0824740246

gy in Health and Disease
Editor: Claude Lenfant

Interventional
Pulmonary
Medicine
edited by
John F. Beamis, Jr.
Praveen N. Mathur
Atul C. Mehta
Copyrighted Material
INTERVENTIONAL
PULMONARY
MEDICINE
Edited by
John F. Beamis, Jr.
Lahey Clinic Medical Center, Burlington
and Tufts University School of Medicine
Boston, Massachusetts, US.A.
Praveen N. Mathur
Indiana University Medical Center
Indianapolis, Indiana, US.A.
Atul C. Mehta
The Cleveland Clinic Foundation
Cleveland, Ohio, US.A.
n
OEKKER
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Current printing (last digit):
1098765432 I
PRINTED IN THE UNITED STATES OF AMERICA
To Shigeto Ikeda, M.D.
("There is more hope with the bronchoscope")
To Jean Franyois Dumon, M.D.
The Father of Interventional Pulmonology
INTRODUCTION
Since its inaugural work was published in 1976, the Lung Biology in Health
and Disease series has presented many novel, sometimes futuristic, volumes.
The topics have ranged from very basic biology to clinical aspects of lung
disease. However, never before has a subject like the one of this volume,
interventional pulmonary medicine, been introduced to the readership.
In a general way, the word "interventional" is associated with surgery
and, in terms of the lung, it evokes lengthy and traumatic procedures such as
thoracotomy, lung resection, and lung transplantation. This is not what the
book is about!
Unquestionably, the technical expertise required to practice interven-
tionaI pulmonary medicine is as great as that demanded for surgical
procedures-dexterity, training, and experience are essential. However, as
will become apparent from reading this volume, broader knowledge and
perspective are needed as well.
Interventional pulmonary medicine has applications as both a
diagnostic tool and a therapeutic procedure. Chapter after chapter of this
new volume leads the readers down avenues that they may have heard
about-but, frankly, very few readers know how far the paths will take
them. Many things that can be done an, disctusse,d; if they are indeed done,
Copyngnrea Ma ena
v
VI Introduction
and done well, these interventions will provide great benefits to the patient,
benefits that no other approach can offer.
In their Preface, the editors are very clear about the opportunities
offered by interventional approaches, but they also do not hide the risks:
"Interventional pulmonary medicine involves the clinical applications of a
number of relatively invasive, high-risk procedures in patients who present
with very highly symptomatic, often potentially fatal, airway and pleural
conditions."
Pulmonary diseases are among the most critical public health
challenges we face today. Taken together, they equal and probably even
exceed the public health burden of cardiovascular disease. Not all types of
pulmonary disease can benefit from an interventional approach, but many
types-acute or chronic, malignant or benign-stand to do so, whether from
the perspective of precise diagnosis or treatment in situ.
The editors of this volume, Drs. John Beamis, Praveen Mathur, and
Atul Mehta, are experts and undoubtedly the leaders in the field of
interventional pulmonary medicine; they, in turn, have reached out to other
experts from the United States and other countries to present broad and
comprehensive views of what interventional medicine offers. It is hoped that
this volume will be an inspiration as welJ as a guide to the pulmonary
community-that it will stimulate greater professional interest in interven-
tional pulmonary medicine and the further use of its approaches when
appropria teo
As the executive editor of the Lung Biology in Health and Disease
series, r feel that it would be incomplete without a presentation of this
approach. To be able to introduce this volume to the readership gives me
considerable satisfaction. r am grateful and thankful to the editors and all
the authors for this opportunity, and for such a valuable contribution to the
senes.
Claude Lenfant, M.D.
Gaithersburg, Maryland
PREFACE
There have been many advances in the world of pulmonary medicine in the
last 25 years. These include areas of imaging, new drug development, and
improvements in ventilator management and leU care. Among these
exciting advances are the development and maturation of the field of
interventional pulmonology. We have had the privilege to be involved in this
field since its inception, and we have worked together on a number of
projects involving interventional pulmonology. We have enlisted many
leading experts in the field-some recognized leaders, some new to the
interventional pulmonology world-in order to present in this book the
state of the art. Although interventional pulmonology is focused on a
number of procedures performed by pulmonologists and critical care
physicians, we have deliberately tried not to present a "how to" book but to
emphasize the science behind the clinical application of these procedures.
lnterventional pulmonary medicine involves the clinical application of
a number of relatively invasive, high-risk procedures in patients who present
with highly symptomatic, often potentially fatal, airway and pleural
conditions. lnterventional pulmonary medicine can be broken down into
several categories: therapeutic bronchoscopy, advanced diagnostic broncho-
scopy, pleuroscopy, percutaneous tracheotom
Y
j
and whole-lung lavage.
Copyrighted Materia
vii
viii Beamis et aL.
The book is organized around these major categories, with initial chapters
dealing with the history of rigid bronchoscopy and interventional flexible
bronchoscopy and a closing segment addressing clinical outcomes and
training.
Although many physicians have contributed to advances in interven-
tional pulmonary medicine, two stand out. Dr. Shigeto Ikeda from Tokyo,
Japan, introduced flexible fiberoptic bronchoscopy-an instrument that has
helped define the field of modern pulmonary medicine. Dr. Ikeda has
provided modern interventional pulmonologists with their major tool both
for advanced diagnostic techniques (such as autofluorescence, TBNA, and
endobronchial ultrasound) and for potentially all therapeutic bronchoscopy
applications, except for the placement of silicone stents and some cases of
critical central airway obstruction. Dr. Ikeda's favorite motto was "never
give up." This seems to be a motto shared by many interventional
pulmonologists as they deal with advanced disease and critically ill patients.
His other favorite motto was "there's more hope with the bronchoscope."
Dr. Jean Franois Dumon of Marseille, France, helped define the field
of interventional pulmonology by emphasizing the therapeutic applications
of bronchoscopy and introducing Nd:YAG laser bronchoscopy and silicone
stents to physicians throughout the world. His creativity and technical
expertise in the field of bronchology have inspired many current
interventional pulmonologists. The death of Dr. Ikeda in 2002 and Dr.
Dumon's recent retirement mark the end of the original era of interventionaI
pulmonology. We have dedicated this book to these superb physicians, who
have been mentors to generations of thoracic physicians. We hope that our
book will chronicle their and others' contributions during the early decades
of interventional pulmonology and will be a resource for the next
generation.
We wish to acknowledge and thank all our contributors. Many are
friends, colleagues, and collaborators. All of them are highly productive,
clinically active individuals and we appreciate the time and effort that they
set aside in order to contribute. We thank Sandra Beberman and Moraima
Suarez from Marcel Dekker, Inc., for their gentle prodding and encourage-
ment to take on and complete this task and to Dr. Claude Lenfant for
inviting us to contribute to the Lung Biology in Health and Disease series.
We also thank our families and local colleagues for their continued support
whenever we take on new projects.
John F. Beamis, Jr.
Praveen N. Mathur
Atul C. Mehta
CONTRIBUTORS
James N. Allen, M.D. Division of Pulmonary and Critical Care Medicine,
Department of Internal Medicine, Ohio State University, Columbus, Ohio,
U.S.A.
Dennis E. Amundson, D.O. Program Director, Pulmonary and Critical
Care Medicine, Naval Medical Center, San Diego, California, U.S.A.
Selim M. Arcasoy, M.D., F.C.C.P., F.A.C.P. Associate Professor, Divi-
sion of Pulmonary and Critical Care Medicine, Department of Medicine,
and Medical Director, Lung Transplant Program, Columbia University
College of Physicians and Surgeons, New York, New York, U.S.A.
Michael H. Baumann, M.D., F.C.C.P. Professor, Division of Pulmonary
and Critical Care Medicine, Department of Medicine, University of
Mississippi Medical Center, Jackson, Mississippi, U.S.A.
John F. Beamis, Jr., M.D. Chair, Division of Internal Medicine, and
Chair, Department of Pulmonary and Critical Care Medicine, Lahey Clinic
Medical Center, Burlington, and Associate Professor, Department of
Medicine, Tufts University School of Medicine, Boston, Massachusetts,
U.S.A.
ix
x
Beamis et al.
Chris T. Bolliger, M.D., Ph.D. Professor, Lung Unit, Department of
Internal Medicine, University of Stellenbosch, Cape Town, South Africa
David A. Bradshaw, M.D. Head, Division of Pulmonary Medicine,
Department of Internal Medicine, Naval Medical Center, San Diego,
California, USA.
E. James Britt, M.D. Professor, Division of Pulmonary and Critical Care
Medicine, Department of Medicine, University of Maryland School of
Medicine, Baltimore, Maryland, U.S.A.
Kent L. Christopher, M.D., F.C.C.P. Associate Clinical Professor,
Department of Medicine, University of Colorado Health Sciences Center,
Denver, Colorado, U.S.A.
Henri Colt, M.D. Professor, Division of Pulmonary and Critical Care
Medicine, Department of Medicine, University of California, Irvine,
Orange, California, U.S.A.
Terrence D. Coulter, M.D. Department of Pulmonary and Critical Care
Medicine, Ferrell Duncan Clinic, Inc., Springfield, Missouri, U.S.A.
Bennett P. deBoisblanc, M.D. Professor, Division of Pulmonary and
Critical Care Medicine, Department of Medicine, Louisiana State Uni-
versity Health Sciences Center, New Orleans, Louisiana, U.S.A.
Jose Pablo Diaz-Jimenez, M.D. Coordinator, Interventional Broncho-
scopy Unit, Department of Pulmonology, Bellvitge University Hospital,
Barcelona, Spain
Armin Ernst, M.D. Director, Section of Interventional Pulmonary
Medicine, Department of Medicine, Beth Israel Deaconess Medical Center,
Boston, Massachusetts, U.S.A.
Lutz Freitag, M.D., F.C.C.P. Medical Director, Department of Pulmon-
ary Medicine, Center for Pulmonary Medicine and Thoracic Surgery, The
Hemer Pulmonary Clinic, Hemer, Germany
Karl Haussinger, M.D. Professor, Center for Respiratory Medicine and
Thoracic Surgery, Asklepios Fachkliniken Munchen-Gauting, Munich,
Germany
Contributors
xi
Felix J. F. Herth, M.D., F.C.C.P. Professor, Department of Pneumology,
Thoraxklinik-Heidelberg, University of Heidelberg, Heidelberg, Germany
Yasuo Iwamoto, M.D., Ph.D. Department of Pulmonary Medicine,
Hiroshima City Hospital, Hiroshima, Japan
Michael A. Jantz, M.D. Assistant Professor, Division of Pulmonary and
Critical Care Medicine, Department of Medicine, University of Florida,
Gainesville, Florida, U.S.A.
Koji Kanoh, M.D. Department of Pulmonary Medicine, Fukushima Coop
Hospital, Hiroshima, Japan
James L. Knepler, Jr., M.D. Assistant Professor of Clinical Medicine,
Division of Pulmonary, Critical Care and Occupational Medicine, Depart-
ment of Medicine, Indiana University Medical Center, Indianapolis,
Indiana, U.S.A.
Kevin L. Kovitz, M.D., M.B.A. Professor, Departments of Medicine and
Pediatrics; Medical Director and Associate Dean for Medical Affairs;
Director, Interventional Pulmonology and Medical Critical Care; Interim
Chief, Section of Pulmonary Diseases, Critical Care and Environmental
Medicine, Department of Medicine, Tulane University Health Sciences
Center, New Orleans, Louisiana, U.S.A.
Robert J. Kruklitis, M.D., Ph.D. Senior Interventional Fellow, Division of
Pulmonary and Critical Care Medicine, Department of Medicine, Uni-
versity of Pennsylvania Medical Center, Philadelphia, Pennsylvania, U.S.A.
Paul A. Kvale, M.D. Professor, Division of Pulmonary and Critical Care
Medicine, Department of Medicine, Henry Ford Health System, Detroit,
Michigan, U.S.A.
Stephen Lam, M.D., F.R.C.P.C., F.C.C.P. Professor, Department of
Medicine, University of British Columbia, and Chair, Lung Tumour
Group, British Columbia Cancer Agency, Vancouver, British Columbia,
Canada
Carla R. Lamb, M.D., F.C.C.P. Department of Pulmonary and Critical
Care Medicine, Lahey Clinic Medical Center, Burlington, Massachusetts,
U.S.A.
xii Beal11is et at.
Pyng Lee, M.D. Consultant, Department of Respiratory and Critical Care
Medicine, Singapore General Hospital, Singapore
Robert Loddenkemper, M.D. Professor, Department of Pneumonology II,
Lungenklinik Heckeshorn, Berlin, Germany
Roberto F. Machado, M.D. Department of Pulmonary and Critical Care
Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
Praveen N. Mathur, M.B.B.S. Professor of Clinical Medicine, Division of
Pulmonary, Critical Care, and Occupational Medicine, Department of
Medicine, Indiana University Medical Center, Indianapolis, Indiana,
USA.
Martin L. Mayse, M.D. Assistant Professor, Division of Pulmonary and
Critical Care Medicine, and Director of Interventional Pulmonology,
Department of Medicine, Washington University in St. Louis, St. Louis,
Missouri, U.S.A.
Annette M. McWilliams, M.B.B.S., F.R.A.C.P. Respirologist, Cancer
Imaging Department, British Columbia Cancer Agency, Vancouver, British
Columbia, Canada
Benjamin D. Medoff, M.D. Associate Director, Medical Intensive Care
Unit, Pulmonary and Critical Care Unit, Massachusetts General Hospital,
Atul C. Mehta, M.B.B.S. Professor and Vice Chair, Department of
Pulmonary, Allergy, and Critical Care Medicine, Head of Bronchology, and
Medical Director of Lung Transplantation, The Cleveland Clinic Founda-
tion, Cleveland, Ohio, U.S.A.
Teruomi Miyazawa, M.D., Ph.D., F.C.C.P. Director and Clinical Profes-
sor, Department of Pulmonary Medicine, Hiroshima City Hospital,
Hiroshima, Japan
Yuka Miyazu, M.D. Department of Pulmonary Medicine, Hiroshima City
Hospital. Hiroshima, Japan
Marc Noppen, M.D., Ph.D. Professor, Respiratory Department, Free
University of Brussels, and Interventional Endoscopy Clinic, Academic
Hospital AZ-VUB, Brussels", l ~ ~ u m M t . I
r...;01"yngnLea a ena
Conlributors
xiii
Dattatreyudu Nori, M.D., F.A.C.R., F.A.C.R.O. Professor, Department of
Radiation Oncology, Joan and Sanford 1. Weill Medical College of Cornell
University; Chair, Department of Radiation Oncology, New York
Presbyterian Hospital; and Chair and Director, Department of Radiation
Oncology, The New York Hospital Medical Center of Queens, New York,
New York, U.S.A.
David Ost, M.D. Director of lnterventional Pulmonology, North Shore
University Hospital, Manhasset, and Assistant Professor, Department of
Medicine, New York University School of Medicine, New York, New York,
U.S.A.
Suhrid Parikh, M.D.t Associate Professor, Department of Radiation
Oncology, Joan and Sanford 1. Weill Medical College of Cornell University,
and The New York Hospital Medical Center of Queens, New York, New
York, U.S.A. .
Jagan Mohan Poli, M.D. Fellow, The New York Hospital Medical Center
of Queens, New York, New York, U.S.A.
Akkamma Ravi, M.D. Assistant Attending Radiation Oncologist, Depart-
ment of Radiation Oncology, Joan and Sanford 1. Weill Medical College of
Cornell University, and The New York Hospital Medical Center of Queens,
New York, New York, U.S.A.
Charles A. Read, M.D. Associate Professor, Division of Pulmonary,
Critical Care and Sleep Medicine, Department of Medicine, Georgetown
University Medical Center, Washington, D.C., U.S.A.
Giinther Reichle, M.D. Center for Pulmonary Medicine and Thoracic
Surgery, The Hemer Pulmonary Clinic, Hemer, Germany
Alicia N. Rodriguez, M.D. Department of Pulmonary and Critical Care
Medicine, Hospital Privado de Comunidad, Mar del Plata, Buenos Aires,
Argentina
tDeceased.
xiv Beamis et al.
Cynthia P. Saad, M.D. Fellow, Department of Pulmonary and Critical
Care Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio, U.S.A.
Mace M. Schuurmans, M.D. Lung Unit, Department of Internal
Medicine, University of Stellenbosch, Cape Town, South Africa
Francis D. Sheski, M.D. Associate Professor, Department of Medicine,
Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
Gerard A. Silvestri, M.D., F.C.C.P. Associate Professor, Department of
Pulmonary and Critical Care Medicine and Allergy and Clinical Immunol-
ogy, Medical University of South Carolina, Charleston, South Carolina,
U.S.A.
Michael J. Simoff, M.D. Division of Pulmonary and Critical Care
Medicine, Henry Ford Health System, Detroit, Michigan, U.S.A.
Franz Stanzel, M.D. Clinic for Pneumonology, Asklepios Fachkliniken
Munchen-Gauting, Munich, Germany
Daniel H. Sterman, M.D. Assistant Professor, Division of Pulmonary and
Critical Care Medicine, Department of Medicine, University of Pennsylva-
nia Medical Center, Philadelphia, Pennsylvania, U.S.A.
Andrew G. Villanueva, M.D. Senior Staff Physician, Department of
Pulmonary and Critical Care Medicine, Lahey Clinic Medical Center,
Burlington, Massachusetts, U.S.A.
Juliette L. Wohlrab, M.D. Fellow, Division of Pulmonary, Critical Care,
and Sleep Medicine, Department of Medicine, Georgetown University
Medical Center, Washington, D.C., U.S.A.
CONTENTS
Introduction
Preface
Contributors
Claude Lenfant
v
vii
ix
1. History of Rigid Bronchoscopy
FeLix 1. F. Herth, John F. Beamis, Jr., and Armin Ernst
1
I.
II.
III.
IV.
V.
Introduction
Preendoscopy Era
Laryngoscopy
Technical Improvements
Further Developments
References
I
2
2
3
9
II
2. Rigid Bronchoscopy: An Interventional Tool with a History
and a Future 13
CarLa R. Lamb and John F. Beamis, Jr.
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
Introduction
Historical Overview
Indications for RB and Patient Selection
Equipment and Technique
Anesthesia and Ventilatory Strategies
Rigid Bronchoscopic Intubation
Recovery and Postoperative Care
Complications and Management
Interventional Outcomes
Growth of RB in the Field of Interventional
Pulmonology
References
13
14
15
17
20
24
28
28
28
29
30
xv
xvi
Beamis et al.
3. Interventional Flexible Bronchoscopy: Historical Perspective 33
Teruomi Miyazawa, Yuka Miyazu, Koji Kanoh, and
Yasuo Iwamoto
I. Introduction 33
II. Developments in Bronchoscopy 34
III. Future Research 43
References 47
4. Therapeutic Flexible Bronchoscopy: Overview 49
Pyng Lee and Atul C. Mehta
I. Introduction 49
II. Therapeutic Bronchoscopy 50
III. Bronchoscopic Equipment 50
IV. Central Airway Obstruction 51
V. Relief of Malignant Airway Obstruction 52
VI. Relief of Benign Airway Obstruction 62
VII. Adult Airway Foreign Body Removal 70
VIII. Bronchovascular Lavage 71
IX. Aspiration of Mediastinal Cysts 72
X. Drainage of Lung Abscess 73
XI. Massive Hemoptysis 73
XII. Bronchoscopy in Intensive Care Unit 74
XIII. Other Applications of Therapeutic Bronchoscopy
76
XIV. Future Applications of Therapeutic Bronchoscopy
76
XV. Conclusion
77
References
78
5. Laser Bronchoscopy for Malignant Disease
89
Jose Pablo D[az-Jimene::. and Alicia N. Rodrigue::.
I. Introduction and Definition of Procedure
89
II. History and Historical Perspective
90
III. Indications and Contraindications
90
IV. Equipment
95
V. Theory and Application
96
VI. Technique
102
VII. Evidence-Based Literature Review
113
VIII. Concl L1sion
122
References
123
Contents
xvii
6.
Laser Bronchoscopy for Benign Disease 127
Henri Colt
I. Introduction and Definition of Procedure 127
II. History and Historical Perspective 128
III. Indications and Contraindications 129
IV. Equipment
133
V. Technique 134
VI. Specific Etiologies of Airway Obstruction 137
VII. Conclusion 152
References 153
7. Cryotherapy: Cold Therapy for the Tracheobronchial Tree 157
James L. Knepler, Jr., and Praveen N. Mathur
I. Introduction 157
II. History 157
III. Scientific Basis 158
IV. Indications 159
V. Clinical Basis 160
VI. Techniques and Equipment 161
VII. Complications 162
VIII. Conclusion
163
References
163
8.
Endobronchial Electrosurgery
167
Roberto F. Machado, Cynthia P. Saad, Atul C. Mehta, and
Terrence D. Coulter
I.
Introduction
167
II.
Background and Physics
168
III.
Instruments
168
IV.
Accessories
169
V. Techniques
170
VI.
Clinical Use
172
VII.
Complications and Treatment Failure
175
VIII.
Comparison to Other Techniques
176
IX.
Argon Plasma Coagulator
176
X.
Conclusion
177
References
178
Xli/II Beamis et al.
9. Endobronchial Brachytherapy 181
Dattatreyudu Nori, Suhrid Parik.h, lagan Mohan Poli, and
Akkamma Ralli
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
XI.
Introduction
History
Catheter Placement
Endobronchial Applicators
Treatment Planning
Dose Prescription Point
Dose and Fractionation
Palliative Endobronchial Brachytherapy
Curative Endobronchial Brachytherapy
Complications: Grading and Management
Conclusion
References
181
182
184
187
187
189
189
192
195
197
198
200
10. Argon Plasma Coagulator
Lutz Freitag and ~ i n t h r Reichle
203
l.
II.
III.
IV.
V.
VI.
Introd uction
Technical and Practical Aspects
Risks and Precautions
Results
Other Indications
Conclusion
References
203
204
209
209
210
211
212
11. Silicone Airway Stents
Mace M. Schuurmans and Chris T. Bolliger
215
I.
II.
III.
IV.
V.
VI.
VII.
VIIl.
Introduction and Definition of Procedure
History
Indications and Contraindications for Stent Placement
Commercially Available Silicone Stents
Evaluation of Patients for Silicone Stent Insertion
Technique
Evidence-Based Literature Review
Conclusion
References
215
216
218
220
225
229
233
236
236
Contents
xix
12.
Self-Expanding Metallic Airway Stents
239
James N. Allen
I. Introduction
239
II. History
240
III. Stent Construction
240
IV. Indications
242
V.
Technique and Sizing
244
VI.
Clinical Efficacy
251
VII. Complications
252
VIII. Conclusion
254
References
255
13. Foreign Body Removal
259
Kevin L. Kovitz and Martin L. Mayse
I. Introduction
259
II. Signs and Symptoms
260
III. Diagnosis
261
IV. Types of Foreign Bodies
261
V. Removal Procedure
262
VI. Surgery
268
VII. Complications
268
VIII. Conclusion
268
References
269
14. Photodynamic Therapy: Early Lung Cancer
271
Stephen Lam and Annette M. McWilliams
I. Introduction 271
II. Principles of Photodynamic Therapy 272
III. Local Staging of Early Lung Cancer 275
IV. Clinical Trials 276
V. PDT Versus Other Endobronchial Modalities
for Treatment of Early Lung Cancer 279
VI. Conclusion 281
References 281
xx
15. Photodynamic Therapy for Palliation of Lung Cancer
David OS!
Beal11is e! al.
287
I.
II.
III.
IV.
V.
Introduction
Technique
Mechanism of Action
Clinical Studies
Role of PDT in a Multimodality Approach
References
287
288
290
296
299
301
16. Bronchoscopic-Mediated Gene Therapy: Past, Present,
and Future
Rober! 1. Kruklitis and Daniel H. Sterman
305
I.
II.
III.
IV.
V.
Introduction
Modes of Delivery
Clinical Trials
Preclinical Trials
Conclusion
References
305
306
309
319
320
322
17. Whole Lung Lavage
Benjamin D. Medoff and Selim M. Arcasoy
329
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
x.
XI.
Introduction
Historical Perspective
Theory of Application
Disease Pathogenesis and Effectiveness of WLL
Indications and Contraindications
Personnel and Equipment
Technique
Physiological Changes During WLL
Physiological Changes After WLL
Conclusion
References
329
330
331
332
334
336
340
344
350
350
352
352
Contents
xxi
18.
Fluorescence Bronchoscopy
355
Franz StaJ1Zel and Karl HCiussinger
I.
355
II.
History and Historical Perspective
358
III.
359
IV. Equipment
360
V. Theory of Application
362
VI. Technique
366
VII. Evidence- Based Li terature Review
367
VIII. Conclusion
374
References
376
19. Transbronchial Needle Aspiration
385
E. James Britt
1. Introduction
385
II. Diagnosis and Staging of Bronchogenic
Carcinoma
388
III. Diagnosis of Lymphoma and Metastatic
Carcinoma 393
IV. Diagnosis of Benign Disease 394
V. TBNA and the Diagnosis of Infections 395
VI. Diagnosis and Treatment of Bronchogenic Cysts 396
VII. Diagnosis of Peripheral Nodules, Masses, and
Infiltrates 397
VIII. Techniques to Enhance Visualization and
Placement Using Transbronchial Needles 400
IX. Diagnosis of Endobronchial Disease 402
X. Complications of TBNA 402
XI. Conclusion 404
References 405
xxii
20. Medical Thoracoscopy: Historical Perspective
Robert Loddenkemper
Beamis eI aI,
411
I.
II.
III.
IV.
V.
VI.
Introduction of Thoracoscopy as a Diagnostic
Method
Thoracoscopy as a Therapeutic Procedure in
Tuberculosis (Jacobaeus Operation)
Thoracoscopy as a Therapeutic Tool in
Nontuberculous Disease
Further Development of Thoracoscopy as an
Important Diagnostic Tool
Discovery of Thoracoscopy for Minimal Invasive
Thoracic Surgery
Perspectives of Medical Thoracoscopy
References
411
414
416
417
420
421
424
21. Medical Thoracoscopy: Diagnosis of Pleural Pulmonary
Disorders
Andrew G. Villanueva and John F. Beamis, Jr.
431
I.
II.
III.
IV,
V
Introduction
Indications for Diagnostic Medical Thoracoscopy
Limitations of Medical Thoracoscopy
Techniques
Conclusion
References
431
431
443
443
446
446
22. Medical Thoracoscopy: Therapy for Malignant Conditions 451
Ju/ielle L. Wohlrab and Charles A. Read
I.
II.
III.
IV.
V
VI.
VII.
VIII,
Historical Perspectives
Equipment
Theory of Application
Technique
Conclusion
References
451
451
452
452
453
456
456
465
465
Contents
23. Medical Thoracoscopy: Therapy for Benign Conditions
Michael H. Baumann
xxiii
469
I.
II.
Ill.
IV.
Introduction
Therapeutic Applications
The Talc Controversy
Conclusion
References
469
471
478
479
479
24. Medical Thoracoscopy: Techniques for Thoracic
Sympathectomy 483
Marc Noppen
I. Introduction and Definition of the Procedure 483
II. History and Historical Perspective 484
IV. Equipment 487
V. Theory of Application 487
VI. Technique 488
VII. Evidence-Based Literature Review 490
VUI. Conclusion 497
References 497
25. Transtracheal Oxygen Therapy 503
Kent L. Christopher
I. History 503
II. Overview of a TTO Therapy Program 505
III. Complications of a Program Utilizing the MST
for Tract Creation 506
IV. Potential Benefits 509
V. Highlights of the Program with the MST for
Tract Creation 512
VI. Lipkin Surgical Procedure and Modified SCOOP
Program 526
VII. Combination of TTO and Demand Oxygen Delivery
Systems 532
VIII. Transtracheal Augmented Ventilation 532
IX. TTAV for Nocturnal Support in the Home 533
X. TTAV for Weaning from Prolonged Mechanical
Ventilation 535
XI. Treatment of Sleep Apnea 537
XII. Conclusion 539
References 540
xxiv
Beamis el al.
26. Chest Tube Placement
545
Francis D. Sheski
I. Introduction
545
II. Historical Perspective
545
IV. Equipment
548
V Technique
551
VI. Evidence-Based Literature Review 556
VII. Concl usion
562
References
562
27. Percutaneous Dilational Tracheostomy 567
Bennett P. deBoisblanc
I. Introduction 567
II. Overview of PDT Procedures 568
III. Comparison of PDT to Open Surgical Tracheostomy 573
IV. Late Complications 578
V Special Situations 579
VI. Preoperative Ultrasound 579
VII. Conclusion 580
References 581
28. Transthoracic Needle Aspiration and Biopsy 585
Carla R. Lamb. David A. Bradshmv, and Dennis E. Amundson
I. Introduction
585
586
III. Indications, Contraindications, and Relative Risks 587
IV. Equipment, Preparation, and Technique 589
V. Safety and Outcome
594
VI. Conclusion
600
References
601
Contents
xxv
29. Effects of lnterventional Procedures on Quality of Life and
Pulmonary Function 609
Mich.ael A. Jantz and Gerard A. Silvestri
I.
II.
III.
IV.
V.
Introduction
Changes in Quality of Life, Performance Status,
and Dyspnea
Changes in Pulmonary Function Testing
Bronchoscopic Interventional Procedures Versus
Conventional Therapies
Conclusion
References
609
610
621
631
631
632
30. Training in lnterventional Pulmonology
Michael 1. Simo!f and Paul A. Kvale
1. Introd uction
II. Trainees
III. Cognitive Skills
IV. Technical Skills
V. Clinical Skills
VI. Who Should Be Trained?
VII. Conclusion
References
639
639
642
642
648
652
654
655
655
Appendix: Procedural Algorithms 657
i. Palliative Therapy for Malignant Central Airway Obstruction 658
2. Medical Thoracoscopy 659
3. Malignant Pleural Effusion 660
4. Large-Bore Chest Tube insertion 661
5. Bedside Pleurodesis 662
INTERVENTIONAL
PULMONARY
MEDICINE
1
History of Rigid Bronchoscopy
FELIX J. F. HERTH
University of Heidelberg
Heidelberg, Germany
JOHN F. BEAMIS, JR.
Boston, Massachusetts, U.S.A
I. Introduction
ARMIN ERNST
Beth Israel Deaconess Medical Center
1
Gustav Killian of Freiburg, Germany, performed the first bronchoscopy in
1887. During the early years of the development of bronchoscopy, the
indications for the procedure were primarily therapeutic: removal of foreign
bodies and dilation of strictures from tuberculosis and diphtheria. In the
early part of the twentieth century, Chevalier Jackson, the father of
American bronchoesophagology, further advanced bronchoscopic techni-
ques and designed modern rigid bronchoscopes. Again, the primary
indication was often therapeutic. In 1963, Dr. Shigeto Ikeda introduced
the flexible fiberoptic bronchoscope primarily as a diagnostic instrument.
Bronchoscopy soon shifted from being a therapeutic procedure performed
by thoracic surgeons and otolaryngologists to a primarily diagnostic
procedure performed by pulmonologists. Currently, next to thoracentesis
and pulmonary function testing interpretation, bronchoscopy is the most
commonly performed procedure by pulmonologists. As pulmonologists
have gained expertise within the field of bronchology, the diagnostic use of
the flexible bronchoscope has expanded and there has been a growing
interest in the use of the instrument for therapeutic purposes. The worldwide
2 Hath et al.
epidemic of lung cancer, which has produced many cases of airway
obstruction by malignant neoplasm and benign stenosis, has replaced
foreign body removal as the main indications for therapeutic bronchoscopy.
Technology has presented bronchoscopists with numerous adjunctive
therapies in addition to the classic forceps used by Killian and Jackson.
These newer therapies include laser, stents, electrocautery, cryotherapy, and
others and can be applied through either rigid or flexible bronchoscopes. In
the United States, because of familiarity and ease of application with topical
anesthesia, most pulmonologists attempt therapeutic interventions with a
flexible bronchoscope. In selected U.S. centers and in some European
countries where expertise in rigid bronchoscopy is more prevalent, the rigid
bronchoscope remains the instrument of choice for therapeutic
interventions [I].
II. Preendoscopy Era
Attempts to gain access to the airways in the living patient were initially
tried by Hippocrates (460-370 Be), who advised the introduction of a pipe
into the larynx in a suffocating patient. In 1542, Vesalius observed that
when he opened the chest of an experimental animal, the heartbeat and
pulsation of the great vessels stopped, but returned again after he introduced
a reed into the airway and inflated the lungs with a bellows [2].
Desault (1744-1795) advised nasotracheal intubation for treatment of
suffocation and removal of foreign bodies. For centuries the inhalation of a
foreign body caused death or produced chronic illness in more than half of
the patients owing to secondary purulent infection, abscess and fistula
formation, and malnutrition. Many instruments were designed to remove
foreign bodies from the airways blindly through the larynx or a
tracheotomy, called "bronchotomy." This opening to the airway was also
used for treatment of subglottic stenosis caused by diphtheria.
III. Laryngoscopy
Early experiments for the inspection of the larynx with the help of mirrors
were performed by Latour (1825), Senn (1829), Belloc (1837), Liston (1840),
Avery (1844), and others [3]. However, in 1854, a singing instructor in
London, Manuel Garcia, was the first to observe his own larynx with the
help ofa dental mirror [4]. Almost simultaneously. in 1856, the laryngologist
Ludwig TLirch in Vienna made his first experiments with a similar device,
which he lent to the physiologist Czermak of Budapest [5]. In the winter
months, the illumination was not sufficient for continuation of their studies!
3
However, it was the introduction of these instruments that made the
diagnosis and treatment of laryngeal diseases possible. Tn 1862, the German
surgeon Victor von Bruns in Tiibingen, aided by this laryngoscopic mirror,
was the first to remove a polyp from a vocal chord [6]. The patient was his
own brother. Without suitable anesthetics, the procedure required weeks of
preparation to gradually desensitize the patient. The surgeon studied the
anatomy of the larynx by using volunteers. One of the major problems that
he faced was the indirect and reverse view of the image.
IV. Technical Improvements
Philipp Boztzini, a general practitioner in Frankfurt, developed his
"illuminator" in 1805. With this device, a suitable light source for the
inspection of the trachea became possible. The somewhat clumsy instrument
consisted of a box containing a candle, the light of which was reflected by a
hollow mirror into a "conductor," and a split metallic tube that could be
spread by a simple mechanism. For the inspection of organs that could not
be visualized by direct inspection, he used a tube with a mirror for reflection
of the light and image [7,8].
The next suitable light source was the instrument developed by
Desormeaux in 1853. He also introduced the word "endoscope" to describe
an instrument to inspect the body cavities [9]. It was in 1867-1868 that A.
Kussmaul performed the first esophagoscopies [10]. The illumination was
insufficient for the inspection of the stomach. The first suitable gastroscope
was introduced in 1881 by Mikulicz and Leiter [11]. It was a closed optic
with lenses and prisms that were electrically illuminated at the distal end by
a glowing platinum wire which had to be cooled by a constant flow of water,
and thus was not suitable for application in the airways [12]. Only after
Thomas A. Edison invented the electric bulb in 1879, and further
miniaturization by Mignon, could distal electric illumination be applied to
endoscopy of the airways.
Tn 1886, the Viennese endoscope maker Leiter produced the first so-
called panelectroscope, a tube that was connected to a handle that contained
an electric bulb and a prism for illumination [13]. The instrument was
modified by many specialists, including Gottstein, who, in 1891, was the first
to attach a metal tube; Rosenheim, who accidentally first passed into the
trachea; and Kirstein in Berlin. Kirstein intentionally tried to intubate the
larynx with the esophagoscope, and after his first experience in 1894, began
systematic direct inspection, which he called "autoscopy" [14]. The
rhinolaryngologist Gustav Killian of Freiburg University attended Kirst-
ein's lecture in Heidelberg on June 4, 1895, at the 2nd Congress of the
4 Herth et al.
Southern German Laryngologists. He immediately recognized the impor-
tance of Kirstein's observation for the diagnosis and treatment of
laryngotracheal diseases and began experiments with this new method [15].
A. Local Anesthesia
Before the use of cocaine for local anesthesia, many attempts were made to
anesthetize the airways with agents such as potassium bromide, ammonia,
belladonna, iodine solution, chloroform, morphine, and others. Nothing
proved to be sufficient. The patients had to be desensitized over several
weeks. The examiner had to be extremely skilled and swift, as operations
had to be performed in seconds before the view disappeared [16,17].
Although Morton in Boston had introduced general anesthesia in
1848, its use was so dangerous that it was only rarely applied in
laryngoscopic operations. In 1882, Sigmund Freud experimented with
cocaine [18]. He advised his colleague Koller, an eye specialist, to use
cocaine solution for pain relief when he suffered from severe conjunctivitis.
Koller immediately realized the importance of this observation and began
feverishly experimenting with this new "miracle drug" on rabbits and
patients. On September 15, 1884, he inaugurated local anesthesia in his
lecture at the Annual Congress of German Ophthalmologists in Heidelberg.
At the same time in Vienna, the laryngologist Jellinek began using cocaine
as a local anesthetic for the inspection of the airways. With the introduction
of reliable topical anesthesia, comprehensive work within the airways
became possible [7].
B. Gustav Killian
At the 1889 meeting of the South German Laryngological Society in
Heidelberg, Gustav Killian gave a short report on a new technique to
examine the dorsal wall of the larynx. Killian had learned about Kirstein's
new technique of direct examination of the trachea at the meeting of the
Laryngological Society in Heidelberg in 1895 (Fig. I). Killian realized at
once the potential of this new method to visualize the trachea, and in 1896
he began experimental work. In tracheotomized patients, he passed the
bifurcation with the "bronchoscope," a somewhat modified esophagoscope,
and noticed that the bronchi were elastic and flexible, and he was "stopped
only when the diameter of the tube was surpassing that of the bronchi" [19].
He then confirmed his findings in cadavers (Fig. 2) and soon was ready
to perform the first direct bronchial endoscopy via the larynx in a volunteer.
He noticed the flexibility of the trachea and how easily he could adjust it to
the angle of the main bronchi and thus introduce the endoscope down to the
Figure 1 The young Gustav Killian.
5
lobar level. In 1897, he became the first person to remove a foreign body via
the translaryngeal route [20].
After further experience and removal of two more foreign bodies,
Killian presented his new method of "direct bronchoscopy" at the 5th
Meeting of the Society of South German Laryngologists in Heidelberg on
May 29, 1898. In the same year, his first publication on direct bronchoscopy
was printed [19]. In the following years, he made technical improvements to
the new method and developed more indications of its use [21,22].
In order fully to understand the importance of endoscopic removal of
foreign bodies [23], one has to consider the state of thoracic surgery in
Killian's time. Most of the patients became chronically ill after aspiration of
a foreign body. They developed atelectasis, chronic pneumonia, and
hemorrhage and half of them died if untreated. Surgical procedures were
restricted to pneumotomy as the bronchus was often occluded by extensive
solid scar tissue [24]. This procedure carried a very high mortality rate.
Lobectomy and pneumonectomy could not be performed because techni-
ques for safe closure of the bronchial stump had not been developed.
6
Herth et al.
Figure 2 Gustav Killian demonstrating bronchoscopy on a cadaver model.
Killian's pupil, Albrecht, reported on 703 patients with foreign body
aspiration between 1911 and In!. In all but 12 cases, the foreign body
could be removed bronchoscopically-a success rate of 98.3%. In addition
to numerous instruments for foreign body extraction, Killian constructed
other devices including a dilator and even the first endobronchial stent
[25,26]. In 1907, Killian received an invitation from the American
Otorhinolaryngological Society. On July 3, 1907, he gave a lecture on his
7
work at the meeting of the German Medical Society of New York. His
presentation was also published in the journal Laryngoscope in the same
year [27]. Lectures were followed by practical demonstrations of his
bronchoscopic and surgical techniques. He eventually met Chevalier
Jackson, who was then already an outstanding pioneer of esophagobronch-
ology at the University of Pennsylvania. Killian was awarded the first
honorary membership of the Society of American Otorhinolaryngology,
became an honorary member of the American Medical Association, and
received a medal in commemoration of his visit (Fig. 3).
Throughout his professional life, Killian continued to improve his
technique, invent new instruments, and describe new applications [28]. He
employed fluoroscopy for probing peripheral lesions and foreign bodies. To
establish the radiographic anatomy of the segmental bronchi, he introduced
bismuth powder into the airways for bronchography. He drained
pulmonary abscesses and instilled drugs to promote clearance via the
bronchial tree. He even used the bronchoscope for "pleuroscopy"
(thoracoscopy) and transthoracic "pneumoscopy" to examine abscesses
that had drained externally [29]. Foreign bodies that had been in place for a
long time and had become imbedded within extensive granulation could be
Figure 3 Dinner in honor of Gustav Killian at the meeting of the Society of
American Otorhinolaryngology, 1907.
8
Herth et al.
successfully extracted after initial treatment of the stenosis by his metallic
dilator. In cases of restenosis, he introduced metallic or rubber tubes as
stents. By 1914, Killian described endoluminal radiotherapy for cancer of
the larynx using mesothorium [30]. In 1915, his coworkers Albrecht and
Bri.inings first described the successful treatment of tracheal carcinoma using
endoluminal brachyradiotherapy [31].
C. Chevalier Jackson
The cradle of laryngology in the late nineteenth century was the London
hospital of Sir Morell Mackenzie. A young U.S. physician from
Pittsburgh, Pennsylvania, Chevalier Jackson (Fig. 4), visited Mackenzie's
hospital in 1886 and was encouraged to pursue a career that eventually
contributed tremendously to our current knowledge of bronchology.
Jackson, whom Killian had met on his visit to the United States in 1907,
together with the instrument maker Pilling, made many improvements in
instruments for bronchscopy and esophagoscopy and is now considered to
be the "father of American bronchoesophagology." In 1890, he
constructed the first endoscope worthy of the name "ror esophagoscop,"
and in 1904, he constructed the first American bronchoscope. Jackson
equipped his bronchoscope with a light carrier, using a miniaturized
electric Mignon bulb at the distal end, and with an additional suction
channel. Stimulated by many patients suffering from aspiration of foreign
bodies, he invented many instruments for bronchoscopic retrieval [32]. In
1907, he published the first systematic textbook on bronchoesophagology,
which he dedicated to Gustav Killian, whom he called the "father of
Figure 4 Chevalier Jackson.
9
bronchoscopy." In his book, Jackson addressed modern issues of quality
management, including analysis and prevention of complications (34). He
described construction of bronchoscopy suites and requirements for
equipment and staff. Jackson was a perfectionist and was convinced that
teaching had to be performed on animals before treating patients. He even
refused to return to England where animal rights activists prevented such
training courses. In 1928, in recognition of his "conspicuous achievements
in the broad field of surgical science," Jackson was awarded the Bigelow
Medal by the Boston Surgical Society [33]. He simultaneously held five
chairs of laryngology at different hospitals in his hometown of Pittsburgh
and in Philadelphia. His son, Ch. L. Jackson, also became a laryngologist
and was his father's successor at Temple University in Philadelphia. He
was the founder of the Pan American Association of Otorhinolaryngology
and Bronchology and of the International Bronchoesophagological Society
and the cofounder of the World Medical Association. Together with his
father, he edited the last edition of the textbook [34]. The Jacksons'
influence extends well into the present as many of today's teachers were
trained by them [35].
D. Japanese Development
In 1907, after studying with Killian in Freiburg, Inokichi Kubo (Fig. 5) of
Kyushu University in Fukuoka was the first to introduce bronchoscopy into
Japan. He was joined by S. Chiba, who, after training with Briinings in
Germany, began practice in Tokyo in 1910. Jo Ono, who was trained by
Jackson in 1934, founded the Japan Bronchoesophagological Society in
1949. Shigeto Ikeda, who later developed the flexible fiberscope, introduced
glass fiber illumination for the rigid bronchoscope in 1962. Ikeda felt that
performing rigid bronchoscopy under local anesthesia with the patient in the
sitting position on "Killian's chair" was too cumbersome. When Ikeda first
introduced the flexible bronchoscope he used it in combination with a
flexible tube that could be straightened by a locking mechanism that allowed
him to introduce the rigid optic at the same time. In our current era of
expanding interventional bronchoscopic procedures, this method of
combining both the rigid and flexible endoscope has been proven to be
very useful [36].
V. Further Developments
The intrinsic advantages of the rigid bronchoscope over the flexible
bronchoscope include the former's ability to serve as an instrument for
ventilation, the size of its operative lumen, and its inherent rigidity. The
10 Herth et al.
Figure 5 lnokichi Kubo and coworkers.
current indications for rigid bronchoscopy include (1) control and manage-
ment of massive hemoptysis, (2) removal of foreign bodies from the
tracheobroncial tree, (3) treatment of airway stenosis, (4) removal of
neoplastic obstruction, (5) placement of bronchial stents, and (6) laser
bronchoscopy. Because the flexible bronchoscope fills a portion of the
airway, its use is problematic in patients with airway obstruction and in
pediatric patients. Finally, when a larger biopsy and removal of obstructing
debris are required, the rigid bronchoscope is superior to the flexible
bronchoscope.
Rigid bronchoscopy is a skilled surgical technique that combines
visualization and therapeutic manipulation of the airway with simultaneous
ventilation of the patient. The modern rigid bronchoscope allows
unparalleled visualization of the larynx, trachea, and proximal portions of
the bronchial tree. Although rigid bronchoscopy has unique capabilities in
the management of thoracic diseases, it can also be considered as a
procedure that is complementary to flexible bronchoscopy for diagnostic
and therapeutic interventions within the tracheobronchial tree.
References
lJ
1. Beamis JF: Therapeutic Bronchoscopy Perspective. In: Beamis JF, Stanley MS,
eds. Proceedings of the J2th World Congress for Bronchology. Bologna:
Monduzzi Editore 2002; 13-21.
2. Becker HD: Gustav Killian-a biographical sketch. J Bronchol 1995; 2:77- 83.
3. Gibb GD: The Laryngoscope: Illustrations of Its Practical Application, and
Description of Its Mechanism. London: Churchill & Sons, 1863.
4. Garcia M: Beobachtungen libel' die menschliche Stimme. Vienna: BraunmLiller,
1878.
5. Czermak 1: Physiologische Untersuchungen mit Garcia's KehlkopfspiegeL
Vienna: Gerold's Sohn, 1858.
6. von Bruns V: Die Laryngoskopie und die laryngoskopische Chirurgie.
TLibingen: Laupp'sche Buchhandlung, 1865.
7. Becker HD, Marsh BR. History of the rigid bronchoscopy. In: Bolliger CT,
Mathur PN, eds. Interventional Bronchoscopy. Basel: Karger, 2000:2-16.
8. Reuter HI, Reuter MA: Philipp Bozzini und die Endoskopie des 19. IH.
Stuttgart: Loenicker, 1988.
9. Killian G: Z'ur Geschichte del' Endoskopie von den altesten Zeiten bis Bozzini.
Arch Laryngol 1915;29:247-393.
10. Kluge F: Die Erstanwendung del' Osophago- und Gastroskopie durch A.
Kussmaul und seine Assistenten 1868. Fortschr Gastroenterol Endoskopie
1986;155-9
II. Mikulicz I: -aber Gastroskopie und Osophagoskopie. Vienna: Urban &
Schwarzenberg, 1881.
J2. von Eicken C: Zur Geschichte del' Endoskopie del' oberen Luft- und
Speisewege. Giessen, v. Mi.inchow'sche Universitatsdruckerei, 1921.
13. Wiesner B: Die Entwicklung der Bronchoskopie und der Bronchologie. Ein
geschichtlicher Dberblick. Atemw Lungenkrankh 1995; 21:541-547.
14. Kirstein A: Autoskopie des Larynx und der Trachea (Besichtigung ohne
Spiegel). Klin Wochenschr 1895; 22:476-478.
15. Killian G: Zur Geschichte der Bronchoskopie und Osophagoskopie. Deutsche
Medizinische Wochenschrift 1911; 35: 1585-1587.
16. Ti.irck L: Klinik der Krankheiten des Kehlkopfes und der Luftrohre nebst einer
Anleitung zum Gebrauch des Kehlkopfrachenspiegels und zur Lokalbehan-
dlung der Kehlkopfkrankheiten. Vienna: Braunmliller, 1866.
17. Elsberg L: Laryngoscopical Medication or the Local Treatment of the Diseases
of the Throat, Larynx, and Neighboring Organs Under Sight. New York:
Wood,1864.
18. Byck R: Cocain Papers by Sigmund Freud. New York: Stonehill, 1974.
19. Killian G: Ueber directe Bronchoscopie. Mlinchner Medizinische Wochen-
schrift 1898; 27:844-847.
20. Kollofrath 0: Entfernung eines Knochenstlicks aus dem rechten Bronchus auf
natlirlichem Wege und unter Anwendung der directen Laryngoscopie.
Minnduer Medizinische Wodenschrift 1897; 38: 1038-1039.
12 Herth et al.
21. Killian G: Description abregee de mon operation radicale sur Ie sinus frontal.
Ann Mal Oreille Larynx 1902; 28:205-209.
22. Killian G: Uber den Mund der Speiserohre. Zschr Ohrenheilk 1907; 55:1-41.
23. Killian G: Uber die Behandlung von Fremdkorpern unter Bronchialstenosen.
Zschr Ohrenheilk 1907; 15:334-370.
24. Naef AP: The Story of Thoracic Surgery. Toronto: Hogrefeand Huber, 1990.
25. Killian G: A Model for Bronchoskopy. Translation of a Paper in Archiv fUr
Laryngologie, 13:1, Berlin, 1902. Harvard, Derby, 1902.
26. Killian G: Tracheobronchoscopy in its diagnostic and therapeutical aspects.
Laryngoscope 1906; 12: 3-15.
27. Killian H: Gustav Killian. Sein Leben. Sein Werk. Remscheid-Lennep: Dustri,
1958
28. Killian G: Die Schwebelaryngoskopie und ihre praktische Verwertung. Berlin:
Urban und Schwarzenberg, 1920.
29. Killian G: Die directen Methoden in den Jahren 1911 und 1912. Semon's Int
Centralbl Laryngol Rhinol 1913; 30: 1-28.
30. Killian G: Zwei FaIle von Carcinom. Berl Klin Wochenschr 1914;7:1-3.
31. Brilnings W, Albrecht W: Direkte Endoskope der Luft- und Speisewege. Neue
Deutsche Chirurgie. Vol 16. Stuttgart: Enke, 1915.
32. Jackson Ch: The life of Chevalier Jackson. An Autobiography. New York:
Macmillan, 1938.
33. Boston Surgical Society: The Presentation of the Henry Jacob Bigelow Medal,
New Engl J Med 1928;199:16.
34. Jackson Ch and Jackson ChL: Bronchoesophagology, 1st ed. Philadelphia,
Saunders, 1950.
35. Marsh BR: Historic development of bronchoesophagology. Otolaryngol Head
Neck Surg 1996; 114:689-716.
36. Ohata M: History and Progress of Bronchology in Japan. Journal of Japanese
Society of Bronchology 1998; 20:539-546
2
Rigid Bronchoscopy
An Interventional Tool with a History and a Future
CARLA R. LAMB
Lahey Clinic Medical Center
I. Introduction
JOHN F. BEAMIS, Jr.
13
Rigid bronchoscopy (RB) remains a cornerstone for the specialty of
interventional pulmonology. Spanning over 100 years, RB has been a shared
interventional tool for the surgeon and the pulmonologist. Providing a
direct channel to the airways, RB allows access for foreign body retrieval,
management of life-threatening hemoptysis, dilatation of tracheobronchial
stenosis, and diagnosis and ablation of tumor, as well as tracheobronchial
stent placement.
Although the evolution of flexible bronchoscopy (FB) in the mid 1960s
led to significant changes in the area of bronchoscopy, RB continues to have
a complementary role in the management of airway diseases. From the late
1980s to 1990s, there was a notable decline in the use of RB by
pulmonologists in North America documented in serial surveys in 1989
and 1999 indicating 8 and 4% of respondents, respectively, were performing
RB [1,2]. Recently, it appears that there has been a renewed interest among
pulmonologists in RB, as more are seeking expertise in the procedures that
define the specialty of interventional pulmonology. This trend appears to be
related to the continued worldwide epidemic of lung cancer and the need for
14 Lamb and Beamis
the development of multidisciplinary cancer treatment centers offering
innovative endobronchial therapies. The increasing number of patients
presenting with central airway obstruction due to malignancy and requiring
urgent palliation has further defined the role of RB. Improvements in the
methods of anesthesia and ventilation for RB have allowed this procedure to
become a routine part of therapeutic and palliative patient care. This
chapter will provide a brief historical perspective of RB and describe the
basic technique, the anesthetic approach, and the complementary role of RB
in the treatment of a variety of benign and malignant pulmonary diseases.
II. Historic Overview
In 1897, Gustav Killian, a German otolaryngologist, was the first to perform
RB when he removed an aspirated pork bone from a man and thereby
avoided the need for a tracheotomy [3]. The success of this procedure led to
the acceptance of RB as an alternative means to access the airway. Killian
later developed innovative bronchoscopes and additional indications and
techniques for RB. These accomplishments established him as the "father of
bronchoscopy." Chevalier Jackson, a laryngologist from Pittsburgh,
Pennsylvania, cultivated an interest in endoscopy during the late nineteenth
century. He emphasized the benefits of distal illumination through the
endoscope. Jackson perfected techniques for endoscopic intubation and
foreign body retrieval and created new models of esophagoscopes and
bronchoscopes. His numerous publications became an instructional guide in
this emerging field. His innovative strategies emphasizing safety and
proficiency, as well as his tireless passion to teach others these techniques,
earned Jackson the title the "father of American bronchoesophagology"
[4,5].
The invention of the flexible bronchoscope in the mid 1960s by Shigeto
Ikeda from the National Cancer Center Hospital, Tokyo, Japan,
represented a defining moment in bronchology [6]. By the mid 1970s,
flexible bronchoscopy had virtually replaced RB, as it allowed a more
effortless access to even the most distal airways. As a result, most
pulmonologists in the United States have not received training in the
technique of RB.
The 1980s and 1990s were marked by the rising incidence of
unresectable lung cancer and by many patients presenting with central
airway obstruction. Multimodality approaches were developed to provide
for more timely and effective palliation. Jean Franyois Dumon, a French
pulmonologist, played a significant role in promoting the use of the rigid
bronchoscope to deliver therapies such as laser, airway dilatation,
Rigid Bronchoscopy
15
endobronchial and endotracheal stent placement, balloon dilatation,
electrocautery, cryotherapy, and argon beam coagulation. Like Killian
and Jackson, Dumon has been an innovator in the field. He has invented
new interventional techniques, bronchoscopes, airway stents, and stent
deployment devices that are utilized throughout the world.
Today, interventional pulmonologists worldwide are continuing this
multimodality bronchoscopic approach in order to offer patients timely
treatment and palliation in the setting of both malignant and benign airway
disease [7]. In experienced hands, RB is felt by many to be the tool of choice
for rendering a safe approach to this patient population. It has specific
advantages over FB in tem1S of securing the airway during diagnostic and
therapeutic manipulations and in maintaining adequate visualization in the
setting of significant hemorrhage. Together FB and RB are complementary
in managing complex airway diseases. This chapter will review our approach
to RB.
III. Indications for RB and Patient Selection
The indications for RB are listed in Tables Ia and Ib [8-11]. The benefits of
RB over FB include the ability to maintain airway control, hemostasis,
shorter intervention times, and larger sample size of biopsies. General
anesthesia during RB eliminates undesirable movement and enhances
patient comfort throughout the procedure. Patient selection and preproce-
dure screening are vital parts of the preparation to assist both the
anesthesiologist and the pulmonologist in anticipating and preventing
possible complications. More specific details will be discussed later in this
chapter. The patient assessment process should include history and physical
examination with specific attention to cardiopulmonary disease, disease of
the cervical spine, history of rheumatoid arthritis, and history of
coagulopathy. Table 2 lists a general preprocedure assessment. Although
RB with general anesthesia is a safe procedure in skilled hands, the majority
Table 1a Indications for Pediatric Rigid Bronchoscopy
Difficulty ventilating or weaning from mechanical ventilation
Tracheobronchial stricture
Lung collapse
Tracheoesophageal fistula
Hemoptysis
Foreign body retrieval
16 Lamb and Beamis
Table 1b Indications for Adult Rigid Bronchoscopy
Foreign body retrieval (e.g., nuts, dental bridges, teeth, coins)
Hemoptysis/removal of blood clots
Tracheobronchial stenosis (posttra uma tic, postinfectious, postinflammatory,
postintubation or tracheostomy, post-lung transplantation with anastomotic
stenosis)
Tracheobronchomalacia
Central Airway Obstruction
Benign tumors (papillomatosis, amyloidosis)
Malignant tumors (bronchogenic, adenoid cystic carcinoma, carcinoid,
mucoepidermoid, metasta tic)
Extrinsic compression (esophageal disease, mediastinal tumors, lymphoma, thymus,
thyroid, germ cell, aortic aneursym)
Diagnosis of structural airway disease
Conduit for introduction of therapeutics
Stents: metallic, hybrid, silicone, "Y"
Laser: carbon dioxide, Nd: YAG, potassium titanyl phosphate
Electrocautery
Cryotherapy
Argon plasma coagulator
Dilatational balloons
Nd:YAG, neodymium:yttrium-aluminum-garnet.
Table 2 Checklist of Patient Data Preprocedure
History and physical
Identify coagulopathies
Coexistent cardiopulmonary disease
Temporomandibular disorders
Cervical spine immobility
Prior complications to anesthesia
Diagnostic test
Oxygen saturation
Electrocardiogram
Complete blood count
Chemistry profile
Coagulation profile
Arterial blood gas
Chest radiograph
Chest computerized tomogram
Rigid Bronchoscopy
17
of patients potentially benefiting from such procedures are often "high risk"
secondary to associated comorbid conditions. Contraindications to RB are
listed in Table 3 [10].
The majority of indications for RB are for introduction of therapies to
the airway (see Table I b). It is the bronchoscopist's experience, expertise,
and preference that determine the selection of therapeutic tools. There are
certain devices, such as the silicone airway stent, that can only be applied
with the rigid bronchoscope.
IV. Equipment and Technique
The rigid bronchoscope is a stainless steel tube with variable lengths and
widths that has not significantly changed from those of Chevalier Jackson
(Fig. I). The adult bronchoscope is generally 40 cm in length with a varying
diameter of9.0-13.5 mm with a barrel thickness of 2-3 111111. Generally, a 10-
or 12-ml11 bronchoscope accommoda tes most adult airways. The most
proximal aspect of the bronchoscope consists of a central opening with side
ports to accommodate biopsy forceps, suction catheters, and ventilator
connectors. Along the distal shaft of the bronchoscope are slitlike openings
that provide additional ventilation ports (Fig. 2). (Note that the shorter
tracheoscopes do not have this feature and accommodate the treatment of
high tracheal lesions without allowing ventilatory leakage above the vocal
cords.) (Fig. 2). The distal beveled edge of the bronchoscope allows safe
passage through the vocal cords, enhances maneuverability through narrow
stenoses when used with a gentle corkscrewing motion, and functions as a
resecting tool for necrotic tumors. The central opening accommodates the
telescopic lens, the flexible bronchoscope, and various stent delivery systems
(Fig. 3). The video telescope provides a magnified view and comes in a
variety of angles in which to view the trachea, mainstem bronchi, and the
Table 3 Contraindications
Unstable cardiovascular status
Life-threatening cardiac arrhythmias
Acute respiratory failure with refractory hypoxemia
Marked diminished range-of-motion of head and neck
Maxillofacial trauma
Head and neck deformity
Cervical spine instability
Inadequately trained bronchoscopist, anesthesiologist, or bronchoscopy assistant
18 Lamb and Beamis
Figure 1 The rigid bronchoscope used at Lahey Clinic Medical Center
demonstrating jet ventilation port, open proximal port with rigid telescope, and
flexible suction device.
five lobar bronchi. The O-degree lens is the most commonly utilized. The
flexible bronchoscope may also be passed through the rigid bronchoscope to
view the more distal and tortuous upper lobe bronchi. Accessory tools for
RB include rigid suction, balloon dilatational devices, and a variety of
biopsy forceps (Fig. 4). There are a number of stent deployment devices:
Figure 5 demonstrates the silicone stent and loading and deployment
devices. The complete ventilating unit with a rigid bronchoscope is seen in
Figure 6. Table 4 describes the basic equipment needs for RB.
Figure 2 Distal end of a rigid bronchoscope and tracheoscope. Note the
tracheoscope does not have fenestrated ventilating side ports.
Rigid Bronchoscopy
19
Figure 3 Proximal end of the universal head of a Dumon-Harrell bronchoscope
demonstrating ports for suction catheters, laser fiber, telescope, flexible broncho-
scope, and ventilation.
Figure 4 Array of rigid biopsy forceps.
20 Lamb and Beamis
Figure 5 Dumon stent with stent loading and deployment devices.
V. Anesthesia and Ventilatory Strategies
Understanding there are numerous ways of successfully achieving anesthesia
and optimal ventilatory control during RB, the following describes the
technique that is practiced at our institution [13-16]. RB is a "shared
airway" in terms of patient management between the bronchoscopist and
Video system
Suction
O:z - Air
blender
Jetting device
Figure 6 Rigid bronchoscope with jet ventilator device and all ancillary
equipment. (From Ref. 12.)
Rigid Bronchoscopy
Table 4 List of Basic Requirements for Performing Rigid Bronchoscopy
21
Personnel
Setting
General equipment
Anesthesiologist, bronchoscopist, assistant, circulating
technician
Bronchoscopy suite or operating room
Ventilating rigid bronchoscopes and tracheoscopes
Light source
Video monitor
Rigid telescope O.30-degree angulation
Forceps: Biopsy and foreign body retrieval (variety of cup and
long alligator, basket snare)
Flexible bronchoscope
Flexible and rigid suction devices
let ventilation system
Eye protector/mouth guard
Syringes, saline, lubricant gel
Tracheal/bronchial stents
Various stent deployment devices, silicone lubricant
Esophageal balloons/endobronchial blocker for tamponade of
airway
Various interventional applications: Nd: YAG laser and laser
safety device, argon plasma coagulator, electrocautery,
cryotherapy
Nd:YAG, neodymium:yttrilim-allllllinum-garnet.
the anesthesiologist. Each shares a common goal to maintain a safe and
effective airway. Although it is possible to perform this procedure with local
anesthetic and intravenous sedation, general anesthesia is the preferred
method. General anesthesia provides analgesia, amnesia, and muscle
relaxation offering a motionless field. Monitoring of the patient generally
includes noninvasive blood pressure assessments, two-lead electrocardio-
graphy (ECG), continuous pulse oximetry, end-tidal capnography, and
nerve stimulation assessment. Invasive arterial monitoring may also be
utilized at the discretion of the medical team.
Premedication with 1-2 mg of intravenous midazolam and 25-50 Ilg of
fentanyl begins prior to entering the operating room in order to provide an
initial mild level of amnesia and analgesia. Supplemental oxygen ;s also
supplied. Preoxygenation is provided via facemask in the operating room.
Induction of anesthesia may employ either inhalational or intravenous
agents. When airway patency depends on intact muscle tone and some
degree of spontaneous patient respiration, an agent such as sevoflurane may
be used. An inhalational agent allows the effects of general anesthesia to be
22 Lamb and Beamis
gradually tested while maintaining some spontaneous respirations. In most
cases, however, intravenous induction of anesthesia with propofol, 1-2 mg/
kg, and fentanyl, 50-100 Ilg, is achieved while the patient is given 100%
oxygen via facemask; an inhalational agent such as isofturane or sevofturane
may also be given. A rapid-acting muscle relaxant such as rocuronium at
0.6 mg/kg is given intravenously while both oxygen and the inhalational
agent are continued for an additional 5 min. Rocuronium is a nondepolar-
izing neuromuscular blocking agent and is most appropriate for these cases
because of the effective muscle relaxation provided and its duration of
action of approximately 20-30 min. After adequate oxygenation and
relaxation have been achieved, the patient is intubated with the rigid
bronchoscope.
Once the bronchoscope is inserted into the trachea, ventilation is
continued using a Venturi jet ventilation system [17]. Oxygen and air, both
supplied at 50 psi, are combined in a mixer. This mixture is channeled to a
manually controlled injector that reduces the pressure relative to how hard
or gently it is squeezed. The hand-held injector connects to a connector
tubing that fits directly into a side port located on the bronchoscope (see
Fig. 6). The jetted gas travels down the rigid bronchoscope, simultaneously
drawing room air via the remaining open ports of the bronchoscope. The
actual oxygen concentration at the distal tip of the bronchoscope is
determined by the mixer setting, as well as the amount of room air
entrained by the Venturi effect through the open ports and is generally
unknown. The hand-held injector is squeezed slowly until one observes the
chest rise and then it is released allowing adequate time for exhalation.
Usually a rate of 8-15 breaths per minute provides adequate oxygenation
and ventilation. Although oxygen saturation can be monitored satisfacto-
rily with a pulse oximeter, in prolonged cases, invasive arterial blood gas
monitoring may be indicated to confirm adequate ventilation. Intermittent
capnography can also assist in ventilatory monitoring [18]. Caution must
be exercised to avoid barotrauma; ventilation should be interrupted during
specimen withdrawal.
Total intravenous anesthesia (TrVA) is continued with a propofol
infusion at approximately 100-150 Ilg/kg/min. These patients receive
TIVA because of the difficulty using an inhalational agent when the
proximal ports of the bronchoscope are open to room air. The
intraoperative phase of these cases is characterized by varying levels of
surgical stimulation and episodes of airway manipulation during which
ventilation is suboptimal or must be temporarily interrupted. The patient
may require intermittent boluses of propofol and fentanyl, as well as
additional neuromuscular blockade. An additional remifentanil infusion
can provide a very potent analgesic effect [19]. Relative to the degree of
Rigid Bronchoscopy 23
stimulation or lack thereof, the blood pressure can be labile and may
require the use of short-acting beta-blockers and vasopressors, respec-
tively. It is important to bear in mind factors that will optimize successful
emergence from anesthesia and extubation by not administering excessive
narcotic or muscle relaxants. Propofol is metabolized relatively quickly
within 5-15 min upon cessation of infusion.
Although the patient is likely to have improved after completion of the
procedure, the procedure itself inevitably generates blood and secretions.
This combined with underlying pulmonary disease, residual anesthetic
effects, incessant coughing, bronchospasm, and laryngospasm often causes
ineffective gas exchange. The irony following a successful intervention of an
obstructing airway lesion is the challenge and even danger from the
subsequent emergence for anesthesia. A variety of methods for anesthetic
management of this final phase include:
1. Awaken the patient while intubated with the rigid bronchoscope.
2. While the patient is fully anesthetized, remove the bronchoscope
and intubate with an endotracheal tube. Awaken the patient with
the endotracheal tube.
3. While the patient is fully anesthetized, remove the bronchoscope
and insert a laryngeal mask airway (LMA; Laryngeal Mask
Company, Henley-on-Thames, UK). Awaken the patient with the
LMA.
Awakening the patient while on the rigid bronchoscope is the strategy used
by most anesthesiologists and is the classic standard of practice. None-
theless, it is helpful to remember that it often makes the patient cough and
gag even in the presence of residual anesthesia, and that patient agitation
does not always indicate readiness for successful extubation. Removing the
rigid bronchoscope prematurely renders the patient emerging from
anesthesia with ineffective gas exchange and possible upper airway
obstruction. Successful awakening following rigid bronchoscope extubation
requires skill and is facilitated by the presence of some prior narcotic, such
as morphine, to blunt the gag and cough reflexes. Our institution also
utilizes the LMA technique. While the patient remains deeply anesthetized,
the rigid bronchoscope is removed and an LMA is placed to function as the
primary airway. Ventilation is continued first with positive pressure and
then with spontaneous ventilation during emergence, The LMA is a cuffed
supraglottic airway device that encircles the laryngeal inlet. It inserts behind
the cricoid cartilage and occupies the hypopharynx. Its use avoids
stimulation of gagging or coughing resulting in a much smoother transition.
Patients with severe reactive airway disease, parenchymal lung disease, and
obesity may benefit from this approach.
24 Lamb and Beamis
VI. Rigid Bronchoscopic Intubation
Following anesthetic induction, the patient's eyes and teeth are protected
with eye shields and a soft plastic tooth guard. In the edentulous patient, a
mouth guard is not necessary; however, the bronchoscopist should always
be careful to avoid excessive pressure or trauma to the gums, tongue, teeth,
and lips. Optimal anterior positioning of the patient's trachea is important
prior to intubation and is best achieved with gentle neck extension and
placement of a towel roll beneath the neck. Particular features of the patient
that may predict a more challenging intubation include micrognathia, severe
kyphoscoliosis, redundant supraglottic tissue, supraglottic tumors, and
limited neck range-of-motion. The bronchoscopist should be positioned at
the head of the supine patient.
Rigid bronchoscopic intubation can be accomplished a number of
different ways. One can directly intubate with the rigid bronchoscope (Fig. 7)
by visualizing anatomical structures through the proximal end of the
bronchoscope. Alternatively, the rigid telescope is passed within the rigid
bronchoscope, but remains approximately I cm inside the beveled edge of
the bronchoscope. Intubation is then carried out while visualizing the
airway structures with a video monitor located at the feet of the patient.
The general approach to this "classic technique" for intubation is as
follows. The right hand is used to hold the rigid telescope and video camera
within the rigid bronchoscope as previously described. The left hand is used
to protect the patient's lips by gently resting the thumb on the lips/gums
while stabilizing the distal end of the bronchoscope during initial entry into
the oropharynx. This is best achieved by placing the middle finger against
the upper teeth and the index finger against the anterior portion of the rigid
bronchoscope. The bevel of the bronchoscope is always placed anteriorly
and introduced in the oropharynx at a 90-degree angle perpendicular to the
patient. At the base of the tongue and upon visualization of the uvula, the
rigid bronchoscope is advanced gently at 1- to 2-cm increments while
simultaneously allowing the right hand to lower the bronchoscope parallel
to the patient. The anterior bevel lifts tbe epiglottis anteriorly, vocal cords
are visualized, and the rigid bronchoscope is rotated 90 degrees and
advanced into the proximal trachea. The bronchoscope is rotated 90 degrees
placing the bevel in the anterior position. A gentle corkscrewing motion is
used to advance further the rigid bronchoscope while avoiding abrasion of
the posterolateral tracheal walls.
A second technique involves direct laryngoscopic intubation (Fig. 8).
Using a straight blade laryngoscope, the vocal cords are visualized. The
rigid bronchoscope is inserted along the laryngoscope like an endotracheal
tube. It is then passed through the vocal cords into the proximal trachea.
Rigid Bronchoscopy
(a)
25
Figure 7 Classic intubation technique with a rigid bronchoscope. (a) "Sniff
position" in which neck is slightly flexed and the head extended. The bronchoscope is
midline with bevel anterior. Rigid telescope is always maintained within the distal
aspect of the rigid bronchoscope. At the entrance of the glottis, the bronchoscope is
rotated 90 degrees. (b) When the bevel is through the vocal cords, the bronchoscope
is rotated back 90 degrees and the proximal end of the bronchoscope is lowered. (c)
The patient's neck is extended as the bronchoscope enters lower airways.
The laryngoscope is usually removed as the rigid bronchoscope enters the
glottis.
The third intubation technique uses an endotracheal tube as a guide
(Fig. 9). The patient is brought to the bronchoscopy suite intubated or
electively intubated by the anesthesiologist. The rigid bronchoscope with the
telescope is advanced anterior or lateral to the endotracheal tube until the
26
Lamb and Beamis
(a)
\
(b)
Figure 8 Rigid bronchoscopic intubation with a laryngoscope. (a) Laryngoscope
positioned to visualize epiglottis. (b) (1) Laryngoscope and bronchoscope in
posterior pharynx; (2) bronchoscope advanced under epiglottis and rotated 90
degrees; (3) bronchoscope advanced through vocal cords as laryngoscope is
withdrawn.
Rigid Bronchoscopy
(a)
27
Figure 9 Rigid bronchoscopic intubation over an endotracheal tube. (a) Initial
position of the bronchoscope. (b) Position of the bronchoscope and endotracheal
tube viewed in the supraglottic pharynx. (c) The rigid bronchoscope is advanced as
the endotracheal tube is withdrawn.
vocal cords are visualized. The endotracheal tube cuff is deflated and the
tube is slowly removed under direct visualization. The rigid bronchoscope is
advanced through the vocal cords into the proximal trachea at this time.
A fourth intubation technique is reserved for patients who have
undergone total laryngectomy. The rigid bronchoscope and telescope are
introduced through the stoma at a 90-degree angle then angled down
parallel to the patient and advanced distally into the trachea. With all the
techniques, the left and right mainstem bronchi are inspected by turning the
patient's head to the right and left, respectively.
28 Lamb and Beamis
VII. Recovery and Postprocedure Care
Because of the high degree of airway compromise and frequent contributing
comorbidities in this patient population awakening from general anesthesia
and the process of extubation require close observation of the patient in a
continuous monitored setting either while in the operating room or an
ambulatory care unit. As previously discussed, recovery from general
anesthesia is typically one of the most critical aspects of the entire
procedure. The most frequently experienced complications during the
recovery period include hypoxemia, paroxysmal cough, bronchospasm, and
cardiac dysrrhythmias. Topical I% lidocaine is sometimes administered
through the rigid bronchoscope prior to extubation followed by nebulized
lidocaine after extubation to decrease paroxysms of cough. The majority of
patients are observed and then discharged to home on the same day of the
procedure.
VIII. Complications and Management
In the setting of an experienced bronchoscopy and anesthesia team,
complications of RB are extremely rare. The expected mortality rate is
0.4-1.0% from RB. All individuals performing RB should be familiar and
skilled in addressing known complications of bronchoscopy (Table 5) [20].
Complications resulting directly from RB are also rare at 0.1-1.8%. The
majority of the complications listed are not life threatening and resolve with
supportive management. Most common are cardiac dysrrhythmias asso-
ciated with hypoxemia that may develop during the procedure or as a
consequence of general anesthesia. A number of studies suggest that patients
with an Anesthesia Society of America class of 3 or 4 and a Karnofsky
performance score of < 70 are at higher risk for such complications [21].
IX. Interventional Outcomes
A number of outcome measures have been reviewed in the literature, with
specific attention to those with symptomatic central airway obstruction
from malignant disease. Both Cavaliere and Mathisen report successful
recanalization in up to 90% of cases [22,23]. Symptoms of cough, dyspnea,
and hemoptysis were significantly reduced after rigid bronchoscopic
debulking of tumor with and without laser therapy. Also noted was a
subjective improvement of quality of life after intervention. Procedure-
related mortality was reported as 0.4%. Cavaliere reported cumulative
survival of 50% at 6 months and 26% at I year. Of these patients, 64.9% had
Rigid Bronchoscopy
Table 5 Complications
Hypoxemia
Cardiovascular instability
Tracheobronchial perforation
Esophageal perforation
Laryngeal edema
Vocal cord damage
Dental trauma
Pneumothorax
Severe bleeding
Mediastinal emphysema
Laryngospasm
Bronchospasm
29
malignant tumors. Ninety-two percent of the interventions were performed
with RB and the rest with FB [24]. Additional predictors of higher success
rates with RB were proximally located diseases. Both distal disease and
upper lobe lesions were more difficult to treat effectively.
Colt reported favorable results of RB with laser resection and/or stent
insertion in patients presenting with acute respiratory failure associated with
central airway obstruction, noting that intervention often allowed immedi-
ate discontinuation of mechanical ventilation [25].
X. Growth of RB in the Field of Interventional
Pulmonology
Pulmonologists seeking formal training and mastery in RB are gaining
momentum as more medical centers are developing centers for excellence in
the treatment of both lung cancer and lung transplant patients. Historically,
pulmonary fellowship training in the United States has been lacking in
respect to the "hands-on' aspects of RB. As a therapeutic tool, RB is
complementary to any multimodality approach to the patient with central
airway disease. It, however, should not be undertaken by inexperienced
hands, as patients generally requiring such interventions are severely
compromised by advanced malignancy and consequent respiratory insuffi-
ciency. Some patients may present in respiratory distress due to abrupt onset
of airway obstruction. Just as practiced by Chevalier Jackson, safety and
proficiency are prerequisites in optimizing such therapies. Collaboration
with experts in the field is necessary to create opportunities for training.
More definitive guidelines have been introduced by national and interna-
30
Lamb and Beamis
tional consensus panels to improve the uniformity of instruction in
proficient technique and application of many aspects of interventional
pulmonology in order to better serve our patient population [26,27].
Acknowledgments
Special acknowledgement and appreciation to Dr. Michael S. Stix, MD,
PhD, and Dr. Paul D. Teague, MD, of the Department of Anesthesiology,
Lahey Clinic, for the contribution of their expertise in both the science and
the art of anesthesia in this unique patient population. Special acknowl-
edgement to Rick Chevalier and Gilberto Gamba, Jr., of Medical
Photography, Lahey Clinic.
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3
Interventional Flexible Bronchoscopy
TERUOMI MIYAZAWA, YUKA MIYAZU,
and YASUO IWAMOTO
Hiroshima City Hospital
Hiroshima, Japan
I. Introduction
KOJI KANOH
Fukushima Coop Hospital
Hiroshima, Japan
33
A revolutionary step took place in the field of bronchology when Shigeto
Ikeda of Tokyo, Japan, introduced fiberoptic endoscopic technology, which
had begun in the 1950s, to bronchoscopy in 1966. Ikeda invented the flexible
bronchoscope, which compared to earlier rigid bronchoscopy, provided
greater visualization of the more distal airways and could be performed
under local anesthesia, thus dramatically changing the field of broncho-
scopy. Stimulated by Ikeda's invention, many new technologies have been
developed and introduced into the field of bronchology at a rapid rate-the
color video camera by Ikeda in 1971, bronchoalveolar lavage by Reynolds in
1974, hematoporphyrin-derivative fluorescence by Cortese in 1978, trans-
bronchial needle aspiration by Wang in 1978, neodymium:yttrium-
aluminum-garnet laser therapy by Toty in 1978, iridium brachytherapy by
Hilarss in 1979, photodynamic therapy by Kato in 1980, video endoscopy
by Ikeda in 1987, silicone stents by Dumon in 1989, autofluorescence by
Lam in 1991, and endobronchial ultrasonography by Becker in 1999 [1].
Currently, the flexible bronchoscope is one of the most important tools for
the diagnosis and treatment of pulmonary diseases.
34 Miyazawa et at.
II. Developments in Bronchoscopy
Prior to 1966, endoscopic examination of the airways employed a rigid
bronchoscope and small electric lamp that was set at the tip of a telescope.
This provided sufficient light for observation, but was not sufficient for
dynamic endoscopic image recording. To overcome this defect, a new system
was designed which replaced the small lamp with optical glass fibers
allowing transmission of brighter light from an outside source. In 1962,
Ikeda asked the Machida Endoscope Company in Tokyo to produce a
telescope for esophagoscopy based on the above design. A long, glass fiber
bundle from the grip part of the telescope was connected to a more powerful
and brilliant light source. This provided sufficient illumination inside the
esophagus to enable the making of an esophageal motion picture. Later,
Ikeda made a small bronchoscopic telescope with similar specifications.
Next, he conceived the idea of developing a rigid type of bronchoscopic
telescope with a long, fiberoptic bundle for illumination.
In the spring of 1964, Ikeda asked Machida to produce a prototype of
the first flexible bronchofiberscope. He made a similar request of the
Olympus Optical Company, also in Tokyo, in late 1965. In the
manufacturing of the flexible bronchofiberscope, the most serious problem
to overcome was the image resolution of the fiberoptic imaging bundle. To
satisfy this requirement, it was necessary to make the size of each optical
glass fiber as thin as possible; thus the size of the 1611 fiberoptic in the
gastrointestinal fiberscopes had to be reduced to 1411. Beginning in 1964, the
first of a series of experimental prototypes was produced. The seventh model
of the scope to be developed became the first practically available flexible
bronchofiberscope. This prototypic flexible bronchofiberscope was com-
pleted on July 23, 1966, and delivered to Ikeda by Machida (Fig. 1). Ikeda
attended the 9th International Congress on Diseases of the Chest in
Copenhagen, Denmark, August 17-19, 1966, and introduced this instru-
ment to those in attendance. The news of his presentation was immediately
transmitted worldwide and was published in The Nell! York Times,
producing an enormous stir within the medical community.
After returning from Copenhagen, Ikeda used the first model of the
flexible bronchofiberscope in clinical examinations and found that several
features needed improvement. He felt that the scope was too flexible, and
that it was sometimes difficult to confirm whether the scope tip was in the
left lung or in the right lung. He determined that the fiberscope should not
be too soft, but should be slightly stiff in order to feel feedback from the
operative end to the operating tip. He reported these points in detail to the
Machida, asking for further improvements. Ikeda also found out that the
image resolution was unsatisfactory because of the irregular alignment of
fnlerventional Flexible Bronchoscopy
35
Figure 1 Prototypes of the first and third flexible bronchofiberscopes developed by
the Machida Company. The third model has angulation capability.
the glass fiber image bundle. To make the scope insertion into upper lobe
bronchi easier, a control mechanism was built into the grip end for
manipulation of the tip. The tip of the scope was divided into two sections:
the apical lens and the image fiber bundle, and the angle section part, which
was a line of circular rings that were connected by two wires. By pulling
these wires, it was possible to flex the tip 180 degrees, thus making a visual
V-turn. In the final model of the flexible bronchofiberscope, the size and
alignment of the image bundle was improved by the use of l ~ glass fibers,
and although the rigid part of the scope tip was shortened to only 8 mm,
180-degree flexion was still possible. The scope also had a I-mm channel
built into the flexible body for suction and biopsy (Table 1). Commercial
production of flexible bronchofiberscopes began in April 1968 [2-4]. These
technical achievements were stimulated by the earlier progress with 180-
degree angulation in gastrointestinal fiberscopes and by the development of
smaller diameter colonoscopes.
The Olympus Company produced its first prototypic bronchofiber-
scope in August 1966. This prototype had no angulation mechanism or
working channel. The Olympus engineers then began research into new
methods to assemble fiberoptic image bundles. They developed a method
36 Miyazawa el at.
Table 1 Specifications of Machida Prototype Bronchofiberscopes
Prototype
Type 4 5,6 7
Date of July 1966 October 1966 December 1966 March and September 1967
manufacture June 1967
Field of view 90 80 80 80 80
(degrees)
Direction of Forward Forward Forward Forward Forward
view viewing viewing viewing viewing viewing
Depth of field 5-30 5-30 5-30 5-30 5-30
(0101)
Distal end outer <1>5 <1>5
<1) 5
<1>5 <ll5
diameter (0101)
Angulation range No angulation Up 100 Up 150 Up 180 Up 200
(degrees) mechanism down 10 down 10 down 10 down 10
<1l, diameter.
quite different from that used in conventional bronchofiberscopes of the
time and which provided better handling and image resolution. This resulted
in the popular type BF-5B fiberoptic bronchoscope which had a working
channel on the control body through which a cytology brush could be
inserted (Table 2).
In September, 1968, Ikeda was invited to the United States by the
National Institutes of Health (NIH) and spoke at the Johns Hopkins
University, Baltimore, MD. His talk was attended by the staff of the NIH,
the Mayo Lung Project Group, and the American Optical Company. He
spoke on the "flexible bronchofiberscope" and showed an endoscopic movie
of his use of the fiberscope in the tracheobronchial tree. His audience was
Table 2 Specifications of Olympus Prototype Bronchofiberscopes
Type Prototype BF-3A BF-5B BF-4B
Date of manufacture August 1966 May 1968 May 1968 August 1968
(commercial) (commercial) (commercial)
Field of view (degrees) 45
66 74
72
Direction of view Forward viewing Forward viewing Forward viewing Forward view! ng
Depth of field (mOl) 5-50 3-50 5-50 3-50
Distal end outer diameter (I) 3.3
() 3.2
<1:> 50 (1)4.0
(mm)
Angulation range (degrees) No angulation Up 180 down 30 Up 130 down 30 Up 160 down 30
mechanism
Working channel inner No working No working <1) 1.4 mOl
<1:>0.60101
diameter channel channel
(), diameter.
Interventional FlexibLe Bronchoscopy 37
intensely interested and gave a rousing applause when they saw the image of
the fiberscope tip entering into the trachea and then advancing into very
small peripheral bronchi. Later in October, Ikeda presented a paper
concerning flexible bronchofiberscopy at the 10th International Congress on
Diseases of the Chest in Washington, DC. Again, his movie attracted the
attention of the participants. In 1970, he demonstrated the technique of
flexible bronchofiberscopy to the staff at the Mayo Clinic, Rochester, MN.
Later when performing flexible bronchofiberscopy, he used a double-jointed
curette technique under fluoroscopic guidance to diagnose patients with
small peripheral lung carcinoma [5]. Ikeda eventually introduced and
popularized flexible bronchofiberscopy throughout the world. Endoscopic
examination of the tracheobronchial tree had thus progressed from the rigid
technique originally described by Gustav Killian, to flexible fiberoptics as
applied by Ikeda [6]. In July 1978, Ikeda established the World Association
for Bronchology and was elected as the first chairman of its Board of
Regents.
By 1980, flexible bronchofiberscopy had became common practice in
chest medicine, and its use was widespread among pulmonologists in nearly
every country. The original role of the flexible bronchofiberscope was as a
diagnostic instrument to visualize lung cancer lesions within the tracheo-
bronchial tree and to perform biopsy, curettage, and brushing to establish a
definitive diagnosis. Because of the development of related technologies,
however, bronchofiberscopy soon became utilized not only for diagnostic
but also for therapeutic procedures.
Jean Francois Dumon is considered to be the pioneer of modern
interventional bronchoscopy. He developed the technique of neodymium:
yttrium-aluminum-garnet (Nd:YAG) laser photoresection originally using
the flexible bronchofiberscopy within a rigid bronchoscope. This has become
the preferred modality for palliative treatment of obstructive malignant
tumors of the airway (7]. While attending the 2nd World Congress for
Bronchology in 1980 in Diisseldorf, Ikeda was impressed by Dumon's
presentation, which was titled "Endoscopic Fiber Laser Irradiation of
Tracheobronchial Stenosis." Immediately following that meeting, Ikeda
visited Marseilles to observe Dumon's endoscopic Nd:YAG laser surgery
(Fig. 2). Beginning in August 1980 [8], Ikeda and his colleague Ono offered
Nd:YAG laser treatment to patients in Japan with airway stenoses. In
addition to Nd:YAG laser therapy, photodynamic therapy (PDT) with
hematoporphyrin derivative (HpD) also proved to be very compatible with
the flexible bronchoscope. In March 1980 [9], Hayata and Kato were the
first to treat early-stage lung cancer with PDT using an argon dye-laser via
flexible bronchofiberscopy. Based on their prior experimental work, they
employed PDT to treat patients with various types of lung cancer. Cortese et
38
MIJ1azmva el al.
Figure 2 Ikeda, the inventor of the flexible bronchoscope, and Dumon, the pioneer
of modern interventional bronchoscopy, pictured in Marseilles in 1980.
a!. also demonstrated the utility of PDT for early-stage lung cancer [11].
Ikeda and Ono began treating patients with roentgenographically occult
lung carcinoma using PDT in July 1981 [10]. Ikeda was also the forerunner
in the development of the videobronchoscope [6,12]. In February 1987, as a
result of the rapid progress in electronic technologies, the Pentax
Corporation (Tokyo, Japan) developed a prototype videobronchoscope
which replaced the fiberoptic image bundle with a small charge-coupled
device (CCD) sensor built into the tip of the core. This advance made it
possible to obtain better image resolution and allowed computer processing
of images and data. For example, the endoscopic findings could be printed
out, copied, and pasted in the patient's medical record (Fig. 3). With the
videobronchoscope, rather than looking through the bronchofiberscope's
eyepiece, bronchoscopists watch a monitor screen during the diagnostic and
therapeutic procedures. By the late 1980s, a clinical TV endoscope with a
small camera at its tip, the so-called "videobronchoscope," was marketed by
Pentax. Olympus and Machida-Toshiba soon followed with their models.
These bronchoscopes provided a very clear image of the endoscopic view on
a coJor screen. Soon after the commercial production began, the
videobronchoscope came into common use in hospitals.
in/erven/lonal Flexible Bronchoscopy
39
Figure 3 Prototypes of the first and second videobronchoscopes developed by the
Pentax Corporation.
After the 10th World Congress for Bronchology in 1998 in Budapest,
Ikeda visited H.D. Becker at Thoraxklinik in Heidelberg to observe the
implantation of a self-expanding stent device made of nitinol, the Ultraflex
stentQl' (Boston Scientific, Natick, MA), which can be easily placed using a
flexible bronchoscope under local anesthesia for the treatment of
tracheobronchial stenosis [13J. We confirmed Becker's experience in a
multicenter study in which 24 stent procedures were performed by flexible
bronchoscopy, and 10 procedures were performed by rigid bronchoscopy
[14J.
Endobronchial ultrasound (EBUS) is another technique that has been
facilitated by the development of flexible bronchoscopy. EBUS can be
performed under local anesthesia by inserting an ultrasonic probe with a
balloon sheath developed by Becker into the working channel of a flexible
bronchoscope. This technique has been proven to be helpful in identifying the
target lesion for transbronchial needle aspiration, clarifying mediastinal and
bronchial wall anatomy, and determining the depth of bronchial wall tumor
invasion [1 5J. Kurimoto et al. reported that EBUS allows visualization of the
laminar structure of the tracheobronchial wall, which is impossible with other
40 Miyazawa et al.
diagnostic imaging methods [16]. Kurimoto has used a three-dimensional
(3D) endoscopic ultrasound system currently under development (EU-IP2;
Olympus). The 3D EBUS images can provide excellent views of the
tracheobronchial wall and peribronchial lesions (Fig. 4)
The Lung Imaging Fluorescence Endoscopy system (LIFE; Xillix
Technologies Corporation, Vancouver, Canada) was developed by Lam and
his coworkers at the British Columbia Cancer Agency. LIFE contains a
helium-cadmium laser light source, two image-intensifier CCO cameras, and
a color video monitor. LIFE has been reported to have significant
advantage over white light bronchoscopy in the detection of focal bronchial
wall dysplasia, carcinoma in situ, and early lung cancer [17]. Somewhat
similar autofluorescence flexible bronchoscopic (AFB) systems were
developed by the Pentax Corporation and Karl Storz Endoscopy in
Germany. The use of both AFB and EBUS at our institution has been a
valuable addition to diagnostic bronchoscopy. We have found these
techniques to be useful in making decisions regarding therapies such as
PDT [18,19].
The Olympus Company has an extensive worldwide sales network and
research facilities, and although it developed its original bronchoscopes after
those of the Machida Company, Olympus now holds the largest portion of
the bronchoscope market. Olympus' research efforts have been extremely
Figure 4 Olympus developed the 3D Endoscopic Ultrasound System. This system
gives us 3D images by moving the scanner regularly along the catheter probe, making
serial images (left; radial image, right; linear image). On the linear image, the
cartilage layer (arrow) has been destroyed by squamous cell carcinoma.
lntervent ional Flexible Bronchoscopy
41
valuable in the development of new flexible bronchoscopes and have
contributed greatly to the progress of bronchology. Specifications of new
models of single- and double-channel bronchoscopes are shown in Tables 3
and 4. Recently, Saka used an ultrathin (2.8 mm) flexible bronchoscope
(Olympus BF-XP40, BF-XP260F) for detecting peripheral tumors with
good results. Once the bronchus had been accessed, and the peripheral
tumor identified, a biopsy forceps was inserted through the channel of the
bronchoscope. This ability to make direct observations of a peripheral
tumor is most useful during the biopsy procedure (Fig. 5).
In 1998, on Ikeda's advice, we asked the Olympus Company to
develop prototypes of a large-diameter flexible bronchoscope with a wider
working channel and a double-channel bronchoscope (the so-called big and
double-channel flexible bronchoscopes) for use in interventional broncho-
scopy (e.g., stenting, balloon dilation, laser ablation, and endobronchial
ultrasonography-guided transbronchial needle aspiration). In recent years,
diagnostic and therapeutic procedures have been performed with these new
flexible bronchoscopes. The working channel of the new "big" broncho-
scope is much wider and provides greater ease of insertion of large
instruments such as forceps, balloons, and probes. Placement of Dumon
stents including Y stents [20,21] has been proven to be safe and effective
with this scope. However, in difficult cases involving carinal tumors or
mediastinal adenopathy, Dumon Y stents had to be deployed using both
rigid and flexible bronchoscopes under fluoroscopic and endoscopic
visualization. Figure 6 shows the release (by rigid bronchoscopy) and
adjustment of a Dumon Y stent using an Olympus XBF-SI40. The tumor
had initially been debulked with an argon plasma coagulator (Erbe USA,
Marietta, GA). Stent deployment was followed by balloon dilation directly
through the bronchoscope channel into each leg of the Y stent. The stent
can be seen fitting snugly around the carina. This technique, using the
Olympus XBF-SI40 to help with Y stent placement, saves time and is more
efficient. Even when the stenosis is located in the left upper lobe bronchus,
which is inaccessible to the rigid bronchoscope, Dumon stents can be placed
under direct visual guidance using the Olympus XBF-SI40 and taking
advantage of its large working channel (Fig. 7).
We speculated that real-time EBUS might be useful to improve the
yield of transbronchial needle aspiration (TBNA) [22]. We therefore
performed EBUS and TBNA simultaneously using a double-channel
flexible bronchoscope (Olympus XBF-2T40) (Fig. 8) or a convex flexible
bronchoscope. In Figure 8, the EBUS image shows the Wang transbron-
chial needle (MWF-3l9, Bard Company, Billerica, MA) as a hyperechoic
spot with an acoustic shadow penetrating into the tumor. In the
photomicrograph, a relatively large aspirate can be seen. We feel that
Table 3 Specifications of the Olympus Single-Channel Bronchoscopes
BF-XP260F BF-XP40 BF-P260F BF-IT260 BF-260 BF-XT40 BF-ST40 XBF-SJ40
()
Optics CCD Fiberoplics CCD CCD CCD Fi beroptics Fiberoptics Fiberoplics
0
Field of view (degrees) 90 90 120 120 120 120 90 90
"b
Deplh of field (mm) 2-50 2 - 50 3 ~ 5 3-100 3-100 3-50 2 - 50 2 ~ 5
~
':
Outside diameter of distal <1>28 <1>2.8 <!J4.0 <1> 5.9 <1>4.9 <1>6.1 <1>6.3 <1>7.2
end (mm)
<ii
Angulalion (degrees) U/D 180/130 180/130 180/130 180/130 180/130 180/130 160/130 160/130
Q.
Outside diameter of flexible <1>2.8 <1>2.8 <1>4.4 <1>6.0 <1>4.9 <1>6.2 <1>6.6 <1>7.9
s: lube (mm)
Q)
Inside diameter of channel (mm) ell 1.2 <1> 1.2 eD2.0 <1>2.8 <1>2.0 <!J3.2 Ql3.7 <1>4.2
<ii
~
Electroca utery No No No Compatible Compatible Compalible Compatible No
Working lenglh (mm) 600 600 600 600 600 550 550 550
TOlal lenglh (mm) 870 890 870 870 870 840 840 840
U/D, up/down; <1>, diameter; CCD, charged couple device.
"""
l'-.J
~
~
l::l
'"
l::l
~
~
~
Inlervenliona! Flexible Bronchoscopy
43
Table 4
Specifications of the Olympus Double-Channel Bronchoscopes
BF-2TIO XBF-2T30 XBF-2T30Y2 XBF-2T40
Optics
Fi beroptics Fiberoptics Fiberoptics Fiberoptics
Field of view (degrees)
90 120 120 120
Depth of field (mm) ~ 5 ~ 5 ~ 5 ~ 5
Outside diameter of distal <D 5.9 <I> II <D 61 <D 7.2
end (mm)
Angulation (degrees) U/D 160/100 90/90 180/130 160/100
Outside diameter of fiexible <D6.0 <I> 11.5 > 6.3 <1>6.8
tube (mm)
Inside diameter of channel <D2.0 >4.5 >2.0 <1>20
(m111) <D1.5 <D 2.0 <D2.0 <D2.0
Electrocautery No Compatible Compatible Compatible
Working length (mm) 550 460 550 550
Total length (111m) 760 740 840 840
U/D, up/down; >, diameter.
EBUS used as an adjunct to TBNA helps in the accuracy and safety of the
procedure.
III. Future Research
We, therefore, believe that future research will provide us with many new
versions of the flexible bronchoscope with new clinical applications, and
that these new scopes will play an important role in interventional
bronchoscopy of the future.
During the 11th World Congress for Bronchology in June 2000 in
Yokohama, Japan, Ikeda announced his retirement, and Hirokuni
Yoshimura was elected Chairman of the Board of Regents of the World
Association for Bronchology. The scientific program of the Yokohama
World Congress induded an intercontinental live video conference linking
the attendees in the conference hall in Yokohama with the bronchoscopy
suites of the Thoraxklinik in Heidelberg, Germany, and the Mayo Clinic in
Rochester, MN. This introduced a new era of bronchological communica-
tion that can provide teleconsulting, teleconferences, teleteaching, and
teleintervention by giving the viewer the impression of being in the middle of
an operating theater thousands of miles away.
Even in retirement, Ikeda continues to be interested in the develop-
ment of bronchoscopy in the new millennium. He has endorsed new
44
Miyazawa et at.
Figure 5 Fluoroscopic image of an ultrathin flexible bronchoscope and an
endoscopic view of a peripheral tumor.
technologies such as the remote control capsule endoscope, which is sent
down the airways by navigation using virtual bronchoscopy. This is the so-
called "micromachine" [1,23].
Dr. Ikeda succumbed to a long illness in December 2001. His motos,
"there is more hope with the bronchoscope" and "never give up" continue
to inspire current diagnostic and interventional bronchoscopists to advance
the science of bronchology.
Figure 6 The operational tip of a wide-diameter bronchoscope (top, left). The
fluoroscopic image of a Dumon Y stent being placed by wide-diameter flexible
bronchoscopy (top, right). A carina! tumor obstructing both main bronchi (bottom,
left). The carinal stent in position (bottom, right).
Figure 7 A Dumon stent held by forceps passed through a wide-channel
bronchoscope (top, left). Fluoroscopic image of a Dumon stent being inserted by
flexible bronchoscopy (top, right). Left upper lobe bronchial stenosis, squamous cell
carcinoma (bottom, left), Endoscopic view of the stent in position (bottom, right).
Figure 8 The tip of a double-channel bronchoscope (top, left). EBUS image showing the ultrasonic
shadow of the TBNA needle within a tumor (top, right). Endoscopic view of EBUS ballon and the
TBNA needle (bottom, left). The resultant aspirate in formalin (bottom, right).
()
.g
':
CD
0..
CD
Ooubk' ( 'h.uHlel
fkondmsCQpe
()( ESt:S ,;.:uided
'fUNA
""
0\

i::l
'" i::l
'" i::l
f2..
Interventional FLexible Bronchoscopy
References
47
I. Becker HD. Bronchoscopy, year 200 I and beyond. C1in Chest Med 200 I;
22:225-239.
2. Ikeda S, Yanai N, Ishikawa S. Flexible bronchofiberscope. Keio J Med 1968;
171-16.
3. Ikeda S. Flexible bronchofiberscope. Ann Otol Rhinol Laryngol 1970; 79:916-
924.
4. Ikeda S. Atlas of Flexible Bronchofiberoscopy. Tokyo: Igaku-Shoin, 1974:6-
10
5. Tsuboi E, Ikeda S. Transbronchial biopsy smear for diagnosis of peripheral
pulmonary carcinomas. Cancer 1967; 20:687-698.
6. Edell ES, Sanderson DR. History of Bronchoscopy. In: Prakash USB, ed.
Bronchoscopy. New York: Raven Press, 1994:7-11.
7. Dumon JF, Reboud E, Garbe L, Aucomte F, Meric B. Treatment of
tracheobronchial lesions by laser photoresection. Chest 1982; 81 :278-284.
8. Ikeda S, Ono R, Kurihara M. Endoscopical treatment using laser energy. J Jpn
Soc Bronchol 1981; 3:47-51.
9. Hayata Y, Kato H, Konaka C, Ono 1, Takizawa N. Hematoporphyrin
derivative and laser photoradiation in the treatment of lung cancer. Chest 1982;
81:269-277
10. Ono R, Ikeda S, Suemasu K. Haematoporphyrin derivative photodynamic
therapy in roentgenographycally occult carcinoma of the tracheobroncheal
tree. Cancer 1992; 69: 1698-170 I.
11. Cortese DA, Edell ES, Kinsey IH. Photodynamic therapy for early stage
squamous cell carcinoma of the lung. Mayo Clin Proc 1997; 72:595-602.
12. Ikeda S. The development and progress of endoscopes in the field of
bronchoesophagology. 1 Jpn Bronchoesophagol Soc 1988; 39:85-96.
13. Becker HD. Stenting of the central airway. 1 Bronchol 1995; 2:98-106.
14. Miyazawa T, Yamakido M, Ikeda S, Furukawa K, Takiguchi Y, Toda H,
Shirakusa T. Implantation of Ultraflex nitinol stents in malignant tracheo-
bronchial stenoses. Chest 2000; 118:959-965.
15. Becker HD, Herth F. Endobronchial Ultrasound of the Airways and the
Mediastinum. In: Bollinger CT, Mathur PN, eds. Interventional Bronchoscopy
Progress in Respiratory Research Vol. 30. Basel: Karger, 2000:80-93.
16. Kurimoto N, Murayama M, Yoshioka S, Nishisaka T, Inai K, Dohi K.
Assessment of usefulness of endobronchial ultrasonography in tracheobron-
chial tumor invasion. Chest 1999; 115:1500-1506.
17. Lam S, Kennedy T, Unger M, Miller YE, Gelmont D, Rusch V, Gipe B,
Howard D, LeRiche lC, Coldman A, Gazdar AF. Localization of bronchial
intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest 1998;
113:696-702.
18. Lam S, Becker HD. Future diagnostic procedures. Chest Surg Clin North Am
1996; 6:363-380.
48 Miyazawa et at.
19. Miyazu Y, Miyazawa T, Kurimoto N, Iwamoto Y, Kanoh K, Kohno, N.
Endobronchial ultrasonography in the assessment of centrally located early-
stage lung cancer before photodynamic therapy. Am 1 Respir Crit Care Med
2002; 165:832-837
20. Dumon IF. A dedicated tracheobronchial stent. Chest 1990; 97:328-332.
21. Miyazawa T, Arita K. Airway stenting in lapan. Respirology 1998; 3:229-234
22. Shannon 11, Bude RO, Orens JB, Becker FS, Whyte RI, Rubin 1M, Quint LE,
Martinez Fl. Endobronchial ultrasound-guided needle aspiration of mediast-
inal adenopathy. Am 1 Respir Crit Care Med 1996; 153: 1424--1430.
23 Mizuno H. Micromachines. 1 lpn Soc Bronchol 2000; 22:590-595.
4
Therapeutic Flexible Bronchoscopy
Overview
PYNG LEE
Singapore General Hospital
Singapore
I. Introduction
ATUL C. MEHTA
Cleveland, Ohio, U.S.A.
The invention of the flexible bronchoscope by Shigeto Ikeda and its
introduction into clinical practice almost 40 years ago have revolutionized
the practice of pulmonary medicine and enhanced our understanding
pulmonary diseases. Flexible bronchoscopy (FB) has evolved into the most
commonly used invasive diagnostic as well as therapeutic procedure in the
practice of pulmonary medicine. Today, flexible bronchoscopy (FB) is widely
performed by pulmonologists, thoracic surgeons, critical care specialists,
otolaryngologists, and anesthesiologists [1-4]. In this chapter, we provide a
review of endoscopic treatment modalities that can be performed with FB
and their indications, technique, outcome, and complications.
A. Flexible Bronchoscope
The flexible bronchoscope with its enhanced flexible distal tip allows the
bronchoscopist to visualize all segmental bronchi with ease. Larger working
channels and better accessory instruments increase its diagnostic yield as
weJl as the range of its therapeutic abilities. The thin flexible bronchoscope
Copyrighted Material 49
50
Lee Q/1d Mehta
not only allows direct visualization of the eighth- through twelfth-
generation bronchi not normally seen with standard FB, but also facilitates
endotracheal intubation in difficult situations such as trauma, hemorrhage,
or anatomical deformities [5]. The ultrathin flexible bronchoscope, which
has an outer diameter of 1.8 mm, a flexible tip, and a channel for biopsy,
enables researchers to examine bronchioles and perform alveolobroncho-
graphy [5], as well as study bronchial epithelial cells collected from airways
that were previously inaccessible [6].
Owing to the rapid advances made in video chip technology,
videobronchoscopy has facilitated teaching and better documentation of
endoscopic images. The addition of chip technology has improved image
quality, and together with laser probes, zoom technology, and computerized
processing give rise to endoscopic microscopy, microconocal scanning
microscopy ~ c o s m , endoscopic optical coherence tomography (ECOT),
endoscopic magnetic resonance tomography, and endobronchial ultrasound
(EBUS), in an attempt to assess accurately the depth and extent of
endobronchial lesions as well as any associated mediastinal abnormality.
II. Therapeutic Bronchoscopy
Bronchoscopy is often employed for diagnostic reasons, but it was
originally invented in the nineteenth century by Gustav Killian as a
therapeutic tool to remove a pork bone that had been aspirated into the
right main bronchus [7]. The therapeutic spectrum for bronchoscopy has
since expanded significantly and is listed in Table I.
III. Bronchoscopic Equipment
A. Rigid Versus Flexible Bronchoscope
For nearly 70 years, the rigid bronchoscope provided the only access to the
airways. The rigid bronchoscope of today is no different from the hollow,
straight, and stainless steel tube used by Chevalier Jackson [8]. However,
since the late 1960s, the flexible bronchoscope has supplanted the rigid
bronchoscope as the instrument of choice for most diagnostic and
therapeutic procedures in adults [4,9]. In fact, a recent survey by Colt and
Prakash [9] of 2500 members of the American College of Chest Physicians
(ACCP) showed that 99% of all bronchoscopies in the United States were
performed with the flexible bronchoscope, with only 4% of respondents
reported having experience in rigid bronchoscopy. Moreover, many training
programs limit exposure of pulmonary trainees to flexible instruments [10].
Therapeutic Flexible Bronchoscopy: Overview
Table 1 Spectrum of Flexible Therapeutic Bronchoscopy
Removal of central airway neoplasms
Malignant/benign
Laser photoresection
Endobronchial electro urgery
Argon plasma coagulation
Brachyt hera py
Cryotherapy
Photodynamic therapy
Dilatation of stricture and stenosis
Stent placement
Intralesional injection
Removal of foreign body
Bronchoalveolar lavage for pulmonary alveolar proteinosis
Aspiration of cysts
Mediastinal
Bronchogenic
Drainage of lung abscess
Hemoptysis
Pulmonary toilet
Endotracheal intubation
Percutaneous dilatational tracheostomy
Pneumothorax/bronchopleural fistula (fibrin glue therapy)
Bronchoscopic volume reduction"
Gene therapy"
"Potential use.
51
Although the versatility of FB has replaced rigid bronchoscopy (RB)
in many indications, RB remains an invaluable tool in adult and pediatric
bronchology, and its application should be considered for better control of
the compromised airway, massive hemoptysis, silicone stent placement, and
removal of large foreign bodies.
IV. Central Airway Obstruction
Central airway obstruction from malignant or benign endobronchial tumors
can result in respiratory failure, and relief of obstruction may be necessary
to avoid mechanical ventilation (MY) and facilitate weaning. As there are
52
Lee and Mehta
no randomized trials comparing efficacy between different therapeutic
modalities, selection of a treatment strategy depends on acuity of
presentation, type of lesion, stage of disease, patient's general status, and
physician's expertise [II] (Fig. I).
V. Relief of Malignant Airway Obstruction
A. Laser Photoresection
The most widely used laser for treatment of malignant tracheobronchial
tumors is the neodymium:yttrium-aluminium-garnet (Nd:YAG) laser. As
Figure 1 Management of malignant central airway obstruction. Central airway
obstruction by primary or metastatic lung cancer is often a medical emergency that
requires immediate intervention. Curative resection by surgery is often contra-
indicated owing to the advanced nature of the disease. and interventional procedures
are necessary to reestablish airway patency and to avoid mechanical ventilation due
to respiratory failure. 'To be followed by ChemoTx and/or XRTx. "Can be used
singly or in combination. LPR, laser photoresection: EBES, endobronchial
electrosurgery; CryoTx, cryotherapy: XRTx. radiotherapy; BrachyTx, brachyther-
apy; PDT. photodynamic therapy; ChemoTx, chemotherapy.
Therapeutic Flexible Bronchoscopy: Overviell'
53
the Nd:YAG laser wavelength is poorly absorbed by quartz material, it can
be transmitted via a flexible fiber through the working channel of the flexible
bronchoscope, The Nd:YAG laser causes tissue coagulation at low power
and vaporization at high power.
Indications
The application of laser to an obstructive lesion restores airway patency,
allows ventilation of distal lung, and drainage of postobstructive
pneumonia. The ideal patient for Nd:YAG laser is one who has a
symptomatic, unresectable, exophytic airway lesion that is either recurrent
or resistant to radiotherapy or chemotherapy. The ideal lesion (Fig. 2) is an
endobronchial tumor that measures less than 4 cm, arises from one wall of
the trachea or main stem bronchus, has a visible distal lumen, and distal
lung collapse of less than 6 weeks. Lesions not amenable to laser are
extrinsic or submucosal, primarily involving lobar or segmental bronchi,
and contiguous with the esophagus. Other contraindications to laser
photoresection (LPR) include abnormal coagulation profile, unstable
cardiovascular status, and high oxygen requirement (Table 2).
Our techniq ue of LPR has been previously described [12], and we
practice the "Rule of Four," an algorithm aimed at reducing the risks of
endobronchial ignition (Table 3).
Figure 2 An ideal exophytic tumor for laser photoresection.
54
Results and Complications
Lee and Mehta
LPR improves airway patency in 79-92% of patients [13-15], while its
coagulative property palliates those with hemorrhagic endobronchial
tumors. LPR is therefore very effective in relieving symptoms of cough,
dyspnea, and hemoptysis, as well as in achieving endoscopic [16],
radiographic [16,17], spirometric [18], and quality-of-life improvements
[19]. It may also obviate the need for MV in patients with respiratory
distress and facilitate weaning as well as extubation of those ventilated
[20,21].
The survival benefit due to LPR is uncertain owing to a lack of
randomized trials. Trials that demonstrated increased survival with LPR
include Brutinel et al. [22], who reported a survival rate of 60% at 7 months
among patients treated with LPR compared with 100% mortality in the
historical group; Eichenhorn et al. [23], who demonstrated an increase in
median survival (340 days vs 198-266 days) among those who underwent
LPR compared with controls who received external beam irradiation (XRT)
alone; and Shea et al. [24], who found additional benefit when
brachytherapy was administered with LPR. There were other studies that
did not show any benefit [25-27], and although Desai and coworkers [25]
observed a better outcome in a subgroup of patients managed with emergent
Table 2 Factors that Influence Outcome of Nd: YAG LPR
Factors
Location
Type of lesion
Appearance
Extent of involvement
Length of lesion
Distal lumen
Duration of collapse
Clinical status:
Hemodyna mics
Oxygen requirement
Coagulation profile
Pulmonary vascular
supply
Favorable
Trachea, main bronchi
Endobronchial
Polypoid, exophytic,
pedunculated
Localized (one wall)
<4 cm
Visible
<4-6 weeks
Stable
<0.4 F102
Normal
Intact
Unfavorable
Lobar and segmental
bronchi
Extrinsic
Submucosal
Extensive (> I wall)
>4 cm
Not visible
>4-6 weeks
Unstable
<0.4 F102
Abnormal
Compromised
Table 3 Rule of Four
55
Maximum length of lesion
Duration of collapse
Initial settings:
Power:
Noncontact
Contact
Pulse duration
Distances:
Endotracheal tube to lesion
Fiber tip to lesion
FB to tip
F102 during LPR
Number of pulses between cleaning
Procedure time
Total number of repeat laser treatments
Life expectancy
Laser team members
4cm
<4 weeks
40W
4W
0.4 sec
>4cm
4mm
4mm
<40%
<40
<4hr
<4
>4 weeks
4
LPR compared with emergent X-ray therapy (XRT), the overall survival
remained dismal.
Measuring survival may not be the best parameter to determine the
efficacy of LPR given its palliative role. In fact, immediate relief of dyspnea,
improved performance, and better quality of life justify its use. Therefore,
LPR should be considered to be complementary to XRT, chemotherapy,
stenting, or surgery as it not only provides the time necessary to institute
these treatments, in certain situations, it may represent the only option for
patients who have had previous therapy.
LPR is a relatively safe procedure with complication rates ranging
from 0 to 2.2 [12,16,28-30]. The most serious complication is the perforation
of a major intrathoracic blood vessel [12,31]. To avoid this fatal
complication, the operator must be adept in the knowledge of airway
anatomy, and keep the laser beam parallel to the bronchial wall at all times.
Endobronchial ignition is another serious complication [32,33], which can
be prevented by setting the laser to single-pulse mode, keeping the fiber
clean, avoiding the use of combustible anesthetic agents and firing at
inflammable materials (bronchoscope sheath, suction catheter, endotracheal
tube), and keeping FI02 at 0.4 or less. Hemorrhage from a vascular tumor
during LPR is often insignificant and easily controlled; on a rare occasion,
RB may be required for suction and tamponade of the site when bleeding
becomes excessive. The occurrence of pneumothorax or pneumomediasti-
56 Lee and Mehta
nium attendant to laser-induced perforation of the tracheobronchial tree or
MY can be avoided by keeping the laser beam parallel to the bronchial wall
and maintaining safe peak airway pressures. Risks for cerebral air embolism
from coaxial cooling of sheathed fibers and retinal damage from reflected
laser light can be minimized by the use of CO
2
instead of air [12] as a coolant
and protective eye goggles, respectively [34]. The composition of the laser
plume has also come under investigation recently with reports demonstrat-
ing intact human papillomavirus (HPV) DNA in the vapors of laser-treated
verrucae [35] and subsequent development of similar lesions in the treating
physicians [36]. Similarly, the DNA of human immunodeficiency virus
(HIV) has also been detected in laser smoke, but culture of the virus in cells
did not occur [37]. We therefore recommend the use of a smoke evacuator
and special protective masks during LPR pending further results on the risks
of viral transmission and infection.
B. Electrosurgery
Endobronchial electrosurgery (EBES) is the application of electrical current
to coagulate or vaporize tissue in the tracheobronchial tree. With
development of grounded bronchoscopes, better probes, electrodes, and
high-frequency electrical generators, a resurgence of interest in EBES for
treatment of lung cancer has occurred. Moreover, equipment and
maintenance costs are very much lower compared with the Nd:YAG laser
[38].
Several probes are available for use in the tracheobronchial tree, and
these can be introduced via the working channel of the flexible broncho-
scope (Fig. 3). EBES is performed with the probe in contact with the target
tissue, and the electrical current set to "coagulate" at high amperage/low
voltage, "cut" at low amperage/high voltage, or "blend" at midway between
"cut" and "coagulate." By applying electrical current via a foot pedal, it
passes from the probe to tissue and finally to a grounded neutral plate
attached to the patient.
Two main techniques of EBES have been described: [I] tumor
debulking by cutting the stalk of a polypoid lesion with a cutting loop and
[2] electrodestruction of tumor by direct contact of the probe. Optimal
results are achieved if the treated area is kept free of blood or mucus.
The argon plasma coagula tor (APC) is an example of noncontact EBES,
and it uses ionized argon gas as a conductor for electrical current between
the electrode and tissue [39]. It is ideal for coagulation of superficial
hemorrhagic lesions and tumors of the upper lobe segmental or superior
Figure 3 Examples of probes lIseful for endobronchial electrosurgery.
57
basal lobar bronchi [40] as well as stent-related obstructive granuloma [41].
However the in-depth tissue necrosis achieved with APC is less compared
with Nd:YAG laser, brachytherapy, and photodynamic therapy (PDT) [38].
Indications, Results, and Complications
EBES has been used successfully to debulk tracheobronchial tumors and
restore airway patency in 70-86% of patients [42,43]. Coulter et al. [43]
reported 86% success when EBES was applied under local anesthesia to a
select group of patients with small endobronchial polypoidal tumors.
Experience with EBES in early lung cancer is, however, limited. A
pilot study [44] examining the efficacy of EBES in 13 patients with
superficial early squamous cell carcinomas and in situ carcinomas measuring
not more than I cm
2
surface area demonstrated a long-term response in 10
patients. Although the number of patients was small, results implied
comparable efficacy ofEBES with PDT and brachytherapy in the treatment
of early lung cancer.
Hemorrhage from vascular tumors, airway fire, and respiratory failure
can occur during EBES but are minimal in experienced hands [45,46].
C. Brachytherapy, Cryotherapy, and Photodynamic Therapy
Airway lesions that do not require immediate restoration of airway patency
can be treated with brachytherapy, cryotherapy, or photodynamic therapy
(PDT). These techniques are used singly or in combination.
58 Lee and Mehta
Brachytherapy
Endobronchial brachytherapy is a form of local radiation treatment that
involves temporary placement of encapsulated radioactive sources within or
near the tumor. The advantages of brachytherapy over external beam
radiation (XRT) include (I) delivery of a higher dose of radiation directly to
the tumor, (2) rapid fall of radiation outside the treatment region, (3) precise
dose localization, and (4) adaptability to tumor shape.
Recent developments have improved the afterloading technique,
thereby making it less hazardous for health care personnel. The tip of a
polyethylene catheter is placed 2-4 cm beyond the endobronchial tumor
under bronchoscopic and fluoroscopic guidance. The flexible bronchoscope
is then removed, the position of the catheter is reaffirmed radiograhically,
and the catheter is loaded with iridium 192 by a remote computerized after-
loading device.
Low-dose-rate (LOR) brachytherapy delivers less than 2 gray (Gy)/hr
to the site of the lesion, and depending on the total dose required, the
catheter is left in place for 48-72 hr. High-dose-rate (HOR) brachytherapy
delivers more than lOGy/hr and is administered as fractionated doses every
2-3 weeks. The major advantage of HOR over LOR brachytherapy is a
dramatic reduction of the treatment time, thereby converting brachytherapy
from an inpatient to an outpatient procedure.
Indications
Patients with endobronchial tumors from primary lung cancer or cancers
metastatic to the airways and residual tumor following surgery are
candidates for brachytherapy. However, the lesion to be treated must be
visible on bronchoscopy, permit the passage and distal placement of a
catheter, and located in the trachea or main stem or lower lobe bronchi.
Outcome studies with brachytherapy revealed similar endobronchial
response rates of 60-89% [47,48] with LOR and 54-94% [49,50] with
HOR, as well as comparable survival rates [51]. The response to
brachytherapy correlated with the tumor s i ~ and good results were
observed with small endobronchial [52] and peripherally located tumors
[49].
Studies have combined brachytherapy with XRT to achieve better
local cancer control, quicker restoration of airway patency, and a lower
radiation dose to surrounding normal lung, but the median survival for
these patients was not changed [53]. Instead, survival benefit was
demonstrated when LOR [24] or HOR brachytherapy [54] was administered
together with Nd:YAG laser than with either therapy alone.
Therapeutic Flexible Bronchoscopy: Overview 59
Respiratory compromise, massive hemoptysis, fistula formation,
radiation bronchitis, airway stenosis, and erosion of the pulmonary artery
have been reported with brachytherapy [55-57]. The risk of massive
hemorrhage is related to the proximity of pulmonary arteries to the main
stem and upper lobe bronchi. In fact, Bedwinek et a!. [55] showed 32% rate
of massive hemoptysis in patients with recurrent tumors involving the right
upper lobe, right main stem, and left upper lobe bronchi. Thus computed
tomography (CT), magnetic resonance imaging (MRI), or digital subtrac-
tion angiography is suggested to exclude tumors in close proximity to major
arteries before brachytherapy. Radiation-induced bronchitis and stenosis as
a result of HDR brachytherapy [57] occurred in 8.7% of the patients and
were observed more commonly with tumors in the trachea and main stem
bronchi, after treatment for curative intent, high total radiation dose, and a
good Karnofsky performance score [57].
Cryotherapy
Cryotherapy causes local tissue destruction by the application of extremely
low temperatures (below -20 to -40 QC). The mechanisms proposed to
explain the effect of cryotherapy are fourfold: (I) Intracellular dehydration,
which occurs when extracellular ice crystals cause increased extracellular
tonicity, drawing water from the intracellular to the extracellular space,
resulting in cell shrinkage and membrane damage. (2) Mechanical cellular
damage, which occurs with rapid freezing and slow warming. (3)
Intracellular ice crystals damage intracellular organelles such as mitochon-
dria and endoplasmic reticulum as well as proteins and enzymes. (4)
Vasoconstriction and microthromi formation in slow flowing venules, which
subsequently lead to devascularization and cell death.
There are three parts to the cryomachine: the console, the cryoprobe,
and the transfer line that connects the console and gas cylinder to the probe.
A liquid cryogen or coolant (usually nitrous oxide or nitrogen) is delivered
under pressure to a specially designed cryoprobe that may be rigid,
semirigid, or flexible. Rigid and semirigid cryoprobes are used via RB,
whereas flexible cryoprobes can be used with FB and RB.
The metallic tip of the cryoprobe is placed in contact with the tumor
and three freeze/thaw cycles with freezing time between 30 and 60 sec are
carried out at each site until the entire visible part of the tumor is frozen.
Tumor cells are more cryosensitive than normal cells, whereas certain tissues
such as fat, cartilage, fibrous tissue, or connective tissue are cryoresistant
[58].
60
Lee and Mehta
Indications
The most common indication for cryotherapy is in the relief of airway
obstruction due to tumor, which may be malignant or benign. However, if
the patient has impending respiratory failure from tracheobronchial
obstruction, surgery, LPR, EBES, or a combination of modalities is the
treatment of choice, as cryotherapy is often ineffective in removing tissue
rapidly. The ideal lesion is a small polypoid tumor accessible to the
cryoprobe, with a visible lumen and functioning lung distally.
Cryotherapy is successful in 50-86% of the patients in relieving airway
obstruction [59,60], and a synergistic response with chemotherapy and
radiotherapy has been observed [61,62]. Several days are required for tumor
necrosis to occur, and bronchoscopy is usually performed 3-4 days
following cryotherapy to clean up sloughed tissue or for repeat treatment
of large lesions. Cryotherapy can also be used to treat granulation tissue and
weblike stenosis as well as for the removal of foreign bodies, mucous plugs,
and blood clots [63,64]. Its role in early lung cancer management is still
under investigation [65].
Complications resulting from endobronchial cryotherapy are few and
minor, although hemoptysis, pneumothorax, tracheoesophageal fistula,
cardiac arrhythmia, and bronchospasm have been reported [66-68].
Photodynamic Therapy
PDT is a two-step process that involves the intravenous administration of a
photosensitizing agent known as dihematoporphyrin ether/ester (OHE;
Photofrin [I) and exposure to laser light.
Following the administration of OHE, which is preferentially retained
by tumor cells and cleared from most healthy tissues within 6 hr except for
the Iung, reticuloendothelial tissues, and the skin, the tumor is exposed to
630-nm wavelength of laser light introduced via a flexible bronchoscope
(Fig. 4). Exposure of OHE to light of proper wavelength results in tumor
necrosis from cell ular destruction by superoxide and hydroxyl radicals as
well as vascular occlusions from thromboxane A
2
release [69]. Clean-up
bronchoscopy is often necessary 2-4 days after the procedure.
PDT is indicated for the palliation of advanced obstructing cancers of the
tracheobronchial tree, and appears to be effective for polypoid tumors for
submucosal and peribronchial disease [70-72]. Moghissi et at [73] found
that the mean endoluminal obstruction of 100 patients treated with PDT
improved by 68%, with corresponding increases in forced vital capacity
After
Tissue
necrosis
61
Figure 4 Photodynamic therapy. Tumor cells retain Photofrin and undergo
destruction on exposure to laser light.
(FYC) and forced expiratory volume in I sec (FEY). Median survival of
advanced lung cancer treated with PDT was also shown to be better than
with other treatment modalities [74].
Other indications for PDT include treatment of synchronous or
metasynchronous [75] and early lung cancers [76,77]. Median survival for
patients with synchronous lung cancers treated with PDT alone or in
combination with surgery was 52 months. Moreover, PDT used preopera-
tively reduced the extent of surgical resection in some patients [78].
Surgery is advocated for treatment of early lung cancer, but in high
surgical risk patients or in those who refuse surgery, PDT may represent an
alternative treatment of cure if the cancer satisfies these criteria: (1)
roentgenographically occult, (2) superficial, < 3 cm
2
in surface area and
62
Lee and Mehta
:( I mm in depth, and (3) squamous cell carcinoma. The overall complete
remission rate with PDT in this group is between 64 and 98% [75-77].
The advantage of PDT over LPR is technical ease and safety. Distal
lobar obstructions not amenable to LPR can be treated with PDT under
local anesthesia. Disadvantages include slow onset of action thus not being
useful for patients with acute respiratory distress; the need for the patient to
avoid sunlight for 4-6 weeks; and frequent clean-up bronchoscopies.
Complications from PDT are minimal, and these include dyspnea from
airway obstruction due to tissue swelling and edema, photosensitivity, and
hemoptysis.
VI. Relief of Benign Airway Obstruction
The techniques described above, except for PDT, can also be used to relieve
airway obstruction due to benign tumor, obstructive granuloma, and
stenosis. LPR is commonly used to treat benign endobronchial lesions such
as hemangiomas, lipomas, myoblastomas, chondromas, leiomyomas,
histiocytomas, and hamartomas [79-81]. Symptomatic obstructive granulo-
mas due to mechanical trauma from endotracheal intubation, foreign body,
tracheostomy tube, transtracheal oxygen catheter, suture material, and
inflammatory processes such as Wegener's granulomatosis or sarcoidosis
can be easily removed by LPR, APC, EBES, and cryotherapy.
Subglottic or tracheal stenosis (Table 4), however, poses a therapeutic
dilemma and challenge to the pulmonolgist as nonsurgical endoscopic
attempts at bougie dilatation, EBES, cryosurgery, or LPR often result in
mucosal trauma, unpredictable healing, and a high rate of restenosis.
Laryngotracheal resection or reconstruction, although successful, can cause
damage to vocal cords and the recurrent laryngeal nerve [82]. Thus, our
approach to subglottic and tracheal stenosis is to perform mucosa-sparing
Nd:YAG LPR or EBES followed by gentle dilatation with an angioplasty
balloon catheter of appropriate size [83]. With careful patient selection
(Table 5) and meticulous postoperative care, our success rate is 67% (see
Fig. 2). The number of repeat treatments is usually limited to three, and if
stenosis recurs after the third treatment, the patient is referred for definitive
surgical intervention (Fig. 5).
A. Balloon Dilation of Benign Tracheobronchial Stenosis
Instead of using increasing izes of rigid bronchoscopes, balloon dilation
can be performed for tracheobronchial stenosis [84-86]. The choice of
balloon depends on the length and diameter of the stenosis as well as the
target diameter to be achieved.
Table 4 Causes of Airway Stenosis
63
Subglottic
Membranous web
Tracheomalacia
Closed first ring
Trauma related
Foreign body aspiration
Systemic disease
Wegener's granulomatosis (WG)
Sarcoidosis
Tuberculosis
Amyloidosis
Inflammatory bowel disease
Papillomatosis
Technique
Tracheal
Membranous web
Tracheomalacia
Vascular anomaly
Trauma related
Foreign body aspiration
Systemic disease
Wegener's granulomatosis
Sarcoidosis
Tuberculosis
Amyloidosis
Inflammatory bowel disease
Papillomatosis
Balloon dilation is performed with a flexible bronchoscope and under local
anesthesia. After the site of stenosis is deemed to be treatable by balloon
dilation, a guide wire (0.89-mm diameter, Cook Inc., Bloomington, IN) is
inserted through the working channel and advanced beyond the stenosis
under fluoroscopic guidance. The appropriate balloon catheter is passed
over wire and sited over the stenosis with the help of radiopaque markers at
the proximal and distal ends of the balloon. To facilitate optimal placement
of the balloon, our practice is to use dilute contrast medium to inflate the
Table 5 Anatomical Features of Stenosis That Predict Outcome
Favorable outcome
Concentric web
Scarring <J cm in vertical length
Absence of tracheomalacia
Unfavorable outcome
Circumferential scarring with cicatricial
contracture
Scarring> I cm vertical length
Tracheomalacia
History of bacterial infection associated
with tracheotomy
Carinal involvement by stenosis
Combined laryngeal and tracheal
stenosis
64
LPRIEBES
followed by dilatation
(repeat twice in
cases of recurrence)
Inoperable
Lee and Mehta
Operable
Figure 5 Management of tracheal stenosis. (Modified from Ref. 86a.)
balloon for better imaging and continuous fluoroscopy. The procedure IS
repeated if necessary to achieve the ideal airway diameter.
Complications
Complications associated with balloon dilation include chest pain,
bronchospasm, and atelectasis, whereas excessive dilation may lead to
laceration or airway rupture causing hemorrhage, pneumothorax, pneumo-
mediastinum, and mediastinitis [87].
B. Airway Stents
A stent is a hollow, cylindrical prosthesis that maintains luminal patency
and dimensions of a tubular structure by opposing extrinsic compressive
forces and providing internal support. Stent insertion for malignant
Therapeutic Flexible Bronchoscopy: Overviell'
65
tracheobronchial obstruction following LPR or EBES results in immediate
relief of acute respiratory distress, successful extubation, and prolonged
survi val [88,89].
Stents are commonly used for the palliation of inoperable tracheobronchial
tumors (Table 6). They are classified as tube and metallic stents, and a
comparison between them is shown in Table 7.
At present, there is no ideal stent, and the evaluation of stent
performance is not dependent upon the immediate therapeutic response but
rather on its ability to maintain long-term patency and associated
complications. Moreover, the ease of insertion of a particular stent should
not result in its inappropriate use and selection over another that is better
suited for a given condition.
Choice of Stent
Tube Stents
Tube stents are indicated for benign and malignant lesions [90]. The main
advantage of a tube stent is the ease with which it can be repositioned and
removed, but it requires a rigid bronchoscope for insertion. Other
disadvantages include migration, granuloma formation, mucous obstruc-
tion, and lack of flexibility in conforming to airway tortuosity [91].
Metallic Stents
Metallic stents are gaining popularity as they can be inserted with FB, in an
outpatient setting, and with the patient under local anesthesia [92,93]. They
are classified according to the method of deployment (Table 8). A balloon-
expandable stent consists of a stent balloon assembly, and relies on the
balloon to dilate it to its correct diameter at the target site. A self-expanding
Table 6 Indications for Stent Placement in Lung Cancer
1. Airway obstruction from extrinsic bronchial compression or submucosal disease
2. Obstruction from endobronchial tumor when patency is <50% after laser
therapy
3. Aggressive endobronchial tumor growth and recurrence despite repetitive laser
treatments
4. Loss of cartilaginous support from tumor destruction
5. Sequential insertion of airway and esophageal stents for tracheoesophageal
fistulas
66 Lee and Mehta
Table 7 Comparison of Dumon (Tube) Stent and Metallic Stents
Characteristics
Mechanical considerations
High internal to external diameter
ratio
Resistant to recompression when
deployed
Radial force exerted uniformly
across stent
Absence of migration
Flexible for use in tortuous airways
Removable
Dynamic expansion
Can be customized
Tissue-stent interaction
Biologically inert
Devoid of granulation tissue
Tumor ingrowth
Ease of use
Can be deployed with FB
Deployed under local anesthesia
with
Conscious sedation
Radiopaque for position
evaluation
Can be easily repositioned
Cost
Inexpensive
-, poor: +. fair: ++, good; +++. best.
Dumon
tent
+
+
+++
+++
++
+
++
++
+
Covered
Wallstent
+++
++
++
++
+++
++
++
+
+++
++
+++
stent has a shape memory that enables it to assume the proper configuration
when released from a constraining delivery catheter (Fig. 6).
Advantages of the metallic stents (Fig. 7) for malignant tracheobron-
chial obstruction are ease of placement, greater airway cross-sectional
diameter, better conformity to tortuous airways, maintenance of mucociJi-
ary clearance, and ventilation acro s a lobar bronchial orifice. Disadvan-
tages include granuloma formation and difficulty in removal and
repositioning after 6 weeks owing to stent epithelialization [94].
The use of balloon-expandable stents (Palmaz and Strecker stents) is
limited to the pediatric population. Although the Strecker stent (Boston
Table 8 Characteristics of Metallic Stents
Bailon-expandable
67
Strecker
Palmaz
Self-expandable
Gianturco Z
Ultraflex
Wallstent
Tantalum monofilament knitted into a wire mesh. Most useful
in narrow stenoses.
Stainless steel tube with rectangular slots along the long axis.
May collapse with strong external pressure such as a vigorous
cough (Johnson and Johnson Interventional Systems Co.,
Warren, NJ).
Stainless steel monofilament bent into a zigzag configuration
to form a cylinder. Fixation achieved by small hooks.
Serious reported complications include bronchial wall
perforation, stent fractures, and granuloma formation
Cylindrical wire mesh of nitinol. Available in covered and
uncovered form. Limited experience.
Wire mesh made of cobalt-based alloy filaments and coated
with silicone. Uncovered metallic ends prevent migration.
Scientific International, Natack, MA) (available 20-40 mm in length) can be
used for accurate stenting of short-segment stenosis in adults (as it does not
foreshorten when deployed), it is uncovered, and therefore unsuitable for
malignant lesions. The Gianturco stent (William Cook Europe, Bjaevrskov,
Denmark), one of the earliest metallic stents, has also fallen out of popularity
because of the high incidence of bronchial and vascular perforations [95].
The Wallstent and Ultraflex (both, Boston Scientific, Natack, MA)
stents are currently the metallic stents of choice, as they are easy to deploy
and are available in covered forms. The Wallstent is a self-expandable wire
mesh of cobalt-based superalloy monofilaments (Fig. 8), whereas the
Ultraflex stent is made of nitinol with a shape memory that deforms at low
temperatures and regains its original shape at higher temperatures (Fig. 9).
The Cleveland Clinic experience of 52 Wallstents for 37 patients (20
neoplasia, 17 benign disease) showed 11 % obstructive granuloma with no
migration or mucous plugging [96], concluding that Wallstents could be
used safely for the indications described and deployed easily with FB.
Recently, Miyazawa [97] reported his experience of 54 Ultraflex stents
deployed via FB or RB in 34 patients with inoperable malignant airway
stenoses. Immediate relief of dyspnea was achieved in 82% of the patients
with demonstrable improvements in spirometry. Retained secretions and
stent migration were not observed, and removal as well as repositioning was
possible in I case of stent misplacement. It was also observed to be effective
68
Lee and Mehta
Figure 6 Expandable metallic Wallstent deployed over a guide wire.
Figure 7 Note Wallstent conforming to the tracheal tortuousity in apatient on
mechanical ventilation without interfering with the endotracheal tube.
69
Figure 8 Covered and uncovered Wallstents.
Figure 9 Covered and uncovered Ultraflex stents.
70
Lee and Mehta
for subglottic stenosis. Herth et al. [98] also showed that the Ultraflex stents
could be placed satisfactorily without the need for fluoroscopy, thereby
minimizing radiation exposure to patients and staff. Although literature on
the Ultraflex stent and its long-term complications is limited, we believe that
given its excellent flexibility and biocompatibility, the Ultraflex stent may
prove to be a good prosthesis for complex malignant airway lesions.
VII. Adult Airway Foreign Body Removal
Prior to the availability of bronchoscopy, foreign body aspiration (FBA)
was associated with high morbidity and mortality. Although historically the
first foreign body was removed with RB, FB has revolutionized the care of
these patients. Today, the flexible bronchoscopy is the instrument of choice
for the diagnosis and removal of airway foreign bodies in adults [99-101], as
it allows better visualization of distal airways, and it can be performed in an
outpatient setting with the patient under local anesthesia. With improved
accessories, increased experience and expertise in FB, and diminished
training in RB, we are confident that FB will playa greater role in the
management of FBA in the future.
A. Technique
Accessories for the Flexible Bronchoscope
Available accessories for foreign body retrieval via FB include grasping
forceps, baskets, multi pronged snares, a magnet extractor, and balloon
catheters. Each device and its indications have been described [102].
Cryotherapy
The cryoprobe, passed through the working channel of a flexible
bronchoscope, can be used to retrieve an airway foreign body by placing
the tip in contact with the object and effecting freezing until the point of
contact is frozen. This adheres the object to the probe and allows for
removal of the object en bloc. Cryotherapy is especially useful for clots,
mucous balls, friable organic material, and small inorganic objects [103,104].
Nd:YAG Laser
Occasionally, laser can assist in foreign body removal by breaking up large
objects, vaporizing surrounding granulation tissue to dislodge embedded
foreign bodies, and blunting the edges of sharp objects to avoid injury of
nearby structures during extraction.
Therapeutic Flexible Bronchoscopy: Overview 7J
Steps to Foreign Body Retrieval
The principle in foreign body removal is to avoid pushing the object distally.
We have found the Fogarty balloon [101,105] to be particularly helpful in
bringing the object proximally into the trachea. Once the object is in the
trachea, the patient is asked to sit up and cough it out. Our success rate with
this technique is 90% for small friable foreign bodies.
Larger foreign bodies, on the other hand, can be broken into smaller
fragments by laser and removed with grasping instruments. It is important
to maintain constant visualization of the object, keep it in the center of the
airway during retrieval, and never remove it through the working channel of
a flexible bronchoscope. Instead, it should be removed as a single unit-
bronchoscope, grasping instrument, and foreign body-via the oral route.
In instances where an endotracheal tube is used, tube withdrawal may be
necessary if it is unable to accommodate the object [101].
VIII. Bronchoalveolar Lavage
Pulmonary alveolar proteinosis (PAP), whjch is characterized by the
accumulation of proteinaceous material in the alveoli, is a rare disease
associated with defective function of alveolar macrophages [106], abnormal
surfactant proteins [107], cytokine imbalance [108], and defective expression
of granulocyte-macrophage colony-stimulating factor (GM-CSF) or its
receptors on alveolar macrophages and type II pneumocytes [109].
Bronchoalveolar lavage or therapeutic whole-lung lavage (either one lung
or sequential two lung lavages per anesthesia session) is considered to be the
most effective treatment for PAP, as it not only mechanically removes the
lipoproteinaceous material through repeated dilution with saline solution,
including removal of anti-GM-CSF antibody, but also possible immuno-
logical effects on the alveolar macrophages and type II pneumocytes [110].
However, the technique requires general anesthesia and an experienced
anesthesiologist competent in placing a double-lumen endotracheal tube
(ETT). In addition, hypoxemia and hemodynamic instability can occur
during whole-lung lavage [III].
Segmental or lobar lavage has been reported to be a therapeutic
alternative to the whole lung lavage but requires special equipment such as a
cuffed bronchoscopic catheter with fluoroscopy [112], or a modified
bronchoscope with an inflated tracheostomy cuff [113], or trypsin as lavage
fluid [114]. Recently, Chen et al. [115] described a novel approach of
multiple lobar lavages using standard FB equipment, local anesthesia, and
normal saline solution for management of PAP. Bronchoscopic lavage was
performed in three patients under local anesthesia (Xylocaine [lidocaine]
72
Lee and Mehta
2%). No parenteral sedation or anesthesia was required and warm saline, in
aliquots of 50 mL, was instilled into the bronchus corresponding to the most
severely affected lobe observed on high-resolution CT scanning. Lobar
lavages were repeated every 2-3 days, and good clinical, physiological, and
radiological responses were demonstrated in patients with less advanced
disease.
IX. Aspiration of Mediastinal Cysts
Mediastinal cysts result from embryological aberrations and anomalous
budding of the primitive foregut and early tracheobronchial tree. They
represent 9% of all primary mediastinal masses in surgical series [116,117].
These malformations can be divided into bronchogenic cysts, esophageal
duplications, and neurenteric cysts. Bronchogenic cysts are the most
common, accounting for 54-63% [117], and are usually located in the
subcarinal or paratracheal area [118].
Most mediastinal cysts are detected as incidental findings on routine
chest radiographs or esophagograms; however, compressive symptoms such
as stridor, dyspnea, persistent cough, or dysphagia can occur. CT plays an
important role not only in differentiating a benign cyst from mediastinal
malignancy (119] but also is a road map for the bronchoscopist to perform
transtracheal or transbronchial needle aspiration for a diagnostic or
therapeutic indication. Thus, the need for invasive mediastinoscopy or
thoracotomy can be avoided.
A. Technique for Transtracheal or Transbronchial Aspiration
The procedure is performed via FB with the patient under local anesthesia
and conscious sedation. Based on the CT location of the mediastinal cyst,
the flexible bronchoscope is introduced to the appropriate level, and a
biopsy system consisting of 120-cm-Iong polyethylene sheath and a 18-,21-
or 22-gauge 12-mm needle (Bard Corporation, Bellerica, MA) is passed
through the working channel of the bronchoscope FB until the needle hub is
visualized. The needle is then inserted into the target site and the underlying
cyst is aspirated using a 30- or 50-mL syringe connected to the proximal
Luer-Lok port. Fluid aspirated from the mediastinal cyst is sent for
cytopathological examination and cultures. CT is performed thereafter to
assess the success of intervention as well as to detect complications such as
bleeding, abscess formation. or pneumomediastinum.
Therapeu! ic Flexible Bronchoscopy: Overview
X. Drainage of Lung Abscess
73
Treatment for lung abscess includes antibiotics, chest physiotherapy, and
surgery where conservative measures fail. Bronchoscopic placement of an
indwelling catheter into abscess cavity is a noninvasive alternative, as it not
only allows for aspiration of pus for culture but also drainage and irrigation
of the abscess. Good results with this method have been demonstrated
thereby obviating the need for surgery [120]; however, care to avoid s p i l l ~
of pus into airways must be exercised.
XI. Massive Hemoptysis
Massive hemoptysis, defined as the volume of expectorated blood that is life
threatening as a result of hypoxia from airway obstruction or hemodynamic
instability from blood loss, accounts for only 4.8-14.0% of all patients with
hemoptysis [121]. Although issues such as optimal timing of bronchoscopy
and preferred instrument (RB vs FB) in the initial assessment remain
controversial [122-124], our practice is early bronchoscopy with a flexible
bronchoscope as it allows better localization of the site of hemorrhage as
well as institution of specific endoscopic treatment to arrest bleeding.
A. Technique for Bronchoscopic Therapy
Topical application of ice-saline lavage or epinephrine (1:20,000) via a
flexible bronchoscope is effective in achieving control of hemorrhage
[125,126]. Endobronchial tamponade can be performed by wedging the tip
of the bronchoscope into the bleeding segment followed by inflation of a
balloon catheter (4-7 French), which is introduced through the working
channel. The flexible bronchoscope is removed over the catheter and the
balloon is left inflated in the bronchus for 24 hr. FB is performed the next
day, and if no further bleeding is observed after deflation of the balloon, the
catheter is removed. Although no complications have been reported
[127,128] with this technique, extended use of balloon tamponade catheters
may result in mucosal ischemic injury and postobstructive pneumonia.
A modification of this technique has also been described. It first
involves placement of an angiographic J guide wire into the affected
bronchial segment via a flexible bronchoscope. The latter is then removed
over the wire and reinserted into the opposite nostril, thereby allowing
better suctioning of blood and visualization of the bleeding site. An
appropriate balloon catheter is then inserted over the guide wire into the
bleeding segment under direct vision [129]. Another modification is the use
of a double-lumen bronchus-blocking catheter which has an inner channel
74 Lee and Mehta
for instillation of cold saline, epinephrine, and thrombin/thrombin-
fibrinogen solutions, an inflatable balloon at the tip, and a detachable
valve. This catheter can be introduced via the working channel of the
flexible bronchoscope and wedged in the bleeding segment for several days
without complications while the patient receives definitive therapy (130).
Other therapeutic modalities shown to be beneficial in the control of
hemorrhagic endobronchial lesions include Nd:YAG laser, EBES and
APC.
XII. Bronchoscopy in Intensive Care Unit
A. Retained Secretions and Atelectasis
Despite widespread acceptance of bronchoscopic suction as treatment for
retained secretions and atelectasis, its superiority over chest physiotherapy
has not been clearly established [131]. Although studies showed that flexible
bronchoscopic suction for whole lung collapse and lobar atelectasis resulted
in better oxygenation in 44% [132] and radiological improvement in 88%
[133], Marini et al. [134] found no difference in the extent of radiological
improvement between therapeutic FB and chest physiotherapy for post-
operative lobar atelectasis.
However, therapeutic FB may be lifesaving for some patients, and
should not be withheld even in the presence of hypoxia [135,136]. Moreover,
clearing thick mucous plugs and secretions by flexible bronchoscopic suction
may facilitate weaning of asthmatics from MV [137,138].
B. Endotracheal Intubation
FB can be used to guide placement of oral or nasal ETTs in patients with
compromised upper airways or in those with restricted neck mobility [139].
It also facilitates change of the ETT without losing control of the airways
[140], placement of double-lumen endobronchial tubes for either one-lung or
two-lung ventilation [141,142], and difficult nasogastric intubation [143]. In
addition, jet ventilation can be applied through the working channel of the
flexible bronchoscope to ensure ventilation of anesthetized and paralyzed
patients until the airways are secured (144).
C. Percutaneous Dilatational Tracheostomy
Recently. FB has become increasingly important in enhancing the safety of
percutaneous dilatational tracheostomy (PT) performed for patients
dependent on MV. PT is a bedside tracheostomy technique that consists
of percutaneous needle puncture of the trachea followed by stepwise dilation
and placement of a tracheostomy tube [145].
Technique
PT is performed in a supine, adequately anesthetized and ventilated patient
in the intensive care unit (leU) with continuous heart rate, oxygenation,
and blood pressure monitoring. A trained operator (pulmonologist, medical
intensivist, or surgeon) and two assistants, one who is competent in FB
(pulmonologist, anesthesiologist) and the second who takes care of the ETT,
ventilatory requirements, sedation, and monitoring, are required for the
procedure.
The patient is positioned with the head extended; an assistant at the
head' of the patient withdraws the ETT under bronchoscopic visualization
until the tip is just below the vocal cords. A skin incision, 1.5-2.0 em, is
placed above the first or second tracheal cartilage interspace, and a 12- or
IS-gauge needle is inserted in the midline under bronchoscopic visualization
to avoid paratracheal insertion or damage to the ETT and cuff. FB is used
intermittently during PT to avoid hypercapnia from decreased minute
ventilation. When free bubbles are aspirated into the syringe, indicating that
the tracheal lumen is entered, lidocaine is instilled to decrease the cough
reflex and a guide wire is introduced into the trachea through the needle.
Dilators of increasing sizes are used until the dilator preloaded with the
appropriately sized tracheostomy tube is inserted. The position of the
tracheostomy tube is checked with FE. The guide wire, dilator, and ETT are
then removed, and a chest radiograph is performed to confirm the position
of the tracheostomy tube and to detect complications, which are discussed
below.
Indications for PT are similar for surgical/open tracheostomy (OT). Major
advantages of bedside PT include obviating the need for transport of
critically ill patients to the operating room (OR) and OR availability. Others
include a smaller skin incision, reduced risks of major hemorrhage, and late
sequelae such as subglottic stenosis [146].
Skin infection, unstable cervical spine, and increased intracranial
pressure are absolute contraindications for PT, whereas high ventilatory
requirements, coagulopathy, marked obesity, and anatomical abnormality
(goiter) are relative contraindicatioris [147]. Although bleeding during the
procedure is commonly encountered and easily controlled, major hemor-
rhage requiring blood transfusion has been reported. Other complications
encountered during PT include mucosal tears, submucosal tunnelization of
76
Lee and Mehta
the tracheal wall, perforation of the posterior tracheal wall causing
tracheoesophageal fistula, paratracheal insertion, barotrauma (pneu-
mothorax, pneumomediastinum, subcutaneous emphysema), ETT and
flexible bronchoscope damage, stomal infection, and early dislodgement
[146-149].
Although similar early and late complications were observed with OT
and PT [149-152], Hazard and coworkers [150] demonstrated a higher
complication rate with OT (45.8%) than with PT (12.5%), increased
occurrence of delayed stomal healing, and significant subglottic stenosis
(88% OT, 27% PT). Accidental decannulation was also observed more
frequently in OT (41%) than PT (12%), which led to two deaths in the OT
group where reinsertion of the tracheostomy tube could not be performed
despite the presence of retention sutures [151].
XIII. Other Applications of Therapeutic Bronchoscopy
Other uses of FB in the leU include administration of surfactant and liquid
ventilation for patients with acute respiratory distress syndrome [153], N-
acetylcysteine for mucous plugging [128], foreign body removal [98], and
instillation of fibrin glue into the affected bronchial segment as treatment for
persistent bronchopleural fistula [154,155].
XIV. Future Applications of Therapeutic Bronchoscopy
A. Bronchoscopic Volume Reduction
Lung volume reduction surgery (LYRS) has been shown to improve
respiratory function, exercise capacity, and quality of life in approximately
75% of recipients with advanced emphysema in both cohort and randomized
studies [156,157]. It is estimated that 1.5 to 2.0 million people with
symptomatic advanced emphysema in the United States could benefit from
LYRS, but to date, only 15-20% of them are considered to be eligible for
surgical LYRS [158]. LYRS involves the removal of damaged and
nonfunctioning lung and "resizing" the overexpanded lung into a normal-
sized chest cage. This procedure results in an increase in vital capacity,
improvement in respiratory mechanics. and palliation of symptoms [159].
Therefore, Ingenito and coworkers [160] experimented with a novel idea to
induce sustained collapse and subsequent scarring of nonfunctioning lung
nonoperatively by FB. This study was conducted in 12 sheep with
emphysema produced by inhalation of papain. The animals were divided
into three treatment groups of four animals: (1) surgical volume reduction
(SYR). (2) bronchoscopic volume reduction (BYR), and (3) bronchoscopy
alone (sham BYR). Collapse of the lung was achieved by (l) filling target
regions of lung with oxygen, an absorbable gas that promotes atelectasis; (2)
rinsing target airways with biocompatible "antisurfactant" solution to
promote destabilization; (3) applying suction to remove residual surfactant
and cause rapid collapse; and (4) injecting a biocompatible fibrin-based glue
to produce sealing and maximze atelectasis. The response to each
intervention was assessed at 8-12 weeks with lung function and lung tissue
examination. Decreases in total lung capacity and residual volume were
observed in both BYR and SYR groups, and tissue examination showed
that BYR caused collapse of the lung with focal scarring in 55% of target
areas. The investigators concl uded that lung volume reduction could be
achieved in animals by FB and fibrin glue, but BYR is still largely
experimental at present.
B. Research and Gene Therapy
In the arena of gene therapy, defined as a medical intervention that modifies
the genome of a living cell, the flexible bronchoscope is an ideal tool for the
delivery of vectors of gene therapy directly to the lungs for in vivo strategies
or cell harvesting for in vitro genetic manipulation, which can then be
reintroduced back into the lung. This represents an exciting field of research
and may herald hope for treatment of hereditary disorders such as alphal-
antitrypsin deficiency and cystic fibrosis and for cancer, bronchitis,
emphysema, and asthma in the future [161-163].
XV. Conclusion
Bronchoscopic techniques like LPR, EBES, APC, cryotherapy, brachyther-
apy, stents, and PDT are effective tools in the palliation and local control of
lung cancer. Therapeutic bronchoscopy is not only effective in relieving
dyspnea, controlling hemoptysis, and improving the quality of life,
importantly it also avoids the need for MY in patients with respiratory
distress, facilitates weaning from MY, and allows time for the institution of
XRT and chemotherapy. In early lung cancer, PDT, cryotherapy,
brachytherapy, EBES, and LPR may represent treatment alternatives in a
select group of patients.
Preliminary results of bronchoscopic LYR on animals belie the
promise of an attractive alternative to surgical LYR for treatment of end-
stage emphysema, whereas the role of FB in gene therapy for pulmonary
diseases will continue to grow as vector technology and specific assays to
detect gene transfer impw
ve
.. ht d M t . I
c.;opyng e a ena
78 Lee and Mehta
As the cost of technology challenges health care delivery systems, the
future for therapeutic bronchoscopy lies in the unrelenting evaluation of its
impact on patient outcome, survival, and cost. Despite the rapid
development of competing technologies for less invasive approaches to
clinical problems, the applications of FB will continue to expand in medicine
as well as research, and reaffirm its role in the twenty-first century as an
essential component of pulmonary practice.
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5
Laser Bronchoscopy for Malignant Disease
JOSE PABLO DiAZ-JIMENEZ
Bellvitge University Hospital
Barcelona, Spain
ALICIA N. RODRIGUEZ
Hospital Privado de Comunidad
Mar del Plata, Buenos Aires,
Argentina
Since the 1930s there has been a clear desire among bronchologists to use
endoscopic methods to eliminate large neoplastic or iatrogenic obstructions
of the central airways. In 1935, Kramer and Som [I] published results of
endoscopic resection of bronchial adenomas in 20 patients. In a follow-up
study years later, they noted that 50% of the 14 patients that had been
adequately treated were cured or free of symptoms [2]. Further attempts at
endoscopic resection of malignant lesions were often abandoned because
potential improvements in pulmonary function were frequently offset by the
significant risk of hemorrhagic complications.
Laser photoresection as well as cryotherapy, electrocautery, brachy-
therapy, photodynamic therapy, and mechanical tumor removal are recent
techniques used in symptomatic patients with either malignant or benign
endoluminal pathology. Since the early 1980s there have been many
advances in the use of lasers in the tracheobronchial tree. There is now a
large body of medical literature attesting to the contribution of lasers in the
treatment of intraluminal airway disease.
89
90 Dfaz-Jimenez and Rodriguez
The term laser is an acronym for light amplified stimulated emission of
radiation. This concept resulted from the theories of stimulated emission
described by Albert Einstein in 1917 [3]. The first laser was produced in
1960, when Maimann used a ruby crystal to manufacture a laser apparatus
that emitted a red-colored radiation [4]. In the last 40 years, laser use has
multiplied vastly in many fields, including industry, communications,
armaments, and especially medicine.
Laser technology was first applied to treat airway conditions in the
1970s. Advances in fiberoptic technology in the late 1970s allowed laser
technology to be combined with endoscopic procedures. The first report of
airway lesions in human beings treated with a neodymium-yttrium-
aluminum-garnet (Nd:YAG) laser was published by Toty et al. in 1979
[5]. The use of the laser has changed the approach to therapy of benign and
malignant tracheobronchial conditions. With the new developments in laser
technology, laser application has become safer, faster, less invasive, and also
less expensive. Once limited to a few centers, laser use is now more
widespread and accessible, and it is expected to be even more so in the
future.
The main goals of laser treatment for malignant airway conditions (Fig. I)
are to remove exophytic, intraluminal, proximal tracheobronchial obstruc-
tions, reestablish ventilation, eliminate secretions accumulated distally to
the obstruction, and relieve related symptoms, such as hemoptysis, cough,
dyspnea, difficulty clearing secretions, or postobstructive infections
(Table I). The need for laser treatment is related to the location of the
tumor rather than to the histological cell type. The best therapeutic results
are obtained with centrally located tumors, which are easily accessible and
allow for safe laser delivery. Moreover, patients presenting with these
tumors are the ones who benefit the most from a symptomatic standpoint,
Table 1 Laser Indications in Malignant Conditions
Remove malignant, primary or metastatic, exophytic, intraluminal, proximal
tracheobronchial obstructions
Symptomatic relief of dyspnea, hemoptysis, cough, postobstructive infections
Decrease lumor burden before other [rea tmenls
91
(a)
(b)
Figure 1
Tracheal tumor before (a) and after (b) treatment.
92 Diaz-Jimenez and Rodriguez
since relief of respiratory distress after laser application is usually
immediate. In symptomatic patients with malignant central airway
obstruction, the relief of that obstruction should be the first therapeutic
measure. Distally located tumors are more difficult to reach and do not
significantly alter ventilation or breathing. In these locations, the main
indication for laser photoresection is drainage of secretions causing infection
distal to the obstruction.
Primary or metastatic malignant lesions are the main indications for
laser therapy. The most common cell type treated is squamous cell
carcinoma of the lung (64%) followed by adenocarcinoma of the lung
(9%). Metastatic lesions to the lung represent approximately 20:;'0 of the
indications. Common primary tumors that produce endobronchial
metastasis are melanoma, colon, kidney, thyroid, and breast carcinoma
[6,7]. Another frequent indication for laser bronchoscopy is carcinoma of
the esophagus, which produces obstruction of the central airways by
direct extension from the primary tumor or from enlarged mediastinal
lymph nodes. Benign lesions such as hamartomas, fibromas, papillomas,
lymphomas, amyloidosis of the airway, and osteoplastic tracheopathy
represent uncommon indications. When applied to treat benign condi-
tions, laser therapy can frequently be a curative treatment. Some
applications may require more than one laser session, which holds true
for both malignant tumors and some benign conditions that have a
tendency to recur. Another less common indication is represented by slow-
growing tumors such as carcinoid tumors and mucoepidermoid and
adenoid cystic carcinoma. When possible, surgical resection of these
tumors is preferable, but laser therapy is a valid alternative when there are
contraindications to surgery [8,9]. Other miscellaneous indications are
treatment of inflammatory granulomas, benign tracheobronchial stenosis
(Fig. 2), papillomatosis, suture removal, control of hemorrhage in
bleeding tumors, and foreign body removal, which often requires
elimination of granulation tissue surrounding the foreign body. Combina-
tion of laser therapy with other palliative methods, such as external or
internal radiotherapy (brachytherapy), is possible in selected cases and can
be very advantageous.
The only absolute contraindications to laser bronchoscopy are the
absence of an intraluminal lesion and complete tracheal or bronchial
obstruction. However, we have found that some of these lesions can be
successfully treated by experienced operators (Table 2). Some other
contraindications listed in the literature include tracheobronchiomalacia
or fractured cartilage rings, tracheoesophageal fistula, ipsilateral vascular
involvement by tumor, and bronchial obstruction with distal collapse for
over 4-6 weeks [10]. However, it is our experience that none of the above is
(a)
(b)
93
Figure 2
Benign tracheal stenosis before (a) and after (b) laser treatment.
Table 2 Laser Contraindications
Absolute Relative
Absence of endoluminallesions (external
compression)
Complete tracheobronchial obstruction
Tracheobronchiolmalacia or fractured
cartilaginous rings
Low performance status, short life
expectancy
Highly obstructive lesions
Pulmonary artery compromise
Bronchial obstruction for over 4-6
weeks
Related to general anesthesia
Cardiovascular instability
Sepsis, coagulation disorders, electrolyte
abnormalities
an absolute contraindication. We have successfully treated large tumors
contiguous with blood vessels and also reopened bronchial segments that
have been closed for more than 4 weeks.
Relative contraindications are related to the risks of general anesthesia
including cardiovascular instability, recent myocardial infarction, arrhyth-
mias, severe hypotension, and unstable cardiac insufficiency. Some other
conditions that might contraindicate endobronchial laser therapy have to be
considered including sepsis, coagulation disorders, and electrolyte abnorm-
alities. A patient with advanced malignancy, low performance status, and a
short life expectancy is not a good candidate for laser therapy.
Some special situations require particularly meticulous care with the
laser (Table 3). Treatment should not be attempted unless the operator has
considerable experience handling the rigid bronchoscope and operating the
laser. These special cases include lesions of the posterior wall of the trachea,
previous radiation therapy to the airway, bilateral main stem bronchial
obstructions, and postpneumonotomy patients.
Table 3 Special Risk Situations
Absence of bronchial lumen
Lesions of the posterior wall of the trachea
Prior airway radiotherapy
Postpneumonectomy pa tien ts
IV. Equipment
95
Several manufacturers produce the medically approved Nd:YAG lasers, all
of which share common characteristics:
Adjustable power: to approximately 100 watts
Adjustable length of laser pulses: from 0.1 to 9.9 sec, allowing
intervals of 0.1 sec
Coupling laser fiber that consists of a quartz core surrounded by a
Teflon sheet
Coaxial flow of gas (air, nitrogen) that cools the tip of the fiber and
prevents accumulation of debris
Foot pedal by which the operator activates the laser and also
controls the coaxial flow of the cooling gas
Two types of laser fibers can be used, contact or noncontact. When
using the noncontact fiber, the laser energy delivered to the tissue can be
controlled by altering the distance between the fiber tip and the target
tissue. Since the 1064-nm wavelength of the Nd:YAG laser is in the
invisible spectrum, another laser is added to the system to provide an
aiming beam. This is usually a helium-neon laser (He-Ne) which produces
red light.
The original Nd:YAG laser machines were as large as refrigerators
and cumbersome to move, and they had a noisy, complicated cooling
system. Now the size of the laser machine is considerably smaller and the
cooling system is much less complicated. It is now very easy to move a laser
from an operating room to a procedure room, for instance. Moreover, the
new diode lasers are even smaller and more portable and are priced at
two-thirds the cost of a Nd:YAG laser. The price of the equipment
varies according to the type and generation of laser and the country in
which the sale takes place, as does the general reimbursement for laser
treatment.
In Spain, a diode laser apparatus can be bought for approximately
$37,000 U.S. dollars. The Nd:YAG laser machine sells for around
$65,000 U.S. dollars. The overall cost for a laser treatment is approxi-
mately $1,800 U.S. dollars considering professional charges (broncho-
scopist and anesthesiologist) and operating room expenses. In South
America, an Nd:YAG laser machine can be purchased for approximately
$60,000 U.S. dollars. Estimated procedure charges including laser
session, anesthesia, and I-day in the intensive care unit (lCU) are $2,600
U.S. dollars.
v. Theory and Application
A. Physical Concepts
The electrons of some atoms, molecules or ions, can be moved to a level of
higher energy by the absorption of external energy that may be derived from
an electrical, chemical, or optical source. The atom then enters a so-called
"excited state," which lasts only a small fraction of time (microseconds to
nanoseconds). After this brief period, the atom falls spontaneously to its
basal state, liberating the previously absorbed energy in the form of photons
of light that are emitted in all spatial directions. This spontaneous emission
of energy is called photonic radiation. The amplification by stimulated
emission of radiation occurs when a number of atoms becomes excited,
forming an "inverted population" that produces energy in the form of
fluorescence as the atoms return to their basal, nonexcited state, which is
also called "ground state." This inverted population must be present for the
production of laser radiation. The stimulated emission occurs when a
photon of a certain wavelength collides with an already excited atom. This
interaction stimulates the production of an identical photon; the two
photons will then be propagated in a synchronous, parallel fashion,
doubling the intensity of the resulting light. Since these two photons are
identical, the light that is created is at the same point and time. This is called
coherent light, and is one characteristic of laser light. These photons
stimulate other excited atoms leading to the production of more identical
photons, and eventually, a cascade of light will be liberated with identical
wavelength properties. The light continues to be emitted as long as the
inverted population lasts.
A laser instrument is manufactured to accommodate all the necessary
elements needed to produce and enhance stimula ted emission of radiation
and to produce a beam of light. The basic ingredients of a laser include a
source of energy, an ionic media, a resonant chamber, and a reflecting
system. The energy source is most commonly electrical, but it could be any
other source of energy, including light from another laser. The ionic medium
is the active medium and gives the laser its name. It can be a solid (Nd:YAG
laser), a liquid (dye lasers), or a gas (C0
2
laser). The medium is contained in
a so-called resonant chamber, or optic cavity, within a cylinder. Two
reflective mirrors, parallel to each other, close the ends of the cylinder; one
of them is highly reflective and the other one is only partially reflective.
Photons reflect back and forth between the mirrors. Some of the light
produced is allowed to exit the device through the partially reflective mirror,
producing the laser beam (Fig. 3). From this point, a series of accessory
instruments such as lenses, mirrors, prisms, or optical fibers are used to
capture the laser ray and to direct, attenuate, and focus it according to need.
97
Figure 3 Laser physics. Photons reflect back and forth between the mirrors and
some of the light so produced is allowed to exit the device through the par'tially
reflective mirror, originating the laser beam.
Laser light differs from other forms of luminous radiation in that it is
monochromatic, meaning that all photons in a laser beam are of the same
wavelength. It is coherent, meaning that all photons are synchronized in time
and space; they are "in phase." This differs from white light, whose photons
travel randomly in all directions. Finally, laser light is collimated, meaning
that all elements of the laser beam are parallel; in contrast to conventional
light that diverges in all spatial directions. Collimation is the characteristic
that allows laser light to be transmitted through optical fibers (Figs. 4 and 5).
For therapeutic medical applications, the effect of laser on tissue can
be classified as thermal, chemical, and acoustic [12].
B. Thermal Effect
A thermal effect is the basis for laser photoresection. When the absorbed
laser energy strikes tissue, it is transformed into heat. The resulting heat
generates tissue destruction by carbonization, vaporization, and/or combus-
tion. Human cell damage occurs at approximately 43-45 C when enzymatic
and protein denaturalization take place [13]. At higher tissue temperatures,
several effects can be observed. For example, there is a characteristic change
in the color of tissue, which becomes pale or whitish owing to protein
denaturalization. Few measurements of carbonization and ablation have
been studied in vivo. The exact temperature at which these changes take
effect is variable and depends on the length of exposure time and the
amount of affected protein. When tissue has been heated to a temperature
between 60 and 65C, thermal clotting of collagen can be seen on
histological specimens. Water vaporization occurs at approximately
100 0c. It is detected grossly by the presence of bubbles. Carbonization
appears at approximately 150C, and ablation of tissue takes place at
I
-- I ==t---__
_ ~ -"-
---
Figure 4 Behavior of laser beam and normal light in contact with a prism.
around 300C. The temperatures of ablation, carbonization, and combus-
tion vary according to tissue perfusion and composition. In addition to the
immediate thermal effects, there is often a delayed thermal effect that can be
observed hours to days after laser application.
Generally, it is difficult to evaluate visually the extent of the thermal
damage produced by the laser. Thus, the therapeutic use of the laser thermal
effect is very much empiric and relies on the experience of the physician
applying the therapy. However, research in this field remains active and
hopefully will produce more specific guidelines on laser use. Every effort
should be made to develop objective methods to evaluate and measure laser
effects on tissue.
C. Acoustic Effect
Laser irradiation in pulses of 10-
6
sec or less introduces high levels of energy
into the target area, leading to a rapid heating of the impacted point. The
mechanical shock wave thus generated produces cellular explosion and is
able to disrupt or ablate the treated tissue without any verifiable thermal or
chemical reaction [14,15]. This laser effect is used mainly in ophthalmology
and urology and for endovascular applications [16-18] .
.1lII:I1I----
----
-----
Figure 5 Behavior or laser beam and normal light in contact with a prism.
99
D. Chemical Effect
The therapeutic application of the chemical effects of the laser is represented
by photodynamic therapy (PDT). During PDT, laser light is focused on a
previously sensitized cell, internal cellular balance is disrupted, and cellular
destruction takes place. The laser chemical effect also has a potential
diagnostic application because of the characteristic fluorescence that
malignant cells exhibit when they are irradiated by a laser light of a
particular wavelength. This provides a mechanism for early detection of
malignant lesions in the airway. Early detection of malignant conditions and
photodynamic therapy are described in detail in Chapters 14 and 15.
E. Laser-Tissue Interactions
The particular behavior of a laser when it strikes tissue depends in part upon
the substance used in the ionic media, which gives the laser its name and
characteristic light wavelength. However, the final result depends on the
interaction between the laser and the thermal, optical, chemical, and
physical properties of the treated tissue. The thermal effect obtained with a
laser light is also directly proportional to the power delivered and the length
of exposure time, and is indirectly related to the targeted area.
Power density is a physical concept that refers to the power
transmitted per unit area of a laser beam. It is measured in watts per
square centimeter [19]. It is inversely proportional to the square of the
diameter of the focal target. Practically, this means that laser effects are
related to the distance between the target tissue and the tip of the laser fiber,
and thus can be altered by moving the fiber closer to or farther from the
treated area, as this movement will increase or decrease the beamed area.
A laser's wavelength will determine the degree of scattering, depth of
tissue penetration, and amount of energy absorbed by the tissue. The
scattering coefficient of a tissue determines the amount of laser energy that is
reflected away from the target. The tissue distribution of the laser light will
depend on the characteristics of the treated organ, particularly its capacity
to reflect, absorb. or transmit the laser beam. Laser light is absorbed by
tissues according to their coloration; a pale and poorly vascularized tumor
will allow the laser beam to pass through without injuring its surface. The
laser effect may occur deep within the tissue. Higher laser absorption relates
to more heat production. It is important, therefore, to master laser-tissue
interactions before attempting laser photoresection in order to prevent
complications.
Some factors influencing the biological effects of laser light include
power at the head and tip of the laser fiber, lasering time, type of fiber
(contact or noncontact), perpendicular versus tangential tissue irradiation,
100 Diaz-Jimenez and Rodrigue::
changes in the distance to the target, local temperature, local blood supply,
length of laser pulses, interval between laser pulses, chromatic character-
istics of the tissue affecting absorption, and scattering coefficients. The
choice of a particular laser will depend on the type of tissue treated and
whether it is used for diagnostic or therapeutic purposes.
F. Types of Lasers
There are many medical lasers available and several that can be applied to
the airway. The lasers most commonly used to treat airway conditions are
described below. See Table 4 for a brief description of other available lasers.
Table 4 Types of Lasers
Argon 488
Argon dye 514
630
Diode 810
630
Type
Nd:YAG
KTP
YAP
Wavelength (nm)
1064
1320
532
10,600
930
1064
1079
1340
Characteristics
Deep penetration
Reliable photocoagulation
Good absorption by water,
facilitating vaporization
Invisible light
Visible, transmitted
through clear tissue,
absorbed by pigmented
tissues
Invisible
Poor hemostatic effects
Minimal damage to
surrounding tissues
Blue-green color. poorly
absorbed by clear tissues'
Becomes red when colorant
added
Visible
Invisible
Advantages/
disadvantages
Optic fiber application
Deep penetration
Good coagulation
Good deep coagulation
Good cutting properties
Minimal thermal damage
to surrounding tissues
Application through
flexible quartz fibers
Good cutting properties
Poor coagulation
Cumbersome application
system
Photodynamic radiation
Small size
Versatile
Good coagulation
Used for photoresection
and photodynamic
therapy
Similar to Nd:YAG
Laser Bronchoscopy for Malignant Disease fO}
The carbon dioxide (C0
2
) laser was the first to be used within the
airways [20]. This laser was first developed in 1964 [21]. It has a wavelength
of 10,600 nm (mid infrared region of the electromagnetic spectrum), which
provides very good tissue absorption, especially tissue with a high water
content. Scattering is minimal, soft tissue vaporization is rapid, and there is
minimal damage to surrounding tissue. CO
2
laser energy tissue penetration
is predictable, making it ideal for surgical applications; it is a "light
scalpel."
The CO
2
laser was used for many years to treat airway lesions, but
after the Nd:YAG laser was introduced, its use has been reserved mainly for
several otolaryngological procedures, such as uvulopalatoplasty (UPPP)
and treatment of laryngeal and upper tracheal lesions. Its application in the
airways is limited by the lack of good coagulation properties, particularly
when treating lesions with blood vessels of 0.5 mm or greater in diameter.
Also, its energy cannot be transmitted through optical fibers but must be
delivered along with a somewhat cumbersome system of mirrors and
articulated arms. In CO
2
laser bronchoscopy there is often a need to connect
the bronchoscope to a micromanipulator and a surgical microscope, which
further limits its use in the airway.
The Gold laser and liquid pigment lasers (argon dye, 630 nm) are used in
PDT to irradiate early malignant lesions that have been previously sensitized
by a photosensitizer. In the liquid lasers, also called tunable dye lasers, the
dye is the active medium and the source of energy comes from another laser
(ruby, argon, krypton, Nd:YAG). Laser radiation passes through the dye
and exits as a specific wavelength that is determined by the dye.
The helium-neon laser does not have any therapeutic application, but it
is often combined with therapeutic lasers in order to produce a visible
aiming light. This allows for accurate application of a therapeutic laser,
since some of them (e.g., Nd:YAG and CO
2
lasers) emit a nonvisible beam.
Because of its unique effects on living tissue and its ideal delivery
properties, the Hd: YAG laser is felt by many to be the preferred laser for use
in the airway. It has very good coagulation properties and great depth of
penetration. It can be applied through optical fibers, and it is easily adapted
for use in either flexible or rigid bronchoscopy; thus, laser energy can be
delivered to any point in the bronchial tree. The laser beam can have
wavelengths of 1320 or 1064nm, both of which are outside the visible
spectrum. Thus, the addition of a helium-neon aiming beam is required to
indicate the area of impact. Also, because of its wavelength, the absorption
ofNd:YAG laser energy exceeds its dispersion for most vascularized tissues.
This allows for optimal coagulation of bulky vascular tumors. The energy
can penetrate nearly 10 mm in depth and can coagulate large blood vessels
(2 mm diameter). The bronchoscopist must understand the biological effects
of the Nd:YAG laser before using it in the treatment of thoracic tumors.
The location of malignant tumors of the tracheobronchial tree and their
relationship with mediastinal organs, particularly the great vessels and the
esophagus, make any mishap during laser application a potential
catastrophe for the patient. In the United States, the Food and Drug
Administration (FDA) approved the Nd:YAG laser for photoresection of
airway tumors in 1984. The Nd:YAG laser is currently the one most used in
the airway [22,23]. Unless specified otherwise, we will refer to the Nd:YAG
laser alone during the remainder of the chapter (Fig. 6).
The 5-KTP laser (potassium-titanyl-phosphate) emits light energy with
double the frequency of the Nd:YAG laser wavelength by using a krypton
crystal. This results in the emission of a green light in the 532-nm
wavelength. By varying the power density, both photocoagulation and
precise vaporization can be obtained. At high power (2-3 W), the green light
is absorbed by red tissue, which makes it useful for treating vascular lesions,
such as angiomata, and to photocoagulate tissue before resection.
The new diode laser is a novel one that has some advantages over the
currently used devices. This laser's smaller size and portability as well as its
great power and versatility have resulted in its gaining popularity for use in
the airways. The active medium is a small ceramic chip that makes the actual
laser machine smaller and less expensive. Current diode lasers (Fig. 7) are
available in two wavelengths, 810 nm for photoresection and tissue ablation
and 630 nm ( 3 nm) for photodynamic therapy.
The YAP laser (yttrium-aluminium-perovskite) shares similar char-
acteristics with the Nd:YAG laser. It can emit various wavelengths
according to the direction of the crystal: 930, 1064, 1079, and 1340 nm.
The 1340-nm emission wavelength of YAP laser has a higher absorption
coefficient in water and body fluids compared to the 1320-nm emission
wavelength of the Nd:YAG laser.
VI. Technique
Either the rigid bronchoscope or the flexible bronchoscope can be used for
laser application in the airway. Since laser bronchoscopy is primarily a
treatment for obstruction of the central airway due to vascular malignant
tumors, many experts prefer the rigid bronchoscope for laser application.
The flexible bronchoscope is reserved for treatment of small distal lesions
producing noncritical obstruction of the airway, and which have less
chance to bleed [24]. In the rigid versus the flexible bronchoscope
controversy, most experts agree that bronchoscopists should use the
method with which they are more proficient. It is also recommended that
Laser Bronchoscopy for NJalignant Disease
Figure 6 Nd:YAG laser.
103
bronchoscopists be equally skilled in the use of both instruments, since far
from replacing each other, they are complementary [25]. Experienced
professionals take advantage of the qualities of both types of broncho-
scopes and often combine their use.
There are some particular advantages and disadvantages when
comparing the two methods. We (and most of our interventional colleagues)
recommend the use of the rigid bronchoscope in all treatments, leaving the
flexible type for special cases. The use of the rigid tube offers better handling
within the airway, allowing adequate ventilation and oxygenation as well as
more room for manipulation, better vision, more efficient aspiration of
fumes, and extraction of tumor fragments. By using the beveled end of the
rigid bronchoscope, mechanical resection is possible. Rigid bronchoscopic
104
Diaz-Jimenez and
Figure 7 Diode laser.
laser resections take less time and are associated with fewer complications,
such as profuse bleeding. With a rigid bronchoscope there can be direct
compression of a bleeding lesion and simultaneous suction of airway
secretions and blood to maintain oxygenation.
Some indications for flexible bronchoscopic laser use include small
lesions, distal lesions, less than 50% obstruction of the airway, recurrent
lesions, narrow-based pedunculated lesions, photocoagulation of bleeding
tumors, small benign tumors, granulomas, and papillomas. Table 5 lists the
advantages and disadvantages of both methods of laser application.
All laser applications must be performed in a setting where life-
threatening complications can be treated. Advanced cardiopulmonary
support equipment should be available, and professionals involved in such
procedures should be proficient in resuscitation maneuvers. Procedures can
be performed under local or general anesthesia. Various methods of
ventilation can be used: manually assisted, intermittent positive-pressure
ventilation, Sanders injection system, and jet ventilation. Some groups are
now using laryngeal masks for laser application, but we have not found this
technique to have any advantage over the more conventional techniques.
Laser Bronchoscopy for Malignanl Disease
Table 5 Rigid Versus Flexible Bronchoscope in Laser Application
105
Type
Rigid
Flexible
Advantages
General anesthesia required, more
comfortable for the operator
and the patient as well
Open tube allows the
simultaneous use of many
instruments
Allows dilatation of the airway
Allows mechanical resection
Less expensive accessories,
virtually impossible to destroy
Better equipped to overcome
serious complications
Technique is widespread
Local anesthesia can be used for
most procedures
Ambulatory procedure
Less expensive (avoids OR time,
extra personnel)
Disadvantages
Requires special training
Requires an experienced team
(anesthesiologist, nursing)
Must be performed in the OR
under general anesthesia
Extended treatment time
Most of the treatments require
more than one session
Aspiration of fume and blood is
less effective
Lack of mechanical resection,
dilatation or compression
capabilities
More expensive accessories
Flammable instruments
[s not prepared to overcome
serious complications,
particularly bleeding
OR, operating room.
The most feared complication in laser photoresection is bleeding. It is
the difficulty in managing severe hemorrhage that highlights the disadvan-
tage of flexible bronchoscopy (FB). Most of the fatalities that have occurred
in patients treated with FB were due to uncontrolled hemorrhage. The
major disadvantages of rigid bronchoscopy (RB) are the need of special
training, which is not widely available in pulmonary training programs, and
the risks of general anesthesia.
In general, however, the risks related to general anesthesia are
frequently overemphasized. Cavalieri et al. [26], in a series of 1505 patients
treated over 1I years, reported an incidence of respiratory insufficiency of
0.5%, cardiac arrest of 0.4%, and acute myocardial infarct of 0.2%. Our
experience is similar. After more than 17 years of performing laser
bronchoscopy and more than 6000 laser applications under general
anesthesia, we have had no fatalities during the procedure and in the
ensuing 48 hr.
A. Laser Application with the Rigid Bronchoscope
We prefer the use of the rigid bronchoscope for laser resections. Almost
100% of the laser treatments performed by our Laser Department employ
the rigid bronchoscope. We reserve the flexible bronchoscope for minor
procedures such as those lesions that become evident during follow-up
bronchoscopy, small tumor recurrences, or as an adjunct during rigid
bronchoscopic resections. We regularly take advantage of both devices
during the same procedure. Frequently, the flexible bronchoscope is
introduced through the rigid tube, allowing us to maintain control of the
airway and to reach distal portions of the tracheobronchial tree.
The procedure is carried out in a specially equipped bronchoscopy
room or in the operating room. Laser safety devices (e.g., darkened
windows, outside signal light, glasses) should be available, as well as basic
and advanced life-support equipment. Personnel involved in the procedure
include the operator bronchoscopist, the anesthetist, one circulating nurse,
instrument nurse (who usually is also in charge of the laser operation), and
one circulating assistant. If possible, one person should be dedicated to
control of the laser apparatus only. The team must be specially trained to:
Recognize and solve special situations related to the procedure
Deliver general anesthesia for endobronchial procedures
Follow and reinforce laser safety rules
Also, a thoracic surgery team and angiography suite should be available in
the institution in the rare situation that a major complication arises.
However, there is no need for these teams to be "standing by." In almost 20
years of practice, we have never needed emergency surgical assistance.
The use of a video camera during laser resection is recommended in
order to allow the team to follow the procedure and anticipate the
bronchoscopist's movements. It is also recommended that all laser
resections be videotaped for documentation purposes.
We used the Dumon-Harrell rigid bronchoscope for all procedures
(Fig. 8). Some other centers use the Storz rigid bronchoscope, which has a
special port for jet ventilation and its own internal light source. This
particular scope can be used without an optical telescope, although
visualization of the airway is poor and not sufficient for precise laser
firing. The Dumon-Harrel model has the advantage of built-in channels
for the laser fiber, a suction catheter, and an aspiration probe, although
107
(a)
(b)
Figure 8 (a) and (b) Dumon rigid bronchoscope.
J08
Diaz-Jimenez and Rodriguez
many times these ports are not used, as ancillary devices can be introduced
through the open end of the bronchoscope tube, making their manipula-
tion easier. The bronchoscope comes equipped with silicone caps, which
can cover the various bronchoscope ports and which can be adjusted
during the procedure to allow better ventilation/oxygenation and to
minimize air losses.
Before the laser bronchoscopy, patients undergo a presurgical
evaluation, which usually includes an electrocardiogram and coagulation
studies. The anesthesiologist is the person in charge of clearing the patient
for surgery. Once this is completed, the patient is admitted to the hospital
and taken to the operating room. The patient must abstain from food and
drink for at least 6 hr before the procedure.
We do not use jet ventilation. Our anesthesia team prefers that the
patient maintain spontaneous ventilation and will manually assist the
patient according to need. A combination of intravenous propofol and
vecuronium is used to achieve sedation and mild muscle relaxation. This
allows the patient to breathe spontaneously during the procedure, but
suppresses the cough reflex. Ventilation is manually assisted according to
end-tidal CO
2
measurements and O
2
saturation. After initial sedation and
muscle relaxation, local anesthesia is applied to the vocal cords and oral
secretions are suctioned to prepare the patient for intubation. We intubate
the trachea with the rigid tube under direct vision with the aid of a rigid
optical telescope. Details on rigid bronchoscopic intubation techniques can
be read elsewhere in this book (see Chap. 2).
When treating malignant endobronchial lesions, the rigid broncho-
scope should be advanced as close as possible to the superior border of the
tumor without actually touching it to avoid laceration and bleeding. The
laser is then set to a power level that achieves more coagulation than
vaporization. The tissue effects are regulated by changing the distance
between the laser fiber and the target. Common laser settings are 0.7- to
1.0-sec pulse duration and energy level of 35-40 W. The tip of the rigid
telescope should be kept inside the bronchoscope at all times. This will
allow a good view and, at the same time, will protect the lens from
becoming coated with tumor debris or blood. A suction catheter is directed
with the right hand, and this can be used as a probe to evaluate the
consistency and friability of the tumor tissue and to suction charred tissue
from the tumor surface.
Initially, brief laser pulses are used to coagulate the tumor by
"sweeping" the surface with the laser beam. A characteristic change in color
can be appreciated as the laser coagulates the tissue. This is used as a guide
to avoid carbonization, which is evidenced by blackening of the tissue. Dark
color, such as that of blood and carbonized tissue, enhances laser absorption
Laser Bronchoscopy for MaLignant Disease
109
and limits deeper penetration. The laser beam should always be fired parallel
to the wall in order to avoid unwanted effects such as wall perforation. As
coagulation is achieved, the tumor can be seen to shrink. Once appropriate
photocoagulation has been achieved, the rigid bronchoscope can be
advanced using the sharp bevel to resect slices of tumor. The rigid tube
should be advanced using a rotating movement such as the one used to
insert a corkscrew. Pressure should be applied in a direction that is parallel
to the airway rather than against the tracheobronchial wall. Digging into the
wall to resect tumor is very dangerous, since it can perforate the airway. As
the tumor is fragmented, pieces can be removed by the suction catheter or
extracted by forceps.
Once the airway lumen approaches a nearly normal caliber or the
tumor has been extracted as much as possible and the airway dilated, the
tumor area is carefully coagulated using brief low-power pulses in order
to prevent delayed bleeding. Finally, the remainder of the tracheobron-
chial tree is examined, and saline lavage and suction are used to clean
debris, secretions, and blood. The bronchoscopist should always keep in
mind that laser treatment of malignant conditions is palliative and that
variable amounts of tumor will be left in the airway. The goal should be
to achieve an airway diameter large enough to allow functional recovery
of the lung located distal to the obstruction, provide drainage of the
airway, and symptomatic relief without damaging the bronchial wall in
the process.
When laser treatment is delivered to coagulate a bleeding tumor
(Fig. 9), the initial firings are aimed at the base of the tumor. As the tumor
shrinks and becomes devascularized, the laser can be directed at the center
of the tumor itself, surrounding the bleeding point but not shooting directly
at it. Bleeding will stop because of retraction of the tissues and coagulation
of deep vessels.
Once the procedure is completed, muscular relaxation is reversed and
the patient is allowed to waken. Patients are usually extubated in the
operating room and then monitored in a recovery room for several hours.
They are usually discharged home the same day, staying overnight only as
an exception. We have found that most patients can be managed safely in a
semiambulatory fashion. A chest radiograph should be ordered after major
resections; we do not consider it necessary after minor procedures.
B. Laser Application with the Flexible Bronchoscope
We use the flexible bronchoscope to treat obstructions compromising less
than 50% of the bronchial lumen and for photocoagulation or vaporization
of benign lesions coagulation of bleedjng tumors that do not require
, Copynglifed Materral
110
Figure 9 Tumor after coagulation by laser.
resection or are not resectable, and peripheral lesions. Laser photoresection
with the flexible bronchoscope can be a long and time-consuming
procedure. It is not uncommon that more than one treatment session is
needed. Some bronchoscopists eject to perform the procedure in two
s s s i o n s ~ t first extensively to coagulate the tumor and the second,
performed 24--48 hr later, to extract pieces of tumor and necrotic tissue.
The flexible bronchoscopic procedure is performed in a bronchoscopy
room equipped according to laser safety standards. Local anesthetic should
be used liberally. The patient is sedated with short-acting benzodiazepines
and small incremental doses of opiates to assure appropriate analgesia.
After topical anesthesia to the nares and posterior pharynx, the fiberoptic
bronchoscope is introduced transnasally. Some short procedures may not
require conscious sedation or analgesia; they are often easily tolerated with
local anesthesia alone.
Laser Bronchoscopy for Malignant Disease 111
Once the lesion is approached, the laser fiber is introduced through the
working channel of the flexible bronchoscope. The fiber tip should be kept
approximately 2.5-3.5 em away from the tip of the flexible bronchoscope to
diminish the risk of fire. The laser machine settings should be programmed
to pulses of less than I-sec duration with a power of approximately 30 W.
Since the laser fiber occludes the working channel of the flexible
bronchoscope, suctioning is inefficient. Multiple interruptions are required
to eliminate smoke and resulting debris and blood. Laser use within a smoky
environment can produce sparks and trigger an endobronchial fire.
Fragments of tumor have to be extracted with biopsy forceps and with
suction. After the procedure, the patient is monitored for approximately 4 hr
in a recovery room and then discharged home.
C. Special Cases
Bilateral Lesions
For bilateral lesions, we initiate photoresection of the more obstructed side.
If complications develop, ventilation and oxygenation can be safely
continued through the less obstructed airway.
Ventilated Patients
The flexible bronchoscope can be used through the endotracheal tube, which
should be wrapped in metallic paper or replaced by a metallic endotracheal
tube. A plastic swivel adapter permits continued mechanical ventilation
during the procedure. Mehta's "Rule of Fours" (see below) should be
strictly followed to avoid potentially severe complications.
D. Laser Safety and Prevention of Accidents
Laser safety requires that the operator have a basic knowledge of laser
physics. Different lasers have different risks associated with their use. For
safety purposes, lasers are classified according to their capacity to cause
damage accidentally [accessible emission limit (AEL) scale]. All surgical
lasers, including the Nd:YAG laser, belong to category IV (hazardous under
all conditions, eyes and skin) [27]. Ocular injury and thermal lesions are the
major potential hazards.
Ocular Lesions
The laser beam can reflect off the shiny surface of instruments and cause
thermal injury to exposed areas and particularly to the retina. All surgical
personnel and the patient are potentially at risk, but the bronchoscopist is
I Copynghted Material
lJ2
Diaz-Jimene::. and Rodriguez
the one in greatest danger, since the laser beam can be reflected back up
through the rigid telescope. To avoid this hazard, the following should be
used: unpolished metallic accessories within the bronchoscope tube in order
to diminish reflection and safety goggles specific for the wavelength of the
laser by patient, personnel and laser operator. Ocular lesions vary according
to the wavelength of the laser in use and are outlined in Table 6.
Skin and Respiratory Mucosa
Injury to the skin and respiratory mucosa is either from direct exposure
to the laser beam (skin) or from ignition of flammable material within
the airway. Burn lesions can be avoided by following simple rules. One
person should be designated to handle the laser machine and be in
charge of laser operation throughout the procedure. Preferably the same
person should be in charge of checking laser function and calibration
before the procedure. This person should also control the key to turn the
laser on and off and ensure that the machine is properly maintained and
properly repaired if broken. Whenever the laser is not in use or the laser
fiber has been withdrawn from the bronchoscope, the machine should be
placed in the "stand by" mode. The use of a foot pedal for firing the
laser reduces the chance that the laser will be discharged accidentally into
the room. When the laser is used in an intubated patient, the
endotracheal tube should be covered by aluminum paper or replaced
with a metallic tube. Laser use with a highly flammable plastic tube
should be avoided. Laser power should be kept below 40 Wand the Fl0
1
below 0.4 (see below).
Hazards Related to Smoke
Several publications have demonstrated the presence of viral particles in
the smoke generated during laser treatment of papillomatosis. The
Table 6 Ocular Hazards
Wavelength (nm)
1,400-10.000 (far infrared)
100-305 (near ultraviolet)
315-400 (near ultraviolet)
400-700 (vi ible spectrum)
700-1,400 (near infrared)
Laser type
CO
2
He-Ne
Excilller
Nd:YAG
KPT
Ocular lesion
Mainly cornea
Mainly lenses
Mainly retina :lI1d
choroid
Laser Bronchoscopy for /VJalignanl Disease
JJ3
presence of human immunodeficiency viral fragments in fumes has been
reported as weI!. The significance of these findings is not known, but they
certainly warrant a good system for smoke evacuation which must be
functioning any time laser treatments are carried out. More research is
needed in this area before making additional recommendations [I I].
Standard operating room laser safety rules have been promulgated and are
outlined in Table 7 [28].
In spite of many potential risks, laser bronchoscopy has an excellent
safety record in nearly 30 years of use for airway conditions. Laser
bronchoscopy used properly in carefully selected patients should result in
nearly zero morbidity and mortality. Besides the general laser safety
principles, other safety rules have been developed specifically for laser use in
the airways: Dumon's "Ten Commandments" [29] are the most well known.
Mehta's "Rule of Fours" was developed for the use of laser with the flexible
bronchoscope. These safety rules are listed in Tables 8 and 9 and additional
rules are outlined in Table 10.
Patient education is an integral part of any laser bronchoscopic
procedure. The patient and family members should understand perfectly
what kind of treatment is planned, what to results to expect, and potential
complications. All questions should be honestly answered. A good
conversation with the bronchoscopist before the procedure is many times
more effective than any premedication in relieving anxiety. During the
procedure local anesthesia should be applied liberally and all efforts should
be made to avoid pain and discomfort. This is particularly important when
the laser treatment is delivered by flexible bronchoscopy, since the patient
will be awake during the procedure.
A. Complications Associated with Laser Photoresection
The use of the Nd:YAG laser in bronchology has been associated with
several serious complications, including death from bleeding (2%), fire and
explosions in the tracheobronchial tree, pneumothorax, bronchopleural or
bronchoesophagic fistula, and hypoxemia (30). Cardiac complications are
not uncommon and are often related to hypoxemia (ischemia, arrhythmia).
These have diminished in frequency with the routine use of continuous
cardiac monitoring and pulse oximetry. Asymptomatic electrocardio-
graphic changes have been reported in 6 and 17% of patients in two
separate prospective studies [31,32]. These changes were associated with
tachycardia and a fall in oxygen saturation. The development of coronary
spasm requiring admission to. a.n intensive. care unit was documented in a
c.;opyngnted Matenal
Table 7 Operating Room Laser Safety Rules
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5. Q.l
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6.
7.
8.
9
10.
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12.
All persons should be aware of areas of laser use. and controlled access to these areas must be maintained.
Regulation laser signs should be placed at all entrances to laser treatment areas.
Doors in the nominal hazard zone should remain closed and windows-including door windows-should be covered as
appropriate to the laser used.
The nominal hazard zone should be occupied only by authorized persons (including patients) or health care personnel
approved by the laser safety officer.
All personnel in the nominal hazard zone should wear protective eyewear labeled with the appropriate optical density and
wavelength for the laser in use.
The patient's eyes and eyelids should be protected from the laser beam by a method approved by the laser safety officer (e.g.,
wet eye pads, laser protective eyewear, laser-specified eye shields).
All persons in the laser treatment area should be protected from laser beam exposure to their skin and other nontargeted
tissues.
Anodized, dull, nonreflective, or matte-finished instruments should be used near the laser site.
When a fiber is used to deliver laser energy through an endoscope, the end of the fiber must extend at least 1cm past the end of
the endoscope.
When a fiber is used through an endotracheal tube, the plastic tube should be wrapped with metallic paper or replaced by a
metallic tube.
Smoke plume inhalation should be reduced by implementing various controls that include, but are not limited to, the use of
high-filtration surgical masks, wall suction units with in-line filters, and smoke evacuator units.
High-filtration laser masks should be worn by personnel during procedures that generate smoke plume.
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A central wall suction system with an in-line filter can be used to evacuate laser plume in situations where minimal plume is
generated.
In circumstances where large amounts of plume are generated, a mechanical smoke evacuation system with a high-efficiency
filter should be used to remove laser smoke plume according to the manufacturers' written instructions. The evacuator
collection system is placed as close as possible to the laser site.
Standard precautions should be used by all health care personnel when using lasers.
All persons in the laser treatment area should be protected from flammability hazards associated with laser usage.
Fire extinguishers and water/saline should be immediately available where lasers are used.
Special fire/flame-retardant drapes or moistened, reusable fabrics should be used to drape around areas that are close to the
laser treatment site.
An endotracheal tube used during laser procedures in the patient's airway or aerodigestive tract should have protection or be
specially designed to minimize the potential for fire.
All persons in the laser treatment area should be protected from electrical hazards associated with laser use.
Laser service and preventive maintenance should be documented. The laser safety officer should review service maintenance
documents before allowing lasers to be put back into service.
Personnel working in the nominal hazard zone should demonstrate competency commensurate with their responsibilities.
Policies and procedures for laser safety should be developed with regard to individual practice settings, applicable standards.
and federal and state regulations. They should be reviewed periodically. revised as necessary, and readily available to all
personnel.
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Table 8 Dumon's Ten Commandments of Laser Bronchoscopy
I. Know the anatomical danger zones: aortic arch, pulmonary artery, and
esophagus being the main hazard areas.
2. Have a well-trained laser team, including an anesthetist specialized in light
general anesthesia and two assistants drilled in emergency response
procedures.
3. Screen patients carefully: Any endoluminal growth is amenable to laser
resection, but purely extrinsic compressions are beyond the reach of the
technique.
4. Use the rigid bronchoscope technique (custom-made open tube, light general
anesthesia, straight telescope, and two suction catheters) for any high-grade
obstruction, especially if malignancy is involved.
5. Monitor blood gases and cardiac performance. At the least sign of hypoxemia,
interrupt treatment long enough to oxygenate the patient, if necessary under
closed-circuit conditions.
6. Fire the laser parallel to the wall of the airway; never aim directly into it.
7. Coagulate at will, but avoid using the laser at high power settings; mechanical
resection after laser coagulation is preferable to laser resections alone
whenever possible.
8. Do not neglect hemorrhage, for even slow bleeding will lead to hypoxemia if left
unattended.
9. Terminate each procedure with a thorough laser irradiation of the resected area,
and a tracheobronchial toilet to remove all secretions and/or debris.
10. Keep the patient under observation in a specially outfitted recovery room for a
reasonable period of time.
Source: Ref. 29.
Table 9 Mehta's Rule of the Fours for Laser Safety with the Flexible
Bronchoscope
I. Keep the fraction of inspired oxygen below 0.4.
2. Limit laser power to 40 W or less for the noncontact fiber and to 4 W or less for
the contact fiber.
3. Limit the duration of the pulse from 0.4 to J.O sec.
4. Keep the tip of the laser fiber at least 4cm from the endotracheal tube tip.
5. Keep the tip of the laser at least 4 mm from the flexible bronchoscope tip.
6. Keep the tip of the laser at least 4 mm from the targeted lesion.
7. Clean the tip of the laser after every 40 firings.
8. The recommended number of laser team members 4.
9. The length of the procedure should be less than 4 hI'.
SOI/rce: Ref. 61.
Table 10 Additional Rules
lJ7
I. Avoid laser shots on silicon prostheses and keep all flammable material far from
the operative field.
2. Maintain close communication with the anesthetist and the rest of the treatment
team during the entire procedure.
3. Avoid hypoxemia by continuous suctioning of the airway.
4. Avoid hemorrhage by coagulating the lesion before attempting resection.
5. Always be mindful of laser action on living tissues.
6. Never use laser in a continuous mode.
7. A number of laser fibers should be kept on hand in case substitution is needed.
Source: From Refs. 30, 62, and 63.
patient who developed ST changes and A-V block during laser broncho-
scopy [33]. Other listed cardiovascular complications include hypotension,
hypertension, ventricular ectopy, supraventricular tachycardia, ventricular
tachycardia, myocardial ischemia, and myocardial infarction [34].
Massive hemorrhage of 250 mL or more has been reported in 1-10% of
cases. Fatal hemorrhage due to pulmonary artery perforation has been
associated with the use of high-power laser settings [35]. Physicians have
learned to use lower power settings during treatments. Early publications
recommended powers up to 90W, whereas current guidelines advise the use
of no more than 40 W for the noncontact fiber and no more than 15 W for
the contact application.
After bleeding, an endobronchial fire is the most feared complication
of laser bronchoscopy (Fig. 10). The risk of fire can be minimized by strictly
following the laser safety guidelines. If fire occurs the flexible bronchoscope,
laser fiber, and all flammable materials should be immediately removed
from the airway. The tracheobronchial tree should be inspected and all
foreign material removed; if extensive thermal injury is verified, mechanical
ventilation may be indicated. A chest radiograph should be ordered in order
to rule out pneumothorax or pneumomediastinum. Some recommend the
use of antibiotics, steroids, and bronchodilators after a fire episode to reduce
mucosal inflammation and avoid infection. Granulation tissue and airway
stenosis are frequent sequelae after airway burns [36]. Others recommend
immediately shutting off the laser and instilling normal saline down the
bronchoscope while simultaneously removing all flammable materials. If the
upper airway has been involved, emergency tracheotomy [37] may be
required. Further evaluation of the injury will determine the need for
mechanical ventilation and monitoring in the ICU.
118
Figure 10 Endobronchial fire.
Intraoperative arterial air embolism has been rela ted to the coolant gas
used to cool the laser fiber tip. Monitoring the laser procedures with
continuous transesophageal echocardiography has shown that the coolant
gas can enter the pulmonary venules and from there continue to the systemic
circulation (38]. Stroke, myocardial ischemia and infarction, and death have
resulted from air embolism (39]. This complication can be avoided by
keeping the laser fiber coolant airflow at the minimum level (31/min) and the
laser fiber tip far from the target tissue during firing. Also, the flexible
bronchoscope should never be advanced to the point where it occludes a
bronchus. Wedging of the bronchoscope creates a high-pressure area distal
to occlusion and promotes air embolism.
Pneumothorax and perforation of the airway have also been reported
(40-42]. The "popcorn" effect is associated with laser energy of high-
power density being absorbed deep below the mucosa within the bronchial
lesion or the airway wall. The tissue temperature increases above the
Laser Bronchoscopy for Malignant Disease JJ9
boiling point of water and pockets of steam or vapor explode and can
result in perforation, rupture, and bleeding [19]. This effect can be avoided
by shooting short laser pulses at different points on the target tissue.
Technical difficulties with aiming or firing the laser are possible and should
be listed as problems, particularly when lesions are located in the upper
lobes.
Postoperative problems include hypoxemia, retention of secretions,
and hemorrhage from detached clots or inadequate clotting of the resected
area [24]. Noncardiogenic pulmonary edema and local hyperinflation are
rare postoperative complications [43,44]. Bleeding following the procedure
is unusual if proper coagulation of the resected area has been performed.
Macha et al. have reported that the eventual cause of death in up to 34.5%
of patients treated with Nd:YAG laser is massive hemorrhage [45]. We
believe this is related to the natural history of advanced cancer rather than
to the laser treatment itself. Most of the deaths that take place soon after
the procedure are due to a cardiovascular cause followed in frequency by
respiratory problems due to persistent obstruction of the airway. Local
heat generation can produce edema resulting in bronchospasm or
laryngospasm. Some feel this justifies the use of postprocedure steroids.
When laser is used to open an obstructed bronchus, drainage of the area
has the potential to disseminate infection to other segments of the lungs. In
this instance, the routine use of postoperative antibiotics might be
indicated [46].
B. Outcomes
There is a lack of standardized, validated outcome measurements for
laser photoresection, making any attempt at summarizing or comparing
results very difficult. Most of the published series rely on measures of
symptom improvement and occasionally quality of life parameters.
Other parameters commonly used are radiographic improvement (i.e.,
resolution of atelectasis, lung reexpansion), improved Karnosfsky status
[47], or changes in different grading scores for dyspnea. Ventilation/
perfusion scans have a variable correlation with symptomatic improve-
ment. A few studies have evaluated lung ventilation/perfusion scans
before and after the procedure. Clarke et al. [37] found scans to be
confusing when evaluating results, as they correlated poorly with
symptomatic relief. However, the V/Q scan has been felt to be a useful
predictive tool, because it has been suggested that if there were no
perfusion to the obstructed area before the laser photoresection, it was
unlikely to return function to the area after therapy. Thus, ventilation/
perfusion scans performed before laser pronchoscopy can help detect
c..;opynghted Matenal
120
patients unlikely to benefit from the procedure, since restoration of
ventilation to nonperfused areas will increase dead space ventilation
without symptomatic improvement and might even worsen symptoms.
Pulmonary function testing performed before and after the procedure
has been found to mirror symptomatic relief [49]. Some investigators
have suggested a combination of clinical and objective parameters in
order to assess therapy better. [10]. Most of us agree that palliation of
symptoms and improvement in quality of life should be regarded as
the main goal of laser photoresection for malignant obstructions.
Published series show that immediate palliation is obtained in most
patients. Poor results are seen in very extensive cancers and distally located
lesions. By rapidly improving critical airway lesions, laser application
improves quality of life and achieves immediate symptomatic relief,
particularly of dyspnea and hemoptysis. The results of selected large series
are depicted in Table II. Some studies also suggest an improvement in
survival [50]. The response to laser resection can often be used as a
prognostic factor, since it has been found that unsuccessful restoration of
airway patency is associated with poor survival [45,51,52]. Several studies
that have compared laser-treated patients with historical controls suggest a
benefit in survival in laser-treated individuals. These are outlined in Table 12.
Critically ill patients can also benefit from laser therapy. An article
Table 11 Laser Results
Number of Malignant Operative
Reference patients conditions Symptomatic relief mortality
64. 164 72 22% immediate
reopening
23 III 50 54% excellent 0
38% improved
8% poor
65 46 27 (partial 85% 3.7%
obstruction)
66 55 45 92% initial treatment 3.6%
69% recurrent
malignancies
67 100 100 68% 2%
68 1310 604 2.7%
69 19 84%
40 400 236 78.3% 0.3%
70 2008 1838 93% 0.6%
71 400 134 100%
0%
Table 12 Laser Bronchoscopy Survival
121
Reference
72
69
35
51
Number of
patients Controls
17 Laser and radiation
versus controls,
radiation only, or
radiation followed
by laser
19 Laser followed by
radiation versus
historical controls
(external radiation
only)
116 Laser photoresection
versus historical
controls
35 Laser and radiation
therapy versus
historical controls
treated with XRT
a
Results
Laser applied first improved
tolerance to radiotherapy,
was associated with
longer palliation of
symptoms and improved
quality of life
Improved survival
Improved survival
Improved survival in
patients undergoing
emergency palliative
Nd:YAG laser resection
'XRT, External radiation therapy.
published in 1993 reported a group of patients requiring mechanical
ventilation because of malignant obstruction of the airways. Mechanical
ventilation could be discontinued in 9 of the 17 patients treated with laser
photoresection; and 7 of the patients lived long enough to receive other
treatment modalities [53].
C. Relation to Other Procedures
Many debulking techniques are now available to treat patients with
symptomatic malignant obstruction of the airways. Mechanical tumor
removal, electrocautery, cryotherapy, photodynamic therapy, and bra-
chytherapy are all alternatives that can provide good results in experienced
hands. However, only laser, mechanical removal, and electrocautery are
able to achieve immediate opening of the airway. All other techniques are
slower acting and not useful for critically obstructing lesions that require
immediate reopening.
J22 Diaz-Jimenez and Rodriguez
Electrocautery was used before laser was available, and it is considered
to be "the poor man's laser." Electrocautery success rates for airway
opening range from 71-100% [54-58]. A recent retrospective study evaluated
the cost effectiveness of the Nd:YAG laser and bronchoscopic electro-
cautery in 31 patients with malignant obstruction of the airways. There was
immediate symptomatic relief in 70% of patients in both groups and similar
survival rates [59]. Laser therapy proved to be significantly more expensive
than electrocautery. Photodynamic therapy appears to be a valid tool for
the curative treatment of early cancers, and it has also shown a potential
role in the palliation of advanced, inoperable, obstructing bronchial tumors.
A prospective controlled randomized study compared the safety and efficacy
of PDT versus Nd:YAG laser photoresection in advanced disease and
randomized 31 patients to each treatment group [60]. The study showed that
symptomatic relief was achieved in both groups. Patients in the PDT group
had a significantly longer time to treatment failure and longer median
survival. The investigators concluded that PDT and conventional Nd:YAG
laser therapy appeared to be equally effective and safe in relieving airway
obstruction in patients with inoperable non-small cell cancer. However,
Nd:YAG laser therapy was found to achieve a better rate of immediate
reopenmg.
When available, laser remains the method of choice for endobronchial
therapy. It can be a complementary therapy to other palliative measures,
and often provides time for further therapies to be offered to patients. It
should be the first therapy considered if airway obstruction is present.
VIII. Conclusion
Since the 1980s endoscopic laser photoresection has increasingly become an
important tool for the bronchoscopic palliation of malignant obstructing
lesions of the airway and for curative therapy in benign obstructing
conditions of the tracheobronchial tree. Rigid bronchoscopy is the preferred
technique for laser bronchoscopy, especially when dealing with foreign
bodies, massive hemorrhage, airway dilatation, airway stents, mucous plugs,
and pediatric indications. Laser bronchoscopy can be used in conjunction
with other forms of therapy. It can provide significant palliation in patients
with malignant or benign airway tumors who are not candidates for surgery.
It also may spare some patients with tracheal stenosis the need for more
invasive surgery. With care taken for good patient selection and technique,
laser photoresection represents a low-risk option to achieve significant
palliation in patients with benign and malignant conditions compromising
the airway.
Laser Bronchoscopy for MaLignan/ Disease
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6
Laser Bronchoscopy for Benign Disease
HENRI COLT
University of California
Irvine, Orange, California, U.S.A.
Open surgery has been and is the traditional and generally universal way to
manage many benign central airways lesions. Results are quite good,
although often highly dependent on the skill and experience of the operating
surgeon. In addition, results are dependent on the etiology and extent of the
airway obstruction, as well as on the operability status of the patient. This is
the arena where laser bronchoscopy first made its mark, allowing
satisfactory airway management of patients who were ill suited for open
surgical resection and reanastomosis.
Laser bronchoscopy for benign central airway obstruction, originally
an extraordinarily controversial topic when applied to patients who were in
fact candidates for open surgery, is now an increasingly accepted therapeutic
modality in certain central airway abnormalities regardless of patient status.
In the following sections, examples of the laser's use, as well as the potential
for abuse will be described. A few recommendations based on the author's
experience will also be provided. Finally, several specific causes of benign
airway obstruction, and the problems they pose to the interventional
bronchoscopist before, during,.and afte.r s ~ r resection will be addressed.
c.;opyngntea Matenal
127
128 Colt
For the purposes of this chapter, laser bronchoscopy can be defined as a
bronchoscopic resectional technique used to photocoagulate and vaporize
tissues causing central airway obstruction. Bronchoscopy can be performed
using either a flexible or a rigid bronchoscope. In many cases, operators
choose to use both types of bronchoscopes during the same procedure.
Reasons for and against this approach are provided in the following
paragraphs. On a similar note, the laser may be used instead of or in
conjunction with other interventional techniques. These include cryother-
apy, electrocautery, argon plasma coagulation, mechanical tissue removal,
balloon and bougie dilatation, and airway stent insertion.
Light amplified stimulated emission of radiation (Laser) has had
medical uses since first introduced in 1960. Interestingly, the use of lasers
was once controversial, especially when pulmonary bronchoscopists
ventured into the airways with curative and palliative intent. The central
aIrways and the larynx were traditionalJy shared territories of
otorhinolaryngologists and thoracic surgeons. Since the advent of the
flexible bronchoscope, pulmonary specialists became increasingly inter-
ventionist, not only for diagnosing central airway disorders but also for
treatment.
Tracheal and bronchial strictures, as well as a benign central airway
tumors, can be, and often are, extremely well managed with the use of open
surgical techniques. These include tracheotomy, temporary or permanent
Montgomery T-tube insertion, and open resection with reanastamosis [1-3].
From an otolaryngological perspective, the decision regarding stricture
management is whether to proceed with an endoscopic or open surgical
intervention. The potential need for tracheotomy is always acknowledged.
In this regard, the otolaryngologist takes into consideration patient
symptoms, etiology of the airway abnormality, medical and surgical risk,
and potential resecta bility (whether the lesion can in fact be removed) of the
obstructing lesion. From a pulmonary bronchoscopist's perspective, these
same elements must also be kept constantly in mind when considering
patients for bronchoscopic laser resection.
Many would say that the otolaryngologist remains the expert in
disorders involving the larynx and immediate subglottis. The laser most
frequently used on vocal cords and laryngeal structures is the CO
2
laser,
whose attributes will be addressed briefly below. Because this laser has
limited applicability in the tracheobronchial tree (and especially because it
cannot be employed through a flexible bronchoscope), it has rarely been
used by pulmonary bronchoscopists, who often limit their practice to the
neodymium-ytterium-aluminum-garnet (Nd:YAG) laser for treating benign
129
central airway lesions. Increasingly, however, bronchoscopists are also using
the potassium-titanyl-phosphate (KTP) laser, whose characteristics can
resemble the cutting quality of the CO
2
laser as well as the photocoagulation
qualities (although substantially reduced) of the ND:YAG laser.
Thoracic surgeons also share the upper trachea, although many
perform complex laryngeal and tracheal resections alone or in concert with
expert otolaryngologists. Open surgical techniques for tracheal and
bronchial resection are often successful, providing many patients with a
one-procedure-one-cure management alternative. Patients must be properly
selected, and operator experience is essential. However, not all patients or
diseases are both resectable and operable. Careful consideration, therefore,
must be given to temporary palliative bronchoscopic procedures that might
enhance potential operability, or even replace an open surgical approach in
case of high surgical risk, excessive medical comorbidities, or anatomical
unresectability of a tracheal or bronchial abnormality.
From a historic perspective, the key point is that the laryngotracheo-
bronchial tree has been and continues to be a shared territory. This author
strongly believes that a multidisciplinary approach is warranted for patients
with both straightforward and complex disorders. A team approach
provides patients with multiple open or bronchoscopic alternatives to
choose from and prevents physicians and surgeons from "burning their
bridges" if one technique is initially chosen over another. The patient's best
interests, therefore, are kept in the forefront.
Web conferencing, video recording, and color digital photography
facilitate consultation among subspecialists. Choosing one approach over
another (especially in view of a paucity of prospective studies) and planning
a management strategy that might involve several steps and several different
specialists are among the most significant challenges facing airway
interventionists today.
For the purposes of this discussion, only tracheobronchial laser broncho-
scopic resections in patients with benign disease will be considered. From a
symptoms perspective, patients with benign central airways obstruction
might present with one or more of the following: cough, stridor, wheeze,
hemoptysis, hoarseness, loss of voice, shortness of breath, difficulty
swallowing, respiratory distress, and respiratory arrest. Onset might be
abrupt or gradual, and can even be progressive over a number of years, such
as the classic stories of patients with central carcinoid tumors or adenoid
cystic carcinomas Other patients might
130 Colt
present with acute or chronic segmental or lobar collapse noted on chest
radiography, repeated bouts of aspiration pneumonia, recurrent pneumonia
in the same anatomical location, or difficulty weaning from tracheotomy or
mechanical ventilation.
Some patients might have a history of prolonged intubation (from
trauma, respiratory failure and chronic obstructive lung disease, neuromus-
cular dysfunction, or postsurgical complications), diffuse airway disorders
(such as tracheopathica osteochondroplastica or papillomatosis), or
systemic disorders (such as polychondritis, sarcoidosis, Behc;et's syndrome,
or Wegener's granulomatosis). Others might have suspected or known
infectious disease that can affect the tracheobronchial tree (such as
tuberculosis, coccidioidomycosis, histoplasmosis, aspergillus, and Klebsiella
rhinoscleroJnatis).
In many patients, the etiology of an airway obstruction is discovered
on flexible bronchoscopy. Benign airway tumors such as lipomas,
papillomas, carcinoid tumors, and hamartomas might be noted. The patient
might have a history of single- or double-lung transplantation. Tracheal or
bronchial strictures from previous airway procedures (such as tracheal or
bronchial resection and anastomoses, tracheotomy, previous laser resec-
tions, stenting, or dilatation procedures) might be also found. The patient
might be a trauma victim (burn injury, chemical airway or inhalation injury,
airway laceration with disruption of tracheobronchial mucosa, and
granulation tissue formation over scarred tissues). The patient might even
have a history of malignant (or benign) airway obstruction prompting
silicone, metal, or hybrid stent insertion. In these cases, it is not uncommon
to discover that obstruction of airway prostheses is caused by inflammatory
granulation tissue formation rather than by recurrent or new tumor
overgrowth. In the face of so many possible benign etiologies of central
airway obstruction, one can only say that exploratory flexible bronchoscopy
is probably warranted in any case of clinical suspicion based on symptoms,
clinical setting, or patient history.
During the bronchoscopic examination, specific features of the lesion
should be noted. These include location (glottic, subglottic, tracheal,
tracheobronchial, or bronchial), shape (circumferential or partial), length
(long, short, number of tracheal rings involved), distances from other
anatomical structures (distance from the vocal cords, cricoid cartilage, main
carina), type of stricture (simple, web-formed, complex), components (firm,
soft, mature, or early), associated abnormalities (malacia, poststricture
dilatation, granulation tissue formation, lack or loss of cartilage, presence of
sutures or purulent material). If possible, the extent of airway obstruction
should be also assessed (total, partial, or percentage of airway lumen
obstructed, diameter and length of the stricture itself).
Laser Bronchoscopy for Benign Disease J31
A careful and systematic examination including all the items listed
above will allow the bronchoscopist to assess appropriately the potential
resectability of the airway lesion. Decisions regarding open surgical,
palliative, or curative bronchoscopic approaches are more readily made.
Consultation might be warranted with other specialists. If a bronchoscopic
approach is being considered, the potential advantages and disadvantages of
laser resection versus other bronchoscopic therapies will also need to be
addressed.
Dependent upon the operator and institutional resources, decisions
regarding which type of laser are required. The urgency of intervention will
depend on the patient's symptoms, overall clinical status, referral logistics,
extent and type of airway abnormality, and underlying diagnosis (or lack
thereof). Contrary to what is sometimes seen in patients with malignant
disease, patients with benign central airway obstruction who are critically ill
and ventilator dependent can usually undergo immediate bronchoscopic
correction of the airway abnormality and are likely to have successful results
including removal from mechanical ventilation, decreased level of care,
discharge from the intensive care unit, increased survival, and improved
quality of life [4].
When considering indications for laser resection, one must also
address advantages and disadvantages of laser compared to other
resectional techniques. In part, such comparisons depend on the skill and
experience of the operators, but also on the type of laser wavelength used
[5]. There are certain accepted advantages, however, to using a laser for
removal of tumor, granulation tissue, or scar tissues causing airway
obstruction. These include, but are not limited to, the following: (I) Instant
gratification: the abnormality is immediately removed without the need for
subsequent clean-out bronchoscopy. (2) Safety: because bleeding, including
that from deep vessels, is readily controlled when using the Nd:YAG
wavelength. This is contrary to the superficial coagulation properties of
argon plasma coagulation or electrocautery. (3) Speed: resection is readily
possible using either the flexible or the rigid bronchoscope. Even large
benign tumors can be removed with relative speed using a combination of
photoresection, coagulation, dilatation, and mechanical debulking. (4)
Potential for cure: removal of benign tumors and treatment of the base of
the tumors might result in a cure, as has been the case in reports of
hamartomas, lipomas, and typical carcinoid tumors.
There are also distinct disadvantages to using laser. These include (1)
Supplemental cost and logistic difficulties: in order to have a laser, a hospital
must have laser credentials and an oversight committee as well as
technicians trained in troubleshooting any mechanical problems that might
occur. In the United St:apF/7gNfijffM'JHJ?Pasjonal fee reimbursement is the
132 Colt
same regardless of which bronchoscopic resectional technique is employed.
If the hospital does not have a laser, it might need to be leased on a daily or
per procedure basis. In addition, the high cost (usually more than 200 U.S.
dollars) of the laser fiber increases hospital expenditures which might not be
covered by insurance depending on payer. (2) Risk of airway fires: When the
laser is used (Nd:YAG or KTP), supplemental oxygen must be reduced to a
FI02 less than 0.4. Any indwelling endotracheal tube, flexible bronchoscope,
suction catheter, or stent can potentially catch fire. Even in the absence of
such materials, airway burns can occur as a result of reflection, scatter, and
direct thermal injury when the laser is used at high-power settings or for a
prolonged period. (3) Risk of the "popcorn" effect and perforation: the
accumulation of steam deep within the tissues resulting from prolonged
laser application, high power, and accumulated energy or displaced power
density easily ruptures tissues. Laser bronchoscopists should be well versed
in laser-tissue interactions. A thorough knowledge of the concepts of power
density, wavelength-tissue absorption characteristics of the laser being used,
and patient and operator safety is warranted. Some of these concepts were
discussed in previous chapters.
It is unclear whether there are any absolute contraindications to laser
bronchoscopy in patients with benign central airway obstruction.
Obviously, only patients with a component of intraluminal (also referred
to commonly as exophytic) disease should be treated. If the obstruction is
caused solely by extrinsic compression, then stenting rather than a
bronchoscopic resectional technique might be warranted. Complete airway
obstruction by an intraluminal abnormality should be approached with
caution, especially if the status of distal airways is unknown. Chances for
stricture recurrence are probably greater than 50% after initial treatment, so
patients and referring physicians should be warned that bronchoscopic
resectional techniques, including balloon dilatation and airway stenting, are
not cure-all procedures, and frequently repeated interventions are necessary
before a stricture is controlled.
In patients who are candidates for a bronchoscopic resection, careful
assessment of the advantages and disadvantages of a laser resection
compared to another modality is necessary. In addition, the most
appropriate laser (C0
2
, Nd:YAG, KTP, or diode), laser fiber (sheathed or
bare, gas cooled or water cooled, contact or noncontact), location
(bronchoscopy suite using topical anesthesia and conscious sedation,
operating room setting using general anesthesia with or without intubation),
and equipment (rigid or flexible bronchoscope, use of ancillary instruments)
111 ust be selected.
Careful attention should be paid to patients with coagulopathies.
Special caution is necessary in patients receiving anticoagulants or
/33
thrombolytic agents. It is probably safer to correct coagulation abnormal-
ities prior to beginning laser resection. In this author's opinion, low platelet
counts (25,000 mL
3
or less) should be reversed. As in standard diagnostic
flexible bronchoscopy, patients with uremia and elevated creatinine levels
are also at increased risk for bleeding. The dangers of general anesthesia
must be carefully weighed against the potential outcomes of noninterven-
tion. In this regard, the anesthetic technique can be altered dependent on the
habits and preferences of the bronchoscopist-anethesiologist team: sponta-
neous-assisted ventilation, gas or intravenous anesthesia, jet ventilation, use
of muscle relaxation or paralysis, performance of procedures using
ventilation through the rigid bronchoscope, or flexible bronchoscopy using
an endotracheal tube or laryngeal mask airway [6].
IV. Equipment
Several different laser wavelengths can be used in patients with central
airway obstruction from benign disease. In the following paragraphs
wavelengths that are currently Food and Drug Administration (FDA)
approved in the United States are briefly described, and specific
recommendations regarding the laser technique are offered.
The carbon dioxide (C0
2
) laser has a wavelength of 10,600 nm, which
puts it in the mid infrared zone of the electromagnetic spectrum. This is a
true "cutting laser," often referred to as a "light scalpel" and a "what you
see is what you get" laser. Tissue vaporization occurs rapidly and with
minimal scatter. Thermal injury is superficial and precise, but coagulation is
limited. Tissue response usually predicts prognosis. This laser energy cannot
be delivered using conventional flexible fibers, and is thus used most
frequently at low power (4 W) and intermittent short bursts (0.1 sec) through
a set of mirrors and articulating arms rather than through the flexible or
rigid bronchoscope. Radial incisions are made at the four corners of a
weblike stricture, which is then dilated gently without tearing tissues.
The Nd:YAG laser has wavelengths of 1064 or 1320nm. Because both
are invisible, a helium-neon laser (like the laser pointer used in auditoriums)
is used as an aiming beam. Laser energy is applied through bare or sheathed
flexible fibers easily placed through a flexible or rigid bronchoscope. The
Nd:YAG laser is the true workhorse of the interventional bronchoscopist.
Absorption of laser energy is increased when tissues are dark (such as on
bleeding areas). Tissue penetration, therefore, is greatest when laser energy
is applied to light-colored tissues.
When making radial incisions on a weblike stricture, it is usually
necessary to increase the j)owec setting ilnd plove the fiber very close to the
copynghtea Malenal
134
Colt
tissue in order to minimize scatter and obtain a clean cut. In reality, this is
difficult using this type of laser, which is one reason many operators prefer
using the KTP laser in such settings. On the other hand, when deep
coagulation is required, such as prior to rigid bronchoscopic debulking of a
tumor, nothing works better than the Nd:YAG laser. Tissues are blanched
as vessels wi thin the tumor vasoconstrict. The tumor is then resected using
the beveled edge of the rigid bronchoscope.
Some operators also use the Nd:YAG laser to vaporize tissues. In
these cases, tissues blacken as laser energy is applied. As the dark tissues
absorb more and more energy, eventually the tissue vaporizes. This can be a
helpful technique for removing granulation tissue, but carries with it the
danger of energy scatter and thermal injury. In general, ND:YAG laser
resections can always be satisfactorily performed using laser energies less
than 40W. Pulse durations are often set at 0.5 or l.Osec.
The KTP laser has a 532-nm wavelength and emits a green light. Dark
(red) tissues highly absorb this wavelength when power settings are 2-5 W.
At these settings, photocoagulation of superficial vessels is possible. In
general, the KTP wavelength creates less thermal injury and less scatter than
the Nd:YAG laser, and is therefore advocated by many operators to remove
granulation tissues and to treat weblike strictures with radial incisions.
Another incision technique frequently advocated is that of making "Mickey
Mouse" ears at the 2 and 10 o'clock positions of a circumferential stricture
before proceeding to gentle dilatation (Fig. I).
The diode laser is available in two wavelengths (630 and 810 nm). The
810-nm wavelength is used for laser resection, whereas the 630-nm
wavelength is used for photodynamic therapy of malignant tumors. This
laser is easily portable and versatile. There is still some debate regarding its
cutting and coagulation properties, and there are no head-to-head studies
comparing this laser to either the Nd:YAG or the KTP laser.
Finally, one might mention the xenon-chloride excimer laser,
characterized by a pulsed ultraviolet emission with a wavelength below
400 nm. This laser cuts precisely without heat propagation into adjacent
tissues. It has been used in corneal surgery. In bronchoscopy, it can be used
to vaporize broncholiths with little or no scattered thermal damage. Excimer
laser energy can also be delivered through flexible fibers.
V. Technique
The object for the laser bronchoscopist is to have ready access to all
necessary instrumentation, as well a to be able to comfort the patient
and reassure team members, such as the bronchoscopy assistant and
135
Figure 1 Postintubation subglottic stricture with first subglottic "Mickey Mouse"
incision being made during laser treatment of circumferential subglottic tracheal
stricture.
anesthesiologist, during the entire procedure. In some cases, procedures
are readily performed through a flexible bronchoscope with patients awake
and seated. This may be the preferred setting for the patient with a small
amount of granulation tissue readily removed by vaporization. Patients
should be warned about possible smoke. Satisfactory suction is manda-
tory. Patients should probably receive some form of conscious sedation to
help decrease procedure-related anxiety. Most laser cases, however, are
performed under general anesthesia in an operating room setting. Laser
selection will depend on the etiology and character of the airway
obstruction. How the laser is used will depend on operator preferences,
laser-tissue interactions (which include energy absorption, scatter, and
reflection), and character of the lesion (color, extent of mucosal and
cartilaginous involvement, size).
There are a few general truths about laser resection of a benign
airway abnormality: (l) laser can be applied at any level of the central
tracheobronchial tree; (2) abundant thermal injury should be avoided,
because it probably enhances recurrent inflammatory tissue formation; (3)
136
CoIl
thin and simple strictures probably respond better than long, thick, old,
and complex strictures; (4) traumatic dilatation and aggressive mucosal
disruption should be kept at a minimum, because they might lead to
recurrent inflammatory tissue formation in the case of benign airway
strictures; (5) delivery of laser energy perpendicular to the airway wall
should be done very carefully because of an increased risk of perforation;
(6) if bleeding develops, areas around the bleeding tissues should be
treated so that feeding vessels constrict. The operator should avoid firing
the laser directly onto the bleeding surface where the Nd:YAG wavelength
will be immediately and superficially absorbed; (7) when cutting through
tissues during resection of a web stricture, a fine, thin incision using the
smallest beam possible and high power density is probably advantageous;
and (8) strictures recur frequently, often requiring more than one
treatment.
One must insist on the need for safety during laser bronchoscopy.
During bronchoscopic resections, one might be working in close proximity
to the glottis, making laryngeal edema and laryngospasm a real risk.
Corticosteroids can be administered preoperatively and postoperatively.
Blood and airway secretions, as well as stimulation from the rigid or flexible
bronchoscope can prompt bronchospasm; inhaled beta-agonists should be
readily available for direct delivery into the airways. One should not forget
to instill topical anesthetic prior to bronchoscopic intervention. This can be
done by the anesthesiologist during rigid laryngoscopy prior to intubation
with the rigid bronchoscope, or through the bronchoscope once the
procedure begins. Patient eye protection with saline-soaked pads and
aluminum foil is mandatory, and of course all personnel in the procedure
room should wear protective goggles when laser is being used. A special
filter can be placed between any camera head and telescope when using the
KTP laser to avoid damaging the camera. Note also that the protective
eyewear for KTP laser is different from that used for ND:YAG laser.
Flammable materials should be kept away from the operating field.
The lowest inspired oxygen (less than 40%) should be employed during laser
firing. Frequent bronchial toilet and washing with saline solution, aspirating
smoke and secretions, and allowing adequate time for tissues to cool during
laser firing might also diminish risks for airway fires. Ideally, both smaller
channel and large-channel flexible or videobronchoscopes should be
available to inspect the airways and remove blood, necrotic tissues, or
secretions. Postoperatively, patients should be monitored closely, especially
if work was done in the subglottis. Late laryngospasm can occur, and
sometimes it might not be possible to intubate easily with an endotracheal
tube: Flexible bronchoscopic intubation or even the rigid bronchoscope
might be necessary.
VI. Specific Etiologies of Airway Obstruction
A. Postintubation Tracheal Stenosis
The most frequent cause for tracheal stenosis is postintubation stricture,
which is closely followed by strictures occurring at the site of prior
tracheostomy. Potential risk factors for postintubation stenosis include high
endotracheal tube cuff pressure and mucosal necrosis, duration of
intubation, chemical irritation, traumatic intubation, and tracheal infection.
Strictures also occur in patients with tracheostomy. In these cases, stenosis
might be related to surgical technique and tracheal wall trauma, as well as
granulation tissue formation and inflammation from tube motion or excess
cuff pressure. Stricture can occur early after tracheotomy, but also very late
and even after removal of the tracheotomy tube. In these cases, the stenosis
is usually a firm circumferential or complex stricture with or without
associated malacia.
A diagnoses of benign postintubation or posttracheotomy stenosis can
be suspected based on symptoms but also on the flow volume loop. In many
cases, however, spirometry and flow volume loops may be normal. Most
interventional bronchoscopists agree that early bronchoscopic examination
is warranted in symptomatic patients with a history of difficult intubation,
previous intubation with or without mechanical ventilation, or a history of
tracheotomy regardless of results of pulmonary function testing.
Open resection of the stricture and reanastomosis is probably the
preferred method of treatment, with satisfactory results being noted in more
than 90% of cases in expert hands. However, there are many limitations. The
maximum amount of trachea that can be removed is between 3 and 5cm.
Failure rates are between 4 and 18%. Complications include tracheal wall
dehiscence, infection, recurrent laryngeal nerve damage, restenosis (with
varying frequency but as high as 8%), and death. Overall, primary repairs
have a better prognosis than repeat surgeries, and patients requiring mid
tracheal repairs generally do better than patients with subglottic involve-
ment. Many patients, however, are poor candidates for open resection
because of medical comorbidities, usage of systemic corticosteroids, high
anesthesia risk, or the presence of active inflammation or infection at or
around the mucosa of the projected resection site [7-10].
No algorithm incorporating surgery and bronchoscopic therapies has
been universally adopted, although several have been proposed [11-12]. In
one study, 10 of IS patients with weblike strictures were cured after laser
resection, and overall, bronchoscopic therapy, including laser and stenting,
was curative in little more than one-third of all patients. It appears that
bronchoscopic treatment employing laser resection should be considered a
first-line treatment in stenosis, especially if the
138 Colt
patient is a poor surgical candidate. In such settings, laser can be safely used
in conjunction with balloon dilatation and stent insertion. Ideally,
bronchoscopic procedures might be performed in an attempt to improve
the overall patient status in preparation for open surgical resection.'
However, results from several studies showed that stenoses frequently recur
in the absence of stent placement even when laser resections and balloon
dilatations are repeated. This might prompt some experts to suggest that
laser resection is warranted as a possible curative intervention in patients
with simple weblike strictures, but that laser resection and stent insertion are
required in more complex strictures. Even in these instances, recurrence of
granulation tissue formation is frequent, prompting some investigators to
advocate the use of mitomycin C (saturated pledgets soaked at a dose of
0.1 mg/mL for 2 min) [13-14].
Every attempt should be made to minimize tissue damage when
performing laser resection of stenotic airways. This can be very difficult, and
success may depend on the type of stenosis as well as on the bronchoscopic
techniques used. Concentric stenoses often require more than one treatment
even when mucosa-sparing techniques such as limited laser resection using
radial incisions and gentle dilatation are employed. One should probably
not expect more than a 75% long-term success rate overall. It also appears
that lengthy scars more than I cm in length and lesions with associated
malacia increased the likelihood for unsatisfactory results. In many cases, it
will be necessary to proceed to open surgical resection or placement of a
silicone stent, which, in the subglottis, has a high likelihood of migration or
of promoting granulation tissue formation that might additionally
compromise the airway. Montgomery T-tubes have also been used
successfully in these settings (see below) [15-17].
There are various ways to perform laser resection of benign stenosis,
and to this author's knowledge, no large comparative studies of resectional
techniques, other than those advocating radial incisions, are available. It is
possible to perform Nd:YAG laser resection of subglottic and upper
tracheal strictures (as well as lower trachea and bronchial strictures) using
only the flexible bronchoscope. This can be done through an armed
endotracheal tube, taking great care to reduce the Flo] to less that 0.4 and
to keep laser power at less than 40 W in order to prevent an airway fire. If
the stricture is weblike and circumferential, radial incisions are made at
approximately the 12, 3, 6, and 9 o'clock positions. Mickey Mouse ears can
be made at the 2 and 10 o'clock positions (see Fig. I). Note that laser
resection can also be performed through the rigid bronchoscope. In this
case, spontaneous assisted ventilation is possible, although there will likely
be a large air leak through the rigid scope, nares, and oropharynx because
the rigid tube is often kept high in the subglottis with the beveled tip just
past the level of the vocal cords. This technique req uires expertise in rigid
bronchoscopy to avoid excess pressure on the larynx. let ventilation is
another way to assure oxygenation and ventilation during laser resection,
but it has the disadvantage of potentially blowing blood, secretions, smoke,
and resected debris onto the target areas.
The radial incisions are made using either the Nd:YAG, diode, or
KTP lasers by placing the noncontact laser fiber very close to the target
tissue in order to cut through the tissues with minimum thermal injury to
adjacent tissues. The stricture can then be dilated using increasing size
bougies or rigid bronchoscopes. Laser resection should avoid exposure of
the perichondrium because chondritis might develop and increase the risk
for recurrent stenosis. It is also possible to dilate the stricture using only one
size rigid bronchoscope by gently applying pressure to the target tissues and
rotating the beveled edge of the scope until the tissues give way. The
diameter of the tracheal lumen can thus be increased to 8, 10, 12, or 13 mm.
By leaving islands of tracheal epithelium between the radial incisions, the
epithelial cover regenerates quickly.
Procedures can be performed on an outpatient or inpatient basis.
Frequently, it may be warranted to keep patients with subglottic strictures
overnight under observation in case mucosal swelling or laryngeal edema
occurs. If purulent secretions are noted, antibiotics should administered,
although the effectiveness and duration of antibiotic treatment are unclear.
Corticosteroids can be administered if laryngeal trauma is suspected (e.g.,
rigid bronchoscopic intubation using a large scope through a small larynx).
Follow-up bronchoscopy is usually performed 4-8 weeks after the
procedure in order to evaluate the response to treatment and to look for
early restenosis. If the patient is symptomatic or has evidence of recurrent
stricture, reintervention is warranted.
Because it is uncommon for interventional bronchoscopists to
encounter patients with ideal lesions: thin weblike circumferential strictures
less than I cm in length and without associated malacia located in the mid
trachea, perioperative adjuvant therapies are often required. These include
systemic corticosteroid administration, intralesional injection of cortico-
steroids during or after laser resection, and administration of perioperative
antibiotics to reduce the potential for infection, edema, and inflammation.
None of these has been the subject of large randomized studies to determine
efficacy.
We advocate a multidisciplinary approach for most patients, with
input provided by all members of the "airway team": pulmol1ologist,
otolaryngologist, thoracic surgeon, anesthesiologist. A management
strategy is developed so that physicians working together simultaneously
or sequentiaJly can evenwaJl'y' re;;olvt the Piltient's problems. Each case is
c.;opyngnrea Matenal
140 Colt
different. In general, we advocate an open surgical approach (or utilization
of Montgomery T-tubes or tracheotomy) if bronchoscopic resection is
unsuccessful after three to four interventions. However, many patients may
not be eligible for surgical resection, and in these cases, other bronchoscopic
and minimally invasive modalities are considered.
B. Respiratory Papillomatosis
Recurrent papillomatosis is caused by the human papillomavirus (HPV)
family. This disease affects children and adults, causing tremendous
psychological and physical hardship [18,19]. Current statistics of the
Recurrent Respiratory Papillomatosis Foundation suggest an incidence of
1.8 per 100,000 persons (about 2000 new cases each year in the United
States). Fewer than 5% of patients have tracheal or proximal bronchial
involvement. First described as warts in the throat in the seventeenth
century, an infectious etiology was confirmed in the twentieth century.
Today, it appears that HPV-6 and HPV-Il are the most frequently causative
organisms, although there does not appear to be a correlation between HPV
type and disease severity. Frequently, papillomas are confined to the larynx,
but can also be found anywhere within the tracheobronchial tree (Fig. 2a
and b).
Numerous bronchoscopic treatments, including use of the CO
2
laser
and Nd:YAG laser, have been advocated for this devastating, recurrent, and
unrelenting disease. Sometimes monthly treatments are necessary to prevent
complete airway obstruction. In addition to laser resection, photodynamic
therapy, cis-retinoic acid, interferon-alpha, and indole-3-carbinol/diindo-
Iylmethane have been advocated with varying results. During laser resection,
the laser plume should be carefully evacuated since viral transmission to
health care providers, although not reported, could theoretically occur.
Remission and recurrence are unpredictable, and late recurrences can occur
many years after treatment of initial disease. One should be wary of frequent
bronchoscopic laser treatments because repeated procedures, in addition to
subglottic involvement and long-standing disease, are presumed risk factors
for enhancing the local spread of this illness.
Another important aspect of care for these patients is that of
malignant transformation of respiratory papillomas. It appears that
radiation, bleomycin treatment, and cigarette smoking are risk factors for
malignant transformation into squamous cell carcinoma. Such malignant
transformation can occur at any time during the course of the illness,
warranting close bronchoscopic surveillance. In patients requiring frequent
bronchoscopic treatments, specimens should be regularly sent for histolo-
gical examination [20].
141
Figure 2
(b)
Single papilloma f o r ~ (a) and after .(b) laser resection.
Copynghled Malenal
142 Colt
C. Wegener's Granulomatosis
Wegener's granulomatosis is an idiopathic systemic disease characterized by
a necrotizing granulomatous inflammation and vasculitis that can involve
the tracheobronchial tree, lung parenchyma, upper airway, and kidneys.
Patients may have limited or multisystem involvement, but about 25% of all
cases are, in fact, limited to the lung or airways, in which case symptoms
include pleuritis, cough, hemoptysis, and dyspnea. Chest radiographs may
reveal cavitating pulmonary nodules, infiltrates, or atelectasis. The presence
of upper airway involvement, an active urinary sediment, and a positive C-
ANCA test increase the likelihood of Wegener's granulomatosis in patients
with tracheobronchial strictures.
Life-threatening tracheal stenosis has been described, and the
incidence of tracheal strictures, often in the subglottis, is about 16%. In
these cases, circumferential inflammation, edema, and fibrosis can extend
for several centimeters below the vocal cords (Fig. 3a and b). In many cases,
additional strictures are found in the bronchial tree, sometimes with
ulcerations and bleeding [21-23]. Treatment of these strictures can be
difficult, and usually stents are required in order to prevent recurrent
strictures, particularly in the face of active disease. Sometimes, there may
also be a role for surgical repair [24-25]
D. Polychondritis, Tracheopathica Osteochondroplastica,
and Amyloidosis
Several localized and systemic diseases are sometimes associated with
characteristic tracheobronchial abnormalities that can be amenable to laser
resection. Relapsing polychondritis, for example, is a rare systemic disease
that affects all types of cartilage. Most frequently, patients develop auricular
chondritis, but they also have cartilage loss in the peripheral joints and nasal
bridge. At least half of the deaths that occur are from respiratory failure due
to gradual collapse of large and smaller airways. The larynx is also
frequently involved, prompting recurrent aspiration and vocal cord
dysfunction.
Laser resection can occasionally be used, but generally stenting is
warranted to maintain central airway patency. Laser resection is occasion-
ally necessary to remove weblike strictures or bands of tissues that cross
segmental bronchi. Usually, however, strictures are caused by diffuse
inflammation and cartilaginous collapse of smaller airways, eventually
extending into the large airways [26,27]
TracheopCllhica oSleochondroplasrica is a rare disease in which cartilage
and osseous nodules form in the tracheobronchial tree causing deformities.
These deformities spare the posterior membranous wall of the airway, and
(a)
(b)
143
Figure 3 Tracheal stenosis from Wegener's granulomatosis before (a) and after (b)
laser resection.
144
Colt
rarely cause severe airway obstruction. Laser therapy is usually unnecessary,
but can be used on rare occasions to remove boney projections [28].
Amyloidosis can affect the tracheobronchial tree in a localized or a
diffuse fashion. Disease can be unrelenting, with gradual and near total
airway obstruction despite repeated attempts at laser resection and stenting.
Mortality is as high as 50%, usually from airway obstruction. Most patients
have symptoms suggestive of asthma, with shortness of breath and
expiratory wheezing. Many have a history of asthma as well. Chest
radiographs are often normal until late in the course of the disease process.
Computed tomographic scans may show bronchial plaques or calcified
masses of amyloid tissue obstructing the airway. Men are affected twice as
often as women, and most patients are in their fifties at the time of diagnosis
[29-31].
Flexible bronchoscopy usually reveals characteristic abnormalities
leading to diagnosis by forceps biopsy. These include a yellowish
submucosal infiltration and airway wall thickening, occasionally with
yellowish plaques or raised, wide-based mucosal and submucosal masses
that cause partial large or small airway obstruction (Fig. 4). Biopsies reveal
Figure 4 Tracheobronchial amyloid. Note pale, infiltrated mucosal appearance
with nodularity.
amyloid deposition, usually of the light chain type. These stain positive on
Congo red staining. There are rare reports of amyloid associated with
tracheopathica osleochondroplastica [32].
Laser resection allows removal of amyloid tissues, but deposi ts recur
quickly and repeat procedures are frequently necessary. There are rare cases,
however, of airway disease remission after laser resection. It is noteworthy
that patient fatalities have been reported from massive bleeding after laser
resection. This may be due to an increased risk of bleeding because of
amyloid infiltration of the bronchial wall vascular system. Surgical resection
is usually unwarranted because of the diffuse airway involvement. Stents can
be inserted, but may be quickly overgrown by recurrent amyloid deposition.
No consistent benefits have been demonstrated despite a wide variety of
medical therapies such as colchicine, oral corticosteroids, or cytotoxic
agents [33,34].
E. Infectious Processes
Infectious processes such as tuberculosis, fungal tracheobronchitis, syphilis,
and Klebsiella rhinoscleromatis infection can cause airway obstruction with
exophytic lesions removable by laser resection. Each can also cause fibrous
bronchial strictures. In patients with syphilis, bronchial gumma can result in
hemdptysis [35,36]. Fluorescent treponemal antibody absorption tests are
almost always positive.
In scleroma, a chronic infection usually confined to the nose, but also
involving the larynx and tracheobronchial tree, airway abnormalities
include granulomatous reactions, fibrous scars, edema, and mucosal
thickening with a pale, dry, yellowish discoloration. Biopsy classically
shows Mikulicz's cells that contain diplococci of K. rhinoscleromatis [37,38].
Fungal infections rarely cause airway obstruction requiring laser
resection, but early and late strictures are reported in patients with
coccidioidomycosis (Fig. 5), cryptococcosis, and histoplasmosis. Stenting
may be warranted in cases of external compression from exuberant
adenopathy or fibrosing mediastinitis. Sometimes, the general broncho-
scopic appearance of fungal lesions with associated mucosal swelling,
erythema, and inflammation can resemble a neoplasm. Careful biopsies and
washings are required, and specimens should be sent for histological,
cytological, and microbiological examinations.
Mycobacterial infection may cause both early and late strictures.
Caseous material and lymph nodes can erode through the airway wall,
requiring rigid bronchoscopy for removal [39-43]. Laser photocoagulation
may be required to prevent or treat associated bleeding. Patients with
tuberculosis may develop both early and late strictures with associated
146
Colt
Figure 5 Pseudomembrane and bronchial stricture from coccidioidomycosis.
mucosal hypertrophy, edema, erythema, and ulcerations. Ulcerations are
more frequently seen in patients who are AFB smear positive. Early on,
these strictures are fragile, and airway wall disruption during bronchoscopy
is a risk, especially if the airway mucosa is thin or necrotic. Late strictures
are usually very finn, circumferential, and complex. Many are elongated.
Laser resection and dilatation should be performed very carefully to avoid
procedure-related perforation and airway wall rupture. Diagnosis may be
made early in the course of the disease process by bronchoalveolar lavage
and washings, but it also can be made by biopsy. Lidocaine should be used
sparingly because of its potential adverse effect on bacteriological culture
results.
F. Stent-Related Granulation Tissue Formation
Granulation tissue is frequently noted as a complication of indwelling
silicone, metal, or hybrid stent . It appears that granulation tissue is found
most frequently around metal stents. This has prompted some investigators
to suggest that metal stents be avoided in patients with benign airway
strictures. Granulation tissue can be resected with either the Nd:YAG or
KTP laser. However, precautions are necessary to avoid setting fire to a
silicone or hybrid stent (Fig. 6), and to avoid breaking the wire mesh of a
metal stent [44,45]. In one experimental study [45], we found that stents were
readily damaged after continuous but short applications of Nd:YAG laser
energy (Table I). During resections, conventional wisdom suggests that
silicone stents be removed, and that the laser fiber be placed very close to
tissues being resected to enhance vaporization and reduce potential scatter.
Frequent cooling of tissues might be helpful, and smoke should be readily
evacuated.
G. Airway Complications After Lung Transplantation
Laser bronchoscopy is occasionally required when granulation tissue
formation occurs in concert with anastomotic problems after lung
transplantation. Recent studies suggest that anastomotic strictures occur
in about 5% of patients, but has been reported in as many as 15% of
transplant recipients [46-49]. Although complications such as firm
strictures, malacia, or dehiscence often are amenable to dilatation or stent
insertion, there are occasional cases in which granulation needs to be
removed using a laser. Because of the fragility of the anastomosis site, care
should be taken to avoid firing the laser perpendicularly onto the airway
wall.
Figure 6 Covered Wallstent damaged by Nd:YAG laser firing. Subsequent firings
could have easily set fire to.Jhe t . I
c;opyngn e a ena
Table 1 Total Number of Pulses (mean SO) and Total Energy in Joules (mean SD) Needed to Damage the Uncovered
Wallstent, Covered Wallstent. and Silicone Stents at Various Power Densities or Power Setting-Distance Combinations
Stent type
......

Co
Power density Total pulses Total energy Total pulses Total energy Total pulses Total energy
75 W/cm
2
60 NA (592 2J)" 36 4.3 359.3 43.1 J 60 NA (594 2.5)"
172 W/cm
2
60 NA (589.3 35J)" 35.6 4 355.3 45 J 60 NA (591 3.6J)"
225 W/cm
2
33 0.5 94.3 26.5 J 2.6 0.5 79.3 13J 3.3 0.5 103 199J
518 W/cm
2
3.3 0.5 96.6 In 2.6 0.5 77 18J 2.6 0.5 79 18.9J
300W/cm
2
1.6 0.5 563 18.5J 1.6 0.5 61.3 17 J 2.3 0.5 78.6 8J
690 W/cm
2
13 0.5 54321.8J 1.3 0.5 40 62 J 1.3 0.5 48 9.1 J
()
o
"'0

CD
0..

CD

Power/
distance
IOW/20mm
10W/IOmm
30W/20mm
30W 10mm
40 W/20mm
40W/lOmm
"Nol affecled.
Source: Ref. 45.
Uncovered Wallstent Covered Wallstent Silicone stent

H. Benign Tumors Such as Lipomas and Hamartomas
Endobronchial lipomas are smooth, round tumors that are readily
resectable using laser [50-52J. Often, tumors have a yellowish tinge,
although colors may vary from gray to pink. Tumors can resemble
carcinoids, but are usually less friable and bleed less easily. Often, lipomas
are pedunculated. Their narrow stalks can be easily severed using a few
bursts of Nd:YAG laser energy without preliminary photocoagulation of
the tumor itself. The tumor can then be removed using a snare, basket, or
forceps through the rigid bronchoscope. Despite appearance, benignity
should never be assumed, and the differential diagnosis of bronchogenic
carcinoma, metastases from cancers that can spread to the airways (such as
colon, breast, kidney and lymphoma), should always be considered. Other
potential diagnoses include liposarcomas, granular cell tumors, carcinoid
tumors, hamartomas, and even sarcoma (although sarcomas usually have a
much more rubbery texture).
Hamartomas are composed of fat, cartilage, and fibrous components.
Most occur within the lung parenchyma, but tracheobronchial tumors have
also been described. Hamartomas occur most frequently in patients between
the ages of 50 and 60 years. Tumors are slow growing and are traditionally
approached through open surgical resection. However, in many cases
lesions can be removed bronchoscopically. Although tumors are often
relatively embedded in the airway wall, they can be resected carefully using
Nd:YAG laser. Occasionally, the tumor might need to be cored out of the
bronchial wall using the beveled edge of the rigid bronchoscope.
Surveillance is warranted because hamartomas can recur locally. Overall,
hamartomas probably account for the majority of benign lung tumors, and
have a suspected incidence of endobronchial obstruction in 3-11 % of cases
[53,54J.
I. Carcinoid Tumors
Atypical and typical carcinoid tumors (Fig. 7a and b) present a fascinating
and often controversial area of discussion among interventional bronch-
oscopists and thoracic surgeons. Both are neuroendocrine tumors, although
they behave differently. Atypical carcinoids are characterized by mitotic
counts of 2-1 0 mi toses/mm
2
of viable tumor. Coagulative necrosis is usually
present. Metastases have been reported in about 50%, and 10-year survival
is 50%. On microscopic examination, typical carcinoids display less than
two mitoses/cm
2
, no features of necrosis, and have a 10-year survival of
more than 90%. Metastases occur in approximately 10% of cases. Overall,
smaller typical carcinoids (less than 3cm) have a less than 10% chance of
metastasis. Carcinoids well IlS adenoid cy.stic carcinoma and other "low-
c.;opynghted Matenal
150
(a)
(b)
Colt
Figure 7 Typical carcinoid tllmor obstructing a lobar bronchus before (a) and
after (b) laser resection.
Laser Bronchoscopy for Benign Disease 15/
grade" malignancies have routinely been referred for curative open surgical
resection [55,56].
In recent years, however, bronchoscopic resection has been increas-
ingly recommended by some experts. This position continues to be hotly
debated. Sergio Cavaliere, one of the most experienced laser bronchosco-
pists in the world, has been a long-time advocate for bronchoscopic
resection of selected carcinoids and other "benign" tumors. Criteria for
resection of these tumors include (I) strict intraluminal involvement and
limited extension of the tumor within the trachea, main bronchi, bronchus
intermedius, and proximal portions of the lower lobe bronchi; (2) low
probability of recurrence (in this regard, one must cite the Mayo Clinic
study of patients with low-grade malignancies, only 50% of whom were
symptom free 6 months after bronchoscopic laser resection [57]; (3) poor
open surgical risk; (4) obvious or predictable symptoms because of
substantial compromise of airway lumen, tumor location, or extent; (5)
recent lobar or pulmonary collapse attributable to the endobronchial tumor;
and (6) confirmation of the benign nature of the tumor by expert surgical
pathology examination.
It is true that many carcinoids and other benign airway tumors are
ideal for bronchoscopic laser resection. Pedunculated stalks are present and
frequently narrow, and tumors may not extend deeply into the airway wall.
In what is perhaps the largest study of bronchoscopic resection of carcinoid
tumors, only 25% of 150 carcinoids were considered to be ideal for resection.
In this study, 35 of 38 typical carcinoids resected remained disease free for
up to 16 years [58]. Also in this study, the investigators noted severe bleeding
during 20% of their resections; definitely a warning that laser resection
should only be undertaken by experienced bronchoscopists using adequate
precautions (rigid bronchoscopy, general anesthesia, training and knowl-
edge of how to manage the bleeding airway). They also identified the ideal
carcinoid tumor for curative laser resection. These are tumors with a
tracheal or bronchial wall footprint of less than 1.5 cm
2
, a total volume less
than 5 cm
3
, minor wall infiltration, and histopathological classification as a
typical carcinoid.
Careful surveillance bronchoscopy should be regularly performed to
detect recurrence. In cases where tumors do not fit these criteria, laser
resection can be attempted in an effort to relieve symptoms and decrease
tumor bulk prior to undertaking open surgical resection. Tumors that are
iceburglike, where tumor grows deep into the airway wall, are not
candidates for curative laser resection. The implantation base of the tumor
can be best ascertained using computed tomographic scanning and by
careful examination after preliminary laser resection of the intraluminal
portion of the tumor [59".(50] . .
vopynghted Matenal
152
Colt
A description of Cavaliere's laser resection technique [58] is
warranted as it has been adopted by many interventional bronchoscopists.
Using the rigid bronchoscope, Nd:YAG laser energy is applied using low-
power density (laser power setting of about 20W, and a long [up to 5-mm]
target tissue to laser fiber tip distance). This allows laser energy to
penetrate deep into the target tissue rather than be absorbed at the tissue
surface. As the carcinoid tumor develops an increasingly whitish
coloration during laser firing, the energy will increasingly penetrate the
tissue causing vasoconstriction of the deep vessels. On the other hand,
if the surface of the tumor is darkened from carbonization during laser
firing or blood, surface absorption will be high. The goal is to use at least
1500 Jjcm
2
of laser energy without causing bleeding or tissue destruction
by vaporization or carbonization. The tumor is then resected using the
beveled edge of the rigid bronchoscope and large forceps. The extent of
tumor implantation in both length and depth is then carefully assessed.
The base of the tumor can then be treated by firing the laser into airway
wall mucosa, recognizing that laser energy penetrates deeply into tissues,
and that one runs the risk of immediate airway wall perforation during
resection or delayed perforation from laser-induced tissue necrosis days
after the resection.
Surveillance might include flexible bronchoscopy, computed tomo-
graphy, and positron electron tomographic scans to help detect regional
mediastinal lymph node involvement. This author feels that both imaging
studies should be performed prior to any decision regarding curative
bronchoscopic resection. In case of partially or totally obstructing tumors,
it is my practice to recommend surgical resection (using parenchymal-
sparing techniques such as sleeve resections) after bronchoscopic removal
of the tumor and after treating the tumor base as described above. Once
the tumor has been resected, I recommend surveillance bronchoscopy every
3 months the first year and then every 6 months for several years thereafter
if the patient has refused open surgery or if the patient's medical status
does not allow an open procedure. However, I also perform frequent
surveillance bronchoscopy even in patients who have undergone surgical
resection.
VII. Conclusion
Many benign causes of central airway obstruction can be treated by laser
bronchoscopy. Treatments can be either palliative or curative, and are easily
combined with other bronchoscopic therapeutic modalities. Resection
techniques depend on operator preferences, target tissue consistence, color,
153
length, and thickness, and location of intraluminal abnormalities. Response
to treatment depends on the etiology, but also on operator experience and
techniques employed. Laser bronchoscopy can be used in conjunction with
open surgical proced ures or instead of open resection and anastomosis in
patients with unresectable or inoperable lesions. Having thorough knowl-
edge of the advantages and disadvantages of all therapeutic modalities
available, a readiness to employ a multidisciplinary approach toward
patient management, and a willingness to learn from personal experience
and from colleagues are common attributes of the expert laser broncho-
scopist.
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surgically respectable tracbeobronchial tumors. 1 Bronchol 2002; 9:90-95.
59. Van Boxem T1, Venmans B1, van Mourik 1C, et al. Bronchoscopic treatment of
intraluminal typical carcinoid: a pilot study. 1 Thorac Cardiovasc Surg 1998;
116:402--406
60. Sutedja TG, Schreurs AJ, Vanderschueren RG, et al. Bronchoscopic therapy in
patients with intraluminal typical bronchial Carcinoid. Chest 1995; 107:556-
558
7
Cryotherapy
Cold Therapy for the Tracheobronchial Tree
JAMES L. KNEPLER, Jr., and PRAVEEN N. MATHUR
Indiana University Medical Center
Indianapolis, Indiana, U.S.A.
I. Introduction
Many patients with endobronchial lesions present with a wide constellation
of symptoms such as cough, dyspnea, stridor, or hemoptysis. Local
treatments such as cryotherapy can alleviate these symptoms with relatively
low risk to the patient. Cryotherapy has gained popularity in treating
certain diseases of the lung, especially endobronchial lesions, both benign
and malignant. This is because cryotherapy is relatively safe, inexpensive,
easy to learn, and can now be performed through a flexible bronchoscope.
Several studies have shown the efficacy of cryotherapy [1,2] in relieving
symptoms caused by endobronchial lesions, as well as its complementary
effects on the conventional therapy of malignant lesions [3].
II. History
Ice has been used since ancient times to treat disease [4]. James Arnott
published the first recorded use of low temperature as therapy for
malignancy utilizing it to treat uterine carcinoma in 1845 [5]. The first
, Copyrighted Material
157
158
Knepler and Mathur
use of automated closed cryoprobes was in 1959 when it was used for the
treatment of Parkinson's disease and subsequently for brain tumors [6-9].
This cryoprobe employed a metal tip and could reach temperatures of
-196C. Gage was the first to use cryotherapy for endobronchial tumors,
doing so in 1968 through a rigid bronchoscope [10]. Rodgers reported the
use of cryotherapy for benign airway strictures during the late 1970s [II].
Sanderson, at the Mayo Clinic, reported the use of cryotherapy in the
palliation of endobronchial tumors in 28 patients [12]. Cryotherapy through
a rigid bronchoscope became widespread in Europe. For example, in France
during the 1980s and early 1990s, more than 2000 patients were treated with
cryotherapy via rigid bronchoscopy by 100 different teams. For some
reason, the technique did not catch on in the United States, and the
subsequent development of the Neodymium:yttnum-aluminum-garnet
(Nd:YAG) laser further diminished the popularity of cryotherapy. How-
ever, in 1994, ERBE-USA, Inc. (Marietta, GA) developed a flexible
cryoprobe that could be used in a flexible bronchoscope, and the technique
has since become more widespread.
III. Scientific Basis
Temperature is a measure of kinetic energy. As temperature drops,
molecular processes in cells will slow and ultimately stop. Thus, a cell
exposed to low temperature will undergo various sublethal stresses followed
ultimately by cell death. The way in which this occurs is dependent on many
factors: the freezing time [15], the thawing time [15,16], the temperature, the
lowest temperature achieved [17], and the number of freeze-thaw cycles [17].
Cryotherapy damages and destroys cells via multiple mechanisms.
Initially, extracellular ice crystals form while the intracellular matrix
remains in a liquid state [18]. If the cell is cooled slowly, the dehydration
of water allows an increase in solute concentration that prevents
intracellular freezing. If the cell is rapidly cooled, water will not have time
to pass the cell membrane; therefore, ice crystals will form in the cell.
Intracellular ice crystals damage various organelles, such as mitochondria
[14] and endoplasmic reticulum. Finally, complete crystallization of the cell
occurs. The rate of cell thawing also affects the amount of cell damage.
After a supraoptimal freezing, slower thawing allows recrystallization,
which is an extremely destructive process [or intracellular organelles owing
to the grinding of ice [19,20]. Therefore, cryotherapy is most destructive to
cells when they are frozen rapidly and thawed slowly.
After cryotherapy a clear line of demarcation appears between tissues
that have been frozen and those that have not been frozen [21]. The effect of
Cryotherapy
159
cryotherapy on tissue is dependent upon the existence of a microcirculation.
Ischemia and infarction occur after cryotherapy in minutes to hours.
Thrombosis occurs rapidly after thawing. This is due to several factors:
vasoconstriction of arterioles and venules, a lowering of intracapillary
hydrostatic pressure, an increase in capillary permeability, a decrease in
blood flow, and the formation of platelet plugs. These changes explain the
hemostatic effects of cryotherapy. Necrosis occurs across the whole area
that was frozen. The tissue is sloughed off after a few days. Therefore,
cryotherapy is not useful for lesions that need to be removed acutely for
impending respiratory failure.
Certain tissues are relatively cryosensitive (skin, mucous membrane,
nerve, endothelium, and granulation tissue), whereas others are more
resistant to cryotherapy (cartilage, fat, nerve sheath, connective tissue, and
fibrosis.) This allows destruction of malignant tissue while relatively
sparring nearby healthy tissue. Fortunately, tumor cells seem to be more
susceptible to cryotherapy than normal cells [21]
IV. Indications
The major indication for cryotherapy is the removal of endobronchial
lesions, both benign and malignant. It is important to note that cryotherapy
is of no benefit in extrinsic compression of the bronchus, as it cannot remove
tissue that cannot be visualized. It can also be used to adhere to
endobronchial objects such as foreign bodies, mucous plugs, and blood
clots to aid in removing them. It is also beneficial in removing granulation
tissue after lung transplantation. It has also been shown to be beneficial in
providing hemostasis after needle biopsy [22].
Benign tracheobronchial lesions tend to be rare. However, these
usually respond well to cryotherapy. Granulation tissue is particularly
susceptible to cryotherapy. In malignancy, tracheobronchial obstruction can
occur as an initial presentation or recur after initial therapy. Since cure is
always the object, surgery or other curative measures should be undertaken
first. When this is not possible, cryotherapy as a palliative measure is
acceptable. The patient's symptoms should be attributable to the
endobronchial lesion. Such symptoms include dyspnea, hemoptysis, stridor
and localized wheeze. If the patient has impending respiratory failure from
an obstructing tumor or stenosis, other modalities should be undertaken, as
cryotherapy is ineffective in rapidly removing tissue.
The prime candidate lesion for cryotherapy is a short, polypoid,
endobronchial lesion that is easily accessible via the bronchoscope and has
functioning lung tissue distal to the lesion., Lesions that are long, totally
160 Knepfer and Mathur
obstruct the airway, or have extensive submucosal involvement are treated
poorly with cryotherapy; other modalities should be considered.
Recently, cryotherapy has been utilized to treat malignancy in
conjunction with chemotherapy and/or radiation therapy. Evidence suggests
that cryotherapy may actually enhance the effects of chemotherapy [23].
This appears to be due to trapping of the chemotherapeutic agent (in this
instance, bleomycin) in the tumor owing to vascular disruption caused by
the freezing. There are studies that demonstrate the benefits of conventional
cancer therapy combined with endobronchial interventions, such as
Nd:YAG laser [24,25] and cryotherapy [3,26].
The optimal treatment of carcinoma in situ (CIS) and other superficial
cancers is debatable and yet to be determined. Endobronchial interventions
such as photodynamic therapy and electrocautery have been shown to be of
some benefit in treating CIS and other early-stage lung cancers [27-29].
Likewise, cryotherapy has been shown to be an effective treatment in some
early superficial carcinomas [30].
v. Clinical Basis
The experience with cryotherapy continues to grow. Most of the early
studies were done in Europe using a rigid bronchoscope, but in North
America the flexible bronchoscopy application is preferred. Maiwand
reported on 600 patients treated with cryotherapy at Harefield Hospital in
London (31). There have been several studies showing the utility of
cryotherapy in malignant endobronchial lesions. These have generally
looked at improvement in symptoms. Most of these have been done utilizing
a rigid bronchoscope. Vergnon reported improvement in six of eight
patients (three had benign lesions) undergoing cryotherapy [32]. These
patients were not candidates for laser therapy or had failed prior laser
therapy. Angebault reported improvement in 7 of8 benign tumors and 16 of
30 malignant tumors [33]. Walsh prospectively studied 33 patients under-
going 81 cryotherapy treatments, and found improvement in lung function
in 58% of the patients and bronchoscopic evidence of relief of obstruction in
77% (2). Mathur showed symptomatic improvement in 17 of 22 patients
treated with cryotherapy through a flexible bronchoscope; most of these
patients had malignancy [I].
The treatment of CIS utilizing cryotherapy is currently under
investigation. Deygas studied cryotherapy performed through a rigid
bronchoscope for early superficial carcinoma in 35 patients [30]. At I
month and at I year there was a 91 % complete response rate. Local
recurrence did occur within 4 years in 10 patients (28%).
Cryotherapy
161
The treatment of benign lesions has not been as thoroughly
investigated, although most benign lesions appear to be responsive to
therapy. Many of the above series included a handful of benign lesions with
a generally good result [1,32,33]. Rodgers showed an improvement in 20 of
24 patients with tracheal strictures who completed therapy [34].
Presently, cryotherapy is clearly indicated for palliation of sympto-
matic nonoperable endobronchial lesions. Future studies will need to be
pursued to determine its utility in benign lesions and in early-stage lung
cancer, such as CIS.
VI. Techniques and Equipment
A. Cryogens
There are two cryogens utilized with bronchoscopy: liquid nitrogen and
nitrous oxide. Liquid nitrogen is widely available and stored near its
saturation temperature (-196C) in vacuum insulated containers. It is
nontoxic and nonflammable. As liquid nitrogen passes through the transfer
line at room temperature, it evaporates and slowly cools the tip. It takes
about I min to reach -196C during the first freeze cycle and 20-30 sec for
subsequent ones. When flow is stopped, the liquid in the transfer line must
be cleared, thus delaying thawing.
Nitrous oxide is used as a cryogen that cools to -89C. It is easily
stored at room temperature in high-pressure bottles. Nitrous oxide expands
from high pressure to atmospheric pressure at the cryoprobe tip (the loule-
Thomson effect). This expansion lowers the temperature and produces
droplets of fluid at the wall of the metal probe as they evaporate. This occurs
quickly, as there is very little metal to cool. Several studies have shown that
the temperature required to destroy tissue is between -20 and -40C. The
temperature of the ice on the tip of the probe is -40C, whereas the
temperature 1mm from the probe is -20C, which is sufficient to destroy
tumor. Nitrous oxide is more expensive than liquid nitrogen.
The actual setup for cryotherapy requires a console, the cryoprobe,
and the transfer line. These are relatively inexpensive and cost about 10% of
the Nd:YAG laser. Otherwise, there are no special accessories needed other
than those used for normal bronchoscopy such as forceps and hemostatic
agents.
B. Flexible Bronchoscopy
Flexible cryoprobes for use with flexible bronchoscopes are now available
(ERBE-USA Inc.). The..vrobe. is 90cro in leJ;lgth and 2.4mm in diameter
, r.;;opyngntea Matenal
162 Knep/er and Malhur
with a tip of 7 mm in length. Therefore, to use this probe requires a
bronchoscope with a working channel of at least 2.6 mm in diameter.
After the bronchoscope is inserted into the airway normally and the
lesion is visualized, the cryoprobe is inserted through the working channel
until it protrudes about 2cm. The probe can be applied tangentially,
perpendicularly, or directed into the lesion. The cryogen is released with a
foot pedal. Ice appears on the probe within 10-J5sec. Freezing is allowed
for 30-60 sec. Often, experienced operators rely on color changes to
determine the optimal length of time of freezing. Thawing starts with the
release of the foot pedal, and can take several seconds. Once thawed, the
probe can be retracted. Several freeze-thaw cycles (usually two to four) are
employed. The probe can be moved 5-6 mm away and the process repeated.
Occasionally, suctioning of blood or debris is required between cycles. When
removing material from the airway, the probe is retracted before complete
thawing occurs. Tissue can be removed with forceps or can be left to necrose
on its own. Sloughing occurs over days, and the patient will then cough up
the necrotic debris. Cryotherapy is continued until tissue removal is
maximized. Repeat bronchoscopy is undertaken at 2 weeks to monitor the
effects of cryotherapy, and further treatment can be administered as needed.
C. Rigid Bronchoscopy
With a rigid bronchoscope, rigid, semirigid, or flexible cryoprobes can be
used. Rigid and semirigid probes are more durable and need less
maintenance; however, flexible probes allow cryotherapy in a wider range
of treatable areas (e.g. the upper lobes). Rigid probes also have a reheating
element that allows thawing in 1-2 sec. Rigid bronchoscopy is undertaken
under general anesthesia in a normal fashion. Of note, in contrast to laser
bronchoscopy, high oxygen concentrations can be used without restriction
during cryotherapy. The distal tip of the bronchoscope should be abollt I cm
above the lesion. The application of the cryoprobe is similar to that done for
flexible bronchoscopy: two to four freeze-thaw cycles, after which the
cryoprobe is moved 5-6 mm to freeze adjacent areas. Repeat bronchoscopy
(either rigid or flexible) is also done within 2 weeks to assess efficacy, to
remove necrotic tissue, and to perform further cryotherapy if necessary.
VII. Complications
One of the attractive features of cryotherapy is the low rate of
complications. In one series of 600 patients, there was one death (from
cardiorespiratory arrest 5 hr after the procedure) [31]. In the same series,
there were two tracheoesophageal fistulas, although one patient had also
Cryotherapy
163
received radiation therapy. Other lesser complications include pneu-
mothorax, atrial fibrillation, bronchospasm, spillage from postobstructive
pneumonia, fever, and bradycardia. Aggravation of cold agglutinin anemia
has also been reported. Vergnon reported one death within 8 days of
cryotherapy from massive hemoptysis [3]. Mathur reported one cardiopul-
monary arrest. The patient survived without any long-term effects [I]. All
things considered, cryotherapy is safer than Nd:YAG laser or electro-
cautery.
VIII. Conclusion
Endobronchial cryotherapy is a safe, inexpensive, and relatively easy to
learn technique to remove endobronchial lesions. Its major drawback is the
delayed effect of treatment; therefore, it cannot be done when rapid results
are necessary. Its major utility today is for the palliation of symptomatic
malignant endobronchial tumors. Time will reveal its usefulness for early-
stage lung cancers.
Cryotherapy may be performed via flexible or rigid bronchoscopy.
Most of the early studies were done using a rigid bronchoscope. However,
with the introduction of the flexible cryoprobe, its use will continue to grow.
References
l. Mathur PN, Wolf KM, Busk MF, Briete WM, Datzman M. Fiberoptic
bronchoscopic cryotherapy in the management of tracheobronchial obstruc-
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2. Walsh DA, Maiwand MO, Nath AR, Lockwood P, Lloyd MH, Saab M.
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3. Vergnon JM, Schmitt T, Alamartine E, Barthelemy JC, Fournel P, Emonot A.
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4. Hippocrate. Aphorismes par. Lyon: J.F. Rabelais, 1532.
5. Arnott J. On the Present State of Therapeutic Enquiry. London, 1845.
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7. Cooper IS, Lee A. Cryothalamectomy-hypothermic coagulation: a technical
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8. Cooper IS. Cryogenic surgery: a new method of destruction or extirpation of.
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9. Cooper IS, Stellar S. Cryogenic freezing of brain tumors for excision or
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10. Gage AA. Cryotherapy for cancer. In: Rand R, Rinfret A, Von Leden H, eds.
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12. Sanderson DR, Neel HB, Fontana RS. Bronchoscopic cryotherapy. Ann Otol
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13. Homasson JP, Renault P, Angebault M, Bonniot JP, Bell NJ. Bronchoscopic
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16. Miller RH, Mazur P. Survival of frozen-thawed human red cells as a function
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17. Gage AA. Critical temperature for skin necrosis in experimental cryosurgery.
Cryobiology 1982; 19:273-282.
18. Mazur P. The role of intracellular freezing in the death of cells cooled at supra
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19. Forsyth M, Macfarlane DR. Recrystallisation revisited. Cryo-Ietters 1986;
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20. Martino MN, Zariteky NE. Ice recrystallization in a model system and in
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25. Macha H, Becker KO, Kemmer HP. Pattern of failure and survival in
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27. Homasson JP, Pecking A, Roden S, Angebault M, Bonniot JP. Tumor fixation
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28. Hayata Y, Kato H, Konaka C, Armeniya R, Ono J, Ogawa I, Kinoshita K,
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8
ROBERTO F. MACHADO,
CYNTHIA P. SAAD, and ATUl C. MEHTA
Cleveland, Ohio, U.S.A.
I. Introduction
TERRENCE D. COULTER
Ferrell Duncan Clinic, Inc.
Springfield, Missouri, U.S.A.
Tracheobronchial obstruction, either benign or malignant, is a recognized
cause of significant morbidity and mortality. Surgical resection provides the
best chance of curative treatment, yet it can only be achieved in a minority
of patients. Recent advances in endoscopic techniques have created a
number of palliative and even curative treatment modalities for patients
with airway obstruction. These include laser photoresection, cryotherapy,
brachytherapy, and photodynamic therapy and endobronchial electrosur-
gery (EBES) [IJ.
The use of EBES was first reported in 1926. The utilization of
electrosurgery through a flexible bronconchoscope, however, was first
reported in the early 1980s by Hooper with varying degrees of success [2,3J.
Since the development of a newer generation of electrosurgical devices, used
primarily in gastrointestinal endoscopy, there has been renewed interest in
its application in the airways. A number of publications have confirmed its
efficacy in the treatmen1 of .airway but studies showing
c.;opyngnrea Malenal
167
168
Machado et al.
superiority of a specific bronchoscopic treatment technique are still lacking.
This method has been considered to be the "economic" version of laser as it
has "laserlike" tissue effects at a small fraction of the cost. The preference of
the treatment technique is based on the expertise and previous experiences
of the bronchoscopist and on theoretical considerations. In this chapter, the
clinical use of this underutilized technique is reviewed.
II. Background and Physics
Endobronchial electrosurgery is defined as the application of high-frequency
alternating electrical current via accessories introduced through the
bronchoscope, to cut, coagulate, or vaporize lesions involving the large
airways. The use of an alternating current at high frequency avoids
stimulation of nerve and muscle fibers. The amount of heat generated and
tissue destruction is directly proportional to its resistance, amount of
current applied (in watts), and duration and size of the contact area between
the probe and the tissue. The degree of the tissue resistance is in inverse
relation to its moisture and vascularity [3-5]. Desired tissue effects, such as
coagulation, cutting, or vaporization, are achieved by applying electrical
current at different settings.
Histological effects of electrocautery application include early
coagulative necrosis with acute inflammation followed by delayed fibrosis.
Van Boxen et al. [6] evaluated the tissue effects of EBES in areas of normal
airway in six patients undergoing resection for non-small cell lung cancer
using a monopolar device with a power setting of 30 Wand variable
application times of I, 2, 3, and 5 sec. After I or 2 sec of application, only
superficial damage was found. After 3 sec, damage extended as far as the
underlying cartilage layer. Cartilage damage was documented in most cases
after 5sec of application. Bronchial wall perforation was not demonstrated
111 any case.
III. Instruments
Electrosurgery equipment (Fig. 1) is a standard and readily available
instrument in most hospitals. The units generally produce three current
modes "cut," "coagulate," and "blend." The cut mode utilizes high current
with low voltage allowing for vaporization of tissue water and cell
destruction owing to a high concentration of electrical energy with minimal
lateral thermal spread. The coagulation mode produces low current with
high voltage providing slow heating that is dispersed over a larger area.
Protein denaturation leads to a viscous coagulum causing hemostasis. The
169
Figure 1 Electrocautery unit (Olympus America Inc., Melville, NY).
blend mode combines the two modalities at a setting midway between the
cut and coagulate modes.
While using the monopolar unit, the patient should be grounded with
an electrode pad, which is placed close to the expected site of cauterization,
allowing for concentration of current from the small surface area (high
current density) probe to the large surface (low current density) neutral
electrode pad. Effective monopolar coagulation depends on a dry surgical
field immediately surrounding the tissue to be cauterized. With a bipolar
unit, no grounding is necessary, since the electric current passes in an arc
form between electrodes localized in the electrocautery probe.
IV. Accessories
The most commonly used electrosurgical accessories (Fig. 2) are:
I. Blunt and spherical probes: used for coagulation and hemostasis
(similar to direct contact laser).
2. Loop snare: used for removal of pedunculated and polypoid
endobronchial lesions. Its use makes possible the complete
removal of the lesion with minimal bleeding as it coagulates while
cutting the lesi!(;bEM1Jhted Material
170
Machado et al.
Figure 2 Electrosurgical accessories (left to right: blunt coagulation probe,
spherical coagulation probe, forceps, knife, and loop snare).
3. Electrocautery knife: used for broad-based surface coagulation
and tissue resection (like webs, scars, and sessile lesions) in narrow
lumens,
4. Electrocautery biopsy forceps: samples and cauterizes endobron-
chial tissue simultaneously, and is best suited for vascular lesions
biopsies and tumor debulking.
All accessones are available for use with both rigid and flexible
bronchoscopes.
V. Techniques
Coagulation with either the blunt or the spherical probes can be achieved
both by either direct contact with the lesion or from a short distance
creating an electrical arc between the applicator and the tissue. The former
provides superficial coagulation, whereas the latter achieves deeper
coagulation. While working on lesions involving smaller airways, the
application must be limited to 3 sec or less given the risk of mucosal and
cartilaginous injury and possible stricture. The loop snare is placed around a
polypoid lesion as close to its base as possible. As the loop is slowly and
gradually tightened around the lesion, blended current is applied, cutting
and coagulating tissue (Fig. 3). Regardless of the mode or technique used, it
Figure 3 Electrosurgery snare technique.
171
is critical to keep the area of treatment as dryas possible and free of debris
to prevent dispersion of the electrical current reducing the tissue effect.
A. Rigid Versus Flexible Technique
Rigid bronchoscopy is more popular in continental Europe, whereas the use
of flexible bronchoscope is preferred in North America [7]. It seems clear
that adequate electrosurgical debulking can be achieved with both
instruments. Selection of modalities depends upon the degree of airway
obstruction, the patient s ability to tolerate general anesthesia, and, most
importantly, the bronchoscopist's expertise.
Rigid Technique
The time-honored rigid technique requires general anesthesia in the majority
of cases. It seems to be of greater value in patients with imminent respiratory
failure or large tumors in the proximal airways where rapid control of
bleeding or tumor debulking is necessary while providing optimal aIrway
and ventilatory control.
Flexible Technique
The flexible technique allows more maneuverability and better reach for
more peripheral lesions. The use of an insulated bronchoscope minimizes
the risk of a shock or burn to both the patient and the operator. The
procedure can be safely performed under local anesthesia, and in most cases
without the need for endotracheal intubation. It can be performed in an
outpatient setting and without the neeci for the/allocation of operating room
Copyngnrea"Matena
172 Machado et al.
personnel. This method is also favored III patients with cervical spine
deformities and facial injuries.
VI. Clinical Use
The classic indication for bronchoscopic electrosurgery is palliation of
unresectable malignant airway obstruction (Fig. 4) [1,4-12]. However,
recent studies have also demonstrated its value in the management of benign
airway obstruction as well as with curative intent in patients with localized
malignant disease (Figs. 5 and 6) [8,9].
Table I summarizes the studies of endobronchial electrosurgery in the
management of malignant and benign airway lesions. As expected, the
majority of patients studied presented with unresectable malignant disease.
Figure 4 Right upper lobe orifice before (top) and after (bottom) probe ablation of
an endobronchial post-transplant Iymphoproliferative disorder lesion causing
obstruction in a lung transplant recipient.
173
Figure 5 Endotracheal hamartoma before (top) and after (bottom) excision with
the loop snare.
The studies have different proportions of patients with malignant disease
and had varying definitions of a satisfactory response. Overall, immediate
and short-term bronchoscopic relief of airway obstruction was obtained in
69-100% of patients. Subjective improvement in dyspnea, control of cough,
and resolution of hemoptysis could be achieved in a similar percentage of
individuals. The mean duration of response was 2.6 months in 17 patients
studied by Sutedja et a!. [10], and the overall survival was not longer than I
year. Unfortunately, objective assessment of lung. function was limited to
only one study, which demonstrated a mean improvement in forced
expiratory volume in I sec (FEY I) of 53% and of 20.6% in the forced vital
capacity (FVC) [II].
Another interesting application of EBES is the management of
radiographically occult lung cancer and typical carcinoid tumors with
curative intent. Thirteen patients with radiographically occult squamous cell
carcinoma underwent electrosur,gery.: - After .a median follow-up of 22
r..;opyngnrea Malenal
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Machado et al.
Figure 6 Main carina demonstrating the right main stem bronchus with a 50%
stricture due to scarring from resolved endobronchial tuberculosis (top). The
electrocautery knife was used to make radial incisions followed by balloon
bronchoplasty (bottom).
months, a complete response was achieved in 80% of cases and no tumor-
related deaths occurred [8]. The results of these studies were comparable to
other techniques such as photodynamic therapy and brachytherapy [12]. In
another study, Van Boxen et al. [13] performed bronchoscopic treatments
(neodymium:yttrium-aluminum-garnet [Nd:YAG laser and electrocautery])
in 19 patients with intraluminal typical carcinoid. A complete response was
obtained in II of 14 patients (78.5%) treated with electrocautery. All
bronchoscopic techniques are inaccurate to access the actual tumor depth;
only empirical visual findings of tissue necrosis are available to the treating
bronchoscopist. Consequently, long-term follow-up of these patients is
necessary before widespread application of any of these methods could be
recommended [6].
175
Table 1 Results of Studies of Endobronchial Electrosurgery in Malignant and
Benign Diseases
Immediate
Reference N Technique response (%) Malignancy
3 4
FB/GA/CS 100 4/4
14 14 FB/GA 7J 6/12
15 18
FB/GA/CS 100 13/18
16 15 RB/GA 73 IS/IS
11 29 RB/GA 96 28/29
17 10 RB/GA 90 10/10
18 17 FB/CS 88 17/17
19 32 RB/FB/CS 84 27/32
10 56 FB/GA/CS 69 49/56
20 38 FB/CS 89 13/38
FB, flexible bronchoscopy; RB, rigid bronchoscopy; GA, general anesthesia; CS, conscious
sedation.
VII. Complications and Treatment Failure
Complications from endobronchial electrosurgery are rare and usually of
minor clinical significance. Airway bleeding has been described in close to
5% of patients [3,8,10,11,13-20]. In the majority of cases, the amount of
hemorrhage is small and inconsequential. Endobronchial ignition has been
reported in two patients treated with flexible scopes [3,15]. In both cases, a
high-inspired fraction of oxygen was utilized during the procedure. Finally,
one case of aspiration pneumonia has also been reported. Other known
complications are pneumothorax, stenosis following circumferential treat-
ment of lesions, and the development of local fibrosis and cartilage damage
[21-23]. If the airway structural support is extensively compromised,
tracheobronchomalacia can follow electrosurgical therapy.
The most frequent cause for electrosurgery failure is related to the
confusing endoscopic appearance of some lesions. Some polypoid-appearing
lesions can be quite extensive and involve distal airways, and their removal
with electrocautery becomes problematic and complex. Vascular lesions
may also pose difficulties during EBES from bleeding. Blood in the area to
be treated creates a wet layer that diffuses the electricity and limits the
effectiveness of electrosurgery [20]. The utilization of laser instead of the
electrocautery in bulky and extensively vascular lesions seems to be more
appropriate. Copyrighted Material
/76 Machado el al.
VIII. Comparison to Other Techniques
The choice of a particular modality is obviously based on lesion's specific
characteristics, expertise of the bronchoscopist, and equipment availability.
As a general rule, however, the acuity and severity of presentation will be the
major determinant factors in the selection of a particular technique. In cases
were immediate tumor debulking is necessary Nd:YAG laser, electro-
surgery, and mechanical removal are the most adequate alternatives. In
nonemergent cases, options like brachytherapy, cryotherapy, and photo-
dynamic therapy can be considered.
Although EBES has been demonstrated to be effective in case series,
there are no prospective studies directly comparing electrocautery to
Nd:YAG laser. A retrospective analysis of 14 patients treated with Nd:YAG
laser and 17 patients treated with electrocautery demonstrated an equal 70%
symptomatic improvement in both groups [9]. In a study conducted at The
Cleveland Clinic Foundation, a series of 118 evaluations for laser
photoresection were performed. Of those, 47 evaluations were deemed to
be amenable to EBES [20]. Forty-two (89%) procedures were successful in
alleviating obstruction, representing a 36% reduction in the need for laser
photoresection. However, Nd:YAG laser still seems to be more effective for
very bulky and lengthy airway lesions as well as those that are very vascular.
Electrocautery is less expensive than laser photoresection. The cost of
setting up electrosurgery, excluding the bronchoscope, is less than $10,000
U.S. dollars, whereas that of setting up Nd:YAG laser could approach
$200,000 U.S dollars [9]. Additional cost savings are offered by avoiding the
need for operating room time and general anesthesia, which are frequently
required when laser is used.
IX. Argon Plasma Coagulator
One of the technical offshoots of EBES is the argon plasma coagulator
(APe). This relatively new noncontact method relies on ionized argon gas as
a current conductor between the probe and the tissue. Although it has been
shown to be effective in the treatment of hemoptysis and obstructive lesions
of the central airways [24-26], it causes only superficial tissue destruction
when compared to the standard electrosurgical probe. Therefore, APC is
not considered to be ideal for bulky lesions. The main advantage of this
technique is its ability to treat sessile lesions located at sharp angles from the
tip of the electrode as the positively charged argon gas flows toward the
negatively charged oozing treatment area, eliminating the need for direct
contact [27] (Fig. 7). The procedure can be performed either with a rigid or a
177
Figure 7 (a) Granuloma involving right main bronchus, (b) APC application of
the lesion (arrow-electric current conducted by argon gas), (c) granuloma
immediately after APC application, (d) right main bronchus appearance after
debulking of ablated lesion.
flexible bronchoscope. While using the latter, proper precautions should be
taken to avoid endobronchial ignition. APe units have the same cost as
electrocautery units and the argon gas is inexpensive. However, the
disposable probes add $200-300 U.S. dollars to the cost of the procedure.
x. Conclusion
Endobronchial electrosurgery is a safe and effective treatment option for a
variety of malignant and benign endobronchial lesions which remains
underutilized [28]. It compares favorably to laser photoresection in the
majority of cases. Electrocautery equipment is relatively less expensive and
readily available in the majority of institutions, and it is a cost-effective
alternative to Nd:YAG laser. When compared to electrocautery, the
equipment for both brachytherapy is more
178
Machado et af.
costly, the procedures are more complex, and the effects are not immediately
apparent.
Electrosurgery seems to be better suited for daily bronchoscopic
practice than laser. With increasing interest in the field of interventional
pulmonology, it is likely to gain in popularity. Argon plasma coagulator
also adds to the armamentarium. However, comparative studies are needed
to establish its definitive role in the management of large airway
obstructions.
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4. 1ackson R. Basic principles of electrosurgery: a review. Can 1 Surg 1970;
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5. Barlow DE. Endoscopic applications of electrosurgery: a review of basic
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1821.
9
Endobronchial Brachytherapy
DATTATREYUDU NORI and
AKKAMMA RAVI
Joan and Sanford I. Weill Medical
College of Cornell University
New York Presbyterian Hospital
and The New York Hospital
Medical Center of Queens
JAGAN MOHAN POll
The New York Hospital Medical Center
of Queens
I. Introduction
SUHRID PARIKH
t
Joan and Sanford I. Weill Medical
College of Cornell University
and The New York Hospital Medical
Center of Queens
An estimated 157,000 patients died of lung cancer in the United States in the
year 2000 [lJ. Although surgical resection offers the best chance for a cure in
this disease, its use is limited to the less than 20% of patients who present
with early-stage, localized lung cancer. The vast majority of the patients
present with locally advanced disease (with/without distant metastases), and
failure to obtain local control continues to be a major issue. Several
Radiation Therapy Oncology Group (RTOG) studies that utilized external
beam radiation therapy have reported local failure rates of 31-51% [2], and
the Veterans Administration Lung Group reported that residual intrathor-
acic tumors were responsible for death in 75% of patients with squamous
tDeceased.
181
182
Nori ef at.
cell carcinoma and 50% of patients with adenocarcinoma and large cell
carcinoma [3].
Endobronchial obstruction is a common and potentially life-threaten-
ing complication in these patients. Twenty to 30 percent of newly diagnosed
lung cancer patients may have an element of atelectasis and postobstructive
pneumonia due to endobronchial disease [4]. Furthermore, despite standard
systemic and locoregional therapies, about 50% of lung cancer patients will
develop symptomatic endobronchial involvement [5]. Thus, management of
endobronchial and peribronchial tumors becomes increasingly important in
the palliative setting.
Even in the setting of curative radiation therapy, most of the patients
present with fairly large and bulky tumors. Although a distinct radiation
dose-response relationship has been established for lung cancer as regards
locoregional control, the proximity of several vital, dose-limiting structures
(heart, esophagus, spinal cord, and adjoining normal lung) constrains the
maximum external beam radiation therapy dose. Endobronchial bra-
chytherapy provides an elegant approach to dose escalation, while sparing
the surrounding normal tissues, in an attempt to improve local control.
Small or occult carcinomas of the lung in medically inoperable patients
constitute another subgroup in which brachytherapy can be used to boost
the external beam radiation dose in a curative setting. Similarly,
endobronchial brachytherapy may be the only viable option in patients
with second lung primary tumors who have received prior lung radiation.
Recently, endobronchial brachytherapy has also been used in
conjunction with bronchial stents. Like intravascular stents, these stents
can stimulate a proliferative reaction leading to the formation of
granulation tissue and obstruction of the stented airway. Kennedy et al.
reported successful inhibition of this proliferative response with the use of
endobronchial brachytherapy in two patients with lung transplantation who
developed anastamotic bronchial obstruction [6].
II. History
Endobronchial brachytherapy is the most common lung brachytherapy
technique. Here, the radiation is delivered from within the tracheobronchial
lumen by one or more afterloading applicators/catheters appropriately
positioned within the trachea or bronchus. The use of brachytherapy for
lung cancer is not new [7]. As early as 1922, Sidney Yankauer, from New
York, described two cases of lung cancer treated by radon capsule
implantation via a rigid endoscope [8]. However, both radium and radon
had significant radiation protection issues, and Ormerod's eloquent
183
summary of these problems, in 1941 [9], led to a virtual abandonment of this
technique. It was not until the 1980s that two seminal developments led to a
virtual renaissance in endobronchial brachytherapy. First was the advent of
modern fiberoptic bronchoscopy, which allowed the insertion of small-
caliber afterloading catheters into every major branch of tracheobronchial
tree even in critically ill patients. These flexible catheters could be inserted
under direct visual guidance and subsequently afterloaded either manually
or with remote afterloaders. The second major development was the
availability of high-activity iridium 192, which could either be obtained as
multiple end-to-end seeds for manual afterloading or as miniature, high-
activity seeds driven by a remote afterloader [10].
A. Pretreatment Evaluation
The need for endobronchial brachytherapy is predicated on the presence of:
Histological diagnosis of invasive lung cancer.
Involvement of the proximal airways (trachea, main stem, or lobar
bronchi).
Predominance of intraluminal disease, as identified by a broncho-
scopy.
The endoluminal disease must be "obstructive enough" to cause
significant clinical symptomatology (cough, shortness of breath,
obstructive pneumonia, and/or hemoptysis).
The patient must have a reasonable performance status and life
expectancy (usually >3 months) to benefit from palliation.
Apart from the standard medical evaluation, Speiser et al.'s Symptom
Index can be used for an "objective" assessment of the patient's overall
clinical status [11]. The same investigators have also described a "obstruc-
tion score" to assess the degree of endoluminal narrowing at bronchoscopy,
whereas the University of Wisconsin group has utilized a "symptom
resolution" data sheet for the determination of response [5]. Prior to the
procedure, the patient's imaging studies (e.g., chest radiographs, computed
tomographic [CT] scans) are carefully reviewed, to obtain a fair estimate of
the location and length of the bronchial narrowing (because of an inability
to pass the endoscope beyond the area of narrowing, it is often necessary to
rely entirely on the preprocedure imaging studies for an estimate regarding
the actual length of the narrowing). It is important to appreciate that
endobronchial brachytherapy may not be the appropriate initial therapy for
patients with airway obstruction, massive postobstructive atelectasis, and a
very marginal pulmonary reserve. These patients usually have very bulky
extra bronchial disease, is only the tip of
184 Nori et ClI.
the proverbial iceberg. They are often on the brink of respiratory failure,
and the added "insult" of bronchial occlusion by the bronchoscope and
brachytherapy catheter may easily tip them into overt respiratory failure.
Alternative approaches are often required to "stabilize" these patients prior
to endobronchial brachytherapy. The techniques available for managing
endobronchial disease are listed in Table 1. Of these, laser therapy, external
beam radiotherapy, and endobronchial prosthesis are the most commonly
utilized modalities in clinical practice.
Based on the extent of the locoregional disease, the presence/absence
of distant metastases, and the patient's general condition, the treatment
intent should be clearly defined as "curative," "palliative," or "recurrent."
This has important implications for the radiation dose and fractionation-
palliative treatments are designed to be quick, effective, and with a low risk
of complications, whereas potentially curative regimens are generally more
protracted and involve elaborate preplanning.
III. Catheter Placement
The first step in endobronchial brachytherapy is the proper placement of an
afterloading catheter(s). It is through this catheter(s) that the radioactive
sources are either manually loaded or driven via a computer-controlled
cable. The procedure is performed in a fully equipped endoscopy suite or in
a dedicated high-dose-rate brachytherapy (HDR) suite. The bronchoscopy
is performed under standard hemodynamic monitoring with the .usual
systemic premedications and topical anesthesia. As a matter of routine
practice, a video camera head is used for photographic documentation of
the lesion (location, length of airway involved, and the percentage of
luminal narrowing). It is extremely useful to measure the distance between
the proximal and, if possible, the distal end of the tumor from a fixed
internal landmark such as the tracheal carina. This allows determination of
Table 1 Techniques for Managing Endobronchial Disease
Biopsy recanalization
Electrocoagulation
Cryosurgery
Laser therapy
Endobronchial prosthesis
External beam radiotherapy
Endobroncbial brachytberapy
l85
the longitudinal tumor dimension, which can be correlated to a reference
point (like the carina) on the simulator radiographs. After inspection of
both sides and determination of the number of catheters required, catheter
placement is carried out through the accessory port (Figs. I and 2). A
radiopaque internal stiffening cable can assist in placing the catheter. In
low-dose-rate (LDR) brachytherapy, the catheter may be introduced
transnasally or across the cricothyroid membrane, and is subsequently
guided by the bronchoscope to lie across the tumor.
The catheter may be positioned in one of two ways: It may be placed
such that the catheter tip is 2 cm beyond the estimated distal end of the tumor,
or it can be passed in as far as it goes so as to wedge it into a smaller peripheral
bronchus. The latter approach may be preferable when the procedure is being
done in a bronchoscopy suite (as opposed to a dedicated HDR brachyther-
Figure 1 Endobronchial brachytherapy catheter being introduced through the
accessory port of the ftexibt!d15J1W9lffif8I1f1taferial
186
Nori el a1.
Figure 2 Schematic showing the bronchoscope introduced across the tumor and
the brachytherapy catheter being placed to cross the lesion.
apy suite), since there is less chance of catheter displacement during patient
movements if it has been properly wedged (if the entire procedure is being
done in a HOR suite, the patient does not have to be moved for simulation, or
subsequent treatment, and catheter movement is less likely).
Because of the prolonged treatment time (1-2 days), wedging the
catheter is particularly useful with LOR brachytherapy. The placement is
confirmed visually and fluoroscopically, and the bronchoscope is withdrawn
under continuous fluoroscopy to maintain catheter position. The catheter is
then secured at the nose, marked with indelible ink to provide a visual alert
Endobronchial Brachylherapy
187
in case of displacement, and as an additional precautionary measure, the
external length from the tip of the nostril is documented (and verified again
prior to actual treatment).
IV. Endobronchial Applicators
A variety of different applicators (catheters) are available for endobronchial
brachytherapy. The major differences involve the caliber, the length (100 vs
150 em), the composition, the presence of a radiopaque tip, the presence of
an inflatable balloon, and the presence of distance markers. Although
various systems of outer sheaths, balloons, and cages have been designed to
hold the catheter in a central location in the airway, in order to avoid
localized hot spots on the bronchial mucosa, these have generally not been
found to be necessary in the vast majority of patients. The simple procedure
of lodging the catheter distal to the obstructed airway is sufficient to hold it
in place. The most common calibers used are either 5 French (1.7 mm) or 6
French (2 mm). The 6 French catheters are better at negotiation acute
curvature such as the right upper lobe, but a 6 French catheter requires a
bronchoscope with a 2.2-mm diameter porthole. In contrast, if a 5 French
catheter is used, a bronchoscope with a 2.0-mm diameter porthole is
sufficient. At the start of each case, it is advisable to ensure that the
bronchoscope port will accommodate the selected catheter.
V. Treatment Planning
Following appropriate placement of the catheter(s), orthogonal radiographs
are obtained, with dummy seeds in place, at the "best" angles as determined
at the simulator (Fig. 3). In LDR therapy, the radioactive source consists of
an iridium 192 seed train with multiple iridium 192 seeds (of uniform
strength) embedded in a nylon ribbon. Radiation therapy treatment
planning is fairly simple and is limited to delineating the exact target site,
target length, and the total dwell time (this depends on the prescribed dose,
the prescription distance from the source, and the source strength, and
usually varies between 24 and 48 hours).
High-dose-rate brachytherapy allows for greater flexibility in treat-
ment planning. The goal of treatment planning is to ensure dose
homogeneity. There are two aspects to this optimization. Clinically, we
try to optimize the treatment by ensuring that the mucosal surface is
circumferentially equidistant from the source. This is not always feasible
when the tumor is eccen1.ric- orohlel1l.'>. are .also encountered at bronchial
"c;opyngnlea lVIarenaT
188
Nori et at.
Figure 3 Simulator film with the catheter in place, with a dummy seed ribbon
(white dots) within it; the superimposed isodose plan shows the highly localized
radiation dose distribution.
bifurcations and where the catheter negotiates acute bends, as in treating the
upper lobe segments.
The other aspect of optimization has to do with treatment planning,
and is related to the progressive narrowing of the tracheobronchial tree.
Usually, the HDR treatment is planned with uniform dwell times along the
catheter. Depending on the diameter of the bronchial tree along the
treatment length, this can lead to substantial overdosing or underdosing.
Sophisticated formulae are available to estimate the progressively decreasing
diameters of the tracheobronchial tree, and ideally, one should select
reference points in each portion of the bronchial tree and use computer
optimization to ensure an isoeffective mucosal dose; however, this can be
quite cumbersome and time consuming.
In practice, the first step in computerized treatment planning involves
189
digitizing the seed positions into the treatment-planning computer.
Optimization points are then placed at target radii in four cardinal
directions, starting from the first active dwell position. As a rough guide,
the first active dwell position is usually placed at approximately half the
radial treatment distance from the catheter. When using multiple catheters
(Fig. 4), it is crucial not to put optimization points closer than' the
prescription distance. The dose to the spinal cord is always estimated at
several levels to ensure that cord tolerance is being respected.
VI. Dose Prescription Point
Because various investigators have used different prescription points, total
doses and number of fractions, meaningful comparison between different
studies is not always possible. Some investigators [12] have suggested
adopting I cm as the standard, but this is not universally accepted [13]. In
fact, prescription depths ranging from 0.5 to 2.0 cm have been used, and these
differences reflect the changing caliber of the tracheobronchial tree, the
eccentric location of some catheters that are pushed to one side by the
endoluminal tumor, as well as the desire to treat some of the peribronchial
tumor. In an attempt to allow meaningful comparison between different
series, the American Brachytherapy Society (ABS) recommends that,
regardless of the actual prescription point, the dose at I cm from the center
of the catheter and at the center of the active source length also be reported
[14]. With improvements in technology, three-dimensional brachytherapy
planning may become feasible and cost effective and may then permit tailoring
of the dose distribution to the three-dimensional shape of the tumor. A margin
of 1-2 cm is usually provided along the long axis of the tumor (to treat any
submucosal tumor extensions and allow for minor catheter movements).
VII. Dose and Fractionation
The dose and fractionation for HDR brachytherapy varies widely, ranging
from 15 Gy in one fraction to four to five fractions of 4 Gy each. The
prescribed dose is, of course, highly dependent on the depth prescribed. A 1-
week interval between fractions is most commonly used. The ABS has
recommended palliative doses of 3 weekly fractions of 7.5 Gy each, or two
weekly fractions of lOGy each, or four weekly fractions of 6 Gy each,
prescribed at a distance of I cm from the source. Depending on the previous
total irradiated dose or location (e.g., the left upper lobe bronchus), the
prescribed depth or number of fractions may be reduced. When
brachytherapy is used in conjunction wilh ex.ternal beam radiation therapy,
r..;opyngnrea Malenal
190
Nori el al.
Figure 4 Treatment or a complex birurcation tumor with two catheters.
191
either in a curative or palliative setting, the brachytherapy dose fractiona-
tion has to be individualized depending on the external beam regimen.
Brachytherapy doses should also be reduced if patients have been treated
with aggressive chemotherapy (which can often have a radiosensitizing
effect), and concomitant chemotherapy should be avoided during the course
of the endobronchial brachytherapy. The majority of patients treated with
an HDR brachytherapy regimen are treated on an outpatient basis.
The less often used LDR brachytherapy regimen involves hospitaliza-
tion of the patient in a lead-lined room during treatment (usually 2 days).
Widely varying dose-fractionation schemes have been used, but the ABS
recommends 30 Gy at I cm when it is used as the sole modality for
palliation, and about 20 Gy at I cm when it is used to supplement external
beam radiation therapy.
A. HOR Versus LOR Brachytherapy
High-dose-rate brachytherapy employs a miniaturized, highly radioactive
iridium 192 source which is driven along the length of the target volume by a
computer-controlled cable. Because of a very active source, the dose delivery
is very rapid and the average treatment time ranges from 3 to 5 min. LDR
brachytherapy uses a series of low-activity iridium 192 seeds encased in a
nylon ribbon; the radiation oncologist manually loads this into the catheter
that has been positioned within the bronchial tree. For the most part, HDR
endobronchial brachytherapy has replaced LDR endobronchial therapy.
HDR brachytherapy has the advantages of outpatient treatment, no
radiation exposure to the medical personnel, lowered costs, and the ability
to handle a high patient throughput. Since the treatment times are very
short (a few minutes as opposed to 1-2 days), patients are much more
comfortable during the treatment and there is little chance of the catheter
becoming displaced. HDR brachytherapy also allows optimization of the
dose distribution to conform to an irregularly shaped tumor volume (see
Fig. 4), and offers the option of modifying subsequent fractions based on
tumor response. The large dose per fraction may also have a radiobiological
advantage, especially in the palliative setting.
B. Role of Prior Laser Recanalization
The general indications/prerequisites for laser recanalization include [15J:
Airway obstruction unresponsive to other therapies
Endobronchial lesion without evidence of extension beyond the
cartilage
Axial length of lesion less
t
th.an. 4
t
cm I
c..;opyngn ea IVla ena
192
Nori et al.
Patent lumen visualized beyond the tumor
Functioning lung tissue beyond the obstruction
Patient able to tolerate less than 50% F102
Also, laser resection is limited to endoluminal/mucosal disease, and does not
address any submucosal or peribronchial disease-this makes the responses
quite short-lived, although repeated resections are possible. Despite these
caveats, some of the major advantages of laser resection prior to
endobronchial brachytherapy include:
Rapid opening up of occluded airway
Opens up a passage for brachytherapy catheter
Improves treatment geometry
Provides better "depth-dose" and thus a higher response rate, which
may also be more durabLe
One of the concerns regarding combining laser resection with
endobronchial brachytherapy is the suggestion of a higher risk of fistula
formation with this combination [16]. Because of this concern, some
investigators have recommended a 1- to 2-week interval between laser
recanalization and brachytherapy, whereas others do not consider this a real
issue and combine both at the same sitting [17,18].
VIII. Palliative Endobronchial Brachytherapy
The single most common indication for endobronchial brachytherapy is
perhaps for palliation. Both LDR and HDR techniques have been used.
Afterloading techniques with LDR irradiation using iridium 192 have
provided good local control and palliation [19]. Several single-institution
reports with LDR brachytherapy have shown symptomatic improvement in
50-100% of patients, radiographic improvement in 17-78%, and broncho-
scopic improvement in 60-93% [20-25]. The results of these studies are
summarized in Table 2.
As discussed above, HDR endobronchial irradiation is now being used
increasingly in many centers to treat both primary and recurrent
endobronchial diseases. The major series reported in the English literature
have been collated in Table 3. As noted, symptomatic improvement ranges
from 50-99%, radiological improvement occurs in 35-100% of patients, and
objective bronchoscopic responses are observed in 75-90% cases.
The variability in reported results can be explained by several factors,
including patient selection, different treatment schema, and the use of
additional treatments (e.g., external radiation, laser). Regardless of these
variations, a consistent aspect of most palliative series is the durability of the
~
l:l...
<::>
~
c;
:::s
C')
~
~
Table 2 Results of Low-Dose-Rate Trials
b;:,
;;
C')
{
;::-
'"
~
":
Symptoms improved (%) X-ray improved (%) Bronchoscopy improved (%) Dose No, of patients Reference
()------------------------------------------
.g 18 65 30 Gy at 5-IOmm NA NA 60
5,19 87 25 Gy at 20mm 59 NA 76
tg. 20 18 16-39 Gy at 10mm 83 NA 70
~ 66 20-30Gyat2mm 78 78 93
:5:22 32 2Q-56Gyat8-16mm 66 21 85
OJ 23 17 30 Gy at 5mm 53 17 60
~ 24 39 7-28 Gy at 10mm 85 91 89
0)' -----------------------------------------------
- NA = not available,
Source: Modified from Nag S, Kelly JF. Horton JL, Komaki R, Nori D. Brachytherapy for lung cancer-recommendations from the American
Brachylherapy Society. Oncology 200 I; 15(3):371-381.
.......
\0
"""
--
'0
-l::..
Table 3 Results of High Dose-Rate Trials
Symptoms improved X-ray improved Bronchoscopy improved
Reference No. of patients Dose (0/0) (0/0) (0/0)
Seagren 20 10 Gy at 10mm x I 94 NA 100
Macha 56 7.5 Gy at 10mm x 3 74 88 75
()
Nori 15 5GyatlOmmx4 80 88 NA
0
Burt 50 15-20 Gy at 10mm x I 50-86 46 88
Fass 15 5-35 Gy at 10mm x 1-6 75 NA NA

Miller 88 10 Gy at 10ml11 x 3 NA NA 80
::J"
CD
Stout 100 15-20 Gy at 10 111m x I 50-86 48 NA
Q.
Zajac 82 10 Gy at 10 mm x 3 80 NA 75
s:
Q)
Khanavkar 12 8 Gy at 5ml11 x 2-8 67 NA 100
CD Aygun 62 5 Gy at 10111111 x 3-5 NA 36 76
Bedwinek 38 6 Gy at 10ml11 x 3 76 64 82
Gauwitz 24 15 Gy at 6 mm x 2 88 83 100
Mehta 31 4 Gy at 20ml11 x 4+ 88 71-100 85
Sutedja 31 10 Gy at 10111111 x 3 82 NA NA
Speiser 144/151 7.5/10 Gy at 10111111 x 3 85-99 NA 80
Zajac 50 5 Gy at 10111111 x 3 82 NA 74
Chang 76 7 Gy at 10111111 x 3 79-95 NA 87
NA = not available.
Source: Adapted from Speiser B. Endobronchial Brachytherapy, Refresher Course Presented at American Society for Therapeutic Radiology and
Oncology, October 1995.

:::.
195
response-there is a significant improvement in between two-thirds and
three-fourths of the remainder of the patients' lives (with marked ameliora-
tion of, or total freedom from, any intrathoracic tumor-related symptoms).
Table 4 represents a summary of the efficacy of endobronchial
brachytherapy in alleviating specific intrathoracic tumor-related symptoms.
IX. Curative Endobronchial Brachytherapy
The most logical patient for curative endobronchial brachytherapy would be
one with in situ cancer of the bronchial mucosa that is detected on routine
screening. The small number of such patients are usually treated with
photodynamic therapy, and there is limited experience with radiation
therapy in this setting.
The standard definitive therapy for unresectable lung cancer is a
combination of chemotherapy and external beam radiation. However, given
the known dose-response relationship, selected patients (those with
predominantly endobronchial tumor) may benefit from endobronchial
brachytherapy either alone or as boost to external beam radiation therapy.
Reddi et al. [27] reported on 32 patients with newly diagnosed advanced
non-small cell lung cancer (NSCLC) who were treated with 60 Gy external
beam radiation therapy followed by a HDR boost of7.5 Gy at I cm with an
optional second and third boost at 2 and 4 weeks if residual tumor was still
present at bronchoscopy. Although the median survival was only 8 months,
100% of the patients experienced full reaeration, and biopsies were negative
Table 4 Palliation of Symptoms
a
Symptoms
Dyspnea
Cough
Hemoptysis
Postobstructive
. b
pneumoma
Response
rate (%)
85
80
95
90
Complete
response (%)
55
30
60
35
Partial
response (%)
30
50
35
55
a There are no real data to indicate that endobronchial brachytherapy improves survival. This is
not surprising as, apart from TNM staging, several other factors, including performance status
and weight loss, have a major impact on patient survival in lung cancer.
b [n patients with malignant airway obstruction and lung collapse, endobronchial brachyther-
apy prior to external beam radiotherapy can allow for substantial "lung-sparing." Patients ex-
periencing complete aeration were spared almost 50% of their ipsilateral lung volume: even those
having a partial response were s.J2ared a.bout 25% of thei.r ipsilateral lung volume [261
Table 5 "Curative" External Beam Radiation Therapy with Supplemental ("Boost") Endobronchial Brachytherapy for Locally
Advanced Lung Cancer
()
No. of External radiation Median survival
0
Reference patients dose (Gy) Technique Dose/fractionation (months)
'b

28 32 60 High dose rate 7.5 Gy/l cm x 3 8
':
CD
29 62 50-60 High dose rate 5.0 Gy/I cm x 3-5 13
0. 30 22 60 Low dose rate 20 Gy/2cm x 2 8.5
s: High dose rate 4.0 Gy/2 cm x 2
Q)
31 54 20-70 High dose rate 7.0 Gy/I cm x 3 NA
CD

32 65 55-66 High dose rate 27-100 Gy/l cm x 2-4 8
33 56 60 High dose rate boost group 4.8 Gy/I cm x 2 10
42 60 Control group 8
NA = not available.
......
'0
0\

:::.

Endobronchial Brachyfherapy
197
in the eight patients in whom they were obtained. Aygun et al. reported a
larger series of 62 patients with a slightly better median survival of 13
months [28J. These somewhat better results may merely represent patient
selection, since this series included some stage r patients; survival in No
patients was 20 months versus 9 months for N+ patients. Table 5
summarizes the results of few reported series.
Another innovative use of brachytherapy involves radiating minimal
residual disease at the surgically resected stump (positive margin or
positive post resection washings). Macha et al. recently reported on 17 such
patients treated with four fractions of 5 Gy prescribed at I cm. Tumor-free
survivals of up to 4 years were noted [33J. In addition, "curative"
endobronchial brachytherapy has been tried in patients with early-stage
lung cancer who are medically inoperable because of poor pulmonary
reserve, advanced age, or patient's unwillingness for surgery. Marsiglia et
al. reported a survival rate of 78% at a medium follow-up of 2 years in 34
patients treated with high dose-rate brachytherapy at doses of 30 Gy in six
fractions [34J.
x. Complications: Grading and Management
Brachytherapy-related hemoptysis has been graded simply as massive
(usually fatal) or nonmassive. A literature review shows fatal hemoptysis
rates of 0-32% in both LDR and HDR series, with mean values of around
5-8%. The variation in the incidence of this fatal complication among
different series can probably be explained by inaccuracies in reporting,
variable length of patient follow-up, different patient populations, varia-
tions in prior, concomitant, and subsequent therapy, different rates of
follow-up bronchoscopies and biopsies, variations in total treated lengths,
total dose, and fraction size [35J. The left upper lobe bronchus is believed to
be a high-risk site; probably because of the close proximity of the pulmonary
artery at this point. This anatomical relationship, along with acute
angulation of the catheter at the take-off of the left upper lobe bronchus,
resulting in a very high dose at the "hot spot," may cause the pulmonary
artery to receive 20-30 Gy for a prescribed fraction of only 6 Gy. Despite all
this, there are no identifiable factors that can consistently predict fatal
hemoptysis (large fraction size->5-6 Gy-especially when the dose is
prescribed deep into the bronchial wall (> I cm)-is a definite risk factor, but
that merely represents a "radiation overdose"). Table 6 summarizes the
reported incidence of fatal hemoptysis in the literature.
Radiation bronchitis and stenosis associated with endobronchial
brachytherapy have been...well d091,1mep!ed. The most likely cause for these
c.;opyngnted Malenal
198
Nori el al.
Table 6 Survey of Literature on Fatal Hemoptysis
No. of % Fatal
Reference Year Dose patients hemoptysis
Seagren 1985 10Gyat 10mm x I 20 28
Macha 1987 7.5 Gy at lOmm x 3 56 7
Nori 1987 20Gyat 10mm x 3 15 0
Burt 1990 15-20 Gy at IOmm x I 50 10
Fass 1990 5-35 Gy at 10mm x 1-6 15 0
Miller 1990 10 Gy at IOmm x 3 88 0
Stout 1990 15-20 Gy at 10mm x 100 NA
Zajac 1990 10 Gy at 10mm x 3 82 10
Khanavkar 1991 8 Gy at 5mm x 2-8 12 50
Aygun 1992 5 Gy at 10mm x 3-5 62 15
Bedwinek 1992 6GyatlOmmx3 38 32
Gauwitz 1992 15 Gy at 6mm x 2 24 4.0
Mehta 1992 4 Gy at 20 mm x 4 + 31 3.0
Sutedja 1992 10 Gy at 10mm x 3 31 32
Speiser 1993 7.5(10 Gyat 10mm x 3 144(151 7.0/8.6
Zajac 1993 5 Gy at 10mm x 3 50 0
Chang 1994 7 Gy at 10mm x 3 76 4.0
NA = not available.
Source: Adapted from Speiser B. Endobronchial Brachytherapy. Refresher Course Presented at
American Society for Therapeutic Radiology and Oncology. October, 1995.
is the high radiation dose to the bronchial mucosa, especially in regions
where the catheter comes into close proximity with the bronchial wall as a
result of tracheobronchial angulations or eccentric catheter lie as a result of
the tumor. Vascular changes in the bronchial wall as a result of, for example,
long-standing smoking, the presence of a large tumor, prior external
radiation therapy, or chemotherapy can all predispose to these complica-
tions. Laser resections, performed in conjunction with endobronchial
brachytherapy, can also predispose to these complications. A grading
system for radiation bronchitis and stenosis has been proposed by Speiser
and Spratling and subsequently modified by the ABS (Table 7). Treatment
suggestions according to grade are summarized in Table 8.
XI. Conclusion
Afterloading HDR brachytherapy is a very useful tool in the clinician's
armamentarium in the care of patients with lung cancer:
Table 7 ABS-Modified Grading of Radation Bronchitis and Stenosis
199
Grade I Mild mucosal inflammatory response with swelling characterized by a
thin, whitish, circumferential membrane. No significant luminal
obstruction. No intervention necessary.
Grade II White fibrinous membrane with exudation causing symptoms such as
cough and/or obstructive problems requiring therapeutic
intervention.
Grade III Severe inflammatory response with marked membranous exudates.
Multiple debridement or other interventions required to reestablish
full lumen of airway.
Grade IV Greater degree of fibrosis with resulting circumferential stenosis leading
to a decrease in luminal diameter.
Grade V Necrosis, tracheal and/or bronchial malacia, or massive hemorrhage
related to the treatment without any evidence of invasion of the
tumor.
Source: Nag S, Kelly JF, Horton JL, Komaki R, Nor; D. Brachytherapy for lung cancer-
recommendations from the American Brachylherapy Society. Oncology 2001; 15(3):371-381.
Table 8
Grade I
Grade II
Grade III
Grade IV
A small number of lung cancer patients do present with early
lesions and exophytic lesions often limited to the bronchus-these
constitute ideal cases for endobronchial brachytherapy.
There is a definite dose-response relationship for intrathoracic
tumor control in the average patient with bulky lung cancer.
Normal structures limit the dose that can be safely delivered via
external beam therapy. Because of this, pathological complete
responses are infrequent with conventional radiotherapy alone.
Unfortunately, uncontrolled bronchial tumors can be very
Treatment of Radiation Bronchitis
Observation
Steroids-oral and/or aerosol fluconazole
Saline-diluted bronchodilators
Narcotic cough suppressants
Mul tiple bronchoscopic debridements
Balloon or bougie dilation
Laser photoresection
Debridement
Stents
Source: Speiser BL, Spratling L. Radiation bronchitis and stenosis secondary to high dose rate
endobronchial irradiation. lnt J Radial,Oneol Bioi y ~ 1993; 25:589-597.
Copynghted Matenal
200 Nori el at.
symptomatic, if not fatal. Endobronchial brachytherapy provides a
simple approach for local dose escalation and thus improved local
control.
Even after high doses of external beam radiation, recurrence at the
primary site is a common problem. Endobronchial brachytherapy
may be the only option for rapid and effective palliation in these
patients.
Because of the field cancerization, second primaries are also not
uncommon-prior external radiation therapy severely limits the
available options in this setting.
Endobronchial treatment can be especially useful in reaerating a
collapsed lung in patients with malignant airway occlusion ("Iung-
sparing" role of endobronchial brachytherapy). Thus, it can
provide quick resolution of symptoms before the patients are
planned for definitive treatment such as chemotherapy and/or
radiation therapy with or without surgery.
Recent technological advances have helped to make this procedure
more appealing to the physician and patient alike, contributing to
its widespread use. Well-designed clinical trials are needed to define
better the role of this modality in the face of competing and
complementary treatment methods.
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10
LUTZ FREITAG and GUNTHER REICHLE
Center for Pulmonary Medicine and Thoracic Surgery
The Hemer Pulmonary Clinic
Hemer, Germany
I. Introduction
Ninety percent of all patients with lung cancer require palliative measures
during the course of their disease [1,2]. In at least one-third, the trachea and
main stem bronchi are involved. Cancer growth in these airways may cause
distressing symptoms such as dyspnea, intractable coughing, hemoptysis,
and postobstructive pneumonia. Interventional bronchoscopy has emerged
as a most valuable part of modern lung cancer management [2]. Several
techniques and devices have been developed to remove, or at least reduce,
the volume of intraluminally growing neoplastic tissue through rigid or
flexible bronchoscopes. Simple mechanical removal with the tip of the
bronchoscope (coring out) or with a large forceps has been replaced or is
usually complemented with laser photoresection or electrocoagulation [3-5].
Longer lasting effects can be accomplished with cryotherapy, photodynamic
therapy, and brachytherapy [2,6].
One basic limitation of any endoscopic tumor removal is the high
degree of vascularization in cancer tissue. Dripping blood and blood clots
can obstruct primarily unaffected bronchi, impairing the already poor
gas exchange. Without 'lJ1 f f i ~ n t hemostyptic technique, it is hardly
c..;opyngnted Matena
203
204 Freitag and Reichle
possible to reopen a tumor-obstructed airway with acceptable risks. The
neodymium:ytrium-aluminum-garnet (Nd:YAG) laser has revolutionized
interventional bronchoscopy, mainly because of its coagulation properties.
The infrared light of the noncontact laser can coagulate tumor vessels under
the surface. The clinically realistic depth of penetration is approximately
6-8 mm. At higher energies the laser is a potent device for cutting and
vaporization. However, in cases of severe hemoptysis with heavy bleeding
from large tumors, even laser coagulation becomes impossible. In a blood-
overflooded bronchus supplying vessels cannot be identified and the laser
energy does not reach its target. Electrocautery, preferably with a hollow
probe and an incorporated suctioning catheter, is a useful alternative, but
owing to its dimensions, it requires a rigid bronchoscope. Cryotherapy is not
feasible under these circumstances as the warm blood dissipates the cold and
vessel shutdown cannot be accomplished.
The latest development in the search for an ideal coagulation device
for endoscopic procedures is the argon plasma coagulator. Early models
were clinically used in the chest cavity in Russia in 1989 [7]. In 1991, devices
with probes became available that could be passed through the working
channel of a flexible endoscope. They were immediately used in the
gastrointestinal (GI) tract [8], and have since then become the most
commonly used instrument for coagulation in the esophagus, the stomach,
and the colon [9,10]. First published reports about the use of argon plasma
coagulation in interventional bronchoscopy appeared in 1996. We
introduced this method in our institution in 1994, and have since used it
in almost 800 patients.
II. Technical and Practical Aspects
Argon plasma coagulation (APe) is a noncontact form of electrocoagula-
tion. Ionized argon gas, the so-called plasma, is used as a conductor for a
high-frequency current between the monopolar electrode and the tissue. An
APC system is composed of an argon gas cylinder, a computer-controlled
high-frequency electrosurgical generator with a gas flow controlling valve,
and an endoscopic probe. A large neutral electrode is taped on the arm of
the patient. After adjusting gas flow, electrical energy, mode, and pulse time,
the device is controlled during the procedure with a double foot switch. The
latest model from ERBE USA Inc. (Marielta, GA) has a color display with
an on-screen display menu explaining the different modes in a graphical
fashion (Fig. 1). A probe attached to the gas source and the electrical
generator is passed through the bronchoscope. The argon plasma beam exits
the tip of this isolated heat-resistant probe and after ignition delivers the
Argon Plasma CoaguLator
205
Figure 1 Latest model APC device (ERBE, Tubingen, Germany) with a color
display and on-screen menu explaining the different application modes in graphical
fashion.
electrical energy to the surface of the tissue where it is transferred into heat.
Within seconds, white brownish crusted debris builds up on top of the
dehydrated tissue (Fig. 2). A field voltage of 500 VI mm between the probe
and the tissue is generated, resulting in a blue-glowing plasma beam up to
10 mm in length (Fig. 3). The tip of the probe should stick at least 10 mm out
of the bronchoscope and should be brought 3-8 mm close to the tissue.
Typical argon gas flows are in the range of 1.0-1.6 LJmin, and electrical
energies are adjusted between 30 and 60 W for the use in the tracheobron-
chial system. The energy can be delivered continuously or pulsed. The
thermal effect on the tissue depends on the power and the time. Basically,
higher power results in a better hemostatic effect. New modes like soft and
forced coagulation with soft, intense, and aggressive effects using different
pulse frequencies and duty cycles are currently being explored. Flexible
probes with diameters of 1.5 and 2.3 mm are available that can be passed
206
Freitag and Reichle
Figure 2 APC endobronchial treatment showing white-brown crusted debris build
up on top of the dehydrated tissue.
through the working channel of a routine flexible-bronchoscope. Recently,
special probes have been developed that can "shoot" perpendicularly or
even slightly backwards. In addition, some investigational devices are
equipped with a suction catheter (Fig. 4).
In contrast to a laser beam, the energy of the argon plasma coagulator
does not necessarily follow a geometrically straight path when it exits the tip
of the probe, nor does it always reach the nearest area of contact. The high-
frequency current follows the lowest electrical impedance, and as blood, like
Argon Plasma Coagula/or
207
Figure 3 APC application with Aexible bronchoscopy showing plasma beam
striking tissue.
other fluids, is a better conductor than dry tissue, the argon plasma beam
energy has to some degree a preferential effect on bleeding tissues. After
desiccation and vessel shutdown, the APC effect becomes self-limiting. This
makes the device so advantageous for the management of hemoptysis. It
offers good coagulation combined with protection against wall perforation.
Argon plasma coagulation can be used for ablation. However, the
depth of penetration is significantly lower than laser or cryotherapy. Even
with high energy, the APC effect is limited to the upper 2-3 mm of the tissue.
Tumor debulking with APC has to be done in several steps in combination
with forceps removal. The plasma beam is sprayed over the tumor surface.
The generated heat dehydrates the tissue and coagulates the superficial
blood vessels. Now part of the devitalized tumor can be removed with a
forceps. As the deeper layers are still vulnerable, careful peeling is required.
The next layer is coagulated and removed and so on until sufficient tumor
debulking has been accomplished. Although it is more time consuming than
YAG laser vaporization, excellent local results can be achieved with this
step-by-step APC technique as illustrated in Figure 5a and b. Working with
208
Freitag and Reichle
Figure 4 APC probe for a rigid bronchoscope. The probe had 90-degree beam
angulation and includes a suction channel.
(a) (b)
Figure 5 Bulky tumor at main carina before (a) and after (b) APC debulking.
Argon PLasma CoaguLator
209
a rigid bronchoscope, larger argon probes with suction channels and a large
optical forceps speeds up the procedure, but basically most APC treatments
can be done with flexible instruments. Whether flexible or rigid broncho-
scopy is selected depends on the individual situation of the institution,
training and experience, and the availability of general anesthesia. Although
we do most of these procedures through the rigid bronchoscope with jet
ventilation under general intravenous anesthesia [12], others achieve
comparable results with the flexible approach [13,14].
Considering its versatility for multiple endoscopic disciplines, an APC
system is comparably inexpensive. The basic hardware sells for less than
$20,000 and prices for probes range from $150 to $250 They can be
sterilized for multiple use. The cost for the argon gas is negligible.
III. Risks and Precautions
Ignition hazards have been reported with laser bronchoscopy [15]. Plastic
tubes, stents, and foreign bodies can be put on fire by the heat of the laser
beam. The argon plasma coagulator is considered to be a safer device, and it
has been used to remove tumor and granulation tissue growing over the
edges of silicone and metal stents [12, 16]. Theoretically, fire is prevented
because the argon beam flushes away the essential oxygen. However, it is
possible to ignite some inflammable materials with APC. In one of our
patients, a flexible bronchoscope caught fire during an APC procedure and
caused severe mucosal damage. The analysis of this accident and laboratory
experiments revealed that most likely a ventilation jet gas stream with high
oxygen concentration and residual heat after the argon flush beam resulted
in a retarded ignition. This previously unreported incident has forced us
always to lower the inspiratory oxygen concentration under 40% during
APC treatments. We can no longer recommend the use of APC close to
Silastic stents. We now use cryotherapy for these indications.
Another safety issue is a possible threat of argon gas embolism if the
activated probe sticks into highly vascularized tissue. We recommend to keep
the probe a safe distance from the lesion and to work in the noncontact mode.
This is not always easy as vision is sometimes obscured by blood, secretion,
and smoke and the patient often coughs producing a moving target.
IV. Results
Crosta and coworkers treated 47 patients who had hemoptysis and stenoses.
Immediate airway patency and hemostais were obtained in 91.5% of the
P
atients [14]. There were..uo complications.. I
r..;opyngntea Nlatena
210 Freitag and Reichle
Morice and coworkers treated 56 patients who had bronchogenic
carcinomas. Thirty-one patients suffered from hemoptysis and 14 from
symptomatic airway obstruction [13]. Regarding hemostasis, the group
reported a success rate of 100%. With a mean follow-up time of 97 92
days, no recurrent bleeding was observed. The degree of airway obstruction
decreased from 76 25% to 18 22%. No complications were reported.
The investigators emphasize the simplicity and safety of the method and
recommend the use of APC in an outpatient setting.
In our institution 821 bronchoscopic APCs were performed in 667
patients until June 2001. Eighty-eight percent of these patients had a
malignant tumor. Three hundred and sixty patients suffered from
symptomatic obstructions of the central airways; in two-thirds of the cases,
trachea or main stem bronchi were involved. In 95% of all cases, the clinical
condition could be improved. In the remaining patients, the length of the
stenosis or the degree of extrabronchial compression had been under-
estimated. In 190 patients, APC was applied because of hemoptysis. Except
in one patient who received emergency thoracotomy, all bleeding could be
stopped by APC. As mentioned before, we performed most of the
procedures with a rigid bronchoscope. Mean treatment time was I hr.
V. Other Indications
There are numerous other indications for APC. For example, it has been
used to treat stent complications [12,16]. In our series, we were successful in
all 80 patients in whom stents had been partly obstructed by tumor or
granulation ingrowth or overgrowth. The possible risk of ignition has to be
considered. Of course, the technique is also feasible in benign obstructions
provided that there is mainly intraluminal growth [12,17]. In some operated
cancer patients, excessive granulation tissue formation could be removed
with APC.
We could not observe any advantage or disadvantage when comparing
the procedure or the results with those of Nd:YAG laser treatment.
A. Early Cancer
A promising option is the use of APC for the eradication of early cancers,
microinvasive cancers, and multiple mucosal metastases. In the GI tract,
APC is already considered to be a reasonable alternative to excessive surgery
in cases of early neoplastic mucosal changes [18]. For the respiratory tract,
the role of APC needs to be established. Very few data are available (19).
One advantage of APC is the fact that areas not accessible by the Nd:YAG
laser can be reached and treated without risk of airway wall perforation.
Argon Plasma Coagulator 211
Figure 6a and b show plasma coagulation of small tumor lesions in two
subsubsegments of an upper lobe bronchus. It is impossible to apply laser
energy because the fiber cannot be bent to such a degree. Our standard
approach in these cases is photodynamic therapy (PDT) or brachytherapy.
We are currently studying the efficacy of APC. This could be a less expensive
treatment avoiding the problems associated with PDT (skin sensitivity).
However, this use might be limited by the low depth of penetration.
Currently, APC cannot be recommended for this indication except in studies
with very close surveillance. Finally, any APC system can be used without
the argon gas in normal electrocoagulation mode with contact probes. It
might be that this mode is the better alternative for early lung cancer unless
new modes of APC prove to be more efficient in deeper tissue layers.
VI. Conclusion
Argon plasma coagulation is a safe and efficient treatment option for
patients with lung cancer invading the central airways. It is a most potent
coagulation technique. At present, it can be considered to be the method of
choice for the management of hemoptysis provided the bleeding lesion is in
the reach of a bronchoscope. APC can be Llsed for tumor debulking. The
procedure is slightly more time consuming than laser photoresection, but it
Figure 6 Superficial cancers in subsubsegments of an upper lobe before (a) and
after (b) APC treatment. Because of the distal location, the lesions could not be
approached with the Nd:YAG laser.
ht
d M t . I
.Cbpyng e a ena
212
Freitag and Reichle
is equally safe and efficient. As the equipment is less expensive and very
versatile, it might replace the Nd: YAG laser in many institutions. APC can
be performed with flexible endoscopes, but we recommend rigid broncho-
scopy in cases of severe tumor obstruction and heavy bleeding. Success rates
regarding hemostasis and relief from tumor obstruction exceed 90% with
very low complication rates. Whether APC is feasible for the eradication of
early cancer lesions remains to be seen. Currently, it cannot be
recommended for this indication because the depth of penetration between
2 and 3 mm might be insufficient.
References
I. Minna JD, Higgins GA. Glatstein EJ. Cancer of the lung. In: De Vita VT,
Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology.
3rd ed. Philadelphia: Lippincott, 1989:591-705.
2. Freitag L, Macha HN, Loddenkemper R. Interventional bronchoscopic
procedures. In: Lung Cancer, SG Spiro, ed. Eur Respir Monogr 17,2001;
6:272-304
3. Cavaliere S, Foccoli P, Toninelli C. Endobronchial laser treatment. Eur Respir
Monograph 1998; 9:49-64.
4. Sutedja G, Bolliger CT. Endobronchial Electrocautery and Argon Plasma
Coagulation. In: Bolliger CT, Mathur PN, eds. Interventional Bronchoscopy.
Basel: Karger, 2000:120-132.
5. van Boxem TJ, Venmans BJ, Postmus PE, Sutedja TG. Endobronchial
electrocautery. A review. J Bronchol 2000; 7: 166-1 70.
6. Vergnon .1M, Mathur PN. Cryotherapy for endobronchial disorders. ]n:
Bolliger CT, Mathur PN, eds. Interventional Bronchoscopy. Basel: Karger,
2000 133-145
7. Kabanov AN, Kozlov KK, Dombrovskii DR, Krivonosov LK. Belousov AP.
[The use of a plasma unit in surgery of the lung and pleura.] Grudn Khir 1989;
(5):44-48.
8. Grund KE, Storek D, Farin G. Endoscopic argon plasma coagulation (APC):
first clinical experiences in flexible endoscopy. Endosc Surg Allied Technol
1994; 2:42-46.
9. Grund KE, Zindel C, Farin G. Argon plasma coagulation through a flexible
endoscope. Evaluation of a new therapeutic method after 1606 uses. Dtsch Med
Wochenschr 1997; 122:432-438.
10. Seitz U, Seewald S, Bohn3cker S. Soehendra N. Advances in interventional
gastrointestinal endoscopy in colon and rectum. Jnt J C%rect Dis 2003; 18:12-
18
II. Schmidt W. Experience with the argon beamer in interventionul bronchology.
Atemw Lungenkrankh 1996; 22: 168-173.
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ReIchle G, Freitag L, Kullmann HJ, Macha HN. Argon plasma coagulation in
bronchology: a new method-alternative or complementary? J Bronchol 2000;
7:109-117.
Morice Re, Ece T, Ece F, Keus L. Endobronchial argon plasma coagulation
for treatment of hemoptysis and neoplastic airwag obstruction. Chest 2001;
119:781-787.
Crosta C, Spaggiari L, De Stefano A, Fiori G, Ravizza D, Pastorino U.
Endoscopic argon plasma coagulation for palliative treatment of malignant
airway obstructions: early results in 47 cases. Lung Cancer 2001; 33:75-80.
Scherer TA. ND-YAG laser ignition of silicone endobronchial stents. Chest
2000; 117:1449-1454.
Colt HG. Bronchoscopic resection of Walistent-asssociated granulation tissue
Keller CA, Hinerman R, Singh A, Alvarez F, et al. The use of endoscopic argon
plasma coagulation in airway complications after solid organ transplantation.
Chest 2001; 119:1968-1975.
May A, Gossner L, Pech 0, Fritz A, Gunter E, Mayer G, Muller H, Seitz G,
Vieth M, Stolte M, Ell C. Local endoscopic therapy for intraepithelial high-
grade neoplasia and early adenocarcinoma in Barrett's oesophagus: acute-
phase and intermediate results of a new treatment approach. Eur J
Gastroenterol Hepatol 2002; 14(10): 1085-1091.
Vonk-Noordegraaf A, Postmus PE, Sutedja TG. Bronchoscopic treatment of
patients with intraluminal microinvasive radiographically occult lung cancer
not eligible for surgical resection a follow-up study. Lung Cancer 2003;
39(1 ):49-53.
11
Silicone Airway Stents
MACE M. SCHUURMANS and CHRIS T. BOLLIGER
University of Stellenbosch
Cape Town, South Africa
Airway stents, or tracheobronchial endoprostheses, are used to treat
obstructing lesions of the central airways, usually defined as comprising
the trachea, both main bronchi, and lobar orifices. Generally speaking, a
stent is a tubelike device made of metal wire, plastic, rubber (often silicone),
or a combination of two such materials (called hybrid or composite stents),
which is inserted into the central airways to reestablish patency of
compressed, strictured, or partially obstructed airways, support weakened
cartilages (tracheomalacia), or seal fistulas or dehiscences. In industrialized
countries, central airway obstruction (CAO) is mainly caused by malig-
nancies, mostly bronchogenic carcinoma; in developing countries, it is
frequently due to benign disorders, such as tuberculosis. In addition to
conventional therapy such as surgery, chemotherapy, and radiotherapy for
malignancies and antibiotic or anti-inflammatory treatment for benign
disorders, various local endoscopic treatment modalities are being used
increasingly. In principle, one distinguishes three main types of malignant
CAO (endoluminal, extraluminal, and mixed obstruction), which are
illustrated in Figure I. Endoluminal obstruction is caused by tumor
215
216
Schuurmans and Bolliger
Figure 1 Types of central airways obstruction. Schematic illustraton of the three
most important types of central airways obstruction shown at the tracheal level with
an identical degree of obstruction. Left, endoluminal obstruction; middle,
extraluminal compression; and right, mixed obstruction.
growing into the airway lumen, extraluminal obstruction by extrinsic
compression, and mixed obstruction is the combination of endoluminal and
extraluminal obstruction, and is often associated with a significant
component of intramural growth. A fourth type of CAO, mainly
encountered in benign disorders, is tracheomalacia, which is due to
insufficient cartilaginous support.
Endoluminal lesions can be treated by coring out with a rigid
bronchoscope and forceps, resection using thermic application (laser, high-
frequency electrocautery, cryotherapy), endoluminal irradiation (bra-
chytherapy), or laser irradiation of previously sensitized cells (photody-
namic therapy). Obstructions caused by extraluminal or mixed lesions with
an important extraluminal component are not amenable to local treatment
other than by stents. The choice of the type and size of the stent is important
in order to minimize possible complications such as stent malposition,
migration, or obstruction by impacted secretions or tumor. This chapter
focuses on the use of airways stents made of silicone inserted to reestablish
airway patency [I]. Expandable stents (metallic) with or without a silicone or
polyester covering are discussed in Chapter 12.
II. History
The origin of the word slenl probably dates back to the British dentist
Charles Stent (1845-1901), who invented a compound to cast dental models
217
and splints. Following this invention well over 100 years ago, his name was
associated with various materials used to hold tissue in place or provide
support for a graft or anastomosis [2]. Today, surgeons and physicians
insert stents into nearly all constricted tubular structures of the human
body, mainly to establish a sufficient lumen or to bridge a gap.
The implantation of airway stents dates back to the late nineteenth
century when Trendelenburg (1872) and Bond (1891) surgically implanted
tubes for the treatment of airway strictures. In 1915, Bri.inings and Albrecht
(1915) implanted rubber prostheses endoscopically into narrowed tracheas
[3]. Although silicone rubber was originally introduced in the 1940s, it was
not until the 1960s that it was used as stent material. The word silicone
should not be confused with the trademarked name Silastic, which
comprises polymeric silicone substances that are used most commonly in
the manufacture of medical prosthetic devices [4].
Montgomery designed the silicone rubber T tube (T tube tracheal
stent) in 1965 featuring an external side limb protrusion through a
tracheostomy. At the same time, the first straight silicone stents without
side limbs were inserted by Anderson and Egnud. These were inserted and
fixed surgically after splitting the trachea [3].
The breakthrough for silicone stent placement as an endoscopic
measure came in 1990 when Dumon presented a dedicated silicone stent for
the trachea and bronchi [5]. These silicone stents became rapidly popular,
and they are currently the most frequently used model worldwide. The first
bifurcated airway prosthesis was developed by Neville and coworkers in
1972 [6]. A Dacron cuffed silicone device was used to replace the
intrathoracic part of the trachea and both main stem bronchi. In the early
1980s, Westaby reported the successful endoscopic insertion of a bifurcated
rubber stent which included a side limb protrusion (T- Y stent) through a
tracheostomy [7] and Clarke introduced a bifurcated stent without side limb
that was held in place by the bronchial limbs and no longer required a
tracheostomy [8]. In the early 1990s, the anatomically shaped bifurcated
Dynamic stent made from silicone with incorporated clasps of steel in the
tracheal leg was introduced by Freitag [9].
Many companies and institutions have been working on the
improvement of silicone, metallic, and hybrid stents in the past years. The
latest developments include stents made of shape memory alloys and hybrid
stents made from metals, polymers, and textiles with optimized histocom-
patibility [10]. The extensive variety of different commercialized stents
shows that there is no single ideal stent (silicone or expandable) for all
situations. The currently available models might all be termed first-
generation stents, which means they are foreign bodies in the airways. In
the near future new aporoaches .such .as b.iQdegrada ble stents (made of
, -r...;opyngnrea Matenal
218
Schuurmol1s and Bolliger
polylactates) might herald the second generation of biocompatible stents
[II].
III. Indications and Contraindications for Stent
Placement
There are three major indications for the placement of tracheobronchial
stents: (1) reestablishing patency of mainly or exclusively compressed central
airways as well as strictures, (2) supporting weakened cartilages in cases of
tracheobronchial malacia, and (3) sealing of aerodigestive and broncho-
pleural fistulas and dehiscences [3]. Depending on the degree and speed of
onset of CAO, stent placement has to be performed as an emergent or
elective procedure. Further, the indication for stent placement in malignant
and benign disease has to be discussed separately as the difference in life
expectancy has clear implications for the choice of stent types.
A. Malignancies
The majority of patients who present with CAO suffer from malignancies
that are primarily bronchogenic carcinoma, metastatic lesions (most often
melanoma, breast, renal, and colon cancer), and direct invasion by
esophageal or thyroid cancers [12]. Most of these tumors are not resectable
because of their advanced stage. A minority of patients are deemed to be
inoperable because of insufficient cardiopulmonary reserves. Thus, the main
therapeutic aim is palliation. Stent placement in malignant CAO is indicated
when a stenotic airway either is compressed from outside or, in mixed
stenoses, if the resection of the endoluminal component is insufficient to
relieve the obstruction [I]. Generally, stent insertion should be considered
whenever the diameter of the affected airway remains below 50% of normal
after endoscopic therapy (tumor resection and/or dilation) [13]. One of the
great challenges for oncologists and pulmonologists is to identify patients
who are at risk for CAO and its consequences (e.g., postobstructive
pneumonia) early enough so that endobronchial treatment can be
performed before a (possibly fatal) complication occurs.
Further indications are loss of cartilaginous support through tumor
destruction of the airway wall and exhaustion of therapeutic options such as
external beam irradiation, brachytherapy, or fast endoluminal tumor
recurrence despite repetitive sessions of endoscopic tumor resection.
Malignant airway fistulas can sometimes be sealed elegantly with stent
placemen t (Table I).
Silicone Ain1'ClY Slents
Table 1 Indications for Airway Stent Placement
2/9
Malignancies
Exclusive or predominant extrinsic compression of large airways
Loss of cartilaginous support through tumor destruction
Airway diameter <50% of normal after endoscopic treatment
Airway diameter >50% of normal after endoscopic treatment to prevent
reobstruction in cases with proven rapid local tumor growth
Airway fistula
Benign lesions
Benign, complex tracheal stenosis as a bridge to surgery (6 months) or definitive
trea tment
Benign tracheal or bronchial stenosis from inflammatory or infectious processes
while waiting for a response to systemic therapy or pending open surgical
resection
Localized or extensive tracheobronchomalacia regardless of cause
Anastomotic strictures after lung and heart transplantation
Tracheal or bronchoesophageal fistula
B. Benign Disorders
Benign disorders that lead to CAO are primarily postintubation stenoses
with or without tracheomalacia after prolonged intubation. With the use of
endotracheal tubes with low-pressure cuffs, these stenoses have become less
frequent in industrialized countries, but they are still encountered quite
often, especially when access to modern intensive care units and highly
trained staff is limited by financial constraints. Other etiologies are
infectious diseases, such as tuberculosis, with enlarged lymph nodes that
can compress airways from outside or penetrate the airway wall, leading to
endoluminal obstruction by caseating material. Rarer conditions are
Wegener's disease with endobronchial involvement, relapsing polychondri-
tis, tracheopathia osteoplastica, fibrosing mediastinitis, and endobronchial
papillomatosis [I]. Anastomotic stenoses or dehiscences after pulmonary
sleeve resections or lung transplantation can sometimes be managed by
endobronchial stents [14].
It is important to differentiate between simple weblike tracheal
stenoses, often occurring postintubation, which are ideal for endoscopic
treatment because the tracheal wall is normal, and complex tracheal
stenoses, defined as involving the wall with destruction of cartilage, where
surgery should always be contemplated. For complex tracheal stenoses,
stent placement should be reserved for inoperable patients or as a means for
achieving immediate symptom relief until surgery can be performed.
220
Temporary stent placement with removal after a mean interval of 18-32
months without subsequent surgery is only possible in 22-35% of all
patients stented for benign tracheal stenosis [15-18].
C. Contraindications for Stent Placement
In life-threatening situations, there are no contraindications to stent
placement because the reestablishment of airway patency by tumor
debulking and/or stent insertion is virtually the only hope to prevent
immediate suffocation. In nonemergent situations, the risk-benefit ratio
must be evaluated and discussed with the patient, especially when
endobronchial manipulations may lead to major and possibly fatal
hemorrhage. Further, in terminal conditions, especially when the patient's
overall condition suggests survival for only days to a few weeks, the benefit
of stent placement, taking cost into consideration, must be carefully
assessed.
IV. Commercially Available Silicone Stents
The Montgomery T tube (Boston Medical Products, Inc., Waltham, MA) is
a T-shaped silicone tube that requires permanent tracheostomy and is
indicated for upper or mid tracheal stenosis after dilatation (prior to or at
time of stent placement). The tracheal leg of the T tube is smooth walled
with tampered distal extremities. A more recent model called the Safe-T-
Tube includes some modifications that make it easier and safer to use. The
tracheal part of the T tube consists of a proximal part extending cephalad
and a distal part extending caudally from the tracheostomy site within the
lumen of the upper and middle third of the trachea. The proximal leg should
end at least I cm below the vocal cords. The external side limb protrudes
through the tracheostomy, maintaining its patency and allowing suctioning
as needed. It has ridges and grooves on the outside allowing a ring washer to
be attached to it to prevent posterior displacement, and it must be plugged
to avoid drying of secretions. T tubes come in multiple sizes from 6 mm
(pediatric) to 16 mm outside diameter [4].
Hood stents (Hood Laboratories. Pembroke, MA) are available as
straight and bifurcated stents made of round silicone tubes. They have been
used successfully for many years to treat obstructions at various levels of the
tracheobronchial tree. The Y-shaped models prevent migration effectively
and the price is reasonable (Table 2). Good skill in rigid bronchoscopy is
required for insertion [3].
The Westaby T-Y tube was the first bifurcated tracheobronchial
prothesis available. It extends into the main bronchi and is difficult to insert.
Silicone Airway Slenls
221
Table 2 Description of Commonly Used Silicone Stents with Approximate Prices"
Steat model
Straight
Dumon
Hood
Polyflex
Bifurcated
Dumon
Hood
Dynamic
Polyflex
Comment
Studs on external surface
prevent migration;
easily removed
Smooth-walled silicone
stent comes in various
lengths and diameters;
custom-designed
models available
Silicone with polyester
mesh
Adapts well to conical
stenoses
Stent-in-stent placement
(telescope technique)
possible
Y stent with studs on
external surface
Both insertion and
removal fairly easy
Smooth-walled silicone Y
stent
Anatomically shaped
bifurcated silicone stent
with stainless steel
struts and flexible
posterior membrane
Special forceps facilitates
placement
Silicone with polyester
mesh; adapts well to
conical stenoses (not
commercialized)
Price (Euro)
450
180
430
1070
330
1260
650
"Prices based on the European market. In the United States, prices may be higher for some slent
models.
The long, relatively rigid stent is available in three diameters from Hood
Laboratories, and is only used for extremely long stenoses from the cricoid
to the upper lobe bronchtopyrighted Material
222 Schuurl11ans and Bolliger
The Dumon stent (Endoxane), Novatech SA, Grasse, France, Bryan
Corp., Woburn, MA) is a cylindrical silicone tube with studs on the outside
for anchorage. It comes in various diameters and lengths, with the smallest
combination being 9 x 20 mm for bronchi and the largest being
18 x 110 mm for the trachea (Fig. 2). Y stents are available in different
sizes (length 40 mm, diameter IS! 13 mm) (Fig. 3). They are the only Y stents
available that can be folded tightly and introduced through a rigid
bronchoscope, which is a clear advantage facilitating insertion. The
manufacturer recommends stent deployment using expensive specialized
equipment consisting of a dedicated stent introducer system and a special
bronchoscope also designed by Dumon (Efer-Dumon) [5,19). Recently, a
whole range of very small pediatric stents has been commercialized as well.
The Dumon stent is the most widely used model and continues to be the
"gold standard" against which all newly developed stents have to compete.
The Polyflex stent (Ri.isch AG, Kernen, Germany) consists of a
polyester wire mesh embedded in a silicone covering. It exhibits a high
Figure 2 Str:light Dumon stcnts.
Silicone Airway Slents
223
Figure 3 Y stents: Duman stent (left) and Dynamic stent (right).
flexibility and comes in many different lengths and diameters, which
includes Y stents. This stent can be deployed to cover stenoses of varying
diameters as well as curvilinear stenoses. There is a new model with studs on
the outside surface currently being evaluated in a multicenter study (C.T.
Bolliger, in press) (Fig. 4). Its low price makes it a direct competitor to the
Dumon stent.
The Dynamic Y stent (Ri.isch AG) is the only stent with a cross section
that imitates the normal airway anatomy [9]. It is made of silicone. The
anterior part of its tracheal leg is horseshoe shaped and is stiffened by metal
hoops and the posterior part consists of a thin movable silicone sheet that
allows fairly normal motions of the posterior membrane (Figs. 3 and 5). The
bronchial limbs are pure silicone without metal clasps. Insertion is usually
done with a dedicated instrument (Rusch Forceps); however, placement is
difficult in unexperienced
C
h n s h t ~ Ol,lssage, of the glottis and correct
opyng, eu lVIatena
224
Schuurl11ans and Bolliger
Figure 4 Polyflex stent with studs on the outside surface.
deployment of the bronchial limbs can be cumbersome depending on the
anatomical presentation of the carina] region. This stent is useful if the
normal airway anatomy is fairly well preserved, such as in purely extrinsic
compressions or in some cases of tracheomalacia. Retained secretions are
relatively rare, and removal of the stent is easily possible. It is available in
three sizes wi th tracheal diameters of II, ] 3, and] 5 mm, which can be cut to
the desired length.
The Orlowski stent (Rusch AG) is available as straight and bifurcated
models of round silicone tubes armored with metal rings. Both models are
very stiff and are therefore hardly used anymore.
The Noppen stent (Reynders Medical Supply, Lennik, Belgium) is
made of a Tygon synthetic cylindrical tube that is thermically molded to a
screw-thread prosthesis, making it far more rigid than stents made of
silicone rubber. It was described by Noppen and coworkers in 1996 and is
available in different sizes. In a recent study, it showed good results in
comparison to the Dumon stenl [20]. Placement requires an external pusher
device. This fairly low-priced slent has the disadvantage that it is only
available for the trachea.
Silicone Ainvay Stel1!s
225
Figure 5 Endoscopic picture: Dynamic stent with perfect tracheal and bronchial
fit.
V. Evaluation of Patients for Silicone Stent Insertion
A. Symptoms, Signs, and Evaluation of CAO
Patients with CAO often present with cough, stridor, wheezing, hemoptysis,
or dyspnea. Others have postobstructive pneumonia or respiratory failure,
sometimes requiring endotracheal intubation and mechanical ventilation.
Many patients, however, are asymptomatic until critical narrowing of the
airway occurs [4]. This is why some interventional pulmonologists perform a
bronchoscopy early in the work-up of a patient with unexplained chronic
cough, adult-onset of asthma, history of tracheal intubation, or smoke
inhalation.
226
Physical findings such as tracheal deviation, asymmetrical thoracic
movements, focal wheezing, rhonchi, or decreased breath sounds are clues
to potential underlying CAO.
Pulmonary function tests are not very helpful in mild to moderate
stenoses. In symptomatic obstructions, however, the flow-volume loop is
extremely useful, and it often exhibits a typical box shape indicating severe
flow obstruction during inspiration as well as expiration. Pathological flow-
volume loops can be useful for monitoring treatment success and possible
relapse of disease [12].
Imaging with chest computed tomographic (CT) scan, taking thin
sections in the area of interest, can be helpful to determine whether the
airways are patent distal to the obstruction and therefore influence planning
of the bronchoscopic procedures. Since the advent of helical CT, three-
dimensional (3D) reconstructions of the central airways have become
possible. However, the role of 3D reconstructions in the management of
CAOs remains to be defined.
Flexible bronchoscopy is the single most important procedure for the
planning of endobronchial interventions such as dilation and stent
placement in the clinically stable patient.
B. Management in Malignant Disease
We have recently proposed an algorithm (Fig. 6) for the general manage-
ment of malignant CAO [21].
The sudden onset of respiratory failure with suspected underlying
CAO represents a situation where emergency rigid bronchoscopy is
indicated to restore airway patency by, for example, coring out large
tumors with the tip of the instrument (recanalization). In all other
situations, elective rigid bronchoscopy is preceded by diagnostic flexible
bronchoscopy to evaluate location, extent, degree, and cause of the
obstruction and to plan the therapeutic approach. This is often a
combination of endoscopic and nonendoscopic modalities. Endoscopic
therapeutic interventions used in connection with endobronchial stent
placement include resection with heat (laser, electrocautery), cryotherapy,
dilation, and brachytherapy. Nonendosopic modalities used here are
external beam radiation and chemotherapy. In principle, we prefer to use
endoscopic measures first, followed by nonendoscopic therapy, whenever
the involved airway causes serious symptoms and/or the degree of
obstruction is >50% of the normal airway diameter. Often, the patient
will suffer from some degree of postobstructive retention of secretions,
atelectasis, or even pneumonia. This is at least a relative contraindication
for external beam irradiation or chemotherapy. On the other hand, an
Silicone Airway StenlS
227
Malignant Central Airway Obstruction
Rigid bronchoscopy
8 +.---- <Lifethreatening?> ----+. S

Flexible bronchoscopy
(+ TNM+CPR)
-s
1
Symptomatic or
< 50% airway 0
I
e
+
s-<Operable?> ----+. 8
+
__s_ur_g_ery __1+------1-
hhh
I Radio/chemotherapy I I Therapeutic endoscopy
1i
recurrency
Figure 6 Algorithm for the management of malignant central airway obstruction.
Terms in hexagonal boxes are conditions, temlS in rectangular boxes are procedures.
Arrows in two directions indicate the tendency of endobronchial tumors to recur and
the repetitive need of multimodality treatment. TNM, tumor, nodal, metastasis
staging system, including histology; CPR, cardiopulmonary reserves of the patient;
interrupted arrows: I, rare cases of primarily inoperable lung cancers which become
secondarily operable after initial therapeutic bronchoscopy usually followed by
neoadjuvant treatment; 2, rare cases of operated lung cancers initially presenting
with central airways obstruction and still being operable after careful restaging of an
endobronchial recurrence. (From Ref. 21.)
airway obstruction of <50% of the normal diameter often does not cause
symptoms and usually disappears completely after conventional radio-
therapy/chemotherapy. In these situations, we refrain from starting with
endoscopic treatment. An exception to this general approach is sometimes
possible in patients presenting with untreated small cell lung cancer or
lymphoma [21]. Even severe airway obstructions, clearly exceeding 50% of
the normal diameter, can react dramatically to initial chemotherapy or
radiotherapy within 1-2 days. In these situations, we start with
chemotherapy and/or radiation therapy first unless the situation is
immediately life threatening.
The type of the initial endoscopic treatment will depend on the nature
and the extent of the the equipment available. In
228
the case of extrinsic compression of the airway, stent placement is the
treatment of choice. In mixed lesions featuring endoluminal obstruction and
extrinsic compression, a combined therapy is recommended with the aim of
reducing the endoluminal component by reduction of the tumor mass
(debulking) and securing airway patency by stent placement. Sometimes this
is followed by brachytherapy to treat the intramural component of the
obstruction or to prevent recurrence of local tumor growth threatening
occlusion above and below the stent [13].
Further, we consider stent placement in patients with residual airway
stenosis of more than 50% of the normal diameter after therapeutic
endoscopy for endoluminal obstruction or in patients with highly
collapsible airway walls due to loss of the cartilaginous support. In the
case of a total obstruction of the airway lumen, we instill some saline into
the occluded area while the patient is in a sitting position. Disappearance
of the liquid or slight bubbling of the air-fluid level indicates minimal
patency. We also try to pass a small brush catheter or a closed forceps
past the tumor. If this is easily possible, the presence of patent airways
distal to the tumor is very likely, but the anatomy or the number of patent
segments cannot be ascertained. We recently conducted a study of the use
of an ultrathin bronchoscope with an outer diameter of 2.8 mm for
assessing airway patency distally to the CAO that cannot be passed with
standard-sized bronchoscopes owing to near total obstruction of the
lumen. This approach proved to be safe and useful in the assessment of
both benign and malignant disease causing CAO [13a].
If stent placement is considered, we usually perform all therapeutic
procedures through a rigid bronchoscope under general anesthesia. When
choosing a silicone model, we currently use either the Dumon silicone
stent, which is time honored, sturdy, and reasonably priced and can be
removed quite easily even years later, or the Polyflex stent. Although the
Dumon stent is most widely used, some limitations of this stent have to be
considered: Because of its cylindrical design. the Dumon stent does not
adapt to a conical stenosis, in curvilinear airways it will kink, and the very
short stents of 2.0-2.5 cm in length have a clear tendency to migrate
because of an insufficient number of studs on the outer surface.
Furthermore, it cannot be placed in narrow stenoses with postdilatational
diameters of less than 10 mm, which does not allow passage of the
smallest stent-carrying Dumon bronchoscope past the stenotic airway
segment.
In situations where silicone stents cannot be used, expandable models
should be considered. The Ultraflex stent (made of Nitinol) especially has
gained widespread lise. It is described in Chapter 12.
Silicone Airway Slenls
229
C. Management in Benign Disease
The basic principle of the treatment of benign disorders leading to
obstruction of the central airways is that curative surgery should be
attempted whenever feasible. The best treatment option should therefore be
discussed by the appropriate specialists; namely, the interventional
pulmonologist, otorhinolaryngologist, and thoracic surgeon. Extensive
resections of the major airways have become feasible as a result of improved
surgical procedures which are performed in specialized centers [22]. There
are, however, quite a number of reasons for benign disorders to become
unresectable: The length of the lesion may exceed resectability (in general,
>50% of the length of the trachea even in very experienced hands); the
disease tends to recur after resection, such as in bronchial papillomatosis, or
the patient is debilitated and will not or cannot undergo surgery. Ideal
indications for exclusive endoscopic treatment are weblike stenoses.
There are several reports on the successful use of silicone stents in
benign tracheal stenoses. Immediate results are practically always satisfac-
tory. Some patients have stents as a "bridge" to surgery. In a considerable
number of patients, stenting proves to be beneficial for several years. Stent
removal can occur after 18-32 months in approximately one-third of these
patients without recurrence of symptoms [15-18]. Whenever stents are used
in benign disorders, models should be chosen that can be removed if
necessary, especially in younger patients with a long life expectancy [I].
VI. Technique
A. Bronchoscopic Assessment Prior to Stent Insertion
In all but life-threatening situations, diagnostic flexible bronchoscopy IS
performed to assess the length and diameter of the stenosis. The length of
the stenosis can be precisely measured by positioning the tip of the scope at
the distal end of the stenosis, holding the scope with the finger tips nearest to
the nose or mouth, and then withdrawing the scope slowly until the
proximal end of the stenosis is reached. The distance the endoscope is
withdrawn measured from the nose or mouth to the position of the finger
tips on t ~ scope, is equivalent to the length of the stenosis. This
measurement technique is also possible during rigid bronchoscopy using
either a suction catheter or a rigid telescope. Only direct visualization results
in perfect measurements of stricture length and diameter. Fluoroscopic
examination with bronchoscopic control provides only an estimation that
may result in placement n.f an i.nadeCl.u.ate
t
stent size.
Copyngnfea IVla enal
230 Schuurmans and Bolliger
B. Stent Insertion
As a general rule, the stent with the largest diameter for the given situation
should be selected to prevent stent migration. The stent length should extend
5 mm beyond the proximal and distal margins of the stricture to prevent
recurrent obstruction by tumor overgrowth or granulation tissue. Prior to
stent insertion, dilatation (with bronchoscopes of increasing size or balloon
inflation) is very often required, and a bronchial toilet should be performed
to remove secretions, blood, or necrotic debris within the airways.
Once the stent is inserted, the exact position can be corrected by
pushing or pulling the stent with the beveled tip of the bronchoscope or
using grasping forceps. Insufficient stent expansion may require additional
dilatation with smaller caliber rigid bronchoscopes, a balloon catheter, or
forceps. Occasionally, a silicone stent may be left in place partially
expanded, since it will gradually expand on its own during the subsequent
24-48 hr, as long as the shape is oval. This specifically applies to both the
Dumon and Polyflex stents. A clear inward fold. however, indicates a too
large diameter necessitating stent replacement. Stents that are too small and
do not appear to be firmly fixed within the airway stricture are at high risk of
migration and should be immediately replaced by larger stents. Because
straight silicone stents sometimes do not adapt well to the bends of the
tracheobronchial tree, certain parts of the stents may protrude into the
airway lumen and facilitate mucus impaction. Airway irritation caused by
friction with the stent end may result in cough and granulation tissue
formation. This may require repeat bronchoscopy, laser resection, or stent
removal [4]. Details on various stent-insertion techniques and available
instruments are not provided here. Such information can be found in books
on interventional pulmonology [3,4].
C. Complications
Although well-placed stents are remarkably well tolerated, they nevertheless
represent foreign bodies in the airways. The most frequent complications are
migration (displacement), impactions of dried secretions within the stent,
and granulation tissue formation or recurrent tumor growth at the stent
ends (Table 3) [23]. Correctly chosen stent size (tight fit. right length) and
stent shape (model with studs or Y stents) can greatly reduce the migration
rate. Concomitant therapies such as radiotherapy or chemotherapy can lead
to reduction of tumor mass and subsequently to stent dislocation due to a
loose fit. In these situations, surveillance bronchoscopies can monitor the
appropriate stent position and adequate diameter. Another rarer complica-
tion is stent infection (microbial overgrowth). Since antibiotic concentra-
tions are often insufficient at the surface of foreign bodies, stent replacement
Table 3 Complications Associated with Silicone Stents
Migration
Mucus impaction
Obstruction of stent ends by granuloma formation or recurrent tUlllor growth
Infection
Halitosis
Hemoptysis
Pain
Cough
19nition (on subsequent laser or electrocautery treatment)
Source: Adapted from Ref. 7.
231
is usually required. Inhalative antibiotics have also been used in this
situation; however, the effectiveness of this measure has not been system-
atically analyzed [24]. Stent displacement or mucus impaction manifest
themselves through more or less sudden onset or worsening of cough and
dyspnea and warrant prompt investigation with a chest radiograph and
flexible bronchoscopy. Mucus impaction can almost always be dealt with by
rinsing and aspirating the sometimes very viscous secretions. Inhalation of
saline or the use of mucolytics (N-acetylcysteine) may prevent or delay
mucus impaction. A displaced stent will often have to be removed with a
rigid bronchoscope, but sometimes the flexible instrument can be used
successfully. Excessive granuloma formation occurs more frequently in
benign disease and more often with metallic stents than with silicone models.
Granulomas can be removed mechanically or with careful laser resection,
electrocautery, or argon plasma coagulation [I]. The endobronchial use of
lasers or electrocautery near silicone stents can cause ignition of the stent
leading to considerable damage. High levels of oxygen increase the chance
of this dangerous complication. Based on in vitro experiments with
neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers and silicone stents,
the oxygen concentration should be kept <40% during laser treatment to
prevent stent ignition. If higher oxygen concentrations are required, pulse
duration needs to be limited or stent removal must be considered before the
laser resection [25].
D. Surveillance After Stenting
Because oxygen saturation may fall during stent insertion, especially when
deployment is difficult, 100% oxygen and assisted ventilation should be
delivered immediately of the stenl. Patients are
Table 4 Selected Larger Studies with Silicone Airways Stents
Reference N
30 206
13 31
29 38
28 57
15 63
18 1058
27 135
20 46
1.7 45
16 42
Indications +outcome (N = number of patients)
Malignant +benign lesions. Complicatons usual.l.y minor (migration
15%, granulation 20.8%, obstruction by secretions or tumor
3.4%). Follow-up 3 years.
Malignant disease. Ninety percent of patients experienced
immediate and lasting relief of dyspnea and improvement in
performance status. Complications occurred in 30%. Median
survival 2.5 months. Nonsignificant increase in survival from 4 to
6 months with adjuvant radiotherapy in squamous cell carcinoma
lIIB subgroup.
Malignant + benign lesions. Migration 28%. Follow-up to 5 months.
Malignant + benign lesions. Stent adjustment frequently required.
All patients had symptomatic relief Patients who died due to
progressive disease had effective palliation for 10.5 5.6 months.
Migration most frequent in transplant patients.
Benign lesions. Migration 17.5%, granuloma 6.3%. obstruction
6.3%. Follow-up to 18 months.
Malignant +benign lesions. Multi-institutional. Migration 9.5%,
secretion 3.6%, granulation 7.9%. Mean duration of stenting
(benign disease) 14 months, (malignancy) 4 months. 7-year
expenence.
Malignant +benign lesions. Mean survival for 85 patients (79 with
malignant disease) was 4 months (0-611 days). Cephalad
migration in 4 of 138 bifurcated Dynamic stents.
Benign +malignant tracheal stenoses. No perioperative mortality.
Comparison of Dumon and Noppen stents. Overall, 50 stents
inserted with uneventful follow-up in 62% versus 67%, and
migration in 7 patients versus I patient, respectively (statistically
nonsignificant results). Migration only in benign disease observed.
Symptompatic cicatricial tracheal stenoses. No procedure-related
mortality. Eleven deaths after a median of 10 months, stent
permanently removed in 10 patients after median of 32 months
(range 9-70 months); four others had symptomatic recurrence
within 6 weeks of removal.
lnoperable tracheal stenosis (benign).Two groups: 24 patients were
stented as temporary treatment (A), 18 had definitive stenting (B).
Removal in 12 patients in group A after a mean interval of 20
months (without requiring restenling in the following 19 months).
Other patients still waiting for removal after a mean 01'20 months.
Mean follow-up of group B 48 months.
N, number of patienls.
SO/lrce: Modified from Ref. 4.
Silicone AirlVay Slenls 233
extubated when hemodynamically stable after the intervention. That stent
placement results in prompt and lasting symptom relief has been shown by
many studies (Table 4).
One day after stent placement, we routinely obtain (I) a chest
radiograph (Fig. 7), (2) a flow-volume loop, and (3) a repeat flexible
bronchoscopy. This guarantees a thorough assessment of the position and
patency of the stent and enables removal of secretions if necessary. Long-
term follow-up should comprise regular clinical investigations and the
performance of flow-volume loops. Routine surveillance flexible bronch-
oscopies after 2-3 months are performed by some interventional pulmonol-
ogists. Matsuo and Colt, however, have recently shown in a study with 101
silicone stents in 88 patients that the occurrence of new respiratory
symptoms is almost always a sign of stent-related complications. They
suggest that flexible bronchoscopy should then immediately be performed.
Based on their study, Matsuo and Colt conclude further that, in the absence
of new respiratory symptoms, routine surveillance bronchoscopies are
probably unnecessary [26]. In patients receiving tumor-specific therapy for
cancer (chemotherapy, radiotherapy) surveillance bronchoscopy may be
warranted to determine whether a stent is still required or if there is an
increased risk of stent migration due to reduced tumor bulk.
Apart from respiratory symptoms, the most important parameter of
patients with stents, or any other form of endobronchial therapy, is the
quality of life, which should be assessed together with pulmonary function
tests. The Karnofsky scale or the World Health Organization (WHO)
activity index are useful assessment tools to quantify the performance status.
They are freq uently used by oncologists as important prognostic indicators,
and can therefore be used to grade patients undergoing endoscopic
treatment, thus allowing comparisons of performance status before and
after interventions.
Most studies of efficacy of airway stent placement have had impressive
results. Because stent placement is the only treatment modality for
exclusively extrinsic compression that will reestablish and maintain airway
patency, it is not possible to perform randomized controlled trials for ethical
reasons. The vast majority of reports are case series [4]. In the evaluation of
these results, the two most important parameters assessed are (I) efficacy of
symptom relief/palliation and (2) rate of complications. Table 4 shows a
summary of selected stents [13,15-17,20,27-30].
234
Schuurl11ans and Bolliger
(a)
Figure 7 Chest radiograph proving the correct position of a Dynamic stent in a
patient with central non-small cell lung cancer. Stent ends are indicated with arrows:
(a) posteroanterior view, (b) lateral view.
Patients with inoperable malignancies requiring stent placement have
a very limited survival owing to an advanced tumor stage. Comparison with
other treatment modalities is rarely possible, so comparative survival data
hardly exist. In one report summarizing the 7-year experience with the
OUl11on stent, patients with inoperable malignancies were stented for a mean
duration of 4 months, with the longest being 4.7 years [18]. Patients with
benign disorders frequently show excellent long-term results, sometimes
(b)
Figure 7 Continued.
235
over many years. In the same report, benign tracheal stenoses were stented
for a mean duration of 14 months, with the longest being 6.2 years [18].
With increasing health care costs, the cost effectiveness of interven-
tions has become increasingly important. Colt and Harrell showed in a
series of 32 patients that therapeutic rigid bronchoscopy with dilatation,
laser resection, and silicon.e sten.t inse(tiQnt allowed level of care changes in
c.;opyngntea Ma enal
patients with acute respiratory failure from CAO [31]. In this series, 62.5%
of the patients were immediately transferred to a lower level of care after
therapeutic rigid bronchoscopy. In 30.4%, the interventions resulted in
extubation or decannulation of the patient.
Although stent placement is practically the only modality for
treatment of airway compression, it is important to realize that it frequently
is used in conjunction with many other treatment modalities. In these
situations, the outcome cannot be attributed to stent placement alone: It is a
result of the multimodal therapeutic approach which depends on the level of
the expertise of the specialists involved as well as the availability of state of
the art eq uipment.
VIII. Conclusion
Silicone stent insertion for CAO is a safe and effective way to reestablish
and maintain airway patency in malignant and selected benign disorders.
Airway compression and collapsible airways that cannot be managed by
surgical resection are the mainstay of stent treatment. Sometimes,
endobronchial tissue obstructing the airways must be resected prior to the
deployment of stents. Airway stents can help secure or improve the results
achieved with a multimodal approch to the CAO. Silicone stents have a
better safety record than metallic stents in benign disease owing to the
virtual absence of serious or fatal adverse events and the fact that they can
always be removed.
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12
JAMES N. ALLEN
Ohio State University
Columbus, Ohio, U.S.A.
I. Introduction
There are many approaches to relieving large airway obstruction, and
although there is considerable overlap in indications, each approach has its
unique advantages and disadvantages. Currently available methods of
relieving malignant and benign obstructions include external beam radiation
therapy, endobronchial brachytherapy, laser, photodynamic therapy, argon
plasma coagulation, cryotherapy, balloon dilation, forceps debridement,
silicone stents, and expandable metallic stents. Metallic stents allow the
physician to attain immediate improvement in airway patency with a
minimal amount of capital investment in equipment. Recent improvements
in stent construction and deployment techniques have resulted in stents
which are better tolerated and are easier to place than earlier generations of
metallic stents. With the knowledge of normal airway anatomy and with
proper attention to the correct choice of stent sizes, expandable metallic
stents can be safely placed into the central airways using bronchoscopy and/
or fluoroscopy. Although these devices are generally safe and well tolerated,
a number of short-term a8d long-term compJications can occur.
opynghted Matenal
239
240 A/kn
II. History
Expandable metallic stents have been applied to a number of organs
including the biliary tree, coronary arteries, peripheral arteries, the superior
vena cava, the esophagus, the colon, and the airway.
The first generation of metallic stents were developed in the 1980s and
included the Gianturco and the Palmaz stents. These stents were very rigid.
The Palmaz stent required a balloon for expansion and deployment.
Because of their rigid nature, these stents did not conform to the often
tortuous nature of the bronchi. Also, their relative lack of flexibility made
them prone to eroding through bronchial walls [I].
The second generation of metallic stents was developed in the 1990s
and included the Wallstent and the Ultraflex stents. Unlike the earlier stents,
these devices were self-expanding, and thus did not require an underlying
balloon for expansion and deployment. Also, they were flexible and
conformed better to the airways.
More recently, both the Wallstent and the Ultraflex stents have
become available with a silicone or polyurethane coating, respectively,
which poses a barrier to the inward growth of tissue such as tumor and
granulation tissue and may help preserve long-term airway patency.
III. Stent Construction
Expandable metallic stents can be constructed with a number of metals. The
most commonly used are steel and a nickel-titanium alloy.
The earliest stents were constructed from stainless steel; examples of
this are the Palmaz [2] (Fig. l[d]) and the Strecker stents. These stents are
relatively rigid and require a dilation balloon for expansion of the stent
within the airway. Because of their rigidity, these stents do not conform well
to the often curved nature of bronchial airways. Further, because of their
rigidity, they can become kinked by coughing, suction catheters, or other
airway instruments, resulting in partial obstruction of the airway [3].
The next development in stent technology was the self-expandable
metallic stent typified by the Gianturco stent [4,5] and the Wallstent [6]. The
Gianturco stent is rarely used in the United States. The Wallstent is woven
from multiple wires braided together into a cylinder (see Fig. I [c]). The
advantages of this stent are that it is flexible, self-expandable, and has
protruding wire ends. The flexibility of the Wallstent permits it to conform
better to curvatures in the airway. Also, it can fit snuggly into a region of the
airway that is composed of several different diameters; for example, a
tapered bronchus. The self-expandable feature of the Wallstent permits its
Selj:Expanding Metallic Airway Stenls
(b)
(c)
(d)
241
Figure 1 Commonly used tracheobronchial stents:(a) Ultraftex stent; (b) covered
Ultraftex stent; (c) Wallstent; (d) Palmaz stent.
placement without a dilating balloon inside of the stent. Instead, the
Wallstent is packaged tightly constricted with an overlying plastic catheter;
as the plastic catheter is withdrawn, the underlying stent expands to
conform to the airway. The protruding wire ends of the stent become
embedded into the tracheobronchial mucosa, thus anchoring the stent into
the airway. These stents are available in multiple lengths and diameters. One
disadvantage of the Wallstent is that when it is in its preexpanded state, it is
considerably longer than when it expands; that is, when its diameter expands
oLltward, its length shortens. Therefore, the final length of the stent depends
on how fully it expands to its full diameter. If the diameter of the airway is
incorrectly estimated, the stent may be longer than anticipated, thus
resulting in the end of the stent obstructing bronchial orifices. Because this
stent is composed of steel, it is easily visualized radiographically but can
pose a limitation to magnetic resonance scanning.
The latest development in expandable metallic stents is that of the
Ultraflex stent, which is composed of a single woven wire made of nitinol, a
nickel-titanium alloy [7] (see Fig. I[a]). In its unexpanded state, this stent is
constricted onto a plastic catheter and kept constricted by a thread wrapped
242 Allen
around it; as the thread is pulled from the catheter, the stent underlying the
thread gradually expands. The Ultraflex stent is available in both proximal
and distal release models which permit the initial positioning of either the
proximal or distal end of the stent as it is deployed. Like the Wallstent, the
Ultraflex stent is self-expanding and does not req uire a balloon for
deployment. Also, like the Wallstent, it is flexible and can conform to the
curvature of the airways Unlike the Wallstent, it does not have bare wire
ends, and thus anchoring within the airway is dependent on the radial force
of the deployed stent. Also, unlike the Wallstent, it does not shorten when it
expands; therefore, reducing the chance of the end of the stent obstructing
bronchial orifices. The Ultraflex stent has a nylon thread braided through
each end of the stent to help maintain the woven integrity of the stent wire.
Because it is made of nitinol, the Ultraflex stent is difficult to visualize
radiographically, but is safer to use in a magnetic resonance scanner than
are the steel stents.
Expandable metallic stents are also available with polyurethane or
silicone-covered surfaces which can retard ingrowth of tumor and
granulation tissue through the stent wire mesh. The stents are covered in
the central portion of the stent with the proximal and distal ends composed
of bare wire mesh [8,9] (see Fig. l[b]).
The cost of each expandable metallic stent is $1,400-$1,800.
Additional costs include the cost of bronchoscopy, medications used for
sedation, balloons, and guide wires. However, the ability to use flexible
bronchoscopy obviates the need for operating r00111 time and inpatient
admission, thus making metallic stents reasonably cost effective.
IV. Indications
Expandable metallic stents are indicated for symptomatic large airway
obstruction when lower risk alternative treatments do not exist or have
failed. Advantages of metallic stents include immediate correction of airway
patency, permanence, ease of placement, ability to be performed as an
outpatient procedure, and ability to be performed using either flexible or
rigid bronchoscopy. These devices are extremely effective at restoring airway
patency and can provide immediate relief of respiratory distress (Figs. 2-4).
There are a number airway conditions which can be treated with
metallic stents (Table I) [10-20]. In general, stents should be reserved for
patients with limiting dyspnea, postobstructive pneumonia. symptomatic
hypoxemia, or failure to wean from the mechanical ventilator. Asympto-
matic airway obstruction should be approached with caution; simply
because an airway stent can be placed does not mean that one should be
Se(rExpanding MetaLLic Airway Stents
(a)
243
Figure 2 Tracheal Watlstent. A 58-year-old man with non-small cell lung cancer
involving the trachea presented with severe dyspnea. (a) Bronchoscopic view of the
mid trachea at the time of presentation. (b) Trachea after placement of a 20 x 40 mm
uncovered Watlstent. After stent placement, dyspnea improved.
placed. However, patients with rapidly progressing obstruction (such as
caused by malignancy) may require stenting to prevent impending
symptomatic obstruction.
Because most metallic stents have a minimum length of 20 mm, their
use is usually limited to airways with lengths of 20 mm or more between
bronchial orifices. For practical purposes, this includes the bronchus
intermedius, right and left main stem bronchi, and trachea. The use of
metallic stents in lobar or segmental bronchi will result in the stent
obstructing smaller branch airways, which can cause atelectasis and
postobstructive pneumonia. In these patients, alternative methods of
relieving airway obstruction are usually preferred. In patients with extensive
mediastinal disease, such as metastatic malignancy or fibrosing mediastini-
tis, stents in more than one airway may be necessary (Fig. 5).
244
(b)
Figure 2 Continued.
V. Technique and Sizing
Allen
The specific technique of placing self-expandable metallic stents has been
previously described [21,22] and will not be covered in detail here.
Expandable metallic stents can be used as a sole treatment modality or
can be combined with other treatment modalities. Which modality to
perform initially depends on several factors including the institutional
availability of different modalities, safety of different modalities, operator
experience, cost, and urgency of need. In nonemergent situations, other
techniques should be used to first establish optimal airway patency when
possible. For example, when treating obstruction due to an endobronchial
tumor, if time and local expertise permits. the tumor should be debulked
first using external beam radiation, laser, argon plasma coagulation, or
cryotherapy prior to placement of a metallic stent. ]n patients with
respiratory failure due to large airway obstruction and in patients with
impending complete obstruction of the airway, placement of metallic stents
prior to other treatment modalities is often preferred in order to obtain
Self-Expanding Metallic Ainvay Slenls
Table 1 Indications for Expandable Metal Stents
245
Non-small cell lung cancer
Metastatic carcinoma
Tracheobronchial malacia
Relapsing polychondritis
Wegener's gran uloma tosis
Tracheobronchial trauma
Posttracheostomy tracheostenosis
Airway compression from
kyphoscoliosis
Idiopathic subglottic stenosis
Tracheal obstruction after placement
of esophageal stent
Small cell lung cancer
Lymphoma
Anastamotic bronchial stricture
Posttuberculosis bronchostenosis
Amyloidosis
Posttrauma tic stenosis
Extrinsic airway compression
Iatrogenic airway obstruction
Fibrosing mediastinitis
(a)
Figure 3 Bronchial Ultraflex stent. A 63-year-old woman with metastatic breast
cancer presented with dyspnea and postobstructive pneumonia. (a) Initial
appearance of the left main stem bronchus with a polypoid endobronchial tumor
causing near complete obstruction. (b) Left main stem bronchus after placement of a
12 x 40 mm uncovered Ultraflex stent. After stent placement, hypoxemia and
pneumonia resolved.
246
Allen
immediate airway patency and to ensure that edema of the obstructing tissue
(as may occur immediately following radiation therapy or cryotherapy) does
not cause more severe airway obstruction. One risk of placing an
expandable metallic stent prior to radiation therapy or brachytherapy is
that as a tumor regresses from the effects of radiation treatment, the airway
diameter can increase and the stent can become loose and migrate. Balloon
dilation of the airway can be used immediately before stent deployment in
order to facilitate placement [23] and can also be use after stent placement if
the stent fails to expand adequately to the desired diameter.
One of the most difficult decisions in stent placement is the selection of
the size of stent to be used. If the stent is too long, it may occlude bronchial
orifices, thus causing airway obstruction. If it is too short, it may either
migrate or insufficiently relieve an obstruction. Although computed
tomographic (CT) scans have been used to estimate airway diameter,
correct stent sizing can be misjudged for a variety of factors including
whether the scan was performed during inspiration or expiration, whether
there are irregularities or variations in airway diameter, and whether oblique
sectioning of images across the airway were taken. If used, CT scans should
be taken with a rapid technique during inspiration using sections every 5mm
or less. In normal adults, the bronchus intermedius is approximately 20 mm
(b)
Figure 3 Continued.
247
(a)
Figure 4 Relief of airway obstruction by the UltraAex stent. A 65-year-old man
with stage nIB squamous cell carcinoma presented with respiratory failure requiring
intubation and mechanical ventilation. (a) AP chest radiograph at presentation with
complete occlusion of the left main stem bronchus by external compression from a
large perihilar tumor. (b) AP chest radiograph after placement of a 12 x 40 mm
uncovered Ultraflex stent in the left main stem bronchus with subsequent restoration
of aeration to the left lung.
long, the right main stem bronchus 20 mm long, the left main stem bronchus
45 mm long, and the trachea 120-140 mm long.
The diameter of the airway both proximal and (when possible) distal
to the obstruction should be measured in order to chose a stent which will fit
snuggly into the proximal and distal airways. For localized obstructions in
the trachea, the stent should ideally extend 10-15 111m proximal and distal to
the obstruction in order to anchor the stent optimally; for longer
obstructions in the trachea and for obstructions in the bronchi, this degree
of proximal and distal extension may not be possible. In patients without
CT scans and in patients in whom the CT scanning does not permit accurate
determination of the normal airway diameter, a judgment of the correct
diameter of stent to chose can be based on the normal airway diameter,
248
Alien
(b)
Figure 4 Continued.
which is approximately 10 mm for the bronchus intermedius, O ~ mm for
the main stem bronchi, and 15-18 mm for the trachea. In order to ensure
that the stent is well anchored, for self-expanding stents, it is desirable to
choose a stent with a diameter approximately 2 mm wider than the
anticipated poststent airway diameter. This results in sufficient radial force
to minimize slippage within the airway and ensures that the stent will
conform tightly to the airway, thus minimizing the risk of secretion
becoming trapped around the stent.
Expandable metallic stents are most easily placed with a combination
of bronchoscopic and fluorscopic guidance. However, placement of stents
using only bronchoscopic guidance is possible [24]. In some centers, rigid
bronchoscopy is preferred for expandable metallic stent placement, but
flexible bronchoscopy is usually sufficient in most cases [25].
Smaller Wallstents can be placed directly through the working channel
of a therapeutic flexible bronchoscope. Ultraflex stents and larger Wallstents
will not fit through tbeftexible bronchoscope and must be passed over a
guide wire and fitted to the obstruction using fluoroscopy or bronchoscopy.
249
Figure 5 Double Ultraftex stents. An 80-year-old man presented with respiratory
failure due to extrinsic compression of both main stem bronchi by a large mediastinal
bronchogenic carcinoma. (a) Initial view of the main carina with both main stem
bronchi approximately 90% occluded. (b) View of the main carina after placement of
. a 10 x 40mm uncovered Ultraflex stent in the left main stem bronchus and a
lOx 20 mm uncovered Ultraflex stent in the right main stem bronchus. Immediately
after placement of the stents, the patient was able to be weaned from mechanical
ventilation and extubated.
Table 2 Complications of Expandable Metallic Stents
Bronchial orifice obstruction
Erosion into the esophagus
Mucous plugging
Granulation tissue
Bleeding
Bent stent wires
Halitosis
Erosion into adjacent blood vessels
Secretion retention
Cough
Growth of tumor through stent wires
Tracheobronchi tis
Migration of the stent
250
(b)
Figure 5 Continued.
Allen
In general, bronchial stents can be passed transnasally, but tracheal stents
usually require transoral placement.
Complete obstruction of an airway should be approached with
caution. If there is no visible lumen, it can be very difficult to place a
guide wire and to place the stent catheter. Although a guide wire can often
be inserted though soft tumors, care must be taken to prevent passage of the
guide wire through the site of the original bronchial wall and into the lung
parenchyma. If the airway beyond an obstruction cannot be visualized
bronchoscopically, there is a risk of malpositioning of the distal end of the
stent with resultant obstruction of a bronchial orifice. The chance of orifice
obstruction can be reduced by selection of the correct stent length based on
a knowledge of the normal airway length.
The expertise for stent placement is not specialty dependent, and
therefore at any given institution, stents may be placed by pulmonologists,
thoracic surgeons, otolaryngologists, or interventional radiologists. Ideally,
the physician placing expandable metallic stents should have a knowledge of
Se1tExpanding Metallic Airway Stenls
251
airway anatomy, a knowledge of the diseases causing the airway
obstruction, and the ability to deal with potential stent complications.
The amount of training necessary for stent placement has not been well
studied, but if possible, physicians placing airway stents should learn stent
selection and technique at institutions with experience in stent placement.
Because the number of metallic stents currently being placed in the airway is
considerably fewer than the number of stents being placed in coronary
arteries and other blood vessels, there are fewer physicians experienced in
airway stent placement than coronary artery stent placement. The minimum
number of stents necessary to be performed with supervision before being
credentiaJled for stent placement is unknown. In our bronchoscopy unit, at
least 10 stents must be placed under supervision for credentialling; however,
it is unlikely that many institutions have a sufficient stent volume for this
number of supervised stents and will need to rely on either fewer numbers of
supervised stents or alternative methods of training in stent placement.
VI. Clinical Efficacy
Expandable metallic stents are effective in providing immediate sympto-
matic relief in patients with large airway obstruction, result in an
improvement in pulmonary function, and are effective in facilitating
extubation in patients with respiratory failure due to large airway
obstruction.
Both malignant and benign diseases of the airway can benefit by
placement of metallic stents. Wilson et a!. found that 77% of 55 patients
with airway obstruction due to lung cancer had symptomatic improvement
following stent placement and 81 % had improvement in wellness inventories
[26]. In a study of 52 stents placed in 32 patients by Dasgupta et aI., all but 1
patient had symptomatic improvement [27].
Metallic stents can be used in young children and infants [28];
however, the stents may need to be removed later in life because of the
development of granulation tissue or because of enlargement of the airway
with age resulting in the stent no longer fitting securely.
Pulmonary function studies improve following placement of expand-
able metallic stents. In a study of eight patients in whom balloon-
expandable metallic stents were placed for benign indications, Eisner found
an average increase in forced vital capacity (FYC) of 388 mL and an increase
in forced expiratory volume in I sec (FEYI) of 550 mL [29]. In a mixed
group of metallic and silicone stents, Gelb also found a significant increase
in both FYC and FEY1 after DO].
Copynghted Matenal
252
Allen
Metallic stents can have a particularly profound clinical effect in
patients with respiratory failure due to large airway obstruction. Shaffer et
a1. found that seven of eight patients with respiratory failure were able to be
weaned from mechanical ventilation after placement of expandable metallic
stents [31]. Patients with large airway obstruction (trachea, main stem
bronchi, or bronchus intermedius) are more likely to benefit than patients
with small airway obstruction (lobar bronchi).
VII. Complications
Although generally safe, complications associated with expandable metallic
stents may occur. These can be grouped into immediate complications
occurring at the time of placement and delayed complications occurring
after placement (Table 2).
A. Immediate Complications
Immediate complications can result from choosing a stent of incorrect
diameter or length, incorrect positioning of the stent, bleeding from airway
trauma during stent placement, hypoxemia during stent deployment, cough,
sore nose, sore throat, and hoarseness.
If the stent diameter is too small for the airway, the stent may migrate
at the time of initial placement. If this occurs, the stent can often be removed
by flexible bronchoscopy using biopsy forceps to grasp the stent. Stents with
protruding wire tips (such as the Wallstent) can be more difficult to remove
in this manner than stents without protruding wire tips (such as the
Ultraflex or Palmaz stent). Stents with protruding wire tips may be more
safely removed using rigid bronchoscopy. If a stent is too short to relieve the
obstruction, it can either be removed and replaced with a longer stent or a
second stent can be placed in an overlapping position with the original stent
in order to provide optimal patency. Occasionally, stents which are too
small in diameter may be expectorated following their placement.
1f the stent is positioned either too far distally or too far proximally, it
can sometimes be repositioned after placement by grasping either the
proximal or distal end of the stent using bronchoscopy forceps and dragging
the stent proximally or distally. Here again, stents with protruding wire tips,
such as the Wallstent, are considerably more difficult to reposition after
placement.
Bleeding, pain, cough, and hoarseness are usually transient and resolve
within several hours of the procedure. Other transient complications can
result from the usual complications of the concurrent bronchoscopy, such as
toxicity from topical lidocaine, complications of sedation, and epistaxis.
SeLf-Expanding MetaLLic Airway Slents
253
B. Delayed Complications
Delayed complications also include migration of the stent as well as growth
of granulation tissue or tumor through the stent wires, erosion of the stent
into adjacent structures, secretion retention, infection, and halitosis [32].
Delayed migration of the stent can result in obstruction of bronchial
orifices which can lead to atelectasis, hypoxemia, and postobstructive
pneumonia. Proximal migration of the stent can sometimes result in the
stent protruding into a larger airway, causing wheezing. In these situations,
the stent must be removed. This can occasionally be accomplished with
flexible bronchoscopy but may require rigid bronchoscopy. If the stent
cannot be easily removed, the wires of the Wallstent can sometimes be cut
with transbronchial scissors; the wire of the Ultraflex stent is too hard to cut
with transbronchial scissors. Laser cutting of Wallstent wires has also been
described [33]. Fractures of the stent can occur spontaneously, especially in
tracheal stents [34]; such fractures can lead to unraveling of the stent.
If there is an endobronchial tumor present prior to placement of the
stent, there is risk of the tumor growing through the stent wires. If
anticipated, this can be retarded by using a covered metallic stent; however,
on rare occasion, a tumor can rupture through the covered portion of the
stent. Additionally, a tumor may grow up or down the airway and occlude
the airway at the proximal or distal end of the stent. In this situation, a
number of secondary treatment options exist. Endobronchial brachytherapy
and cryotherapy are most commonly employed because of the low risk of
damage to the stent using these two methods compared to other methods of
eradicating an endobronchial tumor. If no other options are available, a
second stent can be placed within the original stent but may result in
"sandwiching" the tumor in between the two stents with resultant reduction
in the final airway diameter.
Granulation tissue growth either through the stent wires or at the
proximal or distal end of the stent can be a particularly difficult problem
and occurs in as many as one-third of stents [35]. Granulation tissue is more
likely to occur if a stent is placed in an inflamed airway [36]. Moreover,
granulation tissue is more likely in tracheal as opposed to bronchial stents,
and occurred in 29% of tracheal stents but only 8% of bronchial stents in
one study [32]. The development of granulation tissue in the trachea appears
to be facilitated by ongoing tracheal irritants such as aspiration,
gastroesophageal reflux (37), and smoking. Small polypoid granulations
(causing less than 25% obstruction) are usually asymptomatic and require
no treatment. Larger granulations (greater than 25% obstruction) can cause
cough, hemoptysis, dyspnea, secretion retention, and recurrent airway
obstruction. When significant obstruction occurs, there are a number of
254
Allen
treatment options available. Although oral and inhaled steroids have been
used to treat and to prevent granulation tissue, there are no studies
confirming their efficacy. Cryotherapy is useful to eradicate soft, polypoid
granulation tissue, but dense, fibrotic tissue is more impervious to
cryotherapy [38]. Advantages of cryotherapy for treating stent-associated
granulation tissue are that it is very effective, it does not damage the stent, it
can be repeatedly performed with minimal risk of damage to normal airway
tissues, and it requires less operator training than other methods of
destroying airway tissue such as laser. Argon plasma coagulation has also
been reported to be effective in poststent granulation tissue [39], but there
are no large series regarding safety and complications of this technique in
patients with existing stents. Although generally reserved for recurrent
cancer, endobronchial brachytherapy has been used for airway granulation
tissue with lasting benefit [40]. Direct application of mitomycin C to treat
granulation tissue is promising [41].
Over time, stents can erode into adjacent structures, including blood
vessels, resulting in fatal hemoptysis. Case reports suggest that this may be
more common with rigid stents as opposed to flexible wire stents [42]. The
use of stents to treat airway occlusion due to extrinsic compression by blood
vessels should therefore be approached with caution.
Secretion retention and mucous plugging can occur with any type of
stent and is especially common with silicone stents. Over time, uncovered
metal1ic stents become covered by ciliated epithelial tissue with at least
partial restoration of mucociliary clearance. Covered metal1ic stents do not
undergo epithelialization of the polyethylene surface and secretions can
become retained on the polyethylene lining. This can result in tracheobron-
chitis or airway obstruction from mucous plugs. Bacterial colonization can
also result in halitosis, which is also more common with covered stents and
can sometimes be partially relieved with nebulized antibiotics (e.g.,
tobramycin). Studies of silicone stents have demonstrated that colonization
of the silicone surface occurs most commonly by Staphylococcus aureus,
Streptococcus pneul11oniae, Klebsiella, and Pseudomonas [43]. Distinguishing
granulation tissue development from stent-associated tracheobronchitis on
clinical grounds can be difficult, and bronchoscopy is often necessary to
distinguish these two complications when cough or dyspnea develop after
stent placement.
VIII. Conclusion
Expandable metallic airway stents are a significant advancement in the
evolution of our ability to palliate large airway obstruction. The technical
SetlExpanding Metatlic Airway Slenls 255
ease of placement permits them to be deployed using a flexible broncho-
scope in a variety of clinical settings from the outpatient clinic to the
intensive care unit. Because there are no large studies comparing the clinical
effectiveness of metallic stents to other techniques used to palliate large
airway obstruction, the decision of which method to use depends to a large
degree on the personal preference and technical expertise of the physician.
Although highly effective in the palliation of both malignant and benign
causes of large airway obstruction, expandable metallic stents should be
used in benign condition only after alternative methods with fewer potential
long-term complications have been used. Physicians placing metallic stents
need to be able to recognize the potential immediate and long-term
complications associated with these devices, and need to have the
availability of interventional techniques to treat such complications as
they occur.
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13
Foreign Body Removal
KEVIN L. KOVITZ
Tulane University Health Sciences Center
New Orleans, Louisiana, U.S.A.
I. Introduction
MARTIN L. MAYSE
Washington University in St. Louis
St. Louis, Missouri, U.S.A.
Foreign bodies aspirated into the airway represent a troubling and, at times,
life-threatening compromise of breathing. They are more common in the
pediatric age group, but are seen in adults as well. The event may be
discovered acutely at the time of presentation or many months later. These
patients are typically dealt with by pulmonologists or otolaryngologists and
rarely require referral to the thoracic surgeon. This chapter deals with the
approach to the diagnosis and treatment of this problem. The key is prompt
recognition and protection of the airway. The standard admonition of "first,
do no harm" is most applicable in these situations. There are several good
reviews in the literature [1,2], and this is a topic that deserves repetition as
patients derive great benefit when treated promptly.
There are 3300 deaths per year in the United States due to foreign
body aspiration, a death rate of 1.2 per 100,000 of population, reported as
of 1997 according to the National Safety Council, Accident Facts [3]. The
death rate is 0.7 per 100,000 in the 0-4 year age group and then drops until it
begins to climb in the 45-64 year age group (1.0/ I00,000), 65-74 (2.4/
100000) and 75 and older (11.6/100,000). Although asphyxiating foreign
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259
260 Kovitz and Mayse
bodies are more common in the older adult, nonasphyxiating foreign bodies
are most common in the child younger than 15 years and especially younger
than 3 years [I]. In one study, 72% of affected children were under 3 years
old [4]. Fitzpatrick reported that airway foreign bodies were responsible for
7% of deaths in children less than 4 years old [5], and Altmann reported that
19% of asphyxiation deaths in the province of Victoria, Australia, from 1985
to 1994 in the 0-14 year age group were due to foreign body aspiration [6].
Risk factors for all types of patients are listed in Table I [1,7-9].
II. Signs and Symptoms
The patient with foreign body aspiration mayor may not be witnessed to
aspirate. The key is prevention in the pediatric patient or the neurologically
impaired. Signs and symptoms are related to the size and centrality of the
foreign body. The larger and more central, the more life threatening. The
smaller and more peripheral, the more difficult to recognize. Signs and
symptoms include cough, focal wheeze, fever, respiratory distress, hemop-
tysis, cyanosis, stridor, and tracheoesophageal fistula [10]. The patient may
show the "universal sign" of grasping his or her throat. Fever and signs of a
postobstructive pneumonia may develop over days to weeks [5]. Chronic
symptoms may be as in any chronically ill patient and include fever,
Table 1 Risk Factors
Young age and small objects [7]
Neurological impairment [I]
Organic
Loss of consciousness
Seizure
Strokes, swallowing disorders
Dementia
Various neuromuscular diseases
Intoxication
Sedatives, narcotics
General anesthesia
Alcohol
Iatrogenic [8]
Intubation
Dental procedure
Underlying pulmonary disease
Lack of insurance [9]
Numbers in brackets refer to references.
Foreign Body RemovaL
26/
anorexia, and other similar constitutional symptoms. Subcutaneous
emphysema and other signs of barotrauma may be seen [II]. In the
pediatric age group, one group found [4] that 32% of patients had a history
of choking that increased to 51 % on directed questioning. The family often
trivialized the choking. Symptoms included cough 69.8%, decreased breath
sounds 52.8%, and wheezing 45.1 %. Seeds and nuts were commonly
aspirated and organic materials led to late presentations of pneumonia. Air
trapping (59%) and consolidation (47%) were the most common radio-
graphic presentations. Atelectasis may be frequent (41.8%), and bronch-
iectasis may be seen in late stages [12]. Right-sided foreign bodies are more
common [8]. In essence, most investigators conclude that the pediatric
patient with sudden onset of wheeze and cough should be evaluated for
foreign body aspiration and any suspicion should prompt early broncho-
scopy.
III. Diagnosis
The diagnosis of foreign body aspiration requires a high index of suspicion
in the face of compatible history or suspicious finding. Radiographs (i.e.
fluoroscopy, computerized tomography, chest radiograph) may be useful
but bronchoscopy, typically flexible bronchoscopy, remains the key method
for diagnosis. Only radio-opaque foreign bodies can be seen definitively on
radiographs and findings are typically indirect end result signs of
obstruction (i.e. air trapping, infiltrate, atelectasis, mediastinal shift) [I].
Fluoroscopy is advocated by some as crucial unless the chest radiograph is
diagnostic [7]. Plain radiographs are relatively inaccurate and should not be
used in isolation [13]. Sensitivity of 73% and specificity of 45% demonstrates
further the low reliability of radiographs [14]. Bronchoscopy coupled with a
high index of suspicion is the key to proper diagnosis [15].
IV. Types of Foreign Bodies
The range of types of aspirated foreign bodies extends as far as the
imagination can take you. There are reports of various food particles,
especially bones, nuts and seeds, marbles, pins, and many other objects. The
office of the Medical Examiner of Cook County, Illinois, which includes
Chicago, reported many types of objects, with toy balloons being the most
common cause of aspiration death in the pediatric population [16]. There
may be cultural difference in the types of objects that are aspirated, as the
most common foreign bodies reported seem to vary with location of the
treating institution [4,5,8,12,17]. We have even reported the aspiration of a
262
Kovitz and Mayse
crack pipe in a crack cocaine addict [18]. The foreign body also may be
something used in a procedure, such as parts of tubes, dental materials [8],
or stents (Fig. I).
V. Removal Procedure
The most famous method for the removal of a foreign body from the airway
of a choking patient is the Heimlich maneuver. This is taught in standard
resuscitation classes as grasping the individual from behind and providing
an upward thrust to the upper abdomen below the xiphoid. Recent cadaver
work has suggested that chest compressions from standard cardiopulmon-
ary resuscitation provide higher airway pressures [19]. Most pediatric
foreign bodies may be removed by a properly trained bystander prior to
emergency technician arrival [20]. The Heimlich maneuver, although
effective, has been associated with barotrauma [21]. Although this is an
acceptable approach in an emergency, foreign body removal may require a
more invasive approach.
The removal of an airway foreign body can usually be achieved
endoscopically. It is the rare patient who will require thoracotomy with
Figure 1 Bird's nest-appearing wire mesh stent after removal piece-by-piece from
the trachea as an example of an iatrogenic foreign body.
263
either bronchotomy or possible lobar resection. Prompt recognition will
allow relief of distress and minimize destructive postobstructive equelae to
the lung. Airway protection remains paramount throughout the procedure.
A. Airway Protection
Airway protection deserves its own special mention. The dislodged foreign
body can obstruct a more proximal airway or be dropped and occlude a
different bronchus. A good grasp of the object can reduce the risk of more
significant obstruction. Central obstruction that cannot be readily corrected
can rapidly lead to death. This emphasizes the need for an experienced
operator for this delicate task.
B. Endoscopic Removal
Bronchoscopy is the mainstay of airway foreign body removal. The type of
bronchoscopy, equipment used, and degree of anesthesia is a function of the
type of patient, type of foreign body, equipment availability, institutional
preferences, and experience of the operator (Table 2). Operator experience
and adequate equipment are key. Pins and other sharp objects may have the
sharp edge pointing proximally, and efforts must be made to protect the
airway upon removal by protecting the edge or closing the pin with a
dedicated forceps [22]. Foreign bodies must be removed expeditiously and in
a manner that does not exacerbate the problem.
Table 2 Equipment
Bronchoscope
Flexible or rigid
Variety of forceps
Retrieval basket
Balloons
Airway stabilizer
Rigid bronchoscope
Endotracheal tube
Oral airway
Laryngeal mask airway
Monitoring and support as appropriate to setting
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264
Kovitz and Mayse
Rigid Bronchoscopy
It is the preference of our institution to remove foreign bodies from the
airway using a rigid bronchoscope. This allows for rapid isolation and
removal of the object. Larger objects are more readily removed and a variety
of instruments can be passed through the bronchoscope to aid removal
(Fig. 2). The object can be broken up with forceps or laser if needed.
General anesthesia is required. The bronchoscope is introduced via the
mouth and advanced to the area of the foreign body. A forceps or basket is
used to grasp and remove the object. There are a myriad of specialized
forceps that can be used that are specific to the object. Examples are those
used to close safety pins, grasp nails, round objects, and pins [22]. An object
that is too large to grasp may be broken up mechanically or by laser.
Surrounding granulation tissue can be treated in this way as well.
Cryotherapy probes may also be used to remove granulation tissue or
dislodge the object. If the object cannot be dislodged, a balloon or forceps
can be passed beyond the object and deployed and pulled upward to
dislodge the object. Once grasped, the foreign body is removed through the
channel of the bronchoscope. If it is too large to fit through the channel, the
object is pulled up to the channel and removed en bloc with the
bronchoscope. Care must be taken not to drop the object along the way
and cause further obstruction. If the object is dropped, the scope can be
reintroduced to retrieve it. An object that is pulled proximally and dropped
can obstruct a larger and more critical airway. If the patient is compromised
and the foreign body cannot be readily removed, the object may need to be
pushed back down more distally to improve ventilation and the process of
removal restarted. The main benefits of rigid bronchoscopy are rapid
removal, improved access to larger objects, and an ability to clear additional
obstructing tissue or released blood and secretions. Larger and varied
forceps can deal with larger and varied objects. Figure 3 shows some
examples of baskets, forceps, and a balloon. Relative disadvantages are the
need for general anesthesia and limited access to experienced operators.
Flexible Bronchoscopy
Flexible bronchoscopy has been used quite successfully to remove airway
foreign bodies. The main advantage is the wide availability of flexible
bronchoscopes and trained operators. Foreign body removal with a flexible
bronchoscope still requires an operator experienced in the technique and
adequate forceps, baskets, and ancillary equipment. Airway protection
remains paramount. The flexible bronchoscope should be introduced orally
via an oral airway, laryngeal mask airway, or endotracheal tube.
Introduction via the nose is discouraged, as the foreign body needs to be
265
Figure 2 Rigid bronchoscope introduced into an airway with telescopic guidance
and forceps used to grasp a foreign body.
able to pass during removal. The introduced bronchoscope is advanced to
the area of the foreign body. Surrounding granulation tissue may need to be
removed using cryotherap,.Y, laserhtor fpJceps. The object may need to be
Gopyng ed Matenal
266 Kovitz and Mayse
dislodged with a balloon or forceps passed beyond it and deployed and
pulled up. It may need to be broken up by forceps or laser. It is then grasped
with a forceps, basket, or cryotherapy probe and pulled up and out of the
airway en bloc with the flexible scope (Fig. 4). The use of an endotracheal
tube or laryngeal mask airway facilitates any needed reintroduction of the
bronchoscope. Care must be taken not to drop the object along the way and
cause further obstruction. A concern of using flexible bronchoscopy is the
potential lack of control of the airway and resultant symptomatic
obstruction [23]. If the object is dropped, the scope can be reintroduced
to retrieve it. An object that is pulled proximally and dropped can obstruct a
larger and more critical airway. If the patient is compromised and the
foreign body cannot be readily removed, the object may need to be pushed
back down more distally to improve ventilation and the process of removal
restarted. Fluoroscopy is occasionally used to help find and retrieve a
foreign body that is beyond the visual range. This applies to both flexible or
rigid bronchoscopy. In essence, flexible bronchoscopy can be a safe and
effective method for foreign body removal. However, it is best done with
rigid bronchoscopy readily available in the case of failure [24].
Figure 3 A variety of foreign body removal devices: baskets, balloon, and forceps.
267
Figure 4 Flexible bronchoscope used to visualize a foreign body that is entrapped
by a basket for removal.
268
Kovitz and Mayse
Preoperative Evaluation and Operative and Perioperative Care
for Endoscopic Removal
The preoperative evaluation for foreign body removal is the same as for any
patient undergoing flexible or rigid bronchoscopy and various degrees of
anesthesia. The acuity of the airway compromise will influence the time and
appropriateness of preoperative assessment. Standard monitoring of vital
signs, pulse oximetry, and the like apply as in any endoscopic procedure
situation. The number of personnel will vary with location (i.e., endoscopy
suite vs operating room), the degree of anesthesia, equipment used, and
institutional preferences. A minimum of three people is required. The
primary focus is airway protection and avoiding a worsening of the airway
situation.
VI. Surgery
Surgery represents the last and least desirable option for airway foreign
body removal. An indication would be a foreign body that is or has the
potential to cause serious symptoms and cannot be removed endoscopically.
Significant postobstructive damage and unrelenting infection or destruction
of lung parenchyma or bronchiectasis may require lobectomy [12]. Care
must be taken to avoid impaction of a foreign body as a result of an
attempted endoscopic removal. Occasionally, an irretrievable foreign body
that has a low potential for symptoms is left in place rather than resorting to
surgery (e.g., nonobstructing dental gold crown out of the reach of a
bronchoscope). Candidacy for surgery is assessed in a similar manner to any
other patient undergoing thoracotomy for resectional surgery.
VII. Complications
Complications of bronchoscopy for removal of a foreign body are
infrequent [15,25]. Concerns include worsening the foreign body impaction,
worsening airway obstruction leading to respiratory compromise and death,
tear of the airway, flooding with secretions or blood, and the standard
complications related to bronchoscopy, anesthesia, and intubation.
VIII. Conclusion
Foreign body aspiration is a common and at times life-threatening problem
in children and adults. Risk factors should be understood and minimized if
possible. Successful management requires prompt recognition and experi-
269
enced management. A high index of suspicion is required. Bronchoscopy is
the mainstay of both diagnosis and removal. A wide range of options are
available for endoscopic removal of foreign bodies. The key is airway
protection, an experienced operator, adequate equipment, and rigid
bronchoscopy availability if using a flexible approach initially. Although
prevention of aspiration is best, once aspirated, foreign bodies can be
successfully removed endoscopically to the betterment of the patient and
satisfaction of the team in the right setting.
References
I. Rafanan AL, Mehta AC. Adult airway foreign body removal. Clin Chest Med
2001; 22(2):319-330.
2. Kelly SM, Marsh BR. Airway foreign bodies. Chest Surg Clin North Am 1996;
6(2):253-276.
3. National Safety Council Accident Facts. http://diskworld.wharton.upenn.eduj
ch uac/DataSet/AF8. HTM.
4. Oguz F, Citak A, Unuvar E, Sidal M. Airway foreign bodies in childhood. Int J
Pediatr Otorhinolaryngal 2000; 52(1):11-16.
5. Fitzpatrick PC, Guarisco JL. Pediatric airway foreign bodies. J La State Med
Soc 1998; 150(4):138-141.
6. Altmann A, Nolan T. Non-intentional asphyxiation deaths due to upper airway
interference in children 0 to 14 years. Injury Preven 1995; 1(2):76-80.
7. Tan HK, Brown K, McGill T, Kenna MA, Lund DP, Healy GB. Airway
foreign bodies (FB): a 10-year review. Int J Pediatr Otorhinolaryngol 2000;
56(2)91-99.
8. Chen CH, Lai CL, Tsai TT, Lee YC, Perng RP. Foreign body aspiration into
the lower airway in Chinese adults. Chest 1997; 112(1):129-133.
9. Arjmand EM, Muntz HR, Stratmann SL. Insurance status as a risk factor for
foreign body ingestion or aspiration. Int J Pediatr Otorhinolaryngol 1997;
42( I):25-29.
10. Szmeja Z, Kruk-Zagajewska A, WaSniewska E. Tracheoesophageal fistula
after the removal of esophageal foreign body [Polish]. Otolaryngolog Pol 1999;
53(5):609-612.
11. Saoji R, Ramchandra C, D'Cruz AJ. Subcutaneous emphysema: an unusual
presentation of foreign body in the airway. J Pediatr Surg 1995; 30(6):860-862
12. Cataneo AJ, Reibscheid SM, Ruiz Junior RL, Ferrari GF. Foreign body in the
tracheobronchial tree. Clin Pediatr (Phila) 1997; 36(12):701-706.
13. WaIner DL, Ouanounou S, Donnelly LF, Cotton RT. Utility of radiographs in
the evaluation of pediatric upper airway obstruction. Ann Otol Rhinol
Laryngol 1999; 108(4):378-383.
14. Silva AB, Muntz HR, Clary R. Utility of conventional radiography in the
diagnosis and management of pediatric airway foreign bodies. Ann Otol Rhinol
Laryngol 1998; I07( I Material
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15. Zerella JT, Dimler M, McGill LC, Pippus KJ. Foreign body aspiration 111
children: value of radiography and complications of bronchoscopy. J Pediatr
Surg 1998; 33(11):1651-1654.
16. Lifschultz BD, Donaghue ER. Deaths due to foreign body aspiration in
children: the continuing hazard of toy balloons. J Forensic Sci 1996; 41(2):247-
251
17. Panieri E, Bass DH. The management of ingested foreign bodies in children-a
review of 663 cases. Eur J Emerg Med 1995; 2(2):83-87.
18. Kovitz KL, Mayse ML, Araujo CE, David O. Self stenting with a crack pipe:
the ultimate in "managed care." Respiration. In press.
19. Langhelle A, Sunde K, Wik L, Steen PA. Airway pressure with chest
compressions versus Heimlich manoeuvre in recently dean adults with complete
airway obstruction. Resuscitation 2000; 44(2): I05-1 08.
20. Andazola JJ, Sapien RE. The choking child: what happens before the
ambulance arrives? Prehosp Emerg Care 1999; 3(1):7-10.
21. Nowitz A, Lewer BM, Galletly DC. An interesting complication of the
Heimlich manoeuvre. Resuscita tion 1998; 39( 1-2): 129-131.
22. Pilling Endoscopic Instruments. Pilling Co., Fort Washington, PA. Catalog
No. 99 1001, 1987.
23. Ikeda M, Kitahara S, Inouye T. Large radiolucent tracheal foreign body found
by CT scan caused dyspnea: an admonition on flexible fiberscopic foreign body
removal. Surg Endosc 1996; 10(2):164-165.
24. Swanson KL, Prakash VBS, Midthun DE, Edell ES, Vtz JP, McDougall JC,
Brutinel WM. Flexible bronchoscopic management of airway foreign bodies in
children. Chest 2002; 121(5):1695-1700.
25. Bless D, Plinkert PK. Removal of foreign bodies from the tracheobronchial
system in childhood [German]. HNO 1998; 46(9):799-803.
14
Photodynamic Therapy
Early Lung Cancer
STEPHEN LAM
University of British Columbia
and British Columbia Cancer Agency
Vancouver, British Columbia, Canada
1. Introduction
ANNETTE M. McWILLIAMS
British Columbia Cancer Agency
Vancouver, British Columbia, Canada
Lung cancer is the most common cause of cancer death worldwide [1], and
this imposes an enormous burden on health care. The overall 5-year survival
rate is approximately 14% for non-small cell carcinoma and 5% for small
cell carcinoma [2]. The only patients who achieve long-term survival are
those with resectable early-stage disease, with a 5-year survival rate of 80%
[3,4]. Unfortunately, the majority of victims present with advanced
'inoperable disease. In the last decade, the development of new technology,
such as autoflourescence bronchoscopy, has improved the detection of
bronchial dysplasia and early-stage lung cancer (carcinoma in situ and
microinvasive cancer) in high-risk smokers/exsmokers [5,6]. Methods to
identify high-risk patients are presently being investigated; that is,
computer-assisted image analysis of sputum cells [7,8], immunostaining
using monoclonal antibody to heterogeneous nuclear ribonucleoprotein A21
BI (hnRNP A2/BI) [9], methylation markers [10], and gene mutations [II].
Traditionally, the only treatment available for early-stage lung cancer
was resection. Even though early-stage endobronchial tumors are small by
definition, a lobectomy is ...requiredtind70%t of cases, and in the remaining
c.;opyngh e Ma enal
271
272
Lam and McWilliams
30%, bilobectomy or pneumonectomy is required [3]. This poses difficulties
for long-term smokers with reduced cardiopulmonary reserve. In addition,
approximately 1-4% of patients have synchronous lung cancer [12]. Some
studies report that up to 15% of newly diagnosed early lung cancer cases
have a synchronous lesion [13-15]. Following resection of a primary non-
small cell lung cancer, the risk of development of second primary lung
cancers is 1-2% per year [16]. Therefore, preservation of normal pulmonary
tissue is desirable. A number of endobronchial modalities such as
photodynamic therapy, electrocautery, cryotherapy, and laser therapy
have been developed in the last two decades that can eradicate small,
preinvasive lung cancer in the central airways [17-19].
II. Principles of Photodynamic Therapy
A. Mechanism of Action
Photodynamic therapy (PDT) refers to the use of a photosensitizing drug
and light of a specific wavelength in the presence of oxygen to produce a
photochemical reaction to destroy the tumor. Photosensitizing drugs tend to
have greater accumulation in tumors compared to normal tissues, although
the exact mechanisms of drug uptake and retention in tumor tissue are not
completely understood. Some very effective agents are not truly selective
tumor localizers. Accumulation is probably related to the chemical
properties of the photosensitizers used and tumor tissue properties [20].
Many photosensitizers do not selectively accumulate in malignant cells but
rather in tumor stromal elements, particularly tumor-associated macro-
phages [21-23]. Most photosensitizers are localized in cellular membranous
structures [20].
After absorbing light of a specific wavelength, the photosensitizer
molecule becomes electronically excited. This results in the formation of a
variety of active forms of oxygen, with the principal one being singlet
oxygen, which is highly cytotoxic. If oxygen is not present, or if the levels are
low, the tumor cells become resistant to PDT [24,25]. Owing to the short
lifetime and diffusion distance of singlet oxygen in cells, the damage to
cellular constituents occurs close to the site of the photosensitizer
localization [20]. The photochemical reaction results in damage to
mitochondrial, lysosomal, and plasma membranes, triggering rapid
apoptosis and an inflammatory response. In addition to direct killing of
tumor cells, PDT also leads to secondary events such as ischemic death
subsequent to vascular damage and occlusion of blood supply; ischemia-
reperfusioll injury; rapid and massive infiltration of inflammatory cells from
PhoLOdynamic Therapy: Early Lung Cancer
273
the circulation; tumor killing by activated inflammatory cells; and tumor-
sensitized immune reaction [20,26].
Macrophages, as antigen-presenting cells, have a crucial role in tumor
recognition by the lymphoid population and subsequent development of
tumor-specific immunity. The activity of tumor-sensitized lymphocytes is
not limited to the PDT-treated sites, but also has a systemic effect [20,26]. In
animal models, these lymphoid populations are essential for preventing the
recurrence of the PDT-treated tumor [26].
B. Photosensitizers
Porfimer sodium (Photofrin; QLT Inc., Vancouver, Canada; Axcan Pharma,
Birmingham, AL, U.S.A.) is the photosensitizer that has been most
extensively studied and approved for clinical use in a variety of cancers,
including lung cancer. Both Photofrin and its predecessor, hematoporphyrin
derivative (HpD), are made from hematoporphyrin, and are complex
mixtures of oligomeric esters and ethers of hematoporphyrin. Photofrin and
HpD have several absorption peaks. Although both absorb more strongly at
lower wavelengths, red light at 630 nm is used for clinical treatment as it
penetrates more deeply into tissue with less interference from hemoglobin
absorption. Light treatment is generally performed 24-48 hI' after intrave-
nous infusion to allow differential retention in tumor tissue versus most
normal body tissues except liver and skin. The major shortcoming of
Photofrin/HpD is skin photosensitivity lasting 4-6 weeks and sometimes
several months because of its prolonged retention in the skin [27].
Second-generation photosensitizers are being developed that are purer
compounds with improved tissue penetration and shorter cutaneous
photosensitivity. Benzoporphyrin derivative (BPD) (Verteporfin; QLT
Inc.) is a second-generation photosensitizer. It has a maximum absorption
peak at 690 nm, above the absorption peak of hemoglobin, and is therefore
less attenuated by blood, resulting in deeper light penetration into tissues.
BPD is rapidly accumulated in tumor tissue, requiring only 30-150 min after
intravenous infusion before treatment can be performed. Following
treatment, it is rapidly cleared from the body. Skin photosensitivity lasts
only a few days. BPD has been approved for the treatment of neovascular
age-related macular degeneration and is under investigation for the
treatment of cancer [27].
5-Aminolevulinic acid (ALA)-induced endogenous photosensitization
is an interesting approach that uses the heme biosynthetic pathway to
produce endogenous porphrins, particularly protoporphyrin IX, which is an
effective photosensitizer. ALA reaches optimal tumor concentration in 2-
4 hI' after administration. Its maxirnUJ;l1. absorption peak is 630 nm, and its
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Lam and McWilliams
rapid clearance eliminates cutaneous photosensitivity within 24 hr. ALA has
approval for PDT of actinic keratoses-a premalignant skin lesion.
However, preliminary studies suggest that ALA-PDT may be effective for
carcinoma in situ but not for microinvasive or invasive cancer in the lung
[28].
There are a number of other photosensitizers presently undergoing
investigation, such as lutetium texaphyrin (Lu-tex; Pharmacyclics Sunny-
vale, CA) [20,29], tin etiopurpurin (SnET2; Miravant Medical Technologies,
Santa Barbara, CA) [20,30], meta-tetrahydroxyphenylchlorin (Foscan;
Scotia Pharmaceuticals, Takapuna, North Shore City, NZ) [20,31], N-
aspartyl chlorin e6 (Npe6; Nippon Pharmaceuticals, Tokyo, Japan) [20,32],
polyhematoporphyrin (Photosan; SeeLab, Hamburg, Germany) [33],
hypericin [34], acridine orange [35], porphycenes [36], benzochlorins [37],
indocyanine green [38], bacteriochlorophyll derivatives [39], and pyro-
pheophoride-a methyl ester [40]. The goal is to have a photosensitizing drug
with better tumor selectivity, maximum absorption peak higher than
630 nm, and minimal toxicity such as skin photosensitivity.
C. Clinical Technique
In the treatment of lung cancer, Photofrin is given at a dose of 2 mg/kg in
5% dextrose solution administered intravenously. Twenty-four to 48 hr
later, fiberoptic bronchoscopy is performed under local anesthesia. Red light
(630 nm) is transmitted to the bronchial surface via a quartz fiber inserted
through the biopsy channel of the bronchoscope. The photosensitizer is thus
activated to produce a photochemical reaction designed to destroy the
tumor tissue.
Several light sources have been approved for. clinical use, such as
continuous wavelength lasers (potassium-titanyl-phosphate [KTP] dye laser,
argon dye laser), and pulse lasers (e.g., excimer dye laser). More recently, a
compact, less expensive diode laser has become commercially available
(Diomed Inc., Andover, MA).
The clinical effectiveness of endobronchial PDT depends on the ability
to deliver light to the target tumor tissue. Optical delivery systems have been
designed to match optimally light distribution with tumor geometry. Optical
fibers are commercially available with tips incorporating microlenses or
cylindrical light diffusers. For small superficial early bronchial cancers that
are end-on to the bronchoscope, surface illumination is usually achieved
using a microlens fiber. For tumors that are parallel to the bronchoscope,
nodular/polypoid tumors, and tumors involving smaller branches of the
bronchial tree, a cylindrical diffuser is used. Diffuser tips vary in length from
1.0 to 2.5 cm: The length used is determined by estimating the axial length of
Photodynamic Therapy': Early Lung Cancer
275
the tumor. Current protocols use a power of 200-400 mW/cm
2
to deliver a
total light dose of 100-200 J/cm
2
in a treatmen t time of 500 secs.
A "clean-up" bronchoscopy is required 2 days after treatment to
remove debris, which is usually too viscous for the patient to cough up.
Clean-up bronchoscopy is important to avoid complications such as
infection, respiratory distress, or respiratory failure. If residual tumor is
seen following the clean-up bronchoscopy, a second light treatment can be
performed during the same session.
III. Local Staging of Early Lung Cancer
The major indication for PDT in lung cancer is for early superficial
bronchial cancers where the treatment is potentially curative. PDT is a local
treatment. It cannot treat metastatic disease in lymph nodes or other organs.
PDT provides curative treatment for cancers that have not invaded beyond
the cartilaginous layer of the bronchial wall [41,42]. The risk of regional
lymph node metastases increases with the size of the lesion. Fujimura [14]
found that in surgically resected radiographically occult lesions with
endoscopically visible margins, 23% of lesions 10-29 mm in length and
67% lesions >30mm in length had lymph node involvement. Therefore,
lesions that are best considered for PDT are early-stage lung cancers of
< 10 mm in surface diameter with endoscopically visible margins. Current
evidence shows that accurate staging is essential for the success of PDT.
However, true assessment of the depth of tissue involvement with present
bronchoscopic and radiological techniques remains difficult.
High-resolution computed tomography (HRCT) of the thorax can be
useful in the assessment of early-stage lung cancer to exclude patients with
peribronchial extension who are unsuitable for PDT. In one study assessing
the role of HRCT in patients being considered for endobronchial therapy,
35% of patients with bronchoscopic early-stage lung cancer were found to
have peribronchial extension or nodal enlargement on HRCT. Of patients
with intraluminal disease on HRCT, 90% achieved complete response with
endobronchial therapy. HRCT was inconclusive in patients with post-
obstructive infiltrates [43]. Therefore, HRCT is useful for detection of
peribronchial infiltration; however, HRCT is inaccurate for assessment of
invasion of the bronchial wall.
Endobronchial ultrasound is a new technique that may aid the
clinician in assessment of bronchial cancers for PDT. Using a 20-MHz or
higher frequency ultrasonic probe, different layers of the bronchial wall can
be visualized. A number groups have demon-
276
Lam and McWilliams
strated the potential usefulness of endoscopic ultrasound to delineate tumor
invasion beyond the cartilage layer (44-47].
IV. Clinical Trials
In the majority of clinical trials, outcome was defined as complete, partial,
or no response and progressive disease. However, for curative treatment,
any result less than complete response is unsatisfactory; that is, no evidence
of residual tumor visible on follow-up bronchoscopy, biopsy, and
radiological examination. Furthermore, a complete response based on
short-term follow-up is inaccurate. The time of assessment of a complete
response reported in published studies varied from I to 3 months. A
significant proportion of those who had a "complete response" were found
to have recurrent disease on longer follow-up. Therefore, the actual
complete response rate is lower. Many trials that assessed the use of PDT
in early-stage lung cancer included stage I disease in addition to stage O.
These factors have to be taken into account when evaluating the results of
published reports.
The majority of clinical data in the use of PDT in early lung cancer has
emerged from Japan in the last two decades (12,41,48-55]. The first patient
with early lung cancer treated with PDT was reported in 1980 by Kato et al.
at Tokyo Medical University Hospital. Clinical data up to 1998 from this
center has been previously published (52,53]. Their results were updated at
the recent 8th IPA World Conference of Photodynamic Medicine (June
2001, Vancouver, Canada) (Table 1). Since 1980, 145 patients (191 cancers)
with early non-small cell lung cancer have been treated with PDT, including
99 patients with stage 0 and 56 patients with stage IA disease. There were
141 men and 4 women. The majority of cases (98%) were squamous cell
carcinoma. Complete response was achieved in 86% of lesions, with a
recurrence rate of 13%, thereby resulting in a long-term response of 75%.
Table 1 Pivotal Studies of PDT in Early Lung Cancer
Median
No. of Complete Recurrence Long-term survival
Stage patients response (%) (%) response (%) (yrs)
QLT Inc. 0, lA, IB 102 78 44 43 3.5
Japan O,IA 145 86 13 75 34
Mayo Clinic
Stage 0/1 58 84 22 66 3.5
Photodynamic Therapy: Early Lung Cancer
Table 2 Response Rate According to Lesion Size: Tokyo Medical University
1980-2001
277
No. of Complete Long-term
Tumor size (em) lesions response (%) Recurrence (%) response (%)
<0.5 58 95 16 79
0.5-1.0 78 95 II 85
1.0-2.0 31 81 12 71
;;:,20 24 46 9 42
Total 191 86 13 75
When success of treatment was evaluated according to lesion size, lesions
< I cm had a complete response of 95% and lesions 2 cm had a complete
response of only 46% (Table 2). Treatment success was also related to
whether the distal margin of the tumor could be clearly seen bronchosco-
pically. If the margin was visible, a complete response rate of 92% was
achieved compared to 67% if the margin was not visible. If the lesion was
<I cm and the margin was visible, complete response was achieved in 98%
of cases.
Two other Japanese centers have published smaller studies of PDT in
early lung cancer with lower response rates and higher recurrence rates
compared to the Tokyo Medical University Group (Table 3). Imamura
studied 29 patients (39 cancers) and achieved complete response in 64% of
lesions. Recurrence occurred in 36%, giving a long-term response of 41 %.
Table 3
Worldwide Experience with PDT for Early Lung Cancer
No. of
Complete Recurrence Long-term
Study
patients response (%)
(%) response (%)
Tokyo Medical University
145 86
13 75
Onoit et al. [55]
36
31 33
21
Imamura et al. [13]
29
64 36
41
Radu et al. [58]
36
78
Patelli et al. [59]
23
62 6 58
Sutedja et al. [56]
II
91
Sutedja et al. [57]
30
72 25
54
Lam et al. [60]
102
78
44 43
Mayo Clinic
58
84
22 66
Overall
509
75
31 57
Copyngf1ted Malena!
278
Lam and McWilliams
On evaluation of lesion size, 72% of lesions that were <3 cm
2
achieved a
complete response [13]. Ono studied 36 patients (39 cancers) and achieved a
complete response rate of only 31 %, with a recurrence in 33%. Therefore,
the long-term response was only 21 % [55].
A number of smaller studies emerged from Europe and Canada by
Sutedja [56,57], Radu [58], and Patelli [59], with complete response rates of
62-91 % (see Table 3). The pivotal clinical trial for Food and Drug
Administration (FDA) approval of Photofrin for PDT in early lung cancer
was conducted by QLT Inc. and involved centers in Germany (P505),
Canada (P506), the Netherlands (P506), and France (P507) [60]. A total of
102 patients with radiologically occult (stages 0, lA, and IE) squamous cell
lung cancer were treated. Of these, the FDA panel of experts concurred that
24 patients were not candidates for either surgery or radical radiotherapy
owing to poor lung function, previous surgery/radiotherapy, or multifocal
disease. An overall immediate complete response rate of 78% was achieved
(95% CI = 7-87%). Forty-four percent of the patients had recurrent tumor
on follow-up, giving a long-term response rate of 43% (see Tables 1 and 3).
The median time to tumor recurrence was 2.8 years (range 0.1-10.0 years).
Analysis of the subgroup of the 24 inoperable patients revealed a complete
response of 92% (95% CI = 81-100%). A similar recurrence rate of 46%, a
long-term response rate of 50%, and a median time to tumor recurrence of
2.7 years was observed.
Edell and Cortese also began using PDT at the Mayo Clinic in 1980
[42,61-66]. In 58 nonsurgical patients with early lung cancer, an 84%
complete response rate was achieved after one treatment. Of these 19 (39%)
recurred and had a second PDT treatment. The median time to tumor
recurrence after the first treatment was 4.1 years. Following the second
treatment, II patients (22%) had recurrences. The long-term complete
response rate was 66% (see Tables 1 and 3). They subsequently addressed
the issue of PDT as an alternative to surgical resection in 39 patients with
small bronchial cancers [65]. A 69% complete response was achieved with an
18% recurrence rate. Patients who did not respond or had recurrences were
offered surgery. Of the 12 patients who underwent surgery, 3 were found to
have NI disease. Five patients refused surgery. Three were treated with
brachytherapy and two with a repeat course of PDT. Overall, 22 patients
(56%) were spared surgery.
The worldwide data showed that patients with early lung cancer
treated with PDT achieve a complete response in approximately 75% cases,
with a recurrence rate of about 30%. They therefore require close
bronchoscopic follow-up. A number of studies also describe the need for
repeat trea tments to achieve long-term complete response [55-57,61,65]. The
reason for the high rate of recurrence is multifactorial, but is most likely due
279
to patient and lesion selection. The best response is seen in highly selected
patients with small lesions and visible margins. Inclusion of larger lesions in
some of the clinical trials increased the likelihood of extracartilaginous
extension, lymph node metastasis, and inadequate treatment with PDT.
The most common side effect of PDT is skin photosensitivity, which is
generally mild and varies from 8 to 78% of patients treated. Hayata [48,49]
reported skin photosensitivity of >70% in the early 1980s (using
hematoporphyrin derivative at 2.5-5.0 mg/kg), but this appears to have
been reduced in more recent studies to Patients have to be advised to
stay out of any strong light indoors and outdoors for 4-6 weeks to avoid
skin photosensitivity reaction.
V. PDT Versus Other Endobronchial Modalities
for Treatment of Early Lung Cancer
Photodynamic therapy is only one of the endobronchial treatments that
have become available over the last 20 years. Others include electrocautery,
cryotherapy, brachytherapy, and laser therapy. The amount of published
data regarding these techniques for use in early lung cancer is small, and
there have been no comparative studies between these modalities.
A. Electrocautery
Electrocautery is the least expensive treatment for endobronchial tumors.
The technique is widely used in surgery, and the equipment is available in
many operating rooms. Bronchoscopic electrocautery is the endoscopic use
of high-frequency electrical current that generates heat owing to tissue
resistance, resulting in destruction of tissue. It is usually performed during
flexible bronchoscopy with unipolar electrodes. The treatment generally
takes only several minutes to perform. Treatment should be avoided in
patients with pacemakers or defibrillators because of the risk of ventricular
fibrillation. Complications are uncommon. A small study in early lung
cancer of 13 patients (15 cancers) by the group in Amsterdam showed a
complete response in 80% of lesions with no recurrence during 22 months of
follow-up [19].
B. Cryotherapy
Cryotherapy is a technique where tissue is destroyed by freezing. It is also an
inexpensive and safe method. The aim is to promote the fastest possible
cooling of target tissue to induce intracellular freezing. This is associated
with vascular effects, and thrombosis, which
280 Lam and McWilliams
result in ischemic cellular necrosis over subsequent days. Nitrous oxide is the
most commonly used agent in bronchoscopic cryotherapy. Repeat
bronchoscopy a few days after treatment is needed to remove the debris.
A recent report from France in 35 patients (41 cancers) with early-stage lung
cancer showed a complete response in 91 % of the patients and a recurrence
rate of 28% within 4 years. Therefore, a long-term response of 63% was
achieved; similar to that of PDT [15].
C. Brachytherapy
Brachytherapy refers to the placement of a radioactive source within/near
an endobronchial malignancy to deliver local irradiation. This requires the
insertion of an afterloading polyurethane catheter into the airway adjacent
to the tumor during fibreoptic bronchoscopy. The catheter position is
confirmed radiologically and is then loaded with the radioactive source.
Iridi urn 192 is generally used. High-dose-rate brachytherapy is now used to
reduce treatment time and enable outpatient therapy. Complications of the
procedure are low in experienced hands; however, delayed effects such as
radiation bronchitis, stenosis, fistula formation, and hemoptysis may occur.
In two small studies, the use of high-dose brachytherapy in three to six
sessions reported good response rates similar to PDT [67,68]. Marsiglia
reported 34 patients with early-stage lung cancer with a complete response
of 85% seen over 2 years of follow-up. Perol reported 19 patients with early-
stage lung cancer with a complete response rate of 83%, which fell to 75%
during I-year of follow-up.
D. Laser Therapy
Laser therapy can be used for direct thermal ablation of tissue in
endobronchial malignancy. It has been used extensively in advanced lung
cancer patients as a palliative measure to relieve airway obstruction. The
yttrium-aluminum-garnet (YAG) laser is the most common laser used for
tracheobronchial malignancy. The treatment is conducted with a quartz
fiber inserted into the biopsy channel of aflexible/rigid bronchoscope. The
use of laser treatment for early lung cancer has not been widely studied. The
study by Cavaliere and coworkers showed a complete response rate of 100%
in 22 patients with small bronchial cancers. The long-term outcome of these
patients was not reported. YAG laser therapy is not indicated for tumors
that are located in the bronchial wall parallel to the bronchoscope or for
tumors involving smaller bronchial branches because of the risk of
perforation [18,69].
VI. Conclusion
281
Lung cancer remains an enormous medical problem for our community.
Future focus should be directed toward development and validation of
screening methods for detection of early lung cancer among high-risk
subjects. Photodynamic therapy is the most extensively studied endobron-
chial treatment for early lung cancer. Suitable lesions require careful
assessment bronchoscopically and radiologically. Endoscopic ultrasound
has a definite role in selecting patients for curative endobronchial therapy.
Following treatment, the patients should be closely monitored for recurrent
disease and development of metachronous tumors. Other available
endobronchial treatments such as electrocautery, cryotherapy, and bra-
chytherapy have not been as well studied but appear to have similar
response rates to PDT. PDT and brachytherapy are more expensive
treatments. Electrocautery treatment appears to be the safest and cheapest
for the majority of patients with small bronchial cancers. Further work is
required to evaluate these modalities, but ultimately the choice of technique
may depend on the clinician's experience.
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15
Photodynamic Therapy for Palliation of Lung Cancer
DAVID OST
North Shore University Hospital
and New York University School of Medicine
Manhasset and New York, New York, U.S.A.
I. Introduction
Photodynamic therapy (PDT) involves the use of photosensitizing agents for
treatment of malignant disease. These photosensitizing agents are infused
intravenously and are selectively retained within tumor cells. The agents
remain inactive until activated by light of the proper wavelength. When
activated, these compounds generate toxic oxygen radicals that result in
tumor necrosis. PDT was studied for use in lung cancer in the 1980s, but its
use in the United States remained limited to research. More recently, PDT
using the photosensitizing agent pOL'fimer sodium (Photofrin) received Food
and Drug Administration (FDA) approval, making it more available for
routine clinical use in the United States.
PDT offers a complementary approach to a variety of clinical
problems in interventional pulmonology. Potential applications include
treatment of airway obstruction caused by malignant tumors, including
both metastatic disease to the lung and advanced lung cancer. Other
potential applications include treatment of carcinoma in situ (CIS) and
early-stage lung cancer in nonsurgical candidates. This chapter will focus on
the application of PDT for tceatment of ~ d p c e d lung cancer, including the
c.;opyngntea Matenal
287
288
Ost
technique of PDT, its mechanism of action, a review of clinical studies using
PDT, and an assessment of how PDT fits into a multimodality approach for
the treatment of malignant airway obstruction.
II. Technique
PDT for treatment of advanced lung cancer requires three distinct steps:
delivery of the photosensitizer, subsequent activation with laser light, and
bronchoscopic removal of necrotic debris. If after removal of necrotic debris
there is residual disease and airway obstruction with malignant tissue,
additional activation with laser light followed by more removal of necrotic
debris may be required.
The first step involves infusion of the photosensitizer. This is
accomplished through a simple peripheral IV with infusion of porfimer
sodium (Photofrin) at a dose of 2 mg/kg. After infusion, the patient will be
photosensitive for I month. Therefore, careful instruction must be given
prior to the first infusion regarding appropriate avoidance of direct sunlight.
Indoor light presents no problem, but precautions must be taken to avoid
direct exposure to sunlight in order to avoid a severe photosensitivity skin
reaction. Precautions include the use of long-sleeved clothing, the use of an
umbrella when walking outside, having dark curtains pulled to keep sunlight
out of the house, and the use of a broad-brimmed hat. Typically, a
handbook is given out prior to infusion with concurrent verbal instruction.
The second step is activation of the photosensiti:.er by light. This is
accomplished using an appropriate laser system delivered via the broncho-
scope. The laser fiber can be tailored to fit the clinical situation, with cleaved
probes for forward light projection, bulbous tips for isotropic spherical
distribution, or cylindrical probes for light perpendicular to the axis of the
fiber. These fibers can be inserted into endobronchial tumors directly
(interstitial delivery) or placed alongside the tumor. The wavelength of light
used depends upon the photosensitizer and the desired effect. For Photofrin,
the wavelength used is 630 nm. The wavelength determines the depth of
tissue penetration. At a wavelength of 630 nm, tissue penetration and
subsequent photosensitizer activation can be expected to be approximately
5 mm in depth.
For lung cancer, the most reliable and frequently used fibers are
cylindrical light-diffusing fibers, typically 1.0-2.5cm in length. The reason
for this is related to light dosimetry. Light dosimetry refers to the amount of
light energy delivered to the treatment area. When using a forward-
projecting fiber or a bulbous tip spherical distribution fiber, the dosimetry is
dependent upon certain assumptions that mayor may not be true. For
289
example, when using a forward-projecting fiber, the power output per
square centimeter depends upon the area illuminated. For a fixed-power
output, the power per square centimeter decreases as the area illuminated
increases. Whereas the area illuminated can be accurately measured when
treating skin metastases to the chest wall, this cannot be done within the
airway. If the forward-projecting fiber is closer to the tumor, a smaller area
will be illuminated. In this situation, a higher power per square centimeter
would result. However, estimating the distance to the tumor and
measurement of the area illuminated by a forward-projecting fiber is
difficult. This can result in highly variable power delivery per square
centimeter. Therefore, although the power going to the fiber is controlled,
the power per square centimeter is not. Thus, control of dosimetry may be
adversely affected.
When using a cylindrical light-diffusing fiber, a power of 400 mW/cm
is typically used, with a total energy delivery of 200-300J/cm. Typically,
200] /cm will be used tor CIS, whereas up to 300 J/cm will be used for more
advanced disease. Thus, the initial laser bronchoscopy will consist of simply
placing a nonthermal, cylindrical light-diffusing laser fiber either in or
adjacent to the tumor for 500-750 sec. The photosensitizer, already in the
tissue but previously inactive, will be activated up to a depth of
approximately 5 mm. Tumor necrosis will take place over the next 24-
48 hr. Of note, this is a nonthermal laser, meaning that there will be no
burning of tissue or direct injury to the connective tissue matrix as with
conventional neodymium-yttrium-aluminum-garnet (Nd:YAG) laser ther-
apy.
Twenty-four to 48 hr after the initial laser treatment, the tumor will
become necrotic. Depending upon the size of the tumor and the ability of
the patient to cough, there may be obstruction of the airway with necrotic
debris. The third step involves removal of this necrotic debris. At this time,
repeat bronchoscopy will be needed for pulmonary hygiene. If residual
tumor is present, repeat laser treatment can be done after removal of
necrotic debris, since the photosensitizer will be present with adequate tissue
levels for a prolonged period of time. If an additional laser treatment is
given, repeat pulmonary hygiene bronchoscopy is mandatory in another 24-
48 hr. Aggressive debridement and removal of all necrotic debris with each
bronchoscopy is critical, since this debris will absorb light and l"imit the
efficacy of any additional laser treatments in addition to leading to
atelectasis and respiratory compromise. The tumor debris at this stage is
very avascular and may have the consistency of very thick mucus or be
somewhat gelatinous in nature. Because of the avascular nature of the
tumor at this point, the tissue may appear white if PDT has been successful.
As predicted based on the mechanism of iniury (see Sec. III), there is
Copyngnted Malenal
290
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virtually no bleeding with mechanical debridement if PDT has been
successful.
In clinical practice, we typically begin with the Photofrin infusion
either late Friday afternoon or Monday morning, with Friday being
preferable. This allows the first laser activation procedure to be done on
Monday morning. Tumor necrosis will take place over the next 24-48 hr.
For patients with limited pulmonary reserve, this allows the option of a
pulmonary hygiene bronchoscopy to be done on Tuesday if needed, with
subsequent repeat pulmonary hygiene bronchoscopy on Wednesday. If
residual tumor remains on Wednesday, a second laser treatment can be
given after removal of necrotic debris. This allows for repeat pulmonary
hygiene bronchoscopy to be done on Thursday and Friday as needed. For
patients with good social support and adequate pulmonary reserve, the
entire procedure can be done in the outpatient setting. For patients with
more limited pulmonary reserve, inpatient therapy may be needed.
III. Mechanism of Action
Light has been used for healing since the ancient Greeks, and by 1900
photochemical reactions had been used to kill paramecia. PDT was used to
treat skin cancers in the early 1900s, and a variety of chemicals were used to
promote photochemical cytotoxicity [l]. Hematoporphyrin and its deriva-
tives were subsequently demonstrated to be selectively concentrated or
preferentially retained within malignant cells, including squamous carcino-
mas and adenocarcinomas [2-8]. Newer hematoporphyrin derivatives were
subsequently developed and studied in breast cancer, bladder cancer, and
other malignancies [9-13]. A wide variety of photosensitizing agents have
been studied and developed, including the chlorins, phthalocyanines,
tetraphenylporphine sulfate and the porphines, rhodamine 123, and the
porphyrin-based agents. This discussion will focus on important considera-
tions in relation to Photofrin, since this is the only agent currently approved
by the FDA for photodynamic treatment of advanced lung cancer in the
United States. There are several important interrelated Factors relating to
the mechanism of PDT-mediated injury that need to be considered:
Biochemical properties of photosensitizers
Biophysical properties of photosensitizers
Light dosimetry
Membrane injury
Role of tissue oxygen delivery
Vascular injury, local coagulation, and the immune response
Role of cellular apoptosis
29/
A. Biochemical Considerations
Important biochemical properties include the metabolism and relative
concentration of photosensitizers in tumors. The concentration of the
photosensitizer in the tumor tissue relative to the concentration in normal
tissue is an important consideration, since this determines in part the
selectivity of PDT treatment. A high tumor to normal tissue ratio is
desirable, since this will minimize side effects on nearby normal tissue.
Selective retention or uptake by tumors allows for a relatively high tumor to
tissue concentration ratio of the photosensitizer. The selective retention
associated with the porphyrin-based agents was initially reported by Figge
in 1948 [2]. Most sensitizers range in concentration ratios from two to five to
one. Lipson and colleagues demonstrated that derivatives of hematopor-
phyrin were associated with an even higher tumor to tissue concentration
ratio [4-8]. This tumor to tissue ratio is highest for hematoporphyrin
derivatives at 24-48 hr after intravenous injection, although fluorescence can
be picked up within 3 hr.
The mechanisms involved in selective retention and uptake of
porphyrin-based sensitizers in tumor tissue is an ongoing area of
investigation. Murine models demonstrate that sensitizers are accumulated
and retained by endocytosis via the vascular endothelium [14-16]. This is
due in part to the lipophilic nature of the compounds and their propensity to
bind to cell membranes based on their partition coefficient. The distribution
pattern after intravenous infusion mirrors that of low-density lipoprotein
(LDL) receptors in the various organs, with the greatest amount being in the
liver, followed in descending order by the adrenal glands, urinary bladder,
pancreas, kidney, spleen, stomach, bone, lung, heart, muscle, and brain [17].
The serum half-life is 20-30 hr, but photosensitizing components persist in
the skin at low levels of 2-5% for up to 4-6 weeks [18]. Theories explaining
the high tumor to tissue concentration of porphyrin-based sensitizers
include increased tumor uptake of LDL-associated sensitizers, increased
uptake by tumors due to their lower pH, and the associated increase in
water solubility of the sensitizer with low pH, poor lymphatic drainage of
tumors, tumor angiogenesis factors, and changes within the stromal cells of
tumors that increase uptake [14,15].
These biochemical properties are of clinical relevance. When used for
lung cancer treatment (i.e., PDT), the tumor to tissue ratio is critical; hence,
the typical 48- to 72- hr time interval between injection and light application.
For experimental studies of tumor diagnosis and detection utilizing tissue
fluorescence, it is more practical to have as brief a delay as possible between
injection of the photosensitizer and the diagnostic procedure. In this setting,
the 3-hr time interval between infusion and detection is of more importance.
292
OS!
The utility of future photoactive agents will depend in part upon these
considerations. Ideal agents for treatment would achieve high peak tumor to
tissue ratios more rapidly, allowing more rapid treatment, and would then
break down, minimizing photosensitivity side effects. Currently available
agents such as Photofrin remain active for up to I month, limiting their
utility because of their impact on quality of life. Similarly, shorter time to
detectable fluorescence is an important practical consideration if photo-
active agents are ever to be used on a routine basis for tumor diagnosis and
localization.
B. Biophysical Considerations
Biophysical properties that are of clinical significance include the yield of
singlet oxygen, the amount of tissue penetration, and photostabilityliability.
As described below, PDT cytotoxicity is mediated via a complex set of
interactions including type II photo-oxidation reactions. The photosensiti-
zer must be able to absorb photons of appropriate wavelengths so as to
become a triplet species. The light-excited sensitizer loses or accepts
electrons with generation of secondary radicals to produce singlet oxygen.
Importantly, singlet oxygen can be generated with quantum energies as low
as 0.98 MeV, corresponding to a wavelength of 1220nm. However, most
available sensitizers work efficiently only with wavelengths up to 850 nm
with a quantum yield of 0.2-0.6 [19]. The differences in quantum yield
appear to be related, or at least effected by, the location of the sensitizer in
the cells. In addition, for any given quantum yield, lipophilic sensitizers,
such as Photofrin, seem to be more efficient than hydrophilic sensitizers at
similar quantum yields are.
The quantum energy used to generate the reaction is important
clinically because this affects tissue penetration. The wavelength, as
determined by the quantum energy, directly affects the maximum
absorbance capacity and the depth of tissue penetration. With respect to
the porphyrin family of photosensitizers, the absorption spectra demon-
strate a peak at 405 nm. The use of this peak allows for fluorescence of
tumors to be used as a tumor marker. However, for treatment (PDT), this
wavelength of light is suboptimal, since it is nearly completely absorbed
within I mm of the surface. Thus, for PDT, a wavelength of 630 nm is used.
This allows for penetration to a depth of approximately 5 mm. Obviously,
the development of future photosensitizers will be greatly effected by
consideration of the quantum energies used, their absorption spectra, and
the resultant clinical consequences in terms of depth of penetration.
Finally, all photosensitizers can be destroyed by light, and this may
have an impact on PDT cytotoxicity. When exposed to light, a sensitizer
293
may generate enough energy to destroy tumor tissue but be destroyed and
lose its cytotoxic potential within normal cells, a process described as
photobleaching. This effect is an important consideration, since it allows
minimal damage to adjacent normal tissue while selectively destroying
tumor cells.
c. Light Dosimetry
For optimum efficacy, photosensitizers need to have high quantum yields
using an absorption spectra that allows a clinically useful depth of
penetration while making use of photobleaching properties to minimize
damage to adjacent tissues. However, to be clinically useful, there must also
be careful and tightly controlled light delivery to the site of the
photosensitizer to take optimum advantage of the biochemical and
biophysical properties of the photosensitizer.
PDT is dependent upon accurate delivery of light to the area to be
treated. It is useful to think of PDT in terms of four components: the
photosensitizer's characteristics and concentration at the tumor site, the
light source, the rate of energy delivery (power), and the total energy
delivered. The biochemical and biophysical characteristics of photosensiti-
zers have been described above. With respect to the delivery of light, any
source of light with the appropriate characteristics could be used. In
practice, laser light is used because it offers the advantage of a uniform
spectrum and coherence. For lung cancer, the argon dye pump laser or the
excimer laser is often used, although, in theory, any laser with the proper
wavelength and power could be used.
Important in vivo considerations include the effect of dose-rate
delivery and total energy delivery. While in vitro evidence has suggested that
a high dose rate (power) is associated with improved cytotoxicity, in vivo
data have demonstrated that lower dose rates may be more effective [20,21].
When treating human mesothelioma allografts in nude mice, decreasing the
intensity from 200 to 50 mW/cm
2
actually improved response. The
investigators hypothesized that reduction of the fluence rate or fractionation
may paradoxically increase the treatment effect because of an increase in
singlet oxygen in regions of poor capillary flow. Whether this is the only
mechanism or not, the importance of this study is the empiric observation
that light dosimetry has a clinical impact on response and side effects. Thus,
controlled and reproducible light dosimetry and the technology used to
deliver it are an important consideration for PDT. Studies of dosimetry for
future agents must study both the rate of energy delivery (power) as well as
the total energy delivered.
294 Ost
Difficulty with light dosimetry has also been implicated in the analysis
of treatment failures. In an analysis of 23 patients with intraluminal stage I
lung cancer, Sutejda et al. demonstrated frequent treatment failures with
distal segmental tumors or stump recurrences and attributed this to
insufficient dosimetry and possibly the inability of the light to penetrate
the bronchial stump to an adequate depth [22]. An animal study using
porcine tracheas evaluating light dosimetry supported this theory, demon-
strating that there were significant variations in light dosimetry [23]. This
relates to our preference for cylindrical light-diffusing fibers over forward-
projecting fibers. It is the high level of control and reproducible dosimetry of
the cylindrical light fibers that offers a potential advantage based on these
studies of treatment failures.
D. Membrane Injury
Membrane damage is the basic mechanism of cellular cytotoxicity in PDT.
Porphyrin uptake studies demonstrate initial binding with the plasma
membrane with subsequent extension to the internal cellular membranes
[24]. The plasma membrane and mitochondrial membranes in particular are
targets because of the water-lipid partition coefficient of the photosensitiz-
ing agents Damage. occurs with light activation and is
characterized by formation of multiple areas of membrane injury or blebs.
These progress to form larger balloonlike areas [14,30]. Concurrent with
injury to the plasma membrane, other internal membranes are injured,
including the mitochondrial membrane, nuclear membrane, Golgi appara-
tus, and endoplasmic reticulum [28,31]. There is a resultant inhibition of
oxidative phosphorylation and ATP generation due to the mitochondrial
injury, with a subsequent drop in cellular ATP [31,32]. Studies using
phosphate 31 spectroscopy to assess the metabolic response demonstrate
dramatic decreases in ATP, with virtually undetectable levels 2-4 hI' after
treatment [33,34]. Although nuclear membrane injury occurs and PDT
results in DNA strand breaks, it does not appear that DNA injury plays an
important role in cell death. Importantly, PDT has not been shown to be
mutagenic in vitro [14,29,35]. The end result of these multiple membrane
injuries is that cell ular division and normal function cease, followed shortly
by cell lysis.
E. Role of Tissue Oxygen Delivery
Much of this membrane injury is free radical mediated via a type II photo-
oxidation reaction [14,29]. Because of this, PDT is dependent upon the
availability of oxygen at the site of injury to be effective. In type II reactions,
light energy excites and activates the photosensitizer, energy transfer occurs
Photodynamic Therapy for PaLliation of Lung Cancer
295
from the excited sensitizer to molecular oxygen, and there is generation of
singlet oxygen species [36]. For PDT to be effective, there must be oxygen
available to facilitate this type II photo-oxidation reaction. The singlet
oxygen species and resulting free radical generation leads to the membrane
injury described above. Thus, membrane injury is predicated on the
adequate availability of oxygen to generate free radicals. In vitro evidence
and animal models support the important role of oxygen in PDT injury.
When oxygen is not present or is present at less than 2%, cells become
resistant to PDT [37,38]. Tissue hypoxia models in animals also support the
importance of oxygen in PDT injury. The free radical mechanism of injury is
further supported by the observation that free radical scavengers, such as
1,3-diphenylisobenzofuran, reduce PDT-mediated cytotoxicity [15,39]. The
clinical relevance of this may be that local tumor hypoxia may account for
some cases of resistance to PDT, as has been suggested by some
investigators.
F. Vascular Injury, Coagulation, and the Immune Response
Concurrent with this free radical injury, there are significant vascular,
coagulation, and immune responses that may contribute to the tissue effects
of PDT [14,15]. Part of the in vivo tumor destruction results from the
vascular effect of PDT. Decreased flow occurs, leading to arteriolar and
venular stasis, arteriolar vasoconstriction, thrombosis of venules, and
increasing interstitial edema [40,41]. The neovasculature of tumors may be
particularly vulnerable to PDT, since these vessels, venous derived, may not
have sufficient strength to remain patent in the face of high extravascular
pressures. In addition, PDT results in varying degrees of localized
coagulation. Studies with nuclear magnetic resonance imaging using in
situ fluorine have demonstrated that damage to the tumor vasculature
occurs prior to actual tumor necrosis [42]. Ben-Hur and Orenstein
demonstrated increased coagulation associated with injury to the endothe-
lium from PDT, with resultant red blood cell agglutination and thrombus
formation [43]. The clinical relevance of this is that successful PDT
treatment usually does not result in significant bleeding from the necrotic
tumor unless there has been erosion into a major vessel.
Concurrent with this vascular and coagulation injury is a localized
immune response characterized by platelet and neutrophil activation. This
results in the release of vasoactive compounds including arachidonate
derivatives, such as prostaglandin E2, 12, and thromboxane. The contribu-
tion of these mediators to PDT-induced injury is supported by the
observation that cyclooxygenase inhibitors reduce the effect of PDT on
arterioles [44]. Thus, in addition free radical membrane
Copynghted Matenal
296 Ost
injury and ATP depletion, local vascular injury, coagulation, and the
inflammatory response system play important roles in the mechanism of
action of PDT.
G. Cellular Apoptosis
The role that apoptosis-related proteins play in PDT is an area of ongoing
investigation with some conflicting data. Various studies have evaluated the
role of p53 and bcl-2 protein expression in the response to PDT in both
esophageal and lung cancer. Koukourakis and colleagues, using esophageal
cancer, demonstrated that bcJ-2 protein expression was associated with a
favorable response to PDT and could be used as a predictor of cancer
response [45]. They suggested that this was due to PDT-induced selective
degradation of bcl-2 protein, leading to apoptosis by decreasing the bcl-2/
bax ratio. Because other chemotherapeutic agents also target bcl-2 (i.e.,
taxanes), this may have important clinical applications. However, Kawa-
guchi and colleagues found no relationship between bcl-2 and tumor
recurrence in lung cancer, although they did find a relationship between
tumor size and bcl-2 expression [46]. In this study, the only predictor of
tumor recurrence using multivariate analysis was the T status (using the
TNM classification) of the tumor. Thus, the interaction of PDT with cellular
apoptosis proteins remains to be defined.
IV. Clinical Studies
Potential clinical applications of photosensitizers include early diagnosis
and localization of lung cancer, treatment of CIS, and treatment of
advanced endobronchial disease from both primary and metastatic tumors.
The diagnostic application of photosensitizers makes use of changes in the
fluorescence spectrum of tumor tissue as compared to normal tissue.
Hematoporphyrin derivative-induced fluorescence has been demonstrated
successfully to localize radiographically and bronchoscopically occult
tumors [47--49]. Fluorescence bronchoscopy uses this same principle without
any photosensitizer to try to localize tumors. These diagnostic uses of PDT
are still in the research phase of development. PDT's use in clinical practice
today can be divided into applications for CIS and for advanced
endobronchial disease. This chapter will focus on PDT as a therapeutic
tool in advanced endobronchial lung cancer.
297
A. Case Series in Advanced Endobronchial Tumors
Photodynamic therapy has been evaluated as a potential tool for treatment
of patients with unresectable lung cancer and advanced endobronchial
disease. Since there is currently no method in wide clinical use for the early
detection or cancer localization, this population represents a far larger
group of patients than the CIS group. The standard of therapy for advanced
endobronchial disease currently is Nd:YAG laser resection. Other alter-
natives include radiation therapy, brachytherapy, cryotherapy, and electro-
cautery. Most of the data with PDT comes from case series. There are no
randomized controlled trials using a placebo arm, and randomized trials
comparing PDT with other modalities are rare (Table I). Outcome measures
are also not standardized, further limiting the ability to compare the results
of PDT in different trials. Reports on the efficacy of PDT in this area are
therefore difficult to compare to results with other modalities.
In a large prospective series of 100 patients with advanced inoperable
stage III-IV lung cancer with endobronchial obstruction, PDT resulted in
significant improvement in terms of endobronchial obstruction, pulmonary
function testing, and palliation of symptoms [50]. The mean percentage of
endoluminal obstruction fell from 85.8 to 17.5% with an improvement in
forced vital capacity (FVC) and forced expiratory volume in I sec (FEV
1
) of
430 and 280 mL, respectively. In another series by McCaughan in patients
with advanced primary lung cancer, the mean endobronchial obstruction fell
from 84% prior to PDT to 18% 4 weeks later [51]. Other case series have
Table 1 PDT Versus Nd:YAG Laser in Advanced Lung Cancer
Tumors Photosensitizing
Reference (n) drug Initial response Prolonged response
53 26
Photofrin Similar for % PDT with slight
obstruction PDT advantage with
better for FEV1> respect to %
FVC obstruction
29 211 Photofrin Similar PDT with advantage
wi th respect to %
obstruction
54 31
Photofrin Similar PDT with slight
advantage in
time to treatment
failure
FEY forced expiratory volume in I sec; FYC, forced vital capacity.
I, Copyrighted Material
298
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demonstrated a beneficial impact of PDT on quality of life, dyspnea,
frequency of postobstructive pneumonia, and Karnofsky performance
score. Thus, there is evidence that PDT can perform well for palliation of
advanced endobronchial obstruction.
B. Comparison Trials
In a study by Lam and colleagues, PDT combined with radiotherapy (RT)
was superior to RT alone for patients with advanced endobronchial
obstruction. In this study of 41 patients, PDT plus RT was superior to RT
alone [52]. Only 10% of patients had complete reopening of the airway with
RT alone, whereas 70% had reopening of the airway with combined PDT
and RT.
There have been three randomized trials comparing PDT with
Nd:YAG laser that suggest results with PDT are at least comparable in
selected patients with advanced disease (see Table 1). In a prospective
comparison of PDT versus Nd:YAG laser in 26 patients with stage III
inoperable lung cancer, Moghissi et al. demonstrated better results with
PDT than with Nd:YAG laser therapy [53]. The median percentage of
obstruction was similar in the two groups prior to treatment (83.4% for
Nd:YAG and 88.7% for the PDT group), but after 1 month, the
posttreatment percentage of obstruction was significantly better in the
PDT group (39.1 % for Nd:YAG versus 17% for PDT). There was also a
significantly better change in FEV
1
and FVC in the PDT group. Another
prospective randomized trial of PDT versus Nd:YAG laser conducted in 35
centers in Europe and the United States in 211 patients with partially
obstructive lung cancer demonstrated similar results. In this study, response
rates were similar at I week, but by I month, the PDT group demonstrated a
benefit compared to the Nd:YAG group (Europe, 61 vs 36%; United States,
42 vs 19%) [29]. Improvement in terms of complete response based on
biopsy-proven results was better in the PDT group versus the Nd:YAG
group as well (Europe, 12 vs 3%; United States, 6 vs 5%). In a prospective
randomized trial comparing PDT using a flexible bronchoscope with
Nd:YAG using a rigid bronchoscope, a study by Oiaze-Jimenez and
colleagues demonstrated similar improvements in symptomatic relief after
treatment with increased survival in the PDT group [54]. Conclusions from
this study, however, are limited by the fact that by chance assignment, the
PDT group contained fewer patients with advanced lung cancer.
In a retrospective analysis comparing outcomes with Nd:YAG laser
and PDT, Taber and colleagues found no significant difference in terms of
respiratory failure, hypoxemia, or 30-day mortality [55]. They concluded
that although the treatments were comparable, PDT offered advantages in
299
terms of being technically easier, potentially safer, and not requiring general
anesthesia.
In summary, although there are only limited data, PDT seems to have
comparable efficacy to Nd:YAG and is superior to radiation therapy alone.
Advantages of PDT include the technical ease of the procedure, greater
margin for error, especially in smaller bronchi, less risk of bronchial
perforation, decreased risk of intraoperative hemorrhage, and perhaps
longer duration of response. It may be that this longer duration of response
is secondary to destruction of invisible submucosal tumor that is missed
with the Nd:YAG laser.
C. Limitations of PDT
Importantly, PDT does have limitations in terms of treatment for advanced
endobronchial disease. Among these limitations are extremely high cost
($5000 per patient for the photosensitizer alone), the need for repeat
pulmonary toilet bronchoscopies, and photosensitivity of the skin. In
addition, PDT is primarily effective for endobronchial tumors and is not
effective for obstruction caused by extrinsic compression or submucosal
spread. Notably, Nd:YAG, cryotherapy, and electrocautery are not effective
interventions for these problems either. Airway stenting is probably the
treatment of choice in these situations.
In addition, PDT is much slower than Nd:YAG laser. For patients
with acute respiratory compromise, Nd:YAG laser can achieve relief of
dyspnea much more quickly. Although PDT in mechanically ventilated
patients has been reported, the delay in response makes it less desirable if
Nd:YAG can be done with adequate safety [56].
Finally, because PDT causes significant tumor necrosis and mucous
plugging, based on our experience, we have chosen not to use it when there
is significant tracheal obstruction. In these situations, the concern is that the
resulting tumor necrosis and mucous plugging may result in sudden airway
occlusion and respiratory failure. Thus, in the setting of tracheal
obstruction, based on anecdotal evidence and theoretical concerns,
Nd:YAG is preferable.
V. Role of PDT in a Multimodality Approach
Photodynamic therapy is a promising approach that may complement other
techniques in dealing with several clinical problems. Among the clinical
problems that PDT may be effective in dealing with are those related to CIS
and endobronchial tumors...in patients '<Yith ~ y n e d disease. In each of
r..;opyngnrea Nlatena
300 OS!
these cases, the effectiveness of PDT and its appropriate use need to be
considered as part of a multimodality approach to the problem.
In the case of advanced endobronchial disease, PDT has been shown
to be useful in treating endobronchial tumors that are causing clinically
significant dyspnea or are likely to progress and lead to further clinical
complications, such as postobstructive pneumonia. Careful patient selection
is critical in this setting. Since treatment with PDT in these cases is purely
palliative, only lesions in the larger airways should be treated. If a patient
with metastatic disease has a small lesion visible in a subsegmental airway,
but it is not causing symptoms, it is not worth treating. Similarly, for
patients with no viable lung distal to the obstruction, PDT is not warranted.
The key question is whether or not removal of this localized obstruction will
result in a meaningful change in the patient's symptoms, quality of life, or
later risk of complications. When approaching these complicated patients, it
will be important to combine it with other interventional tools, such as
airway stents, Nd:YAG laser, and cryotherapy. Each tool will have its own
place depending on the problem, and in many cases multiple tools will be
needed. For example, in the case of endobronchial obstruction with
concurrent extrinsic compression, a combined approach using PDT with
stenting may be best. Either tool alone will not work.
A second issue is integrating PDT with radiation and chemotherapy.
Although it certainly appears that PDT plus RT is superior to RT alone,
the optimal sequencing has yet to be refined. Similarly, PDT to date has
shown remarkably few interactions with other chemotherapeutic agents.
Although there are theoretical concerns with interactions with agents that
may generate additional or cumulative free radical injury, whether or not
this leads to a clinically significant increase in complications is unclear.
The large number of patients treated with PDT to date suggests no clear
trend toward increased complications with any particular chemothera-
peutic agent currently in use. There are, however, theoretical advantages
to earlier treatment with PDT prior to chemotherapy or radiation in
patients with advanced lung cancer. By performing endobronchial
interventions such as PDT up front, prior to chemotherapy, higher risk
situations induced by chemotherapy side effects can be avoided in the
future. If a patient develops postobstructive pneumonia while on
chemotherapy and is pancytopenic, any laser intervention by that time
will be too high risk. By performing PDT prior to chemotherapy, this
situation can be avoided. Similarly, based on anecdotal data, we initiate
laser interventions, whether PDT or Nd:YAG, prior to radiation if
possible, since the amount of time to restore a patent airway and reduce
the risk of postobstructive pneumonia is shortened. In addition, by
relieving aIrway obstruction, patients have an improved pulmonary
Photodynamic Therapy for Pallialion of Lung Cancer
301
reserve and are better able to deal with other complications, such as
pneumonia or radiation pneumonitis.
Based on these considerations, it becomes clear that for PDT to be
optimally effective, a team approach integrating PDT into a multimodaJity
treatment program is necessary. The optimum sequencing of these
modalities requires further study, but will always need to be individualized
to the patient.
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Photodynamic Therapy for Palliation of Lung Cancer 303
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16
Bronchoscopic-Mediated Gene Therapy
Past, Present, and Future
ROBERT J. KRUKLITIS and DANIEL H. STERMAN
University of Pennsylvania Medical Center
Philadelphia, Pennsylvania, U.S.A.
I. Introduction
Gene therapy for pulmonary disease, a field still in the experimental stage,
has nonetheless progressed considerably in the past decade. There have been
significant advances in preclinical studies, as well as important developments
resulting from multiple early-phase human clinical trials for a variety of
respiratory disorders (reviewed in Ref. I). Although there are several ways
of delivering therapeutic genes to the lungs, the primary delivery modality
remains flexible bronchoscopy. This chapter will describe the various
methods and disease targets of bronchoscopic-mediated gene therapy,
focusing in particular on the results of clinical studies, and providing a
glimpse into the future of the field.
Gene therapy could potentially be utilized to treat a variety of
pulmonary disorders, including airway, parenchymal, vascular, or pleural
processes. The flexible bronchoscope, because of its unique access to both
large and small airways, serves as an ideal instrument to deliver therapeutic
genes to the tracheobronchial tree-even to small airways and alveoli that
are beyond the reach of the bronchoscope. In addition, bronchoscopic gene
delivery has the capacity disorders, as delivery
305
306
Kruklitis and Sterman
of marker and therapeutic genes via the airways has been successfully
demonstrated to transduce the pulmonary vascular endothelium [2,3]. Gene
delivery for pleural disorders has been accomplished to date via tube
thoracostomy or thoracoscopy rather than via bronchoscopy [4].
II. Modes of Delivery
Once a therapeutic gene and a target cell have been identified, the next step
is to choose the most suitable method for gene delivery. Unless one is
delivering "naked" DNA to the target cell, most gene transfer protocols
involve the use of a vector, which is defined as the means and/or mechanism
by which the desired gene is transferred to the target cell. Gene therapy
vectors may be transferred into the target cells ex vivo, after which the
modified cells are returned to the recipient [5,6], or, alternatively, in vivo via
various routes (e.g., intravenous, intracavitary, intratumoral) to the target
cells of an individual [7,8].
For pulmonary gene transfer, the delivery of vectors in vivo via the
airway would be a feasible and minimally invasive approach. Because of the
complex branching structure of the airways, it is not currently feasible to use
ex vivo gene transfer methods to target the pulmonary epithelium. Given the
versatility of flexible bronchoscopy for a variety of diagnostic and
therapeutic intrapulmonary procedures, it is the ideal instrument for
facilitating gene transfer to the tracheobronchial tree.
Currently, there are three modes of delivering gene therapy vectors via
the bronchoscope: (I) direct instillation of soluble vector, (2)
of vector via specially designed spray catheter, and (3) direct injection of
vector via bronchoscopic needle (Table I). These three modes are used for
different applications (Table 2).
A. Direct Instillation
Soluble gene therapy vectors can be easily delivered through the working
channel of a flexible bronchoscope in a manner analogous to a bronchial
washing or lavage except that the vector solution is instilled without
subsequent removal with suction. This method involves the direct
instillation of viral vectors diluted in a liquid transport medium (i.e. saline)
through the working channel of a flexible bronchoscope. This approach
facilitates directed delivery of vectors into a specific segment or lobe.
Isolation of the targeted segment with a balloon-tipped catheter prior to
instillation can mitigate the risk of spillover into adjacent regions of the
lung. In theory, therapeutic genes can be administered to the entire
tracheobronchial tree using a series of directed vector instillations. After
Bronchoscopic-Mediated Gene Therapy 307
Table 1 Methods of Delivering Endobronchial Gene Therapy via Bronchoscopy
Delivery mode
Instillation
Injection
Advantages
Bypasses upper
respi ra tory tract
Delivery to entire
tracheobronchial tree
possible
Bypasses
tracheobronchial
defense
Highly localized delivery
Disadvantages
Imprecise delivery
Poor efficacy due to
defense barriers
Limited area of vector
administration
bronchoscopic instillation, viral vectors preferentially distribute into the
distal airways (small bronchi, terminal bronchioles) and alveolar spaces [9].
For these reasons, direct instillation may be best utilized in the treatment of
diffuse, parenchymal lung diseases, such as idiopathic pulmonary fibrosis or
bronchoalveolar carcinoma.
B. Spray Catheter
For other respiratory disorders such as cystic fibrosis or asthma, the more
proximal conducting airways are the targeted site, and therefore direct
bronchoscopic instillation is not the ideal delivery method. With the goal of
achieving more efficient delivery of viral vectors to the conducting airways,
transbronchoscopic sprayer devices have been developed (MicroSprayer,
Table 2 Potential Applications of Endobronchial Gene Therapy
Local deli very
Endobronchial tumor
Granula tion tissue/stricture/web
Tracheoesophogeal fistula
Devascularized surgical anastamosis
Diffuse delivery
Cystic fibrosis
Alpha-I-antitrypsin deficiency
Obstructive airway disease (asthma/chronic obstructive pulmonary disease)
Carcinoma in situ, carcinogenic field effects
Diffuse brochioalveolar cell carcinoma
Copynghted Material
308 Kruklitis and Sterman
Penn Century, Philadelphia, PA; Model PW-6p, Olympus, Lake Success,
NY) [10-12]. These sprayers, which are introduced through the working
channel of a flexible bronchoscope, aerosolize the vector-containing solution
into relatively large particles (10-25 flg). Solution particles of this size
preferentially deposit vectors to the large conducting airways, thus
minimizing distal delivery [13] (Fig. I).
Spray delivery of gene therapy vectors could provide a means of
targeting the larger, central airways, avoiding deposition in the smaller
airways and alveoli, which is more likely with nebulizers that generate small
aerosol particles typically of 1-5 ~ in diameter.
Although nebulized aerosolization of gene therapy vectors may
provide a simple, noninvasive means of delivery to the lung parenchyma,
there are important concerns regarding the intact nature and viability of
gene therapy vectors postnebulization. Some nebulizers may damage vectors
via the baffles used to break up the fluid during aerosol generation or
secondary to the addition of heat during ultrasonic nebulization [14].
I-- 3-4 em ---t
Figure 1 Spray device for controlled delivery of viral vectors to the conducting
airways of the tracheobronchial tree. The spray device is inserted through the
working channel of the Ilexible bronchoscope. A nozzle on the end of the spray
device generates aerosolized droplets such that virus is deposited uniformly on the
airway epithelium over 3-4cm. (From ReI'. 13.)
Bronchoscopic-Medimed Gene Therapy 309
In addition, nonbronchoscopic aerosol delivery typically necessitates
usage of greater amounts of gene therapy vector, as a significant proportion
never reaches the lower airways. Rather, this additional undelivered vector
is deposited in the upper airway (nasopharynx, oropharynx), and can
contribute to both local and systemic toxicity. In contrast, bronchoscopic
delivery of therapeutic genes facilitates direct administration into the
tracheobronchial tree, thus bypassing the upper airway completely. This
minimizes the total amount of vector needed resulting in significant
economic and safety benefits.
Unfortunately, there have been significant obstacles to successful
target cell gene transfer encountered with both bronchoscopic instillation
and aerosolization of soluble vector. Gene transfer with soluble vectors has
been quite inefficient; a problem felt mostly to be due to the innate defense
mechanisms of the tracheobronchial tree (reviewed in Ref. [15]). Specifically,
the mucous barrier and mucociliary clearance are able to inhibit
transduction of bronchial epithelial cells and submucosal glands. To be
successful, most gene therapy approaches req uire transduction of a
significant proportion of target cells. Currently, this is not possible with
instillation or aerosolization of soluble vectors; however, a variety of
approaches are being tested to overcome these barriers (see Sec. V).
C. Direct Injection
Direct bronchoscopic needle II1Jection of gene transfer vectors is an ideal
approach for the treatment of focal endobronchial lesions. Endobronchial
malignancy is the primary indication for such an approach; however, other
discrete lesions could also be targeted with this technique (see Table 2). One
advantage of this method is that it bypasses the potent host defense
mechanisms of the airway mucosa. Furthennore, direct intralesional
injection may confine vector delivery to the region of the injection,
minimizing systemic spread of the vector, thereby mitigating the potential
toxicities of gene therapy. Unfortunately, larger endobronchial tumors may
require multiple injections of vector, potentially increasing procedure time,
patient discomfort, and risk of complications.
III. Clinical Trials
The list of potential applications for gene therapy in the treatment of a
variety of pulmonary disorders continues to expand (reviewed in Ref. [I]).
Investigators are developing gene therapies to be delivered to the pulmonary
parenchyma, airways, vasculature, and pleural space. Several studies have
already been completed in which
t
th.erap,eutic. genes have been delivered
vopyngn ecTtvlarenal
310 Kruk/itis and Sterman
bronchoscopically to the airways (Table 3). Initial success, although often
limited, has spawned several interesting new studies. Two diseases have
received most of the attention and effort: cystic fibrosis (CF) and non-small
cell lung cancer (NSCLC).
A. Cystic Fibrosis
Cystic fibrosis is a common genetic disease associated with abnormalities in
a transmembrane chloride channel, which is known as the cystic fibrosis
transmembrane conductance regulator (CFTR). These abnormalities are the
result of one of multiple mutations in the CFTR gene (reviewed in Ref. [16]).
The mutated CFTR gene prevents the normal movement of fluid and
electrolytes across various cellular membranes. In the lungs, this results in
hyperviscous secretions, impairment of mucous clearance, and weakening of
local host defenses [17,18]. Together these abnormalities ultimately are
responsible for the severe pulmonary dysfunction that ensues. In fact,
upward of 90% of CF patients eventually succumb to respiratory
complications [19].
Since the realization that CFTR gene was the abnormal gene
responsible for CF, many investigators have worked to replace the mutant
gene with a wild-type (wt) copy. Early in vitro studies indicated that
expression of a wt CFTR gene in as few as 6-10% of cells could normalize
chloride transport [20,21]. Therefore, it seemed that gene therapy for CF
would be feasible.
In humans, three vector systems, adenovirus (Ad), adeno-associated
virus (AAV), and lipid/DNA complexes (liposomes), have been utilized to
deliver wt CFTR to the respiratory epithelium. To date seven clinical trials
using an adenoviral vector carrying the CFTR transgene have been
reported. Of these, four trials have delivered the adenoviral vector
bronchoscopically. The first trial to instill an adenovirus encoding wt
CFTR gene (Ad.CFTR) bronchoscopically into the lower airways was
performed by Crystal and colleagues [22]. In this study Ad.CFTR was
administered in a dose-escalating fashion to both the nasal and respiratory
epithelium in four patients. Soluble adenovirus (5-20 mL) was directly
instilled via the working channel of a flexible bronchoscope into the airways
of a specified lobe. One patient, who received the highest dose level of
2 x 10
9
plaque =forming units (pfu), developed fevers, hypotension, and
pulmonary infiltrates. This patient completely recovered within 30 days of
treatment. Otherwise this gene transfer trial was well tolerated. In a number
of the posttreatment specimens, in some but not all of the patients, there was
evidence of successful gene transfer and wt CFTR gene expression [22].
Clinical Trials Utilizing Bronchoscopically Delivered Gene Therapy Vectors
129] Adene-
associuted
virus
(19)'
[44J Retrovirus
pS3
(4)'
(58.59J Adenovirus
Ad.LaeZ
(10)
145] Adenovirus
Ad.p53
(9)"
[46] Adenovirus
Ad.p53
(5)'
5 X lOll rrll Not estimated None None
(Stngle)
IOQpfu Moderatc Nonc
(SIngle) staining bleeding and
fever
IOlopru Vector detected None None
at higher dose"
10" pfu Vector detecteJ Fever, chills None
(lip 10 6 in most patIents
monthly Some increase 111 1'5:\
swinlng
Table 3
Disease
Cystic
Cystic fibrosis
()
o
:J!,ySI1C fibrosis
<g.
<ii
Q.
fibrosis
Q)
<ii
::l.
9Endobronchial
NSCLC
Endobronchi;'ll
NSCLC
Endobronchial
NSCLC
Endobronchial
NSCLC
Ref
122J
[23J
124.25]
Vector
(no. of

Adenovirus
(4)"
Adenovirus
(11)
Adenovirus
(20)'
Highest dose
(no. of doses)
2 X 10"
2.1 X 10')
:!.5 x 10....
NR
Gene transfer
DNA. RNA. and protein
RNA detected 3
days
postadministration in
6{11 patients
DNA and RNA detected
preferelltially in
noncpithC'lial cells
NR
Toxicity
1 patient developed fever.
hypotension. and
infiltrate at the highest
dose
2 of J patients at the
highest dose developed
focal infiltrates in
treatment area
Constitutional
symploJ11s-5 patients.
cough-5 patients.
inf,ltrate-4 patients
NR
Concurrent
treatment
Clinical
response
Tumor reg-ression-3
patients
Temporary tumor
regression-6 pltllcnts
Transient local control--l
p.llients
PR-8 patients
SD-12 palienb
Progrcssion-S patlenl:-
b:l
C;
<::>
'"
r,
.g

l::l
CJ
'"
.g
"e
w
-..
.....
Table 3 Continued
Vector
(no. of Highest dose
Disease Ref. patients) (no. of doses) Gene transfer Toxicity
[48) AdenO\ lrUS lOll pfu Intratumoral Fever. chills
NSCLC Ad.p53 (up to p53 mRNA
(7)' 6 doses) inH%
()
Endobronchial ISO) Adeno'irus 7.5 x 10
11
Intratumoral p53 mRNA Fever. flulike
0
<::l NSCLC Ad p53 panicles In 68% symptoms
(5)' (slllgJe)
':
Endobronchial [51] Adenovlrlls 3 x 10
12
Vector detected Fever. chills
CD
Q.
NSCLC Ad.p53 particles in majority
s::
( 19) (three doses)
Q)
Bronchloalveolur [53] Adenovirus 2 x 10
12
NR Well tolerated;
CD
cell carcinoma Ad p53 particles 1 palient with

(14) grade 4
pulmonary
lo'{;city
Concurrent
treatment
isplatm
Clsplalin and vinorelbmc
or carboplatin and
paclitaxel
Radiation therapy-60 Gy
over
6 weeks
None
Clllllcal
response
PR-2 patients
SD-17 patients
ProgresslOn........-4 patients
Not cvalllabk-2 patients
Eqlllv,:Jlcnt local and
surVival responses in
chemotherapy vs
chemotherapy +p5J
CRfPR-12 palients
SD-J patients
Progression-2 patients
Not cvaluable-2 patients
Symptomatic
improvcment........-4
p<.Iticnts
ImproveJ
p.lticnts
w
--
I",
Beta-gal. beta-galactosidase: CR. complcte response: OLCO. carbon monoxide diffusion in the lung; NR. not reported; NSCLC. non small cell lung carcinoma; PR, p"rl1al rC$ponse: SO, stable
disease
"Ad.CFTR was administered mlO the nasal epithelium and a speclfk'd lobe of the lung.
bSixlecn addltlom.ll patients treated by aerosolized delivery or vmll vector.
additional patients were treated by transthoraCiC needle injecllon of viral vector,
dSix additional pauents were treated by tr..lnsthor<lcie needle injection of viral vector.
eTwenty-thrce patients were treated by transthoracic nccdh.: inJectIon of viral vector.
fSeventcen addItional patients were treated by transthoracic needle IIlJeclloll of Viral vector.
gTwenlY addlllonal patients were by transthoracic needle injection of viral vector.
><:
....,
s::
0;;.
I:::>
VJ
::::
Bronchoscopic- Mediated Gene Therapy 313
Subsequently, investigators at the University of Pennsylvania Medical
Center delivered a less immunogenic, replication-deficient adenoviral vector
deleted in the early genes EI and E4 carrying the wt CFTR gene via
bronchoscopic instillation into the conducting airways of II patients with
CF [23]. The vector was preferentially instilled bronchoscopically into sites
without significant bronchiectasis or mucous plugging as determined by
computed tomographic (CT) scan and bronchoscopic examination. The
investigators were able to demonstrate successful wt CFTR gene transfer
into bronchial epithelial cells. This approach, however, proved to be very
inefficient, as CFTR transfection was detected in < I % of bronchial
epithelial cells at 4 days and was not detectable at 42 days. Patients at all
dose levels commonly complained of flulike symptoms such as fatigue,
headache, nausea, and myalgias. Dose-limiting toxicity was noted above
I x lOll viral particles as patients at this level developed high fevers and
persistent pulmonary infiltrates [23].
An additional 20 patients underwent bronchoscopic instillation of
Ad.CFTR in another phase I study designed to assess the effectiveness of
gene transfer [24]. In most patients, this treatment was well tolerated;
however, in several patients, a cough developed with mild hemoptysis in a
single case. Additionally, radiographic infiltrates were observed in four
patients following vector administration. No significant oxyhemoglobin
desaturations were noted in these patients. Of note, the investigators found
that the transfection efficiency was quite low. Furthermore, greater than
95% of successfully transduced cells did not appear to be of epithelial origin.
Overall, less than I% of the airway epithelial cells were effectively
transfected at most doses [25].
AAV has also been used as a vector to deliver a wt CFTR gene to the
bronchial epithelium. The theoretical advantage of AAV over adenoviral
vectors is the prolonged expression of transgenes [26,27] while minimizing
the inflammatory response [28]. A phase I study of AAV.CFTR gene
delivery conducted in CF patients at the University of Florida involved
vector delivery by bronchoscopic instillation into the conducting airways of
the lung [29]. To date, there has been minimal pulmonary inflammation
reported with bronchoscopic instillation of this vector [14]. More recently, a
second trial has been conducted in which AAV.CFTR was delivered to the
lungs of 12 patients with mild CF [30]. This study demonstrated that
aerosolized AAV.CFTR is safe with minimal side effects. Viral DNA was
detectable in bronchial epithelium for up to 30 days following treatment;
however, there was no evidence to support RNA expression, and thus no
evidence of successful transduction.
LiposomaljDNA complexes have also been studied as delivery vectors
in human clinical trials, in patients with CF.
314
Liposome/wt CFTR gene complexes have also been aerosolized into the
lungs of CF patients with some success in transduction of the bronchial
epithelium [31]. Liposomal vectors, however, have yet to be delivered to
humans using bronchoscopic techniques. Aerosol delivery of liposomal/
DNA complexes has resulted in demonstrable fevers, myalgias, and
arthragias in several patients. These side effects were ultimately attributed
to the development of an immunological inflammatory response against the
Iiposomal/DNA complex. The nature and degree of this inflammatory
response might significantly inhibit the successful transfection of airway
epithelium related to repeated delivery of lipid/DNA complexes into the
airways [31].
In summary, the human clinical trials to date have demonstrated
successful bronchoscopic CFTR gene transfer to the tracheobronchial
epithelium in some studies, albeit with low-level gene expression. Overall
transduction efficiency of target cells in the bronchial epithelium will require
dramatic improvement if gene therapy for CF is to become a therapeutic
reality.
Much work and effort is also being invested in preclinical trials and
experimentation in CF. One novel idea involves delivery of a wt CFTR in
utero before the CF phenotype can engender lung destruction. Injections of
retroviral, adenoviral, and AAV vectors into the amniotic fluid have all been
utilized successfully to deliver reporter genes to the pulmonary epithelium in
animals [32,33]. Fetoscopic bronchoscopy, or in utero bronchoscopy, has
been used to deliver the beta-galactosidase reporter gene to the lungs of fetal
sheep via intra tracheal instillation of an adenoviral vector (Fig. 2) [34]. No
acute toxicity was seen in the ovine fetuses. Marker gene expression was
greatest in the pulmonary parenchyma, particularly the type II pneumo-
cytes, extending to the pleural surface. In this study, however, there was no
evidence of gene transfer to the large conducting airways [34]. Nonetheless,
this minimally invasive approach might one day be used specifically to target
the lungs of a human fetus for delivery of therapeutic genes, particularly for
congenital pulmonary diseases such as (XI-antitrypsin deficiency and
surfactant protein B deficiency.
B. Non-Small Cell Lung Carcinoma
Besides cystic fibrosis, NSCLC represents the other major pulmonary
disease category in which bronchoscopic gene transfer technologies have
been tested in human clinical trials (reviewed in Ref. [35]). The focus to date
has been on the treatment of endobronchial NSCLC and bronchioloalveolar
cell carcinoma (BAC). The primary antitumor bronchoscopic gene therapy
315
Tracheal
occlusion
balloon
Adenoviral
particles:
Ad.CMZ.LacZ
'=4'
Operative ports for instrumentation Camera

f
'
};"-
Fetoscope Operative sheath
(c)
(b)
"\
Fetoscope
/ Trocar
(a)
Figure 2 Fetoscopic bronchoscopy. (a) A 1.2-0101 bronchoscope (fetoscope) is
introduced through a transuterine trocar and operative sheath. (b) The operative
fetoscope consists of a bronchoscope and an operative sheath. The operative sheath
has two ports-one for balloon deployment and the other for virus injection. (c) An
inflated balloon completely occludes the proximal trachea. The virus is then instilled
into the airways via a catheter placed distal to the occlusive balloon. (From Ref.
34.)
strategies that have been tested include injection of tumor suppressor genes
and immunostimulatory genes.
Replacement of Tumor Suppressor Genes
The first strategy involves replacement of mutated or absent tumor
suppressor genes. The rationale behind this approach is that correction of
the molecular aberrancy could reverse the malignant phenotype and thereby
restore normal cellular growth and differentiation. The majority of work to
date has focused on the replacement of the p53 gene, which is a tumor
suppressor gene that is responsible, among other cellular actions, for
detecting and repairing damaged DNA [36]. The wt p53 gene, often referred
to as the "guardian of the genome," has multiple tumor inhibitory
properties. Mutation or loss of p53 predisposes to malignant transforma-
tion, with at least 40-70% various mutations
316
and/or deletions in the p53 gene [36-39]. This finding has led to the strategy
of delivering the wt p53 gene bronchoscopically to NSCLC tumors using
gene therapy vectors.
Replacement of the wt p53 gene has resulted in tumor regression both
in vitro and in animal models (reviewed in Ref. [40]). This antitumor effect is
felt to be due to the inhibition of tumor cell growth and the stimulation of
tumor cell apoptosis that occurs with restoration of the wt p53 gene.
Furthermore, there is some evidence of a mild bystander effect; that is, the
killing of neighboring, nongenetically modified tumor cells. The exact
mechanisms responsible for this bystander effect with p53 gene therapy
remain to be fully elucidated [41]; however, possibilities include release of
angiogenesis inhibition [42], activation of the Fas/Fas ligand system [43],
and induction of antitumoral immunological responses.
To date, seven wt p53 gene transfer clinical trials for NSCLC have
been reported in the medical literature. In these trials, viral vectors encoding
the wt p53 gene were delivered by bronchoscopically directed intratumoral
injection into endobronchial lesions. In the first trial, a retroviral vector was
used to deliver the wt p53 gene [44]. Patients, who had previously failed
conventional chemotherapy, were treated with either bronchoscopic
injection (four patients) or transthoracic needle injection (five patients) of
vector into endobronchial or parenchymal tumors, respectively. Overall this
treatment was well tolerated with minimal side effects, and there was
evidence supporting successful gene transfer. More importantly, there was
also tumor regression at the site of injection in three of the patients treated
with bronchoscopic p53 gene delivery; the fourth patient was unable to
complete the treatment protocol owing to complications with anesthesia.
Unfortunately, all of the patients ultimately died of progressive disease at
distant untreated sites [44].
Owing to the difficulties involved in the production of large quantities
of retroviral vectors, all subsequent trials have delivered the p53 transgene
using adenoviral vectors that are easier to produce. In general, endobron-
chial introduction of adenoviral vectors has been well tolerated and
associated with minimal side effects, including a typical fiulike syndrome
(mild fevers, chills, and fatigue). Both single and multiple injection
schedules, in which the adenoviral vector was administered monthly for
up to 6 months, have been assessed. Theoretically, multiple injections should
increase the degree and duration of transgene expression [45,46]. Using both
dose schedules, there was evidence of successful gene transfer into the target
tumor cells; however, the use of multiple doses was associated with
induction of increased titers of antiadenoviral antibodies [47]. On the whole,
p53 gene expression seemed directly to correlate with the dose of vector. As
wi th the prior retroviral trial, there was no evidence of antitumor effects at
317
distan t sites. There were, however, local responses seen in one-third to one-
half of patients at the treatment site, some of which were quite remarkable.
For instance, one patient with a left upper lobe (LUL) endobronchial
malignancy, which was refractory to treatment with conventional
chemotherapy, radiotherapy, and laser therapy, had near-complete resolu-
tion of the lesion following injection of Ad.wtp53.
In order to improve upon these results further, and assist in control of
the distant noninjected tumor, conventional chemotherapy was studied in
combination with bronchoscopic p53 gene delivery [48]. With this approach,
patients who were treated with cisplatin followed by bronchoscopic injection
of Ad.p53 fared somewhat better. In particular, one of five patients treated
with Ad.p53 alone achieved relief of endobronchial obstruction compared
with five of seven patients who were treated with cisplatin and Ad.p53 [49].
These findings are the basis of an ongoing clinical trial assessing the
combination of cisplatin and Ad.p53.
In another trial, patients with advanced NSCLC were randomized to
receive standard chemotherapy with either cisplatin and vinorelbine or
carboplatin and paclitaxel in combination with endobronchial injection of
Ad.p53 vector [50]. Patients enrolled in this trial had not previously received
any chemotherapy. Although there was evidence of successful intratumoral
gene transfer, there was no overall difference in the response rates of lesions
treated with chemotherapy plus Ad.p53 (52%) versus chemotherapy alone
(48%). Additionally, there was no difference in overall survival. There were
response differences seen in those patients receiving the "less effective"
chemotherapy regimen (cisplatin a-nd vinorelbine). In these patients, the
addition of Ad.p53 gene transfer to chemotherapy significantly improved
tumor response rates compared with the chemotherapy regimen alone [50].
In the most recently reported trial, external beam radiation therapy
was combined with bronchoscopically delivered intratumoral Ad.p53
therapy in patients with advanced local-regional disease without evidence
of metastasis [5 l]. Patients enrolled in this study were felt to be ineligible for
conventional chemoradiotherapy or surgical resection because of significant
comorbidities, including poor pulmonary function. Patients received
intratumoral injection of Ad.p53 on days I, 18, and 32 in combination
with external beam ionizing radiation. Overall this approach was well
tolerated with minimal toxicity. Sixty percent of patients had either a partial
or complete response at the site of treatment 3 months following the
completion of therapy. Furthermore, biopsy of the treatment site at 3
months revealed no evidence of residual tumor in 63% of patients. This
response rate is significantly higher than historical controls that were treated
with radiation alone. These impressive results are attributed to the ability of
p53 to increase tumor cells to ionizing
3i8 Kruklitis and Sterman
radiation [52]. Unfortunately, many patients in follow-up were found to
have developed metastatic tumor. This supports the notion that this
treatment is effective at providing local-regional but not distant control of
tumor. Further phase III trials of intratumoral Ad.p53 injection are planned
to determine whether this improvement in local-regional control translates
into either a survival or quality of life benefit. Additionally, patients in this
study will be randomized to receive standard radiation or chemoradiation in
an attempt to improve upon the control of distant disease.
Overall, the use of bronchoscopically delivered intratumoral p53 gene
therapy for the treatment of endobronchial lung cancer is well tolerated,
safe, and relatively effective at achieving local-regional control. This is
important, as local-regional disease is often responsible for considerable
morbidity, and control of this disease often translates into improved
survival. There is no evidence, however, to suggest that this therapy is
effective against nontransduced tumor cells at distant sites.
C. Bronchoalveolar Cell Carcinoma
Bronchoscopic delivery of Ad.p53 has also been studied in patients with
advanced, refractory bronchioloalveolar cell carcinoma (BAC) [53]. Lobar
or multifocal (BACs) represent a subset of lung adenocarcinoma that
typically is resistant to conventional chemotherapy and radiation therapy
[54-56]. In theory, BAC is an ideal tumor to target for bronchoscopic gene
therapy approaches on the basis of the physical location of the tumor as a
thin layer of cells lining the alveoli and distal bronchioles.
For this reason, the Eastern Cooperative Oncology Group conducted
a phase I trial (ECOG E6597) in which Ad.p53 was delivered to the airways
by repeated bronchoalveolar lavage (BAL). This was a dose-escalation study
in which patients received up to 14 separate administrations of Ad.p53 to
their affected lobes. Overall, BAL-mediated delivery of Ad.p53 in BAC
patients was well tolerated, although one patient did develop grade 4
pulmonary toxicity related to the treatment. Of the nine evaluable patients,
four patients had symptomatic improvement, four patients had increases in
their diffusion capacity, and two patient had pathological responses
confirmed on bronchoscopic lung biopsy [53]. Further work is ongoing to
assess the effectiveness of this therapeutic approach both alone and in
combination with chemotherapy.
D. Immunogene Therapy
Another approach for treating thoracic malignancy has been the delivery of
therapeutic genes designed to initiate and/or upregulate local and systemic
antitumor immune responses. A variety of methods have been utilized
Bronchoscopic-Mediated Gene Therapy 3/9
experimentally with these goals in mind (reviewed in Ref. [57]). Several years
ago, French investigators conducted a phase I clinical trial of bronchoscopic
injection of a replication incompetent adenovirus containing the Escherichia
coli gene lacZ (which encodes for the enzyme beta-galactosidase [beta-gal])
into endobronchial tumors [58,59]. This was trial was designed as a
feasibility and safety study of endobronchial gene transfer in preparation for
a subsequent study of endobronchial cytokine gene delivery. Ten patients
were treated in this dose-escalation trial that was. designed to assess the
safety and transduction efficiency of the reporter transgene (beta-gal).
Overall this therapy was well tolerated; however, fever and minor bleeding
from the injection site were noted. There was confirmation of beta-gal
expression in the tumor cells and induction of both antiadenoviral and anti-
beta-gal immune responses. Somewhat surprisingly, localized antitumor
responses were observed in some patients. This antitumor effect was felt to
be due to the generation of an immune response directed against the tumor
cells expressing the foreign beta-gal protein, which likely occurred because
of the immunoreactivity of the unmethylated CPG motifs in the prokaryotic
DNA. Several investigators are currently researching viral vectors that
deliver transgenes that are specifically designed to more effectively stimulate
specific aspects of antitumor immunity [60].
IV. Preclinical Trials
In addition to CF and NSCLC, in which there are active laboratory and
clinical gene therapy research endeavors, there are also several diseases with
exciting in vivo results of bronchoscopic gene transfer that have not yet
made it to the clinic. These preclinical studies will ultimately lead to human
clinical trials for many of these disorders. Brief descriptions of a variety of
pulmonary disorders in which bronchoscopic gene delivery will likely be
employed follow.
Alpha-I-antitrypsin (0:1 A1) deficiency, an autosomal recessive disease
characterized by panacinar emphysema and hepatic cirrhosis, results from a
deficiency of the antiprotease o:lAT (reviewed in Ref. [61]). In theory,
normalization of the o:lAT levels should slow or prevent disease
progression. In fact, levels of o:lAT as low as II J..lm have been shown to
be sufficient to protect the lungs from excessive protease activity. Several
attempts have been made to replace the o:lAT gene in the airway and
alveolar epithelium. Unfortunately, gene delivery in animal models, either
administered systemically or by endobronchial instillation, has only resulted
in transient low-level increases in 0: I AT levels [62,63]. Nonetheless, attempts
to improve the MtNfJJ!i9TeSsion of 0: I AT continue.
320
Gene therapy for asthma has also been proposed. Delivery of
therapeutic genes in animal models of asthma has yielded some insight
into the mechanisms responsible for bronchoconstriction as well as
prospects for novel therapies. Specifically, delivery of Th I-type cytokines,
such as interluikin-12 (IL-12) or interferon gamma, has been shown to
decrease airway reactivity in animal models [64-66]. Whether or not gene
therapy will ever be utilized to treat patients with asthma is unclear,
especially given the relative safety and efficacy of standard asthma
therapeutics. Perhaps gene therapy will one day find a role as an adjunctive
treatment in patients with especially severe steroid-dependent disease. It is
clear, however, if asthma gene therapy ultimately enters into clinical
practice, bronchoscopic instillation will be a potential, and probable, mode
of gene delivery.
Investigators have also begun delivering antioxidant gene therapy
designed to treat a variety of pulmonary conditions such as adult respiratory
distress syndrome and radiation pneumonitis. In one example, Danel and
colleagues delivered adenoviral vectors encoding superoxide dismutase
(SODM) intratracheally in a mouse model of oxidative lung injury [67]. In
another example, Epperly and coworkers have shown that intratracheal
delivery of SODM reduced fibrosis and alveolitis in gamma-irradiated mice
[68]. Finally, surfactant gene therapy is also being investigated for the
treatment of neonatal respiratory distress syndrome and other related
surfactant deficiency states [69,70].
The list of potential applications in which gene therapy is delivered to
the airways is seemingly endless. Investigators are assessing immunosup-
pressive gene therapy to prevent rejection in lung transplant recipients [71].
Additionally, interstitial lung diseases are potential targets using antifibrotic
gene therapy [72,73]. Antimicrobial gene therapy is also being developed to
aide the immune system in eliminating and destroying a variety of pathogens
including bacteria [74-77], mycobacteria [78], viruses [79,80], fungi [81], and
Pneumocystis carinii [82]. Although many of these studies are only in the
preliminary phases of preclinical evaluation, it is clear that if these
treatments are fully developed, they will likely require bronchoscopic
administration.
V. Conclusion
Although bronchoscopic gene delivery will undoubtedly play an important
role in the therapeutic armamentarium of pulmonary diseases in the future,
much work continues on the currently available delivery vectors to make
them safer and more efficacious. In fact, inefficient transduction and vector-
Bronchoscopic-Medialed Gene Therapy
321
related toxicities are the major obstacles for gene therapy to the airways.
Human clinical trial experience, which has accumulated over the past
decade, generally supports the safety of this technology. Nonetheless, the
development of acute lung injury, noted in some of the patients in the cystic
fibrosis trials, is a troublesome occurrence. This morbidity was attributed to
the development of an inflammatory response due to the distal delivery of
adenoviral vectors into the alveoli. As a result, much work is aimed at
developing novel delivery methodologies in which gene therapy is
specifically targeted to the large conducting airways. Examples include
sprayer devices and endobronchial stents capable of gene delivery. In
common, both technologies require bronchoscopy for gene delivery.
Additionally, gene delivery is targeted to the large conducting airways,
and thus in theory should eliminate the inflammation that occurs with distal
delivery of vector. Although not yet specifically tested, it is hopeful that
these innovations will help improve the safety of gene therapy in the
aIrways.
Investigators are also developing methodologies to improve transduc-
tion efficiency, as inefficient transduction has contributed to the Iimittd
clinical effectiveness of gene therapy in the airways. In addition to
optimizing gene delivery vectors, other approaches are being used to
improve transduction. For example, administration of adenoviral vectors
along with surfactant [83,84] or after DNAse treatment [85,86] can enhance
gene expression. Other strategies include the use of calcium chelators, such
as EGTA, to disrupt the tight junctions or polycations that aide in
the internalization of various vectors Both strategies allow
increased vector access to target cells and thus presumably will enhance
transduction.
Another approach is to increase the contact time between the airway
epithelium and the gene delivery vector, as short contact times are felt to
contribute to inefficient transduction [93]. Thixotropic solutions, such as
carboxymethyl cellulose, can reversibly impair mucociliary clearance [94].
This results in an increased contact time between vectors to target cells and
improves transduction efficiency. Stent-mediated gene delivery is also likely
to increase contact time dramatically, and hopefully tranduction efficiency
as well [95]. Real-time bronchoscopic detection of gene transfer will
certainly assist in the minimally-invasive evaluation of gene transfer efficacy
and duration. Experimental methods for this technology involve broncho-
scopic codelivery of the florescent reporter gene green fluorescent protein
(GFP) within a vector containing the therapeutic gene. Repeat broncho-
scopy with incorporation of fluorescent filters into an existing fiberoptic
endoscopic system can facilitate detection of GFP in situ within accessible
tracheobronchial used such a device to
detect expression of GFP from adeno-associated viral and adenoviral
vectors within the bronchial epithelium of New Zealand white rabbits [96].
Ultimately, improved gene transfer efficacy will be essential in order to
realize the full therapeutic potential of bronchoscocpic gene therapy.
Furthermore, in addition to increasing clinical efficacy, enhanced transduc-
tion [90-92] will also likely result in improved safety, as less virus would be
required. Together these advances should help advance bronchoscopic
delivery of various gene therapies into clinical practice.
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69. Korst RJ, Bewig B, Crystal RG. In vitro and in vivo transfer and expression of
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17
Whole Lung Lavage
BENJAMIN D. MEDOFF
Massachusetts General Hospital
I. Introduction
SELIM M. ARCASOY
Columbia University College of
Physicians and Surgeons
Whole lung lavage (WLL) was developed as a therapeutic technique for
patients suffering from pulmonary alveolar proteinosis (PAP), a disease
characterized by massive accumulation of phospholipids and proteins within
the alveolar spaces. Based on the idea of "washing out the lung" [I], WLL
was Llsed successfully for a patient suffering with PAP [2J several years after
the original description of this disease [3]. Subsequent publications
documented dramatic improvements in both symptoms and physiological
parameters after WLL in other patients with PAP. Now over 30 years after
the first use of WLL, the general clinical experience with this technique
suggests that it can dramatically influence the course of PAP.
Although PAP is an uncommon disease, it is encountered frequently
enough that most tertiary care centers should have the capability to perform
WLL. The technique is somewhat complicated and potentially hazardous;
therefore, its use is recommended only in centers with experienced
personnel. The use of a dedicated team of physician specialists, cardiothor-
acic anesthesiologists, nurses, and respiratory or physical therapists is
important for the safe application of WLL. This chapter will review multiple
aspects of this procedure, focLising on the theory of its application and its
physiological effects. Copyrighted Material
329
330 Medoff and Arcasoy
The history of WLL begins with the original description of PAP by Rosen
and colleagues in 1958 [3]. They described 27 patients with a .previously
unrecognized disorder remarkable for " ... the filling of the alveoli with a
PAS-positive proteinaceous material, rich in lipid." Shortly after this
description, Ramirez-Rivera et al. described a technique of segmental
flooding of the lung to wash out the accumulated material [4]. The technique
required placement of a transtracheal catheter followed by an infusion of
100 mL of saline four times daily for 2-3 weeks. After each infusion, the
patient would cough for 45-70 min to bring up 30-40 mL of material. The
technique was difficult to tolerate, but it resulted in radiographic clearing as
well as physiological improvement in patients who underwent the procedure.
Ramirez-Rivera's third patient with PAP refused to undergo the
difficult procedure. He reportedly told his physician to "wash it all out at one
time, Doc" [I]. Two noted physiologists at Johns Hopkins felt that the
procedure would be quite dangerous; however, the patient could not be
deterred, and after approval by the Johns Hopkins Hospital human rights
committee, the patient underwent WLL. The procedure was done with topical
anesthesia. A earlens double-lumen endotracheal tube was placed, and the
lungs were ventilated with 100% oxygen to remove nitrogen. One of the lungs
was then allowed to degas by not ventilating it for 5 min. The investigators
then lavaged this lung once with I L of warm normal saline mixed with
heparin and acetylcysteine and recovered about 450 mL of thick creamy fluid.
The patient reportedly felt well enough to eat breakfast (against physician's
orders) only 2 hI' after the procedure. This experience was published in the
Annals of Internal Medicine in 1966. Shortly after, the investigators modified
the procedure to allow repeated lavages during one procedure.
Following the initial description of the procedure by Ramirez-Rivera,
other investigators began to use and refine the procedure. Wasserman and
colleagues were the first to use general anesthesia for the procedure,
allowing them to do a more thorough lavage of the lung. They reported
using over 20 L of fluid to wash a lung until the effluent was clear; this often
required procedure more than 3 hr in length [5]. Wasserman also showed
that there was no benefit to using normal saline with heparin and
acetylcysteine over normal saline alone [6]. Further refinements reported
over the years incl ude the addi lion of chest physical therapy during the
filling and washout (7], the creation of dedicated WLL teams [8], ventilation
during the instillation [9], and washing both lungs sequentially during one
procedure [10].
Several large case series have now been published that clearly
document profound improvement in oxygenation and lung function
Whole Lung Lavage
331
following WLL [11,12]. More importantly, mortality from PAP seems to be
reduced with the use of WLL [13]. Although a definitive study of the efficacy
of WLL has not been done, nor does it seem likely that it will be done, the
history of this procedure is notable for the incredible impact it has had on
the prognosis of PAP.
III. Theory of Application
Whole lung lavage has been used for disorders remarkable for accumulation
of endogenous or exogenous material in the alveoli and/or airways, which
may lead to symptoms and abnormalities in gas exchange either directly or
due to inflammation and other parenchymal changes. The theory behind
using WLL for such disorders stems from the potential benefit of physically
removing this material both to improve gas exchange and to prevent
deleterious host responses that may lead to inflammation and fibrosis.
During WLL, the infused lavage fluid fills the airways and alveoli, mixing
with the contents of these structures. Depending on the characteristics of the
accumulated material, a certain amount will be suspended in the lavage fluid
and carried out of the lung when the fluid is drained. Repeated flooding of
the airways and alveoli will literally wash away the lumenal contents of these
structures, which include pathological material as well as normal surfactants
and proteins produced by the lung [14].
Numerous disorders in the lung cause alveolar filling with a variety of
different materials derived from endogenous or exogenous sources. These
materials directly cause gas exchange abnormalities and symptoms by
reducing the surface area of the alveolocapillary membrane and obstructing
the flow of gas into and out of alveoli. The following factors need to be
considered to determine whether WLL may be beneficial in a particular
pulmonary disorder:
I. Presence of significant coexisting histopathological change in the
pulmonary interstitium and vasculature. Frequently, the accumula-
tion of material in the lumenal surfaces of the lung is accompanied
by changes in the pulmonary interstitium and vasculature. These
changes include inflammation, edema, fibrosis, and thrombus
formation. In diseases characterized by significant coexisting
changes outside of the alveolar and airway lumen WLL is likely
to be ineffective at correcting the physiological abnormalities.
2. Rate of reaccumulation of the substance removed by WLL. In
disorders that cause rapid reaccumulation of the removed
material, WLL of such disorders are
cystic fibrosis and asthma, in which removed mucous plugs may
return within hours of lavage therapy.
3. Effectiveness of WLL in removing the accumulated substance.
Factors such as solubility, viscosity, density, and particle size will
all have an impact on the ability of WLL to suspend the material
and wash it out of the lung. Viscous nonsoluble material will be
the hardest to remove with WLL. This difficulty may be
compounded if the material blocks off airways, thus limiting
areas of the lung to instillation of lavage fluid. Moreover, host
factors such as lung compliance and airway caliber are also
important, since they may limit the ability of lavage fluid to reach
all areas of the lung.
IV. Disease Pathogenesis and Effectiveness of WLL
Whole lung lavage is typically used to treat PAP. This disease is notable for
the accumulation ofa PAS material in the alveoli (Fig. I). The
material is largely composed of phospholipids and proteins and has the
effect of blocking the diffusion of oxygen and carbon dioxide across the
alveolocapillary membrane. There have been several recent advances in our
understanding of this rare disease. The discovery that mice deficient in the
granulocyte-macrophage colony-stimulating factor (GM-CSF). protein or its
receptor develop a disease similar to PAP has focused attention on this
important protein. Analysis of blood samples from patients with PAP has
demonstrated antibodies to GM-CSF in a number of cases. In addition, the
treatment of PAP with GM-CSF has shown some benefits in a small case
series [15]. It is currently felt that alveolar macrophages require GM-CSF to
effectively clear surfactant with the absence of GM-CSF leading to
abnormal alveolar accumulation of surfactant [16].
In PAP, WLL clearly removes the excess phospholipids and proteins
in the alveoli [14]. Since there is usually very little pathological change
outside of the alveolar lumen, the removal of intra-alveolar material usually
corrects the gas exchange abnormalities seen in this disease. In other
disorders, the effectiveness of lavage will depend on a number of factors, as
discussed in the previous section, including the degree that the alveolar or
airway filling is the cause of symptoms and physiological impairment, the
rate of reaccumulation of the material, and the effectiveness of lavage at
removing the material.
The pneumoconioses are a group of diseases characterized by an
inflammatory reaction and fibrosis following mineral dust exposure. Large
amounts of dust and inflammatory cells filled with dust particles are seen in
Whole Lung Lavage
333
(a)
Figure 1 (a) PAS stain of lung biopsy from a patient with PAP. Note the PAS
positive grallular material within the alveoli. The alveolar spaces are completely filled
with amorphous material. (b) H&E stain of a cytology smear from a patient with
PAP. (c) Electron micrograph of macrophage from a bronchoalveolar lavage in a
patient with PAP. Note the numerous swirled lamellar bodies in the cell cytoplasm
and external to the cell. (Photographs courtesy of Eugene Mark, MD, Department of
Pathology, Massachusetts General Hospital, Boston MA.)
the alveolar spaces and interstitium. In addition, silica exposure can
stimulate a condition that looks like PAP on pathological examination. The
observed alveolar filling pattern has fueled speculations that WLL could
remove dust particles and inflammatory cells, improving lung function and
preventing further damage. Case series have documented some clearance of
inflammatory cells and particulate debris by WLL; however, the overall
efficacy of WLL in relieving symptoms and improving lung disease in these
disorders is questionable.
Lipoid pneumonia results frol11 the aspiration of oil products. It has
been seen most commonly in people who ingest oils (usually mineral or cod
oil) medicinally. Depending on the type of oil aspirated, there may be a
spectrum of findings from bland accumulation of the material to an intense
inflammatory reaction with fibrosis. There are two case reports of WLL
being used to treat large In both cases, there was
334
Medoff anrj Arcasoy
(b)
Figure 1 Continued.
physiological and radiographic improvement after the procedure. The
investigators described large amounts of oil in the lavage drainage, implying
effective clearance of the aspirated material.
Other pulmonary disorders that have been treated with WLL include
alveolar microlithiasis [19,20], radioactive dust inhalation [21], cystic fibrosis
[22-24], and refractory asthma [25)6]. The data are limited to case series,
and the reported efficacy has been variable.
V. Indications and Contraindications
The most common and the only widely accepted indication for WLL is
symptomatic PAP. Given the variable course of this disease and the
complexity of the procedure, it is important that WLL is used in
appropriately selected patients. A list of accepted indications for WLL in
PAP is presented in Table I. Currently, this procedure is considered the
standard of care for PAP.
Whole Lung Lavage
335
(c)
Figure 1 Continued.
Given the success of WLL in patients with PAP, clinicians have tried
the procedure in other diseases that are also characterized by alveolar or
airway accumulation of material. A list of diseases for which WLL has been
used is shown in Table 2. The disorders are grouped by potential benefit.
The data supporting WLL therapy in these diseases are scarce and limited to
small series. Overall no strong recommendations can be made for this
procedure in disorders other than PAP.
Whole lung lavage is potentially a dangerous procedure. In addition to
the obvious strain it places on the respiratory system, WLL also presents a
major stress on the cardiovascular system (see Sec. VIII). Therefore, the lack
of an experienced team is an absolute contraindication to perform WLL. A
list of other contraindications for the procedure is provided in Table 3.
These contraindications are relative and mainly apply to the elective
performance of WLL in patients with significant but not life-threatening
symptoms. In patients who have severe hypoxemic respiratory failure due to
PAP, WLL may be lifesaving and should be considered despite the increased
risk of complications. Copyrighted Material
Table 1 Indications for WLL in PAP
Symptoms attributable to PAP
Dyspnea, severe cough, chest pain, and functional limitation in daily and
occupational activities in association with radiographic and pulmonary function
abnormalities
Hypoxemia at rest or on exertion (Pao2 < 65 mmHg)
Frequent lower respiratory tract infections in association with PAP
Opportunistic infections
Nocardia and mycobacterial infections
"Recommended after adequate antimicrobial therapy.
VI. Personnel and Equipment
The first and most important prerequisite to perform WLL is a dedicated
and experienced team. In most centers, the team will generally consist of a
pulmonologist to lead the procedure, an anesthesiologist with thoracic
surgery experience, one to two nurses, two respiratory or physical therapists,
and a scribe.
Team leader: This is usually a pulmonologist and occasionally a
thoracic surgeon. The team leader is responsible for checking the
position of the endotracheal double-lumen tube after placement.
The team leader also performs a waterseal test to confirm the
functional integrity of the bronchial cuff and lung separation (see
Sec. VII). In addition, the team leader determines the start and end
of each cycle of lavage and termination of the entire procedure
Table 2 Diseases That Have Been Treated with WLL
Likely beneficial:
PAP
Potentially beneficial:
Lipoid pneumonia
Of unclear benefit:
Pneumoconiosis
Alveolar microlithiasis
Radioactive dust inhalation
Cystic fibrosis
Refractory asthma
Whole Lung Lavage
Table 3 Contraindications to WLL
Hemodynamic instability
Recent myocardial infarction
RV failure
Pulmonary hypertension
Untreated pneumothorax
Underlying obstructive lung disease
Arrhythmia
Active pulmonary infection
337
based on the quality of lavage fluid return. Along with the
anesthesiologist, the team leader is also in charge of monitoring
the physiological response to the procedure, including hemody-
namics, cardiac rhythm, oxygenation, patient-ventilator interac-
tions, and observing frequently to detect spillage of lavage fluid into
the contralateral lung. The latter assessment requires careful
monitoring of the volume of lavage fluid instilled and drained.
Anesthesiologist: In addition to inducing and maintaining anesthesia,
the anesthesiologist has the crucial role of controlling the airway
and ensuring proper placement and maintenance of the double-
lumen endotracheal tube. This serves to prevent leakage of lavage
fluid into the contralateral lung. Ideally, the anesthesiologist should
be experienced with thoracic surgery and able to perform broncho-
scopy to assess tube placement and check for the presence of fluid
leakage. The anesthesiologist also assists in the monitoring of vital
signs and patient-ventilator interactions.
Assistant physician: An assistant physician is optional to help with
performance of WLL and monitoring of the patient.
Nurse: In addition to general support, the nurse should prepare the
prewarmed saline solution and other tools necessary for the
procedure.
Respiratory therapists or physical therapists: The therapists provide
manual chest percussion to the lung being lavaged according to the
WLL protocol.
Scribe: A nurse or another team member should be in charge of record
keeping. The following information should be recorded: timing of
each instillation and drainage, oxygen saturation, the volume of
saline instilled and returned with running totals at the end of each
cycle and any problems that afe during the procedure.
, Gopyng7irea IVlarenal
The equipment required is not complex and should be readily available
in every large hospital. Since the procedure is done under general anesthesia,
monitoring machinery, a ventilator, and anesthesia equipment are needed.
An operating room is usually used; however, a special procedure room can
be utilized if it can accommodate patients under general anesthesia. A
double-lumen endotracheal tube (Robertshaw style or equivalent) (Fig. 2) is
used to intubate the patient, and a pediatric fiberoptic bronchoscope is
needed to confirm tube placement. Fifteen to 30 L of isotonic saline, large
bore tubing (T-U-R Y set) for infusion, Y connectors, large-volume clear
drainage bottles, and multiple clamps are needed to set up the lavage
apparatus [27]. A device to heat bags of isotonic saline and maintain them at
37C is also required. Alternatively, an intravenous fluid warmer can be
used to warm the saline solution while being instilled. Emergency equipment
should be available to deal with potential complications. These include a
chest tube tray and Pleurovac, a defibrillator, and vasopressors. A complete
list of the necessary equipment is provided in Table 4.
Depending on the severity of illness of the patient, special monitoring
devices may also be required, including the use of an arterial catheter,
Figure 2 Photograph of a typical double-lumen endotracheal tube.
Whole Lung Lavage
339
pulmonary artery catheter, or transesophageal echocardiography [28]. The
most severely ill patients may be unable to tolerate the physiological stress
of a WLL in these patients, more extraordinary measures may need to be
considered. These measures include extracorporeal membrane oxygenation
[29], partial cardiopulmonary bypass [30], lobar lavage with fiberoptic
bronchoscopy [31], pulmonary artery occlusion [32], or hyperbaric oxygen
conditions [33]. The data supporting such extreme measures are limited to
isolated case reports, so there must be careful consideration of the risks
involved before undertaking WLL in these critically ill patients.
The cost of the procedure will largely depend on the cost of operating
the procedure room, and nursing support and physician fees. The necessary
Table 4 Equipment and Supplies for WLL
Anesthesia Positioning Lavage material Emergency
Vasopressors
Closed tube
thoraocostomy
tray and
Pleurovac
Defibrillator
15-30Lof
isotonic saline
Tubing for cuff-
seal test
Heavy-duty
tubing (T-U-R
Y set)
Intravenous fluid
warmer or other
warming
apparatus
Y connectors
Endotracheal tube
connector
4-5 clamps
Adjustable
intravenous
pole
15-30 large-
volume clear
drainage bottles
Tape measure
Flow sheet
Warming blanket
at 37C
CoPY/ iglited Matetial
Footboard
Beanbag
Pillows
Axillary roll
Large cushion
Stryker frame
(optional)
Ambu-bag
Double-lumen
endotracheal
tube
Standard
endotracheal
tube
Pediatric flexible
bronchoscope
Suction apparatus
340
Medoff and Arcasoy
materials are not particularly expensive, thus their impact on the cost of
WLL is very little.
VII. Technique
Whole lung lavage is usually performed in an operating room. The team and
necessary equipment are outlined in previous sections. Patients are generally
placed on the operating room table, although a Stryker frame has been used
in some centers to perform the lavage while patients are both supine and
prone [34]. One hundred percent oxygen is administered throughout the
procedure. Blood pressure, cardiac rhythm, oxygen saturation, and
temperature are monitored in all patients. A heating blanket is generally
used to maintain body temperature. Neuromuscular blockade is assessed
with a peripheral nerve stimulator. In severely ill patients, placement of an
arterial and/or pulmonary artery catheter may be necessary to measure Pao2
and monitor hemodynamic parameters. Anesthesia induction and neuro-
muscular blockade is followed by endotracheal intubation with a double-
lumen tube (Robertshaw-type left endobronchial tube or equivalent) to
achieve separation of lungs. This tube should be as large as the patient's
glottis can accommodate so that leakage of fluid due to inadequate cuff seal
does not occur. After placement of the double-lumen tube, both the
bronchial and tracheal cuffs are inflated. Correct tube position is checked by
auscultation and confirmed by fiberoptic bronchoscopy. Bronchoscopy
allows fine adjustment of the tube position with special emphasis on the
location of the bronchial cuff and distal end of the left endobronchial tube.
The bronchial cuff should be barely visible on the left below the main carina
(see Fig. 2), and the secondary carina between the left upper and lower lobes
should be seen distal to the end of the left endobronchial tube. Once tube
position is verified, the waterseaI test is used to determine functional
integrity of the bronchial cuff, which is crucial for adequate lung separation
[35]. In this test, a short segment of tubing that fits on each end of the
double-lumen tube is utilized. One end of this tubing is attached to one
lumen of the double-lumen tube while the other end is submerged under
sterile saline solution in a container. As the contralateral lung is ventilated
using airway pressures of 40-45 cm H
2
0, the end of the tubing under saline
is observed for bubbling. Initially, there may be some bubbling as the
inflated lung compresses the nonventilated lung, which is attached to the
tubing under saline. Bubbling should stop after several inflations provided
that there is adequate lung separation by the bronchial cuff. Continuous
bubbling indicates the presence of an air leak around the bronchial cuff and
a need to reposition the double-lumen tube, instill more air in the bronchial
Whole Lung Lavage
341
cuff, or replace the tube. The waterseal test is repeated on the other side
prior to the initiation of the procedure.
The first step is to degas the lung to be lavaged. Preoxygenation prior
to degassing is very important to ensure replacement of alveolar nitrogen
with oxygen. Residual nitrogen bubbles diminish the access of lavage fluid
to the alveolar space and the efficacy of WLL. After separation of the lungs
is confirmed, the lumen of the endotracheal tube that leads to the lung to be
lavaged is clamped proximally at the end of a tidal exhalation (at functional
residual capacity [FRC]). Adequate degassing is achieved in approximately
5-10 min. The WLL system is connected to the appropriate lumen of the
endotracheal tube distal to the clamp (Fig. 3). The patient is maintained by
ventilation of the nonlavaged lung. After degassing is completed, WLL is
initiated. A T-U-R Y set, intravenous tubing, and a Y connector are used
for instillation and drainage of the lavage fluid (Fig. 4). Isotonic saline
solution warmed to 37C is instilled by gravity from 30 to 35 cm height
above the patient's mid axillary line while the drainage section of tubing is
clamped. Instillation of saline with a higher gravitational pressure may lead
to injury to the lung with return of hemorrhagic fluid, spillage into the
contralateral lung, or hydropneumothorax and should be avoided. Once
saline flow slows down or ceases, the inflow section of the tubing is clamped
and the drainage section unclamped to allow the lung to be drained into a
large clear collection bottle by gravity. Depending on the size of the patient's
lungs, aliquots of 500-1500 mL of saline can be used in each cyclt;:. We find it
easier to use to a set volume of saline that the lung can accommodate (e.g.,
1000 mL) during each cycle. This can be determined easily during the first
two to three cycles of lavage and makes monitoring of fluid volumes much
easier. After the first one to two cycles of lavage, a respiratory therapist
performs manual chest percussions to enhance clearance of abnormal
surfactant accumulation [8]. The reason why we do not perform chest
percussions at the start is to make sure that the WLL system is functioning
adequately with no air leak and spillage of saline around the double-lumen
tube cuffs into the proximal trachea and the ventilated lung.
It is crucial to monitor fluid volumes closely to avoid complications,
such as hydropneumothorax or leakage into the contralateral lung. At the
end of each cycle, instilled and drained fluid volumes should be recorded and
added up. Typically, the fluid return after the first cycle of lavage is
approximately 500 mL less than the instilled volume owing to retention in the
residual volume of the lung. In subsequent lavage cycles, the instilled and
drained fluid volumes should be similar and within 100-150 mL of each other;
a large discrepancy should prompt an investigation. Additionally, the lavage
system should be constantly observed for the appearance of air bubbles in
drained fluid or the ventilated side;
342
Medoff and Arcasoy
Figure 3 Photograph of double-lumen endotracheal tube hooked up to ventilator
and lavage setup. White arrows show ventilation, black arrows demonstrate flow of
the lavage fluid.
both of which indicate a leak around the bronchial cuff. If spillage is
suspected, the procedure should temporarily be stopped, the lavaged lung
should be drained completely, and the ventilated lung suctioned. Broncho-
scopy needs to be performed to check the position of the tube.
The lavage effluent from the initial cycles is typically opaque with a
large amount of sediment and gradually clears during subsequent cycles
Whole Lung Lavage
343
Figure 4 Picture of a typical setup for whole lung lavage. Arrows indicate flow of
lavage fluid. In this photograph, a clamp has been placed on the side used to drain
the lung during the filling phase of the lavage.
(Fig. 5). The patient's position is changed to partial right and left lateral
decubitus with the use of pillows to enhance clearing; we do not use a
Stryker frame because of the risk of endotracheal tube dislodgement and
small potential benefit. The procedure is continued until no further clearing
occurs; this usually requires the use of 15-30 L of saline. At the end of the
procedure, the lavaged lung is drained by gravity as much as possible and
both lungs are suctioned thoroughly. Double lung ventilation is then started
and maintained until the patient is ready for extubation. In our experience,
almost all patients can be extubated in the operating room and placed on
100% oxygen via a nonrebreather mask, which is weaned as tolerated in the
recovery unit. A chest radiograph is obtained to exclude pneumothorax or
fluid aspiration into the contralateral lung. The contralateral lung is usually
lavaged on the next day or after several days. Sequential WLL of both lungs
in one session has been reported as well and seems to be well tolerated [10].
The complications of WLL include hypoxemia, leakage of fluid into
the nonlavaged lung, bronchospasm, hydropneumothorax, fever, pneumo-
nia, and adverse effects of endotracheal intubation, such as sore throat and
change in voice.
VIII. Physiological Changes During WLL
Filling of the lung with saline causes profound effects on the cardiopul-
monary physiology. An understanding of these effects is important for
patient safety during the procedure. Although there are a multitude of
complicated physiological changes induced by WLL, they can be grouped
into effects on gas exchange, lung mechanics, and hemodynamics.
A. Effects on Gas Exchange
WLL starts with degassing one lung as described above. This leads to a slow
absorption of alveolar oxygen over minutes until the lung becomes
atelectatic and creates a large area of shunt, which may result in profound
hypoxemia in some patients. Although hypoxic vasoconstriction occurs to a
certain extent to help correct impaired gas exchange, there will always be
some shunting of blood through the degassed lung. The subsequent effects
of WLL on gas exchange depend on the phase of the procedure. As saline is
infused into the lung, the alveoli expand. The density and hydrostatic
pressure of the fluid infused compresses the alveolar vessels decreasing blood
flow to the filled lung. This effect actually improves V/Q matching, and
patients will generally demonstrate improved oxygenation at the end of each
filling phase [36]. As the lung is emptied of fluid at the end of the lavage
cycle, the blood flow will shift back to the lavaged lung thus worsening V/Q
Whole Lung Lavage
(a)
345
Figure 5 (a) Photograph of a lavage bottle several hours after whole lung lavage.
Notice the large amount of dense material that settles to the bottom of the bottle. (b)
Photograph of the first bag of lavage drainage compared to the last bag of drainage
after a 14-L lavage.
346
Medoff and Arcasoy
(b)
Figure 5 Continued.
matching and oxygenation. Measures that can limit hypoxemia during WLL
include placing the ventilated lung dependent (down), thereby increasing its
blood flow by gravitational effects, and occluding blood flow to the
degassed lung with a pulmonary artery balloon catheter during the drainage
phase [32]. Carbon dioxide exchange will depend on the alveolar ventilation
of the nonlavaged lung. Great care should be taken to ensure adequate
ventilation of this lung during WLL. When the procedure is finished, the
lung is not only degassed but void of much of its surfactant and partially
filled with residual lavage fluid (usually 200-400 mL of lavage is never fully
drained out of the lung). As the lung is reinflated and ventilated, there is a
tendency toward atelectasis due to surfactant deficiency and areas of
alveolar flooding. This leads to low V/Q units and hypoxemia after the
procedure. Fortunately, these effects rapidly resolve as the accumulated
lavage fluid is absorbed and the lung replace its lost surfactant [II]. There
are also recent data to suggest that alveolar fluid clearance is enhanced in
patients with PAP after WLL; potentially explaining why these patients may
better tolerate the procedure than those with other disorders [37].
B. Effects on Lung Mechanics
The mechanical changes in the lung induced by WLL largely result from
removing surfactant and the air-fluid interface in the alveoli. Saline-filled
Whole Lung Lavage
.....:::: - ~
~ l e t
// '/
Pressure
347
Figure 6 Pressure volume curve of an air-filled lung (solid line) compared to a saline-
filled lung (dotted line). Arrows indicate inspiration (black) and expiration (white).
lungs do not demonstrate hysteresis and are relatively compliant (Fig. 6) [38]
so filling of the lung is usually not a problem. Once the lavage fluid is
removed, the lung remains surfactant deficient for a period of hours. This
leads to reduced lung compliance and a tendency for the lung to collapse
because of the increased alveolar surface tension. All these factors make the
lung harder to expand and harder to ventilate. The decreased lung
compliance seen postlavage rapidly corrects within hours as the residual
fluid is reabsorbed and surfactant is restored (Fig. 7) [11].
c. Effects on Hemodynamics
The hemodynamic effects of WLL result from the complex interactions
between the heart and lungs. Studies have clearly demonstrated a reduction
in cardiac output and an increase in pulmonary artery pressures during the
filling phase of the lavage (Fig. 8) [36]. These effects of WLL largely result
from changes in intrathoracic pressure and lung volume. Fluid filling of the
lung increases pleural pressure which is reflected to the heart. This will
displace blood from the thorax, reducing the preload of the heart while
simultaneously increasing the back pressure to venous return. The overall
effect is a reduction in the cardiac output. In addition to these pressure
effects, changes in lung volume as well as the distention of alveoli from
lavage fluid tend to reduce alyeotlaJi _"essel. size, increasing pulmonary
c..;opyngn eu lVIarenal
LEFT LUNG LAVAGE
POSTLAVAGE TIME (min)
348
1.2
1.0
0.8
>
\2, 0.6
j
u
0.4
0.2
0
0
PRE-
30 60
PRE-
Medoff and Arcasoy
RIGHT LUNG LAVAGE
POSTLAVAGE TIME (min)
Figure 7 Changes in compliance of lavaged lungs over time. Notice the gradual
return of normal compliance in the lavaged lung over about I hr. (From Ref. II.)
AIRWAY
FLUID IN
LEFT LUNG
(em
3
)
PRESSURE
(mmHg)
VENOUS
ADMIXTURE
(%)
CARDIAC
OUTPUT
(Umin)
2000 l
1000
o

30
20
JO
o
.
40
I I I I I I I

TIME AFTER DEGASSING (min)
Figure 8 Hemodynamic changes in a patient during whole lung lavage. The
changes are correlated to the volume of fluid in the lung. (From Ref. 36.)
Whole Lung Lavage
349
vascular resistance. Moreover, alveolar collapse after the drainage
procedure can also increase vascular resistance by allowing the extra-
alveolar vessels to narrow. This increase in pulmonary vascular resistance
results in right ventricular (RV) strain, which is another potential cause of
reduced cardiac output and hypotension associated with the procedure. RV
dilation occurs after establishing one lung ventilation and then dilates
further during the initial phase of WLL as the lung is filled with saline [28].
As the lung continues to fill with saline, the right ventricular size decreases,
which is likely due to a reduction in venous return (Fig. 9). Patients at risk
can be monitored by transesophageal echocardiography (TEE) [28] to judge
when the lung filling should be stopped based on when the RV area falls to
certain values. Finally, hemodynamic changes may occur owing to the
release of catecholamines from the stress of the procedure, which can lead to
arrhythmias and myocardial infarction, especially in patients who have
important medical comorbidities and are critically ill.
Although the physiological effects ofWLL are complex, in practice the
usual end result is mild to moderate hypoxemia and transient hypotension.
Shortly after the procedure, most of the detrimental effects of WLL start to
resolve. It is the critically ill patient with already compromised gas exchange,
lung mechanics, .and/or hemodynamics who represents the greatest
EDA
o ESA
__ FAC
en en V> en
bJl >0 >0
v; 0
v; 0
"
0. 0.
t- O' 0
(',
'>,
E E
0.
., .,
E
en V>
.,
v; 0
t:
C')
"
cI5
Stage
45
40
35
30 1;'n
8
25 5
20
15
10
5
0
9
8
7
6
"I:
5
t.)
4
3
2
1
0
., .,
en V>
bJl on
0
v;
"
"
C')
""
> >
.9 .9
);i
8
cI5
.S:
V>
v;
Figure 9 Changes in right ventricular dynamics during whole lung lavage. The
right ventricular area initially increased with the start of the lavage but then
decreased with further filling. EDA, end diastolIc area; ESA, end systolIc area; FAC,
fractional area change. (FroncB!*rtgHted Material
challenge to practitioners. Unconventional measures, such as extracorporeal
membrane oxygenation [29], partial cardiopulmonary bypass [30], lobar
lavage with fiberoptic bronchoscopy [31], pulmonary artery occlusion [32],
or hyperbaric oxygen conditions [33], may be considered in critically ill
patients, but these remain experimental.
IX. Physiological Changes After WLL
Although WLL can have detrimental effects on gas exchange, lung function,
and hemodynamics during the procedure and shortly after, it results in long-
term beneficial effects on these parameters. Case series have clearly
documented improvements in oxygenation, forced vital capacity (FVC),
total lung capacity (TLC), and diffusion of carbon monoxide in the lung
(DLCO) in patients with PAP who have undergone WLL. The changes in
these physiological parameters correlate well with symptomatic and
radiographic improvements observed in these patients [11-13]. Figure 10
demonstrates these changes noted in several of the published case series.
In addition to improvements in measures of lung function, one study
has demonstrated an improvement in macrophage function in patients with
PAP after lavage. In this study, alveolar macrophages were isolated both
before and after WLL. Macrophage migration in response to bacterial
products was decreased prelavage with correction to better than normal 6
days after lung lavage [39]. These data suggest that the removal of
phospholipids by WLL could have effects on local immune function in the
lung and may potentially correct the increased tendency for pneumonia seen
in patients with PAP.
X. Evidence-Based Literature Review
Given that WLL is usually applied to patients suffering from unusual and
complex disorders, it is not surprising that there have been no randomized
trials of this procedure. Data from case series strongly support a beneficial
effect for WLL in PAP in terms of both physiological improvement and
reduction in mortality. Nevertheless, since 20-25% of patients have
spontaneous recovery without treatment, conclusive benefits of WLL in
PAP can only be proven by a controlled randomized trial.
The case series by Selecky et al. documented a significant increase in
FVC, TLC, and DLCO in II patients studied. The DLCO was increased by
over 50% in all patients who underwent WLL. Oxygenation was also
significantly improved at rest and with exercise up to 30 mmHg in some
cases [11]. Rogers et al. examined the results in 14 patients and also
Whole Lung Lavage
351
DLCO MVV VC
120
/
mmHg
100
100
t
90
80
9
80
::..---
70
::;
60
60
50
p < .02 p < .00,
P< .OS p <.001 p <.on I
40
L----J L----J l.--.-J l.--.-J
40
L--J
A B A B A B A B A B
140
Precent of
predicted normal
TLC
Figure 10 Changes in TLC, YC, MYY, DLCO, and Pa02 after whole lung lavage.
TLC, total lung capacity; YC, vital capacity; MVY, maximal voluntary ventilation;
DLCO, diffusion capacity of carbon monoxide; Pa02, partial pressure of O
2
in
arterial blood. (From Ref 13.)
documented significant increases in oxygenation at rest (mean of 57-
69 mm Hg, P < .01), oxygenation with exercise (mean 50-68 mmHg,
P<.OOI), DLCO (mean of 13.6-17.3, P<.OOI), and a significant decrease
in shunt fraction (mean 20-11 %, P < .001) [12]. A relatively large case series
from the Mayo Clinic involved 34 patients, 21 of whom underwent WLL.
These investigators documented statistically significant improvements in
TLC (mean 76-83% predicted), FVC (mean 79-87% predicted), DLCO
(mean 52-79% predicted), and Pa02 (mean 63-78 mmHg). Even considering
the 25% spontaneous resolution rate, these data strongly support a
physiological benefit from WLL in PAP.
Improvements in mortality from WLL have also been based on case
series and retrospective reviews. Before the use of WLL, case series have
shown that PAP is a progressive disease in approximately 50% of cases with
an overall mortality rate of 30-32% [3,40]. With the use of WLL, reported
mortality rates have been as low as 0% in some series [13]. The general
consensus among experts is that WLL in PAP reduces the mortality from
the disease.
A small case series has examined the effects of WLL in pneumoco-
niosis. This study reportecLon the effects_ of WLL in 25 coal miners. In this
Malenal
group of patients, WLL decreased the frequency of dyspnea, but there was
no change in measures of lung function [41]. Two other reports with a total
of three patients revealed some clearance of particulate matter from the
lung, with one patient demonstrating symptomatic improvement. There was
no change in the overall lung function of the patients; however, two of the
three patients had only mild disease at baseline [42,43].
There are two case reports of WLL used to treat large oil aspirations
[17,18]. In both cases, there was physiological and radiographic improve-
ment after the procedure. The investigators described large amounts of oil in
the lavage drainage, implying effective clearance of the aspirated material.
XI. Conclusion
Whole lung lavage is a procedure largely used to treat one rare disease, PAP.
It is extremely effective in removing the excessive intra-alveolar proteins and
phospholipids that accumulate in this disease, and the literature suggests
both a significant physiological and mortality benefit of WLL. Based on
available data, the only accepted indication for WLL at the present time is
symptomatic PAP. The effectiveness of this procedure in diseases other than
PAP is questionable.
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18
FRANZ STANZEL and KARL HAUSSINGER
Asklepios Fachkliniken MQnchen-Gauting
Munich, Germany
Bronchoscopy plays a dominant role for diagnosing centrally located lung
cancer. Lung cancer is the most common cause of cancer death in men in
Germany and both men and women in North America. Despite technical
progress in diagnostic and therapeutic techniques, prognosis is still poor.
Because most patients present with symptoms and in a late stage of the
disease, less than 15% of all patients diagnosed with lung cancer survive
their disease [I]. The only patients who achieve long-term survival are those
with resectable early-stage disease [2]. Unfortunately, these patients only
constitute a minority of the lung cancer population [3]. Diagnosis of the
early stages is much more difficult, as the patients are commonly
asymptomatic.
Carcinogenesis is a multistep process that evolves over a considerable
amount of time. The process from early changes of metaplasia through
various stages of dysplasia to severe dysplasia is estimated to take 3-4 years
[4,5]. Severe dysplasia can proceed to carcinoma in situ (CIS) in a time span
of as little as 6 months [4,5] and to invasive cancer in 2-10 years [6]. This
P
rovides a window of time for early c1etecliQn of/lung cancer [7]. These early
CopynyTltea Matena
355
356
Stanzet and Hdussinger
lesions are important to detect, because approximately 10% of moderate
dysplasias and 40-83% of severe dysplasias will progress to invasive cancer
[8-10].
In addition, 50-60% of the squamous cell carcinomas develop in the
central airways [II], which can be reached with the bronchoscope. However,
the majority of these early-stage cancers, even when centrally located, are
missed by conventional white light (WL) bronchoscopy. Bronchoscopic
detection of dysplasia and CIS has identified to only 30% of the total
number of cancers [12]. Why does the detection rate of these early lesions
remain so low? The lesions are usually quite small, only a few cell layers
thick [13], and have an intraepithelial growth pattern [14]. Lam [15]
measured such lesions in 19 patients using a grid. Twenty-eight mild
dysplasias, 9 moderate or severe dysplasias, and 1 CIS were included. Of
these, 55% were smaller than 1.5 mm in size and 45% ranged from 1.5 to
3.0 mm. The largest was a CIS of 3 mm size. Typically, WL bronchoscopy
demonstrates no or only subtle changes which are difficult to differentiate
from nonspecific inflammatory changes. Cases of discrete spur thickening,
subtle mucosal irregularity, minor vessel dilatation, localized edema, or
distorted light reflex [14] can easily be missed even by experienced
bronchoscopists. Flat or superficially spreading lesions of 20 mm or more
in surface diameter and nodular or polypoid lesions of more than 2 mm in
size are usually visible. However, fla t, superficial lesions smaller than 5mm
in diameter are usually invisible by WL bronchoscopy [16,17]. Approxi-
mately 75% of CIS lesions are of the superficial or flat type. Therefore, it is
not surprising that the majority will be missed using conventional WL
bronchoscopy. The methods for localization of early malignant lesions by
systematic segmental washings or brushings are time consuming, cumber-
some, and costly and are often performed under general anesthesia [18-22].
The high rate of multiple epithelial abnormalities in heavy smokers
provides an important reason to detect early malignant changes. Serial
sectioning of the bronchial tree in patients who died from lung cancer found
synchronous CIS in 13.2-22.5% of the patients [23,24]. In resected material
from patients who were operated on and in sectioned material from patients
who died from lung cancer, metaplasias, dysplasias, and CIS were found in
the bronchial tissue in up to 30% of the patients [25]. For resected non-small
cell lung cancer, the rate of metachronous second primary lung cancers has
been reported to be 3.6-4.2% per year [26,27]. A study in Italy found that
among patients with completely resected stage I lung cancer. 17% developed
a second primary tumor during a median follow-up period of 3 years [28].
This suggests the need to detect synchronous or metachronous second
primaries at an early stage [29] either in the preoperative staging process or
in the follow-up program.
357
An exciting discovery has been that early malignant lesions can be
detected without the use of drugs by employing the principle of
autofluorescence [30-32]. The fluorescent properties of various tissues can
differentiate between normal and premalignant or malignant areas. When
illuminated by violet or blue light (wavelength 400-440 nm), normal
bronchial mucosa emits fluorescent light with a major peak in the green
range of about 520 nm and a minor peak in the red range of about 630 nm
[30]. As demonstrated in Figure I, changes such as CIS or severe dysplasia
lead to an almost 10-fold reduction of total fluorescence and a change of the
green/red ratio from 5:3 to 2:3 [30,33]. Several systems have been developed
to detect this phenomenon, and these have been used clinically since the late
1990s.
The first device was the lung imaging fluorescence endoscopy (or laser
induced fluorescence endoscopy, LIFE) system developed by the British
Columbia Cancer Agency staff together with Xillix Technologies, Vancou-
ver, Canada [29). In 1996, the U.S. Food and Drug Administration (FDA)
approved the use of the LIFE system [34). A helium-cadmium-Iaser
generates a monochromatic blue light of 442 nm as excitation light. The
optical bundle of a conventional bronchoscope (Olympus BF 200) is used
for illumination and detection of the autoftuorescent light. In addition to
WL bronchoscopy, LIFE bronchoscopy is performed similar to a routine
800 700 600
Wavelength (nm)
.green
500
o
400
50
100
150
200
250
ReI. intensity
Figure 1 A case of carcinoma in situ demonstrating decrease of autofluorescence.
Note the change in the
358 Stanzel and Hdussinger
flexible bronchoscopic procedure with local anesthesia (14,15]. It adds
approximately an extra 5-15 mins [14,35] to conventional bronchoscopy.
The other two systems use a xenon lamp to produce nonmonochro-
matic blue light of high intensity. The Karl Storz Company, Tuttlingen,
Germany, the Laser Research Laboratories of the Urological Clinic of
Munich-Grosshadern, and the Clinic for Pneumology of the Asklepios
Fachkliniken Munich-Gauting, Gauting, Germany, developed and tested
the D-Light AF System as the first nonlaser system [7,36]. The system can be
used with both fiberscopes and rigid telescopes designed with a special filter
integrated into the eyepiece. The bronchoscopist can look directly through
the bronchoscope or the image can be viewed with a CCD camera and a
monitor. The Pentax Company of Japan has developed and marketed the
SAFE 1000 System (Pentax Asahi Optical, Tokyo, Japan) [37]. It has
similarities to both of the systems described above.
Drug-induced fluorescence was originally used for tumor detection
[38]. The use of a photosensitizer prior to bronchoscopy is required.
Photofrin, a hematoporphyrin derivative, is most frequently used. However,
it has the disadvantages of high cost and potentially dangerous side effects
including a prolonged photosensi tization of the skin [39-41]. Investigators
continue to search for agents with greater tumor selectivity and less skin
sensitization [40,42-45]. Delta-aminolevulinic acid (ALA) has been applied
orally or topically by inhalation [40,46,47]. Initial results indicate a high
sensitivity for detection of dysplasia and CIS [46]. However, bronchial
deposition is highly variable among individuals, and there can be
nonspecific uptake of ALA by inflamed mucosa. Attempts to achieve a
reproducible and homogeneous deposition in the central airways by
specially designed inhalers have not sufficiently solved the problem [46].
The most important disadvantage of drug-induced fluorescence broncho-
scopy is that it requires initial preparation [7,40].
Pioneering observations on the phenomenon of distinct autofluorescent
characteristics of normal tissue and tumor tissue were reported by Sutro and
Burman [48] in 1933. Lipson [49] described the preferential retention of
hematoporphyrin derivatives by tumor tissue and the tumor-localizing
properties of this substance. Subsequently, various detection methods were
developed: drug-induced fluorescence [49] using different sensitizers and
autofluorescence [38] without the need of exogenous substances.
The bulk of research in the last several decades has focused on
hematoporphyrin derivative (HpD) or its partially purified form, dihema-
359
toporphyrin ether/ester (Photofrin) [49-51]. Porphyrin-induced fluorescence
is characterized by emission of red light when excited by violet light. The
main disadvantage of porphyrin-based fluorescence, however, is the risk of
skin photosensitivity [41,42]. To overcome this side effect, various experi-
mental fluorescence bronchoscopic systems were developed [38,52-60]
between 1979 and 1990. New systems employing an eximer-laser and the
low-dose Photofrin II-wavelength method were tested in the early 1990s
[58,60]. These systems, however, could not be validated clinically. Lam [61],
working with lower nonphototoxic doses of Photofrin, found no significant
advantage over autofluorescence alone. More recent research has focused on
substances characterized by higher tumor selectivity and minor skin
sensitization. Along with tetra(m-hydroxyphenyl)chlorine [44], phthalocya-
nines, and meso-tetra(4-carboxyphenyl)porphine, ALA and its esters are
promising substances. Even when employed in therapeutic doses, skin
photosensitization from these agents lasts only a few days [40]. Initial results
using ALA for fl uorescence bronchoscopy in lung cancer are hopeful
[46,62].
The finding that bronchial dysplasia or CIS can be detected without
using photosensitive drugs initiated a revolution in the field of diagnostic
bronchoscopy in the early 1990s [ ~ 32], leading to the development of the
three autofluorescence (AF) bronchoscopic systems mentioned above
[7,36,37,63-66]. Recent studies have focused on clinical evaluation of the
various systems [7,15,67-69].
At present, smoking is responsible for approximately 80% of lung cancer
cases [70]. Currently, one-half of new lung cancer cases develop in former
smokers [71]. Squamous cell carcinoma, especially, has been linked to
smoking. This tumor type develops in the upper layers of the bronchial
mucosa and preferentially in the central airways. Therefore, it is an ideal
target for fluorescence bronchoscopy. Other important risk factors for lung
cancer are age of the patient, exposure to asbestos, uranium, or radon, and
concomitant chronic obstructive pulmonary disease (COPD). According to
the criteria of the International Association of Study of Lung Cancer
(IASLC), the indications for fluorescence bronchoscopy are
Resected (or otherwise treated) lung cancer
Resected (or otherwise treated) head and neck cancer
Clinical or radiological suspicion of lung cancer
Suspicious cytological findings in sputum
Occupational eX"ffi&fffrirjhfe8W1aN!fllHum, or asbestos
360 Stanzel and Hdussinger
COPD
especially if the patient is 40 years of age or older and there is a smoking
history of at least 30 pack years.
Because of the high rate of synchronous tumors, all lung cancer
patients scheduled for resection should undergo fluorescence bronchoscopy
before surgery. Another indication for fluorescence bronchoscopy is the
assessment of the exact tumor extent [72], which is a special interest of
thoracic surgeons and interventional bronchoscopists.
Contraindications to autofluorescence bronchoscopy are similar to
those of conventional bronchoscopy. For drug-induced fluorescence
bronchoscopy, special contraindications unique to each drug must be
considered. Photofrin is contraindicated in patients with porphyria or
known allergies to porphyrins as is ALA. Liver disease is a relative
contraindication for the use of these drugs.
IV. Equipment
Fluorescence bronchoscopic systems include additional technical features in
addition to routine flexible and rigid bronchoscopic equipment. The
required ancillary equipment is available in most endoscopic units and
includes a white light source, a white light camera, and a color monitor. The
systems and their components are listed in Table I.
A. LIFE System
The LIFE system consists of a low-energy helium-cadmium laser as the
excitation light source, a dual-channel charge-coupled device (CCD) camera
system, and an intensifier board with a color monitor. The imaging control
console integrates a touch screen-operator interface, an image data
management system, a video recorder, and a video printer. The LIFE
system works with Olympus fiberbronchoscopes of series BF 20 and higher.
Currently, the system is no longer available. Xillix is working on a second-
generation system called Xillix Onco-LIFE.
B. D-Ught AF System
The main component of the Storz D-Light AF System is a xenon light
source used as both a white light and blue light source. The light source can
be used for thoracoscopy or other endoscopic examinations. and is not
limited only to fluorescence bronchoscopy. Both flexible bronchoscopes and
rigid bronchoscopes with integrated filters are available. The special filters
must be connected to the eyepiece of routine white light bronchoscopes or a
Table 1 Autofluorescence Systems, Components, Prices
Manufacturer
361
System
Components
Ancillaries
Price
Remarks
Xillix
LIFE
Laser light source
Camera system
Intensifier board
Imaging control
console
Video recorder
Video printer
Olympus
fiberscope
Video color
monitor
$250,000
Not available
anymore
LIFE follow-up
product
planned
Karl Storz
D-Light AF SCB
Xenon light
source (B)
Foot switcher (B)
Fluid light cable
(B)
Bronchofiberscope
AF (B)
Tricam SL-PDD
SCB controller
(V)
Tricam SL-PDD
camera (V)
Keyboard/title
generator (V)
SCB cables (V)
Video recorder
Video color
monitor
Telescopes
$46,000 (B)
$79,000 (V)
Pentax
SAFE 1000
Xenon light
source
Camera unit
Controller unit
Pentax fiberscope
Video color
monitor
Video recorder
$100,000'
B, basic set; Y, video set (induding basic set) .
Orticial German price, no price information of the U.S. market available.
Hopkins optical telescope when used for fluorescence bronchoscopy. Fluid
light cables optimize transmission of light from the source to the scope. For
drug-induced fluorescence, there is a special blue light mode, the so called
ALA mode, which is integrated into the D-Light AF System. The filter in
the eyepiece of the bronchoscope for drug-induced fluorescence differs from
those used in the AF detection mode. Its wavelength characteristics are
slightly different to that 445 nm).
362
Stal1Zef and Hdussinger
Two cameras are available for fluorescence bronchoscopy. The
Telecam SL and the Tricam SL are specially adjusted for fluorescence
examination. The newer versions have an integrated Storz Communication
Bus (SCB) (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany) for
synchronization of camera and light source. The video image is displayed on
a color monitor. Both are optional, as the system can work with the unaided
eye. Other ancillaries are a video recorder and a video printer.
C.
The Pentax SAFE 1000 System also employs a xenon lamp (LX-750AF).
Coupled onto a large articulated arm, the two-camera unit (SAFE 1000
Video Camera Box) must be connected to a Pentax fiberscope. The system
contains a fluorescence image video camera controller and a white light
video camera controller (GP-KS 162), enabling modification of brightness
and contrast. The white light and fluorescence images are displayed on a
color video monitor. The system is compatible with the fiberbronchoscopes
of the Pentax X series.
A. Autofluorescence
As demonstrated in Figure I, normal tissues illuminated by violet or blue light
display a significantly higher fluorescence intensity than dysplastic lesions or
CIS, especially for emissions in the green region of the spectrum [30]. There
are several explanations for the decrease in autofluorescence [3] and the
contrast between normal and tumor tissues. Changes occurring in the airway
wall as cancer develops include thickening of the epithelial cell layers, tumor
hyperemia, redox changes in the tumor matrix, and a reduced fluorophore
concentration [73,74]. It is known that the epithelial layer contributes less
than 5% to the overall detectable fluorescence [74,75], and that the bulk of the
fluorescence signal comes from the submucosa [3]. In dysplastic tissues and
CIS, there is an increase in the thickness of the epithelial layer. This results in
a limited penetration of the excitation light to the submucosa [74] and altered
transmission of the fluorescence light from the submucosa to the bronchial
surface [3]. A decrease in the extracellular matrix of the submucosa from
secretion of metalloproteins by preneoplastic or neoplastic tissues results in
reduced f1uorophore concentration and fluorescence [74,76].
Various chromophores in cells and tissue structures are known to emit
fluorescence. The excitation and fluorescence spectra of the dyes typically
show broad bandwidths [77,78]. Another explanation of the abnormal
fluorescence is that that the microvascular density is increased in dysplastic
363
lesions and CIS [79]. The larger blood volume increases the absorption of
the excitation blue light and the emitted autofluorescence light. Thus, the
fluorescence intensity of premalignant and malignant lesions decreases [3].
Tissue autofluorescence is very weak. No more than I% of the
excitation light is transformed to fluorescent light [80]. In addition, about
40% of the blue excitation light is reflected from the surface of the tissue and
masks the weak fluorescence light originating from the submucosa [81]. To
make this weak fluorescence visible, several technical problems had to be
solved. To evoke autofluorescence, an excitation light source in the near
ultraviolet or blue range (400--440 nm) was required [30-32]. The LIFE
system uses a helium-cadmium laser. The excitation light is a monochro-
matic blue (442 nm) light source coupled with a fiberoptic flexible
bronchoscope (Olympus BF 20). A CCD camera system with a green and
a red band-pass filter is connected to the optical lens of the bronchoscope,
picking up the fluorescent light transmitted back through the fiberscope. An
image intensifier board transforms the light intensity and green to red ratio
into a real-time video displayed on a high-resolution monitor. Normal
mucosa has a bright green appearance, whereas areas of reduced
fluorescence display brown-red discoloration [3].
Incoherent blue light used in the D-Light AF System produces
adequate emission from the above-mentioned fluorophores, but the light
penetrates to deeper layers of the tissue because of the blood absorption [7].
The blue reflected light and the red fluorescent light are not reduced by the
same amount as the green fluorescent light [61]. The color of malignant and
premalignant areas appears bluish red and darker. In contrast the color of
normal mucosa is dominated by pale green fluorescence light [7,66]. In
Figure 2, a moderate dysplasia in the right lower lobe bronchus is not clearly
visible in WL mode but detectable by AF mode.
The light source of the D-Light AF System is a high-power xenon
lamp of 400 W. Blue light from 380 to 460 nm filtered out from the light
source sdves as the excitation light (Fig. 3). Specially designed fluid cables
minimize the loss of light [7]. Most of the reflected excitation light must be
eliminated to achieve visibility of the fluorescence light. Therefore, a second
filter is integrated in the eyepiece of the bronchoscope, allowing only 1-2%
of blue but all of red and green light to pass to the camera or the eye (Fig. 3).
This additional blue component increases the overall light intensity and
serves as a reference to provide a color contrast [82].
The D-Light AF System is able to distinguish benign from malignant
tissue using criteria other than color. The image of the bronchial surface is
so brilliant that additional structural information such as the disturbance of
the delicate contour and lines of the mucosa by malignant growth are
detectable [7]. The term been coined to describe
364 Stanzef and Haussinger
Figure 2 Moderate dysplasia. Discrete spur thickening in the WL mode (left).
Bluish red area of reduced autofluorescence in AF mode (right). Note the additional
structural information in the AF mode.
this property of the system. As an option, a beam splitter can be added to
provide spectral detection of the specific autofluorescence [83] which allows
objective criteria to distinguish malignant from benign lesions. Freitag [33]
used a detection fiber in the biopsy channel of a fiberscope to display
spectrometry curves from the region of interest. Overlaying these curves
with the real-time video image on the monitor during examination gives a
second criterion for classifying lesions.
800
...
Observation filter
700
... Autofluorescence
....
"
,
\
.....
600
Wavelength (nm)
.....
;' ,
,
I
500
Excitation
light (blue)
:1
'.
: :
, .
: .
. .
.:-
.' .
... :
...... .
o
400
50
ReI. intensity
100
Figure 3 Excitation light. observation filter. and autofluorescence.
365
The SAFE 1000 System also uses a xenon lamp as light source. The
blue light differs from that of the Storz system and ranges from 420 to
450 nm [37]. During detection all the blue and red light is blocked by a
fluorescence filter which transmits only green light ranging from 490 to
590 nm. An image intensifier amplifies the signal. A video camera displays
the results on a color monitor. Normal mucosa emits autofluorescence
which appears green, whereas the emission from abnormal mucosa appears
dark owing to lack of autofluorescence [37].
B. Drug-Induced Fluorescence
Hematoporphyrin derivative (HpD) or its partially purified form, dihema-
toporphyrin ether/ester (Photofrin), which has been licensed by the FDA for
photodynamic therapy of lung cancer [41,84,85], and ALA are preferentially
retained in tumors [63]. During drug-induced fluorescence, violet light
excites HpD, Photofrin, and ALA, which emit red fluorescence [40,63].
Imaging devices can detect this light. Thus, tumors can be distinguished by
their more intense fluorescence [63]. Experimental fluorescence broncho-
scopy systems developed to use HpD or Photofrin have been limited by the
side effects of the drugs [39,41].
ALA was initially introduced for fluorescence diagnosis in the bladder
[86] and the brain [87]. It is a naturally occurring substance and a precursor
of heme. Exogenous administration leads to protoporphyrin IX accumula-
tion (PpIX). This substance acts as the photosensitizer. The D-Light AF
System can provide excitation for ALA-induced fluorescence from its blue
light band ranging from 380 to 435 nm [40]. Detection can be done either
directly or by spectroscopy. The suspicious areas show a pink color in
contrast to the blue color of the surrounding areas. As shown in Figure 4,
there is a peak three times higher in severe dysplasia than in normal
bronchial tissue in the band near 635 nm [36,40]. This leads to a high color
contrast between malignant and normal tissues [40,46].
'Experiments with cell cultures have indicated that an interval between
60 and 120 min after administration of ALA is optimal for examination
[40,88]. ALA was administered in a dose of 60-250 mg by inhalation or up
to 60 mg/kg body weight by oral application [40,46]. The PpIX levels
stabilize within a 24-hr period [40]. Thus, there is a very short interval of
hyperreactivity of the skin. Awadh reported using a LIFE system 4-5 hr
after oral administration of 25-60 mg/kg ALA when photodynamic therapy
was performed for precancerous lesions [47]. The LIFE examination was
carried out as described above. When blue light of 442 nm was used for
excitation, detection as fluorescence spots was observed with the LIFE
system. Copyrighted Material
366
Stanzel and Haussinger
ReI. intensity
300
Dred
800 700 600
Wavelength (nm)
500
:.
..
. :
Carcinoma in situ --;
; /\
Normal tisSUe\ : \'. ..'
:/ ....
-.... /.... \ .... , ..
..... -;............. / .... ....... .::.
.;e - "':\.-..... :.:.: .....
o
400
50
100
250
150
200
Figure 4 ALA-induced fluorescence. Peak in the red range about 635 nm in a case
of carcinoma in situ.
VI. Technique
Fluorescence bronchoscopy is performed during a routine diagnostic
bronchoscopy. In most departments, flexible bronchoscopy is performed
with local anesthesia and conscious sedation.
A. Autofluorescence Bronchoscopy
An autofluorescence examination adds about 10 min to a routine
bronchoscopy [14]. In examination by the LIFE system, patients undergo
conventional white light bronchoscopy. The light source is then changed to
the helium-cadmium laser and the tracheobronchial tree is examined again
by blue light. Biopsies are taken from all areas that are suspicious for
malignancy in either the white light or the autofluorescence mode. The
SAFE 1000 examination is carried out using a similar protocol.
Using the D-Light AF System, the fluorescence image is displayed on a
color monitor similar to that in the LIFE system. However, it is possible to
perform the bronchoscopy with the unaided eye without a camera. AF
bronchoscopy can also be performed with the rigid tube under general
anesthesia using a special Hopkins optical telescope with integrated filters
[36]. These optics provide a brilliant image of the bronchial surface in the
367
central airways (trachea, main stem bronchi) where the light intensity of a
fiberscope is often unsatisfactory, especially in cases of hyperemia.
B. Drug-Induced Fluorescence Bronchoscopy
Depending on the sensitizer used, various prebronchoscopic applications are
necessary. Thus far only ALA and Photofrin have been studied. ALA,
which is not approved for use in bronchoscopy, has to be applied by
inhalation (60 up to 250 mg) or orally (20-60 mg/kg) 1-5 hr before the
planned fluorescence bronchoscopy. Detection is performed with the Storz
system set in the ALA mode and the AF mode of examination. With the
LIFE system, spots or areas of red or pink fluorescence are looked for. As
for treatment with photodynamic therapy (PDT), Photofrin is given in a
dose of 2 mg/kg 48-72 hr before planned fluorescence bronchoscopy. In our
clinic, we often perform a diagnostic fluorescence bronchoscopy with the D-
Light AF System before starting PDT. Areas suspicious for malignancy are
characterized by brownish red to orange fluorescence in the AF mode, as
shown in Figure 5, and by pink fluorescence when using the ALA mode.
Bleaching of a lesion can be used as an indicator that PDT is complete.
The standard for evaluation of white light and fI uorescence bronchoscopy is
the histological classification of biopsies taken of optically detectable lesions
and random biopsy specimens of normal areas. The true sensitivity of the
Figure 5 Carcinoma in situ. Nodular tumor formation, discoloration in the WL
mode (left). Brownish red to violet and orange fluorescence III the AF mode after
intravenous application of Photofrin 48 hr before (right). Note the clearly visible
margins of the Material
368
Stanzel and HCiussinger
fluorescence mode cannot be determined, because it is not possible to know
if lesions were missed by both the WL and fluorescence mode [14].
Therefore, it is customary to define a "relative sensitivity" as the ratio
between the number of lesions detected by the combined examination
(WL +fluorescence) and the number of lesions found by WL alone to
quantify the value of fluorescence techniques.
A. Autofluorescence Bronchoscopy
Since its introduction several investigations have used the LIFE system for
detection of early lung cancer. Using LIFE, there is an increase of 1.1-2.7
times in the detection rate of premalignant lesions compared to conven-
tional bronchoscopy (Table 2). Lam [15] summarized the worldwide
experience with the LIFE-Lung device which included examinations of
over 1000 patients [65,67,89,91-94,99-102]. The data detailed lesions found
by the WL mode, by the AF-mode, and by random biopsies. The detection
rate using WL bronchoscopy alone was 40%. The rate ranged from 27% in
United States/Canada studies, to 47% in Europe, and 51 % in Japan/
Singapore. The addition of fluorescence bronchoscopy increased the
detection rate by an average of twofold. Again, there were differences
Table 2 Results of Studies (LIFE System)
Sensitivities of WL and WL + LIFE
No. of WL+LIFE Relative
Reference lesions WL (0/0) (0/0) sensitivity
[65] 113 389 84.1 2.2
[89] 19 63.1 895 1.5
[90] 73 51.0 930 1.8
[91] 44 31.8 86.4 2.7
[92] 0 43.3
[67] 142 24.6 66.9 2.7
[93] 79 59.0 85.0 1.4
[94] 83 62.2 85.5 1.4
[95J 2J6 61.2 85.7 1.4
[96] 67 75.0 100.0 \.3
[97] 212 73.8 93.5 1.3
[98] 123 85.3 941 1.1
WL, white light.
FLuorescence Bronchoscopy
369
among investigators. The detection rate was 71% (2.6-fold increase) III
United States/Canada, 83% (1.8-fold increase) in Europe, and 88% III
Japan/Singapore (I. 7-fold increase).
Venmans et a!. [103] commented that in these studies LIFE had always
been applied after conventional bronchoscopy, possibly causing a bias in
favor of the LIFE system. They carried out a study with two anns. In one
arm, LIFE followed WL, and in the other, WL followed LIFE. There was
no difference between the two groups. Kato and Ikeda [90] recommend WL
bronchoscopy first for general information followed by fluorescence
bronchoscopy for a more detailed examination.
There have been few reports on use of the nonlaser light systems to
date. We published the results of a pilot study in 1999 [66] involving 60
patients older than 40 years. The patients had either clinically or
radiologically suspected lung cancer, resected non-small cell lung cancer,
or suspicious cytological findings from sputum or prior bronchoscopy. Of
the 264 biopsies that were taken, 5 showed mild dysplasia, 6 moderate/
severe dysplasia, and I had CIS. In addition, there were 36 invasive
carcinomas. The relative sensitivity for detecting dysplasia or CIS was 2.8.
The results were limited by the small number of premalignant lesions and
the relatively high number of invasive cancers [66, I04].
Over the past 3 years, we have participated in a European multicenter
trial for evaluating the Storz D-Light AF System in early lung cancer
detection. Seventeen hundred patients were recruited, stratified into four
different risk groups, and randomized in two study groups, A and B.
Patients in group A underwent WL bronchoscopy only. The patients in
group B were examined by WL and AF bronchoscopy using WL followed
by AF. The use of these two study groups should avoid a bias between the
methods of WL and AF bronchoscopy [66]. In contrast to other studies, the
results are based on the comparison of prevalences and not of relative
sensitivities. Initial results suggest an increased detection rate in group B.
The prevalence of early malignant findings in group B (WL and AF) was 1.5
higher than in group A (WL only). The results of this study are currently to
be published soon. Published data using the SAFE 1000 System are sparse.
In one study [68], the prevalence of precancerous lesions was very low with
only five moderate dysplasias among 157 biopsy samples. The investigators
reported an increased detection rate of 3.75-fold. In a Japanese study of 79
biopsies [69], the relative sensitivity of the SAFE 1000 System was found to
be 1.9. However, dysplasias were not differentiated as to their severity, and
24 invasive carcinomas were included.
There are differences in the various study designs that may influence
the results and may cause discrepancies. When a high number of invasive
carcinomas are included, for WL detection This
370
Stanzel and Hdussinger
tends to decrease the WL/fluorescence ratio. In the published studies, rates
vary from 7 invasive tumors of a total number of 83 lesions [94] to 15 of 19
[89]. The North American study [67] included 40 invasive lesions of a total
number of 142 lesions. Moreover, there was a surprisingly high rate of WL-
negative invasive tumors in the study. The detection of early malignant
lesions in the WL mode had a sensitivity of 9%. It is not surprising,
therefore, that the relative sensitivity of the combined examination mode
compared to the WL mode was 6.3. However, the AF detection rate was
only 56% [14].
There is a learning curve for the use of fluorescence techniques even for
experienced endoscopists [35,67]. Higher numbers of biopsies were
performed during the learning phase (4.6 vs. 4.0 biopsies per patient), and
the number of preinvasive lesions found was lower (20 vs 102 lesions) [15].
However, even in centers with a relatively high rate of early cancer
diagnoses, indicating a high degree of experience of investigators [90,93,94],
addition of AF bronchoscopy led to an improvement in the diagnostic rate
[14]. Thus, experience with early cancer and fluorescence methods appears
to increase the sensitivity of AF and of WL bronchoscopy. As demonstrated
in Table 2, the relative sensitivity for recent studies was lower; possibly due
to the higher WL sensitivity.
In the reported series, the prevalence of early malignant lesions varies
widely. Lam's series [15] had a prevalence rate of 1.6% for CIS and 19% for
moderate or severe dysplasia. This is a very high r t ~ h i g h r than that
found by sputum cytology studies in patients with chronic obstructive lung
disease [105]. Reasons for this variation include differences in the smoking
habits of the enrolled patients; differences in the criteria for recruiting
patients; prebronchoscopy sputum cytology examination or special cytology
examinations such as computer-assisted image analysis [IS]; inclusion of
higher risk patients with previous bronchial or upper aerodigestive cancers;
genetic susceptibility variations; differences in the experience level of
endoscopists; and differences in the interpretations by the pathologists.
It is difficult to comment on the role of the pathologist in the variation
among studies [92, I 06, I 07]. There are few agreed upon standards of early
malignant changes of the bronchial epithelium, resulting in considerable
variation in interpretations of biopsies among pathologists. In a study by
Venmans [106], the site pathologist reported 45 preinvasive lesions among
343 biopsies. A reference pathologist confirmed only 20 of them: One
preinvasive lesion was upgraded and 35 lesions were downgraded or found
to be unsatisfactory. There is little question that the critical evaluation of
fluorescence bronchoscopy is integrally dependent on biopsy interpretation.
The lack of agreed upon standards leads to an increased interobserver
variation [J08]. We believe that the classification into mild, moderate, and
371
severe dysplasia and CIS should follow the criteria established by the World
Health Organization [IS]. Future studies must have improved diagnostic
accuracy and minimal interobserver variation [109], which can possibly only
be achieved by the development of objective classification methods such as
quantitative image cytometry [IS].
Another important issue involves the definition of the lesion itself.
Frequently, along the edge of invasive cancers there are areas with varying
degrees of early malignant change [25]. In our opinion, such lesions should
not be considered separately. We only include lesions that are at least 2 cm
distant from visible invasive tumors. Biopsy results also depend on the
quality and size of the specimens. Large, deep biopsies taken by rigid forceps
during rigid bronchoscopy under general anesthesia are usually of high
quality; smaller biopsies taken by flexible bronchoscopy are often not as
concl usive.
LIFE will never replace WL bronchoscopy. In the AF mode, much
detail and spatial resolution are lost because of the monocular image [14].
The Storz system, however, enables the autofluorescence examination
without first using the WL mode. By beginning with an autofluorescence
examination, artificial changes which disturb the fluorescence image can be
avoided. However, performing the procedure in this manner requires
optimal illumination, which can be reduced in patients with hyperemic
mucosa, and a careful bronchoscopic technique. Analysis of random
biopsies has established that there are false-negative lesions found by AF.
The exact number of false negatives is not known, as there are no studies of
fluorescence bronchoscopy followed by a complete pathological examina-
tion of bronchial system. A negative autofluorescence image in a true
malignant lesion may be explained by the character of the tumor growth.
Adenocarcinomas and small cell lung cancers grow primarily in the
subepithelial level. Malignant changes at the subepithelial level will not be
visible with autofluorescence, since the light sources may not sufficiently
penetrate into the bronchial wall. In this regard, there are apparently some
differences among the three systems. The D-Light AF System, for example,
seems to penetrate deeper, possibly providing more information about the
subepithelial layer.
Areas of necrosis typically show the phenomenon of hyperfluores-
cence. This may lead to misinterpretation of tumor growth in the AF mode
[14]. Inflammation with its hypervascularization, granulation tissue, which is
rich in capillaries, and previous biopsy sites cause reduced fluorescence
leading to false-positive findings. The explanation for these false-positive
lesions is felt to be at the molecular level and beyond visibility. False-
positive results seem to correlate better with morphometric measurement
and molecular genetic histopathological
372 Stanzel and Hiiussinger
grade [67]. How long false-positive findings can be observed at a previous
biopsy site is not known. In our experience, a biopsy site where a rigid
forceps was used may demonstrate reduced fluorescence from at least 6
months to several years. Radiation therapy, especially brachytherapy, and
PDT alter the airway vascularization. In such cases, problems in
interpreting AF are common. After PDT, we have seen large areas of
scarring in the bronchial mucosa characterized by a nearly homogeneous
dark bluish brown AF color. In such areas, it would be impossible to detect
zones of cancer recurrence unless additional tools, such as spectrometry, are
used.
B. Drug-Induced Fluorescence
A pilot study [46] evaluated ALA-induced fluorescence for detection of early
cancers. Eighty-eight patients with radiological or clinical suspicion of
having lung cancer or with a suspicious sputum cytology were included.
Three hundred and sixty biopsies were performed. It was concluded that this
technique has limited clinical application because of the need to administer
the drug soon before bronchoscopy, as ALA washes out within a few
minutes [46]. Larger visible cancers were unreliably visualized, and the
detection of the borderline invasive cancers was disappointing. The study by
Awadh [47] using LIFE for detection of ALA-induced fluorescence after
oral administration of therapeutic dosages of ALA found widespread false-
positive PpIX fluorescence in five of six patients. Several biopsies or areas
positive on fluorescence revealed inflammation, metaplasia, or mild
dysplasia. In this study, ALA-induced PpIX fluorescence was not specific
for tumor tissue. We initially performed diagnostic fluorescence broncho-
scopy prior to PDT with HpD or Photofrin. This proved to be an excellent
time to study drug-induced fluorescence. However, side effects and costs
have limited clinical use. ALA-induced fluorescence appears to be
promising, because there is no long-lasting skin hyperreactivity. However,
AF bronchoscopy, on the other hand, is advantageous, as it provides more
reliable results without the need of a preprocedural drug. Huber [40] has
described a system that provides the optional use of a combination of AF
technique and ALA-induced fluorescence. To our knowledge, such a system
is not clinically used and does not clearly improve the sensitivity for early
detection [63].
C. Safety
AF bronchoscopy has the same risks as standard diagnostic bronchoscopy.
There are no additional complications associated with an AF examination
[14]. AF bronchoscopy can be performed during routine bronchoscopy
373
without the aid of photosensitizers. Drug-induced fluorescence broncho-
scopy requires the use of a sensitizer. The most important side effect is skin
photosensitivity, which lasts for 24 hr [40,47] with ALA but up to 4-8 weeks
with Photofrin [41]. Nausea, vomiting, and elevation of liver enzyme levels
were occasionally noted in patients who received therapeutic doses [40,47] of
photosensitizers.
D. Relation to Other Procedures
The role of other procedures must be taken into account. The goal of
fluorescence bronchoscopy is to localize early lung cancer. The role of this
technique in relation to other detection methods has yet to be determined.
Technical progress has led to the development of a new generation of
videobronchoscopes (such as the Olympus BF 160 series) which can provide
excellent structural information of the bronchial epithelial surface.
Fluorescence bronchoscopy may still be advantageous, as it provides color
information in addition to structural information. However, the difference
between the two techniques is expected to become smaller as improvement
in WL bronchoscopy continues.
Fluorescence bronchoscopy will be most effective if it is included in a
general program of lung cancer screening, which might also include sputum
cytometry evaluation of high-risk patients [15,95,110, Ill]. Other screening
methods, such as immunostaining of transformed epithelial cells [112] and
polymerase chain reaction-based assays to detect oncogene mutations [113]
may help detect more early cancers and smaller lesions that can be localized
by AF. There is also a need to look beyond the bronchial surface [29].
Endoscopic ultrasound combined with high-resolution computed tomogra-
phy (CT) is a new tool to determine the penetra tion depth of tumors into the
bronchial wall and to detect lymph node invasion [29,114].
The clinician must determine which lesions warrant treatment and
which may remain under close observation. Where do we draw the line
between operative therapy, endobronchial interventional treatment, or
observation [I07]? If a centrally located early lesion without lymph node
involvement is determined to be a dysplasia, should the patient be included
in a chemoprevention program? In cases of CIS, progression to invasive
cancer is to be expected [115]. Several methods of curative endobronchial
treatment such as PDT [41,42], electrocautery [116], and neodymium:yt-
trium-aluminum-garnet (Nd:YAG) laser therapy [117] could be considered
in addition to surgery [118].
All these methods are suitable predominantly for centrally located
lung cancer.
374 Slanzel and Hiiussinger
There is, however, a worldwide shift away from squamous cell
carcinoma to adenocarcinoma which grows in the periphery of the lung,
especially in women [119]. These cancers might only be detectable as small
nodules on a chest CT scan or by llsing smaller bronchoscopes [29] which
can be passed into peripheral airways. In this context, lung cancer screening
programs, which include low-dose spiral CT scans, are needed. Currently,
the whole question of lung cancer screening for those at high risk for the
development of lung cancer is being reexamined. Carefully designed
epidemiological studies making use of new tools are needed to determine
whether or not lung cancer screening can save lives at affordable costs [120].
A complete screening program for high-risk patients might include sputum
cytological examinations, such as cytometry, examination by low-dose spiral
CT, conventional WL bronchoscopy, and fluorescence bronchoscopy and
be followed by staging with endobronchial ultrasound. Hopefully, this will
lead to improvement in the poor prognosis of lung cancer. Nakhosteen [121]
has designed such a program and expects to double the 5-year survival rate.
Improvements in the fluorescence systems need to be made. An
increased light intensity is needed in larger airways, especially in the trachea.
Spectrometry [33,83] or spectrofluorometry [95] can provide a more
objective analysis than the human eye. But to date, this has not been
incorporated into standard fluorescence bronchoscopy.
Optical coherence tomography (OCT) enables high-resolution imaging
at or near the cellular level [122-124]. To date, systems to carry out OCT
bronchoscopy are only in experimental stages. Other methods using
thermoacoustics or optoacoustics for diagnosing malignant tumors are
promising. However, significant issues must be faced with all these
technologies before the transition from the research laboratory to a
clinically applicable, viable biomedical technique can be made.
VIII. Conclusion
Fluorescence bronchoscopy increases our ability to detect early malignant
lesions. This increase is now less obvious than in the originally published
investigations, because improvements in new bronchoscopes and increased
observer experience have improved the detection ability of conventional WL
bronchoscopy. AF methods are not associated with the side effects and
additional costs of fluorescence bronchoscopy employing photosensitizers.
The currently available systems are based on a common principle. There are
minor differences in the systems (Tables 3 and 4). Most of the currently
published data were obtained with the LIFE system. This system is based on
a laser light source, making it the most expensive and most complex. The
Table 3 Technical Aspects of Fluorescence Systems
System
LIFE D-Light SAFE
Light source Helium-cadmium Xenon Xenon
laser
Colors 2 (R/G) 3 (R/G/B) I (G)
Observation Only video Direct and video Only video
(pseudoimage)
PplX Yes Yes (special ALA ?
mode)
ALA, delta-aminolevulinic acid.
375
xenon light-based systems, the Storz system (D-Light AF system, and
Pentax system SAFE 1000 system) are less expensive. The Storz system is
especially easy to handle, allowing an easy change back and forth from the
WL to AF mode. The image is brilliant and adds additional structural
information. The Storz system processes three color signals (green, red,
blue), the LIFE system two (green, red), and the Pentax system only one
(green). With the Pentax system, contrast and brightness can be enhanced.
Further studies to compare the systems must be performed to find out if one
system is more sensitive than another. As yet, there has been no study
comparing all the systems.
In dealing with invasive cancer fluorescence methods, as yet no clear
advantage between them has been found. However, fluorescence broncho-
scopy may have an advantage in detecting resection margins of invasive
Table 4 Clinical Aspects of Fluorescence Systems
System
LIFE
D-Light
SAFE
,
Data
Most (>1000
Less
a
(60 patients)
Sparse
patients)
Price
Highest
Lowest
Middle
Comfort
Low
High
Middle
"Data of 1173 patients to be Material
376 StcuEel and Haussinger
carcinomas or early malignant lesions. This might be especially helpful when
sleeve resections or endoscopic treatments are planned [125J.
Improved detection and localization of early malignancies will provide
more information about the genetics and natural history of lung cancer and
be useful for the study of carcinogenesis and chemoprevention [126J. As
better strategies to deal with these early lesions are developed, the goal to
improve the survival rate of patients suffering from lung cancer may be
achieved.
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19
Transbronchial Needle Aspiration
E. JAMES BRIIT
University of Maryland School of Medicine
Baltimore, Maryland, U.S.A.
I. Introduction
Transbronchial needle aspiration (TBNA) offers the bronchoscopist a
technique for sampling lymph nodes, masses, and infiltrates in the
mediastinum and lung using flexible bronchoscopy. TBNA has been
considered to be less invasive than surgical diagnostic techniques and has
been proven to be suitable for outpatient use.
Adoption of the technique as a standard diagnostic procedure has
been erratic. TBNA has gained variable acceptance within the pulmonary
community. A recent survey of fellows in training which took place two
decades after the first description of the modern technique indicated that
opportunities to learn TBNA were limited [I]. Instructional opportunities
are hampered when the majority of pulmonary trainees learn by apprentice-
ship; often in programs where the faculty may be limited and where
technical and cytopathological support may be lacking. Misconceptions
about the utility and safety of the procedure handicap its use. These
limitations can be overcome [2,3]. At centers where the expertise has been
developed, the technique of TBNA aspiration using flexible bronchoscopy
has made an enormous impact on the diagnosis and treatment of chest
disease.
385
386
Britt
In 1977, Wang established a technique to diagnose mediastinal
adenopathy using bronchoscopy. An esophageal varices needle designed
for passage through a rigid bronchoscope or esophagoscope was adapted
for this use. Five patients who had previously been examined by
conventional flexible bronchoscopy and who had airway findings of
extrinsic compression were reexamined using the new instrumentation. In
three of five cases, a diagnosis of malignancy was established [4]. In this first
series, cases were carefully chosen. Prior to the procedure, the workup of
some patients included esophagrams, angiograms, and chest tomography to
establish anatomical relationships. The amount of preprocedure testing
reflected concerns about structural relationships that were quickly dissipated
after experience with several cases.
In a follow-up report, 32 additional patients underwent rigid
bronchoscopy and TBNA. Twenty patients were eventually proven by
other methods to have bronchogenic carcinoma. In 18 of these patients,
TBNA established the presence of carcinoma in the paratracheal and
peribronchial tissues [5].
It was subsequently appreciated that a similar technique had been
described in the past but, for reasons that are not clear, the investigators
never achieved widespread recognition of their technique [6-8]. The
procedure as originally described had limitations. Few diagnostic bronch-
oscopists possessed the skills to perform rigid bronchoscopy. For patient
comfort, general anesthesia was required. Flexible instrumentation that
could be passed through a flexible bronchoscope was needed in order to
promote wider application of the technique. Prototype flexible instrumenta-
tion was designed and tested. In 1982, Wang reported on the first experience
using flexible instrumentation [9]. Thirty-two patients underwent TBNA.
Eighteen patients were examined to establish the etiology of an abnormal
mediastinum on chest radiography. The utility of using TBNA as a staging
procedure in the mediastinum was introduced in this paper as 10 patients
with a previously diagnosed parenchymal cancer underwent TBNA
examination of their mediastinal adenopathy. Seventy-three percent of the
patients with bronchogenic carcinoma and an abnormal mediastinum were
diagnosed by this technique In a subsequent report of 39 patients who were
examined by TBNA during a I-year period in 1981-1982, Wang was able to
establish yields and sensitivities for a variety of tumors [10]. When lymph
nodes draining right-sided tumors were sampled, the sensitivity was 92%,
and the specificity 100%. For left-sided tumors, the yield was lower, with a
sensitivity of 56% but a specificity of 100%. When compared with the
computed tomographic (CT) scan, TBNA was less sensitive (76 vs. 85%) but
more specific (62% vs. 100%), with a higher positive predictive value (77 vs.
100%) and a similar negative predictive value (73 vs. 71%). Because the
387
TBNA diagnosis is based upon a pathological specimen, the diagnostic
accuracy was higher (76 vs. 85%).
In 1984, Shure and Fedullo reported a series of patients who had
undergone TBNA using another prototype needle [II]. They obtained a 15%
positive aspirate rate in 110 patients with bronchogenic carcinoma.
Transcarinal needle aspiration was limited to the main carina. When the
carina was visibly abnormal, the transcarinal positive rate rose to 38%.
Although the yield in the series was considerably lower than that in the
Baltimore reports, the test was deemed to be useful, because it was simple
and safe and saved a significant number of patients a need for further
operative staging. In previous reports Wang had emphasized the need to
puncture multiple sites in the mediastinum in order to establish a definitive
staging diagnosis. This and other technical factors may have accounted for
the different yields.
The procedure was initially viewed as a technique only to be
performed by highly skilled bronchoscopists in institutional settings rich
in specialized resources. In order for the technique to progress and gain
widespread acceptance, it was necessary that individuals in a variety of
medical environments be able to duplicate the initial success. In 1985,
Harrow, practicing in a community-based referral center, demonstrated that
the TBNA technique was also useful in this setting. In this series, a diagnosis
of malignancy was made using TBNA in 46% of 110 patients examined. In
17%, TBNA was the sole basis for the diagnosis and no further surgical
workup was required [12].
In1986, Shenk, practicing in a referral center, evaluated the reliability
of TBNA as a diagnostic and staging technique [13]. The TBNA data were
confirmed with subsequent surgical staging procedures. Fifty percent of 88
patients evaluated for bronchogenic carcinoma had mediastinal adenopathy
on CT scan. Seventy-five percent of these individuals had either small cell
lung carcinoma (SCLC) or surgically proven mediastinal spread of
small cell lung carcinoma (NSCLC). In these surgically proven cases, TBNA
of mediastinal adenopathy had a sensitivity of 50% but a specificity of 96%
and an accuracy of 78%. The cytological confirmation offered by TBNA
was considered to be an advantage over CT scanning. In a follow-up study
in 1987, Shenk et al. evaluated 91 patients for possible lung cancer. When
TBNA was coupled with conventional techniques of brushing, biopsy, and
washing, the ability to diagnose bronchogenic carcinoma with flexible
bronchoscopy increased from 64 to 71 % [14].
In order to overcome the difficulties of relying solely on cytological
diagnosis, Wang demonstrated than a 19-9auge needle could be used safely
through a rigid bronchoscope for TBNA [15]. Twelve patients who had
failed flexible A preliminary
388
Britt
aspirate with a 21-gauge needle was performed to minimize the risk of blood
vessel puncture. A rigid 19-9auge TBNA was then performed in the same
location. A specific histological diagnosis was made in 10 of the 12 patients.
One specimen was too necrotic for diagnosis, and one procedure was
terminated early. Wang then designed a flexible instrument with a 19-9auge
needle suitable for obtaining histological specimens through a flexible
bronchoscope [16]. He was able to aspirate adequate histological specimens
in 21 of 25 patients (84%) and make a specific diagnosis in 18 (72%).
Shenk reevaluated his TBNA experience using both histological and
cytological needles [17]. In 29 patients, the use of the histological needle
increased the sensitivity of the procedure to 80%. Accuracy rose to 86%. In a
subsequent report, Shink performed flexible TBNA using both 19-9auge and
21-gauge needles in the same locations [18]. He was able to calculate the
sensitivity of both instruments. The sensitivity of the 19-9auge needle was
78.2% alone, and it rose to 85.5% when the aspirated fluid was also analyzed
using cytological techniques. The sensitivity of the 21-gauge needle was
52.7%. Shink recommended that most bronchoscopists use the 19-9auge
needle exclusively. Mehta also evaluated the histological instrumentation
and obtained an adequate diagnostic specimen in 50% of 34 patients. Three
"benign" diagnoses expanded the potential of the technique [19].
During the first 12 years after its introduction, TBNA became firmly
established as the procedure of choice for diagnosing SCLC, and as the
preferred procedure for diagnosing and staging mediastinal disease in many
centers. In Baltimore, it had a measurable impact on reducing the number of
mediastinoscopies performed at the Johns Hopkins Hospital [20].
The technical nuances of performing TBNA have received much
attention. Instruction courses and demonstrations at national meetings [21],
reviews in the medical literature [22], and a virtual reality simulator module
[23] have been developed to aid in dissemination of the technique. Technical
issues surrounding selection of instrumentation, performance of the
procedure, anatomical considerations, and details about specimen proces-
sing have been discussed in numerous publications [24]. These techniques
are not addressed in this chapter. Indications for the performance of TBNA
and the anticipated results will be discllssed as they exist in the literature
today (Table 1).
II. Diagnosis and Staging of Bronchogenic Carcinoma
TBNA has become the procedure of choice for the diagnosis of SCLC. This
disease commonly pi-esents as massive mediastinal adenopathy. The
pathological lymph nodes are immediately adjacent to the carina!,
Table 1 Indications for Performance of TBNA
Diagnosis of bronchogenic carcinoma
Diagnosis of malignant disease of the mediastinum
Staging of malignant disease of the mediastinum
Diagnosis of Iymphoproliferative disease
Diagnosis of metastatic disease
Diagnosis of benign disease of the mediastinum
Sarcoidosis
Infections
Tuberculosis
Multiple other organisms
Diagnosis and treatment of bronchogenic cysts
Diagnosis of peripheral nodules, masses, and infiltrates
Diagnosis of endobronchial disease
389
subcarinal, and paratracheal zones and are easily and accurately aspirated.
Since SCLC is not treated surgically, the need for surgical diagnostic
procedures in the workup and management of patients with SCLC are
obviated with TBNA. Review of the experience in several large series
published between 1983 and 2000 confirms the value of using TBNA to
diagnose SCLC (Table 2). Chin and Haponik examined the use of flexible
bronchoscopy to diagnose SCLC from a single institutional database [25].
During an 8-year study period, 42% of 277 cases of SCLC were diagnosed
by flexible bronchoscopy and TBNA. Over this 8-year study period, the
number of bronchoscopies performed remained constant while the number
of cases in which TBNA was employed rose consistently. In later years, the
trans bronchial needle was the sole instrument used to establish a diagnosis
in 40% of cases. The overall sensitivity of TBNA was 56%. When other
instruments were added to the bronchoscopic technique, the yield rose to
91 %. In patients with positive aspirates, the need for additional, more
invasive diagnostic techniques can be eliminated. Widely variable yields
from TBNA in SCLC have been reported in the literature. A number of
technical factors have been related to the varying results. These include
operator skill and experience, factors in processing of cytological samples,
and cytopathologist support including on-site rapid evaluation [2]. Inter-
estingly, even among experts, the yield from TBNA has begun to decline
over time. This decline reflects the fact that TBNA has become a very simple
and safe adjunct to diagnostic flexible bronchoscopy. The support
equipment necessary to perform the procedure is often kept readily at
hand, and adding a TBNA adds only a few minutes to a procedure. As a
result bronchoscopists h..ave been .able
t
to I attempt TBNA in more
, 'copyngnrea Ma ena
390 Brill
Table 2 Yield of TBNA in the Diagnosis of Small-Cell Carcinoma
No. of No. with No. with
Reference Year patients SCLC TBNA % Yield
[10] 1983 39 8 6 75
[12] 1985 108 II 8 73
[14] 1987 91 22 12 55
[24] 1989 365 81 40 49
[18] 1993 64 17 17 100
[37] 1993 510 29 12 41
[31] 1998 117 21 17 81
[25] 2000 173 173 110/128 86
[30] 2000 360 81 50 62
SCLC, small-cell lung cancer.
challenging circumstances including attempts to reach smaller lesions and to
reach lesions in unusual locations. Understandably, the overall yield would
be expected to decline.
TBNA is also a useful technique for the diagnosis and staging of
NSCLC (Table 3). Whereas patients with SCLC are not surgical candidates,
the goal in patients with NSCLC is to make a diagnosis, stage the tumor,
and offer surgery wherever possible. Established surgical techniques such as
mediastinoscopy and medistinotomy (Chamberlain procedure) have been
the mainstay of lung cancer staging for many years. Video-assisted thoracic
surgery has also enhanced surgical access to staging sites. TB A, however,
can offer staging of mediastinal locations as an outpatient in a single sitting
when incorporated into a diagnostic bronchoscopy. Evidence-based guide-
lines have been formulated to assist in the election of staging techniques
[26]. In many situations, the initial and only diagnostic and staging
procedure can be flexible bronchoscopy. This approach preserves tissue
planes in the mediastinum and saves surgical staging for later steps in the
therapeutic plan; for example, following neoadjuvant therapy.
Several centers have demonstrated that TBNA has had a beneficial
impact on the overall management of lung cancer. Cost analyses have
projected that TBNA is less costly than other staging procedures. Crocket
evaluated 96 patients with mediastinal adenopathy using TBNA. He
estimated a cost savings of $27,335 when TBNA made additional
procedures unnecessary in 22 of 40 patients with malignant disease and in
I of 2 patients with benign disease [27]. In a more rigorous cost analysis of
techniques for staging NSCLC, Harewood demonstrated that endoscopic
ultrasonography-guided fine needle aspiration was the least costly
Table 3 TBNA Yields in Diagnosis of Non-Small Cell Lung Cancer from Selected Series
No. of
Reference Year patients Sensitivity Specifici ty PPY
1986 88 0.5 0.96 089
1988 47 0.14 1.00 1.00
1989 29 0.80 1.00 1.00
1993 61 0.52
1993 64 0.91 1.00 1.00
S;[38] 1994 80 0.79 1.00 1.00
*[39]
1995 56 0.77 1.00 1.00
1998 44 1.00 1.00 1.00
-[31] 1998 134 075 1.00 1.00
[30] 2000 264 093 1.00 1.00
[40] 2001 22 086
PPY, positive predictive value; NPY, negative predictive value.
SOl/ree: Adapted from Ref. 35.
NPY
0.75
0.73
0.44
0.82
0.55
0.81
1.00
0.36
0.84
Prevalence
0.39
0.30
0.86
086
0.79
0.70
0.66
0.88
0.72
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392 Britt
approach, followed closely by TBNA. Both were less costly than positron
emission tomography (PET) scanning and CT-guided fine needle aspiration
[28].
Acceptance of TBNA for lung cancer staging requires a systematic
approach to the procedure, and acceptance of a predictable accuracy and
reliability of the technique. Wang first published a proposed bronchoscopic
lymph node map, which emphasized the relationship of endoscopic airway
landmarks to CT scan-identified nodal positions. The relationship to the
traditional American Joint Commission on Cancer Nodal Stations was
emphasized [29].
In a cooperative systematic evaluation of the role of TBNA in the
staging of bronchogenic carcinoma, Harrow et al. [30] collected prospective
staging data in 360 patients with bronchogenic carcinoma from four
institutions of varying characteristics with skilled endoscopists who were
familiar with TBNA. A standardized protocol was used with specific
attention to the bronchoscopic staging map. This study has defined the
potential for TBNA in practice. TBNA diagnosed 50 of 81 patients with
SCLC for a yield of 62%. In NSCLC, the yield was 48% (135/229). Surgical
staging was eliminated in 29% of patients because of TBNA. TBNA
provided the exclusive diagnosis of cancer in 18% [30]. This study also
provided insight into the factors that can influence the yield for TBNA. The
TBNA yields were higher on the right side (lymph node stations 1,3, 8) than
on the left (lymph node station 4). Wang named these the anterior and right
paratracheal and subcarinal zones on the right and the aortic pulmonary
window on the left. Factors proposed to explain different yields at various
locations include bronchoscopic limitations (all experienced operators
acknowledged the difficulty of achieving optimal angulation for puncture
at the left AP window) and biological factors. The subcarinal and right
paratracheal lymph nodes receive lymphatic drainage from a larger
percentage of lung tissue than do the nodes in the left aortic pulmonary
window.
In 1998, Bilacerogh.l [31] published her extensive series of patients
using both rigid and flexible TBNA techniques in 138 patients. Overall yield
(a diagnosis of malignancy established by TBNA) was 78% by either
technique. The rigid sampling method produced histological specimens in
74% of patients (102/138) and prod uced cytological samples in 17% (24/138)
of patients. In 8.7% (12/138) of patients, sampling was deemed to be
inadequate. The overall yield for rigid bronchoscopy was 78%, which was
higher than 66% reported for cytological TBNA [3 I].
In 2002, Patelli et al. [32] reported on 183 patients with NSCLC who
were evaluated for suspected N2 disease using flexible bronchoscopy. One
hundred ninety-four TBNAs were performed over a 4-year period. Overall,
393
66% of samples were positive for malignancy (127/194). TBNA was the only
positive staging sample in 38% (48/127) of cases. As in other studies, the
yields at lymph node stations 3 and 8 (right paratracheal and subcarinal
locations) were higher (84 and 79%, respectively) than at lymph node station
4 (left paratracheal) where the yield was 52%. Both histological and
cytological needles were used. The yield with a 19-9auge histological needle
was better than that with the 22-gauge cytological needle (78 vs 67%,
respectively), but the difference was not statistically significant.
TBNA has been proven to be particularly helpful to access two
important nodal sites. The left aortopulmonary window (lymph node
station 4) in the left paratracheal zone, at the level of the carina, between 9
and 10 o'clock is directly accessible only by TBNA and flexible
bronchoscopy. It is obscured by the aortic arch during mediastinoscopy
and is often too deep within the mediastinal structures when approached
during video-assisted thoracoscopy. Similarly, the posterior carinal zone
(lymph node station 2) (an area from 5 to 6 o'clock on the imaginary clock
face placed at the level of the carina) is the site most directly accessible by
TBNA.
Recent evidence-based guidelines for invasive staging of NSCLC
indicate that numerous techniques can be employed effectively, and that
selection of the appropriate test will depend upon the availability of local
expertise and patient-specific anatomical and physiological considerations
[26]. An extensive review of published series on the use of TBNA to evaluate
the mediastinum in patients with lung cancer was carried out during the
process of developing evidence-based guidelines [35]. The results with
TBNA compared favorably with other invasive procedures. Ultimately,
positive findings with TBNA saves patients further invasive staging. A
negative result may require further invasive staging. The negative predictive
value of TBNA scored favorably in comparison to mediastinoscopy as the
final definitive technique [35].
III. Diagnosis of Lymphoma and Metastatic Carcinoma
The principal use for TBNA is in the diagnosis and staging of bronchogenic
carcinoma. Bronchoscopists reporting wide experiences with TBNA have
included small numbers of patients diagnosed with lymphoproliferative
disorders or with metastatic tumors. The diagnosis of lymphoma is more
likely to be made with the histological needle, which can yield tissue
fragments in addition to material for cytological analysis. Recurrent
lymphoproliferative disease is more easily diagnosed than primary disease,
because old pathologicalcmaterial may tbe. available for comparison.
opyngntea Ma enal
394
Brill
Enhanced diagnosis is possible with the cooperation of the cytopathologist,
who can use various staining procedures to enhance identification and
characterization of aspirated cells. Flow cytometry may be necessary to
characterize the aspirated lymphocyte population [36]. However, the large
volume of cells required for an adaquate flow cytometric specimen may
require multiple aspirations.
Comparison with old pathological material and newer specialized
staining techniques may also allow recognition of metastatic tumor. For
example, melanoma with its characteristic pigments is easily appreciated.
Certain breast cancer aspirates can be tracked with receptor markers. The
combined skills of the bronchoscopist providing a satisfactory TBNA
sample and the cytopathologist using specialized techniques will enhance the
overall utility of diagnostic bronchoscopy and TBNA [37-40]. The initial
diagnosis of a number of lymphoproliferative diseases, however, will still
require surgical biopsy material.
IV. Diagnosis of Benign Disease
TBNA has been used to obtain histopathological and cytopathological
material to establish the diagnosis of sarcoidosis. The diagnosis requires the
demonstration of noncaseating granulomas and the absence of organisms by
special stains and culture in an appropriate clinical setting. Pauli [41]
reported his extensive experience using TBNA by rigid bronchoscopy. In the
era of rigid bronchoscopy, random bronchial biopsy was often used to
establish a diagnosis of sarcoidosis. Bronchial biopsy was positive in 66% of
patients sampled. Transbronchial biopsy was positive in 72.3% of stage I
patients, but it was positive in only 40.5% of stage 2 patients exal'nined.
There was a significant discordance between techniques. TBNA was positive
alone in 37.8% (73/193) of patients and bronchial biopsy was positive in
11.4% (22/193) of patients. Combined techniques were positive in 77.8%
(156/193). Histological diagnosis of sarcoidosis was obtained in 79.6% of
patients with stage 1 sarcoidosis; the same yield that had been obtained in 60
patients who had undergone a prior nondiagnostic flexible bronchoscopy
[41 ].
Morales systematically examined the utility of TBNA using the flexible
19-9auge Wang histological needle to diagnose sarcoidosis [42]. Fifty-one
consecutive patients suspected of having sarcoidosis underwent TBNA and
transbronchial biopsy for evaluation of stage I or 2 disease. The diagnosis
required the presence of noncaseating epithelioid granuloma; no evidence of
a foreign body or allergic reaction; negative Zhiel-Nielsen, carbol fuchsin,
and methenamine silver stains; and a negative acid-fast culture. Transbron-
395
chial biopsies were positive in 60% of stage I patients and in 76% of stage 2
patients. TBNA was positive in 53% of stage] patients and 48% of stage 2
patients. The combined yield was 83% in stage I and 86% in stage 2 cases.
TBNA provided the exclusive diagnosis of sarcoidosis in 23% of stage I
patients and in 10% of stage 2 patients. These results were lower than those
reported using the rigid technique, but they were clearly easier to obtain.
Bronchial biopsy was not evaluated in this flexible bronchoscopy series. The
yield of TBNA should be compared to the traditional yield of transbron-
chial biopsy in sarcoidosis, where the yield with flexible bronchoscopy has
ranged from 44 to 66% in stage I disease and 83% to 96% in stage 2 disease.
Bilaceroglu reported on her flexible bronchoscopy experience in the
diagnosis of sarcoidosis, and provided a detailed analysis of the diagnostic
value of various instruments [43]. Flexible instruments used included forceps
for endobronchial biopsy (EBB) and transbronchial biopsy (TBBX) and
TBNA needles. EBB was diagnostic in 45% of stage 1 disease, 50% of stage 2
disease, and 58% of stage 3 disease. This compared with TBNA, which was
diagnostic in 61 % of stage 1 and 42% of stage 2 patients, and with TBBX,
which was diagnostic in 52% of stage 1,63% of stage 2, and 83% of stage 3
respectively. An overall diagnostic rate of 91 % was achieved. It appears that
TBNA can and should be used during flexible bronchoscopy for sarcoidosis
in order to enhance the yield, especially in stage I disease.
V. TBNA and the Diagnosis of Infections
Material aspirated from mediastinal and hilar lymph nodes with a TBNA
needle can be cultured, smeared, and stained to look for infectious agents.
The largest experience to date has been in the evaluation of mediastinal
adenopathy in human immunodeficiency virus (HIV)-infected patients
where tuberculosis is a significant issue [44]. In 1990, Serda first described
the use of a TBNA needle to aspirate 30 mL of purulent material from a
subcarinal node in an HIV-positive patient [45]. The material stained
positive for acid-fast bacteria (AFB) and was eventually identified as
Mycobacterium tuberculosis by culture. Other reports soon followed [46,47].
Ina paper on tuberculous mediastinal lymphadenopathy, Baran reported on
performing performing TBNA using rigid bronchoscopy in II of 17 patients
(65%). Five of II (45%) examinations were positive for tuberculosis. Fifteen
of the 17 patients (88%) had a recognizable endobronchial abnormality
ranging from carinaI widening to frank mucosal erosion. HIV studies were
not reported in ihis group, which represented 0.26% of the entire
tuberculosis population in that center [48]. In this and similar populations
[49], the prevalence of was high. Cetinkaya
396
Brill
reported on 28 patients who had mediastinal or hilar adenopathy in whom
expectorated AFB smears were negative [50]. Only one patient had an
endobronchial lesion. Using a 19-9auge flexible needle, they were able to
make a diagnosis in 87% of these patients. In 46% of these patients, TBNA
was the sole means of diagnosis. Diagnoses included tuberculosis in 10 of 10
(100%) cases, sarcoidosis in 7 of 8 (87.5%) cases, and I case each of
lymphoma and SCLC. Ten cases could not diagnosed by TBNA [50].
The development of hilar and mediastinal adenopathy in patients with
HIV/AIDS is a common problem. The possible diagnoses include
tuberculosis, atypical mycobacterial disease, bronchogenic carcinoma,
sarcoidosis, nonmycobacterial infections, Kaposi's sarcoma, and lym-
phoma. TBNA has been proven to be very useful in this population.
Harkin and Rom [51] evaluated TBNA using a 19-9auge histological needle
in 41 patients who were HIV positive and who had mediastinal adenopathy.
A diagnosis was made in 52% of procedures (23/44). TBNA was the only
source of a diagnosis in 32% (13/41) of patients. Fifty-two percent of
procedures were performed in patients suspected of having mycobacterial
disease. TBNA provided the diagnosis in 87% (20/23). Acid-fast smears were
positive in 48% (11/23). Histological specimens were positive in 65% (15/23)
with an immediate on-site diagnosis being made in 74% (17/23). TBNA
provided the only diagnosis in 48% (11/23). Other diagnoses establish by
TBNA included sarcoidosis (2/4), and bronchogenic carcinoma (1/2). Other
bronchoscopic tools and techniques established the diagnosis of Kaposi's
sarcoma, non-Hodgkin's lymphoma, and a variety of infectious diseases. A
diagnosis was lacking but not pursued in five patients. This underscores the
reluctance of some caregivers to pursue a surgical diagnosis in patients with
AIDS.
Empiric treatment of mediastinal adenopathy is problematic. AIDS
patients are frequently on multiple medications, and the potential for
multiple drug interactions presents a pharmacological challenge. TBNA
offers a very good opportunity to establish a specific diagnosis. Multiple
organisms have been aspirated from lymph nodes by TBNA and identified
with specific stains. Nocardia [52] and Cryptococcus [53] were among the first
microorganisms to be identified by TBNA but almost any organism that can
infect mediastinal lymph nodes can be found with TBNA.
VI. Diagnosis and Treatment of Bronchogenic Cysts
TBNA has been used to diagnose and drain bronchogenic cysts.
Historically, the management of bronchogenic cysts has been controversial.
The majority of cysts are asymptomatic when found on chest radiographs or
397
on CT scanning. Symptomatic cysts present with chest pain, dysphasia, and
cough [54]. Approximately one-third of bronchogenic cysts are in close
proximity to the major airways. The most common locations are the
subcarinal zone and the right hilar zone. These are easily punctured and
aspirated by TBNA. Schwartz [55] first reported two cases of bronchogenic
cysts in which TBNA of a large subcarinal mass produced thick yellow clear
fluid suitable for cytological analysis. Schwartz [56] reported another
successful aspiration. Kuhlman subsequently described four additional cases
aspirated by TBNA [57]. McDougal [58] emergently decompressed a 6-cm
paratracheal mass in a 38-year-old smoker using TBNA. He withdrew
60 mL of yellow fluid. The decompression facilitated anesthetic intubation
and ventilation, allowing a definitive surgical procedure to continue. Barzo
[59] aspirated a cyst using TBNA and then injected radiographic contrast to
delineate the extent of the cyst. There were no consequences from the
injection.
Sclerosis of bronchogenic cysts was a therapy used many years ago,
but today, most operators would be concerned about introducing infection
into the mediastinum. Terry editorialized that modern bronchoscopists,
"armed with twentieth century lances:' are like William Tell, challenging
the status quo. He suspected that, in the future, TBNA would be a standard
diagnostic and therapeutic technique in the management of bronchogenic
cysts [60]. My personal informal poll of diagnostic bronchoscoscopists
indicates that many have aspirated bronchogenic cysts with TBNA. Fewer
patients are being sent to surgery and many are followed safely for years.
Unfortunately, a large pooled series of patients with bronchgenic cysts with
long-term follow-up has not been assembled or reported. We aspirated a
bronchogenic cyst discovered incidentally in a patient who had volunteered
for a hypertension study. The cytological report on the aspirated clear
yellow fluid suggested adenocarcinoma. At surgery, a benign pericardial cyst
was removed.
VII. Diagnosis of Peripheral Nodules, Masses,
and Infiltrates
TBNA techniques have been extended to the diagnosis of peripheral
nodules, masses, and infiltrates. In 1983, Shure and Fedullo [61] reported on
their use of a flexible trans bronchial needle to aspirate cytopathological
material from 42 patients with peripheral lung masses ranging in diameter
from 0.8 to 9 cm. Diagnostic procedures included TBNA, transbronchial
biopsy (TBBX), brush (B), and wash (W). The TBNA was positive in 22 of
33 patients proven to for a yield of 52%. The
398
Britt
TBNA produced the highest individual yield. The combined yield of all
instruments was 69%.
In 1984, Wang [62) reported on his initial experience with TBNA and
other instrumentation in the diagnosis of peripheral lesions. Lesions studied
averaged 2.1 0.5 em in diameter. In 23 attempts in 20 patients, TBNA was
positive in 47.8% (11/23) and provided the only diagnosis in 35% 0/23). The
overall combined yield was 55%. In 1991, Wang and Britt reported on the
use of a needle brush designed for use in the diagnosis of peripheral nodules
and masses [63). The needle brush was designed to overcome the anxieties
among bronchoscopists who were reluctant to pass a needle into the
periphery of the lung. Table 4 lists the yields using various bronchoscopic
techniques in diagnosing peripheral lesions. Instruments that are capable of
puncturing a lesion (TBNA and NB) give the highest yield. Reichenberger
[64) published his series of 126 patients with malignant peripheral
pulmonary lesions, and was able to calculate an accurate yield for each
sampling technique. TBNA had the highest yield at 54%. The yield from
conventional instrumentation was lower: 8% for a forceps biopsy, 23% for
brushing, and 37% for washings. In practice, multiple techniques are
employed to maximize the success rate.
In 1967, Tsuboi [65) classified coin lesions and parenchymal masses.
An understanding of this classification is useful in appreciating the impact of
different instruments on the ability to make a diagnosis. When the bronchus
leads directly to the tumor (type I) (currently evidenced by the "bronchus
sign" on CT scan [66)) or when the tumor engulfs the bronchus (type II), the
endobronchial approach is direct. Many diagnostic instruments will produce
a positive sample. When the tumor displaces or compresses the airway (type
III) or when the bronchus is narrowed by external compression or local
adenopathy (type IV), the forceps and regular brush instrumentation "run
away" from the tumor. In these cases, instrumentation which allows the
operator to reach the edge of the lesion, extend a needle or needle brush, and
puncture the lesion increases the yield [67).
Some bronchoscopists prefer to use a single instrument to obtain a
diagnosis. Their goal is to minimize the number of instruments used as a
cost-containment strategy. Our group, on the other hand, prefers to use all
instrumentation available to maximize the yield of a single bronchoscopy.
The cost of disposable brushes, forceps, and needles is much less than the
financial cost and emotional stress of a repeat bronchoscopy. Rapid on-site
cytological evaluation, of course, enhances the yield at any setting [68).
Other large series have been since reported. Gaspasrini [69) reported
on the use of a combined approach in 1027 patients who underwent 1692
diagnostic procedures. The results in this large series are illustrative of the
choices available to diagnose nodules or masses. If the bronchoscopic
Table 4 Yield of Various Sampling Techniques to Diagnose Peripheral Lesions
()
No. of
-Reference Year patients TBNA TBBX RB
':<:
<d76] 1983 33 22 15
~ ]
1984 20 II 3 4
Q{78] 1991 22 8 4 7
81] 1995 37 23 14 10
~ 8 ] 1998 84 48 41 22
:Totals/yields" 196 112/57% 77/39% 43/26%
w
9
3
12/9%
NB
II
11/50%
:'l
i:l
;:;
'" 0-
;;
:::
'"
:::-
!S.
--
~
<I>
t::l..
~
;:,.,
'"
""
:::.
~
0'
;:;
TBNA, Trallsbronchial needle aspiration; TBBX, forceps biopsy; RB, regular brush; W, washings; NB. needle brush.
"Denominator for calculated yield variable based on published numbers.
Vv
'0
'0
400
Britt
approach using TBNA was not successful using rapid on-site cytopatho-
logical assessment, patients immediately underwent percutaneous needle
aspiration (PCNA). Tn this series, the diagnostic yield for malignancy with
forceps biopsy was 53.9%, with TBNA 69.3%, with both instruments 75.4%,
and with PCNA 93.2%. The overall success rate was 95.2%. For benign
disease, forceps biopsy was positive in only 17.4%, TBNA 45.8%, PCNA
45.8%, and the overall yield was 59.5%. Although the yield was better using
PCNA, the complication rate was higher. Pneumothorax was the major
complication of PCNA-occurring in 8.9% of patients. Chest tube drainage
was required in 3%. There was a single air embolism. The most serious
complication of the bronchoscopic approach was major hemoptysis in I% of
patients. One patient developed severe bronchospasm requiring intubation
and overnight mechanical ventilation. Other large series have confirmed the
utility of using TBNA to diagnose peripheral nodules and masses [70]. The
yield in general is lower than with PCNA, but the complication rate is also
lower.
VIII. Techniques to Enhance Visualization and Placement
Using Transbronchial Needles
New imaging technologies are being used to verify placement of
trans bronchial needles and to increase the yield of TBNA. Conventional
CT scanning performed at the time of TBNA was proposed as a useful
adjunct to TBNA. However, this technique was limited by the slow image
reconstruction times required after each adjustment of the bronchoscope.
CT fluoroscopy, on the other hand, allows for dynamic visualization
of the path of the bronchoscope and the transbronchial needle [71]. This
permits precise localization of the needle and verification of placement.
White reported on the use of this technique to assist in the diagnosis of 27
patients [72]. Fifteen had enlarged mediastinal lymph nodes with a mean
diameter of 1.7 cm. Twelve patients had lung nodules or focal infiltrates with
a mean lesion size of 2.2 cm. A diagnosis of lung cancer was established in
six cases. Two false-negative results were recorded. The overall accuracy was
83%. Diagnostic accuracy was 83% for mediastinal lesions and 67% for
parenchymal lesions. Lesions were chosen because of their small size or
difficult location. Dual evaluations using conventional fluoroscopy and CT
fluoroscopy were not performed. Garstead reported his experience with CT
fluoroscopy in 35 patients undergoing TBNA [73], selecting patients with
subcarinal and peritracheal adenopathy who had failed conventional
bronchoscopy, and also including patients with more difficult lymph node
stations. Adequate tissue was obtained in 87.5% of patients (28/32). Twenty-
.
TransbronchiaL NeedLe Aspiration
401
two patients had a specific diagnosis made. Six additional patients had a
technically adequate puncture demonstrating lymphocytes. One was
subsequently shown to have malignancy. In both series, selected patients
with an adequate puncture demonstrating lymphocytes and a CT image
demonstrating that the needle was properly placed were subsequently
followed without surgical confirmation and with a good outcome. Firm
criteria for this approach have not been established.
Endobronchial ultrasound (EBUS) has also been used to localize
central and peripheral lesions to direct needle placement. Shannon [74]
compared EBUS-guided TBNA to standard TBNA in 80 patients. Both
techniques were very sensitive. The yield was 82.6% with TBNA versus
90.5% with EBUS-TBNA. In the EBUS-guided procedures, fewer punctures
were necessary. There was also a negative correlation between lymph node
size and the number of aspirates with TBNA but not with EBUS-TBNA. It
is likely that the value of the EBUS will lie primarily in the localization of
difficult sites and small targets. Herth recently reported on the use of EBUS
to guide TBNA in 242 patients [75]. The use of EBUS-TBNA produced a
high degree of success in 86% of patients and an overall diagnostic rate of
71 %. In contrast to "blind" TBNA, success did not correlate with lymph
node size. In addition, the operators were able to achieve a very high yield of
86% in the difficult 4L location (left aortic pulmonary window).
Dynamic or a real-time imaging with EBUS, however, is not possible
at present. The ultrasound probe must be passed through the working
channel of the flexible bronchoscope, the target localized and imaged, and
the location memorized by the operator. The ultrasound probe must then be
removed, the TBNA needle passed through the working channel, and the
. puncture performed. Ultrasound probes remain costly. Prototypic ultra-
sound probes that are permanently mounted on the tip of a flexible
bronchoscope are in development. However, the working channel of these
bronchoscopes is only I mm in diameter. In contrast, esophagoscopes are
available with attached ultrasound probes and large working channels. This
allows for real-time imaging of needle placement through the esophagus. In
some mediastinal locations, transesophageal ultrasound needle aspiration of
the mediastinum competes with TBNA for staging [76]. When the
ultrasound chip can be permanently mounted on the tip of flexible
bronchoscopes with working channels of 2 mm or larger, real-time imaging
will be possible. It is likely that this technology will be widely accepted and
become the primary tool to aid the performance of TBNA [77].
Radiological imaging techniques have advanced rapidly in the last
several years. Virtual reality images of mediastinal structures generated from
CT scan data sets have allowed radiologists to create a "virtual
bronchoscopy." Airways efIPy,fglillilc'f'MatfifFatparent" in order to "see"
402 Britt
lymph nodes behind the airways [78,79]. As these images become more
routinely available, they also can aid in needle placement for TBNA.
IX. Diagnosis of Endobronchial Disease
TBNA instrumentation has been used to obtain samples of material from
deep within necrotic or vascular endobronchial lesions. Because the TBNA
needle will usually produce less bleeding than forceps biopsy, it has been
used to diagnose bronchial carcinoid tumors [80]. TBNA has also been used
to aid in the delineation of a bronchial resection margin [81,82]. At some
centers, it is the instrument of choice for sampling of bronchial tumors;
selected before forceps or used exclusively [25]. Disposable TBNA needles
are often less costly than disposable biopsy forceps.
X. Complications of lBNA
Complications ofTBNA are uncommon (Table 5). When first introduced to
TBNA techniques, many bronchoscopists expressed concern about the risk
of hemorrhage from puncture of the great vessels. In the precardiac
catheterization era, the medial wall of the left main stem bronchus was
routinely punctured using 18-gauge esophageal varices needles and rigid
bronchoscopy in order to puncture the left atrium and to record left atrial
pressure in mitral valve disease [83,84]. Eighteen-gauge spinal needles were
introduced at the suprasternal notch and angled diagonally through the
aorta, the left atrium, and into the left ventricle to measure the aortic
valvular and mitral valvular gradients in patients preparing for valvular
replacement [85]. Pericardial tamponade was an infrequent complication.
For many years, 16-gauge catheters were routinely used to perform
translumbar aortograms.
Table 5 Complications of TBNA
Bleeding
Pneumothorax
Mediastinal infection
Bacteremia
False-positive results
Needle loss
Bronchoscope damage
403
With this prospective, it is not surprising that hemorrhage has not
been a problem with TBNA. A few drops of blood may ooze out of the
puncture site but are usually easily aspirated and almost always stop within
a few seconds. Mucosal hemorrhage may be more significant when an
exposed needle tip scratches an inflamed or bronchitic airway. This is easily
controlled with topical epinephrine. Mediastinal hemorrhage after TBNA
has been reported without consequence [86]. Superior vena cava syndrome
has not been an obstacle to TBNA [87].
A 21-gauge TBNA needle was used to puncture a smooth orange-red
mass in the left lower lobe of a patient who was being evaluated for
hemoptysis. Life-threatening hemorrhage occurred but was controlled and
stabilized. There was no active bleeding on reexamination in 24 hr. The patient
died suddenly of massive hemoptysis prior to surgery. Necroscopy revealed a
pulmonary artery aneurysm that had eroded the bronchial wall [88].
We aspirated a small white glistening lesion in the right upper lobe
with a 2I-gauge TBNA needle. Because the lesion expanded and collapsed
with respiration, forceps biopsy was deemed to be risky. Blood was easily
aspirated. When indirect imaging could not establish the nature of the
vascular structure, we repeated the TBNA aspiration and performed a
TBNA angiogram. This demonstrated a pulmonary varix, which was later
surgically confirmed.
Pneumothorax and pneumomediastinum following TBNA have rarely
been noted, usually without significant consequences [9,69]. Early cases were
undoubtedly related to punctures in the right paratracheal area beyond the 3
o'clock position where the lung at times abuts the trachea. Today, most
patients have a reference CT scan available for planning the procedure and
aiding in needle placement.
The airways of cigarette smokers undergoing TBNA for diagnosis and
staging of bronchogenic carcinoma are often colonized with bacteria. Also,
the flexible bronchoscope passes through the oral and nasal cavities picking
up oral flora bacteria. As a result concerns about introduction of infection
into the mediastinum have been raised. Bacteremia following TBNA was
documented in one case report [89]. A re'port of polymicrobial bacterial
pericarditis after TBNA was also noted in 1992 [90]. In order to quantify the
risk of contamination of the transbronchial needle, Epstein passed a TBNA
needle through the channel of a flexible bronchoscope inserted transnasally
in seven patients. The TBNA needle was introduced into the airway, then
extended, and then withdrawn with no puncture or aspiration performed.
The needle was then rinsed and cultured using quantitative methods. Up to
10 different aerobic and anaerobic organisms grew with colony counts
ranging from 1.1 x 10
6
to 6.0 x 10
6
microorganisms. It is therefore clear
that the TBNA needle from the bronchoscope
404
Brill
channel. Nevertheless, reports of infection are rare. Witte drew blood
cultures during and after diagnostic flexible bronchoscopy and TBNA on 50
occasions in 47 afebrile patients. Ten percent of patients (5/50) developed
fever to 100.4 degrees or higher within 24 hr of the procedure. None of 120
blood cultures obtained was positive [91]. Prophylactic antibiotic treatment
is not routinely recommended for patients undergoing bronchoscopy or
transbronchial needle aspiration [92].
On occasion, concerns about false-positive cytological results from
TBNA have been raised [93,94]. These reports usually involve transbronchial
needle aspirates obtained from carinal and paratracheal punctures when
large central necrotic lesions were nearby. There usually is no problem when
strict criteria are used to interpret the TBNA cytological specimen. A
diagnosis of malignancy should not be made solely on the finding of a few
malignant cells. Good-quality transbronchial specimens are rich with cellular
material, and clumps of malignant cells are usually obtained. When nodes
are aspirated, there should be a background of lymphocytes and a paucity of
bronchial epithelial cells, ciliated cells, and alveolar macrophages.
A single case of a false-positive TBNA was reported many years ago
when the paratracheal area was punctured to aspirate a paratracheal mass.
The mass was very medial within the right upper lobe and was lying adjacent
to the right paratracheal zone. It gave the appearance of a paratracheal
mass, but in fact at surgery the mass fell away from a clean trachea. Thus,
the mass was intraparenchymal [95]. Careful assessment of CT anatomy and
awareness of this potential pitfall should avoid this problem.
In the early days of TBNA, there were occasional reports of
detachment of the needle from the plastic catheter. Some of the needles
had been reused (a process that never has been recommended by the
manufacturer), altering the properties of the device. Improvements in
manufacturing and design have eliminated this concern.
There have been numerous reports of damage to the flexible
bronchoscope during T8NA [96]. Puncture of the inner working channel
by the exposed needle tip is the most commonly encountered bronchoscope
damage. Careful attention to guidelines and good technique have minimized
scope damage at experienced centers [97]. Technic,al publications should be
consulted for good practice recommendations, which minimize the risk of
damage.
XI. Conclusion
Modern transbronchial needle aspiration using flexible bronchoscopy has
now been available for over 20 years. A substantial literature has developed
405
exploring the utility of this procedure. The instrument and the technique
have been used successfully worldwide, although universal acceptance is
lacking. Much potential for growth and development of the technique
remains. TBNA is an easily learned procedure. Guidelines for performance
of TBNA have been published [98]. TBNA needles should be readily
available to add to any standard diagnostic bronchoscopy. When used in
this fashion, several minutes may be added to a procedure. However, in
many cases, TBNA has the potential to be the definitive diagnostic
procedure and may eliminate the need for more elaborate surgical
procedures. In some centers, the transbronchial needle has become the
primary tissue-sampling tool used during diagnostic flexible bronchoscopy
in lieu of standard brushes and forceps. It is expected that in time more and
more bronchoscopists will appreciate the advantages of TBNA in the
diagnosis and staging of many chest diseases.
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20
Medical Thoracoscopy
ROBERT LODDENKEMPER
Lungenklinik Heckeshorn
Berlin, Germany
I. Introduction of Thoracoscopy as a Diagnostic Method
Thoracoscopy was introduced in 1910 by Hans-Christian lacobaeus (1879-
1937), who at the time was an internist in Stockholm, Sweden. He published
his initial experience in the journal Miinchener Medizinische Wochenschrifi
in a paper entitled "On the Possibility to Use Cystoscopy in the
Examination of Serous Cavities" (1]. He began his "preliminary commu-
nication" by referring to endoscopy of organs with natural openings, such as
the urinary tract, and referred to the work of Max Nitze, who, in 1877,
developed the first cystoscope with a telescopic lens and distal illumination
(2]. lacobaeus then commented that closed cavities like the peritoneum,
pleura, and pericardium had not been examined endoscopically. For this
kind of "cystoscopy," lacobaeus defined three main prerequisites:
I. The possibility to introduce a trocar (or a puncture needle) into
the respective cavity without lacerating the inner organs and
without causing too much pain.
2. The introduction of a transparent medium into the cavity-he
used filtered air febf}fridlNePPMaterial
411
L _
(b)
412 Loddenkemper
3. A cystoscope of such small dimensions that it could be introduced
through the trocar.
Figure I shows the trocar lacobaeus used, which contained an
automatically closing valve, and was built with the assistance of Dr. A.
Ahlstrom, chief of instrument makers at Stille-Werner in Stockholm. The
whole apparatus had a diameter of only 17 Charriere, with the cystoscope
having a diameter of 14 Charriere.
lacobaeus described the basic procedure as follows: The skin was
disinfected and anesthetized with cocaine. Following a small skin incision,
the trocar was introduced with or without prior air insufflation into the
cavity. Once the trocar was introduced, filtered air was insufflated by means
of a simple Politzer air pump. The cystoscope was then introduced through
the trocar and the inspection was performed. lacobaeus then described in
detail how the peritoneum was examined. He called this "Iaparoscopy," and
he initially practiced in over 50 cadavers before successfully performing the
procedure in three patients.
In the second, much smaller part of his discussion, lacobaeus
described the examination of pleural cavities, which he called "thoraco-
scopy." He stated that in this procedure the three main prerequisites are
fulfilled more closely than in laparoscopy, especially in regard to point I
(introduction of the trocar), which he considered to be much less dangerous
in the thorax. He referred to a technique developed by Dr. Israel Holmgren,
who substituted the fluid with air ("exhalation of the exudate"). He also
cited Forlanini's method in which air or nitrogen was blown into the pleural
space, and that under certain circumstances was used as a therapy for
pulmonary tuberculosis. lacobaeus mentioned that he planned to begin
examination of the pleural cavity by using Forlanini's treatment method
(closed pneumothorax). This eventually led to the introduction of
thoracoscopic lysis of pleural adhesions by means of thoracocautery.

-tm
Figure 1
Original trocar (a) and automatically closing valve (b). (From Ref. I.)
Medical Thoracoscopy: Historical Perspective
413
In his pioneer paper, lacobaeus mentioned two cases of pleuritis
exsudativa in which he studied the pleural surfaces after replacing fluid with
air according to Holmgren's technique. Although not initially able to
characterize safely the pleural changes, he expressed his confidence that the
method would be successful with more training, and that it might even
eventually yield prognostic information. lacobaeus closed his publication by
mentioning that he had no experience using the cystoscope in the
pericardium, but that he believed this also might eventually be possible.
lacobaeus was therefore the pioneer of endoscopic techniques in
serous cavities. Today, these techniques are widely used for diagnostic and
therapeutic purposes by internists and surgeons. He apparently was not
aware of the report by Georg Kelling, who worked in Dresden, Germany,
which was published in 1902, also in the journal Miinchener M edizinische
Wochensclmft under the title "On Esophagoscopy, Gastroscopy, and
Coelioscopy." Kelling described his experiences with laparoscopy (coelio-
scopy) in dogs using two points of entry-one for a trocar through which air
was insufflated and one for a trocar through which Nitze's cystoscope was
introduced [3]. Kelling definitely did not perform thoracoscopy', as
incorrectly stated by Unverricht in 1923 [4] and later by several other
authors.
In the following years, lacobaeus and a number of other European
pulmonary specialists from Scandinavia, Germany, Italy, and several other
European countries performed thoracoscopy for diagnostic purposes [5].
lacobaeus himself published a long summary of his experience in 1925,
describing in detail his studies of the etiology and staging of tuberculous
pleurisy, malignant effusion, rheumatoid effusion, empyema, parapneumo-
nic effusion, and idiopathic pneumothorax [6]. He divided tuberculous
pleurisy into different stages, which are observations valid to the present
day. Additional insight into tubercoulous pleurisy was provided by
Unverricht [4], who recognized that in many cases spread of the disease
was hematogenous. In malignant pleural effusion, lacobaeus was frequently
able to differentiate between primary and secondary tumors of the chest
wall, pleura, lung, and mediastinum. He furthermore studied rheumatic and
nonspecific parapneumonic effusions. He thoracoscopically examined more
than 100 cases of empyema, many of which were nontuberculous. He also
appreciated that one frequently could not visualize the defect in idiopathic
spontaneous pneumothorax. Numerous publications from many countries
followed emphasizing the diagnostic value of thoracoscopy [5]. Another
highlight in the early history of diagnostic thoracoscopy was presented by
Felix Cova from Italy in his Atlas T/lOracoscopicon, in which most of the
diseases that could be diagnosed by thoracoscopy were presented in the
form of colored illustrati0UoP'trighted Material
414 Loddenkemper
II. Thoracoscopy as a Therapeutic Procedure
in Tuberculosis (Jacobaeus Operation)
As briefly mentioned above, in his first publication Jacobaeus anticipated
the therapeutic value of thoracoscopy and developed the technique of
cauterizing the adhesions between the parietal and visceral pleurae, which
prevented a complete artificial pneumothorax, which was the basis of
collapse therapy for tuberculosis as introduced by Forlanini in 1880.
Jacobaeus stated that during thoracoscopy he found stringlike or
membranous adhesions within the artificial pneumothorax induced for
pulmonary tuberculosis. This stimulated him to work out a method to
remove these pleural adhesions; a process in which "thoracoscopy finds its
real practical determination" [8]. In 1913, he used the technique with two
different ports of entry under local anesthesia. He usually introduced the
thoracoscope through the patient's back either toward the apex or closer to
the diaphragm (Fig. 2), depending on the location of the adhesions on chest
radiography performed after induction of an artificial pneumothorax [9]. He
considered the choice of the second entry site, which was for introduction of
the galvanocautery, to be most important-in most cases, this was in the
anterior axillary line (Fig. 3). Figure 4 shows the technique of thoracoscopic
cauterization Cburning of membranous adhesions between the chest wall
and the compressed lung"), which was a precursor of what we would today
call minimal invasive surgery.
Thoracoscopy was subsequently accepted worldwide, and during the
ensuing 40 years, was employed almost exclusively for lysis of pleural
adhesions by means of thoracocautery. A number of excellent textbooks were
Figure 2 Technique of thoracoscopic cauterization using two points of entry.
(From Ref. 30.)
415
Figure 3 Radiograph demonstrating adhesions to the diaphragm before electro-
cautery. (From Ref 30.)
written on the subject. The monograph written by O. M. Mistal from
Montana, Switzerland, in 1935 (Endoscopy and Pleurolysis) was the most
comprehensive review during this period [10]. Mistal called the technique
"pleuroscopy" (or "pleural endoscopy"), a term first mentioned in 1923 [II]
in one of his references, and seemingly preferred in the French-language
Figure 4 Electrocautery lys(;op,fit!lhterfSM'iitef'i'af-.
ef
30.)
416 Loddenkemper
literature. The book contained an introduction written by Jacobaeus and
numerous illustrations of all the instruments and techniques used up to that
time, as well as an extensive bibliography containing more than 500 references
from Sweden, Denmark, Finland, Germany, Austria, Switzerland, Italy,
France, Spain, Portugal, Great Britain, Canada, and the United States.
The technique was called the "Jacobaeus' operation," and this was
also the title of Felix Cova's book published in Italian in Milan in 1927 [12].
Models of the thorax were mass produced for teaching purposes [13,14], and
even an intrathoracic film was produced to provide information about this
method of treatment (Fig. 5). The publication by Siebert from Berlin on
"Endothoracic Kinematography" could be considered to be a precursor of
today's video endoscopy [15].
III. Thoracoscopy as a Therapeutic Tool
in Nontuberculous Disease
Anton Sattler, in Vienna, was probably the first to use thoracoscopy in the
treatment of patients with idiopathic spontaneous pneumothorax [16]. He
Collabierte
lunge
Thoracoskop
Pneumothoraxraum
Seitliche
beobachtungsvorrichtung
Figure 5 Schematic drawing or "Kinematography" during thoracoscopy. (From
Ref'. 15.)
417
published a large series of papers on this subject between 1937 and 1981.
Many others, again mainly in Europe, used a similar technique for this
indication. With thoracoscopy, bleeding from torn adhesions or broncho-
pleural fistulas could be cauterized by electrocoagulation or laser. Adhesions
preventing the closure of ruptured blebs could be divided, and localized
pleurodesis could be undertaken.
In 1947, E. Kux, in Germany, used thoracoscopy in the therapy of
hyperhidrosis. He published his experiences in 1954 in a book entitled
Thoracoscopic Interventions in the Nervous System. His main indication for
sympathectomy was upper limb hyperhidrosis. He also described vagotomy
for other indications [17]. R. Wittmoser [18] later described similar
procedures.
lacobaeus also described the use of thoracoscopy in patients with
empyema [6]. Subsequently, this procedure has been used only rarely for
empyema therapy [19-21]. Thoracoscopy may indeed be beneficial in
empyema therapy, as it may be helpful by breaking up loculations of pus
and by removing fibrinopurulent membranes with forceps in order to create
one large, unilocular cavity, thus facilitating drainage and irrigation.
Individual case reports have mentioned further therapeutic uses of
thoracoscopy for drainage and obliteration of cysts [22], removal of a
surgical swab following thoracic surgery [19], removal of a small benign
pleural fibroma [23], pericardial fenestration [24], and treatment of
postoperative chylothorax [25].
In 1963, Roche and coworkers, in France, were probably the first to
report on talc poudrage during thoracoscopy as a means of achieving
pleurodesis in chronic, mainly malignant pleural effusions [26]. The
technique is now widely accepted and recommended because of its high
success rate [27].
IV. Further Development of Thoracoscopy
as an Important Diagnostic Tool
There are several reasons for the initial emphasis on thoracoscopy being
primarily a therapeutic tool. For one, the diagnostic potential was certainly
not fully appreciated. For another, the therapeutic challenges at that time
were focused on tuberculosis despite the description by lacobaeus and Key
in 1921 of five thoracoscopically diagnosed intrathoracic tumors, some of
which were subsequently treated by surgery [28].
In North America particularly, thoracoscopy seems to have generated
considerable scepticism on the part of thoracic surgeons, as demonstrated in a
"Letter to the Editor" New York in 1922 [29].
418 Loddenkemper
Commenting on an article by Jacobaeus in the leading surgical journal
Surgery, Gynecology and Obstetrics [30], Lilienthal, speaking on behalf of
American thoracic surgeons, favored the use of open thoracotomy for
diagnostic purposes while agreeing that thoracoscopy might be of some
therapeutic value in the lysis of pleural adhesions. He stressed the series'
relatively high complication rate of20%, and suggested that thoracoscopy was
not a minor surgical procedure. In Jacobaeus' defense, the cases of chronic
empyema, which included three deaths, followed therapeutic thoracoscopy
for tuberculous pleurisy, and thus these complications were incorrectly
attributed to diagnostic thoracoscopy. Equally discouraging to internists
must have been the pronouncement of a prominent American thoracic
surgeon, J. Alexander from Michigan, who in 1937, stimulated by a case of
severe intrathoracic hemorrhage resulting from thoracocautery, warned
against performing this procedure "in a sanatorium by a physician who is not
surgically trained to rapidly open the thorax and close the artery" [31).
However, there were also internists in the United States who
recommended the use of the thoracoscope in pulmonary diagnosis. As
early as 1924, J. J. Singer from St. Louis stated [32]:
For some reason medical men, as distinguished from surgeons, are very prone
to make every effort to prevent operation and 1110St of us doing chest work will
go a long way to escape the surgeon's knife.... When one considers that in the
use of thoracoscopy we have a means by which the pleural cavity can be
explored through a relatively small instrument without rib resection,. . it is
reasonable to expect medical men to make use of this method.
Singer concluded from his early experiences that "the use of the
thoracoscope is a great aid in the diagnosis of chest conditions." Another
internist, R. C. Matson from Portland, Oregon, who in 1936 used a forceps
introduced through a second entry port to obtain biopsies from lung
tumors, states, "Thoracoscopy is undoubtedly one of the most neglected
procedures in clinical medicine" [33].
In the years between 1950 and 1960, with the advent of antibiotic
therapy for tuberculosis, the era of pneumothorax therapy came to an end.
As the number of tuberculous patients in the industrialized countries
gradually decreased, other diseases became more important to the chest
physician. Consequently, a generation of physicians already familiar with
the therapeutic application of thoracoscopy began to use this technique on a
much broader basis for evaluating many pulmonary diseases. Until 1966,
the total world literature included only about 80 publications relating to
diagnostic thoraco copy. However, by 1982, over 160 papers had been
published describing the clinical applications of thoracoscopy in pleuro-
pulmonary diseases [5].
419
The indications for thoracoscopy were greatly expanded by the use of
various biopsy techniques for localized and diffuse lung diseases. Anton
Sattler in Vienna [34] and Hans-Jiirgen Brandt and coworkers in Berlin
[35,36] were the first to apply thoracoscopy to the complete spectrum of
pleuropulmonary diseases. They systematically studied large numbers of
patients and published their data. Thus, the modern development of this
technique and its dissemination throughout Europe can be attributed to
these groups. Swierenga and coworkers in the Netherlands [22] as well as
Viskum and coworkers in Denmark [37] also reported their experience in a
large number of patients.
Swierenga published the first atlas of color photographs of thoraco-
scopy. This monograph depicted spontaneous pneumothorax as well as
mediastinal and chest wall tumors [38]. Brandt and coworkers at
Lungenklinik Heckeshorn in Berlin summarized their experiences of over
3000 diagnostic thoracoscopies in a textbook and atlas of diagnostic
thoracoscopy published in German in 1983 [39]. In 1985, the English
translation by Michael T. Newhouse from Hamilton, Canada, was
published [5]. He had learned of the technique from Roland Keller [40-
42] during a visit to Basle. Keller, in turn, had been taught by Hans-hirgen
Brandt during a I-year visit to Berlin. Praveen Mathur, from Indianapolis,
studied thoracoscopy under Michael Newhouse [43]. Other U.S. experts
who have promoted thoracoscopy include Henri Colt in San Diego [44] and
Yossef Aelony in Harbor City, California [45]. Both learned the technique
from Christian Boutin in Marseille. Boutin's group published their
thoracoscopy experience in 199\ in a book entitled Practical Thoracoscopy
[20]. Other books on diagnostic thoracoscopy were published in Italy by G.
Alcozer and A. Dorigoni in 1984 [46], in Spain by Quetglas and coworkers
in 1985 [47], and in Israel by D. Weissberg in 1991 [48].
Pulmonologists now use two different techniques for the performance
of diagnostic and therapeutic thoracoscopy. One method, extensively
described in the Atlas of Diagnostic Thoracoscopy by Brandt, et al.,
recommends a single entry site, the use of a 9-mm thoracoscope with a
working channel for accessory instruments, an optical biopsy forceps, and
local anesthesia [5]. The other method, as described in the book Practical
Thoracoscopy by Boutin, et al. requires two entry sites-one for a 7-mm
trocar for the examination telescope and the other for a 5-mm trocar for
accessory instruments including the biopsy forceps, and is performed using
conscious sedation or general anesthesia [20]. Both techniques use rigid
instruments, developed, respectively, by Karl Storz GmbH and Richard
Wolf GmbH, two German-based companies.
Flexible bronchoscopes have also been used for thoracoscopy, mainly
by pulmonologists in N o t f u ~ o o #1e'fEJrfl3/ case reports describe this
420 Loddenkemper
technique, which has been termed "pleuroscopy" [49-51]. Presumably, the
flexible bronchoscopes were used because more suitable instruments were
not generally available. Miller and Hatcher [52] and Oldenburg and
Newhouse [40] abandoned this method because of unsatisfactory results and
are in favour of thoracoscopy with rigid instruments. Flexible broncho-
scopes have several disadvantages: They provide less adequate orientation
within the pleural cavity and smaller biopsies. Special semiflexible
instruments with rigid shafts and flexible tips, similar to those used as early
as 1978 by Takeno in Japan [53], are currently under development.
Another approach to simplify thoracoscopy was the proposal by Ash
and Manfredi to use smaller (12- and 14-gauge) instruments [54]. However,
this technique has not been proven to be successful. A more surgically
oriented modification of the thoracoscopic technique was introduced by W.
Maassen in Essen, Germany, and called "direct thoracoscopy." This
procedure uses a mediastinoscope and general anesthesia with double-lumen
intubation [55]. This technique [56], which resembles an open-lung or pleural
biopsy by a mini thoracotomy, has the advantage that it can be performed in
circumstances where a pneumothorax cannot be induced. Janssen and
Boutin described a similar biopsy technique termed "extended thoraco-
scopy" [57].
In 1980, many of the leading European experts gathered in Marseille
at the First International Symposium on Thoracoscopy, which was
organized by Christian BOlltin [58]. The Congress was attended by
participants from 16 countries and addressed aspects of diagnostic
thoracoscopy. Another international symposium was held in Berlin in
1987 [59]. This conference summarized the current state of the art of
diagnostic thoracoscopy as performed by pulmonologists, and highlighted
the widespread use of this procedure in many European countries.
v. Discovery of Thoracoscopy for Minimal Invasive
Thoracic Surgery
In 1978, K. Semm, a gynecologist in Kiel, Germany, pioneered laparoscopic
surgery for various gynecological indications [60]. In 1982, he was also the
first to perform a laparoscopic appendectomy [61]. In the following years,
laparoscopic techniques were introduced for cholecystectomy and for many
other abdominal surgeries [62]. This development was also made possible by
the tremendous advances in endoscopic technology: Newer endoscopic
telescopes provided extremely high optical resolution with very small
diameter instrumentation. In addition, new endoscopic instruments, such as
forceps, scalpels, staplers, laser fibers, and video cameras were developed.
!vledical Thoracoscopy: HiSlOrical Perspective
42/
These advances in abdominal surgery, along with a trend toward
minimally invasive surgery, stimulated thoracic surgeons to try this
technique for surgery for pleuropulmonary disorders. In the early 1990s,
many reports were published almost simultaneously in Europe [63-65], the
United States [66-72], and other parts of the world [73]. The technique was
called "therapeutic" or "surgical thoracoscopy," as well as "video-
controlled" or "video thoracoscopic surgery" or "minimally invasive" or
"video-assisted thoracic surgery" (VATS) [74].
VATS requires general anesthesia with selective endobronchial
intubation and usually at least three points of entry. This is indeed a
surgical procedure for which an operating theater and disposable, often
expensive, instruments are needed. Textbooks describing the technique and
its multiple indications were published [75,76], and in J994, "Practice
Guidelines" for video-assisted thoracic surgery were proposed by the
Society of Thoracic Surgeons [77].
In the United States, where only a few pulmonary physicians
performep thoracoscopy, a heated debate ensued on whether thoracoscopy
should be performed by pulmonologists or be limited to the domain of the
thoracic surgeon [78-80]. In most parts of Europe, this was not a
controversial issue [81,82], as many pneumologists had been performing
thoracoscopies well before the introduction of VATS. In any debate on this
issue, it is most important to differentiate "surgical thoracoscopy" from the
thoracoscopic technique introduced by Jacobaeus and currently performed
by pulmonologists.
VI. Perspectives of Medical Thoracoscopy
The term medical thoracoscopy was introduced to clarify the difference
between both methods [83]. This is defined as the classic Jacobaeus
technique performed under local anesthesia or conscious sedation, via one
or two points of entry, by a pulmonary physician in an endoscopy suite,
using nondisposable rigid instruments. Since medical thoracoscopy is
considerably less invasive, and less expensive, it should be preferable to
VATS as a diagnostic procedure for pleural disease; for example,
undetermined pleural effusions. The technique has been proven to be
easy, safe [84-86], and, in fact, very similar to chest tube insertion using a
trocar [5]. With thoracoscopy, the pleural cavity can be visualized by
introducing an optical instrument, and biopsies can be taken from all areas
of the chest wall, diaphragm, lung, and mediastinum. If indicated, talc
poudrage can be performed prior to chest tube insertion at the completion
of the procedure [27,87]. Copyrighted Material
422 Loddenkemper
However, since the term thoracoscopy is used to describe both the
medical and the surgical procedures, a certain amount of confusion has
arisen. This has possibly led to some unnecessary surgical interventions for
what are, in fact, medical indications. To clarify further the difference and to
avoid confusion in the future, it might be preferable to use the old term
pleuroscopy, which was introduced in 1923 [10,11]. Weissberg has proposed
"for the sake of clarity" that pleuroscopy [48] should be the accepted term
instead of medical thoracoscopy.
Medical thoracoscopy is today primarily a diagnostic procedure, but it
can also be utilized for therapeutic purposes [88]. Pleural effusions are by far
the leading indication for medical thoracoscopy. Medical thoracoscopy can
be helpful for the diagnosis of exudative effusions of unknown etiology, for
staging of malignant mesothelioma or lung cancer [20,27], and for treatment
by talc pleurodesis of malignant or other recurrent effusions [89], or in cases
of empyema [19,20]. Staging and local treatment of spontaneous pneu-
mothorax are also excellent indications for this procedure [20,87]. More
advanced diagnostic indications include biopsies of the diaphragm, lung,
mediastinum, and pericardium. In addition, medical thoracoscopy offers a
remarkable tool for research as a "gold standard" in the study of pleural
disease [83].
Data from Lungenklinik Heckeshorn in Berlin [88] reflect recent
changes in indications for medical thoracoscopy. During the last three
decades, there has been a definite trend, both in absolute and relative
numbers, toward an increased use of medical thoracoscopy for pleural
effusions. This indication now comprises more than 90% of the 170-200
medical thoracoscopies performed per year at our institution (Fig. 6). In the
last three decades, the proportion of thoracoscopies for malignant pleural
effusions rose from 39% in the 1970s, to 48% in the 1980s, and to 68% in the
1990s, whereas the proportion of procedures for tuberculous pleurisy fell
from 24% to 14% and 8%, respectively in the same time period. The
proportion of pleural effusions of other etiologies also decreased in relative
numbers from 37% to 38% and 24%.
There has also been a corresponding decline in thoracoscopies for
indications other than pleural effusions. This can be explained by several
factors. Imaging techniques such as computed tomography (CT) and
magnetic resonance imaging (MRl), which are routinely available today,
very often establish the diagnosis or allow differentiation between malignant
and benign disease in localized lung and chest wall lesions. VATS or
"surgical" thoracoscopy is preferred in these indications, as diagnosis and
simultaneous removal of the lesion can be carried out. Furthermore, the
need for thoracoscopic lung biopsy in diffuse lung diseases has decreased.
This has resulted from the improved diagnostic results of bronchoscopy
423
Pleural effusion
Diffuse lung disease
Localized lung lesion
Chest wall lesion
Mediastinal tumor
Pneumothorax
Postoperative cavity
90
22
8
/---'--"6--,17
01971-79 (n:1.652)
01980-88 (n:1.519)
.1995-96 (n:369)
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Figure 6 Changing patterns of indications (%) for medical thoracoscopy during
the last three decades at Lungenklinik Heckeshorn, Berlin.
techniques such as trans bronchial lung biopsies and bronchoalveolar lavage,
as well as to the development of high-resolution CT (HRCT), which
improves the definition of structural changes (e.g., the degree of fibrosis),
and can sometimes even provide a specific diagnosis (e.g., in histiocytosis X)
[88].
The low number of pneumothorax patients in our series is explained
by the long-standing policy of Lungenklinik Heckeshorn that the Depart-
ment of Thoracic Surgery cares for almost all patients with spontaneous
pneumothorax (about 70 cases per year). However, the thoracic surgeons
now always include the routine use of an optical instrument at the time of
chest tube insertion to inspect the pleural cavity. They perform the
procedure through a cannula, under local anesthesia, which actually means
that they perform medical thoracoscopy [90]! If large blebs, fistulas, or
adhesions which prevent the closure of fistulas are detected, a VATS
procedure is subsequently performed. This approach of "medical"
thoracoscopy at the time of chest tube placement is frequently also used
for cases of empyema, which are traditionally almost exclusively treated by
the thoracic surgeons at Lungenklinik Heckeshorn.
The main therapeutic advantage of medical thoracoscopy is that talc
poudrage can be performed. This is currently the best conservative option
for pleurodesis. This technique is preferred because a very even
distribution of the talc powder to all parts of the pleura can be achieved
[89]. Talc pleurodesis is effusion and also
424
Loddenkemper
in selected cases of recurrent, benign pleural effusions [45], including
chylothorax (91).
In spontaneous pneumothorax, medical thoracoscopy can be easily
applied for diagnostic and therapeutic purposes depending on the skills of
the operator and the available facilities [22,42,53,87].
Thus, one can predict that the future role of medical thoracoscopy will
be mainly for the diagnosis of unexplained pleural exudates after
nondiagnostic pleural fluid analysis, in the application of talc poudrage
for malignant or recurrent pleural effusions, and for the management of
spontaneous pneumothorax. Medical thoracoscopy can also be used to
perform lung biopsy in diffuse lung diseases [5,92], although there is less
need for this indication owing to the development of other diagnostic
techniques. In the European Union, medical thoracoscopy is an intrinsic
component of pulmonary training programs [93]. In the United States,
according to a recent national survey, 5% of pulmonologists perform
medical thoracoscopy [94]. This procedure may become even more popular
once more respiratory physicians become familiar with its indications and
receive training in its application. It is likely that the procedure of
pieuroscopy will become an important part of interventional pulmonology
[95].
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21
Diagnosis of Pleural Pulmonary Disorders
ANDREW G. VILLANUEVA
I. Introduction
JOHN F. BEAMIS, Jr.
Diseases of the pleura and the pleural space constitute a common problem
in the field of chest medicine. The cause of pleural pathology-whether
pleural thickening, pleural effusion, or pneumothorax-can generally be
determined after obtaining a detailed history, radiographic imaging, and
laboratory testing of aspirated pleural fluid. However, after initial
evaluation, including thoracentesis and closed pleural biopsy, up to 25%
of pleural abnormalities remain undiagnosed [1-4]. Medical thoracoscopy is
a useful diagnostic tool for these cases. In this chapter, we will review the
role of medical thoracoscopy, also called pleuroscopy, in the diagnosis of
pleural disorders of unclear etiology. We will discuss indications, diagnostic
yield, limitations, and biopsy techniques.
II. Indications for Diagnostic Medical Thoracoscopy
Common indications for diagnostic medical thoracoscopy are listed in
Table I and are discussed sections of this chapter.
431
432 Villanueva and Beamis
Table 1 Indications for Diagnostic Medical Thoracoscopy (Pie uroscopy)
Recurrent or persistent exudative pleural effusions that have eluded diagnosis by
other means
Suspected mesothelioma
Cytologically negative pleural effusion in a patient with known bronchogenic
carcinoma
Suspected tuberculous pleural effusion not diagnosed after thoracentesis and closed
pleural biopsy
Chest wall or pleural-based mass
Pleural thickening
Recurrent spontaneous pneumothorax
Interstitial lung disease
The most frequent diagnostic indication for thoracoscopy is an unexplained,
recurrent, or persistent pleural effusion, usually an exudative effusion, for
which thoracentesis and closed-needle pleural biopsy have been nondiag-
nos tic [5-11]. In cases of suspected mesothelioma, the diagnosis can be
difficult to make by cytological examination of pleural fluid and histological
examination of the small samples obtained by closed-needle pleural biopsy.
Medical thoracoscopy improves the diagnostic yield for mesothelioma to
above 90%. [7,12]. Pleuroscopy can be used in patients with known
bronchogenic carcinoma who have cytologically negative pleural effusions.
Since only 6% of such patients will have completely resectable tumors [13],
medical thoracoscopy can be used to identify the small group who could
potentially benefit from surgical resection while preventing surgery for the
majority with unresectable disease. Since the diagnostic yield of a c1osed-
needle biopsy is 70-90% for tuberculous effusions, medical thoracoscopy is
usually unnecessary to establish the diagnosis. Thoracoscopy may be useful,
however, in difficult diagnostic situations, when lysis of adhesions is
necessary, or when larger amounts of tissue are necessary for determination
of drug resistance [14]. Less common indications for medical thoracoscopy
include the presence of a chest wall or pleural-based mass and pleural
thickening without associated pleural effusions. In cases of recurrent
spontaneous pneumothorax, thoracoscopy can be done to determine the
cause of the pneumothorax, to assess for the presence of blebs or bullae in
the affected lung, and to plan treatment [15]. Finally, although lung tissue is
generally obtained by transbronchial biopsy or by thoracic surgeons using
video-assisted thoracic surgery (VATS), investigators have reported the use
medical thoracoscopy to obtain lung tissue in patients with interstitial lung
diseases [16-19].
Diagnosl ic Medica/ Thoracoscopy
433
A. Pleural Effusions of Unknown Etiology
Pleural effusions are a common problem worldwide with an annual
incidence in the United States alone of approximately I million patients
per year [20]. The possible causes of pleural effusions are numerous [20,21],
but the etiology in a particular patient can be determined without the need
for medical thoracoscopy in most cases. Indeed, thoracentesis, a minimally
invasive procedure, remains the most useful procedure for defining the cause
of a pleural effusion. Pleural fluid cellularity, appearance, and chemistry,
along with the clinical presentation, can be used to establish a presumptive
or definitive diagnosis in about 75% of patients [22]. When no diagnosis has
been obtained after an initial thoracentesis that includes a pleural fluid
marker for tuberculosis and cytology, the next steps may include
observation, bronchoscopy, and closed-needle biopsy of the parietal pleura
[20]. Bronchoscopy is useful in revealing the cause of a pleural effusion only
if there is a concomitant parenchymal infiltrate, hemoptysis, massive
effusion, or mediastinal shift toward the side of the effusion [23,24].
Although closed-needle biopsy of the pleura has been considered to be an
important diagnostic tool since its first description in 1955 [25], controversy
regarding its role in today's practice has arisen primarily because of the
availability of medical thoracoscopy [26-28]. It is most useful in the
diagnosis of pleural tuberculosis and less so for pleural malignancy. A
review by Tomlinson and Sahn [29] of over 2500 pleural biopsy results
published in the medical literature noted a yield of 75% for pleural
tuberculosis and only 57% for pleural carcinoma.
Studies describing the diagnostic yield of medical thoracoscopy
consistently show an improvement in the yield compared to thoracentesis
and closed pleural biopsy (Table 2). Loddenkemper et al. [14] prospectively
compared the yield of pleural fluid analysis and closed pleural biopsy with
thoracoscopy in 100 patients. Of the 67 patients with either tuberculous
effusions or malignant pleural effusions, the yield for pleuroscopy was 96%
versus 73% for pleural fluid analysis and closed pleural biopsy. Boutin et al.
[7] found a sensitivity of 87.3% in the diagnosis of 150 malignant pleural
effusions compared to 23% for pleural fluid cytology and 40% for c1osed-
needle biopsy. In a large retrospective study, Enk and Viskum [32] found
that of the 387 patients undergoing medical thoracoscopy for pleural
effusions, 171 had malignant pleural effusions (MPEs). In these patients, the
yield by pleuroscopy was 80% compared to 62% by pleural fluid cytologic
examination. Martensson et al. [33] reported a sensitivity of 80% for MPEs,
and noted that thoracoscopy revealed tumor in 37 of 47 patients (79%) with
MPEs and negative cytology. Menzies and Charbonneau [8] performed
pleuroscopy on 86 patients with pleural effusions undiagnosed after
Table 2 Studies Reporting the Diagnostic Yield of Medical Thoracoscopy for Pleural Effusions of Unknown Etiology"
-4
Uv
-4
Number Yield of thoracentesis (T) and/or closed-
Authors (ref.) Year of cases Diagnostic yield needle pleural biopsy (CPB)
Canto et al. [5] 1977 172 94% for MPE All cases previously undiagnosed after
T; CPB not mentioned
Loddenkemper et al. 1978 100 96% for TB or MPE T and CPB: 73% for TB or MPE
[14]
Oldenburg and 1979 38 88% T: All 38 nondiagnostic
()
Newhouse [31] CPB: 16%
0
Boutin et al. [7] 1981 215 87.3% for MPE T: 23% for MPE
"b

CPB: 40% for MPE
':
Enk and Viskum [32] 1981 387 80.1 % for MPE T: 62% for MPE
CD
CPB not mentioned
0..
Martensson et al. [33] 1985 334 80% for MPE T: 43% for MPE
s:
(Thoracoscopy revealed tumor in 37 of
Q)
CD 47 [79%] with MPE and negative

cytology)
Menzies and 1991 86 96% (44% MPE and 52% benign disease) All had been undiagnosed after T and
Charbonneau [8] CPB
Hansen et al. [34] 1998 136 90.4% All had been undiagnosed after three

thoracenteses

Wilsher and Veale 1998 58 80% overall All patients had been undiagnosed after
[35] 90% if only those in whom full pleural T and CPB
l::
""
""
access was achieved (51 patients)

$::)
Blanc et al. [30] 2002 149 93.3% CPB: 25% ::l
$::l...
MPE, malignant pleural effusions; TB, tuberculous effusions.
b;,
"" aStudies in which thoracoscopy was performed using general anesthesia were excluded.
$::)
::l
c;.
Diagnosl ic MedicaL Thoracoscopy
435
thoracentesis and pleural biopsy. Thirty-eight patients (44%) were
diagnosed with cancer and 45 patients (52%) were diagnosed with benign
disease after medical thoracoscopy. They reported a sensitivity of 91 % and a
specificity of 100%. Blanc et a!. [30] retrospectively compared the yield of
closed-needle pleural biopsy with medical thoracoscopy, and found that
thoracoscopy yielded a precise diagnosis in 43 of 90 cases (47.8%) in which
prior closed pleural biopsy was nondiagnostic, and corrected the diagnosis
given by needle biopsy in Il of 30 patients (36.7%) thought to have pleural
malignancy. The data in these studies [5,7,8,14,30-35] revealed diagnostic
yields of 80-96% for exudative pleural effusions of unknown etiology, and
therefore support the use of medical thoracoscopy in evaluating pleural
effusions that remain undiagnosed after the performance of thoracentesis
and closed-needle pleural biopsy.
The increased diagnostic yield of medical thoracoscopy compared to
pleural fluid cytology and closed-needle pleural biopsy is explainable by the
improved visualization and larger biopsy sample size attained during
pleuroscopy [19]. Cytological examination of the pleural fluid may fail to
diagnose a malignant pleural effusion either because there is insufficient
exfoliation of cells from the pleural surfaces into the pleural effusion or
because there are a lack of cytological characteristics in the collected fluid to
make an accurate diagnosis. The closed-needle pleural biopsy technique is
limited by restricted access and lack of direct visualization of the target
lesions. In patients with metastatic pleural disease, 32-47% have disease
inaccessible to closed-needle biopsy [19J.
Canto et al. [36] reported that of 78 patients with proven metastatic
disease to the pleura, only 53% had involvement of costoparietal pleural
areas accessible to closed-needle pleural biopsy. These investigators also
reported [36-38] that in 84% of patients studied, the metastases were in the
lower hemithorax, on the lung surface or the diaphragm, and were poorly
accessible or totally inaccessible to closed-needle biopsy. In autopsy studies,
investigators have reported that the parietal pleura is less frequently
involved with metastatic pleural disease than the visceral pleura [39,40].
Medical thoracoscopy can overcome these limitations because of the direct
access to the pleural cavity, visualization of both the parietal and visceral
pleura, and larger sizes of the biopsy samples. If full visualization of the
pleural space is not achieved during thoracoscopy, the diagnostic accuracy
of the procedure greatly diminishes [30,35].
436
B. Malignant Pleural Effusions
Carcinoma Metastatic to the Pleura
Villanueva and Beamis
Malignant disease involving the pleura is the second leading cause of
exudative pleural effusions after parapneumonic effusions [20). Lung cancer,
breast cancer, lymphoma, and ovarian cancer account for approximately
80% of tumors metastatic to the pleura [41,42]. Other types of neoplasms
that can metastasize to the visceral or parietal pleura include sarcoma,
melanoma, and carcinomas of the uterus, cervix stomach, colon, pancreas,
and bladder; the primary site of malignancy is unknown in about 6% of
cases [41,42] (Figs. 1-3). MPEs represent the leading diagnostic indication
for medical thoracoscopy [II]. The yield for diagnosing MPE by medical
thoracoscopy ranged from 80 to 96% in reported series [5,7,8,14,31-35].
Loddenkemper reported that the combined yield for pleural fluid cytology,
closed-needle pleural biopsy, and medical thoracoscopy was 97% [II].
Figure 1 Parietal pleura studded with metastatic lung cancer. Anthracotic pigment
can be seen on the lung surface. A chest tube is visible in the lower right of the figure.
Diagnostic Medical Thoracoscopy
437
Figure 2 Metastatic adenocarcinoma of breast origin involving the parietal pleura.
Pleural fluid is present.
The main advantage of pleuroscopy is its ability to achieve early
diagnosis of MPE when pleural fluid cytology and closed-needle biopsy have
failed. It allows inspection of approximately 75% of the visceral pleural
surface as well as of the parietal pleural surface. Boutin reported that in 85%
of patients with MPEs, thoracoscopy revealed visual features suggestive of
malignancy, including nodules, polypoid lesions, localized masses, thickened
pleural surface, and poorly vascularized pachypleuritis [43J. Since appear-
ances can be misleading-some malignancies may appear inflammatory,
whereas some inflammatory lesions can look like tumors-macroscopic
diagnoses must always be confirmed by histology [7J. Biopsies can be
visually directed in instances where tumor deposits appear to be localized. In
addition, biopsy specimens can be obtained from multiple sites and are of
greater size and depth; factors that improve the diagnostic yield [8]. The
larger sample sizes increases the ability of the pathologist to make an
accurate diagnosis; the can better differentiate
438
Figure 3 Metastatic melanoma involving the parietal pleura with hyperpigmented
lesions. A needle used for instilling lidocaine prior to chest tube insertion is visible.
malignant mesothelioma from adenocarcinoma and can perform special
studies such as hormone receptor assays on the tissue.
Mesothelioma
In the past, pathologists found it difficult to make a definitive diagnosis of
malignant mesothelioma without large samples obtained during open
thoracotomy or autopsy. As the incidence of the disease has increased
and with the availability of immunohistochemistry techniques, pathologists
are better able to make the diagnosis. By permitting direct visualization of
lesions, pleuroscopy facilitates the choice of biopsy sites and allows accurate
assessment of the degree of involvement of the diaphragmatic, parietal,
visceral, and mediastinal pleura [44] (Fig. 4). Boutin reported a sensitivity of
thoracoscopic biopsy of 98% (185 of 188 patients) for the diagnosis of
malignant mesothelioma compared with 28% (49 of 175 patients) for pleural
fluid cytology, 24% (33 of 135 patients) for closed-needle pleural biopsy, and
100% (9 of 9 patients) for surgical biopsy [45].
439
Figure 4 Diffuse involvement of the parietal pleura with malignant mesothelioma.
c. Tuberculous Pleural Effusions
Since tuberculous pleural effusions can be diagnosed in 70-90% of cases
with pleural fluid analysis and closed-needle pleural biopsy [14], including
culture for Mycobacterium tuberculosis, medical thoracoscopy is usually
unnecessary to establish the diagnosis. Indeed, Boutin et al. reported that in
their experience thoracoscopy played no significant role in the diagnosis of
this disease, and that the discovery of tuberculous granulomata on
thoracoscopic biopsy was usually fortuitous [43]. They nonetheless
described the endoscopic appearance as a grayish white thickening of the
whole parietal and diaphragmatic pleurae, particularly along the costover-
tebral gutter (Fig. 5). Loddenkemper reported a diagnostic yield of 93% (30
of 32 patients) based on histology and/or culture with pJeuroscopy alone
and 97% (31 of 32 patients) with pleural fluid analysis plus pleuroscopy
compared to 84% (27 of 32 patients) with pleural fluid analysis plus closed-
needle pleural biopsy [14]. Copyrighted Material
440
Villanueva and Beam.is
Figure 5 Characteristic grayish white thickening of the parietal pleura and
diaphragmatic pleura seen in tuberculous pleurisy. Note the presence of adhesions.
D. Differentiating Benign from Malignant Causes of Pleural
Effusions
In cases of pleural effusions that are neither malignant nor tuberculous,
thoracoscopy may provide clues to the etiology. For example, hyaline and
calcified asbestos pleural plaques have distinctive endoscopic characteristics
in that they appear smooth and white and are difficult to biopsy because of
their hard consistency [19,43]. In rheumatoid effusions, the visceral surface
shows a nonspecific inflammation and the parietal surface has a gritty
appearance [19,46].
The main reported value of thoracoscopy, however, is not to make a
specific benign diagnosis (other than tuberculosis) but rather to exclude
malignancy as the cause. Several investigators have reviewed the benign
diagnoses made during thoracoscopy, and although none of them focused
primarily on the outcome of these patients, some reported follow-up data.
Canto et al. [5] described 51 of 208 thoracoscopic biopsies showing normal
pleura, acute pleurisy, or subacute chronic pleurisy; they noted eight
patients in which tumor was not found but later died of generalized
carcinomatosis (a false-negative rate of 6% for MPEs). Boutin [7J reported
that 65 of 215 patients undergoing thoracoscopy had benign causes such as
congestive heart failure, benign asbestos effusions, infectious pleuritis,
cirrhosis, and "idiopathic chronic pleural effusions" (40 patients). These
patients were followed for a least 1 year by mail and telephone inquiry; no
specific mention was made of their outcome. Enk and Viskum [32J reported
on 186 patients diagnosed with nonmalignant pleural effusions from
pleurisy of unknown origin, congestive heart failure, pneumonia, rheumatic
pleurisy, pulmonary infarction, uremia, and cirrhosis. Nonspecific inflam-
441
mation was found on histology in 129 biopsies; no follow-up information on
these patients was provided, although the investigators did cite a 90%
sensitivity in detecting MPEs. In the series reported by Menzies and
Charbonneau [8], 53 of 95 patients were diagnosed with benign disease,
including asbestos-related effusion, chylothorax, Dressler's syndrome,
rheumatoid effusion, lupus pleuritis, pulmonary embolism, congestive heart
failure, and pneumonia; the largest cause of benign effusions was
"idiopathic" (22 of 53 patients). The investigators reported that 94% of
these patients were alive after follow-up of at least I year. They calculated a
negative predictive value of 93% for diagnosing MPE. Hansen et al. [34]
found 56 of 147 patients diagnosed with benign disease after medical
thoracoscopy, 45 of whom had "unspecific inflammation." No follow-up
data were provided. They reported a sensitivity of 88% and negative
predictive value of 78% for malignancy. In a small series, Wilsher and Veale
[35] reported that 5 of 51 patients (10%) had false-negative results for
malignancy. Finally, Blanc et al. [30] retrospectively reported that 57 of 149
thoracoscopies revealed "nonspecific inflammation," and that no diagnosis
other than benign pleural effusion was made during follow-up of 12-70
months. In our experience of approximately 30 patients with the histological
diagnosis of "chronic pleuritis," the outcome has also been favorable, with
only one patient eventually developing an MPE (personal observation).
Despite imperfect data, the information reported in series of patients
undergoing diagnostic medical thoracoscopy suggests that although
pleuroscopy often cannot give a specific histological diagnosis for
nonmalignant, nontuberculous effusions, it is an effective and reliable tool
in differentiating benign from malignant causes of pleural effusions. There is
general agreement, however, that pleuroscopy should not replace pleural
fluid chemistry, microbiology, cytology, and, in appropriate cases, closed-
needle pleural biopsy as preliminary diagnostic procedures [19].
E. Diagnosis of Pleural Thickening
The vast majority of patients undergoing medical thoracoscopy have pleural
effusions with or without pleural thickening. Since pleuroscopy requires the
induction of a pneumothorax, the presence of pleural fluid allows this to be
done safely without great risk of injuring the lung. Few series include
patients undergoing thoracoscopy solely for the diagnosis of pleural
thickening in the absence of a pleural effusion. Investigators reporting
such patients [47,48] performed thoracoscopy under general anesthesia
utilizing double-lumen intubation. Colt [47] noted that 2 of 52 patients
undergoing thoracoscopy had pleural thickening, but did not specify the
final diagnoses in these reported that 9% of their
442
182 patients had a pleural mass as the indication for thoracoscopy; no
specific diagnoses were noted.
F. Recurrent Pneumothorax
Although the main purpose of medical thoracoscopy for spontaneous
pneumothorax is therapeutic-chest tube drainage, pleurodesis, and
coagulation of blebs and bullae-the technique can also be considered to
be diagnostic, since it allows inspection of the lung and pleural cavity
[11,15]. A complete inspection may detect a lung parenchymal laceration, a
malpositioned chest tube within lung parenchyma responsible for a
continued air leak, or visceral and parietal pleural abnormalities such as
endometriosis, congenital cysts, and cavitating or nodular lesions in patients
with granulomatous disorders [15]. The most likely abnormalities are blebs
and bullae, although up to 30% of patients may have normal findings [49]. A
more detailed discussion on the classification of the thoracoscopic findings
in spontaneous pneumothorax and therapeutic approach appear in Chapter
23.
G. Parenchymal Lung Disease
Biopsy of the lung is commonly done by thoracic surgeons performing
video-assisted thoracic surgery, but it has also been described using cup
biopsy forceps during medical thoracoscopy. Boutin et al. reported their
experience with 75 patients with diffuse or localized parenchymal disease in
whom thoracoscopy was used to obtain pulmonary parenchymal specimens
[16]. A biopsy forceps was employed and effective hemostasis was achieved
by electrocautery. This thoracoscopic technique preserved the histological
structure of tissues and provided biopsy specimens larger than those
obtained by bronchoscopy. The overall sensitivity was 92%, ranging from
70% for peripheral lesions to 100% for diffuse diseases. Complications
included pneumothorax in 8 patients and low-grade fever in 11. Another
study reported successful lung biopsies with excellent hemostasis and no air
leakage in 18 patients using a cryoprobe to seal the forceps biopsy site [50].
Despite these reports, we cannot recommend the routine use of medical
thoracoscopy for parenchymal lung biopsy until there is a larger reported
experience about the yield and safety of the procedure. Patients requiring
thoracoscopic lung biopsies should still be referred to the thoracic surgeons
or medical thoracoscopists with extensive experience.
III. Limitations of Medical Thoracoscopy
443
Medical thoracoscopy is a safe technique in the appropriate patient. The
mortality risk is 0.09% [19] and the complication rate is low; Menzies and
Charbonneau reported a major complication rate of 1.9% and a minor
complication rate of 5.6% [8]. The major anatomical contraindication is a
lack of a pleural space due to dense pleural adhesions. Medical contra-
indications include poor performance status, hypoxemia not due to a pleural
effusion, severe pulmonary fibrosis, uncorrectable coagulation disorder,
severe cardiac disease, and mechanical ventilation [19].
If the parietal and visceral pleurae are well visualized during
thoracoscopy, the diagnostic yield is excellent, especially for diagnosing
MPEs. False-negative results are generally due to poor visualization of the
pleural space because of pleural adhesions. Wilsher and Veale [35] reported
a sensitivity of 80% in the diagnosis of pleural malignancy, which increased
to 90% if only those cases in which full pleural access was achieved were
considered. Blanc et al. [30] reported that they were unable to visualize the
pleura in 6 of 149 cases; four were later diagnosed with malignancy and two
with tuberculous effusions.
IV. Techniques
A. Biopsy of the Parietal Pleura
Our recommended pleural biopsy technique is a standard technique that has
been described in detail by Mathur and Loddenkemper [19] and Astoul and
Boutin [51]. Once the pleural cavity is entered, almost complete visualization
of the parietal and visceral pleurae is possible if there are no pleural
adhesions; only the posterior and the mediastinal side of the lung cannot be
seen. Inspecting the pleura and performing biopsies are the two essential
steps of the examination. The thoracoscopist must be knowledgeable about
the anatomy of the thoracic cavity. In the right chest, orientation can be
achieved by locating the point where the three lobes meet; that is, the
junction of the oblique fissure and horizontal fissure. On the left, the oblique
fissure can be used for orientation. The diaphragm can be recognized by the
respiration-related movement. Rib, intercostal muscles, fat, blood vessels,
and nerves are usually well distinguished. The heart and the great vessels are
identified by pulsations that are occasionally transmitted to adjacent parts
of the lung. In its normal state, the pleura is transparent, allowing
visualization of many structures through it. Variable amounts of anthracotic
pigment can be seen within the visceral pleura and the surface of the lung.
Fatty collections are These are long, yellowish
444
plaques located along the ribs and around the pericardium and diaphragm.
Malignancies often have a characteristic appearance, but it may be
impossible to differentiate inflammation from malignancy on visual
inspection. Multiple biopsies should therefore be taken from suspicious
areas.
Parietal pleural biopsies can be performed using illuminated forceps
through a single point of entry (Fig. 6). Before pleural biopsy, the rib and
intercostal space should be identified with a blunt probe, such as the closed
forceps. If the pleura is thick, the rib will feel hard compared with the
spongy intercostal space. When the pleura is thick, the biopsy is simple, with
minimal risk of injuring the intercostal arteries. In contrast, when the pleura
is thin, the biopsy should be performed against one of the ribs (Fig. 7).
Typically four to six biopsies of a suspicious pleural lesion will establish a
diagnosis. When malignancy is suspected but the endoscopic findings are
nonspecific, the number of biopsies should be increased to between 10 and
12 from a variety of areas on the pleural surface.
Figure 6 Optical biopsy forceps used through a single point of entry to obtain
tissue samples of the parietal pleura.
445
Figure 7 Parietal pleural biopsy using the optical biopsy forceps. The operator
uses the forceps to grasp parietal pleura and obtain a sample using a shearing
motion.
B. Biopsy of the Visceral Pleura and Lung Parenchyma
To biopsy the visceral pleura or to obtain a lung biopsy using forceps, a
second entry point is required so that an insulated forceps connected to
electrocautery can be used. Whereas the initial trocar used to enter the
pleural space is usually 7 mm in diameter and 100 mm in length, the second
trocar is insulated and is 5mm in diameter and 100 mm in length. The S-mm
double-spoon insulated coagulating forceps is used through this second
trocar for visceral pleural or lung biopsies. Power should be sufficient to
coagulate the cut surface of the lung without destroying .the histological
features of the specimen. A setting of approximately 100 W is appropriate.
The forceps is used to grasp the selected site along the surface of the lung,
avoiding the edges of lobes or fissures to minimize iatrogenic air leaks, and
to pull the specimen is applied.
446
C. Rigid Versus Flexible Thoracoscopes
Medical thoracoscopy is performed using a rigid endoscope. The use of
fiberoptic broncboscopes in the pleural space has been reported previously
(52), and although it was reportedly feasible, the flexibility of the instrument
made maneuvering and steering within the pleural cavity difficult. Old-
enburg and Newhouse (31) compared the use of thoracoscopic examination
with a flexible versus a rigid endoscope and found that the rigid instrument
was superior because of the greater diagnostic accuracy. They reported that
biopsy samples were significantly larger and easier to obtain using the rigid
thoracoscope. Ernst et al. (53) recently reported the use of a novel semirigid
pleuroscope. The prototype appeared to be easy to maneuver and allowed
adequate biopsy samples of the parietal pleura. Whether it offers any
meaningful advantage over current rigid thoracoscopes remains to be seen.
v. Conclusion
Medical thoracoscopy, which was initially described by lacobaeus (54-56),
has emerged as a valuable tool for the chest physician to evaluate pleural
diseases. Also known as pleuroscopy, medical thoracoscopy allows
thorough inspection of the pleural space and visually directed biopsies of
the pleura. The main diagnostic indication for pleuroscopy is for the
investigation of pleural effusions for which no cause has been found despite
initial testing, including pleural fluid analysis and closed-needle pleural
biopsy. Several studies have shown the increased yield that thoracoscopy
provides, especially if tbe underlying cause is pleural malignancy; the
sensitivity and specificity of pleuroscopy for the diagnosis of malignant
pleural effusions is high according to several studies cited in this chapter. It
is also useful in differentiating benign effusions from malignant effusions
with a high degree of certainty, provided that inspection of the pleural space
and biopsy of the pleura were adequate. Diagnostic medical thoracoscopy
should therefore be considered in those 25% of cases of pleural effusions in
which the etiology is unknown.
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22
Therapy for Malignant Conditions
JULIETTE L. WOHLRAB and CHARLES A. READ
Georgetown University Medical Center
Washington, D.C., U.S.A.
Malignant pleural effusions are the second leading cause of exudative
pleural effusions following parapneumonic effusions. The incidence in the
United States is greater than 150,000 cases per year [I]. Although some
malignant effusions may respond to chemotherapy, the course is often
relentless leading to symptoms of dyspnea, chest pain, and malaise.
Therapeutic thoracentesis provides relief, but the effusion often recurs
within days necessitating frequent procedure-related visits [2]. Medical
thoracoscopy is an alternative modality that can aid in both the diagnosis
and management of malignant pleural effusions. Medical thoracoscopy
allows visually directed parietal pleural biopsies and pleurodesis in a
minimally invasive manner using intravenous sedation and local anesthesia.
It can be performed in an endoscopy suite or operating room.
II. Historical Perspectives
lacobaeus introduced thoracoscopy in the early 1900s for the treatment of
adhesions during collapse [3]. It was subsequently
45/
452
Woh/rab and Read
used for the treatment of pneumothorax and tuberculosis mostly in Europe,
where additional advances in technique were made. These advances
combined with improved endoscopic instruments and video technology
triggered resurgence in the United States and prompted the development of
guidelines for the use of thoracoscopy [4]. Various instruments, including
flexible fiberoptic bronchoscopes, were used to visualize the pleural cavity.
Rigid thoracoscopes provided the best visualization and access [5,6].
Bethune first used insufflated talc to achieve pleurodesis in 1935 [7].
Medical thoracoscopy is indica ted for both diagnostic and therapeutic
management of malignant pleural disease. It is often needed in patients with
advanced malignant diseases, and should be regarded as palliative treatment
for the relief of dyspnea. Patients with recurrent undiagnosed exudative or
known malignant effusions should undergo thoracoscopy (Figs. I and 2).
Patients requiring pleurodesis should demonstrate improvement in symp-
toms and lung reexpansion after thoracentesis. The indications are listed in
Table 1. Not all patients can tolerate medical thoracoscopy; therefore,
careful patient selection is vital. Patients should have a relatively good life
expectancy and performance status with an accessible pleural space and no
medical contraindications to thoracoscopy. The contraindications are listed
in Table 2.
IV. Equipment
A IO-mm rigid thoracoscope (Wolf Medical Instruments Corp. Rosemont,
IL) with a light source and 5-mm operating channel for accessory
instruments is used for single-incision entry. The thoracoscope is inserted
through a lO-mm trocar, which consists of an obturator and a blunt
cannula. The accessory instruments include a biopsy forceps, a catheter for
irrigation and suction, a talc atomizer, and an electrocautery hook. A 28 or
32 French chest tube connected to a Pleurovac system is also used. Other
equipment includes sterile sheets and physicians' gowns, needles, syringes,
scalpel, sutures, compresses, forceps, needle holders, and hemostats. A
thoracostomy pack and scrub pack as well as a Mayo stand are also used.
Mediccd Thoracoscopy: Malignant Conditions
453
Figure 1 Posteroanterior radiograph of the chest demonstrating a large right
pleural effusion secondary to metastatic breast carcinoma. Diffuse sclerotic changes
due to bone metastases are also noted.
v. Theory of Application
Although nearly all neoplasms have the potential to involve the pleura, lung
carcinoma is the most common. Approximately 36% of malignant effusions
are due to lung cancer followed by breast cancer at 25% [8]. The remaining
effusions are due to malignancies such as leukemia, lymphoma, and ovarian
and gastrointestinal carcinomas. No primary malignancy is identified in 5-
10% of malignant effusions [9]. There are several mechanisms by which
cancer can cause a malignant pleural effusion. Tumor emboli to the visceral
pleural surface with s o n ~ y r ~ tflfafBftcJIarietal pleura are the most
454
Wah/rab and Read
Figure 2 Posteroanterior radiograph of the same patient after medical thoraco-
scopy and talc pleurodesis. Diffuse inflammatory changes and a chest tube are noted
in the right hemithorax.
Table 1 Indications for Medical Thoracoscopy
Diagnostic
Exudative recurrent effusion undiagnosed after thoracentesis and/or closed-needle
biopsy
Staging of malignant mesothelioma and lung carcinoma
Therapeutic
Recurrent symptomatic effusion with positive malignant cytology or pleural
biopsy
Relief of symptoms after thoracentesis
No radiographic evidence of conditions that might prevent lung reexpansion such
as visceral pleural entrapment or atelectasis due to bronchial occlusion
Medical Thoracoscopy: Malignant Conditions
Table 2 Contraindications for Medical Thoracoscopy
455
Absolute
Inability to lie in the lateral decubitus position
Previously attempted ipsilateral pleurodesis
Uncorrectable bleeding diathesis
Mechanical ventilation
Pulmonary arterial hypertension
Dyspnea or hypoxemia unrelated to pleural effusion (i.e., severe parenchymal
disease)
Relative
Poor general health of the patient
Life expectancy less than I month
Uncontrollable cough
Severe hypoxemia or hypercapnia
Severe cardiac disease
Previous contralateral pleurodesis
common causes [10]. Direct mechanisms include local effects of the tumor
such as lymphatic obstruction and direct invasion of the pleural space
leadiQg to increased permeability and inflammation. Paramalignant effu-
sions are not caused by pleural involvement of the tumor but by indirect
mechanisms that are tumor related. These include pulmonary embolism,
chylothorax secondary to thoracic duct obstruction, parapneumonic
effusion secondary to postobstructive pneumonia, and transudative effusion
secondary to postobstructive atelectasis and/or low plasma oncotic pressure.
Treatment with radiation and chemotherapy may also lead to pleural
effusions.
Recurrent malignant pleural effusions lead to symptoms of dyspnea,
cough, and chest pain. The effusions can be managed by serial thoracentesis,
chest tube thoracostomy drainage, pleuroperitoneal shunt, pleurectomy, or
pleurodesis. Pleurodesis is a technique that promotes adhesion of the
visceral and parietal pleurae in an attempt to obliterate the pleural space.
This prevents fluid reaccumulation and can enhance a patient's quality of
life by relieving dyspnea. Pleurodesis can be achieved chemically or
mechanically. Chemical agents include talc, tetracycline, doxycycline, and
bleomycin. Talc currently has gained favor as the agent of choice [11]. Talc
is effective, is inexpensive, and has few adverse effects or long-term
complications [12]. Copyrighted Material
456 Wohlrab and Read
VI. Technique
Each patient is carefully evaluated prior to the procedure with a complete
medical history and physical examination. Basic preoperative laboratory
evaluation includes a complete blood count, coagulation studies, chemistry
panel, electrocardiogram, chest radiograph, pulse oximetry, and/or arterial
blood gas. Appropriate informed consent regarding risks and benefits as
well as alternative therapies is obtained. Large-volume thoracentesis is often
performed 1-2 days prior to the procedure to relieve symptoms and to
estimate the potential for lung reexpansion. On the day of the procedure, the
patient is brought to the operating room or bronchoscopy suite. The patient
is placed in the lateral decubitus position with the affected hemithorax
upward. Cushioned support limits the patient's movement. Blood pressure,
electrocardiogram, and cutaneous oxygen saturation is continuously
monitored. Supplemental oxygen is administered to maintain a saturation
greater than 92% and the patient continues spontaneous respiration.
Intravenous sedation with fentanyl and midazolam or propofol is given as
needed for patient comfort. After sterile preparation, drapes are applied.
Local anesthesia is achieved with 10-30 mL of 2% lidocaine (Xylocaine)
infused into the fifth or sixth intercostal space down to the parietal pleural in
the mid axillary line. A single 2-cm incision is made along the superior
margin of the rib, and blunt dissection is performed to the pleural space.
Once the hemostat punctures the parietal pleura, a pneumothorax is induced
and a finger is inserted to assess the adequacy of the pleural space. The
trocar is then inserted through the incision, and any remaining pleural fluid
is evacuated with a blunt tip suction catheter. The trocar is left open and the
pleural space is evaluated with a rigid thoracoscope (Fig. 3). Parietal pleural
biopsies are taken when indicated, adhesions are lysed, and 2-6 gs of dry-
heat sterilized, United States Pharmacopeia--eertified, asbestos-free talc is
insufflated under direct visualization into the pleural space with uniform
distribution (Figs. 4 and 5). The thoracoscope is removed, and a 28-32
French chest tube is inserted through the trocar. The trocar is removed, the
chest tube is sutured in place, and the wound is closed. The chest tube is
placed to 20 cmH
2
0 suction and is removed when the drainage is less than
100 mL per day.
Medical thoracoscopy has been valuable in both diagnosis and treatment of
malignant pleural effusions. Any patient with a new, undiagnosed pleural
effusion should first undergo thoracentesis for evaluation. Pleural fluid
457
Figure 3 Rigid thoracoscope used to visualize the pleural space. The trocar is
positioned in the sixth intercostal space allowing direct access for the thoracoscope
with single-incision technique.
cytology will be diagnostic for malignancy in 60-90% depending on the
extent of pleural involvement [9,13,14]. If the initial cytology is nondiag-
nostic and the effusion reaccumulates, a repeat thoracentesis combined with
a closed pleural biopsy can be performed. The diagnosis of malignant
pleural disease by needle biopsy is limited because of the blind nature of the
procedure and the nonuniform distribution of pleural involvement by the
neoplastic cells. The yield is reportedly 40-79% [14-16]. Visually directed
parietal pleural biopsies by thoracoscopy or thoracotomy have a much
higher yield. Biopsies can also be taken from the diaphragm, mediastinum,
and lung [17]. Medical thoracoscopy has been shown to have a higher
diagnostic yield (95%) than cytology and closed-needle biopsy alone or in
combination [17]. False-negative examinations are due to nonrepresentative
biopsies or extensive adhesions preventing proper access to the malignant
area [5]. Less than 10% of undiagnosed effusions remain elusive after
thoracoscopy [5]. In those cases, video-assisted thoracoscopic surgery
(VATS) under general anesthesia with single-lung ventilation or thoracot-
omy may be indicated for t ~ i f t e Material
458
Wohlrab and Read
Figure 4 Adenocarcinoma of the lung with extensive parietal pleural involvement.
Multiple nodules, hypervascularity, and lymphangitis are noted.
Medical thoracoscopy also has a role in staging lung cancer and
malignant mesothelioma. Canto reviewed a series of 78 patients. Each had
lung cancer with an associated pleural effusion and underwent thoraco-
scopy. No evidence for metastatic pleural disease was found in 14 patients,
thereby allowing full surgical resection in 6 of those who were otherwise
good surgical candidates [18]. The extent of pleural involvement can also be
assessed. This does not correlate with survival, as might be expected, which
is more likely related to the aggressiveness of the tumor [19].
Thoracoscopy is useful in mesothelioma to differentiate benign
asbestotic pleural effusions from malignant disease and for more accurate
staging. The diagnostic yield from pleural fluid is 26%, from closed-needle
biopsy 21 %, and from thoracoscopic biopsy 98% [20]. A visual assessment
of the pleura allows determination of visceral pleural involvement. This is an
important prognostic indicator. Median survival is 33 months if there is no
459
Figure 5 Adhesions can result from multiple thoracentesis. These can by lysed
during thoracoscopy to allow uniform distribution of talc.
visceral involvement compared with 7 months if there is [21]. Thoracoscopy
could also lead to earlier diagnosis of mesothelioma when therapy is more
likely to be effective [22].
There are several treatment options for malignant pleural effusions.
Management initially depends on the treatment potential of the primary
malignancy. Some malignant effusions, such as those associated with small
cell lung carcinoma and lymphoma, may be responsive to systemic
chemotherapy. When systemic therapy is ineffective, palliation can be
achieved with local therapy. Options for local therapy include serial
thoracentesis, pleurodesis, pleurectomy, pleuroperitoneal shunt, or an
indwelling pleural catheter. The choice of treatment modality is dependent
on the patient's general condition and preference as well as institutional
experience. Serial thoracentesis is appropriate in a patient with very limited
life expectancy, contraindication to thoracoscopy, or slowly reaccumulating
effusions. Performing the risk of complications
460 Wah/rab and Read
including pneumothorax, infection, loculation, and pain. Continuous
drainage by an indwelling pleural catheter is generally reserved for patients
with trapped lung and limited life expectancy [23] (Fig. 6). Pleuroperitoneal
shunts require frequent manual pumping and can become occluded
requiring surgical correction. Surgical pleurectomy approaches a 100%
success rate, but carries a significant mortality and a 23% complication rate,
and should be reserved for patients who could tolerate a major surgical
procedure [24].
Pleurodesis is the most widely accepted method for treatment of
recurrent malignant pleural effusions. It can be accomplished mechanically
or chemically. Mechanical abrasion of both the parietal and visceral pleurae
is performed using a sponge forceps or mechanical abrader during
thoracoscopy or thoracotomy [25]. It is more commonly used in patients
with recurrent pneumothorax than in those with recurrent effusions.
Figure 6 Posteroanterior radiograph or the chest in a patient with adenocarcinoma
or the lung demonstrating visceral parietal involvement leading to a trapped lung.
This patient is unlikely to benefit rrom thoracoscopic talc poudrage.
461
Chemical pleurodesis can be achieved via chest tube thoracostomy
(large or small bore), VATS, medical thoracoscopy, or thoracotomy.
Successful pleurodesis depends on complete drainage of the pleural space,
which allows close apposition of the visceral and parietal pleurae combined
with the introduction of an effective sclerosing agent that can be retained in
the pleural space with few systemic effects. Traditionally, pleurodesis was
accomplished via chest tube insertion. This often required prolonged
drainage of the pleural fluid prior to instillation of the sclerosing agent.
Generally, success rates for pleurodesis via tube thoracostomy are less than
that for thoracoscopy [26]. This is somewhat dependent on the agent used,
as talc is more effective than other agents such as tetracycline, doxycycline,
and bleomycin. A full review of chemical agents for pleurodesis in malignant
effusions was performed by Walker-Renard et al. and included 1168
patients. Overall success rates for the tetracyclines and bleomycin were 67%
and 54%, respectively, as compared with talc at 93% [II]. Several reports on
thoracoscopic talc poudrage either by VATS under general anesthesia or by
medical thoracoscopy have confirmed the overall success rate of talc
pleurodesis. Aelony described an 82% success rate in patients with
malignant pleural effusions in a study of 42 patients who underwent
thoracoscopy via general or local anesthesia [27]. Viallat reported a
complete response rate of 86% at I month in a series of 360 cases with
malignant pleural effusions [28]. Danby reported an 88% success rate in a
series of 24 patients [29]. Hartman described a 97% success rate in 39
patients [30]. Milanez reported a 96% success rate in 47 patients [31].
Experience at our own institution demonstrated 91 % success in 30 patients
[3Ia]. These are outlined in Table 3.
An interest in trying to identify patients who would have a successful
pleurodesis has lead to research analyzing pleural fluid characteristics.
Table 3 Results from Various Investigators for
Thoracoscopic Talc Poudrage
Reference Chest tube duration (days) Success (0/0)
[27]
[28]
[29]
[30]
[31]
[32]
[37]
2.7 82
5.3 0.2 86
29 1.2 88
4.0 1.2 97
5.4 3.0 96
3.1 21 91
3.8 + 2.4 96
462 Wahlrab and Read
Studies have demonstrated that pleurodesis success was 75-90% if the
pleural pH was >7.2-7.3 and <50% if the pH was <7.2 [19,32]. This has
recently been challenged by Aelony, who reported successful pleurodesis via
medical thoracoscopy in 88% of 25 patients with malignant pleural effusions
despite a pleural fluid pH ,,; 7.3 with up to 1 year of follow-up [33]. The
failures were attributed to trapped lung. A subgroup analysis including 10
pa tients with a pH ,,; 7.2 demonstrated 100% success. Heffner reviewed
pooled data on pleural fluid pH and concluded that a pleural fluid pH <7.28
was an independent predictor of pleurodesis failure, but that it had limited
predictive accuracy and should not be used in selecting patients for
pleurodesis [34].
The definition of success or failure of pleurodesis has been variable. A
recent statement on malignant pleural effusions by the American Thoracic
Society proposed standardized criteria [I]. Complete success is defined by
resolution of the effusion with prevention of recurrence by symptoms or
chest radiograph until the patient's death. Partial success is defined as
partial reaccumulation of pleural fluid 50% of the original amount) with
decreased symptoms of dyspnea and no need for a second procedure until
the patient's death. Failure of pleurodesis included any patients who
reaccumulated more than 50% of their original effusion or required a second
procedure for relief of symptoms.
When compared to performing pleurodesis via chest tube thoracost-
omy, medical thoracoscopy may offer the advantage of shorter chest tube
duration and, hence, hospitalization. Data from our own institution
demonstrated that patients who underwent talc pleurodesis via medical
thoracoscopy had a mean chest tube duration of 3.1 2.1 days compared
with patients who underwent doxycycline pleurodesis via chest tube at
7.3 5.9 days (P<.OOI) [31a]. Other investigators have had similar chest
tube durations with thoracoscopic talc pleurodesis [27-30]. Kennedy's series
of 58 patients who underwent pleurodesis via talc slurry (75 procedures)
required chest tube drainage for 7 1.l days [35]. This is in contrast to the
findings of Yim, who found no statistically significant difference between
talc slurry and talc insufflation via VATS under general anesthesia with
regard to chest tube duration, hospital stay, and success rate [36]. This study
included 57 randomized patients and resulted in a mean chest tube duration
of 3.8 2.4 days for the VATS group and 4.2 1.8 days for the
thoracostomy group. Preliminary results from the Cancer and Leukemia
Group B (CLB-9334) were presented at the American Society of Clinical
Oncology meeting in 2000 [37]. This study randomized 50 I patients to
receive talc slurry versus thoracoscopic talc insufflation under general
anesthesia. There was no significant difference in success rate or complica-
tions, but no data on chest tube duration were reported.
463
Medical thoracoscopy is a generally safe procedure with relatively few
complications and low mortality. A meta-analysis of video-assisted
thoracoscopic surgery included 5280 procedures and reported a mortality
rate of 0.3% and a complication rate of 3.6% [38]. Colt conducted a
prospective study to assess safety and outcomes in 52 procedures [39]. This
small series reported no procedure-related deaths and only one major
adverse event. In a series of 8000 cases, only one procedure-related death
was reported [40].
Potential complications include those related to anesthesia, the
procedure, or instruments and the pleurodesis agent [41]. Anesthetic risks
include adverse or allergic reactions to intravenous sedation or local
anesthesia, aspiration or respiratory depression, and pressure injuries due to
inadequate cushioning or positioning. Procedure-related risks include
equipment failure, inadvertent trocar insertion below the diaphragm or
into lung parenchyma, compression of intercostal nerves or tissues, and
bleeding. Bleeding can result from laceration of intercostal vessels, visceral
pleural tears, or laceration of vascularized adhesions [41]. Most bleeding can
be controlled with electrocautery, but may require conversion to a
thoracotomy. Other complications include persistent air leaks >7 days,
prolonged chest tube drainage, subcutaneous emphysema, and pain at the
incision site.
The administration of talc as the pleurodesis agent has been associated
with fever, chest pain due to the inflammatory response, infection, and the
adult respiratory distress syndrome (ARDS). Fever is the most common
adverse event with reported frequencies from 16 to 69% [12]. Fever generally
occurs within the first 12 hr and may last for up to 72 hr. Pain has been
reported in up to 7% [II]. Empyema occurs with a 3% or less incidence [12].
Development of ARDS has been reported with both talc slurry and talc
poudrage. Kennedy and Rinaldo each reported three cases attributed to talc
slurry [36,42]. It has also been reported after talc poudrage [43--46]. The
exact mechanism is unclear, and it was thought to be associated with higher
doses of talc (10 gs). This appears not to be the case, as ARDS has been
reported with procedures using 2-5 gs of talc [44--46]. These reports included
talc administration via slurry and poudrage, and it is unlikely that the
adverse reactions are related to the method by which the talc is introduced.
Talc is produced by various manufacturers and has been shown to have
variation in particle size, distribution, and impurities, which could account
for differences in systemic uptake [47]. Talc is sterilized at each individual
institution where potential contamination could occur. Cardiovascular
complications such as arrhythmias and hypotension have also been reported
[36,48]. There is evidence that talc can be systemically distributed. Werebe
and colleagues after the intrapleural
464 Wohlrab and Read
instillation of the equivalent dose of 2.5 and 5.0 gs of talc into the pleural
space of rats [49]. The greatest deposition occurred in the chest wall,
suggesting a probable route of absorption. Talc particles have also been
demonstrated in bronchoalveolar lavage fluid of patients with respiratory
distress after talc administration [46]. There have been no randomized trials
to determine the optimum dose of talc, but 5gs is usually recommended.
Other complications to consider include those related to general
surgical procedures in the postoperative period, such as nosocomial
pneumonia, atelectasis, and thromboembolic disease. Reexpansion pulmon-
ary edema should also be considered, but there is a low risk even when a
large volume of pleural fluid is removed, because equilibration of pressures
is achieved by leaving the cannula open to air.
There are limited data on bilateral pleurodesis. The risk of ARDS
certainly mandates that bilateral procedures should not be performed
simultaneously. Bilateral pleurodesis has been performed in a sequential
manner with variable outcomes. In our own experience, we have performed
10 bilateral pleurodeses. Two patients with lung carcinoma essentially
became respiratory cripples. This was most likely due to more extensive
tumor involvement of the parenchyma combined with preexisting chronic
obstructive lung disease. Patients with metastatic disease such as breast
cancer and otherwise healthy lungs tended to have better results with only
minimal limitation. Eight patients with primary malignancies other than
lung carcinoma had reduced functional status after bilateral pleurodesis, but
overall were at better level of functioning than prior to the pleurodesis. To
our knowledge, there are no data on the use of pulmonary function testing
preoperatively to exclude patients from pleurodesis.
A review of the long-term effect of talc poudrage on lung function by
Lange demonstrated mild restriction at 89% of predicted compared with
those who had catheter drainage alone for spontaneous pneumothorax (96%
predicted) [50]. Although this is important information, it may be less
relevant in a patient population with advanced malignant disease, as their
life expectancy is limited. A review of the effects of pleurodesis with
quinacrine in 10 patients with malignant effusions demonstrated a mean
total lung capacity of 96.5% of predicted with up to 102 months of follow-
up [51].
Prognosis in patients with metastatic malignant pleural disease is
generally poor. Median survival is usually less than 4 months. Early studies
suggested that pleural fluid pH was a predictor of survival [19,32]. Heffner
confirmed reduced short-term survival for patients with a pH less than 7.28,
but also demonstrated that pH has limited predictive accuracy in excluding
patients frol11 pleurodesis based on estimated survival [52]. Burrows et al.
reviewed prognostic factors in 85 patients who underwent thoracoscopic talc
465
pleurodesis [53]. The mean survival was 8 months and there was no
prognostic advantage based on pleural pH, glucose, extent of pleural
carcinomatosis, or age. Patients with a better prognosis had a Karnofsky
Performance Scale (KPS) 70 with a median survival of 395 days versus
patients with a KPS 30 with a median survival of 34 days. Data such as
these can help guide selection of patients suitable for pleurodesis.
There are little data on the cost effectiveness of the treatment of
malignant pleural effusions. Belani et al. performed a cost analysis of
various treatment modalities and reported a cost per symptom-free day
during a 6-month period [54]. The costs included the expense of the
pleurodesis agent, procedure, laboratory tests, and management of any
adverse effects. Analysis determined talc pleurodesis to have a $149 cost per
symptom-free day as compared with bleomycin ($132), tetracycline ($159),
and doxycycline ($218). Talc is the least expensive agent, but when the cost
of thoracoscopy (general anesthesia), operating room expense, and post-
operative care are included, the cost rises considerably. Performing the
procedure in the bronchoscopy suite or with conscious sedation can offset
some of the expense associated with thoracoscopy. Consideration that
medical thoracoscopy could lead to shorter hospitalization could also
reduce overall cost. The CLB-9334 data will include cost analysis for
patients randomized to talc slurry via chest tube thoracostomy versus talc
insufflation via thoracoscopy under general anesthesia [37].
VIII. Conclusion
Medical thoracoscopy is a minimally invasive modality that is useful
diagnostically and therapeutically in the management of malignant pleural
disease. It is highly effective and has minimal morbidity and mortality.
Thoracoscopic talc poudrage relieves symptoms of dyspnea and allows
pleurodesis to be performed quickly and easily, leading to improved
symptoms and quality of life in patients with an already limited life
expectancy.
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23
Therapy for Benign Conditions
MICHAEL H. BAUMANN
University of Mississippi Medical Center
Jackson, Mississippi, U.S.A.
I. Introduction
A. Definitions and Utility of Medical Thoracoscopy
Medical thoracoscopy and its diagnostic utility have been defined in
Chapters 20 and 21. However, a brief review is warranted to outline the
context of medical thoracoscopy as a therapeutic modality in benign chest
diseases. The resurgence of thoracoscopy in the early 1990s led to the
development of medical thoracoscopy [I], an adaptation by "nonsurgeons"
of video-assisted thoracic surgery (VATS). Medical thoracoscopy has also
been called pleuroscopy [2]. Improved medications for conscious sedation
and local anesthesia as well as improved imaging techniques have led to this
resurgence. Compared with VATS, medical thoracoscopy uses fewer chest
entry ports (often only one port) and local anesthesia with conscious
sedation as opposed to general anesthesia. Medical thoracoscopy is often
performed in the bronchoscopy suite in lieu of the formal operating room or
surgical suite [3]. Currently, medical thoracoscopy is being performed by at
least I in 20 practicing pulmonologists [4]; however, controversy surrounds
the role of pulmonologists and other nonsurgeons performing the procedure
[5]. Fueling this absence of clearly defined
469
470
Baumann
training guidelines for pulmonologists and other nonsurgeons to be deemed
competent in medical thoracoscopy. In the meantime, the key for any
nonsurgeon performing medical thoracoscopy is the maintenance of a close
working relationship with their thoracic surgeon colleagues [1,5].
B. Indications
Video-assisted thoracic surgery and medical thoracoscopy have been utilized
in a myriad of benign and malignant chest disorders for both diagnostic and
therapeutic purposes. The reader is referred to Chapters 20, 21, 22, and 24
for additional information regarding these roles. Focusing on the general
topic of therapeutic thoracoscopy in benign disease, many applications have
been reported (Table I). Complicating this picture is the scope of diagnostic
and therapeutic applications of medical thoracoscopy that pulmonologists
and other nonsurgeons feel comfortable with. This picture is further blurred
by the generally broader application of medical thoracoscopy by
nonsurgeons outside the United States and by U.S. nonsurgeons trained
abroad. A recent review of interventional pulmonology primarily confines
medical thoracoscopy to the diagnosis and management of pleural
disorders, but also notes its use in lung biopsy and management of
spontaneous pneumothorax [2]. Hence, this selection of areas for the
therapeutic application of medical thoracoscopy in benign disease reflects
personal bias, which may be too restrictive for some and too broad for
others and will only include diseases in adults.
Table 1 Therapeutic Applications of Thoracoscopy for Benign Conditions
Common applications of medical thoracoscopy
Spontaneous pneumothorax
Recurrent benign efTusions
Tuberculosis (appropriate antibiotic selection based on culture and sensitivity)
Possible role for medical thoracoscopy
Parapneumonic effusion and empyema
Reported therapeutic roles for video-assisted thoracoscopic surgery (VATS)
Pericardial disease
Lobectomy for benign conditions
Esophygeal cysts and benign mediastinal tumors
Thymectomy
Medical Thoracoscopy: Benign Conditions 471
II. Therapeutic Applications
A. Spontaneous Pneumothorax
The timing for and the best interventional approach to spontaneous
pneumothorax (SP) recurrence prevention and air leak management has
been unclear and has led to significant practice heterogeneity [6]. The recently
published American College of Chest Physicians (ACCP) consensus guide-
lines provide management guidance for spontaneous pneumothorax patients
[7]. For recurrence prevention and persistent air leak management
(bronchopleural fistula), the ACCP guidelines deem thoracoscopy as the
preferred intervention [7]. Acknowledged is the fact that available
randomized controlled trials [8,9] do not demonstrate a clear superiority of
thoracoscopy versus limited thoracotomy. Instead, the ACCP expert panel's
preference for thoracoscopy is based on the panel's practice preferences.
Recurrence prevention is recommended after the second occurrence for
primary spontaneous pneumothorax (PSP) and after the first occurrence for a
secondary spontaneous pneumothorax (SSP). The suggested time to monitor
a persistent air leak before a definitive intervention varies from 2 to 14 days
[10-13]. The ACCP guideline recommends persistent air leak intervention
after 4 days and 5 days. respectively, in a patient with a PSP or SSP [7]. This
air leak intervention time is somewhat longer than the recommended 3 days
for both PSP and SSP in a recent text [14]. Notably, preoperative air leaks
decrease the success of a thoracoscopic intervention in SP patients [15], as
they may prolong delays to thoracoscopic intervention [16].
During thoracoscopy, staple bullectomy and a procedure to produce
pleural symphysis should be performed. Intraoperative pleurodesis should
be performed in most SP patients with parietal pleural abrasion being
limited to the upper half of the hemithorax [7]. Despite the prevalence of talc
poudrage in pneumothorax management [17], the ACCP reached no
conclusion regarding the utility of talc poudrage for recurrence prevention
in patients with a PSP. Alternately, talc poudrage is an acceptable
alternative method for pleurodesis in addition to the preferred methods of
parietal pleural abrasion or parietal pleurectomy limited to the upper half of
the chest in SSP patient. The ACCP recommendation for thoracoscopic
intervention for a persistent air leak in both PSP and SSP patients is similar
to that for recurrence prevention [7]. Recurrence rates after thoracoscopic
surgery vary from 2 to 14% as compared with 0 to 7% after limited
thoracotomy [18]. Between 2 and 10% of PSP patients and up to 29% of SSP
patients undergoing thoracoscopy require conversion to thoracotomy owing
to technical problems [18].
Although thoracoscopy provides excellent visualization of the lung
and pleural space, as the lesser success for
472 Bauman.n
recurrence prevention by thoracoscopy compared with thoracotomy may be
due to overlooked bullae. A recent retrospective study demonstrating lower
numbers of resected bullae in PSP patients undergoing recurrence
prevention by thoracoscopy compared to thoracotomy supports this
possibility [19]. Perhaps preoperative assessment of patients using high-
resolution computed tomography (CT) could provide direction to areas
needing closer intraoperative thoracoscopic attention and could enhance
thoracoscopic recurrence success. Despi te controversy, some surgeons
currently use high-resolution CT to plan their operative interventions in
PSP patients [20]. This may be particularly pertinent for patients at high risk
for recurrence-related morbidity and mortality such as divers and pilots.
The ACCP spontaneous pneumothorax panel could not achieve consensus
regarding the utility of chest CT for evaluating PSP patients for risks of
recurrent pneumothoraces and persistent air leaks or for planned surgical
interventions. Computed tomographic assessment in SSP patients is deemed
acceptable in patients with recurrent disease, during management of a
persistent air leak, or for planning a surgical intervention [7].
The ACCP guideline stance on the role of CT of the chest in the
assessment of patients with SP, particularly PSP, may need revision as
information develops. Bense and colleagues note 81 % of nonsmoking, non-
alphal-antitrypsin-deficient patients with a PSP have emphysemalike
changes [21]. The type of CT scanner, thickness of sections (high-resolution
protocol), and observer variability can influence accuracy [22]. Bense and
colleagues [21] and Warner and colleagues [23] both found a correlation
between emphysemalike changes and the occurrence of a PSP. However, no
definite number or size of blebs or score of emphysemalike changes
correlated with an absolute risk of PSP recurrence [23]. Alternately,
Mitlehner and colleagues found no significant CT differences in PSP
patients with and without recurrence [24]. More recent information
continues to fuel the debate, with one recent publication supporting a role
for CT in recurrence prediction and surgical planning [25] and one not
supporting CT analysis as a predictor of PSP recurrence [26]. An additional
study notes that high-resolution CT was a more sensitive method to detect
blebs and bullae than thoracoscopy, but those CT findings were not
predictive of pneumothorax recurrence [27]. Additional studies are clearly
needed to define the role of high-resolution CT in the management of SP,
particularly PSP patients.
Often quoted as integral to the management of a patient with a
spontaneous pneumothorax [28] is the thoracoscopic staging of emphysema-
like changes. This was not incorporated in the ACCP spontaneous
pneumothorax guidelines [7]. Implicit is the assumption that such changes
are etiologically associated with the development of a pneumothorax [28].
Macroscopic stages (visualized by thoracoscopy) commonly used are: stage
J, normal visceral pleura; stage II, some pleural adhesions; stage III, blebs or
bullae (emphysemalike changes) <2 cm in size; and stage IV, bullae with
diameter >2 cm in diameter (28-30). Approximately half of SP patients will
be stages J and 11 and the other half stages III and IV (Table 2) [28].
However, some SP experts cogently refute the etiological role of
emphysemalike changes in the development of PSP, and note that no study
has clearly demonstrated that such changes are the actual cause of a PSP
[31,32]. Paralleling this stance is the proposal in a recent review espousing
medical thoracoscopy with talc pleurodesis alone as being successful in SP
recurrence prevention [31]. The primary data note medical thoracoscopy-
directed talc pleurodesis without any directed therapy for emphysemalike
changes provides 95% recurrence prevention with a mean follow-up of 5
years [30]. A closer look reveals, however, that emphysemalike changes may
playa role in recurrence given a higher risk of pneumothorax recurrence in
patients with bullae >2 cm [30], stage IV patients. Noppen and colleagues
present quite similar findings noting 6.5 and 8.7% recurrence rates in PSP
and SSP patients, respectively, undergoing thoracoscopic talc poudrage [29].
Notably, all emphysemalike changes >2cm (stage IV) were treated with
thermocoagulation [29]. Hence, incorporating talc poudrage alone without
addressing smaller emphysemalike changes provides good recurrence
prevention. Such a therapeutic approach makes management of SP patients
more accessible to the medical thoracoscopist not wishing to risk surgically
manipulating the lung while still maintaining significant recurrence
prevention. The use of thermocoagulation, far less invasive or technically
challenging by comparison to endoscopy-directed stapling, provides a
readily accessible addition to talc poudrage for the medical thoracoscopist
in patients with blebs >2 cm.
Table 2 Thoracoscopic Staging of Spontaneous
Pneumothorax
Stage
I
11
III
IV
% of Patients
33
12
33
21
Source: Adapted from Ref. 28. See text for description of
spontaneous pneumothorax stageopyrighted Material
474
Baumann
B. Recurrent Benign Effusions
One of the most common diagnostic indications for thoracoscopy is in the
patient with an undiagnosed recurrent pleural effusion, often exudative in
nature [33]. The ATS guidelines for needle biopsy of the pleura note that in
10-20% of patients with an exudative effusion a specific etiological diagnosis
will not be established by thoracentesis and pleural biopsy [34]. Thoraco-
scopy should be considered after a nondiagnostic repeat thoracentesis and,
possibly, after the addition of a nondiagnostic pleural biopsy. The exact role
and timing of thoracoscopy and pleural biopsy in the setting of an
undiagnosed exudative effusion continues to be debated [33]. Given the
comparable safety of pleural biopsy and medical thoracoscopy [33], perhaps
moving earlier to thoracoscopy in the evaluation of an undiagnosed effusion
is warranted. I view medical thoracoscopy as a directly visualized closed
pleural biopsy. Further, medical thoracoscopy may be potentially safer than
closed pleural biopsy owing to direct biopsy visualization.
Once the decision has been made to proceed with a diagnostic
medical thoracoscopy, the opportunity for therapeutic recurrence preven-
tion can be simultaneously pursued through talc poudrage. Such a
therapeutic approach can be more comfortably pursued if on-site
cytopathologic support is available. Immediate talc poudrage in the setting
of cytopathologically proven pleural malignancy is reasonable. More
problematic is the approach to a nonmalignant recurrent effusion. Despite
on-site cytopathologic support during a diagnostic medical thoracoscopy,
the thoracoscopist may wish to forgo talc poudrage until final pathologic
and cytopathologic reports are available, if on-site cytopathology does not
clearly diagnose pleural malignancy. Later, thoracoscopic or chest tube-
directed pleurodesis could be pursued if the clinician is satisfied with the
potential cause of the effusion and the appropriateness of pleurodesis. One-
step thoracoscopy and pleurodesis, without a clear diagnosis, may preclude
future easy access to the pleural space if subsequent invasive pleural studies
are required.
After the clinician is comfortable with the underlying diagnosis of a
recurrent symptomatic pleural effusion and the need for recurrence
prevention by pleurodesis, thoracoscopy-directed talc poudrage is reason-
able. Visually inspecting the pleural space prior to talc poudrage may have
the added benefit of excluding heretofore unanticipated causes of the
recurrent effusion. Pleurodesis successfully prevents effusion recurrence in
nonmalignant exudative and transudative effusions [35,36]. Overall pleur-
odesis success in these benign effusion cases is greater with talc (97%) than
the total success of various other unspecified agents combined (60%) [35].
Underlying diagnoses and reported success with chest tube-directed talc
pleurodesis include congestive heart failure (100%), liver cirrhosis (89%),
systemic lupus erythematosus (100%), chylothorax (benign causes including
lymphangiolyomyomatosis) (95%), yellow nail syndrome (100%), nephrotic
syndrome (100%), peritoneal dialysis (100%), and unknown underlying
causes (100%) [35]. These effusions may be benign only in their etiology; 4 of
16 patients (25%) in one series (1 patient each with liver cirrhosis, congestive
heart failure, chylothorax, and undiagnosed effusion) died of their under-
lying disease within 2-6 months of therapy [35]. The two series just noted by
Sudduth and Sahn and by Glazer and colleagues primarily report talc slurry
via chest tube. Thoracoscopy-directed talc poudrage in benign effusions
appears to be equally successful as chest tube-directed talc slurry, with 100%
(II of II) chronic benign effusions reported by Aelony and colleagues
having no effusion recurrence after talc poudrage [37].
c. Tuberculosis
Pleural biopsy and pleural fluid component measurements such as adenosine
deaminase playa central role in the diagnosis of tuberculous pleural effusion
[33]. The diagnostic role of medical thoracoscopy has been reviewed in
Chapter 16. Arguably, medical thoracoscopy may playa central role in the
diagnosis of tuberculous pleural effusions. Often cited in support of medical
thoracoscopy's role in diagnosis of pleural tuberculosis is Loddenkemper
and colleagues' comparison of pleural biopsy and thoracoscopy in this
setting [38]. Mares and Mathur [39] cite this study, noting that thoraco-
scopic biopsy is more likely to obtain diagnostic cultures for tuberculosis
than pleural biopsy. Evaluation of Loddenkemper and colleagues' work
confirms that this is indeed true, but thoracoscopy is routinely incorporated
as a first-step diagnostic procedure. Also, the diagnostic yield of combined
pleural fluid culture and pleural biopsy culture is no different statistically
than the yield of combined fluid culture and thoracoscopy-derived tissue
culture [38].
Regardless of whether one chooses medical thoracoscopy as the
primary diagnostic tool in the evaluation of suspected pleural tuberculosis
or after initial pleural fluid and pleural biopsy analysis are nondiagnostic, a
key issue is the importance of culturing the tuberculous organism. Relying
solely on pleural fluid markers of pleural tuberculosis such as adenosine
deaminase for diagnosis does not provide culture data with its accompany-
ing drug-sensitivity analysis [33]. Continuing concerns for the presence of
multi-drug-resistant tuberculosis [40] make this a key consideration when
choosing a diagnostic approach to a suspected tuberculous pleural effusion.
Hence, thoracoscopy may not only play a role in diagnosis of pleural
tuberculosis but also sensitivity information for
476
Baumann
appropriate treatment. Such drug sensitivity testing is particularly
important in urban areas where drug resistance is prevalent or when
assessing recent residents from geographical areas endemic for drug-
resistant tuberculosis. Unfortunately, the exact incidence of drug-resistant
tuberculosis found in the setting of a tuberculous pleural effusion is
unknown.
D. Parapneumonic Effusions and Empyema
The most appropriate therapeutic approach to a parapneumonic effusion
and empyema is not clearly established. However, new ACCP guidelines
provide evidence-based direction while emphasizing the limited literature
available to base the suggested recommendations [41]. Although not
specifically exploring the role of medical thoracoscopy in parapneumonic
effusion and empyema, these guidelines indirectly provide some direction by
addressing the role of VATS. The ACCP guidelines cite the probable
superiority of immediate VATS over fibrinolytics in the management of
parapneumonic effusion and empyema based on Wait and colleagues' recent
study [42]. Patients treated with immediate VATS had significantly higher
treatment success (91 vs. 44%), shorter length of stay, and shorter duration
of chest tube drainage than the chest tube drainage plus fibrinolytic group
[42]. VATS may also be superior to thoracotomy in empyema patients in a
comparison of VATS and historical control patients undergoing thoracot-
omy [43]. Duration of chest tube drainage and of overall patient care was
significantly shorter in VATS patients [43]. VATS may be useful rescue
therapy in empyema patients failing medical management by either
therapeutic thoracentesis or tube thoracostomy [44]. However, performing
VATS does not necessarily preclude conversion to other surgical procedures
[44].
The ACCP guidelines limit VATS to patients defined as higher risk for
poor outcome (categories 3 and 4) [41]. Category 3 patients are those with a
large, free-flowing effusion ~ 5 0 the hemithorax), loculated effusion, or
effusion with thickened parietal pleura. Also, a category 3 patient could
simply have a positive culture or Gram stain or a pleural fluid pH <7.20. A
category 4 patient has category 3 characteristics as outlined but is found to
have pus in the pleural space [41]. Both of these categories represent
advanced disease. Efforts required to thoracoscopically manage empyema
may be extensive and involve clearing the loculated pleural space of debris.
A limited decortication. using forceps, scissors, and retractors as reported by
Landreneau and colleagues [45] may be required. Such expertise may be
beyond that of many medical thoracoscopists.
The ACCP guidelines note that patients with very low and low risk for
poor outcome, categories 1 and 2, respectively, may not require any
drainage procedure. Category 1 patients include those with minimal, free-
flowing effusion I0 mm on lateral decubitus) with culture, Gram stain,
and pleural fluid pH unknown. Category 2 patients include those with a
small to moderate free-flowing effusion (> 10 mm and <50% the hemi-
thorax) with negative culture and Gram stain and a pH 7.20. Categories I
and 2 patients, from the procedural technique standpoint, would be ideal for
a medical thoracoscopist. However, the procedure may add little to patient
care. Alternately, one could argue that earlier invasive intervention with a
relatively safe procedure such as medical thoracoscopy could prevent
progression to empyema category 3 or 4. Until additional data are available,
I would suggest performing a definitive drainage procedure under
thoracoscopic guidance as soon as possible to prevent potential progression
to category 3 or 4 as reasonable in selected categories I and 2 patients.
Selected patients might include those with continued infectious symptoms
such as fever, increased white blood cell counts, increasing effusion size, or
underlying risks for progressive infection such as diabetes mellitus or other
immunocompromising disease state. At this empyema stage, minimal
adhesions and loculations could be managed with the skills commanded
by medical thoracoscopists.
Prospective randomized controlled studies focusing on the role of
medical thoracoscopy (versus traditional VATS or other therapeutic
interventions) in parapneumonic effusions and empyema remain unavail-
able and are greatly needed. Such studies could delineate the appropriate
timing of medical thoracoscopy intervention and its success compared with
other options. Meantime, some have advocated the use of medical
thoracoscopy at the time of chest tube placement if a therapeutic tube is
indicated for a parapneumonic effusion or empyema [46]. A recent
publication by Colt describes success with medical thoracoscopy in
empyematous patients but notes the potential difficulties. Six of seven
patients (four with failed chest tube drainage) in Colt's small series of
empyematous patients were spared open-chest surgery owing to successful
thoracoscopic debridement [47]. However, Colt, a highly trained and
experienced medical thoracoscopist, notes that thoracoscopic "management
of empyema requires greater experience and technical expertise than that
required for routine thoracoscopy for parietal pleural biopsy or pleurodesis"
[47]. Colt recommends close consultation with a thoracic surgeon if such a
project is tackled [47]. Regardless, early intervention whether by thoraco-
scopy (medical or VATS) or by chest tube placement with fibrinolytics is
advised before significant loculation of the pleural space hampers successful
and expedient pleural Material
478
Baumann
E. Other Therapeutic Applications
Increasing applications of thoracoscopy for both benign and malignant
disease are being reported. Recent reported therapeutic applications of
thoracoscopy (see Table I), all via VATS, include pericardial resection for
both benign and malignant disease [48], removal of benign neurogenic
mediastinal tumors [49], esophageal cyst removal [50], and lobectomy due to
a variety of benign disorders [51]. All of these applications are generally
beyond the scope of a medical thoracoscopist. However, they highlight the
evolving applications of thoracoscopy and the need for the prudent medical
thoracoscopist to resist the temptation to extend his or her skills beyond
their training.
III. The Talc Controversy
Talc, as noted. is frequently the pleurodesis agent of choice in managing
both patients with spontaneous pneumothorax and recurrent effusions.
However, despite its popularity [6] and positioning in the ACCP
spontaneous pneumothorax guidelines [7], talc has been the subject of
recent debate [52,53]. Central to this debate, and undisputed, is the fact that
pleural talc application can be associated with acute respiratory distress
syndrome (ARDS). Debated is the incidence of talc-related ARDS and its
pathogenesis. Varying documentation in reports and a wide disparity in the
incidence of reported talc-related ARDS make interpretation of its
significance difficult. The incidence of talc-related ARDS from pooled
data of over 2300 patients appears <0.75% [52]. However, the reported
incidence ranges from 0 to 33% and may not be clearly dose related [53], as
reported in earlier talc reviews [17]. Perhaps contributing to this marked
variation is the inherent differences in talc preparations based upon their
geographical origin [17,52-55]. Talc may be found widely distributed in the
body after pleural application [52,53], and talc particle size may playa
significant role in developing ARDS [52-55]. This systemic talc distribution
may be key to the precipitation of ARDS [53], or may simply be an epi-
phenomenon [52]. Previous pleural disruption by pleural biopsy and other
invasive procedures may promote systemic talc distribution [54]. Smaller
talc particle size may also enhance systemic distribution and depends upon
the geographical talc ource [55]. Additionally, contamination of talc by
endotoxin [54] and by bacteria [56] may contribute to developing ARDS.
Bacterial contamination is inexpensively and readily obviated with various
sterilization procedures [56]. Given the concerns with talc, particularly for
ARDS, potential recipients need to be clearly informed of talc's potential
risks and benefits. A reasonable alternative to talc poudrage that can be
Medica! Thoracoscopy: Benign Conditions 479
readily accomplished by the medical thoracoscopist is pleural abrasion [53].
If the patient opts for talc poudrage, the appropriate dose of talc is in
dispute. As noted earlier, concerns for larger talc doses directly paralleling
the occurrence of ARDS may not be accurate. Doses of as little as 2 gs by
poudrage have been reported to be associated with ARDS [53]. Alternately,
Kennedy and Sahn's large review notes a dose of talc by poudrage or slurry
of 5 gs as being sufficient for success and comparatively safe [17].
IV. Conclusion
Although the therapeutic applications of medical thoracoscopy in benign
disorders are primarily limited to patients with spontaneous pneumothorax,
recurrent effusions, tuberculosis, and select patients with parapneumonic
effusions, the potential for success is significant. The key to success and
safety is recognizing the appropriate applications and limits of medical
thoracoscopy. If such limits are applied, patient benefit and physician
gratification are substantial.
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24
Techniques for Thoracic Sympathectomy
MARC NOPPEN
Free University of Brussels
and Academic Hospital AZ-VUB
Brussels, Belgium
I. Introduction and Definition of the Procedure
Thoracic sympathectomy (TS) is defined as the anatomical interruption of
the thoracic sympathetic chain. The level of interruption (e.g., T2, T3)
depends upon the indication for TS and the desired therapeutic effects (e.g.,
treatment of essential hyperhidrosis, treatment of chronic pancreatic pain).
Anatomically, interruption can be applied at the preganglionic level [I],
although currently ablation or excision of the sympathetic ganglia (and
sometimes part of the chain itself) is current practice [2].
Thoracoscopic TS (TTS), which combines superior visualization of the
upper thoracic ganglia with minimal postoperative morbidity and dysfunc-
tion, is now the technique of choice. Open surgical approaches are obsolete,
and percutaneous ablation methods are not widely used because of a high
risk of early recurrence, postoperative complications such as pneumothorax,
and difficulties in accurately localizing the ganglia [3].
Most reports on TTS are written by surgeons and typically describe
VATS (video-assisted thoracoscopic surgery) techniques, which employ
keyhole surgical procedures using single-lung, double-lumen ventilation,
disposable trocars, and pleural and
483
484 Noppen
sympathetic chain dissection, and are often followed by chest drainage.
However, successful TTS can also be performed using a less invasive one-
time, '"medical" thoracoscopic sympathetic ablation technique performed
by a pulmonologist [4]. Very recently, several surgical investigators [5-8]
have described less invasive sympathectomy techniques (e.g., using 2-mm-
diameter ultrathin thoracoscopes), which may eventually replace the typical
I O-mm-diameter VATS instruments currently in use. This evolution toward
more simplified procedural techniques hopefully may lead to a convergence
of pulmonologists' and surgeons' opinions on who should perform TTS in
particular and therapeutic thoracoscopy in general.
Thoracic sympathectomy was first performed by Kotzareff [9] in 1920 for
hyperhidrosis. In 1923, Bri.ining performed TS in two patients suffering
from Raynaud's phenomenon [10]. Later, various open surgical techniques
were described with posterior paravertebral [II], posterior midline [12],
cervical/supraclavicular [13], transaxillary [14], or anterior [15] approaches.
Although success rates of open surgical thoracic sympathectomies for relief
of essential hyperhidrosis (which has been, and still is, the main indication
for thoracic sympathectomy) were good (80-100% success rate), the esthetic
discomfort due to the large and sometimes mutilating scars, the high
morbidity and complication rate (permanent Horner's syndrome in up to
20% of cases, pneumothorax, hemothorax, empyema, phrenic nerve injury,
chylothorax, carotid or subclavian artery tear, and respiratory function
impairment) have led to the search of less invasive techniques.
Technically, sympathetic interruption can be achieved by "classic"
surgical dissection and removal [21], electrocoagulation [4,24] phenol
injection [22], or laser ablation [23]. Today, most operators use unipolar
electrocoagulation [24].
In summary, the history of TTS is a perfect example of the evolution
toward minimally invasive interventional techniques, from open thoracot-
omy to ultrathin needle thoracoscopic ablation and medical thoracoscopic
techniques. This evolution can also be seen in other areas in thoracic disease;
[or example, the thoracoscopic treatment of recurrent pneumothorax,
mediastinal lymph node sampling, splanchnectomy, and mediastinal cyst
ablation, and is an example of the constant blurring of the demarcation line
between "surgical" and "medical" approaches. Rather than leading to
endless discussions on who should perform (thoracoscopic) sympathectomy,
this evolution should lead to an increased collaboration between surgeons
and pulmonologists, as has happened in our institution. It is our firm belief
Medical Thoracoscopy: Thoracic Sympathectomy
485
that an open-minded collaboration between surgeons and pulmonologists
leads to a superior quality of care for patients.
A. Indications
In the past, sympathectomy has been used to treat a wide variety of
disorders and syndromes (Table I), although in many former indications,
there is little or no objective evidence of its efficacy [2]. Today, TTS has a
limited number of indications (Table 2).
Essential hyperhidrosis, characterized by pathological sweating of the
axillae or palms of the hands, is currently the main indication for TTS in
adults [2,4,24,25] as well as in children and adolescents [26,54].
Table 1 Conditions That Historically Have
Been Treated by Sympathectomy
Acrocyanosis
Angina pectoris
Arrhythmias
Arteriosclerosis
Arthritis
Buerger's disease
Causalgia
Consti pat ion
Dysmenorrhea
Epilepsy
Gallbladder disease
Glaucoma
Hirshprung's disease
Hyperhidrosis
Migraine
Paget's disease of bone
Pancreatitis
Perniosis
Peptic ulcer
Poliomyelitis
Raynaud's phenomenon
Renal disorders
Retinitis pigmentosa
Venous ulcerations
COPYi iglJted t'iJ1aterial
486
Table 2 Current Indications for Thoracoscopic Sympathectomy
Universally accepted:
Essential hyperhidrosis
Facial blushing
In selected cases:
Raynaud's phenomenon, acrocyanosis, upper limb arterial insufficiency
Buerger's disease
Causalgia
Angina pectoris, long QT syndrome, ventricular and arterial tachycardia
Chronic pancreatic pain
Noppen
In Raynaud's phenomenon, acrocyanosis, and idiopathic thoracic outlet
syndrome, TTS can provide temporary (and occasionally long-standing)
symptomatic benefit [2,27,28,30]. Although no large-scale controlled studies
are available, numerous case series suggest a potential short-term and
intermediate-term benefit in carefully selected patients.
TTS, then, can be considered to be a reasonable alternative for severe
cases of refractory Raynaud's phenomenon (e.g., digital pregangrene), but
probably is difficult to justify in cases with a lesser degree of affliction [2].
In Buerger's disease, the effects of TTS seem to be very short lasting,
especially if the patient continues to smoke [2]. In rare, selected cases of
upper limb arterial insufficiency associated with Buerger's disease, we have
observed significant symptomatic improvement and significant delays in
amputation (personal observations).
TTS has been, and still is, widely used in the treatment of causalgia and
ref/ex sympathetic dystrophy [2,31]. However, its role has recently been
questioned [32], and is limited to a select minority of patients.
Some series also suggest a potential role of TTS in the treatment of a
variety of cardiac disorders, such as severe angina pectoris refractory to
medical or surgical treatment [33] and various arrhythmias including long
QT syndrome [34] and ventricular and paro.c)'smal w'lI'ial tachycardia [35].
Finally, TTS has been proven to be useful in the treatment of jacial
blushing [37] and of chronic pancreatic pain [38]. All levels of sympathetic
interruption can safely be performed by medical TTS.
B. Contraindications
Thorascopic TS requires the presence of an open pleural space. Small apical
pleural adhesions, which may be present in elderly patients, can often easily
be transected. The presence of extensive, organized pleural adhesions (e.g.,
Medical Thoracoscopy: Thoracic Sympathectomy 487
after pleurodesis or remote infection), however, may compromise thoraco-
scopic interventions. Bleeding diathesis is another general contraindication
to TTS [21].
IV. Equipment
Although virtually all medical thoracoscopic interventions can safely be
performed in a dedicated endoscopy suite [39], we prefer to use a fully
equipped operating theater for safety, logistics, and staffing [4]. Whereas
diagnostic thoracoscopies often are performed under local anesthesia and
intravenous sedation, interventional medical thoracoscopies (e.g., for TS)
usually are performed under total intravenous anesthesia with single-lumen
intubation and high-frequency jet ventilation [40].
For medical TS, a simple medical thoracoscopy set is sufficient. Video
assistance is obtained by means of a dedicated video camera and TV display.
Sympathetic ablation is easily achieved by means of a coagulation forceps
heated by a unipolar electrocoagulation unit. No chest drains are needed.
Total cost of the (multiple-use) medical thoracoscopy equipment and
video-assistance display can be estimated at $10,000 in our institution,
where about 100 thoracoscopic interventions are performed per year,
telescopes are renewed every 5 years, and the video camera and imaging and
data storage facilities every 8-10 years.
Segmental postglanglionic fibers synapsing in the paravertebral lower
cervical and thoracic sympathetic ganglia (which form the sympathetic
chain) provide the sympathetic innervation of a variety of internal organs
(heart, lungs [24], abdominal organs including pancreas) and of the blood
vessels and sweat glands of the face and neck, upper limb, and axillary
regions. Thoracoscopic TS is performed at the segmentallevel(s) relevant to
the desired effect of denervation (Table 3). The eight cervical ganglia and the
first thoracic ganglion most often are fused together, forming the stellate
ganglion, lying over the neck of the first rib in both hemithoraces. Ablation
of the stellate ganglion, which supplies the sympathetic innervation of the
face and neck, should be avoided because of the risk for Horner's syndrome.
Each rib caudal to the first rib has his corresponding ganglion,
although great anatomical variability exists [41]. The T2 ganglion is the
major source of sympathetic innervation of the hands; therefore, although
more extensive ablations (T
r
T
3
, T
2
T
4
, even up to T
r
-.T
6
) have been used
in the past for the relief success rates are high only
488
Table 3 Level of Sympathetic Denervation in Function of the Indication
Nappen
Indication
Facial blushing and sweating
Palmar hyperhidrosis
Axillary hyperhidrosis
Upper limb vasospastic disorders, causalgia
Cardiac disorders
Pancreatic denervation
Sympathectomy level
Lower T
1
-T
2
T
2
(T
3
)
T
r
->T
4
(T
s
)
T
r
T
3
Lower T
j
-T
6
(T
1o
)
Ts-Tj,
when the T
2
ganglion. is ablated for this condition (current practice)
[23,42,43J. Limiting the number of levels ablated likely reduces the extent
and severity of side effects; for example, compensatory hyperhidrosis [44J.
Division of the sympathetic chain over the caudal part of the first rib
and coagulation down to the second and third ganglion nevertheless is
effective in relieving facial blushing and sweating in the majority of patients
[37J. For the relief of axillary hyperhidrosis, a T
r
->T
4
ablation (although
contributions can be present from T
s
) is usually advocated [24]. A T
3
ablation offers almost complete sympathetic denervation of forearms and
hands, and thus is employed for relief of various vascular disorders and
causalgia of the upper extremities. For the treatment of cardiac disorders, a
left-sided or bilateral lower T]-T
6
denervation (sometimes up to T
IO
) is
performed [33J. For the relief of pancreatic pain, coagulation is performed
from the fifth to the eleventh rib heads [38J.
The exact pathophysiological mechanism underlying essential hyper-
hidrosis-the main indication for TTS-remains largely unknown. Studies
by Shih [45,46J suggest an overfunctioning of the sympathetic nerve fibers
passing through the T
2
(and to a lesser extent T
3
) ganglia.
Some degree of general hyperactivity of the sympathetic nervous
system also seems to be present [47,48J. Whatever the etiology, ablation of
the responsible sympathetic ganglia offers the highest chance of permanent
relief [24].
VI. Technique
Medical thoracoscopy can be defined as a minimally invasive procedure,
performed by a trained pulmonologist, with the objective I) to diagnose
pleural effusions, thickenings, or masses, and 2) to treat intractable pleural
effusions and recurrent or persistent primary or secondary pneumothoraces.
Medical ThoracoscoPY' Thoracic Sympathectomy 489
Most medical thoracoscopies can safely be performed in an endoscopy suite,
under local anesthesia, conscious sedation and spontaneous ventilation,
using simple, reusable equipment. VATS can be defined as any thoracic
surgical procedure, performed by a surgeon through a keyhole incision;
VATS is performed in an operating theatre, under general anesthesia,
double lumen tube intubation 'and controlled ventilation often using
disposable equipment. As mentioned above, this arbitrary separation has
no scientific basis, and reflects solely eminence-based, often protectionist
ideas, and maybe medical legal issues. Indeed, an increasing overlap between
"typical" medical thoracoscopy, and "typical" VATS is emerging. Hope-
fully, the terms diagnostic and therapeutic thoracoscopy will replace the
former terms. I as a pulmonologist perform TS in an operating theater, but
using "medical" equipment, albeit in patients under total intravenous
anesthesia, yet ventilated through a simple single lumen endotracheal tube. I
would classify this technique as being therapeutic thoracoscopy.
The preoperative workup includes a history (with special emphasis on
previous pleuropulmonary disorders or interventions) and physical exam-
ination, chest radiograph, ECG, pulmonary function tests and biochemistry,
hematology and coagulation blood studies. The patients are placed on the
operating table, under total intravenous anesthesia [40], in supine position,
with the trunk elevated to 30 degrees. If a biaxillary approach is possible,
both arms are spread at 90 degrees horizontally. If an anterior approach is
indicated, both arms are placed alongside the body. After skin disinfection
and sterile draping, a right-sided pneumothorax is created using a
Kiiss needle, which is introduced in the anterior axillary line in the second
or third intercostal space.
About 1000-1500 mL of air is insufflated manually into the pleural
cavity. Thereafter, a 7-mm trocar is introduced after enlargement of the skin
incision and blunt dissection. A thoracoscope (Richard Wolff, Knitlingen,
Germany, or Olympus, Tokyo, Japan) is introduced via the trocar, the
pleural space is inspected, and the sympathetic chain is identified. A second
entry point is created about 3 cm laterally (when using the anterior
approach) or anterocephalad (when using the axillary approach) from the
first trocar. An insulated biopsy forceps connected to an unipolar
coagulation unit is introduced via the second trocar. Adhesions, when
present, are transected. The appropriate ganglion(a) is(are) identified, and
coagulation is carried out over the rib heads using five to fifteen 60 W bursts
(Fig. I). Coagulation is extended 3-4 cm laterally along the rib. The second
trocar is removed and a skin suture placed at its entry point. Then negative
suction is applied to the first trocar. Simultaneously, the ventilation mode is
changed from high-frequency jet ventilation to manual bag ventilation with
high tidal volumes. The and the skin is closed.
490
sympathetic chain
Noppen
2nd rib
3rd rib
Figure 1 Schematic representation of the TrT
J
ganglia that are commonly
coagulated for the treatment of essential hyperhidrosis.
No drains are left in place. The same procedure is thereafter immediately
performed on the left hemithorax. Total operating time averages 20 min.
After recovery in a postanesthesia unit, the patients are transferred to the
hospital ward, and they are discharged several hours later.
A. Essential Hyperhidrosis
Palmar, axillary, and, to a Ie ser extent, facial hyperhidrosis are excellent
indications for TTS. However, there are no controlled studies comparing
surgical or thoracoscopic interventions with other treatments such as local
applications of astringents, medical treatment with anticholinergics, and
iontophoresis. The available medical literature invariably provides the
personal experience of the author(s) and early and late therapeutic results
and complications. A summary of papers on TS, which includes data on
over 4000 patients, is listed in Tables 4 and 5. Relief ofpalmar sweating has
been excellent: immediate success rates vary between 90 and 100%, and most
often reach 95-100%. Long-term success is obtained in 67-100%, and most
often in over 95% of cases. Late recurrences are noted in approximately 5%
of cases; repeat interventions are usually successful. Immediate failures most
often are due to the presence of a parallel neural pathway (Kuntz's fiber) or
because of the inability to create a pleural space. Care should be taken to
include Kuntz's fiber in the ablation field by extending pleural coagulation
4-5 cm laterally over the second rib. Late recurrences probably are due to
nerve regeneration.
Most operators perform a T2-T3 ablation for palmar hyperhidrosis.
However, limiting the intervention to T2 may be just as successful, and result
in a lower incidence of compensatory hyperhidrosis, which is the major side
effect of TS [49]. However, this approach remains controversial [50].
Limiting the intervention to division of the sympathetic trunk caudal to the
T2 ganglion over the third rib (R3 sympathicotomy) also may reduce the
incidence of compensatory hyperhidrosis, but no actual data have been
provided.
Compensatory hyperhidrosis is defined as the development of
increased sweating after TS, especially at the level of the derma tomes
above and below the sympathectomy level. Its incidence varies between 0
and 99% in the reported series. However, rates between 60 and 70% are most
often cited. Of note, the incidence seems higher in the series from China. It is
unclear whether genetic or environmental issues are responsible. Gustatory
sweating is reported in 9-64% of patients. Temporary and permanent
Horner's syndrome occurs in 0-17% of patients. The personal experience
and technique of the operator seem to be crucial determinants of
complication rates. Major complications necessitating other interventions
(e.g., chest tube drainage for persistent pneumothorax, hemothorax, or
conversion to thoracotomy) are rare, especially in larger and more recent
series. Numerous studies have shown that TS causes measurable, but
clinically insignificant, effects on pulmonary, cardiac, and autonomic
function [58-62].
In summary, modern TTS, whether performed by surgeons or
pulmonologists, seems to be a highly effective and safe treatment option
for patients suffering from essential hyperhidrosis. Success is obtained in
95-100% of the patients. Safety is related to the experience of the operator,
use of video assistance [29], extreme care to avoid the T 1 ganglion, use of
smaller-sized and simplified ablation
'0
I"
Table 4 TTS for Essential Hyperhidrosis: Patient Characteristics, Results, and Complications
Immediate Long-term
Pncumothor,lX
No ol Sex Compensatory Gustatory Temporary Permanent Pam, pleur.,1
Rd p..allcnh Age Fl IntCncnllon H A F H A F Follow-up SWCJllng sweating Horner Horner dyspnea Ncur,llgl;l r:l1hology
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"
NR NR 02-D] [100") 1'00"') NR ]4% NR
0'" 0'> nr: NR NR
[SI] 512 NR NR 02-04 [9S,*] 196< 1-5) 45'l NR NR 02'1 NR 2% 1%
[S2] I 2u F 0204 10Or,( NR NR 100% NR NR 2)(s NR NR 0'" 0<> NR
0"' Small
[SJI 150 10-44 72.168 0203 99.30% NR NR lJY.JO'/'> Nt< NR 6mos 21,50% NR U% 0% 0% 0.5%
IS41 SO S 59 3248 02-03 60":'c (,Or; 97.50% NR NR 6--301110<; SUO.:'} NR 0% 0% NR NR 1<1
[S5) 270 13 56 150,120 01 0:!D4 9S'k NR NR 98.10% 95% NR 1-27Yf<; 674nt'" 5070'i NR 250'1- 27"1- NR 2.50'1
[S6) 150 1355 6189 02-04 98'10 NR NR NR NR Nt< NR 50'1 070<;1-

0"
NR _140",
141 1(10 1152 _17/63 D2-01 IQfI% 90% \)0"; "'%
"'"
45"1-
''''
1% ot;} 80% 6% 1%
[2S] 3H 11-67 7/27 D2-1)3 (II) 193"1

[IIWr.,] NR 191%) [IUU'1l] Nt< 1-7mos (rn 16) 51% NR 0% 0% 45_
NR 3%
'"
D2-D5(1\}
'"
[25[ 850 9-72 3311519 02-0] (H) 198%[ [98%[ NR [96%] 198''1 NR 2-800105 (31) 55% 36% 0.4% 02% 39% NR 1"1'
01-04 (A)
Low 01-02
(face) C')
151) 53 15-44 19f34 02-03 100% NR NR 100% NR NR 11-160105 (19) 67.3% NR 17.3'l>b 6'1> NR 1351} 611
ISO] 72 m 21.7 39/33 02-03(52) [93%[ NR NR [93%[ NR NR 3-37 (18) 991< 171Y NR 69C} NR 7C1 8",
D2 (20)
1441 124 15-52 42/82 01-04 (47) [99%) 19n1 NR 199%) [99"'] NR II mos 72% NR 0% 0% NR NR 4...... C)
01-05 (Ax) (7)
...,
l::>
rami camm. (701 99% NR 94.... r NR JIll> NR 0% 0% NR NR C')
n-T4(S)
C)
'" [52) 223 6--15 881135 02-03 (H) (120) 98% 98% NR 98% 98g. NR 3-48 44% NR 0% O'k NR NR 1%
C')
02-04 (A) (103)
(54[ 47 9-34 25/22 02 100% NR NR 100%' NR NR 6-22 (13) 75% 0% 0% NR NR

0'" ';::
[29[ 369 12-56 207/162 315 dir. 0204 93% 93% NR 92% 92% NR 6-32-1 67% 50% NR 10.4% NR NR 5.7%
S4 video D20-l 98% NR NR 90% Nit NR 69% 28% NR O"l- NR NR 3.8C'1"

26 11-17 NR 02-04 100% NR Nil 95% Nil Nil 12-72 63% 63% ..t% 0% NR NR 0'>
S?
71 5-52 20/51 02-03 (H) Nil NR NR [93%[ Nil Nil 1-68 64% 9% 9% 4% Nil 2% 4'"
s::i
"0
02-04 (A) C')

94 14-63 42/5? 020-1) 96% NR NR 96% Nil S-It(, 4M 71% NR ":11 limes
..
NR NR NR ;S.
t;
03-04 (A)
,v)
417 11-60 2281189 02 (69) IOOlJ} NR Nil 95% (3 redo) NR Nil NR NR NR NR NR NR 1% 2-1%
'"
(j)
02-lom)' (254)
R3-tomy (9-1)
38 22-39 11{17 02-03 (H) 100'* NR NR lOOt;} NR NR 5-28 5% Nil NR Nil NR NR Nil
l::>
02-0-1 (A)
IISO 8-56 84196 D2-0-l 100% NR NR NR NR &--12 64q. 4% 0% NR NR Nil 0,""

C')

35 m24 23/12 02-03 97% NR NR
"'
NR NR NR )4l:(. Nil
0'""
0'1 NR NR 00,
C)
467 15-59 164/103 01-0-l (H) lOOt;;. NR Nil 100% Nil NR 1 50% Nil 4<1 1% "most NR 67%
-
02-05 (Al p.tIICn,,'
NR, nOI reponed. H, hands: A. axill:lc: F. fcet: A.x, uxlllary, OCS, sp,H:e
"Four umlateral.
blOO'i\-, after rcmlcrvclltion.
'D3t:1 from Malone's (66) may be Included III that of (67).
oJlncludmg associ,lled Rayllaud's dISC,lSC
'0
Vv
""-
'0
""-
Table 5 Technical Characteristics of Published TIS Procedures for Essential Hyperhidrosis
Ref Ventilation Position Entry port Trocar Insumutl0n Unl/biblcral TmlC Major COnll'hC3110ns
[63[ General single-L laleral dccub. 3rd ICS. ani 11m01 CO, Electroco;Jgulation
0"'
NR 2 x Ihor,l(,"Olomy;
2 )I, pneumoehora
[64[ General slOgk-L [:lIer:.1 and prone nlldlHlllar 9mm CO, Dlsscction on, 30-..-50110
[65[ GencTJI slngleL NR 4th ICS. nlidaxlll,H Ilmm NR Elcctrocoagulal ion on, JOmin
[66J General double-L supine 3rd ICS, .Int. axillar Ilmm CO, Electrocoagulation b; NR
(")
[67J Gcneral NR NR NR NR NR NR b; < I hr
0
[68J General doubleL NR NR NR NR Electrocoagulation uni 30min
[69[ General double-L supine 3rd ICS, ant, :I\lllar Ilmm CO, Electrocoagulation b; 30 mill
[70[ Local supine 2nd ICS. ,Interior NR NR Phenol "n, 30min

[7I[ General doublcL supine 4th ICS, ant. ;Ixill. Ilmm CO, Electrocoagulation
b' NR 2 x bleeding
:::J-
drain
<ii
[72[ General double-L supine NR, ant. a:-.ill. Ilmm CO, Dissection b; 27mm
Q.
(15-75min)
[73J General double-L SUplnC and 3rd ICS. anI. axill 8mm CO, Laser b' 60min
["[ General double-L supine, head up Jrd and 4th ICS, ant. a'''ill. NR CO, Electrocoagulation uni JOO1m I x chest drum
[7;J Gener.J1 doubkL latcrol 5th 1(5, ;lnl + POSI. 3xill. 10+ 10+5mm CO, Dissection b; NR
<ii [43J Gencrtll double-L supine. head Up Jrd ICS. ant 'lx,lI. Ilmm CO, Dissection b, NR
a1.
[23J Generol double-L supine 2nd ICS, mid. e1ilV. 8mm CO, Laser bi NR
-
[76J Gener.JI double-L lUI dccub Jrd ICS, nlld c1av. 7rnm NR Phe-nol bi NR
[77J General doublcL lat. decub 4th ICS. ant nlld. und pos!. 10+ 10+5mm CO, DisSt."Ction b, 4,;-150min
l1'(tllar
[78J GcncrJI doublc-L supine. head Up 3rd ICS, .tnt and mid. axill:'H IO+Smm CO, Eleel rocoaglilatioll uni/bi NR 4 x chest drain
[79[ General double-L lut. dccub. 3rd, 5th, 6th ICS, lint. ;tnd mid NR CO, DIssection bi NR
ll.'\ill"H
[80) General doubleL head up 2nd. 4th, 5th ICS ant. aXillar II +S 5+5.5rnm CO, Dissection
b' NR
[81[ General sing1c-L 2nd ICS. Illid. cia\'. NR CO, Electrocoagulation hi 15mtn
(82[ General double-L 'iUpIOC 3rd ICS. II mill CO, Laser llnj NR
[83J Gener.11 double-L 'iuJ'lInC Jrd ICS, ant axillar 5+5mm CO, Elcctrocoagul:ltlon dlsS<.'Ction bi -to-SO min I x hemothorax
[84) General doub1cL aXIllar NR NR Dissection UIll NR I x I
x ulr lc:lk
185J General doublc-L Jrd 1(5, ;lX11I;H 9mm CO, Dissectii"lll uni NR 4 % Horner 2,5
% cheSI drains
:<:
.g
'"
'"
<1>
>:>...
r:;'
Ig61 General double-L 3rd lCS. ,lnt axillar 1101m CO, Electrocoagulation b, NR 6)( chest dr-jill I 2
)(, thOr3COIOI1l)
1'1
Gener.!! singlcL supine. head up 2nd ICS. mid, cia\'. and IlH (1.1\ 7+Smm A"
Ek-'('lfOCOJgulollon b' 25mm
<")
Cl
(HFJV) to
pgj Gener.!1 double-L 3rd ICS, .1'(111 and 2nd mid c1JV 5mm and }mm CO, Electrocoagukltlon um NR -
<")
supine
Cl
(5) Gener.!1 smglc-L \Cllll$ltlmg 2nd ant .1.:\111. or mid clav lmm CO, Electrocoagulation b' 20mm HemOlhor.:n l'l
1511 Geller.. 1 smglc-L scmislllmg 2nd mid cia\'. SOlm CO, Elecifocollguhllion dIS)i.'Ction B, ..160110 20mJll Hemothorax 0.9 <;f
150) GCll\'r.ll double-L (66) supme (lnl aXlll,Jr NR NR Elect roco,lgulallon b; (66) 30min

singlc-L (6) urn (6) 150110

GenerJI double-L 1.11 decub ax.IIM! tnangle 5+3+Jmm NR Electrocoagulation dissectIon b' NR 1 )( chylolhor.L;"(
521 General smglc-L supme 41h rind 5lh mid axill IOmm CO, EleclrocoJgulatlon laser b, 30mm - s:::;
:tI5'1 Gener:!1 Sillg1e-L supme Jrd Jnt :1'1:111. 10mOl AR Electrocoagulation dlssccllon b, BOlin
'"'

Gencrol NR I.Lleral 4th m,d :.,,;11. IIOlm NR
'"'
:Wmm 2'iC' che,)1 luOC
F;-
cg:
I X
for HCldltl
(jtJ-, General NR IJleral 41h mid .n.ll! NR AR Dissection
'"'
15mm-20mm -
Q.55) Geller,,1 double-L semi "lid c1av or :lnL aXll1 10 or 5+5mm NR EleclrocoJgulatlon um or bl IOmlll-I05,mn
s::,
follo,,,p)
supine/lateral
-
<1>
91 General singk-L ::.upmc .Inlll "':\111 and axLllar 2+101111 CO, Dlssccllon b' 15mm-IJOnlln <")

General double-L :lIlt ,'XIII. :llld axillar 2+2mrn (+2mmJ CO, Elcclroco<lgulJIIOn dissection bl 47mm 28mm 2 1% chest lUbes
a
til'
single-L
-r.sl General doublcL laleral :l'l:lllar/lrl.lngle 2+2+2mm or Elcclroco:tgulatlon dlsSl'Cllon b' 30min "c
(61 Geller.l! doublc-L SJllmg Jrd ,Ind 4,h mid 3\111 2mm AR Electrocoagulullon unl b' 15mm (unl)
30min (bi)
Igi General doublc-L lnteral 41h mid :n.iH. and 5th p.lrt a.\11I 3+2mm CO, Electrocoagulation um bl 56 min (bl)
157) General double-L lal de<:ub J.\III,'r'lrI,tngle 5+3+Jmm AR Elcctrocoagukltlon dissection b' NR I hcmOlhora\
2 chylothof"J\
L, lung; NR. not reported: ICS. mtereo::.lul space
ok
'0
V,
496
Noppen
procedures (e.g., simple electrocoagulation rather than dissection and
removal of the ganglia).
B. Causalgia and Reflex Sympathetic Dystrophy
The role of the sympathetic nervous system in causalgia and reflex
sympathetic dystrophy continues to be debated. There is little evidence
that interrupting the sympathetic supply is more effective than placebo in
alleviating the pain of causalgia and reflex sympathetic dystrophy [32]. On
the other hand, success rates above 90% have been reported in well-
documented, selected cases with refractory disease and successful sympa-
thetic block [53].
C. Raynaud's Phenomenon (Acrocyanosis)
Thoracic sympathectomy offers immediate relief in 65-90% of the cases of
Raynaud's phenomenon; however, recurrence rates are high, and more than
half of the patients will experience recurrence within 1-4 years [27,28,30].
Nevertheless, TS may be worthwhile in selected patients with Raynaud's
phenomenon as long as the patients are well informed of the risks and
benefits of the procedure and accept a high probability of recurrent disease.
D. Buerger's Disease (Upper Limb Arterial Insufficiency)
There are no large or controlled studies of Buerger's disease. Anecdotal
reports suggest that TS may provide temporary benefits [2].
E. Cardiac Indications
The results of TS in long QT syndrome refractory to medical treatment are
variable: some investigators report a decrease in mortality [53], whereas
others have shown disappointing results. TS should be reserved for selected
patients who have been refractory to other treatments.
F. Pancreatic Pain
Low TS that results in a functional splanchnectomy provides significant
pain relief in 64-100% of patients with chronic pancreatitis or pancreatic
cancer [38,53].
Medical Thoracoscopy. Thoracic Sympathectomy
VIII. Conclusion
497
Thorascopic TS is a relatively simple, effective, and safe method for
achieving thoracic sympathetic denervation.
Thorascopic TS can be performed by surgeons and by well-trained
pulmonologists. During the last decade, the methodology for TTS has
shifted toward a less invasive and more simplified procedure. A one-time,
bilateral electocoagulation accomplished with small-diameter medical or
surgical thoracoscopic equipment, single-lumen intubation, and general
anesthesia, performed in a I-day hospitalization setting, has become
standard practice. Excellent and long-lasting results are obtained in essential
palmer, axillary, and/or facial hyperhidrosis and facial blushing with an
excellent safety record.
In carefully selected patients, TTS can provide substantial relief in
Raynaud's phenomenon, causalgia, and reflex sympathetic dystrophy;
Buerger's disease and upper limb vascular insufficiency; selected cardiac
arrhythmias; long QT syndrome and angina pectoris; and chronic
pancreatic pain.
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thoracoscopie. Rev Mal Respir 1990; 7:327-330.
71 Byrne J, Walsch TN, Hederman WP. Endoscopic transthoracic electrocautery
of the sympathetic chain for palmar and axillary hyperhidrosis. Br J Surg 1990;
77: ]046-1 049.
72. Lin Ce. A new method of thoracoscopic sympathectomy in hyperhidrosis
palmaris. Surg Endosc 1990; 4:224-226.
73. Kao Me. Video endoscopic sympathectomy using a fiberoptic CO
2
laser to
treat palmar hyperhidrosis. Neurosurgery 1992; 30: 131-135.
74. Edmonson RA, Banerjee AK, Rennie JA. Endoscopic transthoracic sym-
pathectomy in the treatment of hyperhidrosis. Ann Surg 1992; 215:289-293.
75. Appleby Te, Edwards WHo Thoracoscopic dorsal sympathectomy for
hyperhidrosis: a new approach. J Vasc Surg 1992; 16:121-123.
76. Bardoxoglou E, Reigner B, Enon B, Tolstuchow N, Lescalie F, Peret M,
Chevalier JM. Transthoracic Endoscopy for upper thoracic chemical
sympathectomy. Ann Vasc Surg 1992; 6:390--392.
502 Noppen
77. Pace PF, Brown PM, Gutelius IR. Thoracoscopic transthoracale dorsal
sympathectomy. Can I Surg 1992; 35:509-511.
78. Adams DCR, Wood SI, Tulloh BR, Baird RN, Poskitt KR. Endoscopic
transthoracic sympathectomy: experience in the South West of England. Eur I
Vasc Surg 1992; 6:558-562
79. Friedel G, Linder A, Toomes H. Selective video-assisted thoracoscopic
sympathectomy. Thorac Cardiovasc Surg 1993; 41:245-248.
80. Robertson DP, Simpson RK, Rose IE, Garza IS. Video-assisted thoracic
ganglionectomy. I Neurosurg 1993; 79:238-240.
81. Claes G, Drott C, Gothberg G. Thoracoscopy for autonomic disorders. Ann
Thorac Surg 1993; 56:715-716.
82. Austin II, Budhendranouth D, Schatz SW. Transaxillary endoscopic laser
sympathectomy. Can I Surg 1992; 35:414-416.
83. Chao C, Tsai CT, Hsiao HC, Wu WC, Lee CK. Transaxillary endoscopic
sympathectomy. A report of experience in 150 patients with palmar
hyperhidrosis. Surg Laparosc Endosc 1993; 3:365-369.
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thoracoscopic T2 sympathectomy for hyperhidrosis palmaris. I Am Coll Surg
1994; 179:59-64.
85. Herbst F, Plas EG, Fugger R, Fritsch A. Endoscopic thoracic sympathectomy
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Endoscopic transthoracic sympathectomy in the treatment of primary
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25
Transtracheal Oxygen Therapy
KENT L. CHRISTOPHER
University of Colorado Health Sciences Center
Denver, Colorado, U.S.A.
I. History
In 1982, Henry Heimlich first described the use of a transtracheal catheter
for long-term home oxygen therapy. A canine model [1] was initially used to
demonstrate that a transtracheal catheter was well tolerated and that the
Pao2 continued to increase during supplemental oxygen administration as a
transtracheal catheter tip was placed progressively closer toward the carina.
Heimlich went on to report a limited experience with 14 patients [1], who
underwent percutaneous placement of a transtracheal catheter between the
second and third tracheal rings. Administered transtracheal oxygen (TTO)
flow rates ranged from 0.25 to 1.5 L/min, and results showed a 57%
reduction in resting oxygen flow requirement with TTO as compared to the
nasal cannula. TTO was initially delivered using a custom device consisting
of a l6-gauge Teflon intravenous catheter externally secured by a reversed
pediatric tracheostomy tube that was fastened about the neck with cloth ties.
Heimlich and Carr described their experience with a larger patient
population in 1985 [2]. Govan [3,4], in the United Kingdom, and both
Hoffman [5] and Bloom [6], in the United States, studied TTO delivery using
Heimlich's custom d e v i e ~ i d ~ designed a commercial
503
504 Christopher
product that consisted of a modified 16-gauge Teflon catheter that was
inserted through a companion needle (Micro-Trach, Erie Medical,
Milwaukee, WI). The final version of the Heimlich device (Micro-Trach,
Ballard Medical Products, Drapper, UT) was commercially available from
1990 to 1993 (Fig. 1).
In 1986, Leger and coworkers from Lyon, France, described a TTO
catheter that was inserted using a needle-wire guide dilator-introducer
technique [7]. A small number of patients refractory to nasal cannula
administration were evaluated, and the larger diameter catheter delivered
higher flows (mean 2.9 Ljmin) to achieve adequate oxygen saturations. The
catheter and companion introducer system (Oxycath, Laboratorie Smad,
Labresle, France) were commercially available in Europe but not in the
United States. One year after Leger and colleagues introduced the Oxycath,
Johnson and Cary [8] described an implantation procedure involving
subcutaneous tunneling of a silicone TTO catheter from the mid anterior
chest to extend approximately 2 cm into the lumen of the trachea (Fig. 2).
The catheter (ITOC, Cook Critical Care, Bloomington, IN) was commer-
cially available until the year 2000.
Figure 1 The Heimlich Micro-Trach (Ballard Medical Products, Drappel', UT)
was commercially available from 1990 to 1993.
CATMETER IN l
SUBCUT AtiEOUS
TUNNEl
TO 02
_ SOURCE
\
505
Icron
Figure 2 A subcutaneously tunneled silicone transtracheal oxygen catheter (!TOC,
Cook Critical Care, Bloomington, IN) was available until 2000. (From Ref. 8;
courtesy of the American College of Surgeons and Elsevier Science, New York.)
Our initial experience in TTO was with the management of patients
with severe hypoxemia that was refractory to nasal cannula therapy [9]. We
developed a TTO catheter system in the mid 1980s that utilized a needle-wire
guide-dilator insertion technique [9]. We then on the safety and
efficacy of a comprehensive TTO therapy program in 1987 [10]. The
acronym SCOOP (Spofford Christopher Oxygen Optimizing Program) was
later coined, and the program continues to be the most widely used method
of TTO administration. The SCOOP transtracheal catheters and insertion
trays (Transtracheal Systems, Inc., Denver, CO) have been available for
more than 15 years, and approximately 15,000-20,000 patients have been
treated worldwide. Since the majority of the research and clinical experience
is based upon this technology, and since the only products that are
commercially available in the United States at the present time relate to this
method of TTO administration, the remainder of this chapter will focus on
this method TTO therapy.
II. Overview of a TTO Therapy Program
The SCOOP program for creating the TTO catheter tract was initially
developed around a (MST). The MST
506
Christopher
program has been described in detail elsewhere [11]. We introduced an
alternative surgical method for tract creation in 1996 [12]. The Lipkin
surgical approach [12] presents some potential advantages over the MST,
which include a reduction in potential complications and both streamlined
education and shortened program duration. There continue to be
proponents of both methods of TTO catheter insertion. Both methods of
tract creation will be reviewed. Whether the MST or the surgical path is
taken, the TTO program comprises four clinically defined phases. Phase I is
focused on patient evaluation and preparation. The primary goal is to select
patients properly, while identifying established indications, contraindica-
tions, and precautions. The transtracheal tract is created in Phase II, and the
goals are to create a quality tract and to make certain that the patient
remains clinically stable during either the MST or surgical intervention and
associated postprocedure period. The patient begins TTO therapy in Phase
III, but the tracheocutaneous tract has not fully matured. The major goals
in this phase are to prevent inadvertent catheter removal and prevent
symptoms from adherence of inspissated mucous to the outer surface of the
catheter (mucous balls). To facilitate this, clinicians must periodically
remove the catheter over a wire guide for cleaning in Phase III. The tract is
mature in Phase IV, and patients can be trained to remove the catheter for
cleaning on an individualized cleaning schedule. The goals in Phase IV are
to monitor and prevent complications such as chondritis, keloid formation,
and lost tracts and to facilitate the patient's realization of the benefits of
TTO, including the maintenance of an acceptable level of activity and
optimal quality of life.
III. Complications of a Program Utilizing the MST
for Tract Creation
The potential complications resulting from administration of the TTO
program by the MST are shown in Table 1. The table presents the initial
large experience in United States [10] and compares those results to a more
recent study from the Netherlands [13]. The investigation of Kampelmacher
and colleagues [13] adds additional value, because the Netherlands'
experience with their initial 10 patients is contrasted to results obtained
from their subsequent 65 patients. Complications were infrequent and minor
in severity during the procedure and stent week. Both studies identified a
variety of minor complications during tract maturation (Phase III) and the
more long-term delivery of TTO with a mature tract (Phase IV). The
Kampelmacher study demonstrated that the complication rate markedly
improved after gaining experience with the initial 10 patients. Of note, only
Table 1 TTO SCOOP Program Complications Utilizing a Modified Seldinger Insertion Technique
Christopher et a!. [10] Kampelmacher et a!. [13]
Initial experience Subsequent experience
Frequency
(0/0)
2 3
Patients
(n = 65)
70
Frequency
(0/0)
7
Immature (Phase III) and Mature (Phase IV) Tract Periods
I 10
6 60 I 2
2
Patients
(n = 10)
3
2
Frequency
(0/0)
3
2
() Patients
.g Complication (n = 100)
~ 1 f
to'Procedure and Stent Week (Phase II) Procedure and Stent Week (Phase m
~
(j) Subcutaneous emphysema
Q. Bronchospasm
~
(j)lmmature (Phase III) and Mature (Phase IV) Tract Periods
~ Symptomatic mucous balls 10 10
- Lost tracts 7 7
Cricothyroid puncture 3 3
Cephalad-displaced catheter 3 3
Table 1 Continued
Christopher et al. [10] Kampelmacher et al. [13]
Initial experience Subsequent experience
()
.g

':
CD
Q.

CD

Complication
Bacterial cellulitis
Hemoptysis (> 10-25 mL)
Keloid
Candidal dermatitis
Contact dermatitis
Subcutaneous emphysema and
pneumomediastinum
Chondritis
Inadvertent dislodgement of catheter
Fractured catheter"
Tracheobronchitis
Tracheitis
Patients
(n = 100)
I
2
4
2
3
I
Frequency
(%)
1
2
4
2
3
1
Patients
(n = 10)
4
3
5
I
Frequency
(%)
10
40
30
50
10
Patients
(n = 65)
8
2
7
Frequency
(%)
11
3
9
2
2
"Occurred in one of the initial five patients using the Oxycath (Laboratorie Smad, Labresle, France) before switching to the SCOOP catheters (Transtracheal
Systems, Denver, CO).
Source: Refs. to and 13.
509
four (4%) of the patients in the initial U.S. study chose to discontinue TTO
therapy, and only two subjects (3%) in the Netherlands study elected to
return to nasal oxygen.
Adamo and colleagues reported their initial experience with TTO in 21
patients over a 2 year period [14]. Serious complications using the MST were
infrequent and included respiratory failure, misplacement of catheters into
the anterior and middle mediastinum, and moderate hemoptysis. Although
most other complications were minor and resolved, 14% had mucous balls
and 38% of patients had an episode of catheter dislodgement. After
treatment of their subsequent 31 patients [15], review of their data only
demonstrated a trend for reduction in technical/procedural-related compli-
cations (P = .053), but experience beyond 25 procedures was not associated
with any decrease in complications.
Hoffman and coworkers reported on 40 patients [16]. They
encountered a higher incidence of symptomatic mucous balls (25%) as
well as inadvertent catheter displacement in both the immature (22%) and
mature tract phases (22%). The investigators were unable to reinsert the
catheter (lost tract) with an incidence of7% in Phase III and 7% in Phase IV.
In a more recent report of 56 patients treated over 5 years, Orvidas and
colleagues [17] found that severe complications such as pneumothorax and
pneumomediastinum were rare, but 38% of patients had mucous balls.
Over 16 years have past since the introduction of TTO using the MST.
During that time, there have been rare case reports of I death [18] and 7 Iife-
threatening events due to airway obstruction from mucous balls [19-25]. In
addition, there has been one case report of tracheal perforation [26] and one
report of death due to catheter misplacement [27].
In summary, the literature and extensive clinical experience demon-
strate that TTO utilizing the MST for catheter insertion is safe. Severe or
life-threatening complications are very rare. The most frequent minor
complications encountered with the MST are symptomatic mucous balls,
lost tracts or catheter displacement, keloids, and chondritis. Although staff
experience may tend to reduce technical/procedural complications, experi-
ence does not appear to play a significant role in reducing technical/
procedural complications after 25 procedures. Minor complications do not
seem to be a significant deterrent to use. Patient acceptance rate is generally
on the order of 96%.
IV. Potential Benefits
The potential benefits of TTO therapy compared to nasal oxygen delivery
are shown in Table 2. benefits have been
510
Table 2 Potential Benefits of Transtracheal Oxygen Therapy
Compared to Nasal Oxygen Delivery
Physiological benefits
Reduced erythrocytosis
Reduced pulmonary vascular resistance
Improved cor pulmonale
Improved room air alveolar to arterial oxygen tension gradient
Decreased physiological dead space
Reduced inspired minute ventilation
Reduced work of breathing
Shortened respiratory duty cycle
Improved exercise capacity
Improved oxygenation during sleep
Improved mobilily
Greater exercise tolerance
Longer lasting, lightweight portable oxygen sources
Reduced dyspnea
True 24-hr per day compliance
Greater comfort
Elimination of nasal prongs (cannula) complications
Improved self-image
Reduced hospilal days and cost
Christopher
described in the literature. We reported a marked reduction in erythrocy-
tosis in the treatment of hypoxemia that was refractory to nasal oxygen
therapy [9]. Significant reductions in hematocrit were also seen in patients
thought to be adequately treated with nasal cannula therapy [10]. Domingo
and associates reported reduced pulmonary vascular resistance upon initial
study [28] and follow-up [29] in patients requiring supplemental oxygen.
Another investigation by Domingo's group [30] suggested improved
oxygenation during sleep. Reduced cor pulmonale was particularly notable
in patients with severe refractory hypoxemia [9].
O'Donohue [31] evaluated room air arterial blood gases in patients
who received nasal oxygen therapy during a control period, and room air
arterial blood gases were repeated following administration of TTO. The
room air alveolar to arterial oxygen tension gradient was significantly less
after receiving transtracheal oxygen delivery. In addition, Hoffman and
coworkers [32] demonstrated that exercise capacity was significantly
increased with TTO. Couser and Make [33] showed that TTO decreases
the inspired minute ventilation as a result of a reduction in tidal volume, and
511
Bergofsky and Hurewitz [34,35] documented reduced physiological dead
space with transtracheal gas delivery. Finally, Benditt and Celli's group [36]
reported reduced oxygen cost of breathing and shortened respiratory duty
cycle wi th TTO.
Improved mobility usually results from TTO delivery. Oxygen flow
requirements are reduced by over 50% at rest and approximately 30%
during exercise [10]. Consequently, portable oxygen delivery systems last
longer and patients can take advantage of smaller and lighter units. Mobility
is facilitated by improved exercise tolerance, and patients often experience
reduced dyspnea. Improvement in dyspnea may result from the previously
described reduced physiological dead space, decreased inspired minute
ventilatory requirements, and reduced oxygen cost of breathing.
True 24-hr per day compliance can be achieved with TTO therapy.
Most patients conclude that TTO is more comfortable than the nasal
cannula. Consequently, they are more likely to use TTO continuously. In
one study, the most common reason for patients to seek TTO was the
need for improved comfort [37]. Patients on nasal oxygen may have
suboptimal compliance due to discomfort from chronic irritation around
the nose and ears or from more significant complications such as contact
dermatitis, chondritis, or skin ulceration. Although cosmesis is not a
significant concern for many patients [37], some individuals may be more
compliant with TTO because of improved self-image resulting from the
fact that the delivery device is entirely off the face and can easily be hidden
from view.
The NOTT [38] and MRC [39] data document that survival in
hypoxemic chronic obstructive pulmonary disease (COPD) is directly
related to hours of oxygen use. In the "continuous group" of the NOTT
study, patients only used the nasal cannula approximately 19 hrs per day. It
is likely that 24-hr per day TTO therapy has the potential further to
improve survival. The study by Clifford suggests that this may be the
case [40].
Recent years have brought increasing concern for cost containment.
Prolonged hospitalizations are much more costly than long-term oxygen
therapy in the home. Compared to a nasal cannula control period, Hoffman
[32] showed that hospital days were significantly reduced with TTO. Bloom
[6] also demonstrated that hospital days for patients on TTO were
significantly less than the hospital days during a period when they had
received nasal oxygen. Likewise, the TTO group's hospital days were lower
than seen in a separate nasal cannula control population.
512 Christopher
v. Highlights of the Program with the MST for Tract
Creation
This section discusses the overall program, but is not intended as a
comprehensive educational manual for patient care. The entire SCOOP
Program utilizing MST has been more fully described elsewhere [II).
Comprehensive video, electronic, and printed educational materials are
available through the manufacturer (Transtracheal Systems Inc., Denver,
CO).
A. Phase I: Patient Orientation, Evaluation, Selection,
and Preparation
As noted previously, a primary goal in Phase I is to select the right patient.
The specific indications, contraindications, and precautions for TTO are
shown in Table 3. These recommendations have evolved through data
drawn from scientific publications and extensive day-to-day clinical
experience. Patients considering TTO should first meet well-established
reimbursement criteria for continuous long-term oxygen therapy. TTO is
specifically indicated if the individual experiences complications or
discomfort from nasal prongs that result in suboptimal compliance. Patients
may remove the cannula because of chronic pain or discomfort over the ears
or under the nose resulting from abrasion, maceration, ulceration,
chondritis, or contact dermatitis.
Hypoxemia that is refractory to maximal nasal cannula therapy is a
specific indication for TTO. In addition to refractory patients who have
inadequate oxygen saturations both day and night, there are individuals on
continuous oxygen therapy that selectively experience nocturnal hypoxemia
on nasal prongs. A more subtle subset of patients on long-term oxygen
therapy demonstrate adequate oxygen saturations on spot checks during
periodic brief medical examinations, but continue to experience cor
pulmonale or erythrocytosis on nasal oxygen. These individuals may benefit
from TTO as an alternative delivery system. As noted previously, patients
requiring improved mobility frequently benefit from TTO. Patient
preference is extremely important; TTO should be considered when nasal
prongs promote noncompliance because of cosmetic, discomfort, or
impaired mobility issues.
Contraindications for TTO have been well established. Individuals
with severe anxiety neurosis tend to become more anxious when faced with
the responsibility of catheter self-care. Patients with generalized poor
compliance with medical therapy should not be considered. Those with
severe mental or physical incompetence may not be able to care for the
Table 3 Transtracheal Oxygen Therapy: Specific
Indications, Contraindications, and Precautions
Specific indications
Complications of nasal prongs
Hypoxemia refractory to maximum nasal prong therapy
Cor pulmonale or erythrocythemia on nasal prongs
Nocturnal hypoxemia on nasal prongs
Need for improved mobility
Noncompliance related to nasal prongs
Patient preference
CO/1traindications
Severe anxiety neurosis
Poor compliance with medical therapy
Mental or physical incompetence
Upper airway obstruction
Pleura herniated over puncture site
Precautions
Poor mechanical reserve
Profound hypoxemia
Hypercarbia without acidemia
Large neck or other anatomical abnormality
Mild to moderate anxiety neurosis
Bronchial hyperreactivity
Copious or viscous sputum
Serious cardiac arrhythmia
Bleeding disorder
513
catheter adequately. The presence of a severe upper airway obstruction is
also a contraindication. Barotrauma could potentially result, since oxygen
delivered into the distal trachea at a point below the obstruction may not be
able to escape. Finally, the finding on a chest radiograph of herniation of
pleura over the planned procedure site constitutes a contraindication,
because the MST will likely result in complications such as pneumothorax
or pneumomediastinum.
There are a number of patients who do very well with TTO, but one or
more precautions are identified during their initial evaluation. It is not
uncommon for patients to have a poor mechanical reserve, profound
hypoxemia, or hypercarbia without acidemia. Care must be taken to have
these patients on maximal medical therapy and in stable condition prior to
the elective procedure. Individuals with a serious cardiac arrhythmia,
bleeding disorder, or adequately prepared for
514
Christopher
the procedure and monitored carefully. In patients with a large neck or
other anatomical abnormality, it may be wise either to have an experienced
interventional pulmonologist perform the MST or consider the Lipkin
surgical approach for tract creation.
Some individuals have an element of bronchial hyperreactivity
associated with their COPD. Preprocedure pharmacological control of
airway reactivity is important. The presence of copious or viscous sputum in
patients with diseases such as cystic fibrosis and bronchiectasis should not
necessarily preclude TTO as a treatment option. However, optimal control
of bronchial infection and maintenance of adequate bronchial hygiene are
essential in this preprocedure phase and throughout the entire program.
Individuals with very copious or viscous sputum and those with
uncontrolled bronchial hyperactivity are particularly prone to encountering
difficulty in Phase III owing to the development of symptomatic mucous
balls. Unrelenting cough may also predispose marginally compensated
patients to respiratory muscle fatigue. The presence of mild to moderate
anxiety is not uncommon in patients struggling with severe chronic lung
disease. Aggressive education and reassurance often help these individuals
overcome their fears and they usually do well with TTO. Increased
confidence often comes with improved mobility and activity.
Patients should be fully informed about the potential benefits and risks
of TTO therapy before making a commitment to proceed with MST for
creation of the catheter tract. In addition to a question and answer session
with a knowledgeable health care professional, an ideal orientation includes
an opportunity for the candidate to talk or meet with a transtracheal
patient. A targeted history should not only include historical pulmonary
information, but also details about prior oxygen therapy and compliance
with the nasal cannula.
The physical examination should also include careful inspection of the
nose including nostrils, septum, and mucosa. The ears are examined for
helical chondritis or irritation and other problems such as serous otitis
media. Observations in the neck should include length, thickness, deviation
of the trachea, position of the larynx, and position of anterior neck veins.
The neck anatomy is inspected and palpated with the transtracheal
procedure in mind.
Arterial blood gases on the nasal cannula are helpful to assess the
adequacy of alveolar ventilation and degree of compensation for respiratory
acidosis. The Pa02 and respective liter flow give the patient and physician an
estimate of reduced oxygen flow on transtracheal oxygen. The hematocrit is
a simple test which reflects on the overall adequacy of oxygen therapy. A
follow-up hematocrit on transtracheal oxygen demonstrating a shift from a
high-normal hematocrit to a mid- or low-normal hematocrit is common and
515
suggests better 24-hr per day oxygenation. Prebronchodilator and post-
bronchodilator spirometry is helpful to estimate mechanical reserve and
airway hyperreactivity. Posteroanterior and lateral chest radiographs with a
properly fitted bead chain necklace are helpful in excluding rare individuals
with pleura over the anterior neck and identifying unusual variants of
anatomy before the transtracheal procedure. Additional laboratory data
may be beneficial in individual cases. Special tests may include exercise
oximetry, a 1.0 Fro2 study (to determine the degree of refractoriness to
oxygenation), lung volumes, diffusion capacity, coagulation studies (antic-
oagulant therapy), or an electrocardiogram (arrhythmias).
Patients determined to be good candidates for TTO are scheduled for
an outpatient procedure. They are instructed to take nothing by mouth after
midnight (except for medications with a sip of water) and arrive I hr before
the procedure. A significant other should provide transportation and stay
with the patient throughout the procedure visit.
B. Phase II: The Transtracheal MST Procedure and Stent
Week
The primary goals in Phase I are to create a quality tract and to make
certain that the patient remains clinically stable during the MST and
associated I-week stent period. The MST procedure is usually performed on
an outpatient basis. Most patients with Paco2 <50 mmHg may be given one
oxycodone capsule I hr before the procedure for antitussive, analgesic, and
sedative effects. Patients with Paco2 >50 mmHg may be given diphenhy-
dramine 25-50 mg as an alternative. Cephalexin 500 mg or another
antibiotic effective against Staphylococcus aureus is given for infection
prophylaxis. Patients at risk for bronchospasm receive nebulized bronch-
odilator about 30 min before the procedure.
The procedure should be performed with the patient sitting upright;
and ideal positioning is achieved with an ENT (ear, nose, and throat)
examination chair with a headrest. The back of the chair is angled backward
about 10 degrees, and the headrest is adjusted to slightly extend the patient's
neck. The ideal neck position is the same as when the patient is looking in a
mirror at his or her own anterior neck. The nasal cannula should be
repositioned to arrive from behind; this leaves the anterior neck
unobstructed for the procedure. The most recent posteroanterior and
lateral chest radiographs are displayed in the procedure room on a view box.
A spotlight is focused on the anterior neck.
Procedure site selection and preparation are accomplished utilizing the
upper tier (Fig. 3a) of the procedure tray (T-9 Procedure Tray,
Transtracheal Systems, superficial anatomy of the
516
Christopher
(a)
Figure 3 The preparatory tier of the procedure tray (T-9 Procedure Tray,
Transtracheal Systems, Inc., Denver, CO) is used to select the proper position for the
catheter and prepare the procedure site (a, left). The second tier (b, right) contains
the stent and necessary instruments and supplies to perform the modified Seldinger
procedure.
anterior neck is palpated and special attention is paid to the anterior neck
veins and the position of the trachea. The notch of the thyroid cartilage is
marked using a surgical marking pen with a V, the cricothyroid membrane
is marked with a horizontal dashed line, and the notch of the manubrium is
marked with a gentle U. The cervical trachea rests between the dashed line
and the U and creates a vertical axis. The most stable position for the
catheter is at the crossing of the security necklace and the trachea. A bead
chain necklace is passed around the neck and adjusted with wire cutters to
accomplish a proper fit, which usually accommodates two fingers snugly but
would not be excessively tight with neck hyperextension or a heavy cough.
The crossing point may be marked using the surgical pen with two dashes
laterally over the sternocleidomastoid muscles. In about 85% of patients, the
necklace will cross at the first or second tracheal interspace. In about 10%, it
will cross lower, and in 5%, it will cross the cricothyroid membrane. In this
(b)
Figure 3 Continued
LOWER
TIt
5/7
case, the chain is loosened to permit it to dip to the first tracheal interspace.
A tract should not be created through the cricothyroid membrane, because
it predictably results in hoarseness, difficulty with catheter insertion, keloids,
and chondritis.
Skin anesthesia is performed using a 27-gauge needle with 2%
lidocaine with epinephrine 1: 100,000 at the level where the necklace crosses
the cervical trachea. First, initial intradermal injection spans the medial
aspects of both sternocleidomastoid muscles. Next, the trachea is transfixed
with the thumb and forefinger of the nondominant hand and 1 mL of local
anesthetic is injected from the skin down to the trachea. The 27-gauge needle
is removed and the 20-gauge needle is attached to the syringe. With the
trachea transfixed, the needle is inserted into the trachea at the puncture site,
air is aspirated into the syringe, and the remaining 2 mL of local anesthetic is
quickly injected. The needle is immediately removed to avoid lacerating the
mucosa with coughing, and the patient is permitted to cough. The anterior
neck is then prepped with
518
Christopher
The lower tier (Fig. 3b) of the procedure tray contains the stent and
other necessary supplies for creation of the transtracheal tract and is used
with sterile technique. A sterile drape is applied straight across the chest at
the level of the clavicles. A No. 15 scalpel is used to make a vertical I-cm
incision at the selected puncture site. Attempts should be made to place the
incision to the side of any visible anterior neck vein to avoid bleeding and
bruising. Two passes of the blade are usually required and sequentially
expose dermis and then fat.
The 7-cm 18-gauge thin-wall needle attached to a syringe containing
2 mL of sterile saline is passed through the small incision down to the
trachea. The cartilages are gently palpated with the needle, which is then
popped through the intercartilaginous ligament. The maneuver resembles a
thoracentesis when the rib is palpated with a needle that is passed over the
rib and into the pleural cavity. A common misconception is that the trachea
is parallel to the anterior neck and chest. In most patients, the trachea falls
away from the anterior chest wall at about a 45-degree angle. With the
patient sitting 10 degrees back, the trachea is usually vertical. Passing the
needle horizontal to the floor will usually cause the needle to enter the
trachea perpendicularly. Air is aspirated back, and the syringe is detached
from the needle. The needle is rotated to bring the notch on the hub to the
inferior rim; this directs the bevel of the needle downward. The hub is then
elevated to angle the needle downward toward the carina.
The atraumatic end of the wire guide is inserted through the needle to
the II-cm reference mark. Insertion should feel like passing the wire guide
through the needle into air. If any resistance is met, the needle may be
misplaced outside the trachea. When doubt exists, the wire guide is removed
and the procedure is repeated. After proper positioning of the wire guide,
the needle is removed. A gloved assistant should hold the black reference
mark on the wire guide at the level of the skin to free the physician for the
dilation step.
The dilator is passed over the wire guide with a firm and steady push.
Twirling the dilator is not necessary. To avoid traumatizing the posterior
tracheal wall, the dilator is angled downward toward the carina. When the
dilation of the intercartilaginous ligament reaches the full diameter of the
dilator, less resistance is encountered. Insert the dilator an additional 2em
into the trachea, but do not go beyond the black reference mark at 8 cm. The
dilator is left in place for Imin to fatigue the elastin fibers of the ligament.
The dilator is removed taking special care to leave the wire guide in
place. (Note: This is different from insertion of a central venous catheter
because of the absence of an introducer sheath.) Again, a gloved assistant
holds the black reference mark on the wire guide at the level of the skin. The
previously lubricated stent is immediately inserted over the wire guide. As
519
the tip passes through the neck tissues, it is twirled a full 360 degrees until
the flange comes to rest against the skin. The exchange from the dilator to
the stent is made quickly, because venous oozing is most likely to occur at
this point and the stent tamponades the bleeding.
The stent is stabilized with I-em sutures passed vertically through
full-thickness skin. The small eyelets of the stent are intended to discourage
the use of the necklace, which' could become excessively tight with normal
swelling or subcutaneous emphysema. As the stent is being sutured in
place, the patient is asked to cough gently. This should result in air
regurgitating out of the lumen of the stent. If it does not, a syringe is used
to aspirate air out and confirm that the tip of the stent is in the airway. The
I-em vertical incision is not closed with sutures and should be intentionally
left open to permit the stent to function as a surgical drain. A nonocclusive
dressing is lightly taped over the flange of the stent, and the procedure is
terminated.
At the conclusion of the transtracheal procedure, the patient is taken
to the radiology suite for a posteroanterior and lateral chest radiograph.
This should document the absence of extravasated air (subcutaneous
emphysema, pneumomediastinum, and pneumothorax) and confirm the
intratracheal location of the radiopaque stent. The relationship of the tip of
the stent to the carina is noted. The internal length of the stent is identical to
that of the functioning transtracheal catheter with an internal length of
II em. If the tip of the stent is closer than I cm to the carina, a shorter 9-cm
catheter should be obtained before transtracheal oxygen is started I week
later. In contrast, if the tip of the catheter is 3 or more centimeters above the
carina, the 13-cm catheter may be more appropriate. Placement of the stent
with an open incision and nonocclusive dressing minimizes the potential for
subcutaneous emphysema or barotrauma. The absence of gas flow
minimizes coughing, because the trachea rapidly accommodates to the
presence of just the foreign body. Systemic antitussives and topical lidocaine
further suppress coughing.
All patients are observed for a minimum of 1hr following the
procedure. Patients with impaired mechanical reserve, refractory toxemia,
or chronic hypercarbia may be admitted to an observation unit overnight.
The physician should also admit to an observation unit other patients who
would be a concern at home.
Antibiotic prophylaxis with cephalexin 250 mg TID (or another
antibiotic effective against S. aureus) 1-2 weeks following the procedure is
recommended. Exposure of cartilage may be unavoidable because of fused
tracheal rings. These unusually long periods of prophylaxis appear to be
required because of the avascular nature of cartilage and the presence of a
foreign body. suggests that failure to
520
Christopher
administer an antibiotic for these longer periods may result in tracheal
chondritis 2 or 3 weeks later.
As the topical anesthesia wears off during the i-hr postprocedure
observation time, most patients develop some degree of cough. The severity
of cough is assessed I hr after the procedure, and a cough-suppression plan
is designed. Patients are instructed to resist any urge to cough, because it can
result in respiratory fatigue or subcutaneous emphysema. Nonnarcotic
cough suppressants are dispensed for use as needed. For individuals with the
more severe cough, 4 mL of 0.25% lidocaine may be instilled through the
stent every hour as needed. Patients regularly report that the procedure is
less painful than an arterial blood gas puncture. Patients usually require
only acetaminophen for pain. Aspirin and ibuprofen products are avoided
because their anti platelet effect could cause increased bruising. During the
first hour after the procedure, patients review cough suppression, tract care,
and circumstances which should result in a call to the physician for help. A
follow-up appointment is set for I week later. A phone call the afternoon of
the procedure and the day after the procedure are recommended to confirm
that the patient is not experiencing problems.
During the week following the transtracheal procedure, patients
continue to receive supplemental oxygen via a nasal cannula. Patients are
specifically instructed not to connect oxygen to the stent. Once the open
lumen of the stent is lost because of the use of the channel for oxygen
delivery, experience demonstrates that air cannot adequately leak between
the outer lumen of the stent and the tissues. Consequently, development of
subcutaneous emphysema or other barotrauma complications are possible.
The nonocclusive dressing may be removed after the first day, but the tract
is kept clean and dry. The tract is cleaned twice daily with a cotton-tipped
applicator and 3% hydrogen peroxide. Regurgitation of air through the
stent usually stops after 2 or 3 days when the lumen becomes blocked by
inspissated secretions.
c. Phase III: Transtracheal Oxygen with an Immature Tract
In Phase Ill, the patient begins TTO therapy, but the tracheocutaneous tract
has not fully healed or matured. A major goal in this phase is to teach the
patient proper care in cleaning of the catheter. Other goals in Phase III are
to prevent inadvertent catheter removal, prevent tract problems, and
avoided symptoms from adherence of inspissated mucous to the outer
surface of the catheter (mucous balls). To facilitate this, clinicians must
periodically evaluate the patient and remove the catheter over a wire guide
for cleaning.
Transtracheal Oxygen Therapy 521
Phase III begins 1 week after the transtracheal procedure. During the
first visit, the stent is exchanged for a functioning SCOOP catheter. The
exchange is accomplished with the patient seated in the procedure chair with
a headrest. Nasal prongs are rearranged to arrive from behind so as to free
the anterior neck. A SCOOP catheter is selected based on the position of the
stent relative to the carina on the postprocedure radiographs. A catheter
with an II-em internal length is usually the proper size (SCOOP Catheter,
Transtracheal Systems, Inc., Denver, CO). As shown in Figure 4, a shorter
catheter (9-cm internal length) and a longer version (l3-cm internal length)
are also available to accommodate variations in body habitus. A small
amount of sterile water-soluble jelly is placed on the tip of the catheter. The
customized necklace saved from the initial procedure is passed through the
eyelets of the catheter. The atraumatic end of the wire guide is passed
through the stent up to the black reference mark to clear dried secretions.
Approximately 2 mL of 1% plain lidocaine is drawn into a Luer taper
syringe and then quickly injected through the stent. The crusts about the
stent are cleaned with cotton-tipped applicators dipped in 3% hydrogen
peroxide. The sutures are then cut with the scissors saved from the prior
week. The SCOOP wire guide is inserted to the black reference mark, and
the stent is withdrawn. An assistant holds the black reference mark at the
level of the skin to prevent inadvertent removal of the wire. The SCOOP
catheter with the prethreaded necklace is then passed over the wire guide
and twirled 360 degrees into the tract. When the flange comes to rest against
the skin, the wire guide is removed and the necklace clasp connected.
Inadvertent dislodgement during Phase III is likely to result in lost of the
tract, since the tract is immature and not lined by epithelium. Placing a 2-
inch piece of clear plastic tape over the necklace immediately right and left
of the flange is a simple and effective way to help prevent early
dislodgements.
The patient is fited with a SCOOP oxygen hose, and catheter cleaning
supplies are dispensed. Pulse oximetry is used to titrate transtracheal flow
rates at rest and with exertion. The patient is instructed in cleaning the
catheter in place using instilled saline and a cleaning rod. The individual
should also be observed through a cleaning cycle to confirm proper
technique. The significant other should be encouraged to sit through the
entire session. The patient is educated about security routines to avoid
losing the tract and symptoms which suggest the presence of a mucous ball.
A mucous ball is an accumulation of inspissated mucus which adheres
to the anterior and lateral surfaces of the catheter just above the tip. As
noted earlier, symptomatic mucous balls occur in approximately 10-30% of
patients in Phase III when the catheter is cleaned in place. They generally
disappear in Phase IV the mucous off the
522
Christopher
Figure 4 Most commonly, a catheter with an II-em internal length (middle) is
adequate to place the tip a few centimeters above the carina. Depending upon patient
stature, a shorter 9-cm (left) or longer 13-cm (right) internal length radiopaque
catheter may be appropriate (SCOOP Catheter, Transtracheal Systems, Inc., Denver,
CO). The single cleaning rod accommodates the constant internal plus external
length of 20 em for each catheter.
catheter, allowing it to be expectorated. In many patients, the trachea
adapts, and mucous balls spontaneously diminish in frequency during
Phase III. Although mucous balls can cause a "tickle" cough, dyspnea, or
wheezing, they rarely result in airway obstruction. The pathogenesis of
their formation is related to the volume of dry gas introduced into the
lower airway and baseline secretions. Patients with low FEVI and weak
523
cough are less able to generate the glottic blast to dislodge mucous
balls and are at relatively greater risk. Ineffective cleaning, inadequate
humidification, failure to strip the catheter periodically during Phase III,
and insufficient systemic hydration are iatrogenic factors which predispose
a patient to mucous ball formation. The use of a mucoevacuent, such as
guaifenesin, may be helpful. Clinicians should maintain a high index of
suspicion during Phase III. Mucous balls, which may form in spite of
adequate cleaning and humidification, should be immediately recognized
and treated.
All patients should return for a clinical evaluation and catheter-
stripping within the first week of initiating TTO. The catheter-stripping
technique is very similar to the procedure for exchanging the stent for a
functioning catheter. In brief, the patient uses nasal prongs and 1%
lidocaine is instilled into the catheter. The atraumatic end wire guide is
inserted to the II-cm mark. With the bead chain disconnected, the soiled
catheter is removed and cleaned while the wire guide remains in place with
the black reference mark held at the level of the skin. Water-soluble jelly is
applied to the tip of the catheter, which is then reinserted over the wire
guide. Once the bead chain necklace is attached and secured with tape,
transtracheal oxygen is resumed. The time required for tract maturation,
or the duration of Phase III, is generally 6-8 weeks. The number of visits
required during this phase is determined by the need for reinforced
education and the patient's propensity to develop mucous balls that require
stripping. Detailed customizable protocols for humidification, cleaning
regimens, and scheduled catheter stripping are available from the
manufacturer.
Dislodgment of the catheter during Phase III can result in closure of
the tract in a matter of minutes. Awareness of this potential problem is of
utmost importance. The physician should have a sterile catheter and wire
guide available for possible emergent use. In the event of dislodgment, the
patient must be seen immediately, and the physician should attempt to
reinsert the SCOOP catheter using a small amount of sterile water-soluble
jelly on the catheter tip. If after a few minutes this is not successful, an
attempt to pass a SCOOP wire guide should be made. Local anesthetic is not
injected, since it tends to distort tissues. Often the tract will be open through
soft tissues but closed at the intercartiJagnious space of the trachea.
Prolonged attempts at recovering the tract are not advised, since the wire
guide may make numerous false tracts. If the tract cannot be recovered, the
patient goes home on nasal prongs, and an elective procedure may be
scheduled for a later date. The physician should resist the temptation to do
an unscheduled procedure without preparation and support available with a
planned procedure. Copyrighted Material
524 Christopher
A variety of tract problems may be seen during Phase III. Erythema
may be caused by maceration, abrasion, granulation tissue, contact
hypersensitivity, Candida a/bicans infection, and bacterial cellulitis. All
that is red is not infected. Maceration and abrasion may result from a
necklace which is too tight or a patient who buttons the top button of a shirt
collar. A cuff of granulation tissue is a normal part of healing for most
patients. Granulation tissue is a bright red and friable mass of capillaries,
fibroblasts, and inflammatory cells. If the granulation tissue is exuberant
and is associated with minor bleeding, simple cautery will correct the
problem. Candidal infection is usually an iatrogenic complication from the
use of broad-spectrum antibiotic ointments. Other factors which predispose
to candidal infection include oral steroids, oral antibiotics, and diabetes
mellitus. The best protection against candidaI infection is a clean, dry tract.
Contact hypersensitivity can occur with chlorhexidine residues on the
catheter and other substances that the patient may be applying to the tract.
Patients should only clean with pure soap (e.g. Ivory bar soap). Bacterial
cellulitis is uncommon but would be treated with antibiotics. Tracheal
chondritis is a special issue that deserves discussion.
Cartilage is a unique tissue, because it is avascular and has a tendency
to become colonized by bacteria and behave like a foreign body. Refer to the
earlier discussion justifying the prolonged use of antibiotic prophylaxis
around the time of the procedure. Clinically, about 10% of patients develop
a deep indurated lump around the tract several weeks after the procedure.
The lump is often tender, but unlike an abscess, it is not fluctuant. The
bacteriology is unclear, but the knot appears to be a regional inflammatory
response to colonization of exposed tracheal cartilage. Treatment with oral
antibiotics effective against S. aureus for an additional 3 weeks is usually
effective.
D. Phase IV: Transtracheal Oxygen with a Mature Tract
As noted previously, the goals in Phase IV are to monitor and prevent
complications such as chondritis, keloid formation, and lost tracts and to
facilitate the patient's realization of the benefits of TTO, including the
maintenance of an acceptable level of activity and optimal quality of life.
Phase IV usually begins about 6 weeks after the transtracheal procedure in
patients with slim and medium necks and 8 or more weeks after the
procedure in patients with large necks or no cervical trachea. A customized
cleaning protocol for each patient is desirable, because it takes into
consideration liter flow, mucus production, underlying lung disease, the
patient's level of comfort with catheter removal and insertion, and the
ability to generate an effective cough. A cleaning routine should include
525
cleaning in place at least twice a day. Cleaning in place is the foundation of
care. The frequency may easily be increased or decreased based on the
patient's needs. Removal for cleaning can be done as often as twice a day or
as little as once a week. Daily or twice daily catheter removal reduces the
risk of mucous ball formation and is recommended. Patients who do not
experience mucous balls may prefer to remove the catheter for cleaning less
frequently. A customized cleaning protocol is essential for each patient to
maximize safety and efficiency.
A mature tract is fully lined by squamous epithelium that grows
outward from the trachea. When the patient arrives on the first visit of
Phase IV, tract maturity is assessed. The patient is seated in the procedure
chair with a headrest, and oxygen is delivered by nasal cannula. Topical
lidocaine is optional during this visit. A new catheter is made ready,
threading the patient's necklace through the flange and lubricating the tip
with water-soluble jelly. A wire guide is immediately available, but the
catheter is removed without inserting the wire guide. If the clinician has
difficulty inserting the catheter, the tract is judged to be immature. The
SCOOP catheter is reinserted, and cleaning in place is continued for 2 more
weeks. If the physician can easily insert the catheter, the patient is asked to
demonstrate the removal for cleaning sequence using a second catheter.
During the remainder of the first visit in Phase IV, the patient's
necklace fitting is evaluated, the appearance of the tract is noted, oximetry is
used to adjust flow rates, and education is emphasized. The security routines
and tract care and cleaning are carefully reviewed. The majority of patients
in Phase IV will remove the SCOOP catheter daily or twice daily.
Patients should not immediately go from cleaning in place in Phase III
to twice daily removal for cleaning in Phase IV. The first week of Phase IV is
considered a trial period. During the first week, all patients who remove the
catheter for cleaning do so only at 8 AM. The regular second cleaning should
be done at 4 PM using the in-place technique. Patients who are unable to
reinsert the catheter within 5 minutes should put on nasal prongs and see the
physician immediately for help. If the individual needs help, the physician
inserts a SCOOP catheter with or without the aid of a wire guide. The tract
is declared immature, and the patient returns to cleaning in place for 2 more
weeks. Thereafter, virtually all patients are able to progress to catheter
removal for cleaning. This trial period concept has dramatically lowered the
lost tract rate in Phase IV.
Individuals who successfully remove and reinsert the catheter for I
week may advance to twice a day removal for cleaning. Twice a day removal
for cleaning is preferably done at 8 AM and 4 PM so that any difficulty that
may arise would occur during regular working hours when help is more
easily obtained. should always be done
526 Christopher
using an in-place method; excessive removal and reinsertion may traumatize
the tract and result in tenderness or chondritis.
Late tract problems may appear months or years following the
procedure. Abrasion, maceration, contact hypersensitivity, and C. albicans
infection are uncommon, because the patient has usually learned proper
tract care by this time. Problematic scar tissue develops in about 5% of
patients and causes problems inserting the catheter or visible keloids. Visible
keloids differ from granulation tissue because of their late appearance (pink
rather than red color and keratinized surface). Factors which appear to
result in excessive scar tissue include cricothyroid membrane punctures,
exposure of cartilage during the procedure, excessive catheter removal for
cleaning (more than twice a day), and patient predisposition. Keloids and
chronic tract problems at the level of the cricothyroid membrane are
managed by revising the procedure at a lower site. Small keloids at lower
puncture sites sometimes respond to repeated injection of small amounts of
depo-steroid (e.g., triamcinolone [Kenalog], methylprednisolone [Depo-
MedrolJ) directly into the keloid. Large keloids and chronic tract problems
which do not respond to simpler methods require a Lipkin's surgical method
for tract creation [12]. Problematic patients who continue to experience
chronic tract problems can be successfully treated using the surgical
procedure.
VI. Lipkin Surgical Procedure and Modified SCOOP
Program
Alan Lipkin, an otolaryngoligist, developed a surgical procedure for
revision of previous MST tracts that resulted in recurrent problems such
as chondritis, lost tracts, and keloids. Our further investigation suggested
that the surgical approach has a number of advantages over the MST as a
primary method of tract creation [12]. We have modified the SCOOP
program to be used in conjunction with the Lipkin surgical procedure for
TTO tract creation [12]. The program is an alternative to the SCOOP
program for the MST. The potential advantages of the Lipkin surgical
procedure are shown in Table 4. As noted in the above review of the
literature, the most frequently encountered complications with the MST are
symptomatic mucous balls, lost tracts, chondritis, and keloids. The Lipkin
surgical approach has been shown markedly to reduce the frequency of these
complications [12]. With the MST technique, tracheal cartilage can be
inadvertently exposed and injured. Lost tracts, chondritis, and keloids
largely result from injury to cartilage. With the Lipkin surgical procedure, a
Table 4 The Lipkin Surgical Procedure Compared to the
Modified Seldinger Technique
Reduced complications
Symptomatic mucous balls
Lost tracts
Chondritis
Keloids
Earlier initiation of lranstracheal oxygen lherapy
After 24 hr
Slreamlined lranslracheal oxygen lherapy program
Shorter program duration
Procedure well suited for otolaryngologists
Clinician training simplified
Simplified patient education
Reduced demands on clinician time and resources
Facilitates referral center treatment or out-or-town patients
527
window of cartilage is removed, eliminating cartilage as a potential source of
complications.
The MST procedure requires 42-56 days (6-8 weeks) for the tract
immature. Consequently, the patient is unable to remove the catheter for
cleaning during this time. The inability to remove the catheter for cleaning
predisposes to mucous balls. In contrast, the Lipkin surgical approach
facilitates more rapid tract healing by incorporating a lipectomy and
creation of skin flaps. The surgically created tract is generally mature in 10-
14 days; thus limiting the period of time in which mucous balls are
problematic [12]. Using the MST, oxygen cannot be administered
transtracheally for a period of I week because of the risk of subcutaneous
emphysema, pneumomediastinum, and pneumothorax. Owing to the
surgically created leak between the stent and the stoma that persists for a
few days following the procedure, TTO may be initiated the day following
the surgical procedure without risk of barotrauma.
Another major advantage of the Lipkin surgical procedure is that the
SCOOP program can be significantly shortened owing to a reduction in
Phase II (from 8 to 2 days) and a shortening of the duration of Phase Tn
(from 42 to 56 days to 10 to 14 days). Phase mis the most labor-intense and
educationally intense portion of the program. Training of clinicians can be
streamlined and patient education can be markedly simplified. The
combination of the decrease in unscheduled or emergent visits because of
to complications and the streamlined, shortened program result in reduced
demands on clinician the shortened and
528
Christopher
streamlined program facilitates referral center treatment of out-of-town
patients who otherwise might not have access to TTO.
The following is a brief summary of the program modifications for use
with the Lipkin surgical procedure. The surgical technique and results have
been more fully described elsewhere [12]. Comprehensive video, electronic,
and printed educational materials are available through the manufacturer
(FastTract, Transtracheal Systems Inc., Denver, CO).
A. Phase I: Patient Orientation, Evaluation, Selection,
and Preparation
The pulmonologist and a clinician such as a respiratory therapist or nurse
continue to participate actively in the same orientation, evaluation,
selection, and preparation process for TTO. In addition, the patient meets
with a qualified surgeon, who will discuss the surgical procedure, order any
additional preoperative studies, and obtain informed consent.
B. Phase II: The Transtracheal MST Procedure and Stent
Week
The bead chain necklace is fitted in the usual fashion to identify the proper
site for the transtracheal tract. The procedure is performed in the operating
room, with the patient under local anesthesia and intravenous sedation and
continuous monitoring by an anesthesiologist. Nasal oxygen is provided
throughout the procedure. Although it is rarely necessary, a patient may be
converted to general anesthesia on an emergency basis. The patient is
positioned supine on the operating table with the neck gently extended and a
roll is placed under the shoulders. The head of the bed may be elevated
slightly for patient comfort. The area between the cricoid and sternal notch
is infiltrated with lidocaine 1% with epinephrine 1:100,000. The neck is
prepped and draped. Using cutting cautery, a vertical incision of
approximately 1.5-2.0 cm is centered on the selected site. Flaps of full-
thickness skin are elevated laterally 2 cm in each direction. The cutting
cautery is then used to perform a cervical lipectomy, removing all the fat
down to the level of the strap muscles. The strap muscles are separated at
the midline, exposing the anterior wall of the trachea (Fig. Sa). Occasionally,
division of the thyroid isthmus is necessary.
The previously elevated skin flaps are then used to fashion an
epithelialized tract down to the anterior wall of the trachea. This is
performed by suturing the flaps to the undersides of the previously exposed
sternothyroid muscles with a running suture of 3-0 Vicryl (polyglactin 910,
Ethicon, Sommerville, NJ) or similar absorbable material (Fig. 5b). It may
be reinforced with additional interrupted sutures as necessary. Prior to
(a)
(b)
529
Figure 5 After a vertical incision (a, left), skin flaps have been elevated and cervical
lipectomy has been performed. Strap muscles are separated at the midline, exposing
cervical the trachea. The skin flaps are then approximated (b, right) to the deeper
strap muscles with a running suture. (From Ref. 12; courtesy of Mosby, St. Louis,
MO.)
entering the trachea, the entire surgical field is inspected and complete
hemostasis is obtained. Additional local anesthetic (lidocaine I% without
epinephrine) is injected into the tracheal wall and lumen, particularly at the
point of entry into the trachea. This will help prevent movement and
coughing when the trachea B8!rFgRtJ8!J(1faPirygn in high concentration is
530 Christopher
flowing into the trachea, the electrocautery cutting blade should never be
used to enter the trachea.
The trachea is then entered with a small horizontal incision in the
interspace between two upper tracheal rings previously marked by the
necklace. The blunt end of the tracheal punch (Fig. 6a) is passed through the
incision, the punch is engaged, and a small window of cartilage is resected.
Using the available stylet, the stent (Fig. 6b) is inserted into the tracheal
window. A tracheal dressing is placed over the procedure site, and ties or
straps are then used to secure the stent in proper position. A tracheal collar
is applied to the stent to provide humidity for the patient's comfort. Oxygen
is supplied by a nasal cannula and/or mask to achieve an oxygen saturation
of >90% via pulse oximetry. The postprocedure routine is similar to the
MST program. However, the patient remains in the hospital until the next
day.
(a)
Figure 6 Following approximation of the skin Aaps to the deeper strap muscles
(Fig. 5b), a tracheal punch (Fast Tract Tracheal Punch, Transtracheal Systems, Inc.,
Denver, CO) is used to resect a small window of cartilage (a). A stent (b) with
companion stylet (Fast Tract Stenl, Transtracheal Systems, Inc., Denver, CO) is then
inserted into the tracheal window.
531
(b)
Figure 6 Continued.
c. Phase III: Transtracheal Oxygen with an Immature Tract
Approximately 24 hr after the procedure, most patients are able to advance
to Phase III. As with the MST, the stent is replaced by the functioning TTO
catheter. Gauze is placed between the flange of the catheter and the surgical
site, oxygen flow is titrated for rest and exertion, and the patient is educated
about the care and cleaning of the catheter. The patient is advised that a
noise may occur owing to air coming out of the tract and the voice may be
impaired for a few days. The patient is scheduled for a return visit within 7
days. Tract maturation and progression into Phase IV occurs in
approximately 10-14 days.
D. Phase IV: Transtracheal Oxygen with a Mature Tract
There are no significant changes in Phase IV except that fewer complications
are expected with this methoo of .tract cJ;.e.ation.,
-copyngnrea lVIatena
532 Chrislopher
VII. Combination of TIO and Demand Oxygen Delivery
Systems
TTO has been classified as an oxygen-conserving device. Although TTO
certainly provides other benefits, flow requirements are significantly reduced
during rest and exercise [10]. Since demand oxygen delivery systems
(DaDS) have also been shown to conserve oxygen, we conducted an initial
evaluation to see if the two technologies could be combined [41]. Results
showed that oxygen saturations were adequate and that the devices reliably
triggered via the transtracheal catheter. In a collaborative study with Tiep
[42], a modified DaDS with settable trigger delays (Oxymatic, Chad
Theraputics Inc., Chatsworth, CA) was utilized to evaluate patients on nasal
oxygen and TTO. Although delays in triggering adversely affected nasal
oxygen saturation, triggering delay had no significant impact upon
saturations with TTO. This is probably because the position of the TTO
catheter within the trachea already allows for maximally efficient early
delivery of oxygen. However, results showed that DaDS combined with
TTO was more efficient than with continuous-flow TTO.
In a comprehensive study [43] we compared DaDS to a continuous
flow control with both nasal cannula and TTO delivery. Patients could be
adequately oxygenated during rest, sleep, and exercise with DaDS TTO.
Although patients had adequate oxygen saturations during sleep and rest
with DaDS by nasal cannula, a subgroup of these patients could not
achieved adequate oxygen saturations with exercise. Compared with the
standard continuous-flow nasal cannula therapy, the daily bulk liquid
oxygen use was decreased by 29.4% with continuous-flow TTO, by 48.2%
with DaDS via nasal cannula, and by 49.9% with DaDS combined with
TTO. Thus, the use of a DaDS with TTO maximized the efficiency of TTO
as an .oxygen-conserving device.
Experience shows that TTO is safe and effective when combined with
DaDS, but systems requiring a double lumen have not been compatible
with a single-lumen transtracheal catheter. As with the use of any oxygen-
conserving device or potential combinations of those devices, it is prudent
specifically to evaluate each patient using the device or combination of
devices for intended use.
VIII. Transtracheal Augmented Ventilation
Our early anecdotal experience witb refractory hypoxemia [9] showed that
patients requiring transtracheal flow rates of 4-6 L/min appeared to have
less labored breathing compared to periods when the same patients were
533
receiving nasal oxygen at equal or greater flow rates. As noted earlier, TTO
studies have demonstrated reductions in inspired minute ventilation [33],
physiological dead space [34,35], oxygen cost of breathing, and the
respiratory duty cycle [36]. Reductions in each of those physiological
parameters were inversely proportional to delivered transtracheal flows up
to approximately 6 L/min. Under these evaluations, the reduced minute
ventilation was secondary to reduction in tidal volume [33]. The medically
stable patients evaluated in these studies showed no significant acute change
in PaCo2' We wondered whether higher transtracheal flow rates might
augment ventilation in patients with hypoxemia due to severe lung disease.
Using a canine model [44]. we found that inspired minute ventilation
was significantly reduced with the transtracheal administration of an air/
oxygen mixture at 10 L/min. We then evaluated two TTO patients [45] with
severe hypercarbia associated with chronic respiratory failure. As with our
previous experience, the transtracheal high flow (?: 10 L/min) of a
humidified air/oxygen blend resulted in a marked reduction in tidal volume.
The respiratory rate remained approximately the same, and the minute
ventilation was substantially reduced. The patients were in a stable state and
PaCo2 was unchanged. The two patients then received high-flow transtra-
cheal administration of the humidified air/oxygen blend or transtracheal
augmented ventilation (TTAV) nocturnally on a long-term basis. One of the
patients was later hospitalized for superimposed acute respiratory failure.
He declined intubation, but consented to maximal medical therapy and
continuous TTAV. In contrast to prior experience with stable patients, the
elevation in Paco2 resolved in the acutely ill patient treated with TTAV.
IX. TTAV for Nocturnal Support in the Home
We then evaluated the potential safety and efficacy of TTAV for the
nocturnal home management of a larger number of hypoxemic patients with
chronic severe respiratory disease [46]. The first portion of the study
evaluated patients before and after a 3-month intervention with nocturnal
(Noc) administration of TTAV at 10 L/min. Resting physiological studies
were conducted on standard low-flow transtracheal oxygen (LFTTO).
TTAV, and breathing oxygen-enriched gas without transtracheal flow via a
mouthpiece (MP). Nocturnal polysomnography. bronchoscopy, ventilatory
drive and treadmill exercise were also studied. Results of the first part of the
tion showed that pleural pressure-time index and respiratory duty
cycle were significantly lower when comparing MP to TTAV. In this group
of stable patients, arterial blood gases and the total volume delivered to the
lung (volume delivered by inspired via the upper
534 Christopher
airway) were not significantly changed with MP, LFTTO, or TTAV.
However, the percentage of the total volume delivered to the lung via TTAV
(45%) was significantly greater than the percentage delivered by LFTTO
(20%). Sleep quality and nocturnal oxygenation with TTAV were similar to
LFTTO. Three months ofNoc TTAV had no effect on ventilatory drive. No
evidence of clinically significant mucosal injury was noted on bronchoscopy.
Treadmill exercise tests demonstrated significantly longer exercise time and
increased total work following Noc TTAV. The changes in the slope for
heart rate and pH with exercise were significantly less steep following Noc
TTAV, suggesting improved fitness. The 3-month follow-up in the first
portion of the investigation and the long-term evaluation (29 18 months;
range 6.8-60 months) in the second portion of the study showed that Noc
TTAV was well-tolerated, was safe, and reported high compliance. A
patient receiving TTAV in the home is shown in Figure 7.
Figure 7 A patient receives transtracheal augmented ventilation in the home using
a servo temperature controlled device (SCT 3000, Vital Signs, Denver, CO) that
humidifies the 10 L/min of an air/oxygen blend delivered by custom device
(Transtracheal Systems, Inc., Denver, CO). The patient is accompanied by Thomas
L. Petty, MD.
X. TTAV for Weaning from Prolonged Mechanical
Ventilation
535
We speculated that the physiological benefits of TTAV with respect to
reductions in inspired minute ventilation, respiratory duty cycle, and oxygen
cost of breathing might facilitate the weaning process [47] in patients
requiring prolonged mechanical ventilation. In the setting of long-term
acute care, we assessed medically stable patients who consistently failed to
wean from mechanical ventilation in spite of tracheostomy and weaning
efforts utilizing a variety of ventilatory modes. Prior to treatment,
endoscopic examination showed the absence of glottic or subglottic
obstruction. The existing tracheostomy tube was exchanged for a 6-mm
cuffed tube. The cuff of the tracheostomy tube was fully deflated and a
transtracheal catheter (Transtracheal Systems, Inc., Denver, CO) with a
customized IS-mm cap was inserted into the tracheostomy tube, creating an
airtight seal. An adjustable blend of air and oxygen was passed through a
servo temperature control humidifier. Flows of at least 10 L/min were
delivered through the catheter during spontaneous breathing trials. The
frequency and duration of spontaneous breathing trials with TTAV where
adjusted according to patient tolerance. Once patients demonstrated that
they could be on TTAV for 24 hr or more, they were progressively weaned
with TTO to a low flow that achieved adequate oxygen saturations by pulse
oximetry. At that point, a variety of choices for planned discharge were
considered. Removal of the catheter was one option. Supplemental oxygen
could be discontinued or the patient could receive oxygen by nasal cannula.
Patients could also be discharged on 24-hr TTO therapy or receive a
combination of nocturnal TTAY with daytime TTO.
It was observed that patients on TTAY weans were able to phonate
normaJiy and markedly increased their communication with medical staff
and significant others. The ability to use the glottis in a normal fashion also
improved the effectiveness of cough. Patients, particularly those with
COPD, were able to regain normal glottic function as a variable regulator of
expiratory flow.
We recently reported [48] our experience with TTAV as compared to
conventional weaning methods (CWM) in the treatment of patients
requiring prolonged mechanical ventilation (PMV) in the setting of a
long-term acute care (LTAC) hospital. A 2-year retrospective chart review
of PMV admissions was conducted. Progressive neuromuscular disease
patients were excluded. Therapist-driven protocols were not utilized. CWM
included pressure support, intermittent mandatory ventilation, flow-by,
continuous positive airway pressure, T-piece trials, or some combination.
TTAV was nonrandomly ef$ynehrtRJ'Ma,Jfffb7
d
patients had repeatedly
536
Christopher
failed CWM in LTAC, but full ventilatory support was not required.
Liberation success was defined as 72 consecutive hours off the ventilator.
Results showed that TTAV weaning success rate (73.1%) was greater
than CWM (51.8%); results approached significance (P= .056). The study
was statistically biased against TTAV, because a significantly higher portion
of patients had capo with TTAV than with CWM. There was no age
difference in wean failures, but successfully weaned TTAV patients were
significantly older than successfully weaned CWM patients. Comparing
successful TTAV to CWM and comparing failed TTAV to CWM, there
were no significant differences on admission in gender, severity of illness
scores, admission transfer and gait scores, required FI02, arterial blood
gases on PMV, or spontaneous ventilatory parameters, except that minute
ventilation was significantly lower in those successfully weaned with TTAV
as compared to CWM. No complications with TTAV weans were
encountered. From a clinical standpoint, in spite of the fact that there
was a statistical bias against TTAV due to a higher portion of patients who
were older and had capo, a greater weaning success rate was achieved with
TTAV than with CWM. A patient undergoing a spontaneous breathing trial
is shown in Figure 8.
The potential benefits of TTAV are summarized in Table 5.
Physiological studies of TTO in the flow range of approximately 1-6 L/
min have demonstrated that reductions in physiological dead space, minute
inspired ventilation, respiratory duty cycle, and oxygen cost of breathing are
inversely related to flow. In other words, as flow increases, patients benefit
from reductions in these physiological parameters. Further physiological
improvement occurs with the high flows of 10 L/min with TTAV. In
addition, patients receiving nocturnal TTAV in the home have been shown
to have the ability to perform more work during daytime exercise and
exercise for longer periods. Improved fitness has also been described.
Patients requiring prolonged mechanical ventilation are difficult to
liberate from the ventilator. TTAV appears to facilitate the weaning process.
In addition to the physiological benefits described above, the TTAV wean
modality allows the glottis to function more normally. Patients have an
improved ability to cough effectively. The glottis can function as a variable
regulator of expiratory flow. As with pursed-lips breathing, the ability to
control the glottic aperture finely is beneficial to patients with obstructive
lung disease. TTAV also frees the patient from the ventilator while still
delivering augmentation of ventilation. This improves the mobility, which is
markedly impaired when patients are tethered to a ventilator. Finally,
individuals on prolonged mechanical ventilation are unable to speak while
connected to a ventilator by a tracheostomy tube. During TTAV,
individuals are able to phonate without difficulty. This has a markedly
537
Figure 8 A patient requiring prolonged mechanical ventilation in long-term acute
care facility (Kindred Hospital, Denver, CO) undergoes a spontaneous breathing
trial using transtracheal augmented ventilation. A customized catheter with a cap
(Transtracheal Systems, Denver, CO) is attached to a 6-mm tracheostomy tube
(Portex Ole, SIMS Portex, Inc, Keene, NH) with the cuff deflated. The patient
receives a heated and humidified (SCT 2000, Vital Signs, Denver, CO) mixture of
oxygen and compressed air (Timeter PCS 414, Allied Healthcare Products, St. Louis,
MO). The patient is accompanied by Eric Yaeger, MD, and Ursula Hamel, RN.
positive impact on the will to live and the individual's ability to
communicate with care givers and significant others. TTAV appears to be
a promising method for liberation from PMV.
XI. Treatment of Sleep Apnea
In 1985, we encountered a patient with severe hypoxemia obesity-
hypoventilation syndrome, and associated severe obstructive sleep apnea
[49]. The patient did not receive benefit from nasal CPAP and refused
tracheotomy. He was placed on TTO for long-term oxygen therapy, and
sleep polysomnography was done to evaluate his response to nocturnal
TTO. Results on 3 L/min TTO showed that his apneas and hypopneas
resolved and oxygen Video fluoroscopy during
538
Christopher
Table 5 Potential Benefits of Transtracheal Augmented Ventilation eTTAV)
Flow-dependent phFsiological improvements
Reduced inspired minute ventilation
Reduced work of breathing
Shortened respiratory duty cycle
Decreased physiological dead space
Potential benefits 0/ nocturnal TTA V in the home
Improved duration of daytime exercise
Improved work capacity during exercise
Improved physiological fitness during exercise
Potential benefits 0/ TTA V in liberation from prolonged mechanical ventilation
Normal phonation with improved communication
Improved cough effectiveness
Use of glottis as a variable regulator of expiratory flow
Improved mobility
sleep demonstrated that his hypopharyngeal obstruction was relieved by
TTO. One year later, we reported our experience with four patients [50].
Median apnea plus hypopnea index fell 61 %, but the duration of apneas was
increased. Although nocturnal desaturation occurred with nasal cannula
therapy in this small group, oxygen saturation was greater than 90%
throughout the night with administration of 3 L/min of TTO even in the
presence of prolonged apneas. Sleep efficiency improved with TTO delivery.
In 1990, Chauncey and Aldrich [51] compared nasal cannula oxygen to
TTO in four patients with obstructive sleep apnea who were unable to
tolerate nasal CPAP. At TTO flow rates of 2-3 L/min, there were
improvements in the mean respiratory disturbance index, overall nocturnal
oxygen saturation, and sleep disturbance. In this study, the mean apnea
duration was not increased by TTO and the duration of the longest apneic
spells was decreased by 33-85%. Daytime sleepiness improved and therapy
was well tolerated.
Farney and coworkers have published two studies evaluating TTO for
the treatment of obstructive sleep apnea [52,53]. In the first study [52], five
patients were selected who were either noncompliant with nasal CPAP or
also required continuous long-term oxygen therapy. Each had been
previously documented to have severe obstructive sleep apnea that could
be corrected with nasal CPAP therapy. They concluded that the most
significant observation from the study was that TTO corrected hypoxemia
related to sleep disordered breathing even if some types of respiratory events
such as hypopnea were not completely eliminated. Since TTO was effective
539
and well tolerated, they decided that tracheotomy was not necessary in the
patients who were studied.
In the second study [53], Farney's group evaluated five patients with
severe obstructive sleep apnea who were either noncompliant with nasal
CPAP or also required continuous long-term oxygen therapy. Results
showed that, compared to baseline room air polysomnography studies, TTO
significantly reduced apnea/hypopnea freq uency from 65 to 26 per hour of
sleep and maintained improved nocturnal oxygen satLlrations compared to
nasal oxygen.
In the prior studies of TTO for obstructive sleep apnea, the evaluated
flow rates were in the range of 2-6 L/min, and flow was titrated primarily for
oxygen saturation rather than for correction of obstructive events. More
recently, Schneider's group [54] found that even higher flow rates have the
potential to be efficacious in the treatment of obstructive sleep apnea. This
treatment concept is more consistent with the concept of TTAY, since the
titration flow may be for a physiological effect (resolution of obstruction)
rather than a titration for correcting hypoxemia. We are currently faced
with a clinical dilemma in the management of patients who are
noncompliant with CPAP or refuse tracheotomy. Further studies need to
be done to evaluate the potential role ofTTO and TTAV in the treatment of
sleep apnea.
XII. Conclusion
For over 20 years TTO has been an alternative to the nasal cannula for long-
term oxygen therapy. Safety and efficacy have been demonstrated. TTO
should be administered as a program of care. A modified Seldinger
technique has been the standard in the past, but a more recent procedure for
surgical creation of the tracheocutaneous tract presents a number of
potential advantages. TTO may further increase the oxygen conservation
efficiency of demand oxygen controller devices, and studies have shown
ITO to be a potential alternative to nasal oxygen, continuous positive
airway pressure, and tracheotomy for severe obstructive sleep apnea. TTAV
extends the physiological benefits of TTO and has promise in both the
outpatient nocturnal ventilatory support of patients with severe respiratory
disease and in liberation of patients from prolonged mechanical ventilation.
Acknowledgments
The author thanks Stephanie Diehl. RRT, for her technical assistance and
John Goodman, RRT,
540
Christopher
The author has licensed transtracheal technology patents for
commercial LIse.
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26
Chest Tube Placement
FRANCIS D. SHESKI
Indiana University School of Medicine
Indianapolis, Indiana, U.S.A.
I. Introduction
Chest tube placement (or tube thoracostomy) has been used for nearly a
century, primarily for draining pleural space air or fluid or in the
postthoracic surgical state. Many specialists are trained in the technique:
surgeons, pulmonologists, intensivists, emergency physicians, radiologists,
and perhaps others. The American Board of Internal Medicine requires
competency in chest tube management for its certificate of added
qualification in Critical Care Medicine. To perform the procedure, one
should know the indications and contraindications; the equipment and
anesthesia; the insertion and removal techniques; the management and
troubleshooting of the system; and the potential complications. This chapter
will discuss the historical perspective, indications and contraindications,
equipment, techniques, complications, and data for or against selected
aspects of chest tube placement.
Hippocrates is often accredited with the initial description of draining
empyemas. using tubes [1]. In the latter
545
546
Sheski
nineteenth century, Hunter developed a needle for pleural drainage; Playfair
placed a chest tube with an underwater seal; and Hewitt described chest tube
drainage of an empyema [2--4]. During World War I, the Empyema
Commission published data indicating that chest tube drainage of
postinfluenza empyemas decreased mortality [5,6]. "Routine" chest tube
drainage of empyemas dates from this time. In 1922, Lilienthal described
postoperative chest tube usage, whereas routine postthoracotomy and chest
trauma indications stem from World War II and the Korean War [7-9].
Processes that disrupt the pleura and the pleural space may lead to patient
compromise. Evacuation of this space, with subsequent restoration of
pleural integrity, may be needed to stabilize the patient. The pleural space is
defined by the visceral and the parietal pleurae that line the thorax. The
pleural space normally contains a small amount of fluid in constant flux but
no air. Normal pleural fluid is not clinically detectable [10]. The balance of
hydrostatic and oncotic pressures between the lung, pleural space, and
pleura prevents significant fluid accumulation. Injury to either may lead to
accumulation of air (pneumothorax) or to blood (hemothorax). Inflamma-
tion of the pleura (e.g., pneumonia) or obstruction of the lymphatic or
vascular beds that drain the space (e.g., malignancy) may lead to
accumulation of fluid-pleural effusion-that may cause patient compro-
mise. When one of these disorders is diagnosed, the decision is whether to
drain the space and if so, how. Table I lists common indications for chest
tube placement [11-14]. Although a discussion or a debate over indications
for chest tube placement is not the focus of this chapter, some comments
Table 1 Indications for Chest Tube Insertion
Pneumothorax-large, symptomatic, tension, progressive
Hemothorax
Penetrating chest injury
Empyema or complicated para pneumonic effusion
Pleurodesis
Postthoracic surgery
Bronchopleural fistula
Chylothorax
Large symptomatic effusion
547
regarding common indications such as pneumnothorax and pleural effusion
follow.
A. Pneumothorax
With a pneumothorax, dyspnea, chest pain, and cough are common
symptoms. Some patients are asymptomatic, whereas others have severe
dyspnea and/or hemodynamic compromise (tachycardia and hypotension)
requiring emergent treatment. Symptom relief is a major factor influencing
the decision to intervene immediately or to observe. Long-term treatment is
another therapeutic issue. Spontaneous pneumothorax without an apparent
cause is termed a primary spontaneous pneumothorax (PSP). If an
underlying cause exists, it is called a secondary spontaneous pneumothorax
(SSP). A tension pneumothorax is defined as air under positive pressure in
the pleural space causing compression and shift of the mediastinum, leading
to respiratory and hemodynamic embarrassment. The latter two conditions
usually are treated invasively, whereas the former mayor may not be so
treated. A patient on mechanical ventilation with a pneumothorax is usually
treated with chest tube drainage, because rapid deterioration and death may
suddenly occur. Some surgeons will treat a "large" pneumothorax, often
defined as one occupying >20-25% of the hemithorax on a chest film, even if
the patient is asymptomatic, because such a pneumothorax often resolves
slowly. When the decision is made to drain the pneumothorax, one chooses
between needle aspiration and chest tube placement [12,15].
B. Pleural Effusion
The clinical presentation of a patient with a pleural effusion is rather
variable, depending on the etiology. With an acute pneumonia (para-
pneumonic effusion) fever, chest pain, dyspnea, and productive cough may
occur. Progressive dyspnea with or without cough may lead to a malignant
effusion. A hemothorax with blunt or penetrating trauma may lead to
respiratory failure and shock. Pleural fluid detected clinically or radi-
ologically is abnormal and is evaluated with a thoracentesis and fluid
analysis. The findings influence whether chest tube drainage should follow.
If pus or a complicated parapneumonic effusion is found, suggesting
infection, chest tube placement is often indicated to minimize mortality and
morbidity [12,16]. If a malignant effusion generates symptoms, recurs, and
cannot be controlled with "routine" cancer therapy, then drainage and
pleurodesis is an option via several routes [12,17]. Chest tube placement in
thoracic trauma or surgery evacuates blood or air and allows monitoring of
any subsequent hemorrhCUl:e or. air leaks
t
whjch may influence surgical
lJopyngnrea Ma enal
548 Sheski
management [13,14]. Pleural space drainage in these examples may speed
recovery or prevent the later complication of fibrothorax/trapped lung.
There are no "absolute" contraindications to chest tube placement,
except perhaps patient refusal or lack of an indication. However, some
relative contraindications include coagulopathy, lack of consent, absence of
trained personnel, multiple pleural adhesions that may not allow "blind"
placement, hemothorax without adequate fluid resuscitation, or lack of a
clean site due to infection or injured tissue. Ideally, coagulation defects
should be corrected before placement if possible. For thoracentesis, McVay
and colleagues showed that increased bleeding did not occur when
prothrombin and activated partial thromboplastin times were under twice
control and the platelet count was >25,000. Increased bleeding was seen
when the serum creatinine was >6 mg/dL [18].
IV. Equipment
Table 2 lists basic equipment for chest tube placement. Some kits contain
supplies. Some techniques utilize additional equipment, whereas others
require less. A Mayo stand or other table should be available. Intravenous
(IV) access is a good idea whether or not medication is planned. If IV
analgesia and/or sedation are selected, a narcotic and a benzodiazepine are
Table 2 Basic Chest Tube Equipment
Chest tube
Drainage device
Tape
Suture-O or 2-0 thread with needle
Scalpel
Sterile towels/drapes
Povidine-iodine solution
Gauze pads-4 x 4 inches
Anesthetic-lidocaine HCl
Syringes
Needles-25 and 22 gauges
Kelly clamps
Needle holder
Scissors
Bactericidal ointment
Sterile gowns and gloves, masks, caps
549
commonly used. Having an assistant to medicate and monitor the patient,
get supplies, and manage the drainage device can be helpful.
A. Chest Tubes
Chest tubes are usually plastic, vary in diameter (usually 8-42 Fr), and have
multiple drainage holes. Most have a radiopaque line that identifies the
proximal hole by a break in the line. Chest tubes come with or without a
rigid trocar (Fig. I). Kits where the chest tube is placed over a guidewire
contain dilators and the guidewire, besides a tube (Fig. 2). There are also
kits using a catheter-over-needle technique (Fig. 3). These kits often contain
ancillary supplies, similar to those in Table 2. When attaching the chest tube
to any drainage device, a properly sized connector is necessary to fit the tube
tightly to the tubing.
Figure 1. The top chest tube has a protruding sharp, metal tip (Argyle Trocar
Catheter, Sherwood Medical). The next from the top has a blunt, metal trocar that is
covered by the plastic, radiopaque tip of the tube (Deknatel Trocar Catheter.) The
Argyle Thoracic Catheter and the A Traum Thoracic Silicone Catheter (Axiom
Medical) the bottom two tubs:.s, respe<;tjvelyMdo nQt utilize a trocar.
, c.;opyngnred alenal
550 Sheski
Figure 2. The Thai Quick Catheter Set (Cook) contains: scalpel, needle, guidewire,
several different sized dilators, and a chest tube.
B. Drainage Devices
After the chest tube is inserted, it is attached to a drainage device. This
allows monitoring of any air leak or of fluid output. The device also
prevents retrograde air or fluid flow into the pleural space. The device
usually is a combination of a collection trap connected to a water seal
chamber and a suction regulator (Fig. 4). The chest tube is connected via
tubing to the collection trap. It is marked for measurement. The trap is
connected to the water seal chamber. From a spout with one end submerged
in water, the water seal chamber is connected to the suction chamber is
vented to the atmosphere. This arrangement prevents air from being sucked
into the chest and allows assessment of an air leak (bubbling in the water
seal chamber during expiration.) Bubbling in both respiratory phases
suggests a "large" air leak or a disconnection in the system. The difference
between the water levels of the seal and suction chambers is the applied
suction. Currently, a self-contained, disposable unit is frequently utilized.
Recently developed units eliminate the water in the suction unit and have an
adjustable pressure regulator (Fig. 5). If only air (pneumothorax) is a
concern, and suction is not required a one-way exit valve-a Heimlich
551
Figure 3. The Arrow Pneumothorax Kit contains most of the needed supplies:
drapes, cleaning solution, anesthetic, scalpel, gauze, syringes, needles, catheter-over-
needle, dilator, connector tubing, Heimlich valve, suture, and Bandaid.
valve-that prevents retrograde airflow may be attached (Fig. 6). [19]. This
allows the patient to be mobile. Table 3 lists cost estimates for various chest
tubes, kits, and drainage devices.
v. Technique
There are several chest tube insertion techniques: blunt, trocar, Seldinger,
and catheter-over-needle. Radiographic assessment should precede tube
placement in all but "emergency" situations, such as trauma or suspected
tension pneumothorax. The chest film assists in choosing the entry site and
the direction to insert the tube. Loculated air or fluid may be best
approached under radiological guidance. For pneumothorax, either the
anterior, second intercostal space in the midclavicular line or the anterior or
midaxillary line in the fifth or sixth intercostal space is commonly used [20].
These avoid vessels, such as the internal mammary artery anteriorly. The
tube is directed toward is that air being
552
Suction
:- ht;LC'>
Q,
o. iJ
0'. {j>
Suction control
bottle
Water seal
bottle
Collection
bottle
Sheski
To patient
Figure 4. The three-bottle drainage system is illustrated. The first bottle collects
fluid, the second serves as a water seal, and the third is the suction regulator unit.
(Adapted from Ref. 12.)
Figure 5. The Pleur-Evac (Deknatel) is a commonly used drainage unit, following
the three-bottle strategy, where the suction unit is waterless.
To patient

553

Figure 6. The Heimlich valve allows air to exit but not enter the chest, as shown by
the positive (air out) and negative (closed) marks. (Adapted from Ref. 12.)
less dense than lung will rise to that level. For a pleural effusion, the lateral
approach is used, directing the tube posteriorly and inferiorly, because dense
fluid will collect in the dependent region [I I]. Under radiological guidance,
the site may be anywhere, often guided by the location of the air or fluid.
The skin is prepared in an aseptic manner with povidone-iodine or another
agent and draped to maintain a sterile filed. The chest wall tissues, including
the pleura, need to be sufficiently anesthetized, usually with lidocaine.
Return of air or fluid during lidocaine infiltration suggests proper location.
In addition, one may choose to give intravenous analgesics, especially with a
large tube insertion.
Table 3 Cost Estimates
a
Chest tubes
Argyle straight thoracic. 24-40 Fr
Deknatel trocar, 28-32 Fr
Axiom-Atraum, 28-36 Fr
Arrow Pneumothorax Kit
Cook ThaI-Quick Kit
Drainage devices
Pleur-Evac
Heimlich valve
$5 each
$17 each
$9 each
$35 each
$70 each
$35 each
$13 each
aCost estimates based on local Material
554 Sheski
Initially, each technique requires a skin incision. For the blunt or the
rigid trocar method, the incision needs to accommodate an index finger and
then the tube. Also, some may choose a Z track approach. With the
Seldinger or the catheter-over-needle approach, a smaller knick just large
enough to accommodate the tube is needed. The techniques differ at this
point. For the blunt method, the subcutaneous tissue is dissected bluntly to
the intercostal space with a finger or Kelly clamp (Fig. 7). A hemostat or
Kelly clamp is used to enter the pleural space, followed by a finger,
confirming proper location. Also, this approach detects adhesions and
confirms location. The tube is held with a Kelly clamp and inserted into the
space, directing it appropriately. After the incision is made in the trocar
method, one supposedly pushes the tube-trocar unit through the soft tissue
into the space, directing the tube using the rigid trocar as a stylet (Fig. 8).
Figure 7. The blunt method of inserting a chest tube is demonstrated: using a
hemostat or Kelly clamp to dissect the tissues and then enter the pleural space,
inserting a finger to confirm correct location and detect any adhesions, and finally
placing the tube. (Adapted from Ref. 33.)
555
Figure 8. The trocar method is shown, where the sharp-ended trocar protrudes
from the tube.
Alternatively, one can enter the pleural space as in the blunt method but use
the trocar chest tube, where the trocar serves only as a stylet to guide tube
insertion. This may make it easier to direct the tube. The Seldinger and
catheter-over-needle techniques forgo tissue dissection. In the Seldinger
mode, one enters the pleural space with a needle, places a guidewire through
the needle, removes the needle, sequentially dilates the interspace over the
guidewire, and finally places a tube over the wire before removing the wire
(Fig. 9). For the catheter-over-needle approach, the pleural space is entered
and then the catheter is slid over the needle, where the needle serves as a
stylet (Fig. 10). The latter is used primarily with small-bore catheters,
usually <14-20 Fr. Condensation or fluid in the tube suggests proper
placement. Eventually a radiograph is obtained.
After the tube is inserted, it is attached to a drainage device. Suction
may be applied if desired. The chest tube is sutured using one of several
techniques [21-23]. The site is dressed and the connections are taped.
Dressings should be changed periodically. Fluid output is recorded. Fluid
tidaling in the tubing or water seal chamber indicates that the system is
patent. Any air bubbling in the water seal chamber indicates a leak. If a
continuous air leak occurs, the system should be assessed to determine the
site of leak; that is, injured lung, a break in the system, a tube hole outside
the chest cavity, or a hole in the tube or tubing.
When the pneumothorax is healed (no air leak) or the fluid output is
minimal, the tube is removed. For a pneumothorax, some follow a stepwise
approach: off suction tube up to 24 hr, and
556
Sheski
Figure 9. The Seldinger technique starts with (a) incising the skin; (b) inserting a
needle, and then (c) a guidewire through the needle; (d) withdrawing the needle and
sequentially dilating the hole; (e) inserting the chest tube over the guidewire and
stylet; and finally (I) removing the guidewire and stylet. (Adapted from Ref. 12.)
remove if the lung is expanded. Others do not use suction or clamping and
remove the tube when the lung is expanded and no air leak is evident for a
few to 24 hr [I 1,12,24-27]. In dealing with pleural fluid, an output < I0-
150 mL/24 hr seems safe for removal [11,12,27-29]. All tubes are removed
while the patient exhales, minimizing the risk of air entering the pleural
space. A dressing is applied. If the incision is sutured closed, the suture is
removed in 7-10 days. A posttube removal chest radiograph is optional.
VI. Evidenced-Based Literature Review
Some aspects of chest tube placement may be controversial. In this section,
the following issues are 'discussed: Does the chest tube diameter (size)
matter? What is the role of suction, if any? Is there a "best" algorithm for
removal? Finally, complications are reviewed. Certain aspects are not
557
Figure 10. For the catheter-over-needle approach, one inserts the unit into the
pleural space and slides the catheter over the needle into position, Llsing the needle as
a stylet. The needle is removed.
discussed in detail. They include indications, who (or which specialties)
should be trained to insert chest tubes, does the entry site matter, does Z
tracking or suturing technique matter.
A. Tube Size
Because air (or fluid) flow is related to radius raised to the fourth power in
laminar and to the fifth power in turbulent flow, the chest tube and drainage
system need to have a large enough diameter in order to remove air faster
than the air leaks into the pleural space [30,31]. Conventional wisdom
suggests that for common pneumothoraces, most chest tubes meet this
requirement and the major concern is tube patency. In large air leaks, such
as can occur with traumatic or acute respiratory distress syndrome
(ARDS)-related bronchopleural fistulas, a large-bore tube may be needed
to evacuate the pleural space. For pleural fluid, the wisdom seems to say
that if the fluid is "thin," the diameter should not matter. However, if the
fluid is "thick," such as blood clots or pus, or is talc laden, then a large-bore
tube may be necessary. The presumption is that thick fluid will clog the tube.
The same reasoning is To the
558
Sheski
contrary, Park showed in vitro evidence that differences in fluid flow were
minimal in catheters with diameters>7 Fr [32]. What defines a large- or a
small-bore tube? A tube diameter less than 14-20 Fr is often cited as the
break point, but this seems empiric [11,15,33]. Nonetheless, a tube with a
diameter <20 Fr is defined as small bore in this chapter.
For PSP, SSP, and iatrogenic pneumothorax, Schoenenberger
demonstrated success rates of 82 and 60% at 48 hr and 85% at 72 hr,
respectively, using 20-24 Fr diameter chest tubes [34,35]. At 10 days, the
PSP, SSP, and iatrogenic pneumothorax success rates were 89, 70, and 96%.
Suction was part of the protocol. Successful large-bore chest tube drainage
for empyema seems to range from 35 to 86% (with concomitant use of
antibiotics) [28,36,37]. Ascribing success or failure of pleurodesis to tube size
is problematic, since other factors such as underlying pathology, sclerosing
agent, and technique probably have significantly more impact. Talc slurry
has been reportedly successful in 80-100 % of cases [38,39]. In traumatic
hemothorax, the chest tube is placed to remove blood and limit the risk of
empyema or fibrothorax and to monitor bleeding. This appears to be
successful 80% of the time with large-bore tubes [12,13,14].
Table 4 summarizes literature where chest tubes <20 Fr were used in
treating various pleural space disorders. Some tubes were placed with
radiological guidance. In various instances, the patients had failed blind,
>20 Fr chest tube placement or loculated fluid was present. Overall, small-
bore tube success was about 81 % (687 of 851 cases.) Success rate for
pneumothorax was approximately 80%, empyema was 76%, pleurodesis in
malignant effusion was 79%, and in generic effusion was 68%. Data on
hemothorax were scant and incomplete. Prospective, randomized trials of
large-bore versus small-bore tubes are lacking. In one publication,
Clemensten prospectively and randomly compared tetracycline pleurodesis
using either a 10 Fr or a 24 Fr tube and found no difference in outcome [60].
In general, it appears that tube diameter does not impact on treatment
of pneumothorax and perhaps malignant effusion (pleurodesis.) Presum-
ably, most pneumothoraces are not loculated; therefore, radiological
guidance does not have a major impact. Insufficient numbers of clearly
identified large air leak patients prevent conclusions regarding this
population. Most loculated malignant effusions are not pleurodesis
candidates. Thus, the ame reasoning regarding radiological guidance may
apply. As alluded to previously, many factors likely influence pleurodesis
success-pathology, sclerosing agent, technique. To make a serious
comparison, these factors need to be controlled in a study format. Small-
bore tubes are effective in empyema and may be even more so than large-
bore ones. Empyema often involves loculations, which are better located
with radiological guidance. Clearly, the tube needs to be in the fluid to be
C;hest Tube Placement
559
Table 4 Data on Chest Tubes <20 Fr
Reference Problem (no. of patients) Success Complication
[25] Pneumothorax (53) 28
[40] Pneumothorax (19) 18 Occlusion, dislodged, malposition
Effusion (6) 6
Lung abscess (I) I
[41] Empyema (17) 15 Bacteremia
[42] Empyema (20) 14 Pneumothorax, occlusion,
catheter fracture, infection,
SQ emphysema
Pneumothorax (10) 9
Effusion (9) 5
Lung abscess (4) 4
Mediastinal cyst (I) I
[44] Pneumothorax (10) 8 Pneumothorax
Effusion (3) 3
[29] Empyema (43) 31 Occlusion, pneumothorax
[46] Empyema (16) II Cardiopulmonary arrest
Hemothorax (I)
Effusion (I) I
[47] Effusion (13) 13 Pneumothorax
[48] Pneumothorax (114) 79 Hemothorax, catheter fracture
[49] Malignant effusion (15) II Occlusion, edema
[50]
Empyema (15) 12 Empyema, syncope
Pneumothorax (8) 6
Malignant and benign 12
effusions (19)
[51]
Pneumothorax (10) 9 Malposition
[52]
Pneumothorax (28)
27
[53]
Pneumothorax (16) 16
Dislodged, hematoma
[54]
Empyema (12)
10
[55]
Pneumothorax (71)
60
[56]
Effusion (8)
4
[57]
Malignant effusion (21)
20
[58]
Empyema (79)
94% Overall
Effusion (29)
Hemothorax (10)
[59]
44 Dyspnea, pain
[60]
6
560
Sheski
effective. Successful blind tube placement is unpredictable, except perhaps in
large or free-flowing effusions. In the end, radiological guidance may be
more of a factor than the tube diameter. There are insufficient data on
hemothorax and small-bore tubes to make any judgments.
B. Suction
Once the tube is placed and attached to the drainage device, does it matter if
suction is applied? Powner showed that applying suction to the chest tube in
bronchopleural fistula may either increase or decrease flow through the
injured lung, and stated that many factors probably influence the result;
therefore, each patient should be handled individually [61]. In two separate
studies by Sharma and by So, patients with pneumothorax were randomized
to suction or to water seal. There was no difference in outcome [24,25].
Some suggest using suction if the lung does not expand on water seal, but
otherwise avoiding it to minimize the risk of reexpansion pulmonary edema.
However, this problem has occurred with or without suction [62]. With
pleural fluid, the role of suction is even murkier. Does suction pull the fluid
out faster in comparison to gravity and the pressure gradient from chest to
collection device? A paucity of literature exists on this issue. More than
likely suction is optional in either case.
C. Removal Algorithm
For pneumothorax, the tube is removed when the lung has expanded and
the air leak has stopped. Having the patient cough or deep breathe assesses
for air leak (bubbles in the water seal chamber), but this is not fool proof.
Small air leaks can be difficult to detect. How long after the air leak appears
to have stopped should the tube remain in place? Must one clamp the tube,
and for how long, before removing? Sharma showed a higher percentage of
lung recollapse if the chest tube was removed at 6 hr after air leak cessation
and lung expansion compared to 48 hr [24]. In another study, failure rates
were similar in early and late (72 hr) removal groups. However, So stated
that lung recollapse was the cause in the early group, whereas failure to
expand was the cause in the late [25]. In a prospective study by Martino, 205
trauma patients were randomized for removal when tube drainage was
< 150 mL/ 24 hr, any air leak ceased, and the chest radiograph revealed no
pneumothorax [27]. All patients were on suction. One group was placed on
water seal and the other had the tube pulled. After tube removal, 13
pneumothoraces occurred in the water seal group, whereas 9 occurred in the
other group. However, seven in the no water seal group required reinsertion
of a chest tube, but only one in the water seal group. The conclusion was
that water seal allowed a clinically important pneumothorax to manifest
561
itself before tube removal. In a second study, Davis prospectively
randomized 80 trauma patients with chest tubes to groups with removal
from suction or water seal and found no difference in incidence of recurrent
pneumothorax, but noted that avoiding water seal decreased chest tube
duration and time to removal [26]. None of these investigators clamped the
tube before removal. Studies where this factor is addressed are lacking.
What may make sense is leaving the chest tube on water seal for at least
24 hr after the lung has expanded and the air leak has ceased. This may
allow for the small air leaks to be detected or healed.
In regard to pleural fluid, many questions remain: what is the
minimum output to assure that the tube can be removed without clinically
significant fluid reaccumulation? Does the indication-empyema, blood, or
pleurodesis-influence this value? Again, there is a paucity of investigations
addressing these questions. Outputs of 10-150mLj24hr have been cited,
[11,26,29]. For pus, less might be better. For other indications, perhaps
< 150 mLj24 hr is reasonable.
D. Complications
Table 5 lists complications related to chest tube placement, including tube
malposition [33,63]. The incidence of any complication is low. Training and
subsequent experience undoubtedly affect incidence. Millikan recommended
against the trocar technique to lessen the risk of organ laceration [64].
Inserting a finger into the pleural space before the tube is advanced should
also lessen organ injury and malposition. The impact of catheter-over-needle
and Seldinger techniques on complications is unclear. Radiological guidance
should minimize incidence of organ laceration or of malposition. An
analysis of tube thoracostomy placement by pulmonologists in a teaching
Table 5 Complications
Placement of tube into/lacerate lung, liver, spleen, heart, stomach, diaphragm, colon
Infection/empyema
Hemorrhage
Reexpansion pulmonary edema
Subcutaneous emphysema
Neuralgia
Tension pneumothorax/pneumothorax
Tube malposition
Pain
Bronchopleural fistula
Copynghted Malenaf
562 Sheski
hospital showed an II% complication rate, although most were related to
tube obstruction or dislodgement [65]. There were four complications in II
small-bore tube placements and lOin 115 large-bore tube placements, but
this was not a randomized, controlled trial. Discomfort or pain may be less
with a smaller diameter tube.
VII. Conclusion
Chest tube placement is appropriate for a variety of indications. Good
training rather than specialty alone most likely leads to success with few
complications. Tube placement under radiological guidance is recom-
mended when loculations exist. Tube size does not matter in treating most
pneumothoraces and may not in other conditions as well. Avoid the blind
trocar insertion method. Postinsertion patient and tube care are important,
although these aspects were not described in detail. Suction probably has a
limited role. For pneumothorax therapy, it seems reasonable to leave the
tube on water seal for 24 hr after the lung has expanded and any air leak has
stopped before considering removal. Clamping the tube prior to removal is
optional. When drainage is of fluid, <50-150 mL/24 hr, tube removal seems
safe. Complications are infrequent but do occur.
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27
Percutaneous Dilational Tracheostomy
BENNETT P. deBOISBlANC
Louisiana State University Health Sciences Center
New Orleans, Louisiana, U.S.A.
I. Introduction
Tracheostomy is surely one of the oldest surgical procedures, having its
roots in ancient Babylon circa 2000 Be. It was a seldom-used procedure
looking for an indication until the great diphtheria pandemics l850s when
its popularity rose as a treatment for upper airway obstruction. It was not
until the standardization of the open surgical technique by Chevalier
Jackson in 1909 [I] that mortality associated with tracheostomy dropped
below 10%. Diphtheria antitoxin and antibiotics effectively eliminated the
need for tracheostomy for the relief of upper airway obstruction, but by the
mid 1940s, the need for airway access to remove airway secretions in
poliomyelitis patients in tank respirators had created renewed interest in the
procedure. Although the Sabin and Salk vaccines virtually eliminated
poliomyelitis, the advent of the modern ICU capable of caring for patients
on long-term positive-pressure ventilation resurrected tracheostomy once
again. The tracheostomy technique advocated by Jackson remained largely
unchallenged until 1985 when Pasquale Ciaglia described a new method of
performing tracheostomy Seldinger technique of
567
568
deBoisblanc
passing plastic dilators over a guidewire [2]. In the wake of this description,
there has been an exponential growth of scientific publications describing
benefits, risks, and modifications of percutaneous dilational tracheostomy
(PDT).
From a conceptual point of view, PDT is attractive. Because PDT is
largely dilational rather that incisional, theoretically there should be less
tissue trauma and devitalization resulting in less bleeding, a lower risk of
stomatitis and subglottic stenosis, and better cosmesis. Furthermore, the
tracheostomy tube inserted by the PDT technique should fit more securely,
reducing the risk of inadvertent decannulation. Finally, because PDT is
easily performed at the bedside in the rcu, there should be no need to
transport unstable patients and no delays related to operating room
scheduling resulting in lower costs. This review will examine the various
PDT techniques and their modifications with a focus on comparing PDT to
open surgical tracheostomy.
II. Overview of PDT Procedures
Several different tracheostomy techniques based on the Seldinger technique
may be described as "percutaneous" or "dilational." All PDT techniques
begin in a similar fashion. Patients are sedated and given a narcotic
analgesic. The neck is then extended to open the tracheal interspaces and the
surgical field is prepped. The major difference among the procedures is in
how the tracheostoma is created, leading to significant variation in the rates
of important complications. It is, therefore, important not to lump all PDT
procedures into one group for comparison to open surgical tracheostomy.
A. Ciaglia Technique
The PDT technique that is most widely utilized today is similar to that first
described by Ciaglia [2]. The procedure utilizes a 2-cm skin incision located
directly over the first and second tracheal interspaces, approximately
halfway between the palpable cricoid cartilage and the sternal notch. The
wound is blunt dissected with a hemostat through the subcutaneous fascia.
The existing endotracheal tube then is withdrawn into a position above the
first tracheal interspace so that a need Ie can be inserted through the skin
incision between either the first and second or second and third tracheal
rings without impaling the endotracheal tube. A J-tipped guidewire is then
advanced through the needle toward the carina and the needle is withdrawn.
Beveled plastic dilators are forced over the guidewire to create a
tracheostoma. Once the tracheostoma has been dilated to the appropriate
size, a tracheostomy tube is introduced into the trachea over the same
Percutaneous Dila/iona/ Tracheos/omy
569
guidewire utilizing one of the dilators as an obturator. When properly
performed, the tracheostomy tube passes through the thyroid isthmus up to
30% of the time [3], but bleeding is rare, since the procedure is largely
dilational and the tightly fitting tracheostomy tube may function to
tamponade bleeding vessels.
Since its original report, the Ciaglia PDT technique has undergone
three significant modifications that have likely improved its safety: (1)
moving the interspace of tracheal cannulation one or two tracheal
interspaces caudad from the cricoid cartilage, (2) routine use of flexible
bronchoscopy, and (3) the substitution of a single beveled dilator for the
multiple dilators.
PDT was originally performed in the subcricoid space [2]. Although
randomized, controlled clinical trials have not been performed, observa-
tional experience has suggested that moving the point of tracheal
cannulation two or more tracheal interspaces below the cricoid cartilage
would reduce the potential for subglottic stenosis [4]. Currently, the tracheal
interspace between the first and second or second and third tracheal rings is
the preferred site for PDT.
Flexible bronchoscopy through the existing endotracheal tube was
introduced in 1989 as an adjunct to PDT [5]. Bronchoscopic guidance offers
several theoretical advantages over blind PDT. First, it can facilitate safe
proximal relocation of the endotracheal tube. Second, it ensures midline
intraluminal placement of the needle and guidewire at the appropriate
interspace. Third, it can provide direct feedback to the operator during
dilator passage to help minimize injury to the posterior membranous
tracheal wall. And finally, it is as an excellent instructional tool [6]. Many
centers continue to perform PDT without bronchoscopic guidance, and
prospective randomized evaluations of its value are lacking. Potential
limitations of bronchoscopy include impairment of ventilation and
oxygenation [7,8], the need for additional personnel, and added procedural
time and expense.
A long, single, curved dilator (Blue Rhino, Cook Critical Care,
Bloomington, IN) was recently introduced as a substitute for the mUltiple
stepped dilator approach [9, I 0]. One potential benefit of the single-dilator
Ciaglia technique over the multiple-dilator technique is shorter procedure
time. In a prospective randomized trial of 50 trauma patients requiring
tracheostomy for airway control or prolonged mechanical ventilatory
support, Johnson and colleagues [11] reported that PDT was performed in
~ m n with the single dilator compared to ~ 10min with the multiple
dilators. No major complications occurred with either technique. Addition-
ally, the single dilator has a softer consistency and a more physiological
curvature that theoretical(YOIWJ1ghtooIM8tE9f8l'sure on the membranous
570 deBoisblanc
posterior tracheal wall, potentially making PDT safer. Not having to change
dilators reduces tidal volume loss through the tracheostoma during the
procedure. Air escaping through the tracheostoma under positive pressure
can cause subcutaneous or mediastinal emphysema and can aerosolize blood
into the operative field exposing operators to potential health risks. When
using the single dilator, the tracheostoma remains occluded until the
tracheostomy tube is ready to be inserted.
Skilled airway management during PDT is critical to patient safety.
The usual method involves withdrawal of the endotracheal tube, which has
been providing a secure airway, just prior to inserting the needle and
guidewire. Maintenance of ventilation and oxygenation in an unstable
patient while the endotracheal tube is in a vulnerable position and is
partially obstructed by a flexible bronchoscope can be challenging.
The laryngeal mask airway (LMA) has been advocated as an
alternative to endotracheal intubation. A prospective, randomized, com-
parative study of mechanical ventilation via LMA or endotracheal tube was
conducted in 60 critically ill patients using the Ciaglia technique [12]. In the
LMA group, 33% of patients suffered with potentially catastrophic
complications (e.g., loss of the airway, significant hypoxia, or aerophagia
with regurgitation). In the endotracheal tube group, there was a 7%
incidence of tube impalement and cuff puncture and a 3% incidence of
accidental extubation. The investigators concluded that endotracheal
intubation was safer than an LMA.
In a case series of 250 successive PDT cases, the use of a
microlaryngeal tube to maintain tracheal intubation and ventilation until
the correct position of the tracheostomy tube can be verified was found to be
a safe and effective strategy [13].
B. Other PDT Techniques
In 1989, Schachner described a technique that utilized a dilating plierslike
tracheostome (Rapitrach, Fresenius, Runcorn, Cheshire, England) that
would slide over the guidewire into the trachea in lieu of plastic dilators
[14,15]. This tracheostome was forced open, creating a stoma between the
blades through which a tracheostomy tube could be placed. Unfortunately,
the Rapitrach was associated with a high incidence of posterior tracheal wall
tears and lacerations of the tracheostomy tube balloon leading to its
removal from the U.S. market.
In 1990, Griggs advocated the use ofa custom grooved Howard- Kelly
forceps introduced over the guidewire into the tracheal lumen in a fashion
similar to the Rapitrach [16]. The Griggs technique has enjoyed a more
571
favorable track record than the Rapitrach and has gained some popularity
in Europe.
Four randomized, prospective trials have compared the Ciaglia plastic
dilator technique to one of the forceps dilator techniques. In a comparison
of Rapitrach to the Ciaglia PDT technique, Ambesh and coworkers reported
similar rates of complications [17]. Three trials have compared the Griggs
forceps dilator technique to the Ciaglia PDT technique [18-20]. Anon and
colleagues [18] observed similar rates of serious perioperative complications,
whereas Nates et al. [20] and Van Heurn et al. [19] reported a significantly
lower rate of complications with the Ciaglia PDT technique (Fig. I).
Fantoni and colleagues [21] have developed a technique of translar-
yngeal tracheostomy in which the tracheostomy tube is pulled through the
mouth and larynx and through the anterior tracheal wall from the inside out
(Fig. 2). Translaryngeal tracheostomy begins in a fashion similar to Ciaglia
PDT by pulling the existing endotracheal tube into the larynx to allow a
guidewire needle to be introduced through uninterrupted skin into the
trachea at the first or second tracheal interspace. The guidewire is then
passed through the needle in a retrograde direction alongside the existing
endotracheal tube toward the mouth where it is retrieved with a McGill
forceps. In order to create room for the new tracheostomy tube to transit the
larynx, the existing endotracheal tube must be exchanged for a custom,
Ciaglia
Forceps
40
35
30
25
%
20
15
10
5
0
Nates
(Griggs)
Anon
(Griggs)
Ambesh
(Rapitrach)
Van Hearn
(Griggs)
Figure 1 Comparison of PDT complication rates in randomized, controlled,
clinical trials comparing Ciaglia PDT technique to two forceps PDT techniques,
Griggs or Rapitrach [18-20J. e ~ ~ ~ i s M ~ i differences.)
572
deBoisblanc
Figure 2 Fantoni translaryngeal tracheostomy [21]. Sketch of the trocar-
tracheostomy tube combination being pulled through the anterior tracheal wall
during Fantoni translaryngeal tracheostomy. Once the custom tracheostomy tube
cuff is within the trachea, the custom tracheostomy is rotated to direct the distal end
caudad and the patient is extubated. (Redrawn with permission from Ref. 23.)
small-bore, thin-walled endotracheal tube that can be advanced to the
carina. The J-tip of the guidewire is then attached to the pointed tip of a
special metal trocar-tracheostomy tube combination that is pulled from the
opposite end down through the mouth, across the endolarynx, and into the
trachea where it abuts the inner tracheal wall. A pretracheal incision made
over tented skin covering the bulging trocar allows the trocar to be pulled
upward through the skin. The trocar is then cut from the tracheostomy tube
and the tracheostomy tube rotated so that its cuffed end faces toward the
carina. Fantoni translaryngeal tracheostomy has the theoretical advantage
of directing forces anteriorly away from the fragile posterior tracheal wall.
Serious complications have been reported in 0 ~ 8 5 of patients, whereas
technical difficulties passing the guidewire have been observed in 23-30%
[22-24].
Another PDT technique has recently been described by Frova and
Quintel [25]. In consecutive adult patients requiring an elective tracheost-
omy, PDT was performed with a specially designed one step, screw-type
Percutaneous Di/ational Tracheostomy
573
dilator (PercuTwist, Rusch, Kernen, Germany) using a thread for the
dilation procedure. There was no serious bleeding complications or other
relevant procedure-related side effects. Comparative trials have not been
performed.
III. Comparison of PDT to Open Surgical Tracheostomy
Advocates of PDT point out that because it is largely a dilational procedure,
it has significant theoretical advantages over surgical tracheostomy.
Primarily, reduced tissue trauma and devitalization compared to surgical
tracheostomy should lead to lower rates of bleeding, infection, subglottic
stenosis, and cosmetic deformity. Additionally, because PDT is ideally
suited for bedside use, delays and risks associated with transport to the
operating room are eliminated. In support of this argument, Friedman and
colleagues [26] reported that patients randomized to PDT received a
tracheostomy in approximately I day, whereas patients randomized to open
tracheostomy waited an average of 4 days. Others have countered by noting
that open tracheostomy can be safely performed at the bedside in the ICU
[27], although most surgeons prefer the operating room because of its
superior lighting and instrumentation. Finally, PDT can be accomplished at
the same setting with other bedside procedures such as percutaneous
endoscopic gastrostomy, avoiding the need for additional sedation and
analgesia [28].
A comprehensive literature review of PDT versus surgical tracheost-
omy was reported by Dulguerov and colleagues in 1999 [29]. Using the
MEDLINE search terms tracheostomy and complications, 2\ studies since
1985 reporting the incidence of complications in patients undergoing
surgical tracheostomy were identified. During this same time period, 27
studies reporting complications of PDT were identified. A meta-analysis of
these studies suggested that PDT was associated with significantly greater
risk of perioperative complications, including posterior tracheal wall injury
and death, compared to surgical tracheostomy (Fig. 3). However, PDT was
reported to have a lower risk of postoperative complications. Criticisms of
this analysis have pointed out that the populations of PDT and surgical
tracheostomy patients in these studies were heterogeneous, that various
PDT techniques were lumped together into one group, that the complica-
tions reported in the individual studies were variable and often subjective,
that some complications were clinically unimportant, and that some large
case series of PDT were omitted. Also identified was the historical evolution
of PDT [29] and the steep learning curve [30] that make assessment of PDT
risk a moving target (Fig. was the potential for
574
deBoisblanc
2+----...---
Surgical
after 1984
3 +--------.--..........,.,.--
o
1
6
5-1
4 ~ _ . . . . . . . = = = = = = = = = = - - . _ - - - - -
7 . . .__.mm _
*
1m PDT
%
Serious
Intermediate Minor
Figure 3 Reported periprocedural complications from the meta-analysis of
DulgueroY et al. [29]. (*Statistically significant differences.)
reporter bias, since complications of novel procedures are more likely to be
reported than are complications of a procedure as old as surgical
tracheostomy.
A. Randomized, Controlled Trials
In view of the limitations of case series, an accurate assessment of the risks
and benefits of PDT versus surgical tracheostomy should be based primarily
on prospective, randomized trials with established a priori outcomes
Thirteen randomized trials enrolling 769 patients have been reported
(Table I).
Hazard and coworkers [31] randomized 46 patients with respiratory
failure to either Ciaglia PDT or surgical tracheostomy. PDT was performed
without the aid of bronchoscopy. PDT was performed by one of the
investigators, whereas experienced board-certified surgeons performed all
surgical tracheostomies. Procedural and postprocedural complications were
prospectively recorded. Hemorrhage, infection, and pneumothorax were the
most common early adverse events in both groups, but these complications
occurred significantly more commonly in patients randomized to surgical
tracheostomy (45.8%) compared to those who randomized to PDT (12.5%).
Delayed stomal healing, significant subglottic stenosis, and cosmetic
40
35 -
575
Patients with PDT
complications
30
25
%
20
15
10
5
0
1st 20 21-40 41-60 61-80 81-100
Sequential patient number
Figure 4 Percentage of patients with complications in each quintile of the first 100
PDT procedures performed by one group of operators. PDT complications decrease
with experience. (From Ref 30.)
deformities also occurred more commonly after surgical tracheostomy (88
vs. 27%).
Friedman and coworkers [26] randomized 53 patients to either PDT
performed by one of two intensivists or to surgical tracheostomy performed
by staff surgeons. Although there were no significant differences in the rates
of intraprocedural complications, postprocedural complications occurred
significantly more frequently in patients randomized to surgical tracheost-
omy compared to PDT (41 vs 12%). In the early postoperative period, one
patient with PDT self- decannulated, whereas four patients with surgical
tracheostomies self-decannulated in spite of the presence of retention
sutures. The tracheostomy tubes could not be reinserted in two of the four
surgical tracheostomy patients resulting in death in both. The investigators
recommended that PDT is the preferred procedure for tracheostomy in the
ICU.
In the study by Crofts and coworkers [32], 53 critically ill patients were
randomized to either in the operating
576
Table 1 Prospective, Randomized, Clinical Trials Comparing
Outcomes for PDT vs. Surgical Tracheostomy
deBoisblanc
Study (reference)
Hazard, 1991 [31]
Crofts, 1995 [32]
Friedman, 1996 [26]
Holdgaard, 1998 [33]
Porter, 1999 [34]
Westphal, 1999 [22]
Gysin, 1999 [35]
Heikkinen, 2000 [36]
Stocchetti, 2000 [39]
Freeman, 2001 [37]
Wu, 2000 [38]
Massick, 2001 [30]
Sustic, 2002 [40]
No. of patients
randomized
46
53
53
60
24
120
70
40
80
83
20
100
20
PDT techniques compared
to surgical tracheostomy
Ciaglia
Ciaglia
Ciaglia
Ciaglia
Ciaglia
Ciaglia and Fantoni
Ciaglia
Griggs
Ciaglia and Fantoni
Ciaglia
Ciaglja
Ciaglia
Griggs
room by consulting surgeons or to PDT performed in the lCU by supervised
otolaryngology housestaff. The frequency of complications occurring
during follow-up was not significantly different between the groups. The
incidence of minor hemorrhage (12%) and stomal infection ("S 4%) was very
low in both groups. The investigators concluded that the two procedures are
equivalent in terms of complication rates.
Sixty critically ill patients were randomized by Holdgaard and
colleagues [33] to Ciaglia PDT or surgical tracheostomy. All procedures
were performed in the operating room under general anesthesia. Although
none of the operators had prior experience with PDT, it was significantly
faster and was associated with both significantly less bleeding and lower risk
of infection compared to surgical tracheostomy. Bronchoscopy was not used
in this study, likely contributing to endotracheal tube cuff puncture in five of
the PDT cases. The authors concluded that PDT was superior to surgical
tracheostomy, but that precautions must be taken to avoid cuff puncture.
Porter and lvatury [34] randomized 24 surgical lCU patients to PDT
or surgical tracheostomy performed by supervised surgical housestaff. Both
PDT and surgical tracheostomies were performed at the bedside in the
surgical lCU. Procedural times were shorter for PDT, whereas complication
rates were similar in the two groups. The only procedural death occurred in
the PDT group and was secondary to loss of the existing endotracheal tube
prior to cannulation of the trachea with the guidewire. The investigators
Percutaneous DiLalionaL Tracheoslomy
577
concluded that surgical tracheostomy at the bedside is the preferred method
of tracheostomy in critically ill patients.
Westphal and colleagues [23] randomized 120 patients to Ciaglia PDT
under bronchoscopic control, surgical tracheostomy in the operating room,
or to Fantoni translaryngeal tracheostomy (40 patients each group).
Complications were minor in all groups and were most commonly related
to aspiration of small amounts of blood or saliva. Procedure time was
significantly shorter for PDT and translaryngeal ~ 1 min) tracheostomy
compared to surgical tracheostomy ~ 3 5 min). Patient charges were highest
for surgical tracheostomy, intermediate for PDT, and lowest for translar-
yngeal tracheostomy.
Gysin and colleagues [35] performed a randomized trial of Ciaglia
PDT versus surgical tracheostomy in 70 patients, 36 of whom had head and
neck cancer, whereas the remaining 34 were recruited from the ICU. All
procedures were performed under general anesthesia and endoscopic
visualization by or under the supervision of one of the investigators. An
investigator blinded to the tracheostomy method performed postoperative
evaluation. There were no serious perioperative complications, but minor
complications occurred significantly more frequently in the PDT group,
especially difficult tube placement. Difficult tube placement resulted in false
passage in four patients and conversion to surgical tracheostomy in one. The
investigators suggested that some of the problems with PDT were related to
operator inexperience. They do not report whether they used custom PDT
tracheostomy tubes specifically beveled for easy passage.
In the study by Heikkinen and colleagues [36J, 40 patients were
randomized to PDT using the Griggs technique or to surgical tracheostomy.
They reported that there were no significant differences in complication
rates between the two groups, but that the PDT group required more
intravenous sedation owing to guidewire irritation. There was no mention of
the use of intratracheal topical anesthesia.
Freeman and colleagues [37] studied 80 mechanically ventilated
patients randomized to Ciaglia PDT or surgical tracheostomy. PDT was
performed faster and at lower cost compared to surgical tracheostomy. One
death due to hemorrhage at the tracheostomy site occurred in the group
randomized to surgical tracheostomy. Four patients randomized to PDT
had their tracheostomies converted to surgical tracheostomy and two
because of difficulty passing dilators.
In a preliminary report, Wu et al. [38] described the results of a
prospective randomized trial of Ciaglia PDT versus surgical tracheostomy in
83 ICU patients. There were no differences in the incidence of complica-
tions. Procedural times for PDT were approximately 22 min compared to
41 min for surgical trache(JSfflrighted Material
578
deBoisblanc
Stocchetti et a!. [39] evaluated the effects of three different methods of
tracheostomy on cerebral perfusion pressure in 30 neurosurgical patients
with elevated intracranial pressure. Ten patients each underwent surgical
tracheostomy, Ciaglia PDT, or Fantoni translaryngeal tracheostomy. No
significant procedural complications were reported, but intracranial
pressure was highest in the PDT group, whereas cerebral perfusion pressure
was lowest in the surgical tracheostomy group.
In a report by Massick and colleagues, 100 patients meeting stability
criteria for bedside tracheostomy were randomly assigned to either surgical
tracheostomy or endoscopically guided PDT [30]. No statistically significant
difference was found in the perioperative complication rates between the
two methods. However, the incidence of postoperative complications was
significantly higher for PDT (16 vs 2%). The higher rate of postoperative
complications added an additional patient charge of $436 per patient
undergoing PDT.
In an attempt to determine the preferred method of tracheostomy in
patients with anterior cervical spine fixation following acute spinal cord
injury, Sustic and colleagues randomized 16 patients to surgical tracheost-
omy or ultrasound-guided PDT with the Griggs dilational forceps technique
[40]. None of the patients in either group experienced major perioperative
complications. In each group, there was one case of prolonged bleeding,
which stopped spontaneously. Two patients from the surgical tracheostomy
group developed stomatitis. PDT required less than half the time of surgical
tracheostomy. This study is important in that neck immobility was
previously considered a contraindication to PDT.
In summary, from a review of randomized trials it appears that PDT
has a periprocedural complication rate similar to surgical tracheostomy
when performed by experienced operators. PDT does appear to require
specialized skills and equipment in order avoid complications and the need
for conversion to surgical tracheostomy. Faster procedure times are of
unclear benefit and economic analyses are inconclusive, since they have
largely focused on charges rather than true costs.
IV. Late Complications
The two most common late complications of tracheostomy are subglottic
stenosis and poor cosmetic result. The risk of late subglottic stenosis appears
to be very low (1-4%) for both PDT and open tracheostomy. In a large
series of 827 PDTs performed in 824 patients, the tracheal stenosis rate was
] .6% [4]]. In another large series of 422 POTs in 420 criticaJly ill patients,
100 (29%) were interviewed and offered further evaluation by fiberoptic
579
laryngotracheoscopy and tracheal computed tomography (CT) [42].
Twenty-seven of these patients reported voice changes and 2 reported
persistent severe hoarseness. CT identified mild (11-25%) stenosis in 10
asymptomatic patients, moderate stenosis in 4 patients, 2 who were
symptomatic, and severe stenosis in 1 symptomatic patient. Symptomatic
stenosis manifested by subjective respiratory symptoms after decannulation
was found in 3 of 48 (6%) patients.
In two randomized trials, the incidence unsightly cutaneous scarring
was 9 and 20% in patients who had PDT versus 25 and 40% in those who
underwent surgical tracheostomy [31,35].
V. Special Situations
A. Cervical Spine Injury
The lack of cervical spine clearance and inability to extend the neck are
assumed to be relative contraindications for PDT. Mayberry and colleagues
[43] reported a case series of 28 patients without cervical spine clearance who
underwent PDT, 13 of these had known cervical spine fractures (6 of these
were stabilized with a halo or operative fixation and 7 were stabilized with a
cervical collar). The PDT success rate was 96%, whereas the complication
rate was 7.1 % (2 of 28). No patient had spinal cord injury caused by PDT
and there were no procedure-related deaths.
B. Morbid Obesity
Morbid obesity can theoretically complicate PDT by making airway
management more difficult, by obscuring surface landmarks, and by
requiring custom tracheostomy tubes not designed for PDT. Bedside PDT
was successfully performed in 13 of 13 consecutive obese patients with a
body mass index 27 kgjm
2
, acute respiratory failure, and failure to wean
from mechanical ventilatory support [44]. Procedural complications were
limited to paratracheal tube placement in one patient, which was
immediately identified. Postprocedural complications were limited to a
cuff leak in one patient.
VI. Preoperative Ultrasound
Routine preoperative ultrasound of the base of the neck over the intended
operative site is being advocated as a PDT adjunct [45-47]. Ultrasound can
help identify intended landmarks and can identify large superficial and deep
vessels not visible or palpable (FjK 5). In q ser}'es of 497 PDT procedures,
-Copynyflted Matena
580 deBoisblanc
PDT was abandoned because of bleeding in 6 patients and was noted to be a
problem in a further 18 cases (overall incidence 4.8%). The source of
bleeding in four of these patients was attributed to vessels that could be
imaged by ultrasound, the inferior thyroid vein (two cases), high
brachiocephalic vein (one case), and an aberrant anterior jugular commu-
nicating vein (one case) [47].
VII. Conclusion
In summary, when performed by competent physicians experienced with the
procedure, the risk of serious complications related to PDT appears
equivalent to that of surgical tracheostomy. The single-dilator Ciaglia PDT
kit currently offers the greatest combination of safety with ease of use.
Routine preprocedural ultrasound and bronchoscopy are also recommended.
High riding
innominate
artery
I
~ k n
Inferior
thyroidal
/ vein
Figure 5 Ultrasound of the base of the neck just cephalad to the sternal notch in
an obese volunteer demonstrating a high-riding innominate artery and a large
inferior thyroidal vein. The innominate artery was not palpable through the skin.
Percutaneous Dilaliona/ Tracheostomy
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45 Hatfield A, Bodenham A. Portable ultrasonic scanning of the anterior neck
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37(4):309-31 J.
28
Transthoracic Needle Aspiration and Biopsy*
CARLA R. LAMB
J. Introduction
DAVID A. BRADSHAW and
DENNIS E. AMUNDSON
Naval Medical Center
San Diego, California, U.S.A.
Transthoracic needle aspiration (TTNA) and transthoracic needle biopsy
(TTNB) are established pulmonary procedures that offer rapid and accurate
diagnosis of benign and malignant lung lesions [1-6]. A 1974-1975 survey
reported that only 2% of the transthoracic needle aspirations and 19% of the
transthoracic needle biopsies done in 109 U.S. teaching institutions were
performed by pulmonologists [7]. Our collective anecdotal experience and
an informal survey of physicians in our. region confirm that invasive
radiologists perform the overwhelming majority of percutaneous lung
punctures; generally under computerized tomographic (CT) guidance.
Insufficient training, inexperience, lack of available equipment and ancillary
help, and time constraints are all recognized barriers to pulmonary
physicians who might otherwise offer these procedures.
*The views expressed in this article are those of the authors and do not reflect the
official policy or position of the Department of the Navy, Department of Defense, or
the U.S. government.
585
586
Lamb et at.
This chapter will provide an overview of TTNA/TTNB including
patient selection, indications, contraindications, risks, and outcomes useful
to all physicians who refer patients for transthoracic needle sampling of lung
lesions. Moreover, we will review the technique of fluoroscopically guided
TTNA/TTNB for pulmonologists interested in performing percutaneous
lung biopsy, which is a procedure that complements flexible fiberoptic
bronchoscopy [8-11].
For almost 120 years physicians have utilized invasive puncture techniques
to diagnose infectious and malignant pulmonary diseases [12,13]. The
earliest recorded attempts at percutaneous transthoracic needle lung biopsy
from the 1880s antedated x-ray technology and therefore relied on expert
physical diagnostic skills to locate the lesion. Most procedures were
performed in the setting of advanced lung disease. In the 1920s and 1930s
clinicians utilized large-bore needle/syringe devices in an attempt to perform
both "cutting" and "aspiration" biopsies, and a flurry of case series
reported the efficacy of these new techniques. As might be expected, a
growing body of literature documenting procedural complications, includ-
ing lung collapse, hemorrhage, empyema, and even death, soon followed.
These reported complications and the fear of tumor implantation along the
needle tract eventually lead to some reluctance to puncture the pleura,
especially in the setting of malignant disease [14-16]. The development of
thin-bore "fine" needles and newer cytological methodology combined with
radiographic image intensification and biplane fluoroscopy in the 1960s and
1970s reduced the complication risk and enhanced the yield for diagnosis
[17-20]. Needle aspiration became commonplace, and many medical centers
developed extensive experience in invasive cytologic diagnosis [21-26].
Collaboration with an experienced cytopathologist became routine and
immediate cytological assessment was highly recommended [27,28].
Improvements in technique and better biopsy needles also allowed safer
access to larger core tissue samples providing histological material to
analyze for diagnosis of benign as well as malignant disease. Changes in
materials and miniaturization streamlined previously cumbersome fluoro-
scopic units and eventually brought the procedure to the physician's office.
The twentieth century advent of noninvasive diagnostic tools such as
CT, magnetic resonance imaging, and, more recently, position emission
tomography has further enhanced the diagnosis of lung lesions and staging
of malignant lung masses [29-31]. Recognition of specific "benign"
characteristics of pulmonary nodules and an understanding of the
Transthoracic Needle Aspiration and Biopsy
587
differences in glucose uptake and metabolism between benign and malignant
cells has even obviated the requirement for tissue confirmation under certain
conditions. Nevertheless, directed needle biopsy with CT guidance has
flourished in invasive radiology departments as the full impact and potential
of modern imaging procedures in clinical diagnosis continues to evolve.
Additionally, advances in direct-vision, "semi-invasive" technology such as
video-assisted mediastinoscopy, thoracoscopy, and transesophageal ultra-
sonography now allow access to lung tissue not previously accessible to even
the most skilled invasive radiologist [32-34]. In summary, percutaneous
aspiration cytology and biopsy, especially when performed under direct
radiographic guidance with close cytopathological collaboration, remain
viable and valuable tools in the pulmonary physician's clinical armamentar-
ium as we enter the twentieth century.
III. Indications, Contraindications, and Relative Risks
In 1989, the American Thoracic Society published a very useful and concise
position paper outlining the indications, contraindications, and guidelines
for performing percutaneous transthoracic needle biopsies [351 These are
summarized below.
Indications:
Diagnosis of solitary or multiple lung nodules
Diagnosis of suspected lung metastases in a patient with a known
primary cancer
Confirm the diagnosis of cancer in a patient who is not a candidate
for operational resection
Obtain material for microbiological analysis that is suspected to be
infectious in origin
Obtain diagnostic material from suspicious lymph nodes and other
lesions in the mediastinum
Contraindications:
Uncooperative patient
Intracta ble cough
Lack of informed consent
Insufficient training or supervision of the operator
Lack of adequate eq uipment and/or personnel to provide
emergency care of the patient in case of complications including
pneumothorax, hemorrhage, and cardiac arrest .
Inability to dUrIng the procedure
588 Lamb el al.

Uncorrectable coagulopathy
Severe pulmonary hypertension
Lack of adequate imaging equipment
Inability to visualize the lesion at the time of biopsy
Lesion suspected to be vascular
Patient requiring or anticipated to require mechanical ventilation
Any situation in which the biopsy results would not effect patient
management or prognosis
Conditions associated with increased risk that may require special
considerations:
Presence of severe lung disease such that a pneumothorax or
hemorrhage would cause severe respiratory distress
Bullous emphysema or cystic lung tissue along the needle path
Lesions located immediately adjacent to mediastinal or vascular
structures
Uremia, pulmonary hypertension, and coagulation disorders
associated with increased risk of hemorrhage
Recent myocardial infarction, unstable angina, congestive heart
failure, or uncontrolled cardiac dysrrhythmia
Severe debility, advanced age, or malnutrition
Superior vena cava obstruction
In addition to the cautions cited in the ATS paper, we would add prior
contralateral pneumonectomy as an absolute contraindication. Physicians
should also consider hydatid disease in the differential diagnosis of cystic or
cavitary lung masses. Puncture of a hydatid cyst may result in dissemination
and/or anaphylaxis [36,37]. Highly necrotic lesions have a tendency to bleed
profusely and also warrant appropriate. caution.
The major indication for TTNA/TTNB is the diagnosis of suspected
lung cancer. Bronchoscopy often yields diagnostic material when the lung
lesion is large, centrally located, and associated with a patent or closely
adjacent bronchus. Peripheral lesions less than 2 or 3cm are probably best
approached with TTNA/TTNB [38]. Figure I presents a useful algorithm
that incorporates TTNA/TTNB into the diagnostic evaluation of potentially
malignant pulmonary lesions. TTNA/TTNB is used much less frequently in
the evaluation of infectious or inflammatory processes, although it may be
helpful in HIV-infected or otherwise immunocompromised patients with
parenchymal lung disease [39-41].
Pulmonary nodule or mass
on chest radiograph
Contrast-enhanced CT scan of chest
Positive mediastinum
1 em lymph node
local invasion and/or
loss of tissue planes
Negative mediastinum
589
Flexible fiberoptic bronchoscopy
wjtransbronchial needle aspirate
for assessment of both the
mediastinum and primary lesion
(if both the mediastinum and
primary lesion are nondiagnostic)
Transthoracic needle aspirate
(if nondiagnostic or inflammatory cells)
Mediastinoscopy!
video-assisted thoracoscopy (VATS)
- If 3 em lesion
- Centrally located
- -Bronchus sign
Flexible fiberoptic bronchoscopy

w/transbronchial needle aspirate
(if nondiagnostic)
Figure 1 Algorithm demonstrating a diagnostic approach to the pulmonary
nodule or mass utilizing transbronchial needle aspiration, transthoracic needle
aspiration, and flexible fiberoptic bronchoscopy. (Adapted from Ref. 10.)
IV. Equipment, Preparation, and Technique
In this section, we will outline the equipment, patient preparation, and
technique used to perform TTNA/TTNB under fluoroscopic guidance. The
interested reader is referred to a number of excellent reviews for further
technical details and the perspectives of other experienced physicians [14,42-
47].
Several aspiration and core biopsy needles are commercially available
[48] (Fig. 2). We generally use a 22- or 23-gauge Chiba needle (Cook,
Bloomington, IN) for aspiration of the highly cellular specimens necessary
for a cytological diagnosis of malignancy [49]. The Chiba needle is thin
walled, fitted with a removable central stylet, and beveled 25 degrees at the
tip. It is available in 15- and 20-cm lengths. Core biopsy needles are
generally larger and incorporate a cutting mechanism in order to provide a
histological tissue sample that is especially helpful in the diagnosis of benign
lesions and an experienced cyto-
590 Lamb el al.
Design Gauges
! ;;:';;1;':;' ;;':::;. :;;;;-'&
Chiba
25bevel 22,23
r,; :;;; 1m;;;it:;: ;;:tV: ::r&
Turner 45bevel 16,18,20,22
r,pt Ziti ;;;;:;::i:;;;:;;1I:t>
Madayag 90bevel 22
Greene
L ... i itt;;;;::;;;:,:;: :y:;: :pt>
90bevel 22,23
Westcott !' ::;::i::' =:;;
;;;:::Is#iitri?>
Siotter 20
Franseen
(tit;:;; ;. =;;;: ;;:;;g;; ';:;;6:,*
Trephine 18,20,22
Figure 2 Aspiration/biopsy needles. (Adapted from Ref. 51.)
pathologist is not available [50]. The Turner needle (Cook, Bloomington,
IN) that we use for TTNB, for example, resembles the Chiba needle except
that it has a circumferential cutting tip beveled to 45 degrees [51]. The larger
core biopsy needles are associated with a higher risk of complications,
especially hemorrhage. In order to avoid multiple needle passes through the
chest wall and pleura, some physicians now use a dual or "coaxial" needle
system [52]. Once the thin-walled needle introducer (generally a 19-9auge
needle) is correctly positioned with one pass across the pleura, a smaller
aspiration or cutting needle (generally a 22-gauge needle) can be passed into
the lesion multiple times in order to obtain an adequate specimen (Fig. 3).
Many radiologists now use an automated biopsy gun to sample lung lesions
[53,54].
Our standard TTNA/TTNB procedure tray (Fig. 4) and setup consists
of the following:
I. Sterile gloves and drape
2. Sterile 4 x 4 gauze
3. Betadine (povidone-iodine) solution
591
c
b
a
Figure 3 Diagram of outer (a) and inner (b) needles used in coaxial technique. The
plastic ring (c) marks the desired depth of insertion of the inner needle into the outer
needle and the resultant pass length (d). During sampling, the outer needle is placed
in the peripheral portion of the nodule, whereas the inner needle is used to sample the
majority of available nodule without extending into normal lung deep to the nodule.
(From Ref 52.)
4. Sterile ring forceps or hemostat
5. I% lidocaine without epinephrine
6. 3-mL syringes (two or three)
7. 20-mL plastic or glass syringe (one)
8. 20- and 23-gauge needles
9. #11 scalpel blade
10. Aspiration (Chiba, 22 gauge, 20 em) and/or biopsy (Turner, 20
gauge, 15 em) needles
II. Sterile saline or balanced salt solution (Hank's solution, Life-
Tech., Inc., Stafford, TX) 3-5 mL in syringe to facilitate
specimen retrieval and deposition on the slides
12. Cytology solution (Cytolyte, Cytec Corp.) for fixing and
preserving slide specimens
13. Radiation shields for all personnel and patient
14. Biplane fluoroscopy or C-arm unit (with optimal 180 degrees'
rotation in a single plane)
IS. Material
592
e.
Lamb et al.
Figure 4 A basic procedure tray: (a) 20-mL syringe for aspiration of specimen; (b)
sterile ring forceps for fluoroscopic localization; (c) Turner needle (Cook) with inner
stylet and centimeter depth marker; (d) syringes for topical anesthesia with 1%
lidocaine; (e) size II scalpel blade with sterile gauze; (f) Betadine preparation on
sterile gauze.
TTNA/TTNB should be guided by direct radiographic visualization.
Fluoroscopy, an efficient, cost-effective modality available to many
pulmonary physicians, offers real-time imaging from needle insertion to
specimen retrieval. TTNA/TTNB performed under fluoroscopy can
generally be completed within IS-30 min. [SS]. Although ultrasound may
be useful for peripheral lung masses, especially when they are necrotic, CT
has become the imaging tool of choice for most radiologists performing
transthoracic needle aspirations/biopsies [S6-64]. The CT-guided approach
generally takes more time (I.O-I.S hr) and is considerably more expensive. A
review of local 200 I billing data revealed that the cost of a fluoroscopy-
guided needle lung aspiration/biopsy, including technical and professional
fees, was approximately $SSO.OO as compared to a CT-guided procedure at
approximately $IS26.00. Onsite cytopathologist specimen review increased
the total by $lOS.00.
593
General Approach:
1. Patient preparation: Patients requiring tissue confirmation of lung
nodules/masses should be advised of the significant risk of
pneumothorax and other complications prior to undergoing
TTNA/TTNB. Informed consent must be signed and witnessed.
The patient should be able to follow instructions, perform
controlled shallow breathing, and suppress cough during the
procedure.
2. Patient positioning: A CT scan performed prior to the procedure is
very useful in determining the most direct pathway, measuring the
precise depth of the lesion, and ensuring that bullous lung and
vascular structures are avoided. The patient is asked to lie in the
position that provides the most direct vertical pathway to the
lesion and provides clear visualization of the mass/nodule under
fluoroscopy.
3. Monitoring of the patient: Continuous noninvasive monitoring of
pulse, blood pressure, cardiac rhythm, and oxygen saturation is
recommended.
4. Preparation of the entry site: The ribs and intercostal space should
be identified by careful palpation. After sterile Betadine prepara-
tion and draping, I % lidocaine is injected subcutaneously and
along the superior margin of the rib, thereby avoiding the
neurovascular bundle.
5. Fluoroscopic localization of the lesion: Visualizing a radiopaque
object on the chest wall under fluoroscopy facilitates identification
of the optimal skin entry site. Ring forceps can be used to hold the
syringe/seeker-needle unit in place as the position is confirmed
(Fig. 5). The aspiration/biopsy needle is then advanced with the
inner stylet in place under intermittent biplane or Carm
fluoroscopic guidance to confirm both path and position. A
plastic ring attached to the needle marks the premeasured depth of
the lesion and improves accuracy (Fig. 6).
6. Aspiration/biopsy: After removing the inner stylet, a 20-mL
syringe filled with 3-5 mL of sterile saline is attached to the needle
(Fig. 7). The saline allows one to flush the specimen from the
needle and serves as an indicator for complications. Air bubbles in
the syringe suggest a leak in the seal between the needle and
syringe, passage of the needle through a bronchus, or pneu-
mothorax. Entry into the lesion is suggested by a distinct change
in resistance likened to a "rubber ball filled with sand." Correct
position under f1uoroscop.y. is confirmed when the needle is noted
Copyrigfited Material
594 Lamb et at.
Figure 5 Demonstration of fluoroscopic localization of nodule with ring forceps
following application of topical anesthetic.
to deform or displace the lesion and then move synchronously
with the lesion during respiratory excursions. Centrally necrotic
lesions should be sampled at the margin; otherwise the needle tip is
directed to the center of the lesion. Finally, the needle is rotated
and agitated in an up and down fashion at O.5-1.0-cm depths.
Syringe suction should be maintained at all times, particularly
when exiting the lesion and the chest wall to prevent loss of
specimen. The specimen is then given to the cytolopathologist for
immediate processing and review. Additional passes may be
necessary if a definitive diagnosis cannot be made at the bedside.
7. Immediately following the procedure, fluoroscopy is repeated to
rule out pneumothorax, and then an upright expiratory film is
obtained I hr later prior to discharging the patient.
V. Safety and Outcome
The spectrum of complications associated with fluoroscopy-guided trans-
thoracic needle aspiration/biopsy has been well delineated by a series of
595
Figure 6 Placement of biopsy needle with inner stylet while utlizing predetermined
depth marker.
studies from the 1970s and 1980s (Table I) [14-70]. Additionally, scattered
case reports have also revealed several very infrequent, but potentially Iife-
threatening, complications. As might be expected, pneumothorax is the
most common complication with an incidence between 18 and 49%. Most
pneumothoraces are detected immediately postprocedure, although up to
10% may be delayed. Perlmutt et al. did not find any clinically significant
pneumothoraces beyond those discovered at I hr in their series of 673
patients undergoing transthoracic needle aspiration [71]. Small, asympto-
matic pneumothoraces in otherwise stable patients generally require only a
limited period of observation, follow-up radiograph to ensure stability, and
careful instructions to the patient and caregiver. Reports from the literature
are quite consistent and suggest that less than 10% of all patients undergoing
TTNA/TTNB require pleural catheter drainage. A small-bore catheter
attached to a one-way Heimlich valve is usually sufficient, and most air leaks
resolve within 24 hr [72,73]. Responsible patients with adequate pulmonary
reserve may be safely and cost effectively managed as outpatients [74,75].
Simple aspiration has NfcD&fl;j? to obviate the need for
596
Lamb et al.
Figure 7 Aspiration of nodule with syringe containing sterile saline. A
cytopathologist is present for immediate review of specimens.
chest tube insertion in some patients with large pneumothoraces [76].
Tension pneumothorax is a very rare occurrence, presents within minutes of
the procedure, and constitutes a medical emergency. Physicians performing
transthoracic needle aspiration must be immediately available and prepared
to decompress the pneumothorax promptly.
Obstructive lung disease has often been cited as an important risk
factor for pneumothorax following transthoracic needle biopsy, although
several recent studies now challenge this assertion [77-86]. It does appear,
however, that those patients with airway obstruction who develop
pneumothorax are much more likely to require chest tube drainage. Other
variables that may predict the rate of pneumothorax include lesion location,
size and depth; number of pleural passes; needle size; and operator
experience. Transthoracic needle procedures performed using CT guidance
have a higher pneumothorax rate than those procedures performed using
fluoroscopy [87]. This is likely due to longer procedure times and the greater
amount of lung tissue traversed in reaching smaller, deeper lesions not
amenable to fluoroscopic localization.
:S
Table 1 Sample of Large Studies Utilizing Fluoroscopy in Performance of Transthoracic Needle Aspirates/Biopsies
::;
;:s-
Sensitivity Specificity Accuracy

r;i
Patients in In for r,
requiring diagnosis diagnosis diagnosis
r:;'
chest of of of
Study Year of Study site No. of No. of Pneumothorax tube Other malignancy malignancy malignancy
(reference) publication patients procedures incidence (%) complications (%) (%) (%)
Lalli et al. (65) 1978 Cleveland, OH 1223 1296 24.2 4.4 I death 76 99 86

I hemothorax
{;
22 hemoptysis
::;.
()
l:l
0 I suicide

otumor implants
::;
et al. (66) 1978 SI. Louis. MO 1211 1211 24 14 odeaths 99 87 96 l:l
::;
:::!'
6% hemoptysis l:l...
(j) 4% hemorrhage tl:l
Q.
otumor implants
et al. (67) 1980 Hartford, CT 422 432 27 10 odeaths 97 96 96
(j)
8% hemoptysis

otumor implants
96erquist et al. (68) 1980 Rochester, MN 430 49 21 2 deaths 97 100 82
II % hemoptysis
26% hemorrhage
Todd et al. (43) 1981 Toronto, Canada 1840 2114 31.9 10.4 odeaths 70 96 78
otumor implanl
Khouri et al. (69) 1985 Baltimore, MD 650 650 18 5 odeaths 95 96 95
5% hemoptysis
otumor implants
Stanley et al. (70) 1987 Charleston, SC 458 458 29 10 odeaths 97 97 96
5 hemoptysis
otumor implant
v,
'0
'-l
598
Lamb el at.
Reducing the incidence of TTNA-associated pneumothorax has been
the focus of several investigations. In the 1970s, McCartney et al. reported
injecting autologous blood or Gelfoam through the introducer needle of a
coaxial system following lung biopsy [88]. None of the 25 patients treated
with this technique developed pneumothorax. In response to that initial
report, and similar anecdotal data, at least three randomized controlled
studies of the "blood patch" method have been conducted [89-93]. Two of
the three studies were unable to demonstrate a difference in the
pneumothorax rate [91,92]. The most recent study, however, did show a
significant reduction in pneumothorax; primarily in those patients with
deeper lesions [93]. Other methods of plugging the biopsy needle tract
utilizing fibrin or other tissue adhesives have been even less well studied [ ~
97].
Patient position and activity following lung biopsy may influence the
pneumothorax rate. A dog model suggested a diminished air leak when the
animal was positioned with the puncture site down postprocedure [97]. This
finding prompted several clinical studies. Cassel et al. and Moore et al. both
reported reduced pneumothorax rates, compared to historical controls,
when patients were asked to assume a puncture site-down position for 1-
3 hr following biopsy [98,99]. Moore et al. subsequently prospectively
randomized 310 consecutive patients to a puncture site-up or puncture site-
down position after TTNA but were unable to show a difference in the
overall pneumothorax rate. They did note, however, that fewer patients
placed with the puncture site dependent required chest tube placement [100].
The most recent randomized controlled trial of over 390 patients failed to
show any influence of position on the post biopsy pneumothorax incidence
or requirements for chest tube placement [10 I].
Prophylactic administration of 100% supplemental oxygen to high-risk
patients has been suggested as another way to diminish the incidence of
pneumothorax. Unfortunately, this presents a substantial risk to those
patients with unrecognized chronic CO
2
retention, and therefore empiric
high flow oxygen is not advised. Supplemental oxygen administration does
hasten pneumothorax resolution and should be available for patients who
require treatment.
Pulmonary hemorrhage manifesting as hemoptysis, hemothorax, or
simply radiographic airspace filling following lung biopsy is almost always
self-limited. Rare cases of fatal bleeding have been reported in the literature
[102-104]. Risk factors for significant hemorrhage include an underlying
bleeding diathesis, pulmonary hypertension, or renal failure and the use of a
large-bore cutting needle.
Extremely uncommon complications associated with transthoracic
lung puncture include cardiac tamponade, lung torsion, systemic air
599
embolism, and needle tract tumor implantation. Case reports of cardiac
puncture with subsequent tamponade stress the need for extreme caution
when considering needle aspiration of central lesions [105,106]. These are
best performed under CT guidance. Two cases of lung torsion, one involving
a single lobe, have been reported following transthoracic needle biopsy
complicated by pneumothorax [107,108]. Transthoracic needle aspiration i
one of several procedures now identified as causing systemic air embolism,
although the frequency is extremely low when compared to other procedures
such as cardiopulmonary bypass or neurosurgery [109-112]. Aberle et al.
proposed three possible mechanisms whereby air might enter the systemic
circulation [112]. These include direct introduction of air through the
aspiration needle into a pulmonary vein, migration of air from the
pulmonary artery to pulmonary vein, or creation of a bronchovenous
fistula after puncture of a bronchus. All of these mechanisms presuppose
existence of a pressure gradient that facilitates air passage into the
pulmonary venous circulation as might occur with coughing. The effects
of systemic air embolism depend on the volume of air introduced and organ
affected. Cerebral air embolism may present with sudden unresponsiveness,
seizure, or focal neurological deficits that mimic other central nervous
system catastrophes such as stroke or hemorrhage. General management of
systemic air embolism includes administration of 100% supplemental
oxygen and positioning of the patient in the fully recumbent or
Trendelenburg position. Anecdotal data support the use of hyperbaric
oxygen if a chamber is immediately available. Spread of tumor cells through
the needle tract is of potential concern, but has been only very rarely
reported in bronchogenic carcinoma [113-116]. Malignant mesothelioma,
on the other hand, appears more likely to seed biopsy or thoracoscopic sites,
although the incidence following simple needle biopsy is unclear [) 17].
Fatalities are very rare in reported case series of transthoracic needle
aspiration. Among the 6591 procedures recorded in Table 1, only three
fatalities were reported (0.045%). Nevertheless, each patient must be fully
informed of the potential for serious complications, including death.
Appropriate resuscitative equipment including supplemental oxygen, chest
tubes, airway supplies, intravenous fluids, and hemodynamic drugs must be
immediately available. One reported case of suicide on the way home from a
transthoracic lung biopsy that yielded an immediate cytological diagnosis of
cancer serves as a reminder of the need for caution and sensitivity when
discussing results with emotionally distraught patients [65].
The diagnostic yield for TTNA/TTNB is very high, especially for
malignant lesions. A recent meta-analysis of TTNA/TTNB performed
utilizing various imaging techniques (CT, ultrasound, and fluoroscopic
localization) reported a po6Jepg"'YNII8fffffiilo and specificity of 99% for
600
Lamb et at.
malignant lesions [118]. In our review of large studies using fluoroscopy,
TTNA/TTNB (see Table I) sensitivity for malignancy ranged between 70
and 99%. Nondiagnostic biopsies usually result from poor sampling
techniques or failure to visualize the lesion adequately at the time of
biopsy. Large areas of tumor necrosis may interfere with sampling, and
every effort should be made to aspirate from a solid area of tumor, usually
at the periphery. A CT scan performed prior to fluoroscopically guided
TTNA can be very useful in planning the biopsy approach and alerting the
physician to areas of necrosis not obvious on plain radiographs. False-
positive biopsies are very uncommon, with most series reporting a rate well
under I%. In cases when a false positive biopsy does occur, these lesions
invariably turn out to be highly inflammatory or infectious in nature.
The diagnostic yield of TTNA/TTNB for benign lesions presents a
greater challenge because the small, fragmented tissue samples obtained, as
well as the wide spectrum of benign disease that may present as a pulmonary
nodule or mass [119,120]. For these reasons, it is essential that an
experienced cytopathologist be involved in the handling, processing, and
interpretation of specimens. Cell blocks and special stains (e.g., Gram's
stain, acid fast, Congo red, special culture media) sometimes provide a
specific benign diagnosis while cytology rarely does. A specific benign
diagnosis may obviate the need for thoracotomy; however, nonspecific
inflammation does not rule out malignancy and should never be used as a
reason to forego excision. Ultimately, 20-30% of patients with a
nondiagnostic TTNA/TTNB are found to have cancer [121].
VI. Conclusion
Percutaneous transthoracic needle aspiration and transthoracic biopsy of
the lung remain important modalities for establishing the diagnosis of lung
lesions. TTNA/TTNB complement flexible bronchoscopy and are especially
useful for smaller lesions located in the lung periphery [122]. The
complications associated with percutaneous lung biopsy are well described,
and the high incidence of pneumothorax demands the careful attention of
the attending physician. Although most percutaneous transthoracic needle
aspirations and biopsies are performed by invasive radiologists under CT
guidance, we believe that interested pulmonary physicians with access to
fluoroscopy may safely and effectively perform these procedures. Most
importantly, it is critical that physicians who evaluate patients with lung
disease have a clear understanding of the potential benefits and risks of the
multitude of imaging and invasive procedures currently available, including
TTNA/TTNB, so that they may be applied in a thoughtful manner.
Acknowledgment
601
The authors gratefully acknowledge the contributions of Dr. James H.
Harrell, Pulmonary Division, University of California San Diego, to our
training in pulmonary procedures as well as technical aspects of this chapter.
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608 Lamb et al.
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2002; 23:137-158.
29
Effects of Interventional Procedures on Quality
of Life and Pulmonary Function
MICHAEL A. JANTZ
University of Florida
Gainesville, Florida, U.S.A.
I. Introduction
GERARD A. SILVESTRI
Medical University of South Carolina
Charleston, South Carolina, U.S.A.
Airway obstruction, whether from benign or malignant processes, is a
significant cause of morbidity and mortality. The various endoscopic
modalities discussed in this textbook are becoming increasingly recognized
as an integral component of therapy for tracheobronchial stenosis and
tracheobronchomalacia. Many, although not all, patients with benign
diseases can be relatively "cured" with these therapies. Most patients with
locally advanced lung cancer and endobronchial metastases are not
candidates for curative resections. As such, the best we can hope to do is
extend their life to some degree and to palliate their symptoms. Although
there have been suggestions that interventional bronchoscopic procedures
may prolong the life of patients with major airway obstruction, and our
experience bears this out in select patients, this has not been conclusively
demonstrated in controlled studies. Even if we cannot prolong the life of all
or most patients, the ability to palliate symptoms effectively with these
procedures is worthwhile. The question to be asked, then, is do
interventional procedures produce changes in
609
610
Jantz and Silvestri
symptoms and quality of life? Unfortunately, the number of studies in the
literature which have evaluated changes in quality of life are far less than the
number of studies which merely report technical successes and changes in
airway dimensions. In addition, most studies have noted changes in
performance status scores or dyspnea scores, which can be used as proxy
measurements for quality of life, but are not true measures of quality of
life.[I]
In this chapter, we will review the studies using various bronchoscopic
modalities that have included results on changes in quality of life, functional
status, and symptoms, particularly dyspnea, following the intervention. In
terms of dyspnea, we will focus on studies which used recognized and
validated dyspnea indices rather than report on all studies which only
described dyspnea as "being improved." In addition, we will also review
studies which describe changes in pulmonary function, as this has been used
to gauge efficacy of the intervention and impact on the patient population.
Changes in pulmonary function, however, may not correlate with changes in
quality of life or symptoms and may not be an appropriate study endpoint.
For reference purposes, the Karnofsky performance scale is provided in
Table I and the Eastern Cooperative Oncology Group (ECOG) perfor-
mance scale is provided in Table 2. The Hugh-Jones dyspnea index, which is
similar to other dyspnea indices, is noted in Table 3.
II. Changes in Quality of Life, Performance Status,
and Dyspnea
A. Acute Respiratory Failure Requiring Mechanical
Ventilation
Colt and Harrell reported on their experience with 32 patients requmng
emergent ICU admission for central airways obstruction [2]. Airway
obstruction was caused by bronchogenic lung cancer in 14 patients and
benign disease in 18 patients. Nineteen of these patients required mechanical
ventilation. The 32 patients were treated with neodymium-yttrium-
aluminum-garnet (Nd-YAG) laser resection and/or silicone stent placement
via rigid bronchoscopy; 15 patients underwent stent placement alone.
Partial or total airway patency was achieved in all 32 patients. Mechanical
ventilation was successfully discontinued in 10 of 19 patients (52.6%). Of the
total 32 patients admitted to the ICU, 20 (62.5%) were transferred to a lower
level of care immediately after the intervention. With regard to the 11
patients with malignant disease requiring mechanical ventilation, 2 were
successfully extubated.
Effects on Quality of Life and Pulmonary Function
Table 1 Karnofsky Performance Scale
6J1
General description
Able to carry out normal activities;
no special care required
Unable to work; able to live at home
and care for most personal needs:
varying amounts of assistance
needed
Unable to care for self; requires
equivalent of institutional or
hospital care; disease may be
rapidly progressing
Index Specific criteria
100 Normal; no complaints; no
evidence of disease
90 Able to carryon normal activities:
minor signs or symptoms of
disease
80 Normal activity with effort; some
signs or symptoms of disease
70 Unable to carryon normal activity
or to work; able to care for self
60 Requires occasional assistance but
able to care for most needs
50 Requires considerable assistance
and frequent medical care
40 Disabled; requires special care and
assistance
30 Severely disabled; hospitalization
indicated although death not
imminent
20 Very sick; hospitalization
necessary; active supportive care
necessary
10 Moribund; fatal processes
progressing rapidly
o Dead
Shaffer and Allen described eight patients with respiratory failure
from large airway obstruction requiring mechanical ventilation [3]. Six
patients had malignant airway disease and two had benign disease. Patients
were on the ventilator for 1-91 days prior to the intervention, with three
patients receiving mechanical ventilation for 24-48 hr prior to intervention.
Patients underwent placement of expandable metal stents (EMSs) via
flexible bronchoscopy. Following stent placement, all patients were
successfully extubated within 0-11 days afterward except for one patient
in whom support was with&awri&I1fJawi1'te'fMpes.
612
Jantz and Silvestri
Table 2 Eastern Cooperative Oncology Group (ECOG) Performance Scale
Grade Description
o Fully active, able to carryon all predisease performance without
restrictions
Restricted in strenuous activity but ambulatory and able to carry out
work of a light and sedentary nature
2 Ambulatory and capable of all self-care but unable to carry out any work
activity, up and about more than 50% of waking hours
3 Capable of only limited self-care, confined to bed or chair more than 50%
of waking hours
4 Completely disabled, cannot carry out any self-care, and totally confined
to bed or chair
5 Dead
Stanopoulos and coworkers reported their experience in treating 17
patients with respiratory failure requiring mechanical ventilation from
malignant airway obstruction [4]. Most patients had non-small cell lung
cancer. The duration of mechanical ventilation ranged from 1 to 25 days
prior to intervention. The patients were treated with Nd-YAG laser
resection via rigid bronchoscopy. In 9 of the 17 patients, successful
extubation was achieved. Endobronchial tumor obstruction was the
predominant finding in patients who were successfully extubated, whereas
extrinsic airway compression and submucosal disease were more prominent
in patients unable to be weaned from mechanical ventilation. The median
survival was 98 days (range 5-770) for the successfully extubated patients
Table 3 Hugh-Jones Dyspnea Index
Grade Description
The patient's breathing is as good as that of others of the same sex, age,
and build while at work, on walking, or on climbing hills or stairs
2 The patient is able to walk with healthy persons of the same sex, age,
and build on the level but is unable to keep up on hills or stairs
3 The patient is unable to keep up with healthy persons on the level but is
able to walk a mile or more at a slower speed
4 The patient is unable to walk more than about 100 yards on the level
without a rest
5 The patient is breathless on talking or undressing or is unable to leave
the house because of breathlessness
613
versus 8.5 days (range 1-15) for patients unable to be weaned from
mechanical ventilation.
Zannini and colleagues were also able successfully to wean patients
from mechanical ventilation following stent placement [5]. They placed
Gianturco EMSs via flexible bronchoscopy in six patients with respiratory
failure; four had tracheomalacia, one had kinking of the anastomosis
following lung transplant, and one had extrinsic compression from thymic
carcinoma. All patients had relief of respiratory symptoms and were
extubated 24-48 hr after stent insertion.
The use of photodynamic therapy (PDT) to facilitate liberation from
mechanical ventilation was recently reported by Shah and Ost [6]. Three
patients underwent PDT 48-72 hr after infusion of 2 mg/kg of Photofrin
(porfimer sodium). The first patient, who had bilateral mainstem bronchial
obstruction, received PDT to the near-total right mainstem bronchus
occlusion after successful stenting of the left mainstem bronchus failed to
allow for extubation. The patient was able to be extubated after undergoing
mechanical ventilation for 17 days. The second patient with squamous cell
lung cancer was found to have 99% occlusion of the left mainstern bronchus
after Nd-YAG laser resection of a 75% occlusion of the distal trachea. The
patient was also able to be extubated successfully after PDT, requiring 21
days of mechanical ventilation. The third patient, who had small cell lung
cancer, underwent PDT for 99% obstruction of the bronchus intermedius
after successful stenting for extrinsic compression of the left mainstem
bronchus. At follow-up bronchoscopy, improvement of the bronchus
intermedius was noted but complete obstruction of the more distal airways
was observed. Attempts at weaning were unsuccessful and support was
withdrawn.
B. Laser Resection
Changes in performance status and dyspnea following laser resection are
presented in Table 4. Of note, in the two studies by Gelb et aI., patients with
incomplete airway obstruction were more likely to have improvements in
dyspnea and performance status compared with patients who had complete
airway obstruction due to malignancy [7,8].
C. Stent Insertion
Studies evaluating the effects of stenting alone on functional status and
dyspnea are listed in Table 5. Studies combining stent insertion with laser
resection or balloon dilatation are noted in Table 6. Improvements in
dyspnea were observed in the majority of patients. Significant increases in
functional status, as score and the
6/4 Jantz and Silvestri
Table 4 Performance Status and Dyspnea After Laser Resection for Malignant
Obstruction
Study (reference) No. of patients
19 with complete
obstruction
Gelb and Ebstein (8) 70 with incomplete
obstruction
Gelb and Ebstein [7] 27 with incomplete
obstruction
Findings
Measurement (mean scores)
Karnofsky Improved 41 to 57"
score
MRCDI Improved 3.7 to 2.8"
Karnofsky Improved 30 to 35
score
MRCDI Improved 3.7 to 3.4
Karnofsky Improved 42 to 59"
score
MRC DI Improved 3.6 to 2.5"
score
b
score
Improved 45 to 54"
score
b
VAS-B Improved 57 to 71 b
VAS-W Improved 57 to 71 b
55 successfully
treated
14 unsuccessfully
treated
28
23 with complete
obstruction
Ross et a!. [9]
George et a!. [10]
MRC DI, Medical Research Council dyspnea index; VAS-B, visual analog scale for
breathlessness; VAS- W, visual analog scale for well-being.
p < .05.
bp < .005.
Eastern Cooperative Oncology Group (ECOG) performance scale, were
reported in all studies.
D. Endobronchial Brachytherapy
There have been many published studies evaluating the benefits of
endobronchial brachytherapy. Many of these studies reported changes in
various respiratory symptoms, although few used standardized scoring
systems. In the discussions of brachytherapy in this chapter, we will focus
mainly on studies which reported changes in performance status or
pulmonary function, noting the changes in symptoms which were included
in those reports. We will, however, comment on two recent randomized
615
Table 5 Performance Status and Dyspnea After Stent Insertion for Malignant
Obstruction
Study (reference)
Tan et al. [11]
Zwischenberger
et al. [12]
Wilson et al. [13]
Nakajima et
al. [14]
Tanigawa et
al. [15]
No. of
patients; stent
7, Wallstent
14, Gianturco
or Wallstent
II, Gianturco
22, Gianturco
44, Gianturco
Measurement
Modified ATS or
ATS DI
Karnofsky score
Karnofsky score
MRCor
VAS-B
VAS-W
Hugh-Jones DI
ECOG PS
Hugh-Jones DI
Findings (mean scores
unless specified)
Improved by 2 grades
in 3/7 patients
Improved in 7/14
patients
Improved in 4/9 patients
surviving >2 months
Improved 29 to 52
a
Improved 5 to 4
a
Improved 40 to 63
a
Improved 51 to 65
a
Improved by ;;:, 1 grade
in 21/22 patients
in 17/22 patients
in 35/44 patients
Dr, dyspnea index, ATS, American Thoracic Society; MRC, Medical Research Council; VAS-B,
visual analog scale for breathlessness; VAS-W, visual analog scale for walking; ECOG PS,
Eastern Cooperative Oncology Group performance status.
'p < .05.
trials comparing the addition of brachytherapy to external beam radiation
and comparing brachytherapy to external beam radiotherapy as initial
treatment and the observed changes in symptomatology.
Nori and associates treated 32 patients with malignant airway
obstruction with brachytherapy [22]. Seventeen patients were treated with
brachytherapy as a boost to external beam radiotherapy (group 1) and 15
patients were treated for endobronchial recurrence after prior external beam
irradiation (group 2). Most patients received three to four fractions of high-
dose rate (HDR) brachytherapy at a dose of 4 to 5 Gy at I cm per fraction.
Evaluated I month after treatment, the mean ECOG performance status
improved from 2.2 to 1.2. Prior to intervention, 14 patients had grade 3 or 4
status, whereas 5 patients had this level of severely decreased performance
status afterward. Subjective improvement improved for 15 of 15 patients
with hemoptysis, 10 of 10 patients with dyspnea, and 6 of 7 patients with
cough. Median survival was 17.7 months for group 1 and 7.5 months for
group 2. Copyrighted Material
Table 6 Performance Status and Dyspnea After Stent Insertion with Laser Resection (LR) or Balloon Dilatation (BD) for
Malignant Obstruction
No. of patients; stent; other Findings (mean scores
Study (reference) interventions Measurement unless specified)
() Sawada et al. [16] 14, Gianturco, 3 LRfll BD Hugh-Jones DI Improved by I grade in
0
12/14 patients
"b
'. Miyazawa et al. [17] 34, Ultraflex, II LR/l 0 BD Unspecified DI Improved 3.0 to 1.5
3
'g. Miyazawa and Arita [18] 35, Silicone, 19 LR/16 BD ECOG PS Improved 3.0 to 1.4
......
Bolliger et al. [19] 31, Silicone, number of LR/BD not NYHA DI Improved 3.5 to 2.3
a
s:
specified
Q)
Karnofsky score Improved 36 to 51 a
CD
:::l.
WHO PS Improved 3.0 to 2.1 a
e? Bolliger et al. [20] 27, Wallstent, 15 LR WHODI Improved 3.2 to 1.8
a
Karnofsky score Improved 32 to 55
a
Monnier et al. [21] 40, Wallstent, number of LR not Unspecified DI Improved 3.0 to 1.9
specified
Karnofsky score Improved 40 to 70
OJ, dyspnea index; PS, performance status; ECOG, Eastern Cooperative Oncology Group; NYHA, New York Heart Association; WHO, World
Health Organization.
ap<.OI.
0\
.......
0\
;:;..

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l::l...

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:!.
617
Twenty-nine patients with symptomatic endobronchial recurrence
following maximal external irradiation for bronchogenic carcinoma were
treated with HDR brachytherapy by Hernandez and colleagues [23].
Patients received three fractions every 2 weeks at a single fraction dose of
7.5-10.0 Gy at 1cm. Twenty-six patients completed the protocol. ECOG
performance status (mean grade 1.9 at study entry) improved in 24%,
remained unchanged in 42%, and worsened in 34%. Dyspnea improved in
24%, cough in 24%, hemoptysis in 69% (P < .01), and postobstructive
pneumonitis in 35% of patients. Radiographic evidence of improvement of
atelectasis was noted in 5 of 18 patients (28%).
Cotter and coworkers evaluated changes in performance status in 65
patients with airway obstruction from primary lung cancer [24]. Patients
were treated with external beam radiotherapy at doses of 55-66 Gy and
either intermediate-dose rate brachytherapy in 17 patients or HDR
brachytherapy in 48 patients. Total implant doses ranged from 2.7 to
10 Gy. An improvement in ECOG performance status was noted in 66% of
patients overall. Improvement was noted in 39% (5 of 13) of patients
receiving total doses less than 70 Gy, 72% (13 of 18) of patients receiving
total doses between 70 and 84 Gy, and 74% (20 of 27) of patients receiving
total doses of greater than 85 Gy. Radiographic improvement of atelectasis
was observed in 46% (15 of 33) of patients treated with total dose less than
85 Gy and 70% (19/27) of patients treated with total dose of 85 Gy or higher.
Mean survival of all patients was 12.4 months and did not significantly
differ when stratified for total dose of administered radiotherapy.
Two studies of brachytherapy for treatment of bronchogenic
carcinoma were reported by Huber and associates. In the first study, 44
patients were treated with four fractions of 3.8 Gy at I cm (group I) and 49
patients were treated with two fractions of 7.2 Gy at I cm (group 2) [25].
There was minimal change of the mean Karnofsky performance scores;
60.7-63.8 and 60.0-65.7 for group 1 and group 2, respectively. When
analyzed for patients treated according to protocol, median survivals were
20 and 24 weeks, respectively (P = .29). In the second study, 42 patients were
randomized to treatment with 60Gy external irradiation (group I) and 56
patients were randomized to 60 Gy external irradiation plus two
brachytherapy fractions of 4.8 Gy (group 2) [26]. No changes in Karnofsky
performance scores were noted in either group. Overall median survival was
28 weeks in group 1 and 27 weeks in group 2. When analyzed for treatment
according to protocol, median survival for group 1 was 30 weeks versus 43
weeks in group 2 (P = .08).
Langendijk and colleagues recently conducted a randomized trial
comparing external beam radiotherapy (group 1; 48 patients) and external
beam radiation plus 47 patients) for airway
618 Jantz and Silvestri
obstruction due to non-small cell lung cancer [27]. Patients were treated
with a radical fractionation schedule (60 Gy) or a palliative fractionation
schedule (30 Gy) depending on clinical status. Patients in group 2 also
received two fractions of 7.5 Gy HDR brachytherapy. Response rates were
37 versus 46% (P = .29) for dyspnea, 38 versus 24% for cough, and 82 versus
86% for hemoptysis in group I and group 2, respectively. Median survival
was 8.5 months in group 1 and 7.0 months in group 2 (P= .21).
Stout and coworkers also recently published results of a randomized
trial comparing external beam radiotherapy to brachytherapy in patients
with previously untreated non-small cell lung cancer [28]. Fifty patients
received external irradiation at a dose of 30 Gy (group 1) and 49 patients
received a single fraction of HDR brachytherapy at a dose of 15 Gy at I cm
(group 2). Positive response to symptom endpoints, as assessed by clinicians
at 8 weeks for group 1 versus group 2, respectively, was 78 and 59% for
dyspnea, 67 and 50% for cough, 89 and 78% for hemoptysis, 80 and 61 % for
chest pain, 74 and 57% for tiredness, and 78 and 63% for anorexia.
Assessments of positive response by patients at 8 weeks for group I and
group 2, respectively, were 49 and 38% for dyspnea, 65 and 45% for cough,
90 and 71 % for hemoptysis, 77 and 43% for chest pain (P < .05), 65 and 30%
for tiredness (P < .05), and 77 and 43% for anorexia (P<.05). A higher
percentage of patients in the external beam radiotherapy-only group
achieved good global palliation in assessments by clinicians (91 vs 76%;
P = .09) and by patients (83 vs 59%; P = .029). Twenty-eight percent of
group 1 patients required subsequent brachytherapy at a median of 304
days, whereas 51 % of group 2 patients required subsequent external beam
irradiation at a median of 125 days. Median survival was 287 days in group
I versus 250 days in group 2 (P = .04).
Based on these studies, endobronchial brachytherapy alone has
inconsistent results in improving performance status and a significant
number of patients have no benefit in functional status. Based on the
randomized trials by Huber and coworkers [26] and Langendijk and
associates [27], the addition of brachytherapy to external beam radiation
appears to confer no additional benefit in terms of symptom control,
performance status, or survival. Based on the randomized trial conducted by
Stout and colleagues comparing endobronchial brachytherapy to external
beam radiotherapy [28], it appears that external beam radiation is superior
to brachytherapy as initial treatment for symptoms related to n o n ~ s m cell
lung cancer.
Effects on Quality of Life and Pulmonary Function 619
E. Endobronchial Brachytherapy in Conjunction with Laser
Resection
Changes in performance status following endobronchial brachytherapy
(EB) were evaluated by Mehta and associates [29]. Fifty-two patients with
malignant airway occlusion underwent 55 applications of low-dose rate
(LDR) brachytherapy. Twelve patients underwent Nd-YAG laser resection
of tumor prior to EB and 31 patients had previously received external beam
radiotherapy. Thirty-three patients had improvement in ECOG perfor-
mance status of at least one grade, 17 remained unchanged, and 5
deteriorated posttherapy. Of the 51 patients with dyspnea, 41 improved,
5 remained the same, and 5 worsened. Hemoptysis improved in 81 % (17 of
21), cough in 75% (39 of 52), and pneumonia in 83% (19 of 23).
In a subsequent study, Mehta and colleagues compared patients with
malignant stenoses who were treated with LOR and hyperfractionated
HDR brachytherapy [30]. Sixty-six patients underwent LOR brachytherapy,
whereas 31 patients underwent HDR brachytherapy twice a day for 2 days.
Twelve patients in the LOR group underwent Nd- YAG laser resection prior
to brachytherapy. Mean ECOG performance status improved from 2.2 to
1.8 and from 2.1 to 1.6 in the LDR and HDR groups, respectively. Dyspnea
was lessened in 79% of patients in the LOR group and 75% of patients in the
HDR group. Improvements were noted in 68 and 73% of patients with
cough, in 91 and 100% of patients with hemoptysis, and 82 and 71 % of
patients with pneumonia in the LOR and HDR groups, respectively.
Atelectasis or lung collapse improved in41 of 52 patients (79%) in the LOR
group and 12 of 14 patients (85%) in the HDR groups.
Seventy-nine patients with primary lung cancer were treated with
HDR brachytherapy by Kohek and coworkers [31]. Patients received 5 Gy
per session with total doses ranging from 5 to 25 Gy (mean 11.6). In 26
patients with complete or nearly complete obstruction, Nd-YAG laser
resection was performed to allow for catheter placement. External beam
radiotherapy was administered to 48 patients following brachytherapy at a
total dose of 50-70 Gy. The mean Karnofsky performance score improved
from 68.2 to 77.2 in 58 of the 79 patients. Dyspnea was relieved in 67% of
patients (41 of61), hemoptysis in 86% (6 of7), and cough in 70% (50 of71).
In the 41 patients with atelectasis, radiological evidence of reaeration was
noted in 29 patients (70%). The median survival of the 48 patients who
received additional external beam radiotherapy was 13 months, whereas the
median survival of the 31 patients who did not was 6 months (P < .01).
Ornadel and associates evaluated 117 patients treated with HDR
brachytherapy for recurrent malignant airway obstruction after prior
therapy [32]. Patients underwent a single fraction of 15 Gy at 1cm except
620
Jantz and Silvestri
for four patients who received additional fractions. Nd-YAG laser resection
was performed in 51 patients prior to brachytherapy. Fifty-four percent of
patients had an improvement in ECOG performance status of at least I
grade (p= .0417). Dyspnea improved in 50% (P= .0063).
F. Electrocautery Resection and Argon Plasma Coagulation
Very few studies have been published evaluating changes in quality of life
dimensions after electrocautery resection or argon plasma coagulation, a
form of noncontact electrocoagulation; instead most have focused on the
technical aspects and the success rate of lesion resection (see Sec. lILE for
additional studies evaluating electrocautery). In a series of 56 patients
treated with electrocautery, Homasson reported improvement in dyspnea in
67% and control of hemoptysis in 75% of patients [33]. No further
information was provided about the patient series. Morice and colleagues
treated 60 patients with 70 applications of argon plasma coagulation via
flexible bronchoscopy; 43 patients ha.d bronchogenic carcinoma, 4 had
endobronchial metastases, and 3 had benign disease [34]. Improvement in
dyspnea was reported as being excellent after 37 procedures (53%) and
moderate after 32 procedures (46%). Hemoptysis was controlled in all 56
patients with this symptom.
G. Cryotherapy
Maiwand treated 153 patients with cryotherapy under rigid bronchoscopy
for malignant tracheobronchial obstruction [35]. The Karnofsky perfor-
mance score improved by 54.6%; 76 patients had increases in performance
status. Dyspnea improved in 85 of 133 patients (64%), cough in 82 of 120
patients (68%), hemoptysis in 51 of 55 patients (93%), and chest pain in 25
of 45 patients (56%). In a separate report by Maiwand describing 600
patients being treated with cryotherapy for malignant lesions, dyspnea
improved in 66% (451 patients), cough in 64% (348 patients), hemoptysis in
65% (252 patients), and chest pain in 24% (96 patients) [36].
Marasso and coworkers treated 234 patients with cryotherapy via rigid
bronchoscopy [37]. Of the 243 patients, 190 had malignant stenoses and 44
had benign stenoses. Improvement of dyspnea was noted in 81 % of patients
(87 of 107) and hemoptysis in 93% of patients (58 of 62). Pao2 increased in
120 of 168 patients (71 %). Resolution of lung or lobar atelectasis was noted
in 69% of patients (78 of 115). Twenty-two patients with tracheobronchial
obstruction, malignant in 20 and post-lung transplant anastomotic
strictures in 2, had fiberoptic bronchoscopic cryotherapy performed by
Mathur and associates [38]. Subjective improvement in dyspnea occurred in
12 of 17 patients (71 %) and in all 5 patients with hemoptysis.
H. Photodynamic Therapy
Studies evaluating changes in performance status and dyspnea after PDT
are presented in Table 7. Overall improvements in functional status were
noted in all studies. A randomized trial comparing PDT combined with
external beam radiotherapy versus radiotherapy alone in patients with
airway obstruction from bronchogenic carcinoma was conducted by Lam
and coworkers [44]. Six patients were randomized to PDT followed by
external beam radiation at a dose of 30 Gy in 10 fractions beginning I week
later (group 1), whereas five patients were treated with radiotherapy only at
the same dose (group 2). Karnofsky performance scores at baseline, 4 weeks,
and 12 weeks were 78, 93 (P < .05), and 88 for group I and were 78, 80, and
76 for group 2, respectively. Respiratory symptoms scores (a composite of
dyspnea, hemoptysis, cough, and sputum production) at baseline, 4 weeks,
and 12 weeks were 7, I (P < .05), and 2 (P < .05), respectively, for group I
and 7, 4 (P < .05), and 7, respectively, for group 2. Quality of life was
assessed by the functional living index for cancer, with 22 being the best
score and 154 the worst. Scores at baseline, 4 weeks, and 12 weeks for group
I were 56, 39 (P < .05), and 42, whereas scores for group 2 were 95, 70, and
80, respectively.
III. Changes in Pulmonary Function Testing
A. Laser Resection
Studies which evaluated changes in pulmonary function tests (PFTs) after
laser resection are listed in Table 8. Increases in most spirometric values
were noted in all studies, although some improvements in forced expiratory
volume in I sec (FEV1) and forced vital capacity (FVC) were less than
200 mL. In two studies, the magnitude of change was noted to be much
greater in patients with incomplete airway obstruction rather than complete
airway obstruction [7,8]. In another study, changes in PFTs, radionuclide
lung scans, and 6-min walk were significant for patients with malignant
airway obstruction of the mainstem bronchus but not for patients with
involvement of the bronchus intermedius or lobar bronchi [10]. Similar
observations were noted in two studies in which patients with tracheal
lesions had greater changes in PFTs than patients with bronchial lesions
[48,50].
B. Stent Insertion
Studies that reported changes in PFTs after stenting alone are noted in
Table 9, whereas insertion after laser
Table 7 Performance Status and Symptoms After Photodynamic Therapy for
Malignant Obstruction
No. of Findings (mean scores
Study (reference) patients Measurement unless specified)
McCaughan 18 Karnofsky score Improved 48 to 61
et aL [39]
Dyspnea Improved in 7/16 patients
Supplemental O
2
Decreased in 5/13 patients
req uirements
McCaughan 31 Karnofsky score Improved 57 to 65
et aL [40]
Dyspnea Improved in 15(28
patients
Supplemental O
2
Decreased in 9(19 patients
requirements
McCaughan [41] 13 Karnofsky score Improved 54 to 73
Dyspnea Improved in 9/12 patients
Moghissi et aL 100 WHOPS Pre-tx PS 2 in 47
[42] patients
Post-tx PS 2 in 87
patients
Moghissi et aL 17, PDT after WHOPS Improved 2.2 to 0.7
[43] laser resection
WHO PS, World Health Organization performance status.
resection or balloon dilatation are noted in Table 10. These tables are not
meant to include all case series and case reports in the literature. We have
arbitrarily chosen to incorporate publications which included at least five
patients. As can be seen, most studies consist of a fairly small number of
patients. Almost all studies noted some improvement in PFTs, although
changes in FEV] and FVC were less than 200 mL in some studies. Changes
in oxygenation were inconsistent among the studies.
C. Endobronchial Brachytherapy
Changes in pulmonary function and ventilation and perfusion following
HDR brachytherapy in 19 patients were evaluated by Goldman and
coworkers [70]. PFTs performed 6 weeks after a single fraction of 15 Gy
demonstrated mean increases in FEV
1
from 1.45 to 1.61 L (55.5-62.3% of
Table 8 Changes in Pulmonary Function After Laser Resection for Airway Stenoses
Study
(reference)
Gelb and Ebstein [7]
Gelb and Ebstein [8]
()
.g
~
~ e l et al [45]
CD
0..
~
.....
~ e l et al [46]
91
George et al [10]
Kvale et al [47]
No. of patients
27, Incomplete obstruction of trachea/main bronchus
19, Complete obstruction of main bronchus
70, Incomplete obstruction of trachea/main bronchus
23, Complete obstruction of main bronchus
10. Main bronchus
13, Trachea
28, Main bronchus/LB
6, Benign tracheal
6, Malignant-no prior tx
Measurement
FEV\
FVC
FEV\
FVC
FEV\
FVC
FEV\
FVC
FEV\
FVC
VmaxSO_E
Vmaxso_1
FEV\
FVC
VmaxSO_E
Vmaxso_1
FEV\
FVC
Ventilation
d
Perfusion
d
6min walk
FEV\
FVC
FEV\
Findings (mean values)
52-74% of predicted
a
64-77% of predicted
a
44---48% of predicted
C
46-59% of predicted
a
45-60% of predicted
b
57-69% of predicted
b
47-52% of predicted
C
50-55% of predicted
C
45-72% of predicted
51-84% of predicted
31-75% of predicted
57-85% of predicted
46-72% of predicted
77-82% of predicted
25-56% of predicted
44-64% of predicted
Increased by 220 I11Lb
Increased by 390 mLb
Increased 24-36%b
Increased 25-31 %b
443-512m
b
Increased 358 mL
Increased 183 mL
Increased 428 mL
S;
~
'" 1:;
<:>
;:;
(()
::::
!2..
~
~
t"-<
S;
'"
l::l
~
~
:;:::
~
<::>
;:;
l::l
~
~
;:;
~
(3'
;:;
0\
~
Table 8 Continued
Study
(reference)
()
o
Waller et al. [48]

Mohsenifar et al. [49]
0..
CD
: Gilmartin et al. [50]
No. of patients
9, Malignant-prior tx
142, Trachea/main bronchus/LB
II, Trachea/main bronchus
17, Trachea/main bronchus
Measurement
FYC
FEY
1
FYC
FEY
l
FVC
FEY
1
FVC
VmaxSO_E
YmaxSO_I
FEY
l
PEFR
Perfusion
d
Findings (mean values)
Increased 610 mL
Increased 181 mL
Increased II 5mL
Increased 300 mL
Increased I 10 mL
35-69% of predicted
55-83% of predicted
0.87-1.6 L/sec
1.8-2.6 L/sec
Increased 360 mLa
Increased 0.65 L/sec
a
Increased 10-13%c
0\
N
-l>..
LB, lobar bronchus; tx, treatment; FEYI, forced expiratory volume in I sec; FYC, forced vital capacity; YmaxSO_E. mean maximal expiratory flow at
50% of forced expiratory volume; Ymaxso_1> mean maximal inspiratory flow at 50% of forced inspiratory volume; PEFR, peak expiratory flow rate.
ap < .05.
bp < .01.
cp = not significant.
dQuantitative scintigraphic data of involved areas.
;::
N
i::l
;::
i::l..
V)
::::.:
:3.
Table 9 Changes in Pulmonary Function After Stent Placement for Airway
Obstruction
625
Study No. and type of Findings
(reference); stent patients Measurement (mean values)
Wilson et al. [13], 33-M FEY! Increased 250 mL'
Gianturco FYC Increased 190 mLb
Pa02 Increased 10.8mmHg
b
Yergnon et al. [51], 4-M, I-BS; main FEY! Increased 310mL
b
Endoxane bronchus FYC Increased 500 mLC
Raw Decreased 0.36 kPa/L/sec
c
6-M,2-TS, I-TM; FEY! Increased 520 mL"
intrathoracic FYC Increased 3[0 mL
c
trachea Raw Decreased 0.35 kPa/L/sec
c
6-TS,4-TM; FEY! Increased 430 mL'
extrathoracic FYC Decreased 30 mU
trachea Raw Decreased 0.53 kPa/L/sec"
Gelb et al. [52], Silicone/ 3-M, 2-TS, I\-BS, 1- FEY!
49-72% of predicted
b
Gianturco BM FYC 64-73% of predicted
b
YmaxSO_E
38-72% of predicted'
Hautman et al. [53],
41-M, 3-BS, 7-BM FEY!
Increased 420 mLb
Streckerl
PEFR Increased 1.2 L/sec"
Accuflex/Walistent
Raw Decreased 0.15 kPa/L/sec"
Pa02
Decreased 0.3 mmH{
Rousseau et al. [54], 6-BS FEY!
Increased 440 mL
Walistent/
10-TM FEY!
Increased 6 mL
Gianturco
Jack et al. [55],
27-M,3-TS FEY!
41-51 % of predicted
b
Gianturco
FYC 61-66% of predicted
C
Pa02
Increased \5.[ mmHg"
Tsang and Goldstraw
6-BS FEY!
Increased 750 mL
[56], Walistent
FYC Increased 733 mL
4-M FEY!
Increased 625 mL
FYC Decreased 150 mL
Dasgupta et al. [57],
9-TM & BM
FEY!
Increased by 45%
Walistent
FYC Increased by 35%
Higgins et al. [58],
10-TS & BS
FEY!
Increased 865 mL
Gianturco/Silicone
Increased 200 mLb
Hauck et al. [59],
14-M
FEY!
Accuflex/Strecker
FYC Increased 400 mL"
PaOo
Increased 6 mmHg
b
Increased 37-61%b
Perfusion
d
Increased 27-46%a
Eisner et al. [60],
8-TS & BS
FEY
1
Increased 550 mL
Palmaz/Walistent
Tojo et al. [61],
5-M
FEY!
Increased 702 mL
Gianturco/Endoxane
FYC Increased 514mL
Yergnon et al. [62],
9-TS
FEY!
Increa ed 634 mL
a
Silicone
Table 9 Continued
Study
(reference); stent
Abdullah et aL [63],
Endoxane
Wasserman et aL [64],
Endoxane/Rusch-Y
Kshettry et aL [65],
Palmaz/Gianturco/
Wallstent
No. and type of
patients
5-M, 2-TS, I-BS
5-M
5-BM,3-BS
Measurement
FEV!
FVC
FEV!
FVC
Raw
FEV!
FVC
Findings
(mean values)
Increased by 75%
Increased by 54%
Increased 1142 mL
Increased 292 mL
Decreased 0.47 kPa/L/sec
Increased 530 mLb
Increased 340 mLC
M, malignant; BS, bronchial stenosis; TS, tracheal stenosis; BM, bronchomalacia; TM,
tracheomalacia; FEV!> forced expiratory volume in I sec; FVC, forced vital capacity; Raw,
airway resistance; VmaxSO.E, mean maximal expiratory flow at 50% of forced expiratory
volume; PEFR, peak expiratory flow rate.
a
p
< .01.
b
p
< .05.
l = not significant.
Quantitative scintigraphic data of involved areas.
predicted) and FVC from 2.17 to 2.48 L (63.9-74.0% of predicted) (P < .05
for both). There was no significant change in total lung capacity, residual
volume, airway resistance, or diffusion capacity. Radionuclide lung scans 6
weeks after treatment showed improvement in ventilation of the abnormal
lung from 17.0 to 27.7% and in perfusion from 15.1 to 21.9% (P < .005). The
mean 5-min walking distance increased froni 305 to 329 m (P < .0 I). Patients
with occlusion of a mainstem bronchus had greater improvement than
patients with lobar bronchus occlusion. Dyspnea improved in 89% of
patients, cough in 37%, and hemoptysis in 100% (n = 6). Atelectasis of a
lobe or lung improved on follow-up radiographs in 9 of 13 patients (69%).
D. Endobronchial Brachytherapy in Conjunction with Laser
Resection
In the previously mentioned study by Mehta and associates, 52 patients were
treated with LDR brachytherapy, 12 of whom also underwent Nd-YAG
laser resection prior to catheter placement [29]. PFTs were available for 14
patients. The mean FEY
t
increased from 1.5 to 2.1 L and the mean FYC
increased from 2.3 to 2.9 L. Improvements in PFTs were also reported in the
previously noted study by Ornadel and coworkers [32]. Of the 117 patients
treated with HDR brachytherapy, the mean FEV
t
improved from 1.30 to
Copynghted Material
627
Table 10
Changes in Pulmonary Function After Stent Placement in Conjunction
with Laser Resection (LR) or Balloon Dilatation (BD) for Airway Obstruction
No. and type Findings
Study (reference); stent
of patients Measurement (mean values)
Miyazawa et al. [17], 16-M; LR and FEV
I
]ncreased 340 mL"
Ultraftex BD
FVC Increased 490 mL"
Miyazawa and Arita 10-M; LR and FEV
I
Increased 380 mL"
[18], Endoxane BD
FYC Increased 450 mLb
Pa02 Increased 15.0mmHg"
Hauck et al. [66], 10-M; LR and FEY
j
Increased 200 mLb
AccuftexjStrecker BD
YCIN
Increased 200 mLb
YmaxSO_E Increased 0.2 Ljsec
C
Raw Decreased 0.1 kPajLjsec
C
Pa02 Increased 6 mmHg
C
Remacle et al. [67], 18-M; LR PEFR Increased 1.02 Ljsec
Gianturco
PIFR Increased 0.92 Ljsec
Hsu et al. [68], 6-BS and TS; FEY
1
48%-60% of predicted
C
Endoxane
LR and BD FYC 55%-64% of predicted
b
Susanto et al. [69], 6-BS and BM; FEY
1
Increased 548 mL
Palmaz BD
M. malignant; BS, bronchial stenosis; TS, tracheal stenosis; BM, bronchomalacia; FEV
1
, forced
expiratory volume in I sec; FVC, forced vital capacity; VCIN, inspiratory vital capacity;
VmaxSO.E, mean maximal expiratory flow at 50% of forced expiratory volume; Raw, airway
resistance; PEFR, peak expiratory flow rate; P1FR, peak inspiratory flow rate.
"p<.OI.
bp < .05.
c
p
= not significant.
1.38 L (P = .0504) and the mean FVC improved from 1.92 to 2.06 L
(P = .041).
Macha and colleagues evaluated 56 patients with malignant obstruc-
tion of the trachea or mainstem bronchus following treatment with three
fractions of 7.5 Gy HDR brachytherapy [71]. Twenty-nine patients with
mainstem bronchial occlusion underwent Nd-YAG laser resection prior to
catheter placement. PFTs, available for 20 patients, although it was not
specified how many of demonstrated increases
in mean values of FEYI from 1.62 to 2.13 L, FYC from 2.61 to 3.31 L, peak
expiratory flow rate (PEFR) from 3.91 to 5.16Ljsec, and Pao2 from 67.7 to
74.1 mmHg (P < .001 for all). The severity of dyspnea was reduced in 44
patients (79%). In the 25 patients with atelectasis, radiographic evidence of
reaeration was noted in 22 (88%).
Recently, Chella and associates published the results of a randomized
trial comparing Nd-YAG laser resection only versus laser resection plus
HDR brachytherapy in patients with non-small cell lung cancer [72]. Fifteen
patients were randomized Nd-YAG laser treatment alone (group I),
whereas 14 patients were randomized to Nd-YAG laser resection followed
by 3 weekly fractions of 5 Gy beginning 15-18 days after laser debulking
(group 2). The FEYI improved from 1.35 to 2.16 L (52.4% of predicted), the
FYC improved from 2.08 to 3.34 L (60.9-74.2% of predicted), and Pao2
improved from 63.7 to 74.6mmHg in group 1. In group 2, FEY] increased
from 1.43 to 2.32 L (53.2-65.4% predicted), FYC increased from 2.11 to
3.47 L (62.8-77.0% of predicted), and Pao2 increased from 65.4 to
75.6 mmHg. The symptom-free period was 2.8 months in group I and 8.5
months in group 2 (P < .05). Fifteen further endoscopic interventions were
required in group I versus 3 in group 2 (P < .05). Overall median survival
was 7.4 months and 10.3 months in group 1 and group 2, respectively
(P=ns).
E. Electrocautery Resection
Sutedja and coworkers treated 17 patients with malignant airway obstruc-
tion with electrocautery resection via flexible bronchoscopy [73]. PFTs were
obtained in eight patients, with two patients having greater than a 15%
improvement from baseline values. Blood gases significantly improved in 2
of 12 patients. Dyspnea was improved in 8 of 11 patients (73%) and
hemoptysis in all 4 patients.
Fifteen patients with recurrent central airway obstruction from
bronchogenic carcinoma after previous external beam radiotherapy were
treated with electrocautery resection (diathermy) and radioactive gold grain
implantation under rigid bronchoscopy by Ledingham and Goldstraw [74].
All of the II patients who were alive I month after intervention had
improved symptomatically. FEYI improved in all 11 patients from 30 to
120% (mean 69%). Reexpansion after total lung collapse was noted in two of
two patients and after lobar collapse in three of six patients.
Petrou and colleagues treated 29 patients with central airway
obstruction with electrocautery resection in combination with stent
placement in nine patients and radioactive gold grain insertion in one
patient via rigid bronclf38rJ!!Jf'gMJb patients had malignant
tumors, 3 had benign neoplasms, I had amyloidosis, and I had a
postintubation stricture. All 9 patients requiring urgent treatment and 19
of the 20 patients treated electively reported symptomatic improvement.
PFTs were available in eight patients with a mean improvement in FEY, of
53.1 % (range 8-142%) and in FYC of 20.6% (range 0-100%).
F. Cryotherapy
In the previously mentioned study by Maiwand evaluating cryotherapy for
treatment of malignant tracheobronchial obstruction in 153 patients, PFTs
demonstrated an increase in FEY, by 65% (1.34--1.45 L) (P= .001) and FYC
by 58% (1.93-2.02 L) (P= .035) [35]. Two other studies by Maiwand and
associates have reported changes in pulmonary function after cryotherapy
via rigid bronchoscopy. In one study, 21 patients were treated for tracheal
or bronchial obstruction from granulation tissue after lung or heart-lung
transplantation [76]. PFTs were obtained in 20 patients. FEY, improved by
34% (mean change 285 mL) and FYC by 28% (mean change 372 mL)
(P< .001 for both). In the second study, 33 patients underwent cryotherapy
for malignant tracheobronchial stenoses [77]. Seven of 29 patients (24%) had
an increase in FEY, and FYC, although specifics were not provided. Six-
minute walking distance increased in 6 of 22 patients (27%). The Medical
Research Council (MRC) dyspnea score improved in 10 of 27 patients
(37%), whereas hemoptysis improved in 6 of 9 patients (67%). Radiographic
improvement of atelectasis was improved in 7 of 29 patients (24%).
G. Photodynamic Therapy
In a study by Moghissi and' coworkers treating 100 patients with airway
obstruction from bronchogenic carcinoma, PFTs were also obtained in
addition to performance status following PDT [42]. Six to 8 weeks after
treatment, the mean FEY, increased from 1.38 to 1.66 L and mean FYC
increased from 2.07 to 2.50 L. Improvement in pulmonary function was also
reported in another study by Moghissi and colleagues [43]. In that study, 17
patients with malignant airway obstruction were treated with Nd-YAG laser
resection followed by PDT 4--6 weeks later. Sixteen of 17 patients had
increases in spirometric values. FEY1 improved by a mean of 327 mL (range
0-890 mL) and FYC improved by a mean of 470 mL (range 0-1020 mL).
Lam and associates noted changes in pulmonary function in their
previously reviewed trial of six patients randomized to PDT plus external
beam radiotherapy (group 1) versus five patients randomized to external
beam irradiation alone (group 2) [44]. FEYI, expressed at percent predicted,
at baseline, 4 weeks, and 12 weeks was 60, 77, and 75 for group 1 and 65, 77,
and 61 for group 2, predicted FYC were 66,
630
Jantz and Silvestri
79, and 78 for group 1 and 76, 92, and 80 for group 2, respectively.
Radionuclide scans were also performed in the study. Perfusion to the
affected area was 26, 35, and 30 for group 1 at baseline, 4 weeks, and 12
weeks, respectively, and 26, 36, and 32% for group 2, respectively. Changes
in ventilation paralleled those for ventilation. Improvements in spirometry
and ventilation-perfusion did not achieve statistical significance.
Changes in PFTs among 7 of 10 patients with endobronchial
obstruction from advanced lung cancer following PDT were also reported
by LoCicero and coworkers [78]. Dyspnea and cough were reported as being
decreased in most patients afterward. One week after PDT, PFTs were
obtained with some improvement observed for FEV, in four patients, FVC
in two patients, and PEFR in five patients. Overall, however, mean FEV1
increased by 69 mL, FVC by 195 mL, and PEFR by 0.11 L/sec.
H. Balloon Dilatation
Balloon dilatation has been used to treat both benign and malignant
stenoses. Most descriptions in the literature consist of case reports and small
case series. In the larger case series to date, improvements in respiratory
status have been noted in 13 of 14 adult patients with benign
tracheobronchial stenoses [79], 9 of 13 adult patients with benign bronchial
stenosis [80], and 20 of 37 pediatric patients with benign tracheal stenoses
[81]. Changes in PFTs were not reported in these studies. Hautman and
colleagues have recently described PFTs before and after balloon dilation
via flexible bronchoscopy in their series of 78 patients with malignant
tracheal and bronchial stenoses, predominantly from bronchogenic carci-
noma [82]. Of the 126 stenoses, 69 (54.7%) were due to extrinsic
compression, 46 (36.5%) were due to extrinsic compression with an
exophytic component, 6 (4.8%) were mainly exophytic, and 5 (4.0%) were
fibrous stenoses. Subtotal or high-grade obstruction was present in 109
(86.5%) of the stenoses. Balloon dilatation alone was performed in 29
patients, whereas balloon dilatation was used to prepare a lesion for stent
placement in 16 patients, to facilitate brachytherapy catheter placement in
13 patients, and to dilate an already implanted stent in 20 patients. Seventy-
nine percent of all stenoses improved in diameter. In the patients who
underwent balloon dilatation alone, improvement was noted immediately in
71 and in 43% at a mean follow-up time of 112 91 days. PFTs were
obtained 72 hr before and after balloon dilatation in 42 patients. The mean
FEV
l
increased from 1.79 to 1.83L (P=.028) and mean PEFR increased
from 4.63 to 4.92 Lisee (P = .047). There was no change in mean airway
resistance. Dyspnea improved in only 12 of 32 patients, however, in keeping
with the small changes in PFT. Atelectasis did resolve in five of eight cases,
631
postobstructive pneumonia in II of 12 cases, and lung abscesses .111 both
cases.
IV. Bronchoscopic Interventional Procedures Versus
Conventional Therapies
To our knowledge, excluding the previously mentioned trial by Stout and
coworkers comparing brachytherapy to external beam radiation, only one
other randomized trial has been performed comparing airway interventional
procedures to conventional therapy. The Medical Research Council Lung
Cancer Working Party randomized 75 patients with airway obstruction
from non-small cell lung cancer to treatment with external beam
radiotherapy or treatment with brachytherapy, laser resection, or cryother-
apy [83]. The study was originally intended to enroll 400 patients, but the
study was terminated secondary to failure to accrue patients. Sixteen of the
patients did not undergo the treatment to which they were randomized.
Based on intention-to-treat analysis, evaluation at 4 months demonstrated
similar improvements in dyspnea (32% for radiation therapy vs 28% for
endoluminal intervention) and palliation of major thoracic symptoms (27 vs
22%). Improvement in WHO performance status was greater in the
endoluminal intervention group (38%) compared with the external beam
radiotherapy group (14%). Median survival was 182 days for the radiation
therapy patients and 150 days for the interventional patients.
V. Conclusion
Very few studies exist which have evaluated the impact of interventional
procedures using true quality of life measurement tools. Based on changes in
performance status scores as a surrogate for quality of life, most of the
reviewed interventional modalities do appear to have some benefit. Most,
but not all, studies demonstrated changes in performance status. In some.
studies, however, improvements were noted in only approximately 40-60%
of patients. Most reports did show overall improvements in dyspnea as well
as other symptoms such as cough and hemoptysis. Analyses of changes in
pulmonary function testing demonstrate mixed results. Some studies showed
substantial improvement, whereas others demonstrated minimal or no
change. In some studies that had statistically significant improvements, the
absolute changes were arguably small and of questionable clinical
significance. Subsets of patients in these reports, however, had very large
changes in pulmonary funtlapyrighted Material
632
Jantz and Silvestri
Although there are little data demonstrating that these interventions
may prolong life, our experience and that of others suggests that this is the
case for some patients. More importantly is the ability to change the quality
of life and palliate symptoms in patients with airway obstruction,
particularly those with malignant airway stenoses who will not have
survival benefit from these procedures. Based on the available data, it can be
argued that endobronchial interventional procedures do improve functional
status and symptomatology in most, but not all, patients. Given the current
literature, however, additional studies evaluating patients with true quality
of life instruments should be performed to strengthen the evidence that these
modalities are indeed of benefit. Although significant logistical problems
would be present, trials to evaluate the benefits of airway interventional
procedures compared to conventional modalities should be considered. At
this time, we believe that it is worthwhile to perform these procedures in
patients who are not candidates for curative procedures. The difficulty arises
in being able to predict ahead of time who will benefit from the intervention.
Additional research in this area would also be welcome.
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30
Training in Interventional Pulmonology
MICHAEL J. SIMOFF and PAUL A. KVALE
Henry Ford Health System
Detroit, Michigan, U.S.A.
I. Introduction
Interventional pulmonology is a growing field within the broader discipline
of pulmonology. The use of lasers through a bronchoscope began in the
early 1980s; since then the role of interventional pulmonology has continued
to expand. As new techniques and more advanced procedures are
developed, it becomes important to consider what constitutes optimal, or
even acceptable, training of those individuals who wish to practice
interventional pulmonology in the future.
The term interllentional pulmol1ology requires definition. A joint task
for of the American Thoracic Society (ATS) and the European Respiratory
Society (ERS) was convened to develop a position paper to define
interventional pulmonology and propose' standards for training. They
stated that interventional pulmonology is "the art and science of medicine as
related to the performance of diagnostic and invasive therapeutic
procedures that require additional training and expertise beyond that
required in a standard pulmonary medicine training program" [I]. Thus,
interventional pulmonolog't-..would ,1ypicaUvtinclude all the techniques listed
vopyng"rea Mai enal
639
640
Simaff and Kvale
in Table I; currently, only a small number of pulmonary fellowship T1
programs provide training in these techniques.
Several questions arise as we look at training: (l) What constitutes the
optimal training format for interventional pulmonology? (2) Is there a role
for all pulmonologists to be trained in interventional techniques, or should
only a few centers that see a significant caseload be responsible for providing
these services? (3) How do we integrate new techniques and technologies
into the current practice of interventional pulmonology?
Training in flexible bronchoscopy, a basic skill for the interventional
pulmonologist, was initially addressed in 1976 by the American College of
Chest Physicians (ACCP) [2]. Only nonspecific standards for training in
endoscopy were delineated. For example, the number of procedures
required for proficiency is described as " ... adequate to ensure competence
to the satisfaction of the preceptor." In 1982, the Section of Bronchoscopy
of the ACCP established both cognitive and clinical objectives for training
in flexible bronchoscopy. Although more comprehensive, this document
continues to lack specifics for training programs to outline more exact
requirements [3].
Table 1 Techniques That Are Considered Part of Interventional Pulmonology
Generally accepted as interventional pulmonology procedures:
I. Rigid bronchoscopy
2. Laser bronchoscopy
3. Endobronchial brachytherapy
4. Cryotherapy
5. Photodynamic therapy
6. Endobronchial electrosurgery
7. Argon plasma coagulation
8. Stenting (Silastic, metallic, hybrid)
9. Balloon tracheobronchoplasty and airway dilatation
10. Pieuroscopy (medical thoracoscopy)
II. Percutaneous tracheostomy
Considered to be additional interventional pulmonology procedures:
I. Transbronchial needle aspiration biopsy
2. Transthoracic needle aspiration biopsy
3. Endobronchial ultrasound
4. Autoftuorescence bronchoscopy
5. Transtracheal oxygen catheter insertion
6. Bilateral whole lung lavage for the management of pulmonary alveolar
lipoproteinosis
Training in Interventional Pulrnonology 641
As certification requirements become more comprehensive, the
American Board of Internal Medicine has attempted to formalize the
evaluation, documentation, and certification of pulmonary physicians who
perform fiberoptic bronchoscopy [4]. In addition to this statement, several
other documents address the topic of training and competency in flexible
bronchoscopy earnestly but broadly [5-9]. No group or consensus has come
to the forefront and made recommendations that are uniformly used.
One of us (P.A.K.) published recommendations for credentialing in
laser bronchoscopy based upon survey results after formal training of over
150 physicians at 3-day courses and again after 1-2 years' experience using
laser by those physicians who had completed the training course [10]. A
more complete set of recommendations for minimum training standards for
most interventional pulmonology procedures was included in the proposals
by the ATS/ERS task force [I]. The Jnterventional Chest/Diagnostic
Procedures NetWork of the ACCP has also developed a consensus
statement that attempts to outline both the initial training requirements
and the requirements recommended to maintain competency in all of the
procedures characterized as interventional pulmonology procedures [II].
Although this statement specifies minimum numbers for training in each
procedure, neither it nor the ATS/ERS statement provides a method to test
a specific skill through a formalized assessment method.
Despite these newly avaliable recommendations, formal guidelines to
train individuals in flexible bronchoscopy, rigid bronchoscopy, and the other
numerous procedures in the still evolving field of interventional pulmonol-
ogy are limited. The continued development of new techniques and
technologies creates even greater difficulties in defining precise standards
for training in a dynamic field such as interventional pulmonology. Without
current standardization, the goals set forth in this chapter are intended to
establish a framework for the training of interventional pulmonologists. No
attempt will be made to establish specific training requirements for each
technique and procedure as was suggested in the ATS/ERS or ACCP
statements [I,ll]. Instead, this set of recommendations may serve for the
development of training requirements for a consensus statement by
professional organizations at some future date. Regular reviews and updates
of any such guidelines will be needed in order to adjust for new
interventional pulmonology techniques continually being developed.
Training in interventional pulmonology should include the teaching
and development of cognitive, technical, and clinical skills as part of a
formal curriculum. Training for any procedure is more involved than simply
performing a certain number of the procedures in question. Competency
implies not only the ability to perform a procedure, but also states that the
person performing the N'Ja1eMwwledge to choose patients
642 Simaff and Kvale
properly, to be efficient, and to have acceptable results. It is therefore a
global competency, as a clinician in interventional pulmonology that must
be developed in the trainee, not merely experience in the technical aspects of
the procedure.
II. Trainees
A sound foundation in clinical pulmonology and bronchoscopy are needed
before training begins for interventional pulmonology. To be a good
interventional pulmonologist, one must first be a good pulmonologist. It is
recommended that trainees have completed a minimum of 18 months of
clinical work in pulmonary and/or pulmonary and critical care medicine.
The interventional trainee must possess skills that are above average with a
flexible bronchoscope and other procedures. Typically, the minimum
number of diagnostic procedures that are recommended in the preceding
citations are not sufficient before a trainee begins to work in the field of
interventional pulmonology. We prefer that interventional pulmonology
trainees have a minimum of 100 diagnostic bronchoscopies before they
begin to train in interventional pulmonology. The continuing practice of
interventional pulmonology, especially given the urgent nature of the
problems that a typical patient has when these services are needed, requires
a dedication to this specific discipline in order for the practitioner of
interventional pulmonology to be effective. We screen our applicants for
training with these thoughts in mind.
The opportunities for subspecialization within the broader field of
pulmonary medicine includes sleep medicine, environmental medicine, and
others at various training programs. Owing to this broadening of training
opportunities, prospective trainees should identify their future goals and
plans to ensure the training provided them will be practical for their future
practice.
At our institution, we are now more inclined toward a dedicated
fourth year of training in interventional pulmonology after the completion
of a 3-year pulmonary or pulmonary and critical care medicine fellowship.
As the complexity of the work being performed expands with the advent of
new technology and techniques, the time demand and energy required to
master this broadening field would require much more training.
III. Cognitive Skills
Much of the time spent in interventional pulmonology training programs is
spent teaching the technical skills. We believe that cognitive skills must be
Training in Interllentional Pulmonology
643
developed for an interventional pulmonologist to realize the full potential of
these services. Many of the current practitioners and teachers are pioneers in
this area, having developed the techniques that are now available. An
understanding of core information regarding the multiple techniques used
has allowed current interventional pulmonologists to expand the field as
they have. By possessing a sound foundation of cognitive skills, practicing
interventional pulmonologists will be able to use their skills creatively to
treat patients in a multimodal manner, and just as importantly new
techniques and applications will be developed. This has certainly been the
case during the past two decades since interventional pulmonology first
emerged.
The learning and teaching of cognitive skills can be augmented by
careful selection of texts and establishing a core curriculum. Videotapes,
slide sets, and computer CDs can add to clinical teaching. Didactic
presentations of a variety of topics in interventional pulmonology, whether
at local, regional, or national meetings, are needed for the new student as
well as current practitioners. Participation at regional courses in interven-
tional pulmonology can also benefit the students by further expanding their
knowledge of procedures already used as well as learning new techniques. It
is the responsibility of those training students to establish a curriculum that
incorporates many of the topics discussed here to educate fully the new
interventional pulmonologist.
Cognitive skills begin with a review of the physical and physiological
principles of airway resistance and flow, ventilation-perfusion relationships,
reexpansion physiology of lungs that have become atelectatic or frankly
destroyed by disease processes, cancer biology and growth, tissue response
to ionizing radiation, laser and electrical physics and tissue interaction, and
tissue healing. The responsibility to develop a precise set of educational
objectives with these and other topics rests with the directors of training
programs in interventional pulmonology. Ideally, the directors of such
programs can develop a standardized approach and educational tools to
improve overall training. Didactic sessions need to be provided to create an
environment that promotes further development of trainees' cognitive skills.
Postgraduate courses, if they are offered, must augment any and all training
with an equal portion of didactic time to the theoretical basis of treatment as
well as the practical aspects of the techniques to be taught.
A core curriculum should be developed and provided to trainees. An
interventional pulmonology core curriculum should include detailed
instruction of airway, vascular, and lymphatic anatomy. Interpretation of
imaging techniques available for the assessment of airway-related disease
must be stressed: computed tomography (including three-dimensional
reconstruction, positron emission
644
Simaff aYJd Kvale
tomography, magnetic resonance imaging, perfusion scanning, and any
other advanced techniques the individual institutions might offer. The
interventional pulmonologist must learn not only standard anatomy but
also the specific anatomy of pulmonary lymphatics for instance. Under-
standing the lymphatic drainage patterns of all lobes of the lung allows the
bronchoscopist to know where to look for potential disease extension [12].
Much of the work that interventional pulmonologists do involves
patients with lung cancer. It is important that trainees have extensive
knowledge in all aspects of diagnosis, staging, and managing lung cancer.
Participation at institutional tumor boards is a good way to augment that
experience and training and is highly recommended. The potential for cure
of selected unusual airway cancers such as mucoepidermoid carcinoma and
carcinoid must be placed alongside the possibility that localized airway
treatment via interventional pulmonology techniques may leave residual
disease and treatment failure.
The practice of interventional pulmonology also includes managing a
variety of unique diseases. Education about tracheal stenosis is very
important, including the known pathophysiological mechanisms that lead to
stenosis of the trachea. The surgical options (otolaryngological and
thoracic) that are also available to patients with this condition must be
emphasized so that interventional pulmonology techniques are not
inappropriately applied when surgery is a better option. Interventional
pulmonologists must also become familiar with less common conditions
such as endobronchial pappillomatosis, tracheobronchomalacia, polychon-
dritis, and pulmonary alveolar proteinosis. The practice of interventional
pulmonology requires that the practitioners must be able to perform the
appropriate procedure, but they must also become experts in the disease
processes that they manage.
A. Ablative Techniques (Lasers/Electrocautery/Argon
Plasma Coagulation) and Tissue Interaction
It is important to have a complete understanding of laser physics and tissue
interaction in order to avoid unintended injuries to normal structures and
achieve the desired result in the tissues to be treated. Likewise, a principle of
the safe use of lasers to avoid injury to one's self or to other members of the
laser team must be taught. Most institutions have laser safety classes and
laser safety officers who handle many of these issues. The American
National Standards Institute (ANSI) has al 0 created a reference (ZI36.1)
for the safe Lise of lasers [13J.
The differing properties of a variety of lasers (KTP, Nd:YAG, CO
2
,
argon dye), and the different aspects of tissue interaction that they cause,
Training in lnterventional Pulmonology
645
should be taught. Understanding the differences in tissue interaction by
contact and noncontact laser techniques and the different power outputs
required between the two methods of treatment will help the trainee to avoid
complications and obtain the desired results.
Electrosurgery and argon plasma coagulation have safety issues and a
different set of interactions of electrical current and tissue response to
electrical injury. The training program needs to assure that knowledge of the
basic physical principles of these sources of energy be available to its
trainees. An understanding of the flow characteristics and other properties
of argon gas can change the effectiveness of this tool and maximize its
clinical capabilities. Similarly, an understanding of the mechanisms of
cellular damage by freezing as well as the pathology of various tissue
responses to freezing will allow for an improved clinical use of cryotherapy.
Ablative techniques are one of the cornerstones of interventional
pulmonology. As such, some understanding of the "aftermath" of these
interventions needs to be further understood. Wound healing is a topic that
is taught in all surgical training programs, and it must be taught as part of
learning interventional pulmonology procedures. Stimulation of the
subepithelial fibroblasts occurs with any ablative technique and probably
with all of the stents the problems that a typical that are currently in use.
The effects of this stimulation may effect the management and follow-up of
many patients.
B. Photodynamic Therapy
The mechanism of tissue destruction with photodynamic therapy is an
important aspect of using this modality effectively. Using photodynamic
therapy requires complete knowledge of the phamacokinetics and pharma-
codynamics of the photosensitizing drug being used. The fundamentals of
dosing and dosimetry calculations must also be taught to clinicians to
perform this procedure efficiently and safely for their patients. With
complete understanding of the variety of ablative procedures at the disposal
of the intervention pulmonologist, the entire armament of tools becomes
more productive.
C. Endobronchial Brachytherapy
Brachytherapy is a technique that allows the delivery of ionizing radiation to
the tissues that are close to the source of the radioisotope that is used in
treating selected malignancies. Brachytherapy is usually performed for
recurrent airway cancers, although it can be used as the initial treatment in
highly selected patients. The interventional pulmonology trainee must be
taught how to use this how to properly select
patients who are likely to benefit from brachytherapy. A collaborative
relationship with a radiation oncologist is needed for the proper use of
endobronchial brachytherapy. Nevertheless, the interventional pulmonolo-
gist must be taught the basics of radiation dispersion fields, therapeutic
planning, and the function of modern afterloaders to optimize this method
of treating patients.
D. Stents and Tissue Responses to Stents
Using stents effectively in a clinical setting requires knowledge not only of
how to put them in but also of the mechanical properties of different kinds
of stents. This should include understanding the mechanical properties, the
stress-strain relationships, and applicability of all stents. Having this
knowledge allows the interventional pulmonologist to use the correct stent
for different clinical applications. The trainee should be taught about the
process of endothelialization (which occurs with some stents), the effects on
fibroblast stimulation, and the pathophysiological changes the stent will
have on the airway. This knowledge will assist the trainee for improved
long-term management of patients who have stents placed in their airways.
E. Medical Thoracoscopy
As the practice of medical thoracoscopy expands within the field of
interventional pulmonology, a new set of cognitive skills is required. A
comprehensive review of pleural anatomy and physiology is imperative to
develop a complete skill set in this procedure. Expertise in the full scope of
pleural procedures should be expected prior to advancing to this procedure,
including thoracentesis, closed pleural biopsy, chest tube placement and
management, and pleurodesis. Only with a solid understanding of the
techniques, indications, and limitations of these procedures will a fuller
comprehension of the utility and advantages of medical thoracoscopy
become evident, making the interventionalist much more effective in the
performance of these procedures.
F. Percutaneous Dilatational Tracheostomy
Percutaneous dilatational tracheostomy continues to grow in popularity in
medical intensive care units. It is appropriate for those physicians with a
significant understanding of tracheal anatomy to perform this procedure
after proper training. The trainee must learn about the management of
tracheostomies, including complications (both immediate and long-term),
daily management, a working knowledge of the variety of tracheostomy
Training in InterventionaL PulmonoLogy
647
tubes and their various advantages and disadvantages, as well as when and
how to design and order custom tubes.
G. Whole Lung Lavage
Single or bilateral whole lung lavage is not commonly considered an
interventional pulmonology procedure, but we feel that interventional
pulmonologists are best suited to perform this technique. Interventional
pulmonologists who wishes to add this technique to their practice must be
versed in regional lung physiology, insertion of double-lumen endotracheal/
endobronchial tubes, and how to check their position and isolation of each
lung from the other lung. The concepts of a complete team approach to
care, including anesthesiologists, nurses, and physical therapists who
understand and can completely participate in performing this procedure,
is crucial. This is true for most of the procedures that interventional
pulmonologists perform, but nowhere is it more crucial than when
performing whole lung lavage.
H. Endobronchial Ultrasound
The newest endobronchial imaging techniques are also often performed by
interventional pulmonologists. Performing endobronchial ultrasound
requires an excellent understanding of airway anatomy; the images and
anatomical relationships take on a different appearance from traditional
cross-sectional anatomy (computed tomography), and this requires that the
trainee learn new spatial relationships. What can be accomplished with this
imaging method must be balanced by an understanding of the limitations of
this imaging technique. Instruction of ultrasound technique and the
mechanics of the technique are important to its successful teaching.
I. Autofluorescence Bronchoscopy
In order to optimize autofluorescence technology, a solid understanding of
light physics is required. A complete understanding of this technology is
paramount to establish the necessary baseline skills and knowledge for the
future. Newer endobronchial imaging techniques such as spectroscopy or
optical coherence tomography (OCT) will emerge, and knowledge of the
various applications and limitations will lead to a more complete under-
standing of the technique
648 Simoff and Kvale
IV. Technical Skills
Hands-on teaching is required for the technical skills of interventional
pulmonology. One-on-one instruction is needed for trainees to gain
experience with the various instruments that are available (Fig. I). In FI
many regards, this is the most difficult area to define, because it is based on
clinical situations that arise during a training period, the dexterity and
competence of the trainee, and the demands the instructor places on those
they train (Fig. 2). F2
Everyone who has worked with a new trainee in bronchoscopy has
been impressed that some quickly pick up the technique. Many individuals
possess very good hand-eye coordination, excellent spatial relations, and
have an intrinsic understanding of the three-dimensional volume which they
are only partially visualizing. These individuals have intrinsic skills that may
make them more capable of learning advanced techniques. It is therefore
very important that individuals selected for interventional training be
chosen with these skills in mind. A trainee must have excellent basic skills
prior to being considered for further teaching. A strong foundation in
flexible bronchoscopy with transbronchial and endobronchial biopsies,
Figure 1 Training on a model is an important component of training in
interventional pulmonology.
Training in lntervenlional Pull11onology
649
Figure 2 The final aspect of all training includes working with patients. Here the
staff (M.S.) assists the interventional fellow in a case.
transbronchial needle aspiration, and bronchoalveolar lavage should be
required of anyone seeking advanced training in interventional pulmonol-
ogy. Many people may want to be trained, the burden of who, is often
placed upon instructors to train only those who are capable of learning.
Transbronchial needle aspiration biopsy (TBNA) is regarded as an
interventional technique by the ATS/ERS guidelines, but we feel that this
procedure should be part of all pulmonary training programs that include
instruction in diagnostic bronchoscopy. TBNA is an important and useful
technique in the diagnosis and staging of lung malignancies. In a survey
performed by the ACCP, pulmonologists regularly
650
Simaff and Kvale
used TBNA in their practice [14]. In another survey, only 10% of fellows
were being taught routine use of TBNA [15]. In a follow-up to the ACCP's
initial 1991 survey, the American Association for Bronchology reported the
number of pulmonologists routinely using TBNA increased to 28% [16].
Despite this improvement, efforts need to be used to correct this current
practice discrepancy to provide patients comprehensive diagnostic services.
A complete understanding of pulmonary anatomy and the nodal relation-
ship to the endobronchial position is required to perform this procedure
well. All bronchoscopists should perform TBNA; if it is not a skill that is
part of a bronchoscopist's current practice, it should be added and mastered
before beginning to learn any other interventional techniques. This
procedure should be a standard modality employed by all pulmonologists
in the evaluation and staging of lung cancer cases and otherwise where
clinically indicated.
Several publications contain suggestions that a certain number of
supervised flexible bronchoscopies be performed to ensure competence in
the procedure [4-6,8,9]. The Section on Bronchoscopy of the ACCP places a
minimum number of supervised procedures at 50 [3]. Dull's study suggests
that the proficiency of a bronchoscopist with 100 procedures is similar to a
bronchoscopist with more than 400 procedures, which he states suggests
that a minimum of 100 supervised procedures be performed by trainees who
desire certification [17]. While we have not collected data in as formal a
manner as Dull has collected his data, it is our perception that the learning
curve has not reached a plateau until approximately 100 flexible
bronchoscopies have been performed by our trainees. It is for this reason
that we believe a minimum of 100 diagnostic bronchoscopies, including
ample experience with TBNA, before a trainee can be considered for
additional training in interventional pulmonology procedures.
We recognize that a minimum number of procedures may not
adequately describe whether a trainee is ready to begin learning the
advanced techniques of interventional pulmonology. With the exception of
the few published criteria we have cited, there are no other specific methods
to establish a minimum number of flexible bronchoscopies for assuring
competency, let alone the vast array of interventional procedures now used.
Currently, trainees are judged to be competent or not by their instructors. It
is based upon this subjective assessment of skills that most new practitioners
obtain hospital privileges to perform the variety of procedures currently
used in interventional pulmonology. The combined ERS/ATS task force's
guidelines attempts to assign a minimal number of each procedure that must
be performed to be considered trained in each technique [I]. We also
recommend numbers of each procedure that must be performed yearly to
maintain competence (Table 2). The ACCP Interventional Chest/Diagnostic 12
Training in Interventional Pulmonology
Table 2 ERSjATS Recommendations for Training
651
Procedure
Rigid bronchoscopy
TBNA
Autofluorescence
Endobronchial ultrasound
Transthoracic needle aspiration
Laser
Electrosurgeryjargon
plasma coagulation
Cryotherapy
Stenting
Brachytherapy
Percutaneous tracheostomy
Transtracheal O
2
therapy
No. for initial
training
> 20
> 25 with 22-gauged needle
with> 10 (+), then
19 gauge
Proven expertise in
diagnostic bronchoscopy
40
> 10
>20
> 10
> 10
> 10
>5
>10
5-10
>5
No./year for
competency
10-15
25
5-10
10-15
5-10
5-10
5-10
5-10
5-10
10
>5
Procedures NetWork has a similar suggested numerical method (Table 3)
[II]. Even if a fixed number is assigned to each technique, we believe it
remains the instructor's responsibility to assure that the individual is truly
trained and felt to be competent in all procedures that the trainee wishes to
use in their practice.
In order to comply with suggestions such as these for training in a
formal educational program, it seems unlikely that most pulmonologists
who have already entered practice can learn all of the skills that are
considered under the rubric of interventional pulmonology. Although
participating in a course can lay down the foundation for learning
interventional procedures, it is the supervised practice of these skills that
will perfect the technique for the new practitioner. This may require working
with a colleague who practices interventional pulmonology or possibly a
thoracic surgeon who may possess the skill set that is desired. Overall it
takes a significant commitment on the part of a practicing pulmonologist to
learn new skills to expand his or her practice. The old medical adage of see
one, do one, teach one has no place for training in interventional
pulmonology.
T3
Table 3 ACCP Interventional Chest/Diagnostic Procedures NetWork
Recommendations for Training
Procedure
Rigid bronchoscopy
TBNA
Autofluorescence
Endobronchial ultrasound
Laser
Electrosurgeryjargon
plasma coagulation
Cryotherapy
Brachytherapy
Stenting
Fine-needle aspiration
(transthoracic needle
aspiration)
Tube thoracoscopy
Medical thoracoscopy
Percutaneous pleural biopsy
Percutaneous tracheostomy
Transtracheal O
2
therapy
v. Clinical Skills
No. for initial
training
100
20
25
20
50
15
15
10
5
10
20
10
10
20
5
20
10
No./year for
competency
25
10
10
10
10
10
5
5
5
10
5
10
10
5
Practicing interventional pulmonologists cannot offer their patients the best
management if they are facile in only a single technique. For instance,
cryotherapy may offer benefits over laser in certain clinical situations. There
are clinical situations when the use of a Silastic stent may be more preferred
over a flexible metallic stent. Photodynamic therapy is an excellent
technique for early-stage cancers, but it is of lesser value for bulky
malignancies that are better treated by ablative methods.
Clinical skills can best be defined as using the correct technique or
combination of techniques to treat the individual patient most comprehen-
sively. When an interventional pulmonologist is consulted, the clinical
problem must be addressed in the broadest possible way, and it should
include the patient's functional status, comorbid conditions, specific
Training in lnterventional Pulmonology
653
location of the disease process, all possible treatment options, and others.
Future interventional pulmonologists must be trained with a comprehensive
array of diagnostic and therapeutic modalities to give them the ability to
pick and choose among the methods they offer to their patients. When
several types of treatment are judged to be equally efficacious, individual
physicians will more than likely choose one of these techniques as their
preferred method. The rationale for choosing one technique versus another
may be cost, operating room availability, or simply operator preference for
a particular technique. The key to clinical education, however, is that the
student has been trained and is clinically competent in several techniques
that have complementary clinical indications.
An example may help to illustrate this point. An interventional
pulmonologist who predominately uses a Nd:YAG laser is presented with a
patient on a ventilator requiring 80% inspired oxygen because of an
obstructed airway. From a purely technical perspective, a preliminary
assessment leads to the conclusion that the airway can be effectively treated
with an ablative instrument. By intervening, there is a high probability that
the patient will clinically improve, improving the oxygenation and
permitting weaning from the ventilator. However, with this very high
oxygen requirement, the Nd:YAG laser cannot be used, because of the
potential fire hazard in such a high-oxygen environment (FI0
2
> 40%).
Debulking the tumor would be nearly impossible if the interventional
pulmonologist did not have another safer method to use in this set of
circumstances. Since cryotherapy is not hazardous in a high-oxygen
environment, it could be used as an alternative to help such a patient.
The availability of multiple devices, as well as the training and experience to
choose properly among them and use them effectively, allows for the
optimal practice of interventional pulmonology.
The practice of interventional pulmonology is not straightforward in
most cases. It requires experience and inventiveness to develop solutions for
complicated problems. No clinical pathways exist to give the interventional
pulmonologist answers to problems; instead, creative plans sometimes need
to be devised. The only way these skills can be taught is at the bedside with
patients and clinical problems placed before the teachers and students.
Clinical skills cannot easily be taught in a short course. Instructors
may do their best to share their clinical experience with trainees, but the
straightforward problems placed in front of students with models and/or
animals are not the complicated clinical pictures that are often seen in
practice. The practice of interventional pulmonology is often looked at as
being "interesting" or "fun." Thus, some individuals hope to add these skills
during a standard fellowship or add these skills to their practices by
attending minicourses. clinical training, future
654
Simaff and Kvale
interventionalists could enter their practice without adequate preparation. It
is therefore the responsibility of those training these individuals to ensure a
wide spectrum of clinical exposure and experience.
With guidance and experience, competent interventional pulmonolo-
gists will develop their own solutions to complicated problems. Sometimes
they may differ from those who taught them, but it is the basic skills that
have been learned that give them the foundation from which to make these
decisions and in the future grow and expand their practice of interventional
pulmonology.
VI. Who Should be Trained?
We believe that the issue of who should be trained is best addressed by
determining how many interventional pulmonologists are needed to provide
the services that the population requires? Should there be many people
doing small numbers of interventional cases throughout an area, or instead
regional centers that can and will manage a larger volume of cases? The
latter, with several interventional pulmonologists located at regional centers
that offer expansive services to a large patient population, appears to be the
ideal option. This model implies that these regional centers would offer
comprehensive treatment programs with complete interventional services,
have easy and immediate access to physicians for patients, and provide
opportunities for education. This may not be realistic in all settings; some
pulmonologists may feel obliged to offer these services because a center with
comprehensive services may not be readily available.
When this is the case, we recommend that the pulmonologist should
learn a single technique and become proficient with it in order to manage the
majority of the situations that may arise. A less expensive ablative device,
such as an argon plasma coagulator, might be ideal for such an approach.
Pulmonary physicians who adopt a limited services interventional program
should have a relationship with a referral center as well.
We believe that it is not practical for physicians in private practice
settings to offer advanced techniques, as they will practice these techniques
infrequently and sporadically. If a small group of pulmonary physicians has
only a single member of the group who is trained to perform interventional
pulmonology procedures, patients in need of these services may not be able
to be treated because that individual practitioner is unavailable (for some
reason). The equipment used for interventional procedures is expensive.
Reimbursement from third-party payers for interventional procedures is not
good, particularly as a function of the time it takes to perform such
procedures. The preoperative, operative, and postoperative time involved in
Training in Inlervenlional Pulmonology
655
managing this complicated patient population will require a significant
amount of time away from standard clinical practice. In addition,
malpractice insurance premiums are typically higher for pulmonary
physicians who practice interventional pulmonology. Thus, the practice of
interventional pulmonology at specialized centers with several interven-
tional pulmonologists offers considerable benefits.
Fellowship-based training programs should remain the standard for
training in interventional pulmonology. This model allows the time and
exposure to a comprehensive array of procedures and education in
interventional pulmonology. Similar to other procedure-oriented specialties
(i.e., surgery, otolaryngology, or urology), a fellowship-based program
allows excellent supervision and mentoring for the trainees. If appropriately
designed, these programs should provide cognitive training and directed
instruction of all of the relevant techniques with hands-on experience with a
diverse patient population. If the training program is a large regional center,
often an adequate number of procedure opportunities will exist for the
trainee. Larger centers often have created an environment that can stimulate
discussion and reevaluation of cases and techniq lies to expose the trainee
fully to a complete education in interventional pulmonology.
VII. Conclusion
The practice of interventional pulmonology is an exciting and growing field.
Physicians who provide these services should be comprehensively trained.
These physicians should practice in settings that have a critical mass of
trained practitioners and enough case material to maintain proficiency for
the procedures that are being performed. Having partners with similar
training as well as professional relationships between the interventional
pulmonologists, cardiothoracic surgeons, and otolaryngologists can assure
an optimal practice environment.
References
I. Bollinger CT, Mathur PN, et al. ERSjATS statement on interventional
pulmonology. Eur Respir J 2002; 19:356-373.
2. Tucker GF, Sanderson DR, et al. Standards for training in endoscopy.
Statement of the Committee on Bronchoesophagology American College of
Chest Physicians. Chest 1976; 69:665-666.
3. Bone RC, Aviles A, et al. Guidelines for competency and training in fiberoptic
bronchoscopy. Chest I Material
656
Simaff and Kvale
4. Hudson LD, Benson JA. Evaluation of clinical competence in pulmonary
disease. Am Rev Respir Dis 1988; ]38:1034-1035.
5. Faber LP. Bronchoscopy training. Chest] 978; 73 (suppl):776-778.
6. Rocco G, Rizzi A, Robustellini M, et al. Training and competence III
bronchoscopy. Chest 1993; 103:1305-1306.
7. American Thoracic Society. Guidelines for fiberoptic bronchoscopy in adults.
Am Rev Respir Dis 1987; 136:1066.
8. Haponik EF, Russell GB, Beamis JF, et al. Bronchoscopy training, current
fellows' experience and some concerns for the future. Chest 2000; ] 18:625-630.
9. Baillie J, Ravich WJ. On endoscopic training and procedural competence. Ann
Intern Med 1993; 118:73-74.
10. Kvale PA. Training in laser bronchoscopy and proposals for credentialing.
Chest 1990; 97983-989.
II. ACCP Interventional Chest/Diagnostic Procedures NetWork. Procedural
Standards Guidelines Chest 2003; 124:2329-2340.
12. Hata E, Hayakawa K, Miyamoto H, Hayashida R. Rationale for extended
lymphadenectomy for lung cancer. Theoret Surg 1990; 5: 19.
13. American National Standards Institute. Safe Use of Lasers. (pub 106) 2000;
ANSI Z 136.1.
14. Prakash UBS, Offord KP, Stubbs SE. Bronchoscopy in North America: the
ACCP Survey. Chest 1991; 100:1668-1675.
15. Haponik EF, Shure D. Underutilization of transbronchial needle aspiration:
experiences of current pulmonary fellows. Chest 1997; 112:251-253.
16. Colt HG, Prakash UBS, Offord KP. Bronchoscopy in North America: survey
by the American Association for Bronchology, ]999. J Bronchol 2000; 7:8-25.
17. Dull WL. Flexible fiberoptic bronchoscopy: an analysis of proficiency. Chest
1980; 77:65-67
APPENDIX: PROCEDURAL ALGORITHMS
I. Palliative Therapy for Malignant Central Airway Obstruction
2. Medical Thoracoscopy
3. Malignant Pleural Effusion
4. Large-Bore Chest Tube Insertion
5. Beside Pleurodesis
657
658 Appendix
Procedural Algorithm 1: Palliative Therapy for
Malignant Central Airway Obstruction
Laser
Stent
APC
EBES
Th rapeutic endoscopy
Rapid
-----.. 8
~
Life-threatening?
~
Radiation/Chemotherapy
~ ,-------'====::;-r--------'
Intrinsic tumor
External compression
Symplomatic or
>50% aiJ\vilY
obstruction
~ ~
ti #
<:EndobronchIal recurrence:>
..--
8-----
+
Cryotherapy
PDT
Brachytherapy
Therapeutic endoscopy
Slow
Appendix
Procedural Algorithm 2: Medical Thoracoscopy
Take history and do physical examination.
Review chest radiographs.
Review CT scan of chest.
Assess perlinclll laboratory data.
Assess anesthesia risk.
Strategy based on indication and site of pleural
abnormalities
659
Recovery: complete arousal from
conscious sedation.
Monitor vital signs.
Take chest radiograph to verify chest
tube position.
I_I Prepare patient and equipment

Prepare operating or
procedure room.
Prepare instrument trays.
Prepare thoracoscopy
instruments including video
camera,
Chose ideal first point of entry
(usually 4th-7th ICS mid-axillary
line).
Additional access under
thoracoscopy guidance.
Pleural biopsies under direct
vision (at least 5 to 7).
Handle pleural biopsies similar (Q
closed pleural biopsies.
Send pleural nuid if indicated
similar to thoracentesis.
For pJeurodesis choose agent.
If using talc then use no morc
then 6 gm.
Cover the entire pleural cavity.
j
Perform thoracoscopy
- (pleuroscopy)
-.
1-.
Informed consent
Position patient
Protect pressure points
Monitor vital signs
Give supplemental oxygen
Helpful hints:
Local infiltration
of incision siles
with lidocaine;
titrate midazoam
and fentanyl for
sedation and
analgesia
Postprocedure management:
Monitor daily chest tube drainage.
Watch for air leak.
Take daily chest radiograph.
Change dressing every 48 hours.
Control pain.
Encourage incentive spirometry and ambulalion.
Prevenl deep vein thrombosis.
Remove chest tube when drainage is less then 1.50
cc124 hours.
660
Procedural Algorithm 3: Malignant Pleural Effusion
Take history and do physical examination.
Review chest radiographs.
Assess pertinent laboratory data.
Is primary tumor chemothcrnpy* or radiation-sensitive?
Perform diagnostic thoracentesis.
Appendix
I
I
Performance status
J
Poor perfonnance status (KS < 30%
life expectancy < 3 months)
Repeated thoracenteses or indwelling
pleural catheter
Good perfonnance status
Consider pleurodesis either by bedside
chest tube placement or medical
thoracoscopy.
Trapped lung
fndwelling pleural
catheter; self-
drainage al home
Assess if the lung will reexpand.
Perform large volume thoraccmcsis.
Review chest radiographs with
bilareral decubitus views.
Review CT scan of chest for presence
of adhesions.
Consider bronchoscopy if central
airways obstruction suspected.
1
Lung will expand
Pleurodesis by bedside chest tube placemelll (doxecycline or laic
slurry) or medicallhoracoscopy (taJc spray)
Trapped lung found on medical thorncoscopy
Appendix
661
Procedural Algorithm 4: Large-Bore Chest Tube Insertion
I'luid:
axillary line
U,ually below 5th ICS
Direct tube or
inferiorly (dependent
position)
--
Take hi'\lory and do phy.. ical
cxamimHlon.
Review chest radiograph...
A\sess coagulnlion profile.
Review indication
and insertion site
--
Air:
2nd or 3rd ICS mid-
clavicular line or 3rct-5lh
ICS on nlldaxll1ary line.
Direct tube anteriorly and
!-upcnorly.
Position patient
Sedalion and
Helpful hints:
Maintain sterile field.
Secure tube connecting,
Secure <llld tube.
Observe air leak or fluid
drainage so Lhat transportation 01"
the paticnI is ensy and chest b
not pulled oul.
Daily observe nucluation in
water seal c1wmbcr.
--.
1
Insert chest tube
[
Prepare equipment and patient I
-L-
L- _ Prepare instrument tray.
Select method of insertion:
blunt dissection
guide wire
Prepare thoracic drainage device.
And don't foq;ct:
Abundant local
Incision large enough 10 easily insert tube into
pleural space
Place finger in chest cavity to make sure there
is no adhesion.
Avoid extra pleural tube insertion.
Avoid large and breast.
ReCOVfQ':
Take chest radIograph to venfy proper tube
position.
Reposition or replace improperly positioned
chest tube.
Daily chest x-rays until the tube IS removed.
662 Appendix
Procedural Algorithm 5: Bedside Pleurodesis
Prepare instrument trays.
Choose agent.
Prepare sclerosing agent.
Administer sedation and
analgesia.
--
Take history and do physical examinmion.
Review chest radiographs. ---.
Assess pertinent laboratory data.
Choose appropriate agent and technique
Prepare patient and equipment
j
Do large volume
thoracentesis
Lung expanded?
Trapped lung?
Adhesions?
Consider bronchoscopy
if central airways
obstruction suspected.
Position patient.
Insert chest tube.
--
Helpful hinLI;:
Drain all Ouid first.
Use sterile technique.
Recovery:
Take chest radiograph to verify chest
tube position and lung expansion.
Monitor vilal signs.
Control p;;lin.
Postproccdure management:
Monitor daily ehest tube drainage.
Watch degree of airleak.
Daily chc;t radiograph.
Change dressing every 48 hours.
Control pain.
Encourage inccnIivc spirometry and
Prevenl deep vein thrombosis.

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Editor: Claude Lenfant

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