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Borderline Resectable

Carcinoma Pancreas

Borderline Resectable Carcinoma


Pancreas
i.e. T3N0M0 or T3N1M0 (7th AJCC )
Defined as Ca pancreas with involvement
of major peripancreatic vessels with
possiblity of curative resection
Mortality and complication rates after R0
resection similar to resectable disease
(T1/T2 N0 M0)

Introduction
Adenocarcinoma of the pancreas is the fourth highest cause of
cancer-related death among men and women in the USA and
worldwide
8090 % of patients have locally advanced (30-40%) or
disseminated disease at presentation
15-20% able to undergo complete surgical resection with negative
margins
Median overall survival of patients who undergo complete resection
with negative margins ranges between 12 and 26 months
Median overall survival of 5 to 6 months in unresectable disease
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer Statistics 2010. CA
Cancer J Clin 60:227300

Approximately one third of patients presenting with


locally advanced pancreatic cancer will be marginally or
borderline resectable
Free surgical margins are difficult to attain, owing to the
close anatomical relationship between the pancreas and
the main visceral vessels
Even microscopic, positive surgical margins have a
negative impact on survival, and patients in such
situations have the same dismal prognosis as patients
who do not undergo resection and are treated with
chemoradiotherapy only

1. What is the definition of borderline resectable pancreatic cancer?


2. Radiological workup with computer tomography (CT) and magnetic
resonance imaging (MRI). Is there a place for positron emission tomography
(PET)-CT?
3. What does endoscopic ultrasonography (EUS) add?
4. Is it necessary to obtain a tissue biopsy of the tumor? What is the preferred
method?
5. Is a staging laparoscopy necessary?
6. What are the possible chemotherapy combinations in the neoadjuvant
setting?
7. What is the place of neoadjuvant chemoradiation?
8. What is the place of chemotherapy followed by chemoradiotherapy?
9. Surgical therapy controversies:
9.1. Is there any advantage in an extended versus standard lymphadenectomy in
duodenopancreatectomy for pancreatic head cancer?
9.2. What is the place of vascular resection and reconstruction?

10. What is the place of chemotherapeutic treatment after resection?

Evolving Assessment and Definition of


Borderline Resectable Pancreatic Cancer
In the past, the determination of whether a pancreatic cancer
was resectable, unresectable, or borderline resectable was
made at surgical exploration
The development of modern imaging techniques with
improved resolution has allowed for the preoperative staging
of patients. Institutions vary in the use of these techniques
and the criteria that are used to stratify patients.
There is no definite consensus on which approach is best.
The common theme is to use some combination of
complementary imaging modalities to define the size,
geometry,and extent of vascular involvement of disease.

Rational of defining borderline resectable pancreatic ductal


adenocarcinoma as a unique entity is based on 4 clinical
observations
Complete resection of the primary tumor and regional lymph nodes
is mandatory for long-term survival
The incidence of margin-negative resection following surgery de
novo decreases with increasing involvement SMV-PV and SMA
Resection of the SMV-PV and hepatic arterybut not the SMAat
pancreatectomy is associated with acceptable outcomes
Chemotherapy and chemoradiation may be used to select patients
with favorable physiology and tumor biology who may benefit from
aggressive operations

Within this context, borderline resectable tumors


are best conceptualized
those that involve the mesenteric vasculature to a
limited extent
those for which resection, while possible, would likely
be compromised by positive surgical margins in the
absence of preoperative therapy or vascular resection

A uniformly accepted set of criteria that define


patients with borderline resectable PDAC does
not exist

Definition
2 most commonly cited definitions
are those proposed by
MD Anderson group
Americas Hepatopancreatobiliary
Association (AHPBA)/Society for Surgery
of the Alimentary Tract (SSAT)/Society of
Surgical Oncology (SSO, and modified by
the NCCN)

Sites of venous invasion that may be


potentially resectable

M D Anderson definition
Borderline tumors are defined as
those that
abut the SMA
abut or encase the CHA over a short
segment
occlude the SMV-PV confluence, with
suitable vein above and below such that
venous reconstruction is possible

American Hepato-Pancreato-Biliary
Association 2008 Consensus Conference
Borderline resectable tumors are
Involvement, abutment, encasement, or thrombosis of the
SMV or portal vein over a short distance with
reconstructable vessels above and below the area of
involvement and no arterial involvement;
GDA involvement up to or around a short segment of the
hepatic artery

Abutment of the SMA with less than 180-degree


involvement.

Comparison of different radiological


definition
AHPBA

MD Anderson

NCCN 2012

SMV-PV Abutment,
encasement
,or occlusion

Occlusion

Abutment with
impingement
or
narrowing

SMA

Abutment

Abutment

CHA

Abutment or Abutment or
short-segment shortencasement segment
encasement
No abutment Abutment
or
encasement

Celiac
trunk

Intergroup trial 2013

Interface between tumor


and vessel measuring
180. or greater of the
circumference of the
vessel wall, and/or
reconstructabled
occlusion
Abutment
Interface between tumor
and vessel measuring
less than 180. of the
circumference of the
vessel wall
Abutment or
Reconstructabled, shortshortsegment interface
segment
between tumor and
encasement
vessel of any degree
No abutment Interface between tumor
or encasement and vessel measuring
less than 180.of the
circumference of the

Modified M D Anderson
classification
In addition to this established anatomic definition of borderline
resectable they has included two additional subsets of patients who
often escape accurate classification into a specific stage of disease
Type A: Anatomical borderline resectable
Type B: Patients with indeterminate or questionable metastatic disease
Type C: Patients with a suboptimal performance status or extensive medical
comorbidities requiring prolonged evaluation that preclude immediate major
abdominal surgery

Inclusion of these latter two groups into the borderline resectable


category allows for accurate staging of all patients who present with
newly diagnosed pancreatic cancer and specifically, the identification of
a subset of patients who are marginally resectable or operable based on
anatomic or clinical criteria
Such classification of patients by stage is necessary to allow for stagespecific therapy both on- or off-protocol

Radiological workup
There is no evidence-based consensus on the optimal
preoperative imaging assessment of patients with
suspected pancreatic cancer
A clue to determining the resectability of pancreatic
cancer in the absence of metastatic disease is the
assessment of vascular invasion, which is best displayed
by CT

CT is the technique of choice for determining the first


intervention, allowing a TNM staging evaluation in a
single non-invasive examination
Buchs NC et al (2010) Vascular invasion in pancreatic cancer. Imaging
modalities preoperative diagnosis and surgical management. World J
Gastroenterol

Pancreas protocol CT should be a dual-phase exam with images


obtained during the
Pancreatic phase:
Intermediate between the arterial phase and venous phase
Ideal for both detection and local staging of pancreatic adenocarcinoma

Hepatic phase:
For hypovascular metastasis

Noncontrast images
For detecting calcifications and confirming that enhancement is present on
postcontrast images

Recent studies found that images obtained in the arterial phase


are unnecessary, as they are inferior to those obtained in the
pancreatic phase or the hepatic phase for detection and staging of
pancreatic adenocarcinoma
Ichikawa T et al. (2006) MDCT of pancreatic adenocarcinoma:
optimal imaging phases and multiplanar reformatted imaging. AJR
Am J Roentgenol 187:15131520

Lus Five grade scale


Most commonly used system for predicting vascular
invasion by pancreatic adenocarcinoma
Based on the degree of contact between tumor and a
vessel
Tumor contiguity with >50% of the perimeter of a vessel
was found to be the optimal threshold for predicting
vascular invasion, with a sensitivity of 84% and specificity
of 98%
Tear drop SMV is found to be highly specific sign for
vascular invasion
Lu DSK et al. (1997) Local staging of pancreatic cancer: criteria for
unresectability of major vessels as revealed by pancreatic-phase, thinsection helical CT. AJR Am J Roentgenol 168:14391443

Five grade scale


Category Description

Comment

Grade 0

No contiguity of tumor with a vessel

Vascular invasion in 0%
of cases

Grade 1

Tumor contiguous with <25% of the Vascular invasion in 0%


circumference of a vessel
of cases

Grade 2

Tumor contiguous with 2550% of


the circumference of a vessel

Vascular invasion in
57% of cases

Grade 3

Tumor contiguous with 5075% of


the circumference of a vessel

Vascular invasion in
88% of cases

Grade 4

Tumor contiguous with >75% of the


Vascular invasion in all
circumference of a vessel or any
cases
vessel constriction

Predicting vascular invasion by tumor using


50% tumor contiguity with vessel as threshold
Authors

Sensitivity (%) Specificity (%)

Lu et al

84

98

OMalley et al

46

99

71

86

78

79

49

100

97

91

Nakayama et al.
veins only
Nakayama et al.
arteries only
Li et al. veins
only
Li et al. arteries
only

Overall resectability and need for


venous resection
Catego
ry

A
B
C

Description

Overall
Resection
Rate

Resection
without
venous
resection

Fat plane separates the tumor and/or the


normal
100
95
pancreatic parenchyma from adjacent
vessels
Normal parenchyma separates the
100
95
hypodense tumor from adjacent vessels
Hypodense tumor is inseparable from
adjacent vessels, and the points of
89
55
contact form a convexity against the
vessels
Hypodense tumor is inseparable from
adjacent vessels, and the points of
47
47
contact form a concavity against the
vessels or partially encircle the vessels
Hypodense tumor encircles adjacent
Loyer EM et al. (1996) Vascular involvement in pancreatic
vessels, and no fat
plane is identified
0
0
adenocarcinoma:
reassessment by thinsection
CT. Abdom Imaging
between the tumor and the vessels 21:202206

Lymph Nodal Assessment


Roche et al compared theassessmentof peripancreatic lymph
nodes usingCTwith histopathologicassessmentof inpatientswith
pancreaticductaladenocarcinoma

Sensitivity of 14% and a specificity of 85% if a short-axis


diameter of 10 mm is used as the sole criterion for tumor
involvement
Using a short-axis diameter of 5 mm as threshold increased
sensitivity to 71%, but reduced specificity to 64%.
Morphologic features (rounded nodes, clustered nodes,
nodes with no fatty hilum) were not found to be helpful
The authors concluded that in a patient with pancreatic
adenocarcinoma, the finding of enlarged peripancreatic
lymph nodes on CT should not preclude attempted resection
Roche CJ et al. (2003) CT and pathologic assessment of prospective
nodal staging in patients with ductal adenocarcinoma of the head of
the pancreas. AJR Am J Roentgenol 180:475480

Metastasis Assessment
Liver and peritoneal surfaces are common sites for distant metastases
When a lesion is large, the diagnosis of metastatic disease to the liver is
usually straightforward.
A commonly encountered problem when staging cancer patients with CT is the
presence of small (<10 mm) hypodense lesions that are often described by
radiologists as too small to characterize or indeterminate.
Although usually benign, Schwartz et al. found that such lesions represent
metastases in 11.6% of patients with cancer [28].

Percutaneous biopsy may yield a definitive diagnosis, but is often technically


difficult.
In practice, resection is often attempted despite the presence of these lesions.
Schwartz LH et al. (1999) Prevalence and importance of small
hepatic lesions found at CT in patients with cancer. Radiology
210:7174

Restaging after NACT/RT

Kim et al evaluated the effect of NACT/RT on preoperative accuracy of


multidetector CT for resectability and tumor staging CA HOP
Retrospective study
38 patients evaluated, 12patientsreceivedneoadjuvantCTRT
Accuracy in determiningresectabilitywas 83% (10 of 12)
inpatientswho had receivedneoadjuvantCTRT and 81% (21 of 26)
inpatientswho had not, without significant difference (P > .05)
T-stagingaccuracy was 67% (eight of 12) withneoadjuvantCTRT and
95% (19 of 20) without it, with a significant difference (P = .0185)
They concluded that NeoadjuvantCTRT reduces the accuracy of tumor
restaging after treatment ofpancreaticheadcancer, but this effect is
not so great as to affect the determination ofresectability

Kim YE et al (2009) Effects of neoadjuvant combined chemotherapy


and radiation therapy on the CT evaluation of resectability and staging
in patients with pancreatic cancer. Radiology 250(3):758765

MRI
Superior to CT for the detection of liver
metastases
But accuracy of this technique in diagnosing
vascular invasion is quite similar to that of CT
Reserve this expensive and time-consuming
technique for those patients with iodine
allergies, renal insufficiency, pregnancy or
inconclusive CT results
Soriano A et al (2004) Preoperative staging and tumour resectability assessment of
pancreatic cancer; prospective study comparing endoscopic ultrasonography, helical
computed tomography, magnetic resonance imaging and angiography. Am J Gastroenterol

PET
Accurate in diagnosing small tumors (< 2 cm), peritoneal
implants and metastases
Not useful for evaluating lymph nodes or vascular invasion.
Differentiate inflammatory pathologies from tumoral pathologies
and malignant pathologies from benign pathologies with a
sensitivity of 85100 % and a specificity of 6999 %, values that
are often higher than the CT values.
Thus, the coupling of PET with CT (PETCT) provides more
information than CT alone
Complementary to CT
Sendler A et al (2000) Preoperative evaluation of pancreatic masses
with positron emission tomography using 18F-fluorodeoxyglucose:
diagnostic limitations. World J Surg 24:11211129

EUS
Highest detection rate of tumors < 20 mm in size
More accurate than CT for the detection of venous invasion.
Not a first-line diagnostic technique
However, once a diagnosis is suspected with inconclusive
CT findings or no pancreatic head mass
To confirm the presence of a tumor
Assess vascular invasion by Doppler
Specially accurate in detecting PV and SV infiltration
Less sensitive in detecting SMA and SMV involvement
Permit the accurate placement of a needle biopsy
Varadarajulu S et al (2005) The role of endoscopic ultrasonography
in the evaluation of pancreatico-biliary cancer. Gastrointest Endosc
Clin N Am 15(3):497511

EUS-FNAC has a PPV in the range of


9297% but a NPV of only 4050%
Considered superior to nonhelical or
single-detector CT in detecting small
(< 2 cm) primary pancreatic cancers,
although this difference is not
significant compared with MDCT
Stessin AM et al (2008) Neoadjuvant radiation is associated with
improved survival in patients with resectable pancreatic cancer: an
analysis of data from the surveillance, epidemiology, and end
results (SEER) registry. Int

For detection of peripancreatic lymph node


metastasis in pancreatic cancer, endoscopic
sonography is superior to CT
Morphologic features such as absence of an
echogenic center and a rounded rather than ovoid
outline suggest malignant invasion, even in
normalsized nodes.
However, due to the limited field of view of
endoscopic sonography, CT is better at detecting
paraaortic and mesenteric nodes
Hoffman JP et al(1998) Phase II trial of preoperative radiation
therapy and chemotherapy for patients with localized, resectable
adenocarcinoma of the pancreas: an Eastern Cooperative

Tissue biopsy
Tissue diagnosis prior to the start of treatment is considered mandatory by
most authors and institutions when the patient is considered for neoadjuvant
treatment.
The three available techniques for pancreatic cancer tissue biopsy
ERCP
Transabdominal FNA
EUS-guided FNA.

EUS-FNA has the highest sensitivity, specificity, diagnostic accuracy and


positive and negative predictive values
The possibility of tumor dissemination is lower with EUS-FNA than with
percutaneous image-guided FNA
EUS-FNA has a low complication rate (12 %), with complications from this
procedure including bleeding, pancreatitis and perforation.
Micames C et al (2003) Lower frequency of peritoneal
carcinomatosis in patients with pancreatic cancer diagnosed
by EUS-guided FNA versus percutaneous FNA. Gastrointest

STAGING LAPAROSCOPY: ROUTINE


OR SELECTIVE?
No level 1 data
Despite its apparent benefits, the value of staging
laparoscopy is not universally accepted
Opinions range from recommending its routine use for
all patients before laparotomy to not performing
laparoscopy in any circumstance
A complimentary staging method to overcome this shortfall is
necessary, and ideally one that accurately upstages a
patients pancreatic cancer with the least physical insult

Pros
Inadequate sensitivity for occult small-volume metastatic disease even by high quality
CT
Accurate laparoscopic examination can be performed efficiently and does not affect
subsequent resection
Hospital stays, costs, and overall morbidity are obviously reduced when an unnecessary
open laparotomy is avoided for unresectable or occult metastatic disease.
29

Protects the quality and comfort for the patients final stage of life
Numerous studies have consistently shown that up to one-third of patients thought to be
resectable by state-of the-art imaging will be disqualified for surgery at laparoscopic
staging
Some suggest adding laparoscopic ultrasonography to extend the yield, as is possible by
identifying and sampling small intrahepatic metastases

Cons
Critics argue that most studies probably
overestimate the value of staging laparoscopy
They maintain that if todays highest-quality
imaging is properly used, only a minority of
patients will actually benefit
They counter the cost-effectiveness argument
by claiming that excess resources are used to
achieve the occasional success

Selective Approach
Some evidence has emerged to support a selective approach to staging
laparoscopy
The goal has become optimizing yield while preserving the diagnostic value of
staging laparoscopy by obeying specific clinical selection criteria
Tumor location is perhaps most important. Distinct subsets of peripancreatic
tumors warrant staging laparoscopy such as large (>3 cm) primary tumors,
and all lesions in the neck, body, or tail of the pancreas.32
If high-quality imaging is in any way suggestive of occult metastatic disease
(equivocal peritoneal/liver metastases, low-volume ascites), staging
laparoscopy makes sense.
Even subtle clinical indicators of advanced disease, such as marked weight
loss and pain, hypoalbuminemia, and high CA 19-9 levels, may warrant
laparoscopy.33
White R et al (2008) Current utility of staging laparoscopy for
pancreatic and peripancreatic neoplasms. J Am Coll Surg 206:445450

Consensus Statement for apparent


resectable pancreatic cancer, staging
laparoscopy should be used
selectively on the basis of clinical
predictors that optimize yield i.e.
Pancreatic head tumors of >3 cm
Tumors of the pancreas body and tail
Equivocal findings on CT scan
High CA 19-9 levels (>100 U/mL)

Neoadjuvant treatment
Aim:
Increase resectability rates
Evaluate the patients sensitivity to treatment and
increase survival

Optimal neoadjuvant therapeutic strategy in


potentially resectable pancreatic cancer controversial.
Chemotherapy and chemoradiotherapy are the
main options
Gillen S (2010) Preoperative/neoadjuvant therapy in pancreatic
cancer: a systematic review and meta-analysis of response and
resection percentages. PLoS Med 7(4):e1000267

In a recently published meta-analysis


111 studies (4,394 patients)
56 of which were phase I and II studies of patients with resectable and
unresectable/ borderline resectable pancreatic cancer were included
Neoadjuvant chemotherapy (96.4 %)
Radiation therapy (93.4 %)

Results
33.2 % of the patients initially presenting as unresectable/borderline
resectable cases underwent curative surgery after neoadjuvant treatment.
The median survival of these patients after resection was 20.5 months,
which was similar to that of patients with initially resectable tumors.
Despite the heterogeneity of the included studies, these data suggest the
importance of re-evaluating all patients with locally advanced/borderline
resectable tumors after neoadjuvant therapy for selecting potential
candidates for surgery.
Gillen S et al (2010) Preoperative/neoadjuvant therapy in pancreatic
cancer: a systematic review and meta-analysis of response and
resection percentages. PLoS Med 7(4):e1000267

Neoadjuvant treatment is particularly important in patients with borderline


resectable tumors, which are those that have a greater chance of being
completely resected after neoadjuvant treatment
A series published by the M. D. Anderson Cancer Center
160 marginally resectable pancreatic cancer patients who were classified as marginally
resectable
125 (78 %) received neoadjuvant therapy (chemotherapy, chemoradiation or both) and
were reevaluated for surgery
Sixty-six (41 %) of these patients underwent pancreatectomy following neoadjuvant
therapy
62 (94 %) exhibiting negative margins at surgery
The median survival for the 66 patients who underwent surgery after neoadjuvant
treatment was 40 months, whereas the median survival for the 94 patients who were to
undergo pancreatectomy was 13 months (p = 0.001)

They concluded that this neoadjuvant approach allowed for identification of the
marked subset of patients that was most likely to benefit from surgery, as
evidenced by the favorable median survival in this group.
Katz MH et al (2008) Borderline resectable pancreatic cancer: the
importance of this emerging stage of disease. J Am Coll Surg
206(5):833848

Neoadjuvant chemoradiation
A recent extensive review of radiochemotherapy
in the multimodal treatment of pancreatic cancer
Only phase II studies or a retrospective analysis
Resectability rate
10-20% in initially unresectable tumors
36-74% in borderline resectability tumors

The local recurrence rates are not always reported,


but the available data are consistent with a notably
low incidence of this event: 6 -26 %
Brunner TB et al (2010) The role of radiotherapy in multimodal
treatment of pancreatic carcinoma. Radiat Oncol 5:6476

Role of CT followed by CT/RT?


Another strategy in the neoadjuvant-based treatment of locally advanced
pancreatic cancer is the use of chemotherapy followed by chemoradiotherapy
The purpose of this approach is to select those chemotherapy patients who
will benefit from chemoradiotherapy and those who have not experienced
disease progression following chemotherapy.
The Groupe Cooperateur Multidisciplinaire in Oncologie (GERCOR) published
data for a series of 181 patients from phase II and III studies of locally
advanced pancreatic cancer who had been treated with gemcitabine-based
chemotherapy followed by chemoradiotherapy (55 Gy RT plus 5-FU in
continuous infusion)
53 patients (29.3 %) developed metastases in the first 3 months of chemotherapy and,
therefore, were not eligible for chemoradiotherapy
Of the remaining 128 (70.3 %) whose disease had progressed, 72 (56 %) received
chemoradiotherapy (group A), and 56 (44 %) continued with chemotherapy (group B)
In groups A and B, the median PFS values were 10.8 and 7.4 months, respectively (p =
0.005), and the median OS values were 15 and 11.7 months, respectively (p =
0.0009).
Huguet F et al (2007) Impact of chemoradiotherapy after disease
control with chemotherapy in locally advanced pancreatic
adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol
25(3):326331

Another study from the M. D. Anderson Cancer Center


323 consecutive patients with locally advanced CA Pancrease
received treatment with chemoradiotherapy or induction
chemotherapy followed by chemoradiotherapy
247 patients received chemoradiotherapy as their initial treatment
76 patients began with gemcitabine-based chemotherapy for 2.5
months. The patients received a single dose of 30 Gy RT followed
by 5-FU concurrent continuous infusion (41 %), gemcitabine (39 %)
or capecitabine (20 %)
The median OS and PFS were 8.5 and 4.2 months, respectively, in
the chemoradiotherapy group, and 11.9 and 6.4 months,
respectively, in the chemotherapy followed by chemoradiotherapy
group (p\0.001)
There were no differences in the patterns of relapse (local and
remote) between the two groups.
Krishnan S et al (2007) Induction chemotherapy selects patients with
locally advanced, unresectable pancreatic cancer for optimal benefit
from consolidative chemoradiation therapy. Cancer 110(1):4755

The ECOG 1200 phase II trial directly compared


chemoradiotherapy with induction chemotherapy
followed by chemoradiotherapy and surgery,
aiming to assess posterior free margins in patients
with borderline resectable pancreatic cancer
The study was closed early because of low
recruitment.
Preliminary data was in favor of induction CT
followed by CT/RT
Landry J et al (2010) Randomized phase II study of gemcitabine plus radiotherapy
versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5fluorouracil for patients with locally advanced, potentially resectable pancreatic

In summary, neoadjuvant CT could increase the


chances of resection in some patients, thus
prolonging their survival to match that of patients
with tumors that are resectable from the beginning
However, the field needs to identify treatment
schemes that deliver better results in these
patients and complete randomized studies with
different drug combinations in addition to
comparing neoadjuvant chemotherapy with other
preoperative treatment strategies.

In summary, the published studies


investigating induction CT followed by
CT/RT are promising because they suggest
that CT may identify those patients who
will benefit the most from CT/RT
However, the benefit and safety of this
approach should be evaluated in RCT and
compared with the other neoadjuvant
treatment options

Vascular resection and reconstruction at


pancreatico-duodenectomy: technical
issues

Least standarized
Less frequently addressed in the literature

Management of the
portal vein
Depending on the site of tumor invasion of the SMV-PV, extent
of venous resection required
Different technical options for resection and reconstruction are
available.
Tangential resection is possible when the lesion is adherent to a
small part of the lateral or posterior wall of the PV and SMV.
Repair is accomplished with vein patch harvested from the great
saphenous vein or elsewhere if the venous lumen is significantly
narrowed.

When a segment of the PV has to be sacrificed, primary end-toend anastomosis should be made with preservation of all
venous branches, including the splenic vein, whenever feasible
without using an interposition graft.

The resection and reconstruction of PV/SMV should be deferred until the rest of
the operative specimen has been completely detached from all the surrounding
structures including the SMA, and proximal and distal controls must be secured
for the PV, SMV and splenic vein
To avoid the need for venous anastomosis before the removal of the specimen
Minimize the time for venous occlusion

Concurrent inflow occlusion of the SMA at the same time as venous clamping is
frequently employed to reduce small bowel edema, making subsequent biliary
and pancreatic reconstruction less difficult.
Systemic heparinization at the time of venous resection and reconstruction is not
a routine practice, but when considered necessary, 2500 - 5000 U could be given
at the time of clamping.
Anticoagulation after surgery is adequate with aspirin alone, but the patient
should be put on heparin, followed by coumadin, if clot is found on postoperative
imaging studies

Under normal circumstances, a loss of 2 cm or less of


the PV/SMV needs no additional maneuver before an
end-to-end venous anastomosis could be done
without tension
With extensive mobilizations which allow the maximal
cephalad displacement of the distal SMV stump, plus
the division of the SV to improve the longitudinal
mobility of the PV/SMV, vein graft can be successfully
spared even for a segmental loss of 7 to 10 cm
On the other hand, some authors advocated the use
of an interposition graft to bridge the ends of the
PV/SMV instead of a routine sacrifice of the SV

Management of the
splenic vein

The SV is divided when

tumor invasion at its junction with the PV is evident


extra mobility for a direct end-to-end anastomosis between the PV and SMV is necessary,
rarely to provide better exposure for a thorough nodal clearance and soft tissue
dissection at the proximal 3 to 4 cm of the SMA.

After division of the SV, a mandatory reconstruction is not a universally


accepted practice. Some claimed that most patients would have no problem as
the venous flow from the spleen and stomach could return to the systemic vein
or the SMV through the short gastric vein and the esophageal vein
In fact, recent studies on the anatomical relationship between the inferior
mesenteric vein (IMV), SV and SMV using helical CT venography demonstrated
that 48.3% to 68.5% of a normal population have their IMV joined to the SV,
thus sparing the IMV/SV confluence when the SV is ligated closely to the PV
On the other hand, a significant proportion of patients have their IMV joining to
either the SMV (18.5% to 31%) or the junction between the SMV and SV (7.6%
to 13.8%), and would run a potential risk of segmental left-side venous
hypertension with resulted splenomegaly, hypertensive gastropathy,
esophageal varices and hemorrhage with SV ligation.

Although the number of patients studied was small, they concluded that left-side
venous hypertension is not an inevitable event after SV ligation without
reconstruction.
Many had adopted a selective approach for SV reconstruction. In the absence of
an intact natural confluence between the SV and IMV, the two veins are
anastomosed together with 8-0 non-absorbable sutures so that the venous
drainage of the spleen and gastric remnant is preserved without making the
more difficult anastomosis between the shortened SV and PV.
Using surrogate markers including the changes of platelet count and spleen
volume before and after surgery, Ferreira et al found that such selective
approach is feasible in obviating venous congestion during a short term follow-up

Graf O,. Anatomic variants of mesenteric veins: depiction with helical CT venography. AJR Am J Roentgenol 1997
Strasberg SM. Pattern of venous collateral development after splenic vein occlusion in an extended Whipple procedure : comparison with
collateral vein pattern in cases of sinistral portal hypertension. J Gastrointest Surg 2011

Management of SMV and its


first order branches
When the main trunk of the SMV and the junction of the ileal and jejunal
branches are invaded by the tumor, segmental resection follow by
reconstruction is necessary
As the small bowel would have adequate venous return if only one of the
two major branches remains intact, the jejunal branch is usually sacrificed
as it is usually posteriorly located with a thin wall, and difficult to access
for the anastomosis to the SMV trunk.
While the ileal branch is always the preferred choice for reconstruction
after segmental excision, additional consideration must also be given to its
caliber
Based on the experiences gathered at the MD Anderson Cancer Center, an
ileal branch of adequate caliber should have a diameter of 1.5 times larger
than that of the SMA as seen on CT scan.
Katz MH. Anatomy of the superior mesenteric vein with special reference to the surgical management of first-order branch
involvement at pancreaticoduodenectomy. Ann Surg 2008

Selection of vein
substitution
Following segmental resection of the PV/SMV truck,
interposition graft with different materials is
occasionally required.
In a review, primary anastomosis (88.6%) was used
most frequently, followed by autologous vein graft
(9.7%) and synthetic vein graft (1.7%)
The use of autologous graft is largely preferred over
synthetic graft as the operative field after PD is
potentially contaminated, especially if anastomotic
leakage does occur

While the preferred autologous vein varies according to


individual centers, the accessibility of the vein graft, ease of
procurement and the absence of long-term sequelae after
its harvesting are the prime considerations for selection
The use of internal jugular vein, superficial femoral vein and
IMV has been reported but gained limited enthusiasm.
At the Mayo Clinic in Rochester, the left renal vein (LRV) is
used to re-establish the venous continuity when a primary
end-to-end anastomosis fails

Tseng JF et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004
Fleming JB. Superficial femoral vein as a conduit for portal vein reconstruction during pancreaticoduodenectomy. Arch Surg 2005.

Reports on the outcome of artificial graft are sparse as most surgeons


would use it as the last option.
Theoretically, the use of PTFE has the advantage that the external
reinforcement ring could help to maintain a better patency when used
in the high-flow, low-pressure and high-volume portal system.
An anecdotal report made by Stauffer et al showed encouraging results.
Postoperatively estimated cumulative graft patency at one month for
their 9 patients was 100%, as compared with 86%, and 60% after
autologous vein and primary anastomotic repairs, respectively
Retrospective experiences reported elsewhere suggested differently. In
a series of 18 patients with PTFE reconstruction, the actual rate of
thrombosis was 33%, as compared to a combined 12% in 13 primary
end-to-end and 29 lateral venorrhaphy repairs. There was no
statistically significant difference. None of the 4 patients in the same
series who had used LRV for reconstruction developed graft thrombosis

In summary, adequate preop assessment of any patient planning for


PD must include a CT which had been scrutinized by the surgical team
involved
Examinations should focus not only the relationship between the
lesions and the neighboring major vessels, but also a thorough
elucidation of the vascular anatomy, such as the orifices of the celiac
axis and SMA, the presence of replaced right hepatic artery and the
relationship between the SMV and its major tributaries.
Even if major arterial stenosis is not detected on preoperative CT, a
trial clamping of the GDA, and confirmation of a good hepatic arterial
flow before committing to proceed with a PD should be taken as a
routine.
Furthermore, careful palpation along the right distal border of the
hepato-duodenal ligament, supplemented by intraoperative Doppler
ultrasound, would be advisable to rule out the presence of a replaced
or accessary right hepatic artery missed by CT.

Is there any advantage in an extended


versus standard lymphadenectomy
The idea of resecting extended soft tissue and lymph nodes
to decrease local recurrence and increase survival has been
supported by some groups.
Four prospective randomized trials were conducted to
compare standard and extended lymphadenectomy in terms
of survival and morbility and mortality benefits.
Two multi-institutional studies were performed in Japan and
Italy The other two studies were performed in large volume
institutions in the USA
All four studies concluded that extended lymphadenectomy
was feasible, increased surgical time, carried morbidity and
mortality rates similar to those for standard
lymphadenectomy and exhibited no benefit for long-term
survival.

These studies also detected a worsening in the


quality of life for the extended lymphadenectomy
group primarily because of severe diarrhea that
improved with time. The diarrhea was attributed to
the circumferential resection of lymphatic and
neural tissue around the SMA.
There is no survival benefit from extended
lymphadenectomy associated with
duodenopancreatectomy for pancreatic carcinoma,
and patient quality of life may worsen after this
procedure.

Outcome
Givonni et al
Review of literature from January
2000 to March 2008
final study population was composed
of 12 articles

Giovanni Ramacciato et al. Does Portal-Superior Mesenteric Vein


Invasion Still Indicate Irresectability for Pancreatic Carcinoma? Ann
Surg Oncol (2009) 16:817825.

Study Populations
Study

Year

Inclusion
period

No. patients : No. patients :


Pancreatic CA PV/SMVR

Shibata et al.4

2001

19831998

74

28

Kawada et al.5

2002

19901997

43

28

Nakagohri et al.6 2003

19922001

81

33

Capussotti et al.7 2003

19881998

100

22

36

13

Howard et al.8

2003

Poon et al.9

2004

19982002

50

12

Zhou et al.10

2005

19992003

32

32

Jain et al.11

2005

19822004

48

48

Riediger et al.12

2006

19942004

125

40

Shimada et al.13

2006

19962004

149

86

Al-Haddad et
al.14

2007

19982005

76

22

Kurosaki et al.15 2008

19872005

77

35

891

399

Total

Study

Intraoperative findings

Shibata et al.4
Kawada et al.5

Type of
procedure

Operative

Blood

Length of
PV/SMV

PV/SMV
occlusion

time (min)

loss (ml)

resected (cm)

(min)

PD 82%, TP 11%
453
DP 7%
PD 71%, PPPD
551
11%, TP 18%

1583
3083

Nakagohri et al.6 PD 75%, DP 25%a


Capussotti et al.7 PD 100%
Howard et al.8
Poon et al.9
Zhou et al.10
Jain et al.11
Riediger et al.12
Shimada et al.13
Al-Haddad et
al.14

PD 46%, PPPD
54%
PD 92%, PPPD
8%
PD 100%

308b
408

1567

660

800

353

1420

3.9

2040

700

1.55

815

3b

20.5b

Total PD 46%,
390
subtotal PD 54%
PD 19%, TP 8%,
500b
PPPD 74%b
PD 56%, TP 6%,
667
PPPD 38%

1686

PD 86%, TP 9%, DP 5%

Kurosaki et al.15 PD 100%

510

1200

Histopathology of resected
specimens
Lymphnodal
Involvement

Study

Venous invasion

Resection margins ?

Shibata et al.4

7/12 (58.3%)

8 (28.6%)

Kawada et al.5

21/28 (75%)

18 (64%)

24 (86%)

Nakagohri et al.6

17/33 (51.5%)

8 (24.2%)

32 (97%)

13 (39%)

Capussotti et al.7

18/22 (81.8%)

5/6 (83.4%)

15 (68.2%)

17 (77.2%)

Howard et al.8

13/13 (100%)

3 (23%)

7 (54%)

8 (62%)

Poon et al.9

6/12 (50%)

1 (8.3%)

4 (33.3%)

Zhou et al.10

20/32 (62.5%)

5 (15.6%)

25 (78%)

Jain et al. 11

Perineural invasion

Riediger et al.12

16/29 (55.2%)

13 (32.5%)

Shimada et al.13

58/86 (67.4%)

33 (38.4%)

Al-Haddad et al.14

14/19 (73.7%)

Kurosaki et al.15

15/35 (42.9%)

38 (44%)
13 (59%)

14.30%

20 (57.1%)

34 (97.1%)

Study

Perioperative results and


survival
Hospital

Morbidity

Mortality

stay (days)
Shibata et al.4

9 (32%)

1/28 (4%)

Kawada et al.5 68.8

13 (46%)

1/28 (4%)

Nakagohri et al.6

Median

1-Year

5-Year

survival (mo)

survival (%)

survival (%)

31

2/33 (6.06%)

15

58

9 (33.3)a

0 (0%)

15a

68.5a

8.4a

Howard et al.8 14

7 (54%)

1/13 (7.7%)

13

83

Poon et al.9

5 (41.7%)

0/12 (0%)

19.5

10 (31.3%)

0/32 (0%)

12

8 (16.7%)

3/48 (6.25%)

16a

22 (42%)a

2 (4%)a

22

10.9

1/86 (1.2%)

14

12

Capussotti et
al.7

25.5a

15

Zhou et al.10
Jain et al.11
Riediger et
al.12
Shimada et
al.13

44

Al-Haddad et al.14
Kurosaki et al.15

59
18

0/22 (0%)
12 (34%)

1/35 (2.9%)

41.9b
20

Perioperative Results and


Survival
Mortality rates ranged from 0 to 7.7%.
Regarding specific mortality rates, in 11 studies no
deaths related to the PV/SMV resection and
reconstruction were reported, whereas in 1 study (as
mentioned above), one patient developed portal and
died 2 days after the second operation
The mean hospital stay ranged from 12 to 68.8 days
Complication rates for pancreatectomy with PV/SMV
resection ranged from 16.7% to 54%

The most frequent complications were pancreatic fistula, delayed gastric


emptying, and intra-abdominal abscess, as in standard pancreatectomies
Eight studies that compared morbidity rates after pancreatectomy with or
without PV/SMV resection reported no differences between the two
procedures regarding complication rate
In 11 studies, no specific complications for the venous resection and
reconstruction were reported, whereas 1 study reported 1postoperative
thrombosis of the anastomotic site of the PV that required reoperation and
led the patient to death

Median survivals after pancreatectomy combined with PV/SMV resection


for pancreatic carcinoma are reported One-year survival ranged from 31%
to 83%, and 5-year survival ranged from 9% to 18%

Conclusion

Pancreas protocol CT is investigation of choice


EUS is complementry to CT
Preop tissue biopsy is needed when planning for NACT/RT
The optimal strategy for the neoadjuvant treatment of in
potentially resectable cases has not been definitively
established, although preferred at most centres
Meticulous surgical technique for vascular anastomosis
End to end primary anastomosis is most common
reconstruction performed
Autologous graft is preffered over synthetic graft
Portal vein/superior mesenteric vein resection combined
with pancreatectomy is a safe and feasible procedure

Conclusion
In light of our current knowledge, there is no survival benefit from
extended lymphadenectomy associated with duodenopancreatectomy for
pancreatic carcinoma, and the quality of life of patients may worsen.

Acceptable morbidity and mortality rates, comparable to those observed


for pancreatectomies without venous resections
Furthermore, this procedure has substantially increased the number of
patients undergoing curative resection and provides important survival
benefits in selected groups of patients
Hence, pancreatectomy combined with venous resection should always
be considered in case of suspected tumor infiltration of portal and/or
superior mesenteric vein to achieve clear resection margins, in absence
of other contraindications for resection

If a segmental PV or SMV resection of 2 cm or more is


required, a primary end-to-end venous anastomosis
with preservation of the SV is the primary goal.
While autologous vein graft is often elected over
synthetic graft, the use of left renal vein or internal
jugular vein as the natural venous substitute had
gained the most supports
Artificial vascular graft, especially ring-enforced PTFE
graft, has received more attention in recent years,
their application should remain cautious at present

Thank You

Drawback of these studies:


Small number
Methodological problems
Non randomized studies
Many of these studies included
heterogeneous patient populations,
including both advanced pancreatic cancer
and metastatic disease as cases of locally
advanced tumors with borderline or
marginal resectability.

When the presumed cut ends are judged to be too


short for a tension-free venous anastomosis, the
first step to overcome the problem is a complete
mobilization of the right colon together with its
mesocolon, and the root of the mesentery. In
addition, the root of the transverse mesocolon is
also detached from the anterior surface of the
duodenum and pancreas.
During PD, the ligament of Trietz, the third and
fourth parts of the duodenum, and proximal
jejunum should have been mobilized from the
posterior abdominal wall.

If necessary, the falciform ligament,


right coronary ligament and the right
triangular ligament could be divided
to allow placement of surgical packs
to displace the proximal PV stump
caudally to further ease the tension
at the proposed venous anastomosis
during construction.

Both criteria differentiate borderline resectable


from unresectable cancers on the basis of
radiographic evidence for limited SMA
involvement (predicted radiographically by a
tumor-SMA interface less than 180) that would
allow resection of the tumor without resection of
the artery because pancreatectomy with
concomitant resection and reconstruction of the
SMA has generally been found to be futile

2 classifications differ primarily in the extent to which radiographic


evidence of tumor involvement of the SMV-PV discriminates
borderline resectable primary tumors from resectable ones.
The MD Anderson group, which favors the use of neoadjuvant
chemoradiation for both resectable and borderline resectable
cancers, considers venous occlusion to represent the cutoff;
tumors that radiographically abut (<180 tumor-vessel
interface) or encase (>180 interface) the SMV-PV are
considered resectable.
In contrast, the AHPBA/SSAT/ SSO considers venous abutment the
cutoff; all tumors with any degree of abutment or encasement of
the SMV-PV are considered borderline resectable