndrome A Comprehensive
Overview. Crit Care Nurse February 2012 vol. 32 no. 1 19-31
2. Kirkpatrick AW, Roberts DJ, De Waele J, Jaeschke R, Malbrain ML, De Keulenaer B, et al. Intra-abdominal
hypertension and the abdominal compartment syndrome: updated consensus definitions and clinical practice
guidelines from the World Society of the Abdominal Compartment Syndrome. Intensive Care Med. 2013
Jul;39(7):1190-206. doi: 10.1007/s00134-013-2906-z. Epub 2013 May 15.
3. Kirkpatrick AW, Sugrue M, McKee JL, Pereira BM, Roberts DJ, De Waele JJ, et al. Update from the Abdominal
Compartment Society (WSACS) on intra-abdominal hypertension and abdominal compartment syndrome: past,
present, and future beyond Banff 2017. Anaesthesiol Intensive Ther. 2017;49(2):83-87. doi:
10.5603/AIT.a2017.0019. Epub 2017 May 14.
4. Bob H Saggi, Rao Ivatury, Harvey J Sugerman. Abdominal compartment syndrome. Surgical Treatment: Evidence-
Based and Problem-Oriented. 2001
5. Malbrain ML, Chiumello D, Pelosi P, Bihari D, Innes R, Ranieri VM, et al. Incidence and prognosis of
intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological
study. Crit Care Med. 2005 Feb;33(2):315-22.
6. Malbrain ML, Chiumello D, Pelosi P, Wilmer A, Brienza N, Malcangi V, et al. Prevalence of intra-abdominal
hypertension in critically ill patients: a multicentre epidemiological study. Intensive Care Med. 2004;30:822-829.
7. Vidal MG1, Ruiz Weisser J, Gonzalez F, Toro MA, Loudet C, Balasini C, et al. Incidence and clinical effects of
intra-abdominal hypertension in critically ill patients. Crit Care Med. 2008 Jun;36(6):1823-31
8. Reintam A, Parm P, Kitus R, Kern H, Starkopf J.. Primary and secondary intraabdominal
hypertension—different impact on ICU outcome. Intensive Care Med. 2008 Sep;34(9):1624-31.
9. Malbrain M. The Pathophysiologic Implications of Intra-abdominal Hypertension in the
Critically ill. Antwerp, Belgium: Katholieke Universiteit Leuven; 2007.
10. Kron IL, Harman PK, Nolan SP. The measurement of intra-abdominal pressure as a criterion for abdominal re-
exploration. Ann Surg. 1984 Jan;199(1):28-30.
11. Abdulgafoor M. Tharayil, Adel Ganaw, Syed Abdulrahman, Zia M. Awan, Sujith M. Prabhakaran
Abdominal Compartment Syndrome: What Is New? http://dx.doi.org/10.5772/intechopen.68343
12. Al-Abassi AA, Al Saadi AS, Ahmed F. Is intra-bladder pressure measurement a reliable indicator for raised intra-
abdominal pressure? A prospective comparative study. BMC Anesthesiol. 2018 Jun 19;18(1):69.
13. Luckianow GM, Ellis M, Governale D, Kaplan LJ. Abdominal compartment syndrome: risk factors, diagnosis, and
current therapy. Crit Care Res Pract. 2012;2012:908169.
14. Papavramidis TS, Marinis AD, Pliakos I, Kesisoglou I, Papavramidou N. Abdominal compartment syndrome -
Intra-abdominal hypertension: Defining, diagnosing, and managing. J Emerg Trauma Shock 2011;4:279-91
15. Leanne Hunt, Steve A Frost, Ken Hillman, Phillip J Newton, Patricia M Davidson. Management of intra-
abdominal hypertension and abdominal compartment syndrome: a review. J Trauma Manag Outcomes. 2014; 8: 2.
16. Pereira BM, Pereira RG, Wise R, Sugrue G, Zakrison TL, Dorigatti AE, Fiorelli RK, Malbrain MLNG. The role of
point-of-care ultrasound in intra-abdominal hypertension management Anaesthesiol Intensive Ther.
2017;49(5):373-381
17. Van Damme L, De Waele JJ. Effect of decompressive laparotomy on organ function in patients with abdominal
compartment syndrome: a systematic review and meta-analysis. Crit Care. 2018 Jul 25;22(1):179.
18. Braha B, Mahmutaj D, Maxhuni M, Neziri B, Krasniqi S. Correlation of Procalcitonin and C-Reactive Protein with
Intra-Abdominal Hypertension in Intra-Abdominal Infections: Their Predictive Role in the Progress of the Disease.
Open Access Maced J Med Sci. 2018 Mar 5;6(3):479-484
19. Cheatham ML. Abdominal compartment syndrome: pathophysiology and definitions. Scand J Trauma Resusc
Emerg Med. 2009 Mar 2;17:10.

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 ENHANCED RECOVERY AFTER UPPER GASTROINTESTINAL SURGERY
Vikram Kate, Archana Elangovan, R. Kalayarasan, Mohsina Subair

INTRODUCTION
Enhanced Recovery After Surgery (ERAS) is an evidence based multimodal approach that aims at hastening the
patient’s recovery by attenuating the stress response to surgery1,2. It includes evidence-based elements in the
preoperative, intraoperative and post-operative period, which in turn reduces the stress of surgery. These
protocols are developed based on the advancements in the field of Surgery, Anaesthesia and Nutrition and is
continuously evolving3. Its successful implementation requires a committed multidisciplinary team including the
nurses, dietician, physiotherapists, occupational therapists, pain team, theatre staff, Anaesthetists, Surgeons,
Hospital management, Audit team and the patient4.

The traditional perioperative care elements have a strong hold in the minds of surgeons and have been taught
over generations as the standard of care5. Prolonged preoperative fasting, mechanical bowel preparation,
nasogastric (NG) tube insertions, drain tube insertions and prolonged bed rest, to name a few. However, the
recent evidences have broken these dogmas and have proven that few of these practices are often not evidence
based6,7,8. The field of perioperative care has been revolutionized with the introduction of Fast track protocols or
ERAS Pathways whose primary goals are to improve the quality as well as the speed of recovery by providing a
‘painless stress-free and safe’ surgery to patients. It still remains unacceptable to majority of surgeons in India,
to deviate from the traditional practices. Hence the implementation of ERAS is still limited to fewer centres and
experimental studies.

EVOLUTION OF ERAS
Significant advances in the fields of Anaesthesia and Surgery in the 1990s, like regional anaesthesia and
minimally invasive surgeries lead to tremendous improvement in the patient’s functional recovery. Professor
Henrik Kehlet introduced the concept of ‘Fast track surgery’ in 1997. The landmark study by Kehlet proposed
that understanding the pathophysiology of surgical stress response is important in order to discern the
postoperative morbidity. Modifications of these factors will improve the outcome of surgery. It was proposed
that multimodal interventions rather than a single drug regimen or technique will significantly improve the
recovery and reduce the morbidity and costs9. ERAS was first introduced for colonic procedures in 1997.
Following its success, it was further studied extensively and applied in other surgeries. Fast track protocols were
further refined in 1999. A collaborative group on the peri-operative care was established in the year 2010, called
the ERAS Study group. In the year 2005, they established the consensus protocol for colonic surgeries. Later in
2010, it was registered officially as a non-profit medical society in Stockholm, Sweden.10They have established
guidelines for different procedures including colonic surgery, pancreaticoduodenectomy, elective rectal/pelvic
procedures, radical cystectomy, gastrectomy and liver surgery11-16. Modified guidelines are introduced in other
specialities like gynaecology, orthopaedics and breast and reconstructive surgery.

ATTENUATION OF SURGICAL STRESS

The body’s reaction to surgical stress is the metabolic response to injury. This response includes all factors
associated with surgery such as fasting, anxiety, tissue damage, hypothermia, blood loss, pain, fluid shifts,
hypoxia, prolonged bed rest, ileus and cognitive imbalance. The stress response is mediated by hormonal and
metabolic changes which leads to haematological, endocrine and immunological responses, which in turn
parallels with the degree of tissue injury. It is further aggravated by post-operative complications. The neuro-
hormonal response to stress causes an escalation of counter regulatory hormones like cortisol, adrenaline,
glucagon and adrenocorticotropic hormone (ACTH). It shifts the body’s overall metabolism to a catabolic
state17. A key factor in the post-operative morbidity is the insulin resistance induced by cytokines (TNF and IL-
6). The elements of ERAS like preoperative fasting guidelines, carbohydrate loading, gylcemic control etc. helps
in reducing insulin resistance and also shifts the metabolism to anabolic state18-20. The central and peripheral
nervous system acts in a common pathway to trigger the catabolic response of tissue trauma. Administration of
epidural and local anaesthesia blocks these pathways and thereby reduces the counter regulatory hormones. It
thus helps in reducing insulin resistance, reducing hyperglycaemia and protein catabolism21,22. The metabolic
response can be a threat to the body and mind and needs to be optimised adequately for successful return to
preoperative levels23.

COMPONENTS OF ERAS
The components of ERAS are given below. An overall outline on the components and outcome of ERAS
protocols are given in Fig 1 and Fig 2 respectively.

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PREOPERATIVE ELEMENTS
• Preoperative dedicated information, counselling and education: Reduces the anxiety and improves the
patient compliance.11,24,25
• Adequate medical optimisation of the patient preoperatively, like cessation of alcohol and smoking at
least 4 weeks ahead of surgery, optimising the co-morbid conditions, correcting the nutritional status :
Reduction in the post-operative morbidity by improving the functional capacity. 26-29
• Mechanical bowel preparation is not recommended on a routine basis before bowel surgeries: Many
Randomised Control Trials (RCT) have proved that bowel preparation before surgery does not reduce
the complications like anastomotic leaks and wound infection. Moreover, it causes dehydration and
significant distress to the patient. 30-32
• Allow Clear fluids up to 2 hours and solids up to 6 hours ahead of surgery: A recent meta-analysis from
Cochrane has shown that preoperative fasting from midnight does not increase the pH or reduce the
contents. Intake of clear fluid with high complex carbohydrate levels have shown to reduce hunger,
anxiety, postoperative lean body mass loss and lessens postoperative protein loss. 33-36
• Routine administration of sedative drugs before surgery is not warranted: Administration of long acting
sedatives delays the post-operative recovery by impairment of oral intake and mobility. 37
• Prophylaxis for thromboembolism should be given, like compression stockings, intermittent pneumatic
compression and pharmacological prophylaxis: There is a high chance of DVT in malignancies,
previous pelvic surgeries, corticosteroids intake, hypercoagulable states and extensive co-morbidities.
Administration of the above mentioned prophylactic measures have shown to significantly reduce the
incidence of DVT.38-40

PREOPERATIVE

INTRAOPERATIVE

POST-OPERATIVE

AUDIT

Fig 1: Components of ERAS

ALLOWS EARLY REDUCES EARLY RECOVERY

REDUCES THE
APPLICATION OF MOBILITY AND COMPLICATIONS, AND BETTER
RESPONSE TO
ERAS PROTOCOL RESUMPTION OF REDUCED OVERALL
SURGICAL STRESS
BOWEL HABITS HOSPITAL STAY OUTCOME

Fig 2: ERAS- Outcome of ERAS-Response to Surgical stress

INTRAOPERATIVE ELEMENTS
• Antibiotic prophylaxis 30 to 60 min before surgery, with additional doses in case of long procedures in
accordance with the half-life of the antibiotic used: It has shown to significantly reduce the surgical site
infection. Skin preparation techniques like application of chlorhexidine- alcohol and hair clipping are also
proven to reduce the SSI.41,42

151
• Anaesthetic techniques should be optimised to allow rapid awakening post-surgery: Adequate fluid
management, analgesia and hemodynamic parameters intraoperatively, helps in reducing the surgical stress
response and improves recovery.43
• If >/= 2 risk factors are present for post-operative nausea and vomiting (PONV) as per Apfel score,
prophylaxis is recommended.44,45 Risk factors for PONV are as follows-female gender, non-smokers,
history of motion sickness, administration of nitrous oxide, parenteral opiates and volatile anaesthetic
agents. Pharmacologic and non-pharmacologic prophylaxis have shown to significantly reduce the post-
operative incidence of nausea and vomiting.
• Minimal access surgery is preferred: Minimal access techniques have been shown to significantly reduce
the post-morbidity and recovery time.46-48
• Routine use of nasogastric tube is not recommended: Many RCTs have shown that there is an early
resumption of bowel habits and reduced pulmonary complications on avoiding nasogastric tubes. 6,49
• Maintenance of normothermia: Routine maintenance of core body temperature to >36 C with warming
devices like warming mattress, forced-air heating blankets or circulating water garment systems prevents
incidence of hypothermia, wound infection, bleeding and some adverse cardiac events. 50-52 Active warming
should be continued post-operatively.
• Goal directed fluid therapy: Judicious fluid administration decreases tissue edema, ileus and reduces the
cardiorespiratory complications.52,53
• Avoid routine use of drains: Routine peritoneal drainage is neither advantageous nor disadvantageous as
per the current literature. Avoiding routine use of drains decreases the port-operative mobility.

POST-OPERATIVE ELEMENTS
• Trans urethral catheter should be removed after 1-2 days: It reduces the risk of urinary tract infection and
reduces immobility.56,57
• Early mobilisation: It reduces incidence of pneumonia, muscle weakness and insulin resistance. 58-60
• Avoid hyperglycemia, judicious use of insulin: It reduces the incidence of post-operative morbidity .61.62
• Optimisation of nutritional status, Early feeding post-operatively: It maintains nitrogen equilibrium and
minimises insulin resistance.63-65
• Administration of chewing gums, peripheral mu-opioid inhibitors and laxatives: Reduces pot-operative
ileus
• Opioid sparing, multimodal analgesia: Reduces ileus and post-operative nausea and vomiting.66-70

AUDIT
• A systematic audit is imperative to determine the compliance and clinical outcome for a successful
implementation of ERAS protocol.71.72
• A validated tool should be used to report the patient’s experience and recovery.

ERAS IN GASTROINTESTINAL SURGERY

ERAS has been widely studied in colorectal surgeries. Many RCTs including the LAFA trial and subsequent
meta-analysis have proved that there is a significant reduction in the post-operative morbidity and length of
hospital stay.60,72 ERAS society guidelines of colorectal surgeries is well established and safety has been
proven.11 It has also proven efficiency in liver surgeries. It was further standardized with the publication of
ERAS society guidelines for liver surgeries in 2016.16 Many RCTs have proven safe applicability of ERAS in
major liver resections.73,74 Pancreatic surgeries have specific complications like delayed gastric emptying or
pancreatic fistula formation. Literature reviews have acknowledged the safety of ERAS in pancreatic surgeries,
though there still is a necessity of a multicentre, large scale randomised trials. A recent RCT by Takagi et al, has
shown significantly less complication rate and readmissions and improved quality of life on application of ERAS
in pancreatic surgeries.75

Implementation of ERAS in emergency surgical procedures is possible with exclusion of some components
followed in elective surgeries, like carbohydrate loading, need for drains, limited availability of minimally
invasive surgeries etc.76 It was studied in colorectal emergencies where in it reduced the time to first flatus, time
to resume feeds and hospital stay.77 The ERAS protocol patients had significantly less post-op complications like
respiratory infections and urinary tract infections and decreased presence of catheters and drains. A systematic
review conducted by Paduraru et al78 showed that the application of 11 to 18 of 20 elements of elective surgeries
were feasible, with a reduced post-operative morbidity, equal or reduced mortality and reduced length of hospital
stay. Hence with certain changes in the protocol, ERAS seems to be possible and effective in emergency
surgeries. Further studies are needed to establish it role in emergency surgeries.

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ERAS IN ELECTIVE UPPER GI SURGERY

One of the earliest RCTs conducted for gastric surgeries in 2010 included 8 components of ERAS including
early feeding, showed a significant fall in the duration of hospital stay. The readmission rates and the post-
operative morbidity were not significantly different.79 Similar study conducted in 2012, showed that the length
of hospital stay was significantly reduced in open distal gastrectomy, whereas it was similar in laparoscopic
distal gastrectomy.80 In the year 2014, ERAS society published guidelines for gastric surgeries and since then it
has been widely studied, with proven effectiveness. The recommendations are as follows15:
 Artificial nutrition preoperatively on a routine basis is not warranted. If the patient is significantly
malnourished, enteral nutrition or oral supplements can be given before surgery (Evidence- low)
 Preoperative oral pharmaconutrition was not found to be beneficial in gastrectomy patients (Evidence-
moderate)
 Minimal access surgeries like laparoscopic distal and total gastrectomy has reduced the postoperative
morbidity. (Evidence- high for LADG, moderate for LATG)
 Routine use of nasogastric tube is not indicated (Evidence- high)
 Routine use of abdominal drains should be avoided. It has shown to improve the recovery and reduce
the drain related complications (Evidence- high)
 Patients can be started on orals as tolerated from postoperative (POD) 1 in total gastrectomy. If the
patient is malnourished or is unable to meet at least 60% of daily requirement by POD 6, nutritional
support has to be given. It has to be individualized, preferably high energy oral sips. (Evidence-
moderate)

A retrospective study of 984 patients conducted in 2016 showed that fast track protocols alone can significantly
reduce the recovery time irrespective of the surgical technique. It further proved the safety and effectiveness of
application of ERAS protocol in Minimally invasive surgery for gastric cancer. It can also be applied safely in
carcinoma stomach patients.81 In a prospective RCT reported in 2017, in patients undergoing curative
gastrectomy for gastric cancer, it was found that application of the protocol reduced the hospital stay, reduced
the post-operative complications (grade 3 or higher), reduced the cost of hospitalization and significantly
improved the post-operative body weight when compared to conventional group.81 A meta-analysis and
systematic review of 13 RCTs including 1092 participants, on application of ERAS in gastric cancer surgery was
reported in 2018. It proved that adherence to the protocol hastens recovery, reduces morbidity, reduces cost,
improves the nutritional status and health related quality of life, but the readmission rates were found to be
higher, compared to earlier meta-analysis. Further studies are required to precisely analyse the elements of
ERAS protocol in gastric surgeries.83

Esophagectomy with lymphadenectomy is one of the most complex procedures, associated with a high morbidity
and mortality.84 Implementation of ERAS in esophageal surgeries is one of the active areas of research, to
improve the perioperative care and outcome. With the introduction of minimally invasive surgeries ,
improvement in the gastric conduit and anastomotic techniques, ERAS gradually matured in esophagectomy.85-87
A systematic review and meta-analyses of 13 studies including 1 RCT reported in 2017, showed that there was a
reduction in the length of hospital stay and non-surgical morbidity on application of ERAS protocol.88 Another
meta-analysis study which followed the above mentioned study including 13 publications showed no significant
change in the morbidity, but the length of hospital stay was reduced.89 Further studies are warranted to prove the
efficiency of ERAS in esophagectomy.

ERAS IN EMERGENCY UPPER GASTROINTESTINAL PROCEDURES

Very few studies have been conducted on implementation of ERAS in upper gastrointestinal surgeries. An RCT
conducted in 2014 on application of ERAS in emergency laparoscopic repair of perforated peptic ulcer disease
has showed a significant fall in the duration of hospital stay with comparable morbidities. In this study 47
patients were included who presented with duodenal ulcer perforation less than 1 cm in size. In the ERAS
protocol group, post-operative care factors like avoidance of nasogastric (NG) tubes, early feeding, early
removal of urinary catheter and avoidance of opioid analgesia were followed. 90 A similar study conducted at
our centre in 2017 has proved the efficacy of ERAS in repair of perforated duodenal ulcers.91 A total of 100
ASA class I and class II patients were included. In this study as many elements in the pre, intra and post-op
setting of the ERAS protocol, which was possible in the emergency setting, was applied. Preoperative elements
like adequate patient counselling, multimodal analgesia, insertion of epidural catheters (if not contraindicated)
were included. Curtailed use of NG tubes and drains were used, wherein they were removed when the quantity
was less than 300ml and 100 ml respectively. Patients were initiated on unrestricted protein rich fluids once
presence of bowel sounds was noted. It was gradually advanced to normal diet over 24 hours. Post-operatively
patients were ambulated on the day of surgery. There was a significant reduction in the hospital stay by 4 days
and post-operative complications (pulmonary complications, urinary tract infections, PONV and surgical site

153
 infections). A significant early recovery and early initiation of feeds with resumption of bowel habits were noted
in the ERAS protocol group. The leak rates were comparable in both the groups91. The ERAS protocols in
elective and emergency upper gastrointestinal surgery in published studies are shown in Table 1.

ISSUES AND PROBLEMS IN IMPLEMENTATION OF ERAS

A strong multidisciplinary team and patient’s compliance is needed for the implementation of ERAS protocol.
Strict adherence to the protocol is shown to be associated with reduced complications.72,92 There are various
hindrances in the strong implementation of the protocol as follows:93
 Difficulty of the surgeon to break the traditional principles and follow ERAS.
 Relatives of the patients often expect a prolonged hospital stay for adequate recovery.
 They believe that major surgeries need a long time to recover.
 Inadequate training of paramedical workers and supporting staff about the principles of ERAS.
 Belief of the patients that a prolonged bed rest is needed for an adequate recovery.
 Resistance to change in few members of the team.94

A study by Ljungqvist et al has showed that an increase in the compliance rate by 50-90%, reduced the
complications by 20% and the duration of hospital stay by 4 days.95 Another study has showed that at least an 80
% compliance rate is needed for a decrease in the length of hospital stay. To achieve this rate it takes 6 months
and 30 successfully treated patients.96 Similar results were obtained by many RCTs conducted that followed.2,97
Few authors suggest a strict audit of the patient’s compliance weekly, which allows implementation of any
needed changes in the protocol.98 Patient education also plays a vital role.

CONCLUSION
Enhanced Recovery After Surgery is an evidence based multimodal approach that aims at hastening the patient’s
recovery by attenuating the stress response to surgery. A strong multidisciplinary team with a clear
understanding of the elements of ERAS coupled with willingness to change is the need of the hour for a
successful implementation of ERAS.

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Table 1: ERAS protocols in Elective and Emergency Upper Gastrointestinal surgery.
ELECTIVE/ YEAR AUTHORS PROCEDURE DESIGN SAMPLE COMPONENTS MORBIDITY DURATION READMISSION
EMERGENCY SIZE EVALUATED (%) OF IN- RATE
PATIENT
STAY
ELECTIVE 2010 Wang et al20 Gastrectomy RCT 45 vs 47 8 including early enteral 20% vs 14.9% 6 vs 8 days 2.2% vs 2.1%
feeding
2012 Yamada et Laparoscopic RCT 91 vs 100 6 including judicious use 7.6% vs 12% 9 vs 9
al100 and Open Distal of drains, NG tube and
Gastrectomy early enteral feeding --
2016 Liu et al81 Minimally Retrospective 984 10.1% vs 9.6% 6 vs 11
invasive study ---
gastrectomy --
2016 Sugisawa et Curative Prospective 121 11 including epidural 10.7% 8 days 0%
al82 Gastrectomy Phase II Trial analgesia
2017 Tanaka et Gastrectomy RCT 73 vs 69 8, including no bowel 4.1% vs 15.4% 9 vs 10
al99 preparation and early
feeding ---
EMERGENCY 2014 Gonenc et Laparoscopic RCT 21 vs 26 6 5/21 vs 7/26 3.8 vs 6.9 4/21 vs
al90 Graham’s repair 2/26(p=0.471)
2017 Mohsina et Open repair of RCT 50 vs 49 10 including truncated 18 vs 63 5.3 vs 9.7
al91 perforated use of NG tubes and
peptic ulcer drains ----

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 HYPERTHYROIDISM
C B Singh

Hyperthyroidism is a state of excess circulating thyroid hormones due to increased thyroid gland production of
hormone and can range in severity from subclinical hyperthyroidism to life-threatening thyroid storm. The term
thyrotoxicosis describes the state of increased circulating thyroid hormone without distinguishing the source of
thyroid hormone excess. In the United States, the prevalence of hyperthyroidism in general population is
reported in 2007 as 1.2%, of which 0.7% was found to be subclinical hyperthyroidism.1The most common cause
of thyrotoxicosis is Graves’ disease. Other common causes are toxic multinodular goiter (TMNG), solitary toxic
adenoma and thyroiditis. Rare causes of thyrotoxicosis include thyroid-stimulating hormone (TSH)–secreting
pituitary adenoma, struma ovarii, functional metastasis from differentiated thyroid cancer, and secondaries in
thyroid gland causing destruction-induced thyrotoxicosis.

CAUSES OF HYPERTHYROIDISM
Common Causes Rare causes of thyrotoxicosis
 Graves’ disease  TSH-secreting pituitary adenoma
 Toxic MNG  Trophoblastic tumors
 Solitary autonomous nodule (toxic adenoma)  Hydatidiform mole
 Thyroiditis  Choriocarcinoma
 Subacute  Struma ovarii
 Lymphocytic/painless  Functional metastasis from thyroid cancer
 Drug-induced
 Iodine-induced
 Amiodarone-induced
 Thyrotoxicosis factitia

Graves’ disease
Graves’ disease is caused by an activating autoantibody that targets the TSH receptor. Graves’ disease is more
common in women, with a female to male incidence ratio of approximately 7 to 10:1.1 Patients with Graves’
disease may have thyroid-stimulating hormone receptor antibodies (TRAb) which can be thyroid stimulating
antibodies (TSAb) or thyroid stimulation-blocking antibodies (TSBAb) simultaneously. Thyroid-stimulating
antibodies (TSAb) bind to the TSH receptor, activating adenylate cyclase, causing increased production of
thyroid hormone as well as increased thyroid growth and vascularity. Pathognomic features of Graves’ disease
are goitre with bruit, proptosis, ophthalmoplegia, conjunctival irritation, localized dermal myxedema and hair
loss. The proptosis and ophthalmoplegia seen in Graves’ disease are attributable to infiltrative orbitopathy. The
underlying pathophysiology of Graves’ophthalmopathy is uncertain. TRAb are thought to target the retro-orbital
tissues by binding to a TSH receptor antigen, which initiates a subsequent T-cell inflammatory infiltrate.
Fibroblasts stimulated by cytokines produce glycosaminoglycans cause mass effect leading to ophthalmopathy in
20% to 40% of such patients.2 Ocular manifestations are severe in only 3% to 5% and show intense pain, double
vision, or loss of vision and they require treatment with glucocorticoids, orbital radiotherapy and orbital
decompressive surgery to improve the associated symptoms of proptosis, chemosis, and vision loss . Systemic
glucocorticoids exert anti-inflammatory and immunosuppressive actions thereby causing inhibition of cytokine
release, by interfering with the function of T and B lymphocytes, and a consequent reduction in
glycosaminoglycan production by orbital fibroblasts.3 Localized dermal myxedema can occur in 0.5% to 4.3% of
patients and is almost always associated with preexisting Graves’ ophthalmopathy. Up to 13% of patients with
severe Graves’ ophthalmopathy may develop myxedema.2 It usually occurs in the anterior leg, and therefore is
called ‘‘pretibial myxedema’’ though it can also occur at other dependent or trauma prone areas areas. Most
common form of Graves’ dermopathy occurs in up to 43% of patients as diffuse nonpitting edema due to
lymphatic compression and obstruction by dermal deposition of glycosaminoglycans. The involved dermis
contains an increased content of hyaluronic acid and chondroitin sulfates, caused by activation of fibroblasts by
cytokines, interleukin-1α and transforming growth factor-β.2 Other forms are a plaque form showing raised
plaques on a background of nonpitting edema in up to 27% or sharply circumscribed tubular or nodular
myxedema in 18% patients. The less common type is a asymmetric, raised, firm, pink-to-purple, brown plaques
of nonpitting edema. The rarest form of myxedema is the elephantiasic variant occurring in 5% of myxedema
cases and consists of nodular lesions that may be fungating or polypoid, along with significant lymphedema.4
Graves’ disease may also present with thyroid acropachy, which most commonly consists of clubbing of distal
fingers and toes, soft tissue swelling of the hands and feet, and periosteal bone formation.5 Thyroid acropachy
occurs in 0.1% to 1% of patients with Graves’ disease and almost always occurs in patients with coexisting
ophthalmopathy and myxedema.

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Toxic multinodular goiter
Toxic MNG (TMNG) is the second leading cause of thyrotoxicosis. TMNG generally arises in a multinodular
thyroid gland that subsequently develops autonomously functioning nodules over time. The prevalence of
TMNG varies inversely with iodine sufficiency, and TMNG is more prevalent in populations exposed to iodine
insufficiency. It is caused by somatic mutations in TSH receptor gene, leading to constitutive receptor activation
and upregulation of cyclic adenosine monophosphate (cAMP) signaling in 60% of nodules while other
mechanisms are responsible for nodule formation in rest of gland. It usually presents in individuals older than 50
years of age with prior long history of multinodular goiter.1 The clinical presentation of the thyrotoxicosis is
usually mild. As older population is being affected, cardiovascular manifestations of thyrotoxicosis, such as
palpitations, tachycardia, and atrial fibrillations are common. Radioactive iodine uptake and scanning reveals
normal to increased uptake and a heterogeneous pattern, with focal areas of increased uptake in hyperfunctioning
nodules.1

Toxic adenoma
Toxic adenoma is hyperfunctioning solitary autonomous nodule. Pathologically it is caused by a mutation in
TSH receptor gene, causing constitutive receptor activation. Like TMNG, it generally evolves slowly, with frank
nodule autonomy occurring only after the nodule has been present for many years. Unlike TMNG, it presents
with solitary toxic nodule usually in third and fourth decades.1 It is one of the most frequent causes of isolated
T3 toxicosis, showing normal T4 with isolated elevation of T3. Ultrasound reveals a nodule, which shows
increased uptake on radioactive iodine uptake scanning with suppressed uptake in remainder of the gland.1.

Thyroiditis
Thyroiditis is an inflammation following autoimmune process that causes follicular disruption and release of
follicular contents, including thyroglobulin and stored thyroid hormone. Release of stored thyroid hormone leads
to the transient hyperthyroid state. Thyroiditis can be painful or painless with variability in tenderness. Type I
amiodarone induced thyroiditis may not cause hyperthyroid state. Radioactive iodine scanning typically shows
homogeneous low or absent tracer uptake in thyroiditis`.

Types of thyroiditis that cause thyrotoxicosis

Silent, lymphocytic, or painless thyroiditis
Postpartum thyroiditis
Subacute thyroiditis
Drug-induced thyroiditis
Amiodarone
Lithium
-interferon
Interleukin-2

Subacute ‘‘de Quervain’s’’ thyroiditis

It is one of the most common causes of painful thyromegaly and is also called granulomatous giant cell
thyroiditis. The reported incidence of this condition is 4.9 cases per 100,000 population per year.6 Subacute
thyroiditis is often preceded by a viral infection like adenovirus, echovirus, influenza, coxsackie, and mumps
virus and is thought to be due to a consequent autoimmune response. Markers of autoimmunity appear in acute
phase and persist for many years. The incidence peaks in summer, coincident with the peak of enterovirus
season. Thyroid gland is infiltrated by mononuclear cells with classic finding of a central core of colloid
surrounded by multinucleated giant cells, leading to granuloma formation sometimes.7 Pain and tenderness
occurs in thyroid region with or without fever, together constituting hallmark clinical presentation. The pain may
also radiate to jaw or ear. They also report hoarseness of voice, dysphagia, palpitations, nervousness, and
emotional lability in up to 50% of patients. Laboratory evaluation shows suppressed TSH, elevated T4 and T3,
ESR,TLC and thyroglobulin levels. The course of disease consists of an acute thyrotoxic state till follicular
stores of thyroid hormones are depleted which then leads to euthyroid status. Permanent hypothyroidism is
reported in approximately 5–15% of patients.8

Hashimoto’s or lymphocytic thyroiditis

It has generally silent, painless course and is also called sporadic thyroiditis, subacute lymphocytic thyroiditis,
and painless thyroiditis. It is thought to occur due to an acute exacerbation of underlying thyroid autoimmunity
and characterized by a infiltration of lymphocytes. Patients generally belong to third to sixth decade with a
female to male ratio of 1.5 to 2:1. Disease course encompasses phase of thyrotoxicosis, then brief euthyroidism
and a subsequent hypothyroid phase. Permanent hypothyroidism occurs immediately, if ever in 5% to 20%.9
Goiter is seen in 50% to 60% of patients. Suppressed TSH in acute phase and anti - thyroperoxidase antibodies
are hallmark of this disease. The ESR is generally normal.

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Postpartum thyroiditis
Postpartum thyroiditis is also a manifestation of thyroid damage by autoimmunity in the form of immunologic
resurgence after relative immunosuppression of pregnancy. Lymphocytic infiltrate and histopathologic findings
closely resemble silent thyroiditis. The initial hyperthyroid phase usually lasts from 2 to 10 months postpartum
which is symptomatic in 33%. It may end up in euthyroidism or 60% develop a hypothyroid phase. Permanent
hypothyroidism occurs in 20% of women immediately after the onset of thyroiditis. Up to 70% of patients
develop recurrent episodes of postpartum thyroiditis with subsequent pregnancies.10

Drug-induced thyroiditis
Several drugs can cause thyroiditis, including amiodarone, lithium, interferon-, and interleukin-2. Lithium can
cause thyrotoxicosis by inducing silent thyroiditis.

Iodine-induced hyperthyroidism
Iodine-induced hyperthyroidism can occur after administration of radiographic contrast media or use of
amiodarone or high iodine content foods like kelp and seaweed. Two major clinically inapparent phase of
thyroid disorders like nodular thyroid disease and Graves’ disease can precipitate into hyperthyroidism after
iodine exposure.

Amiodarone-induced thyrotoxicosis
Amiodarone is a widely used antiarrhythmia medication and it contains approximately 37% iodide as 75 mg
iodide per 200 mg tablet. Amiodarone is well known to produce both hyperthyroidism (AIT) and
hypothyroidism (AIH). AIH occurs with greater frequency in iodine-replete populations while AIT is more
prevalent in iodine insufficient populations, later reported in 1% to 23%.11 Amiodarone causes thyrotoxicosis
through two mechanisms. Type I AIT occurs due to underlying latent autoimmunity that is exacerbated by the
iodine load liberated by normal metabolism of amiodarone as seen in those who harbour indolent TMNG and
Graves’ disease. Otherwise Amiodarone can also induce a destructive thyroiditis that releases prestored thyroid
hormone, leading to thyrotoxicosis which is called as type II AIT. Both types have to be recognised, as their
treatments are different.

Thyroid stimulating hormone–secreting pituitary adenoma

TSH-secreting pituitary adenoma is a rare (less than 1% of all pituitary adenomas) cause of hyperthyroidism.
Laboratory evaluation typically demonstrates elevated serum T4 and T3, with inappropriately normal or modest
elevation of serum TSH. Most of them are macroadenomas. When clinically suspected, it can be diagnosed
radiologically. Lack of suppression of TSH 48 hours after exogenous administration of T3 300mg at noon, is
seen against background of baseline TSH, due to thyrotroph autonomy. Normally it falls to less than 10% of the
baseline TSH value. A high molar ratio of 1 of the α –subunit in (mg per liters) to TSH (in mIU per liters) ratio
can differentiate pituitary adenoma from thyroid hormone resistance syndrome.12

Thyroid hormone resistance

Thyroid hormone resistance is another rare cause of hyperthyroidism. 75% of these cases have family history of
such cases with autosomal dominant inheritance while 21.3% cases are sporadic.12 Patients present with elevated
serum thyroid hormone levels and inappropriately normal or frankly elevated TSH. Resistance to thyroid
hormone is always partial and variable.13 Resistance to thyroid hormone is of two types : (a) generalized
resistance to thyroid hormone (GRTH) and (b) pituitary resistance to thyroid hormone (PRTH). In GRTH,
thyroid hormone receptors in all tissues show variable resistance to T3. Resistance at the level of pituitary
thyrotrophs means elevated circulating T4 and T3 to effect normal pituitary feedback but normal TSH level.

This condition is characterised by a mutation in one allele of the thyroid hormone receptor isoforms TRb1 or
TRb2 or both. TRb2 is mostly expressed in hypothalamus and pituitary while TRb1 is expressed in the liver and
kidney. Testing of TRb gene defects can be done to reach to a diagnosis.13

Familial dysalbuminemic hyperthyroxinemia

More than 99% of both T4 and T3 are bound to thyroid binding globulin (TBG), transthyretin, and albumin.
Bound hormone represents a circulating storage pool, while unbound or free hormone is available for uptake into
the tissues. The TBG has a higher affinity for T4 and T3 than transthyretin or albumin, and therefore, it is these
latter proteins that are primarily responsible for the immediate delivery of thyroid hormone to peripheral tissues.
Familial dysalbuminemic hyperthyroxinemia (FDH) is a cause of euthyroid hyperthyroxinemia. Patients with
FDH are clinically euthyroid without true hyperthyroidism and have a normal TSH level. FDH occurs due to a
variant of serum albumin which has preferential affinity for T4, thereby causing elevation in T4 levels and
inherited as autosomal dominant manner with prevalence of 0.17%.14 There is elevated total T4, elevated or
normal free T4, normal TSH and normal T3.

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Thyrotoxicosis factitia
Thyrotoxicosis factitia, the ingestion of exogenous thyroid hormone, is the most common cause of extrathyroidal
source thyrotoxicosis. Thyrotoxicosis factitia can also be seen, in mild forms, with the treatment of thyroid
cancer when suppressive doses of levothyroxine are given. Surreptitious use of thyroid hormone is seen in
people suffering from psychiatric illnesses or when it is ingested as weight loss therapy. Epidemics of
thyrotoxicosis factitia have been reported regionally when bovine thyroid material was found in ground beef at a
local slaughtering plant.15 Laboratory values reveal elevated T3 and T4, along with suppressed TSH and so low
radioactive iodine uptake during thyroid scan.

Struma ovarii
Struma ovarii is another rare cause of thyrotoxicosis from an ovarian tumor usually consisting of cystic teratoma
with differentiation into thyroid tissue. Struma ovarii is seen in 0.3% to 1% of all ovarian tumors while only 2%
to 4% of all ovarian teratomas are struma ovarii. Clinically, women with struma ovarii may present with an
abdominal mass along with overt or subclinical thyrotoxicosis. I 123 or I131 scan is frequently negative in thyroid
region but shows uptake in the pelvis.16

Metastatic thyroid carcinoma causing thyrotoxicosis

Thyrotoxicosis due to metastasis from thyroid cancer is unusual and its extent depends upon the amount of
functional differentiated thyroid cancer cells. Most of metastasis occur from follicular cancer. Diagnosis may be
difficult after thyroidectomy for thyroid cancer when Levothyroxine (LT4) suppressive therapy is going on and
already suppressed TSH levels are there.

Hyperthyroidism and pregnancy

Hyperthyroidism during pregnancy affects mother and fetus both. Fetal complications like intrauterine growth
retardation, prematurity, stillbirth, low birth weight, and neonatal hyperthyroidism are seen frequently. Maternal
complications like eclampsia, miscarriage, and placenta abruptio, congestive heart failure or thyroid storm are
seen. True hyperthyroidism during pregnancy occurs in 0.1% to 0.4%. Normal variation of thyroid functioncan
occur in women who are pregnant and leads to suppressed TSH and elevated total T4 and total T3. Graves’
disease occurs in up to 85% of all pregnancy related hyperthyroidism.17

Thyroid storm
Thyroid storm was first described by Lahey in 1926 as ‘‘the crisis of exophthalmic goiter’’18 in large number of
patients who presented with an exacerbation of their underlying Graves’ disease. Dysfunction of the
cardiovascular system, thermoregulatory system, gastrointestinal-hepatic system, and central nervous system
(CNS) forms core of thyoid storm. In 1993, Burch and Wartofsky developed a novel scoring system to
standardize the diagnosis.19 Recently there has been a decline in incidence of thyroid storm due to more frequent
screening, earlier diagnosis of hyperthyroidism and improved prevention of thyroid storm. Data suggests that
thyroid storm accounts for between 1% and 2% of hospital admissions for thyrotoxicosis. In a nationwide survey
in Japan, the incidence of thyroid storm in hospitalized patients was 0.2 per 100 000 per year, or approximately
0.22% of all patients with thyrotoxicosis and 5.4% of all patients admitted in hospital with thyrotoxicosis.20
More appropriate preoperative preparation has lead to a marked reduction in prevalence of surgically induced
storm. Thyroid storm most commonly occurs in women and those with underlying Graves’ disease. Mortality
rate of as high as 75% in hospitalized patients have been reported in past which in present times hovers around
10% to 30%. Multiple organ failure is the most common cause of death, followed by congestive heart failure,
respiratory failure, arrhythmia, disseminated intravascular coagulation, gastrointestinal perforation, hypoxic
brain syndrome, and sepsis.20 A heightened response to thyroid hormone along with increased or abrupt
availability of free hormones and enhanced binding to thyroid hormone receptors is implicated. Transition from
simple thyrotoxicosis to the metabolic crisis of thyroid storm usually requires a superimposed insult. Thyroid
surgery was previously the most common precipitant of storm but owing to adequate preoperative preparation
these days, it is rarely seen. Incomplete treatment of hyperthyroidism or an interruption in drug therapy increases
the risk. Total T4 and T3 concentrations in patients in crisis are not necessarily high but mean dialyzable fraction
of T4 and mean free T4 concentrations are significantly higher probably due to a decrease in the hormone-
binding capacity associated with various stressors.21Adrenergic activation also plays a major role which can be
dampened through therapy with a nonselective -adrenergic antagonist propranolol.

Reported precipitants of thyroid storm are infections (most common), thyroid surgery/surgical storm,
nonthyroidal surgery, trauma, vigorous manipulation of the thyroid gland, thyroiditis, parturition, burn,
myocardial infarction, pulmonary embolism, cerebrovascular accidents, medications such as anesthetics/
salicylates/ pseudoephedrine/ and amiodarone, interferon treatment, radioactive iodine treatment, exposure to
iodinated contrast, withdrawal of antithyroid treatment, infections, diabetic ketoacidosis, hypoglycaemia, H1N1
infection, emotional stress and intense exercise.

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The diagnosis of thyroid storm is based on clinical findings. It requires urgent treatment to reduce the mortality
risk. The patient will exhibit exaggerated signs and symptoms of hyperthyroidism accompanied with
manifestations of multiorgan decompensation. High grade fever (104-106º F) is always present with tachycardia
out of proportion to the underlying illness. Profuse sweating and significant insensible fluid loss, palpitations,
tachycardia, exercise intolerance, dyspnea on exertion, widened pulse pressure, cardiac ischemia, or atrial
fibrillation, heart failure, cardiovascular collapse and shock are also seen.22The CNS manifestations are always
present in the form of agitation, delirium and confusion to stupor, obtundation, and coma.20 Gastrointestinal
symptoms like nausea, profuse vomiting, severe diarrhea, liver dysfunction and hepatomegaly and jaundice are
seen frequently.

Diagnostic Criteria for Thyroid Storm a

a
Adapted from Burch and Wartofsky. A score of 45 or greater is highly suggestive of thyroid storm; a score of 25 to 44 is
suggestive of impending storm, and a score below 25 is unlikely to represent thyroid storm.

Medical Treatment of Thyroid Storm

Treatment of thyroid storm targets the synthesis and release of thyroid hormone and minimization of the effects
of circulating hormones and prevent end-organ damage. The first-line therapy consists of halting new thyroid
hormone production by administration of antithyroid drugs (thionamides). Propylthiouracil (PTU) is favoured at
much higher doses of 600 to 1500 mg ( 250 mg every 4 hours) per day in divided doses every 4 to 6 hours
following loading dose of 600mg (500 to 1000 mg). Methimazole is given as 80 to 120 mg daily in divided
doses every 4 to 6 hours.23 Both these drugs can be given as rectal suppositories. In addition to thionamides,
nonradioactive iodine administration also decreases new hormone synthesis. Inorganic iodine may be given
orally as a saturated solution of potassium iodide as 5 drops (0.25 mL or 250 mg) every 6 hours or as Lugol’s
163
solution with 8 drops given every 6 hours.19,24Oral iodinated contrast agents iopanoic acid and sodium ipodate
can also be used. Iodine should be dosed at least 30 minutes after administering thionamides to avoid the iodine
serving as a substrate for new thyroid hormone production and worsening the hyperthyroidism. When iodine
administration is not possible due to iodine induced anaphylaxis, lithium may be given as 300 mg every 6 to 8
hours with frequent monitoring of serum levels (goal is 0.6-1 mEq/L)19,23 Propranolol is the most commonly
used β-blocker as it decreases the conversion of T4 to T3 in the periphery at dose of 60 to 120 mg orally every 6
hours or IV propranolol as 0.5 to 1.0 mg slow IV push and then 1 to 2 mg at 15-minute intervals or Esmolol as
initial bolus of 0.25 to 0.5 mg/kg followed by a continuous infusion rate of 0.05 to 0.1 mg/kg per minute.25

Clinical presentation of thyrotoxicosis

Hyperthyroidism causes an imbalance in metabolism and energy production. There is a hypermetabolic state in
which energy production exceeds energy expenditure. Hypermetabolism causes increased heat production,
resulting in perspiration, heat intolerance, raised body temperature and heightened cardiovascular activity,
manifesting as increased heart contractility, tachycardia and vasodilation. Thyroid hormone is necessary for
normal growth and development, and it regulates cellular metabolism.

The presentation of thyrotoxicosis is variable among patients. Thyrotoxicosis leads to an apparent increase in
sympathetic nervous system output. Younger patients tend to exhibit symptoms of sympathetic activation, such
as anxiety, hyperactivity, palpitations, sweating and tremor, while older patients have more cardiovascular
symptoms, including dyspnoea, atrial fibrillation and unexplained weight loss. Due to persistant
hypermetabolism, symptoms of thyrotoxicosis frequently include generalized weakness attributable to the
cardiorespiratory effects of thyrotoxicosis and fatigue attributable to associated myopathy.26 Neuropsychiatric
changes are also seen leading to restlessness, agitation, anxiety, emotional lability, psychosis, and even coma.
Behavioral studies have confirmed poor performance in the domain of memory and concentration testing which
is proportional to the degree of hyperthyroidism.27Gastrointestinal manifestations of hyperthyroidism include
increased frequency of bowel movements caused by increased motor contraction of the small bowel and
consequent rapid transit of intestinal contents.26 It causes changes in menstrual cycle in women, resulting in
oligomenorrhea or amenorrhea. The etiology of the menstrual irregularity is unclear but may be attributable to
the effects of thyroid hormone on gonadotropin- releasing hormone (GnRH) signaling, causing disruption of
normal luteinizing hormone (LH)/follicle-stimulating hormone (FSH) pulsatility.1 An increase in total estrogens
is noted as a result of an increase in sex hormone–binding globulin which thereby decreases metabolic clearance
of estradiol and also leads to an increase in conversion of androstenedione to estrone and estradione. For this
reason approximately 10% of male patients experience symptoms of decreased libido or gynecomastia and
development of spider angiomas.26

Thyroid hormone exerts effects on the systemic vasculature as well as on the heart itself. Thyroid hormone
decreases systemic vascular resistance through a direct vasodilatory action on the smooth muscle, which is
mediated by endothelial derived nitric oxide and other endothelial derived vasodilators. T3 has property of
affecting heart directly through genomic mechanisms which influence myofibrillary proteins, calcium pump
regulation by sarcoplasmic reticulum membrane protein phospholamban, calcium-activated ATPase, and various
plasma membrane transporters. In addition, T3 acting through nongenomic pathways, alters the performance of
sodium, potassium, and calcium channels. The manifestations of these changes include increased heart rate,
cardiac contractility, and cardiac output.28Tachycardia is the most common cardiovascular sign of hyperthyroid
state which along with increased force of cardiac contractility leads to palpitations. Examination will reveal a
strong apical impulse, increased pulse pressure, and a hyperdynamic precordium. ‘‘ eans-Lerman scratch’’ is
heard as mid-systolic scratching sound best heard over the upper part of the sternum or second left intercostal
space or at the apex at the end of expiration, due to hyperdynamic precordium rubbing against the pleura.1,26

Laboratory testing of Thyroid function test

Hyperthyroidism classically shows suppressed TSH level (usually less than 0.05 mU/mL) in combination with
an elevated serum free T4 and T3 levels in 95% of patients. TSH assessment alone may be appropriate for routine
screening in an asymptomatic patient or in suspected subclinical hyperthyroidism, but confirmation of
hyperthyroidism requires assessment of T4 and T3.26 Free hormone concentrations than total levels are more
representative of hyperthyroidism as they obviate confounding by interference of protein binding as total T3 and
T4 reflects mainly protein bound hormone concentrations.

Thyroid-stimulating hormone receptor antibodies

There are two types of TSH receptor antibodies (TRAb) i.e. thyroid stimulating antibody (TSAb) and TSH-
stimulation blocking antibody (TSBAb). TSAb causes Graves' hyperthyroidism while TSBAb causes
hypothyroidism. Both TSAb and TSBAb block TSH-binding to thyroid cells as TSH receptor antibodies
(TRAb). Clinicall active TSBAb patients have hypothyroidism and clinically active TSAb patients present with
Graves' patients with hyperthyroidism though both conditions may have detectable levels of both TSBAb and

164
TSAb. The measurement of TRAb is done to diagnose and help in management of Graves’ disease. The routine
assay to detect TRAb is TSH-binding inhibitor immunoglobulin (TBII) assay. The TBII assay measures all
antibodies to the TSH receptor and is not specific for antibodies that only cause thyroid stimulation. A second
generation of this assay using recombinant TSH receptor has been developed and has a reported sensitivity of
98.6%.29

Thyroxine/triiodothyronine ratio
The ratio of T4 to T3 frequently has a characteristic pattern in different thyrotoxic states. Evaluation of the T3/T4
ratio may be a useful tool in the initial diagnosis of hyperthyroidism when radioactive iodine uptake testing is
not readily available or is contraindicated. Approximately 2% of thyrotoxic patients in the United States have an
increase in serum free T3 and normal T4. This is referred to as ‘‘ 3 toxicosis’’30 Graves’ disease and toxic
nodular goiter typically present with increased T3 production, with a T3/T4 ratio greater than 20. In cases of
thyroiditis, iodine exposure, or exogenous levothyroxine intake, T4 is the predominant hormone and the T3/T4
ratio is usually less than 20.30

Other laboratory findings

Hyperthyroidism may also cause hyperglycemia, hypercalcemia, elevated alkaline phosphatase, leukocytosis,
and elevated liver enzymes. The hyperglycemia is typically mild and is caused by catecholamine-induced
inhibition of insulin release and increased glycogenolysis. Mild hypercalcemia and elevated alkaline phosphatase
occur because of direct TSH stimulation of osteoblastic bone resorption.

Nuclear medicine scanning

Radioactive iodine uptake study and scan is done by using radioactive isotope of iodine, either I123 or I131.
Isotope is ingested and taken up in thyroid where it emits  radiation. External detection of  radiation,
scintigraphic imaging, and calculation of fractional iodine uptake by the thyroid gland is done. The amount of
radiation delivered to the thyroid by I123 is approximately 1% of that delivered by the same amount of I131. For
the purposes of scanning and computing uptake, an approximate dose of up to 5 mCi (0.19 MBq) I131 or up to
300 mCi (11.11 MBq) of I123 is given orally as sodium iodide. After administration of the isotope, relatively
early and delayed uptake data are acquired. Generally, uptake at 6 and 24 hours is obtained after dosing.31 The
normal values for the 24-hour radioiodine uptake range between 5% and 25%, and the average 6-hour uptake
reference range is between 5% and 15%. Increased fractional uptake typically indicates de novo synthesis of
thyroid hormone, whereas decreased uptake generally indicates that new hormone synthesis is not the underlying
cause of the thyrotoxicosis. Graves’ disease generally demonstrates homogeneous uptake throughout the gland.
With markedly increased thyroid hormone synthesis and turnover in Graves’ disease, there can be a paradoxic
finding of elevated uptake at 4 or 6 hours after radioiodine dosing but a normal uptake at 24 hours as a result of
accelerated clearance of the radioactive iodine. TMNG generally has a heterogeneous pattern of uptake with
hyperfunctioning nodules that demonstrate increased radionuclide uptake on scan. These nodules appear on a
background of partially or completely suppressed uptake in the uninvolved areas of the thyroid gland. Solitary
toxic nodules have a radioactive iodine scan pattern demonstrating increased uptake in the hyperfunctioning
nodule and decreased uptake in the remainder of the gland. Thyrotoxic conditions typically associated with
decreased radioactive iodine uptake include exogenous thyroid hormone intake, thyroiditis, and iodine
intoxication. The main cause of the decreased isotope uptake in all these conditions is suppression of TSH.

Thyroid ultrasonography in the evaluation of hyperthyroidism

Sonographic assessment can identify thyroid nodules and goiter that may not be readily apparent on
examination. Additionally, Doppler ultrasonography flow assessment may provide particularly useful
information about several thyrotoxic states.

TREATMENT OF HYPERTHYROIDISM
Management of thyrotoxicosis is tailored to its specific etiology. Hyperthyroidism caused by thyroid autonomy
typically involves the use of antithyroidal drugs that exert multiple effects on thyroid hormone synthesis and
release. -adrenergic receptor blockers are also useful to mitigate the increased adrenergic tone caused by
hyperthyroidism and symptom relief.

Thionamides
Thionamides are the most commonly used antithyroid medication. Two classes of thionamides exist: thiouracils
and imidazoles. Methimazole and carbimazole constitute the imidazole group, whereas propylthiouracil (PTU) is
the only thiouracil. Once ingested, carbimazole is rapidly metabolized to methimazole. Thionamides act to halt
synthesis of thyroid hormone by interfering with thyroid peroxidase–mediated oxidation of iodide, iodine
organification and iodotyrosine coupling. Also, thionamides inhibit the thyroperoxidase catalyzed coupling
process through which iodotyrosine residues are combined to form T4 and T3. PTU, but not methimazole or
carbimazole, also possesses the extrathyroidal action of blocking peripheral conversion of T4 to T3 in peripheral

165
tissues through inhibition of type 1 deiodinase.32 In cases of thyroid storm or severe thyrotoxicosis, this added
benefit may be useful. When treating thyrotoxicosis that is not life threatening, the usual starting dose of PTU is
300 mg/d in three divided doses, whereas the starting dose of methimazole is 15 to 30 mg/d in a single dose.
Common adverse side effects associated with antithyroid drug use are abnormal sense of taste, pruritus,
arthralgias, and urticaria, which occur in approximately 1% to 5% of cases. Antihistamine therapy may eliminate
cutaneous reactions and allow continued use of the medication. Alternatively, switching to another thionamide
may be necessary. Up to 50% of patients have cross-reactivity between methimazole or carbimazole and PTU. In
such cases, discontinuation of thionamide therapy and preparation for definitive treatment with radioactive
iodine is usually required. Agranulocytosis is a rare but potential fatal complication of thionamide therapy that
typically occurs within the first 3 months of treatment.33 Agranulocytosis may arise idiosyncratically at any time
during treatment. Another rare but serious side effect of antithyroid drug therapy is hepatotoxicity, which is
reported in 0.1% to 0.2% of treated patients.

-Adrenergic receptor blockade

Controlling the cardiovascular and hyperadrenergic manifestations of thyrotoxicosis is best achieved through -
adrenergic receptor blockade. Propranolol in doses greater than 160 mg/d can decrease T3 levels by up to 30%.
Atenolol can be used with doses ranging between 50 and 200 mg/d; however, twice-daily dosing may be
required in some instances to accomplish adequate control. Metoprolol at dose of 100 to 200 mg/d or nadolol at
dose of 40 to 80 mg/d, can also be used.32

Iodine
Inorganic iodine therapy may be particularly useful for the acute management of more severe thyrotoxicosis.
Iodine has several actions in the treatment of thyrotoxicosis. At high concentrations, iodine blocks release of
prestored hormone, decreases iodide transport, and prevents iodide oxidation in follicular cells. At lower
concentrations, iodide can accelerate thyroid metabolism. Inhibition of thyroid metabolism by iodide is known as
the Wolff-Chaikoff effect and is only transient. After approximately 48 hours iodide transport system adapts to
the higher concentration of iodide by modulating the activity of the sodium-iodide symporter. Within 1 to 2
weeks, complete escape from inhibition occurs. Oral formulations of inorganic iodine include a saturated
solution of potassium iodide (SSKI) and Lugol’s solution. Three to 5 drops of Lugol’s solution are required daily
(assuming 20 drops per mL at a concentration of 8 mg per drop) or 1 drop of SSKI daily (assuming 20 drops per
mL at a concentration of 38 mg per drop) is required.32The oral iodinated contrast agents iopanoic acid and
sodium ipodate have also been used for control of severe thyrotoxicosis.

Potassium perchlorate
Potassium perchlorate is an indispensable agent for the treatment of AIT and as second-line agent in patients
who are intolerant of thionamide therapy. Perchlorate is used as a bridge to definitive ablative therapy with
radioactive iodine or thyroidectomy in patients intolerant to antithyroid drugs.

Lithium
Lithium directly decreases thyroid hormone secretion and also inhibits coupling of the iodotyrosine residues that
form iodothyronines (T4 and T3). For treatment of thyrotoxicosis, the dose for lithium is 300 mg administered
every 8 hours.

Cholestyramine
Cholestyramine is an anion exchange resin that has been shown to decrease reabsorption of thyroid hormone
from the enterohepatic circulation. Cholestyramine functions by binding thyroid hormone in the intestine,
decreasing its reabsorption. Cholestyramine administered orally at a rate of 4 g four times daily, in combination
with methimazole or PTU, has been found to cause a more rapid decline in thyroid hormone levels than
thionamide therapy alone.34

Radioactive iodine
Radioactive iodine thyroid ablation is the most widely used definitive treatment for hyperthyroidism attributable
to Graves’ disease or Toxic MNG in the United States. The major long-term side effect of radioactive iodine
therapy is permanent hypothyroidism. Short-term side effects after treatment include radiation thyroiditis (which
can present as anterior neck tenderness), as well as gastritis and sialadenitis. An estimate of the dose needed to
deliver an activity sufficient for complete gland ablation requires consideration of thyroid gland weight and the
24-hour radioactive iodine uptake. The administration of radioactive iodine to a thyrotoxic patient poses a minor
risk of acute exacerbation of hyperthyroidism. Usually, patients become hypothyroid after ablative doses of
radioactive iodine within 2 to 3 months of treatment. Persistent hyperthyroidism 6 months after therapy may
require retreatment with radioactive iodine to achieve complete ablation.35

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Dermopathy
Most cases of dermopathy are mild and do not require treatment while severe cases raise cosmetic concern and
are treated with topical glucocorticoid therapy like 0.2% fluocinolone acetonide cream ( midpotency steroids ) or
topical clobetasol propionate (high potency ) over affected area and covered with an occlusive dressing ( plastic
film dressing) for at least 12 hours daily. Initially period of 4 to 6 weeks is recommended, while watching for
side effects like atrophy of skin, telangiectasia, or ecchymoses. Compressive dressings remove fluid
accumulation in elephantiasic form.36

Thyrotoxicosis factitia
Treatment for thyrotoxicosis factitia is simply discontinuation of the thyroid hormone. Simultaneously the
immediate cardiovascular concerns are to be addressed aggressively. A recent massive ingestion of thyroid
hormone, is countered by decreasing absorption, with either activated charcoal or gastric lavage, or by giving
cholestyramine to cause rapid binding of thyroid hormone in the enterohepatic circulation, thereby increasing
their fecal excretion.

Struma ovarii
Treatment of struma ovarii consists of salpingoophorectomy or total abdominal hysterectomy with or without
bilateral or unilateral oophorectomy depending on the extent of capsular invasion and the desire for preserved
fertility. Preoperative euthyroid status is achieved with thionamide therapy.

DISEASE SPECIFIC TREATMENT

Graves’ disease
Antithyroid drugs in an effort to attain permanent remission. Methimazole at a dose of 5 to 10 mg/d or PTU at a
dose of 100 to 200 mg/d is typically given for 12 to 18 months. Overall recurrence rate after antithyroid drugs is
approximately 50% to 60%.- adrenergic receptor blockade is required for control of cardiovascular symptoms.
The definitive treatment is subtotal or preferably total thyroidectomy. At some places treatment with radioactive
iodine is preferred. Treatment of Graves’ ophthalmopathy requires intravenous and oral glucocorticoids-
prednisone 60 to 100 mg/d for several months which show 60% response rate. Glucocorticoid are also standard
of care for Graves’ ophthalmopathy patients whose thyromegaly is treated by radioactive iodine.

Toxic multinodular goiter and solitary toxic adenoma

Antithyroid drug therapy normalizes thyroid function but without definitive cure
Recurrent hyperthyroidism always on discontinuation
Radioactive iodine ablation and thyroidectomy offer durable cure
Radioactive iodine ablation preferred for both conditions to achieve permanent hypothyroidism.
Usual dose is 15 and 30 mCi
Recurrence rate of 20% after radioactive iodine. Treated with second course of radioactive iodine or
thyroidectomy
Thyroidectomy can also be first-line therapy

Thyroiditis
Supportive and pain management
Beta-blockade
Persistent pain - prednisone 40 mg/d for 7 to 10 days, tapered over 1 to 2 weeks.35
Beta blockers only for silent thyroiditis and postpartum thyroiditis

Treatment of thyrotoxicosis in pregnancy

Primary treatment for hyperthyroidism during pregnancy is thionamides
PTU and methimazole cross the placenta and concentrate in fetal thyroid
Methimazole during pregnancy – cause a scalp defect called aplasia cutis congenita, choanal and esophageal
atresia,and minor facial dysmorphisms
PTU is safe - 200 mg or less per day
Thionamides safely discontinued if spontaneous remission in 3rd trimester
Surgery for contraindication to antithyroid drugs, airway obstruction or medical noncompliance.
- blockade and Inorganic iodine – before surgery
Fetal hyperthyroidism occurs in approximately 1% of pregnancies associated with maternal Graves’ disease.37

References
1. Larsen PR, Davies TF, et al. Thyrotoxicosis. In: Larsen PR, Kronenberg H elmed S et al editors. Williams’
textbook of endocrinology. 10th edition. Philadelphia: WB Saunders Co; 2002. p. 374–421.

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2. Fatourechi V. Pretibial myxedema: pathophysiology and treatment options. Am J Clin Dermatol 2005;6(5):295–
309.
3. Smith TJ. Dexamethasone regulation of glycosaminoglycan synthesis cultured human fibroblasts: similar effects of
glucocorticoid and thyroid hormone therapy. J Clin Invest 1984;64:2157–63.
4. Bull RH, Coburn PR, Mortimer PS. Pretibial myxedema: a manifestation of lymphoedema? Lancet 1993;341:403–
4.
5. Jabbour SA. Cutaneous manifestations of endocrine disorders. Am J Clin Dermatol 2003; 4(5):315–31.
6. Fatourechi V, Aniszewski JP, Jacobsen SJ, et al. Clinical features and outcome of subacute thyroiditis in an
incidence cohort: Olmstead County, Minnesota, study. J Clin Endocrinol Metab 2003;88(5):2100–5.
7. Farwell A . Subacute thyroiditis and acute infectious thyroiditis. In: Braverman L Utiger RD editors. Werner’s
and Ingbar’s the thyroid. 9th edition. hiladelphia: Lipincott Williams Wilkins; 2005. p. 536–47.
8. Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348(26):2646–55.
9. Nikolai TF, Coombs GJ, McKenzie AK, et al. Lymphocytic thyroiditis with spontaneously resolving
hyperthyroidism (silent thyroiditis) and subacute thyroiditis: long-term followup. Arch Intern Med 1982;142:2281–
3.
10. Lazarus JH, Ammari F, Oretti R, et al. Clinical aspects of recurrent postpartum thyroiditis. Br J Gen Pract
1997;47(418):305–8.
11. Harjai KJ, Licata AA. Effects of amiodarone on thyroid function. Ann Intern Med 1997; 126(1):63–73.
12. Refetoff S. Resistance to thyroid hormone. In: Braverman L Utiger R editors. Werner’s and Ingbar’s the
thyroid: a fundamental and clinical text. 9th edition. Philadelphia: Lipincott, Williams, and Wilkins; 2005. p. 1109–
29.
13. Olateju T, Vanderpump M. Thyroid hormone resistance. Ann Clin Biochem 2006;43: 431–40.
14. Arevalo G. Prevalence of familial dysalbuminemic hyperthyroxinemia in serum samples received for thyroid
testing. Clin Chem 1991;37(8):1430–1.
15. Hedberg CW, Fishbein DB, Janssen RS, et al. An outbreak of thyrotoxicosis caused by the consumption of bovine
thyroid gland in ground beef. N Engl J Med 1987;316:993–8.
16. Grandet PJ, Remi MH. Struma ovarii with hyperthyroidism. Clin Nucl Med 2000;25(10): 763–5.
17. Bach-Huynh TG, Jonklaas J. Thyroid medications during pregnancy. Ther Drug Monit 2006;28(3):431–41.
18. Lahey FH. Apathetic Thyroidism. Ann Surg. 1931;93(5): 1026-1030.
19. Burch HB, Wartofsky L. Life-threatening thyrotoxicosis. Thyroid storm. Endocrinol Metab Clin North Am.
1993;22(2):263-277.
20. Akamizu T, Satoh T, Isozaki O, et al. Diagnostic criteria, clinical features, and incidence of thyroid storm based on
nationwide surveys. Thyroid. 2012;22(7):661-679.
21. Carhill A, Gutierrez A, Lakhia R, Nalini R. Surviving the storm: two cases of thyroid storm successfully treated
with plasmapheresis. BMJ Case Rep. 2012;2012.
22. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344(7):501-509.
23. Nayak B, Burman K. Thyrotoxicosis and thyroid storm. Endocrinol Metab Clin North Am. 2006;35(4):663-686.
24. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management
guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr
Pract. 2011;17(3):456-520.
25. Clark OH DQ, Kebebew E. Textbook of Endocrine Surgery. 2 nd ed. Philadelphia, PA: Elsevier Saunders;
2005:216-219.
26. Dabon-Almirante CL, Surks M. Clinical and laboratory diagnosis of thyrotoxicosis. Endocrinol Metab Clin North
Am 1998;27(1):25–35.
27. MacCrimmon DJ, Wallace J, Goldberg WM, et al. Emotional disturbance and cognitive deficits in
hyperthyroidism. Psychosom Med 1979;41(4):331–40.
28. Klein I, Ojama K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001;344(7):501–8.
29. Costagliola S, Morgenthaler NG, Hoermann R, et al. Second generation assay for thyrotropin receptor antibodies
has superior diagnostic sensitivity for Graves’ disease. J lin ndocrinol etab 1999;84(1):90–7.
30. Ladenson P. Diagnosis of thyrotoxicosis. In: Braverman L Utiger RD editors.Werner’s and Ingbar’s the thyroid.
9th edition. Philadelphia: Lipincott, Williams & Wilkins; 2005. p. 660–4.
31. Intenzo CM, dePapp AE. Scintigraphic manifestations of thyrotoxicosis. Radiographics 2003;23(4) :857–69.
32. Cooper D. Treatment of thyrotoxicosis. In: Braverman L Utiger RD editors. Werner’s and Ingbar’s the thyroid.
9th edition. Philadelphia: Lipincott, Williams & Wilkins; 2005.p. 665–94.
33. Pearce SH. Spontaneous reporting of adverse reactions to carbimazole and propylthiouracil in the UK. Clin
Endocrinol (Oxf) 2004;61:589–94.
34. Tsai WC, Pei D, Wang T, et al. The effect of combination therapy with propylthiouracil and cholestyramine in the
treatment of Graves’ hyperthyroidism. lin ndocrinol (Oxf) 2005; 62(5):521–4.
35. Burman K. Hyperthyroidism. In: Rakel R Bope editors. onn’s current therapy. hiladelphia: Saunders; 2006.
p. 806–11.
36. Schwartz K Fatourechi V Ahmed D et al. Dermopathy of Graves’ disease (pretibial myxedema). J lin
Endocrinol Metab 2002;87(2):438–46.
37. Burrow GN. Thyroid function and hyperfunction during gestation. Endocr Rev 1993;14: 194–202.

168
 THYROIDITIS
Tarun Sekhri

INTRODUCTION
Inflammation of thyroid gland is known as thyroiditis. The etiologies may range from autoimmune to
infectious origins. The clinical presentations are diverse, ranging from an exquisitely painful thyroid gland
to painless or no goiter. The patient may be euthyroid, hypothyroid or thyrotoxic at the time of initial
presentation.
The thyroiditis may eventually take one of the following courses:
 acute
 subacute, or
 chronic

TYPES OF THYROIDITIS(Table 1)
Acute Thyroiditis
 Infectious
 Non- Infectious
Subacute Thyroiditis
Autoimmune Thyroiditis
 Chronic autoimmune thyroiditis
Hashimoto’s thyroiditis
Atrophic thyroiditis
Focal thyroiditis
Juvenile thyroiditis

 Silent Thyroiditis
 Postpartum Thyroiditis
Riedel’s Thyroditis

ACUTE INFECTIOUS THYROIDITIS:

 It is rare, serious, acute inflammatory disease of the thyroid. It includes all forms of infection, other
than viral, and is caused by invasion of the thyroid by bacteria, mycobacteria (1), fungi, protozoa. The
disorder is quite rare. In the adult , Staphylococcus aureus and Streptococcus pyogenes are the
pathogens in over 80% patients(2) In children, alpha and beta- haemolytic Streptococcus and a variety of
anaerobes are the cause for almost 70% of cases, while mixed pathogens are found in > 50% of cases(3,4)

Protective mechanisms of thyroid:
The infections of the thyroid gland is extremely rare because of the following reasons (5)
 Very good perfusion
 Efficient lymphatic drainage
 Capsulation of the thyroid
 High concentration of iodine

Routes of Infection: in acute infectious thyroiditis, the following routes of infection may be responsible for
causation of infection in a gland which otherwise has a high concentration of Iodine.
 Piriform sinus fistulae(6) Lymphatic or hematogenous spread (usually in the setting of preexisting
thyroid disease)
 Infected branchial arch anomalies
 Ruptured esophagus
 Retro- and parapharyngeal abscesses
 Neck trauma
 Fine needle aspiration cytology (FNAC)

Clinical picture:
Over 90% will present with thyroidal pain, tenderness , fever and local compression leading to dysphagia and
dysphonia. The thyroid is tender to palpation with unilateral or bilateral lobar enlargement. This may be
associated with erythema and warmth of the skin. Majority of patients are euthyroid.
Investigations:
 WBC count and Raised ESR/CRP
 ATPO negative
 Normal TFT

169
  Normal thyroid RAIU
 99mTechnetium Scan - cold defect in the involved lobe
 USG - enlarged irregular mass of mixed echogenicity
 FNAC - purulent material is confirmatory of suppurative thyroiditis, allows for identification of the
causative agent

Treatment:
 Antibiotics based on the findings of the culture from FNAC, and
 Surgical drainage (or excision) of any area of fluctuance or abscess as per the requirement.

SUBACUTE THYROIDITIS (SAT)

Spontaneously remitting, painful, inflammatory disease of the thyroid that may last for weeks to
months. It is the most common cause of the painful thyroid.

Etiology:
• There is no clear evidence for a specific aetiology. Because it frequently follows an upper respiratory
infection, a viral aetiology is often proposed.
• There is an apparent genetic predisposition for SAT, HLA BW 35 reported in all ethnic groups.(7,8)

Clinical picture(more than 50% of the patients may have the following signs and symptoms)(8,9,10)

Symptoms Signs Laboratory findings

Pain in neck or thyroid Tender, firm thyroid Elevated ESR
Constant, dull pain Fever Elevated T3 & T4
Fever Acutely ill Elevated CRP
Dysphagia Clinical Thyrotoxicosis 24 h RAIU <5%
Malaise
Fatigue
Anxiety
Sweat

Lab investigations:
 Elevated erythrocyte sedimentation rate (>55mm/h)
 Normal or slightly elevated leukocyte counts
 Increased serum IL-6 and Tg concentrations during the thyrotoxic phase
 Low radio iodine uptake (< 5% in 24 hrs)
 Biochemically thyrotoxic, hypothyroid or euthyroid depending upon the phase of SAT
 Ultrasound may show generalised, multiple or single regions of hypoechogenicity with evidence of
low-to-normal vascularity on color doppler
 FNAC :Infiltration with neutrophils and mononuclear cells
• Disruption of follicles
• Typical lesion characterized by central core of colloid surrounded by a large number of
individual histiocytes (giant multinucleated cells).

 Thyroid antibodies are transiently detectable at low titers in a minority of patients

Clinical course:
 May last 2 to 6 months without treatment
 Recurrences reported in about 20% of the patients
 Permanent hypothyroidism is rare (1-5%)

Treatment:
Antithyroid drugs have no role in treatment.

Beta blockers may be required.

 In milder cases:
 Salicylates/NSAIDs for pain and tenderness
 In more severe cases:
 Corticosteroids (prednisone 40-60mg/day) for a more dramatic and rapid effect (slowly tapered over
the next 6 to 8 weeks and then discontinued)

170
SILENT/PAINLESS THYROIDITIS:
 It is characterized by transient thyrotoxicosis with low RAIU, and a small, painless, non tender goiter.
 Thyrotoxicosis results from damage of follicular cells by the inflammatory process, with leakage of
preformed thyroid hormones in the bloodstream.
 The overall prevalence of silent thyroiditis as a cause of thyrotoxicosis ranges from 4 to 15%
 greater prevalence in previously iodine-deficient areas, but recently exposed to sufficient iodine
 the female/male ratio is ~ 2:1

Etiology:
Etiology is autoimmune.

Clinical picture:
There are 3 phases:
 thyrotoxicosis,
 hypothyroidism,
 recovery
Persistent hypothyroidism may also develop in about 5%.
Silent thyroiditis presents with a relatively abrupt onset of symptoms of mild thyrotoxicosis:
 tachycardia
 heat intolerance
 sweating
 nervousness
 weight loss

Lab investigations:
 Biochemically thyrotoxic, euthyroid or hypothyroid as per the phase
 Low RAIU
 Positive ATPO and ATg antibodies
 Serum Tg and urinary iodine concentrations are increased
 FNAC;extensive lymphocyte infiltration, collapsed follicles and degeneration of follicular cells
 USG: decreased or heterogeneous echogenicity. During the toxic phase, the vascularity is
markedly decreased

Treatment:
No role of Antithyroid drugs
Beta blockers may be used, if needed
Transient use of thyroxine, very infrequently

Postpartum Thyroiditis:

Occurrence of hyperthyroidism and/or hypothyroidism during the 12-month postpartum period in women who
were euthyroid during pregnancy
 Variant of Autoimmune (Hashimoto’s) Thyroiditis
 Follows Delivery
 Autoimmune Damage to the Follicles with Release of Thyroid Hormone
 Painless with Small Goiter
 Variable Triphasic Course just like painless thyroiditis
 Suppressed Radio Iodine Uptake
 Sedimentation Rate-<30 mm/h

Risk factors for development of PPT:

 positive TPOAb in the first trimester of pregnancy11
 type 1 diabetes mellitus
 a history of chronic autoimmune thyroiditis or Graves’ disease, or a previous episode of PPT
during a preceding pregnancy

Treatment of PPT:
 Mild thyrotoxicosis usually does not require therapy
 If symptomatic, beta blockers are given
 No role for anti thyroid drugs
 Treatment of hypothyroid phase may not be necessary.

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  If hypothyroid phase is prolonged or symptomatic, levothyroxine may be given, then withdrawn after
6 to 9 months to determine whether thyroid function is normalized or not.

Hashimoto’s Thyroiditis:
Hashimoto’s thyroiditis or Chronic lymphocytic thyroiditis or Chronic autoimmune thyroiditisis is the most
common type of thyroiditis12. This is also the most common cause of long term hypothyroidism

Variants:
 Classic Hashimoto’s thyroiditis
 Atrophic Hashimoto’s thyroiditis (primary myxedema)
 Juvenile lymphocytic thyroiditis
 Focal thyroiditis
 Post-partum thyroiditis
 Silent (painless thyroiditis)

Classic Hashimoto’s:
 Middle-aged woman
 Goiter. At presentation, patient may be euthyroid or hypothyroid
 Chronic course with almost universal development of hypothyroidism

Clinical picture:
 Diffusely enlarged glands with unequal gland size
 Pyramidal lobe may be palpable
 Moderate to massive enlargements may occur
 the gland is nontender, firm or rubbery in consistency, with a bosselated surface
 the thyroid gland is reduced in size in atrophic thyroiditis
 Patients may present a goiter with or without hypothyroidism.
 A feeling of tightness in the neck may occur, but compression of the trachea is uncommon

Epidemiology:
 the disease is most often diagnosed between the ages of 50 - 60 years,
 5 to 7 times more frequently in women than in men;
 the prevalence of thyroid antibodies(which correlates with autoimmune thyroiditis)is higher in
communities with sufficient iodine intake and increases from 6% to 27% in the second to sixth decades
of life in women.

Lab investigations:
1.Antithyroid antibodies are positive:
 TPOAb95% patients
 TgAb60-80% patients
2.Thyroid radionuclide scan and radioactive iodine uptake (RAIU) are not crucial to the diagnosis
(normal, low, or high).
3.An ultrasound pattern of the thyroid: diffusely reduced echogenicity
4.FNAB- cytological smears of Hashimoto’s thyroiditis are rich in lymphocytes and oxyphil cells

Riedel’s Thyroiditis
It is a rare, chronic inflammatory disorder of unknown etiology, characterized by dense fibrosis involving the
thyroid and adjacent tissues, and extracervical areas (fibrousmediastinitis, retroperitoneal fibrosis, retro-
orbital fibrosis, sclerosing cholangitis, and pancreatitis).

Clinical picture:
 A patient will present with a long history of a painless, progressively increasing anterior neck mass ,
 It occurs mainly in middle-age or elderly women
 Pressure symptoms: Dysphasia, cough, hoarseness, stridor, attacks of suffocation may appear.
 Most patients are euthyroid at initial presentation
 A stony-hard or woody thyroid mass that varies in size from small to very large, may involve one or
both lobes, and is fixed to surrounding structures

Lab Investigations
1. Thyroid antibodies are present in up to 45% of patients.
2. Serum calcium may be low due to parathyroid invasion.

172
 3. Differentiation from thyroid carcinoma or lymphoma of the thyroid requires open biopsy, since FNAB
may be difficult to interpret.

Treatment
 Surgical treatment is necessary to relieve pressure on the trachea and to establish diagnosis.
 Corticosteroids are of little or no value.
 The course of the lesion may be slowly progressive, may stabilize, or remit.
 Extrathyroidal fibrotic lesions may complicate the prognosis.

Table 2:Comparison between different types of thyroiditis13

Sporadic painless Acute infectious Subacute thyroiditis
thyroiditis thyroiditis
Etiology Autoimmune Infectious Unknown
Sex ratio (F:M) 2:1 1:1 5:1
Incidence <1% Rare 5%
Age of onset (yr) All ages, peak 30-60 Children, 20-40 20-60,80% 40-50
Children No Yes Rare
Genetic predisposition Low Low Moderate, HLA Bw-35, DRw8
Pathology Lymphocytic infiltration Abscess formation Giant cells, granuloma
Prodrome None Upper respiratory Viral illness
infection
Goiter Non-painful persistent Painful, transient Painful, transient

References
1. Sekhri T, Gopalakrishnan S, Sahoo M, Mitrabasu. A young girl with thyroid enlargement due to tuberculous
thyroiditis. The Indian Practitioner, 2007 April,60(4);245-246
2. Berger SA, Zonszein, et al.Infectious diseases of the thyroid gland.(Review).Rev. Infect Dis 1983;5(1):108-122.
3. Brook I. Microbioplogy and management of acute suppurative thyroiditis in children. Int J
PediatrOtorhinolaryngol 2003;67(5):447-451.
4. Chi H , Lee YJ, et al. Acute suippurative thyroiditis in children. Pediatr Infect Dis J2002;21(5):384-387.
5. Womack NA. Thyroiditis. Surgery 1944;16:770-782
6. Takai S, Miyauchi A, et al. Internal fistula as a routeof infection in acute suppurative thyroiditis.
Lancet1979;1(8119):751-752
7. Kabalak T, Ozgen AG. Familial occurrence of subacute thyroiditis. Encode J 2002;49(2):207-209.
8. Lazarus JHSilent thyroiditis and subacute thyroiditis. In: Braverman LE, Utiger RD, eds. The Thyroid.
Philadelphia, PA: Lippincott-Raven;1996:577-591
9. Fatourechi V, Aniszewski JP, et al.Clinical features and outcome of subacute thyroiditisin an incidence cohort:
Olmsted countyMinnesota, study. J Clin Endocrine Metab 2003;88(5):2100-2105.
10. Pearce EN, Bogazzi F, et al. The prevalence of elevated serum C- reactive protein levels in inflammatory and non
inflammatory thyroid disease. Thyroid 2003;13(7):643-648
11. Samuels MH. Subacute, silent, and postpartum thyroiditis. Medical Clinics of North America.2012;96(2):223–233.
12. Hiromatsu Y, Satoh H, Amino N. Hashimoto's thyroiditis: history and future outlook. Hormones
(Athens) 2013;12:12–18.
13. Farwell AP. In: Braverman LE, Cooper DS, eds The Thyroid 10 th Ed .Lippincort Williams & Wilkins;2013:415

173
 WELL DIFFERENTIATED THYROID CANCER
Amit Agarwal , Suneel Mattoo, Rashid Mohd

Introduction
Differentiated thyroid cancer (DTC) originates from follicular epithelial cells within the thyroid gland. This is
the most common type of thyroid cancer and has a favourable prognosis. Papillary thyroid cancer (PTC)
accounts for about 85% of DTC while follicular thyroid cancer (FTC) accounts for about 12% 1. Thyroid cancer
has increased by three fold in the last few decades, so it is increasingly important for physicians and surgeons to
understand the goals of treatment and appropriate follow up 2. Thyroid cancer has excellent survival rates, so the
focus must be not only to reduce the risk of recurrence, but to minimize treatment-related morbidity. Treatment
for thyroid cancer includes surgery, radioactive iodine (RAI) and thyroid stimulating hormone (TSH)
suppression3.

Evaluation
DTC usually presents with a thyroid nodule. The evaluation should begin with the performance of a complete
ultrasonography of the neck and guided fine needle aspiration (FNA) cytology from the nodules having features
suspicious of malignancy which include calcifications, hypoechogenicity, or irregular margins, taller than wider
in the transverse view. Guidelines have been laid down by the American Thyroid Association (ATA) regarding
the minimum size of the nodules to be biopsied4. Cytology should be reported according to the Bethesda System
for Reporting Thyroid Cytopathology (TBSRTC) which includes the following categories: Non-
diagnostic/unsatisfactory (ND/UNS), benign, atypia of undetermined significance/follicular lesion of
undetermined significance (AUS/FLUS), follicular neoplasm/suspicious for a follicular neoplasm (FN/SFN),
suspicious for malignancy (SUS), and malignant5.

Repeat FNA is recommended in case of a non-diagnostic/unsastisfacory cytology. In AUS/FLUS, the options

include repeat FNA, molecular testing and or an initial diagnostic lobectomy. In FN/ SFN, further risk
stratification is done and initial total thyroidectomy or diagnostic lobectomy or molecular testing may be
considered. If molecular testing is not available, intraoperative frozen section biopsy can be considered as an
option to determine the need for initial total thyroidectomy. Cases of SUS and confirmed malignancy usually
undergo total thyroidectomy5.

Lymph node metastasis is preset in 20-50 % cases 6-10. The lymph nodal basin of thyroid is also evaluated on
ultrasonography. Suspicious lymph nodes (LN) are the ones that have lost their fatty hilum, are more round
versus oval in shape, or have hyperechogenicity, cystic changes, microcalcifications or peripheral vascularity11,
12
. ATA recommends that all suspicious LNs or those more than 8-10 mm should have a FNA if a diagnosis of
malignancy will change management4. Besides, thyroglobuln (Tg) washout of LN can increase the sensitivity of
FNA13 .

Contrast enhanced CT scan or MRI is indicated in case of extrathyroidal extension, and retrosternal/
retrocalvicular extension14. Sometimes, bronchoscopy and/or esophagoscopy may be required to demonstrate
intraluminal extension of tumor4.

TSH is done in all patients. High levels of TSH are associated with increased risk of malignancy15, 16.
Voice assessment includes history regarding change in the character of voice, indirect/ direct laryngoscopy or
transcutaneous ultrasonography.

Treatment
For papillary microcarcinomas defined as PTC<1 cm), active surveillance may be considered 4, 17. Follow up US
is done at at six months after diagnosis, and then yearly to evaluate size of the PMC and LNs. Suspicious LNs
should undergo FNA with Tg-washout . Indications for rescue surgery include increase in size of the PMC
>3mm or metastasis in LN.

The most recent 2015 ATA guidelines propose lobectomy is acceptable for DTC <4cm without extrathyroid
extension or LN metastases, with no history of neck radiation or familial thyroid cancer4. It may also be
considered in minimally invasive FTC and in cases of indeterminate cytology. The advantage to lobectomy is
avoidance of hypoparathyroidism, bilateral RLN injuries, and the possible need for hormone replacement
therapy.

Completion thyroidectomy can be considered in case the final histopathology is widely invasive FTC with
extension beyond the capsule and/or > 4 blood vessel invasion, or positive margins with residual tumor or
malignancy in patients with indeterminate cytology or if the patient has undergone hemithyroidectomy/

174
lobectomy initially. Completion thyroidectomy should either be done early within three days of the initial
operation, or delayed until at least three months after. Delaying surgery does not result in worse oncologic
outcomes and may increase the safety and completeness of the procedure18.

Near-total thyroidectomy or total thyroidectomy (TT) is recommended for any tumor >4cm, tumors with
extrathyroidal extension, regional LN or distant metastases, or if postoperative RAI is definitively planned4. This
may be the case in patients >45 years of age, previous neck radiation, contralateral or multifocal disease, or
familial thyroid cancer. The advantages of TT include decreased recurrence rates, improved surveillance with Tg
levels, and it facilitates the use of RAI. Disadvantages include increased risk of complications such as RLN
injury, hypocalcemia with hypoparathyroidism.

PTC spreads lymphatically, first and most commonly to the central compartment level VI, and less commonly to
the lateral compartments19. FTC metastasizes hematogenously.Only <5% of FTCs develop LN metastases. The
ATA guidelines recommend therapeutic central LN dissection (CLND) along with TT for any clinically positive
LNs in level VI, and therapeutic lateral LN dissection for any biopsy proven metastatic LN in the lateral neck4.
Surgery for LN disease should include a compartment-oriented neck dissection rather than “berry picking” in
order to decrease persistent or recurrent disease20. Central LN dissection includes either unilateral or bilateral
removal of level VI LNs including prelaryngeal, paraesophageal, pretracheal and paratracheal LN basins. Lateral
LN dissection includes removal of LNs from levels II-V.

Prophylactic CLND for PTC is controversial. It is recommended by the ATA for advanced T3 or T4 PTC or if
lateral neck lymphadenopathy is identified4. It is not recommended in cases of T1 or T2 PTC, non invasive PTC
or FTC without lymphadenopathy, indeterminate FNA results, or BRAF mutation in the primary tumor. Many
reviews have failed to show benefits of routine CLND20. On the other hand, several studies have pointed out that
the advantages of prophylactic CLND include possible slight improved disease-free survival and decreased local
recurrence21-23. The disadvantages of prophylactic CLND include increased morbidity, particularly with higher
risk of both hypocalcemia and hypoparathyroidism.

Serum Tg levels and high-resolution neck US are the commonest and reliable methods for postoperative
surveillance that will identify the majority of recurrences. Postoperative Tg surveillance may be stimulated or
unstimulated. Stimulation is done either with rhTSH or thyroid hormone withdrawal for 3-4 weeks24. rhTSH is
costly but patients maintain a good quality of life.

Whole-body radioiodine scanning (WBS) with I-123 or I-131 and treatment must be done under stimulated
conditions as TSH directly stimulates the sodium-iodine symporter uptake of iodine in most normal thyroid
epithelial or follicular cells and DTC tissue. Thus, preparation for WBS includes raising serum TSH >30mIU/L,
the level needed for thyroid tissue to concentrate radioactive iodine and identify residual or recurrent disease25.

The ATA guidelines recommend radioactive iodine should be considered after TT in intermediate risk DTC with
high risk variants, if the primary tumor >4cm, microscopic extrathyroidal extension, in patients >45 years of age,
or if metastases is found in clinically relevant central LNs or any lateral or mediastinal LNs. Radioactive iodine
treatment is recommended for high risk DTC of any size with extrathyroidal extension, local or distant
metastases as it shows improved disease-free survival. The goals of RAI treatment include: remnant ablation to
destroy residual normal thyroid tissue, or as adjuvant therapy for suspected or proven residual or metastatic
disease to improve disease free survival. Doses range from 30-100 mCi for treatment of high risk or persistent
disease involving LNs to therapeutic doses of 100-200 mCi to treat distant and/or bone metastases4. Caution is
raised for these therapeutic doses as bone marrow suppression can occur. Contraindications for RAI therapy are
pregnancy and breast-feeding.

Post therapy scans are recommended three to seven days after treatment to identify any remaining thyroid tissue
that is radioiodine avid26 .If the WBS is negative, which means there is no activity outside of the thyroid bed,
with undetectable Tg levels and negative neck US, there is no need to repeat a WBS27, 28. In high risk or
persistent disease with uptake outside of the thyroid bed, large thyroid remnants obscuring uptake of LNs, or
patients with anti-TgAbs, diagnostic WBS six to 12 months after RAI treatment is indicated with I-123 or low
dose I-131 for better quality images. In high risk patients with negative WBS but high Tg levels, consider a
FDG-PET CT scan, which may be more sensitive to aggressive histology variants29.

Follow up
Tumour persistence or recurrence is more common than the risk of mortality in DTC. The estimated the risk of
persistent DTC ranges from 7% to 28% (depending on the study), and the risk of recurrent DTC in patients who
respond well to treatment is 0.2−1.4% 30-32.

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The ATA risk stratification system classifies the likelihood of persistent and/or recurrent disease as low (<5%),
intermediate (5–20%) or high (>20%) based on features documented at the time of diagnosis4.(Table 1)
The initial risk of recurrence should be refined (Dynamic risk assessment) during follow-up in light of a patient’s
response to treatment4 (Table 2). The response should first be assessed 6–18 months after the initial treatment,
and it should be predominantly based on serum thyroglobulin and anti-thyroglobulin antibody assays and
imaging.

Table 1: ATA Risk of Thyroid Cancer Recurrence4, 35

176
Table 2: Patient’s responses to treatment4,35

177
Table 3: Follow up protocols in patients with PTC4,35

Radio-iodine Refractory (RR) Thyroid Cancer

According of the ATA, RR-DTC is defined in patients with the following conditions4,36 (i) the foci never
concentrate RAI; (ii) despite previous evidence of RAI concentration, the foci lose the ability to be RAI-avid;
(iii) despite the significant concentration of RAI, concentration is present in some foci but not in others; or (iv)
metastasis progress within one year after RAI therapy For RR-DTCs, the probability of being cured by further
RAI therapies is very low, and adverse effects, including leukemia, secondary tumors, and lung toxicity, may be
increased.
RR-DTC is associated with the abnormal function of sodium- iodide symporter (NIS), the decreased expression
of other iodine handling genes, including Tg, thyroperoxidase (TPO), and thyroid-stimulating hormone receptor
(TSHR)37.
18F-FDG PET/CT (fluoro-18-deoxy-glucose positron emission tomography) has been accepted for investigating
DTC with high stimulated Tg levels (> 10 ng/mL) and negative RAI-WBS as a standard of care for RR-DTC.
The higher the Tg level, the higher the sensitivity of the 18F-FDG PET/CT scan38.
RR-DTC could be asymptomatic for a long time. Watchful waiting with TSH suppression should be taken into
consideration for patients with an indolent disease; unresectable metastatic cancer; asymptomatic, stable, or low
tumor burden; low likelihood of developing the rapidly progressive disease, and no adverse impact from disease
burden,
Local therapy indicated in RR-DTC is determined by the location (aerodigestive tract, lung, extra cervical lymph
nodes, brain, and bones), number of lesions, tumor burden, and technical feasibility. Main local therapies include
surgery, external beam radiation (EBRT), radiofrequency ablation (RFA), ethanol ablation, and laser ablation.
For patients with RR-DTC that progresses despite TSH suppression and local therapy, therapeutic options have
been historically limited. Presently, targeted chemotherapy holds promise in the therapy of RR-DTC. Sorafenib
and lenvatinib are the only two multitargeted kinase inhibitors that have been approved by the US Food and
Drug Administration (FDA) for use in patients with progressive RR-DTC, while most of the other agents remain
investigational. Multikinase inhibitors can inhibit VEGF or PDGF, and thus inhibit angiogenesis by depriving
the tumor of a vascular supply. Signaling pathways, such as the MAPK/ERK and PI3K/AKT pathways, regulate
cell proliferation, and targeted therapies interfere with these pathways39,40.

Other drugs under investigation in case of de-differentiated thyroid cancer include BRAF and MEK inhibitors,
including dabrafenib and selumetinib, showed significant enhancement of RAI incorporation and notable
efficacy in a subset of patients with PTC41,42, immunotherapy43,44 with pembrolizumab, an anti-PD-1 antibody
and gene therapy45.

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MEDULLARY THYROID CARCINOMA (MTC)

Sunil Chumber, Dhritman Maitra

Introduction
Medullary thyroid cancer, first described in 1959 by Hazard, Hawk and Crile, comprises 4-10% of all thyroid
cancers.

Pathology
It arises from the parafollicular C cells of thyroid gland which develop from the neural crest cells derived from
the ultimobranchial bodies.C-cells are concentrated around the upper poles of the thyroid gland and secrete
calcitonin which is also demonstrated by immunohistochemistry in MTC.These tumours also secrete
carcinoembryonic antigen (CEA), histaminase,neuron-specific enolase, calcitonin gene-related peptide,
somatostatin, thyroglobulin, thyrotropin-stimulatinghormone, adrenocortical releasing hormone, gastrin-related
peptide, serotonin, chromogranin, substance P, and propriomelanocortin.
Microscopically, the tumours comprise of sheets of infiltrating neoplastic cells separated by collagen and
amyloid. C-cell hyperplasia has been identified as a precursor of MTC.Spread occurs via lymph nodes.
Metastases may occur to lungs, liver, bones, brain and subcutaneous tissues. Local invasion is also a common
feature. Histological features of aggressiveness include vascular invasion, lymphatic invasion, invasion of the
thyroid capsule, and extranodal spread of tumor in lymph node metastases.

Clinical Course
Patients may present with thyroid lumps with or without features of compression and cervical lymphadenopathy.
Sometimes in advanced cases with high calcitonin levels, secretory diarrhea may be present.The course varies
from very aggressive to relatively indolent.There are several syndromic associations with variable presentations.
Aggressiveness is governed by genetic mutations in specific codons. Histological features of aggressiveness
include vascular invasion,lymphatic invasion, invasion of the thyroid capsule,and extranodal spread of tumor in
lymph node metastases.Death occurs mostly by invasion of trachea in the neck or mediastinum or by
compression due to bulky lymphadenopathy.

Etiology
Cases may be sporadic or inherited as a part of Autosomal Dominant syndromes like Mutiple endocrine
neoplasia (MEN)2A,2B and Familial MTC(FMTC) brought about by mutations in the RET proto-oncogene
located in chromosome 10. However, mutations in different codons lead to different phenotypic
expressions.Patients with hereditary MTC have bilateral,multifocal disease in 80% cases and present at a much
earlier age.Sporadic ones peak at 50-60 yrs of age and has a marginal female preponderance
MEN 2A patients also have C cell hyperplasia, diffuse medullary adrenal hyperplasia giving rise to
phaeochromocytomas (40-45%), asymmetric parathyroid hyperplasia and cutaneous lichen amyloidosis.Some
patients have coexistent Hirschsprung’s disease.
MTC associated with MEN 2B is the most virulent. Though hyperparathyroidism is never present,40-50% cases
have phaechromocytomas. They are also associated with mucocutaneous ganglioneuromas and marfanoid
habitus.
FMTC is not associated with any other endocrinopathy, presents much later and has a very indolent course.

Diagnosis
Clinical and family history of neck lumps or any history suggestive of the associated endocrinopathies are
extremely helpful. Invasive tumours may cause hoarseness,stridour,dysphagia and so on.Identifying patients and

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prospective patients from families with known mutations and subjecting them to genetic testing is of prime
importance.

As a rule all MTCs are presumed to be hereditary unless proved otherwise.

Sometimes even before the appearance of clinically appreciable lumps ,serum calcitonin and or,CEA may be
raised and indicate the presence of disease.Penatgastrin or calcium stimulated calcitonin evaluation may help to
diagnose patients even before there is florid rise in serum calcitonin levels.High levels of calcitonin spell a poor
prognosis,whereas high levels of CEA correlate well with distant metastasis.Investigations to rule out
hyperparathyroidism(serum PTH and calcium) and phaeochromocytoma(serum metanephrines or 24-hr. urinary
catecholamines).

Fine needle aspiration cytology and biopsy with or, without immunocytochemistry/immunohistochemistry for
calcitonin almost always clenches the diagnosis.

Ultrasound(USG) neck picks up subclinical nodules and is also advised in patients with palpable disease.A CT-
neck may act as a valuable adjunct to USG to assess the tumour extent and lymph nodal involvement.

CT thorax,abdomen and bone scan are selectively advised in patients with very high levels of calcitonin and
CEA to look for metastasis. A preoperative indirect laryngoscopy is done to document the vocal cord status.

FDG-PET,DOTANOC PET,Hybrid somatostatin receptor scintigraphy along with CT(SPECT),antiCEA

monoclonal antibody tagged with Iodine123,Iodine131,Indium 111,Tc99m have been used to detect occult
metastases.Patients with metastases ,expressing higher levels of somatostatin receptors have better response with
peptide receptor radionucleotide therapy(PRRT) with Lutetium and hence these investigations help in treatment
planning.

Treatment of patients with palpable disease

Surgery is the mainstay of treatment in the form of total thyroidectomy.In MEN2a patients cervical thymectomy
is also indicated to increase the likelihood of removal of ectopic parathyroids if any.
If MTC is detected in the postoperative specimen in a patient who has undergone less than total
thyroidectomy,then completion thyroidectomy has to be undertaken unless the histopatholgical examination
detects unifocal lesion in the lobe examined,there is no C cell hyperplasia,calcitonin levels are normal and there
is no family history of MTC.

Prophylactic bilateral central compartment lymph node dissection is carried out removing all fibrofatty tissue
between the carotid sheaths on two sides,hyoid bone superiorly and innominate vessels inferiorly.Lateral
compartment neck dissection is advocated in presence of palpable lymphadenopathy.ATA recommends to
perform prophylactic lateral compartment neck dissection in patients with a primary of size>1.5 cm or in
presence of palpable lymph nodes in the ipsilateral central compartment.

In order to achieve complete central compartment lymph node clearance the parathyroids are invariably
devascularised in which case the parathyroids are removed ,sliced and autotransplanted.In patients with FMTC
and MEN2B,autotransplantation may be done in the sternocleidomastoid or the brachioradialis muscle of the
non-dominant forearm.However in patients with MEN2A,since there is a possibility of hyperparathyroidism
developing in the graft,it is preferable to implant the graft in the non-dominant forearm for ease of future
surgical exploration, if required.If a parathyroid gland is found to be already enlarged during the time of
surgery,it should be excised anyway.

Phaeochromocytomas ,if present ,should be removed prior to thyroid surgery.

Prophylactic Surgery
It is indicated in RET mutation carriers.In FMTC and MEN 2A ,it may be postponed till after 5 years of age if
annual calcitonin levels and neck ultrasound are normal.If however mutations are present at codon 634 it is
advised to get the surgery done before 5 years.
In MEN 2B patients and mutations in codon 918,surgery is indicated below 1 year of age.

Central neck dissection is unnecessary if prophylactic thyroidectomy is done early.However, in some patients
undergoing prophylactic thyroidectomy microcarcinoma has been detected in the specimen even in presence of
normal stimulated calcitonin levels.So often a prophylactic surgery is actually therapeutic when looked at
retrospectively after the biopsy report is available.So sometimes central neck dissection is added even in the
prophylactic setting if serum calcitonin is raised or USG neck picks up some suspicious nodules.

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Non-surgical treatment for metastases
External beam radiation therapy or radioactive iodine(which is concentrated by follicular cells only) have not
been effective in MTC.Combination chemotherapy using 5-FU with dacarbazine or streptozocin have not
shown overwhelming response.Chemoembolization and radiofrequency ablation have been used for metastatic
liver lesions.

RET kinase inhibitors have been studied as agents for molecular targeted therapy.Vandetanib which also inhibits
VEGFR and EGFR is the only US-FDA approved drug for the treatment of advanced and progressive MTC.
Lutetium based peptide receptor radionucleotide therapy(PRRT) holds promise and so does anti-CEA
monoclonal antibody(labetuzumab) in the treatment of metastases.

Postoperative followup and prognosis

It is done with annual serum CEA and calcitonin levels along with clinical evaluation and imaging if
needed.Prognosis is worsened by presence of lymph nodes.Prognosis is best in FMTC,followed by MEN2A and
sporadic cases and worst in patients with MEN 2B.Very high levels of calcitonin indicate poor prognosis.

CYSTIC NECK SWELLINGS

Amit Gupta

Introduction
Encountering patients with a head and neck mass is frequently met and the intricate anatomy of this important
region often results in mystifying situations in identifying these lesions. Patient age, location, size, onset, and
duration of swelling are important points for making a precise diagnosis. The common pathologies usually are
from enlargement of lymph nodes (lymphoproliferative disorder, inflammatory process, or infiltration by
metastatic malignant cells), thyroid gland (goitre, thyroiditis, benign and malignant tumors), salivary glands
(sialadenitis, cysts, benign and malignant tumors), and various cysts like thyroglossal and branchial cysts,
epidermoid and dermoid cysts, and lipomas. Cystic swellings can be classified according to anatomical location
(Table:1).

Lateral neck swellings Midline neck Swellings

Fluid Fluid
 Thyroid gland cyst  Thyroglossal cyst
 Branchial cyst  Dermoid cyst (sublingual or
 Cystic hygroma (lymphangiomaa) suprasternal)
 Sebaceous cyst  Subhyoid bursa
 Sebaceous cyst
Abscess Abscess
 Cold abscess (TB cervical lymphadenitis)  Cold abscess
 Parapharyngeal abscess  Pyogenic abscess.
 Parotid abscess
Blood Blood
 Hemangioma  Hemangioma.
 Aneurysm (carotid or subclavian)  Aneurysm (innominate artery)
Air ---
 Laryngocele
 Pneumatocele
 Pharyngeal diverticulum
Table: 1 Classification of cystic neck swellings

THYROGLOSSAL DUCT CYSTS

These represent vestigial remainder of the tract of descending thyroid gland from foramen cecum, at tongue
base, into the lower anterior neck during fetal development. in the 1st decade of life. More than 25% of
thyroglossal duct cysts present before the age of 5, and 40% present by the age of 10. TDCs are present in
approximately 7% of the general population; up to 62% of these may contain ectopic and functional thyroid
tissue, thereby enabling the development of thyroid-related tumours. Malignant neoplasms rarely arise in
thyroglossal cysts, in less than 1% of cases.

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Embryology
During the 3rd week of gestation, an epithelial thickening develops at the tuberculum impar on the anterior
pharyngeal wall. This thickening, the median thyroid anlage, divides into a bilobed structure representing the
developing thyroid gland. Rostral growth of the embryo results in caudal displacement of the median thyroid
anlage with persistence of a median stalk stretching to the tuberculum impar. Canalization of the median stalk
produces the thyroglossal duct, which typically courses ventral to the hyoid anlage, but can pass through or
dorsal to it. In the 5th week of gestation, the duct degenerates and is resorbed. Secretion by epithelium-lined
remnants of the duct can lead to thyroglossal duct cyst formation. The stimulus for secretion is unknown but can
occur at any time, accounting for the appearance of cysts later in life. They present as a midline or paramedian
cystic mass adjacent to the hyoid bone. (fig:1).
Unless infected, the cyst is smooth and mobile without communication with the overlying skin. After an upper
respiratory infection, the cyst may enlarge or even suppurate.

Diagnosis
Requires nothing more than a careful history and physical examination. A typically positioned mass that rises in
the neck with swallowing or with protrusion of the tongue is diagnostic. If the mass is atypical in location or
distorted by inflammation, ultrasonography can be helpful. Confirmation of the thyroid in its normal location by
palpation or demonstration by ultrasonography may be important to avoid incidental excision of a partially
descended thyroid. Preoperative evaluation of thyroglossal duct cyst includes: cervical and chest radiography,
ultrasound scan, scintigraphy with 131I and thyroid function tests. An ultrasound exam is useful in malignancy
by demonstrating a mural nodule, calcification or lymph node metastases. Computerized tomography has also
been used in case of malignancy and ectopic cysts. Clinical confirmation of aberrant thyroid tissue is proved by a
radioactive iodine scan. The ultrasound-guided fine-needle aspiration (FNA) is only moderately sensitive for a
preoperative evaluation of TDCs. Cytomorphologic features are not always specific, but associated with clinical
and radiological signs, they may be helpful for an accurate diagnosis. Thyroid epithelium is rarely identified.
The differential diagnosis involves: dermoid cyst, epidermoid cyst, branchial cleft cyst, lymph nodes,
lymphangioma, thyroid pathology.

Fig:1 Locations of thyroglossal cyst Fig:2 Sistrunk procedure for thyroglossal cyst

Management
Cyst aspiration and ablative sclerotherapy have been proposed as an alternative to surgical excision, although
this approach may result in a palpable remnant. Surgical management of a thyroglossal duct cyst requires
removal of the cyst, the tract, and the central portion of the hyoid bone (Sistrunk procedure),(fig;2) as well as a
portion of the tongue base up to the foramen cecum. He incorporated resection of the central hyoid bone and the
tract extending to the foramen cecum with excision of the cyst. This manoeuvre reduces the incidence of
recurrence to less than 5% from 25% when cystectomy alone is performed. Prior to excision of a thyroglossal
duct cyst, an imaging study is performed to identify functioning thyroid gland in the lower neck. This ensures
that the cyst does not contain the only functioning thyroid tissue in the patient. The most potentially dangerous
complication after thyroglossal duct excision is postoperative wound hemorrhage with resultant airway
compromise. Recurrence after thyroglossal duct cyst excision occurs in approximately 5% of patients, typically
within 1 year of the procedure. Recurrence can be caused by distortion of the tissues by inflammation or
inadequate resection of the hyoid bone or the central stalk leading to the foramen cecum. The presence of
multiple tracts can also lead to recurrent disease. Rupture of the cyst at the time of excision has similarly been
associated with an increased incidence of recurrence.

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BRANCHIAL CLEFT ANOMALIES

Comprise a heterogeneous group of congenital malformations derived from incomplete in utero resorption of
the pharyngeal clefts and pouches. Fistulae, cysts, sinus tracts, and cartilaginous remnants of the first and second
branchial clefts are the most common manifestations. These anomalies are excised to prevent the morbidity of
subsequent infection.

Embryology
During the 3rd to 5th gestational week, the primitive pharynx develops four pairs of endodermally lined pouches
along its inner walls (fig:3).
An equal number of ectodermally lined clefts form on the surface of the embryo. These pouches and clefts
approximate each other, creating intervening mesodermal arches. Proliferation of the mesoderm later in gestation
obliterates the epithelial out-pouchings, with the exception of the first branchial cleft and pouch, which develop
as the auditory canal, tympanic membrane, and middle ear. Persistence of a branchial cleft or pouch results in a
cervical anomaly located along the anterior border of the sternocleidomastoid muscle from the tragus of the ear
to the clavicle.

First branchial cleft cysts Second and third branchial cleft cysts are found along the anterior border of the
sternocleidomastoid muscle and can produce drainage via a sinus tract to the neck skin. Secondary infections can
occur, producing enlargement, cellulitis, and neck abscess that requires operative drainage. Branchial cysts
appear after the 1st decade of life and are located higher in the neck than the external ostia of sinuses and
fistulae. A cyst is identified as a palpable mass at the level of the carotid bifurcation. These lesions can be
confused with and should be distinguished from cystic hygromas, hemangiomas, lymphadenopathy, and,
particularly, lymphatic or metastatic tumors. Ultrasonography differentiates solid and cystic masses and is the
only imaging study routinely performed. Further diagnostic studies with computed tomography(fig:4), magnetic
resonance imaging, or fine-needle aspiration biopsy might be indicated, particularly for solid masses.

Fig:3 Schematic diagram branchial arches with Fig: 4 CT scan showing second branchial cleft
clefts and pouches cyst at the level of sternocleidomastoid

Patients with evidence of infection are treated with antibiotics until the inflammatory process has fully resolved.
At times, incision and drainage is necessary. Unlike thyroglossal duct cysts, branchial cleft anomalies are related
anatomically to nerves and vessels, which are vulnerable to injury during drainage procedures. To ensure safety,
adequate sedation or general anesthesia is advised.

Branchial cleft cysts are of variable size and have no associated skin opening. Surgical excision is preferred to
establish the definitive diagnosis of a branchial cleft cyst and to avoid non treatment of a masquerading head and
neck regional metastasis. Morbidity is attributable to the injury of adjacent structures at the time of surgery or to
incomplete excision of the anomaly(fig:5).

The incidence of these complications is increased by inflammation occurring before or at the time of surgical
excision. Recurrence is rare unless infection was present, in which case rates exceed 20%. For these reasons,
excision is indicated once a branchial cleft anomaly has been diagnosed. Cystic metastasis from squamous cell
carcinoma of the tonsil or tongue base to a cervical lymph node can be confused for a branchial cleft cyst in an
otherwise asymptomatic patient.

DERMOID CYSTS
Developmental abnormality, inclusion of ectoderm along the lines of fusion, thus in the neck they are always
midline & usually above the hyoid bone. The cyst wall is usually thick & lined by stratified squamous

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epithelium containing skin appendages, hair follicles sebaceous & sweat glands. The cyst contains hairs &
cheesy epithelial debris. Cystic painless mass in the midline of the neck Cystic painless mass in the midline of
the neck between the submental region & the suprasternal notch. The cyst is not translucent & not attached to the
overlying skin. In submental dermoids sometimes there is a swelling in the floor of mouth pushing the tongue
upwards swelling in the FOM pushing the tongue upwards. Treatment is Complete surgical excision.

CYSTIC HYGROMAS
These are synonymous with lymphangiomas, developmental anomalies, which result from a failure of lymphatic
structures to anastamose with the venous system. The majority (up to 75%) of cystic hygromas involve the
jugular lymphatic network in the neck. Twenty percent occur in the axilla, and the remainder is found throughout
the body, including the retroperitoneum, mediastinum, inguinal region, and pelvis. The majority of cystic
hygromas present in the first 2 years of life (fig:6). Cystic hygromas represent fewer than 5% of congenital neck
masses.

Embryology
Development of the lymphatic system has been theorized to be of either venous origin (centrifugal spread), with
the development of lymphatic channels as sprout off large central veins, or of mesenchymal origin (centripetal
spread) with lymphatics developing as a confluence of mesenchymal spaces (centripetal spread).

An additional theory combines both potential origins with several distinct phases. The first phase begins at 7
weeks' gestation with development of lymphatic buds (lymphatic primordial), which sprout from veins forming
plexuses. These buds give rise to paired axillary and jugular sacs. In the second phase, the sacs enlarge and
develop channels with matched venous structures, namely the jugular and axillary veins. With continued
widening and enlargement of these sacs, the primordial buds coalesce. Finally, all lymphatic primordia fuse, and
a single continuous system develops. The formal thoracic duct and cisterna chili develop by the 10th week.
Failure of these sacs to form communicating channels with respective venous structures results in the formation
of cystic hygromas. Cystic hygromas occur in approximately 1% of foetuses between weeks 9 and 16 of
pregnancy.(fig: 7).

Fig:5 Technique of excision of second branchial

Fig: 6 Cystic hygroma in an infant
cleft fistula

Fig: 7 Fetal ultrasound performed at 16 weeks of Fig: 8 Barium Swallow showing pharyngeal
gestation showing the cystic hygroma pouch

Cystic hygromas present as soft, compressible, cystic masses that often distort adjacent structures. These are
usually painless, unless infected or hemorrhagic. They may expand, resulting in airway obstruction. When noted

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prenatally by sonography, appropriate intervention may be planned if airway compromise is suspected. The
EXIT (ex utero intrapartum treatment) procedure entails caesarean section with maintenance of placental
perfusion to the neonate while an adequate airway is secured. This may entail endotracheal intubation or creation
of a tracheostomy.

Diagnosis is usually clinical, although radiologic confirmation may be obtained via sonography or computerized
tomography. These tests reveal multiloculated cystic structures with well-defined boundaries. Associated
vascular malformations may be identified within the cystic hygroma as well. Magnetic resonance imaging may
offer clearer tissue margins.

Cystic hygromas are one of four types of lymphangiomas: cavernous lymphangioma, lymphangioma, cystic
hygroma, or hemangiolymphangioma. Lymphatic malformations such as lymphangiomas and cystic hygromas
can be difficult management problems. Because of their predisposition to track extensively into the surrounding
soft tissues, complete removal to these lesions is often difficult. Management of cystic hygromas universally
includes surgical excision. With surgical excision, recurrence rates for cystic hygroma have been reported at 6%
to 50%. Recurrence of cystic hygromas can be attributed to previously unidentified cystic tissue, or incompletely
resected lesions. Recurrence and regrowth occur with incomplete removal and cosmetic deformity or nerve
damage can result when extensive surgical dissection is performed for large lesions.

Other techniques (i.e., cryotherapy, diathermy, sclerotherapy) have marginal success, and may exacerbate
infection. Sclerosing agents may have a role in the therapy of cystic hygromas in situations in which anatomy
prevents complete surgical resection. Therapy in these special situations may include repeated aspiration of the
macrocystic lesions and injection of OK-432 (picibanil), a sclerosing agent. A pronounced inflammatory
response can occur with the treatment, necessitating observation for airway compromise.

SEBACEOUS CYSTS
These are common masses presenting in older patients. They are slow growing, but may become fluctuant and
painful when infected. Diagnosis is made clinically; the overlying skin is adherent to the underlying mass and a
punctum is often seen. Excisional biopsy confirms the diagnosis and is curative.

PHARYNGEAL POUCH (ZENKER’S DIVERTICULUM)

Herniation of pharyngeal mucosa through an area of weakness between the oblique & transverse parts of the
inferior constrictor muscle (Killian’s dehiscence). Cause is neuromuscular in-coordination with delayed
relaxation of the cricopharyngeal sphincter during swallowing leading to increased intraluminal pressure pulsion
diverticulum. More common in males above 60 years of age. Clinical features are gurgling sound while drinking,
regurgitation of undigested food, dysphagia due to partial oesophageal obstruction and risk of aspiration
accompanied by severe spasms of coughing. On examination, there is soft posterior neck swelling (usually on
left side) empties on pressure with a gurgle. (fig:8)

LARYNGOCELE
It is an air-filled dilatation of laryngeal ventricle & saccule. They are of two types:
 Internal (20 %): confined to interior of larynx.
 External (30%): expands into neck through thyrohyoid membrane.
 Combined (50%)
Thought to prevail in blowing jobs as trumpet players or glass blowers. Coexistence of laryngeal cancer (acts as
a valve allowing air under pressure into the ventricle) is seen. Male to female ratio 5: 1 Bilateral in 20% cases.
Clinical presentation include hoarseness of voice & stridor, lateral neck swelling that increases by Valsalva’s
manoeuvre. 10% present with infected sacs (laryngopyocele). X-ray and CT scan shows air within the sac
(fig:9).
Treatment is endoscopic excision for the internal type. Lateral external approach excision for the external &
combined types.

RANULA
A ranula is a mucus extravasation cyst involving a sublingual gland and is a type of mucocele found on the floor
of the mouth (fig:10). Ranulas present as a swelling of connective tissue consisting of collected mucin from a
ruptured salivary gland caused by local trauma.

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Fig:9 Axial CT images and coronal reconstruction
demonstrate air-filled saccular formation communicating Fig:10 Ranula in floor of mouth
with the airway.

There are two types of ranula, the most common or simple variant which is usually confined to the oral cavity
and the cervical ranula which can extend from the sublingual space around or through the mylohyoid muscle to
the submandibular space. These are usually treated by marsupialization. Ranula should be distinguished from
lymphangiomas that arise in a similar location in the floor of the mouth.

References
1. Agaton-Bonilla FC, Gay-Escoda C. Diagnosis and treatment of brachial cleft cysts and fistulae. A retrospective
study of 183 patients. Int J Oral Maxillofac Surg 1996;25:449
2. Fageeh N, Manoukian J, Tewfik T, et al. Management of head and neck lymphatic malformations in children. J
Otolaryngol 1997; 26: 253.
3. Sistrunk WE. Technique of removal of cysts of the thyroglossal tract. Surg Gynecol Obstet 1928;46:109.
4. Mahomed A, Youngson G. Congenital lateral cervical cysts of infancy. J Pediatr Surg 1998;33:1413.
5. Eisele DE, Netterville J, Hoffman H, et al: Parapharyngeal space masses. Head Neck 21:154, 1999.
6. Smith CD. Cysts and sinuses of the neck. In: O'Neill JA Jr, Rowe MI, Grosfeld JL, et al., eds. Pediatric surgery, 5th
ed. St. Louis: Mosby-Year Book; 1998:757.
7. Tran-Ngoc-Ninh, Tran Xyan-Ninh. Cystic hygroma in children: a report of 126 cases. J Pediatr Surg 1974;9:191
8. Todd NW. Common congenital anomalies of the neck. Embriology and surgical anatomy. Surgical Clinics of North
America 1993; 73: 599–610
9. Siddiq A Sood S Strachan D. haryngeal pouch (Zenker’s diverticulum). ostgraduate edical Journal 2001;
77: 506–1
10. Stell PM, Maran AG. Laryngocele. Journal of Laryngology and Otology 1975; 89: 915–24.

APPROACH TO A PATIENT WITH PAROTID SWELLING

Jainendra Arora, Swapnil Kushwaha

INTRODUCTION
Salivary glands are exocrine organs responsible for the production and secretion of saliva. These glands are
divided into major and minor salivary gland categories. The major salivary glands are the parotid, the
submandibular, and the sublingual glands. The minor glands are dispersed throughout the upper aerodigestive
submucosa (ie, palate, lip, pharynx, nasopharynx, larynx, and parapharyngeal space).
Tumors of the salivary glands are relatively uncommon and represent 3-4% of head and neck neoplasms. They
may be broadly categorized into benign neoplasms, tumor like conditions, and malignant neoplasms.

ANATOMICAL CONSIDERATIONS
• The parotid gland is the largest of the salivary glands. It is located in a compartment anterior to the ear and
is invested by fascia that suspends the gland from the zygomatic arch. The parotid compartment contains
the parotid gland, nerves, blood vessels, and lymphatic vessels, along with the gland itself.
• The compartment may be divided into superficial and deep portions, but the space has no discrete anatomic
divisions. The superficial portion contains the facial nerve, great auricular nerve, and auriculotemporal
nerve. The deep portion contains the superficial temporal vein, which unites with the internal maxillary
vein to form the posterior facial vein.
• The parotid compartment is a wedge-shaped 3-dimensional area with superior, anterior diagonal, posterior
diagonal, and deep borders. It is bounded superiorly by the zygomatic arch; anteriorly by the masseter

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 muscle, lateral pterygoid muscle, and mandibular ramus; and inferiorly by the sternocleidomastoid muscle
and the posterior belly of the digastric muscle.
• The deep portion lies lateral to the parapharyngeal space, styloid process, stylomandibular ligament, and
carotid sheath. The deep anatomic relationship is important because tumors may arise in the deep portion
and grow into the parapharyngeal space and may manifest as intraoral masses. These tumors are termed
dumbbell tumors when they grow between the posterior aspect of the mandibular ramus and the
stylomandibular ligament. This position causes a narrow constricted portion with larger unrestricted
portions on either side, forming a dumbbell shape.
• The parotid is a unilobular gland through which the facial nerve passes. No true superficial and deep lobes
exist. The term superficial parotidectomy or parotid lobectomy refers only to the surgically created
boundary from facial nerve dissection.
• The Stenson’s duct drains the parotid gland. Initially it is located approximately 1 cm below the zygoma
and runs horizontally. It passes anteriorly to the masseter muscle and then penetrates the buccinator muscle
to open intraorally opposite the second maxillary molar.
• The facial nerve exits the skull via the stylomastoid foramen located immediately posterior to the base of
the styloid process and anterior to the attachment of the digastric muscle to the mastoid tip at the digastric
ridge. The nerve travels anteriorly and laterally to enter the parotid gland. Branches of the facial nerve that
innervate the posterior auricular muscle, posterior digastric muscle, and stylohyoid muscle arise before the
nerve enters the parotid gland. Just after entering the parotid gland, it divides into 2 major divisions: the
upper and lower divisions. This branch point is referred to as the pes anserinus. Subsequent branching is
variable, but the nerve generally forms 5 branches. The buccal, marginal mandibular and cervical branches
arise from the lower division. The zygomatic and temporal branches arise from the upper division.
• Branches of the external carotid artery provide arterial supply to the parotid gland. The posterior facial vein
provides venous drainage, and lymphatic drainage is from lymph nodes within and external to the gland
that leads to the deep jugular lymphatic chain.

DIFFERENTIAL DIAGNOSES OF PAROTID SWELLING

1. Infectious:
a. Child: Mumps, Coxsackie
b. Adult: S. aureus
2. Non-infectious benign:
a. Epithelial: Pleomorphic adenoma Warthin’s tumor Oncocytoma
b. Non-epithelial: Lymph node, Cysts, Lipoma, Lymphoepithelial lesion, Hemangioma
3. Non-infectious malignant:
a. Mucoepidermoid carcinoma
b. Adenoid cystic carcinoma
c. Mixed malignant tumor
d. Acinic cell carcinoma
e. Adenocarcinoma
f. Squamous cell carcinoma
g. Diffuse (sialadenosis, sialadenitis, sialolithiasis) v/s Discrete mass (tumor)
h. Unilateral (bacterial sialadenitis, sialolithiasis, neoplasm) v/s Bilateral (sialadenosis, mumps-viral
sialadenitis)

The diagnosis of a parotid swelling is built on three pillars: History, Physical examination and Investigations.
Taking a good and targeted history, performing a careful and revealing physical examination and choosing the
right investigation require skill and acumen.

HISTORY FOR PAROTID SWELLING

1. Detailed history about the swelling:
• Onset and duration: Rapid (inflammatory), slow growing (neoplastic, sialadenosis, chronic
sialadenitis)
• Any history of rapid increase in size recently (rapid increase in size following years of slow growth
suggests a malignant change in the pre existing benign tumor)
• Rapid increase in size from the onset usually suggests a malignant tumor
• Any history of change in size of swelling during eating (in sialolithiasis the gland may swell during
eating and may diminish in size in between meals)
• Any history of pain during eating (in sialolithiasis there is a dull aching pain over the swelling
during eating)
• Painful (acute inflammatory, malignancy)
• Any history of purulent discharge from the opening of duct in the mouth
• History of impairment of facial nerve function

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 • History of difficulty in mouth opening
2. Contributing Factors:
• Exposure to radiation or toxins (lead or mercury)
• History of sarcoidosis S gren’s disease tuberculosis gout amyloidosis
• Recent facial trauma, surgery, or dental work
• Immunization history (specifically measles, mumps, rubella [MMR] vaccine)
3. Associated Symptoms: xerostomia, sialorrhea, weight loss, fever

PHYSICAL EXAMINATION FOR PAROTID SWELLING

1. Examine if the swelling lies in the parotid region?
 Boundaries of parotid region:
– Anteriorly: Posterior border of mandible
– Posteriorly: Mastoid process and the sternocleidomastoid muscle
– Superiorly: Zygomatic arch
– Inferiorly: Posterior belly of digastric muscle
2. Examine if the swelling is really a parotid mass?
 Characteristics of parotid mass:
– Swelling in the front, below and behind the ear
– Raises ear lobule
– Retromandibular groove obliterated
– Positive curtain sign- parotid gland cannot be moved above the zygomatic arch
3. Examine the swelling for following characteristics?
 Local rise in temperature: Raised temperature (inflammatory)
 Tenderness: Non tender (benign) v/s Tender (inflammatory or malignancy)
 Surface: Smooth (benign) v/s Nodular/Irregular (malignancy) v/s Ill defined (inflammatory)
Margins: Well defined (benign) v/s Irregular (malignancy) v/s Ill defined (inflammatory)
Consistency: Soft/Cystic/Firm (benign) v/s Hard (malignancy)
 Mobility and fixity: Mobile (benign) v/s Fixity to skin and masseter muscle (malignancy)
4. Examine if the deep lobe of parotid gland is involved?
 Inspect the oral cavity, enlargement of the deep lobe of parotid gland will push the tonsil and the
pillar of the fauces towards the midline.
 Palpation of the deep lobe of parotid gland by bidigital palpation- keeping one finger in the tonsillar
fossa and the other finger in the upper part of the neck behind the mandible.
5. Examination of the parotid duct?
 Inspect the orifice of the parotid duct on the buccal aspect of the cheek opposite the upper second
molar tooth. Examine for induration or discharge at the duct orifice.
 Palpate the parotid duct as it lies on the masseter muscle by a finger rolling across the masseter
muscle as the patient clenches his teeth to make the muscle taut. The terminal part of the duct is
palpated bidigitally between the index finger inside the mouth and thumb over the cheek.
6. Examine if the facial nerve is involved?
 Inspect for the clinical signs of facial nerve palsy and assess the functions of the facial nerve. It is
involved in malignancy where the nerve is infiltrated.
7. Examine if the lymph nodes are involved?
 Assess the pre, post auricular and cervical lymph nodes as they may be enlarged in inflammatory
and malignant conditions.
8. Examine if the mobility of the jaw is restricted?
 Jaw mobility is restricted in inflammatory and malignant conditions.
NOTE: Opposite parotid gland and all other salivary gland should be examined carefully.

Features suggestive of malignancy

• Nodular surface
• Irregular margins
• Hard consistency
• Skin fixity or ulceration
• Fixed swelling
• Facial nerve palsy
• Cervical lymph nodes enlarged
• Restricted jaw mobility

DIAGNOSTIC STUDIES FOR PAROTID SWELLING

Is imaging of parotid swelling required?

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Imaging of parotid swelling, such as plain Roentgenogram, Ultrasonography, CT scan, MRI scan, sialography,
and Technetium-99m Isotope Scan is required only after clinical examination in some cases. Diagnostic imaging
is usually used for the evaluation of salivary gland tumors especially in case of malignancies. Imaging generally
cannot distinguish between benign and malignant tumours. Therefore, whether to request imaging and what
imaging to request should be left on the surgeon’s discretion based on the clinical findings. The surgeon may
request CT scan or MRI scan to better determine the relationship of the tumour mass to the facial nerve and to
exclude deep extension to the parapharyngeal space. Even though the facial nerve itself cannot be seen on CT or
MRI scan, it lies on the retromandibular vein, which is visible on contrasted CT and MRI. MRI is the most
sensitive study to determine soft-tissue extension and involvement of adjacent structures. Unfortunately, imaging
studies lack the specificity for differentiating benign and malignant neoplasms. Diagnosis of salivary gland
tumors is frequently aided by the use of FNA. In the hands of an experienced cytologist familiar with salivary
gland pathology, FNA can provide an accurate preoperative diagnosis in 70% to 80% of cases. This can help the
operative surgeon with treatment planning and patient counselling, but should be viewed in the context that a
more extensive procedure may be ultimately required. The final histopathologic diagnosis is confirmed by
surgical excision.
1. Ultrasonography (USG):
a. USG is widely accepted as the first imaging modality of choice for assessment of lymph nodes
and soft-tissue diseases in the head and neck, including major salivary glands.
b. Linear, high frequency (7.5 to 12 MHz) transducer which shows high resolution images is used
for the evaluation of the salivary glands, but with high frequency the imaging depth is
compromised so it is not a good modality for the evaluation of deep lobe of parotid gland.
c. It can differentiate normal glandular parenchyma, inflammatory process (with or without
liquefaction), cystic lesions, tumors, lymph nodes and calculi. The real time capability and
high resolution of USG makes it useful for guiding FNAC.
d. The interpretation is based on individual ultrasound features of parotid gland masses with
reference to shape (oval, lobulated or irregular), margins (circumscribed, spiculated or ill-
defined), echogenicity (anechoic, hypoechoic, isoechoic or hyperechoic), echotexture
(homogeneous or heterogeneous) and vascularization. Vascularization is assessed in four
grades: Grade 1 indicates no vessels visible in the mass in colour Doppler flow imaging
(CDFI) low-flow mode; Grade 2 indicates a few vessel segments of no more than three blood
vessels visible in the whole mass; Grade 3 indicates up to five vessels visible in the mass; and
Grade 4 indicates more than five vessels visible in the mass.
e. It is useful for differential diagnosis of diseases of the salivary glands:
i. In acute inflammation, salivary glands are enlarged and hypoechoic with increased
blood flow; they may contain multiple small, oval, hypoechoic areas.
ii. In chronic inflammation, salivary glands are normal sized or smaller, hypoechoic, and
inhomogeneous.
iii. Sialolithiasis appears as markedly hyperechoic lines or points with distal acoustic
shadowing.
iv. Sialosis appears as enlarged hyperechoic glands without focal lesions or increased
blood flow.
v. he US features of S gren syndrome include inhomogeneous salivary glands with
scattered small, oval, hypoechoic or anechoic areas, usually well defined, and
increased parenchymal blood flow.
vi. Pleomorphic adenomas are usually hypoechoic, well-defined, lobulated lesions with
vii. posterior acoustic enhancement that may contain calcifications; Warthin’s tumors are
usually oval, hypoechoic, well-defined lesions that often contain anechoic areas and
are often hypervascularized.
viii. Malignant neoplasms of the salivary glands may have irregular shapes, irregular
borders, blurred margins, and a hypoechoic inhomogeneous structure or may have a
benign appearance.
ix. Salivary gland cysts have well-defined margins, anechoic contents, posterior acoustic
enhancement, and no internal blood flow.
f. However, USG appearances of some diseases may overlap and has imaging and resolution
limitations, thus producing diagnostic pitfalls.
2. CT or MRI scan:
a. When clinical examination is non-yielding and it is sometimes not possible to visualize and
analyze examined lesions completely at USG because of their location for example– deep lobe
of the parotid gland or area behind the mandible. In these situations, performance of further
imaging examinations—CT or MRI scan is highly recommended.
b. Also, in cases of suspected malignant lesions, further diagnostic methods either by CT or MRI
should be applied to assess possible infiltration of bones, deep structures invisible at USG (the

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 base of the skull, para-pharyngeal space), nerve and muscle infiltration and to evaluate deep-
lying lymph nodes. CT scanning provides better detail of the surrounding tissues, whereas
MRI demonstrates the mass in greater contrast than a CT scan.
c. CT and MRI scan play an important role in the management of patients with salivary gland
tumors, as they are more sensitive and specific than USG. CT, with its good anatomic
resolution, soft tissue contrast, and detailed morphology, can provide meaningful information
to surgeons during the procedure. MRI, with its good spatial and contrast resolution and
avoidance of radiation exposure and interfering factors, such as imaging parameters and iron
accumulation, could also provide useful information.
d. ADVANTAGES AND LIMITATIONS OF CT SCAN:
i. CT findings of diffuse glandular calcifications suggest chronic sialadenitis, whereas
calcifications within a mass are commonly seen in a pleomorphic adenoma. A solid
mass is more easily differentiated from a cystic mass using CT compared to MRI.
ii. Although the facial nerve usually is not visualized on CT, the course of the nerve can
be traced from the stylomastoid foramen better on MRI. In addition, the Stensen duct
usually is not seen on both modalities unless it is dilated.
iii. CT is superior in detecting heterotopic calcification or invasion of the mandible or
skull base.
iv. In some patients with a dense parotid gland, a small tumor or diffuse cell infiltration
cannot be detected. Furthermore, direct coronal images cannot be obtained in some
patients who cannot extend their necks.
v. The CT appearance of benign and malignant tumors can overlap. A low-grade
mucoepidermoid carcinoma can be cystic and contain calcifications, much like a
pleomorphic adenoma. Higher-grade tumors tend to be more attenuating and more
homogeneous.
vi. CT scan criteria for lymph node metastasis include any lymph node larger than 1-1.5
cm in greatest diameter, multiple enlarged nodes, and nodes displaying central
necrosis. Lymph nodes harboring metastasis also may appear round rather than the
normal kidney bean shape, and evidence of extracapsular extension may be identified.
e. ADVANTAGES AND LIMITATIONS OF MRI SCAN:
i. MRI is superior to CT in demonstrating tumor margins, and MRI is the procedure of
choice for evaluating a non tender palpable parotid mass. Common sequences are T1-
weighted, T2-weighted, and inversion recovery fast spin-echo sequences.
ii. As a result of increased cellularity and decreased mucous production, high-grade
malignancies tend to have low signal intensity with both T1- and T2-weighted
sequences, whereas benign and low-grade malignancies are bright on T2-weighted
images.
iii. In cases of a pleomorphic adenoma, T1-weighted images typically demonstrate
intermediate signal intensity, with isointense-to-hyperintense signal on T2-weighted
images. Contrast enhancement can be homogeneous or heterogeneous.
iv. A Warthin’s tumor has homogeneous intermediate-to-hyperintense signal on T1-
weighted images and intermediate signal intensity with focal hyperintense areas on
T2- weighted images. Typically, these tumors are not contrast enhancing.
v. Common benign pleomorphic adenoma can evolve into malignant carcinoma ex
pleomorphic adenoma or malignant mixed tumor. MRI can demonstrate the change
from high T2 signal intensity with benign tumors to low-to-intermediate T2 signal
with malignant tumors.
f. MRI contrast agents are controversial and usually reserved for use when a palpable mass is not
seen on a non enhanced study. The use of contrast agents is indicated in evaluating the
postoperative gland.
3. Radiography:
a. Plain-film evaluation of the parotid gland is of limited clinical value. Radiographs can
demonstrate sialolithiasis or involvement of the adjacent mandible (bone resorption).
Sialolithiasis must have high calcium content and must be atleast 2-3 mm to be viewed on
plain radiograph. Views used to examine the parotid gland include open-mouth lateral images
with an extended chin, postero-anterior images, and bilateral oblique images.
b. CT is 10 times more sensitive than plain radiography in detecting small calcium deposits.
c. Sialography may help to differentiate inflammatory versus neoplastic processes, but this test is
infrequently performed and is of limited value in the evaluation of parotid masses.
Sialography or the in ection of water-soluble contrast material into the parotid duct is used to
demonstrate ductal anatomy fistulas S gren’s disease or sialoliths.

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 d. The sensitivity of sialography in detecting tumor is 85% at best, when performed by an
experienced examiner. This rate is low compared with that of CT and MRI. Sialography is
contraindicated or not recommended in the workup for a suspected malignant parotid tumor
because come believe that the pressure generated by the injection of contrast material can
disseminate tumor cells. Sialography should be reserved for the diagnosis of inflammatory
conditions.

4. Technetium-99m Isotope Scan:

a. The parotid and other salivary glands concentrate technetium-99m pertechnetate; however,
nuclear medicine studies are not the preferred imaging modality for evaluating a parotid
swelling. Gallium-67 citrate, technetium-99m (99m Tc) pertechnetate, and thallium-201
chloride have been used to evaluate salivary gland tumors.
b. It is a rarely utilized investigation but is the imaging modality of choice for functional
evaluation of the salivary glands. It is used to differentiate a Warthin’s tumor and oncocytoma
from other salivary gland neoplasms as they appear as ‘hot spot’ unlike others.
c. Nuclear medicine studies lack the resolution to show bony invasion. Most malignant tumors
are cold on scintigraphy.
d. In detecting malignant parotid tumors, gallium-67 citrate scanning has a sensitivity of 85% and
specificity of 38%. The low specificity is secondary to uptake by a pleomorphic adenoma.
e. Scanning with99m Tc pertechnetate has 75% sensitivity and 88% specificity for evaluating
oncocytoma or Warthin’s tumor.
f. As a single test, cross-sectional imaging such as CT or MRI provides more information than
scintigraphy.
g. With technetium, most tumors are relatively photopenic compared with the remainder of the
gland and easily missed. Decreased activity in the gland is nonspecific and can represent
benign or malignant neoplasm, metastasis, abscess, focal atrophy or the changes of S gren
syndrome. Two neoplasms—Warthin’s tumor and oncocytoma — concentrate pertechnetate
and are seen easily.

5. Fine Needle Aspiration:

a. FNA is a technique which is commonly used for the evaluation of both neoplastic and non
neoplastic lesions which occur in salivary glands. The characteristic cytological features of the
common salivary gland lesions have been well-delineated in literature making it as the best
diagnostic modality in salivary gland tumors. However, there also exist cytologic pitfalls and
overlapping features that make an accurate diagnosis difficult in few cases.
b. Fine needle aspiration of the parotid swelling or an enlarged lymph node may be performed to
obtain a tissue diagnosis. Most surgeons recommend excision of a parotid mass whether it is
benign or malignant unless a patient's comorbidity precludes safe surgery.
c. It is used for discrete nodules of the parotid gland and differentiates cysts, inflammatory
processes, lymphoma, and other neoplasms.
d. The sensitivity of this procedure is greater than 95% in experienced hands, with sensitivity for
benign tumors of 88-98% and a specificity of 94%. Its sensitivity for detecting malignant
tumors ranges from 58-96%, and its specificity is 71-88%. However, only a positive diagnosis
should be accepted; negative results indicate the need for further attempts at obtaining a
histologic diagnosis, including repeat fine needle aspiration.
e. The results of the fine needle aspiration provide a histologic diagnosis and assist in
preoperative planning and patient counselling. It may not distinguish benign from malignant
epithelial lesions sometimes because malignancy of parotid epithelial cells is related to the
behavior of the tumor cells in relation to tissue planes and surrounding structures rather than
cellular architecture, which may be rather normal even in malignancy. Therefore, nonepithelial
lesions may be diagnosed with accuracy, but epithelial lesions may require further
investigation.
f. If fine needle aspiration is unsuccessful in obtaining a diagnosis, an incisional biopsy or core
needle biopsy should not be performed for further histological investigation.

6. Open Biopsy:
a. Incisional biopsy or core needle/ trucut biopsy is contraindicated in salivary gland tumors as it
risks tumor seeding, fistula formation, facial nerve injury, and violation of tumor margins.
b. Incisional biopsy is ideal investigation only for tumors of minor salivary glands.
c. The standard biopsy approach for a parotid swelling is a superficial parotidectomy with
preservation of the facial nerve. For 80-90% of parotid neoplasms, this procedure is both
diagnostic and therapeutic.

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TREATMENT FOR CAUSE OF PAROTID SWELLING
1. Acute Sialadenitis:
a. Rehydration
b. Warm compresses
c. Antimicrobial therapy (may require parenteral antibiotics for severe cases)
d. Sialagogues (e.g. Pilocarpine)
e. Salivary gland massage
f. Oral irrigations
g. If no resolution after 2–3 days then consider CT or USG to evaluate for abscess (may require
I&D)
4. Sialolithiasis:
a. Gland massage
b. Bimanual expression
c. Transoral incision
d. Sialodochoplasty (reconstruct duct)
e. Gland excision if recurrent or if stone is lodged within substance of the gland
5. Salivary gland tumor:
a. Step 1: Superficial parotiectomy
b. Step 2: Frozen section
c. Step 3:
i. Benign:Stop
ii. Malignant – Low/Intermediate grade: Total parotidectomy with CN VII preservation
iii. Malignant – High grade: Extended or Radical parotidectomy with CN VII resection
and Modified radical neck dissection
iv. CN VII impaired and unseparable from tumor: Nerve excision followed by attempt of
immediate grafting
d. Step 4: Postoperative radiotherapy for malignancy
6. Prognosis: Low grade mucoepidermoid carcinoma > Acinic cell carcinoma > High grade
mucoepidermoid carcinoma > Malignant mixed tumor > Adenoid cystic carcinoma > Squamous cell
carcinoma
7. Indications of radiotherapy:
• High grade tumor,
• large primary lesion,
• perineural invasion,
• bone invasion,
• cervical lymph node metastasis,
• positive surgical margins.
8. Indications of neck dissection:
• Clinically apparent cervical lymphadenopathy,
• tumors > 4 cm (risk of occult metastases > 20%),
• high grade histology (occult metastases > 40%).
• Elective neck dissection for adenoid cystic carcinoma is not recommended (low risk of occult
nodal metastases).

FREQUENCY
• The reported incidence of all salivary gland tumors in literature is reported 0.4 to 13.5 per 100000 population.
The incidence of malignant tumors ranged from 0.4 to 2.6 per 100000 population.

• Almost 70% of tumors are in the parotid gland, around 2% to 10% in submandibular and sublingual gland and
9 to 20% in the minor salivary glands. Out of these 60-80% are benign and 20-40 % are malignant. Depending
upon the site also the risk of malignancy changes, as 75% of parotid gland tumors are benign, slightly more than
50% of tumors of the submandibular gland, 90% of sublingual gland and 60-80% of minor salivary gland tumors
are found to be malignant.
• The incidence of salivary gland neoplasms peaks in the fifth decade of life. The average age of patients is 55
years for malignant neoplasms, and about 40 years for benign tumors. Females are more commonly affected than
males, though in case of some individual tumors this relationship changes.
• Pleomorphic adenomas (benign mixed tumors) are the most common benign salivary gland tumors comprising
85% of all salivary gland neoplasms. In children the most common benign salivary gland tumors are
hemangiomas; however the Pleomorphic adenoma is still the most common benign epithelial salivary gland

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tumor in children. The commonest benign tumor of parotid gland is Pleomorphic adenoma, and Warthin’s tumor
being the second on the list.
• Mucoepidermoid carcinoma is the most common malignant tumor of parotid gland in both adults and children,
while adenoid cystic carcinoma is the most common malignant tumor of submandibular gland, sublingual gland
and the minor salivary glands.

ETIOLOGY
1. Viruses- Epstein Barr virus and papiloma viruses have been implicated in the pathogenesis of
lymphoepithelial carcinoma but till now no definite association has been proven.
2. Radiation- Exposure to ionizing radiation has been implicated for development of both benign and
malignant salivary gland tumors. Survivors of Japanese atomic bombings have shown and increase in
3.5% increase in benign ad 11% of malignant salivary tumors. Therapeutic radiation to head and neck
region is linked to high risk of developing salivary gland tumors especially for Mucoepidermoid
carcinoma. Same is true for radioactive iodine therapy used for thyroid ablation as radioactive iodine
gets concentrated in salivary glands also.
3. Occupation- People working in rubber manufacturing industry, plumbing industry, wood workers etc, are
more prone to develop salivary gland tumors because of their exposure to silica and nitrosamines.
4. Smoking- There is a strong association between Warthin’s tumor and smoking.
5. Trisomy 5 and translocation of chromosome 11 is implicated in the pathogenesis of Mucoepidermoid
carcinoma.
6. Polysomy of chromosome 3 and 17 is associated with adenoid cystic carcinoma.
7. Increased risk is found in females with early menarche and nulliparity.

CLASSIFICATION: 2005 WHO classification is salivary duct tumors

I. Adenomas (Benign) II. Carcinomas (Malignant) III. Non – epithelial tumors
a) Pleomorphic adenoma a) Mucoepidermoid carcinoma a. Hemangioma
b) Warthin’s tumour b) Adenoid cystic carcinoma b. Lipomas
c) Oncocytoma c) Acinic cell carcinoma IV. Neurofibromas
d) Myoepithelioma d) Adenocarcinoma (NOS) V. Sarcomas
e) Basal cell adenoma e) Oncocytic carcinoma VI. Malignant lymphomas
f) Canalicular adenoma f) Malignant myoepithelioma VII. Secondary tumors
g) Sebaceous adenoma g) Basal cell adenocarcinoma VIII. Unclassified tumors
h) Ductal papilloma h) Sebaceous carcinoma IX. Tumor like conditions
i. Inverted ductal papilloma i) Salivary duct carcinoma a. Sialadenosis
ii. Intraductal papilloma j) Cystadenocarcinoma b. Oncocytosis
iii. Sialadenoma papilliform k) Carcinoma in pleomorphic c. Benign lymphoepithelial
i) Cystadenoma adenoma lesion
j) Papillary cystadenoma l) Squamous cell carcinoma d. Salivary gland cysts
k) Mucinous cystadenoma m) Small cell carcinoma e. Cystic lymphoid hyperplasia
n) Undifferentiated carcinoma in AIDS

STAGING FOR MALIGNANT SALIVARY GLAND TUMORS: AJCC 8th

I. Primary tumor (T)
 TX Primary tumor cannot be assessed
 T0 No evidence of primary tumor Tis Carcinoma in situ
 T1 Tumor =2cm in greatest dimension without extraparenchymal extension
 T2 Tumor >2cm but not more than 4cm in greatest dimension without extraparenchymal
extension
 T3 Tumor >4cm and/or tumor has extraparenchymal extension
 T4a Moderately advanced disease-Tumor invades the skin, mandible, ear canal, and/or facial
nerve
 T4b Very advanced disease -Tumor invades skull base and/or pterygoid plates and/or encases
carotid artery
II. Regional lymph nodes (N)
 NX Regional nodes cannot be assessed
 N0 No regional lymph node metastasis
 N1 Metastasis in a single ipsilateral lymph node =3cm in greatest dimension
 N2a Metastasis in a single ipsilateral lymph node >3cm but not more than 6cm in greatest
dimension
 N2b Metastasis in multiple ipsilateral lymph nodes, none >6cm in greatest dimension

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  N2c Metastasis in bilateral or contralateral lymph nodes, none >6cm in greatest dimension
 N3 Metastasis in a lymph node >6cm in greatest dimension

III. Distant metastasis (M)
 M0 No distant metastasis
 M1 Distant metastasis

DESCRIPTION OF SOME COMMON SALIVARY GLAND TUMORS:

(I) Pleomorphic adenoma (benign mixed tumor):
• It is the most common salivary gland tumor. It arises most commonly in parotid gland then less
commonly in submandibular gland, sublingual gland and relatively rare in minor salivary gland.
• It is also known as benign mixed tumor as both epithelial and mesenchymal components are present.
Epithelial component (epithelial and myoepithelial cells) forms a trabecular pattern within
mesenchymal component (stroma). The epithelial cell types can be cuboidal, basaloid, squamous, clear,
and spindle cells. The stroma can be mucoid, myxoid, chondroid, fibroid and even osteoid.
• Grossly the tumour is smooth, lobular, and a well defined capsule. Compressed gland substance forms
the capsule of the tumour, but the tumor extends through normal glandular parenchyma in the form of
finger-like pseudopodia, but this is not a sign of malignant transformation. So enucleation is not done to
avoid recurrences.
• It is usually unicentric but the recurrences are multicentric.
• It is a painless slow growing benign tumor, located commonly in the superficial lobe of the parotid
gland. It can grow to large sizes over several years without causing much symptoms.
• It usually does not involve the facial nerve. Very rarely the facial nerve can be involved by direct
compression of the nerve by the size of the tumor. More commonly the facial nerve gets involved when
they undergo malignant transformation, to form carcinoma ex-pleomorphic adenoma, a risk that
increases with time (9.5% chance to convert into malignancy in 15 years). This involvement is a direct
infiltration and in all cases of facial nerve involvement in pleomorphic adenoma the diagnosis should be
a malignant transformation unless proved otherwise. Although it is "benign" the tumor is aneuploid, it
can recur after resection, as it invades normal adjacent tissue and does not have a true capsule.
(II) Warthin’s tumor (adenolymphoma):
• Also known as papillary cystadenoma lymphomatosum, monomorphic adenoma or adenolymphoma, is
benign cystic tumor of the salivary glands containing abundant lymphocytes and germinal centers
(lymph node-like stroma).
• It is named for pathologist Aldred Scott Warthin, who described two cases in 1929.
• The tumour is almost exclusive to parotid gland being second most common benign tumour of parotid
gland.
• Generally neoplasm of older men, age 4th to 7th decade. Slowly growing tumour in the tail of parotid
gland, 12% bilateral.
• Its etiology is unknown, but there is a strong association with cigarette smoking. Smokers are at eight
times greater risk of developing Warthin's tumor than the general population.
• his tumour gives hot spot on 99 c pertechnetate scan because of it’s high metabolic rate.
• Warthin's tumor is highly unlikely to become malignant (1%).
• Warthins tumor is lined by a bilayered epithelium, comprising of inner columnar eosinophilic or
oncocytic cells and outer smaller basal cells. The stroma contains dense lymphoid tissue that may
harbor germinal centers and mantle zones. That is the reason for it to be named cystadenolymphoma,
but this should not be confused with malignant lymphoma.
• It is well demarcated by a thin capsule. Very rare to have nuclear atypia or mitotic activity. Microscopy
shows multiple papillae filled with a lymphoid stroma are seen to be projecting into cystic spaces.

Difference between 2 common benign tumors:

Pleomorphic adenoma Warthin tumor (Adenolymphoma)
Incidence 70-80 % 10%
Gender/Age F>M; 40 yrs M>F; smoker; 50-70 yrs
No./Site Single/Unilateral May be multiple/bilateral
Consistency Smooth/Nodular/Firm Smooth/Soft/Cystic
Histology Pleomorphism 2 layer epithelium and lymphoid tissue
99m Tc scan Cold spot Hot spot

(III) Mucoepidermoid carcinoma:

• This is the most common malignancy of the parotid gland and the second commonest malignancy of the
submandibular gland, the sublingual gland and the minor salivary glands.

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 • This is also the most common malignant salivary gland tumour of childhood.
• This is the most common radiation induced tumor of salivary glands.
• Patients present with a solitary, rapidly growing mass. The history is usually short for around six
months.
• In major glands most are asymptomatic but few others complain of pain, dysphagia, facial nerve palsy
and trismus. Usually not causes facial nerve paralysis unless high grade. In minor glands most are
symptomatic, experiencing pain, dysphagia, hemorrhage and ulceration, etc.
• This tumor comprises of epidermoid (squamous) cells, mucin producing cells and intermediate cells.
Greater the epidermoid content, more malignant is the behaviour.
• It is multicystic with solid component. Cystic spaces are lined by mucous cells along with intermediate
cells and few epidermoid cells.
• Mucoepidermoid carcinoma is classified as low, intermediate or high grade depending on the absence
or presence of the following criteria:
1. Neural invasion 2 points
2. Necrosis 2 points
3. >4mitoses per high power field 3 points
4. Anaplasia 4 points
5. Less than 20%cystic spaces relative to solid 2 points
areas
– Grading:
o Low grade: if total score is 0-4 points
o Intermediate grade: if total score is 5-6 points
o High grade: if total score is 7+ points

Low grade type High grade type

Mucin producing cells predominate Squamous cells predominate
Well differentiated Poorly differentiated
• For mucoepidermoid carcinoma elective neck dissection is recommended.
• Post operative radiotherapy is recommended for high grade tumour and lymph nodal metastasis
• High grade mucoepidermoid carcinoma has perineural spread.

(IV) Adenoid cystic carcinoma (Cylindroma):

• This is the second commonest malignancy of the parotid gland and the commonest malignancy of the
submandibular gland, the sublingual gland and the minor salivary glands.
• Most common site of origin is in minor salivary gland located in oral cavity (hard palate) followed by
sinonasal tract.
• It has neurotropic properties, and the most common nerves involved are facial nerve, mandibular branch
(V3) and maxillary branch (V2) of trigeminal nerve.
• It has a perineural spread (80%) and a hematogenous spread. Spread to the regional lymph nodes only
in 20-25% of cases.
• It can have long periods of indolence with sudden spurts of growth. In some patients it might have an
aggressive course. High incidence of distant metastasis but indolent growth.
• It is tracherous tumor as it appears benign even it is malignant. It may grow along the Haversian system
of bone with showing bone destruction.
• Skip lesions along nerves are common, leading to treatment failure, because of difficulty in treating full
extent of invasion.
• Recurrences are frequent and almost always late and difficult to predict. Recurrences by the
pathological variant are also predictable e.g. solid (100%), cribriform (89%), tubular (59%).
• Incidence of distant metastasis is correlated with stage of disease. The commonest distant metastatic site
is lung (70%) followed by liver and bone for adenoid cystic carcinoma. Tumor follows the nerves for
metastasis. Lung metastasis are usually multiple and prolonged survival without treatment is not
unusual.
• Morphologically, three growth patterns have been described: cribriform or classic pattern; tubular; and
solid or basaloid pattern. his pattern is similar to the cylindroma of skin and this is the reason it’s other
older name.
• Most common type is cribriform pattern and is characterised by Swiss cheese appearance.
• The tumors are categorized according to the predominant pattern. Grading:
– Low grade: tubular and cribriform pattern
– Intermediate grade: 30% to 70% solid pattern
– High grade: >70% solid pattern
• It shows slight male preponderance. It causes pain and facial paralysis (which may be early symptom
and prominent) due to its tendency to invade perineural tissue.
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 • MRI is the radiological IOC as it detects early perineural spread and intracranial extension.
• Surgical excision is the management of choice, if margins are positive then give adjuvant radiotherapy.
• Elective neck dissection is not recommended with adenoid cystic carcinoma.

SAFETY IN LAPAROSCOPIC CHOLECYSTECTOMY

Nitin Agarwal, Sunil Satihal

Introduction
Medical technology is proliferating at a good pace in India; this is especially true with regard to laparoscopic
surgery. The challenges for healthcare providers lie mainly with respect to adequate training of healthcare
personnel so that effective and safe use of technology is possible for a large number of patients. In ‘routine’
procedures like laparoscopic cholecystectomy (LC), the expectations of the patient are and should be very high;
surgeons must understand this responsibility. The scientific uncertainties and empirical nature of healthcare
dictate that we cannot promise guarantees like the automobile or the airline industry; however, we should
minimize errors and offer minimum standards of care.

LC compared to the open approach is the standard of care for symptomatic cholelithiasis with the proven
benefits of less postoperative pain, shorter hospital stay, cosmesis, and better patient satisfaction. While LC has
been shown to be safe, the most feared complication of LC is iatrogenic bile duct (BDI) or vascular injury, with
a reported incidence ranging from 0.15 to 0.6%. In open cholecystectomy, the rate of BDI has been reported to
be approximately 0.1 to 0.3%. Although relatively rare, given the high volume of LC, the societal burden of BDI
may be significant and the resulting effect on patients’ outcomes of iatrogenic BDI may be severe. herefore,
BDI during LC is a serious intraoperative event that must be avoided as it leads to increased risk of serious
morbidity, mortality, and length of stay, in addition to reduced quality of life and long-term survival. LC is
usually the first minimal access procedure for residents and trainees all over the world. Hence, it is of paramount
importance to be aware of 100% safety from the beginning of a surgical career. The precautions have to be
exercised at all the stages right from the general assessment till the postoperative follow-up.

Cholecystectomy can lead to complications that may seem out-of-proportion to the index operation, viz, biliary
stricture, cholangitis, biliary cirrhosis or liver atrophy. This should ensure that due empathy and precautions are
exercised at all stages, i.e., general assessment, pre-operative work-up, intra-operative steps and postoperatively.
The various measures can be summarized in the following write-up.

The hospital and the clinical unit must be geared up to follow the WHO safety checklist (Figure 1) to ensure that
wrong patient, wrong-site, or wrong-side surgery is near-eliminated. Patients of cirrhosis or liver failure,
cardiorespiratory problems or renal dysfunction need cautious anesthetic assessment for laparoscopy. Low
pressure pneumoperitoneum (8-10 mm Hg) has been tried, but its routine use is controversial. Predictors of
difficulty (clinical, radiological) may guide a surgeon in deciding the appropriate instrumentation or position on
the list. Suspected biliary obstruction must be investigated non-invasively and managed as per institutional
policy. Thorough preparation of basic steps a day before is essential for a trainee surgeon, if possible, use
simulators to improve skills.

INDICATIONS:
➢ Symptomatic cholelithiasis
➢ Asymptomatic cholelithiasis ? Diabetes Mellitus (poor follow-up capacity, poorly controlled, high risk
of empyema) Sickle cell disease N hronic Immunosuppression Incidental (young age patient’s
wishes)
➢ Acalculous cholecystitis (biliary dyskinesia)
➢ Gallstone Pancreatitis
➢ GB polyp >1cm in diameter
➢ Porcelain gallbladder

CONTRAINDICATIONS :
Absolute :
➢ Refractory coagulopathy
➢ Suspicion of carcinoma
Relative :
➢ Previous upper abdominal surgery

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 ➢ Cholangitis
➢ Diffuse Peritonitis
➢ Cirrhosis or Portal hypertension
➢ COPD
➢ Cholecystoenteric fistula
➢ Morbid Obesity
➢ Pregnancy

General assessment and pre-operative work-up

Figure 1: WHO safety checklist

The preoperative work-up of the patients (on outpatient basis) includes:

1. History of the gall bladder disease along with co-morbid disease(s):
● Nature and Severity of symptoms
● Duration of symptoms
2. General physical examination of the patient.
3. Per abdominal findings on the basis of Clinical examination.
4. Routine investigations viz:
● Complete blood count
● Coagulation profile
● Kidney function tests (Blood urea & Serum Creatinine)
● Serum electrolytes
● X-ray chest (P.A. view)
● Electrocardiogram (ECG)
5. Specific Investigations viz:
● U.S.G Abdomen
● Liver function tests (Total bilirubin with Direct and Indirect bilirubin, Liver Enzymes)

Patients undergoing LC should have preoperative liver function tests (LFTs). Elevated LFTs should raise
concerns about complicating conditions such as cholangitis, choledocholithiasis, or, Mirizzi syndrome (a
gallstone impacted in the distal cystic duct causing extrinsic compression of the CBD.

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In a patient with typical biliary colic, the only diagnostic study necessary before laparoscopic cholecystectomy is
an abdominal ultrasound (US) revealing gallstones. US shows the size and number of stones, the thickness of the
gallbladder wall, the presence or absence of peri-cholecystic fluid, and the diameter of the CBD and other
components of the biliary ductal system.

Atypical symptoms warrant other investigations viz. upper gastrointestinal endoscopy, computed tomography
(CT), or cardiac and pulmonary evaluation. Magnetic Resonance Cholangio-pancreatography (MRCP) may be
useful to evaluate the common duct in patients with elevations of transaminases or CBD dilatation on US.
Preoperative Endoscopic Retrograde Cholangiopancreatography (ERCP) with clearing of the stones may be
needed in certain situations.

On the day prior to surgery, patients are advised to take light diet and adequate sedation on the night prior;
fasting for at least 6-8 hours before surgery. Patients are advised to empty the bladder before being shifted to the
operation theatre. A single dose of prophylactic antibiotic, i.e. a second generation cephalosporin, is
administered during induction.
Laparoscopic cholecystectomy requires basic set of instruments which include:
1. Anesthesia equipment with monitors
2. Operating Table
3. Video Monitors
4. Suction & Irrigation
5. Electrosurgical unit with grounding pad equipped with current monitoring system
6. Laparoscopic equipment in a cart on wheels
a. Light source
b. Insufflator
c. Camera Processor Unit
7. Instrument table with following laparoscopic instruments
a. No. 15 scalpel blade and handle
b. Veress needle and Hasson’s cannula
c. Gas insufflations tube
d. Fiber optic cable to connect laparoscope with the light source
e. Video camera with cord
f. Set of haemostatic forceps
g. Trocars and Cannulas
h. Atraumatic graspers
i. Locking tooth grasper
j. Maryland dissectors curved
k. Scissors
l. Right angle dissector
m. Clip applicator with clips
n. L – Hook Dissector
o. Spatula

Operation Theater planning

Position of the patient: Supine, monitors are placed on the right side of the patients near the head end.
Endotracheal tube along with naso-gastric tube was placed after the induction of anesthesia. Surgeon stands on
the left side of the patient with the first assistant (camera person); in the French technique the surgeon may stand
between the lithotomized legs. The staff nurse (with second assistant-in four port technique) stands on the right
side of the patient. The second assistant is required in four port technique for the retraction of the gall bladder
fundus during the operative procedure. For the sake of brevity, we have not discussed reduced-port strategy or
Single Incision Laparoscopic Surgery (SILS) here.

Trocar Position & Choice of Laparoscope

Four Port Method:
Two 10 mm trocars (supra-umbilical for camera port and epigastric port) and two 5mm trocar (right
mid-clavicular line subcostal region and right anterior axillary line umbilical level). I prefer to place the
umbilical trocar first, then the epigastric under vision slightly right of the midline through the top half of
the falciform ligament, then the umbilical level trocar for retraction of fundus. This allows me to avoid
puncturing the branch of the inferior epigastric artery and also, customization of the subcostal port
based on the position of the neck of the GB.
1. Pneumoperitoneum is created by insufflating carbon dioxide through closed technique (Open
technique uses Hassan cannula vide infra). Here, a spring-loaded Veress needle with protective blunt tip
is inserted via a small 10 mm incision above the umbilicus with the patient in 15 degree Trendelenberg

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 position. The anterior abdominal wall is kept lifted during the time when veress needle is inserted. The
intraperitoneal location of the needle is confirmed by the saline drop test, where in saline is drawn into
the peritoneal cavity by the negative pressure. Once the needle is confirmed in the peritoneal cavity, the
carbon dioxide gas is insufflated. The usual preset intra-abdominal pressure used is 12 mm of Hg with
the flow rate of 10 litres per minute. The amount of gas used for insufflations before the start of surgery
is 1.2 – 1.5 liters.

Pneumoperitoneum & safe access

• Open vs closed technique
– Not very different (safety-wise)
– Use open technique to familiarize oneself with dissection for level II laparoscopy (TEP,
nephrectomy)
– Overall time will be the same (closer faster and easier in open method)
• Using Veress needle: precautions
– Check the needle
– Beware of umbilical hernia/ adhesions
– Customize penetration angle
– Tests for intraperitoneal entry (use the monitor)
• <5mm Hg and >0.5 L/min
• ercussion and aspiration
• Symmetrical distension
• Be vigilant for extraperitoneal insufflation
For the open technique, the use of S-retractors and Hasson’s cannula is useful.
• Special considerations for adhesions (more for experienced surgeons)
– almar’s point/ 9th-10th intercostal space entry
– Optical trocars
– Initial placement of 5 mm canula
2. Primary port placement : While elevating the anterior abdominal wall manually, 10 mm cannula is
inserted through the same incision used for creating pneumoperitoneum. Trocar is inserted, directed
towards the pelvis. A 10 mm Telescope is placed through the primary cannula and peritoneal cavity is
inspected for injury. The liver is inspected and the state of the gallbladder is noted. The falciparum
ligament, left lobe of liver and stomach is also inspected. The patient is placed in the reverse
Trendelenberg position (usually 15°) and the table tilted to the left to allow a clear view of the
gallbladder area, due to falling away of right colon and small bowel.
3. Secondary port placement: An epigastric 10 mm port is placed about one-third the distance between
the xiphoid and umbilicus (a high port gives optimal working space in Indian patients), entering the
peritoneal cavity under direct vision to the right of the falciparum ligament by applying even pressure
and no sudden jerky movements. Another 5 mm port is placed under direct vision in the mid-clavicular
line 2-3 cm below the right costal margin. Fourth port (5 mm) is placed in the anterior axillary line at a
point about level with umbilicus (vide supra).

The stomach is deflated to allow good vision and prevent inadvertent thermal injury. Once the
secondary ports have been established, instruments are used to perform dissection through the epigastric
port and midclavicular port, inserting a grasping forceps through the fourth port and and grasping the
upper edge/ fundus of the gallbladder, pushing in cephalad direction anterior to the liver towards right
shoulder.

All the adhesions are separated and the gallbladder is cleared and neck of the gallbladder reached.
Tense GBs can be aspirated at this point; the colon may be carefully avoided if there are omental
adhesions. Hemostasis is important during dissection so that light remains bright for the subsequent
steps.

A hook electrocautery/ Maryland dissector can be used to divide the peritoneal layers that cover the
infundibulum and cystic duct by blunt stripping action. The aim is to dissect posteriorly and elongate
the GB pedicle as very few variations are seen posteriorly.

Identification of the Rouviere’s sulcus helps in correct localization of the CBD plane. It is a 2.5 cm
sulcus running to the right of the liver hilum, anterior to the caudate process and containing the right
portal triad with its branches. (Figure 2)

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 Figure 2: Rouviere’s sulcus

Dissection of the Calot’s Triangle: Dissection starts high up in the neck of gallbladder and is kept
close to the gall bladder until the anatomy is well-defined.

Hook dissector can be used to liberate the lower portion of gallbladder from its attachment to liver, both
laterally and medially. The narrowing of the gallbladder infundibulum into the cystic duct is clearly
defined in its entire circumference by:
● Anterior dissection in alot’s region using L-hook
● A clear view of cystic duct by complete exposure of continuum of posterior cystic duct going
upto infundibulum and the lower portion of gallbladder
● During dissection of cystic duct, the cystic artery is generally identified slightly cephalad to
cystic duct. After identification, it should be clearly elevated with either a Maryland dissector
or hook so at least 1 cm is dissected completely from surrounding structures.
● A large window of space is created behind the gallbladder , the infundibulum and the cystic
duct and cystic artery – “Critical view of Safety”.

Use the Critical View of Safety (CVS) method of identification of the cystic duct and cystic artery

Three criteria are required to achieve the CVS:

• The hepatocystic triangle is cleared of fat and fibrous tissue. The hepatocystic triangle is defined as the
triangle formed by the cystic duct, the common hepatic duct, andinferior edge of the liver. The common
bile duct and common hepatic duct do not have to be exposed.
• The lower one third of the gallbladder is separated from the liver to expose the cystic plate. The cystic
plate is also known as liver bed of the gallbladder and lies in the gallbladder fossa.
• Two and only two structures should be seen entering the gallbladder.
Confirming the CVS – the CVS can be confirmed using a Doublet View. The Doublet View has two
components: The Anterior and the Posterior

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Visualization of the doublet view (anterior) Visualization of the doublet view (posterior)
Consider an Intra-operative Time-Out during laparoscopic cholecystectomy prior to clipping, cutting or
transecting any ductal structures to confirm that the CVS has been achieved utilizing the Doublet View. The
‘Elephant’s Trunk’ Or Ganesha sign has a similar purpose.

The choice of instruments and energy sources remains with the surgeon and is guided by cost and availability.
Apply two ligaclips on distal portion of cystic duct and one clip as close to the gallbladder as possible under
direct vision and divide the cystic duct with scissors; preferably, the cystic artery should be dealt with similarly
but later, to avoid possible avulsion.

4. Dissection of gallbladder from liver bed: Dissect the gallbladder off the liver bed using monopolar
cautery (hook/ spatula) starting behind the Hartman’s pouch. During the dissection gentle traction is
applied to the gallbladder. The assistant can rotate the fundus to allow triangulation and stretching of
the areolar tissue. The gallbladder is not completely removed from its liver bed, and, by leaving the
fundus attached, the liver can be inspected along with the gallbladder fossa carefully for accessory
cholecystohepatic ducts of Luschka and bleeding. Using irrigation and suction, the liver bed is closely
scrutinized and dealt with as necessary. Inspect the cystic duct and cystic artery at this stage to ensure
that the clips are in position.
5. Extraction of the Gallbladder: Insert the large grasping forceps through the epigastric port to hold the
neck of the gallbladder which is then extracted partially through the port. If the stones are large, crush
them within the gallbladder or extract in parts through the epigastric port using ovum forceps. After
removal of the gallbladder, liver bed is inspected once again.
In case of bleeding or bile spillage, a non-suction drain 14/16 Fr is placed in the sub-hepatic pouch of
orrison’s inserted through the 5 mm port and positioned under vision. Few surgeons now insert
drains routinely. Remove the secondary ports under vision. The table is straightened and the gas is
expelled. The skin incisions are closed with cosmetic 3-0 sutures and the patient is shifted to the
recovery room. In uneventful cases, the patient may go home as a day case.

Intra-operative safety
The surgical judgment that a zone of significant risk is being approached can be made when there is failure to
obtain adequate exposure of the anatomy of the hepatocystic triangle or when the dissection is not progressing
due to bleeding, inflammation or fibrosis. Consider laparoscopic subtotal cholecystectomy or cholecystostomy
tube placement, and/or conversion to an open procedure based on the judgment of the attending surgeon.

When it is practical to obtain, the advice of a second surgeon is often very helpful under conditions in which the
dissection is stalled, the anatomy is unclear or under other conditions deemed “difficult” by the surgeon.
– Reduced-port strategies are for experienced surgeons
– Break up operation into steps
– ‘Anxiety is good’
– Use the grips and angles which suit you best
– Keep the field dry
– Use of electrosurgical units (burn-pull-burn)
• Use only when required
• Fulguration and dessication (BLUE) commonly used
• rgonomics
– Left hand is the key
– Trocars towards GB, avoid blood vessels on the parietal wall
– Modify trocar sequence as per the case
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 – Right and left hand angle as wide as possible
– Operating end of instruments seen at right angles to telescope
• 5th port and NG tube if necessary
• Posterior dissection is essentially partial retrograde dissection and lengthening of duct (posterior
anomalies rare)
• Liver should be visible through ‘window’
• GB-cystic duct junction more important
• Elephant’s head and trunk
• lipping
– Grip
– Make sure end is visible
– Withdraw away from clip
– Don’t clip stones in the cystic duct
– When in doubt→ Suture
• Role of Intra-op. Cholangiography is doubtful today; not used in most centers.
• Difficult to ustify and advocate partial cholecystectomy laparoscopically
• For spilled stones use retrieval bag.
• Suspect CBD when
– Horizontal course to D2
– Not occluded by large clip, 2 ducts, large artery behind, too much dissection
• Conversion is not failure
• ake informed consent always
• riteria for conversion
– Unclear anatomy ( irizzi’s short cystic duct etc.)
– Failure to progress ..time??
– Injuries: vessels, viscera, bile duct
– CBD stones not managed at the present set-up laparoscopically

Postoperative safety
• LF ’s when in doubt
• Rely only on overall clinical picture
• For day cases have a written communication explaining all possibilities
• When leak is suspected, DRAINAGE is the key
• Always ask the patient to discuss H report with you
• In difficult cases serial LF ’s for 6 months

REMEMBER
• Learn at least ONE point from all teachers
• Define standard steps for your own technique
• Break up surgery into STEPS
• Posterior dissection and lengthening of cystic duct is the key
• lip only when sure
• Left hand is the surgeon: right is the facilitator
• onversion is not failure

LAPAROSCOPIC APPENDECTOMY
Naveen Sharma

The common indications for laparoscopic appendectomy are the same as that for open appendectomy: acute
appendicitis and interval appendectomy after successful nonoperative management of an appendix lump. Less
common but reasonable indications are appendicular abscess, appendicular perforation peritonitis; and small
distal appendix neoplasms. This discussion will be confined to the standard laparoscopic technique; single port
surgery and natural orifice surgery shall not be discussed further.
The benefits of laparoscopy include early discharge from hospital, a decrease in postoperative pain, and
decreased wound related complications. This comes at a cost of increased postoperative pelvic abscesses and
stump apendicitis due to a longer appendix stump left behind after the procedure.[1] They may be a higher rate
of bowel injuries if monopolar electrosurgery is employed to manage the mesoappendix.

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The standard technique usually employs 3 ports. Sometimes an additional port can be inserted in the right upper
abdomen for retraction. We prefer to employ a nylon suture inserted through an epidural needle to snare the
appendix and stabilize it against the anterior abdominal wall. We prefer the open technique of inserting the first
12.5 mm blunt tipped port above the umbilicus. The skin incision is made just large enough to accommodate the
cannula thereby preventing any gas leak from the trocar site. The first 5 mm port is usually placed in the left iliac
fossa taking care to avoid accidental injury to the inferior epigastric vessels by transilluminating the anterior
abdominal wall. . The second 5 mm working port is placed 2 cm above the pubic symphysis in the midline. It is
preferable to insert the suprapubic port last since the peritoneum is lax here and an instrument placed through the
other port may help stabilize peritoneum during port placement. Other port placements have also been described.
Some surgeons prefer to use the suprapubic port as the camera port.

After a quick general survey of the peritoneal cavity to detect unexpected pathology, the operating table is tilted
to the left and the head end of the table is lowered. This serves to move the small bowel away from the surgical
field. The first step is to identify the cecum. If it is obscured by omental adhesions, these are dissected away
from the ileocecal area. The tenia coli are followed downward to reveal the location of the appendix. The
appendix is gently grasped using a laparoscopic Babcock grasper and the extent of adhesions is assessed. If the
tip is clearly visible and the adhesions are few, we prefer to pass a loop of nylon 1-0 through an epidural needle
inserted through the right iliac fossa just overlying the appendix and to “lasso” the appendix through it. This is
similar in principle to the technique described by Nageswaran et al though the execution is different.[2]

The view to aim for is one where the ileum, cecum and appendix are all seen clearly. Subramanian et al proposed
a critical view of safety during laparoscopic appendectomy to prevent stump appendicitis. [3] If the
mesoappendix is thin, we use either bipolar electrosurgery or a harmonic scalpel to create a window in the
mesoappendix just adjacent to the base of the appendix, and ligate the mesoappendix with a free suture before
using energy to divide it. However, if the mesoappendix is thickened, the dissection using the same energy
sources is begun near the tip of the appendix, the mesoappendix being successively divided just adjacent to the
tip of the appendix till the base is reached. The other options for dividing the mesoapendix are clips and stapler.
The correct identification of the point where the base of the appendix joins the cecum is the most important step
of surgery; a centimeter distal leaves a stump long enough to embarrass the surgeon with recurrent appendicitis
after performing an appendectomy whereas going proximal on the cecum with a suture may lead to an insecure
closure and possibility of a fecal fistula.

The appendix base can be secured using an commercial endoloop, a Roeder/Tayside knot prepared in the
operating room using 2-0 polygalactin, a free 2 handed ligature, laparoscopic titanium clips (LT 400 usually),
vascular clips, and a GI stapler. Our preference is the commercial endoloop - two of them towards the “stay”
side and one on the “go” side. When the commercial endoloop is not available, we use free ties to ligate the
stump laparoscopically. The suture on the “go” side is left slightly longer to make extraction easier. Most
surgeons have abandoned the practice the burying the appendix stump at open appendectomy and the same can
be a reasonable decision at laparoscopy. However if the surgeon is a strong believer in the burial of the appendix
stump, a Z-stich usually is more expedient compared to a purse-string suture.

A small piece of ribbon gauze can be used to gently mop clean the area and apply a dab of povidone iodine at the
transected end of the appendix. Irrigation and suction with normal saline is preferably avoided to minimize risk
of pelvic abscess. [4] After checking for hemostasis, we bag the specimen, usually in a glove finger or a glove
bag.[5] We prefer to use a 5 mm telescope through one of the 5 mm ports at this stage of surgery and use the
larger port for extraction of the specimen. The port sites are infiltrated with local anaesthetic at the conclusion of
the procedure to further minimize postoperative pain. The patient is usually allowed orally next morning and
discharge if postoperative recovery appears unremarkable.
Acknowledgements: Dr. Tushar Mishra (AIIMS Bhubaneswar) and a lot of senior Surgeons whom we have
grown up listening to and who have influenced our minds so much that we have internalized their ideas.

References
1. Jaschinski T, Mosch C, Eikermann M, Neugebauer EAM. Laparoscopic versus open appendectomy in patients with
suspected appendicitis: a systematic review of meta-analyses of randomised controlled trials. BMC Gastroenterol
[Internet]. 2015 Apr 15 [cited 2018 Aug 30];15:48. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25884671
2. Nageswaran H, Maw A. The nylon-tape retraction technique for laparoscopic appendicectomy. Ann R Coll Surg Engl
[Internet]. 2016 Mar [cited 2018 Sep 1];98(3):230. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26741667
3. Subramanian A, Liang MK. A 60-year literature review of stump appendicitis: the need for a critical view. Am J Surg
[Internet]. 2012 Apr [cited 2018 Aug 31];203(4):503–7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22153086
4. Hajibandeh S, Hajibandeh S, Kelly A, Shah J, Khan RMA, Panda N, et al. Irrigation Versus Suction Alone in
Laparoscopic Appendectomy: Is Dilution the Solution to Pollution? A Systematic Review and Meta-Analysis. Surg
Innov [Internet]. 2018 Apr 20 [cited 2018 Sep 1];25(2):174–82. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/29353527

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5. Holme JB, Mortensen FV. A powder-free surgical glove bag for retraction of the gallbladder during laparoscopic
cholecystectomy. Surg Laparosc Endosc Percutan Tech [Internet]. 2005 Aug [cited 2015 Sep 13];15(4):209–11.
Available from: http://www.ncbi.nlm.nih.gov/pubmed/16082307

LAPAROSCOPIC VENTRAL HERNIA REPAIR (IPOM)

Anubhav Vindal, Rushil Jain
With the advances in laparoscopy in the last 2 decades, and the advantages of minimizing the access, there is
hardly any surgery that does not have a laparoscopic counterpart. Hernia repair is one of the commonest
surgeries performed by a general surgeon. Laparoscopy is a valid alternative to traditional open techniques for
the treatment of hernias. It is associated with a lower incidence of postoperative pain, permits rapid recovery of
normal physical activity with similar success rates as with open repairs.1-4

LAPAROSCOPIC INCISIONAL AND PRIMARY VENTRAL HERNIA REPAIR

Abdominal wall hernias can be classified into primary ventral and incisional hernia.5 There are four main types
of primary ventral hernias: umbilical, paraumbilical, epigastric and spigelian.6 Incisional hernia is a common
long-term complication of abdominal surgery and is estimated to occur in 3% to 13% of laparotomy incisions.7
However, its incidence is greater than 23% in patients who have developed an infection in the laparotomy
wound.8,9 Approximately 50% of incisional hernias develop within the first 2 years after the primary operation,
and 74% develop after 3 years.10,11 The recurrence rate of incisional hernia, after primary closure is high, ranging
between 10% and 50%, and has been reduced to 3% to 18% after the introduction of prosthetic materials
(meshes) in hernia repair.7,12,13 Incisional hernias represent about 80% of all ventral hernias.14

An increasing interest in laparoscopic surgery and the availability of new materials have encouraged the
adoption of laparoscopic techniques in incisional and primary ventral hernia repair. Laparoscopic ventral hernia
repair (LVHR) was introduced into surgical practice by LeBlanc and Booth in 1991.15 It is based on the same
physical and surgical principles as the open underlay procedure described by Stoppa,16 Rives,17 and Wantz.18
Placement of a large prosthesis in the preperitoneal space allows for intraabdominal force to be dispersed over a
greater surface area, which may contribute to the strength and durability of the repair.19 Essential to the success
of the laparoscopic approach is adequate mesh fixation. Current approaches to LVHR involve fixation of the
mesh with permanent transfascial sutures and tacks.20

Technique
The laparoscopic technique has numerous variations of the methodology used by surgeons, although several
common steps are followed by all. The procedure starts with entering the peritoneal cavity by using a Veress
needle, an open Hasson method, or an optical trocar allowing view of the abdominal wall layers during
penetration and establishing a pneumoperitoneum of 12-15 mmHg. Three trocars are used, one 10-12 mm trocar
and two 5-mm, which are placed as laterally as possible on the abdominal wall, so they are at an adequate
distance from the hernial orifice. A complete adhesiolysis of the abdominal wall, possibly the most difficult part
of the procedure, is then performed. The adhesions in the abdomen are lysed using cold scissors (preferable),
electrocautery or an ultrasonic scalpel. Once adhesiolysis has been completed, full visualization of the abdominal
wall provides an additional technical advantage of visualization of small clinically occult fascial defects (“Swiss
cheese”). The sac contents are then gently reduced into the peritoneal cavity, while the peritoneal sac is left in
situ.

The periphery of the hernia defect is evaluated by direct vision and palpation and is marked on the abdominal
wall skin with a marker. The carbon dioxide should be released prior to measurement, revealing the true size of
the hernia defect. The cranio-caudal and lateral measurements are taken to define the size of the prosthetic mesh.
The surgeon should add 5 cm to these measurements in both directions, which provides an adequate overlap of
the aponeurotic edges of the hernia by the mesh. Some surgeons suggest a 10 cm overlap, especially if the
patient is morbidly obese, or if the hernia is recurrent or of large size.21 The size of mesh that most closely
approaches this measurement is selected for the repair.

After selection of the appropriate-sized mesh, 4 to 6 sutures are placed on the edges of the prosthetic mesh. The
prosthetic mesh is rolled tightly and inserted in the peritoneal cavity through the 10-12 mm trocar. It is unrolled
inside the abdomen and spread under the defect to ensure adequate overlap beyond all areas of fascial defect.

The mesh is then secured in place to prevent migration and chances of recurrence. For this either metallic tacks,
permanent or absorbable polymeric helical fasteners, strap devices or sutures can be used.22

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For placement of the trans fascial sutures, two-mm skin incisions are made on the abdominal wall. With the help
of a Berci fascial closure instrument (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany) or the Endoclose
(Autosuture) inserted through each skin incision into the peritoneal cavity, the 2 ends of each suture pre placed
on the mesh are grasped and drawn outside through the skin incisions by separate passages and at different
angles. The suture ends are tied down extracorporeally and buried subcutaneously.

The spiral/helical/strap devices are placed in the form of two concentric circles, one at the periphery of the mesh,
and the other one surrounding the fascial defect (“Double rown”) spaced around 2 cm from each other and 1
cm from the margin of the mesh.

Controversies in Laparoscopic Ventral Hernia Repair

(A) Laparoscopic versus Open repair

LVHR achieves adequate closure of the hernia defect by using intraperitoneal mesh fixation with minimal soft
tissue dissection. The technique has all the advantages of the laparoscopic approach. By placing the mesh
intraperitoneally, the intraabdominal pressure pushes upwards and holds the mesh into position. However, there
are some points of comparison when choosing between open and laparoscopic approaches.

i. Operative Time & Cost

Perceived disadvantages of laparoscopic incisional hernia repair are longer operating times and the
increased cost of equipment and expensive specialized mesh. In fact, several retrospective and
prospective comparative studies have shown that the laparoscopic approach does not take longer in
experienced hands.23,24 The increased procedural cost is compensated by several factors like faster
recovery and lower re-admission rates, reducing the costs of bed occupancy. Lower recurrence rates
might reduce the need for repeat surgery.
ii. Post operative recovery
Several studies have suggested that LVHR is associated with less postoperative pain, earlier recovery,
and a shorter convalescence period compared with the open techniques.25 The patients feel more
comfortable and tolerate oral intake earlier than after the open procedure. Open surgery requires
considerable soft tissue dissection. Large incisions and extensive dissection may result in considerable
postoperative pain, ileus, wound haematoma and wound infection, all contributing to prolonged hospital
stays, delayed return to normal activities and increased risk of deep venous thrombosis/pulmonary
embolism.
Meta-analyses have shown that length of hospital stay is shorter by 2–3 days and carries lower
complication rates.6,24 Laparoscopic repair can often be successfully carried out in a day-case setting
and rates of re-admission to hospital are lower after laparoscopic surgery.25-27
iii. Intra operative complications
The laparoscopic approach carries the risk of intestinal or bladder injury intraoperatively.28 Adhesions
to the abdominal scar represent a significant problem during LVHR, with the risk of bowel injury
around the neck of the hernia during dissection. Injury of a hollow organ is a very serious event and
should be recognized and treated immediately. An incidental enterotomy may occur during initial trocar
placement or may result from adhesiolysis. If the enterotomy remains unnoticed, it may result in an
acute abdominal condition and sepsis within a few hours after surgery.
iv. Post operative pain
Series have demonstrated lesser or comparable postoperative pain for laparoscopic and open
approaches.29 Chronic pain lasting beyond 12 weeks at the site of a transabdominal suture has been
reported and has an incidence of 1.3% to 3.3%.19,30,31
v. Seroma formation
The commonest complication of laparoscopic incisional hernia repair is seroma formation at the site of
the hernia (10–50%) as the hernia sac is left in situ.32 The incidence of seroma can be reduced by the
use of compression bandages or binders that can be worn by the patient for up to 10 days
postoperatively. The majority of seromas resolve naturally and require no treatment; those that persist
or cause significant discomfort may be aspirated, but only 2–5% require intervention.32
vi. Infection
In LVHR the mesh comes into minimal contact with the patient’s dermal flora while it is introduced
intraperitoneally. Minimal tissue dissection in the laparoscopic approach further reduces the risk of
infection.29

vii. Clinically occult hernia

As described earlier, with laparoscopic approach, minimal fascial defects, known as “Swiss cheese”
defects, which may be missed during the open repair, can be identified and closed with one mesh.29
Clinical examination is often misleading because multiple defects may be associated with a single

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 incisional hernia. This may be the reason of the lower rates of recurrence of the laparoscopic technique.
These defects when missed, may present as a site of recurrence at a later date.32
viii. Cosmesis
The main disadvantage of the laparoscopic approach is that the hernia sac is usually retained in place
and in case the scar is ugly, offers limited cosmetic advantage to the patient. On the other hand, the scar
can be excised in an open repair, giving excellent cosmetic results. This can be dealt with by using the
hybrid techniques, where the sac and the scar are excised by the open approach followed by the
intraperitoneal mesh placement by the laparoscopic approach
ix. Loss of domain
The components’ separation is a simple procedure which detaches the external oblique from the rectus
muscle allowing upto 10-cm advancement into the midline on each side of the abdomen.32 This confers
a spherical shape to the abdominal cavity and increases capacity allowing return of viscera without risk
of abdominal compartment syndrome.33 This procedure was not available to the laparoscopic surgeon
till recently. However, many reports have now shown good results with laparoscopic component
separation technique.34 The procedure is still evolving and has several variations.
x. Recurrences
Sains et al35 noted a trend towards lower hernia recurrence rates following the laparoscopic approach.
Pierce et al36 demonstrated a significantly lower recurrence rate with LVHR compared with OVHR
series. Although recurrence can still occur after LVHR, it does not surpass 5% to 10% in most series.29

(B) Methods of Fixation

i. Mesh Fixation with Tacks and Sutures
A variety of reports are available on this type of mesh fixation, which represents the traditional
technique in LVHR. LeBlanc et al27 have also suggested the importance of suture anchorage at 4-cm to
5-cm anchorage intervals around the perimeter of the mesh to minimize the risk for mesh migration.
Both absorbable and permanent sutures had greater fixation strength than metallic tacks, although
absorbable sutures had a significant loss of strength compared with permanent sutures at eight weeks.19
ii. Mesh Fixation With Tacks Alone
Several studies have claimed the efficiency of tack-alone mesh fixation in LVHR. However, there is a
general idea that tacks do not have the same holding strength as full-thickness abdominal sutures.29
Experimental studies have also demonstrated the superiority of transabdominal sutures compared with
tacks for mesh fixation. Series have shown early recurrences when metallic tacks alone were used for
fixation.37-40
iii. Soft Fixation with fibrin glue
Few reports of soft fixation of mesh using fibrin glue have shown promising results with reduction in
early post operative pain compared to fixation with tacks and sutures.29 Long term results on the rates of
recurrences using this approach are awaited.

(C) Choice of Mesh

Several types of mesh have been used for ventral hernia repair: the first generation or the uncoated meshes, the
second generation or the tissue separating (barrier) meshes and the third generation or the biological meshes. The
uncoated meshes are no longer used in the laparoscopic approach, because it may create adhesions with bowel
loops. These are replaced by the more popular and the most commonly used barrier meshes. Several varieties
and brands are available, each with its own distinctive properties. The choice of a particular mesh is largely
dependent on the surgeon’s preference. The third generation biological meshes are the most recent addition to
the armamentarium. These have been treated to eliminate all cells and proteins other than collagen, which may
evoke adverse reactions to the host. There is no clear indication for the use of these meshes although some
studies have shown that these meshes tolerate infection better than the second generation meshes, and therefore
may have advantage when used in a contaminated field (post accidental enterotomy in LVHR).
There are no long-term clinical or experimental data to support the use of most mesh products presently in use.
Hence it is difficult to advocate the use of any particular type of mesh over another.

NEWER TECHNIQUES FOR LAPAROSCOPIC VENTRAL HERNIA REPAIR

IPOM plus
The treatment of abdominal wall hernias is a challenge, both conventionally and laparoscopically. The size of the
hernia gap, in particular with the classical IPOM as bridging method, has a great influence on the shear forces to
the mesh and, therefore, on possible bulging phenomenon and the forces acting on the fixation points.41 Ideally
the mesh overlap should be proportional to the size of the hernia defect.42 The larger the break gap, the more the
overlapping of the inserted mesh should be.43 Therefore, the standard IPOM reaches its limits with large defects.
Based on these principal came in a newer novel technique – IPOM PLUS which involves open functional
morphological aspects of the abdominal wall reconstruction, the closure of the linea alba or defects and

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subsequent sufficient overlap with a mesh. With the closure of the abdominal wall defect, the area of overlap
with the mesh also increases. In addition to the well-known advantages of laparoscopic care (lower wound
infection and seroma rate, shorter hospital stay) this technique does not lead to the destruction of intact muscle
compartments.41,44,45
However patients with very large defects require additional endoscopic component separation before performing
IPOM PLUS procedure. The meta-analysis of Tandon et al. has demonstrated significant advantages for the
fascial closure before laparoscopic hernia repair for adverse hernia site outcomes (recurrence, mesh eventration,
tissue eventration, bulging) and postoperative seroma formation.46

LAPAROSCOPIC TRANSPERITONEAL SUBLAY MESH REPAIR

Currently, laparoscopic IPOM repair is the only commonly used laparoscopic technique for abdominal wall
hernia repair. There are only very few reports on endoscopic sublay repair of abdominal wall hernias.47 A
disadvantage of the laparoscopic IPOM technique is the intraperitoneal position of the mesh, which may lead to
adhesions, fistula formation, and further damage of the bowel and other viscera. For the prevention of these
complications, expensive compound meshes with antiadhesive properties have to be used. Compared with
conventional polypropylene and polyester meshes, many of the available compound meshes seem to reduce
adhesion formation at least in the animal model. However, the problem of a foreign body inside the abdominal
cavity has not been solved yet. Additionally, in the laparoscopic IPOM repair the mesh has to be fixed very
intensively with many non- or long-term absorbable sutures, tacks, or staples, which again may lead to
adhesions, fistula formation and other damage to the bowel and acute and chronic pain. This problem of mesh
fixation might explain the literature finding that the laparoscopic IPOM repair does not lead to less acute and
chronic pain compared with open mesh repair.48,49 Another disadvantage of the laparoscopic IPOM repair is that
in most of the cases the hernia defect is not closed and only bridged by the mesh.50 Accordingly, the
laparoscopic IPOM repair relies on the strength of the mesh and its fixation.48 Another flaw is that the hernia
sack stays in situ and can lead to chronic seroma formation.

The open sublay repair with retromuscular mesh placement avoids direct contact between
intestine and synthetic prosthesis. It allows easy dissection and removal of the hernia sack and reconstruction of
the abdominal wall with defect closure. A disadvantage of open sublay repair is a significantly higher infection
rate, which has been reported in the literature.47-52 The laparoscopic transperitoneal sublay technique combines
the advantages of the open sublay repair and laparoscopic IPOM repair. It allows the use of standard
polypropylene and polyester meshes. The laparoscopic transperitoneal sublay mesh repair though technically
demanding, is a safe and effective technique for the treatment of small- and medium-size ventral and incisional
hernias. It combines the advantages of the lap. IPOM repair and open sublay repair.

PREPERITONEAL ONLAY MESH RPAIR (PPOM)

Intraperitoneal onlay mesh repair is a current technique for laparoscopic repair of ventral and incisional hernias.
However, the placement of synthetic mesh intraperitoneally may potentially lead to mesh-induced complications
such as adhesive intestinal obstruction, enterocutaneous fistula, or even mesh erosion into organs. Inspired by the
concept of laparoscopic inguinal hernia repair, a novel technique: preperitoneal onlay mesh repair (PPOM) was
developed.53,54 This involves placing the mesh in the preperitoneal plane to help eliminate mesh-induced
complications. The peritoneal flaps are carefully created with synthetic mesh placed on the preperitoneal plane,
and then it is completely closed with sutures. The patients treated by this novel procedure usually have
uneventful recovery except for a small seroma.

References
1. Bueno J, Serralta A, Planells M, et al. Inguinodynia after two inguinal herniorrhaphy methods. Surg Laparosc Endosc
Percutan Tech. 2004;14:210 –14.
2. Mahon D, Decadt B, Rhodes M. Prospective randomized trial of laparoscopic (transabdominal preperitoneal) vs open
(mesh) repair for bilateral and recurrent inguinal hernia. Surg Endosc. 2003;17:1386 –90.
3. Onofrio L, Cafaro D, Manzo F, et al. Tension-free laparoscopic versus open inguinal hernia repair. Minerva Chir.
2004;59:369 –77.
4. Smith JR, Demers ML, Pollack R, et al. Prospective comparison between laparoscopic preperitoneal herniorrhaphy and
open mesh herniorrhaphy. Am Surg. 2001;67:11–7.
5. Kingsnorth A, LeBlanc K. Hernias: inguinal and incisional. Lancet 2003;362:1561–71.
6. Sajid MS, Bokhari SA, Mallick AS, Cheek E, Baig MK. Laparoscopic versus open repair of incisional/ventral hernia: a
meta-analysis. Am J Surg. 2009;197:64–72.
7. Mudge M, Hughes LE. Incisional hernia: a 10-year prospective study of incidence and attitudes. Br J Surg. 1985;72:70 –
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8. Bucknall TE, Cox PJ, Ellis H. Burst abdomen and incisional hernia: a prospective study of 1129 major laparotomies.
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9. Carlson MA, Ludwig KA, Conlon RE. Ventral hernia and other complications of 1000 midline incisions. South Med J.
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10. Pollock AV, Evans M. Early prediction of late incisional hernias. Br J Surg. 1989;76:953–4.

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11. Anthony T, Bergen PC, Kim LT, et al. Factors affecting recurrence following incisional herniorrhaphy; World J Surg.
2000;24:95–100; discussion 101.
12. Luijendijk R, Hop W, Van den Tol M, et al. A comparison of suture repair with mesh repair for incisional hernia. N Eng
J Med.2000;343:392–398.
13. Anthony T, Bergen P, Kim L, et al. Factors affecting recurrence following incisional herniorrhaphy. World J Surg.
2000;24:95–101.
14. Friedrich M, Muller-Riemenschneider F, Roll S, et al. Health Technology Assessment of laparoscopic compared to
conventional surgery with and without mesh for incisional hernia repair regarding safety, efficacy and cost-
effectiveness. GMS Health Technol Assess. 2008;4:Doc01.
15. LeBlanc KA, Booth WV. Laparoscopic repair of incisional abdominal hernias using polytetrafluoroethylene:
preliminary findings. Surg Laparosc Endosc. 1993;3:39–41.
16. Stoppa RE. The treatment of complicated groin and incisional hernias. World J Surg. 1989;13:545–54.
17. Rives J, Pire JC, Flament JB, et al. Treatment of large eventrations. New therapeutic indications apropos of 322 cases.
Chirurgie. 1985;111:215–25.
18. Wantz GE. Incisional hernioplasty with Mersilene. Surg Gynecol Obstet. 1991;172:129 –137.
19. Cobb WS, Kercher KW, Heniford BT. Laparoscopic repair of incisional hernias. Surg Clin North Am .2005 Feb;85:91–
103, ix.
20. Heniford BT, Park A, Ramshaw BJ, Voeller G. Laparoscopic repair of ventral hernias: nine years’ experience with 850
consecutive hernias. Ann Surg. 2003 Sep;238:391–9; discussion 399-400.
21. Cassar K, Munro A. Surgical treatment of incisional hernia. Br J Surg. 2002;89:534 –45.
22. Morales- onde S adet H ano H Bustos artı´n J orales-Mendez S. Laparoscopic ventral hernia repair
without sutures—double crown technique: our experience after 140 cases with a mean follow-up of 40 months. Int Surg.
2005; 90(3 Suppl):S56–S62
23. Olmi S, Scaini A, Cesana GC, Erba L, Croce E. Laparoscopic versus open incisional hernia repair: an open randomized
controlled study. Surg Endosc. 2007; 21: 555–9.
24. Goodney PP, Birkmeyer CM, Birkmeyer JD. Short-term outcomes of laparoscopic and open ventral hernia repair: a
meta-analysis. Arch Surg. 2002; 137: 1161–5.
25. Franklin ME, Dorman JP, Glass JL, Balli JE, Gonzalez JJ. Laparoscopic ventral and incisional hernia repair. Surg
Laparosc Endosc. 1998;8:294 –9.
26. Heniford BT, Park A, Ramshaw BJ, Voeller G. Laparoscopic ventral and incisional hernia repair in 407 patients. J Am
Coll Surg. 2000;190:645– 50.
27. LeBlanc KA, Booth WV, Whitaker JM, Bellanger DE. Laparoscopic incisional and ventral herniorrhaphy: our initial
100 patients. Hernia. 2001;5:41– 5.
28. Heniford BT, Park A, Ramshaw BJ, Voeller G. Laparoscopic repair of ventral hernias. Nine years’ experience with 850
consecutive hernias. Ann Surg. 2003;238:391– 400.
29. Misiakos EP, Machairas A, Patapis P, Liakakos T. Laparoscopic ventral hernia repair: pros and cons compared with
open hernia repair. JSLS 2008;12:117–25.
30. Perrone JM, Soper NJ, Eagon JC, et al. Perioperative outcomes and complications of laparoscopic ventral hernia repair.
Surgery. 2005;138:708–15; discussion 715-6.
31. Yavuz N, Ipek T, As A, Kapan M, Eyuboglu E, Erguney S. Laparoscopic repair of ventral and incisional hernias: our
experience in 150 patients. J Laparoendosc Adv Surg Tech. 2005 ;15:601–5.
32. Kingsnorth A, Banerjea A, Bhargava A. Incisional hernia repair – laparoscopic or open surgery? Ann R Coll Surg Engl.
2009; 91: 631–6.
33. Ramirez O Ruas Dellon AL. ‘ omponents separation’ method for closure of abdominal-wall defects: an anatomic
and clinical study. Plast Reconstr Surg. 1990; 86: 519–26.
34. Parra MW, Rodas EB. Minimally invasive components separation-an updated method for closure of abdominal wall
defects. J Laparoendosc Adv Surg Tech A. 2011 Jul 20.[Epub ahead of print]
35. Sains PS, Tilney HS, Purkayastha S, et al. Outcomes following laparoscopic versus open repair of incisional hernia.
World J Surg. 2006;30:2056 –64.
36. Pierce RA, Spitler JA, Frisella MM, et al. Pooled data analysis of laparoscopic vs. open ventral hernia repair; 14 years of
patient data accrual. Surg Endosc. 2007;21:378 –86.
37. LeBlanc KA, Whitaker JM, Bellanger DE, Rhynes VK. Laparoscopic incisional and ventral hernioplasty: lessons
learned from 200 patients. Hernia 2003;7:118–24.
38. Franklin ME Jr, Gonzalez JJ Jr, Glass JL, Manjarrez A. Laparoscopic ventral and incisional hernia repair: an 11-year
experience. Hernia 2004;8:23–7.
39. Morales-Conde S. Laparoscopic ventral hernia repair: advances and limitations. Semin Laparosc Surg. 2004
Sep;11:191–200.
40. Barber FA, Herbert MA, Richards DP. Sutures and suture anchors: update 2003. Arthroscopy 2003 ;19:985–90.
41. Schreinemacher MH, Emans PJ, Gijbels MJ, Greve JW, Beets GL, Bouvy ND. Degradation of mesh coatings and
intraperitoneal adhesion formation in an experimental model. Br J Surg 2009; 96(3):305–313
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abdominal hernia—5 years of experience. olski rzegla˛d hirurgiczny 2014; 86(8):353–358
43. Jenkins ED, Yom V, Melman L, Brunt LM, Eagon JC, Frisella MM, Matthews BD. Prospective evaluation of adhesion
characteristics to intraperitoneal mesh and adhesiolysis-related complications during laparoscopic reexploration after
prior ventral hernia repair. Surg Endosc 2010; 24:3002–3007
44. Ellis H .Intraabdominal and postoperative peritoneal adhesions. J Am Coll Surg 2005; 200:641–644.
45. Muysoms FE, Bontinck J, Pletinckx P. Complications of mesh devices for intraperitoneal umbilical hernia repair: a
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A randomised, multi-centre, prospective, observer and patient blind study to evaluate a non-absorbable polypropylene
mesh vs. a partly absorbable mesh in incisional hernia repair. Langenbecks Arch Surg 2012; 397(8):1225–1234.
47. Miserez M, Penninckx F. Endoscopic totally preperitoneal ventral hernia repair. Surg Endosc 2002; 16:1207–1213.
48. Sauerland S, Walgenbach M, Habermalz B, Seiler CM, Miserez M. Laparoscopic versus open surgical techniques for
ventral or incisional hernia repair. Cochrane Database Syst Rev. doi:10.1002/14651858.CD007781.pub2, March 16,
2011
49. Sajid MS, Bokhari SA, Mallick AS, Cheek E, Baig MK. Laparoscopic versus open repair of incisional/ventral hernia: a
meta-analysis. Am J Surg 2009; 197:64–72
50. Schumpelick V, Binnebo¨sel M, Conze J. Clinical results after open mesh repair. In: Schumpelick V, Fitzgibbons RJ
(eds) Hernia repair sequelae. 2010; Springer, New York, pp 227–232.
51. Park A, Birch DW, Lovrics P. Laparoscopic and open incisional hernia repair: a comparison study. Surgery 1998;
124:816–821
52. McGreevy JM, Goodney PP, Birkmeyer CM, Finlayson SR, Laycock WS, Birkmeyer JD. A prospective study
comparing the complication rates between laparoscopic and open ventral hernia repairs. Surg Endosc 2003;17:1778–
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10(2):119-127.
54. Yang PG, Tung LK. Preperitoneal onlay mesh repair for ventral abdominal wall and incisional hernia: a novel
technique. Asian J Endosc Surg. 2016; 9(4):344-347.

FUNDOPLICATION FOR GERD — CURRENT STATUS

Pawanindra Lal, Anubhav Vindal

Introduction
Gastro-oesophageal reflux disease (GERD) is one of the most common chronic disorders of the gastrointestinal
tract, and its incidence has increased all over the world over the last few years.1 The prevalence of GERD has
been found to be much higher in Asia than quoted in earlier studies and Indian race has been found to be at an
increased risk for the development of GERD and its sequalae.2 Forty percent of symptomatic GERD patients
develop erosive reflux oesophagitis, with the potential sequelae of impaired quality of life, haemorrhage, peptic
stricture formation, and Barrett’s oesophagus.3,114 After diagnosis of GERD, patients generally require lifelong
treatment. With the advent of proton pump inhibitors, some patients are able to heal oesophagitis, and those who
cannot; antireflux surgery is a satisfactory maintenance therapy, and potentially the only option for patients who
have medically refractory GERD.

Indications for surgery

Guidelines of the Society of American Gastrointestinal Endoscopic Surgeons provide specific indications for
antireflux surgery:4
1. Patients who have failed medical management.
2. Patients who opt for surgery despite successful medical management (due to lifestyle consideration
including age, time or expense of medication etc).
3. atients who have complication of G RD (Barrett’s stricture grade 3 or 4 oesophagitis).
4. Patients who have atypical symptoms (asthma, hoarseness, cough, chest pain, aspiration) and reflux
documented on 24 hour pH monitoring.

Requirements to proceed with an antireflux procedure in such patients are: 5

1. Increased oesophageal exposure to gastric juice documented by 24 hour oesophageal pH monitoring.
2. Presence of a mechanically defective lower sphincter on manometric studies.
3. Adequate oesophageal body motor function on manometric studies.

More recently, the Society of American Gastrointestinal and Endoscopic Surgeons Guidelines Committee has
published guidelines for surgical treatment of gastroesophageal reflux disease. 6 According to these guidelines,
when the diagnosis of reflux is objectively confirmed, surgical therapy should be considered in individuals who:
1. Have failed medical management (inadequate symptom control, severe regurgitation not controlled with acid
suppression, or medication side-effects)OR
2. Opt for surgery despite successful medical management (due to quality-of-life considerations, lifelong need
for medication intake, expense of medications, etc.)OR
3. Have complications of G RD (e.g. Barrett’s oesophagus peptic stricture) OR
4. Have extra-esophageal manifestations (asthma, hoarseness, cough, chest pain, aspiration)

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Coexistence of Barrett’s oesophagus with gastroesophageal reflux symptoms is considered by many a clear
indication for antireflux surgery.6 Surgical intervention for asymptomatic Barrett’s oesophagus is more
controversial, however It is important to note that the preoperative workup of these patients including history,
symptom scoring, endoscopy, pH- and mano-metry and other laboratory investigations be taken up in a
dedicated way. This ensures that the diagnosis and the decision to go ahead with surgical treatment are based on
a sound footing. This is one of the main reasons why different canters and different investigators have widely
varying success rates performing similar surgeries on a matched subset of patients.

The aim of preoperative investigations is to select reflux patients appropriate for surgical treatment to optimize
outcomes. There is currently no consensus, and significant variability, among surgeons regarding which studies
should be obtained before surgery, and in what order.

1. Oesophagogastroduodenoscopy (OGD): Is likely the one study that all patients should have
preoperatively, as it can confirm the diagnosis of GERD or identify other etiologies of esophagogastric
mucosal abnormalities and allows biopsies to be taken.
2. pH-metry: Important for patients when the diagnosis of GERD cannot be confirmed on OGD or
diagnostic uncertainty exists. A normal 24-h intraesophageal pH study after an H2-blocker- and proton
pump inhibitor (PPI)-free interval should strongly suggest an alternate diagnosis and lead to additional
diagnostic investigations.
3. Oesophageal manometry: Frequently performed before surgery and advocated by many experts in order
to identify conditions that might contraindicate fundoplication (such as achalasia) or modify the type of
fundoplication according to a tailored approach based on esophageal motility. Nevertheless, there is no
support in the literature for mandatory preoperative manometry6, and there are numerous studies
refuting the need for a tailored approach to fundoplication.
4. Barium swallow: Frequently obtained test for better delineation of the anatomy. May be particularly
valuable in patients with large hiatal hernias who have a shortened oesophagus.

Other preoperative tests have been examined, such as gastric emptying studies6, but there are no data to support a
correlation between their results and postoperative outcomes. This test may be important, however, in patients
who require reoperation, as it may provide indirect evidence for vagal nerve injury during the original surgery.

Surgical management
Surgery for gastro-oesophageal reflux disease (GERD) has been in a state of evolution over the last 70 years.
Nissen’s fundoplication, Belsey’s wrap, and Hill’s gastropexy have all been introduced, studied, and modified.
Different approaches have been used, including thoracotomy, laparotomy, thoracoscopy, laparoscopy, and
robotic-assisted techniques.

Historical Aspects
Surgery for GERD has evolved from anatomical repair of hiatal hernia to physiological restoration of
gastroesophageal junction. In 1919, Angelo Soresi published the first treatise describing elective surgical repair
of hiatus hernia.7 This operation consisted of reduction of the hernia and closure of the opening of the
diaphragm. In 1950, Richard Sweet from Massachusetts General Hospital published the transthoracic technique.8
These surgeons of the first half of the 20th century had focused on correcting an anatomic defect. To their
dismay, many patients had successful restoration of anatomy but persisting symptoms.

Allison should be credited for initiating the modern era of antireflux surgery.9 In 1951 Philip Allison reported a
technique for repair of hiatal hernia in the treatment of GERD. He described left thoracotomy, restoration of the
abdominal length of the oesophagus, posterior crural repair, and left phrenic nerve crush. The long-term results
of this operation, however, were unsatisfactory. Allison reported a 20-year retrospective survey of 553 patients
operated on for various types of hiatal hernia.10 Only 66% of the patients had symptomatic relief, and 49% had
recurrence of the hiatal hernia.

Another important contributor was Lucius Hill. He demonstrated that the antireflux barrier consisted of the
gastroesophageal valve, the lower oesophageal sphincter (LES), the diaphragm, and posterior fixation of the
gastroesophageal junction.11 His technique aimed to re-establish the 180º fold that was lost in patients who have
severe reflux. Using an upper midline incision, he placed sutures between the proximal lesser curvature of the
stomach, the median arcuate ligament, and the anterior and posterior phrenoesophageal fascial bundles. He
included placement of cardio-diaphragmatic sutures for fixation of the GE junction, along with closure of the
hiatus.

The identification of the lower oesophageal sphincter and use of manometry were reported in 1956. 12
Osophageal pH monitoring would come 2 decades later. These tools linked anatomy and physiology to permit

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accurate diagnosis of reflux disease and provided an objective standard for evaluation of surgery. In the midst of
this physiologic revolution, Rudolph Nissen and Ronald Belsey developed the operations used by most surgeons
in the 21st century.13

The Belsey procedure was developed by Ronald Belsey in late 1940s in Bristol, England.14 His initial operation
underwent multiple modifications before the final version, Mark IV, in 1967. 15 His repair emphasized
physiology over anatomy. It was designed to restore all the normal functions of a competent cardia. It is a partial
fundoplication or an enveloping of distal oesophagus with the gastric fundus over 270°. The Belsey procedure is
difficult to teach and communicate and has fewer margins for error. 16

In 1936, Rudolph Nissen excised the cardia of the stomach in a patient who had an esophageal ulcer, and
anastomosed the oesophagus to the stomach. He buttressed the suture line by wrapping the fundus of the
stomach around it and the lower oesophagus.17 Years later Nissen astutely noted that the patient had no
heartburn, and rightfully attributed that to the ‘‘wrap’’ used at his surgery. In 1955, Nissen performed
“gastroplication” surgery on 2 patients with excellent clinical outcome.18 It involved wrapping both anterior and
posterior walls of the stomach around the lower 6 cm of the oesophagus using 4 or 5 interrupted sutures, 1 or
more of which also incorporated part of the anterior wall of the oesophagus. The wrap was performed around a
large-bore indwelling intraesophageal stent. Although this provided good control of reflux, it was associated
with a number of side effects that have encouraged modification.

Fundoplication in the Open Era

In the 1970s, Nissen's fundoplication was rapidly adopted worldwide and became the most popular antireflux
operation. The original operation underwent modifications by Nissen himself, as well as by other surgeons.
These include taking care to use only the gastric fundus to envelope the oesophagus in performing the
fundoplication, sizing the fundoplication with a 60-Fr bougie and limiting the length of the fundoplication to 1-2
cm.19 With wider application of the Nissen procedure, it became evident that a successful Nissen fundoplication
is not simply a matter of wrapping the stomach around the lower oesophagus and sewing it in place. Rather, a
good deal of judgement and experience is required to determine, how tight and how long to make the
fundoplicatioon, what portion of the stomach should be used and what conditions preclude the use of the
operation. Consequently, Nissen fundoplication has contributed to a number of severe postoperative
complications. Most can be attributed to surgical technique and inaccurate selection of patients for operation. If
the fundoplication is constructed too long or performed as a wrap rather than an enveloping of the oesophagus by
the fundus, permanent dysphagia may result. Such a fundoplication precludes physiologic belching and
vomiting.

In the United States, Donahue et al.20 and Demeester and Johnson21 worked to improve on Nissen's operation.
They were the first to truly understand the physiologic mechanism of Nissen's and modified it by division of
short gastric vessels and the creation of a loose floppy wrap. Demeester and Johnson evaluated the optimal
length of the wrap and convincingly showed that a loose wrap of just 2 cm was sufficient for reflux suppression
and reduced the incidence of troublesome postoperative bloating and dysphagia. It is this modification of the
original Nissen fundoplication that is most commonly performed today in the laparoscopic era.

Due to the complexity of the variables determining the success of Nissen’s fundoplication and the multitude of
postoperative problems associated with an improper procedure, Dor et al.22 and Andre Toupet23 proposed
construction of a partial wrap (less than 360°) in an effort to minimize the postoperative symptoms plaguing
patients who underwent Nissen fundoplication. The partial fundoplications are usually constructed by covering
either the anterior or posterior wall of the distal oesophagus with the stomach. This necessitates suturing the
fundus of the stomach to the oesophagus as the primary and most important portion of the procedure. This suture
line is subject to a great deal of stress and as a consequence has a limited durability. Although the partial
fundoplication operations are successful in preventing reflux and permitting physiologic belching when they
remain intact, they disrupt with a distressing frequency115.

Following four decades of experience with open antireflux procedures, long-term outcomes following open
surgery have been well described. Postoperative hospital stay ranges from 7 to 14 days 24,25, short-term morbidity
is acceptable 26,27, and long-term success is achieved in the majority of patients.26,28 Rossetti and Hell 29 reported
that 87.5% of patients, followed for more than 10 years after a 360° fundoplication without short gastric vessel
division, were free from reflux symptoms and adverse sequelae. Similarly, DeMeester et al.26 reported a 91 per
cent success rate for the Nissen fundoplication procedure at mean follow-up of 45 months. Adverse outcomes
following open Nissen fundoplication include persistent dysphagia and gas bloat syndrome.26.27.30 Many patients
also have troublesome early dysphagia which resolves as follow-up matures.31

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Uncontrolled reports suggest that the performance of a partial fundoplication variant may reduce the incidence of
postoperative dysphagia.24 However, this proposal has not been supported by the results of published
randomized trials.15,30-33 Three trials have compared Nissen fundoplication with posterior partial
fundoplication31-34, and none of these found any significant increase in the likelihood or severity of dysphagia
following Nissen fundoplication.

An overall assessment of all of these randomized trials has failed to demonstrate important advantages to support
the routine application of a posterior partial fundoplication.25 However, this cannot be extrapolated to the
alternative technique of anterior partial fundoplication; it is possible, but certainly not proven, that this
modification could result in outcome improvements.24,36

Laparoscopic Era
There has been increasing interest in the surgical management of gastroesophageal reflux disease, particularly
after the introduction of minimal invasive techniques in 1991.37 Since laparoscopic Nissen fundoplication was
first described in 1991 by Dallemagne et al.37 laparoscopic antireflux surgery has been embraced enthusiastically
in many centres.1,38-43 The laparoscopic approach to antireflux surgery now offers a potentially more acceptable
surgical option for patients with gastro-oesophageal reflux because of the reduced postoperative pain and more
rapid recovery. This has led many symptomatic patients, who previously did not wish to undergo open antireflux
surgery, now to request a laparoscopic fundoplication.44,45

Laparoscopic antireflux surgery (LARS) requires surgeons to learn a new range of operating skills. There is a
definable learning curve, during which procedures are associated with extended operating times and an increased
risk of complications.46 With increased experience and improvements of advanced laparoscopic and esophageal
surgical skills, there has been a significant decline in early and long-term complications. In a review of more
than 10,000 reported laparoscopic antireflux procedures, morbidity was uncommon (6%), mortality was rare
(0.08%), and the reoperation rate was low (4%).47 In addition to symptomatic improvement, the effectiveness of
LARS has been objectively confirmed with 24-h pH monitoring, which clearly demonstrates excellent control of
esophageal acid exposure more than five years after surgery.48

Initial nonrandomized studies comparing open and laparoscopic approaches to fundoplication suggested that
although the laparoscopic approach took more time to perform, the incidence of postoperative complications
such as incisional pain and respiratory compromise was lower, and postoperative disability and hospital stay
were shorter. Since then, multiple randomized studies also have been performed.49-53 In 1997, Laine and
coworkers53 reported a randomized trial of 110 patients comparing laparoscopic versus open Nissen
fundoplication. During the 3-month follow-up period, 24-hour pH tracing was normal in 97% of the patients in
the laparoscopic Nissen fundoplication group and 68% of the patients in the open group. Likewise, LES pressure
had increased by 80% in the laparoscopic group and only 40% in the open group. The mean duration of the
operation was 88 minutes in the laparoscopic group and 57 minutes in the open group. The average hospital stay
was 3.2 days in the laparoscopic group, versus an average 6.4-day stay in the open group. Similarly in 2002,
Chrysos and colleagues51 reported a randomized trial of laparoscopic versus open Nissen fundoplication in 106
patients. This showed the open group to have more pain as well as more frequent respiratory complications. At
12-month follow-up, both open and laparoscopic groups were shown to have increased lower LES tone. Follow-
up pH monitoring confirmed reduction of reflux in both groups as well.

The promising early outcome studies for laparoscopic antireflux surgery are now supported by the initial results
of randomized trials, confirming that this approach reduces the early morbidity of surgery for gastrooesophageal
reflux. Further medium-term outcome studies also confirm that the laparoscopic method controls pathological
reflux as effectively as the traditional open operation. All published studies report that laparoscopic antireflux
surgery reduces hospital treatment costs and early surgical morbidity.54-60

To achieve good results, however, surgeons should be aware of the potential for certain complications which are
commoner following laparoscopic surgery and the need to adopt strategies to avoid them. At present, a short
loose Nissen fundoplication performed laparoscopically, with or without division of the short gastric vessels, is
an appropriate surgical treatment for gastro-oesophageal reflux disease.

Until the results of long-term studies are available, the true outcome of laparoscopic antireflux surgery and its
status compared with open antireflux surgery must remain uncertain.

Based on the available level 1 evidence, laparoscopic fundoplication should be preferred over its open alternative
as it is associated with superior early outcomes (shorter hospital stay and return to normal activities, and fewer
complications) and no significant differences in late outcomes (failure rates).6 Nevertheless, antireflux surgeons

213
should be aware that laparoscopic fundoplication takes longer to perform and has a higher incidence of
reoperations, at least in the short term.

Modifications of Laparoscopic Nissen’s Procedure

The postoperative problems associated with a classical Nissen’s procedure have led to the investigation of a
range of modifications that seek to improve outcome in patients after antireflux surgery. Watson et al.61
investigated whether division of the short gastric vessels during laparoscopic Nissen’s fundoplication affected
postoperative outcome. They do not suggest significant outcome differences.

For a long time, the use of a large bougie in the oesophagus has been advocated to avoid the construction of a
too-tight total wrap. Philip Donahue introduced the ‘‘floppy Nissen fundoplication’’ in a dog model.62 Using a
15 Hegar dilator underneath the fundoplication and a 50 French oesophageal bougie during the creation of the
fundoplication, he ensured a standard, large diameter to the wrap. Dr. Tom DeMeester further modified this
technique in his landmark study in 1986.26 He used a 60 French oesophageal bougie, shortened the
fundoplication length to 1 cm, and performed complete mobilization of the gastric fundus with division of the
short gastric vessels. Objective data have now been attained to support the use of a similar indwelling device to
reduce obstructive side effects.63
The consensus that has seemed to have emerged is to ensure a short loose wrap, irrespective of whether the short
gastric vessels are divided or not. Recently, a number of surgeons have advocated tailoring the antireflux
procedure according to various features assessed before operation.64-67 Our own experience with Nissen’s
fundoplication has been very good and majority of them have been with the Rosetti modification.116

Laparoscopic Partial Fundoplication

Nissen fundoplication has undergone many modifications in the form of partial fundoplication. These partial
fundoplications have been found to be effective, well tolerated, leading to improved quality of life with
acceptable rate of long term side effects in GERD.31,68-70,115

There is a paucity of information available on the comparison of a laparoscopic complete wrap versus a
laparoscopic partial wrap. In the largest series with significant numbers of each operation, a partial wrap
appeared to be chosen by surgeon preference or when there was impaired esophageal motility.71-73 Studies done
to compare laparoscopic Nissen fundoplication and laparoscopic partial fundoplication have failed to find the
advantage of one wrap over the other.74-77,115 Studies have shown that laparoscopic Nissen fundoplication is
associated with higher incidence of dysphagia and lesser incidence of recurrence as compared to laparoscopic
partial fundoplication.51,56,78,79 Another study has shown more incidence of recurrence in laparoscopic partial
fundoplication with similar dysphagia.80 Fibbe et al.81 compared laparoscopic partial and total fundoplications in
200 patients with esophageal motility disorders and found no difference in postoperative recurrence of reflux and
concluded that no tailoring of the surgical management is necessary. Similarly, Laws et al.82 found no clear
advantage of one wrap over the other in their prospective, randomized study comparing these two groups.
Moreover, in a meta-analysis of 9 prospective randomized trials including open and laparoscopic total versus
partial fundoplications in 793 patients, no statistical difference was found in new onset dysphagia or recurrence
of reflux.76 Our own study found that partial anterior fundoplication (Dor) has equivalent short term results as
compared to Nissen’s 360 degress wrap.115

Total wrap supporters acknowledge the fact that the wrap needs to be “floppy” to minimize postoperative
dysphagia. It should also be noted that a floppy Nissen fundoplication is safe and effective in patients suffering
from a defective esophageal peristalsis. Finally, proponents of the total fundoplication note the decreased the
effectiveness of a partial fundoplication in controlling reflux. Advocates of partial fundoplication claim that it
results in fewer side effects than a 360° fundoplication. Complications such as gas bloat and persistent dysphagia
appear to be less frequent. Partial fundoplication was recommended as the initial procedure of choice for patients
who have poor esophageal motility.83 Patients suffering from postoperative dysphagia had their 360° wraps
revised to partial fundoplication.84 Some authors propose partial wraps as the operation of choice, regardless of
esophageal motility.85 Unfortunately, long-term follow-up revealed a high failure rate of partial wraps in terms
of control of acid reflux. Jobe and coworkers 86 showed a worse outcome with a partial fundoplication than with
total fundoplication. Other authors noted that as many as 50% of the patients who had partial fundoplication had
evidence of reflux when studied postoperatively.87

A large randomized trial with open antireflux surgery has reported that posterior partial fundoplications are
associated with less troublesome complaints of gas–bloat and rectal flatus.31 In addition, another trial comparing
a total with a partial anterior fundoplication performed laparoscopically suggested similar advantages with this
partial fundoplication.88 It has been argued that some partial fundoplication procedures augment various
constituents of the valvuloplasty components of the competence in the gastroesophageal junction and as a
consequence were associated with a very low incidence of mechanical complications.89

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Based on the available level 1 evidence, partial fundoplication is associated with less postoperative dysphagia,
fewer reoperations, and similar patient satisfaction and effectiveness in controlling GERD compared with total
fundoplication up to 5 years after surgery.6 Nevertheless, the paucity of long-term follow-up data that compare
the effectiveness of the procedures makes it hard to recommend one type of fundoplication over the other,
especially in an era when the long-term effectiveness of surgical treatment for GERD is questioned. It should
also be noted that a body of literature suggests that anterior partial fundoplication may be less effective in the
long term, and retrospective data suggest that partial fundoplication may not be as effective as total in the long
run.6 Nonetheless, the evidence suggests that surgeons appropriately trained in minimally invasive techniques
who perform surgery for GERD may minimize postoperative dysphagia by choosing partial fundoplication or
short total fundoplication (1–2 cm) over a large bougie (56 French) and maximize the effectiveness of the
procedure by choosing total fundoplication or longer (at least 3 cm) posterior fundoplication.6 Controlled studies
that take into account these guidelines are needed.

Anterior versus Posterior partial fundoplication

A randomized, controlled clinical trial addressed the question of whether there are important differences between
the anterior and the posterior partial fundoplication in terms of reflux control and side effects.90 It found
significant differences in favour of the posterior fundoplication regarding the level of reflux control. The reasons
that were postulated for this observation are that the buttressing effect of an anterior versus a posterior wrap
might differ. The posterior fundoplication elevates the abdominal portion of the oesophagus from its native bed
in the hiatus and by necessity angulates the gastroesophageal junction. This angulation might have the potential
to cause some oesophageal outflow obstruction.

Hence, a posterior partial fundoplication performed laparoscopically was followed by adequate reflux control
assessed both objectively and subjectively but an anterior partial fundoplication gave unacceptable results both
in terms of reflux control and esophageal acid reflux variables.90

270° Partial Anterior fundoplication

Various case series suggest that the 270° anterior partial fundoplication is associated with less postoperative
dysphagia, improved ability to belch and less risk of gas bloat symptoms.24,91 Although this technique has been
less widely applied than the posterior variant, the outcomes of uncontrolled prospective assessment have
suggested advantages.

Recently, the results of a trial comparing a laparoscopic 270° anterior partial fundoplication with a Nissen’s total
fundoplication showed a reduced incidence of dysphagia and gas-related problems in the former group 13 yet
equivalent control of reflux in both at 6 months follow-up. A subsequent longer follow-up of patients having a
similar 270° anterior partial fundoplication suggested reassuring outcomes.92

The way the anterior fundoplication is constructed is different from the posterior fundoplication variants, as the
fundus sits in front rather than behind the oesophagus.

A 270° anterior partial fundoplication may not be as effective for the prevention of reflux as Nissen’s
fundoplication. The Nissen’s technique creates an over competent valve whilst anterior fundoplication restores
the GEJ to a more physiological state.36 If the durability of anterior fundoplication is proven to be as good as that
of the Nissen fundoplication, there can be a strong case for its routine application in patients with GERD
requiring surgery.

180° Partial Anterior fundoplication

As a modification of the 270° anterior partial fundoplication, another variant in the form of 180° partial anterior
fundoplication has been advocated. A more anatomical reconstruction of the antireflux mechanism by anterior
180° partial fundoplication has been shown to have a lower incidence of dysphagia and other side effects, such
as flatulence, than Nissen’s fundoplication.88

A possible explanation for the reduced incidence of dysphagia following 180° anterior fundoplication may be the
more “physiological” manometric profile of the lower oesophagus seen after 180° anterior fundoplication.
Anterior 180° fundoplication reduces the resistance to bolus transport seen after Nissen’s fundoplication.88

90° Partial Anterior fundoplication

Further modification of anterior fundoplication leading to the development of a 90° anterior fundoplication has
also been tried.93 Various comparisons between 90° anterior fundoplication and Nissen’s fundoplication have
been reported. In one series only 18% of patients reported postoperative inability to belch, which is lower than
the 60% to 80% reported after 270° anterior or Nissen’s fundoplication.93 The early outcome of the 90° anterior

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fundoplication suggests that the reduction in postoperative dysphagia is even more pronounced than that seen
after Nissen’s or 180° anterior fundoplication.93

It is unlikely that the 90° fundoplication will replace Nissen’s fundoplication in the majority of patients requiring
antireflux surgery, however, there are some patients for whom this procedure might be preferable: patients with
an adynamic oesophagus, patients with a giant paraesophageal hernia or intra-thoracic stomach, where there is
no certain disorder of the reflux mechanism, and patients (typically women) for whom the avoidance of
excessive flatus is important.

Laparoscopic fundoplication versus medical treatment

Several recent randomized controlled trials comparing laparoscopic fundoplication to medical treatment have
been published. The LOTUS trial, a large European multi-center trial comparing maintenance therapy of
esomeprazole (PPI) to a standardized laparoscopic Nissen fundoplication reported 5-year outcomes of 372
patients in 2011.94 Relief of GERD symptoms at 5 years was higher in the PPI group (92% vs. 85%), however
limited by the fact that the trial design required pre-enrollment symptomatic response to PPI use. Nearly a
quarter (23%) of patients in the PPI group required an increase in their dosage to maintain symptom control.
While heartburn and regurgitation improved in the surgery group, they remained stable in the PPI group over
time with regurgitation being significantly worse in the PPI group. Perioperative mortality and morbidity was
low, 0% and 3% respectively.

Anvari reported the 3-year outcomes of 93 patients in a Canadian randomized controlled trial of laparoscopic
Nissen versus PPI.95 Outcome was assessed via a GERD symptom scale, visual analog scale (VAS) for overall
symptom control and 24 h pH monitoring at baseline and 3 years. Primary treatment failure (redofundoplication
or PPI use) occurred in 12% of patients in the surgical arm and 16% in the PPI arm (inadequate reflux control
despite maximal PPI dosage). Antireflux surgery was superior to PPI for heartburn-free days, overall VAS
control of symptoms and quality of life. Gastro-esophageal reflux score was significantly improved in both
groups after 3 years and although the percent time of pH <4 on 24-h pH study was less in the surgical group
(mean 2.1% vs. 4.3%), although the difference did not reach statistical significance.

Another recent systematic review showed that surgical management of GERD is more effective than medical
management with respect to patient-relevant outcomes in the short and medium term.96 The authors concluded
that the review of patient-relevant outcomes in the short and medium terms support the recommendation that
fundoplication be evaluated as a treatment alternative for long-term medical therapy or for patients with chronic
GERD and insufficient symptom control under medical treatment. However, given the scarcity of long-term
data, the relationship between the benefit and harm of antireflux surgery compared with permanent medical
treatment still is unclear, and fundoplication should be considered very cautiously for selected patients.

Fundoplication and Barrett’s Oesophagus

An expanded role for surgical management has been proposed, with some surgeons now claiming that earlier
surgical correction of pathological reflux may prevent progression to the complications of Barrett’s oesophagus
and stricture formation.45,64,97 With more and more evidence suggesting that antireflux surgery may affect the
natural history of Barrett’s oesophagus, and ultimately the risk of esophageal cancer, surgical therapy may be
considered for patients with Barrett’s oesophagus, especially for young patients and those with symptomatic
Barrett’s oesophagus.

However, it must be remembered that the evidence in this regard is circumstantial and more studies evaluating
the natural history of Barrett’s oesophagus after antireflux surgery are needed to arrive at a definite conclusion.

Endoscopic Modalities for GERD

These treatment modalities are primarily designed for patients with little or no significant hiatal hernia and are
delivered trans-orally, via upper endoscopy. There are principally three different types of these new treatment
options.

First, radiofrequency energy delivered to the lower oesophageal sphincter (LES) theoretically adds bulk to the
LES and changes the sphincter’s compliance.98

A second endoscopic therapy for GERD involves the creation of a mechanical barrier at the gastroesophageal
junction (GEJ). An ethylene vinyl alcohol copolymer is endoscopically injected within the submucosa or
muscular layers of the oesophageal wall 1-2 mm caudal to the Z line. Another system entails the submucosal
placement of a poly-acrylo-nitrile based hydrogel prosthesis (1.5 mm × 18 mm) above the GEJ.99

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The third category of endoluminal procedures employs direct, endoscopic tightening of the LES. This can be
achieved by either sewing or plicating the LES.100

EsophyX (Endogastric Solutions, Redwood City, WA), is a device to create an incisionless fundoplication
(Transoral incisionless fundoplication (TIF)) and is the only such device which is FDA approved. Long-term
data are not yet available for EsophyX. In short term follow-up, from 6 months to 2 years, EsophyX may be
effective in patients with a hiatus hernia ≤ 2 cm with typical and atypical GERD.101 Further studies are required
to define optimal techniques and the most appropriate patient selection criteria, and to further evaluate device
and technique safety.

Stretta system (Mederi Therapeutics Inc. Greenwich, CT) is currently the only FDA approved system for the
radiofrequency treatment of GERD. The Stretta procedure is considered appropriate therapy for patients being
treated for GERD who are 18 years of age or older, who have had symptoms of heartburn, regurgitation, or both
for 6 months or more, who have been partially or completely responsive to antisecretory pharmacologic therapy,
and who have declined laparoscopic fundoplication.101

Robotic fundoplication
The use of robotic surgery has been reported to be safe and feasible with similar outcomes during up to 1-year
follow up compared with laparoscopic antireflux surgery.102-105 Most of the available randomized controlled
trials have reported a significant increase in operating times and cost when the robot is used.102,104,106 While
robotic assistance can be safely and effectively used for fundoplication, its higher cost compared with
conventional laparoscopy and similar short-term patient outcomes make it a less than ideal initial choice.
Nevertheless, further study regarding learning curves and surgeon workload with the robotic technique are
needed before stronger recommendations can be made.

Our Experience at MAMC (India)

Our own experience in laparoscopic fundoplication has been quite favourable. In all 125 patients with confirmed
diagnosis of GERD and with indications for surgical therapy were operated in the last decade. The follow-up of
all of these patients is available and ranges from 6 months to 10 years.

Each of the patients underwent extensive preoperative diagnostic work-up both to confirm the diagnosis of
GERD, as well as to gauge its severity. A total of 75 patients underwent laparoscopic Nissen fundoplication
(LNF), while 50 were chosen for laparoscopic Toupet fundoplication (LTF), based on the merits of each case.

The mean duration of surgery in the LNF group was 99 minutes (range 80-140) while it was 115 minutes (range
90-150) in the LTF group (due to the larger number of sutures that need to be applied in the latter). The average
duration of hospital stay in LNF patients was 3.31 days and in LTF patients was 3.17 days. Likewise, time taken
to return to routine work post operatively was also similar in the two groups, 12.6 days for LNF, and 11.5 days
for LTF group.

Postoperatively there was found to be a significant decrease in GERD symptoms, Demeester score and Modified
Visick grade in all the patients, regardless of the type of procedure performed. This may be due to the extensive
and diligent pre-operative workup and characterization of the patients’ symptoms and tailoring the therapy
accordingly. Only 10 patients of LTF (20%) complained of temporary post operative dysphagia that lasted for
only 2 weeks. There were no such complaints in the LNF group. The post operative Quality of Life (assessed
using VAS) was also found to be similar in both the groups – LNF: 2.31 to 8.33 and LTF – 2.58 to 8.58.

A study performed by the first author compared LNF with LTF and found that both the procedures are effective
in the management of GERD, and show comparable improvements in symptoms and objective assessment of
patients in the short term (6 weeks).107 They further noted that LTF was technically more demanding and took
longer to perform than LNF, which was however associated with a higher incidence of transient post operative
dysphagia. All patients showed an objective and significant increase in LES pressures, LES length and normal
pH with sustained beneficial effects on long term studies carried out 6 month to 4 years post operatively.

Summary
As was stressed earlier, the preoperative workup of patients with suspected GERD is very important and should
be performed in all cases. Under no instance should this surgery be taken lightly as a surgery performed
incorrectly or in an undeserving patient can spell disaster. It is a highly specialized treatment modality and
should be carried out in a dedicated center by an experienced surgeon to ensure the best results.

The question of which fundoplication technique offers the best outcomes for patients undergoing surgery for
GERD is controversial.11,24,26 Whilst uncontrolled studies have reported good results following laparoscopic or

217
open surgery for floppy Nissen’s anterior or posterior fundoplication,24,91,108-113 they have done little to resolve
this controversy. Indian patients seem to do very well with a floppy Nissen Fundoplication and benefits are
sustained and objectively proven.

TEN GOLDEN STEPS OF LAPAROSCOPIC FUNDOPLICATION116:

(Pawanindra Lal)

1. Correct Selection of patients symptomatic for Reflux – This is my DeMeester and Modified Visick
Symptom scoring of heartburn and regurgitation. Such patients with moderate to severe symptoms
must undergo Manometry and 24 hr pH metry. Only patients who have positive pH metry i.e. pH < 4
for >4% of time in a 24 hour period, will be truly benefited.
2. Rule out Short Oesophagus & Oesophageal Dysmotility disorders: Former can be done by a
combination of upper GI endoscopy and Barium Swallow. When detected they will need a ollis’s
gastroplasty though it is expremely rare. Latter are detected by manometry and if present, only partial
wraps should be offered to volume refluxers.
3. Choosing the right operation: In majority of cases, it is possible to perform the Rosetti modification
of laparoscopic Nissen’s i.e. preservation of the short gastric vessels. If the fundus is small, a partial
wrap should only be performed.
4. Preservation of Vagal Branches and Short Gastric Vessels: It has been observed that majority
surgeons divide the entire lesser curvature omentum from pars flaccid to the hiatus which destroys
vagal branches. In our opinion, this is completely unnecessary and avoidable. As above, nearly 9/10
wraps can be accomplished without division of the short gastric vessels thereby preserving nerve
supply and blood supply to the gastric fundus. Post operative gastric bloating is not seen in Rosetti
odification of Nissen’s.
5. Development of an adequate Retro-oesophageal window: To achieve a tension free wrap, it is
essential to develop a large retro-oesophageal window and taking the posterior vagus with the
oesophagus thus preserving any nerve damage due to stretching and avoiding ischemia of thew fundal
wrap. This is enables by adequate mobilization of the lower 5-7 cms of the oesophagus by gentle
dissection around both crura and traction with the penrose drain around the gastro-oesophageal
junction.
6. Avoiding Dysphagia due to a Tight Crural Repair: It has now been proven that dysphagia after
fundoplication is more often due to a tight crural repair rather than due to a tight fundal wrap. Bougie
is not required and one or two sutures are enough ensuring open crural hiatus after releasing the
traction on the oesophagus.
7. Adequate intra-abdominal length of the oesophagus: his is ensured in a Nissen’s operation by two
or three sutures applied at a gap of 1 cm each around the lower oesophagus. The commonest mistake
is to make a warp around the proximal stomach or an inadequate wrap which decreases the intr-
abdominal length of oesophagus thereby losing the benefit of this important anti-reflux mechanism.
8. Shoe Shine Maneouvre: Shoe Shine maneouve enables the surgeon to avoid any twist or rotation in
the wrap as it comes around the lower 2-3 cms of the oesophagus.
9. Stabilization of the wrap with crural sutures: The wrap can be stabilized by taking one suture on
either side between right crus and wrap and left crus and wrap thereby taking away the traction from
the anterior wrap sutures.
10. Prevent Post operative Emesis: It is of cardinal importance to completely prevent any emesis in the
post-operative period which has the risk of disrupting all the crural and fundal wrap sutures by the
sutures cutting through the tissue. This is especially important in the first 24 hours and it is useful to
add a prokinetic anti-emetic drug like metocopramide and continue it for the first week after surgery.
The patients are startedon clear liquids for first 24-48 hours and then shifted to non clear fluids for the
first week. Liquid diet is continued for two more weeks and then converted to pourable liquid diet for
another two weeks. This is followed by semi solid diet for a two weeks and then normal food can be
started after total of 6 weeks.

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98. Triadafilopoulos G, DiBaise JK, Nostrant TT, Stollman NH, Anderson PK, Wolfe MM, Rothstein RI, Wo JM, Corley
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99. Fockens P, Bruno MJ, Gabbrielli A, et al. Endoscopic augmentation of the lower esophageal sphincter for the treatment
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Surgical Techniques. 2010 Jun 1;20(5):441-6.

LAPAROSCOPIC SPLENECTOMY
Deborshi Sharma, Saurabh Sekhar
The normal spleen is 100-200 grams, bluish purple wedge-shaped structure which is friable and fragile,
vascularly rich solid organ protected by left 9,10,11th ribs. Superior, anterior and lateral border of the spleen are
bounded by diaphragm and rib cage. Splenic flexure of colon rests at the tip of the lower pole of the spleen.
Upper pole of kidney and adrenal rests just posterior to lower
pole as well. Medially tail of the pancreas is found at the level
of hilum with 30% of spleens abutting this structure. Also
medially slightly more anterior are short gastric vessels
leading to proximal greater curvature of the stomach.
Spleen is suspended by gastrosplenic, lienorenal, splenocolic,
phrenosplenic and splenorenal ligaments. Gastrosplenic and
lienorenal contain blood supply. Rest of ligaments are
reflections of peritoneum that cradle spleen from superior
pole laterally to the inferior pole. They are avascular unless
portal hypertension is present. Spleen develops around 5th
weak of gestation, mesodermal elements close to pancreas
fuse to form spleen. Imperfect fusion leads notching and
lobulations. Complete failure of fusion leads to the formation
of accessory spleen. Majority of the accessory spleen is found
in a splenic hilar region or may be located throughout the
abdomen and occasionally in the pelvis.

Spleen is supplied by 2 sets of vascular structure - short gastric vessels and splenic vessels. 3-5 short gastric
vessels drain fundus and left greater curvature of stomach and pass between two layers of gastrosplenic
ligaments to end generally in splenic branches. The splenic artery - anatomy is highly variable. However, 2
major configurations are described - Distributed and Magistral as by Michels (Figure shows A. Distributive type
B. Magistral type of splenic vascularisation).
The distributed supply is characterized by a short main splenic trunk and relatively early branch which are long
numerous and have transverse connections. The magistral supply is notable for longer main splenic trunk with
relatively late and limited terminal branches. In general, splenic vein branches are posterior and becomes more
variable close to the spleen. In addition, there are branches from a splenic artery to the tail of the pancreas, so it
is preferable to ligate or embolism distal to pancreatic branches to avoid possible pancreatic injury.
Laparoscopic splenectomy was first described by Delaitre and Maignien in 19911, is now widely accepted as a
safe and feasible technique for most splenectomy cases. Less intra-operative bleeding, subordinate postoperative

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pain, shorter hospital stay, and better cosmetic results are some of its advantages and nowadays it is the standard
approach. Its anatomic landmarks are often consistent and require no reconstruction, thus considered as an ideal
organ for laparoscopic removal.

INDICATIONS
Indications for laparoscopic splenectomy are same as open splenectomy, except for the trauma cases, where the
role of laparoscopy is still debatable. Indications for routine splenectomy can be divided into three categories:
(1) benign hematological diseases; (2) malignant hematological diseases; and (3) splenic cysts.

Benign hematological diseases

Patients with immune thrombocytopenic purpura are the most common indication for splenectomy (excluding
trauma). ITP is an acquired autoimmune disorder characterized by a low peripheral blood platelet count, without
abnormalities in the erythroid and myeloid/lymphoid lineages2. The ITP-associated thrombocytopenia is the
result of the production of anti-platelet antibodies which bind to the platelets resulting in the destruction of the
platelets through phagocytosis, the spleen is considered as the primary site for phagocytosis. Splenectomy is
considered a second-line therapy, mainly for patients with chronic ITP (presence of the disease for > 12 mo), as
the first-line therapy consists of high doses of corticosteroids and/or intravenous immunoglobulin. A
splenectomy can be suggested also in patients who receive near-toxic doses of immunosuppressive therapy3,
remissions under medical therapy and relapsed case. In all these cases laparoscopic splenectomy is considered a
method of choice as spleen is usually normal-sized.

Patients with hereditary spherocytosis the first line therapy are mainly medical4. Splenectomy is preserved for
moderate or severe forms of the disease. Moreover, the laparoscopic approach allows also a simultaneous
cholecystectomy, which in the majority of patients with hereditary spherocytosis is required due to symptomatic
cholelithiasis.

Thrombocytopenia thrombotic purpura is another indication for laparoscopic splenectomy, although it is rarely
performed, as plasma therapy has very good response rates. Patients with autoimmune hemolytic anemia can be
also benefited from a laparoscopic splenectomy. Other benign hematology diseases that can be partially or
completely treated with a laparoscopic splenectomy are Evans syndrome and hemoglobinopathies, such as sickle
cell anemia, β-thalassemia, and hemoglobin sickle cell disease.

Routine preoperative search for accessory splenic tissue should be done using high-resolution CT. Many claims
that a minimally invasive approach restricts spotting of accessory splenic tissue, however, it is well established
that a thorough search of the peritoneal cavity during the laparoscopic splenectomy has similar detection rates
compared to open splenectomy.

Malignant hematological diseases

In malignant hematological diseases, a laparoscopic approach serves mainly diagnostic and palliative purposes.
Patients with Hodgkin’s lymphoma can be benefited by staging procedure5. But, many surgeons hesitate to
perform a staging laparoscopy for Hodgkin lymphoma, as finding infiltrated nodes, especially in iliac and celiac
regions is considered to be more difficult through laparoscopy. The second reason, spleen must be removed
intact for pathologic analysis and for avoiding tumor cells dissemination. Majority of patients with Hodgkin’s
lymphoma have splenomegaly, so an additional 8-10 cm incision is required or alternatively, a hand-assisted-
laparoscopic-splenectomy (HALS) should be considered. In non-Hodgkin lymphomas, the role of laparoscopic
splenectomy is restricted to palliative purpose, when the patient suffers from abdominal pain and obstipation,
due to splenomegaly, or for correction of cytopenia. An elective laparoscopic splenectomy can be performed in
patients with non-Hodgkin lymphoma for acquiring a histological diagnosis.

Other malignancies where laparoscopic splenectomy has a diagnostic or therapeutic role are myeloproliferative
diseases (e.g., myelofibrosis), and lymphoproliferative diseases, (e.g., chronic lymphocytic leukemia or chronic
myelogenous leukemia). Primary splenic malignancies are very rare, comprising mostly lymphangiosarcomas,
malignant vascular tumors (e.g., hemangiosarcomas) or malignant lymphomas6. Most are metastatic (e.g., of
malignant melanoma or ovarian cancer). In all these malignancies, patients usually present with splenomegaly,
so laparoscopic splenectomy may be difficult. Alternatively, HALS procedure is used, which also results in low
conversion and morbidity rates7.

Splenic cysts
Splenic cysts can be classified in three large categories; infectious7 (abscess or hydatid cysts), nonparasitic
(congenital or post-traumatic) or malignant ones. Nonparasitic cysts represent approximately 75% of splenic
cysts[35] and are usually asymptomatic. Rarely can nonparasitic cysts cause symptoms, mainly abdominal pain,
fullness, nausea, vomiting, flatulence and diarrhea, and irritation of the left diaphragm followed by a cough or

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pneumonia? It is believed that the presence of symptoms is due to the large size of cysts, usually greater than 5
cm, at which point it is unlikely that the cyst will resolve automatically, and rupture even with minor trauma is
likely to occur. Although a laparoscopic partial splenectomy is rarely indicated in adults, in cases of large
nonparasitic cysts a partial splenectomy, cystectomy, or cyst decapsulation can be performed, preferably through
laparoscopy, as this preserves the immunologic function of the spleen and therefore prevents the potentially fatal
complication of post-splenectomy sepsis. In contrast to the asymptomatic course of nonparasitic cysts, patients
with infectious cysts, and especially splenic abscesses, may present with sepsis, and if they remain untreated, the
mortality rate is high. Infectious cysts are usually produced from septic emboli from especially in a pre-installed
sepsis or immunodeficiency conditions. An open splenectomy is considered still the standard approach for
treatment, mainly due to the need of an emergency procedure in a usually compromised patient; however, it has
been shown that infectious cysts can be successfully managed with a laparoscopic procedure and/or conservative
therapy. The lower postoperative morbidity that a minimally invasive approach can offer is of high significance
for the immunocompromised patients.

Splenic artery aneurysms are relatively rare, with a prevalence of 0.04% and commonly asymptomatic8.
Treatment of splenic aneurysms is indicated if the aneurysms become symptomatic, in women of childbearing
age, in the presence of portal hypertension, before liver transplantation, if the diameter exceeds 2 cm, and in case
of pseudo-aneurysm formation, regardless of size. Here interventional therapies are in the first line; however, if
these therapies are not applicable, a laparoscopic removal of an aneurysm or partial splenectomy is done.

Splenomegaly: It was considered to be a contraindication for a minimally invasive approach, but with
technology and the acquired experience have allowed the use of laparoscopic splenectomy in many cases of
splenomegaly. It is strongly suggested that when the spleen is up to 1000 g (or its maximal diameter is up to 15
cm), it should be removed with the laparoscopic approach. However, the laparoscopic technique is correlated
with longer operative times, increased blood loss, higher conversion rates, more peri-operative complications
and longer total length of hospital stay. For that reason, laparoscopic splenectomy in cases of splenomegaly
should be performed by experienced surgeons. When the spleen size exceeds 1000 g the role of laparoscopy is
controversial.However, spleen over 2000 g (or maximal diameter > 23 cm) is considered contraindication for
laparoscopic splenectomy8.

Trauma: Though exploratory laparotomy remains the gold standard treatment laparoscopic approach offers
better detection and identification of possibly simultaneous diaphragmatic and visceral injuries. In a recent study
by Ermolov et al9, it has been shown that although a laparoscopic splenectomy for splenic injury was associated
with significantly longer operating time compared to open splenectomy, patients after laparoscopy had better-
recovering conditions. But in hemodynamic instability and high bleeding rate (> 500 mL/h on serial ultrasound
examinations), the laparoscopic approach should be avoided.

Pre-operative Management
The first management is careful counseling of patient about the procedure. Potential complications should be
reviewed in the pre-operative discussion. Surgical problems like related to anesthesia, Deep venous thrombosis,
Intra-operative bleeding, Infection and overall mortality. Laparoscopic complications like an effect of
pneumoperitoneum, entry injuries and tracer site hernia. Operative splenectomy complications like increased of
left-sided pulmonary complications, postoperative bleed from short gastric or splenic vessels, pancreatic fistula,
left upper quadrant access, injury to adjacent organs and postoperative splenic/portal vein thrombosis.
Treatment-related problems like failure and thrombocytosis. In all patients scheduled for an elective laparoscopic
splenectomy, the spleen size and volume should be preoperatively measured with an abdominal sonography. The
acquired information can be very useful not only for planning the right approach but also for diagnosing
coexistent conditions, which should be intra-operatively evaluated (e.g., cholelithiasis in patients with hereditary
spherocytosis). Patients should undergo also a high-resolution computed tomography of the abdomen, to detect
any existing accessory spleens. In addition, in elective operations, it is recommended that vaccination against S.
pneumoniae, H. influenzae, and N. meningitidis should be carried out preferably 15 d prior to surgery.
Vaccination can be performed also 10 d after the operation, especially when the patient is operated on an
emergency basis. Moreover, it is recommended that patients with autoimmune thrombocytopenia and platelet
count less than 20 × 109/L should be preoperatively treated with corticosteroids and/or immunoglobulins, in
order to reduce intra-operative blood loss.

Standard laparoscopic approach

There is three patient’s position described: anterior, hemilateral and lateral. The anterior position was the first
one described. At this position, omental pouch and splenic hilum are well visualized. Moreover, concurrent
procedures (e.g., cholecystectomy, biopsy) and conversion to open laparotomy (if required) can be easily
performed10. However, it has a disadvantage of moderate visualization and therefore dissection of the ligament
structures and dorsal vessels and procedures in the area of splenic hilum could be burdensome, especially when

224
the hilum is close to the pancreatic tail11. In the hemilateral position,
the patient is positioned in the right lateral decubitus position at an
angle of approximately 45°. The hemilateral position allows easy
division of short gastric vessels and better access to the posterior
surface of the spleen and perisplenic ligaments (described by
Delaitre 1995 “hanged spleen” approach). Additionally, dissection
and ligation of hilar vessels are easier, because the pancreatic tail is
spared. Hemilateral positions are currently preferred by the majority
of surgeons as it is widely adjustable and provides better access to
anatomic landmarks. In the lateral position, a patient’s abdomen is
vertical to the operating table. Here the dissection of ligaments and
hilar landmarks is even easier than in other positions, thus an injury
to the pancreas can be avoided. In a series compared lateral vs
anterior positions, a lateral position was associated with shorter
operative time, fewer peri-operative and postoperative complications and shorter length of hospital stay12. The
first port is inserted just medial to the anterior axillary line at the costal margin depending on patient’s body
habitus and spleen size. Thus, the camera port in this scheme is located to the left of the surgeon. The second
port (5 or 10 mm) is then inserted 2 cm below the costal arch in the midaxillary line. The third port is introduced
near the posterior axillary line near the costal margin. This is a 12-mm trocar to accommodate a linear stapler.
Here, surgeon and camera operator stand on the patient’s right side. If an additional assistant is needed, they will
stand on the patient’s left. For resection of a large spleen, the trocars must be positioned in a more medial and
caudal orientation. Port placement must allow adequate distance from the spleen to avoid inadvertent injury to
the capsule and permit actuation of the instruments, especially the linear stapler.(Figure below)

Operation begins with obtaining abdominal access, usually with an open cutdown technique or Veress needle,
except for patients with massive splenomegaly, due to the high risk of injury. Regardless of checking for
accessory spleens, it is recommended that before initiating splenic mobilization, diagnostic laparoscopy should
be performed. Thereafter working trocars are placed; the placement depends mostly on surgeon’s preference. In
general, one trocar can be placed just off the midline/subxiphoid region in the left subcostal position and another
one can be placed in the anterior axillary line in the left subcostal region. After mobilization of the splenic
flexure, an additional trocar may be placed laterally off the tip of the 11th rib, as it may be highly assistive in
cases of splenomegaly. As, in open surgery some prefer, early ligation of splenic artery (ELSA) by identifying
artery and vein on superior border of pancreas and cliping it. This will devascularize spleen and reduce splenic
size. Then, posterior avascular attachments and short gastric vessels are divided and the spleen is retracted in
order to obtain complete access to the splenic hilum and the pancreatic tail. The splenic hilum is then divided
with an endoscopic stapler with a vascular load. Endovascular stapler provides an easy and stable division of
hilum12. After the hilum division, homeostasis is ensured and staple line bleeding can be controlled with clips or
homeostatic agents. At this point, however, an injury of the pancreatic tail is possible, so when this procedure is
not completely safe, the hilar vessels can be alternatively divided with an electrothermal bipolar vessel sealer or
ultrasonic coagulating shears. These are reported to be safe, providing low blood loss and short operative time.
Now the spleen can be grasped by the handle of the splenocolic ligament placed into a strong bag. Here it is
important to avoid spillage of splenic tissue, especially in patients with malignancies. The spleen is mainly
removed morcellated, except cases where intact removal of the spleen is needed. A use of drainage is not
recommended, but when a pancreatic injury has occurred or is suspected, drainage is mandatory13.

HALS
HALS is an alternative to laparoscopic splenectomy that combines benefits of both open and laparoscopic
techniques. HALS splenectomy can be used with the anterior, hemilateral or lateral positioning. In HALS
surgeon’s non-dominant hand is inserted through hand-assist devices (in order to maintain the
pneumoperitoneum) into the abdominal cavity. Thus, an additional incision 7-8 cm is made in upper or lower
midline or right abdomen. This technique facilitates medial retraction, rotation, and elevation of the spleen.
Moreover, intra-operative complications such as hemorrhage may be better controlled. HALS is generally used

225
in splenomegaly and is associated with fewer intra-operative complications, lower conversion rate, shorted
operative time and therefore the significantly shorter total length of hospital stay14.

Single-incision laparoscopic splenectomy

Laparoscopic splenectomy has been also reported that can safely and successfully be done through a single
incision, using a single port through which the working trocars are inserted in the abdominal cavity. The basic
concepts of laparoscopy are followed in single-incision laparoscopic splenectomy (SILS); an umbilical or peri-
umbilical incision is made and a specific port system is applied; either 2 or 3 single ports through this incision
only, or 1 single-incision port (e.g., SILS™ port of Covidien, Mansfield, MA) are applied. Then the operation is
continued just like standard laparoscopic splenectomy. Undoubtedly, a SILS is considered to be more technically
challenging.

Intraoperative complications
Bleeding is the main intra-operative complication, and the main reason to convert the operation to open. It
usually comes as a result of injuries of the hilar or short gastric vessels, the splenic capsule, and/or splenic
parenchyma during the surgical procedures and especially during the ligation of the vessels mentioned above, or
during the dissection and ligation of the splenic hilum. When an intraoperative bleeding cannot be safely and
promptly managed, the conversion should be considered. Laceration of adjacent organs and structures, especially
the pancreas and gastric or diaphragmatic wall damage can occur. The incidence of pancreatic injury in most
cases results in the pancreatic fistula15. Therefore, it is important to place a drainage tube when a pancreatic
injury is suspected; otherwise, it can be placed postoperatively through a CT-guided cannulation.

Postoperative complications
Early postoperative complications after laparoscopic splenectomy include postoperative bleeding, subphrenic
collections or abscess, deep vein thrombosis, thrombosis of the splenoportal axis, pneumonia and atelectasis,
pancreatitis, ileus, abdominal wall infections, abdominal wall hematomas and abdominal wall hernias.

Portal or splenic vein thrombosis (PSVT), which may occur even within months after surgery and can be proved
lethal. It is a potentially life-threatening complication that can occur within months after surgery16.
Consequences of PSVT are intestinal infarction/intestinal ischemia and portal hypertension. There are some
underlying diseases which are correlated with PSVT like myeloproliferative disorders, hemolytic anemia,
hypersplenism or hematological malignancy and splenomegaly. Interestingly the bigger the size of the spleen,
the higher the incidence of PSVT. Diagnosis of PSVT may be challenging as its symptomatology is unspecified.
Therefore it is recommended that patients with a high risk of PSVT should receive postoperatively
anticoagulation therapy as prophylaxis. When the diagnosis of PSVT is secured, immediate anticoagulant
therapy with intravenous administration of heparin should be started.

Another splenectomy-associated postoperative complication is the overwhelming post-splenectomy infection

(OPSI). OPSI is suspected when a patient after splenectomy presents with sudden systemic infection,
occasionally dermatorrhagia and DIC, whereas no obvious site of the infection is present17. It starts as a simple
respiratory infection, but it rapidly progresses to hyperpyrexia, headache, shivering, jaundice, anuria, septic
shock, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndromes (MODS), coma, and
death. The primary pathogenic bacteria of OPSI are S. pneumoniae, N. meningitides, and H. influenza. Proper
vaccination of patients after splenectomy, an incidence of OPSI has been substantially reduced compared to the
past. Although laparoscopic splenectomy is clearly superior to standard laparotomy in terms of postoperative
infections, an incidence of OPSI remains similar because this complication is related more to spleen removal
than to the surgical approach18,19.

References
1. Delaitre B, Maignien B. [Splenectomy by the laparoscopic approach. Report of a case] Presse Med. 1991;20:2263.
2. Palandri F, Polverelli N, Sollazzo D, Romano M, Catani L, Cavo M, Vianelli N. Have splenectomy rate and main
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Surg Laparosc Endosc Percutan Tech. 2009 Jun;19(3):190-4

LAPAROSCOPIC ANTERIOR RESECTION

Deep Goel, Sarabjit Singh, V.P. Bhalla

RECTAL CANCER
Incidence and epidemiology The incidence of rectal cancer in the European Union is ∼125 000 per year, i.e.
∼35% of the total colorectal cancer incidence, reflecting 15–25 cases/100 000 population per year and is
predicted to increase further in both genders. The mortality is 4–10/100 000 population per year. The mean age
at diagnosis is 70 years but current trends in data shows that it being increasingly diagnosed at younger age
group.

Causative Factors
Aetiologies and risk factors for rectal cancer are different from colon cancer reflecting different environmental
exposures and so also is its treatment strategy. (1,2,3)

Risk and Protective factors

Risk factors Protective factors
High body mass index Healthy lifestyle and exercise
High body or abdominal fatness Consumption of garlic, milk, calcium and
Diabetes type II high dietary
Intake of red or processed meat and Regular use of non-steroidal anti-
Tobacco as well as moderate/heavy alcohol inflammatory
Chronic ulcerative colitis and rohn’s drugs (NSAIDs)
disease Protective effect of vitamin D

Pathogenesis
The majority of rectal cancers develop via the chromosomal instability (CIN) pathway. About 13% are caused
by deficient mismatch repair (dMMR). (4)

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Signs and symptoms
Symptoms due to Primary tumor Symptoms due to Secondaries
Bleeding (present in 60% of Jaundice
patients) Back pain, pelvic pain
Change in bowel habits (43%): Headache and convulsions
Occult bleeding (26%): Hemoptysis
Abdominal pain (20%):
Pelvic pain
Urinary symptoms
Perforation and Peritonitis (3%)

Digital rectal examination (DRE) and a proctosigmoidoscopy play vital role in assessment.

DRE- DRE enables assessment of location, size , upper border ,extent of fixity, , distance of tumor from the
anorectal ring , and extent of circumferential involvement and extent sphincter involvement

Proctosigmoidoscopy-allows delineation of tumor orientation, circumferential involvement and extent of

proximal involvement.

Colonoscopy - A full colonoscopy should be performed because at least 5% of patients with rectal cancer have
synchronous lesions .defined as two or more distinct primary tumors diagnosed within six months of an initial
CRC, separated by normal bowel, and not due to direct extension or metastasis. If full colonoscopy is not
feasible CT colonography or double contrast barium enema can be used as an alternative.
CEA Levels -CEA, has a low diagnostic ability to detect primary CRC, CEA levels are more in cigarette
smokers than in non-smokers However, CEA levels is of value in already diagnosed cases . Patients with pre
treatment CEA >5ng/ml has poor prognosis in comparison with those with low CEA level for same stage. CEA
level help in treatment planning , follow up and in assessment of prognosis.

Endorectal ultrasound (ERUS) - ERUS is a OPD based procedure that can be used to clinically assess the
depth of bowel wall penetration (T stage) and LN involvement (N stage ). Its accuracy in assessing T stage and
N stage is comparable to MRI.(6,7)

MRI:- MRI helps in assessment of tumor location, morphology ,tumor size , extra mural spread i.e Depth of
Invasion (DOI I.e.T stage ) relationship to MRF and sphincters , peritoneal reflection , EVMI ( Extramural
venous invasion) lymph nodes (LN >8mm, irregular border and mixed signal intensity are considered malignant)
, bony metastasis and CRM ( Circumferential Resection Margin).Pelvic MRI with high resolution T2 weighted
images is considered as the best modality for distinguishing T2 from T3 tumors.Distinguishing T1 From T2 is
difficult on MRI .ERUS has edge over MRI is its ability to distinguish T0,T1,T2 tumors which may be helpful
in considering local versus radical resection . However the MRI is superior to ERUS for evaluating the
mesoerctal fascia and pelvic lymph nodes that are remote from the rectum(6,7) . MRI is essential component in
treatment planning . It can help in assessing the need for neoadjuvant therapy.(8)
MRI restaging:- MRI can be used to judge the response to initial treatment . Adequate restaging parameters
include changes in T category, DOI, EMVI, lymph node status, and CRM. The response of the primary tumor
can be assessed based upon the degree of tumor volume reduction, the magnetic resonance tumor regression
grade (mrTRG), and evaluation of the tumor on diffusion-weighted imaging. A greater than 80% volume of
tumor reduction is indicative of a favorable response following neoadjuvant therapy. (9,10)

STAGING
AJCC TNM STAGING OF RECTAL CANCER(11)
Primary tumor (T) includes the following:
TX - Primary tumor cannot be assessed or depth of penetration not specified
T0 - No evidence of primary tumor
Tis - Carcinoma in situ (mucosal); intraepithelial or invasion of the lamina propria
T1 - Tumor invades submucosa
T2 - Tumor invades muscularis propria
T3 - Tumor invades through the muscularis propria into the subserosa or into non-
peritonealized pericolic or perirectal tissue
T4 - Tumor directly invades other organs or structures and/or perforates the visceral
peritoneum
T4a Tumor penetrates to the surface of the visceral peritoneum
T4b Tumor directly invades or is adherent to other organs or structures
Regional lymph nodes (N) include the following:
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 NX - Regional lymph nodes cannot be assessed
N0 - No regional lymph node metastasis
N1 - Metastasis in 1-3 pericolic or perirectal lymph nodes
N2 - Metastasis in 4 or more pericolic or perirectal lymph nodes
N2a Metastasis in 4-6 regional lymph nodes
N2b Metastasis ≥7 regional lymph nodes

Distant metastasis (M) include the following:

MX - Presence of metastasis cannot be assessed
M0 - No distant metastasis
M1 - Distant metastasis

Management Plan-The management for patients with rectal cancer can be complex and highly individualized
process. The management plan is reviewed by a multidisciplinary team and individualized treatment plan is
made. Multimodal therapy that combines radiation therapy , chemotherapy and surgery is accepted as the
standard of care.
Carcinoma in situ and treatment of early cancer (T1N0M0)- Local excision can be used to manage early stage
rectal cancers. The procedures are associated with lesser operative morbidity and better anorectal functioning
,however high local recurrence (11% to 29%) remains the issue of concern(12,13) and necessitates close follow
up.

Criteria for local excision of rectal cancer

Tumor Location and size
With in 15 cm from the anal verge
Diameter < 3cm
Tumor involves < 1/3 circumference of the rectum
Mobile non fixed
T1/N0 in preoperative MRI or ERUS

Histologic features
Well or moderately differentiated
No lymphovascular or perineural invasion
No mucinous or signet cell component
T1 on final histological examination.

Patients undergoing local resection may need radical resection if

1)Final pathological specimen reveals more locally invasive tumor or lesion has other high risk pathological
feature.
2)Patient experiences local recurrence

In general local excision should be offered to patients with low risk disease and one who fully understand that
local excision is a associated with higher risk of recurrence and need for close follow up

T2N0 Rectal Cancer- Standard treatment is radical excision with Total mesorectal excision. If lymph node are
found to be positive , postoperative adjuvant chemotherapy (CRT) is recommended. In very selected T2N0
rectal cancers, neoadjuvant chemotherapy can be considered when a bulky tumor is in proximity to the upper
part of anorectal sphincter precluding sphincter preservation.(13)

Locally Advanced Rectal Cancer (T3-T4/Nx or Tx/ N1-N2)-Patients with transmural and/or node-positive (T3-
T4/Nx or Tx/ N1-N2) disease without evidence of distant metastases, multimodality therapy involving a
combination of TME, Neoadjuvant chemoradiation therapy (CRT), and chemotherapy is indicated. (14,15)

Distant Metastatic (M1) Disease. It is estimated that about half of the patients with rectal cancer will develop
metastatic disease at some point in time. Without treatment, metastatic rectal cancer has a median overall
survival of about 6 months
Management of distant metastasis is complex and challenging task. Treatment strategies are based mainly on
factors related to (1) the primary lesion (related symptoms, resectability), (2) the extent of metastases (sites,
resectability), and (3) the patient factors (age, comorbidities, ability to withstand major surgeryand wishes
regarding quality of life). Systemic chemotherapy is used commonly as the initial treatment modality. After
restaging, resection of the primary and metastatic disease can be considered as either combined or staged
operations. Alternatively, upfront surgical resection, either combined or staged procedures, can be considered in

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patients with limited metastatic disease. In selected patients with stage IV disease, systemic chemotherapy may
provide effective palliation that obviates the need for surgery .

Metastatic rectal cancer can be broadly classified as unresectable and diffusely metastatic, resectable extra
hepatic metastasis and liver only metastasis. Each of these can present either synchronously with the primary
tumour or in a metachronous fashion after treatment of the primary.

Colorectal liver metastases (CRLM):- 60% of patients with colorectal cancer develop liver
metastases.Resection when possible remains the best option, in patients having borderline resectable or
unresectable disease (80% to 90%). combination chemotherapy regimens may convert patients who were
initially inoperable to potentially resectable. Hepatic artery infusion (HAI) chemotherapy has emerged as an
attractive adjuvant t to systemic chemotherapy and may increase the conversion rate to resectable disease.(16, 17)

Principles of surgery
Wide excision of tumor to achieve histological negative proximal, distal andcircumferential margins along with
resection of Mesorectum and lymph nodes up to inferior mesenteric artery pedicle is the target .Sphincter
preservation is done only if its possible to achieve histological negative distal margin .

Total Mesorectal Excision

TME has become standard of surgical care for cancers of rectum. In 1979 Heald and colleagues popularized the
TME technique for rectal cancer, which has since gained widespread acceptance. Sharp meticulous dissection is
done in the avascular (Holy) plane between presacral fascia and mesorectal fascia. TME technique has been
associated consistently with significantly lower locoregional failure rates .(33,34,35) For most middle and low rectal
cancers, the entire mesorectum is mobilized and resected however for upper rectum cancers, usually located
above 10 cm from the anal verge, a tumor-specific excision, in which the mesorectum is divided at a right angle
to the bowel 5 cm distal to the mucosal edge of the tumor. Is sufficinent. Mesorectal excision also preserves the
autonomic nerves and reduces intraoperative bleeding.(18)

Circumferential Resection Margin

The CRM status refers to the adequacy of the surgical resection margin relative to the 360-degree radial
extension of the primary tumor High-resolution rectal MRI with diffusion-weighted sequences can be used
preoperatively to accurately predict involvement of the CRM.To achieve a negative CRM ,total mesorectal
excision (TME) including complete removal of mesorectal fascia enveloping fat pad around the rectum
containing terminal branches of IMA,lymphatics and perirectal lymph nodes.is done, The prognostic
significance of a negative CRM is well established a positive CRM is an independent predictor of LR and
decreased survival; in patients with tumor growth <1 mm from the CRM, local control is obtained in only 34%,
in contrast to patients with a negative CRM, who have a local control rate of 92%. (19,20)

Distal Resection Margin

Distal resection margins (DRMs) of 2 to 5 cm have been the traditional standard in rectal cancer surgery.
Currently most accepted distal margin is 2 cm along with TME.It is found that distal intramural spread is found
beyond 1 cm from the primary tumor in only 4 to 10% of rectal cancers.(21) Currently, the American Society of
Colon and Rectal Surgeons recommends a distal mural resection margin of 2 cm in its most recent Practice
Parameters for the Management of Rectal Cancer (Revised).(22) With the improvement in surgical techniques and
incorporation of neoadjuvant chemotherapy (CT) and radiotherapy (RT) a negative margin of 1 cm or less is
acceptable for low rectal lesions at or below the mesorectal margin and it compares 2 cm margin in terms of loco
regional recurrence rate.(23,24).

Autonomic Nerve Preservation

Injury to the pelvic autonomic nerves can be associated with significant genitourinary dysfunction and
morbidity. Autonomic nerve preservation, as promoted by Enker and colleagues (1995), requires an
understanding of the anatomy of the pelvic nerves . The TME sharp dissection technique facilitates the
identification and preservation of the pelvic autonomic nerves.

SURGERY

Sphinter preseverving rectal resection

1) Anterior resection :- Anterior resection is the gold standard operation for rectal cancer. The tumour bearing
rectum with its mesorectal package is resected and the colon mobilised and anastomosed to the rectal stump.

Low Anterior resection :- When tumor resection is performed below the pelvic peritoneal
reflection. The anastomosis may be either hand sewn or stapled. (25,26)

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 Ultra Low Anterior resection :- When tumor resection is performed below the pelvic floor . (25,26)

2) Inter Sphinteric Resection. ISR was first described Schiessel and colleagues .In ISR, a transanal approach is
used to excised tumor along with part or the entire internal anal sphincter (IAS) after TME, to obtain adequate
distal margin. Restoration of bowel continuity is achieved by performing a hand-sewn coloanal anastomosis.(27)

3) Trans anal excision Trans anal excision is done for a lesion located below the peritoneal reflection and
usually 6 to 8 cm from the anal verge.. Full-thickness excision of the rectal lesion with perirectal fat is done to
achieve negative margin.(28)

4) Transanal Endoscopic Microsurgery - TEM is used to excise mid and upper rectal lesions. Tumors as high
as 10 cm anteriorly, 15 cm laterally, and 18 cm posteriorly can be excised with the TEM approach. TEM
requires a specialized 40-mm diameter endoscope and long endoscopic operating equipment. Carbon dioxide
insufflation facilitates exposure, while a binocular microscope on the TEM endoscope provides a constant,
sixfold magnified 3D 220-degree view of the operative field.(29)

5) Transanal Minimally Invasive Surgery It is a new technique that uses conventional laparoscopic equipment
and single incision laparoscopic to resect lesions in the mid or upper rectum. The port is introduced into the
rectum, CO2 is used for insufflation, and a conventional laparoscopic camera (most commonly a 5-mm 30-
degree or 45-degree scope) is used to visualize the lesion. A full thickness resection with a 1-cm margin is then
performed with laparoscopic graspers and thermal devices. The rectal defect is closed transversely with
absorbable sutures.(30,31,32)

B)
B1) Abdomino Perineal Resection. Abdominoperineal resection (APR) is the operation of choice for low-lying
rectal cancers, recurrent rectal cancers, and as salvage therapy for anal cancers.The procedure involves the
complete removal of the anus (including the sphincter complex), rectum, and distal colon using both anterior
abdominal and perineal incisions, resulting in a permanent colostomy. Both open and laparoscopic approaches
can be used.

B2) Extralevator abdominoperineal excision (ELAPE) It is a relatively new surgical technique for low rectal
cancers ,In this technique levator ani are excised as near as possible to the pelvic wall along with total
mesorectal excision up to coccyx and pelvic peritoneal dissection anterior to Denonvillier's fascia allowing to
excide a cylindrical specimen . This technique not only help in achieving tumor free margin due to wider
excision it also reduces the risk of perforation with cancer cells spillage in the body by avoiding the separation
of levator ani from the rectum. (33,34)

PREOPERATIVE PREPARATION
Preoperative preparation of rectal cancer patients who commonly present with chronic cardiovascular or
respiratory conditions includes a comprehensive medical assessment and “prehabilitation”. Prehabilitation is a
multimodal strategy that includes a nutritional assessment, control of anemia, and an adapted program of
exercises to improve the patient’s cardiologic and respiratory function.

Bowel preparation-- Mechanical Bowel preparation is associated with decrease in the rate of surgical site
infections, anastomotic leakage, and procedure-related hospital readmission Whole bowel irrigation is not
recommended for stenosing tumours.(35,36)
Perioperative preparation

Epidural anesthesia is planned for improved pain control.

Parenteral prophylactic antibiotics are administered just prior to surgical incision Usually a second-generation
cephalosporin, metronidazole, or clindamycin with a cephalosporin, ciprofloxacin or gentamicin, based on
preference or allergy to penicillin or depending on patients’ allergies and/or sensitivities.(28,29)
Other perioperative preventive measures against surgical site infection include tight blood glucose control in
diabetics, hair removal using clippers, and maintenance of normothermia and adequate oxygenation during
anesthesia.

DVT Prophylaxis- To prevent deep venous thrombosis (DVT), all patients should have sequential compression
devices and receive heparin or low-molecular-weight heparin (LMWH) subcutaneously prior to stating surgery
or at the most within 2 hours of surgery.

Low Anterior Resection

Deciding Between an Open or Laparoscopic Approach

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Laparoscopic versus Open technique:- Both procedures have same oncologic outcomes ,however laparoscopy
has added advantage of early recovery and less blood loss.

LAPROSCOPIC LOW ANTERIOR RESECTION

Done in rectal and rectosigmoidal growth located 4 cm proximal to dentate line

Port placement usually 4 to 5 ports are required

1) 10 mm umbilical port for 30 degree camera 2) 5mm port midclavicular port on right side
3) 10 mm port at right iliac fossa 4) 5mm midline port above symphysis pubis

Diagrammatic representation of Port

Position of the patient and operating
Placement in Laparoscopic Low
team
Anterior Resection

Steps
Proper positing – Modified lithotomy with sleep head position( Lloyd Davis position ) with the legs carefully
padded in stirrups, both arms tucked at the side, helps in easy access of mescolon

Scan QR code to see video on Nerve Sparing technique

Laparoscopic Anterior Resection

Ligation of Inferior Mesenteric vessels (Low tie or High tie)-After adhesions have been separated Mesocolon is
opened adjacent to sacral promontory and proceeded upwards. Left ureter and gonandal vessels are identified .
Inferior Mesenteric artery is ligated before and beyond the origin of left colic artery depending upon age and
vascular anatomy by using endovascular staplers ,clips or ligatures. IMV is divided at the lower border of
pancreas.Low-tie arterial ligation with preservation of the left colic artery will result in a more predictable blood
supply to the colon proximal to the anastomosis, but may not give sufficient tension-free length. Low tie is
considered to be helpful in patients with atherosclerotic disease affecting the celiac and superior mesenteric
arteries. (37) High tie is helpful in harvesting a greater number of lymph nodes for histopathological examination
by including the apical (D3) group of lymph nodes at the root of the IMA(38) .However high ligation is associated
with injury to nerve fibers.

Mobilization of Splenic flexure and transaction of left colon- Surgeon shifts his position in between legs.
Dissection is started from left paracolic gutter , renocolic , splenocolic , gastrocolic and pancreaticocolic
ligaments are divided. After the splenic flexure is mobilized left colon is transacted using linear GI stapler.

Mobilization and transection of the rectum – After the splenic flexure is mobilized surgeon goes back to right
side. Incised peritoneum is extended downwards on right side of the rectum towards the pelvis. Superior
hypogastric plexus and hypogastric nerves are preserved. Peritoneum is incised on the left side and in front in U
Shaped manner . Dissection is carried out in avascular plane. Lateral mobilization is done by dividing lateral
liganments. Anterior mobilization is done along the Denonvillier’s fascia upto the apex of prostrate. Rectum is
transected using reticulating stapler.

Anastmosis creation - Anvil is properly placed using polyprolene 2’0 pursue string suture . Circular stapler
cartridge is passed through the anus towards the rectal stump and is perforated just adjacent to the staple line in
middle. Cartridge locked to anvil . After rotating the shaft in counter clockwise direction , the stapler is fired and

232
is held in position for minute. Clockwise rotation 3/4 of circle is done stapler is disengaged and removed.
Completeness of both the doughnuts are checked for completeness . Leak test is done.

Reconstruction Options After Anterior Resection--Reconstruction techniques after an LAR can be divided into
straight coloanal anastomoses (SCA) in either an end-to-end or side-to-end fashion, or creation of a colonic
reservoir with either a colonic J pouch (CJP) or a transverse coloplasty pouch (TCP). The colonic reservoir
techniques were developed in an attempt to improve functional outcomes over an SCA after a very low anterior
resection, but they are technically challenging, and have a higher leak rate and also no long-term (>1 year
postoperatively) differences in terms of continence, leak rate, and overall quality of life have been noted

Diverting stoma and its reversal.--Diverting stomas have been found to not only decreased anastomotic leak but
also reduce pelvic sepsis rate after restorative LAR for rectal cancer. Also there is low likelihood of stoma
reversal in patients who were not diverted initially but who later developed anastomotic leaks. The ileostomy
reversal is usually scheduled 3 months after surgery, however can be postponed if chemotherapy is required.

Complications
Intraoperative complications
1)Hemorrhage- Occur during vascular ligation of the IMA, IMV, or the rectosigmoid mesentery. Presacral
hemorrhage during transabdominal or transanal TME can occur during posterior dissection or anterior dissection
along the incorrect plane by avulsion of the Presaccral venous plexus .Rarely site of bleeding can be anastmosis
2)Rectal perforation It may be identified and repaired at the time of surgery but may present in a delayed fashion
as an abscess, leak, or fistula
3)Organ injury -small bowel, colon perforation, vaginal and bladder perforation have been reported
4)Ureteral injury
5)Urethral injury
6) Iliac vessels injury

Postoperative Complications
1)Anastomotic leaks with pelvic sepsis and anastomotic strictures
2)Urinary dysfunction, including urinary retention ,urinary incontinence,
3)Sexual dysfunctions like retrograde ejaculation and impaired erectile dysfunction in men and impaired vaginal
lubrication in women
4)Defecatory dysfunction leading to fecal incontinence, tenesmus, and fecal urgency (LAR syndrome)

Adjuvant therapy
Radiotherapy
National Institutes of Health Consensus Conference recommended in 1990 that postoperative radiotherapy and
fluorouracil based chemotherapy become the standard of care in T3 and lymph node positive rectal cancers.
These randomized controlled trials showed that radical resection followed by adjuvant chemotherapy and 5
weeks of daily external beam radiation therapy to the pelvis, significantly increased locoregional control and
overall survival.
The Swedish and Dutch trials were the first to demonstrate that pre operative radiotherapy significantly lowered
local recurrence rates. The German Rectal Cancer Group compared preoperative with postoperative CRT (long-
course RT with concurrent chemotherapy) for patients with stage II or III disease. Preoperative CRT was found
to be associated with fewer acute and chronic toxicities and an improved 5-year local recurrence rate.
Locally advanced tumors are now treated with either short-course radiation therapy (5 Gy/day × 5 days)
followed by surgery within 1 week, or long-course chemoradiation (1.8 to 2.0 Gy/day over 5 to 6 weeks to a
total dose of 45 to 50 Gy along with 5-fluorouracil-based intravenous or oral capecitabine chemotherapy)
followed by surgery 8 to 12 weeks later.(39,40,41)
Multiple studies comparing short-course and long-course regimens have shown that they both reduce local
recurrence rates by more than half, but the benefits on OS are less clear.

Follow-up
Follow-up Care in Stage II and III Colorectal Cancer
Guidelines on follow-up care for survivors of stage II and stage III colorectal cancer were issued
by the following organizations:
Cancer Care Ontario endorsed by American Society of Clinical Oncology (ASCO)
European Society of Medical Oncology (ESMO) 2013
National Comprehensive Cancer Network (NCCN)2018
American Society of Colon and Rectal Surgeons (ASCRS) 2015
All four guidelines agree that patients with resected colon cancer (stage II and III) should undergo regular
surveillance for at least 5 years following resection, and that surveillance should include regular reviews of

233
medical history, physical examination, and carcinoembryonic antigen assays, as well as colonoscopy and
abdominal and chest computed tomography (CT). The frequency of the surveillance testing differs as shown in
the table below.

NCCN (2018)
History and physical exam Every 3-6 mo for 2 y, then every 6 mo to 5 y
CEA Every 3-6 mo for 2 y, then every 6 mo to 5 y
Chest CT Every 1 y for 5 y
Colonoscopy At 1 y, 3 y, and 5 y if negative
Abdominal CT Every 1 y for 5 y; scans to include pelvis

Targeted therapy
Targeted therapy in rectal cancer is an emerging tool. Epidermal growth factor receptor (EGFR ) and vascular
endothelial growth factor (VEGF)are over expressed in rectal cancer and have poor prognosis . Current studies
have better outcomes of anti-EGFR and anti-VEGF treatment in management of rectal cancer due to increase
tumor oxygenation and increase drug penetration effect (42) . The currently FDA approved medications are
1)Bevacizumab
2)Cetuximab

Neoadjuvant chemotherapy
Currently role of neo-adjuvant chemotherapy is being investigated. In the phase II/III PROSPECT
(Chemotherapy Alone or Chemotherapy Plus Radiation Therapy in Treating Patients With Locally Advanced
Rectal Cancer Undergoing Surgery) trial, patients with stage II or stage III rectal cancer are being randomized to
receive either six cycles of neoadjuvant FOLFOX (fluorouracil, leucovorin, oxaliplatin) followed by immediate
TME if the tumor has decreased in size by at least 20% (responders) or neoadjuvant CRT followed by TME if
the tumor is stable or has progressed (nonresponders), or a control arm of neoadjuvant CRT for 5 to 12 weeks
immediately followed by TME and eight cycles of adjuvant FOLFOX. This trial is still ongoing and final results
are not yet available, but results from a pilot trial of 32 patients who were treated according to the experimental
arm are encouraging ..(43,44,45)

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Following Neoadjuvant Chemoradiation Therapy. American Journal of Gastroenterology volume 99, pages109–112 (2004).
7. Srinivas R. PuliEmail authorMatthew L. Bechtold JyotsnaB. K. Reddy Abhishek Choudhary Mainor R. AntillonWilliam R. Brugge. The role of
endoscopic ultrasound in the evaluation of rectal cancer ; Int Semin Surg Oncol. 2006; 3: 36; doi: 10.1186/1477-7800-3-36
8. Taylor FG, Swift RI, Blomqvist L, Brown G. A systematic approach to the interpretation of preoperative staging MRI for rectal cancer. Am J
Roentgenol. 2008;191:1827-1835
9. Patel UB, Blomqvist LK, Taylor F, et al. MRI after treatment of locally advanced rectal cancer: how to report tumor response—the MERCURY
trial experience. AJR Am J Roentgenol. 2012;199(1):W35-W42.
10. Yu SK, Tait D, Chau I, Brown G. MRI predictive factors for tumor response in rectal cancer following neoadjuvant chemoradiation therapy—
implications for induction chemotherapy? Int J Radiat Oncol Biol Phys. 2013;87(3):505-511
11. Danielle M Hari, MD, Anna M Leung, MD, Ji-Hey Lee, et al AJCC-7TH Edition Staging Criteria for Colon Cancer: Do the Complex
Modifications Improve Prognostic Assessment? J Am Coll Surg. 2013 Aug; 217(2): 181–190.
12. Joseph M Plummer, Pierre-Anthony Leake, and Matthew R Albert Recent advances in the management of rectal cancer: No surgery, minimal
surgery or minimally invasive surgery .World J Gastrointest Surg. 2017 Jun 27; 9(6): 139–148.
13. Glynne-Jones R, Wyrwicz L, Tiret E, et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann
Oncol 2017; 28:iv22.
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1731-1740.
15. Schrag D, Weiser MR, Goodman KA, Gonen M, Hollywood E, Cercek A, Reidy-Lagunes DL,
16. Gollub MJ, Shia J, Guillem JG, Temple LK, Paty PB, Saltz LB: Neoadjuvant chemotherapy without routine use of radiation therapy for patients
with locally advanced rectal cancer: a pilot trial. J Clin Oncol 2014; 32: pp. 513-518.
17. Ketan R. Sheth, M.D. and Bryan M. Clary, M.D.Management of Hepatic Metastases from Colorectal Cancer Clin Colon Rectal Surg. 2005
Aug; 18(3): 215–223.
18. Luai R. Zarour,1 Sudarshan Anand,2,3 Kevin G. Billingsley et al Colorectal Cancer Liver Metastasis: Evolving Paradigms and Future Directions
Cell Mol Gastroenterol Hepatol. 2017 Mar; 3(2): 163–173.
19. Heald R J, Husband E M, Ryall R DH. The mesorectum in rectal cancer surgery—the clue to pelvic recurrence? Br J Surg. 1982;69(10):613–
616.
20. Quirke P, Durdey P, Dixon M F, Williams N S. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection.
Histopathological study of lateral tumour spread and surgical excision. Lancet. 1986;2(8514):996–999.
21. Adam I J, Mohamdee M O, Martin I G. et al. Role of circumferential margin involvement in the local recurrence of rectal
cancer. Lancet. 1994;344(8924):707–711.

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intramural spread and of patients' survival. Br J Surg. 1983;70(3):150–154.
23. Monson J RT, Weiser M R, Buie W D. et al. Practice parameters for the management of rectal cancer (revised) Dis Colon
Rectum. 2013;56(5):535–550.
24. Kuvshinoff B, Maghfoor I, Miedema B. et al. Distal margin requirements after preoperative chemoradiotherapy for distal rectal carcinomas: are
< or = 1 cm distal margins sufficient? Ann Surg Oncol. 2001;8(2):163–169.
25. Park I J, Kim J C. Adequate length of the distal resection margin in rectal cancer: from the oncological point of view. J Gastrointest
Surg. 2010;14(8):1331–1337.
26. Seow-Choen. Ultra-low anterior resection for low rectal cancer: five key tips to make it easy Techniques in Coloproctology; March
2009, Volume 13, Issue 1, pp 89–94
27. Kim NK, Lim DJ, Yun SH, Sohn SK, Min JS. Ultralow anterior resection and coloanal anastomosis for distal rectal cancer: functional and
oncological results. Int J Colorectal Dis. 2001 Aug;16(4):234-7.
28. Naotaka Murakami ,Yoshito Akagi .Intersphincteric resection for very low rectal cancer: A review of the updated literature. Wiley online
library; https://doi.org/10.1002/ags3.12003
29. Morson BC, Bussey HJ, and Samoorian S.: Policy of local excision for early cancer of the colorectum. Gut 1977; 18: pp. 1045-1050
30. BuessClancy C, Burke JP, Albert MR, O'Connell PR, and Winter DC: Transanal endoscopic microsurgery versus standard transanal excision for
the removal of rectal neoplasms: a systematic review and meta-analysis. Dis Colon Rectum 2015; 58: pp. 254-261
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35. Mattias Prytz, Eva Angenete, Jan Ekelund, and Eva Haglind Extralevator abdominoperineal excision (ELAPE) for rectal cancer—short-term
results from the Swedish Colorectal Cancer Registry. Selective use of ELAPE warranted int J Colorectal Dis. 2014; 29(8): 981–987.
36. Scarborough J, Mantyh C, Sun Z, Migaly J. Combined mechanical and oral antibiotic bowel preparation reduces incisional surgical site infection
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37. Poggio J. Perioperative strategies to prevent surgical-site infection. Clin Colon Rectal Surg. 2013;26(3):168-173.
38. Lange M M, Buunen M, van de Velde C JH, Lange J F. Level of arterial ligation in rectal cancer surgery: low tie preferred over high tie. A
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362–373.
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chemoradiotherapy (COREAN trial): survival outcomes of an open-label, noninferiority, randomised controlled trial. Lancet Oncol.
2014;15:767-774

PANCREATIC NECROSIS
Sushanto Neogi

Pancreatic necrosis is one of the most morbid and controversial consequences (establishment of diagnosis and
most appropriate treatment) of acute pancreatitis. The incidence of acute pancreatitis is increasing at a rapid pace
all around the world. United Kingdom reports 1,85,000 cases of acute pancreatitis per year of which 80% are
because of mainly alcoholism and next by gall stones.1 Acute pancreatitis is found to vary in severity, from mild
self-limiting pancreatic inflammation to pancreatic necrosis which can have life-threatening sequelae. Severity
of acute pancreatitis is mainly linked to the presence of systemic organ dysfunctions with or without necrotizing
pancreatitis.2 Mortality of acute pancreatitis is 2-10% and severe acute pancreatitis develops in 25% of all
patients of acute pancreatitis.2 In Indian subcontinent gall stones is twice more commoner cause as compared to
alcohol as cause of acute pancreatitis.3
Many classification systems have been defined which aid in establishing the morbidity and mortality in patient
so of acute pancreatitis.

Out of them, Classification based on severity4 is one of them

• Mild acute pancreatitis- absence of organ failure and local or systemic complications
• Moderately severe acute pancreatitis- no organ failure or transient organ failure less than 48 hours
with or without local complications
• Severe acute pancreatitis- persistent organ failure more than 48 hours that may involve one or
multiple organs

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 Commonly criteria used for diagnosing organ failure in critically ill patients. (Table1)5

The types of fluid collections seen in acute pancreatitis:

Course of disease in severe acute pancreatitis

The disease follows two main phases.

The first phase

In the first 14 days, there is systemic inflammatory response syndrome because of release of inflammatory
mediators. It might be self limiting by the body’s response and the process stops, but in patients with necrotizing
pancreatitis, organ failure also occurs even without any evidence of infection.
In addition to organ failure, other derangements like hypovolemia (because of increased capillary permeability
and intravascular fluid losses) occur. About 60% of deaths occur in severe acute pancreatitis in the first week
itself.6

The second phase

This phase is dominated by sepsis related complications which is said to result from infection of the pancreatic
necrosis and subsequent sepsis related complications. This is also associated with systemic complications like
renal, pulmonary and cardiovascular failure.7
In the natural course of disease, infection in pancreatic necrosis occurs in approximately 40% to 70% of patients
and is the most important risk factor for mortality. Of all of deaths in acute pancreatitis, two thirds are due to late
septic complications and multi organ failures.8

Diagnosis of pancreatic necrosis

Initial evaluation is of any pancreatitis is by evaluation for hemodynamic instability. Most of mild pancreatitis
may be hemodynamically stable but with increase in severity of pancreatitis the incidence of shock increases.
Evaluation of serum lipase, amylase and C reactive protein is helpful in prognosis and diagnosis. But, serial
measurement of lipase and amylase cannot be used for predicting response or altering treatment.
Imaging studies do not have much role in the initial phases of the disease as there is no evidence to suggest that
early Computer Tomography (CT) improves clinical outcomes. Secondly, the complete extent of pancreatic and
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peripancreatic necrosis usually becomes clear around 72 hours after the onset of acute pancreatitis.9 Presence or
absence of pancreatic necrosis and the percentage of necrosis can be assessed using CT severity score and
prognostication done. Since CT is the most common investigation done, so prognostic scoring using CT have
been developed.

Modified CT Severity Index (CTSI)10

Scores are generated by estimating pancreatic inflammation and necrosis to give a score out of 10.

Pancreatic inflammation
0: normal pancreas
2: intrinsic pancreatic abnormalities with or without inflammatory changes in peripancreatic fat
4: pancreatic or peripancreatic fluid collection or peripancreatic fat necrosis
Pancreatic necrosis
0: none
2: 30% or less
4: more than 30%
Extrapancreatic complications
2: one or more of pleural effusion, ascites, vascular complications, parenchymal complications and/or
gastrointestinal involvement
Total score
Total points are given out of 10 to determine the grade of pancreatitis and aid treatment:
0-2: mild
4-6: moderate
8-10: severe

Treatment
Risk assessment of the patients should be done and patients divided into low risk and high risk patients. Ideally
patients of acute pancreatitis who fall in the high risk group should be treated in Intensive care units (ICU) or
High Dependency units (HDU) with intensive monitoring of vitals and early intervention in case of any
deterioration in parameters.
All treatment starts with supportive care to maintain hemodynamic stability. This involves use of fluid like
normal saline or ringer lactate solutions to refill the intravascular space. Early aggressive fluid therapy is most
beneficial in the first 12 to 24 hours and as high as 250-500ml per hour of crystalloid solutions may have to be
administered. The role is to decrease the blood urea nitrogen.

Oxygen supplementation by nasal prongs should be started in view of hypoxia which is common in almost all
patients of acute pancreatitis. The patients may require Intubation and positive pressure ventilation in case of
respiratory failure.

Role of ERCP is controversial. Based on a variety of studies it is difficult to recommend ERCP in absence of
cholangitis. Prophylactic ERCP has not been shown to alter the outcome in severe acute pancreatitis. 11,12
The next step is pain management. Best management is by using narcotic analgesics but can be modified
according to the patient’s needs.

Routine use of antibiotic in severe pancreatitis is not recommended. It is recommended for extra-pancreatic
infections like cholangitis, catheter related sepsis, pneumonia, etc. If sterile necrosis is found on CT or
ultrasound guided FNAC, use of prophylactic antibiotic is not recommended. In infected necrosis, or those who
do not improve after 7-10 days of conservative management, specific or broad spectrum antibiotic should be
given for 14 days or more. Where required, imipenems, imidazoles and quinolones can delay or sometimes avoid
intervention as they have good pancreatic penetration.13

Role of enteral nutrition is established in mild pancreatitis and should be started as soon as nausea and pain has
subsided. Infectious complications in severe pancreatitis can also be prevented with enteral or naso gastric feed
by preventing transmigration of bacteria across bowel wall. Parenteral nutrition is started only if patient does not
tolerate orally or the caloric requirements are not met by enteral route.14

All necrosis need not be drained. These are also called walled off necrosis (WON) It is only in presence of
infection which can be suspected by air in the necrotic area. In other patients Ultrasound or CT guided FNAC of
the necrosis followed by gram stain and culture is done to prove infection. If any of these are positive, the usual
approach was to surgically drain these necrotic debris in form of surgical necrosectomy.

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Now a days other surgical techniques are available and a step- up treatment for infected pancreatic necrosis is
recommended.

Endoscopic techniques- Endoscopic transmural drainage is the preferred drainage route for WON. The initial
results of endoscopic transmural drainage with a single plastic stent was disappointing because of ineffective
drainage of solid necrotic material by thin caliber plastic stent. Later this was modified in number of ways like,
larger tract dilation, placement of multiple stents, insertion of nasocystic catheter (NCC) along with aggressive
irrigation, use of fully covered self-expanding metallic stents (FCSEMS)/lumen apposing metal stents, and direct
debridement of solid necrotic tissue by endoscopic necrosectomy, These procedures have led on to considerable
improvement in the results of endotherapy and are currently recommended as first line treatment in the step up
approach.15,16

Percutaneous drainage- this was developed because of the morbidity of 30 to 95% and mortality of 13 to 39% in
open necrosectomy. In patients undergoing percutaneous drainage, only 12% progressed to multi organ failure
whereas 40 % progressed in open necrosectomy group, but had no significant difference in mortality.17

VARD retroperitoneal access- (video assisted retroperitoneal access)- this is done by a 5cm incision in the left
flank and the percutaneous drain path is used for direct access and laparoscopic optic introduced through this
pathway and Co2 introduced through the drain tract. Instruments used in open surgery are used for
necrosectomy.18

Open necrosectomy- this procedure has been the standard treatment since time immemorial, but now it is
recommended as the last step in the step up approach when all other methods have failed to completely treat the
patient.19

Bibliography
1. Baron TH, Morgan DE. Acute necrotizing pancreatitis. N Engl J Med. 1999;340:1412–7.
2. Singh VK, Bollen TL, Wu BU, Repas K, Maurer R, Yu S, et al. An assessment of the severity of interstitial
pancreatitis. Clin Gastroenterol Hepatol. 2011;9:1098-103.
3. Tandon RK. Management of Acute Pancreatitis: Indian Guidelines and Protocols. J Gastroenterol Hepatol., 2013; 16:
267-70.
4. Banks PA, Bollen TL, Dervenis C, Goosezen HG, Johnson CD, Sarr MG et al. Classification of acute pancreatitis--
2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62:102.
5. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for Sepsis and Organ Failure and
Guidelines for the Use of Innovative Therapies in Sepsis. The ACCP/SCCM Consensus Conference Committee.
American College of Chest Physicians/Society of Critical Care Medicine. Chest Jl, 1992;101:1644-55.
6. Gloor B, Reber HA. Effects of cytokines, and other inflammatory mediators on human acute pancreatitis. J Int Care
Med 1998; 13 : 305–12.
7. Beger HG, Bittner R, Block S, Buchler M. Bacterial contamination of pancreatic necrosis. A prospective clinical study.
Gastroenterology 1986; 91 : 433–8.
8. Uhl W, Schrag HJ, Wheatley AM, Büchler MW. The role of infection in acute pancreatitis. Dig Surg 1994; 11: 214–9.
9. Working Group IAP/APA Acute Pancreatitis Guidelines. IAP/APA evidence-based guidelines for the management of
acute pancreatitis. Pancreatology. 2013;13:e1-15.
10. Balthazar EJ. Acute pancreatitis: assessment of severity with clinical and CT evaluation. Radiology 2002; 223:603-13.
11. Neoptolemos JP, London NJ, James D, Bailey IA, Fossard DP, Carr-Locke DL. Controlled trail of urgent endoscopic
retrograde cholangiopancreatography and endoscopic sphincterotomy versus conservative management for acute
pancreatitis due to gallstones. Lancet 1988;3:979–83.
12. Fan ST, Lai EC, Mok FP, Lo CM, Zengh SS, Wong J. Early treatment of acute biliary pancreatitis by endoscopic
papillotomy. New Engl J Med 1993;328:228–32.
13. Elmunzer BJ, Scheiman JM, Lehman GA, Chak A, Mosier P, Higgins PD, et al. A randomized trial of rectal
indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012;366:1414–22.
14. Petrov MS, Kukosh MV, Emelyanov NV. A randomized controlled trial of enteral versus parenteral feeding in patients
with predicted severe acute pancreatitis shows a significant reduction in mortality and in infected pancreatic
complications with total enteral nutrition. Dig Surg 2006;23:336–45.
15. Bang JY, Hawes R, Bartolucci A, Varadarajulu S. Efficacy of metal and plastic stents for transmural drainage of
pancreatic fluid collections: A systematic review. Dig Endosc 2015;27:486-98.
16. Varadarajulu S, Phadnis MA, Christein JD, Wilcox CM. Multiple transluminal gateway technique for EUS-guided
drainage of symptomatic walled-off pancreatic necrosis. Gastrointest Endosc 2011;74:74-80.
17. van Santvoort HC, Besselink MG, Bakker OJ, Hofker HS, Boermeester MA, Dejong CH, et al Dutch Pancreatitis Study
Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362:1491-502.
18. Logue JA, Carter CR. Minimally invasive necrosectomy techniques in severe acute pancreatitis: role of percutaneous
necrosectomy and video-assisted retroperitoneal debridement. Gastroenterol Res Pract. 2015;69:3040.
19. da Costa DW, Boerma D, van Santvoort HC, Horvath KD, Werner J, Carter CR, et al. Staged multidisciplinary step-up
management for necrotizing pancreatitis. Br J Surg. 2014;101:e65-79.

238
 HYDATID DISEASE
R S Mohil, Sandhya

Hydatid disease is known to mankind since the time of Hippocrates who called it ‘livers full of water’. he word
has a Greek origin (hudatis) and means watery vesicle. It is a chronic helminthic disease caused by the
metacestode (larval stage) of the tapeworm Echinococcus. There are three known forms of echinococcosis in
humans : a) Cystic hydatidosis caused by E. granulosus , b) Alveolar hydatidosis caused by E.multilocularis, c)
Polycystic echinococcosis caused by E.vogeli. Though all are known to be endemic , mixed infections are
extremely rare. The most commonly encountered among the three is cystic hydatid disease.

E. granulosus cysts most often occur in the liver (70%) or lungs (20%). However, 10% of cysts can be found
anywhere in the body, including the spleen (6%), heart (2%), kidney (2%), and brain (< 2%). E. granulosus
infections usually present as solitary cysts, and have single-organ involvement. In 10–15% of patients, there can
be involvement of two organs depending on the specific geographic region and strain of parasite. The present
review will be covering hepatic Echinocochal granulosis.

LIFE CYCLE
Echinococcus granulosus is a small tapeworm that typically infects carnivores, such as dogs, foxes, and wolves,
after the consumption of offal from infected intermediate hosts, such as sheep or pigs. The adult E. granulosus
resides in the small bowel of the canids (definitive hosts). The gravid proglottids release the eggs that are passed
in the feces. After ingestion by the suitable intermediate hosts (sheep goat etc.), the eggs hatch in small bowel
with the release of oncosphere that penetrates the intestinal wall and enters the circulation reaching the various
organs. In these organs, especially lungs and liver the oncosphere develops into a cyst which gradually enlarge,
producing protoscolices and daughter cysts. The definitive host become infected by ingesting cyst containing
organs of the intermediate host. The protoscolices evaginate and attach to the intestinal mucosa and develop into
adult worms. The humans are called as the accidental dead end intermediate hosts, get infected in the same way
as the other intermediate hosts by the eggs in the contaminated water, food and by handling infected dogs.

Fig 1 : Life cycle of E. grannulosus

Pathology
In human infection, the first stage is the asymptomatic incubation period, during which ingested eggs release
oncospheres that are able to penetrate the human intestinal wall.
These oncospheres enter the portal venous system, which provides access to the liver, lungs, and various other
organs. Next, the oncospheres begin cyst development. Cysts are usually unilocular, and can range anywhere
from 1 cm to 15 cm in diameter. The larva of the E. granulosus after getting lodged into the organs, especially
liver and lungs, forms a chitinous coating around itself. The host body responds by the formation of a fibrous
capsule around the parasite in an attempt to encase it. The parasite cyst gradually grows in size over a period of
time and is covered by various layers. The cyst itself can be divided into endocyst and pericyst. The endocyst is
made up of two distinct layers : a) the inner germinative layer ( the actual live parasite) and b) outer laminated
layer ( protective cuticle layer ). The pericyst also called as ectocyst is formed by the interaction of the endocyst
with the host tissue and it can also be divided into two layers : a) inner exocyst ( an inflammatory layer with the
grannulomatous tissue aimed at resorbing the released antigen from the endocyst) and b) outer adventitial layer (
composed of compressed Glissonian biliovascular elements ).

The hydatid cysts of brain and lungs do not have pericyst. The adventitia is an integral part of the host and
cannot be readily separated from the liver. Separation of exocyst from the adventitial layer is the basis of
239
subadventitial cystectomy for the treatment of hydatid cyst. The cyst formation is a slowprocess and usually
visible to naked eye by 3 weeks. The size increases by almost 1-1.5mm per month. The daughter cyst formation
is considered to be a defensive mechanism and occurs by endogenous vesiculation. These are similar to mother
cyst with the exception of pericyst.

EPIDEMIOLOGY
According to the World Health Organization (WHO), E. granulosus is endemic in areas of South America,
Eastern Europe, Russia, the Middle East, and China, where human incidence rates are as high as 50 per 100,000
person-years. In certain areas, such as slaughterhouses in South America, prevalence varies from 20% to as high
as 95%. The type of strains available and the typical intermediate host vary by region. The most common
intermediate hosts are farm animals, such as sheep, goats, swine, camels, horses, and cattle, as well as mule deer.
Of these, small ruminants, such as sheep and goats, are the most commonly affected. The sheep strain (G1) is the
one most frequently associated with human echinococcal cysts. The WHO has declared echinococcosis as one of
the Neglected Tropical Diseases (NTDs).

CLINICAL FEATURES
The clinical features depend on the organ in which the parasite has lodged itself. The patient with an
uncomplicated cyst could be asymptomatic detected incidentally on some imaging done for some other disease
or the patient can present with nonspecific symptoms like fatigue, weight loss and malaise (especially in children
in endemic area – hydatid cachexia) or it coud be cystem specific like pain abdomen, jaundice, vomiting in
hepatic hydatid cyst; chronic cough, dyspnea, chest pain, hemoptysis, expectoration of membranes in pulmonary
hydatid cyst; headache, dizziness, neurological deficits in CNS involvement.

Complicated liver hydatid cyst : a) suppuration:- The cyst can secondarily get infected by bacteria leading to
suppuration. Then the clinical features are of pyogenic liver abscess. The most common cause of infection is
CystoBiliary Communication (CBC).
b) obscure rupture:- Injury or blie seepage into the cyst can cause the rupture of lamellated membrane resulting
in release of protoscoleses into the space between pericyst and endocyst forming a multivescicular cyst. Clinical
significance of the multivescicular cyst is that the host is exposed to the antigens of the cyst and contents of the
cyst cannot simply be aspirated and also the cyst parasite is viable.
c) free intraperitoneal rupture:- the patient can present with peritonitis, anaphylactic shock or disseminated
abdominal hydatidosis. d) intrabiliary rupture:- i) minor silent rupture with eventual death of parasite; ii)
symptomatic rupture with biliary colic, cholangitis, jaundice and germinal membranes in feces .

DIAGNOSIS
Radiology:- Calcification can be seen on radiographs in up to 30% of Hydatid cyst cases. The calcifications are
usually curvilinear or ring-like, and are deposited in the pericyst. Calcification can progress throughout all stages
of CE. However, it is implied that once a cyst is entirely calcified, the pathogen is inactive/dead.
Ultrasound:- USG is the investigation of choice for the diagnosis of liver hydatid cyst. It’s cheap noninvasive
enables interventional procedure and there is no radiation exposure.

The WHO Informal Working Group on Echinicoccosis (IWGE) originally developed by Gharbi and colleagues
in 1981has classified the CE based on USG characteristics into following categories.
Garbi WHO- Description Status
class IWGE class
CL Unilocular anechoic cyst, with no wall Active
I CE 1 CL + well defined wall + mobile internal echogenicities (hydatid sand) Active
III CE 2 Multivesicular, rosette like, honeycomb like cyst (daughter cysts) Active
II CE 3A Cyst with detached membranes (water lily sign) Transitional
III CE 3B Cyst with daughter cysts in solid matrix Transitional
IV CE 4 Cyst with heterogenous contents without daughter cysts Inactive
V CE 5 Solid cyst with calcified wall Inactive
On ultrasound, the cyst wall usually has a hypoechoic layer, flanked by an echogenic line on either side. The
pathognomonic signs of hydatid cyst in USG are i) Simple unilocular cyst with punctuate echogenic foci-
hydatid sand (protoscolises) seen on moving the patient ii) “floating membrane” – rupture of endocyst & if
rupture is complete –“ water lily sign” iii) multivesicular cyst like honeycomb (rosette) pattern with multiple
septae (daughter cysts) iv) Daughter cysts separated by the hydatid matrix can produce a “wheel-spoke pattern.”
The matrix is composed of detached membranes, which may appear as serpentine linear structures, broken
daughter vesicles, scolices, and hydatid sandv v) cyst wall calcification (USG limited information) USG also
helps in i) screening in endemic ares and family members; ii) planning the treatment; iii) interventions; iv)
intraoperative mapping; v) post-op follow up
240
CT Scan:- Sonographic failures can occur for a multitude of reasons, including obesity, excessive bowel gas,
and previous surgeries. CT has a sensitivity rate approaching 94%, and is helpful in the determination of
position, number and plays a crucial role during the perioperative period for detection of complications, such as
biliary and vascular involvement, cyst ruptures, demonstration of any exogenous vesiculation and any
underlying infection.

MRI & MRCP:- Recommended in i) subdiaphragmetic; ii) extraabbdominal; iii) disseminated abdominal;
iv)jaundiced patients

Serology:- In humans, infection with Echinococcus induces an antibody response, most commonly IgG
(predominantly IgG1 andIgG4), followed by IgM, IgA, and IgE. However, in approximately 30–40% of patients,
no antibodies of any kind are detectable, even in individuals who have circulating parasitic antigens. The
serological tests for the diagnosis of have evolved over time from historical asoni’s intradermal test to the
present day ELISA, IHA and immunoblotting. These utilize native and recombinant antibodies and a hydatid
fluid fraction. Immunoblots reportedly have the highest sensitivity (80%), followed by ELISA (72%) and
immunoelectrophoresis (31%). In the initial phase the protein antigen mixture of hydatid fluid (HF) was used for
ELISA. The results were variable with wide range of sensitivity and specificity. (Se - 64-100%, Sp - 87-100%)
In an attempt to overcome this, ELISA and Immunoblot were done using purified antigens EgAgB (Se - 60-
85%,) & EgAg5 (Se - 50-87%); their recombinant forms RecEgAgB1 (Se - 55-94%); somatic extract of
protoscoleces EgPpsSom (Se - 69-96%) and many other recombinant antigens malate dehydrogenase
(RecEgMDH), the calcium binding protein (RecEgCaBP), the actin filament fragmenting protein (RecEgAFFP),
the RecEgEpC1, the thioredoxin peroxidase (RecEGTPx) with variable results.

The high false negativity has been attributed to cyst location other than the liver, early (CE1) and inactive (CE4
and CE5) cyst stages, serum collection before treatment, single and small cysts. The high variability of the
sensitivities is explained by antigenic diversity (EgAgB1-5) and genotypic variation (G1 & G2). If the
preliminary test with IgG ELISA is negative and there are no imaging or other signs of CE, patients do not
require further work up. However, imaging results suggestive of CE in a seronegative patient necessitate
repeated and extended serologic testing or consideration for medical and/or surgical intervention if the patient is
symptomatic. In patients who are seropositive and have positive imaging findings, a secondary antibody test is
performed, using either an Arc 5 test, IgG4-ELISA, or immunoblot for antibodies against E. granulosus antigens.
Secondary tests are used to rule out false-positive cross-reactivities. However these serological tests are not very
useful in the follow up of patients on treatment as antibodies are known to persist in patients with inactive cysts.
In actuality, many of the serologic tests that have been developed are applicable only for research purposes, and
are not broadly employable in clinical settings, especially in developing countries. Therefore, there is an
emphasis on imaging modalities for diagnosing CE.

ERCP:- With the introduction of MRCP, the indications of ERCP have changed. The ERCP is indicated in the
preop period only when associated with the cholangitis for endoscopic sphinterotomy. The relative indication is
identification of hydatid debries in CBD. Indications of endoscopic sphincterotomy in the postoperative period
are i) hydatid debries in CBD; ii) high output biliary fistula; iii) biliary fistula lasting more than 3weeks; iv)
jaundice; v) stricture at papilla

MANAGEMENT
The hydatid disease can be managed by watch and wait, medical therapy, percutaneous interventions and
surgical interventions.

Watch-and-wait method : The fact that some cysts are heavily calcified and remain as fairly inactive structures
has been used to justify this strategy for cyst types CE4 and CE5. Follow-up with ultrasound in these cyst types
is suggested, as opposed to serologic studies used to assess for activity. Serologic studies are not as reliable
given their results vary depending on cyst stage, location, and size.

Medical therapy:- Medical treatment alone is not satisfactory. It has low cure (10%–30%) and high recurrence
(3%–30%) rates. It should be used as an adjuvant to surgery and percutaneous treatment. Medical treatment can
be used alone in patients who have disseminated disease, who have co morbid diseases precluding surgery, and
who have small (<5 cm) CE1 and CE3a cysts in the liver and lungs. Among the chemotherapeutic agents for
hydatid disease the best studied are abendazole and mebendazole. These are known to selectively bind to the β
tubulin of the parasite resulting in inhibition of the microtubule formation and in turn cell division. Treatment
should be administered continuously for 3 to 6 months. Chemotherapy is a useful adjunctive therapy to
percutaneous treatment or surgery to prevent secondary CE; albendazole is initiated at least 4 days before
surgery (WHO suggests 4–30 days preoperatively) and should be continued for at least 1 month following

241
surgery or percoutaneous procedure. The treatment dosage for a typical 70-kilogram person is 400 mg BID for
28 days. The most common toxic effect is an elevation of liver enzymes during long-term therapy, which can
occur in 20% of cases. As a drug class, benzimidazoles are also known to have suppressive effects on bone
marrow, which usually subside with cessation of the agent. Contraindications include: 1) large cysts that are
likely to rupture; 2) inactive or heavily calcified cysts; 3) early pregnancy; 4) chronic hepatic conditions and
bone marrow suppressive disorders where treatment results in adverse side effects. Addition of praziquantel to
albendazole is said to increase the efficacy of the treatment.

Percutaneous Interventions for Hydatid Cyst:- Ever since PAIR (Puncture Aspiration Injection and
Reaspiration) has been approved by WHO for the treatment of selected types of hydatid cysts, many other
percutaneous approaches have been introduced including MocaT (Modified Catheterisation) and percutaneous
drainage. Indications include WHO-IWGE classification CE1 and CE3a cysts (single compartment cysts) < 5 cm
that have not responded well to medical therapy, and in combination with medical therapy for cysts > 5 cm.
Contraindications are percutaneously inaccessible cysts, superficial cysts due to a risk of spillage, cysts
communicating with biliary structures, inactive cysts, and complex multiseptated cysts.

The well studied PAIR procedure involves aspiration, injection of scolicidal agent, and the reaspiration of
contents. The fluid that is initially aspirated is evaluated for viable proctoscolices, which confirms the diagnosis.
It is also evaluated for biliary–cystic communication by testing for the presence of bilirubin in the fluid. The
scolicidal agent that is injected is left for approximately 15 minutes, after which there is separation of the
germinal membrane from the surrounding cyst. Currently, three solutions are most commonly used: 70–95%
ethanol, 15–20% hypertonic saline, or cetrimide solution. The overall complication rate ranges from 10 to 40%.
The incidence of anaphylaxis is the same as for open surgery (probable range, 0.1% to 0.2%); infection (2% to
10%); local recurrence(0% to 4%); biliary fistulas, rupture, and obstruction (3% to 6%). In one of the systemic
review of literature, the reported rate of anaphylaxis due to percutaneous treatment (PT) is only 0.03%. (the rate
of anaphylaxis secondary to drug reaction in literature is 0.1%) The analysis of the available literature shows that
the traditional fear of lethal anaphylaxis and allergic reactions in PT of echinococcal cysts has been exaggerated.
Favorable results have been reported following PAIR interventions worldwide with follow-up periods exceeding
5 years. Pretreatment and posttreatment chemotherapy is mandatory.

Surgery:- The rationale for surgical management of liver ECs is that the surgery is the most effective treatment
applicable to all cysts, removing the parasite. The cystobiliary communication can be managed by surgery and
has an acceptable morbidity & mortality with low recurrence rate. There are basically two types of surgical
approaches namely radical and conservative.

Radical Surgeries - The rationale for radical procedures is that the total removal of the cyst and exocysts is
associated with the lowest recurrence rate, post-operative chemotherapy and intraoperative protoscolicidal
agents are unnecessary if the cyst is not entered, biliary fistula and cavity-related complications are low, calcified
cysts can be removed and in expert hands the mortality & morbidity are acceptable. Radical procedures are
closed cystectomy, open cystectomy, near-total open cystectomy, subadventitial cystectomy, anatomic &
nonanatomic liver resection and completion cystectopericystectomy in residual cavities. The radical procedures
have low recurrence (0%~3%) and complication (0%~26%) rates but have high intraoperative risk. These
procedures should be performed by experienced hepatobiliary surgeons in hepatic surgery centers.

Conservative Surgeries – These are the tissue sparing procedures, limited to removing the parasite with the part
or most of pericyst left in situ. These procedures can be performed safely by general surgeons without any need
for a specialized team for HPB surgery. Since the liver parenchyma is not entered there is no threat to the hepatic
vasculature and bile ducts. It is applicable to multiple bilateral cysts and when performed correctly the
morbidity, mortality and recurrence rates are acceptable. Conservative surgeries are easy, safe, and rapid, but
with high morbidity (6%~47%) and recurrence (4%~25%) rates. The most common complications are bile
leakage and fistulas and the other known complications are cavity infection and abscesses, intraperitoneal
spillage, vascular injury and bleeding, sepsis, cholangitis, and anaphylactic shock. The main goals of these
procedures are
Safe Decompression of the Cyst - Abdomen is packed with colored packs soaked with scolicidal agent (20%
saline), initial aspiration of 50-100 ml of fluid followed by suctioning the remaining contents is done, extraction
of laminar membrane and daughter cysts if any.

Identification of CBC and sterilization of cyst cavity - Cyst cavity is washed with saline and packed with gauze
pieces which are left in situ for few minutes, removed and inspected for bile stain. If there are no evidence of
CBC definitive sterilization is performed with protoscolicidal agents. The effective scolicidal time of each agent
is different. (10 min for 15%. 20%. and 30% saline; alcohol 96% or70% or 48% or35%; 10% povidone iodine;
10% formalin and 5% chlorhexidlne gluconate, 15 min for 3% hydrogen peroxide, 5 min for silver nitrate,

242
Cetavlon and Savlex ) The number of complications have been said to be associated with instillation of
scolicidal agents like acute toxic reaction, anaphylaxis, hypernatremia, air embolism, metabolic acidosis,
peritoneal adhesions. The caustic sclerosing cholangitis is a serious complication resulting from instillation of
scolicidal agent in case of CBC. The agents which enter the bile ducts result in destruction of mucosa which is
rapid and progressive leading to cholangitis, obstruction bile ducts and detoriation of liver function. Hence the
CBC is an absolute contraindication for the instillation of scolicidal agents.

Management of Cystobiliary Communication - This essentially depends on the number of CBC, type, site, size of
the orifice, the involved bile duct, patient status. Small terminal CBCs can be managed with simple sutures. The
overall procedures have been classified into 5 groups

Suture of CBC (simple suture, suture with T-tube CBD drainage, intralameral pericystectomy )
Internal drainage procedures ( biliodigestive bypass, transduodenal sphincterotomy, internal transfistular
drainage with or without transduodenalsphincteroplasty)
External drainage procedures ( bipolar drainage, cystobiliary disconnection)
Reconstructive procedures ( pericystojejunostomy, intracavitary biliodigestive bypass, bile duct repair)

Management of Residual Cystic Cavity- The residual cavity can be managed by simple closure of the cyst,
marsupialization, external tube drainage, introfexion, capitonnage, omentoplasty, myoplasty.

Laparoscopic approach:- The reported advantages are minimal invasiveness, reduced wound complications, less
postoperative pain, shorter hospital stay, quick social and professional reinsertion. Disadvantages include the
limited manipulation area that increases the operative risk and the potential spillage due to the difficulty in
drainage of the cyst by laparoscopy.

Complications:- Most common complications are surgical site infection, chest infection, subphrenic abscess,
biliary leaks and liver abscess and rarely anaphylaxis. The size of cyst and IL4 levels are reported to be the
independent risk factors associated with perioperative anaphylaxis. As mentioned earlier post op complications
are slightly more frequent with conservative surgeries when compared to radical surgeries while the intra op
complications are more common with radical approach. Any stable external biliary leak for more than 10days is
biliary fistula, managed endoscopically with CBD clearance and papillotomy. The recurrence rate of hydatid cyst
in literature ranges from 0.9% to 30%, the common causes being missed exogenous vesiculation, retained vital
protoscolices or part of germinal membrane.

Follow up:- The patients are followed up with USG once in 6 months during initial few yrs along with
serological tests after 24 months. The rising titres of antibodies is of significance after about 2yrs of surgery.

References
1. Fischer’s astery of Surgery 6th Edition
2. Serological Diagnosis and Follow-Up of Human Cystic Echinococcosis: A New Hope for the Future? Raúl Manzano-
Román, Carlos Sánchez-Ovejero, Ana Hernández-González, Adriano Casulli, and Mar Siles-Lucas. Hindawi Publishing
Corporation BioMed Research InternationalVolume 2015, Article ID 428205.
3. New Options in the Management of Cystic Echinococcosis – A Single Centre Experience Using Minimally Invasive
Techniques. Alexandru Cosmin Popa, Okan Akhan, Marius Septimiu Petruåescu, Loredana Gabriela Popa,Corina
Constantin, Patricia Mihãilescu et al. Chirurgia.2018;113(4):486-496.
4. Surgical approaches to hepatic hydatidosis ranging from partial cystectomy to liver transplantation. Sanjay Goja, Sujeet
Kumar Saha, Sanjay Kumar Yadav, Anisha Tiwari, and Arvinder Singh Soin. Ann Hepatobiliary Pancreat Surg
2018;22:208-215.
5. Open Surgery for Hepatic Hydatid Disease. Erdogan Sozuer, Muhammet Akyuz, Sami Akbulut. Int Surg 2014;99:764–
769.
6. Hepatic Echinococcal Cysts: A Review. Tina Pakala, Marco Molina and George Y. Wu. J Clin Transl Hepatol.2016.
7. Role of Chemotherapeutic Agents in the Management of Cystic Echinococcosis. Yasar Nazligul, Metin Kucukazman,
Sami Akbulut. Int Surg 2015;100:112–114.
8. Factors Associated with Echinococcosis-Induced Perioperative Anaphylactic Shock. Jianrong Ye, Qin Zhang, Yan
Xuan, Siyu Chen, Long Ma, Yongqiang Zhang et al. Korean J Parasitol Vol. 54, No. 6: 769-775, December 2016.
9. Justified Concern or Exaggerated Fear: The Risk of Anaphylaxis in Percutaneous Treatment of Cystic Echinococcosis—
A Systematic Literature Review. Andreas Neumayr, Giuliana Troia, Chiara de Bernardis, Francesca Tamarozzi, Sam
Goblirsch, Luca Piccoli et al. PLoS Negl Trop Dis 5(6): e1154. March 2011.
10. Global Distribution of Alveolar and Cystic Echinococcosis Review Article. Deplazes P et al. Adv Parasitol. 2017

243
 SURGERY IN CARCINOMA GALL BLADDER
Vikas Gupta, Irrinki Santhosh, Yashwant Raj Sakaray

Introduction
Gallbladder cancer though rare, is the most common malignancy of the biliary tract. However its incidence is
higher in areas like Chile, Bolivia, and Ecuador, as well as some areas of India, Pakistan, Japan and Korea. The
raising Incidence over past 20 years may be attributed to improved radiological evaluation techniques, increasing
prevalence of laparoscopic cholecystectomy leading to raise in incidentally discovered Carcinoma Gall badder 1.
Despite the increasing incidence of gallbladder cancer, laparoscopic cholecystectomy has permitted earlier
detection and improved survival of what was once considered a disease associated with a dismal prognosis2.

Role of Surgery in Carcinoma Gall bladder

Complete surgical tumour resection is the only curative treatment for GallBladder Cancer. A complete resection
is often challenging owing the anatomical proximity of Gall bladder to vital structures such as the porta hepatica
and, the propensity for hepatic invasion with early lymphatic metastases 2.
“Radical cholecystectomy” was first proposed by Glenn and Hays in 1954 in which the gallbladder bed with a
rim of liver tissue and lymphatic tissue within the hepato-duodenal ligament were excised en bloc. An “extended
radical cholecystectomy” that was proposed in 1982 differs in that the lymphatic tissue within the hepato-
duodenal ligament, the postero-superior head of the pancreas, with dissection around the portal vein, and
common hepatic artery are removed en bloc with the gallbladder, a rim of liver tissue, and the extra hepatic bile
duct3. During surgical resection, it is imperative to avoid incising the gallbladder or spilling its contents as this is
associated with tumour seeding.
The extent of surgical intervention may range from simple cholecystectomy (Only in T1a lesions ) to being
combined with Extended Right hepatectomy, with or without regional lymph node dissection. At a minimum,
definitive surgery includes removal of involved liver parenchyma as well as regional lymph nodes. While the
appropriate surgical intervention varies with the stage of the disease, there remains a paucity of randomised data
to definitely guide management.

Patents of carcinoma Gall bladder can be divided in to two discrete groups

(1) Disease that presents incidentally following unsuspected laparoscopic cholecystectomy
(Incidental Carcinoma Gall bladder)
(2) Patients with suspected preoperative malignancy of gall bladder
Incidental Carcinoma Gall Bladder:
Incidental gallbladder cancer following cholecystectomy is found in approximately 0.2% to 1.1% of all
laparoscopic cholecystectomies4. When discovered intra-operatively, the procedure should be aborted and the
patient should be transferred to a hepato-biliary centre. Outcomes of patients with an incidental finding of
gallbladder cancer have a better prognosis than non-incidentally-discovered disease, provided the patient is
staged and managed appropriately with R0 resection5. Critically, however, the presence of any residual disease
following attempted resection dramatically reduces disease-free interval and disease-specific survival, with
survival comparable to stage 4 gallbladder cancer. Disease-free survival in patients with residual disease was
reported to be 11.2 months, compared with 93.4 months in patients without residual disease 6.

Pre-Operative Workup
Following referral of cases with incidentally-discovered gallbladder cancer within the gallbladder specimen post-
cholecystectomy, high-resolution imaging is uniformly utilized to evaluate for residual disease, nodal
metastases, and identification of distant metastatic disease. Given associated post-operative changes, the role of
ultrasound imaging is limited. However, review of pre-cholecystectomy ultrasound findings in order to
determine the location of the tumor are often helpful, in addition to discussing intra-operative findings with the
referring surgeon.

Whereas computed tomography (CT) or magnetic resonance imaging (MRI) provide critical information in re-
staging patients following laparoscopic cholecystectomy, the role of fluorodeoxyglucose positron emission
tomography (FDG-PET) is not established. FDG-PET scans have shown a sensitivity of 78% and a specificity of
80% in detecting residual disease7. In addition, FDG-PET helped detect metastatic disease in 29% to 55% of
patients who had undergone cholecystectomy8. Significant false-positivity associated with non-specific FDG-
avidity in the post-cholecystectomy gallbladder fossa has also been elucidated in these studies. A recent report
from our institution correlated CT and MRI findings with FDG-PET scans in patients with gallbladder cancer9.
FDG-PET directs a change in management, however, in only 13% of patients with incidental gallbladder cancer,
compared to 31% in patients with in-situ gallbladder cancer.

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Surgical Re-staging of Incidental Post-Cholecystectomy Gallbladder Cancer
Selection for re-operation is based on surgical staging, as evaluated by the AJCC staging system above. In
general, M1 disease is considered unresectable, with no role for surgical intervention. Approximately one-
quarter of patients with gallbladder cancer have metastatic disease10. Since there is limited role for palliative
surgical intervention in this disease process, unnecessary laparotomy should be avoided, and starting with
staging laparoscopy provides a logical approach in the treatment of incidentally-discovered post-
cholecystectomy gallbladder cancer. In a review by Butte and colleagues to evaluated the role of staging
laparoscopy in patients with incidental gallbladder carcinoma, in 136 patients, staging laparoscopy was carried
out in 46 patients, of whom 10 had disseminated disease 11. Only 2 of these patients, however, had disease
detected during laparoscopy, prior to conversion to laparotomy (yield 4.3% and accuracy 20%). While
disseminated disease was a relatively infrequent event, the likelihood of disseminated disease correlated with
increasing T-stage, positive margin at initial cholecystectomy, and increasing tumor grade. Given the low risks
associated with the procedure, high yield, and significant benefit associated with avoidance of unnecessary
laparotomy in this population, we perform staging laparoscopy in all patients undergoing resection of incidental
gallbladder cancer at our institution.

Timing of Completion Radical Cholecystectomy

There are now data that delaying re-resection of patients with incidental gallbladder cancer may improve patient
selection. Ausania and colleagues reported results using a treatment algorithm with intentional delayed staging
of incidental T2 and T3 gallbladder cancer following cholecystectomy by 3 months. This permitted careful
evaluation for residual disease and extrahepatic spread, as well as observation of the biologic behavior of the
tumor12. Importantly, the authors were able to show that this strategy permitted the avoidance of unnecessary
laparotomy in patients who, arguably, may not have benefited from surgical resection. This was done without
adversely affecting survival in patients who remained candidates for resection. Median overall survival among
the 24 patients who underwent radical resection was 54.8 months. There were 24 patients who were found to be
unresectable on pre-operative imaging and 1 found to be unresectable at operation, in whom median survival
was 9.7 months.

Non Incidental Carcinoma Gall Bladder

Early diagnosis of gallbladder cancer is uncommon in patients presenting with non-incidental gallbladder cancer.
Interestingly, outcomes are significantly worse compared with incidentally-discovered disease, even when
matched for disease stage. Patients present with a wide spectrum of symptoms and signs owing to the advanced
stage at diagnosis which includes jaundice, abdominal pain, abnormal stools, vomiting, and presence of a
palpable mass, as well as non-specific symptoms such as weight-loss, lethargy, and loss of appetite.Infrequently,
patients may present with generalised phenomena related to underlying malignancy, such as venous
thromboembolism (VTE), including migratory thrombophlebitis (Trousseau's sign), or with signs and symptoms
that may be secondary to metastatic disease at presentation, such as shortness of breath in the case of pulmonary
metastases or pathologic bone pain and/or fracture in osseous metastases.

Jaundice as a Presenting Sign

In patients with jaundice as their initial presenting sign, suggests malignant invasion of the porta hepatis. A
retrospective study by Hawkins et al had revealed that not only advanced disease is more likely in patients
presenting with Jaundice but also a significantly worse median disease specific survival when compared to non
jaundiced patients (6 vs 16 months)13. However mere presence of jaundice should not preclude resection in
carcinoma Gallbladder. There are no reported survival differences in patients with jaundice who could undergo
R0 resections which is possible in only 50% of jaundiced patients. Presence of Jaundice should prompt a
meticulous evaluation of patient for resectability and explanation of guarded prognosis in view of advanced
disease and need for extended resections.14 The need for neoadjuvant therapy and need for preoperative
interventions like endoscopic or percutaneous decompression of biliary tree are almost unavoidable in such
patients.

Workup
All the patients should be evaluated with baseline blood investigations like Hemogram, Renal function tests,
Liver Function tests, Coagulation profile. Ultrasonography is the first investigation performed to evaluate the
resectability. Radiologic staging is often carried out using CECT or MRI to evaluate the extent of tumor invasion
and depth, nodal metastases, and distant disease, with an ability to accurately delineate anatomic anomalies and
detect vascular involvement, invasion into the biliary tree, hepatic parenchymal invasion, and nodal metastases.
It is estimated that 75% of cases are already considered unsuitable for resection in non-incidentally-diagnosed
patients. FDG-PET, which is associated with lower false-positive rates than in incidentally-diagnosed post-
cholecystectomy disease, has been utilized with over 80% sensitivity and specificity in differentiating between

245
malignant and non-malignant pathology and is also useful in evaluating the non cerebral extra abdominal and
abdominal metastatic disease15.

Staging Laparoscopy is considered appropriate in patients with carcinoma gallbladder owing to the facts that
there is no role for palliative surgery and also the incidence of occult metastasis is high in Carcinoma Gall
bladder. The benefits of discovering occult metastases at laparoscopy compared with laparotomy are obvious
and include less pain, less morbidity, quicker hospital discharge, more rapid resumption of normal activity, and
earlier start of palliative therapies. In about 48% patients staging laparoscopy shows evidence of metastasis, who
otherwise were considered resectable after the initial staging work up.

Need for Pre-operative Tissue Diagnosis

Gallbladder cancer is characterized by an ability to seed the peritoneum, biopsy tracts, and surgical wounds, and,
as such, unnecessary biopsy may increase the risk of tumor dissemination 16,17. In unresectable patients,
percutaneous biopsy offers a reliable diagnosis with a documented sensitivity of approximately 88%18. Attempts
to provide a pathologic diagnosis by removing the gallbladder are ill-advised, given the significant risk of tumor
spillage. However Preoperative guided Biopsy is indicated in patients who need neoadjuvant therapy, or in
unresectable patients who need palliative therapy. In patients undergoing neoadjuvant therapy biopsy should
preferably planned from non primary lesions like involved lymphnodes whenever possible to avoid spillage from
gall bladder and hence theoretically effecting the chances of peritoneal seeding.

Extent of Surgical Resection of Non-Incidental Gallbladder Cancer

In cases of non-incidental gallbladder cancer, many of the principles discussed following incidental diagnosis of
gallbladder cancer apply, with the principle objective being attainment of negative surgical margins, including
wedge, anatomic, or more extensive hepatic resections, with portal lymphadenectomy, and extrahepatic bile duct
resection only in the attainment of negative duct margins19. Simple cholecystectomy is almost never the
treatment of choice in cases of non-incidental gallbladder cancer, given that T1a tumors, by definition, are
unlikely to present or be detected radiologically in non-incidental disease.

Surgical Treatment Early (T1 and T2) Gallbladder Cancer

Since T1a gallbladder cancer only extends into the lamina propria, a simple cholecystectomy is often considered
sufficient for the treatment of these tumors. With negative margins, cure rate after simple cholecystectomy has
ranged from 85% to 100%20. Therefore, no additional resection is warranted in this group of patients.
With T1b tumors, survival data did not similarly support the concept that simple cholecystectomy would suffice.
Principe et al reported a 1-year survival rate of 50% only following margin negative simple cholecystectomy,
despite lack of invasion of the tumor into the peri-muscular connective tissue21.The reduced survival rate and
importance of radical resection in this setting arises due to a 10% incidence of residual disease and 10-20%
incidence of lymph node metastasis. There is a potential locoregional recurrence rates of up to 20% to 50% 22.
Radical resection, including re-resection of the hepatic bed (segments IVB and V) and portal nodal
lymphadenectomy, is recommended for T1b tumors detected incidentally post-cholecystectomy.

With T2 tumors, early studies showed 5-year survival rates of 20% to 40% after cholecystectomy, compared
with 70% to 80% in patients who underwent radical resection23,24. While residual disease rates are, once again,
increased with increasing T-stage, nodal involvement is thought to occur in approximately one-third of cases.
Radical resection, including re-resection of the hepatic bed in an operation that includes segments IVB and V,
with portal nodal lymphadenectomy, is recommended for T2 tumors. Re-resection additionally provides accurate
staging information, which allows patients to be referred for appropriate adjuvant therapy.

Of recent interest in the treatment and selection of patients for resection with T2 disease is tumor location. In a
recent multi-institutional study by Shindoh and colleagues, the authors examined 437 patients with gallbladder
cancer who were analyzed with tumor location defined as “hepatic side” or “peritoneal side” given the anatomic
discrepancy described above between the 2 locations25. The authors showed that in patients with tumors on the
hepatic side, patients had higher rates of vascular invasion, neural invasion, and nodal metastases when
compared with tumors located on the peritoneal side (51% vs. 19%, 33% vs. 8%, and 40% vs. 17%,
respectively). Five-year survival rates were 64.7% versus 42.6% (p=0.0006) for peritoneal and hepatic tumors,
respectively, with tumor location serving as a predictor of liver and distant nodal recurrence despite radical
resection. Additional studies have confirmed the importance of tumor location in T2 disease, and even
recommended reservation of radical resection for T2 cancers located on the hepatic side26.

Surgical Treatment of Advanced (T3 and T4) Gallbladder Cancer

Treatment of T3 incidental gallbladder cancers is similar to T2 cancers, and includes a radical resection of the
gallbladder fossa with portal nodal lymphadenectomy. Outcomes following radical resection of T3 disease,
range widely from 21% to 63%, with an operative mortality below 5%. The incidence of residual disease and

246
lymph node metastases is higher again, estimated at 36% and 46%, respectively27. With advanced disease stage,
the need for more extensive hepatic and bile duct resections are often indicated to attain a negative surgical
margins28.

In the case of T4 disease, the role of extensive vascular reconstructions in the treatment of gallbladder cancer has
not been shown to provide a durable survival benefit. The peri-operative morbidity and mortality associated with
extensive reconstructions generally outweigh any survival benefit, and extensive resection and vascular
reconstruction is generally not recommended. The role of neoadjuvant therapy in the treatment of advanced
gallbladder cancers (T3 and T4) is discussed below.

Surgical Treatment of the Extrahepatic Bile Duct

Routine resection of the extrahepatic bile duct has not been uniformally associated with improved outcomes29.
Rather, resection of the common bile duct has been shown to increase peri-operative morbidity, with little
additional benefit when performed empirically30. Unless there is a positive cystic duct margin to warrant
additional re-excision, bile duct resection can be avoided. In cases where there is concern, intra-operative frozen
section of the cystic duct stump margin can help determine the need for Hepatic duct resection (HDR). If
detected, a positive duct margin warrants bile duct excision in order to ensure negative margins. In this setting,
bile duct resection may be performed following adequate exposure with a Kocher maneuver and division of the
duct at the level of the duodenum. Reconstruction is then carried out with a Roux-en-Y hepaticojejunostomy. In
the case of jaundice arising from malignant infiltration of the bile duct, the prognosis is often poor, so a biliary
stent and neoadjuvant chemotherapy is warranted31. Finally, resection of the extrahepatic bile duct has not been
associated with a more effective portal nodal lymphadenectomy.

Surgical Treatment of the Hepatic Margin and Extended Liver Resections

In terms of radical re-resection, recommendations for liver resection have varied from limited 2cm wedge
resections of the gallbladder fossa to routine extended right hepatectomy. In reality, the size of the wedge liver
resection will depend on the pathologic depth of the tumor and stage of disease, ranging from limited segment
IVB and V wedge resections, to formal anatomic resections. With the aid of intra-operative ultrasound, vascular
anatomy should be delineated to guide the resection margin, ensuring full tumor clearance and identifying
branches of the middle hepatic vein to allow for a controlled transection. Pedicles to segment 4b can be dissected
in the umbilical fissure and divided before parenchymal transection begins. The main right anterior sectoral
branches must be carefully preserved, although the pedicle to segment V is often also divided. In larger tumors,
dividing the entire right anterior pedicle may be necessary. Pringle occlusion of the hepatic vascular inflow is
helpful during parenchymal transection.

With respect to extended hepatic resections, if the tumor invades hepatic inflow vascular structures, particularly
the right portal vein with larger tumors, a right hepatectomy may be required in order to ensure adequate tumor
clearance and an R0 resection. The importance of meticulous pre-operative planning must not be underestimated
in this setting. If clearly visualized, right inflow involvement may be used as justification for administration of
neoadjuvant chemotherapy. This provides an opportunity for response to therapy to be determined, with potential
avoidance of an unnecessary extensive operation. In cases where extended hepatectomy is necessary, bile duct
resection is often also necessary, due to the size of the tumor. In a study by D'Angelica and colleagues, empiric
resections of liver (15 of 36 patients) and bile duct (32 of 68 patients) did not predict outcome after resection for
gallbladder cancer. Instead, there was an increased rate of peri-operative morbidity among patients who
underwent major hepatectomy and common bile duct excision, with outcome correlating only with tumor
biology and disease stage. These data are used to justify our approach of using extensive resection only as
needed to clear disease.

Finally, in well-selected patients, the resection of other organs, including stomach, colon, and duodenum, in the
absence of distant metastatic disease, may be resected to ensure an R0 resection. Combined
pancreaticoduodenectomy with hepatectomy can be performed but there is considerable morbidity associated
with such procedures.

Need for Lymphadenectomy :

Lymph node dissections have historically ranged from excision of the cystic duct lymph node to a complete
portal lymphadenectomy with pancreaticoduodenectomy in the Japanese literature 32. In our experience, the
addition of hepatic and pancreatic resections contributes to additional morbidity without significant improvement
in long-term survival, and is not recommended.
The presence of N1 nodal disease is not considered an absolute contraindication to surgical resection. Presence
of nodal metastatic disease adversely affects the long term survival. More extensive nodal involvement that
extends outside the hepatoduodenal ligament (N2) is considered unresectable, given the major post-operative
morbidity and mortality associated with resection without any significant survival benefit 33. Additional celiac

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and para-aortic lymph node metastases are considered M1 disease, and surgical resection is contraindicated. The
highest peri-pancreatic lymph node marks the transition between the N1 and N2 fields, and has been found to be
prognostic of disease-specific and recurrence-free survival in biliary tract adenocarcinoma in a retrospective
study34.

At laparotomy, every effort should be made to carefully examine lymph nodes outside the radical resection field.
As such, the exploration should begin with a Kocher maneuver to evaluate aortocaval and retropancreatic nodes,
with careful examination of celiac nodes. Any suspicious nodes should be evaluated intra-operatively with
frozen pathologic assessment, and, if positive, the procedure should be reconsidered.

A standard portal lymphadenectomy for gallbladder cancer beyond T1a includes nodes in the porta hepatis,
gastrohepatic ligament, and retroduodenal space (N1 nodes). While resection of those nodes has never been
evaluated in a prospective setting to determine whether there is any positive effect on survival, lymph node
evaluation in this setting provides accurate staging and prognostic information at the very least. Indeed, the
detection of lymph node disease, particularly in early stage gallbladder cancer, may influence the decision to
administer adjuvant systemic Chemotherapy.

Outcome after surgery

Gallbladder cancer is generally considered to confer a poor prognosis as the tumour typically remains silent until
an advanced and often non-curative stage. Historically gallbladder cancer had an overall 5-year survival less than
5%. The recent advent of aggressive surgical resection with advances in perioperative care has markedly
improved outcomes. Ongoing improvements in surgical techniques have resulted in a decline of both morbidity
and mortality. In patients who undergo R0 curative resection, 5-year survival, by contrast, is 21–69%.
Nevertheless, the French Surgical Association has demonstrated that 85% of T3/T4 tumours have an overall
survival of only 2–8 months.

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heterozygosity in patients with gallbladder stones suggest causal association with gallbladder cancer. Ann Surg. 2014;
260:1073–1080.
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fluoro-2-deoxy-D-glucose for gallbladder cancer diagnosis. Am J Surg. 2004; 188:171–175.
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a case report. Surgery. 1993; 114:120–124.
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iatrogenic tumor dissemination. Arch Surg. 1993; 128:1054–1056.
18. Akosa AB, Barker F, Desa L, et al. Cytologic diagnosis in the management of gallbladder carcinoma. Acta Cytol. 1995;
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11:985–994.

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20. Shirai Y, Yoshida K, Tsukada K, et al. Radical surgery for gallbladder carcinoma. Long-term results. Ann Surg. 1992;
216:565–568.
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Hepatogastroenterology. 2006; 53:660–664.
22. de A,X, Roa I, Burgos L, et al. Gallbladder cancer in Chile. A report on 54 potentially resectable tumors. Cancer. 1992;
69:60–65.
23. Shirai Y, Yoshida K, Tsukada K, et al. Radical surgery for gallbladder carcinoma. Long-term results. Ann Surg. 1992;
216:565–568.
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and management. Ann Surg. 1996; 224:639–646.
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22:2779–2786.
27. Dixon E, Vollmer CM Jr. Sahajpal A, et al. An aggressive surgical approach leads to improved survival in patients with
gallbladder cancer: a 12-year study at a North American Center. Ann Surg. 2005; 241:385–394.
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11:985–994.
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Surg 2011. 35:1887–1897.
30. D'Angelica M, Dalal KM, DeMatteo RP, et al. Analysis of the extent of resection for adenocarcinoma of the gallbladder.
Ann Surg Oncol. 2009; 16:806–816.
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gallbladder cancer. Ann Surg Oncol. 2004; 11:310–315.
32. Matsumoto Y, Fujii H, Aoyama H, et al. Surgical treatment of primary carcinoma of the gallbladder based on the
histologic analysis of 48 surgical specimens. Am J Surg. 1992; 163:239– 245.
33. Niu GC, Shen CM, Cui W, et al. Surgical treatment of advanced gallbladder cancer. Am J Clin Oncol. 2015; 38:5–10.
34. Kelly KJ, Dukleska K, Kuk D, et al. Prognostic significance of the highest peripancreatic lymph node in biliary tract
adenocarcinoma. Ann Surg Oncol. 2014; 21:979–985.

CURRENT CONCEPTS IN COMPONENT SEPARATION

Pramod Shinde

Introduction
In Ventral hernia repair , closure of the defect is one of the most significant challenges, especially in a wide
defect, recurrent hernia, large hernias with loss of domain and Obesity. Laparoscopic repair introduced by Karl
Le Blanc in 1993, brought with it an era of “bridging repair” without closure of defect. Now many publications
have underlined the advantages of closure of defect. Defects larger than 6 to 8 cms in the midline cannot be
closed primarily, without some form of “release” procedure in order to bring the widely separated, Rectus
Abdominis and lateral abdominal wall, back to their paramedian location and reconstitute the Linea alba. This
release technique constitutes and is named as “ omponent separation”.

The first such technique was introduced by Ramirez in his landmark paper in 1990: He proposed and
demonstrated that large midline defects ranging from 6 cms to 20 cms could be closed by taking an incision on
External Oblique aponeurosis lateral to the Leinea semilunaris on both sides. This brought in an era of
Component separation.

The need for Midline closure

Laparoscopic IPOM repair gave rise to Bridging technique, where a mesh could be put without closing the
defect. This gave rise to problems like higher Seroma rates, persistent bulge after surgery, prolapsing of the mesh
into the defect, pseudo-recurrence and sometimes true recurrence. Loss of midline alignment of Recti and Linea
alba give rise to a significant loss of Abdominal wall function causing:
 Lack of Spine support promoting Lordosis and backache,
 Lack of effective Valsalva manoeuvres causing difficulty in micturition, defaecation and parturition,
 Lack of satiety causing unwanted eating and obesity,
 Lack of adequate respiratory function,
 Progressive widening of defect ultimately leading to loss of domain.

This has brought back the focus on achieving midline closure in all Abdominal Hernia repairs: the EHS
guidelines also recommend closure of midline defect, even using Component separation techniques when defects
are larger.

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Most recently, a large study has also supported reduction in recurrence rate after closure of defect in Ventral
hernia repair.

Types of Component Separation

Many types of Component separation were introduced in the last decade:
After Anterior component separation, Carbonell described the posterior component separation in which a plane
was developed between Internal Oblique muscle and Transversus abdominis , and mesh was inserted in a
retromuscular position.
Yuri Novitsky developed an innovative technique of “ Transversus Abdominis release: the TAR procedure.
Anterior component separation and Posterior component separation were the two main types which evolved over
the years as robust techniques.

Anatomical Basis of Component separation

The Abdominal wall consists of two paramedian vertical muscles, the Recti enclosed in the Rectus sheath, and
three flat muscles which extend from paraspinal region to the lateral border of the Rectus sheath; they extend
from the Costal margin to the Iliac crest and the Pubic rami. The Transversalis fascia is an investing layer below
the Transversus Abdominis.
The nerves arising from the spinal column travel between the Internal Oblique and the Transversus Abdominis
muscle, up to the Linea semilunaris and then enter the Rectus Abdominis at its lateral border after entering the
Rectus sheath space: thus the space between the External Oblique and Internal Oblique muscle does not contain
any major traversing nerves: this forms an important part of the basis on which Anterior Component separation
rests.

The three lateral muscles meet medially to form the

Linea semilunaris and the Rectus sheath: however,
they do not meet at the same point or line, as
described traditionally in old anatomical text books:
the two significant points to be noted are:
1. The Internal Oblique muscle divided into
two lamellae: the anterior and the posterior;
the posterior lamella merges with the
posterior Rectus sheath.
2. The Transversus abdominis muscle is
inserted into the posterior rectus sheath
medial to the attachments of the other two
flat muscles, just below the posterior
lamella of the Internal Oblique muscle.

These facts discovered by Dr Yuri Novitsky gave rise to the TAR procedure: thus the Posterior rectus sheath
composed of the posterior lamella of the Internal Oblique can be incised vertically in its lateral part to reveal the
muscular fibres of Transversus Abdominis muscle. These fibres can then be divided, so that the Transversus
muscle is released from its insertion.

Indications for Component Separation in Hernia repair

Component separation is a complex procedure with its owns set of complications and morbidity: hence it is
undertaken in the following indications:
1. Large midline defects measuring more than 6 to 8 cms.
2. Loss of Abdominal wall due to resection for any cause, trauma, or infection
3. Removal of infected mesh with closure of defect
4. Loss of domain inorder to increase the intra-abdominal space and facilitate defect closure
5. Non-midline hernias with large defects
6. For treatment and prevention of raised Intra-abdominal pressure.

Preoperative workup
All patients will need routine biochemical and physiological tests to evaluate the fitness for a major surgery,
detection and control of co-morbidities, and tests related to planning and execution of hernia repair:

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Investigations related to evaluation of hernia and its surgery:
1. Clinical exam:
 This needs to be focussed on almost all the aspects of hernia:
 The site of hernia is a significant factor. Midline hernias also need to be evaluated as per their site;
upper abdominal hernias reaching up to Xiphisternum will be more difficult to repair due to proximity
of ribcage and retrosternal area. Non-midline hernias will add to the complexity of the repair
 Size of the defect is the most important factor to determine whether Component separation will be
necessary or not: the transverse diameter is more important in the midline hernias, hence should be
measured with a scale. Associated divarication should also be measured in terms of both dimensions
 Reducibility is an important factor and should be attempted gently in all patients.
 The skin on the hernia and surrounding region has to be evaluated for scars, fixity to underlying bowel,
thinning, ulcerations and infection.
 Condition and tone of the Abdominal wall is to be evaluated in recumbent, head-raising and erect
posture. In case of multiple scars, pliability of wall will be an important factor.
 Abdominal fat in the subcutaneous region and intra-abdominal has to be evaluated.
 Lastly, loss of domain has to be judged, although there are no accurate criteria to do so clinically

2. Ultrasound:
 Ultrasound is a versatile imaging modality which is not being used to it’s full potential: hernia size
contents and occult defects can be evaluated. Intra-abdominal associated pathology is always the main
focus; however, Abdominal wall anatomy can be beautifully demonstrated with Ultrasound.
 This is specifically used to delineate 1. the margins of the defect, Recti and their separation and 2.
marking of the Linea semilunaris.

3. CT Scan:
 CT Scan forms the mainstay of investigation for a large, complex and recurrent as well as Incisional
hernia. Apart from the review of intra-abdominal contents and ruling out other pathology, every other
aspect of hernia and Abdominal wall should be
 Contents of hernia sac, their volume, type, vascularity of contents, loculi, multiplicity of defects are
evaluated; abnormal findings should be looked for. Here, volumetry of the Sac and Abdominal cavity is
done and the ratio calculated in order to determine whether there is loss of domain.
 The defect is then evaluated for its site, size in both dimensions, surrounding adjacent structures and
presence of (previous ) mesh if any.
 The abdominal wall anatomy is the next important part: The Recti have to be evaluated for their
separation, width, atrophy, scars and relation to hernia defect. Then the flat muscles have to evaluated
for individual anatomy, presence or absence of any, any defects and even their thickness in millimeters,
and relation to hernia defect.
 The Linea Semilunaris is one of the most important landmark to look for and describe.
 Bowel type in the sac and intra-abdominally, adhesions, fistula, proximity to mesh, vascularity, kinks
and cut-offs all need to be looked for
 Lastly identification of previous mesh and fixation is a challenging part: surrounding fat stranding,
adhesions, collections, fistulisation needs to be documented.

4. Respiratory function: In the setting of large ventral hernias requiring Component separation, respiratory
status, its health and insufficiency has the most important bearing on postoperative outcomes and decision
making at all stages, since all these procedures raise the intra-abdominal pressure and can precipitate
respiratory insufficiency .

Preoperative optimisation
Although almost all comorbidities are important to control, Smoking, Obesity and Hb1ac have been shown to
have a direct bearing on the outcomes.
1. Smoking: this is known to have delayed healing due to deficient collagen building and hence higher
recurrence rates. Also the nicotine is known to be associated with tissue ischaemia adding to tissue (
Skin flap) necrosis and delayed healing. The present recommendation is to stop smoking for a minimum
period of four weeks before surgery.
2. Obesity: Obesity with BMI above 40 is known to have higher recurrence rates, approaching almost 100
percent above BMI 50. Raised intra-abdominal pressure due to visceral fat inside the abdomen leads to
recurrence rates apart from surgical site occurrences and medical problems. Hence BMI above 40
should undergo medical or surgical weight loss, unless the patient presents in an emergency setting. If
forced to operate due to Obstruction, it would be prudent to defer definitive repair to a later date after
weight reduction.

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 3. HbA1c: Peri-operative hyperglycaemia has been shown to increase surgical site infection rate. Hence
the recommendation is to bring the HbA1c below 7 before undertaking surgery.
4. Infection: although we do not have a uniform policy of investigating for MRSA colonisation in India,
this and any other infection will have a direct bearing on the outcome of surgery.

Anterior Component separation

The classic open Anterior Component separation procedure necessitates raising of large skin flaps so that the
External Oblique aponeurosis is exposed lateral to the Linea semilunaris. This can and does lead to skin flap
necrosis in a large percentage of patients due to interruption of the perforators supplying the Skin. This fact gave
rise to many modifications like Peri-Umbilical Perforator sparing Anterior component separation and
Endoscopic Anterior component separation. Thus the different types of Anterior Component separation
techniques are:
1. Classical Open Anterior Component Separation
2. Peri-Umbilical Perforator sparing Anterior component separation
3. Endoscopic Anterior Component Separation ( Subcutaneous technique)
4. Endoscopic Anterior Component Separation ( Sub-External Oblique technique)

ANTERIOR COMPONENT SEPARATION: OPEN SURGERY TECHNIQUE

Background
Complex Abdominal Hernias with large defects have been repaired with various techniques: However, Midline
closure of Abdominal wall with defects more than 8 cms, has always been a problem, till Ramirez came up with
his paper in 1990, describing Anterior Component Separation. This technique made it possible to mobilise the
anterior Abdominal wall and close the defect. Soon many modifications came up to obviate the need to avoid the
necrosis of skin flaps.

Indications
1. Large midline defects more than 6 to 8 cms
2. Closure of Abdominal wall (midline)defects due to trauma, sepsis or malignancy
3. Abdominal Compartment Syndrome, either to treat or prevent raised IAH.

Technique
1. Opening the Abdomen with excision of diseased skin, bad scar, previous Skin Graft, or Ulcer.
2. Reduction of Hernial Contents to Abdominal Cavity.
3. Adhesiolysis: it is important to free the Abdominal Wall completely upto the Anterior Axillary line
4. Raising the skin flaps: the skin flaps have to be raised beyond the Linea Semilunaris till Anterior
Axillary line and sometimes even beyond that, to expose the External Oblique Aponeurosis. The Flaps
have to be raised from Costal Margin to inguinal region. The External Oblique Muscle is now incised 1
to 2 cms lateral to the Linea Semilunaris, from the Costal Margin to Inguinal Region: in Upper
Abdominal defects, the Incision shoud be extended above the Costal margin.

Adhesiolysis Raising the skin flaps

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 Raising the skin flaps Raising the skin flaps

5. Separation of External Oblique from the Internal Oblique Muscle: this plane is avascular: this dissection
can be extended all the way up to mid-Axillary line. This will release the underlying Internal Oblique
and Transversus Abdominis Muscle so that the Rectus muscle, sheath and the Linea alba can be pulled
towards midline for closure
6. The same procedure is repeated on the other side.

7. Mesh placement: this can be done either in the Retro-rectus plane or as an Onlay: In the Onlay method,
a large mesh is used to cover entire Abdominal wall from the lateral cut edge of External Oblique
Aponeurosis to the other.
8. Reconstitution of midline: The Linea alba is recreated by suturing the medial edge of Rectus sheath to
each other in the midline by using a nonabsorbable suture: in case of Retro-Rectus mesh placement, the
posterior Rectus sheath and the anterior Rectus sheath is closed separately.
9. Skin closure is done after placing drains to drain the large subcutaneous space.

Precautions to be taken during the Surgery

1. Skin flaps vascularity should be preserved as far as possible by limiting dissection, preserving subcutaneous
fat with the Skin, deliberate preservation of perforators, etc.
2. Watch for raised Intra-abdominal pressures during closure by monitoring the peak airway pressures.
3. Use Macroporous Mesh
4. Prevent contact of Mesh with the Skin.

Complications
1. Raised IAP
2. Wound Infection SSI
3. Skin flap Necrosis
4. Mesh Infection
5. Intestinal Obstruction
6. Peritonitis due to missed/delayed Intestinal Perforation
7. Recurrence

Peri-Umbilical Perforator sparing Anterior Component Separation

The morbidity of Surgical site occurrences and skin flap necrosis prompted many variations of techniques to
preserve the periumbilical perforators: One of the first such techniques was reported by Dr Dumanian.
Ramirez’s paper showing Open Anterior component separation clearly shows the perforators to skin flaps being
divided. In order to preserve these perforators. Techniques to preserve them were developed: one of them was to
take an incision in the subcostal space parallel to it, create a tunnel lateral to linea semilunaris and divide the
External Oblique through the tunnel.

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The other technique is to leave the Umbilicus ant the connecting skin intact and work around it to divide the
External Oblique: this was proposed by Maas et al. This technique although being used in some centres, has now
being overtaken by the Endoscopic Component separation technique. Some results of this technique are listed
below in the table.

Publication n Wound occurences Followup Recurrence

months
Sukkar et al, 2001 51 13.7 % 24 3.9%
Saulis et al, 2002 41 4.9 7.3%
Butler % Campbell 38 26.3 12.4 3%

Technique of Endoscopic Anterior Component Separation:

Endoscopic Component separation was introduced by Lowe et al. They describe a sub External Oblique
technique. Same procedure was done by Jorge Daes using a subcutaneous approach to divide the External
Oblique. A single port technique has also been described. (Single port component separation: endoscopic
external oblique release for complex ventral hernia repair.

Subcutaneous Technique
Linea semilunaris is marked on the Skin using Ultrasound. An incision is taken lateral to the Linea semilunaris
for placement of balloon and trocar: this port is placed in the lower quadrant for upper Abdominal hernias and
vice versa. The subcutaneous space is expanded with balloon. A camera port is inserted in the subcutaneous
space either in subcostal region or lateral iliac fossa, lateral to the Linea semilunaris
 The subcutaneous space is expanded using Co2 or Telescopic dissection
 Once the space in developed from Costal margin to Inguinal region, additional working port is inserted
 Then The External Oblique aponeurosis is incised (cut) lateral to the Linea semilunaris, from costal
margin to Inguinal region.
 The edges of cut External Oblique are separated.
 Additional dissection done between External and Internal Oblique.
 This procedure is repeated on both sides.
 This releases the underlying muscles so that closure of midline becomes possible

The Sub- External Oblique approach/Technique

This can be done as a part of Open Ventral Hernia repair, or Laparoscopic Repair with IPOM Plus.

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Technique
A small incision in taken generally in the subcostal region, lateral to the Linea semilunaris

External Oblique muscle is identified & incised between sutures.

The space between External & Internal Oblique is dissected with a balloon or finger

A 11 mm Trocar is introduced between External & Internal oblique.

Telescope is introduced & CO2 insufflation started.
The space between External and Internal Oblique in further expanded by blunt Telescopic dissection and then a
working port introduced laterally.

The port positions on the right side can be flexible: this is an example of port postions:
The External Oblique aponeurosis is now seen on the roof and this is incised 1 to 2 cms lateral to the Linea
Semilunaris from costal margin to inguinal region.

The cut edges are separated with blunt and sharp dissection.
Further dissection is done between External and Internal oblique muscle.

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The division of External oblique muscle is feasible and done all the way going above the Costal margin upto 7th
or 6th intercostal space: this is especially helpful in Epigastric hernia defects.
The procedure is repeated bilaterally: the port positions are shown in the figure.
After Completing the Endoscopic Component Separation, the Midline is reconstituted by closing the Medial
edges of Rectus Sheath: At this point decision is made as to where to place the Mesh: The Mesh can be placed
either in Retro-Rectus Position or as an Onlay Mesh.

The final result will be a secure closure of midline without excessive raising of flaps.

How wide a defect can be closed by the Endoscopic Anterior Component Separation:
o A defect of as wide as 16cms can be closed in Umbilical region.
o At the Xiphisternum and pubic region the defect of maximum 8 to 10cms can be closed.

Advantages of Endoscopic Anterior Component Separation:

o It can be done in open as well as Laparoscopic Repair.
o The Component Separation can be done with open technique or Endoscopic technique.
o The Endoscopic technique can be combined with Open ventral Hernia Repair as well as
Laparoscopic Repair.

Posterior Component Separation: the TAR procedure

The TAR Procedure

First conceptualised and developed by Dr Yuri Novitsky, the TAR procedure has rapidly taken over most other
variations of Posterior Component separation.

Anatomical basis of TAR

The posterior Rectus sheath although looks like a single white membranous structure, it is made up of multiple
layers.
The white looking posterior Rectus sheath can be incised gently to minimal depth to expose the underlying
Transversus Abdominis muscle fibres in the upper part of abdomen; in the lower part, the muscle fibres are
replaced by aponeurotic part hence difficult to identify though not impossible.
The anatomical basis is the fact that a plane can be developed between the Transversus abdominis muscle and
underlying Transversalis fascia all the way laterally and even posteriorly into the retroperitoneal region: this
space is then used to place a large mesh.
Another anatomical basis is the fact that this sub-Transversus space is continuous with the pelvic extraperitoneal
space in the caudal region and also with the sub-xiphoid and sub-diaphragmatic space. Thus the Mesh cover can
extend from retrosternal space to retropubic space.

The TAR procedure : technique

 A long midline incision is taken from Xiphisternum to Pubis.

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 Abdomen and the sac of Hernia are opened and adhesiolysis is done to free the Anterior Abdominal
wall upto flanks.
 The Falciform ligament, its fat and part of peritoneum or sac is preserved.
 The Rectus sheath is opened at its medial edge, leaving part of sac attached to it as far as possible
 The Rectus muscle is lifted anteriorly and the Retro-Rectus space is created
 The neurovascular bundles going into Rectus muscle are identified and preserved.
 Posterior Rectus sheath is observed: Most patients the Transversus Abdominis fibres will be visible
whilst they are inserting themselves into the posterior Rectus sheath in the Epigastric region.
 The posterior Rectus Sheath is incised in upper (cranial) part : just medial to the neurovascular bundles,
in order to preserve them. This incision is on the posterior lamella of internal oblique.
 This incision opens up the space below it showing the Transversus Abdominis fibres getting inserted
into Posterior Rectus Sheath.
 These fibres are picked up on Mixter clamp bit by bit and divided, releasing the Transversus muscle
from it’s insertion.
 This dividing of Transversus insertion is done from costal Margin to Arcuate line.
 Then the space between Transversus Abdominis muscle fibres and Transversus Abdominis muscle
fibres and Transversalis fascia is developed by dissecting towards flank with a peanut dissector going
all the way on to Posterior abdominal wall.
 Inferiorly the dissection is carried into the Pelvis and Retropubic space
 Superiorly the dissection continues in the sub-xiphoid area upto central tendon of diaphragm: for this
the posterior Rectus sheath is divided from the costal margin keeping above the underlying peritoneum
and medially, the Falciform ligament
 Any button holes in the peritoneum and fascia are carefully closed.
 After complete dissection on both sides it is generally observed that the Recti can be brought medially
for midline closure; the posterior rectus sheath with parts of sac can also be brought to the midline for
closure.
 After completing the procedure on both sides, the midline is closed by suturing both the posterior
Rectus sheath to each other.
 Now a large 30X30cms Polypropelene large pore mesh is placed above the posterior Rectus Sheath and
Transversalis fascia in a diamond shape, extending from sub-xiphoid region to both Cooper's ligaments.
Most patients will need two meshes placed in a pentagon fashion also called as “Home plate
configuration”.

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  Two sutures are taken to fix the mesh to ooper’s ligament.
 No other sutures are generally required
 The anterior midline is reconstituted by suturing the medial edge of Anterior Rectus Sheath to create
Linea alba using a non-absorbable or a delayed absorbable suture.
 A complete midline closure is achieved most of the times.
 If not, bridging with heavy-weight polypropylene mesh with an absorbable/dual mesh to protect the
underlying bowel can be used.
 Drains are kept.
 Peak plateau airway pressure are measured before and after midline closure: a difference of up to 6 is
acceptable. Beyond a difference of 6, the patient will need respiratory support with ventilator in the
post-operative period.
 In case the Peak Pressures remains high, the midline has to be opened to prevent Abdominal
Compartment Syndrome due to raised IAP.

Postoperative management
This consists of Respiratory monitoring and management, wound management and management of
complications, if any. Most patients are ambulatory on the next day and rest of the management is like a routine
hernia repair. Wound has to be carefully evaluated, and managed. Any evidence of skin necrosis and exposure of
the mesh needs to be managed aggressively with debridement. Drains are kept till the drainage decreases below
30 to 50 ml. Last but not the least, DVT prophylaxis is a must in all patients.

Advantages and applications of TAR procedure

TAR is a very versatile procedure and can be done as an extension of Retro-Rectus repair. It can be done as a
unilateral procedure if the defect is not very wide, and closure can be achieved. The real advantage of TAR is
that it can be used for non-midline hernias since it offers not only release with closure of defect, but a wide
coverage with mesh. It can also be used in patients with stoma where relocation of the stoma can be done
through the mesh. It can be offered to patients with Parastomal hernias with or without concomitant midline
hernias.

Indications of TAR
1. Complex midline hernias with defects larger than 6 to 8 cms.
2. Recurrent hernias with wide defects
3. Complex hernias with loss of domain: of course these patients need a specialised preoperative
management for loss of domain.
4. Non-midline hernias
5. Hernias associated with a stoma
6. Parastomal hernias.

Complications of TAR
1. Acute respiratory insufficiency
2. Surgical site occurrences
3. Raised IAP
4. Abdominal Compartment syndrome
5. Skin flap necrosis with exposure of mesh
6. Intestinal Obstruction
7. Disruption of Posterior sheath with herniation of bowel.
8. Haemorrhage
9. Seroma
10. Mesh infection
11. Recurrence.

Endoscopic approaches to Posterior Component separation the TAR

1. Laparoscopic TAR
2. e-TEP approach
3. Robotic approach

Laparoscopic TAR
Laparoscopic TAR procedure was reported by Igor Belyanski and others and is now being done in many centres.
It can be done for midline hernias as well as lateral hernias. It is done using six port technique with an option for
an additional 7th port.
For midline hernias, the procedure is begun with three lateral ports one side: the ports are placed as far laterally
as possible, mostly in the anterior axillary line: After adhesiolysis and evaluation of the defect, additional ports
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are inserted on the contralateral side. The Retro-muscular space is entered at the edge of the defect by incising
the medial margin of the defect, which is also the medial margin of the Rectus sheath. The Posterior rectus
sheath is dissected off the Rectus muscle preserving the neurovascular bundles entering the rectus muscle.
An incision is taken on the posterior rectus sheath just medial to the neurovascular bundles to expose the
Transversus fibres insertion: these fibres are then divided serially from Epigastric region to caudal region along
the posterior rectus sheath till Arcuate line is reached.

Now the divided distal Transversus muscle is dissected off the underlying Transversus fascia proceeding
laterally towards opposite anterior axillary line: the opposite side trocars are now withdrawn and brought inside
above the dissected flap so that the dissected flap can be further dissected off the Transversus muscle all the way
to posterior axillary line and retroperitoneal region up to the lateral border of Psoas muscle. This dissection is
carried into the pelvis to develop the space of Bogros and Retzius to expose the ooper’s ligament. Cranially,
the posterior rectus sheath is divided near costal margin as the sub-xiphoid space is developed to expose the
Diaphragmatic fibres. This completes the dissection on one side.

Then the camera and working instruments are shifted to the other side and similar dissection is done on
nondissected side. After complete TAR aspect , now all the six trocars are anterior to the dissected posterior
rectus sheath and the peritoneo-fascial flap. The posterior rectus sheath is now closed in the midline using
delayed absorbable sutures: a seventh port in the midline is helpful at this juncture. Once the posterior rectus
sheath is closed, now the bowel are insulated and out of vision and the working ports are all in the
extraperitoneo-fascial space.

The anterior midline is now closed to recreate the midline and Linea alba, using nonabsorbable or delayed
absorbable sutures: Barbed self-locking sutures are used. Lastly, an appropriate sized large macroporous medium
weight polypropelene mesh is spread across to cover from sub-xiphoid region to retro-pubic space: the mesh is
fixed to the Coopers ligaments. Drains are kept and ports closed.

e-TEP access and eTEP TAR

eTEP was first described by Jorge Daes for Inguinal hernia repairs. This was done by using higher port for
Retro-rectus access and then regular TEP.

Igor Belyansky has progressed on the extended TEP (e-TEP) approach

popularised by Jorge Daes for groin and lower abdominal hernias and used
it to develop an endoscopic approach to PCST/TAR. The group of e-TEP
pioneers includes Belyansky, Novitsky, Daes, Radu and Ramana, and their
index series of endoscopic retromuscular cases is under publication
currently.

A balloon is used to develop a space in the left upper retro-rectus area. The
balloon is inserted by a simple cutdown and muscle split till the posterior
rectus sheath (PRS) is reached. Under endoscopic vision, the retro-rectus
space is developed. Once this is done, additional 5 mm ports are placed
medial to the semilunar line. At least one contralateral port is usually needed, though more may be used, if
bilateral TAR is indicated. An important part of the procedure is to cross over to the other side by dividing the
Linea alba. This is done in the upper retro-rectus space. The entire falciform ligament is mobilized down along
with the PRS. The dissection extends caudally till the hernia sac is safely and sharply entered. Adhesiolysis is
completed, and the lower extraperitoneal space is fully exposed like in the open PCST.

The Posterior Rectus sheath is incised laterally and the Transversus Abdominis is exposed. The TAR is
accomplished along the full length of the flank. Space creation is as in the open procedure.
Rectus sheath closure (both the anterior as well as the posterior) is made far easier with the barbed sutures
available in the market. The mesh is fixed to the Cooper’s ligament in all cases. Rest of the mesh fixation is easy
with fibrin glue which, however, becomes an expensive fix. It is possible that minimal fixation may also work,
though there are concerns of early post-operative mesh displacement. There is currently no evidence to
recommend one over the other.
The mesh covers the 12 mm and other ports.

Patients typically go home the day after the surgery. The surgery takes time, but the patient has much less pain
and has higher QOL scores as compared to open.

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Robotic TAR:
As would be expected, Robotic TAR procedure is now used in most centres having the facility: Robotic
approach adds to the ease of suturing and some papers have also reported decreased hospital stay and decreased
morbidity after robotic TAR procedure

References
1. (Laparoscopic repair of incisional abdominal hernias using expanded polytetrafluoroethylene: preliminary findings.
LeBlanc KA, Booth WV. Surg Laparosc Endosc. 1993 Feb;3(1):39-41 ),
2. (Outcomes of bridging versus mesh augmentation in laparoscopic repair of small and medium midline ventral hernias.
Mitura K, Skolimowska-Rzewuska M, Garnysz K. Surg Endosc. 2017 Jan;31(1):382-388. doi: 10.1007/s00464-016-
4984-9. Epub 2016 Jun 10)
3. (Meta-analysis of closure of the fascial defect during laparoscopic incisional and ventral hernia repair. Tandon A,
Pathak S, Lyons NJ, Nunes QM, Daniels IR, Smart NJ. Br J Surg. 2016 Nov;103(12):1598-1607. doi:
10.1002/bjs.10268. Epub 2016 Aug 22. Review.)
4. (Ramirez OM, Ruas E, Dellon AL. "Components separation" method for closure of abdominal-wall defects: an
anatomic and clinical study. Plast Reconstr Surg (1990) 86(3):519–26 ).
5. (Assessment of predictive factors for recurrence in laparoscopic ventral hernia repair using a bridging technique.
Hauters P, Desmet J, Gherardi D, Dewaele S, Poilvache H, Malvaux P. Surg Endosc. 2017 Sep;31(9):3656-3663. doi:
10.1007/s00464-016-5401-0. Epub 2017 Jan 11.)
6. (Decreased re-operation rate for recurrence after defect closure in laparoscopic ventral hernia repair with a permanent
tack fixated mesh: a nationwide cohort study. Baker JJ, Öberg S, Andresen K, Rosenberg J. Hernia. 2018 May 10. doi:
10.1007/s10029-018-1776-2.)
7. (Component Separation vs. Bridged Repair for Large Ventral Hernias: A Multi-Institutional Risk-Adjusted
Comparison, Systematic Review, and Meta-Analysis.
8. Holihan JL, Askenasy EP, Greenberg JA, Keith JN, Martindale RG, Roth JS, Mo J, Ko TC, Kao LS, Liang MK;
Ventral Hernia Outcome Collaboration Writing Group. Surg Infect (Larchmt). 2016 Feb;17(1):17-26. doi:
10.1089/sur.2015.124. Epub 2015 Sep 16. Review.)
9. (Carbonell AM, Cobb WS, Chen SM. Posterior components separation during retromuscular hernia repair. Hernia
(2008) 12(4):359–62. doi: 10.1007/s10029-008-0356-2 ),
10. (Novitsky YW, Elliott HL, Orenstein SB, Rosen MJ. Transversus abdominis muscle release: a novel approach to
posterior component separation during complex abdominal wall reconstruction. Am J Surg (2012) 204(5):709–16. doi:
10.1016/j.amjsurg.2012.02.008 ).
11. (Laparoscopic component separation in the single-stage treatment of infected abdominal wall prosthetic removal.
Rosen MJ, Jin J, McGee MF, Williams C, Marks J, Ponsky JL. Hernia. 2007 Oct;11(5):435-40. Epub 2007 Jul 24.)
12. (A novel approach using the enhanced-view totally extraperitoneal (eTEP) technique for laparoscopic retromuscular
hernia repair. Belyansky I, Daes J, Radu VG, Balasubramanian R, Reza Zahiri H, Weltz AS, Sibia US, Park A,
Novitsky Y. Surg Endosc. 2018 Mar;32(3):1525-1532. doi: 10.1007/s00464-017-5840-2. Epub 2017 Sep 15.)
13. (Surg Endosc. 2018 Feb;32(2):727-734. doi: 10.1007/s00464-017-5729-0. Epub 2017 Jul 20. Comparative analysis of
open and robotic transversus abdominis release for ventral hernia repair. Bittner JG 4th1,2, Alrefai S3, Vy M3, Mabe
M3, Del Prado PAR4, Clingempeel NL3)
14. (Saulis A, Dumanian GA: Periumbilical rectus abdominis perforator preservation significantly reduces superficial
wound complications in “separation of parts” hernia repairs last Reconstr Surg 109:2275 2002. ).
15. (Maas S M, De Vries R S, Goor H van, de Jong D, Bleichrodt R . ndoscopically assisted “component separations
technique” for the repair of complicated ventral hernias. J Am oll Surg. 2002;194(3):388–390.).
16. (Sukkar SM1, Dumanian GA, Szczerba SM, Tellez MG. Challenging abdominal wall defects. Am J Surg. 2001
Feb;181(2):115-21.)
17. (Saulis AS, Dumanian GA. Periumbilical rectus abdominis perforator preservation significantly reduces superficial
wound complications in "separation of parts" hernia repairs.Plast Reconstr Surg. 2002 Jun;109(7):2275-80; discussion
2281-2.)
18. (Butler CE, Campbell KT. Minimally invasive component separation with inlay bioprosthetic mesh (MICSIB) for
complex abdominal wall reconstruction. Plast Reconstr Surg. 2011 Sep;128(3):698-709)
19. (Lowe JB, Garza JR, Bowman JL, et al. Endoscopically assisted “components separation” for closure of abdominal
wall defects. Plast Reconstr Surg 2000;105:720e730) .
20. (Endoscopic subcutaneous approach to component separation. Daes J. J Am Coll Surg. 2014 Jan;218(1):e1-4. doi:
10.1016/j.jamcollsurg.2013.09.020. Epub 2013 Oct 3 )
21. (Elstner KE, Read JW, Jacombs ASW, Martins RT, Arduini F, Cosman PH, Rodriguez-Acevedo O, Dardano AN,
Karatassas A, Ibrahim N. Surg Endosc. 2018 May;32(5):2474-2479. doi: 10.1007/s00464-017-5949-3.)
22. (Rives-Stoppa incisional hernia repair combined with laparoscopic separation of abdominal wall components: a novel
approach to complex abdominal wall closure. Cox TC, Pearl JP, Ritter EM. Hernia. 2010 Dec;14(6):561-7. doi:
10.1007/s10029-010-0704-x. Epub 2010 Jul 27.)

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 RADIOLOGY FOR PG EXAMS
Nikhil Gupta

In this word document, I will mention abdominal X rays, Barium studies and CT. Rest all will be covered in my
talk. All delegates will get a CD of that.

Abdominal X rays
Understanding x ray films is something that all clinical students should get to grips with. Starting out as a doctor,
you will not need to be an expert but you will need to know the basics. The abdominal radiograph is one of the
most commonly requested images, and all medical students should have a knowledge of common radiological
interpretations. The standard abdominal radiograph (AXR) taken is a supine projection: x rays are passed from
front to back (antero-posterior projection) of a patient lying down on his or her back. In some circumstances an
erect AXR is requested: its advantage over a supine film is the visualisation of air-fluid levels. A decubitus film
(patient lying on his or her side) is also of use in certain situations. Although an AXR is a plain radiograph, it has
a radiation dose equivalent to 50 postero-anterior chest x rays or six months of standard background radiation.
As with any plain radiograph, only five main densities are seen, four of which are natural: black for gas, white
for calcified structures, grey representing a host of soft tissue with a slightly darker grey for fat (as it absorbs
slightly fewer x rays). Metallic objects are seen as an intense bright white. The clarity of outlines of structures
depends, therefore, on the differences between these densities. On the chest radiograph, this is easily shown by
the contrast between lung and ribs—black air against the white calcium containing bones. These differences are
much less apparent on the AXR as most structures are of similar density—mainly soft tissue.

Technical features
It is important, as with any image, that the technical details of an AXR are assessed. The date the film was taken
and the name, age, and sex of the patient are all worth noting. This ensures you are interpreting the correct film
with the correct clinical information and it also may aid your interpretation. You would be a little concerned if
you saw what appeared to be a calcified fibroid on an AXR when holding the notes of Mr Alok Agarwal. Next
ask what type of AXR is it: supine, erect, or decubitus? Unless specifically labelled the film is taken to be
supine.

Presenting the AXR

This is the supine abdominal radiograph of a 42 year old women taken yesterday. It is technically satisfactory.
The amount and distribution of gas within the bowel is normal. There is no bowel dilatation. There is no
evidence of extraluminal air. Soft tissue outlines of the psoas muscles and kidneys are seen. The kidneys are
normal in size and shape. There are no apparent bony lesions or abnormal calcification. Incidentally, sterilisation
clips can be seen within the pelvis indicating previous gynaecological intervention.

Intraluminal gas
Begin by looking at the amount and distribution of gas in the bowels (intraluminal gas). There is considerable
normal variation in distribution of bowel gas. On the erect AXR, the gastric gas bubble in the left upper quadrant
of the film is a normal finding. Gas is also normally seen within the large bowel, most notably the transverse
colon and rectum. Important characteristics of bowel loops to bear in mind are their size and distribution (where
they are situated in relation to other structures). Normal small bowel should measure less than 3 cm in diameter,
whereas normal colon should measure less than 5 cm in diameter. The diameter of the caecum may be greater,
but if it is greater than 9 cm it is abnormal. Large bowel should lie at the periphery of the film, with small bowel
distributed centrally. Small and large bowel can also be distinguished, most easily when dilated, by their
different mucosal markings. Small bowel has valvulae conniventes that transverse the full width of the bowel;
large bowel has haustra that cross only part of the bowel wall. These features are important in the next part of
this series, which considers abnormal intraluminal gas. Occasionally, fluid levels in the small bowel are a normal
finding.

Extraluminal gas
Gas outside the bowel lumen is invariably abnormal. The largest volume of gas you might see is likely to be
under the right diaphragm: this occurs after a viscus has been perforated. This gas within the peritoneal cavity is
termed pneumoperitoneum. Gas in the right upper quadrant within the biliary tree is a “normal” finding after
sphincterotomy or biliary surgery, but it can indicate the presence of a fistula between the biliary tree and the
gut. Beware of gas in the portal vein, as this can look very similar to biliary air. Gas in the portal vein is always
pathological and frequently fatal. It occurs in ischaemic states, such as toxic megacolon, and it may be
accompanied by gas within the bowel wall (intramural gas).

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Places to look for abnormal extraluminal gas
● Under the diaphragm ● In the biliary system ● Within the bowel wall

Calcification
Calcium is visible in a variety of structures, both normal and abnormal, and becomes more common with
advancing age. However, review the following areas in particular for evidence of calcification: cartilage of ribs,
blood vessels (chiefly the aortoiliac and splanchnic arteries), pancreas, kidneys, the right upper abdominal
quadrant for gallbladder calculi, and the pelvis, which may contain a variety of calcified structures, most
commonly phleboliths.

Soft tissues and bone

A review of the soft tissues entails evaluating the outlines of the major abdominal organs. Observing these
structures is made easier by the “fatty” rim (properitoneal fat lines) surrounding them. In fact, the loss of these
fat planes may indicate an ongoing pathological process, such as peritonitis. Look at the size and position of the
liver and spleen. Look at the position and size of the kidneys, lateral to the midline in the region of the T12-L2
vertebrae (a useful way of identifying vertebrae: the lowest one to give off a rib is T12 and serves as a reference
point). The renal outline is usually three to three and a half vertebral bodies in length. Also, look for the clear
outline of the psoas muscle shadow(s). Finally, try to identify the outline of the bladder, seen more clearly if full,
within the pelvis. The appearance of what looks like a soft tissue mass in the region of the stomach is more often
than not actually a gastric pseudotumour. This is a normal finding on the supine film and represents gastric fluid
lying within the fundus. The assessment of bones entails evaluating the spine and pelvis for evidence of bony
pathology. Osteoarthritis frequently affects the vertebral bodies, as well as the femoral and the acetabular
components of the hip joint. aget’s disease may also be identified, commonly along the iliopectineal lines of the
pelvis. Your bone survey should also check for fractures, especially subtle femoral neck fractures in elderly
people. The spine and pelvis are also common locations for metastatic deposits. In the spine this is classically
seen as “the absent pedicle.”

Large bowel obstruction and paralytic ileus

Most intraluminal gas is in the large intestine, which has the greatest luminal diameter of the intestinal tract. A
diameter of more than 5 cm suggests a large bowel obstruction and would be considered abnormal (except in the
caecum). As the intestine is a large long tube, any obstruction, either from within or by external compression,
prevents the passage of faecal material and gas. Consequently, both will build up proximal to the obstruction,
causing dilation. Unless the ileocaecal valve is incompetent this gas-faecal material mix will be contained
entirely within the large bowel. With time, the passage of a motion will empty any faecal material and gas distal
to the blockage. This gives the appearance of a “cut off” point on the radiograph. This is an important sign to
appreciate, as it is indicative of a mechanical large bowel obstruction. The large bowel can also dilate with
paralytic ileus. In this condition, the bowel is adynamic (not undergoing normal peristalsis). This allows gas—
which everyone swallows normally—to accumulate in the bowel, but importantly this air is contained within
both the small and large bowel. There is also no evidence of a “cut off ” as it is bowel peristalsis, not obstruction,
that is the problem. Two other pertinent radiological signs help confirm that it is the large bowel that is
obstructed. Firstly, large bowel has distinct transverse bands, termed haustra. These do not cross the full
diameter of the bowel, unlike the transverse valvulae conniventes of the small bowel. These can both be seen on
plain radiograph. Secondly, large bowel is found at the radiograph’s periphery as opposed to the small bowel
loops, which take up central positions. This has been referred to as a “picture frame” of large bowel and the
“picture” of small bowel within the frame.

Small bowel obstruction

In small bowel obstruction, dilated small bowel loops are seen centrally on the radiograph. The valvulae
conniventes should be visible across the whole width of this dilated bowel. The dilated bowel diameter is greater
than 3 cm but usually less than 5 cm. There are likely to be several dilated bowel loops. The number of small
bowel loops gives an indication of the level at which the obstruction within the small bowel has occurred: the
higher the obstruction, the fewer the number of loops seen. Unlike large bowel obstruction, no gas should be
seen within the large bowel. So far we have considered supine abdominal radiographs. An erect film may show
further evidence of small bowel obstruction: fluid levels, indicating an air-fluid interface. An erect film tends to
show multiple small fluid levels, a “stepladder” appearance (Figure 1).

Volvulus
A volvulus is the twisting of bowel about its mesentery, causing intestinal obstruction. The two most common
sites are the sigmoid and the caecum. With a sigmoid volvulus, an extremely dilated loop of sigmoid bowel
forms two large compartments which look like a coffee bean (hence the name of the sign). This single loop
usually fills most of the lower abdominal radiograph (Figure 2). On erect abdominal radiographs a fluid level
may be noted. In caecal volvulus, the caecum is displaced to the upper left abdominal quadrant from its normal

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location (the right lower quadrant). This leaves the area empty so the term “empty caecum” is used. The volvulus
usually consists of a single loop, again showing a fluid level on an erect radiograph. Distal to the volvulus the
large bowel is empty.

Figure 1: Step ladder pattern in small bowel Figure 2: Volvulus of sigmoid colon
obstruction (multiple air-fluid levels)

Toxic megacolon, acute pancreatitis, duodenal obstruction, and meteorism

Toxic megacolon, seen in inflammatory bowel disease (especially ulcerative colitis), has an associated risk of
bowel perforation. It is seen as grossly dilated large bowel, typically the transverse colon, with “thumb printing”
evident. In acute pancreatitis a small sentinel loop (a collection of intraluminal gas) of bowel may be seen: the
inflamed pancreas paralysing the adjacent bowel, making it adynamic. Duodenal obstruction, congenital or
acquired, gives the appearance of two gas bubbles, one in the duodenum and the normal gastric air bubble; this is
termed the “double bubble” sign. Meteorism (excessive swallowed air) is particularly common in crying children
and hyperventilating adults. Although there are prominent bowel loops, there is no cut off point: the bowel has
been likened to crazy paving.

Pneumoperitoneum
A most important and potentially devastating finding is that of free intraperitoneal gas, which is known as
pneumoperitoneum. Emergency surgical intervention is likely to be necessary, as pneumoperitoneum usually
indicates a perforated viscus. The supplementary plain radiograph should be an erect chest radiograph that
visualises gas collecting beneath the diaphragm. Depending on the volume of gas in the peritoneum, it may be
apparent under one or both hemidiaphragms. As you may recall from the first part of the series (normal
radiographs) a gastric air (“gas”) bubble is usually seen in the left hypochondrium on the erect film. This can
make distinguishing free air on this side problematic. For this reason, identification of free gas on the right side
is more straightforward. The air is trapped between the underside of the diaphragm and the upper surface of the
liver. A small volume of gas has a crescentic appearance (Figure 3). Should a supine abdominal radiograph be
the only film available—if, for example, the patient is too ill to undergo an erect chest radiograph—there are
radiological signs that help identify free gas on the radiograph. The falciform ligament sign is seen when free air
outlines the falciform ligament, identified as a thin straight line starting in the right upper quadrant, where it
originates, and ending near the umbilicus, where it terminates. In Rigler’s sign, gas can be seen on both sides of
the bowel wall. This makes the serosal surface of the bowel easily visible.

Figure 3: Pneumoperitoneum Figure 4: hilaiditi’s syndrome

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Chilaiditi’s syndrome
Chilaiditi’s syndrome is an important normal variant on the erect chest radiograph, which must be distinguished
from pathological free gas under the diaphragm. In this phenomenon, gas is seen between the hemidiaphragm
and the liver or spleen. On close and careful observation this should be identified as gas filled large bowel, most
likely transverse colon (apparent, as haustra are seen within the gas filled structure). This gas is still contained in
the bowel loop (Figure 4).

Subphrenic abscess
This is a localised collection of free gas and fluid, which usually forms under the right hemidiaphragm, above
the solid liver. This gas collection usually occurs above the 11th rib.

Biliary gas
On the plain abdominal x ray film, gas is not normally identified in the biliary system, either intra- or
extrahepatic. There are, however, situations when gas might be seen as branching “tree-like” streaks of black
projected in the liver shadow. After endoscopic retrograde cholangiopancreatography with sphincterotomy, gas
may travel from the duodenum into the biliary tree as the sphincter of Oddi in the second part of the duodenum
is incompetent. Similarly, after a gallstone has been passed, the sphincter may become dilated. Biliary fistulas
are less common but may develop with a gallstone ileus. Fistulation between the gallbladder and adjacent bowel
allows a route for gas into the biliary system. The final aetiology is cholangitis. If the biliary ducts are infected
with gas forming organisms, gas will be produced, and contained, in the ducts, effectively creating a negative
contrast to the surrounding soft tissue of the liver.

Miscellaneous causes
The final causes of extraluminal gas are conditions where gas has escaped from the lumen of the gastrointestinal
tract but remains within the bowel wall; this is known as intramural gas. This gas may migrate to the portal vein
and is effectively an “ante mortem” sign, except in the case of neonatal necrotising enterocolitis. Necrotising
enterocolitis is a condition seen in premature babies when gas “leaks” into the bowel wall. In bowel wall
infarction, abscesses may form, which produce gas contained in the bowel wall. Pneumatosis coli, a condition
where blebs of gas form on the bowel wall, is of obscure aetiology and makes the bowel wall look like “bubble
wrap.” These blebs may rupture to produce a pneumoperitoneum.

Normal structures that calcify ● Costal cartilage ● Mesenteric lymph nodes ● Pelvic vein clots (phlebolith) ●
Prostate gland

Abnormal structures that contain calcium

Calcium indicates pathology ● Pancreas ● Renal parenchymal tissue ● Blood vessels and vascular aneurysms ●
Gallbladder fibroids (leiomyoma)
Calcium is pathology ● Biliary calculi ● Renal calculi ● Appendicolith ● Bladder calculi ● Teratoma

What are barium X-rays?

A barium X-ray is a radiographic (X-ray) examination of the gastrointestinal (GI) tract. Barium X-rays (also
called upper and lower GI series) are used to diagnose abnormalities of the GI tract, such as tumors, ulcers and
other inflammatory conditions, polyps, hernias, and strictures.

The use of barium with standard X-rays contributes to the visibility of various characteristics of the GI tract.
Barium is a dry, white, chalky powder that is mixed with water to make barium liquid. Barium is an X-ray
absorber and appears white on X-ray film. When instilled into the GI tract, barium coats the inside wall of the
esophagus, stomach, large intestine, and/or small intestine so that the inside wall lining, size, shape, contour, and
patency (openness) are visible on X-ray. This process shows differences that might not be seen on standard X-
rays. Barium is used only for diagnostic studies of the GI tract.

In addition to drinking barium, air is often inserted into the bowel for a lower GI X-ray. For an upper GI X-ray,
some patients may be given baking soda crystals (similar to Alka-Seltzer) to further improve the image. These
types of procedure are called air-contrast or double-contrast GI studies.

Fluoroscopy is often used during a barium X-ray. Fluoroscopy is a study of moving body structures—similar to
an X-ray "movie." A continuous X-ray beam is passed through the body part being examined, and is transmitted
to a TV-like monitor so that the body part and its motion can be seen in detail. In a barium X-ray, fluoroscopy
allows the radiologist to see the movement of the barium through the GI tract as it is instilled through the mouth
or the rectum.

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Reasons for performing barium X-ray procedures may include the following:
1. Abdominal pain
2. Bleeding from the rectum
3. Unexplained vomiting
4. Bowel movement changes
5. Chronic diarrhea or constipation
6. Pain or difficulty swallowing
7. Unexplained weight loss
8. Unusual bloating
9. To detect anatomical abnormalities

Additional procedures are often performed in addition to barium X-rays. These procedures may include
endoscopic examinations (an endoscope is a thin, flexible tube that is inserted into a body cavity and, using
fiberoptic technology, provides direct visualization of the inside of the cavity), computerized tomography (CT)
or magnetic resonance imaging (MRI) scans, and intra-cavity ultrasound.

here are three types of barium X-ray procedures:

1. Barium enema (also called lower GI series)
2. Barium small-bowel follow through
3. Barium swallow (also called upper GI series)

Barium enema
A barium enema involves filling the large intestine with diluted barium liquid while X-ray images are being
taken. Barium enemas are used to diagnose disorders of the large intestine and rectum. These disorders may
include colonic tumors, polyps, diverticula, and anatomical abnormalities.
Usually, a barium enema can be performed on an outpatient basis. The patient may be asked to do the following
in preparation for a barium enema:
Drink clear liquids the day before the examination.
Follow a special liquid diet one to two days prior to the procedure.
Take a laxative, suppository, or drug to cleanse the bowel.
Refrain from eating and drinking after midnight on the night before the examination.
These measures are done to empty the large intestine, as any residue (faeces) can obscure the image. However, a
barium enema may be done without preparation, for example, to diagnose hirschsprung's disease.
Barium enemas are performed in two ways:
Single-contrast image. The entire large intestine is filled with barium liquid. Single-contrast images show
prominent abnormalities or large masses in the large intestine.
Double-contrast image. A smaller quantity of thicker barium liquid is introduced to the large intestine, followed
by air. Double-contrast images show smaller surface abnormalities of the large intestine, as the air prevents the
barium from filling the intestine. Instead, the barium forms a film on the inner surface.
Although each hospital may have specific protocols in place, generally, a barium enema procedure follows this
process:
The patient will be positioned on an examination table. A rectal tube will be inserted into the rectum to allow the
barium to flow into the intestine. The radiologist will use a machine called a fluoroscope (a device used for the
immediate showing of an X-ray image). During the procedure, the machine and examination table will move and
the patient may be asked to change positions.
Additional X-rays may be made immediately after the procedure in order to obtain greater details of the area
under examination. Often, additional X-rays are made after the barium has been excreted from the bowel, which
is usually one or more days after the procedure.
After the procedure, a small amount of barium will be expelled from the body immediately. The remainder of the
liquid is later excreted in the stool. Barium liquid may cause constipation and light coloured stools. Following
the examination, the patient may be asked to eat foods high in fiber and drink plenty of fluids to help expel the
barium from the body. If you do not have a bowel movement for more than two days after your exam or are
unable to pass gas rectally, call your physician promptly. You may need an enema or laxative to assist in
eliminating the barium.

Barium small-bowel follow through

A barium small-bowel follow through involves filling the small intestine with barium liquid while X-ray images
are being taken. Barium small-bowel follow through is used to diagnose disorders of the small intestine, such as
ulcers, tumors, and inflammatory bowel disease, a group of disorders that includes Crohn's disease and
ulcerative colitis.

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Usually, a barium small-bowel follow through can be performed on an outpatient basis. Patients may be asked to
refrain from eating or drinking after midnight on the night before the examination. An enema or laxative may be
given on the day before the test to clear faeces from the bowel.
Although each hospital may have specific protocols in place, generally, a barium small-bowel procedure follows
this process:
The patient is given a bottle of barium to drink. The patient is positioned on the examination table.
The radiologist uses a machine called a fluoroscope (a device used for the immediate showing of an X-ray
image). X-rays are taken every 20 to 30 minutes over the next hour or two until the entire small bowel is
opacified. This exam can take several hours
Following the examination, the patient may be asked to eat foods high in fiber and drink plenty of fluids to expel
the barium from the body. If you do not have a bowel movement for more than two days after your exam or are
unable to pass gas rectally, call your physician promptly. You may need an enema or laxative to assist in
eliminating the barium.

Figure 5: Barium enema, Figure 6: Normal Barium meal Figure 7: Bird’s beak sign
malignancy descending colon follow through (smooth tapering at lower end)
showing apple core appearance on barium swallow in achalasia

Upper GI series
An upper GI series is an examination of the esophagus and stomach using barium to coat the walls of the upper
digestive tract so that it may be examined under X-ray. An upper GI that focuses on the esophagus is also known
as a barium swallow. Barium swallows and upper GI series are used to identify any abnormalities such as
tumors, ulcers, hernias, pouches, strictures, and swallowing difficulties.
Usually, these tests can be performed on an outpatient basis. Patients may be advised not to eat or drink after
midnight on the night before the examination.
Although each hospital may have specific protocols in place, generally, the procedure follows this process:
The patient will be asked to drink the barium liquid and to swallow baking soda crystals. It is important not to
belch, as the gas assists the radiologist in evaluation. The patient will stand behind a machine called a
fluoroscope (a device used for the immediate showing of an X-ray image). The patient may be asked to move in
different positions and to hold his or her breath while the X-rays are taken. If the small intestine is to be
examined, the patient may be asked to drink additional barium and a series of X-rays will be taken until the
barium reaches the colon.
Following the examination, barium may cause constipation. The patient may be advised to drink plenty of fluids
and eat foods high in fiber to expel the barium from the body. If you do not have a bowel movement for more
than two days after your exam or are unable to pass gas rectally, call your physician promptly. You may need an
enema or laxative to assist in eliminating the barium.

Computed Tomography
From its origins in the 1970s to today, computed tomography (CT) has evolved into one of the primary
diagnostic tools of the abdomen, and it continues this ongoing technological progression every day. When first
unveiled by Sir Godfrey Hounsfield in 1972, computed tomography was a revolution in radiological imaging.
This revolution continued in the 1990s with the innovation of spiral (or helical) CT, which allowed for more
continuous scanning and improved z-axis resolution. Spiral CT allowed for better three-dimensional imaging and
diminished the disadvantages of previous two-dimensional, uniplanar scans by allowing for increased table
speed and more distinct longitudinal resolution. This increase in table speed is valuable in a trauma setting, and
also significantly reduces the amount of radiation exposure to the patient for any continuous area. The radiation
exposure is further decreased as the pitch (pitch [p] = d/s, where d is table feed per rotation and s is slice
thickness) is increased.
Spiral CT works by obtaining a volumetric block of raw data in a spiral rather than a planar manner, with the
patient moving in a continuous z-axis direction while the tube and detector array rotate around the patient. This
266
continuous motion allows for a much larger volume to be covered, with less radiation exposure per volume
covered when compared with sequential CT. The volumetric data images captured by the CT are described as
voxels (the three-dimensional equivalent of 2D pixels, or picture elements). An additional method of increasing
the speed of image acquisition is increasing the number of rows of detectors. With more parallel rows of
detectors, the number of simultaneous readings can be increased without increasing the heat load of the tube, a
limitation of early CT scanners. The fundamental principle in improving resolution and image quality is to
utilize the smallest collimation and highest pitch possible. This goal is easier to achieve with multidetector CT
arrays than with the standard spiral CT array. Accordingly, the advent of multidetector computed tomography
(MDCT) has vastly improved imaging technology, especially as it relates to the representation of vascular
anatomy.

Hounsfield Units
In order to differentiate between different types of fluid and tissue in the abdomen, it is important to understand
the concept of Hounsfield units (HU) and how they are derived. Historically, the recreated images from CT
scanners had a wide range of values of 12-bit digital data, measured in standard transform (ST). The inventor of
the original CT, Sir Godfrey Hounsfield, developed a method to standardize the density measurements between
different machines. Hounsfield's absolute density scale defined air as the minimum density, with a value of –
1000 HU, and placed water as the benchmark of 0. The most dense material in the human body, bone, has an
upper limit of +1000 HU. The raw data could be translated to HU by the equation HU = ST scale + offset (e.g.
scale = 1.0, offset = -1000). This scale can be applied directly to the analysis of free fluid in the abdomen,
especially as it relates to identifying blood. The appearance of blood in intra-abdominal hemorrhage can vary
depending on the recency of the bleed, and this can help to determine if there is active bleeding or if clotting has
occurred. Clotted blood has a heterogeneous appearance and is generally between 45 and 70 HU. Clotted blood
tends to congregate close to the original hemorrhage site, producing the so-called "sentinel clot." Freely flowing
blood, however, will have a less dense appearance, and typically ranges from 20 to 45 HU.4 Blood can also be
identified by extravasation of contrast material, which can accumulate in the abdominal cavity or demonstrate
sites of vascular disruption.
Contrast Use
Abdominal CT scans can be done without the use of radiopaque contrast agents, termed a non-contrast enhanced
CT or NECT. The advantage of NECT is that the intense radiodensity of these contrast agents can obscure areas
of abnormality, like small renal or ureteral stones. Conversely, the use of a contrast enhanced CT, or CECT, can
provide better distinction between tissues and various structures. Most abdominal CT scans are done with
intravenous radiocontrast as this approach helps in the identification of inflammatory and neoplastic processes.
Intravenous contrast agents use iodine as the radiopaque agent bound to either an organic (non-ionic) or ionic
compound.
Barium sulfate, an insoluble powder suspended in water is a common radiocontrast used to fill the lumen of
gastrointestinal structures during radiography. Many hospitals are using a water soluble iodine product
(Diatrizoate Meglumine and Diatrizoate Sodium Solution) before CT scanning when visualization of the
gastrointestinal lumen is desired. Both agents can be administered by mouth, nasogastic tube, or rectal enema,
depending on the structures to be visualized.

Energy Sources in Laparoscopic surgery

(Chapter Taken From Guidelines prepared by IAGES)
Pawanindra Lal

This chapter has been written with the following objectives for the benefit of the laparoscopic surgeons who are
using various types of energy sources in day to day practice for the purpose of cutting tissues and achieving
hemostasis.

Aims & Objectives

 To learn about the general principles of diathermy & newer energy sources.
 Understnd the reasoning for using cutting or coagulation mode
 Understand the safety principles
 Apply these principles in laparoscopic surgery
 Evolving Recommendations on the basis of Levels of Evidence available in literature.

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ELECTROSURGERY IN LAPAROSCOPY
INTRODUCTION
A basic understanding of electrophysics is essential for surgeon to safely apply electrosurgical technology for
patient care and avoid complications. iv Electrosurgery is one of the most commonly used energy systems in
laparoscopic surgery.v The risk of complications is directly linked to the surgeon’s fundamental knowledge of
instruments, surgical technique, biophysics, relevant anatomy, and safe technical equipment. When principles of
appropriately applied, electrosurgery is safe and effective. Electrothermal injury may result from direct
application, insulation failure, direct coupling, and capacitive coupling.vi

Fig 1: Electrocautery is passive tranfer of heat

Electrocautery is NOT Electrosurgery

The terms electrocautery and electrosurgery are frequently used interchangeably; however, these terms define
two distinctly different modalities.
Electrocautery: Is the use of electricity to heat an object that is then used to burn a specific site – for example, a
hot wire
Electrosurgery: Refers to cutting & coagulation of tissue using high frequency electrical current. vii

Fig 2: Electrosurgery causes oscillatory movements of ions in cells which converts kinetic energy to thermal energy which
causes desired effect of cutting and coagulation.

BASIC PRINCIPLES OF ELECTROSURGERY

 Energy in wattage (power) is the product of current and voltage.
 Power is the amount of current times the voltage level at a given point measured in wattage or watts
(W). It corresponds to the rate of work being performed.
 Current (I) is what flows on a wire or conductor like water flowing down a river. Current flows from
negative to positive on the surface of a conductor. Current is measured in amperes (A) or amps.
 Voltage (V) is the difference in electrical potential between 2 points in a circuit. It is the push or
pressure behind current flow through a circuit and is measured in volts (V).
 Resistance determines how much current will flow through a component. Resistors are used to control
voltage and current levels. A very high resistance allows a small amount of current to flow. A very low
resistance allows a large amount of current to flow. Resistance is measured in ohms.
 Ohm’s law, shows the relationship between the properties of electrosurgical energy i.e. V = I x R
 The function of cutting/coagulation is neither that of Voltage nor of the Current but depends on Power
in Watts.

268
  Power (P) = V x I (Watts). The number reflected on the electrosurgical unit is the Wattage.
 Energy = P x Time

TYPES of ELECTROSURGERY
 Monopolar
 Bipolar

In monopolar electrodes, radio-frequency currents flow from the generator through the active electrode, into
target tissue, through the patient, the dispersive electrode, and then return to the generator.viii If the return
electrode is properly placed, the desired electrosurgical effect takes place only at the active electrode, not at the
dispersive electrode.

In bipolar electrodes, both arms of the circuit are delivered to the surgical instrument, and no return electrode
plate is required to placed on the patient.ix The flow of current is restricted between these two poles. The poles
are in close proximity to each other, so lower voltages are used to achieve the tissue effect.
Most modern bipolar units employ the cutting waveform, because it is a lower voltage waveform, allowing
homeostasis to be established without unnecessary charring.x Bipolar electrosurgery has a more limited area of
thermal spread compared with that of monopolar electrosurgery.xi,xii

Technically both monopolar and bipolar energies are “bipolar” as there is always an active electrode and and a
passive electrode.

Fig 3: Difference between Monopolar & Bipolar Electrosurgery – Patient receives the energy between active and
passive electrode through which the enegy is passing in Monopolar where as only the small tissue held between
the bipolar forceps receives the enery is Bipolar.

WAVEFORM
A pure cutting waveform (current mode) is a continuous, unmodulated, undamped waveform.
A coagulation waveform is an interrupted, modulated, and damped current with an initial high waveform that
quickly dissipates.(10,6)xiii
The coagulation mode produces an interrupted waveform with a duty cycle that is “on” about 6% of the time, ie,
6% on, 94% off. Blended modes are actually variations of the “cutting” current. As the duty cycle (amount of
time the current is on) diminishes, the voltage must correspondingly increase, provided the power remains
constant. The percentage duty cycle can vary, eg, 80% on, 20% off; 66% on, 34% off; and 50% on, 50% off, and
so forth. The term “blended” does not refer to a blend of currents, but rather to a blend of surgical effects.
The blended mode permits the surgeon to cut and to coagulate at the same time. With cooling periods, cell wall
explosion and vaporization are accompanied by slow dehydration of cellular fluid and protein.

269
Fig 4: Alternating Current is used in all electrosurgery.

WHY DO PATIENTS DON’T GET SHOCK

The reason why patients don’t get electrical neurological or muscular stimulation is not because the patient is
anaestheteised. It has been seen that neuro-muscular stimulation caeses with high frequency current more than
100 KHz which is known as Radio Frequency Current.

Fig 5: Electrosurgery works in RadioFrequency range.

One of the Principal difference between Cutting and Coagulation Modes for Monopolar Diathermy is the
difference in the voltage and current. Coagulation has high voltage and low ampereage and Cutting has high
ampereage and low voltage. Blend modes are in between.

TISSUE EFFECTS
 Cutting
 Fulguration
 Desiccation
When a radio frequency (500 Hz to 3 MHz) alternating current is applied across the cell, these cations and
anions rapidly oscillate within the cytoplasm and elevate the temperature within the cell. If the intracellular
temperature reaches about 70°C to 80°C, protein denaturation occurs, initiating the process of “white
coagulation” or Electrocoagulation.

270
 COMPARISON BETWEEN
COAGULATION AND CUTTING

PURE BLEND1 BLEND2 BLEND3 PURE

COAG CUTTING

Fig 6. Comparison between Coagulation and Cutting

If the temperature rises quickly to 90°C, the cells lose water content (dehydration), but preserve architecture in
the process termed desiccation.xiv Electrosurgical desiccation can occur using either the cutting or coagulating
current modes on the generator.
When the temperature quickly reaches 100°C and beyond, the intercellular water boils. Subsequently, the
formation of steam and intracellular expansion results in explosive vaporization of the cell. The cutting effect
(vaporization) is usually produced using a pointed or thin loop-shaped electrode held near to, but not in contact
with, the tissue. This concentrates the current at its tip. The current then arcs to the tissue, rapidly elevating the
local intracellular temperature and causing vaporization.xi
Finally, if the cellular temperature reaches 200°C or more, the process of carbonization (fulguration) occurs.
The fulguration effect is a process in which the tissue is superficially carbonized through high-voltage
electrosurgical archingxi, i.e. holding the electrode a short distance away from the tissue, the electric current is
delivered by way of sparks “ umping” across the air space and contacting the tissue. The most common surgical
indication for fulguration is rapid control of bleeding across a wide area, such as oozing capillary beds.
To avoid charring, it is better to keep the electrode moving during the procedure. For example, a monopolar
electrode with coagulation current and near-contact technique can fulgurate tissue; a bipolar electrode with
cutting current and both blade contact technique can desiccate tissue.(12,13,14)xvxvixvii

Fig 7:Cutting Fig 8:Fulguration Fig 9:Dessication

271
Fig 10: Comparison of the three tissue effects.

Fig 11: Effect of voltage and modulation on seal quality

Grade A Recommendation:
Low Voltage Cutting Current in Monopolar Electrosurgery or Bipolar Electrosurgery which also uses low
voltage cutting current, is the preferred mode for contact coagulation in laparoscopic surgery.
Statement:
Cutting Current must be used for cutting and coagulation in laparoscopic surgery

Level of evidence in Bipolar electrosurgery

Bipolar electrosurgery has a more limited area of thermal spread so the maximal lateral thermal spread is
within 5mm and so the depth limited to the serosal layer, better to use bipolar than monopolar.v,vii,ix
Disadvantages of bipolar electrosurgery include the increased time needed for coagulation due to a low
power setting, charring, and tissue adherence with incidental tearing of adjacent blood vessels. v,vii,ix
(Level 2)
Level of evidence in Bipolar electrosurgery between cutting and coagulation current
Effect of voltage & Modulation on seal Quality using bipolar electrosurgery between cutting and coagulation
current studied by Soderstrom concluded
Low voltage continuous current causes causes coagulation in Full thickness of tissues while high voltage
modulated coagulation current causes Incomplete coaptive coagulation with superficial coagulation insulate
deeper
MAS layers
Safety from coagulation effect , caramelized superficial layer stick to instrument and cause tear and
Considerations
v
further bleeding.
When electrosurgery is used in the context of minimal access surgery, it raises a new set of safety concerns
(Level
Some 1) are:
of these
 Direct Coupling
 Insulation Failure
 Capacitive Coupling

ELECTROSURGICAL INJURY
Injury from inadvertent energy transfer has a reported incidence of 1 to 5 recognized injuries per 1,000 cases.

272
Electrosurgical injury occurs when the electrosurgical unit is accidentally activated while the active electrode is
in close proximity to another metal instrument and current from the active electrode flows through the adjacent
instrument through the pathway of least resistance, and potentially damages adjacent structures or organs not
within the visual field that are in direct contact with the secondary instrument. (15)

Fig 12: Direct Coupling when an active elctrode makes an unintentional contact with another electrode or
conductive instrument

Level of evidence to avoid direct coupling.

• It can be prevented with visualization of the electrode in contact with the target tissue and avoiding
contact with any other conductive instruments prior to activating the electrode. xvi (Level 3 )
Grade C Recommendation
• Direct visualization of all laparoscopic instruments should be done to avoid direct coupling injuries
using high voltage coagulation current.
• STATEMENT- All instruments should be kept under direct vision as far as possible while using energ

Insulation failure
Insulation failure is the main cause of laparoscopic electrosurgical injuries and distal third of laparoscopic
instruments being the most common site of insulation failure.
Eighteen percent of insulation defects are located in the section of the instrument most likely to create a
catastrophic electrosurgical injury. Originally described as ‘‘Zone 2 ” by Voyles and Tucker, the location along
the instrument, which is outside the view of the monitor but distal to the protective cannula, carries the highest
risk for creating an injury that even the most attentive surgeon is unable to detect. xviii

Level of evidence in Insulation failure

Excessive use of reusable instruments, particularly with repetitive passage through trocars and frequent
mechanized sterilization are the leading cause of insulation failure.
By lowering the concentration of the current used, preferably cutting current and use of an active electrode
monitoring system, the risk of accidental burns can be reduced. xiv(Level 2c)
Recommendations (Grade B)
Disposable instruments have a lower incidence of insulation failure compared with reusable instruments.
Cutting current is preferred
Prolonged activation of an electrosurgical instrument should be avoided.
STATEMENT – Cutting current should be preferred to avoid damage to insulation.

Capacitive Coupling
Capacitive coupling is electrical current that is established in tissue or in metal instruments running parallel to
but not directly in contact with the active electrode. This occurs when electric current is transferred from one
conductor (the active electrode) through intact insulation and into adjacent conductive materials (eg, bowel)
without direct contact. (16)xix’

Level Of Evidence to prevent capacitive coupling

Hybrid cannulas (Plastic collar) convert metal trocar into a high energy capacitor.
Ironically, the use of metal trocars can actually reduce this risk by allowing the stored energy from a capacitor to
dissipate over the large surface area of the patient’s skin.
The use of an active electrode monitoring system and limiting the amount of time that a high voltage setting is
used can also eliminate concerns about capacitive coupling
273
Capacitive coupling is increased by open circuits and use of 5-mm cannulas (versus 10 mm), and higher
generator voltages ; avoid all this. (Level 2C )
Recommendation Grade B
Metallic trocar should preferred over plastic trocars while using coagulative current in order to prevent
capacitive coupling.
Use Active electrode monitoring system to and limiting the amount of time that a high voltage setting is used can
also eliminate concerns about capacitive coupling.
Statement- Hybrid cannulas must not be used.
Use of all metal cannula reduces capacitive coupling.

Fig 14: Capacitative Coupling: This is seen in

Fig 13: Any break in the insulation may provide an
hybrid canulas which have a plastic collar thereby
alternate pathway for the flow of current
converting the canula into a high energy capacitor.

Advanced Bipolar Electrosurgery

Advanced bipolar electrosurgery includes
LigaSure
EnSeal.
In advanced bipolar electrosurgery, the tissue impedance is monitored with continuous adjustment of the
generated voltage and current to maintain the lowest possible power setting to achieve the desired tissue
effect.(17)xx

BIPOLAR VESSEL SEALING DEVICES – LIGASURE (VALLEYLAB)

Delivers high current (4 A), low voltage (180 V) along with pressure from the jaws to tissue.
Can seal vessels up to 7 mm in size.
System monitors energy expended while denaturing the collagen and elastin within the vessels walls.
During cooling phase, cross linking re-occurs creating a new seal.
Computer algorithm adjusts the current and voltage based on real-time measures of tissue impedance - constant
delivery of wattage over a broad range of tissue types.
Lateral spread 2 mm
Can withstand 3 times SBP. (18)xxi

BIPOLAR VESSEL SEALING DEVICES – ENSEAL (SURGRx)

It uses a bipolar electrode to concentrate energy on tissue within the plastic jaws of the instrument and it claims
to offer improved efficacy by utilizing a temperature sensitive matrix (nanopolar thermostats) embedded within
the jaws of the device that controls the energy delivered to the electrode-tissue interface.
The instrument can seal vessels between 1 and 7-mm. (19)xxii

BIPOLAR VESSEL SEALING DEVICES – PLASMAKINTETIC (GYRUS)

Plasmakinetic generates Low voltage, high current in pulses and is based on Vapour pulse Coagulation.
V ’s pulse-off periods allow tissue to cool and moisture to return to the targeted area, greatly reducing hot
spots and coagulum formation.This technology also results in evenly coagulated target tissue, minimal thermal
spread, less sticking, and enhanced hemostasis.(19)

274
ULTRASONIC ENERGY
The Harmonic scalpel is an ultrasonic surgical instrument for cutting and coagulating tissue, operating at a
frequency of 55.5 kHz/second or 55,500 cycles per second.

There is no electrosurgical current generated.

The combination of mechanical energy and the heat that is generated causes protein denaturation and formation
of a coagulum that seals small blood vessels.
The device has demonstrated the ability to coagulate blood vessels up to 5mm in diameter with less heat,
charring, and thermal injury to surrounding tissues.(20)xxiii

LOW POWER [CUSA]

Vibrates at 23.5 - 25 KHz
Longitudinal displacement at tip 200 – 360 µm.
Cavitation occurs in tissues with high water content
Little coagulation because of cooling by saline irrigation and little tissue contact
Collagen rich tissue spared.

HIGH POWER [HARMONIC ACE]

Vibrates at 55.5 KHz
Longitudinal displacement of 80 – 200 µm.
Local temperature increases to 800 C.
Denatures proteins by vibration and creates a sticky coagulum that seals vessels.
Can seal vessels upto 5 mm [FDA approval 3 mm]

Transfer of mechanical energy to the tissues

Breaks tertiary High frequency

hydrogen bonds vibration of tissues

Generation of heat from

Denaturation of proteins
internal tissue friction

COAGULUM

Fig 15: Mechanism of Ultrasonic Energy in forming a coagulum

ULTRASONIC ENERGY - ADVANTAGES

No charring of tissues – planes maintained
Absence of coagulated tissue sticking to active element.
No heat sink effect as is seen in electrosurgery in case of blood vessels.
Much lower temperatures [800 versus 4000 in electrosurgery]
Can be used as a blunt dissector.
Less coagulating time, Less or no smoke
No electric current.

Comparison of four energy-based vascular sealing and cutting instruments

Harmonic ACE®, LigaSure® and EnSeal® vessel fusion system. The diameters of the vessels, speed and
adequacy of the cutting and sealing process, and bursting pressures were compared.xxi

The bursting pressures with nSeal™ were significantly higher than with all the other instruments. Harmonic
A ™ was the fastest sealing instrument and LigaSure was slowest. EnSeal & LigaSure created less radial
thermal damage to the adventitial collagen of the vessels. (Level 2B Grade B)

HEAD TO HEAD STUDIES

Harold et al [21]xxiv
Ligated vessel burst pressure compared Ultrasonic/Ligasure/Titanium clips/Plastic clips
275
Ligasure > US burst pressure for 4-7 mm
Clips highest burst pressure
Ligasure as good as clips for 4-5 mm
Thermal spread energy sources ~2mm (13)
Hruby et al [22]xxv
Harmonic Ace (up to 5mm), Ligasure (up to 7 mm)
Consistent reproducible force
Harmonic ACE is two times faster

Comparison between ligasure and harmonic

Ligasure vessel sealing device proves to have a hand over HS as it depends on the surgeon convenience to use
which of the energy sources when it comes to the handling and manourevilibity during surgery resulting in an
overall faster, bloodless and safer experience. (Level 2 B)
Estimated blood loss was significantly less in bipolar vessel sealer when compared with harmonic scalpel. The
bipolar vessel sealer is a reliable and safe tool for reducing intraoperative blood loss in patients undergoing total
laparoscopic hysterectomy. (23,24)xxvixxvii
RECOMMENDATION (grade B)
Bipolar sealing devices are better in vessel sealing than ultrasonic shears with less lateral thermal damage
compared to harmonic .
Ultrasonic device Is faster and has more maneuverability than Bipolar sealing devices.
STATEMENT- Bipolar sealing devices should be used for achieving better vessel sealing upto 7 mm.

EMERGING TECNOLOGY THUNDERBEAT®

THUNDERBEAT® is integration of both bipolar and ultrasonic energies delivered simultaneously from a single
versatile instrument. With benefits of each individual energy; the ability to rapidly cut tissue with ultrasonic
energy; and the ability to create reliable vessel seals with bipolar energy. (25)xxviii

Fastest in class cutting speed thereby reducing operation time.

Reliable 7 mm vessel sealing.
Precise dissection with fi ne Jaw design.
Always available bipolar energy for hemostasis without cutting.
Minimal thermal spread.
Fewer instrument exchanges.
Reduced mists generation help to maintain visibility

Recommendation (Grade B)
Combined use of ultrasonic energy & bipolar electrosurgery using low voltage cutting mode provides rapid
cutting & reliable sealing of vessels upto 7 mm.
STATEMENT - Combined ultrasonic and bipolar technology may be used for optimum vessel sealing.

REFERENCES
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1. Christopher MJ, Ketsia BP, Ian BN, et al. Electro surgery. Cur Surg. 2006;63:458
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2. Wu MP, Ou CS, Chen SL, Yen EYT, Rowbotham R. Complications and recommended practices for electrosurgery in
laparoscopy. Am J Surg. 2000;179:67–73.
3. 1Nezhat CH, Nezhat F, Brill I, Nezhat C. Normal variations of abdominal and pelvic anatomy evaluated at laparoscopy.
Obstet Gynecol. 1999;94:238 –242.
4. 1Masserwah NN, Cosgriff N, Slakey DP. Electrosurgery: History, principles, current and future uses. J Am Coll Surg
2006;202(3):520-530
5. 1Tucker RD, Schimitt OH, Sievert CE, et al. Demodulated low frequency currents from electrosurgical procedures. Surg
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25. World Journal of Laparoscopic Surgery, January-April 2014;7(1):41-44 43

UPPER LIMB ISHCAEMIA

Robbie George, Prasenjit Sutradhar

Limb Ischemia can present as acute or chronic limb ischemia. Identification and categorization of the same is
important as treatment decisions and interventional techniques differ in both cases.
Upper extremity ischemia accounts for less than 5% of patients presenting for evaluation of limb ischemia, with
a significant proportion of cases being caused by autoimmune/connective tissue diseases, nevertheless those who
present with acute ischemia from surgical causes need urgent intervention to prevent limb loss.
Prior to dealing with ischemia it is necessary to understand upper limb vasculature.

Figure 1Neck Vessels Figure 2Upper Limb Vessels

Vessels of the Upper limb

The Arterial inflow starts with the Subclavian artery which has a direct aortic arch origin on the left side
and originates from the brachiocephalic artery on the right.
1. Subclavian Artery – Divided in to three parts by the scaleneus anticus muscle- with the parts being
medial, behind and lateral to the muscle.
a. First part-Branches include the vertebral artery, internal thoracic (mammary) artery,
thyrocervical trunk
b. Second part–origin of costocervical trunk (splits into superior intercostal artery and deep
cervical artery)
c. Third part – origin of dorsal scapular artery

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 2. Axillary Artery - continuation of subclavian beyond lateral border of 1 st rib. Divided by pectoralis
minor into 3 parts
a. First part –origin of superior thoracic artery
b. Second part –origin of thoraco-acromial artery and lateral thoracic artery
c. Third part – origin of subscapular artery, Anterior humeral circumflex artery, Posterior
humeral circumflex artery.
3. Brachial artery – continuation of the axillary artery in the arm beyond the lower margin of teres major
muscle. Branches include profunda brachii artery (deep brachial artery), superior ulnar collateral artery,
inferior ulnar collateral artery, radial artery, ulnar artery. The radial and ulnar are terminal branches in
the forearm which form the palmar arch vessels.

The upper limb is relatively immune to the effects of arterial occlusion when compared to the lower limb by
virtue of two excellent collateral groups-at the scapula and the elbow. Anastomosis between the 1st part of the
subclavian artery, 2nd part of the axillary artery and the intercostal vessels over the scapula ensure that collateral
flow to the upper limb is secure in spite of occlusive disease in the major inflow vessels. Elbow collaterals fed
by the deep brachial artery maintain distal flow to the forearm in case of brachial occlusions.

Definition of ischemia

Acute ischemia is any sudden decrease in limb perfusion causing a potential threat to limb viability.
Chronic critical limb ischemia (CLI) defined as > 2 weeks of rest pain, ulcers, or tissue loss attributed to arterial
occlusive disease.

Upper limb ischemia can be further classified by duration i.e. acute vs. chronic, Anatomic location and vessel
size involvement. Knowledge of the territory involved has implications for management decisions.

Important anastomosis around the shoulder and elbow

Figure 3 Scapular Anastamosis Figure 4 Elbow Anastamosis

Etiology:
Acute ischemia
o Embolism – greater damage as collateral circulation deficient
 Cardiac source
 ventricular aneurysm
 atrial fibrillation associated thrombus
 myocardial thrombus post MI
 endocarditis
 cardiac tumours Figure 5 Aortic Arch Thrombus
 Atheroembolism from ulcerated plaque
 Aortic arch
 Innominate artery
 Subclavian artery
 From aneurysms of
 Arch
 Subclavian

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  Innominate artery
 Axillary or Brachial artery
 Ulnar artery
 Primary Aortic mural thrombus
 Paradoxical embolus i.e. DVT via ASD/VSD
 Vessel thrombosis due to Atherosclerotic obstruction- doesn't commonly cause severe acute
ischemia
 Prothrombotic state / sepsis
 Vasospasm- esp. drug induced in ICU
 Aortic dissection
 Bypass graft occlusion
 Traumatic
 Iatrogenic
 Post vascular / orthopaedic intervention
 Arterial drug injection

Chronic ischemia

Arterial Vasospasm
o Ergotism
o Idiopathic vasospastic Raynaud's syndrome
o Vinyl chloride exposure

Large-Artery Causes
o Atherosclerosis
o Thoracic outlet compression
o Arteritis -Takayasu's, Giant cell
o Fibromuscular disease
o Iatrogenic injury
o Dialysis steal syndrome

Small-Artery Causes
o Connective tissue diseases
o Scleroderma
o Rheumatoid arthritis
o Sjögren's syndrome
o Systemic lupus erythematosus
o Myeloproliferative disorders Figure 7 Bilateral cervical ribs
o Thrombocytosis
o Leukemia
o Polycythemia
o Buerger's disease
o Hypersensitivity angiitis
o Cold injury
o Vibration injury
o Henoch-Schönlein purpura Figure 8 Radio Ulnar Disease
o Cytotoxic drugs

Table 1: Arterial involvement related to disease process

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Risk factors
o Elderly age
 6 P’s
o Smoking
o Diabetes  Pain
o Hypertension  Paresthesia
o Hyperlipidemia  Paresis
o Obesity  Pallor
o Cervical ribs  Pulselessness
o Trauma
o Drug abuse
 Poikilothermia
o Connective tissue disorders
o Profession

Acute Upper Limb Ischemia

Presentation: of large vessel occlusion

Patients with upper limb ischemia will typically present with history of
 Limb weakness/ paralysis
 Rest Pain / claudication
 Temp loss / cold digits
 Colour changes
 Trauma / intervention
History of additional co morbid conditions needs to be elicited
 Arrhythmia / chest pain / cardiac disease
 Smoking
 Hypertension
 Diabetes mellitus
 CVA
 Hyperlipidemia
 Family history
 Prothrombotic state
 Cold induced discolouration of fingers
 Systemic symptoms of tiredness, malaise, fever
 History s/o connective tissue disorders- dry eyes/dry mouth/arthritis
 Exposure to vibrating tools

Patients with acute ischemia will have shorter timelines ranging from a few hours to a couple of weeks with
typically the absence of claudication.
Clinical examination of the patients require a detailed assessment of pulses in the limb ,the sensory / motor
status, skin changes along with a systemic examination of the cardiac system.
Careful clinical examination will rule out plausible venous or neurogenic causes which can on occasion have
similar presentations.
Patients presenting with acute ischemia/ compartment syndrome need urgent identification of the same as
revascularization within the” golden period” of 6 hours has excellent outcomes.

Category Description / Findings Doppler Signal

Prognosis Sensory loss Muscle weakness Arterial Venous
I. Viable Not immediately None None Audible Audible
threatened
II. Threatened
a. Marginally Salvageable if Minimal or none None Inaudible Audible
promptly treated
b.Immediately Salvageable with Moderate, rest Mild, Moderate Inaudible Audible
immediate pain
reconstruction
III.Irreversible Major Tissue loss Profound, Profound, Inaudible Inaudible
or permanent anesthetic paralysis (rigor)
nerve damage
inevitable

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Table 2 SVS classification of acute limb ischemia (Rutherford)
Investigations
Diagnosis of arterial tree occlusion is essentially clinical. Radiological investigations help to define the level and
cause of occlusion and also quantify collateral circulation to enable decision making regarding revascularization
options. This would include PVR, Arterial Doppler study, CT / MR angiogram or conventional contrast
angiography. In India CT Angiography is the investigation of choice for the speed, accuracy and quality of
reliable information it provides.
Imaging studies aren’t mandatory in all cases for eg. a patient with Atrial Fibrillation and an ischemic hand with
a palpable axillary pulse will have a brachial artery embolus that needs to be addressed surgically.
Additional investigations would include complete blood count, renal profile, liver function tests, coagulation
profile, lipids, diabetic profile and ECG and 2D ECHO for cardiac assessment. Some or all of these
investigations can be deferred dependent upon the urgency of treatment required.
CPK levels help assess muscle damage in patients with acute ischemia but should not delay or determine the
need for treatment.

Management
Patients with acute ischemia should undergo some form of revascularization unless the ischemia is irreversible
or co-morbid conditions preclude such interventions. The latter situation can be a patient with an acute massive
MI and a distal embolus to the hand. Such situations require significant senior clinical input and judgment for
appropriate decision-making. It should be appreciated that acute upper limb ischemia often occurs in a
population with significant other medical conditions that can complicate the outcome.

Figure 9 Doppler and PVR study of Upper limbs Picture 10 CT angiogram showing right
brachial occlusion
Steps of management:
1. Assess and document the degree of compromise in terms of sensory/motor weakness, compartment
syndrome, tissue loss etc. Assess and document whether there is any evidence of neurological deficit
especially of the cerebellar system-emboli entering the arm can also go through the vertebral artery.

2. Clinical assessment of level of arterial occlusion- if the subclavian pulse is not well palpable in the
supraclavicuar fossa it is preferable to obtain an urgent CT of the aortic arch and upper limb to identify
central pathology. If the subclavian pulse is very prominent remember to consider the possibility of a
subclavian artery aneurysm.

3. If no contra-indications administer Intravenous Heparin at 80 u/kg- the usual dose is around 5000U.
This dose will need to be halved for patients with renal compromise. Administer appropriate analgesia.

4. Patients in Category IIb need urgent surgery in the form of an embolectomy/bypass/thrombo-aspiration.

Judge the need for a concomitant fasciotomy- this is relatively uncommon. Patients in Category IIa
should undergo revascularization at the earliest providing medical co-morbidities permit. Category 1
can be managed electively if needed. Category IIa and 1 can be candidates for endovascular strategies if
appropriate. Category 4 will likely need an amputation- this should be carried out urgently if there is
compartment syndrome. Leaving an ischemic limb attached will likely lead to myoglobinuria/Acute
Kidney Failure and/or sepsis.

Surgical Management
Class I – These patients can be treated with anticoagulation and observation/elective surgery

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Class II / III – Patients with advanced ischemia are treated with open / endovascular intervention techniques
Embolectomy–performed under local anaesthesia via transbrachial route
Thrombolysis– Catheter directed procedure using Urokinase / Alteplase
Fasciotomy – Done for compartment syndrome
Bypass – done for failed embolectomy/ thrombolysis
Amputation - Indicated in non salvageable limbs
Most patients with acute upper limb ischemia are managed by a trans-brachial embolectomy. The Brachial artery
and its branches are exposed just below the elbow with a vertical/lazy S incision (if crossing the elbow crease).
The artery is opened transversely just above its division and embolectomy carried out typically with a Fogarty
No.3/4 catheter for the proximal vessel and a No. 2/3 for the distal vessels. Once adequate flow is restored the
vessel is closed with Prolene 6/0 sutures and reperfusion confirmed by examination of fingertips for capillary
return and presence of pulses at the wrist. If required the embolectomy can be supplemented by instillation of 1
lakh Units of Urokinase or 5mg of tPA into the distal vasculature prior to arteriotomy closure. Always assess the
forearm and hand for compartment syndrome at the end of the procedure.
Continue therapeutic anti-coagulation post-operatively. This would be typically in the form of Low Molecular
Weight Heparins like Enoxaparin (1.5mg/kg OD or 1mg/kg BD) that would then be converted to oral
anticoagulation either in the form of Vita K antagonists like Warfarin or Acitrom or in the form of newer oral
anticoagulants like Rivaroxaban, Dabigatran or Apixaban.

Figure 11 Transbrachial embolectomy Figure 12 Catheter directed brachial artery

thrombolysis. Pre and Post
Endovascular Management
Category 1 and IIa patients may be considered for endovascular management. This can be in the form of catheter
thrombo-aspiration with catheter directed thrombolysis supplemented by angioplasty as required. Such
techniques are especially helpful in patients with acute on chronic ischemia where the arterial tree may be
already significantly diseased and also collateralized. Thrombo-aspiration technologies like the use of Angiojet,
Penumbra with Indigo system etc. can be considered in such cases.

Chronic ischemia
Presentation
Patients with disease involving the large vessels and small vessels present differently.
Large vessel occlusion may be completely asymptomatic or present with upper limb claudication. More
commonly the reduced BP on the affected arm is what brings the disease process to notice.
Patients with significant claudication can be considered for endovascular revascularization/open surgical bypass
dependent on the pathology and anatomy of disease.
Patients with occlusion of the 1st part of the subclavian artery proximal to the vertebral artery can present with a
Subclavian steal syndrome. These patients are perfusing their upper limb through reversed flow through the
vertebral artery. They may develop dizziness/collapse on exercise of the upper limb, which causes a relative intra
cerebral arterial insufficiency. This diagnosis can be confirmed by provocative exercise and confirmation of
reversal of flow in the ipsilateral vertebral artery.
Patients with small vessel disease typically present with col induced pain and colour change or with very painful
ischemic ulcers/erythema in the fingers. The peripheral pulses will typically be palpable and history will often
reveal co-existent arthritis/dry eyes/systemic complaints. Often these patients will already be under treatment for
auto-immune pathology.

Investigations:
Investigations required will depend upon the suspected pathology and vessel size involvement that is suspected.

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Haematological and biochemical tests for assess for etiology such as CBC, Lipid Profile, Blood Sugar,
Prothrombin Time. Assessment of auto-immune disorders- ESR, CRP, Anti phospholipid antibody, Rheumatoid
factor, Anti-nuclear antibody titre should be carried out when auto-immune pathology is suspected.
Radiological investigations especially CT/MR angiogram are helpful to assess large vessel disease. Doppler
Ultrasound is a useful modality provided it is performed by an experienced and reliable technologist.

Medical Management
This is the main stay of management in patients with upper limb arterial ischemia that is a result of vasospastic
or small vessel disease and collateralized adequately. Thoracic sympathectomy/ periarterial digital
sympathectomy for vasospastic disorders is of low efficacy duration of effect 3 to 6 months.
o Smoking cessation
o Control of the active auto-immune process using steroids/other immunosuppresants such as
Methotrextae or the newer disease modifying agents- this should be done under the supervision of a
rheumatologist
o Control of hypertension/ diabetes/ hyperlipidemia
o Antiplatelet therapy with Aspirin 75mg daily may have a role that is yet unproven
o Calcium channel blockers (Nifedepine extended release 30mg/d in divided doses)
o Topical nitrates for areas of ulceration
o Adequate analgesia
o Phosphodiesterase (Cilostazole) inhibitors may have a role that is yet unproven
o Keep upper limbs warm and avoid cold exposure
o Prostaglandin infusion therapy can provide significant pain relief in auto-immune disorder
associated rest pain

Surgical Management
Indicated in patients with upper limb claudication, rest pain, gangrenous change / tissue loss or subclavian steal
syndrome. It is also indicated for those with aneurysm disease- the commonest being subclavian aneurysms
secondary to thoracic outlet compression. Majority of the procedures are open with endovascular procedures
limited to the axillary / subclavian artery segment.

Procedures:
1. The first part of the subclavian artery is approached almost exclusively by endovascular means and is
treated with angioplasty and stenting as appropriate. All interventions in this area carry a small risk of a
stroke in the vertebral artery territory.
2. Open surgery in the Thoracic Outlet- this is most commonly performed for arterial thoracic outlet
syndrome and involves resection of the scalene anticus, scalene medius and the cervical rib and if
required the first rib. This procedure creates adequate space for the subclavian artery as it exits the chest
and enters the arm. This is often combined with some form of arterial reconstruction either as an
intimectomy/aneurysm repair or an interposition bypass.
3. Bypass graft – Synthetic grafts are preferred for bypasses to the subclavian or axillary artery while
autogenous vein preferred as
choice of conduit for more distal bypasses.

Figure 11 Cervical ribs pre and post excision

Figure 12 Palmar artery bypass

Conclusion:
Upper limb ischemia is a relatively uncommon problem. However acute ischemia can be a critical situation as it
is often complicated by associated co-morbidities.
Chronic ischemia is often secondary to auto-immune processes that involve small vessels or secondary to
anatomical anomalies within the thoracic outlet or atherosclerotic disease. Extensive collateral circulatory
networks around the shoulder and elbow protect the upper limbs from the effects of occlusive disease more so
than in the lower limbs.

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A through clinical assessment, supported by appropriate blood and radiology investigations can help ensure limb
preservation and salvage for most patients.

THE ANDI (ABERRATION IN NORMAL DEVELOPMENT AND INVOLUTION)

Anurag Srivastava

Significance of Terminal Ductal Lobular Unit (TDLU) : Since TDLU is most hormone responsive part of breast
parenchyma, most hormones exert their influence on structure and function of mammary gland through these
TDLU.
Do you know that most diseases of the breast arise from growth of TDLU- viz. firoadenoma, cancers - ductal
and lobular types , breast cysts. Mastalgia or breast pain occurs due to excessive proliferation of ductolobular
tissue in the premenstrual period under the influence of oestrogen and progesterone. Recently the regression of
TDLU around the cancer on histology has been linked to its prognosis. Yang et al. Breast Cancer Research 2012,
14:R64 http://breast-cancer-research.com/content/14/2/R64.

Figure 1 : The Terminal Ductal Loblular Unit

Cyclical Changes with in the mammary gland with menstrual cycle:

Since the beginning of menstrual cycle till menopause, the mammary glands are continuously undergoing
changes in size, volume, consistency, cellular architecture, vascularity and secretary function. These changes are
brought about by various hormones and nervous stimuli. Main hormones influencing the structure and function
of breast tissues are the oestrogen and progesterone along with Prolactin and Oxytocin. The cyclic changes in the
mammary tissue reflect the day to day variation in the blood levels of oestrogen and progesterone occurring
through the menstrual cycle.

Figure 2 : The Hormonal changes during menstrual cycle

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Oestrogen and progesterone act as growth factor for ductolobular tissue. Oestrogen helps in inducing the initial
duct development and stromal development. It also increases the breast vascularity and helps in deposition of fat
in the breast.
Progestrone acts on tissue primed by oestrogen. It helps in lobule and alveolar development and in branching of
the mammary ducts. It later induces proliferation and secretion within lobules. In the premenstrual period ,
progesterone is responsible for water retention and increase in breast volume by increasing its water content.
The main hormone responsible in bringing about milk secretion is Prolactin. It acts on ductolobular tissue
initially primed by oestrogen and progesterone.
Insulin , growth hormone and gluocorticoid hormones have a minor role in development and functions of breast
tissue.

The ANDI concept has been helpful in understanding of most benign conditions of the breast. It replaces old
terms like- fibroadenosis, fibrocystic disease and chronic mastitis as these old terms do not have any correlation
between clinical features and histological changes. Most benign conditions can be explained as the aberration in
the normal development , growth and later involution of breast after age 35 years.
Simple explanation of benign breast disease on basis of ANDI concept:
Breast pain or Mastalgia: Mastalgia is the commonest symptom of benign breast disease. In the initial part of
menstrual cycle, oestrogen level rises and falls to very low level by day 14 ( see figure2) . On the day 14,
Ovulation occurs resulting in formation of Corpus luteum. Corpus luteum secrets both oestrogen and
progesterone
which rise to a peak level from day 18 to day 24. Since, oestrogen and progesterone are growth factors to
ductolobular tissue , they induce mitosis within the breast parenchyma increasing the total mass of breast tissue.

To this is added the excess water and fat in the premenstrual phase. All these excess mass of cells, water and fat
have to be accommodated within the skin envelope of the breast , which like a balloon stretches with increased
tension and increased pressure on the pain nerve endings. You can appreciate that this pain and tenderness would
increase from day 18 onwards and reach its zenith ( peak) level around day 26 to day 28. With the onset of
menstrual flow, the levels of hormones suddenly drop to very low or a nadir level. As, these hormones serve as
growth factors, we can understand that the absence of mitogenic fertiliser ( just as the plants shrivel when you
stop giving them “water and fertiliser”) would result in shrinkage of ductolobular tissue , less interstitial water
and less fat- overall less tension on the pain nerve endings. Thus, the lady feels comfortable as the pain and
tenderness eases of with the onset of menstrual flow. She lives comfortably for two weeks in the follicular phase
of menstrual cycle, only to be troubled with the next bout of mastalgia from day 14 onwards in the luteal phase.
These cycles of pain may progressively increase in severity and duration to the extent that ladies may get
psychologically withdrawn and are likely to be labelled as “Neurotic”. When the pain is very severe, the lady
forgets the relation of pain with menstrual cycle and may
deny any relationship with menstruation or may state that
the pain is present through the month (hence, wrongly
labelled as non-cyclical mastalgia ). Therefore, it is
important to record the pain experience in a diary. It is
recommended that a breast pain chart be filled for at least
two menstrual cycles to see the pattern of pain in relation
to particular days of the cycle.

Conditions that can be explained by the ANDI

Hypothesis
A large number of benign breast conditions can be
explained on the basis of the concept of aberration form
the normal growth, development and involution.
These conditions are summarized in the following table

• Surgery: There is very limited role for surgery in treatment of mastalgia. Surgery can be useful in selected
patients with a discrete, small trigger spot whose symptoms may be relieved by excision of spot [38].

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 INTRODUCTION
CHRONIC LIMB
ULCERS
 An ulcer is defined as an area of discontinuation of the
surface epithelium.
Prof. Mohammad Aslam
Chairman,
Department of Surgery,
JN Medical College,
Aligarh Muslim University, Aligarh.

CHRONIC WOUNDS
• Wounds that do not heal within three months of their development are How do wounds heal
considered chronic[1]

• Wounds cause patients severe emotional and physical stress , a significant • Haemostasis
finantial burden on patients and whole healthcare system [2]
• Inflammation
• Chronic wounds are those wounds that have failed to proceed through an
orderly and timely reparative process to produce anatomic and functional
integrity over a period of 3 months. • Proliferation or Granulation

1. MUSTOE.T 2004 . AMERICAL JOURNAL OF SURGERY

2. AUGUSTIN M AND MAIER K. 2003 . DERMATOLOGY AND PSYCH
• Remodelling or Maturation

Chronic wounds
The wound healing cascade impairs and arrests at different stages
Hemostasis

Platelet Aggregation
Neutrophil Immigration CHRONIC WOUND

Monocyte Immigration

Granulation
Re-epithelialization

Wound Closure

Scar Formation

Remodeling

Normal Healing Process

286
Local factors that impede wound healing Systemic factors that impede wound healing
• Inadequate blood supply
• Advancing age and • Systemic malignancy
• Increased skin tension and terminal illness
• General immobility
• Poor surgical apposition • Obesity
• Chemotherapy and
radiotherapy
• Wound dehiscence • Smoking
• Immunosuppressant
• Poor venous drainage • Malnutrition drugs, corticosteroids,
• Presence of foreign body and foreign body • Deficiency of vitamins anticoagulants
reactions • and trace elements • Inherited neutrophil
• Continued presence of micro-organisms & disorders, such as
leucocyte adhesion
Infection deficiency
• Excess local mobility, such as over a joint • Diabetes and CRF

Appearance of a chronic wound Chronic Wounds Appearance

Approach has been criticised for being too simplistic as wound healing is a
continuum
and wounds often contain a mixture of tissue types.

Wound healing continuum Necrosis

Wound Healing Continuum (Gray et al. 2005) have

been developed. This tool incorporates intermediate
colour combinations between the four key colours

287
 Sloughy Granulation

EPITHEALISING
Factors which influence wound infection
1. The quantity of micro-organisms
2. Quality –Virulence and antibiotic resistance
3. The patients resistance to the level of bacteria in the
wound( immune response)
Microbial bio-burden within wounds can range from
contamination, colonisation, critical colonisation and
infection.

1.Organims from surrounding

Clinical Signs of wound infection
Wound
Contamination skin- Regional flora-
Deptheroids, Anerobes
Classical Signs
Hand
Wound hygeine 1. Increased pain
Colonization
3.Organisms from External
Wound Surface environment- through direct or 2. Copious amounts of exudate
indirectly – Pseudomonas,
Critical Multiresistant organisims etc
Colonization 3. Malodour

Wound Fecal and urinary management systems

4. Cellulitis
Infection

2.Organisms from GIT and GUT

5. Pyrexia
Advance Wound Gram Negatives such as E.coli,
Infection Klebsiella, Enterobacter, Anerobes 6. Abscess Formation

288
Additional Signs Classification of Chronic Limb Ulcers
• Increase in size of wound
A). VASCULAR
• Delayed wound healing
ARTERIAL VENOUS LYMPHATICS
• General unwellness • Atherosclerosis
• Burger’s
• Dark discoloured granulation tissue • Vasculitis
• Raynaud’s disease
• Increased friability
• Pocketing at base of wound.

• B). INFECTIVE C). TRAUMATIC D). NEOPLASTIC

E). SYSTEMIC METABOLIC F). NEUROPATHIC
• Pyogenic • Radiation • Melanoma
• Thermal burn • Squamous cell • Ulcerative colitis • Cord lesion
• Osteomyelitis
• Bites carcinoma • Diabetes • Peripheral neuropathy
• Tuberculosis • Basal cell
• Syphilis • Sickle cell anemia • Trauma
carcinoma
• Fungal disease • Kapoi’s sarcoma • Tabes dorsalis

CLINICAL ASSESSMENT OF LEG ULCER

289
 LEG ULCER

HISTORY
PHYSICAL EXAM

PAINFUL ULCER PAINLESS ULCER NORMAL VASCULATURE

CHRONIC VENOUS ULCER
Associated
Signs/Symtoms History of trauma

• Chronic venous insufficiency- People who have developes

•Rest pain Chronic edema Chronic ulceration
•Cool extremity Erythema Elevetaed edges
Varicosities Decreased cutaneous
•Weak/absent pulses sensation Purulent exudate
•Hairless skin
Pigment changes
Ulcer Parasthesias/Numbness/ Traumatic ulcer irreversible skin damage as a result of sustained ambulatory
Burning
Skin biopsy Hammer Toes
Skin biopsy
Culture of exudate Skin biopsy hypertension
Arteriography

Doppler Neoplastic ulcer

Arterial ulcer ultrasound Neurotrophic ulcer Infectious ulcer

Diffrentials Differentials

• Chronic venous ulcer- Defined as break in skin , present for

Differentials
Venous ulcer Differentials
•Emboli/thromboli Differentials Burn/heat
•Arteriosclerosis obliterans
Diabetes mellitus
Exogenous Squamous cell
Frostbite more than 6 months that is presumed to be wholly or partially
•Thromboangitis obliterans Bacterial carnoma Pressure
•Hypertensive ulcer Differentials
neurotoxins
Alcoholism Fungal Basal cell carcinoma Post radiation due to venous disease.
•Raynauds disease Sarcoidosis Mycobacterial Lymphoma Insect bite
•Vasculitis/pyoderma •Venous occlusion Treponemal Sarcoma
Leprosy
gangrenosum •thrombophlebitis Viral metastasis
Syphilis
•Sickle cell disease

Why do patients with chronic venous

What are the risk factors for VLU?
insufficiency develop VLU?
• CVI most common cause of VLU • Age older than 55 years
• VLU patients have venous hypertension, or abnormally sustained • Family history of CVI
elevation of venous pressure on walking • Ulcer history, parental history of ankle ulcers
• Caused by vein valve reflux, outflow problems or both
• Higher body mass index
• Venous outflow issues
• History of pulmonary embolism
• Venous obstruction
• Venous reflux in deep veins, history of superficial/DVT
• Poor function of calf muscle pump impairs venous system's ability
to return venous blood to heart • Lower extremities skeletal or joint disease
• Ankle movement limitations contribute to calf muscle pump failure • Number of pregnancies
• Physical inactivity
• Severe lipodermatosclerosis

Venous Ulcer Presentation Chronic venous insufficiency

• Shallow, moist and red

• Often copious drainage
• Gaitor area
• Brawny staining of skin
• Leg edema

290
 Venous leg ulcer DIAGNOSIS
• Typically based on clinical history and physical examination
 Presence of CVI
 Single, painful ulcer with irregular, flat borders and granulating or
fibrinous bed on medial lower third of legs
• Color duplex ultrasonography to characterize venous disease in all
patients
• Ankle-brachial index to exclude concurrent PAD
• If VLU do not improve within 4 weeks of active therapy: consider
biopsy

Overall approach to treatment? What is the role of compression therapy?

• Treatment goals
• Reduce edema and pain
• Heal ulcers
• Prevent recurrence
• Systematic approach needed
• Assess frequently and escalate treatment if unresponsive
• Simplest treatment: bed rest with leg elevation
• Elevate legs above heart 30 minutes, 3 to 4x/d + at night
• Reduces swelling, improves venous microcirculation
• Most patients struggle to follow this recommendation
• Cornerstone therapy
• Because sustained leg elevation often difficult to achieve
• Gold standard: multiple elastic layers for graduated compression
• Increases interstitial hydrostatic pressure
• Improves venous return
• Reduces venous hypertension and edema
• Improves ulcer healing rates
• Use cautiously with CHF and with arterial insufficiency
• Don’t use with severe arterial insufficiency

V.A.C.® Therapy: Mechanisms of Action (MOA)

Combined Effects of Macrostrain and Microstrain

1. Saxena V, et al. Vacuum-Assisted Closure: Microdeformations of Wounds and Cell Proliferation. Plastic and Reconstructive Surgery,
2004; 114(5): 1086-96.
2. Wilkes R, et al. Effects of Dressing Type on 3D Tissue Microdeformations During Negative Pressure Wound Therapy: A Computational
Study. Journal of Biomechanical Engineering, March 2009; 13(3): 031012-1-12.
3. Ingber DE, et al. Fibronectin Controls Capillary Endothelial Cell Growth by Modulating Cell Shape. Proceedings of the National Academy
of Sciences of the US, 1990; 87:3579.
4. Greene AK, et al. Microdeformational Wound Therapy: Effects of Angiogenesis and Matrix Metalloproteinases in Chronic Wounds of 3
Debilitated Patients. Annals of Plastic
Surgery, April 2006; 56(4):418-422.

291
 What is the role of venous surgery in
What is the role of medication?
treatment and prevention?
• To improve healing in combination with compression • Venous surgery
• Aspirin • Doesn’t improve healing but reduces recurrence
• Pentoxifylline • Open surgery has significant potential morbidity
• To reduce LDS inflammation, pain, induration • Cochrane review found no evidence for benefit or harm
• Stanozolol • Subfascial endoscopic perforator surgery
• Oxandrolone • Safer, possible improved healing, decreased recurrence
• Horse chestnut seed extract (active ingredient: aescin) • Minimally invasive procedures
• To reduce pain (based on neuropathic origin) • Treat CVI and recurrence
• Amitriptyline, gabapentin, pregabalin • Endovenous thermal ablation (laser, radiofrequency, steam)
• US-guided foam sclerotherapy; cyanoacrylate embolization

RISK FACTORS FOR ARTERIAL LEG

ARTERIAL LEG ULCER
ULCER
• CHRONIC LIMB ISCHEMIA- Persistent rest pain that requires • Men > 45years
regular adequate analgesia for atleast 2 weeks, with resting ankle • Women >55 years or premature menopoause
pressure of <50mm Hg or toe pressure of 30mmHg • Family history
• Smoking
• Hdl<35mg/dl
• Hypertension
• Presence of gangrene /ulcer of the foot /toes with the same resting • Diabetes mellitus
pressure • Eleveted plasma fibrinogen leveland homocysteine level
• Sedentary life style

Clinical categories of chronic limb

Fontaine classification- severity of CLI
ischemia
• Stage I- Asymptomatic
• Stage II- intermittent claudciation limiting lifestyle
• Stage III- Rest pain due to ischemia
• Stage IV- Ulcer/ Gangrene due to ischemia

292
 Patho - physiology of Arterial ulcer Presentation
• Claudication
• Macrovascular • Microvascular
– Fatty streak – High blood viscosity • Rest pain
– Fibrous plaque – Endothelial swelling
– Complicated lesion – Platelet/ RBC/ PMN plugging • Ulcer
• Ulcer – Incresed permiability and tissue
• Hemorrahage edema • Gangrene
• Calcification – Reduced and unevenly distributed
flow
• Necrosis

Ankle Brachial Pressure Index

(ABPI) IMAGING
• ABPI{Leg} = P{Leg} / P{Arm}
• P leg - blood pressure of dorsalis pedis / posterior tibial arteries • USS + Doppler – duplex scan • CT/MR Angiography
• P Arm - brachial systolic blood pressure
• Less than 0.9 is abnormal
• ABPI < 0.5 is better predictor of non healing

TREATMENT FOR CHRONIC

DUPLEX SCAN
ARTERAIL ULCER
• USS + Doppler
• Can visualise the vessels, • Local
stenosis, plaques
• Can see the flow and its quality
• Regional
• Non invasive
• Good for infrainguinal vessels
• Systemic
• Abdomial vessels – obscured by
bowel gas

293
LOCAL Indications for revascularization
• Wound toilet • Disabling claudication
• Process of removal of slough, dead
tissue, foreign bodies and draining
pus. • Rest pain

• Following a wound toilet the wound • Tissue loss

base is made suitable for future
granulation and epithelialisation.
(Fontaine stage IIB, III, IV)
• Ischaemic ulcer – if infected / wet –
wound toilet before revascularization /
otherwise (dry scab, dry gangrene )
revascularization and then wound
toilet

• Surgical Angioplasty and/ Stenting

1.Bypass
2.Endarterctomy

• Endovascular
1.Angioplasty and/
2.Stenting

• Amputation

Treatment of Systemic causes

NEUROPATHIC ULCERS
• Correct anaemia, vitamin deficiency and other nutritional • Common are Diabetic ulcers; Leprosy .
deficiencies. • DIABETIC ULCERS :
• Neuropathy & peripheral vascular disease are important etiological
• Optimization of underlying comorbidities. factors.

• Role of antibiotics in wound - indicated only in patients with

evidence of local or systemic infection.

294
 PATHOGENESIS • b)Autonomic neuropathy- hypohydrosis of foot

a)Neuropathy - loss of protective pain sensation &motor dysfunction

fissures & calluses

repetitive trauma
ulceration

ulceration.

c)Atherosclerotic changes in Lower Limb vessels CLINICAL FEATURES

Thickening of capillary BM & endothelial gaps
• Burning,numbness,itching,paresthesias of distal extremeties.
• Claudication history present.
Increased vascularpermeability • Location –at pressure sites.
a.Plantar surface overlying the I & V metatarsal heads.
b.Plantar surface of great toe& the heel.
Ulcer.
• Ulcer-”punched out” with thick rim of callus surrounding the
ulcer.
• Dryness &fissuring of surrounding skin.

DIABETIC FOOT ULCER INVESTIGATIONS

• Routine hemogram; Blood sugar levels;
• Hemoglobin AIc- glycated Hb levels-
• 3-6% normal
• 7-8% - well controlled diabetes
• > 9% -neuropathy & nephropathy.

• Contrast Arteriography.

• MRA &Contrast Tomographic angiography.

295
MANAGEMENT
• Aggressive debridement mechanical/ enzymatic.
• Treatment of associated arterial diseases.
• Restoration of circulation to the lower extremity.
• Dry necrotic ulcers-Hydrocolloid dressing &Hydrogels.
• Orthotic devices-decrease pressure at the site.
• Becaplermin gel-topical application

REFRENCES
1. Mustoe.t 2004 . Americal journal of surgery REFRENCES Cont…
2. Augustin M and Maier K. 2003 . dermatology and psych
3. Brook I, Frazier EH. Aerobic and anaerobic microbiology of chronic venous leg ulcers. International Journal 11. Barwell, JR et al. Comparison of surgery and compression with compression alone in chronic venous
of Dermatology 1998;37:426-8. ulceration (ESCHAR study): randomised controlled trial. Lancet. 2004 Jun 5;363(9424):1854-9.
4. Halbert AR, Stacey MC, Rohr JB, Jopp-McKay A. The effect of bacterial colonization on venous ulcer 12. Lazarides M K, Giannoukas A D. The role of hemodynamic measurements in the management of venous and
healing. Australasian Journal of Dermatology 1992;33:75-80. ischemic ulcers. Int J Low Extrem Wounds. 2007;6:254–261. [PubMed]
13. Mekkes J R, Loots M A, Der Wal A C Van, Bos J D. Causes, investigation and treatment of leg ulceration. Br
5. Harker J. The effect of bacteria on leg ulcer healing. British Journal of Community Nursing 2001;6(3):126- J Dermatol. 2003;148:388–401. [PubMed]
34. 14. Hume M. A venous renaissance? J Vasc Surg. 1992;15:947–951. [PubMed]
6. Hansson C Hoborn J Moller A Swanbeck G The microbial in venous leg ulcers without clinical signs of 15. Lawrence P F, Gazak C E. In: Gloviczki P, Bergan J, editor. Atlas of Endoscopic Perforator Vein Surgery.
infection Dermato-venereologica 1995;75(1):24-© 2011 KCI Licensing, Inc. All rights reserved. DSL#11- London: Springer-Verlag; 1998. Epidemiology of chronic venous insufficiency.
0136 16. Adam D J, Naik J, Hartshorne T, Bello M, London N JM. The diagnosis and management of 689 chronic leg
ulcers in a single-visit assessment clinic. Eur J Vasc Endovasc Surg. 2003;25:462–468. [PubMed]
7. C, J, A, G. flora infection. Acta 30. 17. Nelzén O, Bergqvist D, Lindhagen A. Venous and non-venous leg ulcers: clinical history and appearance in a
8. Bowler PG. The 105 bacterial growth guidelines: reassessing its clincial relevence in wound healing. population study. Br J Surg. 1994;81:182–187. [PubMed]
Ostomy and Wound Management 2003;49(1):44-53. 18. Nicolaides A N, Allegra C, Bergan J, et al. Management of chronic venous disorders of the lower limbs:
guidelines according to scientific evidence. Int Angiol. 2008;27:1–59. [PubMed]
9. Davies CE, Hill KE, Newcombe RG, Stephen P, Wilson MJ, Harding KG, Thomas DW. A prospective study 19. Labropoulos N, Patel P J, Tiongson J E, Pryor L, Leon L R, Jr, Tassiopoulos A K. Patterns of venous reflux
of the microbiology of chronic venous leg ulcers to reevaluate the clincial predictive value of tissue biopsies and obstruction in patients with skin damage due to chronic venous disease. Vasc Endovascular Surg.
and swabs. Wound repair and regeneration 2007;15(1):17-22. 2007;41:33–40. [PubMed]
20. Nicolaides A N, Hussein M K, Szendro G, Christopoulos D, Vasdekis S, Clarke H. The relation of venous
10. Nelson, EA, et al. Compression for preventing recurrence of venous ulcers. Cochrane Database Sys Rev.
ulceration with ambulatory venous pressure measurements. J Vasc Surg. 1993;17:414–419. [PubMed]
2000;(4);CD002303.

REFRENCES Cont…
21. Pappas P J, You R, Rameshwar P, et al. Dermal tissue fibrosis in patients with chronic venous insufficiency
is associated with increased transforming growth factor-β1 gene expression and protein production. J Vasc
Surg. 1999;30:1129–1145. [PubMed]
22. Bergan J J, Schmid-Schönbein G W, Smith P D, Nicolaides A N, Boisseau M R, Eklof B. Chronic venous
disease. N Engl J Med. 2006;355:488–498. [PubMed]
23. Renner R, Simon J C. Current therapeutic options of chronic leg ulcers. J Dtsch Dermatol Ges.
2008;6:389–401. [PubMed]
24. Hirsch A T, Criqui M H, Treat-Jacobson D, et al. Peripheral arterial disease detection, awareness, and
treatment in primary care. JAMA. 2001;286:1317–1324. [PubMed]
25. Bartholomew J R, Olin J W. Pathophysiology of peripheral arterial disease and risk factors for its

Thank You
development. Cleve Clin J Med. 2006;73(Suppl 4):S8–S14. [PubMed]
26. Paraskevas K I, Baker D M, Vrentzos G E, Mikhailidis D P. The role of fibrinogen and fibrinolysis in
peripheral arterial disease. Thromb Res. 2008;122:1–12. [PubMed]
27. Leon L R, Rodriguez H E, Labropoulos N. In: Mansour M, Labropoulos N, editor. Vascular Diagnosis.
Philadelphia, PA: Elsevier Saunders; 2005. Arterial occlusion: thrombotic versus embolic. pp. 223–236.
28. Schweitzer M E, Morrison W B. MR imaging of the diabetic foot. Radiol Clin North Am. 2004;42:61–71,
vi. [PubMed]
29. Khachemoune A, Kauffman C L. Diagnosis of Leg Ulcers. The Internet Journal of Dermatology. Available
at: www.ispub.com. 2002. Available at: www.ispub.com
30. Hafner J, Schneider E, Burg G, Cassina P C. Management of leg ulcers in patients with rheumatoid arthritis
or systemic sclerosis: the importance of concomitant arterial and venous disease. J Vasc Surg.
2000;32:322–329. [PubMed]
31. Treiman G S, Copland S, McNamara R M, Yellin A E, Schneider P A, Treiman R L. Factors influencing
ulcer healing in patients with combined arterial and venous insufficiency. J Vasc Surg. 2001;33:1158–1164.
[PubMed]
32. Padberg F, Jr, Cerveira J J, Lal B K, Pappas P J, Varma S, Hobson R W., II Does severe venous
insufficiency have a different etiology in the morbidly obese? Is it venous? J Vasc Surg. 2003;37:79–85.
[PubMed]

296
 Fluid Therapy in
Surgical Patients Objectives
• Understand Volume replacement of fluids
• Fluids used in clinical practice
• Estimate of losses
Dr Pawanindra Lal • Changes during metabolic response to
MS, DNB, FCLS, FRCS(Ed), FRCS(Glasg), FRCS(Eng), FACS, FAMS
trauma/surgery
Director Professor & Head of Surgery
Maulana Azad Medical College & LN Hospital, University of Delhi. • Fluid replacement after surgery
Chairman, Division of Minimal Access Surgery,
Head, Clinical Skills Centre,
• Fluid replacement for special conditions
Editor-in-Chief – MAMC Journal of Medical Sciences,
Examiner for MS,DNB,FNBE(MAS),MRCS,FRCS
Dr B C Roy National Awardee 2016

Colloid Volume Expanders Intravenous Solutions

Fluid Source Conc Mol Wt IV stay Fluid Glucos Na K Cl Ca Lacta
e (g/l) te
5% Dextrose 50 - - - - -
HES Maize starch 6% 265000- 50%, 8
450000 hrs 0.9% Saline - 154 - 154 - -
Dextran Bacterial 6% 70000 50%,8hr
70 4.3%D, 0.18% 43 31 - 31 - -
S
Dextran Bacterial 10% 40000 <Dex 70
40 Ringer’s - 131 5 112 2 28
Lactate
Hemaccel Heat 3-4% 35000 50%, 4
degraded hrs
cattle gelatin

Recommended Daily Requirements

Nutrient Per kg Body wt For 70 Kg Sodium Deficit (mmol):
Water (ml) 35 2450 Normal Na – measured Na x 0.2 x body wt.
Non Prt Cal 30 2100 Treatment for Hyponatremia
CHO (g) 2.0 140 Define the problem
Fluids Na<150-0.9% saline
Fat (g) 3.0.70 210 Na>150-5%D
Prt (g) 0.7 50 Rate & Volume
50%of deficit + continuing losses + normal requirement
Nitrogen(g) 0.1 7 Treat primary cause
Na (mmol) 1-1.5 70-105 Close Monitoring
K (mmol) 1.0 10
Vit B (mg) 0.5 35 Normal Na Requirement = 1-2mmol/Kg/day
Vit C (mg) 1.0 70 Fluid Requirement = 30-35 ml/Kg/day

297
 NORMAL POSTOPERATIVE FLUID Body Weight Fluid Requirements*
REQUIREMENTS (60-70 KG)
• Normal Urine output 1500 ml • For 0-10 Kg Give 100 mL/kg/d A
• For the next 10-20 kg Give an additional 50 mL/kg/d B
• – Insensible loss (24 hours) 700 ml • For weight > 20 kg Give 20 mL/kg/d C
• – Loss in faeces 300 ml
• Total 2500 ml • For a 12 kg child, fluid requirement is (100 mL x 10 = 1000 mL)
for the first 10 kg and (50 mL x 2 = 100 mL) for next 2 kg i.e.
1100 mL/24 hr.
• 30-35 ml/kg body weight • For a 70 Kg adult, fluid requirement is (100 mL x 10 = 1000
mL) + (50 mL x 10 = 500 mL) + (20 mL x 50 = 1000 mL) = 2500
mL.

Urine Measurements after

Intravenous Solutions
Surgery/Trauma
Fluid Glucose Na K Cl Ca Lactat Stay

Parameter Normal Post Op Duration (g/l) e Time

1 hr
Volume 1500 ml 500 ml 2-3 days 5% 50 - - - - - 7%
Na 70-90 mmol 5-20 mmol 2-5 days K Dextrose
50-80 mmol 100 mmol 1-3 days N2 0.9% - 154 - 154 - - 22
10 G 12-20 G 4-10 days Saline %
4.3%D, 43 31 - 31 - -
In the first 48 hours, due to Metabolic Response to 0.18% S
Trauma, body conserves water and Na and K is Ringer’s - 131 5 112 2 28 22
released from surgical/trauma site Lactate %

For the Subsequent 48 hours

For First 48 Hours
So essentially, the postoperative requirement of
fluids in the first 48 hours in the absence of any
pre-existing derangement would be:
2.5 to 3L i.e. 5 to 6 vacs of 5% Dextrose only i.e.
water without any added electrolytes.
Na+ —(1-1.5 meq/kg body weight)
K+ (1 meq/kg body weight), needs to be given over 24 hrs.
Therefore first calculate Na+ as 1-1.5 x 60 kg = 60-90 meq
i.e. 77 meq in 500 ml or 154 meq in 1000 ml
Therefore either 500 ml or 1000 ml of NaCl can be given to replace
Na.
A. 500 ml-NaCl (Body weight 60 kg)
2.0 L—5% Dextrox
(4 x 500)
Add 60 meq (3 ampules) of K
Therefore, 1 ampule each in any 3 vacs of 5%
B. 1000 ml–NaCl
2000 ml–5% Dextrox
For K, add 60 meq/1 ampule each in 3 vacs of 5% D.

298
Secretions Na K Cl HCO3 Volume
Saliva 2-10 20-30 8-18 30 0.5-2L Intravenous Solutions
Gastric 9-116 0-30 8-154 0-15 0.1-4L
Fluid Glucose Na K Cl Ca Lactat Stay
Duodenum 140 5 80 - 0.1-2L
(g/l) e Time
Ileum 80-150 2-8 45-137 30 0.1-.9L 1 hr

Colon 60 30 40 - - 5% 50 - - - - - 7%
Dextrose
Pancreas 115-185 3-7 55-95 115 0.1-.8L
0.9% - 154 - 154 - - 22
Bile 130-160 3-12 90-180 35 0.05-.8L Saline %
Stool 35 70 20 - - 4.3%D, 43 31 - 31 - -
Diarrhoea 30-140 30-70 73 20-80 - 0.18% S
Ringer’s - 131 5 112 2 28 22
Mixed - -
Lactate %
Gastric 120 10 100
Aspirate

Fluid and Electrolyte Replacement for High Fluid Loss

like NG Aspirate/Ileostomy Output

Scenario A: in a 60 kg man with intestinal

obstruction.

• NG Aspirate – 2L
• Urine Output–1.2L
• Electrolytes Na- Within Normal
K- Limits
Add 800 ml of insensible loss.
The total volume required for infusion is 3.2 L +
800=4.0 L.

Fluid and Electrolyte Replacement for High

Fluid Loss like NG Aspirate/Ileostomy Output Fluid Therapy
Volume Calculated 4.0 L
First calculate Na requirement
a. Loss in NG aspirate has Na®120 meq and K®10 meq/L (T
therefore 2L has 240 meq of Na & 20 meq of K

DO NOT CHASE URINARY OUTPUT

b. Normal 24 hours requirement for Na and K for
Na+—1-1.5 meq/kg–60-90 meq
K+—1 meq/kg–60 meq
Hence total requirement Na+–240+60 = 300 meq
K+ –20+60 = 80 meq (A higher previous 24 hours output could be due
500 ml of 0.9% saline has 77 meq/(154 meq/L) or » 75 meq
Hence to give 300 meq of Na-2L of 0.9% saline are required to excessive fluid in the previous days ration).
So out of 4.0 L—2 L is 0.9% saline, therefore remaining 2 L is 5% dextrose
Additional 4 ampules of K+ (20 x 4 = 80 meq) have to be added that is 1
ampule in each vac of 5% dextrose.

299
 Fluid management in Trauma Colloid Volume Expanders
Scenario B: Fluid Source Conc Mol Wt IV stay
A 60 kg young male patient with profound
hypovolemic shock due to blunt Chest and HES Maize starch 6% 265000- 50%, 8
Abdominal injury in a RTA. The appropriate fluid 450000 hrs
therapy is: Dextran Bacterial 6% 70000 50%,8hr
A. First Instance–Start crystalloids and colloid 70
volume expanders. Dextran Bacterial 10% 40000 <Dex 70
B. Arrange blood–to be started as soon as 40
bleeding controlled or to manage outgoing loss. Hemaccel Heat 3-4% 35000 50%, 4
degraded hrs
cattle gelatin

Role of 5% Dextrose in daily ration

Dextrose Saline
• The Dextrose saline solution is different from
(5% Dextrose + 0.9% saline which is normally
available in India) which is a hypertonic
solution as it has 280 all mosmoles due to 5%
Dextrose and 308 mosmoles due to saline, all
in 500 ml.
5% Dextrose fills the need of balance water after
Na+ needs have been calculated in a daily
ration. Besides, 4 vacs of 5D contains 100 g of
glucose (25 g of glucose per vac) providing 400
Kcal. These calories are not important for
patient’s needs from caloric point of view but
provide obligate glycolytic cells like brain, RBC’s,
WBC’s and renal medulla with glucose for
aerobic glycolysis.

Pressure gradient in the circulation

FLUIDS IN BURN PATIENTS: Mean BP
Arteries Arterioles Capillaries Veins
Critical level of shock: 100
ADULTS: >15% of Body Surface Area burnt.
CHILDREN: >10% of Body Surface Area burnt.
mm
Parkland Formula Using Ringer’s Lactate for the first 24-48 hours: of
4 ml x Body Weight in Kg x % of Burns Hg
(up to a max of 50% burns i.e. even for burns > 50%, we use maximum
50% in the formula)
1. Half of the calculated volume in the first 8 hours from time of
burns.
2. Other half in the next 16 hours. 32

Example: 40% burns in 60 Kg woman. 12

4 x 40 x 60 = 9600 ml of Ringers Lactate. 0

0
4800 ml in the first 8 hours and 4800 ml in the next 16 hours.
Aorta Right side
(Adapted from J H Green, Oxford University Press) of heart

300
 Formation and reabsorption of tissue fluid
(Adapted from J H Green, Oxford University Press)
Oedema
Capillary loop
Oedema is defined as an excessive amount of tissue fluid
25 mm Hg
25 mm Hg
37 mm Hg
Rate of formation of tissue fluid > rate of absorption
17 mm Hg

Plasma protein deficiency Disturbance of reabsorption

7 gm/100ml
• DVT→ High venous pressure
Tissue fluid (no plasma proteins) • Congestive heart failure
25 mm Hg Oncotic pressure • Starvation / malnutrition
1 mm Hg Hydrostatic Pressure • Liver disease • ↑ Capillary permeability due to
• Nephrotic syndrome damage from infection, anoxia
Intracellular fluid from CCF, histamine release
• Blocked lymphatics
• Sodium retention
Lymphatic

Formation and reabsorption of tissue fluid

(Adapted from J H Green, Oxford University Press)
Muir & Barclay formula for initial fluid
replacement
Capillary loop
4.5% Human Albumin (Human Plasma Protein Fraction –
25 mm Hg HPPF).
25 mm Hg
37 mm Hg The replacement volume is ;
17 mm Hg
0.5 ml X Body Weight in Kg X % of Burns

The calculated volume is administered in every period of 6

Plasma protein deficiency Disturbance of reabsorption successive periods of 4,4,4,6,6 and 12 hours i.e. in 36 hours
7 gm/100ml Tissue fluid from the time of burns. Since, the fluid administered in the
(no plasma proteins) • DVT→ High venous pressure form of colloids, the volumes required are much less.
• Starvation 25 mm Hg • Congestive heart failure
• Liver disease • ↑ Capillary permeability due to
However, as discussed earlier, this regimen has been
• Nephrotic syndrome damage from infection, anoxia associated with a higher mortality as compared to crystalloid
Intracellular fluid from CCF regimen.
• Blocked lymphatics

Lymphatic

Summary
• Fluid Therapy has to be carefully adjusted to
body weight, losses and electrolyte levels. All Things are difficult before they are easy!
• Crystalloids are administered with daily
calculation on the basis of fluid charts.
• Be aware of metabolic response to
surgery/trauma in the post-operative period
• Familiarize with all fluids in wards
• Individualize fluid therapy for each patient as Thomas Fuller
per condition and requirements. Historian
1608-1661

301
 Robotic Surgery
Arun Prasad

Robotic surgery is essentially another way of doing laparoscopic surgery albeit with better
technical inputs and technology.

BACKGROUND

What is the one thing which has accompanied human since the beginning? Nonetheless, it is
development. Human has undergone all sorts of development. Be it technical, economical or
social; curiosity and need of human has led to consistent discoveries and inventions. One of
the prominent sectors where the need of development has always been felt is the sector of
medical treatment. New and effective ways for diagnosis and treatment are being
continuously developed to reduce the risk, cost and enhance the overall results. Robotic
Surgery is one of the most advanced forms of surgeries that are surfacing in medical sector.
Robotic surgery has indeed marked the beginning of revolution in surgeries.

HISTORY

The Czech playwright Karel Capek is credited with introducing the word ‘robot’ in his play
Rossum's Universal Robots in 1921. The word stems from the Slavic word robota meaning
serf labour. Later popularized by science fiction writer Isaac Asimov in the 1940s, robotics
finally became reality in 1961 with the first industrial robot, UNIMATE, at a General Motors
factory assembly line in Trenton, NJ, USA . Whereas industrial robots typically are used to
operate in areas that are dangerous or not easily accessible by humans, medical surgical
robots were first introduced in the 1980s to augment the medical staff by imparting
superhuman capabilities: high motion accuracy and enabling interventions that would be
otherwise physically impossible.

Robotics was first introduced in urological surgery in the late 1990s for both prostate and
renal access. ProBot (prototype from Imperial College, London, UK) was a robotic resection
device with seven degrees of freedom.

MODERN ROBOTICS

The da Vinci® Surgical System (Intuitive Surgical Inc.) emerged as the state-of-the-art
telesurgical system ( Figure 4). This master-slave robotic system replicates the surgeon's
exact movements on the master controls onto robotic instruments in the patient using their
EndoWrist® technology. A binocular lens and camera system transmits magnified 3D images
to the surgeon console. The most recent edition, the da Vinci Si, was launched in April 2009
introducing improved high-definition imaging and further streamlining of the entire system.

WHAT IS ROBOTIC SURGERY

Need of robotic surgery was felt when no effective methods were found to tackle the
shortcomings of minimal invasive surgeries which are supposedly more efficient than the
conventional surgeries. Robotic surgery is one of the most practical use of robotics and is
proving its worth every day.

To be specific, robotic surgery is used to move the instruments while surgery. Instead of
using the surgery instruments by hand, robotic arms are used which are controlled by efficient
surgeons with the help of advanced computers. The movements of the surgeon are translated
to the robotic arms while observations are made through computer screens. Commonly it is
also known as robotic-assisted or computer assisted surgery.

PARTS OF ROBOTIC SURGERY HARDWARE

Robotic surgery brings the power of computers to the finger tips of the surgeon. The robotic
system consists of a console, robot and a patient-side cart. It is a sophisticated, but
expensive tool controlled by a surgeon.

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The surgical console has a built-in, three-dimensional vision on a real-time image screen
where the surgeon views the target area in high definition and 15X magnification ( Figure 6).
The robotic instruments which work on the human tissues are attached to the robotic arms
and are very fine and precise ( Figure 7).

The entire system uses a mechanical robotic pulley system and software algorithms to
synchronize different functions. Within the console, the surgeon has foot and hand controls to
facilitate different movements and use energy sources as needed during surgery ( Figure 8).
One or two assistant surgeons work at the patient-side providing assistance.

WHY ROBOTIC SURGERY ?

But why one should opt for robotic surgeries? Reason is utterly simple.
1. It is a less invasive procedure and robotic arms are much easier to use than the
instruments in endoscopic surgery.
2. Accurate and precise dissection and suturing ( Figure 9).
3. Control of 4 robotic arms by the surgeon makes co-ordination easier and less tiring
specially for advanced minimal access surgical procedures ( Figure 10).
4. A 3D vision right in front of the eyes where the entire field in front of the surgeons
face is the operative area. This makes it easy to concentrate ( Figure 6).
5. Moreover, it reduces hand tremors and movements which might have decreased the
preciseness of surgery.
6. All critical part of body which are hard to access can be easily reached with the help
of robotic arms.
7. Reduced trauma to the body,
8. Less anaesthesia,
9. Often less blood loss and need for transfusions,
10. Less post-operative pain and discomfort,
11. Less risk of infection,
12. Shorter hospital stay,
13. Faster recovery and return to normal daily activities and
14. Less scarring are a few advantages of robotic surgery.
(The last few are true for any minimal access surgical procedure )

Robotic surgery in India has gained momentum in a very few years. India is one of the few
countries which are credited to perform first robotic surgery all by their own.

As of the end of 2012, 1752 da Vinci systems were installed in >1500 hospitals, in 44
countries around the world: 1285 in the USA, 316 in Europe, and 151 in the rest of the world.
Globally >400 000 robotic procedures were completed in 2012.

The use of the current robotic system continues to be further refined. Increasing experience
has optimized port placement reducing arm collisions to allow for more expedient surgery.
Improved 3D camera magnification up to ×15 provides improved intraoperative identification
of structures . Robotics has probably improved the learning curve of laparoscopic surgery
while still maintaining its patient recovery advantages and outcomes.

The fundamental premise of robotic surgery is that any technology which assists a surgeon to
operate with precision will result in better outcomes for the patient.

Currently, the robotic surgery in India is in its infancy. There are only 25 robots for a country
having a population of over one billion. Of these, six were added in 2012. India is ideally
suited for robotic surgery as the surgeons are skilled, the patient volume is high and a full
spectrum of complex diseases are encountered. In India particularly, multi-speciality robotic
surgery has a great future.

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WHAT ARE THE CONS
1. High initial capital expenditure costs and high costs for robotic instruments that have
a limited life span and therefore have a recurring cost for each case.
2. The surgery initially requires extra time and manpower. With proper training, the
surgeon can become very proficient quickly, and operative times will drop.

Robots are here to stay and have impacted the delivery of healthcare in a way that few
technologies have in the history of surgery. Robotic technology has altered the fundamental
foundations of surgery in the United States. The reason for this dramatic shift over essentially
a ten-year period is the rapid dissemination of the technology and technique.

Robotic technology has provided some fundamental advantages to the surgeons. It has
allowed those not laparoscopically trained to be able to offer their patients a minimally
invasive alternative. For those who are laparoscopically trained it has given a platform for
operating at a technically superior level.

In India the assimilation of robotic technology has already occurred but has not expanded or
entered the mainstream. There remains a lack of access to the technology and a deficit in
educational opportunities. The reason undoubtedly is not for a lack of utility of the
instrumentation or the lack of benefit to the patient. The reason has primarily been cost.
Robotic technology is expensive and is showing no signs of becoming cheaper.

Robotic technology is in India and will without question grow in the near future. The
technology requires education and training for safe implementation. It also requires economic
backbone; the cost of this advanced technology must be taken on by either the hospital,
surgeon or the patient. The best approach is likely an evidence-based evaluation of the
technology at centers with expertise in laparoscopic procedures, at institutions where there
are experts in the field of prostatectomy and where the volume is substantial enough to allow
frequent enough utilization to keep the surgeon and the team experienced [14].

So the challenge for all Indian surgeons is to educate themselves first about the values of the
next generation of technology, examine the alternatives and then selectively apply it in an
evidence-based manner. This approach provides the most likely opportunity for patient safety
and surgeon success.

SPECIALTIES

The major specialities practicing robot-assisted surgery are

1. General surgery : vast majority of abdominal surgical procedures are being done with
the assistance of robot. Best suited are Bariatric surgery like gastric bypass, hiatal
surgeries, adrenalectomy and colorectal surgery for cancer.
2. Urology : (60-70 per cent of overall robotic procedures). Radical prostatectomy,
Partial nephrectomy & Pyeloplasties are good examples.
3. Gynaecology : most of the procedures can be done with the help of robot),
4. Thoracic &cardiac surgery : selected coronary artery surgery and mitral valve
reconstruction can be done with the help of the robot-assisted approach. Thymus and
lung surgery is also rapidly gaining acceptance.
5. ENT & Neurosurgey : For transoral and transnasal surgeries.

TECHNOLOGY AND TECHNIQUE

The robotic surgical system has three components. These components are the surgeon
console, the robotic cart (patient-side cart) and the vision system ( Figure 1).

The surgeon console ( Figure 8) is the place where the surgeon can perform the operation.
This instrument provides an ergonomic position and three dimensional images. Three
dimensional images help the surgeon to overcome visual limitation during the operation and
also provide a similar vision like open surgery. The conventional laparoscopic surgery system
only provides two dimensional visions. The most recent robotic surgical system is equipped
with HD technology also with three dimensional images. Three dimensional HD images are

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the most optimal imaging technology in laparoscopic surgery and provide a direct hand-eye
instrument alignment and a natural depth perception for precise operation near dangerous
anatomical structures.
The surgeon performs the operation in an ergonomic position in the robotic surgical system.
The most important ergonomic posture is the sitting position. The surgeon sits in the chair
and grasps the master controls with the hands and wrists naturally positioned during the
robotic assisted procedure. Robotic surgery causes less operator fatigue when compared
with conventional laparoscopic surgery and the ergonomic position for the surgeon sitting at
the console might be the important reason.

The robot ( Figure 11) is equipped with four arms. One arm is used for the endoscope holder
and the other three arms are used for surgical arms which perform the operation. The robotic
arm, which holds the endoscope provide a stable vision without unnecessary movement. If
the endoscope is moving unnecessarily, it is like doing an operation in a moving car or train.
In conventional laparoscopic surgery, the assistant surgeon holds the endoscope and the
vision provided by the assistant surgeon cannot be as stable as like the vision provided by the
robotic arm. In the robotic assisted procedure, the master surgeon can move the vision
according to their needs. This feature can make the operation run smoothly and the operation
time shorter than conventional laparoscopic surgery.

The hand instruments ( Figure 12) in the robotic surgical system, has tips that are designed
to mimic the dexterity of the human hand and wrist. It allows several degrees of freedom and
articulation. We can almost move the tips in 360 degrees as per the need of the situation to
do dissection and suturing.

Motion scaling is a characteristic of the robotic surgical system. The computer in the robotic
surgical system can scale down a surgeon’s hand movements into micromotions. Thus,
detailed surgery can be easily performed using the robotic surgical system.

CONCLUSION

Super human movements, precision and accuracy is what robotic surgery promises us today.
Improvements of the robotic surgical system are continuously being made to overcome the
technical limitations found during the surgeries.

At present, the scope for robotics in India is limited because of cost considerations. The future
of robotic surgery in India also will depend on the same factor.

Therefore it is successful in those hospitals only where cost recovery and profit making from
the robot is not the aim. The robot is bought and is being used as an overall advancement of
technology and services provided.

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