Self-Expanding Stents in Gastroenterology [1 ed.] 9781617118104, 9781617110283

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Adler

There is a tremendous interest in information on stents in the world of gastrointestinal endoscopy. Many physicians did not train in an era where these stents were available, but they are now being called upon to place them. Self-Expanding Stents in Gastrointestinal Endoscopy looks to provide physicians with the necessary and unique all-in-one resource on stents. Self-Expanding Stents in Gastrointestinal Endoscopy by Dr. Douglas G. Adler covers the use of self-expanding stents. This book will cover the use of all available devices in all clinical contexts, with step-by-step instructions from experts in the field on how to use them and, just as importantly, what not to do when using these devices.

Benefits and Features: • Soup-to-nuts format covers the use of all devices available on the market in all clinical situations • All chapters authored by recognized experts in the world of stents who have independently published extensive research in gastrointestinal endoscopy • Over 150 color photographs to guide readers from start to finish through all steps of learning about the procedures Self-Expanding Stents in Gastrointestinal Endoscopy brings attention to the use of self-expanding stents in benign and malignant diseases, the avoidance and management of complications, and the future of these devices. ®

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Self-Expanding Stents in Gastrointestinal Endoscopy is the perfect go-to book for

I N C all O R P O R A Tgastroenterologists, E D practicing fellows, and general and colorectal surgeons.

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Self-Expanding Stents in Gastrointestinal Endoscopy Editor: Douglas G. Adler

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in Gastrointestinal Endoscopy

Self-Expanding Stents in Gastrointestinal Endoscopy is illustrated with more than 150 color photographs, as well as many tables and diagrams.

Self-Expanding Stents

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Self-Expanding Stents in Gastrointestinal Endoscopy

SLACK Incorporated

DOUGLAS G. ADLER, MD, FACG, AGAF, FASGE Associate Professor of Medicine Director of Therapeutic Endoscopy Gastroenterology and Hepatology University of Utah School of Medicine Huntsman Cancer Institute Salt Lake City, Utah

www.slackbooks.com ISBN: 978-1-61711-028-3 Copyright © 2012 by SLACK Incorporated All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without written permission from the publisher, except for brief quotations embodied in critical articles and reviews. The procedures and practices described in this publication should be implemented in a manner consistent with the professional standards set for the circumstances that apply in each specific situation. Every effort has been made to confirm the accuracy of the information presented and to correctly relate generally accepted practices. The authors, editors, and publisher cannot accept responsibility for errors or exclusions or for the outcome of the material presented herein. There is no expressed or implied warranty of this book or information imparted by it. Care has been taken to ensure that drug selection and dosages are in accordance with currently accepted/ recommended practice. Off-label uses of drugs may be discussed. Due to continuing research, changes in government policy and regulations, and various effects of drug reactions and interactions, it is recommended that the reader carefully review all materials and literature provided for each drug, especially those that are new or not frequently used. Some drugs or devices in this publication have clearance for use in a restricted research setting by the Food and Drug and Administration or FDA. Each professional should determine the FDA status of any drug or device prior to use in their practice. Any review or mention of specific companies or products is not intended as an endorsement by the author or publisher. SLACK Incorporated uses a review process to evaluate submitted material. Prior to publication, educators or clinicians provide important feedback on the content that we publish. We welcome feedback on this work. Published by:

SLACK Incorporated 6900 Grove Road Thorofare, NJ 08086 USA Telephone: 856-848-1000 Fax: 856-848-6091 www.slackbooks.com

Contact SLACK Incorporated for more information about other books in this field or about the availability of our books from distributors outside the United States. Library of Congress Cataloging-in-Publication Data Self-expanding stents in gastrointestinal endoscopy / [edited by] Douglas G. Adler. p. ; cm. Includes bibliographical references and index. ISBN 978-1-61711-028-3 (alk. paper) I. Adler, Douglas G., 1969[DNLM: 1. Endoscopy, Gastrointestinal--methods. 2. Stents. WI 141] 616.3’307545--dc23 2012000349 For permission to reprint material in another publication, contact SLACK Incorporated. Authorization to photocopy items for internal, personal, or academic use is granted by SLACK Incorporated provided that the appropriate fee is paid directly to Copyright Clearance Center. Prior to photocopying items, please contact the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923 USA; phone: 978-750-8400; website: www.copyright.com; email: [email protected]

DEDICATION For my father, who never gave up.

CONTENTS Dedication................................................................................................................................. v Acknowledgments.....................................................................................................................ix About the Editor ......................................................................................................................xi Contributing Authors ........................................................................................................... xiii Preface ...................................................................................................................................xvii Chapter 1

Esophageal Stents in Benign Disease ..........................................................1 Sanjay R. Hegde, MD and Eric Goldberg, MD

Chapter 2

Esophageal Stents in Preoperative Esophageal Cancer Patients ............. 21 Kathryn R. Byrne, MD; John C. Fang, MD; and Douglas G. Adler, MD, FACG, AGAF, FASGE

Chapter 3

Esophageal Stents in Patients With Malignant Dysphagia Due to Unresectable Disease ..................................................................... 35 Kulwinder S. Dua, MD, FACP, FRCP, FASGE

Chapter 4

Complications of Esophageal Stents and Their Management ................ 59 Gulshan Parasher, MD and Jess D. Schwartz, MD, FACS, FCCP

Chapter 5

Metal Biliary Stents in Benign Pancreaticobiliary Disease .....................77 Michelle A. Anderson, MD, MSc and Richard S. Kwon, MD, MSc

Chapter 6

Metal Biliary Stents in Patients With Potentially Resectable Pancreaticobiliary Malignancy ................................................................. 93 Tyler M. Berzin, MD, MS; Ram Chuttani, MD; and Douglas K. Pleskow, MD, AGAF, FASGE

Chapter 7

Metal Biliary Stents in Patients With Unresectable Pancreaticobiliary Malignancy ............................................................... 109 Waqar Qureshi, MD, FRCP, FASGE

Chapter 8

Metal Biliary Stent Complications and Their Management ................. 121 Jessica I. Chan, BS, MS and Douglas G. Adler, MD, FACG, AGAF, FASGE

Chapter 9

Gastroduodenal Stents ............................................................................. 139 Christopher J. DiMaio, MD

Chapter 10

Gastroduodenal Stents Versus Surgery for Malignant Gastric Outlet Obstruction................................................................................... 167 Ali A. Siddiqui, MD

viii

Contents

Chapter 11

Colonic Stents as a Bridge to Surgery in Patients With Colonic Obstruction ................................................................................ 181 John Y. Nasr, MD and Andres Gelrud, MD, MMSc

Chapter 12

Colonic Stents as Palliative Therapy in Patients With Malignant Large Bowel Obstruction ......................................................................... 193 Sergey V. Kantsevoy, MD, PhD

Chapter 13

Complications of Colonic Stenting and Their Management ............... 207 Sonia Gosain, MD; Kevin Halsey, MD; and Peter Darwin, MD

Chapter 14

The Future of Self-Expanding Stents in Gastrointestinal Endoscopy..................................................................... 219 Jeffrey L. Tokar, MD

Financial Disclosures ............................................................................................................235

ACKNOWLEDGMENTS I am indebted to Carrie Kotlar of SLACK Incorporated for her help with and support for this project. Her steadfast backing of this project allowed for the conversion of an idea into a reality. I am also deeply indebted to my loving wife and children for their unwavering support of this endeavor and all of the resources it required.

ABOUT THE EDITOR Douglas G. Adler, MD, FACG, AGAF, FASGE received his medical degree from Cornell University Medical College. He completed his residency in internal medicine at Beth Israel Deaconess Medical Center/Harvard Medical School. Dr. Adler completed both a general gastrointestinal fellowship and a therapeutic endoscopy/endoscopic retrograde cholangiopancreatography fellowship at Mayo Clinic in Rochester, Minnesota. He then returned to the Beth Israel Deaconess Medical Center for a fellowship in endoscopic ultrasound. Dr. Adler is currently an Associate Professor of Medicine and Director of Therapeutic Endoscopy at the University of Utah School of Medicine in Salt Lake City. Working mostly out of the School of Medicine’s Huntsman Cancer Institute, Dr. Adler’s clinical, educational, and research efforts focus on the diagnosis and management of patients with gastrointestinal cancers, with an emphasis on therapeutic endoscopy. He is the author of more than 150 scientific publications and book chapters and editor of the previously published book Curbside Consultation in GI Cancer for the Gastroenterologist: 49 Clinical Questions.

CONTRIBUTING AUTHORS Michelle A. Anderson, MD, MSc (Chapter 5) Assistant Professor of Medicine University of Michigan School of Medicine Division of Gastroenterology Ann Arbor, Michigan Tyler M. Berzin, MD, MS (Chapter 6) Staff Physician, Center for Advanced Endoscopy Division of Gastroenterology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Kathryn R. Byrne, MD (Chapter 2) Assistant Professor University of Utah School of Medicine Division of Gastroenterology and Hepatology Salt Lake City, Utah Jessica I. Chan, BS, MS (Chapter 8) University of Utah School of Medicine Salt Lake City, Utah Ram Chuttani, MD (Chapter 6) Director of Endoscopy Chief, Interventional Gastroenterology Beth Israel Deaconess Medical Center Harvard Medical School Boston, Massachusetts Peter Darwin, MD (Chapter 13) Associate Professor University of Maryland School of Medicine Department of Gastroenterology and Hepatology Baltimore, Maryland Christopher J. DiMaio, MD (Chapter 9) Director of Therapeutic Endoscopy Assistant Professor of Medicine Division of Gastroenterology Mount Sinai School of Medicine New York, New York

xiv

Kulwinder S. Dua, MD, FACP, FRCP, FASGE (Chapter 3) Professor, Department of Medicine Medical College of Wisconsin Division of Gastroenterology and Hepatology Milwaukee, Wisconsin John C. Fang, MD (Chapter 2) Associate Professor University of Utah Health Sciences Center Department of Gastroenterology and Hepatology Salt Lake City, Utah Andres Gelrud, MD, MMSc (Chapter 11) Associate Professor of Medicine University of Pittsburgh Medical Center Division of Gastroenterology, Hepatology, and Nutrition Pittsburgh, Pennsylvania Eric Goldberg, MD (Chapter 1) Assistant Professor of Medicine Director of Endoscopic Training and Research University of Maryland School of Medicine Baltimore, Maryland Sonia Gosain, MD (Chapter 13) GI Fellow University of Maryland School of Medicine Division of Gastroenterology and Hepatology Baltimore, Maryland Kevin Halsey, MD (Chapter 13) Assistant Professor University of Missouri Healthcare Department of Gastroenterology and Hepatology Columbia, Missouri Sanjay R. Hegde, MD (Chapter 1) Assistant Professor of Medicine Division of Gastroenterology Tufts Medical Center Boston, Massachusetts

Contributing Authors

Contributing Authors

Sergey V. Kantsevoy, MD, PhD (Chapter 12) Director of Therapeutic Endoscopy The Melissa L. Posner Institute for Digestive Health and Liver Disease Mercy Medical Center Baltimore, Maryland Richard S. Kwon, MD, MSc (Chapter 5) Assistant Professor Division of Gastroenterology University of Michigan Medical School Ann Arbor, Michigan John Y. Nasr, MD (Chapter 11) Gastroenterology Fellow University of Pittsburgh Medical Center Division of Gastroenterology, Hepatology, and Nutrition Pittsburgh, Pennsylvania Gulshan Parasher, MD (Chapter 4) Associate Professor of Medicine Director of Endoscopic and Clinical Services Division of Gastroenterology and Hepatology University of New Mexico School of Medicine Albuquerque, New Mexico Douglas K. Pleskow, MD, AGAF, FASGE (Chapter 6) Associate Clinical Professor of Medicine Harvard Medical School Co-Director of Endoscopy Beth Israel Deaconess Medical Center Boston, Massachusetts Waqar Qureshi, MD, FRCP, FASGE (Chapter 7) Professor of Medicine Chief of Endoscopy Baylor College of Medicine Houston, Texas Jess D. Schwartz, MD, FACS, FCCP (Chapter 4) Assistant Professor of Surgery University of New Mexico Health Science Center Department of Surgery Division of Thoracic and Cardiovascular Surgery Albuquerque, New Mexico

xv

xvi

Ali A. Siddiqui, MD (Chapter 10) Associate Professor of Medicine Division of Gastroenterology and Hepatology Jefferson Medical College Philadelphia, Pennsylvania Jeffrey L. Tokar, MD (Chapter 14) Assistant Professor Fox Chase Cancer Center Department of Medicine Director, GI Endoscopy Philadelphia, Pennsylvania

Contributing Authors

PREFACE In 1999, when I was a brand new gastroenterology fellow at the Mayo Clinic in Rochester, Minnesota, I performed my first endoscopic stenting procedure: the placement of an esophageal stent in a patient with malignant dysphagia from metastatic esophageal cancer. I was amazed at the speed and ease of the procedure from a technical standpoint, and I was nothing short of astonished at how soon the patient’s dysphagia symptoms improved. This procedure, for me, was truly “ground zero” and my formal introduction to the world of interventional and therapeutic endoscopy, and I knew that it would shape my career from that point on. A short time later, I assisted Dr. Todd H. Baron in the placement of a colonic stent in a patient with a life-threatening malignant large bowel obstruction. The patient was critically ill and clinically unstable, and the surgeons were understandably less than enthusiastic about operating. In contrast to the aforementioned esophageal stent placement procedure, this case was neither speedy nor easy. Our endoscopic visualization was terrible, the fluoroscopy unit we had at our disposal was ancient, and the malignant stricture in question was sharply angulated, all of which complicated our efforts at every step of the case. We were able to complete the procedure, but we emerged from the endoscopy room drenched in sweat and concerned that we might have caused a perforation. Fortunately for all concerned, there were no complications and the patient was able to decompress her large bowel and proceed to an elective surgery at a later date. Despite the risks involved, it was very exciting stuff for me. I remember commenting afterward that I felt like Dr. Baron and I were somewhat analogous to Neil Armstrong and Buzz Aldrin landing on the moon in the Sea of Tranquility in 1969; both endeavors were risky, utilized new and relatively untested technology, and in one way or another lives were on the line. Fast forwarding to the current day, self-expanding metal stents (SEMS) have come a long way. Stent placement of any kind was once regarded as a high-end procedure, performed rarely and only at a tertiary referral center. Now, self-expanding stents of all kinds (esophageal, biliary, gastroduodenal, and colonic) are placed on a daily basis in a variety of settings by endoscopists in an almost routine fashion. The literature on these stents has expanded exponentially, as have the number and types of SEMS currently available around the world. There is an enormous interest in these devices from the point of view of patients, physicians (gastroenterologists, oncologists, and surgeons, among others), and industry, and innumerable stent-related research studies are being carried out at this time around the globe. I utilize SEMS of all kinds in my daily practice as a therapeutic endoscopist at a large tertiary referral cancer center, and I know for a fact that without these devices we would be profoundly handicapped with regard to the treatment of dozens of conditions. Over a decade after my first stent placement, I still find stent technology to be both fascinating and miraculous. In creating this book, I wanted to craft a definitive resource for physicians regarding the use of any type of SEMS in any clinical situation that one might face. In the pages that follow, esophageal, biliary, gastroduodenal, and colonic stents are reviewed in great

xviii

Preface

detail. Each chapter includes a great number of endoscopic and radiologic images to fully convey key concepts to the reader. Complications and limitations of stent technology are covered as well in an attempt to minimize poor outcomes. Lastly, a chapter on the future of SEMS is included to highlight the developmental nature of stent technology and to also demonstrate that the best is yet to come. I hope that you find this book to be a helpful and valuable addition to your library and an aid to your daily clinical practice. Douglas G. Adler Salt Lake City, Utah

1

Esophageal Stents in Benign Disease Sanjay R. Hegde, MD and Eric Goldberg, MD

Esophageal stents have an established role in the palliation of dysphagia in patients with malignant esophageal strictures.1,2 However, the role of esophageal stents in benign esophageal disorders is still evolving. This chapter will review applications of esophageal stents in a variety of benign esophageal disorders, including refractory benign esophageal strictures and esophageal perforations, leaks, and fistulae.

REFRACTORY BENIGN ESOPHAGEAL STRICTURES Benign esophageal strictures are common in clinical practice. Dysphagia is typically associated with narrowing of the luminal diameter of the esophagus to 13 mm or greater.3 Additionally, dysphagia can be objectively scored using a widely used dysphagia score that can be useful in gauging treatment response (Table 1-1). Historically, the most common etiology for benign esophageal strictures has been so-called “acid-peptic” strictures related to gastroesophageal reflux disease (GERD). However, the incidence and frequency of anastomotic and radiation related strictures has increased in recent years.4 The majority of benign esophageal strictures respond to esophageal dilation therapy within 1 to 3 dilation sessions. Approximately 25% to 35% of benign esophageal strictures require additional dilation sessions.5 Esophageal dilation is safe and has a relatively low complication rate including a 0.1% to 0.4% perforation rate and 0.1% risk of significant bleeding.6,7 Dilation therapy can be performed using either a bougie or a hydrostatic balloon dilator. Neither modality has demonstrated superiority in the immediate relief of dysphagia or the need for repeat dilation at 1 year.8 Complex strictures are less likely to respond successfully to dilation therapy and can be technically more difficult to dilate. The features of complex strictures include (1) length greater than 2 cm, (2) angulation, (3) irregular contour, and (4) a severely narrowed luminal diameter (Table 1-2). Additionally, anastomotic strictures along with strictures related to radiation therapy or caustic injury have lower response rates to dilation therapy.4 The use of fluoroscopy or narrow diameter endoscopes may aid in the management of such strictures. There is no consensus on the definition for refractory esophageal strictures. However, a recent definition proposed by Kochman et al has proven useful and has been applied in

-1-

Adler DG, ed. Self-Expanding Stents in Gastrointestinal Endoscopy (pp 1-20). © 2012 SLACK Incorporated.

2

Chapter 1

Table 1-1. Dysphagia Score Score

Symptoms

0

No dysphagia

1

Intermittent solid food dysphagia

2

Unable to swallow solids

3

Unable to swallow pureed food

4

Unable to swallow liquids

Reprinted with permission from Mellow MH, Pinkas H. Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction. Analysis of technical and functional efficacy. Arch Intern Med. 1985;145(8):14431446. Copyright © 1985 American Medical Association. All rights reserved.

Table 1-2. Features of Complex Esophageal Strictures Length >2 cm Angulation Irregular contour Severely narrowed luminal diameter

several studies investigating the treatment and management of refractory benign esophageal strictures. A refractory stricture may be defined as an anatomic restriction due to cicatricial luminal compromise or fibrosis that results in the clinical symptom of dysphagia in the absence of inflammation. Such strictures cannot be dilated to a diameter of 14 mm or greater over 5 dilation sessions at 2-week intervals. A stricture may be defined as recurrent when one cannot maintain a satisfactory luminal diameter for 4 weeks once the target diameter of 14 mm has been achieved.9 When a stricture meets criteria for a refractory stricture, alternatives to dilation therapy should be considered. Intralesional steroid injection with 4-quadrant injections of 0.5 mL of 40 mg/mL triamcinolone within the narrowest point of the stricture in combination with dilation therapy and twice-daily proton pump inhibitor (PPI) therapy have been shown to increase the time interval between dilation sessions.10 Another approach to refractory strictures involves the use of electrocautery with a needle-knife to disrupt the stricture. This strategy has been used with variable success.11,12 Additionally, self-dilation therapy can be considered in highly motivated patients.13 When these measures fail or are not viable options, one may consider placement of an esophageal stent for the treatment of a benign refractory esophageal stricture.

STENTS AND BENIGN ESOPHAGEAL STRICTURES: AN OVERVIEW Esophageal stents have been evaluated for use in the treatment of benign esophageal strictures. Currently, only one self-expanding plastic stent (SEPS), the Polyflex stent

Esophageal Stents in Benign Disease

3

(Boston Scientific, Natick, MA), has been approved by the Food and Drug Administration (FDA) for use in benign esophageal disease. Partially covered self-expanding metal stents (PCSEMS) have been studied with unfavorable results, mostly related to the difficulty of their removal. Recently developed, fully covered self-expanding metal stents (FCSEMS) such as the Alimaxx-E and ES stents (Merit Endotek, South Jordan, UT) and the Boston Scientific Fully Covered Wallflex stent are also available but are currently not FDA approved for the management of benign esophageal strictures, and their use in patients with benign disease must be considered off-label. The ideal stent for treatment of benign esophageal disorders should have the following characteristics: easy deployment, easy removability, low rate of migration, high rate of symptomatic relief/resolution of underlying problem, and low complication rate.2 Currently, no available stents are ideal, but early results with SEPS and FCSEMS hold promise for better results with improved stent design in patients with refractory benign esophageal strictures, perforations, leaks, and fistulae.

Self-Expanding Plastic Stent /Polyflex Stent The Polyflex SEPS is currently the only available stent that is FDA approved for the treatment of benign esophageal disease. Polyflex stents are composed of a polyester netting embedded with a silicone inner lining. These stents are impregnated with radioopaque markers at the proximal end, midpoint, and distal end of the stent to aid positioning during deployment. The proximal end of this stent is flared to prevent distal migration while the mid and distal portions of the stent are of the same diameter as the main portion of the stent shaft. The inner diameter of the shaft and distal end of the stent are available in sizes of 16, 18, and 21 mm, with 20, 23, and 28 mm proximal flare sizes, respectively. The stent delivery system is assembled by the physician immediately prior to deployment. The assembly process can be challenging even for experienced endoscopists and can be considered a drawback for the use of this stent. The introducer systems range in size from 12 to 14 mm, depending on the diameter of the stent to be utilized. Deployment is performed under fluoroscopic guidance over a guidewire, with or without endoscopic guidance from an endoscope advanced alongside the stent delivery catheter. When selecting the length of a stent, it should cover the entire stricture. The endoscopists should leave approximately 1 to 2 cm of stent above and below the stricture, anatomy permitting. Once deployed, this stent can be repositioned or removed from either the esophagus or the stomach (if the stent has migrated) using a rat-tooth forceps at the proximal edge of the stent with steady, constant traction that allows the stent to dislodge from the esophageal wall. A modification of this technique uses a 2-channel therapeutic upper endoscope with 2 rat-tooth forceps simultaneously grasping the proximal aspect of the stent. The forceps are crossed over one another by applying torque on the scope, and then the stent is removed with gentle traction. Additionally, the distal aspect of the stent can be grasped with a rat-tooth forceps, invaginating the stent into itself when traction is applied, thus facilitating removal. Finally, polypectomy snares can also be used to lasso the stent, thereby facilitating proximal repositioning or removal of these stents14 (Figures 1-1 and 1-2). Early studies investigating the use of SEPS for benign esophageal strictures demonstrated high rates of technical success for deployment (greater than 95%) and favorable clinical outcomes. In a study of 15 patients with benign esophageal strictures by Repici et al, technical success was reported in 100% of patients and clinical success in

4

Chapter 1

Figure 1-1. Endoscopic image of a Polyflex stent that has migrated into the stomach in a patient with a refractory benign esophageal stricture following deployment.

Figure 1-2. Same patient as seen in Figure 1-1 undergoing removal of the migrated stent using a rat-tooth forceps.

80%. The rate of stent migration in this study was low at 6.6%.15 In another early study investigating the use of the Polyflex stent for benign esophageal disease in 21 patients (17 patients with benign esophageal strictures and 4 patients with esophageal fistulae), technical success was 100% and clinical success was 80%. However, the migration rate was alarmingly high at 57.1%.16 More recent data on the Polyflex stent for benign esophageal disease have continued to demonstrate high rates of technical success but lower rates of clinical success and high rates of stent migration. In a prospective study of 40 patients with refractory benign esophageal strictures treated with the Polyflex stent by Dua et al, the clinical success rate was lower than in earlier studies (40%). Complications included stent migration in 22%, and there was one death from massive bleeding due to stent erosion

Esophageal Stents in Benign Disease

5

into a major vessel.17 In another study of 30 patients with benign esophageal disease (8 patients had stents for benign refractory strictures, 11 for anastomotic strictures, 5 for radiation induced strictures, and the remainder for fistulae/leaks; some patients may have had multiple indications for their stent and this is not clearly identified in the original manuscript) by Holm et al, unacceptably low rates of symptom relief (6%) and high rates of overall stent migration (81%) were observed. In this study, stent migration was more frequent in proximally and distally deployed stents (68.1% and 70.4% migration rates, respectively) and less frequent with stents deployed in the midesophagus (30%). Interestingly, the etiology of the stricture influenced migration rates as well. Anastomotic strictures were noted to have a stent migration rate of 75% while radiationrelated strictures had lower migration rates (28.6%). This difference may be explained in part by the length of stricture because anastomotic strictures tend to be shorter, thereby contributing to higher rates of stent migration.18 In another recent study by Oh et al involving 13 patients with benign refractory esophageal strictures, there was a low clinical success rate (23%) and high migration rate (30%).19 With regard to the overall efficacy and safety of SEPS placement for benign refractory esophageal strictures, a systematic review of 10 studies and 130 patients by Repici et al demonstrated an overall technical success rate of 98%, an overall clinical success rate of 52%, and an overall rate of early stent migration (less than 4 weeks) of 24%. Excluding migration as a complication, there was still an overall complication rate of 9% with one death (0.8%).20

Partially Covered Self-Expanding Metal Stents and Refractory Benign Esophageal Strictures PCSEMS have been studied in the treatment of benign esophageal disease. Their use has been limited by difficulty of stent removal and high complication rates. Partially covered stents that are readily available include the Wallflex and older generation Ultraflex stents (both from Boston Scientific). These stents tend to be more difficult to remove due to tissue embedment along the uncovered proximal and distal portions of the stent. Furthermore, these stents are associated with new stricture formation secondary to granulation tissue at the ends of these stents. In an early study of 8 patients treated with PCSEMS for benign esophageal disease, 4 patients (50%) had major complications. Two patients developed strictures above the stent, one patient had stent migration, and one patient died of exsanguination from stent erosion into the aorta.21 In another study of 29 patients who had PCSEMS placed for benign esophageal strictures, new stricture formation was seen in 41%, stent migration in 31%, chest pain or worsened reflux occurred in 21%, and tracheoesophageal fistula developed in 6% of patients.22 Given these high complication rates, PCSEMS are, in general, not recommended for use in patients with benign refractory esophageal strictures.

Fully Covered Self-Expanding Metal Stents and Refractory Benign Strictures Recently, FCSEMS have been developed to address the limitations of PCSEMS. While removability has been enhanced, there are higher rates of migration with FCSEMS. The Alimaxx-E esophageal stent is the best studied FCSEMS for treatment of

6

Chapter 1

Figure 1-3. Endoscopic image of an esophageal ulcer seen following removal of a FCSEMS in a patient with a refractory benign esophageal stricture.

refractory benign esophageal strictures. This stent is made of nitinol, is fully covered with a polyurethane covering, and is available in several diameters and lengths. Unlike SEPS, FCSEMS are preloaded on a delivery system that does not require assembly prior to stent deployment, making them somewhat easier to deploy. Also, the delivery systems for FCSEMS are thinner and can more easily traverse tight strictures. The shaft of the stent comes in 18 and 22 mm diameters. The proximal flare is 5 mm greater than the shaft diameter (23 and 27 mm, respectively). The distal flare is 3 mm greater than the shaft diameter (21 mm and 25 mm, respectively). Available lengths for this stent are 7, 10, and 12 cm. Ideally, the stent is deployed with 1 to 2 cm of stent length placed proximal and distal to the ends of the stricture. The stent has a blue knotted string that is attached circumferentially to the proximal flange of the stent and can be grasped using a rat-tooth forceps. When gentle pulling traction is applied to this knot, it acts as a “purse string” and changes the configuration of the stent from a cylinder to a cone, allowing for relatively easier removal and repositioning of the stent. Removal of this stent is usually accomplished using a therapeutic upper endoscope with forceps. A double-channel endoscope can allow removal using 2 forceps simultaneously. Other removal techniques include using a combination of a snare and a rat-tooth forceps.23 Several studies have evaluated the use of this stent in the treatment of refractory benign esophageal strictures. In an early study by Eloubeidi et al, 7 patients with refractory benign esophageal strictures were treated with the Alimaxx-E stent. Symptomatic relief of dysphagia was seen in 29% of patients with a stent migration rate of 36%. In this study, all placed stents were successfully removed. Eighty-two percent of the stents placed were considered easy to remove, while 18% of stents were moderately difficult to difficult to remove. Fifty percent of the patients in this study developed ulceration at the distal end of this stent, and 23% of patients developed ulcers along the proximal edge of the stent, all of which resolved with stent removal (Figure 1-3). Four patients in this study developed pseudopolyps at either the proximal or distal edge of the stent, and 2 patients were noted to have severe tissue reaction. These findings resolved after stent removal.23

Esophageal Stents in Benign Disease

7 Figure 1-4. Endoscopic image of a fully covered Alimaxx-ES stent in a patient with a refractory benign esophageal stricture. (Reprinted with permission of Douglas G. Adler, MD.)

Figure 1-5. Fluoroscopic image of a fully covered Wallflex stent in a patient with a long distal esophageal benign stricture. (Reprinted with permission of Douglas G. Adler, MD.)

Subsequent studies involving the use of this stent in the treatment of benign refractory esophageal strictures have demonstrated migration rates that range from 37% to 50% and dysphagia relief in 21% to 100% of patients.24-26 Stents were easily removed in each of these studies. Rarely, issues with stent fracture during retrieval were encountered. Recently, a newer version of this stent, the Alimaxx-ES stent, has been developed (Figure 1-4). In addition to the polyurethane covering, the stent has a silicone lining and antimigration struts. Additionally, this stent is available in smaller shaft diameters (12, 14, and 16 mm) than previously available stents. There are currently no published reports on the use of this stent in the treatment of refractory benign esophageal strictures. The fully covered Wallflex stent is also available (Figure 1-5); however, there are no published reports at this time on the use of this stent in the treatment of refractory benign esophageal strictures.

8

Chapter 1

Figure 1-6. Fluoroscopic image of a fully covered Wallflex stent in good position following placement in a patient with a long segment refractory benign esophageal stricture.

Figure 1-7. Same patient as Figure 1-6 showing distal migration of the stent several weeks following deployment.

Comparisons of Self-Expanding Plastic Versus Metal Stents for Benign Refractory Strictures When comparing SEPS and FCSEMS for the treatment of benign refractory esophageal strictures, they are comparable with regard to migration rates and rates of clinical success/dysphagia relief. Migration rates for SEPS range from 6.6% to 80%. Migration rates for FCSEMS range from 36% to 50% (Figures 1-6 and 1-7). Clinical success rates for SEPS range from 6% to 90%. Clinical success rates for FCSEMS range from 21% to 100% (Tables 1-3 and 1-4). A meta-analysis by Thomas et al reviewed 8 studies with a total of 199 patients treated with self-expanding removable stents (Polyflex and nitinol SEMS) for benign

Esophageal Stents in Benign Disease

9

Table 1-3. Studies of Self-Expanding Plastic Stents (Polyflex Stent) for Benign Esophageal Strictures Study

N (patients)

Oh et al19

Migration Rate

Clinical Success

13

30%

8 (benign) 11 (anastomotic)

81% (benign) 75% (anastomotic)

Dua et al17

40

22%

40%

Karbowski et al40

19

30%

90%

Evrard et al16

17

57%

80%

Repici et al15

15

6.6%

80%

Holm et

al18

23% 6% (overall)

Table 1-4. Studies of Fully Covered Self-Expanding Metal Stents and Refractory Benign Strictures Study

N

Stent Type

Migration Rate

Clinical Success

Eloubeidi et al26

19

Alimaxx-E

37%

21%

Senousy et al25

14

Alimaxx-E

39%

100%

7

Alimaxx-E

50%

71%

7

Alimaxx-E

36%

29%

Bakken et

al24

Eloubeidi et

al23

esophageal strictures. The overall efficacy of self-expanding removable stents was 46.2% with a migration rate of 26.4%.27 Comparison of dysphagia improvement for Polyflex stents versus nitinol stents in this study favored Polyflex stents (55.3% versus 21.8%, p = 0.019). It should be noted that 6 of the 8 studies in this analysis were studies in which the Polyflex stent was used, and none of the studies involving nitinol stents included recent data on FCSEMS.

Biodegradable Stents Biodegradable stents have recently been developed for use in the management of benign esophageal strictures. The ELLA Biodegradable Stent (ELLA-CS, Hradec Kralove, Czech Republic) is made of a biodegradable polymer, polydioxanone, that dissolves and is reabsorbed within 2 to 3 months after deployment. The stent itself is radiotransparent and has radio-opaque markers at both ends. The stent has a shaft diameter of 25 mm and ranges in length from 6 to 13.5 cm. The stent is loaded onto a 9-mm delivery catheter with a dilator tip.

10

Chapter 1

A recent study using the ELLA Biodegradable Stent in 21 patients with refractory benign esophageal strictures was notable for a significant decrease between pre- and poststenting dysphagia scores (3 versus 1, p < 0.01) at a median of 53 weeks follow up. Forty-five percent of patients in this study were dysphagia-free at the end of this study. A lower migration rate was seen with this stent (9.5%) when compared to previously published data for SEPS and FCSEMS. No major complications occurred; however, 3 patients were noted to have severe chest pain postprocedure and 1 patient was noted to have minor bleeding postprocedure. More data are needed regarding this stent before it can be recommended for widespread clinical use in patients with refractory benign esophageal strictures.28

Technical Considerations for Placement of Esophageal Stents for Refractory Benign Esophageal Strictures As part of the preprocedure evaluation for patients being considered for esophageal stent placement, one should confirm that the patient truly has a refractory benign stricture and that adequate dilation therapy has been attempted, possibly including appropriate adjunctive therapies to dilation, such as intralesional corticosteroid injection. Endoscopic measurements of the luminal diameter and the location of the proximal and distal aspects of the stricture should be noted to gain a sense of the stricture’s length and degree of complexity. If the luminal diameter is narrower than the stent delivery catheter, then appropriate esophageal dilation should be performed prior to stent deployment. Ideally, the proximal aspect of a stent should be 2 to 3 cm distal to the upper esophageal sphincter to avoid issues of airway compromise, but this is not always possible. In patients where accurate measurements are not available, a barium esophagram can sometimes be helpful in delineating the stricture prior to therapy. The location of the distal aspect of the stricture in relation to the gastroesophageal (GE) junction should also be noted. As increased rates of migration are seen with stents that traverse the GE junction, a larger diameter stent should be considered for distal strictures. The patient should be properly positioned for fluoroscopy for stent placement. Orienting the patient supine can make fluoroscopic imaging easier. Fluoroscopic marking of the proximal and distal aspects of the stricture along with the upper esophageal and lower esophageal sphincter can be made on scope withdrawal with a guidewire in place by external placement of paper clips affixed to the patient’s skin with tape (Figure 1-8). Alternative approaches include recognition of nearby anatomic landmarks (ribs, vertebral bodies, etc) to denote the proximal and distal end of the stricture, injection of fluoroscopically visible solutions such as lipiodiol, or endoscopic placement of clips at the proximal and distal aspects of the stricture. Esophageal stent deployment is typically performed under fluoroscopic guidance, allowing visualization of the stent deployment in real time. While a stent can be deployed under endoscopic guidance, endoscopic visualization alone does not allow for visualization of the distal deployment of the stent. Alternatively, a stent can be deployed under simultaneous endoscopic and fluoroscopic guidance. Simultaneous endoscopic and fluoroscopic guidance during deployment may not add much to the overall visualization over fluoroscopy alone, but in some situations this can be helpful. Gentle

Esophageal Stents in Benign Disease

11 Figure 1-8. Fluoroscopic marking of the desired proximal end of a SEPS via the use of an external marker, in this case, a paper clip.

neck extension can facilitate passage of the stent delivery system. This is particularly true for the Polyflex stent, which has a larger and stiffer delivery catheter. Careful and steady communication between the endoscopist and assistant is critical during stent deployment to ensure proper placement of the stent. Once the stent is deployed, the endoscope is typically reintroduced to confirm positioning of the stent and repositioning can be performed if needed. Patients typically experience pain after stent deployment (so common is this finding that some do not consider this to be a “complication” as much as an expected “side effect”). This is particularly true for Polyflex stent placement and usually subsides within 72 hours of placement. With Polyflex stent placement, it is our practice to admit patients for postprocedure observation and to receive adequate analgesia with subsequent discharge the following day. If a patient develops signs of airway obstruction or stridor, intra- or postprocedurally, the stent should be removed immediately if possible or an airway stent should be placed simultaneously to esophageal stent placement. For patients with distal strictures, worsening heartburn and other GERD symptoms may be seen, and these patients are maintained on PPI therapy. Of note, newer stents are being designed with antireflux valves to address this issue. Stents that are placed for benign indications are typically removed 4 to 6 weeks following initial placement. We often obtain a chest x-ray prior to removal to confirm the presence and position of the stent. If the stricture appears to have improved/resolved on subsequent endoscopic evaluation, the patient is given a trial of “stent-free” existence. For patients who continue to have persistence of their stricture, the stent can be replaced and possibly upsized if appropriate. Patients are advised to seek medical attention if they develop chest pain, fever, or worsening dysphagia.

12

Chapter 1

Figure 1-9. Endoscopic image of a representative benign tracheoesophageal fistula. Note the endotracheal tube visible through the esophageal lumen.

ESOPHAGEAL STENTS FOR BENIGN ESOPHAGEAL PERFORATIONS, LEAKS, AND FISTULAE Esophageal stents have been used in the treatment of benign esophageal perforations, leaks, and fistulae and have been investigated as an alternative to surgery in appropriately selected patients (Figure 1-9). Much of the esophageal stents data for these indications comes from retrospective case series because prospective and/or randomized studies in this patient population are difficult to accomplish (Table 1-5). The features and technical specifications of several widely available stents described in this chapter are listed in Table 1-6.

Esophageal Perforation Traumatic esophageal perforation is a serious injury with high morbidity and mortality if untreated. Perforation of the esophagus is most common after instrumentation or surgery (iatrogenic perforation) but can also occur spontaneously in the setting of vomiting with severe retching (Boerhaave’s syndrome). Conservative management in this setting includes keeping patient nothing by mouth (NPO), treatment with intravenous antibiotics, nasogastric tube placement to divert secretions, and mediastinal drainage when an esophageal leak is detected. Patients with a free perforation may require surgical management with primary esophageal repair or esophagectomy. Septic complications from fluid collections outside of the esophageal lumen are the most common cause of morbidity and mortality. Primary surgical closure with mediastinal drainage within 24 hours of the injury has been shown to improve survival.29 Surgery still carries high morbidity and mortality, particularly in patients with mediastinal contamination.

PCSEMS

SEPS, PCSEMS, FCSEMS

FCSEMS

SEPS, PCSEMS, FCSEMS

Van Heel et al34

Swinnen et al38

Van Boeckel et al39

SEPS

Freeman et

Siersema et al33

SEPS

al32

Freeman et

SEPS

Stent Type

al31

Hunerbein et al35

Study

297

88

33

11

19

17

9

N

85%

77.6%

97%

100%

89%

94%

89%

Initial Sealing of Leak

59%

47.7%

100%

100%

47%

35%

100%

Pts. Requiring Mediastinal Drainage

25%

14%

30%

18%

21%

18%

22%

Pts. Requiring Endoscopic Reintervention

13%

8%

12%

9%

2%

6%

0%

Pts. Requiring Surgical Reintervention

Table 1-5. Studies Evaluating Esophageal Stents for Treatment of Benign Perforations and Leaks

7 weeks

12 weeks

5 weeks

7 weeks

3 weeks

7 weeks

4 weeks

Stent Dwell Time

13%

6.8%

13%

0%

0%

0%

0%

Mortality

Esophageal Stents in Benign Disease 13

Boston Scientific

Boston Scientific

Boston Scientific

Merit Endotek

Merit Endotek

Boston Scientific

Wallflex

Ultraflex

Alimaxx-E

Alimaxx-ES

Wallflex

Manufacturer

Polyflex

Stent

Nitinol

Nitinol

Nitinol

Nitinol

Nitinol

Polyester

Material

10/12/15

7/10/12

7/10/12

10/12/15

10/12/15

9/12/15

Length (cm)

25/18/23 28/23/28

17/12/15 19/14/17 21/16/19 23/18/21 27/22/25

23/18/21 27/22/25

23/18/23 28/23/28

25/18/23 28/23/28

20/16/16 23/18/18 28/21/21

Diameter Proximal Flare/Shaft/Distal Flare (mm)

Covered (Permalume silicone covering)

Covered (Polyurethane covering and silicone inner lining)

Covered (Polyurethane)

Partially covered (Permalume silicone covering)

Partially covered (Permalume silicone covering)

Covered (Silicone)

Covering

6.2

7.4

7.4

6.2

6.2

12 to 4

Delivery System Diameter (mm)

Table 1-6. Features of Widely Available Self-Expanding Plastic Stents, Partially Covered Self-Expanding Metal Stents, and Fully Covered Self-Expanding Metal Stents

14 Chapter 10

Esophageal Stents in Benign Disease

15

Nonoperative management of benign esophageal perforations and leaks using endoscopic therapy has been studied as a potential treatment strategy. Limited data are available on the use of endoscopically placed clips and injection of gluing agents in this setting.30 Increasing data are available on the use of retrievable esophageal stents in patients with benign esophageal perforations and leaks and have demonstrated promising results.

Self-Expanding Plastic Stents and Esophageal Perforation In a prospective study of 17 patients with iatrogenic esophageal perforations treated with Polyflex stents, leak occlusion was achieved in 94%. Fourteen of 17 patients (82%) were able to initiate oral nutrition within 72 hours of stent placement in this study, and 1/17 patients (6%) experienced a continued leak requiring operative repair. All stents were removed (at a mean of 52 days after initial placement), and the average length of hospital stay for patients in this study was 8 days.31 In another prospective study of 19 patients with benign spontaneous esophageal perforations treated with Polyflex stents, leak occlusion was noted in 89% of patients, ability to initiate oral nutrition was noted in 79% of patients, and stent migration was noted in 21% of patients. Stents were removed at a mean of 20 days and mean length of hospital stay in this study was 9 days.32

Self-Expanding Metal Stents and Benign Esophageal Perforation In an early study of 11 patients with esophageal perforation (from causes including Boerhaave’s syndrome, postsurgical fistulae in patients following epiphrenic diverticula repair, and perforation occurring postpneumatic dilation for achalasia) treated with PCSEMS (4 patients with the Ultraflex stent and 7 patients with the Flamingo Wallstent [Boston Scientific]), 10/11 patients (91%) demonstrated complete sealing of their perforations. Two of 11 patients (18%) eventually required surgery due to either incomplete sealing of their perforation or incomplete drainage of the pleural cavity. The remaining 9 patients (82%) in this study recovered uneventfully and were able to resume a normal diet within 7 to 18 days. Median time to stent insertion was 60 days and median time to stent retrieval was 7 weeks.33 In another study of 33 patients with benign esophageal perforations (19 iatrogenic, 10 Boerhaave’s, and 4 other), 32 (97%) patients were noted to have complete sealing of their perforations with placement of removable esophageal stents. Seventy percent of the stents used in this study were partially covered Ultraflex stents. Ninety-day mortality in this study was 15%. Recurrent leakage was seen in 36% of patients requiring placement of additional stents. Three (9%) patients in this study failed stent therapy and underwent esophageal resection. The median dwell time for stent placement was 5 weeks and extraction related complications were associated with leaving in stents for greater than 6 weeks.34

Esophageal Stents for Postesophagectomy Leaks In patients with postesophagectomy anastomotic leaks, there are case series data supporting the use of the Polyflex stent. In one series of 19 patients with anastomotic leaks after esophagectomy (10 patients treated with surgical re-exploration and 9 patients receiving large-diameter SEPS) a median of 8 days after initial surgery, leak occlusion was

16

Chapter 1

seen in 8/9 (89%) of patients who received SEPS. Initiation of oral intake in patients treated with SEPS was earlier (11 days) when compared to patients treated with conservative management (18 days). None of the patients receiving stents in this study required surgical re-exploration via thoracotomy. Mean time to stent removal was 4 weeks, and stent placement led to a shorter hospital stay.35 In another case series of 12 patients with esophageal anastomotic leaks (ranging from 20% to 70% of the esophageal wall circumference) who were treated with large diameter SEPS, complete leak closure was seen in 91.6% of patients. The one patient in this study who had a persistent leak after stent removal was treated with successful placement of 3 endoscopic clips to close the residual defect. None of the patients in this study required surgical re-exploration.36

Esophageal Stents in the Treatment of Benign Tracheoesophageal Fistulae Limited data are available on the use of esophageal stents for the treatment of benign tracheoesophageal fistulae. In one study of 12 mechanically ventilated patients with postintubation tracheoesophageal fistulae, treatment with PCSEMS was associated with successful fistula closure in all patients. No stent migration was observed. It should be noted that 9/12 patients in this study died of their underlying primary disease.37

Partially Covered Self-Expanding Metal Stents for Benign Upper Gastrointestinal Perforations, Leaks, and Fistulae In a study of 88 patients with benign upper gastrointestinal perforations and leaks treated with the Ultraflex stent (including patients with postbariatric surgery leaks, other postoperative fistulae, Boerhaave’s syndrome, and iatrogenic perforations), initial resolution of perforations and leaks was seen in 77.6% of patients, and 84.2% of patients had leak closure after repeated endoscopic intervention. Endoscopic reintervention was required in 14% of patients and surgical reintervention was required in 8% of patients. The stent migration rate was 11.1% and the major complication rate (bleeding, perforation, tracheal compression) was 5%. Stent removal was successful in 96.1% and was facilitated by the placement of a Polyflex stent within a previously placed Ultraflex stent in 78.9% of patients.38

Systematic Review of Esophageal Stents for Benign Perforations, Leaks, and Fistulae In a review of 25 studies and 267 patients treated with esophageal stents (SEPS or SEMS) for benign esophageal perforations and leaks, leak closure was achieved in 85% of patients; time to stent placement ranged from 4 to 16 days, and mean stent dwell time was 7 weeks. The most common indication for stent placement was anastomotic leak (51%) followed by postendoscopic perforation (25%), Boerhaave’s syndrome (17%), tracheoesophageal fistula (4%), and other indications (3%). In this study, 13% of patients eventually needed surgery, and there was a significantly increased need for endoscopic reintervention in patients who were treated with SEPS versus PCSEMS (26% versus 13%, p < 0.001). Concurrent drainage of mediastinal fluid collections was performed in 59% of patients. Overall mortality was 13%, with septic complications from abscess formation being the most common cause of death. Major stent-related complications occurred in 3% of patients with 2 stent-related deaths.39

Esophageal Stents in Benign Disease

17

Technical Considerations for Placement of Esophageal Stents for Treatment of Benign Perforations, Leaks, and Fistulae The approach to stenting benign esophageal perforations, leaks, and fistulae takes into consideration the timing of the injury, the size of the defect, and comorbidities of the patient. Since many leaks will spontaneously close, the authors recommend confirming the presence of a leak before considering any intervention. While plain films (chest x-ray and/or soft-tissue x-rays of the neck) may show pneumomediastinum and/or subcutaneous emphysema, they cannot demonstrate the presence and/or severity of an active leak. Contrast studies (computed tomography [CT] chest or Gastrografin swallow) are necessary to identify the presence of a leak. If CT or Gastrografin swallow does not demonstrate convincing evidence of leakage of contrast, then one can conservatively manage the patient with NPO status and intravenous antibiotics. A contrast study can be repeated in 72 hours and if there is still no evidence of contrast leakage, one can gently advance the patient to oral intake. If contrast studies demonstrate leakage of contrast, the patient should be kept NPO, treated with intravenous antibiotics, and surgical consultation should be obtained to pursue a mediastinal drainage procedure. If the injury is above the pyriform sinuses, otolaryngology/ear-nose-throat consultation is appropriate; if the injury is below the pyriform sinuses, then thoracic surgical consultation is appropriate. If a patient is a poor operative candidate or the leak is recognized after more than 24 hours, a discussion with the appropriate surgical consultant should take place prior to making a decision to place a stent. When placing a stent for treatment of an esophageal perforation, the location of the defect should be confirmed endoscopically. If the location of the defect can be confirmed endoscopically, some endoscopists would mark the site, either with external fluoroscopically visible markers or by endoscopic clip placement at the leak site. Large caliber SEPS or FCSEMS can be deployed under fluoroscopic guidance. One can inject contrast under fluoroscopic visualization immediately after stent deployment to confirm occlusion of the perforation/leak. The stent may stay in for approximately 4 to 6 weeks (the exact optimal length of time is unknown), at which time stent removal should be performed followed by a contrast study to confirm healing of the leak. If the leak persists after removal, then one may consider stent replacement or surgical intervention. Similar principles can be applied for benign esophageal fistula. It is not uncommon for stents to become embedded within hyperplastic granulation tissue, which can make stent removal challenging. Placement of the same diameter SEPS or FCSEMS within the embedded stent can induce pressure necrosis of hyperplastic granulation tissue and both stents can be removed more easily within 7 to 14 days.38,39

CONCLUSION The role of esophageal stents in the treatment of benign esophageal disease continues to evolve. When contemplating the placement of SEPS, PCSEMS, and/or FCSEMS for benign esophageal disease, careful patient selection is crucial. Currently designed stents are limited by relatively high migration rates and variable clinical efficacy in the treatment of refractory benign esophageal strictures. The data for retrievable esophageal stents as an alternative to operative management of benign esophageal perforations, leaks, and fistulae

18

Chapter 1

are promising. However, these patients still have a relatively high morbidity and mortality, and a multidisciplinary approach is often required when managing these patients. More data are still necessary before esophageal stents can be recommended for widespread use for the treatment of benign esophageal disease.

REFERENCES 1.

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11. 12. 13. 14. 15.

16. 17.

18. 19. 20.

Knyrim K, Wagner H-J, Bethge N, Keymling M, Vakil N. A controlled trial of an expansile metal stent for palliation of esophageal obstruction due to inoperable cancer. N Engl J Med. 1993;329(18):1302-1307. Sharma P, Kozarek R. Role of esophageal stents in benign and malignant diseases. Am J Gastroenterol. 2009;105(2):258-273. Dakkak M HR, Maslin SC, Bennett JR. Oesophagitis is as important as oesophageal stricture diameter in determining dysphagia. Gut. 1993;34(2):152-155. Lew RJ, Kochman ML. A review of endoscopic methods of esophageal dilation. J Clin Gastroenterol. 2002;35(2):117-126. Pereira-Lima JC, Ramires RP, Zamin I, Cassal AP, Marroni CA, Mattos AA. Endoscopic dilation of benign esophageal strictures: report on 1043 procedures. Am J Gastroenterol. 1999;94(6):1497-1501. Hernandez LV, Jacobson JW, Harris MS. Comparison among the perforation rates of Maloney, balloon, and savary dilation of esophageal strictures. Gastrointest Endosc. 2000;51(4 Pt 1): 460-462. Silvis SE, Nebel O, Rogers G, Sugawa C, Mandelstam P. Endoscopic complications. Results of the 1974 American Society for Gastrointestinal Endoscopy Survey. JAMA. 1976;235(9):928-930. Scolapio JS, Pasha TM, Gostout CJ, et al. A randomized prospective study comparing rigid to balloon dilators for benign esophageal strictures and rings. Gastrointest Endosc. 1999;50(1):13-17. Kochman ML, McClave SA, Boyce HW. The refractory and the recurrent esophageal stricture: a definition. Gastrointest Endosc. 2005;62(3):474-475. Ramage JI, Rumalla A, Baron TH, et al. A prospective, randomized, double-blind, placebocontrolled trial of endoscopic steroid injection therapy for recalcitrant esophageal peptic strictures. Am J Gastroenterol. 2005;100(11):2419-2425. DiSario JA PP, Bichi¸s-Canoutas C, Alder SC, Fang JC. Incision of recurrent distal esophageal (Schatzki) ring after dilation. Gastrointest Endosc. 2002;56(2):244-248. Hordijk ML SP, Tilanus HW, Kuipers EJ. Electrocautery therapy for refractory anastomotic strictures of the esophagus. Gastrointest Endosc. 2006;63(1):157-163. Dzeletovic I, Fleischer DE. Self-dilation for resistant, benign esophageal strictures. Am J Gastroenterol. 2010;105(10):2142-2143. Wong R, Adler D, Hilden K, Fang J. Retrievable esophageal stents for benign indications. Dig Dis Sci. 2008;53(2):322-329. Repici A CM, De Angelis C, Battaglia E, et al. Temporary placement of an expandable polyester silicone-covered stent for treatment of refractory benign esophageal strictures. Gastrointest Endosc. 2004 Oct;60(4):513-519. Evrard S, Le Moine O, Lazaraki G, Dormann A, El Nakadi I, Devière J. Self-expanding plastic stents for benign esophageal lesions. Gastrointest Endosc. 2004;60(6):894-900. Dua KS, Vleggaar FP, Santharam R, Siersema PD. Removable self-expanding plastic esophageal stent as a continuous, non-permanent dilator in treating refractory benign esophageal strictures: a prospective two-center study. Am J Gastroenterol. 2008;103(12):2988-2994. Holm AN, de la Mora Levy J, Gostout CJ, Topazian MD, Baron TH. Self-expanding plastic stents in treatment of benign esophageal conditions. Gastrointest Endosc. 2008 67(1):20-25. Oh Y, Kochman M, Ahmad N, Ginsberg G. Clinical outcomes after self-expanding plastic stent placement for refractory benign esophageal strictures. Dig Dis Sci. 2010;55(5):1344-1348. Repici A HC, Sharma P, Conio M, Siersema P. Systematic review: the role of self-expanding plastic stents for benign oesophageal strictures. Aliment Pharmacol Ther. 2010;31(12): 1268-1275.

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21. Wadhwa RP, Kozarek RA, France RE, et al. Use of self-expandable metallic stents in benign GI diseases. Gastrointest Endosc. 2003;58(2):207-212. 22. Sandha GS, Marcon N. Expandable metal stents for benign esophageal obstruction. Gastrointest Endosc Clin N Am. 1999;9(3):437-446. 23. Eloubeidi MA, Lopes TL. Novel removable internally fully covered self-expanding metal esophageal stent: feasibility, technique of removal, and tissue response in humans. Am J Gastroenterol. 2009;104(6):1374-1381. 24. Bakken JC, Wong Kee Song L, de Groen PC, Baron TH. Use of a fully covered selfexpandable metal stent for the treatment of benign esophageal diseases. Gastrointest Endosc. 2010;72(4):712-720. 25. Senousy B, Gupte A, Draganov P, Forsmark C, Wagh M. Fully covered Alimaxx esophageal metal stents in the endoscopic treatment of benign esophageal siseases. Dig Dis Sci. 2010;55(12):3399-3403. 26. Eloubeidi MA, Talreja JP, Lopes TL, Al-Awabdy BS, Shami VM, Kahaleh M. Success and complications associated with placement of fully covered removable self-expandable metal stents for benign esophageal diseases (with videos). Gastrointest Endosc. 2011;73(4): 673-681. 27. Thomas T, Abrams KR, Subramanian V, Mannath J, Ragunath K. Esophageal stents for benign refractory strictures: a meta-analysis. Endoscopy. 2011;43:386,393. 28. Repici A VF, Hassan C, van Boeckel PG, et al. Efficacy and safety of biodegradable stents for refractory benign esophageal strictures: the BEST (biodegradable esophageal stent) study. Gastrointest Endosc. 2010;72(5):927-934. 29. Zwischenberger JB, Savage C, Bidani A. Surgical aspects of esophageal disease. Perforation and caustic injury. Am J Respir Crit Care Med. 2002;165(8):1037-1040. 30. Fischer A, Schrag HJ, Goos M, von Dobschuetz E, Hopt UT. Nonoperative treatment of four esophageal perforations with hemostatic clips. Dis Esophagus. 2007;20(5):444-448. 31. Freeman RK, Van Woerkom JM, Ascioti AJ. Esophageal stent placement for the treatment of iatrogenic intrathoracic esophageal perforation. Ann Thoracic Surg. 2007;83(6): 2003-2008. 32. Freeman RK, Van Woerkom JM, Vyverberg A, Ascioti AJ. Esophageal stent placement for the treatment of spontaneous esophageal perforations. Ann Thoracic Surg. 2009;88(1): 194-198. 33. Siersema PD, Homs MY, Haringsma J, Tilanus HW, Kuipers EJ. Use of large-diameter metallic stents to seal traumatic nonmalignant perforations of the esophagus. Gastrointest Endosc. 2003;58(3):356-361. 34. van Heel NCM, Haringsma J, Spaander MCW, Bruno MJ, Kuipers EJ. Short-term esophageal stenting in the management of benign perforations. Am J Gastroenterol. 2010;105(7): 1515-1520. 35. Hünerbein M, Stroszczynski C, Moesta KT, Schlag PM. Treatment of thoracic anastomotic leaks after esophagectomy with self-expanding plastic stents. Ann Surg. 2004;240(5): 801-807. 36. Schubert D, Scheidbach H, Kuhn R, et al. Endoscopic treatment of thoracic esophageal anastomotic leaks by using silicone-covered, self-expanding polyester stents. Gastrointest Endosc. 2005;61(7):891-896. 37. Eleftheriadis E, Kotzampassi K. Temporary stenting of acquired benign tracheoesophageal fistulas in critically ill ventilated patients. Surg Endoscopy. 2005;19(6):811-815. 38. Swinnen J EP, Rigaux J, Kahegeshe L, Lemmers A, Le Moine O, Devière J. Self-expandable metal stents for the treatment of benign upper GI leaks and perforations. Gastrointest Endosc. 2011;73(5):890-899. 39. van Boeckel PG, Sijbring A, Vleggaar FP, Siersema PD. Systematic review: temporary stent placement for benign rupture or anastomotic leak of the oesophagus. Aliment Pharmacol Ther. 2011;33(12):1292-1301. 40. Karbowski M, Schembre D, Kozarek R, Ayub K, Low D. Polyflex self-expanding, removable plastic stents: assessment of treatment efficacy and safety in a variety of benign and malignant conditions of the esophagus. Surg Endosc. 2008;22(5):1326-1333.

2

Esophageal Stents in Preoperative Esophageal Cancer Patients Kathryn R. Byrne, MD; John C. Fang, MD; and Douglas G. Adler, MD, FACG, AGAF, FASGE

The management of esophageal cancer patients with dysphagia presents many unique problems. Patients may already have malnutrition secondary to their catabolic state from malignancy and then patients with esophageal cancer also have further weight loss caused by malignant dysphagia from their obstructing tumor. Locally advanced cancer is extremely common at the time of presentation (Figure 2-1). The decision of which patients receive preoperative (neoadjuvant) therapy is somewhat dependent on the institution at which they receive treatment; however, most patients with locally advanced disease will receive neoadjuvant chemotherapy and radiation. The timeframe of neoadjuvant therapy typically lasts 2 to 3 months, creating a significant amount of time in which patients with malignant dysphagia will need supplemental nutritional support in an attempt to arrest or reverse weight loss. Options for nutrition include nasoenteric feeding tubes, percutaneous gastrostomy or jejunostomy tubes, total parenteral nutrition (TPN), or oral feeding assisted by placement of an esophageal stent. The use of nutritional support during the neoadjuvant timeframe is important in improving postsurgical outcomes. Numerous studies have demonstrated that malnourished patients are more likely to have perioperative complications and poor outcomes.1-3 Nutritional support is particularly important during the neoadjuvant period since patients may develop radiation-induced dysphagia, which can further worsen their difficulty with swallowing and further impede oral intake. This chapter will provide an overall review of treatments for patients with malignant dysphagia in the preoperative setting with an emphasis on the role of self-expanding stents.

- 21 -

Adler DG, ed. Self-Expanding Stents in Gastrointestinal Endoscopy (pp 21-34). © 2012 SLACK Incorporated.

22

Chapter 2

Figure 2-1. (A) Endoscopic image of a A large, partially obstructing esophageal adenocarcinoma in a patient with dysphagia. (B) 7.5 MHz endoscopic ultrasound image of the same mass as in A showing tumor invasion to the adventitia (arrow), concordant with T3 disease. The patient is thus a candidate for neoadjuvant therapy.

B

NONSTENT OPTIONS IN PREOPERATIVE PATIENTS WITH DYSPHAGIA Chemoradiation therapy has been demonstrated to reduce tumor size and improve symptoms of dysphagia in approximately 50% of esophageal cancer patients.4,5 As this improvement in dysphagia may take many weeks, there is often a need for supplemental nutrition during this timeframe in an attempt to arrest weight loss or even allow weight gain. In addition to dysphagia being caused by the tumor itself, therapy with radiation may also cause esophagitis that also contributes to dysphagia and odynophagia. There are multiple options to consider for nutritional supplementation during neoadjuvant therapy including TPN, enteral feeding via a Dobhoff tube, percutaneous endoscopic gastrostomy (PEG), surgically placed jejunal (J) tube, and esophageal stenting (with a variety of stents from which to choose). In general, enteral feeding is preferred if at all possible and TPN avoided with higher rates of infectious and other complications, higher cost, and longer length of hospital stay in patients with TPN.6-10 Dobhoff tubes represent a simple method of providing enteral nutrition and are safe and inexpensive. Downsides include discomfort, embarrassment, and the lack of oral food intake. In addition, the smaller diameter tubes often become clogged or migrate,

Esophageal Stents in Preoperative Esophageal Cancer Patients

23

requiring frequent replacement. Although technically successful in almost all esophageal cancer patients, PEG tube placement should be considered carefully and in conjunction with the surgical oncologist in preoperative patients. PEG tubes will fix the stomach to the anterior abdominal wall, which could potentially interfere with the use of the stomach as a conduit after esophagectomy.11,12 More importantly, PEG placement may compromise the vascular supply to the stomach, endangering its use later as the conduit after esophagectomy. The mainstay of enteral access tubes in this patient population has been surgically placed J tubes. The advantage of a J tube over a PEG tube is the avoidance of potential adhesion of the stomach with its attendant surgical complications during esophagectomy. The disadvantages include the need for surgical placement and the potential for delay of initiation of chemotherapy. In addition, radiologic and endoscopic percutaneous jejunostomy are not widely available. Oncologists often wait 1 to 2 weeks after J-tube placement to initiate chemotherapy to allow time for healing of local inflammation at the insertion site. Although surgically placed J tubes have few major complications, there are several common minor complications. A study of 43 patients with esophageal cancer undergoing surgical J-tube placement had tube dislodgement in 20% of patients and tube blockage in 13% of patients.13

STENTS IN PREOPERATIVE PATIENTS Esophageal stents in the neoadjuvant setting provide the unique advantage over the other options for nutritional supplementation in that they allow patients to have an oral diet. Self-expanding stent placement is almost always successful and leads to rapid improvement in dysphagia symptoms usually within days. Malignant dysphagia is typically graded on a scale from 0 to 4 as follows14 : 0 = No dysphagia 1 = Dysphagia to normal solids 2 = Dysphagia to soft solids 3 = Dysphagia to solids and liquids 4 = Inability to swallow saliva Multiple studies have demonstrated significant improvement in dysphagia in patients after esophageal stent placement.15

TIMING AND TECHNIQUE OF STENT PLACEMENT Esophageal stent placement can be performed once it has been determined that the patient has locally advanced disease and will require neoadjuvant therapy. Patients are classified as having locally advanced disease if they have tumor invasion through the muscularis propria (consistent with T3 disease) or local nodal disease (N1, N2, or N3 nodal involvement). Locoregional staging is most commonly performed via endoscopic ultrasound (EUS) but can be evaluated by computed tomography (CT) or CT/positron emission tomography (PET) scan as well.

24

Chapter 2

Figure 2-2. The Polyflex SEPS.

Stent placement can be performed at the same time as or after EUS staging. Stent placement should never be performed prior to EUS staging, because the ability to perform staging would be compromised. EUS staging followed by immediate esophageal stent placement in patients with locally advanced disease has been demonstrated to be safe and effective.15 In one prospective study, 13 patients with locally advanced esophageal cancer underwent stent placement immediately following EUS and had significant improvement in dysphagia scores 1 week postprocedure. This method of simultaneous EUS staging and stent placement minimizes the number of procedures for patients to undergo and allows immediate oral feeding.

PUBLISHED DATA ON SELF-EXPANDING ESOPHAGEAL STENTS Esophageal self-expanding stents are divided into two main types: self-expanding metal stents (SEMS) and self-expanding plastic stents (SEPS). There are multiple types of SEMS, including covered, partially covered, and uncovered. The outer material of SEMS is composed of either nitinol (nickel-titanium alloy) or stainless steel, with the covering composed of a silicone or polyurethane coating. The Polyflex stent (Boston Scientific, Natick, MA) is the only available plastic stent in the United States and is composed of a polyester mesh with silicone coating (Figure 2-2). The fully covered SEMS (FCSEMS) approved by the Food and Drug Administration (FDA) include Alimaxx-E (Merit Endotek, South Jordan, UT), Niti-S (Taewoong-Medical, Seoul, Korea), Wallflex (Boston Scientific), Hanarostent (M.I. Tech, Gyeonggi-do, Korea) (Figure 2-3), and Esophageal Z and Evolution (Wilson-Cook Medical, Winston-Salem, NC). Another FCSEMS that is not currently FDA approved is the Choostent (M.I. Tech). Partially covered stents include the Ultraflex (Boston Scientific) and Wallflex. Uncovered stents are no longer clinically used secondary to high rates of tumor ingrowth.

Self-Expanding Plastic Stents There have been several published studies that evaluate the Polyflex SEPS in the preoperative setting. This is partially due to the fact that this was the first fully covered esophageal stent that was made commercially available.

Esophageal Stents in Preoperative Esophageal Cancer Patients A

B

C

D

25

Figure 2-3. (A) The Alimaxx-E fully covered esophageal stent. (B) The Evolution fully covered esophageal stent. (C) The esophageal Wallflex fully covered esophageal stent. (D) The Hanarostent fully covered esophageal stent.

The Polyflex stent was evaluated for use in malignant esophageal strictures prior to neoadjuvant therapy in a pilot study involving 6 patients.16 The stent placement success rate was 83% (5/6 patients), with restoration of oral nutrition occurring in 100% of stented patients. There was distal stent migration in 3/5 (60%) patients. Another small study of just 5 patients evaluated the use of Polyflex stents in the preoperative setting demonstrated dysphagia relief in 100% of patients, with optimal calorie needs met within 24 hours of placement.17 There was only one case of migration in this small series, which was discovered at the time of surgery. A prospective study of 13 patients with Polyflex stent placement for locally advanced esophageal cancer prior to neoadjuvant therapy showed significant decrease in dysphagia scores after 1 week and no cases of perforation or bleeding.15 There were 6 cases (46%) of stent migration.

26

Chapter 2

It is believed that a significant contributor to stent migration in all of these studies is the tumor response to neoadjuvant therapy. The data overall suggest that stent migration in this setting can, somewhat paradoxically, be viewed as a positive finding, as it suggests tumor responsiveness to neoadjuvant therapy. One option is to schedule a patient for esophagogastroduodenoscopy (EGD) with stent removal during neoadjuvant therapy in an attempt to remove the stent before it migrates and at a time when the patient is likely to have concomitant treatment response, thus allowing the patient to transition to oral intake without the stent in place. Several studies have evaluated the efficacy of placing a Polyflex stent versus more traditional enteral feeding methods in patients with esophageal cancer undergoing neoadjuvant therapy. A retrospective study comparing the efficacy of Polyflex stents versus surgical jejunostomy tubes involving 36 total patients (12 Polyflex, 24 J tube) showed that Polyflex stent placement was an effective alternative for nutritional supplementation in esophageal cancer patients undergoing neoadjuvant chemoradiation therapy.18 Stent placement was successful in 92% of patients, and there was significant improvement in dysphagia scores. There were no significant differences in success rate, mean increase in patient weight, complication rates, or mean increase in patient albumin levels between the Polyflex group and the J-tube group. Another study comparing multiple modalities of providing nutrition during neoadjuvant therapy for esophageal cancer patients retrospectively compared the effectiveness of oral diet alone, enteral supplementation with a feeding tube, and placement of a Polyflex stent. Stent patients had a lower rate of interruption of chemoradiotherapy, less percentage of body weight loss, greater improvement in serum albumin levels, and lower rates of major operative complications.19 There was no mortality or major complications with stent placement.

Fully and Partially Covered Self-Expanding Metal Stents FCSEMS are advantageous for use in the neoadjuvant setting to facilitate stent removal either endoscopically or at the time of surgery. FCSEMS have the advantage of significantly decreased risk of tumor ingrowth, although they are more prone to migration than uncovered or partially covered SEMS (PCSEMS). PCSEMS balance issues with tumor ingrowth (common with fully uncovered stents) and migration (more common with fully covered stents) with the disadvantage of the possibility of tumor and tissue ingrowth of the uncovered portion (and the concern that the stent may not be removable once tumor ingrowth develops). Fully uncovered stents are no longer used clinically secondary to high rates of tumor ingrowth. A pilot study using FCSEMS in 11 patients prior to neoadjuvant therapy showed significant improvement in dysphagia scores at 1, 3, and 6 months after placement compared with baseline.20 Eight of the stents were ultimately removed: 1 from a complication (tracheoesophageal fistula), 1 from migration, 1 from incorrect deployment, and 5 that were deemed to have satisfied their purpose. All of the stents that were ultimately removed were characterized as “very easy” to remove. The methods used to remove the stents included a single rat-tooth forceps (3 cases), 2 forceps through a double-channel endoscope (3 cases), and forceps with snare (2 cases). Although a downside of using PCSEMS is the possibility of tumor and tissue ingrowth of the uncovered portion, there is a recently described stent-within-stent technique of removing PCSEMS that have become embedded in the esophageal wall. A fully covered

Esophageal Stents in Preoperative Esophageal Cancer Patients

27

stent (this can be either a SEPS or SEMS) is deployed within the lumen of the previously placed and embedded partially covered stent. Approximately 1 to 2 weeks later, both stents are then simultaneously removed endoscopically. The theory behind the success of the stent-within-stent technique is that the radial force created by the second stent causes pressure ischemia and then resulting necrosis on the ingrown tissue, which then allows both stents to be subsequently removed. In one study, a total of 23 stent-within-stent procedures were performed in 19 patients with the placement of a fully covered stent (9 SEPS, 14 SEMS) within the previously placed PCSEMS, then with subsequent removal of both stents.21 In 91% of the procedures (21/23 cases), both stents were able to be successfully removed in a single procedure after a median of 12 days (range from 5 to 18 days). Of the other 2 cases, one required a repeat stent-within-stent procedure and the other case was complicated by severe bleeding (that was able to be treated endoscopically).

Use of Self-Expanding Metal Versus Plastic Stents Numerous studies have been performed comparing the use of SEMS versus SEPS regarding improvement in dysphagia symptoms and complications in a palliative setting; however, there is much less data comparing SEMS versus SEPS during neoadjuvant therapy. The efficacy of esophageal stent placement for dysphagia relief in patients with locally advanced esophageal cancer in the neoadjuvant setting was performed in one study of 38 patients (13 patients received SEPS and 25 patients received SEMS).22 Of the patients who received SEMS, 10 were Niti-S (fully covered), 7 Ultraflex (partially covered), 5 Hanaro (fully covered), 2 Choo (fully covered), and 1 DoStent (M.I. Tech; fully covered). Both SEPS and SEMS were highly effective for immediate dysphagia relief with instant relief of symptoms in 37 of 38 (97.4%) patients. There were a total of 12 cases of stent migration (2 cases of immediate migration, 3 cases of early stent migration, and 7 cases of late stent migration during neoadjuvant therapy). There was no increased rate of stent migration with use of the SEPS compared with the covered SEMS (Ultraflex, Hanaro, or Niti-S).

COMPLICATIONS Complications from esophageal stent placement are generally divided into immediate, early, and delayed complications. Immediate complications include stent misdeployment, bleeding, airway compromise, esophageal perforation, and issues related to patient’s sedation. Early complications (within 7 to 10 days of stent placement) include chest pain, nausea/vomiting, bleeding, and sensation of a foreign body. Delayed complications (greater than 30 days after procedure) include tumor ingrowth, tumor overgrowth, stent migration, bleeding, perforation, tracheoesophageal fistula formation, and reflux. The rates of major complications of stent placement vary widely between studies. We will focus primarily on complications of esophageal stent placement in patients receiving neoadjuvant therapy in the preoperative setting.

Migration Stent migration is perhaps the most commonly encountered problem with covered devices, particularly in the setting of neoadjuvant therapy. As the tumor decreases in

28

Chapter 2 A

B

C

Figure 2-4. (A) Radiographic image of an esophageal stent (arrow) that has migrated into the stomach during neoadjuvant therapy for esophageal cancer. (B) Endoscopic image from same patient as in A showing stent in gastric body. (C) Stent shown in B following endoscopic removal with a rat-tooth forceps.

size with positive response to chemoradiation therapy, the stent is more prone to migrate as there is less of a stricture to help anchor the stent in the face of esophageal peristalsis and food passage. The lack of any uncovered stent struts further increases the chance of migration as the design of FCSEMS is inherently more prone to migration (Figure 2-4). There have been several studies showing esophageal stent migration rates in the setting of neoadjuvant therapy. In a prospective study of patients with locally advanced esophageal cancer undergoing neoadjuvant therapy, Polyflex stents were placed for treatment of malignant dysphagia in 13 patients.15 Six of the 13 (46%) Polyflex stents had distal migration. Five of these stents were removed from the stomach during EGD and 1 stent was removed at the time of surgery. In another report in 5 esophageal cancer patients preparing to undergo neoadjuvant therapy, Polyflex stents were placed for treatment of dysphagia.17 There was one case (20%) of stent migration. The stent

Esophageal Stents in Preoperative Esophageal Cancer Patients

29

Figure 2-5. Chest x-ray showing proximal stent migration. A Polyflex stent (arrow) has migrated proximally in a patient with esophageal adenocarcinoma at the esophagogastric junction. The stent was removed with a rat-tooth forceps.

migration was discovered at the time of the operation and was removed without complication. A larger study of 25 patients receiving Polyflex stents prior to neoadjuvant therapy had an overall migration rate of 24%.19 It was noted by the authors that most of the cases of migration were directly related to using a shorter (90 mm) and more narrow (16 mm) stent, and now they only use stents that are at least 120 mm in length and at least 18 mm in width in patients who will undergo neoadjuvant therapy. A recent prospective study evaluating SEPS placement for treatment of dysphagia in 32 patients undergoing neoadjuvant therapy had 8 cases (25%) of stent migration.23 Only two of these patients required stent replacement (Figure 2-5). There are several options to consider after discovering that an esophageal stent has distally migrated. The stent could be removed endoscopically prior to surgery or just left in place to be removed later at surgery. In patients with an intact pylorus, the stent is unlikely to migrate beyond the stomach (although very rarely this can occur). Stent removal is likely only indicated if the migrated stent is causing pain or pyloric obstruction. As demonstrated in several studies, distal stent migration to the stomach was discovered at the time of surgery and the stents were able to be removed without complication at that time.16,17 If the patient has undergone a previous Billroth I or Billroth II surgery, the stent may migrate distally. Stents that do migrate into the small bowel may pass spontaneously or lodge in the small bowel or colon. Stent migration can be asymptomatic or require endoscopic or surgical removal. Symptoms are generally the best indication for any interventions. Removal of a migrated stent from the stomach can at times be a straightforward and brief procedure or may develop into a protracted and difficult experience for both the endoscopist and the patient. In general, the procedure goes best if there is no significant ongoing esophageal stenosis. Most covered stents come with a “retrieval loop”—a suture that, when pulled, allows the proximal end of the stent to collapse in a purse-string manner. The retrieval loop can be grasped with a forceps (preferably a rat-tooth forceps) pulled through the gastroesophageal (GE) junction to the esophagus and out through the mouth. A snare may be used to grab the proximal end of the stent for removal as well. Some prefer

30

Chapter 2

to use double-channel endoscopes and grasp the device with multiple instruments, but there are no published data to advocate this approach over the use of standard endoscopes. It has been debated whether or not hemoclips should be placed with initial esophageal stent placement to attempt prevention of stent migration. A Korean study examined 38 total patients with SEMS placement for gastrointestinal malignancies and placed hemoclips to anchor the stents in one group and no hemoclips in the other.24 There were 0/19 cases of early stent migration in the hemoclip group and 5/19 (29%) early stent migrations in the nonclipping group.

Chest Pain Chest discomfort is a very common complication after esophageal stent placement. Pain may be either short lived or constant. The majority of the data involving chest pain after esophageal stent placement in the neoadjuvant setting have been reported with Polyflex stents. Twelve of 13 patients in a prospective study receiving Polyflex stents for dysphagia in locally advanced esophageal cancer prior to neoadjuvant therapy had chest discomfort after stent placement.15 The chest pain severity did not correlate with size or location of the stents. Although the chest discomfort was graded as mild to moderate in most of the patients, one patient did have severe postprocedure pain and required hospital admission for analgesic pain control. One patient in another study placing Polyflex stents for nutritional support during neoadjuvant therapy experienced pain from esophageal spasm requiring hospital admission 2 days after stent placement.19 According to the authors, the pain resolved within 24 hours with administration of calcium channel blockers and oral analgesics. Another study that involved placing Polyflex stents for dysphagia prior to neoadjuvant therapy showed 8 out of 12 (67%) patients experienced mild to moderate chest pain immediately after stent deployment.18 The authors report the pain was treated with analgesics and relieved within 1 to 2 days in all cases. In contrast to the above studies, a recent prospective study evaluating SEPS placement for treatment of dysphagia in 32 patients undergoing neoadjuvant therapy only reported chest pain as a complication in 2 (6.3%) patients.23 In a pilot study of 11 patients treated with FCSEMS prior to neoadjuvant therapy, 3 (27%) patients experienced chest pain immediately after stent deployment.20 These patients were all admitted for observation with a range of hospital stay from 1 to 4 days (mean of 2 days).

Tumor Ingrowth/Overgrowth Although tumor ingrowth and overgrowth is a common problem with esophageal stents used in the palliative setting for esophageal cancer, it is much less of an issue in the neoadjuvant setting as the stent is in place for a much shorter duration. There was 1 (8%) case of tumor overgrowth among 13 patients treated with Polyflex stents for malignant dysphagia prior to neoadjuvant therapy.15 In most cases, tissue ingrowth or overgrowth can be treated with additional stent placement or less commonly by using argon plasma coagulation.

Esophageal Perforation Esophageal perforation is a rare complication following esophageal stent placement. Several studies have shown that overall complications, including perforation, are more common in patients who have previously received chemotherapy or radiation therapy

Esophageal Stents in Preoperative Esophageal Cancer Patients

31

prior to having an esophageal stent placed, although this tends to reflect older data and may be less true with current neoadjuvant therapy protocols.25 Perforation appears to be a very rare complication of esophageal stent placement in patients receiving a stent for malignant dysphagia prior to the initiation of neoadjuvant therapy. Numerous studies involving placement of esophageal stents (both SEPS and SEMS) prior to neoadjuvant therapy did not report any cases of esophageal perforation as either an immediate or a late complication.15,16,18-20,23

Bleeding Bleeding can also occur after esophageal stent placement, especially in patients who develop nausea with vomiting or retching. This can cause superficial mucosal trauma/ maceration of the tumor. This usually leads to a small amount of hematemesis, but it is extremely uncommon to have a significant amount of bleeding from an esophageal stent in any clinical situation. Several studies with placement of esophageal stents (both SEPS and SEMS) prior to neoadjuvant therapy did not report bleeding as a complication, likely reflecting that any bleeding that did occur was low volume and not of clinical consequence.15,16,18-20,23

Gastroesophageal Reflux Disease Gastroesophageal reflux disease (GERD) commonly occurs in patients after esophageal stent placement, particularly if the stent is placed across the GE junction. A study of 100 consecutive patients with esophageal SEMS placement for palliation of malignant dysphagia showed that 40 patients had reflux, food regurgitation, or vomiting as a new symptom following stent placement.26 There was a significant increase in the amount of GERD symptoms in patients whose stents were placed across the GE junction. Twentynine (54%) patients with stents placed across the GE junction experienced GERD symptoms, compared with only 11 (11%) patients with stents positioned completely above the GE junction. There have been several studies that have evaluated the efficacy of using specialized esophageal antireflux stents to help alleviate symptoms of GERD. These stents have an antireflux valve on the distal end of the stent. A study comparing antireflux stents (19 patients) (Esophageal Z-Stent with Dua antireflux valve [Wilson-Cook Medical]) versus conventional stents (22 patients) in the setting of palliative treatment of malignant dysphagia showed no significant differences in complication rates, survival rates, esophageal/respiratory symptoms, or quality of life between the 2 groups.27 A larger study (65 total patients) was performed by the same group as a multicenter, randomized trial using the same antireflux stent and also showed no significant differences in quality of life between the antireflux stent group and the conventional stent group.28 A study of 36 patients receiving SEMS across the GE junction for palliation of malignant esophageal dysphagia evaluated GERD symptoms comparing a conventional esophageal stent (M.I. Tech), an early-model antireflux stent (DoStent), and a modified antireflux stent (M.I. Tech).29 The modified antireflux stent has an S-type antireflux valve with a long leaflet within the stent body. Results showed that the DeMeester score was significantly lower with the modified antireflux stent than in the other 2 groups. These stents could just as easily be used in the neoadjuvant setting as in the palliative setting.

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Chapter 2

Minimal specific data on GERD in patients who have stents placed in the neoadjuvant setting exist, but it has been our experience that the frequency and severity of GERD in these patients is very similar to that seen in patients who receive stents for palliative purposes. High-dose acid suppression therapy with twice daily proton pump inhibitor (PPI) is typically required for patients who have stents placed across the GE junction. We generally recommend therapy for as long as the stent is in place.

CARE FOLLOWING THE COMPLETION OF NEOADJUVANT THERAPY Many patients who undergo neoadjuvant therapy will not ultimately become surgical candidates secondary to the development of metastatic disease, significant complications of chemoradiation therapy, or a personal decision by the patient. In this situation, the patient will already have a palliative esophageal stent in place to enable continuing oral nutrition. If a patient is still deemed to be an operative candidate after completion of neoadjuvant therapy, the decision of how to remove the esophageal stent is both endoscopist and surgeon dependent. The stent can be removed in the operating room at the time of esophagectomy or the stent can be removed endoscopically prior to surgery. Ten out of 11 Polyflex stents placed for malignant dysphagia during neoadjuvant therapy were reported by the authors of one study to be “easily retrieved” using a rat-tooth forceps prior to surgery.18 The other stent was removed at the time of surgery secondary to the surgeon’s preference. A recent prospective study evaluating SEPS placement for treatment of dysphagia in 32 patients undergoing neoadjuvant therapy had 20 patients ultimately able to undergo esophagectomy.23 Stents were removed prior to surgery in 3 patients, directly after induction anesthesia in 2 patients, and with the resected specimen in 15 patients. The article reports that none of the surgeons reported any difficulties with stent removal.

CONCLUSION Ensuring adequate nutrition in esophageal cancer patients is particularly important in the neoadjuvant setting because there is typically a 2- to 3-month gap between diagnosis and performing an esophagectomy while the patient receives radiation and chemotherapy. During that time, it is essential to maintain adequate nourishment to avoid perioperative complications and poor outcomes. Although there are many other options for providing nutritional support during this setting (including J tube, gastrostomy tube [G tube], Dobhoff tube, TPN), esophageal stent placement provides the unique advantage of allowing oral nutrition, hydration, and medication delivery. Esophageal stenting also avoids having a surgical procedure for a J tube, the possible interference of G-tube placement with esophagectomy, the inconvenience of a Dobhoff tube, and the numerous complication risks of TPN. There are many different options for esophageal stent placement in the preoperative setting, including SEPS, FCSEMS, and PCSEMS. Esophageal stent placement, regardless of the type chosen, is almost always successful, provides rapid improvement in dysphagia symptoms, and has few major complications.

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Windsor A, Braga M, Martindale R, et al. Fit for surgery: an expert panel review on optmising patients prior to surgery, with a particular focus on nutrition. Surgeon. 2004;2(6):315-319. O’Gorman RB, Feliciano DV, Matthews KS, et al. Correlation of immunologic and nutritional status with infectious complications after major abdominal trauma. Surgery. 1986;99(5): 549-556. Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg. 1999;134(1):36-42. Herskovic A, Martz K, al-Sarraf M, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992;326(24):1593-1598. Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002;20(5):1167-1174. Heys SD, Walker LG, Smith I, Eremin O. Enteral nutritional supplementation with key nutrients in patients with critical illness and cancer: a meta-analysis of randomized controlled clinical trials. Ann Surg. 1999;229(4):467-477. Kudsk KA, Minard G, Croce MA, et al. A randomized trial of isonitrogenous enteral diets after severe trauma. An immune-enhancing diet reduces septic complications. Ann Surg. 1996;224(4):531-540; discussion 540-543. Moore FA, Feliciano DV, Andrassy RJ, et al. Early enteral feeding, compared with parenteral, reduces postoperative septic complications. The results of a meta-analysis. Ann Surg. 1992;216(2):172-183. Braga M, Gianotti L, Gentilini O, Parisi V, Salis C, Di Carlo V. Early postoperative enteral nutrition improves gut oxygenation and reduces costs compared with total parenteral nutrition. Crit Care Med. 2001;29(2):242-248. Mazaki T, Ebisawa K. Enteral versus parenteral nutrition after gastrointestinal surgery: a systematic review and meta-analysis of randomized controlled trials in the English literature. J Gastrointest Surg. 2008;12(4):739-755. Epub 2007 Oct 16. Ohnmacht GA, Allen MS, Cassivi SD, Deschamps C, Nichols FC 3rd, Pairolero PC. Percutaneous endoscopic gastrostomy risks rendering the gastric conduit unusable for esophagectomy. Dis Esophagus. 2006;19(4):311-312. Stockeld D, Fagerberg J, Granström L, Backman L. Percutaneous endoscopic gastrostomy for nutrition in patients with oesophageal cancer. Eur J Surg. 2001;167(11):839-844. Jenkinson AD, Lim J, Agrawal N, Menzies D. Laparoscopic feeding jejunostomy in esophagogastric cancer. Surg Endosc. 2007;21(2):299-302. Epub 2006 Nov 21. Mellow MH, Pinkas H. Endoscopic laser therapy for malignancies affecting the esophagus and gastroesophageal junction. Analysis of technical and functional efficacy. Arch Intern Med. 1985;145(8):1443-1446. Adler DG, Fang J, Wong R, Wills J, Hilden K. Placement of Polyflex stents in patients with locally advanced esophageal cancer is safe and improves dysphagia during neoadjuvant therapy. Gastrointest Endosc. 2009;70(4):614-619. Epub 2009 Jun 21. Siddiqui AA, Loren D, Dudnick R, Kowalski T. Expandable polyester silicon-covered stent for malignant esophageal strictures before neoadjuvant chemoradiation: a pilot study. Dig Dis Sci. 2007;52(3):823-829. Martin R, Duvall R, Ellis S, Scoggins CR. The use of self-expanding silicone stents in esophageal cancer care: optimal pre-, peri-, and postoperative care. Surg Endosc. 2009;23(3): 615-621. Epub 2008 Mar 25. Siddiqui AA, Glyn C, Loren D, Kowalski T. Self-expanding plastic esophageal stents versus jejunostomy tubes for the maintenance of nutrition during neoadjuvant chemoradiation therapy in patients with esophageal cancer: a retrospective study. Dis Esophagus. 2009;22(3):216-622. Epub 2008 Dec 22.

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19. Bower M, Jones W, Vessels B, Scoggins C, Martin R. Nutritional support with endoluminal stenting during neoadjuvant therapy for esophageal malignancy. Ann Surg Oncol. 2009;16(11):3161-3168. Epub 2009 Jul 28. 20. Lopes TL, Eloubeidi MA. A pilot study of fully covered self-expandable metal stents prior to neoadjuvant therapy for locally advanced esophageal cancer. Dis Esophagus. 2010;23(4): 309-315. Epub 2009 Sep 24. 21. Hirdes MM, Siersema PD, Houben MH, Weusten BL, Vleggaar FP. Stent-in-stent technique for removal of embedded esophageal self-expanding metal stents. Am J Gastroenterol. 2011;106(2):286-293. Epub 2010 Oct 12. 22. Langer FB, Schoppmann SF, Prager G, et al. Temporary placement of self-expanding oesophageal stents as bridging for neo-adjuvant therapy. Ann Surg Oncol. 2010;17(2):470-475. Epub 2009 Oct 27. 23. Brown RE, Abbas AE, Ellis S, et al. A prospective phase II evaluation of esophageal stenting for neoadjuvant therapy for esophageal cancer: optimal performance and surgical safety. J Am Coll Surg. 2011;212(4):582-588. 24. Park SY, Park CH, Cho SB, et al. [The usefulness of clip application in preventing migration of self-expandable metal stent in patients with malignant gastrointestinal obstruction]. Korean J Gastroenterol. 2007;49(1):4-9. 25. Kinsman KJ, DeGregorio BT, Katon RM, et al. Prior radiation and chemotherapy increase the risk of life-threatening complications after insertion of metallic stents for esophagogastric malignancy. Gastrointest Endosc. 1996;43(3):196-203. 26. Elphick DA, Smith BA, Bagshaw J, Riley SA. Self-expanding metal stents in the palliation of malignant dysphagia: outcome analysis in 100 consecutive patients. Dis Esophagus. 2005;18(2):93-95. 27. Wenger U, Johnsson E, Arnelo U, Lundell L, Lagergren J. An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study. Surg Endosc. 2006;20(11):1675-1680. Epub 2006 Sep 6. 28. Blomberg J, Wenger U, Lagergren J, et al. Antireflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol. 2010;45(2):208-216. 29. Shim CS, Jung IS, Cheon YK, et al. Management of malignant stricture of the esophagogastric junction with a newly designed self-expanding metal stent with an antireflux mechanism. Endoscopy. 2005;37(4):335-339.

3

Esophageal Stents in Patients With Malignant Dysphagia Due to Unresectable Disease Kulwinder S. Dua, MD, FACP, FRCP, FASGE

Malignancy involving the esophagus can cause difficulty in swallowing either due to luminal obstruction (strictures) and/or due to luminal disruption (fistulae and leaks). These lesions can be intrinsic to the esophagus or located in the mediastinum, causing extrinsic compression. Primary esophageal cancer is the most common cause for malignant dysphagia and is one of the leading causes of cancer death worldwide.1 Dysphagia is the most common presenting symptom in the majority of patients with esophageal cancer. Since the esophageal wall normally has excellent compliance, patients generally do not complain of dysphagia until more than 50% of the esophageal lumen is obstructed or, in absolute terms, the luminal diameter has decreased to 12 mm or less. Hence, the majority of patients do not have symptoms early in the course of their disease and the onset of dysphagia generally implies the existence of advanced disease. Not surprisingly, at presentation, more than 50% of esophageal cancers are unresectable, and the overall prognosis is poor with a dismal 5-year survival rate of less than 20%.2-4 Despite a poor prognosis, relieving dysphagia effectively and rapidly with minimal complications, side effects, or reinterventions is important for maintaining nutrition and hydration, preventing aspiration, giving medications, and allowing the patient to taste and swallow food, thereby overall improving quality of life. The aim of palliations should be to maintain an open (stricture) and functional (seal fistulae) orogastric pathway until the patient’s demise. Surgery in a palliative setting can be associated with significant morbidity and mortality, and palliative chemoradiation, besides also being associated with significant side effects, does not relieve dysphagia immediately. Currently, self-expanding metal stents (SEMS) are the most commonly used modality to palliate malignant dysphagia and fistula. This chapter will focus on the use of esophageal stents in patients with malignant dysphagia due to unresectable disease.

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Adler DG, ed. Self-Expanding Stents in Gastrointestinal Endoscopy (pp 35-58). © 2012 SLACK Incorporated.

36

Chapter 3

ESOPHAGEAL STENTS The concept of using hollow tubes to palliate dysphagia is not new. In 1885, Charles J. Symonds, for the first time, placed a prosthesis across a malignant esophageal stricture. Decades later (1970s), stents made of semirigid plastic tubes were introduced. Celestin’s tubes were 16 to 18 mm in diameter, required preinsertion dilation, and were associated with high complication rates.5-10 As a result of this, esophageal stents to palliate malignant dysphagia were not popular and alternative options were sought. With the introduction of SEMS, interest in using stents for palliation was revived. Advantages of SEMS over semirigid plastic stents are as follows: • The delivery system is thinner as the stent is constrained to a smaller diameter, hence preinsertion dilation is not required in most patients. • SEMS can expand to diameters larger than the plastic stent despite a thinner delivery system. • Unlike the abrupt stretching from plastic stents, SEMS expand more gradually. • Since SEMS are flexible, they can conform to the shape of tortuous strictures. • If needed, it is possible to deploy another SEMS into a previously placed stent. Although SEMS have virtually replaced the semirigid plastic tubes in the Western world, these plastic tubes are still being used in some countries where cost is a major issue.

Self-Expanding Metal Stents There are several types of SEMS available in the United States (and many more varieties worldwide). Those SEMS that are cleared by the Food and Drug Administration (FDA) and available for use in the United States (Table 3-1 and Figure 3-1) include but are not limited to the following: • Wallflex, Ultraflex, and Wallstent (Boston Scientific, Natick, MA) • Evolution and Z-Stent (Wilson-Cook Medical, Winston Salem, NC) • Alimaxx-ES (Merit Endotek, South Jordan, UT), Hanarostent (M.I. Tech, Gyeonggi-do, Korea), and Niti-S (Taewoong-Medical, Seoul, Korea) Some of their features are shown in Table 3-1. Although they differ in their characteristics, the broad principles of design and the techniques for placement remain the same.

Design and Delivery System The majority of the currently used SEMS are made of a nickel-titanium metal wire alloy (nitinol). Nitinol is compatible with magnetic resonance imaging (less than 3 Tesla-units), maintains its memory, and has virtually replaced stainless steel because of its flexibility, thereby easily conforming to the shape of the stricture. Nitinol is woven (braided stents tend to foreshorten on release and nonbraided stents do not) into a tubular structure that is constrained to a thin diameter (7 to 10 mm) on a delivery catheter. Hence, minimal to no preinsertion dilation of the stricture is required. Except for one variety of Niti-S stent, none of the currently FDA-approved delivery catheters can be passed through the accessory channel of an endoscope. The inner catheter can accept a 0.035-inch guidewire

103, 123, 153

105, 125, 155

Length (mm)

103, 123, 153

105, 125, 155

18

23

Diameter (mm)

18

23

Length (mm)

80, 100, 120

80, 100, 120

Diameter (mm)

18

20

Nitinol

Material

Nitinol

Material

Nitinol

Material

Also available with a proximal release mechanism

Length (mm)

Diameter (mm)

Delivery Catheter (mm)

8

Yes

Yes

Foreshortening

Yes

Yes

Foreshortening

EVOLUTION STENT

6.3

Delivery Catheter (mm) 6.2

8

Yes

Yes

Foreshortening

ULTRAFLEX STENT

6.3

Delivery Catheter (mm) 6.2

WALLFLEX STENT

Table 3-1. Some Self-Expanding Esophageal Stents Available in the United States

Yes

Yes

Recapture

Only FC

Recapture

Only FC

Recapture

PC/FC

Covering

PC/FC

Covering

PC/FC

Covering

(Continued )

Wilson-Cook Medical

Company

Boston Scientific

Company

Boston Scientific

Company

Esophageal Stents in Patients With Malignant Dysphagia 37

80, 100, 120, 140

18

Stainless steel

Material

70, 100, 120

70, 100, 120

18

22

Nitinol

Material

Yes

Foreshortening

7.4

7.4 No

No

Foreshortening

ALIMAXX-ES STENT Delivery Catheter (mm)

8

Delivery Catheter (mm)

Recently a 12-mm diameter Alimaxx-ES stent was also released by Merit Endotek.

Length (mm)

Diameter (mm)

Stent has to be manually loaded immediately prior to deployment. Also available with an antireflux valve (Dua AR Z-Stent).

Length (mm)

Diameter (mm)

Z-STENT

No

Recapture

Yes

Recapture

Table 3-1. Some Self-Expanding Esophageal Stents Available in the United States (continued)

FC

Covering

PC/FC

Covering

(Continued )

Merit Endotek

Company

Wilson-Cook Medical

Company

38 Chapter 3

Material

Nitinol

Length (mm)

60, 80, 100, 120, 150 60, 80, 100, 120, 150 60, 80, 100, 120, 150 6.5

6.5

5.8

90, 120, 150

90, 120, 150

90, 120, 150

16

18

21

Polyester

Material

14

13

12

Delivery Catheter (mm)

Stent has to be manually loaded immediately prior to deployment.

Length (mm)

Diameter (mm)

Yes

Yes

Yes

Foreshortening

Yes

Yes

Yes

Foreshortening

POLYFLEX STENT

Delivery Catheter (mm)

Also available with proximal release mechanism. A 3.5-mm diameter delivery system, through-the-scope stent is also available. Also available with an antireflux valve

20

18

16

Diameter (mm)

NITI-S STENT

No

No

No

Recapture

Yes

Yes

Yes

Recapture

Table 3-1. Some Self-Expanding Esophageal Stents Available in the United States (continued)

FC

Covering

PC/FC

Covering

Boston Scientific

Company

Taewoong Medical

Company

Esophageal Stents in Patients With Malignant Dysphagia 39

40

Chapter 3

Figure 3-1. Self-expanding esophageal stents. Partially covered: (A) Ultraflex stent. (B) Evolution stent. (C) Z-Stent. Fully covered: (D) Evolution stent. (E) Z-Stent. (F) Wallflex stent (G) Alimaxx-ES. (H) Polyflex (self-expanding plastic stent).

Esophageal Stents in Patients With Malignant Dysphagia

41

or a stiffer Savory-Gillard wire. The outer catheter keeps the stent constrained on the inner catheter, and the stent is deployed by withdrawing the outer catheter (except for the Ultraflex stent, which is constrained by a thread knitted over the stents and deployed by unraveling the thread). The majority of SEMS are distal release devices; they deploy expanding from the distal to the proximal end (Wallflex, Ultraflex, Evolution, Z-Stent, Alimaxx-ES, Niti-S, Hanarostent, and Wallstent). A variant of Ultraflex stent and Niti-S stent can deploy from the proximal end downward; these are proximal release devices. All SEMS come preloaded except for the Z-Stent, which has to be loaded immediately prior to placement. Once released, the stent expands to its preset diameter that can range from 16 to 23 mm. Nitinol achieves is maximum radial force at body temperature, and the expansion is gradual. Recently, small caliber (12 to 14 mm) diameter Alimaxx stents were made available for use in very tight strictures. SEMS come in various lengths.

Antimigration Features To prevent migration, stent designs can be like a cone with a wider upper end or like a “dog bone” with flared flanges at the upper and lower ends. The diameter of these flanges can range from 21 to 25 mm. Stents that are coated with plastic generally have a smooth inner surface and a rough surface on the outside. Some stents (Alimaxx) have downward facing “fins” to reduce the migration rate. However, the main feature that prevents migration is tissue bulging into the uncovered interstices of the stent, eventually leading to tissue ingrowth and embedding of the stent.11-18

Covering Fully uncovered stents are rarely used at the present time. To prevent tumor and tissue ingrowth, the majority of the currently available stents are either fully or partially covered with a plastic material (eg, polyurethane or silicon). In partially covered SEMS (PCSEMS), a small segment at the upper and lower ends is left uncovered for tissue anchoring. The partially uncovered segment of the stent often develops granulation tissue, embedding the stent and making removal difficult. For this reason, uncovered or PCSEMS have been associated with high complication rates when used for benign indications with an intention to remove them at a later date.11-18 Fully covered stents do not allow tissue ingrowth and do not anchor as well as PCSEMS and hence are prone to migration.

Additional Features As previously mentioned, some stents deploy by releasing from the proximal to the distal end (proximal release Ultraflex, Niti-S) for precise placement across strictures near the upper esophageal sphincter (UES). After release, the majority of stents tend to foreshorten, and this may become an issue where precise placement is required. In these situations, stents that do not foreshorten (Alimaxx, Z-Stent) can be used. Currently, the majority of stents have a purse-string–like thread attached to the upper end. After deployment, this thread can be grasped with a forceps passed through the accessory channel of the endoscope and the stent can be pulled upward for precise positioning. Stents placed across the gastroesophageal (GE) junction can predispose patients to reflux with risks of aspiration. Stent with antireflux valves are available. The ones available in the United States are the Dua antireflux Z-Stents (Figure 3-2) and the antireflux Niti-S stent, while there are several other varieties manufactured in South Korea that will

42

Chapter 3

Stent

Antireflux valve

Retroflexed endoscopic view of the antireflux valve

Antireflux valve

Stent

Figure 3-2. Self-expanding esophageal Dua antireflux Z-Stent. Retroflexed endoscopic views show the lower metal cage just beyond the GE junction and the antireflux valve.

likely be available in the United States in the near future. Most modern stents are highly deformable and can adequately deploy in irregular or highly angulated stenoses (Figure 3-3). Radioactive/drug-eluting stents are also being investigated (see Chapter 14).

Esophageal Stents in Patients With Malignant Dysphagia

43

Figure 3-3. Esophageal Wallflex stent showing maintenance of luminal patency despite severe angulation.

Self-Expanding Plastic Stents The self-expanding plastic stent (SEPS) known as the Polyflex stent (Boston Scientific) is a tube made of woven polyester strands that is fully covered internally with a smooth silicone membrane (see Table 3-1 and Figure 3-1). The covering does not allow tissue ingrowth and the plastic material presumably induces less granulation tissue reaction compared to metal. Hence, these stents can be removed. For this reason, this is the only stent that FDA has cleared for indications that would require removal (ie, benign strictures, although other devices are frequently removed in an off-label manner). The proximal end is flared out to reduce the risks of migration. To enhance radiological visualization, barium impregnation and radio-opaque markers are placed at the upper, mid, and lower parts of the stent. The markers are colored blue for endoscopic visualization. Polyflex stents do not come preloaded and require several simple steps to load. Although this feature may not be as user friendly as SEMS, it has the advantage of allowing the physician the options of removing, reloading, and reusing the same stent if it is deployed incorrectly. Unlike SEMS, preinsertion dilation may be required since the diameter of the delivery system of Polyflex stents is large (12, 13, and 14 mm for the 16, 18, and 21 mm diameter stents, respectively).

Biodegradable Stents Biodegradable stents are made of material that can be metabolized (polylactide/ polydioxanon) by the body and hence are ideally suited for benign indications. They have a limited role to play in the palliation of malignant esophageal obstruction and are currently not available for use in the United States.

Radioactive/Drug-Eluting Stents To locally treat malignant tissue and to reduce tissue hyperplasia, stents have been laden with chemotherapy agents like 5-fluorouracil or paclitaxel or with radiation-emitting

44

Chapter 3

material. Pilot studies in animals have shown encouraging results.19-22 These devices are currently not available in the United States.

TECHNIQUE Placing expandable stents in the esophagus is an advanced procedure that requires proficiency in complex diagnostic evaluations and therapeutic interventions including managing complications related to the procedure. Additional skills in the use of fluoroscopy and interpretations of radiology images are required. Since the procedure can be associated with significant immediate, early, or late complications and the patient’s (or family’s) expectations at times may be unrealistic, a proper informed consent, preferably also involving key family members, is highly recommended.

Approach Expandable esophageal stents improve quality of life by palliating symptoms and should not interfere with or delay other treatment options that have the potential for prolonging survival. Hence, a multidisciplinary approach in which all of the subspecialties in the care of the patient are involved in the decision making is essential. Those referred for esophageal stents often have advanced (terminal) cancer. These patients are generally malnourished, have poor respiratory functions (pneumonia from aspiration/fistula), and may have multiple comorbidities. Patients should be evaluated for their fitness to undergo upper gastrointestinal endoscopy and the need for anesthesia-assisted sedation. In those not fit for endoscopy, fluoroscopic approaches (that may not require sedation) can be considered. Esophageal stenting will neither be cost effective nor carry an adequate risk-benefit ratio in patients who are moribund or have less than 2 to 4 weeks of expected survival. However, the decision to place a stent in these patients can be made on a case-by-case basis. For example, despite a short expected survival, intractable coughing or aspiration from a fistula may merit intervention. Patients with associated oropharyngeal dysphagia (eg, from stroke or brain metastases) will not benefit with esophageal stenting. On the other hand, those who can swallow a soft consistency/well-chewed diet may not get additional benefits from stenting since this is generally the maximum level of food consistency to be expected from stents. The patient’s dentition and chewing ability will also influence the outcome. Partial or impending compression of the trachea/main bronchus can occur from either a mediastinal mass or from an upper esophageal cancer. Esophageal stents can further compress the airways. Hence a computed tomography (CT) scan of the upper chest should be obtained and airway stenting should be considered prior to placing an esophageal stent in patients with suspected airway compromise. Since the delivery system of most of the expandable stents is thin, minimal to no preinsertion dilation is required. Hence, strict aspirin/anticoagulation management prior to the procedure is not essential. Since food stasis above the area of obstruction can predispose to aspiration, adequate consideration should be given to keeping the patient nothing by mouth (NPO) and the need for airway protection (especially if the procedure is being performed in the supine position). Alternatively, the procedure can be performed in the semiprone position.

Esophageal Stents in Patients With Malignant Dysphagia

45

Prior to placing an esophageal stent, precise evaluation of the stricture characteristics is of paramount importance. Stricture length, location, diameter, the presence of any associated fistula, and possible airway compression can be assessed by reviewing prior radiology imaging studies. Direct endoscopic evaluation is usually possible by traversing the stricture with a regular or an ultrathin endoscope (4- to 5.5-mm diameter). For tight strictures that do not allow even a narrow endoscope to pass, a guidewire (0.035 or 0.025 inches) can be advanced through the stricture. Fluoroscopic confirmation that the wire has passed into the stomach is essential since malignant strictures can be associated with leaks and fistula. The stricture length can then be assessed by gently dilating the stricture to allow the thin endoscope to pass by injecting contrast into the lumen or by using a wire-guided retrieval balloon. With the balloon technique, the balloon is advanced into the stomach then inflated with contrast and pulled back until it impacts at the lower end of the stricture, thus allowing accurate assessment of the proximal and distal ends of the stenosis.

Procedure Although several types of expandable stents are available, the broad principles of deployment remain the same for all. The most commonly used technique is a combined endoscopic and fluoroscopic approach, although stents can be placed with either of these alone if performed properly.

Endoscopic and Fluoroscopic Guidance Optimal stent deployment involves placing the stent across the stricture with approximately 2 cm of the stent positioned above and 2 cm below the stricture. To accomplish this, the upper and lower ends of the stricture may need to be marked with either external or internal markers. For external marking, a guidewire (preferably a stiff wire) is first advanced to the antrum (avoid looping into the fundus) through the accessory channel and while maintaining wire position, the endoscope is slowly withdrawn until the tip of the endoscope reaches the lower end of the stricture. With fluoroscopic guidance, a radioopaque marker is taped to the patient’s skin at the level of the endoscope tip (Figure 3-4). Similar steps are repeated for the upper end of the stricture. Patient movements can alter the accuracy of external markers. To restrict movement, it is preferred that the patient be in either supine or prone positions rather than left lateral decubitus. The stricture ends can also be marked internally by injecting a radio-opaque material (ie, lipidol). Although patient movements do not affect the accuracy of internal markings, the injected material tends to get absorbed and this may become an issue in situations when there is a delay in stent deployment. Stents that require preloading (eg, Polyflex stent, Z-Stent) should be loaded and ready to use prior to internal marking. In situations where the endoscope cannot be passed through the stricture, the lower end can be externally marked by passing a balloon catheter as previously described. Alternatively, if the length of the stricture is known (barium esophagram, CT scan) and the right length of the stent selected, one can just mark the upper end of the stricture and deploy the stent, focusing on the upper end either by fluoroscopy or by an endoscope passed parallel to the delivery system. It should be noted that many experienced endoscopists no longer feel the need to place any external markings and simply measure the stricture based on contrast injection and fluoroscopic markers such as the ribs or the vertebrae. Stent deployment should be gradual so that minor adjustments can be made during deployment. Close communication with the assistant is essential. Although fluoroscopic

46

Chapter 3 A

B

Figure 3-4. Steps in the deployment of an expandable metal esophageal stent using endoscopic and fluoroscopic guidance. (A) Upper esophageal squamous cell cancer with a tracheoesophageal fistula (arrow). (B) On withdrawing the endoscope and maintaining guidewire position, the lower end of the malignant stricture is identified in the endoscopic view. Keeping the endoscope tip at this location and using fluoroscopy, a paper clip is attached to the patient’s chest at the level of the endoscope tip using an adhesive tape (alternatively a radioopaque material can be injected into the tissue for internal marking). Similarly, the upper end of the stricture is also marked.

Esophageal Stents in Patients With Malignant Dysphagia C

D

Figure 3-4 continued. (C) SEMS deployment using fluoroscopic guidance and external markers. A: Upper and lower ends marked as previously described. B: Delivery catheter with a constrained expandable stent passed over the guidewire. C to F: Stent is deployed (distal release) while maintaining position in relation to the external markers so that there is at least 1.5 to 2 cm of expanded stents on either sides of the external markers. (D) Adequate stent position confirmed fluoroscopy and endoscopy. A barium study showed free flow of barium through the stent with no leakage (sealed fistula). .

47

48

Chapter 3

monitoring is adequate during deployment, one can also use endoscopic guidance by passing an endoscope alongside the stent and watching the upper end of the stent in relation to the upper end of the stricture. During deployment, the expanding stent tends to pull the delivery catheter distally. Steady countertraction is required to maintain position. If a partially expanded stent has moved distally, the stent can be pulled up by traction on the delivery catheter to regain position. For stents that deploy below the desired position, one can reposition the stent by pulling it upward via grasping the thread attached to the stent or grasping the upper edge of the stent with a rat-tooth forceps. If the lower end of a partially expanded stent has been inadvertently pulled into or deployed into the stricture, the stent can be recaptured (this feature is available in the Evolution stent, the fully covered Wallflex stent, and the Niti-S stent) to start the deployment process again. In some instances, the misplaced stent may need to be removed immediately by using a rat-tooth forceps and inserting a new stent. Once deployed, it is not essential to pass an endoscope through the stent to confirm its position since this can lead to stent migration.

Endoscopy Guidance Only An increasing number of stents are being deployed without fluoroscopy (Figure 3-5.) The endoscope is passed through the stricture (if necessary, a thin endoscope can be used) and the stricture length is determined. This information can also be obtained from prior radiology studies (eg, an esophagram or a CT scan), especially if a standard endoscope cannot pass through the stricture and one does not have a thin endoscope. A stent approximately 4 cm longer than the stricture length is selected. A guidewire is passed through the accessory channel of the endoscope and the lower end of the wire positioned in the antrum. The endoscope is then withdrawn and over the guidewire and the constrained stent is advanced across the stricture. The endoscope is reinserted parallel to the stent catheter. The stent is then deployed slowly while carefully monitoring and maintaining a steady position of the top end of the stent in relation to the top end of the stricture as the stent is being deployed. The desired position of the upper end of the expanded stent should be 2 cm above the upper end of the stricture. If this distance is less than 2 cm, the stent can be grasped by a forceps passed through the accessory channel of the endoscope and pulled up. With the top end of the stent accurately positioned, the bottom end will also be at the correct level provided the right length of the stent was selected.

Fluoroscopic Guidance Only Deployment of stents with fluoroscopic guidance only is not as commonly used in the United States as in some other countries like the United Kingdom. The stricture’s location and length are evaluated and marked using barium studies and a stent is inserted with fluoroscopic guidance. As the majority of these procedures can be performed without sedation, an immediate barium esophagram can be obtained to evaluate proper placement.

CHOOSING A STENT Currently, there are several varieties of expandable stents available worldwide, and each stent has its own unique characteristics. Since one type of stent does not “fit all,” choosing the right stent for a particular stricture is very important to minimize side effects and complications. To achieve this, first, the operator should have expertise in using a variety

Esophageal Stents in Patients With Malignant Dysphagia

49

Figure 3-5. Expandable metal stent (nonforeshortening AlimaxxES stent) deployment using endoscopic guidance in a patient with metastatic squamous cell cancer located within 3 cm below the UES. (A) Mass with stricture. (B) The constrained stent was passed over a guidewire and the endoscope inserted parallel to the stent. The green ring marks the level at which the top end of the stent will expand. This was positioned 2 cm above the upper end of the stricture (1 cm below the UES) and while maintaining this position with close endoscopic guidance, the stent was deployed (C and D). Since the stent selected was 4 cm + length of the stricture, proper location of the top end of the stent 2 cm above the top end of the stricture will ensure that the stent has adequately bridged the stricture.

of stents and have experience managing stent-related complications. Second, an understanding of the stent characters (diameter of delivery system and of the expanded stent, release mechanisms, foreshortening or nonforeshortening, covering, flexibility, antireflux features, etc) is essential.23 The length of the selected stent should be long enough to bridge the stricture and have additional length of stent on either side of the stricture. Stents with a thinner diameter (eg, 12-mm diameter Alimaxx stent) are preferable for tight strictures while larger diameter covered or partially covered stents form a better seal in patients with fistulae.

Stenting Across the Gastroesophageal Junction The need for an antireflux mechanism for lower esophageal strictures where the stent crosses into the stomach is debatable. Although antireflux measures may suffice in most cases, acid suppression does not reduce the risk of aspiration from food refluxing into the esophagus since many of these patients may have gastroparesis with food stasis (narcotic use, vagus nerve invasion). The incidence of GE reflux reported with stents placed across the GE junction ranges from 25% to 80%. In a recent multicenter study of 44 patients, 11 of which had tumors at the GE junction, 3/11 patients developed reflux symptoms and 3 died secondary to aspiration pneumonia.24 The authors recommended the need for

50

Chapter 3

antireflux SEMS. Currently the Dua antireflux Z-Stent and the antireflux Niti-S stent are the only 2 approved antireflux stents available in the United States. Results from studies using antireflux SEMS versus standard open SEMS have been mixed.25-32 In a prospective randomized study, Laasch et al showed significantly lower incidence of reflux symptoms with the Dua antireflux Z-Stent compared to a standard stent.29 There was an aspirationrelated death within 24 hours after placement in the standard stent group compared to none in the antireflux stent group. Similarly, others have also shown benefits of using antireflux stents for tumors at the GE junction.30-32 Homs et al found that the FerX-ELLA antireflux stent (not available in the United States) failed to prevent GE reflux. Similarly, another study using the Dua antireflux Z-Stent did not show any advantage of using an antireflux stent over a standard stent.27,33 Using the FerX-ELLA, another study also found no advantage over giving proton pump inhibitors to the patient.34 In a recent meta-analysis, Sgourakis et al found conventional self-expanding stents and antireflux stents to be equally effective with regard to GE reflux disease.35

Stenting the Proximal Esophagus Several studies have shown that it is possible to place stents across malignant strictures located in the proximal esophagus (strictures located 2 to 3 cm or less below the UES) and even across the UES as in those with head and neck cancers.36-39 Stents in this location may produce a foreign body sensation (globus) and can be associated with higher complication rates (pain, aspiration, new fistula formation, migration). Reported early complication rates have varied from 0% to 25% and late complications as high as 100%. However, in a recently published retrospective study of 151 patients with proximal esophageal cancer, SEMS-related complication rates were similar between proximal and distal esophageal cancers (early 6.5% versus 9.7% and late 20.4% versus 15.1%, respectively). Improvement in dysphagia score and the median survival were also similar between the 2 groups.40 Since expandable stents in this location can compress the trachea or the right/left main bronchus, prior evaluation of the airways is essential. Precise positioning of the upper end of the stent in the limited space between the stricture and the UES can be difficult especially if one uses stents that foreshorten. As such, an increasing number of stents are being placed in this location with direct endoscopic guidance. Proximal release (Ultraflex, Niti-S) or nonforeshortening stents (Alimaxx, Z-Stent) are preferable for precise placement, although foreshortening stents can also be used. During deployment, if the upper end of the stent opens into or very near the upper end of the stricture, the stent can be grasped with a forceps and pulled up to a location below the UES. Since space is limited and the proximal esophageal diameter is smaller, reasonable dysphagia relief can be accomplished using smaller-diameter SEMS (ie, Alimaxx 12-mm stents). This approach will potentially reduce the possibility of tracheal compression, globus sensation, and pain. Partially uncovered stents will reduce the risk of migration. SEMS with modifications including softer and smaller diameter upper flange are also available abroad. Patients with laryngeal and hypopharyngeal cancers and strictures from cancers in close proximity to the UES will require stenting across the UES. Smaller diameter stents like the 12-mm Alimaxx stent, 14- to 16-mm tracheobronchial stents, or even 10-mm biliary stents can be used. These patients have usually undergone major surgeries, prior radiation, and have a tracheostomy for airway protection. Reduced neohypopharyngeal mucosal sensitivity from radiation helps achieve better patient tolerance.

Esophageal Stents in Patients With Malignant Dysphagia

51

Extrinsic Compression Extrinsic compression of the esophagus from primary lung cancer, metastatic disease to the mediastinum, or lymphadenopathy can cause significant dysphagia. Because these lesions can be associated with impending airway compression, it is essential to review a prior chest CT scan and consider placing an airway stent prior to deploying the esophageal stent. Subclinical airway compression can develop into overt compression after esophageal stent deployment. If this is suspected, one can pass a bougie or inflate a balloon (diameter equal to the diameter of the expanded stent) into the proximal esophagus and observe for stridor. Unlike intrinsic fleshy and bulky tumors that undergo pressure necrosis with expanding stents, strictures from extrinsic compressions may require stents with stronger radial force. This may cause chest discomfort and pressure necrosis, both of which can promote fistula formation. In a retrospective review of 13 patients with mediastinal tumors, SEMS (Z-Stent) significantly improved dysphagia scores with acceptable complication rates (around 30%, predominantly chest pain and migration).41 There are limited studies comparing the outcomes of using SEMS in extrinsic esophageal compression with intrinsic lesions of the esophagus. Bethge et al compared 24 patients with extrinsic compression to 22 patients with intrinsic lesions and found that dysphagia scores improved significantly better in the intrinsic group (from 3 to 1) compared to the extrinsic group (3 to 2; p < 0.001).42 In a recent prospective study of 50 patients with extrinsic malignant esophageal compression, SEMS were successfully placed in all patients. Severe complications occurred in 5/50 (10%) patients that included perforation from dilation prior to stent insertion (n = 2) and hemorrhage in 3 patients. Two patients (4%) died from bleeding. Recurrent dysphagia occurred in 8 patients (16%), all of whom were treated with endoscopic interventions.43

Fistulae and Leaks Like strictures, fistulae and leaks can occur from intrinsic or extrinsic lesions of the esophagus and are generally associated with strictures. Principles of placing SEMS or SEPS in patients with fistulae and leaks are similar to those with strictures alone. To reduce the risk of migration despite the fistulae, it is still recommended to use a partially covered stent for better anchoring. However, since most of the partially uncovered SEMS shorten on expansion, it is important to place the stent in such a way that the covered portion of the stent continues to seal the fistula despite shortening. It is also suggested to use a stent with a larger diameter flange so as to form a good seal between the stent and the esophageal wall to avoid food tracking along the outside of the stent. All patients should have an esophagram at some point following stent placement to document no leakage before feeding. If leakage persists, the stent can be adjusted or an additional stent can be placed through the first one to affect a better seal of the fistula.

52

Chapter 3

EFFICACY OF STENTS IN THE PALLIATION OF MALIGNANT DYSPHAGIA As prior studies have demonstrated that semirigid stents are inferior to esophageal SEMS and are associated with more complications, esophageal SEMS are now essentially considered standard of care.5-10 Of note, one atypical study comparing plastic stents to SEMS showed no significant difference in procedure-related complications or mortality rate between the 2 groups.44 Many studies have looked at the efficacy of SEMS in the palliation of malignant dysphagia and/or malignant fistulae.5-10,24,26,27,30,32,35,37-40,44-60 Technical success rate in placing these stents has almost approached 100%, but functional success is lower as patients may still not tolerate oral intake secondary to chest pain, anorexia, or inadequate sealing of fistulae. Generally, patients can swallow liquids and semisolids and rarely progress to a full diet. No significant differences in outcomes were found when 3 SEMS of different designs were compared.52,56,57 However, in other comparative studies, EsophaCoil (coiled wire that springs open with high radial force, Medtronic InStent, Eden Prairie, MN) and an old version of the esophageal Wallstent with sharp edges (Boston Scientific) were associated with higher complication rates; these stents are no longer available.53,61 Similarly, completely uncovered SEMS are no longer available as tissue/tumor ingrowth led to stent occlusion requiring reinterventions.55 Partially covered stents prevent ingrowth but this increases their tendency to migrate.59 Compared to fully covered SEMS (which carry an even higher risk for migration), PCSEMS are preferred for palliating malignant dysphagia/fistula.62 In the recent past, several studies were published on the use of the fully covered SEPS (Polyflex) in the management of malignant dysphagia/fistulae and leaks. Results showed good technical success rates in stent deployment along with significant success in relieving dysphagia symptoms.63-73 When compared with SEMS, SEPS were associated with significant chest pain and high migration rates (up to over 30%) resulting in a poorer functional success.65,74 Currently, SEPS are used mainly in situations where stent removal is indicated (benign strictures, bridge to surgery) and are less than ideal for palliating malignant dysphagia.

Quality of Life Although dysphagia scores significantly improve with SEMS, very few studies have looked at its effect on quality of life. Maroju et al studied 30 patients treated with the Ultraflex stent. Quality of life score improved significantly from 62 to 94 before stenting to 80 to 133 poststenting. Pain was the most common complaint noted on follow up.75 In another study on 33 patients, quality of life was assessed by using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3) and EORTC QLQ-Esophagus (OES) 18 questionnaire (a quality of life scale specifically designed for esophageal diseases) before and at 1, 4, and 8 weeks after placement of the stent.76 Dysphagia, global health status, deglutition, eating, other symptom scales, and all functional scores improved in a statistically significant manner after stenting from baseline, and the majority of these improvements in quality of life persisted until 8 weeks. Similar to the previous study, there was no improvement in pain.

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Few studies have compared SEMS to other palliative treatment modalities like brachytherapy. The Dutch Stent or Intraluminal Radiotherapy for Inoperable Esophageal Cancer study reported better overall quality of life score with brachytherapy with major improvements also in dysphagia and eating scales.77 Using simple scores that included age, gender, length of the tumor, World Health Organization performance score, and the presence of metastases, Steyerberg et al developed a prognostic model to guide treatment selection.78 It should be noted that the onset of the beneficial effects of brachytherapy is slow and, in general, only at 30 days is the effect of brachytherapy on dysphagia comparable to that of SEMS at insertion.

Radiotherapy/Chemoradiotherapy Radiotherapy (RT)/chemoradiotherapy (CRT) is at times given palliatively to patients who already have a SEMS in place. In general, dose reduction is unnecessary if multiple fields are used.79 There is a tendency toward higher complication rates in those receiving RT after a SEMS has been placed, likely due to multiple stresses on the esophageal and mediastinal tissues.80 A more common scenario than previously described is seen in the patient who has already received RT/CRT, has progressive disease in the face of treatment, and needs a SEMS for palliation of his or her dysphagia. Data on the risks of placing SEMS in those who have received prior RT/CRT are mixed. In one series of 200 patients, except for chest pain, there was no increased risk of complications in those who received prior chemoradiation.81 Similarly, a recent meta-analysis (16 randomized controlled trials with pooled 1027 patients) also showed previous CRT had no impact on complications, procedural deaths, and overall patient survival.35 Other studies have shown higher SEMS-related complication rates in those with prior RT/CRT.8,80,82-85 In a review of 116 patients, prior chemoradiation was associated with significantly higher risks of major stent-related complications with an odds ratio of 5.59 (95% CI: 1.7 to 18.1).85 Another study compared patients with CRT (n = 56) and patients with no treatment before and after SEMS insertion (n = 60). Early and late major complications occurred more frequently in those with prior CRT (23.2% versus 3.3%, p < 0.002 and 21.6% versus 5.1%, p < 0.02, respectively), and prior CRT was an independent predictor for major post-SEMS complications (odds ratio of 5.59; 95% CI: 1.7 to 18.1).80 A recent study from MD Anderson Institute (Houston, TX) questioned the efficacy and safety of using SEMS for palliating dysphagia in patients with unresectable malignancies.86 In this study, although SEMS were effective in immediately relieving dysphagia, they were associated with frequent complications (37%) requiring reinterventions. These data were felt to favor nonendoscopic interventions. Another randomized study comparing 108 patients who received SEMS to 101 patients who received single-dose brachytherapy (12 Gy) has been published.87 Compared to brachytherapy, dysphagia score improved more rapidly after SEMS. At 30 days, improvement in dysphagia scores was similar between the 2 groups. Beyond 30 days, the dysphagia scores were better in the brachytherapy group and complications occurred more frequently in the SEMS group (p = 0.02).

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Combined Approach In those with longer expected survival, one approach could be to place a potentially removable expandable stent (fully covered stent) for immediate relief and give concurrent CRT. The stent can be removed after 4 to 6 weeks to avoid delayed stent-related complications by which time CRT would have taken effect.88 Shin et al placed removable covered nitinol stents in 47 patients 1 week before starting radiotherapy.89 The stents were removed in 24 patients 4 weeks after therapy and left in place in 23 patients. The dysphagia score improved in both groups. Overall, treatment in this situation should be individualized.

CONCLUSION A multidisciplinary approach is recommended in treating patients with malignant dysphagia. Expandable esophageal stents are currently the most widely accepted modality for palliating malignant dysphagia and/or fistulae in patients with unresectable disease. There are several varieties of expandable stents available, although the basic principles of deployment remain the same. The operator should have appropriate training and skills to choose the right stent for a given patient. PCSEMS are the preferred variety in patients with unresectable disease since they are less prone to migration compared to fully covered stents, can reduce tumor ingrowth, and can be used to seal fistulae. Expandable stents can be placed as an outpatient procedure using minimally invasive approaches (endoscopy, fluoroscopy, or both) and the relief in symptoms is almost immediate. Technical and functional success rates are more than 90%. Stents are ideal for those with short life expectancy and alternative nonsurgical palliative options like RT/CRT should be considered in those with longer expected survival.

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31. Wenger U, Johnsson E, Arnelo U, Lundell L, Lagergren J. An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study. Surg Endosc. 2006;20(11):1675-1680. 32. Lee S, Osugi H, Tokuhara T, et al. Self-expandable metallic stent for unresectable malignant strictures in the esophagus and cardia. Jpn J Thorac Cardiovasc Surg. 2005;53(9):470-476. 33. Blomberg J, Wenger U, Lagergren J, et al. Antireflux stent versus conventional stent in the palliation of distal esophageal cancer. A randomized, multicenter clinical trial. Scand J Gastroenterol. 2010;45(2):208-216. 34. Sabharwal T, Gulati MS, Fotiadis N, et al. Randomised comparison of the FerX Ella antireflux stent and the ultraflex stent: proton pump inhibitor combination for prevention of poststent reflux in patients with esophageal carcinoma involving the esophago-gastric junction. J Gastroenterol Hepatol. 2008;23(5):723-728. 35. Sgourakis G, Gockel I, Radtke A, et al. The use of self-expanding stents in esophageal and gastroesophageal junction cancer palliation: a meta-analysis and meta-regression analysis of outcomes. Dig Dis Sci. 2010;55:3018-3030. 36. Eleftheriadis E, Kotzampassi K. Endoprosthesis implantation at the pharyngo-esophageal level: problems, limitations and challenges. World J Gastroenterol. 2006;12(13):2103-2108. 37. Macdonald S, Edwards RD, Moss JG. Patient tolerance of cervical esophageal metallic stents. J Vasc Interv Radiol. 2000;11(7):891-898. 38. Shim CS, Jung IS, Bhandari S, et al. Management of malignant strictures of the cervical esophagus with a newly-designed self-expanding metal stent. Endoscopy. 2004;36(6):554-557. 39. Verschuur EM, Kuipers EJ, Siersema PD. Esophageal stents for malignant strictures close to the upper esophageal sphincter. Gastrointest Endosc. 2007;66(6):1082-1090. 40. Parker RK, White RE, Topazian M, Chepkwony R, Dawsey S, Enders F. Stents for proximal esophageal cancer: a case-control study. Gastrointest Endosc. 2011;73(6):1098-1105. 41. De Gregorio BT, Kinsman K, Katon RM, et al. Treatment of esophageal obstruction from mediastinal compressive tumor with covered, self-expanding metallic Z-stents. Gastrointest Endosc. 1996;43(5):483-489. 42. Bethge N, Sommer A, Vakil N. Palliation of malignant esophageal obstruction due to intrinsic and extrinsic lesions with expandable metal stents. Am J Gastroenterol. 1998;93(10): 1829-1832. 43. van Heel NC, Haringsma J, Spaander MC, Bruno MJ, Kuipers EJ. Esophageal stents for the relief of malignant dysphagia due to extrinsic compression. Endoscopy. 2010;42(7): 536-540. 44. O’Donnell CA, Fullarton GM, Watt E, Lennon K, Murray GD, Moss JG. Randomized clinical trial comparing self-expanding metallic stents with plastic endoprostheses in the palliation of oesophageal cancer. Br J Surg. 2002;89(8):985-992. 45. Bethge N, Knyrim K, Wagner HJ, Starck E, Pausch J, Kleist DV. Self-expanding metal stents for palliation of malignant esophageal obstruction—a pilot study of eight patients. Endoscopy. 1992;24(5):411-415. 46. Domschke W FE, Matek W, Rodl W. Self-expanding mesh stent for esophageal cancer stenosis. Endoscopy. 1990;22:134-136. 47. Fischer A, Thomusch O, Benz S, von Dobschuetz E, Baier P, Hopt UT. Nonoperative treatment of 15 benign esophageal perforations with self-expandable covered metal stents. Ann Thorac Surg. 2006;81(2):467-472. 48. Neuhaus H, Hoffmann W, Dittler HJ, Niedermeyer HP, Classen M. Implantation of selfexpanding esophageal metal stents for palliation of malignant dysphagia. Endoscopy. 1992;24(5):405-410. 49. Ramirez FC, Dennert B, Zierer ST, Sanowski RA. Esophageal self-expandable metallic stents–indications, practice, techniques, and complications: results of a national survey. Gastrointest Endosc. 1997;45(5):360-364. 50. Schaer J, Katon RM, Ivancev K, Uchida B, Rosch J, Binmoeller K. Treatment of malignant esophageal obstruction with silicone-coated metallic self-expanding stents. Gastrointest Endosc. 1992;38(1):7-11. 51. Fleischer DE, Bull-Henry K. A new coated self-expanding metal stent for malignant esophageal strictures. Gastrointest Endosc. 1992;38(4):494-496.

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52. May A, Hahn EG, Ell C. Self-expanding metal stents for palliation of malignant obstruction in the upper gastrointestinal tract. Comparative assessment of three stent types implemented in 96 implantations. J Clin Gastroenterol. 1996;22(4):261-266. 53. Schmassmann A, Meyenberger C, Knuchel J, et al. Self-expanding metal stents in malignant esophageal obstruction: a comparison between two stent types. Am J Gastroenterol. 1997;92(3):400-406. 54. Song HY, Park SI, Jung HY, et al. Benign and malignant esophageal strictures: treatment with a polyurethane-covered retrievable expandable metallic stent. Radiology. 1997;203(3): 747-752. 55. Vakil N, Morris AI, Marcon N, et al. A prospective, randomized, controlled trial of covered expandable metal stents in the palliation of malignant esophageal obstruction at the gastroesophageal junction. Am J Gastroenterol. 2001;96(6):1791-1796. 56. Siersema PD, Hop WC, van Blankenstein M, et al. A comparison of 3 types of covered metal stents for the palliation of patients with dysphagia caused by esophagogastric carcinoma: a prospective, randomized study. Gastrointest Endosc. 2001;54(2):145-153. 57. Sabharwal T, Hamady MS, Chui S, Atkinson S, Mason R, Adam A. A randomised prospective comparison of the Flamingo Wallstent and Ultraflex stent for palliation of dysphagia associated with lower third oesophageal carcinoma. Gut. 2003;52(7):922-926. 58. Elphick DA, Smith BA, Bagshaw J, Riley SA. Self-expanding metal stents in the palliation of malignant dysphagia: outcome analysis in 100 consecutive patients. Dis Esophagus. 2005;18(2):93-95. 59. Saranovic D, Djuric-Stefanovic A, Ivanovic A, Masulovic D, Pesko P. Fluoroscopically guided insertion of self-expandable metal esophageal stents for palliative treatment of patients with malignant stenosis of esophagus and cardia: comparison of uncovered and covered stent types. Dis Esophagus. 2005;18(4):230-238. 60. Kim ES, Jeon SW, Park SY, et al. Comparison of double-layered and covered Niti-S stents for palliation of malignant dysphagia. J Gastroenterol Hepatol. 2009;24(1):114-119. 61. Naso P, Bonanno G, Aprile G, et al. EsophaCoil for palliation of dysphagia in unresectable oesophageal carcinoma: short- and long-term results. Dig Liver Dis. 2001;33(8): 653-658. 62. Irani S KR. Esophageal stents: past, present, and future. Techniques in Gastrointestinal Endoscopy. 2010;12:178-190. 63. Bethge N, Vakil N. A prospective trial of a new self-expanding plastic stent for malignant esophageal obstruction. Am J Gastroenterol. 2001;96(5):1350-1354. 64. Conigliaro R, Battaglia G, Repici A, et al. Polyflex stents for malignant oesophageal and oesophagogastric stricture: a prospective, multicentric study. Eur J Gastroenterol Hepatol. 2007;19(3):195-203. 65. Conio M, Repici A, Battaglia G, et al. A randomized prospective comparison of self-expandable plastic stents and partially covered self-expandable metal stents in the palliation of malignant esophageal dysphagia. Am J Gastroenterol. 2007;102(12):2667-2677. 66. Costamagna G, Shah SK, Tringali A, Mutignani M, Perri V, Riccioni ME. Prospective evaluation of a new self-expanding plastic stent for inoperable esophageal strictures. Surg Endosc. 2003;17(6):891-895. 67. Decker P, Lippler J, Decker D, Hirner A. Use of the Polyflex stent in the palliative therapy of esophageal carcinoma: results in 14 cases and review of the literature. Surg Endosc. 2001;15 1444-1447. 68. Dormann AJ, Eisendrath P, Wigginghaus B, Huchzermeyer H, Deviere J. Palliation of esophageal carcinoma with a new self-expanding plastic stent. Endoscopy. 2003;35(3): 207-211. 69. Karbowski M, Schembre D, Kozarek R, Ayub K, Low D. Polyflex self-expanding, removable plastic stents: assessment of treatment efficacy and safety in a variety of benign and malignant conditions of the esophagus. Surg Endosc. 2008;22(5):1326-1333. 70. Ott C, Ratiu N, Endlicher E, et al. Self-expanding Polyflex plastic stents in esophageal disease: various indications, complications, and outcomes. Surg Endosc. 2007;21(6): 889-896.

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71. Pennathur A, Chang AC, McGrath KM, et al. Polyflex expandable stents in the treatment of esophageal disease: initial experience. Ann Thorac Surg. 2008;85(6):1968-1972; discussion 1973. 72. Radecke K, Gerken G, Treichel U. Impact of a self-expanding, plastic esophageal stent on various esophageal stenoses, fistulas, and leakages: a single-center experience in 39 patients. Gastrointest Endosc. 2005;61(7):812-818. 73. Szegedi L, Gal I, Kosa I, Kiss GG. Palliative treatment of esophageal carcinoma with selfexpanding plastic stents: a report on 69 cases. Eur J Gastroenterol Hepatol. 2006;18(11): 1197-1201. 74. Verschuur EM, Repici A, Kuipers EJ, Steyerberg EW, Siersema PD. New design esophageal stents for the palliation of dysphagia from esophageal or gastric cardia cancer: a randomized trial. Am J Gastroenterol. 2008;103(2):304-312. 75. Maroju NK, Anbalagan P, Kate V, Ananthakrishnan N. Improvement in dysphagia and quality of life with self-expanding metallic stents in malignant esophageal strictures. Indian J Gastroenterol. 2006;25(2):62-65. 76. Madhusudhan C, Saluja SS, Pal S, et al. Palliative stenting for relief of dysphagia in patients with inoperable esophageal cancer: impact on quality of life. Dis Esophagus. 2009;22(4): 331-336. 77. Homs MY, Essink-Bot ML, Borsboom GJ, Steyerberg EW, Siersema PD. Quality of life after palliative treatment for oesophageal carcinoma—a prospective comparison between stent placement and single dose brachytherapy. Eur J Cancer. 2004;40(12):1862-1871. 78. Steyerberg EW, Homs MY, Stokvis A, Essink-Bot ML, Siersema PD. Stent placement or brachytherapy for palliation of dysphagia from esophageal cancer: a prognostic model to guide treatment selection. Gastrointest Endosc. 2005;62(3):333-340. 79. Chen YK, Schefter TE, Newman F. Esophageal cancer patients undergoing external beam radiation after placement of self-expandable metal stents: is there a risk of radiation dose enhancement? Gastrointest Endosc. 2011;73(6):1109-1114. 80. Lecleire S, Di Fiore F, Ben-Soussan E, et al. Prior chemoradiotherapy is associated with a higher life-threatening complication rate after palliative insertion of metal stents in patients with oesophageal cancer. Aliment Pharmacol Ther. 2006;23(12):1693-1702. 81. Homs MY, Hansen BE, van Blankenstein M, Haringsma J, Kuipers EJ, Siersema PD. Prior radiation and/or chemotherapy has no effect on the outcome of metal stent placement for oesophagogastric carcinoma. Eur J Gastroenterol Hepatol. 2004;16(2):163-170. 82. Kinsman KJ, DeGregorio BT, Katon RM, et al. Prior radiation and chemotherapy increase the risk of life-threatening complications after insertion of metallic stents for esophagogastric malignancy. Gastrointest Endosc. 1996;43(3):196-203. 83. Sumiyoshi T, Gotoda T, Muro K, et al. Morbidity and mortality after self-expandable metallic stent placement in patients with progressive or recurrent esophageal cancer after chemoradiotherapy. Gastrointest Endosc. 2003;57(7):882-885. 84. Iraha Y, Murayama S, Toita T, et al. Self-expandable metallic stent placement for patients with inoperable esophageal carcinoma: investigation of the influence of prior radiotherapy and chemotherapy. Radiat Med. 2006;24(4):247-252. 85. Raijman I, Siddique I, Lynch P. Does chemoradiation therapy increase the incidence of complications with self-expanding coated stents in the management of malignant esophageal strictures? Am J Gastroenterol. 1997;92(12):2192-2196. 86. Ross WA, Alkassab F, Lynch PM, et al. Evolving role of self-expanding metal stents in the treatment of malignant dysphagia and fistulas. Gastrointest Endosc. 2007;65(1):70-76. 87. Homs MY, Steyerberg EW, Eijkenboom WM, et al. Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial. Lancet. 2004;364(9444):1497-1504. 88. Dua KS. Stents for palliating malignant dysphagia and fistula: is the paradigm shifting? Gastrointest Endosc. 2007;65(1):77-81. 89. Shin JH, Song HY, Kim JH, et al. Comparison of temporary and permanent stent placement with concurrent radiation therapy in patients with esophageal carcinoma. J Vasc Interv Radiol. 2005;16(1):67-74.

4

Complications of Esophageal Stents and Their Management Gulshan Parasher, MD and Jess D. Schwartz, MD, FACS, FCCP

Prior to the advent of self-expanding metal stents (SEMS), fixed-diameter plastic stents were used for palliation of malignant dysphagia. Placing these devices involved esophageal dilation to a large diameter followed by insertion of a plastic stent either via rigid esophagoscopy using a pulsion technique or an open traction technique requiring a laparotomy and gastrotomy under general anesthesia.1-3 During the past 2 decades, with the advent of SEMS, endoscopic approaches to palliation have supplanted the need for this type of surgical intervention. SEMS offer quality symptomatic palliation in patients with the following: locally unresectable or advanced metastatic esophageal cancer, malignant tracheoesophageal fistulae, poor functional status patients unsuitable for surgery, recurrent disease post-treatment, as an adjunct to patients receiving definitive chemoradiation therapy, and are also of great use in a variety of benign esophageal conditions. Numerous studies have shown SEMS to be associated with fewer complications and better efficacy (85% to 100%) than fixed-diameter plastics stents used previously.4-6 More recently, experience with SEMS for palliation has encouraged the use of stents for benign diseases in which stent removal is desired. To fill this need, self-expanding plastic stents (SEPS) that had the advantage of ease of removal due to their fully covered nature were developed.7 Accordingly, SEPS have been primarily used for the management of benign esophageal conditions, such as refractory benign esophageal strictures, esophageal perforations, and leaks, but can play a role in patients with malignant disease as well.8,9 Today, a wide variety of self-expandable stents are available differing in their design, alloy material, diameter, radial expansile force, and presence or absence of a covering. These differences provide unique advantages but are also associated with differing rates of complications. While extremely beneficial, placement of an esophageal stent can lead to both early and late complications in approximately 30% to 35% of the cases in most series.1,4-6,10 Such complications may be related to stent design, tumor characteristics, previous therapies, and operator experience.10-13 Since the introduction of SEMS, the complications associated with esophageal stent placement have gradually evolved over time. Progressive modifications in stent design, including material and delivery systems, and improved operator experience have helped decrease the incidence of such complications. This chapter

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focuses on the complications associated with self-expanding esophageal stents and their management.

GENERAL PREPROCEDURAL PLANNING The most important consideration in minimizing complications is to thoroughly understand the indications and contraindications for the procedure. Careful patient selection will help avoid unnecessary complications. Prior to proceeding with stent placement, the following should be considered in detail: • A thorough review of the patient’s history and a physical examination, as well as review of pertinent imaging studies, should be conducted. • Informed consent including a detailed description of the procedure, along with the expected benefits and risks, including both early and late complications, should be obtained in all patients who undergo esophageal stent placement. • As part of the preprocedural planning, a visual map of how the stent will look after deployment is necessary. A review of the patient’s anatomy and tumor characteristics, such as location, shape, length, and tumor-associated complications (eg, any associated fistula), allows for careful planning and an increased likelihood of successful placement of the stent. In addition, preprocedural bronchoscopy should be considered in patients with bulky proximal esophageal or mediastinal neoplasms, especially those presenting with respiratory symptoms and possible tracheal compression. Combined tracheal and esophageal stenting may be necessary in these circumstances. • Plans for the patient to undergo chemotherapy, radiation, and surgery should always be considered because this may have significant implications for the patient and for the stent placement procedure. • Anticipate other ancillary procedures or techniques that may be needed, such as prestent dilation, laser ablation of large exophytic tumors, and percutaneous gastrostomy. • The endoscopist should have an excellent working knowledge of the various types of available stents along with their unique characteristics in order to achieve a high rate of success. • Provide adequate sedation or general anesthesia with consideration for minimizing the risk of aspiration. Patients with proximal cervical esophageal neoplasms should undergo stent placement procedure with airway protection and/or intubation. • Finally, it is important to perform the procedure with well-trained nurses and ancillary staff familiar with the equipment and technical aspects of the procedure. Even when these preprocedural precautions are followed, and despite a very high initial success rate in palliation of malignant dysphagia and tracheoesophageal fistula, some patients will invariably develop complications after esophageal stent placement.10,11,14,15 Complications resulting in death from a terminal event related to conscious sedation, aspiration, stent malposition, bleeding, or esophageal perforation occur in 0.5% to 2% of patients.10 Complications associated with esophageal stent placement have not been shown, however, to be related to a patient’s age, sex, or stent location.16 There is no significant difference in complication rates of patients who undergo stent placement for proximal or distal carcinoma.17 In one survey of 212 endoscopists who had placed a total of

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Table 4-1. Complications of Esophageal Stents Intraprocedural Complications

Early Postprocedural Complications (2 weeks)

Conscious sedation-related events

Chest pain

Stent migration

Aspiration

Gastroesophageal reflux disease

Tracheoesophageal fistula

Stent malposition

Globus sensation

Bleeding

Bleeding

Incomplete expansion

Perforation

Esophageal perforation

Immediate migration

Early stent occlusion

Tracheal compression

Delayed stent occlusion

434 SEMS, the overall rate of immediate technical complications was 5.4%.10 The complications included misplacement (0.3%), failed expansion (3.9%), failed deployment (0.8%), and migration (0.3%). The overall rate of immediate patient complications was 14.7%, including chest pain (12.2%), perforation (0.6%), bleeding (0.6%), and death (1.4%). Delayed technical complications occurred in 18.1%, including tumor overgrowth and ingrowth (11.3%) and stent migration (6.8%). Delayed patient complications were noted in 26.9%, including gastroesophageal reflux disease ([GERD] 3.7%), recurrent dysphagia (8.2%), tracheoesophageal fistula (2.8%), bleeding (3.9%), perforation (0.8%), and death within 30 days that was not related to immediate stent placement (7.4%).10 To help simplify the approach to stent-related complications and their management, it is useful to classify complications based on the time of onset following stent placement (Table 4-1): intraprocedural complications, early postprocedural complications (less than 2 weeks status poststent placement), and late postprocedural complications (more than 2 weeks status poststent placement).

INTRAPROCEDURAL COMPLICATIONS Sedation-Related Events and Aspiration Conscious sedation with intravenous medications is used for esophageal stent placement in a large number of patients with uncomplicated mid and distal esophageal neoplasm. During the procedure, some physicians recommend having the head of the bed elevated to 30 degrees to minimize aspiration. Vigorous suction should be considered prior to tumor visualization in patients with distal neoplasm as a large column of secretions and food contents are often encountered. Alternatively, lavage with a large bore cannula (eg, nasogastric tube) should be considered to clear the esophagus of its contents. Continuous oropharyngeal suction is recommended to minimize oral secretions because this is critical in preventing aspiration. One study reported an incidence of aspiration in 3.4% of patients; despite broad spectrum antibiotics, one-third of the patients who developed aspiration died in subsequent follow up.18 General anesthesia with airway protection

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should always be considered in patients with proximal esophageal neoplasm. Prophylactic antibiotics should be considered in patients who are considered to be at high risk of aspiration during the procedure.

Stent Malposition Displacement or misplacement may result from miscalculating the stricture length or from failing to control for stent movement during deployment, resulting in malposition and inadequate proximal or distal margins. In addition, stent foreshortening is a potential pitfall leading to malposition and inadequate palliation of dysphagia. These pitfalls can be avoided with the liberal use of fluoroscopy and careful endoscopic visualization of the proximal and distal margins of the stent during the deployment itself. Radio-opaque markers are a useful option to delineate the desired proximal and distal landing zones and allow for calculation of the length the stent must bridge in order to provide effective palliation of dysphagia. Attempts should be made to remove or reposition a malpositioned stent using forceps snare or even balloon dilation. Alternatively, placement of another stent to salvage the first may also be considered. This may be challenging in patients where proximal margin of the stent is compromised and lies inside the tumor.

Tracheal Compression Tracheal compression during esophageal stent deployment is a rare but serious and potentially life-threatening complication that can usually be prevented with careful vigilance. This typically occurs when the esophageal stent is oversized to the point that the tumor mass compresses the airway during stent expansion. This can be avoided by tumor debulking with laser therapy and/or rigid esophagoscopy with tumor coring and débridement. The incidence of tracheal compression has been reported to occur in 1.7% to 5% of patients undergoing esophageal stent placement.18,19 In one series of 81 patients, stridor developed immediately after insertion in 3 patients with a lesion within 4 cm of the upper esophageal sphincter. In all patients, the stent was immediately removed, and they were managed conservatively.20 Esophageal stent placement should be reconsidered (or a prophylactic airway stent placed) if tracheal compression is suspected based on patient’s symptoms, computed tomography (CT) scan, bronchoscopy CT, or if balloon dilation leads to respiratory distress.21 Finally, depending upon the severity of symptoms, tracheal compression may sometimes require immediate stent removal and/or endotracheal intubation with concomitant airway stent placement.

Bleeding Severe bleeding requiring transfusion in the early and late periods following stent deployment is rare. Poststent hemorrhage is reported to be between 3% and 8%.11,22-25 It is usually mild and self-limiting. Bleeding is most likely related to stent-induced trauma to the tumor. Tissue abutment close to the distal end of the stent can result in mucosal ulcerations in the esophagus or stomach. Bleeding incidents have been reduced by modifications in stent design, including elimination of the wire hooks at the end of the stent and by softening the tips of the wire struts. Severe bleeding complications may occur in patients with bulky exophytic tumors, patients with coagulation abnormalities, and in those patients who have had concomitant laser or radiation treatment.26,27

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Endoscopic techniques can readily achieve hemostasis in most cases, with injection therapy being the most frequently used technique. Alternatively, endoclips or bipolar cauterization may be used in selected cases. Patients developing severe hemorrhage should undergo angiography and selective catheterization and angioembolization of the bleeding vessels.28 Bleeding may also be related to the type of stent placed, as has been seen with Gianturco Z-Stents.12,29,30 Identification of significant bleeding should prompt appropriate postprocedural monitoring in either a monitored unit or an intensive care unit. Rarely, fatal hemorrhage from aortoesophageal fistula related to stent erosion into the aorta has been reported as a late complication following stent placement for both benign and malignant disease.27,29,31-33 Studies have suggested a relationship between prior chemotherapy and radiation treatment and hemorrhage.12,27 In one series of 22 patients with advanced T4 tumors who underwent chemotherapy and radiation treatment, 6 of the 8 patients with tumor invasion into the aorta died of sudden massive hemorrhage after a median of 31 days.27

EARLY POSTPROCEDURAL COMPLICATIONS Chest Pain Following stent placement, patients can experience varying degrees of chest pain and discomfort. The etiology of chest pain is felt to be related to stent compression of the tumor and esophageal wall and associated movement of mediastinal structures. Early chest pain (which can be severe) occurs in a majority of patients, but prolonged chest pain is usually seen in 13% to 17% of patients.11,34 In one series, mild chest pain was noted to be as high as 27%.35 Pain symptoms can last as long as 2 to 3 weeks but this is usually well controlled with simple over-the-counter analgesics or prescription opioids. In rare cases, epidural anesthesia is required for pain relief.18 This is typically seen in large, proximal lesions and/or the use of rigid and large-diameter stents.11 Previous chemotherapy and radiation can increase the incidence of retrosternal chest pain.36 Suspicion for perforation should always be maintained in patients with persistent or worsening pain. Immediate imaging with chest x-ray, CT scan, or esophagram should be obtained to rule out esophageal perforation. Alternatively, chest pain may be a manifestation of gastroesophageal (GE) reflux especially in patients with a stent bridging the GE junction.

Globus Sensation Globus sensation has been described mostly in patients who undergo SEMS placement for proximal esophageal neoplasm. The incidence is reported to be between 8% and 18%.37,38 Careful selection of patients who need proximal esophageal stents, placement of stents with decreased radial force, and detailed attention to the proximal “landing zone” may be helpful in avoiding this problem. For proximal esophageal stents, a distance of at least 2 cm below the upper esophageal sphincter should be maintained if possible.

Incomplete Expansion Incomplete expansion may be the result of a severe, angulated stenosis, a large extrinsic compressing mass, or the use of a stent with low expansile strength. The incidence of incomplete expansion is low at 1.1%.18

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Figure 4-1. (A) This image demonstrates A incomplete expansion of a SEPS (Polyflex stent [Boston Scientific, Natick, MA]) in a patient with a refractory benign stricture related to corrosive ingestion. (B) The stent was initially repositioned with a forceps followed by balloon dilation to achieve complete expansion.

B

Predilation of the stricture may be helpful in preventing such complications but comes with an increased risk of bleeding and/or other complications. Incomplete expansion can result in persistent dysphagia, bleeding, food bolus impaction, and tissue ingrowth. Our preferred approach in these cases is to consider balloon dilation after incomplete expansion has been confirmed by endoscopy or fluoroscopy (Figure 4-1A). Balloon dilation or passing the endoscope through the stent results in complete expansion in most cases18 (Figure 4-1B). Removal of the existing stent, if possible, with snare or forceps followed by dilation and replacement of a stent with increased expansile force should also be considered. Failure of these maneuvers may necessitate the need for rigid endoscopy, laser therapy, and/or tumor debulking.

Early Stent Migration Early stent migration is a rare complication (0% to 10%) and in most cases is a result of both operator and tumor factors.39 Stent migration is almost always distal and typically occurs when the stent is positioned across the GE junction. Immediate stent migration has been associated with the following: • Use of fully covered stents • Short stents involving the GE junction • Stent malposition

Complications of Esophageal Stents and Their Management A

65

B

Figure 4-2. (A) Chest x-ray and (B) CT scan demonstrating anchoring overlapping stents to prevent stent migration in a patient with diffuse papillomatosis and esophageal squamous cell carcinoma.

• Tumor anatomy resulting in inadequate anchoring or landing zones • Very short segment strictures • Soft, easily compressible neoplasms that do not serve as good anchoring tissue for stents Adequate endoscopic or fluoroscopic evaluation of the stricture, avoidance of excessive predilation, and adequate apposition of the stent to the proximal esophagus will help decrease the incidence of early migration. In addition, in procedures involving long strictures, the use of an anchoring, overlapping double stent may prove helpful to prevent migration (Figure 4-2). A wide variety of techniques have been described for removal of migrated stents, including the use of snares, alligator or rat-tooth forceps, and dilating balloons. Endoscopic placement of a second stent to remove the original stent may also be needed in some patients. In some cases, removing the stent may not be an option and leaving it behind may be a prudent alternative, especially in patients with limited survival.40 Thus far, there is no evidence that surgically removing a stent that has completely migrated into the stomach is safer than leaving it in situ unless the patient is symptomatic.41 Operator experience and a good knowledge of the patient’s anatomy are helpful in preventing early stent migration.

Early Stent Occlusion Early stent occlusion is most commonly related to a food bolus impaction (Figure 4-3). One recent large study reported overall food impaction rate of 3% and was seen more in patients with shorter stent length.42 Patients with esophageal stents must modify their diet to prevent large boluses of food from becoming impacted within the stent. All patients should be formally counseled poststent placement regarding their diet. Eating leafy vegetables and raw fruits could result in partial or complete stent occlusion and should be avoided. Food bolusrelated stent occlusion is best managed by endoscopic removal or dislodgement using a Roth net, polypectomy snare, or grasping forceps. Fluoroscopic dislodgement is also effective, and a small percentage of patients may spontaneously pass the food bolus.42 Early stent

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Figure 4-3. (A) Food impaction. An A Ultraflex (Boston Scientific) stent completely obstructed with food 3 weeks following stent placement for unresectable esophageal cancer. (B) Same patient as in A following endoscopic removal of food and restoration of stent patency. (Reprinted with permission of Douglas G. Adler, MD.)

B

occlusion is rarely caused by tumor or tissue ingrowth. However, large exophytic tumor masses, necrotic tissue, or blood clots compressing the proximal margin may sometimes be responsible for early stent occlusion. Ablative treatments such as laser, argon plasma coagulation, and rarely mechanical débridement with a snare may prove useful in this scenario. These need to be performed cautiously to avoid stent injury or migration.

LATE COMPLICATIONS Stent-Related Gastroesophageal Reflux It is important to ascertain whether or not chest pain is related to acid reflux. Stents placed across the GE junction serve as an open conduit for reflux of acid and food contents, resulting in reflux esophagitis and aspiration (Figure 4-4). Patients who have had a stent placed across the GE junction should be educated about the potential risk of aspiration. Instruction about antireflux measures, including raising the head of the bed to 30 degrees and maintaining an upright or semiupright position at all times especially

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Figure 4-4. Severe GE reflux seen on barium contrast study in a patient with a stent bridging the GE junction.

during meals should be reinforced with the patient. Additionally, these patients should be placed on high-dose proton pump inhibitors to control acid production and should avoid eating for approximately 1 to 2 hours prior to going to sleep. Modifications in stent design including an antireflux sleeve with a one-way valve (Dua antireflux Z stent [Wilson-Cook Medical, Winston-Salem, NC]) appear to have reduced GE reflux in animal studies. The results in humans with this device have not been as promising.43 The antireflux valve stents are similar with regard to complication rates and quality of life.44,45 Despite the above preventative measures, approximately 30% of patients who undergo stent placement across the GE junction will experience GERD.46

Stent Occlusion Due to Tissue Hyperplasia and Tumor Ingrowth Tissue hyperplasia and tumor ingrowth is seen in approximately 17% to 36% of patients with uncovered stent placement and can be of varying degree, which may not manifest itself clinically. As such, the reported rate in the literature may be significantly under-reported. The incidence is less in patients with covered stents.11,25,47 Tumor overgrowth can occur at the proximal or distal end with extreme cases resulting in tight strictures and significant symptoms. When this occurs, our approach has been to place a second covered stent through the existing stent to create an area of overlap (so-called stent-within-stent deployment). Covered stents have minimal or no ingrowth; however, tumor overgrowth and benign hyperplasia may occur at the side of the stent. In one series, 13 patients with recurrent dysphagia secondary to tumor ingrowth in previously placed

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SEMS underwent endoscopic reintervention. SEPS were inserted into the already placed SEMS, resulting in palliation of dysphagia in all patients until death.48 Uncovered or partially covered esophageal stents placed for benign conditions may become epithelialized and embedded in the esophageal wall, making endoscopic retrieval impossible. Surgical removal is the only option in this setting (which often defeats the initial purpose of placing the stent). One recent study reported up to 50% nonretrieval in patients with stents left for greater than 6 weeks.49 In patients with conditions warranting stent removal and who develop significant ingrowth or hyperplasia that precludes immediate stent removal, placement of a second expandable plastic or covered metal stent into the initial stent can result in pressure necrosis of the hyperplastic tissue, allowing subsequent removal of both stents.50 Alternatively, dilation and thermal ablation of hyperplastic tissue using argon plasma coagulation are less preferred methods but may be useful in selected cases.

Tracheoesophageal Fistula Stent-related tracheoesophageal fistula can arise from progressive tumor growth with involvement of the trachea, radiation treatment, and/or a result of tissue ischemia and necrosis as a consequence of esophageal dilation and stent placement. These fistulas are best managed by placement of a second covered stent within the existing stent.51,52 In some cases, definite closure of the fistula may be difficult due to stent migration and/or the presence of a large-diameter fistula. In the setting of a malignant fistula, consideration should always be given to the placement of an airway stent. “Kissing stents” placed in these situations can be a very valuable treatment for a difficult problem and seldom result in the proliferation or enlargement of the fistulous tract.53-55 Nonetheless, a persistent fistula may result from inadequate sealing of the defect despite kissing stents (Figure 4-5). Placement of a large fully covered stent may be helpful in this situation. As most fistulae tend to be in the middle esophagus in proximity to the airway, it is prudent to consider covered stents in large necrotic tumors in this location.

Delayed Migration The overall risk of delayed stent migration ranges from 2% to 8%.41 The migration rate for covered stents is higher and ranges from 10% to 35%, presumably due to reduced friction between the membrane and the esophageal wall.1,41,56 Delayed migration appears less likely to be operator dependent, while concomitant chemotherapy and radiation may result in significant tumor shrinkage and resultant stent migration distally (Figure 4-6A). Endoscopic stent removal is much easier in this situation than in cases of early migration as the tumor mass has usually been reduced, leaving an easier passage to traverse with the endoscope and stent. In addition, changes in stent design and material have made the endoscopic retrieval of esophageal stents easier. Many stents now have proximal sutures that allow the closure or narrowing of the proximal stent diameter. This aids in easy retrieval. Our practice is to use a polyp snare or alligator forceps to grasp the stent or suture and to gently remove the stent under direct vision (Figure 4-6B). In challenging cases with sharply angulated and long strictures, however, removal can remain technically difficult. GE junction lesions are associated with an increased risk of migration as these lesions tend to be shorter in length, are often easily compressible, and may not provide an anchoring point for the distal portion of the stent (which may be left “dangling” in the

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A

B

Figure 4-5. (A) Persistent tracheoesophageal fistula despite double tracheal and esophageal stents as seen on contrast study. (B) Post-treatment with insertion of a long covered stent within the existing esophageal stent and subsequent closure of the fistula.

gastric cardia). Leaving an adequate margin of 3 to 4 cm above the proximal edge of the tumor and avoiding pre- or poststent dilation is helpful. Large-diameter stents and stents with larger proximal flanges are helpful in preventing delayed migration. Uncovered or partially covered stents placed in these positions are less prone to migration but are associated with other complications such as bleeding tissue, tumor overgrowth, or ingrowth.

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B

Figure 4-6. (A) Chest x-ray and CT scan showing distal migration of an esophageal stent into the stomach in a patient with distal esophageal adenocarcinoma following neoadjuvant therapy. (B) Endoscopic view of a migrated esophageal stent in stomach. The stent was retrieved with a snare after failed initial attempts at removal with a rat-tooth forceps.

The majority of migrated stents remain in the stomach (assuming the patient has an intact pylorus) and are, in general, amenable to endoscopic removal. Rarely, stents may migrate distally, causing obstructive ileus, small or large bowel obstruction, and perforation related to the stent or stent fragments, necessitating surgery.41,57-59 Spontaneous unrecognized passage of esophageal stents has also been reported.41 Recent improvement in stent designs and materials makes them less prone to these serious complications. Symptomatic migrated stents can often be removed endoscopically and therefore surgery

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is rarely needed. Very aggressive attempts at removal of migrated esophageal stents are discouraged especially in patients with advanced malignancy and short expected survival.

Stent-Induced Esophageal Perforations The incidence of esophageal perforations has been reported to be 2% to 8% of cases.60 With modifications in stent design, material, and delivery system, the incidence of stentinduced perforations has decreased. Important factors that may predispose the patient to esophageal perforation during stent placement include prestent dilation, guidewire-related trauma, prior esophageal surgery, aggressive attempts at bypassing the stricture with the endoscope, and sharply angulated long strictures. Avoidance of excessive predilation, initial use of soft-tip biliary wires, and ultrathin endoscope may help minimize the risk of esophageal perforation during stent placement. Early diagnosis of esophageal perforations is critical to successful management and delay may result in significant morbidity from a large leak resulting in hydro- or pyopneumothorax resulting in mediastinitis (Figure 4-7A). Patients who experience intractable chest, upper back, or shoulder pain or crepitus should be immediately evaluated by chest x-ray followed by oral contrast study with a chest and neck CT scan. Small contained perforations can generally be managed conservatively with nothing-by-mouth status, intravenous pain medications, antibiotics, and close inpatient observation. Large perforations may require surgical repair (Figure 4-7B). If a perforation is encountered during the placement of an esophageal stent, many physicians would argue to nonetheless complete the stent deployment as it may help treat/seal the perforation. Perforations associated with a benign condition such as a stricture may be better treated surgically. Classic surgical training dictates that a fistula (in this case, the esophageal perforation) will not heal when a distal obstruction or stricture is present.61 In this setting, formal esophagectomy is usually indicated. This may require a staged approach with initial resection, drainage of the mediastinum, and the creation of a cervical esophagocutaneous “spit” fistula. Later reconstruction, with either a gastric pull up or colonic interposition, could be used to re-establish continuity of the alimentary tract. Delayed perforations can be a result of concomitant chemotherapy and radiation treatment, aggressive attempts at endoscopic retrieval, or stent-induced trauma to proximal and distal normal esophageal mucosa. Delayed perforations are difficult to manage and have increased mortality up to 50%.60 Mediastinitis related to perforation may be treated with percutaneous drainage so long as the perforation is covered by a stent. If the degree of contamination is significant, this should be treated with surgical intervention. The “unresectable” patient may be best served with the combination of covered stent deployment and formal thoracotomy. Perforation in these cases may be treated with a pedicled flap closure using intercostal pedicle flap or omental flap.62

Pouch Formation Tumors with significant esophageal dilation above the stenotic area can be responsible for the formation of a semicircumferential “dead space” or pouch between the stent and the esophageal wall (Figure 4-8). This can result in the entrapment of food particles with stasis, resulting in bacterial overgrowth, fermentation, and chronic inflammation.63 The use of stents with large flanges and a limited proximal margin of stent may be helpful in preventing this complication.

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B

Figure 4-7. (A) Stent-related perforation after 2 weeks in a patient with esophageal adenocarcinoma. Persistent dysphagia poststent placement required balloon dilation of the stent. Persistent symptoms and further work up showed an esophageal perforation and leak from the area of the tumor and hydropneumothroax as shown on CT scan. (B) Chest x-ray and CT scan following repair with restenting of the esophagus, right thoracotomy, and diaphragm muscle flap closure of the esophageal perforation.

Rare Miscellaneous Complications A variety of rare complications including severe life-threatening hemorrhage, fistulae, and infections due to stent-related trauma and erosion into surrounding structures have been reported. Although remote, the possibility of these rare events should be entertained in patients with esophageal stents and unexplained symptoms. Spinal epidural abscess, erosion of stent into left common carotid artery, and stent-related compression of left atria resulting in hemodynamic compromise have all been reported.64,65 Gastropleural fistulae and pneumocephalus resulting from involvement of the paravertebral space by esophageal stents have also been described as late complications of a migrated esophageal stent.66,67

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Figure 4-8. Endoscopic view of an esophageal stent demonstrating potential dead space (arrow) around the proximal edge of the stent which can result in pouch formation.

CONCLUSION Self-expanding esophageal stents remain an attractive option for palliation of malignant dysphagia and tracheoesophageal fistulae. The endoscopist’s experience, patient selection, deployment methodology, and careful attention to detail are of great importance in determining the overall success of the procedure. In general, rates of serious complications with self-expanding esophageal stents are low, but significant complications can occur. Careful selection of individual cases is critical to the success of the procedure. Early recognition of complications and subsequent endoscopic and/or surgical reintervention may improve overall outcomes. Continued improvement in stent design and the recent use of biodegradable stents may further decrease the incidence of such complications.

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29. Dirks K, Schulz T, Schellmann B, Stolte M, Lutz H. Fatal hemorrhage following perforation of the aorta by a barb of the Gianturco-Rösch esophageal stent. Z Gastroenterol. 2002;40(2):81-84. 30. Siersema PD, Tan TG, Sutorius FF, Dees J, van Blankenstein M. Massive hemorrhage caused by a perforating Gianturco-Z stent resulting in an aortoesophageal fistula. Endoscopy. 1997;29(5):416-420. 31. Mukherjee S, Kaplan DS, Parasher G, Sipple MS. Expandable metal stents in achalasia—is there a role? Am J Gastroenterol. 2000;95(9):2185-2188. 32. Kennedy C, Steger A. Fatal hemorrhage in stented esophageal carcinoma: tumor necrosis of the aorta. Cardiovasc Intervent Radiol. 2001;24(6):443-444. 33. Grundy A, Glees JP. Aorto-oesophageal fistula: a complication of oesophageal stenting. Br J Radiol. 1997;70(836):846-849. 34. Cheng YS, Li MH, Chen WX, Chen NW, Zhuang QX, Shang KZ. Complications of stent placement for benign stricture of gastrointestinal tract. World J Gastroenterol. 2004;10(2):284-286. 35. van Boeckel PG, Siersema PD, Sturgess R, Dwyer L, Raijman I, Hirdes MM, Vleggaar FP. A new partially covered metal stent for palliation of malignant dysphagia: a prospective follow-up study. Gastrointest Endosc. 2010;72(6):1269-1273. 36. Homs MY, Hansen BE, Van Balkenstesin M. Prior radiation and/or chemotherapy has no effect the outcome of metal stent placement for oesophagogastric carcinoma. Eur J Gastroenterol Hepatol. 2004;16:163-170. 37. Macdonald S, Edwards RD, Moss JG. Patient tolerance of cervical esophageal metallic stents. J Vasc Interv Radiol. 2000;11(7):891-898. 38. Verschurr EM, Kuipers EJ, Siersema PD, Esophageal stents for malignant strictures close to the upper esophageal sphinchters. Gastrointestinal Endosc. 2007;66:1082-1090. 39. Christie NA, Buenaventura PO, Fernando HC, et al. Results of expandable metal stents for malignant esophageal obstruction in 100 patients: short-term and long-term follow-up. Ann Thorac Surg. 2001;71(6):1797-1801. 40. Di Fiore F, Lecleire S, Antonietti M, et al. Spontaneous passage of a dislocated esophageal metal stent: report of two cases. Endoscopy. 2003;35(3):223-225. 41. De Palma GD, Iovino P, Catanzano C. Distally migrated esophageal self-expanding metal stents: wait and see or remove? Gastrointest Endosc. 2001;53(1):96-98. 42. Song M, Song HY, Kim JH, et al. Food impaction after expandable metal stent placement: experience in 1,360 patients with esophageal and upper gastrointestinal tract obstruction. J Vasc Interv Radiol. 2011;22(9):1293-1299. 43. Dua KS, Kozarek R, Kim J, et al. Self-expanding metal esophageal stent with anti-reflux mechanism. Gastrointest Endosc. 2001;53(6):603-613. 44. Wenger U, Johnsson E, Arnelo U, Lundell L, Lagergren J. An antireflux stent versus conventional stents for palliation of distal esophageal or cardia cancer: a randomized clinical study. Surg Endosc. 2006;20(11):1675-1680. 45. Homs MY, Wahab PJ, Kuipers EJ, et al. Esophageal stents with antireflux valve for tumors of the distal esophagus and gastric cardia: a randomized trial. Gastrointest Endosc. 2004;60(5):695-702. 46. Valbuena J. Endoscopic palliative treatment of esophageal and cardial cancer: a new antireflux prosthesis. A study of 40 cases. Cancer. 1984;53(4):993-998. 47. Adam A, Ellul J, Watkinson AF, et al. Palliation of inoperable esophageal carcinoma: a prospective randomized trial of laser therapy and stent placement. Radiology. 1997;202(2):344-348. 48. Conio M, Blanchi S, Filiberti R, De Ceglie A. Self-expanding plastic stent to palliate symptomatic tissue in/overgrowth after self-expanding metal stent placement for esophageal cancer. Dis Esophagus. 2010;23(7):590-596. 49. van Heel NC, Haringsma J, Spaander MC, Bruno MJ, Kuipers EJ. Short-term esophageal stenting in the management of benign perforations. Am J Gastroenterol. 2010;105(7):1515-1520. 50. Hirdes MM, Siersema PD, Houben MH, Weusten BL, Vleggaar FP. Stent-in-stent technique for removal of embedded esophageal self-expanding metal stents. Am J Gastroenterol. 2011;106(2):286-293. 51. Siersema PD, Hop WC, van Blankenstein M, et al. A comparison of 3 types of covered metal stents for the palliation of patients with dysphagia caused by esophagogastric carcinoma: a prospective, randomized study. Gastrointest Endosc. 2001;54(2):145-153.

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52. Wang MQ, Sze DY, Wang ZP, Wang ZQ, Gao YA, Dake MD. Delayed complications after esophageal stent placement for treatment of malignant esophageal obstructions and esophagorespiratory fistulas. J Vasc Interv Radiol. 2001;12(4):465-474. 53. Nomori H, Horio H, Imazu Y, Suemasu K. Double stenting for esophageal and tracheobronchial stenoses. Ann Thorac Surg. 2000;70(6):1803-1807. 54. Siersema PD, Schrauwen SL, van Blankenstein M, et al. Self-expanding metal stents for complicated and recurrent esophagogastric cancer. Gastrointest Endosc. 2001;54(5):579-586. 55. Cook TA, Dehn TC. Use of covered expandable metal stents in the treatment of oesophageal carcinoma and tracheo-oesophageal fistula. Br J Surg. 1996;83(10):1417-1418. 56. Dai Y, Chopra SS, Kneif S, Hünerbein M. Management of esophageal anastomotic leaks, perforations, and fistulae with self-expanding plastic stents. J Thorac Cardiovasc Surg. 2011;141(5):1213-1217. 57. Harries R, Campbell J, Ghosh S. Fractured migrated oesophageal stent fragment presenting as small bowel obstruction three years after insertion. Ann R Coll Surg Engl. 2010;92(6): W14-W15. 58. Henne TH, Schaeff B, Paolucci V. Small-bowel obstruction and perforation. A rare complication of an esophageal stent. Surg Endosc. 1997;11(4):383-384. 59. Zhang W, Meng WJ, Zhou ZG. Multiple perforations of the jejunum caused by a migrated esophageal stent. Endoscopy. 2011;43(Suppl 2):E145-E146. 60. Siersema PD. Treatment options for esophageal strictures. Nat Clin Pract Gastroenterol Hepatol. 2008;5(3):142-152. 61. Rolandelli R, Roslyn JJ. Surgical management and treatment of sepsis associated with gastrointestinal fistulas. Surg Clin North Am. 1996;76(5):1111-1122. 62. Wright CD, Mathisen DJ, Wain JC, Moncure AC, Hilgenberg AD, Grillo HC. Reinforced primary repair of thoracic esophageal perforation. Ann Thorac Surg. 1995;60(2):245-248; discussion 248-249. 63. Ell C, Hochberger J, May A, Fleig WE, Hahn EG. Coated and uncoated self-expanding metal stents for malignant stenosis in the upper GI tract: preliminary clinical experiences with Wallstents. Am J Gastroenterol. 1994;89(9):1496-1500. 64. Ali AT, Kokoska MS, Erdem E, Eidt JF. Esophageal stent erosion into the common carotid artery. Vasc Endovascular Surg. 2007;41(1):80-82. 65. Sganzerla P, Passaretti B, Perlasca E, Giovannelli A. An unusual case of acute fatal pulmonary congestion: oesophageal stenting. Int J Cardiol. 2007;117(2):e64-e65. 66. Furlong H, Nasr A, Walsh TN. Gastropleural fistula: a complication of esophageal selfexpanding metallic stent migration. Endoscopy. 2009;41(Suppl 2):E38-E39. 67. Qu X, Yang W, Han T, et al. Pneumocephalus after interventional therapy in esophageal cancer. Clin Neurol Neurosurg. 2010;112(8):707-709.

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Metal Biliary Stents in Benign Pancreaticobiliary Disease Michelle A. Anderson, MD, MSc and Richard S. Kwon, MD, MSc

Early self-expanding metal stents (SEMS) were uncovered or partially covered. Because of this, tissue can enter the spaces between individual cells of the uncovered portion of the stent (through epithelial hyperplasia, embedding of the stent wires, or tumor ingrowth) and render the stent endoscopically unremoveable.1-5 For these reasons, the use of uncovered and partially covered SEMS is generally limited to use in conditions resulting from malignant disease or in patients with a significantly shortened life expectancy. The advent of fully covered SEMS (FCSEMS) has broadened the use of these stents to treat benign diseases of the pancreatic and biliary systems. This chapter will focus on FCSEMS and will review the available devices, indications, and contraindications for use; techniques for placement; and retrieval, as well as how to prevent complications and to manage them when they occur. Finally, we will discuss potential areas of utilization of these stents in the future.

EQUIPMENT This review will focus on FCSEMS rather than partially covered or uncovered SEMS. Currently there are only 2 FCSEMS available in the United States—the fully covered Wallflex stent (Boston Scientific, Natick, MA) and the Viabil stent (ConMed, Utica, NY). Both of these stents have been approved for use in benign conditions (and hence are removable after deployment) in the pancreatic and biliary systems in Canada and Europe but not in the United States, where they are used in these locations in an off-label manner.

INDICATIONS AND OUTCOMES FCSEMS have been used in the bile duct and pancreatic duct for both benign and malignant indications, although there are no stents that are currently approved for use in

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the United States for benign disease. Despite this, the use of FCSEMS has been described for more than 10 years for a variety of benign conditions, including persistent pancreatic duct leaks, refractory bile duct strictures due to chronic pancreatitis, and for treatment of iatrogenic injuries. Although initially thought to provide prolonged stent patency over uncovered or partially covered SEMS, FCSEMS do not clearly provide a stent patency duration advantage in the setting of malignant disease.6,7 In contrast, FCSEMS have been successful in achieving technical success in situations where plastic stents have failed.

Benign Biliary Obstruction The most common cause of benign biliary strictures (BBS) is surgical injury to the biliary system, most commonly occurring during cholecystectomy.8 Other causes include chronic pancreatitis, gallstone-induced strictures, strictures in the setting of primary sclerosing cholangitis (PSC), and those related to liver transplantation. The effectiveness of plastic stents for treatment of biliary strictures secondary to chronic pancreatitis has been disappointingly poor with long-term patency rates averaging only 35.9%.9 This is particularly true in patients with calcific chronic pancreatitis and strictures of the common bile duct where failure of endoscopic therapy is 17 times more likely than among patients with chronic pancreatitis and no calcifications.10 In recent years, improved efficacy has been achieved through the use of multiple plastic stents placed simultaneously and in parallel in the bile duct with progressive increase in the number and diameter of the stents with each successive endoscopic retrograde cholangiopancreatography (ERCP) until the desired outcome is achieved.11-13 In a study comparing multiple plastic stents to single plastic stents for common bile duct stenosis secondary to chronic pancreatitis, patients undergoing the multistent protocol all had near normalization of liver chemistries and a 1- to 3-mm increase in common bile duct diameter after placement of 4 or 5 simultaneous plastic stents over a mean of 14 months.11 In contrast, patients who had received only a single plastic stent experienced only minimal correction of liver chemistries and no change in common bile duct diameter. The effectiveness of a multistent approach for treatment of biliary strictures is significantly better in postoperative BBS with technical and clinical success rates exceeding 90%.9 In a retrospective study of 45 patients who had undergone endoscopic therapy with multiple simultaneous plastic stents for treatment of postoperative strictures, 89% of patients (40/45) experienced clinical success (defined as endoscopic resolution of the stricture and sustained normalization of liver chemistries after a mean follow up of 48.8 months).14 Outcomes in this series of patients after very long-term follow up (mean of 13.7 years) suggest that this benefit is sustained with only 20% of patients experiencing a recurrence in their strictures or stricture-related symptoms.15 Given the improved performance of multiple plastic stents for nonchronic pancreatitisinduced strictures, most endoscopists reserve the use of FCSEMS for those situations in which plastic stents have failed (Figure 5-1). Nevertheless, it is important to recognize that resolution of strictures with plastic stents may only be achieved after several endoscopic procedures spanning a minimum of several months or up to 1 year of therapy and requiring a commitment on the part of the patient and the clinician to a long-term therapy plan. For these reasons, many centers have begun to explore the role of SEMS in benign disease. Early generations of covered SEMS were partially rather than fully covered and although these were effective in the treatment of cholestasis and cholangitis related to chronic pancreatitis-induced strictures, long-term patency was poor and stent dysfunction common.5,16 Since the development of FCSEMS, there have been several uncontrolled

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Figure 5-1. (A) Occlusion cholangiogram demonstrating extravasation of contrast from the cystic duct stump (arrow) in a patient who underwent cholecystectomy complicated by bile leak which failed to respond to stenting with a 10 Fr plastic biliary stent. (B) Placement of a 10-mm covered metal stent (Viabil). (C) Repeat occlusion cholangiogram 9 weeks later demonstrating resolution of the bile leak. (Reprinted with permission of Christopher Lawrence, MD.)

trials reporting on the use of these stents to treat benign biliary obstruction. In a small Dutch case series, FCSEMS were used to treat strictures of the common bile duct in 6 patients with underlying chronic pancreatitis.17 Despite being fully covered, SEMS were not removable in 2 patients and were left in place. In one of these patients, plastic stents inserted through the SEMS have been used to maintain common bile duct patency during follow up (31 months at the time of publication). In the other patient, the distal end of the stent was trimmed with argon plasma coagulation but no additional stenting or other therapy was needed during 32 months of follow up. In the 4 patients in whom the SEMS were successfully removed following a treatment period of 3 to 6 months, all patients had stricture resolution, although one patient experienced a recurrence of his stricture after 6 months, necessitating hepaticojejunostomy. In the largest single series of FCSEMS for BBS, FCSEMS were placed in 44 patients over a 15-month period.18 Resolution of the stricture was achieved in 34 (83%) patients although the median follow up at the time of publication was only 3.8 months. The likelihood of successful treatment of the stricture differed between those with underlying pancreatitis and those with strictures due to other causes (58% versus 92%, p = 0.01 by intention-to-treat analysis). Complications occurred in 10 (22.7%) patients and included pancreatitis (n = 3) and migration (n = 2). Stents were successfully removed in all subjects in whom it was attempted (41/44) and was not attempted in the remaining patients as they died from unrelated causes before stent removal was deemed necessary. In a smaller Spanish series, FCSEMS were used to treat 20 patients with a variety of benign biliary conditions ranging from idiopathic, iatrogenic, and stone-related inflammatory strictures.19 All stents were successfully extracted after a mean dwell time of 132 days (36 to 270 days) and complete resolution of the condition warranting SEMS was observed in 14 patients (70%).

Pancreatic Duct Strictures For patients with pain secondary to chronic pancreatitis, ductal drainage is often undertaken with the goal of decompressing the pancreatic duct and alleviating pain. Although there have been numerous uncontrolled trials suggesting that endoscopic

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therapy can be effective in this setting,20-23 2 prospective, randomized trials comparing endoscopic with surgical drainage have shown that surgery is more effective in providing long-term pain relief.24,25 The randomized trials referenced compared endoscopic stenting with plastic stents to surgical drainage. No studies have compared FCSEMS with surgical drainage in patients with painful chronic pancreatitis and pancreatic duct strictures. In a nonrandomized case series from Italy, investigators used multiple simultaneous plastic stents to successfully treat chronic pancreatitis-induced strictures of the pancreatic duct in 18 of 19 patients.26 The observation that increasing the overall diameter of the stricture with multiple stents could produce more favorable outcomes then set the stage for SEMS in the treatment of pancreatic duct strictures. In the first US study of FCSEMS for chronic pancreatitis, stents were placed into the pancreatic duct in 6 patients with painful chronic pancreatitis, concomitant pancreatic duct stricture, and upstream pancreatic duct dilation.27 All subjects had failed endoscopic therapy with plastic stents. FCSEMS (8- or 10-mm diameter) were placed following pancreatic sphincterotomy and pancreatic duct stricture dilation with 4- or 6-mm balloon dilators. Stents were successfully removed after 3 months in 5 patients and left in 1 patient who was diagnosed with pancreatic cancer. In 4 of the 5 subjects who successfully completed the protocol, pain scores 4 weeks after FCSEMS placement improved from a mean of 6.4 ± 2 to 1.6 ± 1.8 (p = 0.024) on a visual analog scale (0 being no pain and 10 being the worst pain imaginable). In 2 patients, pain recurred following removal of the stent while 2 remained free of pain 4 and 8 months later. A second, larger series of FCSEMS for benign pancreatic ductal strictures from South Korea reported similar outcomes.28 Pain relief was achieved in all 13 patients who underwent FCSEMS placement and all had improvement or resolution of their pancreatic duct stricture. Stents were removed successfully in 9 subjects after 2 months while the remaining 4 subjects experienced spontaneous, distal migration. Other complications included mild pancreatitis (3), cholestatic liver dysfunction (2), and proximal stent migration (1). All 3 subjects who developed pancreatitis had undergone pancreatic duct stricture dilation with a balloon or a Soehendra stent extractor prior to stent placement. In both this study as well as that of the previous study,27 there were no stent-induced changes of the pancreatic duct outside of the remodeling of the targeted stricture. Using a modified version of a FCSEMS, the Korean group recently reported on an additional series of 32 patients treated for symptomatic pancreatic duct strictures.29 The modifications included a greater range of SEMS diameters (6 to 10 mm), flared stent ends, and an alternating size of the cells within each stent, which produced a “bumpy” conformation expected to lower rates of migration. In this series, there were no migrations and all stents were easily removed. All patients experienced pain relief while the stents were in place although 5 had their pain recur during a mean follow up of 5 months (range 3 to 7 months), 3 with stricture recurrence. Unlike the previously reported studies, 5 out of 32 (15.6%) patients experienced stent-induced strictures though all were clinically asymptomatic at least at initial discovery. An additional caveat to this study is that a majority of patients (26 out of 32) had pancreatic duct stones, 19 of whom underwent extracorporeal shockwave lithotripsy prior to FCSEMS placement. Thus, it is impossible to know how this additional therapy may have affected outcomes if performed alone. There are additional case reports on the use of FCSEMS for treatment of a patient with a refractory postoperative pancreatic duct leak and through the minor ampulla for treatment of chronic pancreatitis and pancreas divisum (n = 3).30,31

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Although these early studies are promising, there is a myriad of issues surrounding the use of SEMS, fully covered or not, in the pancreatic duct for benign disease. Given the relatively short-term follow up of the referenced studies as well as the difficulties associated with accurately measuring pain and quality of life in this disease, it is unclear what the long-term benefits or side effects of these stents will be. It is quite likely that these stents, by nature of their fully covered design, could impair pancreatic exocrine function and could increase the risk of stone or stricture formation in the secondary and tertiary branches of the pancreas.32 In turn, this could lead to impairment of organ function as well as an increase in pain over time. A particularly troubling aspect to the use of these stents in this setting is the apparent equipoise between stent migration and the creation of stent-induced pancreatic duct strictures.33 Finally, it has been shown that patients with chronic pancreatitis can fail to have relief of their symptoms despite resolution of their strictures and conversely that they can have persistence of their pain despite resolution of their pancreatic duct strictures.20,29 Given this, any endoscopic therapy that can have serious sequelae should be looked at cautiously.

Self-Expanding Metal Stents in the Treatment of Bile Duct Leaks After Cholecystectomy Bile leaks are among the most common complications of laparoscopic cholecystectomy, occurring in an estimated 0.4% to 2.1% of cases.34-36 Bile leaks arise most frequently from the cystic duct remnant but can also occur from the duct of Luschka or from the common hepatic, common bile, or intrahepatic ducts if there has been injury to the duct itself. The standard therapy for bile leaks after cholecystectomy is ERCP with sphincterotomy, placement of a temporary plastic biliary stent, or a combination thereof. ERCP successfully identifies the site of the leak in more than 98% of cases.37 This approach is successful in more than 85% of patients undergoing a single ERCP and in more than 98% in patients who undergo an additional 1 to 2 more ERCPs with stent change.38 For the remaining 2% of patients, options include further attempts at endoscopic stenting with one or more plastic biliary stents, as well as percutaneous or transhepatic drainage, all of which may also fail and necessitate return to the operating room. Recently, the utility of FCSEMS for management of persistent or complex bile leaks following cholecystectomy has been reported. In one case series, FCSEMS were placed in 7 patients who had undergone cholecystectomy for gallstone-related disease; most (6 of 7) had leaks originating from the cystic duct remnant.39 All of these patients had complete resolution of the bile leak, although one of these patients developed a stricture of the common hepatic duct just below the confluence. No therapy for this stricture was undertaken, and the patient was asymptomatic after 221 days of follow up. Stents were successfully removed in all 7 patients. Choledochoscopy, performed selectively in this study, revealed several patients with ulcerations in the bile duct at the points where the anchoring fins of the stent (a design feature used to prevent migration) contacted the bile duct. Another, smaller case series reported successful use of earlier generations of covered SEMS in patients who developed complex bile leaks after attempted cholecystectomy with incomplete removal of the entire gallbladder.40

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Self-Expanding Metal Stents in the Treatment of Liver Transplant Complications (Leaks and Strictures) Bile leaks are a common complication of liver transplantation, occurring in 1.5% to 12% of cadaveric transplants and in a higher proportion of living related transplants.41-43 The most frequently occurring site for the bile leak is at the duct-to-duct anastomosis, followed by one of the cystic duct remnants. The majority of these cases can be successfully treated with temporary endoscopic or percutaneous placement of a plastic biliary stent, although leaks are persistent in 4% to 16% of patients.42,44,45 Although uncovered and partially covered stents in this setting are contraindicated, several relatively small series of patients with post-transplant bile leaks successfully managed with FCSEMS have recently been reported (Figure 5-2). The first series describes outcomes from a mix of patients with bile leaks resulting from either complicated gallbladder surgeries or following liver transplantation.39 Out of the 13 patients in this series, 5 were patients who had developed leaks following orthotopic liver transplant. Four of these patients had leaks at the anastomotic site while one had a leak in a left radical branch of the biliary tree. All 5 patients received a Viabil stent and all had resolution of their leaks. Four of these patients had the FCSEMS successfully removed while the last patient died with the stent in place due to infectious complications unrelated to the stent or the bile leak. This same group later published results from an extended cohort of 17 patients receiving FCSEMS for treatment of bile leaks after transplant.46 Overall, bile leaks resolved in 16 out of 17 patients over a median of 102 days (range 35 to 427 days). The next series reported on the use of a FCSEMS not available in the United States, the Niti-S FCSEMS (Taewoong Medical, South Korea).47 In this study, 5 patients with bile leaks following orthotopic liver transplantation were treated with the Niti-S stent after ERCP with standard therapy including sphincterotomy and stenting with plastic stents had failed. Stents were left in place for 2 months with successful retrieval and resolution of the leaks in all 5 patients.

CONTRAINDICATIONS There are no absolute contraindications for placement of FCSEMS. Relative contraindications include those conditions or circumstances that would render a patient inappropriate for any endoscopic procedure (eg, cardiac or pulmonary disease severe or unstable enough to make endoscopy dangerous, inability to provide informed consent). Although dilation of the bile or pancreatic duct at the site of a stricture prior to deployment of these stents is generally not required, it may be necessary to allow passage of the delivery catheter through the stricture. Altered anatomy affecting the pancreatic or biliary ducts directly (eg, hepaticojejunostomy) or surgeries that render the pancreatic and biliary systems inaccessible (eg, Roux-en-Y gastrojejunostomy) may make placement of SEMS difficult or impossible. As is the case for the placement of plastic stents or uncovered SEMS, access to the biliary or pancreatic ducts may be provided by way of a laparoscopic gastrostomy tube, although this technique has not yet been reported for placement of a FCSEMS.48-50 Although the successful use of covered SEMS has been described in the treatment of iatrogenic injury of the bile duct, manufacturers of the biliary FCSEMS recommend that they not be deployed in

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Figure 5-2. FCSEMS for a bile leak following liver transplantation. (A) Flouroscopic image of an intractable anastomotic bile leak (arrow) following liver transplantation. The patient failed to respond to several months of treatment with plastic biliary stents. (B) Endoscopic image of a fully covered Viablil stent placed in a transampullary manner in the same patient. The leak ultimately healed after 3 months of treatment and the stent was removed. (Reprinted with permission of Douglas G. Adler, MD.)

B

patients with known or suspected perforations of the bile or pancreatic duct.51,52 In addition, FCSEMS should not be deployed in the intrahepatic ducts due to their large diameter (8 or 10 mm) because this may lead to perforation or other complications.

PREPARATION Patient preparation for placement of FCSEMS is not different than that of the typical patient undergoing ERCP and should include a careful history, physical, and informed consent. Since many patients will require sphincterotomy of one or both sphincters as well as possible dilation, these procedures will frequently fall into the realm of “high risk” for procedure-related bleeding.53 Accordingly, the risks and benefits of holding antithrombotic agents to lower the risk of procedurally induced hemorrhage should be carefully considered and determined for the individual patient in question.53,54 If there

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is an expectation that incomplete drainage will be accomplished or that contrast will be retained in the biliary or pancreatic systems, one should consider administration of preand postprocedure antibiotics.55

TECHNIQUE In almost all cases, placement of a FCSEMS will require a diagnostic ERCP with cannulation and injection of appropriate ducts as indicated to direct placement. As a first step, it is very important to define the extent of the problem that is being targeted. In the case of a stricture, one must illustrate the proximal and distal extents of the stricture and use this to determine the length of the stent chosen for treatment. For biliary strictures in patients with intact gallbladders, it is also important to determine the site of take-off of the cystic duct and, if possible, to place the stent so that the most cephalad portion lies below that position to lower the risk of cholecystitis. If this origin is not obvious on initial injection, injecting through an occlusion balloon while the balloon is inflated and the catheter is being withdrawn can be very helpful. The choice of a “below-the-balloon” or an “above-the-balloon” injector device may vary based upon whether a prior biliary sphincterotomy has been performed or not. For example, if the patient has an intact sphincter, injection with a below-the-balloon catheter starting at the level of the hilum and slowing retracting will almost always illustrate the cystic duct take-off while a similar technique in a patient with a prior sphincterotomy will frequently result in the contrast simply pouring into the duodenum through the patulous orifice. Although many routinely perform a sphincterotomy (either biliary or pancreatic depending upon where the stent is being deployed) when placing a SEMS, this is not an absolute requirement. There are no data to show that sphincterotomy has any meaningful benefit for patients undergoing transampullary biliary stenting for any indication. The diameter of the delivery device of both of the currently approved FCSEMS available in the United States is 8.5 Fr. These catheters are easily passed through a standard ERCP scope accessory channel although one may encounter resistance when passing the delivery devices through tight strictures. Dilation of biliary strictures prior to delivery of the FCSEMS is generally not necessary but may be helpful in the treatment of pancreatic duct strictures. FCSEMS are deployed over a guidewire positioned with the tip in the intrahepatic ducts. Like other SEMS, FCSEMS are released as the covering catheter is drawn back over the delivery catheter. The Wallflex stent is reconstrainable when less than 80% of the stent has been deployed while the Viabil stent is not reconstrainable. When deploying the stent, one should attempt to place the stent midway through the stricture if possible as this may lower the risk for proximal or distal migration. Moreover, most experts advise that the distal portion of the stent be positioned so that at least 5 mm of the stent extends into the duodenal lumen to facilitate removal in the future.40 Stents that undergo foreshortening on full expansion may need an additional 2 to 4 mm of intraluminal placement. Traction on the delivery catheter is generally necessary to prevent deploying the stent within the bile duct. Although patients undergoing SEMS placement with intact biliary sphincters typically have very little foreshortening when the “point of no return” is reached on the deployment catheter, those with sphincterotomies may see additional, albeit minimal, foreshortening. Successful delivery of FCSEMS typically results in the rapid drainage of contrast from the biliary or pancreatic ductal system following deployment.

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When FCSEMS are placed in the pancreatic duct for treatment of pancreatic strictures or leaks, it is advisable to remove pancreatic duct calculi prior to stent deployment, recognizing that this may not be possible in all patients. This commonly requires the employment of extracorporeal shock wave lithotripsy and may necessitate additional procedures. Surprisingly, the deployment of FCSEMS in the pancreatic duct does not routinely result in pancreatitis. This may be related to the underlying obstructive conditions present in patients with chronic pancreatitis.

REPOSITIONING One of the 2 currently available FCSEMS (Wallflex) comes on a reconstrainable delivery device such that the stent can be pulled back into the covering sleeve if deployment has not gone beyond a predesignated point (this being less than approximately 70% to 80% of the device length). In this way, one can adjust the stent if it migrates or foreshortens on delivery. However, it is important to avoid repeatedly reconstraining the SEMS since this may damage the outer sheath or the stent or impair the fluidity of the deployment. Although manufacturers do not recommend repositioning SEMS after they are deployed, I have found that it is possible to do so, using either a rat-tooth forceps or a snare, particularly if this is attempted immediately after deployment.

EXCHANGE AND REMOVAL The 2 FCSEMS currently approved for use in the United States have approval for removal and hence are used in benign conditions (specifically for treatment of benign strictures) in both Canada and Europe. In a retrospective review using data from 4 large academic centers, the method, safety, and ease of removal of one of these stents (Viabil) was recently published.56 In this study, investigators reviewed all cases in which a FCSEMS was removed over a 4-year period from 2004 to 2008. In total, 190 patients had undergone placement of this FCSEMS for malignant obstruction (76%), benign stricture (20%), or refractory bile leak (4%). Removal was attempted and was successful in 37 using a snare (n = 29) or a forceps (n = 8). There were no perforations or transfusion-requiring bleeding in any patients who underwent SEMS removal although stent-related complications were seen in 4 patients including secondary strictures in 2, secondary stricture plus cholangitis in 1, and a confined bile leak (into tumor) in the last patient. It should be noted that in 2 of the 3 patients with secondary strictures, the SEMS that were placed were larger than the duct receiving the SEMS. The authors hypothesize that the oversized stents stimulated the duct and contributed to the formation of the secondary strictures. This would be supported by the observation that the strictures occurred at the proximal margin of the stent rather than another point (eg, where the anchoring fins projected from the stent sides). Several methods for retrieving and removing FCSEMS have been described. The most commonly employed technique involves snaring the distal end of the stent in the lumen of the duodenum and withdrawing the stent either through the accessory channel of the endoscope (although this has the potential to result in scope damage) or by withdrawing the entire scope from the patient with the stent secured by the snare at its end. Another technique is using a rat-tooth forceps to grab the distal end of the stent and withdrawing

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the endoscope with the stent grasped firmly at its end from the patient. If there is resistance to movement of the stent, additional traction force may be applied by switching to a double-channel therapeutic endoscope and using 2 forceps, one down each accessory channel, to simultaneously grasp the stent. Other unique methods for removal of FCSEMS have been described. In one case report, the endoscopist passed a snare through a 10 Fr pushing catheter.57 After snaring the distal end of the stent, the stent was drawn up into the catheter and then the catheter was removed with the stent contained within it from the endoscope. In this way, damage to the accessory channel was avoided and the scope did not have to be completely removed and reintroduced to continue therapy. In another case report, a through-thescope continuous radial expansion (CRE) balloon dilator (Boston Scientific) was successfully used to simultaneously extract 2 FCSEMS from the bile duct. The stents had been placed in tandem and with slight overlap in order to treat a persistent bile leak in a patient following cholecystectomy. The method was attempted after a standard approach of pulling the distal stent with a rat-tooth forceps failed as the 2 stents had become interlocked and inseparable with distal retraction.58

COMPLICATIONS: INCIDENCE, PREVENTION, MANAGEMENT Stent Migration Stent migration, more common with FCSEMS than with partially covered or uncovered SEMS, is estimated to occur in up to 37.5% of cases, and is particularly frequent when used to treat complications of liver transplantation.5,6,17,18,47,59,60 Although FCSEMS typically migrate in a distal direction, proximal migrations have been reported and can be more difficult to correct. In one case report, a FCSEMS migrated proximally in the common bile duct, coming to lie in a transverse or horizontal plane and making endoscopic removal impossible.61 Palliation was achieved using a plastic stent passed through the metal stent. In recent years, manufacturers have altered stent design in an attempt to overcome stent migration. One example of this is the biliary Viabil stent, which has anchoring fins along the exterior length that are intended to hold the stent in place. A second example is the Niti-S pancreatic stent (Taewoong Medical, Seoul, Korea—not available in the United States), which has alternating cell sizes along the length of the stent. This alteration results in a “bumpy” conformation to the stent and nonuniform radial pressure of the stent within the duct, both of which are thought to contribute to decreased rates of stent migration. In a recently published paper, double-pigtail plastic stents were deployed within FCSEMS to anchor them and to prevent migration. In this randomized, controlled study, investigators placed FCSEMS in 33 patients with BBS; 16 of these had their FCSEMS positioned and deployed in the usual fashion (nonanchored) while the other 17 underwent placement of a 5 Fr plastic double-pigtail through the FCSEMS with the same wire used to deploy the FCSEMS (anchored group). The positioning of the plastic stent was done so that the proximal end (toward the liver) lay in the right or left main hepatic duct while the distal end was allowed to curl around the edge of the FCSEMS and into the duodenum. The migration rate was assessed using monthly surveillance films of the abdomen

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with confirmation on endoscopy. Significantly fewer patients who underwent placement of an anchored stent experienced migration than those patients who had a traditional stent placement (1/16 [6.3%] versus 7/17 [41.2%], p = 0.024).62 It should be noted that the FCSEMS used in this study is not approved for use in the United States.

Stent-Induced Strictures There have been several studies showing that SEMS (both covered and uncovered) can induce strictures of the bile duct and the pancreatic duct. This is particularly frequent when FCSEMS are placed for treatment of liver transplant complications and when used in the pancreatic duct (where ductal changes including frank stenosis are seen in up to 47% and 15.6% of cases, respectively).29,46 Some have hypothesized that stents with flared ends may induce a relative ischemia at the flare, which causes local ischemia leading to strictures.29 In one study using the Viabil stent in 17 patients with post-transplant bile leaks, 8 (47%) patients developed stent-related strictures, 6 (35%) of which were clinically significant and required further endoscopic therapy.46 The authors propose that this may be a result of the high radial force of this particular SEMS.63 In support of this theory, they demonstrated ulceration of the bile duct at the level of the stent in 3 of 6 patients who underwent cholangioscopy following FCSEMS removal.46 In animal studies of one type of FCSEMS (Wallflex), FCSEMS were placed endoscopically into the normal bile ducts of miniature pigs. After 3 months, stents that had not migrated spontaneously (6/10) were removed endoscopically. Bile ducts from the euthanized animals showed superficial and acute inflammation initially and chronic inflammation but no scarring or fibrosis if euthanasia was delayed 1 additional month after FCSEMS removal.64 A second theory purports that strictures are due to the placement of oversized stents in narrow ductal systems.56

Cholecystitis The incidence of cholecystitis following covered SEMS placement is estimated at 7.1% and is thought to occur due to occlusion of the cystic duct orifice by the stent covering.5 Based on this premise, some have advised deployment of the proximal end of the stent below the takeoff of the cystic duct in patients with intact gallbladders although this does not always prevent the complication.5 Alternatively, the placement of a plastic gallbladder stent prior to deployment of the biliary FCSEMS has been used successfully to prevent cholecystitis but is rarely performed in practice.18

Cholestasis and Choledocholithiasis Formation Despite the larger diameter of SEMS, patients undergoing placement of biliary SEMS frequently develop cholestasis without frank stent occlusion. In one study in which FCSEMS were used to treat bile leaks following liver transplantation, almost all patients (10/11 who underwent follow-up ERCP after stent placement) developed de novo choledocholithiasis and/or luminal debris.39 One theory is that food debris and bacteria migrate between the duodenal lumen and the bile duct and act as a nidus for stone formation.39 The placement of pancreatic SEMS has also been associated with cholestasis and is believed to be due to occlusion of the biliary orifice by the stent covering.28 This may be avoided by performing biliary sphincterotomy if not previously done. In a study of

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32 patients who underwent placement of a FCSEMS for treatment of a pancreatic duct stricture in the setting of chronic pancreatitis, biliary sphincterotomy was performed in all patients who had not previously undergone biliary sphincterotomy.29 There was no evidence of cholestasis on close biochemical follow up in any study subject.

Pancreatitis The placement of FCSEMS in the bile duct is complicated by pancreatitis in 6.8% of patients.18 Although this is thought to occur due to extrinsic compression of the pancreatic orifice by the biliary SEMS, the actual mechanism is unclear and may be due to a variety of nonstent factors such as the cannulation or other maneuvers performed during the procedure. At this point in time, the published data does not definitively support SEMS placement as a cause of post-ERCP pancreatitis. Surprisingly, placement of FCSEMS in the pancreatic duct does not uniformly result in pancreatitis (further bolstering the lack of association between SEMS placement and post-ERCP pancreatitis) as might be expected given that the side branches are blocked by the stent covering. Reasons for this are unclear but may be due to the chronic relative obstruction of pancreatic juice outflow present in most patients with chronic pancreatitis. It should be noted that although removal of plastic stents from the pancreatic duct does not typically lead to post-ERCP pancreatitis, this complication has been seen following the removal of FCSEMS in the pancreatic duct, likely due to the more traumatic nature of FCSEMS removal.18

Pain Occasionally, patients will experience abdominal pain in the absence of pancreatitis following deployment of SEMS, which, if persistent, may require stent removal.65 The etiology of the pain is unclear but may be related to radial forces of a stent diameter that is larger than the normal duct.

FUTURE DIRECTIONS The use of covered metal stents is rapidly changing and case reports of innovative uses continue to be published. Recently, use of these stents has been reported for control of bleeding after biliary sphincterotomy. In 5 patients who had undergone biliary sphincterotomy for a variety of benign indications and experienced postsphincterotomy bleeding, FCSEMS were placed across the ampullary orifice to tamponade the bleeding site.66 All 5 patients had normal platelet counts and international normalized ratios less than 1.5. In 4 of these patients, traditional methods for hemostasis such as endoclips and epinephrine injection were attempted and failed prior to placement of the FCSEMS. In all 5 patients, bleeding was controlled and no further intervention for bleeding was required. In 3 of these patients, the stents were easily removed 2 to 8 weeks after treatment while the stents had spontaneously migrated in the 2 remaining patients without recurrence of bleeding or other complication. FCSEMS have also been used transluminally and percutaneously for facilitation of necrosectomy in the setting of acute pancreatitis.67

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Recently, there have been several reports on the use of FCSEMS to address iatrogenic injury. In one study, 2 patients who had sustained periampullary perforations at the time of sphincterotomy were treated with FCSEMS.19 Both papillary perforations responded to stenting although one patient had to undergo surgery for a duodenal perforation distant from the sphincterotomy site. In other case reports, FCSEMS have been used to treat bile duct injuries occurring during partial hepatectomy as well as a bile leak following radiofrequency ablation of colorectal cancer metastases.51,52 There are no data on the use of FCSEMS for PSC, gallstone-induced strictures, or biliary strictures resulting from chronic infections of the bile duct. There is a case report of a SEMS (likely uncovered) that was used in a patient with PSC to treat biliary strictures prior to liver transplant. At the time of transplantation, the stent had to be removed by pulling each individual wire, which induced massive, life-threatening bleeding.68 Whether FCSEMS might result in a different outcome is unclear and routine use of these stents in patients awaiting liver transplant cannot be advised at this time.

CONCLUSION FCSEMS are now widely available, and the future will likely show a continued increase in both their indications and overall use. FCSEMS offer clinical benefits in a variety of benign conditions and will likely be most useful to practitioners in the management of recalcitrant pancreaticobiliary strictures, although other roles for these devices will likely become more common over time. FCSEMS may allow for treatment of atypical pancreaticobiliary difficulties in select patients.

REFERENCES 1. Bethge N, Sommer A, Gross U, von Kleist D, Vakil N. Human tissue responses to metal stents implanted in vivo for the palliation of malignant stenoses. Gastrointest Endosc. 1996;43(6):596-602. 2. Kahaleh M, Tokar J, Le T, Yeaton P. Removal of self-expandable metallic Wallstents. Gastrointest Endosc. 2004;60(4):640-644. 3. Deviere J, Cremer M, Baize M, Love J, Sugai B, Vandermeeren A. Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents. Gut. 1994;35(1):122-126. 4. Rossi P, Bezzi M, Salvatori FM, Maccioni F, Porcaro ML. Recurrent benign biliary strictures: management with self-expanding metallic stents. Radiology. 1990;175(3):661-665. 5. Cantu P, Hookey LC, Morales A, Le Moine O, Deviere J. The treatment of patients with symptomatic common bile duct stenosis secondary to chronic pancreatitis using partially covered metal stents: a pilot study. Endoscopy. 2005;37(8):735-739. 6. Kullman E, Frozanpor F, Soderlund C, et al. Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. Gastrointest Endosc. 2010;72(5):915-923. 7. Telford JJ, Carr-Locke DL, Baron TH, et al. A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. Gastrointest Endosc. 2010;72(5):907-914. 8. Lillemoe KD, Melton GB, Cameron JL, et al. Postoperative bile duct strictures: management and outcome in the 1990s. Ann Surg. 2000;232(3):430-441.

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9. van Boeckel PG, Vleggaar FP, Siersema PD. Plastic or metal stents for benign extrahepatic biliary strictures: a systematic review. BMC Gastroenterol. 2009;9:96. 10. Kahl S, Zimmermann S, Genz I, et al. Risk factors for failure of endoscopic stenting of biliary strictures in chronic pancreatitis: a prospective follow-up study. Am J Gastroenterol. 2003;98(11):2448-2453. 11. Catalano MF, Linder JD, George S, Alcocer E, Geenen JE. Treatment of symptomatic distal common bile duct stenosis secondary to chronic pancreatitis: comparison of single vs. multiple simultaneous stents. Gastrointest Endosc. 2004;60(6):945-952. 12. Draganov P, Hoffman B, Marsh W, Cotton P, Cunningham J. Long-term outcome in patients with benign biliary strictures treated endoscopically with multiple stents. Gastrointest Endosc. 2002;55(6):680-686. 13. Pozsar J, Sahin P, Laszlo F, Forro G, Topa L. Medium-term results of endoscopic treatment of common bile duct strictures in chronic calcifying pancreatitis with increasing numbers of stents. J Clin Gastroenterol. 2004;38(2):118-123. 14. Costamagna G, Pandolfi M, Mutignani M, Spada C, Perri V. Long-term results of endoscopic management of postoperative bile duct strictures with increasing numbers of stents. Gastrointest Endosc. 2001;54(2):162-168. 15. Costamagna G, Tringali A, Mutignani M, et al. Endotherapy of postoperative biliary strictures with multiple stents: results after more than 10 years of follow-up. Gastrointest Endosc. 2010;72(3):551-557. 16. Behm B, Brock A, Clarke BW, et al. Partially covered self-expandable metallic stents for benign biliary strictures due to chronic pancreatitis. Endoscopy. 2009;41(6):547-551. 17. Cahen DL, Rauws EA, Gouma DJ, Fockens P, Bruno MJ. Removable fully covered selfexpandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series. Endoscopy. 2008;40(8):697-700. 18. Mahajan A, Ho H, Sauer B, et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video). Gastrointest Endosc. 2009;70(2):303-309. 19. Garcia-Cano J, Taberna-Arana L, Jimeno-Ayllon C, et al. Use of fully covered self- expanding metal stents for the management of benign biliary conditions. Rev Esp Enferm Dig. 2010;102(9):526-532. 20. Eleftherladis N, Dinu F, Delhaye M, et al. Long-term outcome after pancreatic stenting in severe chronic pancreatitis. Endoscopy. 2005;37(3):223-230. 21. Delhaye M, Arvanitakis M, Verset G, Cremer M, Deviere J. Long-term clinical outcome after endoscopic pancreatic ductal drainage for patients with painful chronic pancreatitis. Clin Gastroenterol Hepatol. 2004;2(12):1096-1106. 22. Cremer M, Deviere J, Delhaye M, Baize M, Vandermeeren A. Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients. Endoscopy. 1991;23(3):171-176. 23. Gabbrielli A, Pandolfi M, Mutignani M, et al. Efficacy of main pancreatic-duct endoscopic drainage in patients with chronic pancreatitis, continuous pain, and dilated duct. Gastrointest Endosc. 2005;61(4):576-581. 24. Cahen DL, Gouma DJ, Nio Y, et al. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis. N Engl J Med. 2007;356(7):676-684. 25. Dite P, Ruzicka M, Zboril V, Novotny I. A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis. Endoscopy. 2003;35(7):553-558. 26. Costamagna G, Bulajic M, Tringali A, et al. Multiple stenting of refractory pancreatic duct strictures in severe chronic pancreatitis: long-term results. Endoscopy. 2006;38(3): 254-259. 27. Sauer B, Talreja J, Ellen K, Ku J, Shami VM, Kahaleh M. Temporary placement of a fully covered self-expandable metal stent in the pancreatic duct for management of symptomatic refractory chronic pancreatitis: preliminary data (with videos). Gastrointest Endosc. 2008;68(6):1173-1178. 28. Park do H, Kim MH, Moon SH, Lee SS, Seo DW, Lee SK. Feasibility and safety of placement of a newly designed, fully covered self-expandable metal stent for refractory benign pancreatic ductal strictures: a pilot study (with video). Gastrointest Endosc. 2008;68(6):1182-1189.

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29. Moon SH, Kim MH, Park do H, et al. Modified fully covered self-expandable metal stents with antimigration features for benign pancreatic-duct strictures in advanced chronic pancreatitis, with a focus on the safety profile and reducing migration. Gastrointest Endosc. 2010;72(1):86-91. 30. Baron TH, Ferreira LE. Covered expandable metal stent placement for treatment of a refractory pancreatic duct leak. Gastrointest Endosc. 2007;66(6):1239-1241. 31. Liao Z, Li ZS, Wang W, et al. Endoscopic placement of a covered self-expandable metal stent in the minor papilla in patients with chronic pancreatitis and pancreas divisum. Endoscopy. 2009;41(Suppl 2):E302-E303. 32. Ostroff JW. Pain and chronic pancreatitis: are we really ready for metal in the pancreatic duct? Gastrointest Endosc. 2008;68(6):1179-1181. 33. Binmoeller KF. Fully covered metal stents in the pancreatic duct: balancing trade-offs. Gastrointest Endosc. 2010;72(1):92-94. 34. Scott TR, Zucker KA, Bailey RW. Laparoscopic cholecystectomy: a review of 12,397 patients. Surg Laparosc Endosc. 1992;2(3):191-198. 35. Barkun AN, Rezieg M, Mehta SN, et al. Postcholecystectomy biliary leaks in the laparoscopic era: risk factors, presentation, and management. McGill Gallstone Treatment Group. Gastrointest Endosc. 1997;45(3):277-282. 36. Adamsen S, Hansen OH, Funch-Jensen P, Schulze S, Stage JG, Wara P. Bile duct injury during laparoscopic cholecystectomy: a prospective nationwide series. J Am Coll Surg. 1997;184(6):571-578. 37. Sandha GS, Bourke MJ, Haber GB, Kortan PP. Endoscopic therapy for bile leak based on a new classification: results in 207 patients. Gastrointest Endosc. 2004;60(4):567-574. 38. Ryan ME, Geenen JE, Lehman GA, et al. Endoscopic intervention for biliary leaks after laparoscopic cholecystectomy: a multicenter review. Gastrointest Endosc. 1998;47(3):261-266. 39. Wang AY, Ellen K, Berg CL, Schmitt TM, Kahaleh M. Fully covered self-expandable metallic stents in the management of complex biliary leaks: preliminary data - a case series. Endoscopy. 2009;41(9):781-786. 40. Baron TH, Poterucha JJ. Insertion and removal of covered expandable metal stents for closure of complex biliary leaks. Clin Gastroenterol Hepatol. 2006;4(3):381-386. 41. Shah JN, Ahmad NA, Shetty K, et al. Endoscopic management of biliary complications after adult living donor liver transplantation. Am J Gastroenterol. 2004;99(7):1291-1295. 42. Solmi L, Cariani G, Leo P, Miracolo A, Nigro G, Roda E. Results of endoscopic retrograde cholangiopancreatography in the treatment of biliary tract complications after orthotopic liver transplantation: our experience. Hepatogastroenterology. 2007;54(76): 1004-1008. 43. Park JS, Kim MH, Lee SK, et al. Efficacy of endoscopic and percutaneous treatments for biliary complications after cadaveric and living donor liver transplantation. Gastrointest Endosc. 2003;57(1):78-85. 44. Morelli J, Mulcahy HE, Willner IR, et al. Endoscopic treatment of post-liver transplantation biliary leaks with stent placement across the leak site. Gastrointest Endosc. 2001;54(4): 471-475. 45. Pfau PR, Kochman ML, Lewis JD, et al. Endoscopic management of postoperative biliary complications in orthotopic liver transplantation. Gastrointest Endosc. 2000;52(1):55-63. 46. Phillips MS, Bonatti H, Sauer BG, et al. Elevated stricture rate following the use of fully covered self-expandable metal biliary stents for biliary leaks following liver transplantation. Endoscopy. 2011;43(6):512-517. 47. Traina M, Tarantino I, Barresi L, et al. Efficacy and safety of fully covered self-expandable metallic stents in biliary complications after liver transplantation: a preliminary study. Liver Transpl. 2009;15(11):1493-1498. 48. Gutierrez JM, Lederer H, Krook JC, Kinney TP, Freeman ML, Jensen EH. Surgical gastrostomy for pancreatobiliary and duodenal access following Roux en Y gastric bypass. J Gastrointest Surg. 2009;13(12):2170-2175. 49. Lopes TL, Wilcox CM. Endoscopic retrograde cholangiopancreatography in patients with Roux-en-Y anatomy. Gastroenterol Clin North Am. 2010;39(1):99-107.

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50. Mutignani M, Marchese M, Tringali A, et al. Laparoscopy-assisted ERCP after biliopancreatic diversion. Obes Surg. 2007;17(2):251-254. 51. Blasco J, Real MI, Montana X, et al. Percutaneous repair of an iatrogenic laceration of the left bile duct with a covered stent. J Vasc Interv Radiol. 2001;12(9):1112-1115. 52. Thompson PM, Hare CM, Lees WR. Bile duct disruption following radiofrequency ablation: successful repair using a covered stent. Cardiovasc Intervent Radiol. 2004;27(4): 383-385. 53. Anderson MA, Ben-Menachem T, Gan SI, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc. 2009;70(6):1060-1070. 54. Chan FK, Abraham NS, Scheiman JM, Laine L. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Antiinflammatory Drugs and Anti-platelet Agents. Am J Gastroenterol. 2008;103(11):2908-2918. 55. Banerjee S, Shen B, Baron TH, et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc. 2008;67(6):791-798. 56. Kasher JA, Corasanti JG, Tarnasky PR, McHenry L, Fogel E, Cunningham J. A multicenter analysis of safety and outcome of removal of a fully covered self-expandable metal stent during ERCP. Gastrointest Endosc. 2011;73(6):1292-1297. 57. Koornstra JJ, van Dullemen HM, Weersma RK. A safe technique for removing a malpositioned covered biliary self-expandable metal stent. Endoscopy. 2008;40(Suppl 2):E165. 58. Luigiano C, Ferrara F, Fabbri C, Bassi M, Cennamo V, D’Imperio N. Insertion of two overlapping new covered metal stents for closure of a complex biliary leak and description of a safe technique for their removal. Endoscopy. 2011;43(Suppl 2):E211-E212. 59. Wamsteker EJ, Elta GH. Migration of covered biliary self-expanding metallic stents in two patients with malignant biliary obstruction. Gastrointest Endosc. 2003;58(5):792-793. 60. Isayama H, Nakai Y, Kawakubo K, et al. Covered metallic stenting for malignant distal biliary obstruction: clinical results according to stent type. J Hepatobiliary Pancreat Sci. 2011;18(5):673-677. 61. Manouras A, Archodovassilis F, Lagoudianakis EE, et al. Vertical rotation and impaction to the choledochal duct of a migrated biliary self-expanding metal stent. Surg Laparosc Endosc Percutan Tech. 2007;17(5):416-417. 62. Park JK, Moon JH, Choi HJ, et al. Anchoring of a fully covered self-expandable metal stent with a 5F double-pigtail plastic stent to prevent migration in the management of benign biliary strictures. Am J Gastroenterol. 2011;106(10):1761-1765. 63. Isayama H, Nakai Y, Toyokawa Y, et al. Measurement of radial and axial forces of biliary selfexpandable metallic stents. Gastrointest Endosc. 2009;70(1):37-44. 64. Bakhru MR, Foley PL, Gatesman J, Schmitt T, Moskaluk CA, Kahaleh M. Fully covered selfexpanding metal stents placed temporarily in the bile duct: safety profile and histologic classification in a porcine model. BMC Gastroenterol. 2011;11:76. 65. Kahaleh M, Behm B, Clarke BW, et al. Temporary placement of covered self-expandable metal stents in benign biliary strictures: a new paradigm? (with video). Gastrointest Endosc. 2008;67(3):446-454. 66. Shah JN, Marson F, Binmoeller KF. Temporary self-expandable metal stent placement for treatment of post-sphincterotomy bleeding. Gastrointest Endosc. 2010;72(6):1274-1278. 67. Navarrete C, Castillo C, Caracci M, Vargas P, Gobelet J, Robles I. Wide percutaneous access to pancreatic necrosis with self-expandable stent: new application (with video). Gastrointest Endosc. 2011;73(3):609-610. 68. Narumi S, Hakamda K, Toyoki Y, et al. Biliary hemorrhage after removal of an expandable metallic stent during liver transplantation. Liver Transpl. 2008;14(11):1578-1581.

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Metal Biliary Stents in Patients With Potentially Resectable Pancreaticobiliary Malignancy Tyler M. Berzin, MD, MS; Ram Chuttani, MD; and Douglas K. Pleskow, MD, AGAF, FASGE

After colon cancer, pancreatic cancer is the second most common gastrointestinal malignancy, and it continues to carry a grave prognosis with a 5-year survival rate of only 5.6%. Surgical resection remains the only curative treatment for pancreatic cancer; however, only 15% of patients present with early, potentially resectable disease.1 TNM (defined as the size of the tumor and whether it has invaded nearby tissue, regional lymph nodes that are involved, and distant metastasis) and American Joint Committee on Cancer (AJCC) staging classifications exist for pancreatic cancer, however, determination of resectability ultimately rests on the presence or absence of (1) metastatic disease and (2) major vascular invasion (ie, invasion into the celiac artery or superior mesenteric artery or substantial involvement of the portal or superior mesenteric veins). Although numerous imaging modalities, including endoscopic ultrasound, play a role in pancreatic cancer staging, pancreatic protocol helical computed tomography (CT) scans are critical for determination of surgical resectability, mostly due to their ability to identify metastases as well as their ability to assess local extent of disease. However, small metastatic implants can be missed by CT scan, and staging laparoscopy with cytologic washings can detect occult metastatic disease in approximately 25% of patients with potentially resectable disease on CT scan.2 Thus, staging laparoscopy can be undertaken prior to moving forward with pancreaticoduodenectomy and has been shown to increase the curative resection rate in pancreatic cancer from 27% to 50% in a recent meta-analysis.2 Importantly, there is increasing evidence that neoadjuvant chemotherapy may also improve the rate of curative resection, although this can delay surgery significantly.3 For patients presenting with obstructive jaundice due to a potentially resectable pancreatic head mass, early endoscopic retrograde cholangiopancreatography (ERCP) with biliary stenting offers several potential benefits. First, cytologic brushing obtained during

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the ERCP may provide a definitive diagnosis. Second, biliary drainage by insertion of a plastic or metal stent may provide symptomatic relief of pruritis and jaundice, particularly in patients for whom surgery will be delayed (ie, those with comorbidities needing assessment or those who will undergo neoadjuvant therapy). Third, there is evidence to suggest that preoperative biliary drainage may improve immune function, nutritional status, and coagulation, although definitive evidence for a benefit in human studies is lacking.4 The interval between symptomatic presentation and surgical resection may be an increasingly relevant concern as the role of neoadjuvant chemotherapy evolves. The primary focus of this chapter is to explore possible roles of self-expanding metal stents (SEMS) for biliary drainage in patients with potentially resectable pancreatic cancer prior to operative resection.

PLASTIC VERSUS METAL BILIARY STENTS IN PANCREATIC MALIGNANCY Several important technical characteristics of biliary stents must be taken into consideration in the setting of endoscopic biliary drainage for patients with potentially resectable pancreatic cancer. First, it is imperative that the placement of a biliary stent not interfere with the performance of subsequent pancreaticoduodenectomy. Additionally, an ideal stent would also provide long-term biliary palliation in the substantial group of patients who are found to be unresectable (or to be poor surgical candidates) during further evaluation or staging laparotomy. An ideal stent should also have a low rate of migration, limit tissue ingrowth, and preserve biliary patency for as long as possible. For these and other reasons, biliary SEMS are gaining increasing favor over plastic stents for the management of malignant obstructive jaundice in patients planned for operative resection.

Plastic Biliary Stents Plastic (polyethylene) stents have been in use for endoscopic biliary procedures since the 1970s. The advantages of plastic stents include low cost as well as ease of deployment and endoscopic removability. Further, the presence of a plastic biliary stent is generally not felt to impact technical aspects of an ensuing Whipple resection as the stent does not embed into surrounding tissue. The major disadvantage of plastic stents is the risk of stent occlusion, which is related to the relatively narrow 7 to 10 Fr diameters of most commonly used biliary plastic stents and the accumulation of sludge and bacterial biofilm.5 Late stent occlusion is the most common complication of plastic biliary stent placement, occurring in one-third to one-half of patients, usually within 4 to 5 months if not sooner.6 Cholangitis and recurrent jaundice are typical manifestations of stent occlusion and require subsequent ERCPs to remove and replace stents. In patients with pancreatic cancer awaiting surgery and in those deemed to not be surgical candidates, stent occlusions and their attendant hospitalizations and repeat ERCPs can incur costs and morbidity. A recently published randomized control trial generated renewed concerns regarding the prevalence of plastic biliary stent complications in the preoperative period.7 This study compared outcomes in patients diagnosed with resectable pancreatic head cancer who underwent resection within 1 week of diagnosis versus those who first underwent ERCP with biliary stent placement followed by surgery in 4 to 6 weeks. In this study, 46% of

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patients in the ERCP arm developed complications related to the ERCP or stent, including 26% who developed cholangitis. Nearly one-third of patients in the study required a second ERCP for plastic stent exchange (generally for stent occlusion and/or cholangitis) prior to surgery. The authors concluded that routine preoperative biliary drainage for patients with pancreatic head cancer increased the rate of preoperative complications without any demonstrable difference in postoperative complications. The study was limited by an unusually high failure rate during ERCP (that is difficult to account for) and the lack of use of neoadjuvant therapy, somewhat limiting its value. The authors also commented, as did an accompanying editorial, that SEMS may provide a more effective alternative to plastic stents in this setting, warranting further clinical study on the use of SEMS for preoperative biliary drainage.7,8

Self-Expanding Metal Stents Biliary SEMS offer several specific benefits over plastic stents. The most commonly used biliary SEMS are 10 mm in diameter, nearly 3 times larger than most plastic stents. Multiple trials in patients with unresectable pancreaticobiliary malignancy have demonstrated that biliary SEMS have a longer duration of patency than plastic stents.9-12 For unresectable disease, the importance of long-term patency, particularly in patients who are likely to survive beyond 3 to 6 months, is a primary reason that biliary SEMS have become standard of care for palliation of obstructive jaundice.13 In patients with potentially resectable pancreaticobiliary malignancy, the issue of longterm stent patency is also relevant, both for patients who are later found to be unresectable at laparoscopy (avoiding the short-term need for a second ERCP for palliation) and also for patients in whom surgery may be delayed. Improved long-term patency reduces the likelihood of cholangitis and recurrent jaundice and thus limits the need for repeat ERCP.10,11 For potentially resectable pancreatic cancer, several issues need to be taken into consideration in determining whether biliary SEMS are appropriate for routine use. The first issue is whether placement of a metal biliary stent placement will impact technical aspects of surgical resection. There was early reluctance to use SEMS in patients with potentially resectable cancer because of concerns that a metal stent would interfere with aspects of surgical resection.14 There is now substantial experience with SEMS in the preoperative setting, and it has become increasingly evident that preoperative SEMS placement does not complicate the performance of the Whipple procedure.15-17 Cost is a second important issue regarding the appropriateness of preoperative biliary SEMS for potentially resectable pancreatic cancer. The use of a biliary SEMS adds approximately $1000 to the cost of an ERCP compared to a plastic stent, which may cost as little as $80.18,19 Cost-effectiveness analysis, taking into account stent occlusion rates and the cost of repeat ERCP and hospital care in the setting of delayed stent occlusion, has supported the use of SEMS for both potentially resectable and unresectable pancreatic cancer when stent patency is required beyond 4 to 5 months.19,20 It is also worth noting that some patients present to ERCP for malignant obstructive jaundice before a final determination has been made regarding whether or not to proceed with surgical resection. For these patients too, initial placement of a biliary SEMS may avoid the need for repeat ERCPs, particularly in patients ultimately deemed not to be surgical candidates, and does not complicate any potential surgery for those who proceed to pancreaticoduodenectomy.

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TECHNICAL FEATURES OF BILIARY SELF-EXPANDING METAL STENTS A range of biliary SEMS are available from numerous manufacturers, each with subtle variations in size, materials, and delivery system (Table 6-1). The majority of currently available biliary SEMS are made of nitinol, a nickel-titanium alloy with unique properties of superelasticity and temperature-sensitive shape memory. At or below room temperature, nitinol stents are easily constrained in a narrow delivery system, but when heated to their “transformation temperature” (which typically approximates body temperature), the stent becomes superelastic and capable of exerting chronic radial expansile force against the surrounding bile duct wall. The delivery systems for currently available biliary SEMS range from 6.0 to 8.5 Fr in diameter and can be deployed through either a diagnostic or therapeutic duodenoscope. It is common practice to use the therapeutic duodenoscope in nearly all cases, except when luminal strictures necessitate use of the smaller scope. Stent deployment is generally achieved by withdrawal of a covering, restraining sheath, although the precise mechanism varies by manufacturer. The endoscopist must be particularly mindful of 2 characteristics of deployment, which vary by stent: stent reconstrainability and foreshortening. Certain stents, such as the Boston Scientific (Natick, MA) Wallflex stent, can be partially deployed and then reconstrained and repositioned if necessary, whereas others cannot be reconstrained after the initial steps of deployment have begun. Additionally, depending on the design of the woven nitinol wire, some stents maintain the same length before and after deployment, whereas others foreshorten by as much as 40% during deployment. There is no evidence that one stent type is definitively superior to others, but endoscopists should be familiar with the properties of any given stent and its associated deployment catheter prior to use.

Stent Size Biliary strictures due to pancreatic cancer typically involve the lower bile duct. Generally 4- or 6-cm length stents are adequate to cross the stricture. These shorter stents are also easier to remove en bloc with the surgical specimen during resection. For longer strictures or strictures located higher in the biliary system, stent lengths of up to 10 cm may be necessary, although these stents may encroach on the hepatic hilum and should be placed with care in this situation. To limit stent migration, it is best to have 1 to 2 cm of the stent above the proximal extent of the stricture. In general, it is preferable to choose the shortest length stent that will extend 1 to 2 cm above the stricture and will protrude about 0.5 to 1 cm from the ampulla after deployment so that the stent can fully bridge the obstruction and be easily recannulated in the future if necessary. Although 6-, 8-, and 10-mm diameter biliary SEMS are available, 10-mm diameter stents are used most frequently as the larger diameter may help preserve biliary patency for the maximum possible time.

Uncovered, Partially Covered, and Fully Covered Stents Biliary SEMS were originally available only as uncovered steel mesh models. The incorporation of new alloys such as nitinol has been accompanied by other important

Alveolus

ConMed

ConMed

Taewoong Medical

Boston Scientific

Boston Scientific

Olympus

Cook

Flexxus

Gore Viabil

Niti-S

Wallflex

Wallstent

X-Suit NIR

Zilver (G257 and G635 models)

Manufacturer

Alimaxx-B

Stent

U

U

P, U

C, P, U

U

C

U

U

Covered (C) Partially Covered (P) and/ or Uncovered (U)

Table 6-1. Currently Available Biliary Self-Expanding Metal Stents

6, 8, and 10 mm x 4, 6, and 8 cm (635 model stent also available in 8, 9, 10, and 12 mm diameters)

8 and 10 mm x 4, 6, 8, and 10 cm

8 and 10 mm x 4, 6, and 8 cm (10 cm- UC only)

8 and 10 mm x 4, 6, and 8 cm (10 cm = UC only)

8 and 10 mm x 4 to 10 cm and 12 cm

8 and 10 mm x 4, 6, 8, and 10 cm

8 and 10 mm x 4, 6, 8, and 10 cm

8 and 10 mm x 4, 6, and 8 cm

Stent Sizes Diameter (mm) x Length (cm)

7.5 Fr coaxial sheath

7.5 Fr coaxial sheath

8.0 Fr coaxial sheath

8 to 8.5 Fr coaxial sheath

8 to 8.5 Fr coaxial sheath

8.5 Fr coaxial sheath

7.5 Fr pistol grip

6.5 Fr pistol grip

Delivery System Diameter and Mechanism

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developments in stent design. In particular, several biliary SEMS are now available with polymer coatings along the length of the stent. The use of polymers to partially or fully cover the length of the stent is intended to limit tumor ingrowth and thus prolong luminal patency. In patients undergoing resection for pancreatic cancer, both covered and uncovered stents can be removed en bloc within the resected tumor specimen.15 Clinical evidence has been mixed with regard as to whether there is any meaningful difference in the long-term patency rates of covered versus uncovered stents in pancreaticobiliary malignancy with recent randomized trials demonstrating no significant difference in stent patency.21-23 A consistent finding of these studies has been that covered stents have a higher rate of migration (2% to 9%) than uncovered stents (0% in the referenced studies). It is possible that the risk of stent migration may be higher in patients receiving neoadjuvant therapy due to tumor shrinkage. Despite initial concerns regarding the risk of cholecystitis in patients with an intact gallbladder, it does not appear that covered biliary SEMS placement carries a substantially higher risk of cholecystitis than uncovered SEMS placement, and thus the presence or absence of a gallbladder does not alter our decision making regarding stent selection.23 It is worth noting that there is early evidence that fully covered biliary SEMS can be successfully removed endoscopically, which, in general, is not a possibility with uncovered stents due to embedment of the stent into the surrounding bile duct walls, tissue hyperplasia, and tumor ingrowth into the stent mesh.24 While stent removability is of much greater importance in benign disease than in malignant biliary strictures, it nonetheless may provide greater clinical flexibility to manipulate and even exchange SEMS in the setting of prolonged patient survival. Currently, covered SEMS are not specifically designed or approved by the Food and Drug Administration for removability, but we expect that covered SEMS removability will continue to be of interest to biliary endoscopists. For hilar strictures, uncovered SEMS are preferred for 2 reasons. First, placement of an uncovered stent above the bifurcation into the right or left hepatic duct is felt to be less likely to cause occlusion of the main or segmental branches of the opposite side. Additionally, wire access into the opposite side is still feasible by passing a wire through the mesh of the stent, and indeed, it is also possible to deploy a second SEMS into the opposite hepatic duct system through the wall of the first stent as an alternative to sideby-side placement in some clinical settings. As a general rule, covered SEMS should not be deployed across the hilum.

TECHNICAL CONSIDERATIONS DURING SELF-EXPANDING METAL STENT PLACEMENT IN POTENTIALLY RESECTABLE PANCREATIC CANCER Patient Selection For patients who present with painless obstructive jaundice, CT cross-sectional imaging is commonly obtained early in their clinical course. If a pancreatic mass is detected, our approach is to perform endoscopic ultrasound with fine needle aspiration to establish a diagnosis. We also assess for evidence of potential resectability based on absence of tumor invasion into the celiac artery or superior mesenteric artery and limited involvement of the

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portal or superior mesenteric veins. In jaundiced patients, we then generally proceed with preoperative ERCP with placement of a plastic biliary stent or fully covered biliary SEMS, with the latter approach being increasingly common due to the previously described advantages of SEMS in the preoperative setting, particularly if surgery is likely to be delayed beyond 1 to 2 weeks.17 When a malignant-appearing stricture is found on ERCP in patients without a known diagnosis or evidence of a pancreatic mass on imaging, our practice is to obtain cytology and to place a plastic biliary stent rather than a covered SEMS, given the diagnostic uncertainty at the time of endoscopy.

Endoscopic Approach In patients with potentially resectable pancreatic cancer being considered for covered SEMS placement, the first step after selective biliary cannulation is to measure or estimate the approximate length of the common bile duct stricture as seen on cholangiogram. Most distal biliary strictures due to pancreatic malignancy can be effectively bridged with a 4- to 6-cm by 10-mm covered biliary SEMS, although in some patients with severe stenoses, an 8-mm diameter SEMS is a viable option as well. A rough estimate of the required stent size can be obtained by estimating the length of the stricture against the width of the 12-mm duodenoscope on fluoroscopy. A more precise estimate of stricture length can be obtained by advancing the tip of a biliary cannula to the top of the stricture and then pulling back until the tip of the catheter is at the ampulla. The distance the cannula has been withdrawn from the instrument channel of the duodenoscope can then be measured with a tape measure. We typically choose a SEMS that is 2 cm longer than the measured distance from the top of the stricture to the ampulla. It is matter of debate whether to perform an endoscopic sphincterotomy prior to SEMS placement. While it is left to the individual endoscopists whether or not to perform biliary sphincterotomy to facilitate SEMS deployment, 2 well-constructed published studies have shown that sphincterotomy may increase complication rates with no impact on successful SEMS placement, risk of pancreatitis, or stent patency.25,26 The appropriateness of sphincterotomy for SEMS placement is a matter that deserves further study. In preparation for SEMS placement, the guidewire should be advanced into one of the intrahepatic branches (Figure 6-1). This is important because most modern biliary guidewires have flexible, hydrophilic tips that may not be stiff enough to safely guide the stent introducer on the correct trajectory. Adequate advancement of the guidewire into the intrahepatics ensures that the stiffer portion of the wire will guide the stent introducer. The SEMS introducer catheter is then advanced along the guidewire and through the papilla. Although the specific steps of SEMS deployment vary by manufacturer, generally there is a radio-opaque maker at the proximal and distal ends of the stent to allow for proper placement across the stricture and endoscopically visible markings to help with final stent deployment location. The SEMS should be deployed such that there is at least 1 to 2 cm of stent proximal to the area of stricture and 0.5 to 1 cm at the distal end of the stent protruding from the ampulla (Figures 6-2 and 6-3). During controlled deployment of the SEMS by an assistant, the endoscopist can monitor and adjust stent position using the fluoroscopic image to view the upper portion of the stent in relation to the top of the stricture and the endoscopic view to visualize the lower

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Figure 6-1. Stricture in the lower common bile duct with upstream biliary dilation due to adenocarcinoma of the pancreatic head. The guidewire has been advanced into the intrahepatics such that stent delivery will occur over the stiffer portion of the wire.

Figure 6-2. Successful deployment of 6 cm x 10 mm covered biliary SEMS across the lower common bile duct stricture.

end of the stent, crossing the ampulla. The lower end of the stent should be maintained in a position approximately 0.5 cm beyond the ampulla under continuous endoscopic visualization as the stent is deployed (Figure 6-4). Extra care must be taken to deploy foreshortening SEMS in order to ensure that the stent does not retract into the ampulla during deployment. Fully covered foreshortening SEMS will tend to “pull back” into the ampulla more than uncovered or partially covered SEMS, so we generally aim to have a slightly longer segment of the fully covered stent visible at the ampulla during deployment (Figure 6-5).

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Figure 6-3. Endoscopic view following successful deployment of 6 cm x 10 mm covered biliary SEMS across a lower common bile duct stricture. Approximately 0.5 cm of the stent is protruding beyond the ampulla.

A

B

Figure 6-4. (A) Endoscopic view of covered biliary SEMS advancement into major papilla prior to stent deployment. The lower end of the stent is not yet visible endoscopically and the stent must be advanced further prior to initiating deployment. (B) Endoscopic view of covered biliary SEMS advancement into major papilla prior to stent deployment. The lower end of the stent is visible and the stent is in good endoscopic position to initiate deployment under endoscopic and fluoroscopic visualization.

Impact of Neoadjuvant Therapy While the use of neoadjuvant chemoradiotherapy for potentially resectable pancreatic cancer is not yet standard of care, there is substantial ongoing research that may alter the standard “surgery-first” approach to pancreatic cancer.3 In an early study of neoadjuvant therapy for localized pancreatic cancer, initial concern was raised regarding

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Figure 6-5. Endoscopic image of a fully covered biliary Wallflex stent placed in a patient with pancreatic cancer with some ampullary/duodenal extension. Note the retrieval loop visible at the bottom of the stent (arrow). (Reprinted with permission of Douglas G. Adler, MD.)

increased complication rates in patients with biliary obstruction and/or biliary stents, leading to delays in or cessation of neoadjuvant therapy.27 This was contradicted by a later study that provided evidence that neoadjuvant therapy can be delivered safely in patients who require endoscopic biliary stenting for jaundice prior to or during chemoradiation.28 The use of neoadjuvant therapy almost always prolongs the period between initial diagnosis and eventual operative resection and thus may favor the use of biliary SEMS over plastic stents in this patient group. In a recent retrospective review of 49 patients with resectable or locally-advanced pancreatic cancer who underwent ERCP with plastic stent placement prior to neoadjuvant therapy, approximately half of the patients required a second ERCP.29 In this study, 29/49, or slightly more than half of all patients, ultimately underwent Whipple resection (after a median of 150 days). Nearly half of these patients required a second ERCP prior to surgery due to stent occlusion and/or cholangitis. Other studies have raised similar concerns regarding plastic stent complication rates in the setting of neoadjuvant therapy for pancreatic cancer, prompting recommendations to use biliary SEMS as a standard of practice in patients receiving neoadjuvant therapy prior to operative resection.15,30 We expect that the use of biliary SEMS for potentially resectable pancreatic malignancy will continue to broaden as the role of neoadjuvant chemotherapy expands.

ROLE OF SELF-EXPANDING METAL STENTS IN OTHER POTENTIALLY RESECTABLE BILIARY MALIGNANCIES Presently, while there is increasing published experience with the use of SEMS for certain patients with potentially resectable pancreatic cancer, there is very limited experience regarding the appropriateness of SEMS for jaundice in other potentially resectable pancreaticobiliary malignancies such as cholangiocarcinoma and ampullary carcinoma.

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Figure 6-6. Fluoroscopic image of an uncovered SEMS placed in a patient with a resectable, distal cholangiocarcinoma who underwent neoadjuvant therapy prior to pancreaticoduodenectomy. (Reprinted with permission of Douglas G. Adler, MD.)

Cholangiocarcinoma In our experience, several factors favor initial plastic stent placement over the use of SEMS in jaundiced patients with potentially resectable cholangiocarcinoma. First, in patients with cholangiocarcinoma presenting with jaundice and the finding of a biliary stricture on ERCP, there is often diagnostic uncertainty prior to cytologic diagnosis. This is particularly true in patients with primary sclerosing cholangitis for whom any dominant stricture could harbor cholangiocarcinoma or may simply reflect severe cholangiocyte/ductal inflammation. Any diagnostic uncertainty regarding a benign versus malignant diagnosis favors the use of plastic stents because of ease of removability in the case of a benign diagnosis and the ability to further interrogate and sample the stricture (after stent removal) via cytology or histology on subsequent ERCP procedures.31 An additional factor favoring the initial use of plastic stents in potentially resectable cholangiocarcinoma is the complex nature of strictures in a disease that may involve any part of the biliary tree, sometimes in a multifocal manner. The presence or absence of hilar involvement is the key determining factor in stent selection for cholangiocarcinoma. In the rare patient with cholangiocarcinoma in which the tumor only involves the lower common hepatic duct or common bile duct, a covered or uncovered SEMS may be a reasonable option if there is likely to be a significant period of time (several months) between diagnosis and operative resection (Figure 6-6). For cholangiocarcinoma involving the hilum, however, the use of covered SEMS across the bifurcation may occlude the opposite hepatic duct, increasing the risk of cholangitis and obstruction, thus precluding future

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biliary access to that segment. SEMS placement in hilar cholangiocarcinoma is a complex endeavor and may require the placement of bilateral uncovered SEMS in side-by-side or stent-within-stent configurations. At present, we prefer to undertake such procedures as a palliative maneuver. Thus, for cholangiocarcinoma with hilar involvement, initial use of plastic stents is preferable to uncovered SEMS if there is any diagnostic uncertainty or any possibility of operative resection.

Ampullary Carcinoma At present, there is no specific role for biliary SEMS in potentially resectable ampullary carcinoma. For patients with ampullary carcinoma, our practice is to first assess for the possibility of endoscopic resection using cross-sectional imaging and endoscopic ultrasound evaluation. In the case of endoscopic resection of ampullary adenomas or small, localized ampullary cancers, we generally place plastic pancreatic and/or biliary stents in order to protect pancreatic and biliary patency as the resection site scars and heals, although there are limited data to guide whether this practice is mandatory. For ampullary cancers that are not amenable to endoscopic resection, which includes the vast majority of ampullary cancers, we routinely place plastic biliary stents if the patient is jaundiced prior to operative resection (Figure 6-7). It is possible that if neoadjuvant chemotherapy becomes a routine consideration for ampullary cancers, then the use of biliary SEMS may be considered for jaundiced patients in whom operative resection may be delayed. It should be noted that the endoscopic removal of ampullary cancers is nonstandardized and the majority of these patients are treated surgically in short order.

FUTURE CONSIDERATIONS The applications of biliary SEMS continue to expand beyond palliation of jaundice in patients with unresectable malignancy. For jaundiced patients with potentially resectable pancreatic cancer, the larger diameter and greater expansile force provided by SEMS may provide a more reliable bridge to surgery than plastic stents, particularly if surgery is delayed beyond several months. These advantages may be of even greater importance if the surgery-first dogma in pancreatic cancer is replaced by broader use of neoadjuvant chemoradiotherapy prior to operative resection, which seems likely given the current trend in the surgical oncology literature. Biliary SEMS are substantially more expensive than plastic stents, however, longer duration of jaundice palliation and the potential avoidance of costly repeat ERCPs may make biliary SEMS more cost effective overall in appropriately selected patient populations.

Metal Biliary Stents in Patients With Potentially Resectable Malignancy A

B

C

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Figure 6-7. Preoperative stenting in ampullary cancer. (A) Endoscopic image of a large fungating, ulcerated ampullary cancer with partial gastric outlet obstruction as well. The patient had no evidence of distant disease. (B) Biliary access is obtained via cannulation during ERCP. (C) A plastic biliary stent is placed to provide preoperative biliary decompression. The patient proceeded to surgery within 2 weeks for curative resection. (Reprinted with permission of Douglas G. Adler, MD.)

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Sleisenger MH, et al. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management (8th ed). Philadelphia, PA: Saunders; 2006. Hariharan D, Constantinides VA, Froeling FE, Tekkis PP, Kocher HM. The role of laparoscopy and laparoscopic ultrasound in the preoperative staging of pancreatico-biliary cancers—a meta-analysis. European Journal of Surgical Oncology. 2010;36(10):941-948. Artinyan A, Anaya DA, McKenzie S, Ellenhorn JD, Kim J. Neoadjuvant therapy is associated with improved survival in resectable pancreatic adenocarcinoma. Cancer. 2010 Nov 18. Epub ahead of print. van der Gaag NA, Kloek JJ, de Castro SM, Busch OR, van Gulik TM, Gouma DJ. Preoperative biliary drainage in patients with obstructive jaundice: history and current status. J Gastrointest Surg. 2009;13(4):814-820. Weickert U, Venzke T, König J, Janssen J, Remberger K, Greiner L. Why do bilioduodenal plastic stents become occluded? A clinical and pathological investigation on 100 consecutive patients. Endoscopy. 2001;33(9):786-790. Libby ED, Leung JW. Prevention of biliary stent clogging: a clinical review. Am J Gastroenterol. 1996;91(7):1301-1308. van der Gaag NA, Rauws EA, van Eijck CH, et al. Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. 2010;362(2):129-137. Baron TH, Kozarek RA. Preoperative biliary stents in pancreatic cancer—proceed with caution. N Engl J Med. 2010;362(2):170-172. Prat F, Chapat O, Ducot B, et al. A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct. Gastrointest Endosc. 1998;47(1):1-7. Davids PH, Groen AK, Rauws EA, Tytgat GN, Huibregtse K. Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Lancet. 1992;340(8834-8835):1488-1492. Kaassis M, Boyer J, Dumas R, et al. Plastic or metal stents for malignant stricture of the common bile duct? Results of a randomized prospective study. Gastrointest Endosc. 2003;57(2):178-182. Soderlund C, Linder S. Covered metal versus plastic stents for malignant common bile duct stenosis: a prospective, randomized, controlled trial. Gastrointest Endosc. 2006;63(7):986-995. Snady H. Interventional endoscopy, neoadjuvant therapy and the gastroenterologist. Hematol Oncol Clin North Am. 2002;16(1):53-79. Reed DN Jr, Vitale GC. Interventional endoscopic retrograde cholangiopancreatography and endoscopic surgery. Surg Clin North Am. 2000;80(4):1171-1201. Wasan SM, Ross WA, Staerkel GA, Lee JH. Use of expandable metallic biliary stents in resectable pancreatic cancer. Am J Gastroenterol. 2005;100(9):2056-2061. Lawrence C, Howell DA, Conklin DE, Stefan AM, Martin RF. Delayed pancreaticoduodenectomy for cancer patients with prior ERCP-placed, nonforeshortening, self-expanding metal stents: a positive outcome. Gastrointest Endosc. 2006;63(6):804-807. Decker C, Christein JD, Phadnis MA, Wilcox CM, Varadarajulu S. Biliary metal stents are superior to plastic stents for preoperative biliary decompression in pancreatic cancer. Surg Endosc. 2011;25(7):2364-2367. Arguedas MR, Heudebert GH, Stinnett AA, Wilcox CM. Biliary stents in malignant obstructive jaundice due to pancreatic carcinoma: a cost-effectiveness analysis. Am J Gastroenterol. 2002;97(4):898-904. Chen VK, Arguedas MR, Baron TH. Expandable metal biliary stents before pancreaticoduodenectomy for pancreatic cancer: a Monte-Carlo decision analysis. Clin Gastroenterol Hepatol. 2005;3(12):1229-1237. Moss AC, Morris E, Leyden J, MacMathuna P. Do the benefits of metal stents justify the costs? A systematic review and meta-analysis of trials comparing endoscopic stents for malignant biliary obstruction. Eur J Gastroenterol Hepatol. 2007;19(12):1119-1124.

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21. Telford JJ, Carr-Locke DL, Baron TH, et al. A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. Gastrointest Endosc. 72(5):907-914. 22. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut. 2004;53(5):729-734. 23. Kullman E, Frozanpor F, Söderlund C, et al. Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. Gastrointest Endosc. 72(5):915-923. 24. Kasher JA, Corasanti JG, Tarnasky PR, McHenry L, Fogel E, Cunningham J. A multicenter analysis of safety and outcome of removal of a fully covered self-expandable metal stent during ERCP. Gastrointest Endosc. 2011;73(6):1292-1297. 25. Artifon EL, Sakai P, Ishioka S, et al. Endoscopic sphincterotomy before deployment of covered metal stent is associated with greater complication rate: a prospective randomized control trial. J Clin Gastroenterol. 2008;42(7):815-819. 26. Banerjee N, Hilden K, Baron TH, Adler DG. Endoscopic biliary sphincterotomy is not required for transpapillary SEMS placement for biliary obstruction. Dig Dis Sci. 56(2): 591-595. 27. Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16(1):317-323. 28. Pisters PW, Hudec WA, Lee JE, et al. Preoperative chemoradiation for patients with pancreatic cancer: toxicity of endobiliary stents. J Clin Oncol. 2000;18(4):860-867. 29. Boulay BR, Gardner TB, Gordon SR. Occlusion rate and complications of plastic biliary stent placement in patients undergoing neoadjuvant chemoradiotherapy for pancreatic cancer with malignant biliary obstruction. J Clin Gastroenterol. 2010;44(6):452-455. 30. Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487-3495. 31. Ayaru L, Kurzawinski TR, Shankar A, Webster GJ, Hatfield AR, Pereira SP. Complications and diagnostic difficulties arising from biliary self-expanding metal stent insertion before definitive histological diagnosis. J Gastroenterol Hepatol. 2008;23(2):315-320.

7

Metal Biliary Stents in Patients With Unresectable Pancreaticobiliary Malignancy Waqar Qureshi, MD, FRCP, FASGE

Pancreaticobiliary malignancy is frequently unresectable at initial presentation. Selfexpanding metal stents (SEMS) have become the treatment of choice for the palliation of unresectable pancreaticobiliary disease. Metal stents relieve jaundice and prevent cholangitis by allowing bile drainage from an obstructed biliary system. This has been, and remains, the most common role for metal biliary stents. Occasionally, pancreatic malignancy will lead to duodenal obstruction, requiring a luminal SEMS in addition to a biliary stent. Metal stents have evolved rapidly to combine flexibility with radial strength while at the same time minimizing the chance of migration. Drug eluting and biodegradable stents promise to widen indications for stenting and also reduce procedure-related complications. In this chapter, the design of biliary metal stents, the advantage over plastic stents, and the indications for their use are discussed. The various types of stents available as well as the management of complications such as tumor ingrowth and migration are discussed with a focus on their use in patients with unresectable pancreaticobiliary malignancies.

BRIEF OVERVIEW OF METAL BILIARY STENTS Biliary SEMS are most commonly used in malignant obstruction caused by unresectable pancreatic cancer, cholangiocarcinoma, cancer of the ampulla of Vater, and gallbladder cancer. SEMS are made via intertwining strands of stainless steel or a combination of nickel and titanium called nitinol into cylindrical shapes of various sizes and dimensions. Nitinol is more flexible and has better “shape memory” than steel. SEMS may be uncovered, partially covered, or fully covered. The covering material is usually made of silicone, polyurethane, or related compounds. These coverings are quite resistant to gastric acid

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Adler DG, ed. Self-Expanding Stents in Gastrointestinal Endoscopy (pp 109-120). © 2012 SLACK Incorporated.

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and pancreatic enzymes.1 SEMS may have a larger diameter at one or both ends to minimize the risk of migration. Although covered stents prevent tumor migration and occlusion, they are more prone to migrate. Uncovered stents are difficult, if not impossible, to remove once there has been tumor ingrowth and pseudoepithelialization. There is some concern that covered biliary stents may predispose to cholecystitis or pancreatitis if they migrate and cover a respective ductal orifice.2-4 Reports are conflicting, with cholecystitis more likely due to malignant involvement of the cystic duct orifice that stent obstruction. Bakhru et al reported 8 cases of pancreatitis and 3 cases of cholecystitis following covered SEMS placement.5 More recent reports suggest that the main complication seen in partially covered metal stents compared to uncovered SEMS is migration. The earlier findings of cholecystitis and pancreatitis being more common in the covered SEMS group did not seem to be the case.6,7 The material composition of SEMS, nitinol versus steel, does not seem to affect patency rates.8 Some SEMS have gold or platinum radio-opaque markers, which help both with placement and to check the position of the stent later on with a plain radiograph (Figures 7-1 and 7-2). SEMS are placed in a compressed state on a delivery system and deployed usually with the retraction of a covering sheath when in position. Most biliary stent delivery systems are through-the-scope with a diameter of 6 to 8.5 Fr and will go through common 4.2- or 4.8-mm working size channels of most duodenoscopes. Uncovered biliary stents can be used anywhere in the biliary tree, including proximally within the liver, so that side branches are still able to drain through the SEMS into the lumen. Covered biliary stents are largely only used in the distal duct.

METAL VERSUS PLASTIC STENTS IN PATIENTS WITH UNRESECTABLE BILIARY STRICTURES The question of whether or not to place a metal or a plastic stent in a patient with an unresectable tumor has long been debated in the literature. Arguments in favor of metal stents include their wider diameter, established longer patency rates, and reduced (but not eliminated) need for repeat biliary interventions. Arguments against metal stents mainly focus on cost (ie, over $1000 for a metal stent versus approximately $80 for a plastic stent). Arguments in favor of plastic stents include their ease of use and near-universal removability while arguments against plastic stents focus on the need for, and cost of, repeated biliary interventions in terminal patients. Wagner et al, in a prospective randomized study of 62 patients, demonstrated that SEMS were superior to plastic stents for palliation of hilar tumors independent of disease severity, Bismuth class, or drainage quality.9 In a study of 154 patients comparing outcomes in those treated with metal versus plastic stents for advanced pancreatic cancer, stent occlusion requiring reintervention was seen in 21 of 63 (33%) patients in the group of patients receiving plastic stents after a medial period of 57 days. In those receiving metal stents, 17 of 91 (19%) patients experienced obstruction requiring reintervention after a median period of 126 days.10 Perdue et al looked at adverse outcomes in patients with hilar cholangiocarcinoma, comparing 28 patients receiving plastic stents to 34 receiving SEMS in Klatskins tumors. These authors found the incidence of cholangitis, stent occlusion, migration, perforation, and need for further endoscopic retrograde cholangiopancreatography (ERCP) or

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Figure 7-1. Ex vivo images of some commonly used biliary SEMS. (A) Uncovered biliary Wallflex stent (Boston Scientific, Natick, MA). (B) Partially covered biliary Wallflex stent. (C) Fully covered biliary Wallflex stent with retrieval loop visible at top of stent.

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Figure 7-1 continued. (D) Uncovered Zilver stent (Cook Medical, Bloomington, IN). (E) Uncovered Alimaxx-B stent (Merit Endotek, Salt Lake City, UT). (F) Covered but fenestrated Viabil stent (ConMed, Utica, NY). Figure 7-2. Typical postdeployment endoscopic image of a biliary SEMS in a patient with unresectable pancreatic adenocarcinoma via an Alimaxx-B stent. Note bile drainage. (Reprinted with permission of Douglas G. Adler, MD.)

percutaneous transhepatic cholangiography occurred in 11 of 28 (39.3%) patients in the plastic stent group compared to 4 of 34 (11.8%) patients in the SEMS group (p = 0.017). In this study, risk factors for adverse outcomes included plastic stents and bilirubin level but not Bismuth type.11

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Raju et al looked at 100 patients with inoperable cholangiocarcinoma in which 48 patients had SEMS placed and 52 had plastic stents. The mean patency times were 5.56 months for the metal stents and 1.86 months for the plastic stents. The mean reintervention rate was 1.53 for the SEMS group and 4.60 for the plastic stent group. This study concluded that SEMS not only stayed patent longer but were more cost effective (despite the higher cost of the stent itself) given the lower need for reintervention, making SEMS placement the initial approach in inoperable hilar cancers.12 Metal stents are being increasingly used as initial stents for inoperable biliary malignancies over plastic stents. Although metal stents are superior to plastic stents in terms of patency, metal stent diameter rather that stent design seems to be important for prolonged patency, although comparisons between different stent types are relatively few in number. In one study comparing the nitinol open cell Zilver stents, 6 and 10 mm were compared to a 10-mm stainless steel Wallstent. SEMS occlusions were more frequent in the 6-mm SEMS whereas both the 10-mm SEMS (regardless of manufacturer) were equivalent despite differences in stent design, material, and expansive forces.13

BILATERAL VERSUS UNILATERAL METAL STENTS FOR CHOLANGIOCARCINOMA Patients with malignant hilar biliary strictures have, in general, a very poor prognosis. Most patients in this situation will be found to have unresectable disease at the time of presentation. Similarly, most of these patients have bilateral biliary obstruction. Bilateral drainage can be technically difficult in these patients. In general, it is not difficult to drain a single biliary system (left or right) but the placement of a second stent is often complicated by a severe stenosis, the presence of the initial biliary stent, and local anatomic factors. There is some debate in the literature about whether both the left and right biliary ducts need to be drained or if decompression of the dominant biliary system is sufficient. Although it is clear that SEMS are superior to plastic stents for hilar cholangiocarcinoma,9,11,12 it is unclear if bilateral metal stenting is superior to unilateral stenting.14 De Palma et al evaluated 157 patients randomly assigned to receive either unilateral or bilateral drainage for malignant hilar tumors. In their intention-to-treat analysis, patients undergoing unilateral drainage had a significantly higher rate of successful endoscopic stent insertion than those undergoing bilateral drainage (88.6% versus 76.9%, p = 0.041). Patients undergoing bilateral drainage had a significantly higher rate of complications than those in the unilateral drainage group (26.9% versus 18.9%, p = 0.026). Median survival did not differ between the 2 groups. Overall, these authors did not feel that bilateral stent placement was not warranted in all patients.15 In contrast, Naitoh et al conducted a retrospective study of 46 consecutive patients with malignant hilar biliary obstruction treated by endoscopic biliary drainage using SEMS. Unilateral metal stenting was performed in 17 patients, and bilateral metal stenting was performed in 29 patients. In this study, there were no significant differences between the 2 groups in successful stent insertion, successful drainage, and complications. Cumulative stent patency was significantly better in the patients who received bilateral stents (p = 0.009). When specifically looking at patients with cholangiocarcinoma, cumulative stent patency was significantly better in those undergoing bilateral stenting (p = 0.009), whereas there were no intergroup differences seen in patients with gallbladder carcinoma.

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Figure 7-3. Fluoroscopic image of 2 Zilver stents (arrows) placed in a Y configuration across a hilar stricture in a patient with cholangiocarcinoma. Notice the radio-opaque markings at either end of the stents.

These authors concluded that bilateral drainage with SEMS for malignant hilar obstruction was superior to unilateral drainage.16 From an endoscopic perspective, there are 2 ways of achieving bilateral drainage in malignant hilar obstruction. The simplest approach is to obtain access to the left and right hepatic ducts with separate, parallel guidewires and then place the 2 SEMS next to each other so that the SEMS sit alongside each other. The recent introduction of low-profile SEMS delivery catheters makes this a relatively easy technique to master. Another option is to first place a SEMS across the hilum into either the left or the right hepatic duct and then to place a second SEMS through the metal mesh of the first SEMS into the other hepatic duct, thereby creating a “Y” configuration to the 2 stents. This technique may require dilation of the mesh of the first stent to achieve and is, in general, felt to be more technically difficult. This technique, however, has an excellent success rate.17,18 This is sometimes easier with an open cell structure stent such as the Zilver stent than the closed cell structure of the Wallstent (Figure 7-3) but can be accomplished with any stent design by an experienced endoscopist. There are, unfortunately, no good studies comparing these techniques. Dowsett et al estimated that one-forth to one-third of the liver needs to be drained to relieve jaundice.19,20 Preprocedure abdominal magnetic resonance imaging with highquality magnetic resonance cholangiopancreatography is extremely helpful in planning targeted drainage so that unnecessary contrast injection is avoided to areas that may not get drained (ie, if a patient has a severely atrophic left lobe of the liver due to malignancy, this segment of the biliary tree may not need to be drained at all because doing so may not improve the patient’s serum bilirubin level). Targeted decompression and careful need to

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avoid overinjection of contrast have made endoscopic decompression and internal SEMS placement preferred as the initial approach.21 On occasion and particularly in advanced disease, percutaneous drainage is also required.

PERCUTANEOUS VERSUS ENDOSCOPIC APPROACH IN HILAR CHOLANGIOCARCINOMA Both endoscopic and percutaneous drainage options exist for advanced hilar cholangiocarcinoma. Some patients have very complex anatomy with complex strictures. These patients can be very challenging clinically and may require combined endoscopic and percutaneous drainage to relieve their biliary obstruction and jaundice. Few studies have looked at possible advantages of one over the other. In general, endoscopic drainage is preferred for reasons of patient comfort, but a multidisciplinary approach is often helpful to ensure that adequate drainage is obtained. Paik et al performed a retrospective study of 85 patients with type III or IV hilar cholangiocarcinoma in which 41 underwent percutaneous SEMS and 44 patients received endoscopic SEMS. In this study, the rate of successful biliary decompression was significantly higher in those receiving percutaneous SEMS than in those receiving endoscopic SEMS (92.7% versus 77.3%, respectively, p = 0.049). Overall rates of complications were similar for both groups, but one fatality from biliary sepsis occurred in a patient who received an endoscopic SEMS. Median survival of patients in whom biliary drainage was successful during the initial procedure, regardless of which procedure was performed, was longer when compared to patients who had unsuccessful biliary drainage (8.7 months versus 1.8 months, respectively, p < 0.001). Once successful biliary decompression had been achieved, median survival and stent patency duration were similar in the 2 study groups. Overall, these authors suggested that percutaneous SEMS placement was a viable alternative to endoscopic SEMS placement in this challenging group of patients.22

WHEN DUODENAL OBSTRUCTION COMPLICATES UNRESECTABLE MALIGNANT BILIARY OBSTRUCTION Gastric outlet obstruction (GOO) is frequently encountered in patients with malignant biliary obstruction, and most patients with GOO have unresectable disease. While patients in this situation can undergo a gastrojejunostomy (often with a concomitant biliary bypass), combined placement of a metal biliary SEMS and an enteral SEMS is now commonplace. Several studies have described successful combined biliary and duodenal SEMS placement in a single or sequential manner.23-26 It is, in general, preferable to treat the bile duct stricture first (if it can be reached) and then to treat the duodenal stricture. When unresectable pancreatic cancer or distal cholangiocarcinoma presents with jaundice, the duodenum may also be involved, making it difficult to reach the ampulla without first managing the duodenal obstruction. This can be managed by first placing a metal gastroduodenal stent to gain access to the ampulla. In some patients, attempts to access the bile duct can be delayed for several days while the duodenal SEMS expands. When duodenal obstruction is distal to the ampulla (eg,

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involving the third part of the duodenum seen in cancers of the uncinate process of the pancreas), it is generally easier to insert a biliary stent followed by a duodenal stent. Strictures from unresectable pancreatic cancer involving the pylorus or duodenal bulb but not the ampulla are somewhat more challenging and may require dilation of the stricture to get to the ampulla to place a biliary SEMS followed by a duodenal stent. The most technically challenging situation is when the GOO is at the level of the ampulla, making it difficult (or even impossible) to locate and/or cannulate. Sometimes a rendezvous procedure with percutaneous transhepatic cholangiogram or by endoscopic ultrasound is necessary to stent the common bile duct prior to deployment of a duodenal stent. If it is not possible to reach the area of the ampulla because of tumor involving and/or obstructing the duodenal lumen, a gastroduodenal SEMS can be placed first with subsequent attempts at ERCP performed through the interstices of the enteral stent, although this can be an extremely challenging procedure. Duodenal and biliary stenting with SEMS can be achieved at a single procedure or sequentially. Sometimes the duodenal stent may not expand enough despite balloon dilation to let the duodenoscope through and returning 2 to 3 days later allows the stent to expand enough to pass through the duodenal stent and perform ERCP for biliary stent placement. Katsinelos et al looked at sequential or simultaneous placement of SEMS for duodenal and biliary obstruction from pancreatic head cancer in 39 patients with combined duodenal and biliary obstruction due to unresectable pancreatic cancer using data from 4 tertiary referral centers. Biliary or duodenal stenting failed in 7 (17.9%) patients. Overall median survival was 9 months in the remaining 32 patients. Median duodenal and biliary stent patency was 3 months (range: 1 to 12 months) and 9 months (range: 2 to 22 months), respectively (p < 0.05). Nine of 32 (28.1%) patients required some form of reintervention before their death. No major complications or death occurred in relation to endoscopic treatment. Overall, the study showed that combined biliary and duodenal SEMS placement was technically feasible but that the failure rate was not insignificant when attempting to perform both procedures, especially in one session.23

OCCLUDED BILIARY SELF-EXPANDING METAL STENTS IN PATIENTS WITH UNRESECTABLE DISEASE Most patients who undergo biliary SEMS placement for unresectable disease will not require further interventions (ie, the stent will remain patent for the remainder of the patient’s life). Complications of SEMS include stent occlusion, migration, bleeding, or perforation. Management of biliary stent occlusions are discussed here. Ways to manage occluded metal stents include placement of a plastic stent within the occluded metal stent and mechanical cleaning of the obstruction via the use of occlusion balloons or baskets to remove stones/sludge or the insertion of a second SEMS (Figures 7-4 and 7-5). In one study of 54 occluded SEMS, 24 were managed with a plastic stent, 25 had a second metal stent inserted, and 5 required only mechanical clearing of the obstruction. In this study, both plastic and second SEMS were effective, although plastic stents were shown to be more cost effective.27

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Figure 7-4. Obstructed SEMS management with plastic stents. (A) Endoscopic image of an occluded biliary SEMS in a patient with pancreatic adenocarcinoma. The stent is occluded due to both sludge material and tumor ingrowth. (B) Using a sphincterotome, a guidewire is advanced through the lumen of the stent into the proximal biliary tree. (C) Two plastic stents are placed side by side through the obstructed SEMS. The patient can now drain bile through and between the stents. (Reprinted with permission of Douglas G. Adler, MD.)

C

Rogart et al reported management of 27 occluded metal stents that were placed for palliative purposes. In this study, a total of 60 ERCPs were performed to treat SEMS occlusions in 27 patients. The success rate was 95%, with 52% of patients requiring more than one intervention. Placing a second SEMS through the existing SEMS (n = 14) provided the lowest reocclusion rate (43% versus 55% and 100%), the longest time to reintervention (172 days versus 66 and 43 days, p = 0.03), and was associated with a trend toward longer survival (285 days versus 188 and 194 days) when compared with plastic stent placement and mechanical balloon cleaning, respectively. The authors concluded that in the management of occluded SEMS placed for palliation, a second SEMS insertion provides for longer patency and survival, decreases the number of subsequent ERCPs by 50% compared with plastic stents, and is cost effective.28

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Figure 7-5. Obstructed SEMS management with metal stents. (A) Endoscopic image showing tumor ingrowth in a previously placed biliary SEMS in a patient with unresectable pancreatic cancer. (B) Occlusion cholangiogram showing tumor ingrowth in a previously placed biliary SEMS in a patient with unresectable pancreatic cancer. (C) Fluoroscopic image after placement of a second SEMS within the first SEMS. (D) Final endoscopic appearance of stent-withinstent deployment. (Reprinted with permission of Douglas G. Adler, MD.)

In a retrospective study specifically addressing the issue of management of obstructed biliary SEMS placed for palliative purposes, 38 patients who developed obstruction were identified. These 38 patients developed a total of 44 occlusions. Management via the placement of a second SEMS was performed in 19 patients, insertion of a plastic stent through the SEMS was performed in 20, and mechanical cleaning of the SEMS was performed in the remaining 5. Endoscopic management was successful in 43/44 patients (98%). No complications occurred. There was no difference in patency rates between the 3 groups. Incremental cost-effective analysis in this study showed that plastic stent insertion is the most cost-effective option.29 Overall, re-establishing patency in an occluded biliary SEMS has a high technical success rate and comparable efficacy regardless of which type of stent is used. Practices vary widely, and management is best individualized.

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CONCLUSION SEMS have become the standard to care for palliation of unresectable pancreaticobiliary disease. SEMS improve the quality of life in these patients and make surgery unnecessary. Covered stents were developed to prevent tumor ingrowth, although stent migration is a problem. Although earlier trials showed an increased risk for pancreatitis or cholecystitis with covered stents, more recent randomized trials have not borne this out. Although large randomized trials are needed with regard to the more appropriate use of SEMS, there is no doubt that their development and use has improved the quality of life and in many cases avoided surgery and its related morbidity or mortality in patients with a limited life span.

REFERENCES 1. Kim JH, Song HY, Shin JH, et al. Membrane degradation of covered stents in the upper gastrointestinal tract: frequency and clinical significance. J Vasc Interv Radiol. 2008;19 (2 Pt 1):220-224. 2. Fumex F, Coumaros D, Napoleon B, et al. Similar performance but higher cholecystitis rate with covered biliary stents: results from a prospective multicenter evaluation. Endoscopy. 2006;38(8):787-792. 3. Isayama H, Komatsu Y, Tsujino T, et al. A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut. 2004;53(5):729-734. 4. Yoon WJ, Lee JK, Lee KH, et al. A comparison of covered and uncovered Wallstents for the management of distal malignant biliary obstruction. Gastrointest Endosc. 2006;63(7):996-1000. 5. Bakhru M, Ho HC, Gohil V, et al. Fully-covered, self-expandable metal stents (CSEMS) in malignant distal biliary strictures: mid-term evaluation. J Gastroenterol Hepatol. 2011;26(6):1022-1027. 6. Telford JJ, Carr-Locke DL, Baron TH, et al. A randomized trial comparing uncovered and partially covered self-expandable metal stents in the palliation of distal malignant biliary obstruction. Gastrointest Endosc. 2010;72(5):907-914. 7. Kullman E, Frozanpor F, Söderlund C, et al. Covered versus uncovered self-expandable nitinol stents in the palliative treatment of malignant distal biliary obstruction: results from a randomized, multicenter study. Gastrointest Endosc. 2010;72(5):915-923. 8. Weston BR, Ross WA, Liu J, Lee JH. Clinical outcomes of nitinol and stainless steel uncovered metal stents for malignant biliary strictures: is there a difference? Gastrointest Endosc. 2010;72(6):1195-2000. 9. Wagner HJ, Knyrim K, Vakil N, Klose KJ. Plastic endoprostheses versus metal stents in the palliative treatment of malignant hilar biliary obstruction. A prospective and randomized trial. Endoscopy. 1993;25(3):213-218. 10. Weber A, Weber A, Kehl V, et al. Prognostic factors for survival in patients with unresectable pancreatic cancer. Pancreas. 2010;39(8):1247-1253. 11. Perdue DG, Freeman ML, DiSario JA, et al. Plastic versus self-expanding metallic stents for malignant hilar biliary obstruction: a prospective multicenter observational cohort study. J Clin Gastroenterol. 2008;42(9):1040-1046. 12. Raju RP, Jaganmohan SR, Ross WA, et al. Optimum palliation of inoperable hilar cholangiocarcinoma: comparative assessment of the efficacy of plastic and self-expanding metal stents. Dig Dis Sci. 2011;56(5):1557-1564. 13. Loew BJ, Howell DA, Sanders MK, et al. Comparative performance of uncoated, selfexpanding metal biliary stents of different designs in 2 diameters: final results of an international multicenter, randomized, controlled trial. Gastrointest Endosc. 2009;70(3):445-453. 14. Deviere J, Baize M, de Toeuf J, Cremer M. Long-term follow-up of patients with hilar malignant stricture treated by endoscopic internal biliary drainage. Gastrointest Endosc. 1988;34(2):95-101.

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15. De Palma GD, Galloro G, Siciliano S, Iovino P, Catanzano C. Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar biliary obstruction: results of a prospective, randomized, and controlled study. Gastrointest Endosc. 2001;53(6): 547-553. 16. Naitoh I, Ohara H, Nakazawa T, et al. Unilateral versus bilateral endoscopic metal stenting for malignant hilar biliary obstruction. J Gastroenterol Hepatol. 2009;24(4):552-557. 17. Chahal P, Baron TH. Expandable metal stents for endoscopic bilateral stent-within-stent placement for malignant hilar biliary obstruction. Gastrointest Endosc. 2010;71(1):195-199. 18. Kanno Y, Ito K, Fujita N, et al. Single-session endoscopic bilateraly-configured placement of metal stents for hilar malignant biliary obstruction. Dig Endosc. 2011;23(1):91-96. 19. Dowsett JF, Vaira D, Hatfield AR, et al. Endoscopic biliary therapy using the combined percutaneous and endoscopic technique. Gastroenterology. 1989;96(4):1180-1186. 20. Polydorou AA, Cairns SR, Dowsett JF, et al. Palliation of proximal malignant biliary obstruction by endoscopic endoprosthesis insertion. Gut. 1991;32(6):685-689. 21. Freeman ML, Overby C. Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding metallic stents. Gastrointest Endosc. 2003;58(1):41-49. 22. Paik WH, Park YS, Hwang JH, et al. Palliative treatment with self-expandable metallic stents in patients with advanced type III or IV hilar cholangiocarcinoma: a percutaneous versus endoscopic approach. Gastrointest Endosc. 2009;69(1):55-62. 23. Katsinelos P, Kountouras J, Germanidis G, et al. Sequential or simultaneous placement of self-expandable metallic stents for palliation of malignant biliary and duodenal obstruction due to unresectable pancreatic head carcinoma. Surg Laparosc Endosc Percutan Tech. 2010;20(6):410-415. 24. Maire F, Hammel P, Ponsot P, et al. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of pancreas. Am J Gastroenterol. 2006;101(4):735-742. 25. Moon JH, Choi HJ, Ko BM, et al. Combined endoscopic stent-in-stent placement for malignant biliary and duodenal obstruction by using a new duodenal metal stent (with videos). Gastrointest Endosc. 2009;70(4):772-777. 26. Mutignani M, Tringali A, Shah SG, et al. Combined endoscopic stent insertion in malignant biliary and duodenal obstruction. Endoscopy. 2007;39(5):440-447. 27. Katsinelos P, Beltsis A, Chatzimavroudis G, et al. Endoscopic management of occluded biliary uncovered metal stents: a multicenter experience. World J Gastroenterol. 2011;17(1):98-104. 28. Rogart JN, Boghos A, Rossi F, et al. Analysis of endoscopic management of occluded metal biliary stents at a single tertiary care center. Gastrointest Endosc. 2008;68(4):676-682. 29. Tham TC, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents. Gut. 1998;42(5):703-707.

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Metal Biliary Stent Complications and Their Management Jessica I. Chan, BS, MS and Douglas G. Adler, MD, FACG, AGAF, FASGE

Biliary self-expanding metal stents (SEMS) are commonly used to restore bile duct patency in patients with malignant biliary obstructions or benign biliary strictures. Due to their superior stent patency over plastic stents, metal stents are preferentially placed in patients with malignant obstructions and with a life expectancy greater than 3 months or in those in whom surgical interventions will be delayed. Metal stents have also been used in patients with benign biliary strictures secondary to surgical procedures or inflammatory processes. The overall complication rate associated with the use of metal biliary stents in patients with malignant biliary obstructions or benign biliary strictures is highly variable, with some complications being frequently encountered and others almost never occurring. The metal biliary stent’s design, coating, metal, length, location with the bile duct, process of placing it, and even the pathology of the patient’s bile duct influence the development of complications. This chapter will review the complications of metal biliary SEMS and their management.

STENT MIGRATION Stent migration, proximally or distally, is most commonly defined as displacement of the stent more than 1 cm from the original postprocedural position. Distal displacement (toward the duodenum) is more frequently reported by investigators than proximal displacement (toward the liver). Patients with biliary stent migration often present with abdominal pain, elevated liver chemistries, and/or cholangitis, although they can be asymptomatic as well if the stent is still in adequate position despite the migration. Abdominal imaging with computed tomography scan, magnetic resonance imaging, or radiographs as well as endoscopy can be used to determine if stent migration has occurred. Multiple investigators have found very low rates of migration with uncovered nitinol or stainless steel SEMS in patients with malignant biliary obstruction, ranging from 0% to 2.4%.1-7 Partially or fully covered stents are associated with higher rates of migration compared to uncovered metal stents. The coating that reduces tumor ingrowth also reduces stent embedding and anchoring, causing higher rates of migration.

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Fully covered SEMS (FCSEMS), with polyurethane, polycarbonate, silicon, or polytetrafluoroethylene coatings and without anchoring fins, have a reported migration rate between 3.0% to 8.3% in patients with malignant biliary obstructions.2-4,7,8 FCSEMS with anchoring fins have a lower rate of migration, similar to uncovered SEMS, 0% to 1.4%.9,10 Partially covered metal stents are coated throughout the central portion of the stent, leaving the distal and proximal ends bare to allow for tissue embedding. Reported migration rates for partially covered SEMS (PCSEMS) in patients with malignant biliary obstructions are between 1.7% to 12%, similar to those of FCSEMS.5,6,11-13 When placing a stent in a patient with distal biliary obstruction in a transampullary fashion, the distal end of the stent is generally left in the duodenal lumen, and thus the stent is only anchored by the uncovered proximal end of the stent, increasing the risk of migration.7 In patients with benign biliary strictures caused by surgical procedures and inflammatory processes such as cholecystectomy, hepatectomy, liver transplantation, chronic pancreatitis, and sclerosing cholangitis, surgery and the placement of multiple plastic stents is common practice, although SEMS are increasingly being used in this context. Reported migration rates for uncovered SEMS in patients with benign biliary strictures range from 4% to 7.7%.14,15 Stent migration rates for PCSEMS and FCSEMS are greater at 5% to 14% and 25% to 33%, respectively.16-22 FCSEMS with anchoring fins have the lowest rate of migration, 0% to 4.5%.20,23,24 In general, the migration rates of SEMS deployed in patients with benign biliary strictures are greater than that of those used to treat malignant biliary obstructions, although no study to date has directly compared the two. Unlike the placement of SEMS in malignant biliary obstructions, SEMS are often placed in benign biliary strictures after balloon dilation or the (often repeated) placement and removal of plastic stents.14-16,18,19 The average follow-up time of these investigations is longer than that of malignant biliary obstructions given increased patient survival in benign disease. Additionally, inflammatory biliary strictures often spontaneously resolve, leading to complete distal migration of the SEMS, although this is not strictly considered a complication as it may imply overall improvement of the patient.17-19 These factors may contribute to a higher stent migration rate in benign biliary strictures. Stent migration can lead to recurrent biliary obstruction, abdominal pain, and duodenal perforation. Although biliary sphincterotomy during stent placement is common practice, recent investigations have shown that it may be a risk factor for stent migration and is thus not clearly indicated prior to stent placement.25,26 Management of partially or fully covered stents that have migrated distally is generally simple and safe and includes removal with snares or rat-tooth forceps, placing a second stent within the prior stent, or trimming the distal end with argon plasma coagulation as needed.13,20,23,27,28 Proximally migrated stents, especially those that are fully above a persistent stricture, can be more challenging to remove. These patients often require a combination of balloon dilation and forceps or snare extraction or placement of a second stent distal to the previous one to create an adequate distal channel to allow the proximal stent to pass distally.13 The removal of proximally or distally migrated uncovered SEMS is more difficult and often requires a combination of multiple techniques, including removal with snares or “hot” biopsy forceps, surgical removal, trimming with argon plasma coagulation, and tissue coagulation.29-31 Complications can include bleeding, perforation, or pancreatitis.29 Removal of

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uncovered stents can be very difficult technically and, in some cases, impossible if the stent has developed significant hyperplastic tissue ingrowth.

TISSUE INGROWTH With tissue ingrowth, stents may become occluded by growth of malignant or nonmalignant tissue through the stent mesh/interstices. At locations of healthy tissue, the uncovered SEMS becomes incorporated into the bile duct wall with resulting benign epithelial hyperplasia.32 This can progress to the point where patients become obstructed due to tissue ingrowth. Tissue ingrowth in patients with malignant biliary obstruction, however, is more often due to direct tumor ingrowth as opposed to epithelial hyperplasia.4,33-35 Patients with an occluded biliary SEMS may present with abdominal pain, pruritus, jaundice, elevated liver chemistries, and/or cholangitis. Tumor ingrowth is the most common cause of stent dysfunction in patients with uncovered SEMS.1,5 In patients with malignant biliary obstruction, the rate of tumor ingrowth in uncovered SEMS has been reported between 10.9% and 29%.1,2,5,6,35,36 Tissue ingrowth is much less common in covered stents due to the efficacy of the coating. The rate of tumor ingrowth in partially and fully covered SEMS is 0% to 8.8% and 0% to 4.8%, respectively.2,4-6,11,35 SEMS used to maintain patency in benign biliary strictures also become occluded with tissue ingrowth, almost exclusively due to epithelial hyperplasia. Tissue ingrowth occurred in 10% and 58% of uncovered SEMS placed in patients with chronic pancreatitis and liver transplants, respectively.37,38 In a study of 14 patients with benign biliary stenoses treated with partially covered stents, stent occlusion due to tissue ingrowth occurred in 5 (36%) patients.16 A smaller study of only 7 patients with FCSEMS used to treat benign biliary strictures found no tissue ingrowth.21 These studies reflect the limited data available on covered SEMS in benign biliary disease. Management of occluded SEMS includes irrigation (which is often ineffective if used as monotherapy); sweeping the obstructed stent with occlusion balloons to dislodge sludge, stones, debris, or tissue; insertion of a second stent within the first stent (stent-withinstent deployment); surgical removal; and percutaneous biliary drainage.39,40 Of note, patients with occluded biliary SEMS who undergo stent-within-stent placement can have plastic or metal stents placed, often with equal ease (Figure 8-1). Occluded stents managed with mechanical cleaning without an additional stent placement are the most likely to occlude and have the shortest duration of patency following intervention, with studies reporting 21 to 34 days of patency.41-43 Inserting a plastic stent or a SEMS within the occluded SEMS provides longer patency and is associated with a mean time to occlusion ranging from 75 to 192 days.14,42,43 In one study of 46 patients with occluded biliary SEMS, the placement of a covered SEMS in a stent-within-stent fashion was associated with longer stent patency than the placement of an uncovered SEMS but with a downside of increased cost.39 In an additional study of 77 patients with occluded biliary SEMS treated with placement of an additional stent (stent-within-stent fashion), patients with a secondary covered SEMS experienced significantly longer stent patency than those with a secondary plastic stent.44 Furthermore, patients who had a covered SEMS as either the primary or secondary stent had a better cumulative stent patency and survival time than those who received only uncovered SEMS.

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Figure 8-1. (A) Occlusion cholangiogram showing tumor ingrowth (arrow) in a SEMS placed 5 months previously in a patient with unresectable cholangiocarcinoma. (B) Over a guidewire, a second and longer biliary SEMS is placed across the occluded initial SEMS.

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Figure 8-1 continued. (C) Postdeployment image showing stent-within-stent configuration with restored biliary patency.

TISSUE OVERGROWTH Tissue overgrowth, defined as malignant or nonmalignant tissue proliferation at the proximal or distal ends of the biliary SEMS, is another common cause of biliary SEMS occlusion (Figure 8-2). Similar to nonmalignant tissue ingrowth, benign epithelial hyperplasia forms due to the presence of the stent and can progress to occlude the ends of the SEMS. In patients with malignant biliary obstruction, tumor overgrowth may be due to increased tumor burden or (rarely) stent foreshortening. The distal or the proximal end of the stent may become occluded depending on the direction of malignant growth and the postprocedural position of the stent. Patients with tissue overgrowth often present with abdominal pain, pruritus, jaundice, elevated liver chemistries, and/or cholangitis. Tumor overgrowth is less common than tumor ingrowth in patients with uncovered biliary SEMS. Most investigators have reported a low tumor overgrowth rate (approximately 3%) ranging from 0% to 5.9%.1,4-6,23,33,36 In one notable study of 41 patients treated with uncovered metal stents, tumor overgrowth occurred in 8 (19.5%) patients, more than would be expected given most of the currently available literature.2 Tumor overgrowth is more common than ingrowth in patients with malignant biliary obstructions treated with covered SEMS. The coating inhibits the malignancy from growing through the stent mesh but does nothing to prevent or reduce tissue overgrowth. The tumor overgrowth rate of PCSEMS is generally reported to be between 1% and 4%, although it has been found to be as high as 7%.5,6,11-13 In patients with FCSEMS, tumor overgrowth occurred between 6.7% and 13.8% in several recent studies.2,4,36 A metaanalysis of biliary SEMS in patients with malignant obstructions found that patients with covered SEMS were twice as likely to develop tumor overgrowth as patients with uncovered SEMS.7

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Figure 8-2. (A) Tissue ingrowth and some overgrowth in a previously placed biliary SEMS that was placed in a patient with pancreatic cancer 4 months previously. (B) Access to the bile ducts is obtained via a sphincterotome and a guidewire is advanced into the proximal biliary tree. (C) A new biliary SEMS is placed within the original biliary SEMS to restore biliary patency.

In patients with benign biliary strictures, tissue overgrowth due to mucosal hyperplasia has been reported by a limited number of investigators. Tissue in the proximal portion of PCSEMS in 3 (2%) patients caused stent failure in a trial of 149 patients with benign biliary disease.13 A further study of 79 patients with various benign biliary strictures reported mucosal hyperplasia development at the uncovered portion of the PCSEMS in 6 (8%) patients.17 One technique to decrease the incidence of tumor overgrowth involves placing the stent to cover as much of the bile duct as possible above and below the malignancy and in a balanced and centered position.45,46 Although such “overstenting” decreases the incidence of tumor overgrowth, it can still occur.

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An occluded biliary SEMS due to tissue overgrowth can be managed via sweeping the obstructed stent with an occlusion balloon to dislodge sludge, stone, debris, or tissue; insertion of a second stent within the first stent (stent-within-stent deployment); endoscopic or (rarely) surgical removal; and percutaneous biliary drainage.13,14,39 Stent patency in occluded biliary SEMS due to tumor ingrowth/overgrowth, sludge, stone, or debris is restored for the longest time period with the placement of a covered SEMS in a stent-within-stent fashion. The placement of a secondary uncovered SEMS or plastic stent or mechanical cleaning is associated with a shorter stent patency interval (see Tissue Ingrowth).

OCCLUSION DUE TO SLUDGE Accumulation of sludge, stones, or debris within the lumen of the stent is a common cause of SEMS dysfunction. Sludge formation is thought to be caused by the tumor (which can lead to an irregular biliary ductal lumen), intraductal debris, biliary infection, biofilm production, foreign body material serving as a nidus for stone formation, and/or stent incorporation into the bile duct wall.7,13,26,47 In most patients, stone formation is likely multifactorial in etiology. Patients with biliary stasis due to kinked, fractured, migrated, or partially deployed stents are prone to stent occlusion from sludge accumulation and stone formation.48 Abdominal pain, pruritus, jaundice, elevated liver chemistries, and/or cholangitis are often reported in patients with an occluded stent due to sludge, stones, or debris. In patients with malignant biliary obstruction treated with uncovered SEMS, the sludge-based occlusion rate ranges from 2.1% to 5.9%, with an additional trial finding a sludge occlusion rate as low as 0%.1,2,4-6,35,36,48 There was no difference between the sludge occlusion rate of nitinol and steel uncovered SEMS in a study of 101 patients with malignant biliary obstructions.35 The sludge occlusion rate in patients with PCSEMS is similar to that of uncovered SEMS, 1.2% to 5.9%.5,6,11,13 Patients with FCSEMS used to treat malignant biliary obstructions, however, have a slightly higher sludge occlusion rate ranging from 4.3% to 6.7%.2,4,9,36,48 A meta-analysis of biliary SEMS in patients with malignant obstructions found that patients with a covered SEMS were 3 times as likely to develop sludge formation as patients with an uncovered SEMS.7 The coating on covered stents provides a surface for attachment and development of bacterial biofilm, much like the surface of plastic biliary stents, leading to a higher sludge formation rate.7 In patients with benign biliary strictures, occlusion due to sludge, stones, or debris has been reported by a limited number of investigators. Stone formation in 2 (0.05%) patients caused stent failure in a meta-analysis of 375 patients with benign biliary disease treated with a variety of metal stents.14 In a further study of 149 patients treated with PCSEMS, no stents in patients with benign biliary strictures occluded due to sludge/stone formation.13 Although symptomatic occlusion due to sludge/stone formation occurs in less than 7% of patients, the presence of some sludge in the lumen of uncovered and covered biliary SEMS is common upon examination. Debris and sludge were found in the lumen of all 10 SEMS that were removed for various reasons in a trial of 70 patients with partially covered biliary stents.9 In an additional study of 112 patients with unresectable biliary tumors

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Figure 8-3. (A) Stent occlusion occurred in this patient due to sludge formation. Of note, the patient has a Roux-en-Y gastric bypass and the stent was reached with a colonoscope. The stent was swept with an occlusion balloon as shown until clear. Copious sludge is seen still in the stent and to the left of the stent. (B) Final endoscopic appearance of stent after repeated balloon sweeps. Note fully patent lumen. (C) Final fluoroscopic appearance of stent following repeated balloon sweeps. Note fully patent lumen.

treated with uncovered stents and PCSEMS, postmortem examinations performed on 9 patients with covered stents and 10 patients with uncovered stents found sludge in the lumen of all examined stents.6 The use of larger diameter (10 mm) SEMS is associated with a lower frequency of occlusion from sludge, debris, stones, and tumor ingrowth and overgrowth than smaller diameter (6 mm) stents.1 However, stent occlusion secondary to intraluminal sludge, debris, or stones is still a common cause of dysfunction for larger diameter biliary SEMS. SEMS occlusion secondary to sludge, stone, or debris is most commonly managed via sweeping the obstructed stent with an occlusion balloon repeatedly until the stent lumen has been cleared (Figure 8-3). Flushing the stent with saline solution to dislodge

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intraluminal obstructions may or may not be employed as an adjunctive technique but is rarely used in isolation.34,43,48 The insertion of a second stent within the first stent (stentwithin-stent deployment) is also frequently used to restore patency.6,9 Rarely, a biliary basket can be used to ensnare a recalcitrant stone, or cholangioscopic lithotripsy can be used to break up larger stones.14,49 The placement of a covered SEMS within the lumen of a biliary stent occluded with sludge (stent-within-stent deployment) provides a longer patency period than that of mechanical cleaning or intraluminal placement of other types of stents (see Tissue Ingrowth).

CHOLANGITIS Cholangitis is characterized by the combination of fever, right upper quadrant pain, and elevated total serum and conjugated bilirubin levels.2,8,9 The exact etiology of cholangitis secondary to SEMS placement is unknown. Restenosis of the SEMS is known to cause cholangitis via blockage of the stent, resulting in incomplete or failure of drainage of the bile duct.50 Indeed, cholangitis is more frequently encountered in patients with occluded biliary stents than in patients with no evidence of stent occlusion.50 Repeated episodes of cholangitis can lead to the formation of biliary sludge, which can contribute to restenosis and in turn lead to cholangitis.51 Cholangitis is also hypothesized to be caused by the reflux of food contents through the stent and colonization of the bile duct with gut bacteria in patients with transampullary stents.50-52 A multiple logistic regression model of a retrospective study of 108 patients with malignant biliary obstructions treated with SEMS found that transpapillary stent placement and restenosis were both positively associated with occurrence of cholangitis.51 Data thus far have been conflicting whether there is a difference in the rate of cholangitis between uncovered and covered SEMS in patients with malignant biliary obstructions.4,51 In patients with uncovered stents, PCSEMS, and FCSEMS, cholangitis was reported in 5.5% to 8.0%, 6.7% to 9.3%, and 2.9% to 3.7% of patients, respectively.4,9,14,20,41,50,53-55 Reports of cholangitis due to SEMS placement in patients with benign biliary strictures are limited. In a trial of 149 patients with benign biliary strictures, only 1 patient developed cholangitis (0.7%).13 Cholangitis is almost always easily and successfully managed with oral or intravenous antibiotic therapy and occasionally stent replacement5,9 (Figure 8-4).

PANCREATITIS Acute pancreatitis is defined by the presence of severe upper abdominal pain and at least a 3-fold elevation in serum amylase or lipase levels above the upper limit of normal.35,56 The practice of biliary sphincterotomy prior to stent placement is widespread and, in theory, reduces the risk of pancreatitis by increasing the room for the SEMS to expand in and potentially reducing pressure on the pancreatic duct (ie, preventing the SEMS from occluding the pancreatic duct) and by minimizing tension at the pancreatic orifice.26,56 Several recent large studies, however, have called this concept into question and have

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Figure 8-4. Ascending cholangitis in a patient 2 months postplacement of a fully internalized stent for hilar cholangiocarcinoma. Note copious pus draining from ampulla.

found no statistically significant difference between the pancreatitis rates in patients with and without a sphincterotomy prior to SEMS placement in malignant biliary obstructions.25,26,56 This is likely due to the fact that in most patients with pancreatic cancer and malignant biliary obstruction, the pancreatic duct is already obstructed by the malignant mass with resulting atrophy of glandular tissue and chronic obstruction of the main pancreatic duct, reducing the risk of pancreatitis significantly.25,26 There have been concerns that covered SEMS may increase the incidence of pancreatitis due to pancreatic duct obstruction from the stent covering.2,5,20 However, pancreatitis rates in patients with covered SEMS to treat malignant biliary obstructions are similar to that of uncovered SEMS, 0% to 7.9% and 0% to 8.7%, respectively.2-6,8,11,13,35,56,57 Additionally, many investigators report finding no statistically significant difference in pancreatitis rates between patients with covered and uncovered SEMS.3,5-7,56 Pancreatitis rates in patients with covered SEMS to treat benign biliary strictures range from 2% to 14% and are higher than that of patients with covered SEMS to treat malignant biliary obstructions.13,18,20,23 Rates may be higher in patients with benign biliary strictures because there is less likely to be atrophy of glandular tissue and chronic obstruction of the main pancreatic duct.20 Pancreatitis can be successfully managed with conservative treatment or without any intervention in mild cases and with stent removal, drainage, or surgery in moderate and severe cases.6,9,58

BLEEDING Bleeding related or secondary to biliary SEMS placement may result from postsphincterotomy bleeding, maceration of friable tumor tissue, pressure of the stent on the sphincterotomy site, or mucosal erosion of the bile duct wall or duodenum from mechanical contact with the stent itself (Figure 8-5). Patients who undergo sphincterotomy before SEMS placement are clearly more likely to experience bleeding than patients who undergo

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Figure 8-5. Bleeding status post-SEMS placement. Bright red blood was seen draining from the ampulla immediately following SEMS placement in a patient with cholangiocarcinoma involving the left hepatic duct. The bleeding stopped spontaneously in several minutes and no other treatment was needed.

stent placement without a sphincterotomy.25,26 The exact cause of bleeding can be difficult to elucidate as postsphincterotomy bleeding can occur up to 10 days after the procedure.59 Bleeding is often identified during the initial stent placement procedure endoscopically or afterward by clinical signs and symptoms ranging from melena to hemodynamic compromise that warrants repeat endoscopy.25,56 Patients with bleeding may experience a hemoglobin decrease, upper abdominal pain, hemobilia, fatigue, and/or melena, although they can be asymptomatic as well if the bleeding is mild and self-limited. Gastrointestinal bleeding occurred in 0% to 5% of placements of uncovered and covered SEMS in patients with malignant biliary obstructions or benign biliary strictures.1,2,6,9,17,18,35,48,60 Of note, the majority of the patients in these studies had undergone sphincterotomy prior to stent placement and experienced mild to moderate gastrointestinal bleeding that did not require blood transfusion. There have been reports of gastrointestinal ulceration secondary to stent placement that have led to severe hemorrhage and/ or death, although these are rare occurrences.6,54 It has been hypothesized that covered SEMS may be associated with a lower bleeding rate since they have been successfully used to mechanically tamponade postsphincterotomy bleeding and close perforations.6,61,62 However, studies have found no significant difference in bleeding complications in patients with uncovered and covered stents.2,6,48 Bleeding secondary to SEMS placement is commonly and successfully treated endoscopically with epinephrine injections, hemoclips, and/or electrocautery.5,9,48 Severe cases may require embolization and blood transfusion.6

DUODENAL PERFORATION Duodenal perforation secondary to a biliary SEMS is an uncommon complication, although it is a severe complication that can be fatal if untreated. Perforation may occur during the insertion of a biliary stent or following endoscopic manipulation of the stent,

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at the sphincterotomy site, or the site of the stricture.62 Most reported cases of duodenal perforation, however, represent late sequela from distally-migrated biliary stents. The diagnosis of duodenal perforation requires a high level of clinical suspicion as the symptoms of perforation are often nonspecific and can vary widely. Patients may present with general malaise, nausea, vomiting, fever, abdominal pain, an acute abdomen, leukocytosis, and/or overt septic shock.63 Perforation is graded based on the amount of contrast that leaks through the opening and its subsequent management.64 The incidence of duodenal perforation secondary to an indwelling biliary SEMS is low, and unfortunately most studies are not large enough to accurately measure its value. The majority of studies have found no cases of duodenal perforation in patients that received biliary SEMS to treat malignant biliary obstructions.1,56,65-67 Other investigators report rates of duodenal perforation from biliary SEMS ranging from 0.08% to 2.9%.4,5,10,25,68 Retroperitoneal perforations are often managed with broad spectrum antibiotics, bowel rest, parenteral alimentation, nasogastric decompression, stent removal, and/or covered stent placement across the opening.5,62,63 Severe, intraperitoneal, or uncontained free duodenal perforation necessitates emergent surgical interventions to divert gastric contents and biliary flow away from the affected area.5,63

OTHER COMPLICATIONS Patients with cholecystitis secondary to stent placement often present with right upper quadrant pain, fever, and/or leukocytosis.69 Cholecystitis may occur in patients often within days of stent placement due to occlusion of the cystic duct by the stent causing impaired gallbladder emptying and/or due to filling with nonsterile contrast medium.69 In theory, covered stents should cause cholecystitis more often than uncovered stents if placed across the opening of the cystic duct due to the coating. However, reports are conflicting. Investigators report an incidence of cholecystitis in patients with uncovered and covered SEMS ranging from 1% to 10.4% and 2.5% to 11.5%, respectively.45,55,69-71 Cholecystitis can be fatal but is often successfully managed with antibiotics, percutaneous cholecystostomy, stent removal, and even cholecystectomy.54,69,70 Stent occlusions due to blood clot or food debris are rare complications of biliary stenting.72 Patients often present with symptoms characteristic of stent occlusion such as elevated liver chemistries and/or jaundice. In a retrospective trial of 104 patients with uncovered and covered SEMS to treat malignant biliary obstructions, only one patient experienced stent occlusion due to blood clot obstruction (1.0%).26 In a further randomized prospective study, only 1 out of 241 patients with uncovered SEMS to treat malignant biliary obstructions had stent occlusion secondary to blood clot formation (0.4%).1 Several investigators have found incidence rates of occlusion secondary to food impaction ranging from 1.6% to 4.3% in patients who received biliary SEMS.5,55 Blood clot or food debris within the stent lumen may be easily cleared by flushing with saline or using an occlusion balloon.26,72 Few reports have described biliary SEMS fractures and their complications; however, those that have report high fracture incidences ranging from 7% to 8%.73,74 Early stent fractures (those occurring within a few months of deployment) may be related to manufacture failure. Late stent fractures could be due to metal fatigue, tumor progression, or repeat treatments for tumor ingrowth.73,75 The majority of reported stent fractures are

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Figure 8-6. Fractured biliary SEMS. A 73-yearold man developed pancreatic cancer and had a transampullary biliary SEMS placed. He presented with ascending cholangitis 8 weeks later. Endoscopic retrograde cholangiopancreatography revealed a fractured SEMS with jagged metal struts visible at an ulcerated ampullary orifice (arrow). The cause of the SEMS fracture was never ascertained.

in patients with nitinol stents, which are stiffer and less resistant to bending than nonnitinol stents.74,76 Patients with stent fracture often present with recurrent jaundice and/or cholangitis (Figure 8-6). Distally broken stent ends can cause gastrointestinal bleeding or obstruction further down the bowel. Stent fracture is most commonly managed by placing a new stent through the fractured one.73,77 There are reports of metal biliary stents perforating the bile duct wall to form duodenobiliary and portobiliary fistulas.78,79 The development of a portobiliary fistula from stent erosion is exceedingly rare, and reports are very limited. It is hypothesized to be caused by a stent that is too short or is misaligned, resulting in biliary ductal erosion and perforation into the portal vein.79 Patients with a portobiliary fistula often present with hematochezia, melena, hemobilia, right upper quadrant pain, and/or anemia.79-81 Reports of portobiliary fistulas secondary to stent erosion have been managed by placement of a second stent (stent-within-stent technique) to change the original stent’s alignment.79 Perforation of the colon from migrated SEMS is a further rare complication of biliary stenting.82 Patients with comorbid abdominal pathologies that cause obstruction of normal elimination of foreign bodies, such as colonic diverticula or strictures, may be at increased risk of perforation from migrated stents.83

CONCLUSION The most common complications of metal biliary stent placement include stent occlusion due to tissue/tumor ingrowth, overgrowth, and sludge accumulation, as well as stent migration in covered SEMS. Covered stents were developed to reduce the high rate of tissue/tumor ingrowth associated with uncovered metal stents. Due to the coating, these stents have a lower rate of tissue/tumor ingrowth but a higher rate of tissue/tumor overgrowth, sludge accumulation, and migration than that of uncovered metal stents. In turn, a

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covered SEMS may be a better option for patients with a resectable distal malignant biliary obstruction or with a benign biliary stricture, since they are more easily removed than an uncovered stent. For patients with unresectable distal malignant biliary obstructions, uncovered SEMS are preferred. Occlusive complications in this setting are, in general, easily managed with either balloon sweeps to remove sludge and/or stones or the placement of a second stent (stent-within-stent fashion) should it become occluded by benign or malignant tissue. Less common complications of metal biliary stenting include cholangitis, pancreatitis, cholecystitis, bleeding, and duodenal ulceration. Cases of stent fracture, occlusion from food debris or blood clot, bile duct perforation, and colon perforation in patients with metal biliary stents have been reported. Patients with many of these complications may present with similar clinical symptoms and require further diagnostic tools such as computed tomography to determine etiology.

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13. Ho H, Mahajan A, Gosain S, et al. Management of complications associated with partially covered biliary metal stents. Dig Dis Sci. 2010;55(2):516-522. 14. Siriwardana HP, Siriwardena AK. Systematic appraisal of the role of metallic endobiliary stents in the treatment of benign bile duct stricture. Ann Surg. 2005;242(1):10-19. 15. van Berkel AM, Cahen DL, van Westerloo DJ, Rauws EA, Huibregtse K, Bruno MJ. Selfexpanding metal stents in benign biliary strictures due to chronic pancreatitis. Endoscopy. 2004;36(5):381-384. 16. Cantu P, Hookey LC, Morales A, Le Moine O, Deviere J. The treatment of patients with symptomatic common bile duct stenosis secondary to chronic pancreatitis using partially covered metal stents: a pilot study. Endoscopy. 2005;37(8):735-739. 17. Kahaleh M, Behm B, Clarke BW, et al. Temporary placement of covered self-expandable metal stents in benign biliary strictures: a new paradigm? (with video). Gastrointest Endosc. 2008;67(3):446-454. 18. Behm B, Brock A, Clarke BW, et al. Partially covered self-expandable metallic stents for benign biliary strictures due to chronic pancreatitis. Endoscopy. 2009;41(6):547-551. 19. Chaput U, Scatton O, Bichard P, et al. Temporary placement of partially covered self-expandable metal stents for anastomotic biliary strictures after liver transplantation: a prospective, multicenter study. Gastrointest Endosc. 2010;72(6):1167-1174. 20. Park do H, Lee SS, Lee TH, et al. Anchoring flap versus flared end, fully covered selfexpandable metal stents to prevent migration in patients with benign biliary strictures: a multicenter, prospective, comparative pilot study (with videos). Gastrointest Endosc. 2011;73(1):64-70. 21. Bruno M, Boermeester M, Rauws E, Gouma D, Fockens P. Use of removable covered expandable metal stents (RCEMS) in the treatment of benign distal common duct (CBD) strictures: a feasibility study [abstract]. Gastrointest Endosc. 2005;61(5):AB199. 22. Cahen DL, Rauws EA, Gouma DJ, Fockens P, Bruno MJ. Removable fully covered self-expandable metal stents in the treatment of common bile duct strictures due to chronic pancreatitis: a case series. Endoscopy. 2008;40(8):697-700. 23. Mahajan A, Ho H, Sauer B, et al. Temporary placement of fully covered self-expandable metal stents in benign biliary strictures: midterm evaluation (with video). Gastrointest Endosc. 2009;70(2):303-309. 24. Kuo MD, Lopresti DC, Gover DD, Hall LD, Ferrara SL. Intentional retrieval of viabil stentgrafts from the biliary system. J Vasc Interv Radiol. 2006;17(2 Pt 1):389-397. 25. Artifon EL, Sakai P, Ishioka S, et al. Endoscopic sphincterotomy before deployment of covered metal stent is associated with greater complication rate: a prospective randomized control trial. J Clin Gastroenterol. 2008;42(7):815-819. 26. Banerjee N, Hilden K, Baron TH, Adler DG. Endoscopic biliary sphincterotomy is not required for transpapillary SEMS placement for biliary obstruction. Dig Dis Sci. 2011;56(2):591-595. 27. Kasher JA, Corasanti JG, Tarnasky PR, McHenry L, Fogel E, Cunningham J. A multicenter analysis of safety and outcome of removal of a fully covered self-expandable metal stent during ERCP. Gastrointest Endosc. 2011;73(6):1292-1297. 28. Ishii K, Itoi T, Sofuni A, et al. Endoscopic removal and trimming of distal self-expandable metallic biliary stents. World J Gastroenterol. 2011;17(21):2652-2657. 29. Kahaleh M, Tokar J, Le T, Yeaton P. Removal of self-expandable metallic Wallstents. Gastrointest Endosc. 2004;60(4):640-644. 30. Egan LJ, Baron TH. Endoscopic removal of an embedded biliary Wallstent by piecemeal extraction. Endoscopy. 2000;32(6):492-494. 31. Familiari P, Bulajic M, Mutignani M, et al. Endoscopic removal of malfunctioning biliary selfexpandable metallic stents. Gastrointest Endosc. 2005;62(6):903-910. 32. O’Brien SM, Hatfield AR, Craig PI, Williams SP. A 5-year follow-up of self-expanding metal stents in the endoscopic management of patients with benign bile duct strictures. Eur J Gastroenterol Hepatol. 1998;10(2):141-145. 33. Kim HS, Lee DK, Kim HG, et al. Features of malignant biliary obstruction affecting the patency of metallic stents: a multicenter study. Gastrointest Endosc. 2002;55(3):359-365. 34. Bueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc. 2003;58(6):879-884.

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35. Yang KY, Ryu JK, Seo JK, et al. A comparison of the Niti-D biliary uncovered stent and the uncovered Wallstent in malignant biliary obstruction. Gastrointest Endosc. 2009;70(1):45-51. 36. Krokidis M, Fanelli F, Orgera G, Bezzi M, Passariello R, Hatzidakis A. Percutaneous treatment of malignant jaundice due to extrahepatic cholangiocarcinoma: covered Viabil stent versus uncovered Wallstents. Cardiovasc Intervent Radiol. 2010;33(1):97-106. 37. Deviere J, Cremer M, Baize M, Love J, Sugai B, Vandermeeren A. Management of common bile duct stricture caused by chronic pancreatitis with metal mesh self expandable stents. Gut. 1994;35(1):122-126. 38. Roumilhac D, Poyet G, Sergent G, et al. Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation. Liver Transpl. 2003;9(4):394-400. 39. Togawa O, Kawabe T, Isayama H, et al. Management of occluded uncovered metallic stents in patients with malignant distal biliary obstructions using covered metallic stents. J Clin Gastroenterol. 2008;42(5):546-549. 40. Siriwardana HP, Siriwardena AK. Systematic appraisal of the role of metallic endobiliary stents in the treatment of benign bile duct stricture. Ann Surg. 2005;242(1):10-19. 41. Rogart JN, Boghos A, Rossi F, et al. Analysis of endoscopic management of occluded metal biliary stents at a single tertiary care center. Gastrointest Endosc. 2008;68(4):676-682. 42. Bueno JT, Gerdes H, Kurtz RC. Endoscopic management of occluded biliary Wallstents: a cancer center experience. Gastrointest Endosc. 2003;58(6):879-884. 43. Tham TC, Carr-Locke DL, Vandervoort J, et al. Management of occluded biliary Wallstents. Gut. 1998;42(5):703-707. 44. Cho JH, Jeon TJ, Park JY, et al. Comparison of outcomes among secondary covered metallic, uncovered metallic, and plastic biliary stents in treating occluded primary metallic stents in malignant distal biliary obstruction. Surg Endosc. 2011;25(2):475-482. 45. Lee BH, Choe DH, Lee JH, Kim KH, Chin SY. Metallic stents in malignant biliary obstruction: prospective long-term clinical results. AJR Am J Roentgenol. 1997;168(3):741-745. 46. Lee MJ, Dawson SL, Mueller PR, et al. Percutaneous management of hilar biliary malignancies with metallic endoprostheses: results, technical problems, and causes of failure. Radiographics. 1993;13(6):1249-1263. 47. Lopez RR Jr, Cosenza CA, Lois J, et al. Long-term results of metallic stents for benign biliary strictures. Arch Surg. 2001;136(6):664-669. 48. Krokidis M, Fanelli F, Orgera G, et al. Percutaneous palliation of pancreatic head cancer: randomized comparison of ePTFE/FEP-covered versus uncovered nitinol biliary stents. Cardiovasc Intervent Radiol. 2011;34(2):352-361. 49. Bakhru MR, Kahaleh M. Expandable metal stents for benign biliary disease. Gastrointest Endosc Clin N Am. 2011;21(3):447-462. 50. Misra SP, Dwivedi M. Reflux of duodenal contents and cholangitis in patients undergoing self-expanding metal stent placement. Gastrointest Endosc. 2009;70(2):317-321. 51. Okamoto T, Fujioka S, Yanagisawa S, et al. Placement of a metallic stent across the main duodenal papilla may predispose to cholangitis. Gastrointest Endosc. 2006;63(6):792-796. 52. Das A, Sivak MV Jr. Endoscopic palliation for inoperable pancreatic cancer. Cancer Control. 2000;7(5):452-457. 53. Bezzi M, Orsi F, Salvatori FM, Maccioni F, Rossi P. Self-expandable nitinol stent for the management of biliary obstruction: long-term clinical results. J Vasc Interv Radiol. 1994;5(2): 287-293. 54. Fumex F, Coumaros D, Napoleon B, et al. Similar performance but higher cholecystitis rate with covered biliary stents: results from a prospective multicenter evaluation. Endoscopy. 2006;38(8):787-792. 55. Nakai Y, Isayama H, Komatsu Y, et al. Efficacy and safety of the covered Wallstent in patients with distal malignant biliary obstruction. Gastrointest Endosc. 2005;62(5):742-748. 56. Coté GA, Kumar N, Ansstas M, et al. Risk of post-ERCP pancreatitis with placement of self-expandable metallic stents. Gastrointest Endosc. 2010;72(4):748-754. 57. Li Sol Y, Kim CW, Jeon UB, et al. Early infectious complications of percutaneous metallic stent insertion for malignant biliary obstruction. AJR Am J Roentgenol. 2010;194(1):261-265.

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58. Rerknimitr R, Kongkam P, Kullavanijaya P. Outcome of self-expandable metallic stents in low-grade versus advanced hilar obstruction. J Gastroenterol Hepatol. 2008;23(11): 1695-1701. 59. Simmons DT, Petersen BT, Gostout CJ, Levy MJ, Topazian MD, Baron TH. Risk of pancreatitis following endoscopically placed large-bore plastic biliary stents with and without biliary sphincterotomy for management of postoperative bile leaks. Surg Endosc. 2008;22(6): 1459-1463. 60. Yoon WJ, Ryu JK, Yang KY, et al. A comparison of metal and plastic stents for the relief of jaundice in unresectable malignant biliary obstruction in Korea: an emphasis on cost-effectiveness in a country with a low ERCP cost. Gastrointest Endosc. 2009;70(2): 284-289. 61. Itoi T, Yasuda I, Doi S, Mukai T, Kurihara T, Sofuni A. Endoscopic hemostasis using covered metallic stent placement for uncontrolled post-endoscopic sphincterotomy bleeding. Endoscopy. 2011;43(4):369-372. 62. Baron TH. Covered self-expandable metal stents for benign biliary tract diseases. Curr Opin Gastroenterol. 2011;27(3):262-267. 63. Miller G, Yim D, Macari M, Harris M, Shamamian P. Retroperitoneal perforation of the duodenum from biliary stent erosion. Curr Surg. 2005;62(5):512-515. 64. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc. 1991;37(3):383-393. 65. Ornellas LC, Stefanidis G, Chuttani R, et al. Covered Wallstents for palliation of malignant biliary obstruction: primary stent placement versus reintervention. Gastrointest Endosc. 2009;70(4):676-683. 66. Decker C, Christein JD, Phadnis MA, Mel Wilcox C, Varadarajulu S. Biliary metal stents are superior to plastic stents for preoperative biliary decompression in pancreatic cancer. Surg Endosc. 2011;25(7):2364-2367. 67. Simmons DT, Petersen BT, Gostout CJ, Levy MJ, Topazian MD, Baron TH. Risk of pancreatitis following endoscopically placed large-bore plastic biliary stents with and without biliary sphincterotomy for management of postoperative bile leaks. Surg Endosc. 2008;22(6): 1459-1463. 68. Demarquay JF, Dumas R, Peten EP, Rampal P. Argon plasma endoscopic section of biliary metallic prostheses. Endoscopy. 2001;33(3):289-290. 69. Suk KT, Kim HS, Kim JW, et al. Risk factors for cholecystitis after metal stent placement in malignant biliary obstruction. Gastrointest Endosc. 2006;64(4):522-529. 70. Kahaleh M, Brock A, Conaway MR, et al. Covered self-expandable metal stents in pancreatic malignancy regardless of resectability: a new concept validated by a decision analysis. Endoscopy. 2007;39(4):319-324. 71. Bezzi M, Zolovkins A, Cantisani V, et al. New ePTFE/FEP-covered stent in the palliative treatment of malignant biliary obstruction. J Vasc Interv Radiol. 2002;13(6):581-589. 72. Cowling MG, Adam AN. Internal stenting in malignant biliary obstruction. World J Surg. 2001;25(3):355-359; discussion 359-361. 73. Rasmussen IC, Dahlstrand U, Sandblom G, Eriksson LG, Nyman R. Fractures of selfexpanding metallic stents in periampullary malignant biliary obstruction. Acta Radiol. 2009;50(7):730-737. 74. Peck R, Wattam J. Fracture of Memotherm metallic stents in the biliary tract. Cardiovasc Intervent Radiol. 2000;23(1):55-56. 75. Ell C, Fleig WE, Hochberger J. Broken biliary metal stent after repeated electrocoagulation for tumor ingrowth. Gastrointest Endosc. 1992;38(2):197-199. 76. Yoshida H, Tajiri T, Mamada Y, et al. Fracture of a biliary expandable metallic stent. Gastrointest Endosc. 2004;60(4):655-658. 77. Donahue DG, Saltzman JR, Krims P. Stent fracture in malignant biliary obstruction. Gastrointest Endosc. 1993;39(6):864-865. 78. Moon SK, Cheung DY, Kim JH, et al. A case of choledochoduodenal fistula as a delayed complication after biliary metallic stent placement in distal cholangiocarcinoma. Korean J Gastroenterol. 2008;51(5):314-318.

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79. Chaitowitz IM, Heng R, Bell KW. Management of iatrogenic porto-biliary fistula following biliary stent. Australas Radiol. 2007;51 Suppl:B316-8. 80. Peynircioglu B, Cwikiel W. Utility of stent-grafts in treatment of porto-biliary fistula. Cardiovasc Intervent Radiol. 2006;29(6):1156-1159. 81. Quinn C, Johnston SD. Portobiliary fistula at ERCP. Gastrointest Endosc. 2007;65(1):175-177. 82. Namdar T, Raffel AM, Topp SA, et al. Complications and treatment of migrated biliary endoprostheses: a review of the literature. World J Gastroenterol. 2007 28;13(40):5397-5399. 83. Akbulut S, Cakabay B, Ozmen CA, Sezgin A, Sevinc MM. An unusual cause of ileal perforation: report of a case and literature review. World J Gastroenterol. 2009;15(21):2672-2674.

9

Gastroduodenal Stents Christopher J. DiMaio, MD

Endoscopic placement of enteral self-expanding metal stents (SEMS) has been a major advance in the palliation of malignant gastric outlet obstruction (GOO). This modality offers a minimally invasive alternative to surgical bypass, feeding tubes, and venting gastrostomy tubes and allows for rapid relief of nausea and vomiting, improved oral food intake, and overall improved quality of life.1-4 This chapter will focus on the role of gastroduodenal SEMS in the management of malignant GOO.

INDICATIONS FOR ENTERAL SELF-EXPANDING METAL STENTS The most common underlying etiologies of malignant GOO are primary luminal disease from gastric cancer and extrinsic compression from advanced pancreaticobiliary malignancy. Other intrinsic neoplastic processes as well as extrinsic compression from metastatic disease to the serosa, adjacent organs, and lymph nodes can also lead to GOO (Table 9-1). Enteral SEMS are indicated for palliation of malignant GOO in patients who are not candidates for curative surgical resection. The majority of patients with malignant gastroduodenal obstruction will likely have advanced disease and thus be poor surgical candidates, thereby making them appropriate candidates for an enteral SEMS. It should be noted that the use and acceptance of SEMS for this purpose is institution dependent; some centers still predominately perform surgical bypass for the relief of malignant GOO while others heavily favor SEMS for these patients. Thus, multidisciplinary evaluation and discussion should be considered a standard part of the management of this patient population. Evaluation of the use of enteral SEMS as compared to surgical bypass will be addressed in Chapter 10 of this book.

CONTRAINDICATIONS FOR ENTERAL SELF-EXPANDING METAL STENTS Patients with multifocal obstruction are at high risk for stent failure if all sites of obstruction are generally not amenable to SEMS placement. Enteral SEMS placement

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Adler DG, ed. Self-Expanding Stents in Gastrointestinal Endoscopy (pp 139-166). © 2012 SLACK Incorporated.

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Table 9-1. Etiology of Malignant Gastric Outlet Obstruction Intrinsic Obstruction Gastric cancer Small bowel cancer (duodenum, proximal jejunum) Ampullary cancer Lymphoma

Extrinsic Compression Pancreatic cancer Cholangiocarcinoma Hepatocellular carcinoma Lymphoma Metastatic disease to serosa, adjacent organs/lymph nodes

is contraindicated in patients with necrotic tumor or tumor-associated perforation or bowel ischemia because they are at increased risk for procedure-related complications. It is critical that pertinent cross-sectional imaging be reviewed prior to any endoscopic intervention. Patients with either gastrointestinal or extraluminal lymphoma can present with malignant GOO. However, unlike with primary gastrointestinal malignancies or metastatic disease, resolution of the obstruction typically occurs with systemic medical and/or radiation therapy. Thus, caution should be applied when considering the use of enteral SEMS in this population because currently available enteral SEMS are not designed for removal. From a technical standpoint, the ability to safely and successfully place an enteral SEMS requires its advancement over a wire. Thus, the inability to advance a wire across the stricture is a major contraindication to enteral SEMS placement.

PREPROCEDURE EVALUATION Patient Evaluation and Selection Patients with GOO typically present with symptoms of nausea, vomiting, early satiety, anorexia, and weight loss. When GOO is clinically suspected, initial evaluation with a computed tomography (CT) scan of the abdomen with both oral and intravenous contrast is recommended. Radiographic findings of marked gastric and/or duodenal distention with an associated focal point of obstruction are diagnostic of GOO (Figures 9-1 and 9-2). If no transition point is identified, then an alternative diagnosis such as gastroparesis or small bowel hypomotility from peritoneal carcinomatosis, opioid use, or other causes, as well as further evaluation, should be considered. CT imaging can also identify conditions that are contraindications to SEMS placement, such as multifocal obstruction and the presence of necrotic tumor or free air. Plain abdominal x-rays and dedicated contrast studies (ie, upper gastrointestinal series, small bowel follow-through) often have little role in the initial evaluation of patients with GOO. Abdominal x-rays may demonstrate gastric and/or small bowel distention; however, they cannot provide the detail of a quality CT. In our experience, dedicated contrast studies are time consuming, may increase the risk of aspiration, and may not provide any further information regarding extraluminal processes that may be the underlying etiology of the obstruction.

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Figure 9-1. Malignant GOO from primary gastric cancer (arrow).

Figure 9-2. Marked gastric distention.

When the diagnosis of malignant GOO remains in doubt, direct visualization by endoscopic evaluation should be considered (Figure 9-3). However, it is advisable that the endoscopist and patient be prepared for enteral SEMS placement at the time of said endoscopic evaluation to avoid putting the patient through multiple endoscopic procedures. Before any consideration is given to endoscopic placement of an enteral SEMS, patients must be assessed to determine if they are suitable candidates for undergoing an upper endoscopy. Given that patients with advanced malignancy often have multiple comorbidities, care must be taken to ensure that the patient is not moribund and will be able to tolerate sedation/anesthesia and the procedure itself.

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Figure 9-3. Malignant GOO at junction of first and second portion of the duodenum, secondary to extrinsic compression from pancreatic adenocarcinoma.

Patient Preparation Patients with GOO are at high risk for aspiration events during sedation and endoscopy due to retained gastric contents. It is often beneficial for patients to undergo gastric evacuation via nasogastric tube 24 hours prior to endoscopy, as this may reduce the risk of an aspiration event. Given the increased risk for aspiration, general anesthesia and an endotracheal tube may be warranted for gastroduodenal stent placement procedures. Patients can be positioned supine, prone, or in the left lateral decubitus position. Each has its own benefits and limitations in regard to aspiration risk and ease of fluoroscopic visualization.

Equipment and Room Set Up Gastroduodenal stent placement requires fluoroscopic guidance. Thus, these procedures are typically performed in an endoscopy room equipped for endoscopic retrograde cholangiopancreatography (ERCP). All currently available enteral SEMS are deployed via a through-the-scope over-thewire system and come in a variety of sizes (Table 9-2). Deployment of the stent occurs by employing backward tension on the stent introducer, resulting in retraction of the overlying sheath and thus allowing for stent expansion. Some available stents can be “recaptured” in the sheath to allow for repositioning prior to full deployment. Both types of commercially available enteral SEMS in the United States have a 10 Fr introducer system. As such, a therapeutic endoscope with a large working channel (>3.3 mm) is required for placing these stents. Therapeutic gastroscopes, colonoscopes, and duodenoscopes are all suitable endoscopic platforms for delivering enteral stents. Duodenoscopes offer the added advantage of allowing for biliary SEMS placement in patients with concomitant biliary obstruction during the same procedure. Placement of a guidewire across the stricture allows for safe delivery of the undeployed stent (Figure 9-4). Other items that are employed in the evaluation of strictures and should be readily available include water-soluble radiographic contrast, biliary catheters, and balloon catheters. Injectable radio-opaque solutions and/or external markers may also be desired and should be available.

Boston Scientific Inc. (Natick, MA) Boston Scientific M.I. Tech (Seoul, South Korea) M.I. Tech

Taewoong Medical Inc. (Seoul, South Korea) Taewoong Medical Inc.

Taewoong Medical Inc.

Enteral Wallstent

Niti-S Pyloric/ Duodenal Uncovered Stent (D-Type) ComVi Niti-S Pyloric/ Duodenal Stent

Niti-S Pyloric/ Duodenal Covered Stent

Hanarostent

Enteral Wallflex Hanarostent

Manufacturer

Stent Name

Uncovered

Covered (both ends bare) Covered (one end bare)

Nitinol

Nitinol

Nitinol

Covered

Uncovered Uncovered

Uncovered

Type

Nitinol

Nitinol Nitinol

Elgiloy

Material

16 to 20

18, 20

16, 18, 20, 22, 24

18

22 18

20

Stent Diameter: Body (mm)

Table 9-2. Currently Available Through-the-Scope Self-Expanding Metal Stents

22 to 26

n/a

n/a

22

27 22

22

Stent Diameter: Flared Ends (mm)

6, 9, 10, 12

6, 8, 10

4, 6, 8, 10, 12

6, 8, 11, 14, 17

6, 9, 12 6, 8, 11, 14, 17

6, 9

Stent Length (cm)

10.5/180

10.5/180

10.2/120, 180, 210, 230 10.5/180

10/230 10.2/120, 180, 210, 230

10/135, 230

Delivery System Diameter (Fr)/ Length (cm)

Gastroduodenal Stents 143

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Figure 9-4. Wire placement across the stricture.

TECHNIQUE Evaluation of Stricture Before any attempts at enteral stent placement, a proper evaluation of the malignant obstruction is necessary. This will allow for selection of the optimal stent size/length and ensure the best outcome. Determination of stricture length can be performed in a variety of ways. Direct endoscopic measurement can be performed if the obstruction can be traversed with the endoscope. However, this will not be possible in the vast majority of cases. As a result, fluoroscopic evaluation of the stricture will need to be employed. The most common method to evaluate the stricture employs the use of a biliary catheter and a guidewire to cannulate the lumen of the stricture and to obtain (and maintain) deep guidewire access to the small bowel distal to the obstruction. Contrast injection through the catheter under fluoroscopy can allow for delineation of the stricture length and architecture. Repeated contrast injections followed by saline flushes may also allow for visualization of the gastrointestinal lumen distal to the obstruction, and thus help to rule out multifocal obstruction. In our gastrointestinal unit, the preferred method for fluoroscopic evaluation of malignant GOO employs the use of a contrast-filled balloon (Figure 9-5). A wire is first advanced across the stricture under fluoroscopic guidance. Our preference is to use a 0.035-inch Jagwire (Boston Scientific, Natick, MA) because this accessory has both a hydrophilic tip, which allows for ease of wire access with limited tissue damage, and a stiff wire shaft, which reduces looping and provides a stable platform for stent insertion, although no specific wire can be recommended for all procedures. A through-the-scope balloon (eg, continuous radial expansion (CRE) balloon dilator or biliary stone extraction balloon) is then advanced over the wire, across the stricture. The balloon is then inflated with contrast and slowly withdrawn under fluoroscopic visualization until resistance is encountered (see Figure 9-5B). This point represents the distal aspect of the stricture. Contrast injection through the wire port of the balloon catheter can then be performed to confirm absence of distal points of obstruction.

Gastroduodenal Stents A

145 Figure 9-5. Use of the balloon method and external markers to denote stricture. (A) The scope is inserted to the point of obstruction. (B) A CRE balloon is advanced across the stricture, inflated with contrast, and slowly withdrawn until resistance is encountered. This represents the distal aspect of the stricture. External markers (paper clips) are used to denote the proximal (p) and distal (d) margins of the stricture.

B

Use of Markers to Denote Margins Once the stricture length has been determined, the proximal and distal margins of the stricture can be denoted with the use of radio-opaque external markers if desired in order to guide stent placement (see Figure 9-5B), although this is not universally performed. In cases where the obstruction is able to be traversed endoscopically, markings made via

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Figure 9-5 continued. (C) The stent is C deployed across the stricture. Note the equal length of stent that is proximal and distal to the stricture.

the use of endoscopically placed clips or submucosal injection of contrast agents such as lipiodol can be used. Of note, many endoscopists do not use markers of any kind and simply rely on the combined endoscopic and fluoroscopic images to achieve optimal stent placement. Regardless of whether the stricture is able to be traversed, it is our practice to always use external markings by way of paper clips to denote the proximal and distal tumor margins. With the patient in the supine position, we first perform the previously described balloon method to identify the distal tumor margin. This location is then marked by simply taping a paper clip to the patient’s abdomen under fluoroscopic guidance. To mark the proximal margin of the stricture, we drive the endoscope up to the stricture. Fluoroscopy is used to localize the scope tip, and the corresponding spot on the patient’s abdomen is marked by taping a paper clip. In cases in which we are able to traverse the stricture, we find it helpful to also mark the location of the ampulla in order to avoid traversing it with the stent when possible (Figure 9-6).

Choice of Stent Commercially available stents come in various lengths, ranging from 6 to 15 cm. When deciding upon what length SEMS to employ, one should choose a stent that will allow for approximately 2 cm of stent to extend both proximal and distal to the stricture margins. Once deployed, most enteral SEMS will typically foreshorten by approximately 25% as they expand. Thus, having an extra expanse of stent on either side of the stricture will ensure that the stent fully opens and completely covers the entire stricture, thus decreasing the risk of stent failure and possibly migration. Stent diameters range from 18 to 24 mm, with the 20 and 22 mm diameters being the most commonly employed. Most stents that are currently available have a flared proximal

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A

B

Figure 9-6. External markers are used to mark the location of the (A) major papilla and (B) the distal tumor margin.

end (either 22 or 27 mm), which may reduce the incidence of distal migration. There are no comparative studies evaluating the efficacy of different stent diameters. In our experience, the use of a 22-mm diameter stent is effective and well tolerated.

Stent Deployment All currently available enteral SEMS are deployed via a through-the-scope over-thewire introducer system. Balloon dilation of the stricture prior to stent placement is typically unnecessary, as the stent introducer can usually be advanced easily across the

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Chapter 9 C

D

E

Figure 9-6 continued. (C, arrow) The proximal tumor margin. (D) The undeployed stent is advanced over a guidewire. (E,F) The stent expands postdeployment.

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149

F

Figure 9-6 continued. Note that the enteral stent does not cross the region of the papilla, allowing for future endoscopic biliary access if necessary.

stricture, and the radial expansile force of available enteral SEMS is strong enough to overcome the compressive force of the tumor. Simultaneous fluoroscopic and endoscopic imaging is almost always required for safe and optimal stent placement. Enteral SEMS are designed as distal-release systems. Thus, fluoroscopic guidance is required to ensure that the distal end of the stent has flared open appropriately. As the sheath is withdrawn from the stent, endoscopic monitoring of the proximal end of the stent is necessary to ensure that an adequate amount of stent is deployed proximal to the obstruction. For optimal stent placement, the endoscopist should aim to leave equal amounts of stent both above and below the stricture (see Figure 9-5C and 9-6F). In order to prevent stent erosion and/or impaction in the duodenal bulb, it is our practice to deploy the proximal end of the stent in the prepyloric stomach when possible, although duodenal bulb placement is completely appropriate if it produces optimal centering of the stent across a stricture (Figure 9-7). Stent position can be easily assessed fluoroscopically by confirming that both ends of the stent have flared open completely, in addition to noting the location of the stent waist in relation to the external markers, ensuring that there are equal amounts of stent both above and below the stricture. Once placed, enteral SEMS are considered permanent and removal should not be attempted as a general rule. However, in the time frame immediately after placement, the stent can be manipulated to ensure optimal placement. If the stent needs to be adjusted proximally, gentle traction can be applied with the use of a grasping forceps. If the stent needs to be advanced further inward, one could consider gently pushing the stent forward with the endoscope or a CRE balloon. However, this technique may increase the risk of migration and/or perforation and should only be attempted by an experienced endoscopist. If the stent is too short, then immediate removal with a grasping forceps followed by placement of a new longer stent

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Figure 9-7. Successful deployment of enteral SEMS. The proximal end of the stent is deployed in the prepyloric stomach to prevent impaction against the duodenal bulb.

should be considered. Alternatively, a second stent can be placed in a coaxial fashion (ie, stentwithin-stent) to extend the initial stent proximally of distally as needed. Once stent deployment has successfully occurred, care should be taken to avoid aggressive manipulation of the stent. It is generally not recommended to attempt passage of the endoscope across a newly placed stent, so as to avoid stent dislodgement. Contrast injection through the stent can be performed to confirm patency but is often unnecessary.

OUTCOMES Technical Success A vast amount of literature has been published over the past 2 decades reporting the international experience with endoscopic enteral stenting. The majority of these studies are retrospective and do not employ the use of the same stent. Furthermore, most individual studies evaluate the use of enteral SEMS in patients with malignant GOO secondary to various diseases, including hepatopancreaticobiliary neoplasms, gastric cancer, and primary malignancies of the small bowel and ampulla and extrinsic compression from metastatic disease. However, regardless of stent model used, the reported rates of technical success (defined as the ability to deploy the stent across the stricture) are extremely high, ranging from 91% to 100%.2,5-15 Given that all currently available enteral stents employ similar introducer systems and deployment devices, it is generally felt that in regard to the technical aspects of stent placement, little difference exists among the various stents that are commercially available.

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Table 9-3. Gastric Outlet Obstruction Scoring System Level of Oral Intake

Score

No oral intake

0

Liquids only

1

Soft solids

2

Low-residue or full diet

3

Clinical Success The goal of placing enteral stents is to relieve the symptoms of nausea and vomiting, as well as to improve oral nutritional intake and overall quality of life. To this end, enteral stents are highly effective with reported clinical success (defined as relief of clinical symptoms of GOO) being achieved in well over 80% in the majority of published reports.5,7,8,10-12,14,16 One useful measure of outcome in patients with malignant GOO is the use of a dietary scoring system to assess improvements in oral nutritional intake. The Gastric Outlet Obstruction Scoring System (GOOSS), developed by Adler and Baron, allows for the assessment of oral food intake before and after the procedure (Table 9-3). Adler et al reported their experience in 36 patients with malignant GOO who underwent enteral SEMS placement.6 Overall, 31/36 (86%) of patients had improvement in their dietary intake. The median preprocedure GOOSS score was 0, compared to a median postprocedure score of 2.0 (p < 0.0001). Furthermore, the majority of patients were able to resume eating within 24 hours of the procedure, and all patients were able to resume eating within 7 days. A meta-analysis consisting of 606 patients from 32 pooled studies showed that clinical success was achieved in 526 (89%) patients in the group who had an enteral SEMS successfully placed. Oral intake was possible in all of these patients, with 87% taking soft solids or full diet and with final resolution of symptoms occurring after a mean of 4 days.16

Complications A variety of complications can occur both during and after enteral SEMS placement. Perforation of the stomach or small bowel is the most feared complication since management may require surgical intervention. Early perforation may be encountered at various time points: during the endoscopic evaluation of the stricture by the advancement of the scope, wire, or catheter across the stricture; during advancement of the undeployed stent across the stricture; after balloon dilation of the stricture; after stent expansion postdeployment; and after attempted passage of the endoscope through the stent (Figure 9-8). Furthermore, intestinal perforation can be delayed.17 When examining the published case series with the largest numbers of patients, perforation rates range from 0% to 6%.2,6,8,10-12,14 Given the often friable nature of a malignant gastroduodenal stricture, mild self-limited oozing is not atypical during endoscopic enteral SEMS placement. Severe, life-threatening bleeding is extremely rare and occurs less than 1% of the time.16 However, early massive bleeding secondary to duodenal stent placement and subsequent balloon dilation has been reported.18

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Figure 9-8. (A) Duodenal perforation A caused by attempted scope passage across an enteral SEMS. (B) The defect was successfully closed by endoscopic clip placement.

B

Cholangitis has been reported in up to 6% of cases.2,12,19 This may be due to “jailing” and obstruction of the major papilla by a duodenal stent that crosses the area of the papilla. However, synchronous biliary obstruction is very common in patients with malignant GOO, particularly those with pancreaticobiliary neoplasms, and thus the association may be more reflective of the natural history of the disease. Stent migration occurs in 0% to 14% of cases.2,5-8,10,11,14 A large meta-analysis reported a stent migration rate of 5%.16 Similar to perforation, stent migration can occur at any time during or after stent deployment. Furthermore, stents can migrate either proximal to the site of obstruction or distal to it (Figures 9-9 and 9-10). Stent migration can be managed in a number of ways. If the stent has migrated proximally completely out of the stricture, then endoscopic stent retrieval and removal can be considered. Otherwise,

Gastroduodenal Stents A

153 Figure 9-9. (A) The enteral SEMS proximally migrated into the stomach. (B) New SEMS placed after retrieval/removal of migrated stent.

B

endoscopic stent revision can be performed with insertion of one or more overlapping stents inside the in situ stent in order to extend it proximally or distally as necessary. In cases of distal stent migration in which the stent is no longer accessible by standard endoscopic means, retrieval attempts with enteroscope-assistance devices can be considered. However, given the theoretical risk of small bowel perforation, early surgical consultation should be obtained versus simple observation, as the stent may not cause any symptoms and the patient may have a short life expectancy anyway. The most common complication of enteral SEMS placement is stent obstruction, with incidence reported from 7% to 29% and pooled analysis data reporting 17%.5-8,14,16 Stent obstruction may be a result of technical issues (eg, insufficient coverage of the stenosis), stent malfunction (eg, stent fracture), or food impaction (Figure 9-11). However, the most common etiology of enteral stent obstruction is disease progression.16 Local tumor progression can result in tumor overgrowth at the proximal and/or distal ends of

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Figure 9-10. Distal migration of enteral SEMS (box).

Figure 9-11. Food impaction.

the stent, as well as tumor ingrowth through the interstices of the stent wall (Figure 9-12). In addition, mucosal tissue hyperplasia, secondary to the stent embedding into the gastroduodenal wall, can result in tissue overgrowth and ingrowth and result in subsequent stent obstruction (Figure 9-13). In general, enteral stents maintain a patency of roughly 180 days; however, mean patency rates as little as 82 days and as high as 307 days have been reported.5,7,9,11 Management of enteral stent obstruction can be safely performed by the insertion of one or more overlapping stents within the obstructed stent (see Figure 9-12).20

ROLE AND TIMING OF BILIARY SELF-EXPANDING METAL STENT PLACEMENT WITH REGARD TO DUODENAL STENTING Patients with pancreaticobiliary neoplasms are at risk for developing both biliary obstruction and GOO. Assessment of coexisting or impending biliary obstruction needs to be performed when gastroduodenal stent placement is being considered.

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A B

C

Figure 9-12. (A) Tumor ingrowth treated by placement of (B,C) overlapping stents.

Patients With Pre-Existing Biliary Obstruction Most commonly, patients with pancreaticobiliary neoplasms will develop biliary obstruction first, before the onset of GOO.21,22 In these cases, endoscopic biliary decompression should be performed. If duodenal obstruction subsequently develops at a later time, enteral stent placement can and should be pursued. However, it is important to note the type of in situ biliary endoprosthesis because this can have an important impact on procedure planning. In patients with an indwelling metal biliary SEMS, enteral stent placement can be performed safely, even if the enteral SEMS crosses the area of the papilla because the biliary SEMS will drain easily through the interstices of the enteral SEMS. On the other hand, if there is an indwelling plastic biliary stent, then placement of an enteral stent across the area of the papilla will result in jailing of the plastic biliary stent, prohibiting its removal and thus placing the patient at increased risk for subsequent cholangitis when it occludes. In these situations, it is generally recommended that plastic

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Figure 9-13. Hyperplastic tissue (A) over- A growth and (B) ingrowth.

B

biliary stents be exchanged for a biliary SEMS prior to placement of an enteral stent.7,23 In some cases, this may require balloon dilation of the gastroduodenal stricture in order to gain access to the major papilla. In cases in which the plastic biliary stent cannot be reached endoscopically, then consultation with interventional radiology should be obtained prior to enteral stent placement because the plastic stent can often be pushed out of the bile duct and a metal biliary SEMS can be placed, all in an antegrade fashion.

Patients With Simultaneous Biliary and Duodenal Obstruction Synchronous biliary and duodenal obstruction has been reported to occur in roughly one-quarter of patients at the time of presentation.7,24,25 For patients with simultaneous biliary and duodenal obstruction, endoscopic biliary SEMS placement should be performed prior to the placement of a duodenal stent (Figure 9-14). The success of combined endoscopic stenting often depends on the anatomy and location of the duodenal obstruction. Mutignani et al described 3 types of bilioduodenal strictures: Type I stenosis occurs

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A

B

Figure 9-14. Simultaneous biliary and duodenal obstruction with GOO proximal to the major papilla. (A,B) ERCP and biliary SEMS placement.

at the level of the duodenal bulb or upper duodenal genu, but without involvement of the papilla; Type II stenosis affects the second part of the duodenum with involvement of the papilla; and Type III stenosis involves the third portion of the duodenum, distal to and without involvement of the papilla25 (Figures 9-14 to 9-16). In instances where the major papilla cannot be reached secondary to gastroduodenal obstruction, then one or more options can be considered. Balloon dilation of the duodenal

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D

Figure 9-14 continued. (C,D) Duodenal SEMS placement. Note that the duodenal SEMS does not cross the papilla, allowing for future biliary access if necessary.

obstruction can be performed in order to allow passage of the duodenoscope across the stricture. There is a theoretical increased risk of perforation with this technique; however, safety and success have been reported.7,24,25 Another option is to place an enteral SEMS and use this for access to the papilla. This may require a second endoscopic session 24 to 48 hours later to allow time for the stent to fully expand and thus facilitate scope passage.

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A

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E

F

Figure 9-15. Simultaneous biliary and duodenal obstruction with duodenal obstruction distal to the major papilla. (A) Enteral SEMS placed across second and third portion of duodenum. (B to D) Biliary cannulation, followed by biliary SEMS placement, is performed. (E,F) Enteral SEMS is distal to the major papilla.

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B

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D

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F

Figure 9-16. (A) Type II bilioduodenal obstruction. (B,C) Selective biliary cannulation through the interstices of indwelling duodenal stent. (D) Balloon dilation of interstices of biliary stent to facilitate biliary SEMS insertion through the side wall. (E,F) Successful biliary SEMS placement with resultant extrusion of pus.

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For patients with Type II bilioduodenal obstruction where the enteral SEMS will cross the region of the papilla, ERCP is typically more challenging because biliary cannulation will need to be performed through the interstices of the enteral stent. When this situation arises, papillary access and selective biliary cannulation can be facilitated by one or more of the following techniques: balloon dilation of the interstices of the enteral stent, removal of the mesh with a rat-tooth grasping forceps, or by creating a fenestration in the side wall of the enteral stent using argon plasma coagulation (ie, at 80 Watts, 1 L/minute).25-27 Once endoscopic biliary access is achieved, then a biliary SEMS can be safely and easily placed through the interstices of the enteral SEMS (see Figure 9-16). Overall, combined endoscopic stenting in malignant biliary and duodenal obstruction is highly successful with reported technical success rates of well over 90% in multiple series.7,24,25 Other endoscopic alternatives for biliary drainage in the setting of duodenal obstruction and an inaccessible papilla make use of therapeutic endoscopic ultrasound (EUS). EUS-guided biliary drainage is an emerging technique whereby the biliary tree can be accessed across the gastrointestinal lumen using standard EUS needles and endoscopic accessories, with subsequent transmural placement of biliary stents into the intrahepatic ducts (hepaticogastrostomy) or extrahepatic ducts (choledochoduodenostomy).28,29 EUSguided biliary access and placement of a metal biliary SEMS across an existing duodenal stent has also been reported.30 In instances where endoscopic biliary access and decompression is not feasible, duodenal stent placement can still proceed safely and effectively. Biliary SEMS placement will then need to be accomplished percutaneously by interventional radiology.

Patients With Gastroduodenal Obstruction But No Biliary Obstruction If patients have gastroduodenal obstruction but no biliary obstruction, it is often helpful to perform an ERCP to prophylactially place a biliary SEMS prior to gastroduodenal stent placement. Many of these patients, even if they are not jaundiced, will be found to have a biliary stricture and/or impending jaundice upon obtaining a cholangiogram.

MID/DISTAL SMALL BOWEL OBSTRUCTION In cases of mid or distal small bowel obstructions that cannot be reached with conventional endoscopes, the placement of an enteral SEMS with the use of small bowel enteroscope-assistance devices has been reported. Ross et al reported a case in which double-balloon enteroscopy was employed to reach a malignant small bowel obstruction in the fourth portion of the duodenum.31 Lennon et al described 2 cases in which spiral overtube-assisted enteroscopy was performed to reach a stricture at the ligament of Treitz in one patient and an obstruction at the proximal jejunum in another.32 In both of these case reports, the enteroscope was withdrawn from the patient and an overtube was left in place. Stent placement was thus performed through the overtube under fluoroscopy without endoscopic guidance.

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OBSTRUCTION AT SURGICAL ANASTOMOSIS Malignant GOO can present when tumor recurrence occurs at the site of a surgical anastomosis, such as at the esophagojejunostomy in patients who are post-total gastrectomy, or at the gastrojejunostomy in patients who are postpartial gastrectomy or pancreaticoduodenectomy, and in those who have undergone bariatric procedures. In these instances, enteral SEMS placement is both safe and feasible, with technical and clinical success rates matching those of patients with native anatomy.2,5,7,33 Of note, patients with tumor recurrence at a gastrojejunostomy may present with either isolated afferent loop obstruction, isolated efferent loop obstruction, or both. It is our practice to place bilateral enteral SEMS in these patients at the initial endoscopic session if at all possible, even if there is only unilateral obstruction because unilateral limb obstruction often portends bilateral limb obstruction, and thus placement of bilateral stent eliminates the need for repeat endoscopic sessions (Figure 9-17). Also, placement of bilateral stents helps maintain patency of the uninvolved ostomy by preventing compression from one stent.

PERITONEAL CARCINOMATOSIS Patients with peritoneal carcinomatosis are at increased risk for multifocal intestinal obstruction. As a result, the presence of this condition has traditionally been considered a relative contraindication to enteral SEMS placement.21,34-36 However, new data support the use of enteral SEMS in select patients with peritoneal carcinomatosis who have a dominant GOO and no radiographic evidence of frank multifocal obstruction. Mendelsohn et al reported on a group of 192 patients with malignant GOO who underwent enteral SEMS placement. There was no significant difference in the clinical outcome of those patients with carcinomatosis (n = 116) compared to the group without carcinomatosis (n = 76) (81% versus 84%, p = 0.95).37 This study highlights the importance of reviewing crosssectional imaging to assess for multifocal intestinal obstruction. If multifocal obstruction is present, then enteral SEMS placement should not be pursued unless all sites of obstruction can be palliated with one or multiple enteral stents.

CONCLUSION The ability to endoscopically place enteral SEMS for the palliation of malignant GOO has been a major advance in the management of patients with advanced malignancy. This technique is associated with very high technical and clinical success rates and has an acceptably low risk of major complications. Enteral SEMS can offer the patient a minimally invasive alternative to feeding tubes, venting gastrostomy tubes, and surgical bypass. Combined endoscopic stenting of the bile ducts and duodenum offers an effective double bypass in patients with coexisting biliary and duodenal obstruction.

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B

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Figure 9-17. (A) Malignant GOO at gastrojejunostomy. (B,C) Enteral SEMS were placed across the efferent and afferent limbs.

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Maetani I, Akatsuka S, Ikeda M, et al. Self-expandable metallic stent placement for palliation in gastric outlet obstructions caused by gastric cancer: a comparison with surgical gastrojejunostomy. J Gastroenterol. 2005;40:932-937. Telford JJ, Carr-Locke DL, Baron TH, et al. Palliation of patients with malignant gastric outlet obstruction with the enteral Wallstent: outcomes from a multicenter study. Gastrointest Endosc. 2004;60:916-920. Espinel J, Sanz O, Vivas S, et al. Malignant gastrointestinal obstruction: endoscopic stenting versus surgical palliation. Surg Endosc. 2006;20:1083-1087. Maetani I, Tada T, Ukita T, et al. Comparison of duodenal stent placement with surgical gastrojejunostomy for palliation in patients with duodenal obstruction caused by pancreaticobiliary malignancies. Endoscopy. 2004;36:73-78. Yim HB, Jacobson BC, Saltzman JR, et al. Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction. Gastrointest Endosc. 2001;53: 329-332. Adler DG, Baron TH. Endoscopic palliation of malignant gastric outlet obstruction using self-expanding metal stents: experience in 36 patients. Am J Gastroenterol. 2002;97:72-78. Kaw M, Singh S, Gagneja H, et al. Role of self-expandable metal stents in the palliation of malignant duodenal obstruction. Surg Endosc. 2003;17:646-650. Mosler P, Mergener KD, Brandabur JJ, et al. Palliation of gastric outlet obstruction and proximal small bowel obstruction with self-expandable metal stents: a single center series. J Clin Gastroenterol. 2005;39:124-128. Kim TO, Kang DH, Kim GH, et al. Self-expandable metallic stents for palliation of patients with malignant gastric outlet obstruction caused by stomach cancer. World J Gastroenterol. 2007;13:916-920. Havemann MC, Adamsen S, Wøjdemann M. Malignant gastric outlet obstruction managed by endoscopic stenting: a prospective single-centre study. Scand J Gastroenterol. 2009;44: 248-251. van Hooft JE, Uitdehaag MJ, Bruno MJ, et al. Efficacy and safety of the new Wallflex enteral stent in palliative treatment of malignant gastric outlet obstruction (DUOFLEX study): a prospective multicenter study. Gastrointest Endosc. 2009;69:1059-1066. Keränen I, Udd M, Lepistø, Halttunen J, et al. Outcome for self-expandable metal stents in malignant gastroduodenal obstruction: single center experience with 104 patients. Surg Endosc. 2009 Sep 3. Epub ahead of print. Shaw JM, Bornman PC, Krige JE, et al. Self-expanding metal stents as an alternative to surgical bypass for malignant gastric outlet obstruction. Br J Surg. 2010;97:872-876. Nassif T, Prat F, Meduri B, et al. Endoscopic palliation of malignant gastric outlet obstruction using self-expandable metallic stents: results of a multicenter study. Endoscopy. 2003;35:483489. Im JP, Kang JM, Kim SG, et al. Clinical outcomes and patency of self-expanding metal stents in patients with malignant upper gastrointestinal obstruction. Dig Dis Sci. 2008;53: 938-945. Dormann A, Meisner S, Verin N, et al. Self-expanding metal stents for gastroduodenal malignancies: systematic review of their clinical effectiveness. Endoscopy. 2004;36:543-550. Thumbe VK, Houghton AD, Smith MS. Duodenal perforation by a Wallstent. Endoscopy. 2000;32:495-497. Saleem A, Bakken J, Baron TH. Early massive bleeding after duodenal self-expandable metal stent placement for palliation of malignant gastric outlet obstruction (with video). Gastrointest Endosc. 2011 Mar 21. Epub ahead of print. Van Hooft J, Mutignani M, Repici A, et al. First data on the palliative treatment of patients with malignant gastric outlet obstruction using the Wallflex enteral stent: a retrospective multicenter study. Endoscopy. 2007;39:434-439. Patel MM, Gerdes H, Markowitz AJ, et al. Occlusion of endoluminal stents from tumor ingrowth can repeatedly be treated with insertion of additional coaxial stents. Gastrointest Endosc. 2010;71:AB242.

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21. Baron TH, Harewood GC. Enteral self-expandable metal stents. Gastrointest Endosc. 2003;58:421-433. 22. Laasch HU, Martin DF, Maetani I. Enteral stents in the gastric outlet and duodenum. Endoscopy. 2005;37:74-81. 23. Hyodo T, Yoshida Y, Yamanaka T, et al. Duodenal stenosis after endoscopic biliary metallic stent placement for malignant biliary stenosis. Gastrointest Endosc. 2000;52:64-66. 24. Maire F, Hammel P, Ponsot P, et al. Long-term outcome of biliary and duodenal stents in palliative treatment of patients with unresectable adenocarcinoma of the head of the pancreas. Am J Gastroenterol. 2006;101:735-742. 25. Mutignani M, Tringali A, Shah SG, et al. Combined endoscopic stent insertion in malignant biliary and duodenal obstruction. Endoscopy. 2007;39:440-447. 26. Vanbiervliet G, Piche T, Caroli-Bosc FX, et al. Endoscopic argon plasma trimming of biliary and gastrointestinal metallic stents. Endoscopy. 2005;37:434-438. 27. Topazian M, Baron TH. Endoscopic fenestration of duodenal stents using argon plasma to facilitate ERCP. Gastrointest Endosc. 2009;69:166-169. 28. Iwamuro M, Kawamoto H, Harada R, et al. Combined duodenal stent placement and endoscopic ultrasonography-guided biliary drainage for malignant duodenal obstruction with biliary stricture. Dig Endosc. 2010;22:236-240. 29. Belletrutti PJ, DiMaio CJ, Gerdes H, et al. Endoscopic ultrasound guided biliary drainage in patients with unapproachable ampullae due to malignant duodenal obstruction. J Gastrointest Cancer. 2011;42(3):137-142. 30. Belletrutti PJ, Gerdes H, Schattner MA. Successful endoscopic ultrasound-guided transduodenal biliary drainage through a pre-existing duodenal stent. JOP. 2010;11:234-236. 31. Ross AS, Semrad C, Waxman I, et al. Enteral stent placement by double balloon enteroscopy for palliation of malignant small bowel obstruction. Gastrointest Endosc. 2006;64:835-837. 32. Lennon AM, Chandrasekhara V, Shin EJ, et al. Spiral-enteroscopy-assisted enteral stent placement for palliation of malignant small-bowel obstruction (with video). Gastrointest Endosc. 2010;71:422-425. 33. O’Connor A, Leyden J, McEntee G, et al. Palliative stenting of recurrent malignancy at gastrojejunostomy anastomotic sites. Ir J Med Sci. 2004;173:219-220. 34. Subharwal T, Irani FG, Adam A. Cardiovascular and Interventional Radiological Society of Europe. Quality assurance guidelines for placement of duodenal stents. Cardiovasc Intervent Radiol. 2007;30:1-5. 35. Kastanos K, Subharwal T, Adam A. Stenting of the upper gastrointestinal tract: current status. Cardiovasc Intervent Radiol. 2010;33:690-705. 36. Lopera JE, Brazzini A, Gonzales A, et al. Gastroduodenal stent placement: current status. Radiographics. 2004;24:1561-1573. 37. Mendelsohn RB, Gerdes H, Markowitz AJ, et al. Carcinomatosis is not a contraindication to enteral stenting in selected patients with malignant gastric outlet obstruction. Gastrointest Endosc. 2011;73(6):1135-140.

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Gastroduodenal Stents Versus Surgery for Malignant Gastric Outlet Obstruction Ali A. Siddiqui, MD

Gastric outlet obstruction (GOO) is a clinical syndrome that is exemplified by postprandial vomiting and upper abdominal pain as a result of mechanical obstruction of the upper gastrointestinal tract. GOO can be caused not only by obstruction of the stomach but also by duodenal or extraluminal disease. In the past, benign diseases, as a result of peptic strictures, were the predominant cause of GOO.1,2 However, since the discovery of Helicobacter pylori and the use of proton pump inhibitors, the incidence of GOO as a result of peptic ulcer disease has dramatically decreased. In current practice, up to 80% of GOO cases are a result of advanced malignant disease in the upper gastrointestinal tract.2-4 Advanced pancreatic cancer extending into the stomach or duodenum is the most common cause of malignant GOO; 15% to 25% of patients with pancreatic cancer present with GOO.3-5 The second most common cause of malignant outlet obstruction is adenocarcinoma of the distal stomach, which accounts for approximately 30% of GOO cases.4 Other causes of malignant GOO include primary neoplasms of the duodenum, ampulla, biliary tract, or gallbladder; gastric carcinoids; lymphomas; and extrinsic lesions. Acute and chronic peptic ulcer disease is still the predominant cause of benign GOO; other uncommon etiologies of benign GOO include gastroduodenal Crohn’s disease, caustic ingestion, chronic pancreatitis, large gastric antral polyps, and postsurgical complications.2,6 Clinical symptoms of GOO are nausea, vomiting, dehydration, and abdominal pain. Although some patients will present with a picture of chronic or subacute GOO, some will manifest a more precipitous course and present with acute obstruction. Patients with acute malignant outlet obstruction are often severely ill with dehydration and a painful distended abdomen at the time of presentation. Concomitant malnutrition is also frequently seen, given the fact that these patients almost always have advanced cancer. Therefore, these patients are in poor clinical condition and have a short life expectancy if they are not treated.5,7,8 In patients with malignant GOO, the major clinical goal is to restore the ability to tolerate an oral diet and improve quality of life.9 Given that median survival in this subset may

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Table 10-1. Indications and Contraindications for Placement of Enteral Stents in Patients With Malignant Gastric Outlet Obstruction Indications Inoperable malignant gastroduodenal outlet obstruction Extrinsic compression by neoplastic or nodal disease Anastomotic tumor recurrence after surgery Malignant fistulae to adjacent organs Benign strictures refractory to balloon dilatation and not amenable to surgery

Contraindications Curable disease by multimodality treatment Uncorrectable coagulopathy Terminally ill patients—limited life expectancy Peritoneal carcinomatosis with distal small bowel obstruction Free gastrointestinal perforation Bowel ischemia Sepsis Adapted from Katsanos K, Sabharwal T, Adam A. Stenting of the upper gastrointestinal tract: current status. Cardiovasc Intervent Radiol. 2010;33:690-705

be as short as 3 months, the ideal procedure should restore oral intake quickly, have few complications, shorten hospital stay, and not have a negative impact on survival. Surgical bypass via gastrojejunostomy has been the traditional mainstay of therapy. However surgical intervention is associated with a high morbidity and mortality, and a gastrojejunostomy may function poorly in patients with extensive disease.8,10,11 The advent of endoscopically guided placement of self-expanding metal stents (SEMS) offers this highrisk group of patients an effective alternative to surgery. The high success rates with early restoration of oral intake, low morbidity, and mortality after SEMS placement make this an attractive palliative option to surgery.10,11 This chapter will review the published literature, including cost analyses, to educate the reader on which patients with malignant GOO are best treated with stents and which should undergo palliative surgery as well as focus on the merits and detractors of both interventions.

SELF-EXPANDING METAL STENTS FOR GASTRIC OUTLET OBSTRUCTION The first endoscopic placement of SEMS was reported by Truong et al in 1992.12 Since then, SEMS has become a viable nonsurgical, palliative therapy for patients with unresectable malignant GOO.7-10,13-16 Placement of SEMS has been associated with higher clinical success rates, less morbidity and mortality, and a shorter hospitalization than palliative surgery.17,18 Endoscopic therapy has become more successful as this approach has increased in popularity.16 Indications and contraindications for placement of SEMS are summarized in Table 10-1.

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Figure 10-1. (A) Hydrophilic biliary guidewire (stiff 0.035-inch) preloaded on a straight biliary catheter is used to traverse the malignant duodenal stricture. (B,C) Water-soluble radiographic contrast is used to define stricture length as well as to confirm both proper position and luminal patency. (D) The stent delivery system is passed over the guidewire through the endoscope working channel. (E) The stent is deployed under endoscopic and fluoroscopic guidance; it is important to keep the proximal position in the desired location while the stent is deployed from the distal end. (F) Once fully deployed, the stent is carefully inspected fluoroscopically to confirm proper position and expansion.

Clinical and Technical Success of Self-Expanding Metal Stents for Malignant Gastric Outlet Obstruction The main goals of placement of a SEMS include symptomatic relief of outlet obstruction, resumption of diet with improved nutritional intake, and improvement in the patient’s quality of life. No clinical trials have indicated that there is any improvement in survival after relief of obstruction either by endoscopic or surgical means. The effectiveness of endoscopic stent placement is characterized by technical and clinical success. Technical success is defined by successful stent placement and adequate expansion of the stent across the stricture as evaluated endoscopically or by performing a contrast/imaging study.19 Clinical success is defined as resolution of the patient’s symptoms and the improvement in oral intake after stent placement and maintenance of nutrition during follow-up without the need for palliative surgery.5,19 Figure 10-1 demonstrates in chronological order how an enteral stent is placed under fluoroscopic guidance. Reports have noted a clinical success of 79% to 91% in patients with malignant GOO who underwent SEMS placement.20,21 A review of 32 publications showed an average clinical success rate of 89%.19 Adler and Baron’s Gastric Outlet Obstruction Scoring System (GOOSS) (0 = no oral intake, 1 = liquids only, 2 = soft solids, 3 = low-residue or full diet) is widely used when evaluating the oral intake before and after the stent placement.7 This scale is used to objectively evaluate the efficacy of any treatment for GOO, including gastroduodenal SEMS.

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GOOSS improvement is the primary end point in many studies for SEMS evaluation. Multiple clinical trials have shown that there is improvement in the GOOSS scale after placement of a SEMS.8,9,13,19,22,23 A prospective trial by van Hooft et al showed that there was a 75% improvement in the GOOSS scale 1 week after stent placement, with 56% of patients able to resume intake of solid food.24 These patients had a statistically significant improvement in their obstructive symptoms and 90% of them were able to resume oral intake 1 day after stent placement. Masci et al undertook a prospective trial in which they evaluated 38 patients with endoscopic placement of SEMS for upper gastrointestinal obstruction. On follow up at day 30, 79% of patients were able to tolerate oral intake. On day 90, 11 patients were alive, and 91% of them were tolerating a solid or soft diet; at day 180, all 5 patients who were alive continued to eat solid or soft food without problems.21 Adler et al specifically evaluated 36 patients with malignant GOO in their ability to tolerate a regular diet after SEMS placement.7 After endoscopic placement of the stent, 31/36 patients had symptomatic relief and 61% were able to resume a regular diet without any obstructive symptoms. They noted that 58% of patients had improvement at day 1, with 86% showing improvement by day 3, probably as a result of further stent expansion. Telford et al retrospectively evaluated 176 patients with SEMS placement after presentation with malignant outlet obstruction.25 Eighty-four percent of patients resumed oral intake after stent placement for a median duration of 146 days. Interestingly, chemotherapy after enteral stent insertion was associated with prolongation of oral intake. It should be noted that the clinical success of stent placement and resumption of oral intake depends upon several different factors such as overall patient performance status, type/location of tumor, and the influence of chemoradiotherapy as well as opioid use. Chemoradiotherapy can potentially decrease the growth of tumor, decrease tumor burden, and hence slow tumor ingrowth into a SEMS. Increased stent patency as a result of chemotherapy has been detected in both prospective and retrospective trials in patients with malignant GOO.15,25 The technical success for SEMS is dependent on multiple factors, including location of the tumor, severity of stenosis, an altered anatomy, and the angulation of the bowel loop.26 Clinical trials have indicated that the technical success for endoscopically placed SEMS is 92% to 100%.15,21,22,25,27,28 It should be noted that some patients may not show symptomatic improvement after SEMS as a result of poor peristalsis in a chronically dilated stomach,29 poor gastric motility due to neural invasion by the tumor, or unrecognized distal small bowel strictures.27,30,31 Figure 10-2 shows an endoscopic view of a successfully deployed enteral stent. In van Hooft’s multicenter study, stent placement was technically successful in 90% of patients.22 Six percent of these patients had endoscopic evidence of tumor overgrowth or ingrowth after a median time of 121 days after stent placement; all patients were successfully treated by placement of an additional enteral stent. Mosler assessed outcomes in 36 patients who had SEMS placement for malignancy over a 13-year period from 1991 to 2003.32 Stents were successfully placed in 33/36 (92%) patients. The authors postulated that their technical success rate may have been lower than reported in other studies since the stents used in the earlier years were not specially designed to be used for enteral strictures. It is now recognized that the combined usage of endoscopic and fluoroscopic visualization of the stenosis during the procedure allows the gastroenterologist to achieve an improved technical success rate, even when there is near complete gastric or small bowel

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Figure 10-2. Endoscopic view of a successfully deployed duodenal SEMS.

obstruction. This was confirmed by Kaw et al where SEMS were successfully placed in 32/33 (97%) of patients who had complete obstruction.20 Since covered SEMS have been shown to be advantageous over uncovered stents in malignant esophageal stenosis, Kim et al evaluated the role of covered enteral SEMS (Niti-S, Taewoong Medical, Seoul, Korea) for malignant GOO.33 They performed a prospective, randomized trial comparing the technical and clinical success as well as the 8-week patency of covered and uncovered SEMS in patients with malignant pyloric obstruction. Both groups had a technical success rate of 100% and comparable clinical success rates (covered SEMS, 95% and uncovered SEMS, 90%) and 8-week patency rates. Restenosis, as a result of tumor ingrowth, was more common in the uncovered SEMS group (25% versus 0% in the covered SEMS group, p < 0.05). Overall patient survival and stent patency did not differ between groups. The results of the study were equivocal and suggest that both covered and uncovered stents are effective palliation for malignant GOO.

Patency of Stents Stent patency has a median range of 146 to 385 days.7,15,21,22,24,27-29,34,35 Most SEMS remain patent and cause persistent resolution of GOO symptoms in the majority of patients until their death. The median stent patency remains the same, irrespective of the cause of GOO.22,24,33 The main causes of loss of patency are tumor ingrowth/overgrowth and stent migration.15,30 Chemotherapy after stent placement decreases the incidence of tumor ingrowth and overgrowth and increases in duration of stent patency. Additionally, chemotherapy may decrease disease progression and therefore prolong patient survival.25

Complications of Self-Expanding Metal Stents The overall complication rates range from 11% to 43% and can be divided into immediate (occurs within 1 day after SEMS placement), early (4 to 14 days after SEMS placement), and late (more than 14 days after SEMS placement).21,36 Immediate and early complications include stent obstruction, malposition of the stent, perforation, aspiration as a result

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of sedation during the procedure, and bleeding. Late complications include bleeding, perforation, stent migration, and stent occlusion.

Perforation Perforation is a potentially life-threatening complication of SEMS placement. It often requires immediate surgical intervention. Fortunately, bowel perforation is very rare and happens in less than 1% of patients.15,19 The cause of SEMS-related perforation is often a result of erosion by the metal ends of the stent through the intestinal wall. Additionally, administration of palliative chemoradiotherapy after stenting may increase the risk of gut perforation.9

Migration of the Stent Migration is higher for covered SEMS (20% to 26%)16,35 compared to uncovered stents (0% to 11%).26,31,37 Patients who receive chemoradiotherapy after stent placement have a higher rate of migration.15 Stent migration is typically managed by placement of a new stent across the malignant stenosis.15,19 The migrated stent may spontaneously pass the rectum or may eventually lead to bowel obstruction and require surgical intervention.18,31,34 Kim et al evaluated migration rates in patients who received uncovered versus covered stents for malignant GOO. As expected, stent migration was more common in the covered SEMS group (26%) than in the uncovered SEMS group (3%).33

Stent Obstruction Obstruction is the most common complication (~15%) observed after stent placement.30,38 SEMS obstruction is a result of impacted food material, tumor ingrowth or overgrowth, or stent collapse. In the case of impacted food, this can easily be removed endoscopically6,15,30; whereas tumor ingrowth or overgrowth or stent collapse can be successfully treated by placement of a new SEMS through the previously placed stent or hydrostatic dilation.19,30

Abdominal Pain Self-limiting abdominal pain can occur after stent placement and usually resolves within 24 to 48 hours.39 Patients with persistent pain can be treated effectively with analgesics.19,31,40

Hemorrhage Significant hemorrhage after SEMS placement is a rare complication, happening in less than 1% of patients.5,19 In the majority of cases, bleeding can be managed conservatively; if there is significant bleeding, vascular embolization may be needed.5

Biliary Obstruction Biliary obstruction specifically due to an enteral SEMS after placement of an enteral stent occurs in 1% to 6% of cases.6,28,30 It has been suggested that covered SEMS may increase the risk of biliary obstruction because they cover the ampulla of Vater.5,41 This underlies the use of uncovered stents or the performance of biliary decompression prior to stent placement in the second portion of the duodenum.35 Other investigators have disagreed with this approach because they have found that biliary obstruction after covered stent placement was not as high as previously thought. These investigators suggest that the covering membrane of the stent does not totally approximate around the duodenal wall and allows bile to drain through the space between the stent membrane and the duodenal wall.31,42

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Quality of Life Endoscopic palliation of malignant GOO has been shown to improve quality of life as indicated by improved Karnofsky scores after stent placement.10,43 A randomized trial using the SF-36 Physical Health scores, a validated quality-of-life indicator, showed that scores were significantly higher 1 month after SEMS placement when compared to laparoscopic surgical bypass for the palliation of malignant GOO.44 It should be noted that this was a small study that recruited only 10 patients. In the trial by van Hooft et al, 51 patients with malignant GOO who had SEMS placement were found to have improvement of their overall World Health Organization performance score; the global quality of life did not improve.22 This study suggested that quality of life indicators in these patients should not focus primarily on oral food intake but also look at other factors such as mental support and pain.

SURGICAL THERAPY FOR GASTRIC OUTLET OBSTRUCTION Patients with advanced malignancies who develop gastroduodenal obstruction have been treated primarily with surgery in the past. The 2 surgical options in the management of malignant GOO are resection or palliative gastrojejunostomy, based upon the stage of the disease. While patients with localized disease can undergo surgical resection, the vast majority of patients have advanced disease that precludes curative resection. The main goal in these patients is palliation of symptoms. The traditional approach to palliation of malignant GOO has been to perform an open gastrojejunostomy. More recently, laparoscopic gastrojejunostomy has become more commonplace with the aim of reducing surgical morbidity and mortality. While palliative surgery does not affect long-term survival, it is extremely effective in symptom control. With the increased safety and efficacy of endoscopic enteral stenting, the utilization of surgery has declined dramatically.

Clinical and Technical Success of Palliative Surgery for Malignant Gastric Outlet Obstruction The aim of palliative surgery for malignant GOO is as follows: • To enable oral food intake after improving obstructive symptoms and/or pain • To allow the patient to be discharged from the hospital and to remain comfortable at home • To improve the overall quality of life Clinical success was defined as relief of symptoms and/or improvement of oral intake. Technical success was defined as technical feasibility to perform a gastrojejunostomy. The clinical success in patients with malignant GOO who underwent surgery is 56% to 100%.8,10,11,13,17,18,44,45 A meta-analysis by Hosono et al showed an overall clinical success rate of 77%.18 In a decision model analysis, laparoscopic and open gastrojejunostomy were found to have similar clinical outcomes.45

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When using the GOOSS as an objective indicator of food intake, Jeurnink et al showed that 1 week after gastrojejunostomy, the GOOSS score improved in 64% of patients, with 50% able to resume a liquid diet and 14% able to tolerate solid food. 8 Another prospective study by the same group showed that after 60 days, food intake was significantly better after surgery than after stent placement. In addition, patients after surgery had more days with a GOOSS score of 2 or more. As with patients who undergo enteral stenting, the technical success for surgery is dependent on factors including tumor bulk, location of the tumor, motility factors, and the presence of altered anatomy.26 Clinical trials have indicated that the technical success for surgical bypass for malignant GOO ranges from 92% to 100%.6,8,10,11,13,44-49 A systematic review of the 44 publications for the period January 1996 to January 2006 indicated that the technical success of surgery was 99%.8 Laparoscopic gastrojejunostomy is alternative therapy to open surgery that has demonstrated, in some studies, reductions in morbidity, mortality, and hospital stay. However, the conversion to open surgery can be as high as 20%; also, a certain level of experience is necessary to achieve good technical results. Several studies have concluded that laparoscopic gastrojejunostomy may not be superior to the open gastrojejunostomy for the palliation of malignant gastrointestinal obstruction.11,45,50

Complications of Surgical Palliation of Gastric Outlet Obstruction The overall perioperative mortality from surgical palliation from malignant GOO in older clinical trials has been as high as 30%.51,52 Recent studies have reinforced this by showing that their overall perioperative mortality rates after surgical bypass were 29% to 31%.53,54 For the purpose of most studies, complications from surgical gastrojejunostomy have been divided into major and minor complications. Major complications are classified as life-threatening or severe complications such as perforation, severe hemorrhage, jaundice, sepsis after surgery, or severe abdominal pain, often requiring hospitalization.8,45 Major complications can be classified as early (7 days or less after surgery) or late (more than 7 days after surgery). Minor complications included mild pain, wound infection, mild fever, or vomiting without evidence of reobstruction; these are not life threatening and can be treated conservatively. Early major complication frequency in patients who underwent surgery ranged from 0% to 26%.8,11,13,17,18,44,45,47,50 Early major complications after surgery were predominantly jaundice and bleeding. In most patients, a reintervention was required. Late major complications were observed in 0% to 33% of patients. The most commonly observed late complications after surgery included leakage at the anastomotic site with abscess formation, dysfunction of the gastrojejunostomy, and fevers. Minor complications (11% to 61%) after surgery delayed gastric emptying and wound infections. Persistent obstructive symptoms of surgery due to anastomotic strictures or tumor regrowth/overgrowth can occur in up to 9% of cases. However, reintervention for recurrent obstructive symptoms is needed in only 1% of cases.

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COMPARISON OF STENTS VERSUS SURGERY FOR THE PALLIATION OF MALIGNANT GASTRIC OUTLET OBSTRUCTION Comparison of outcomes for stents and surgical gastrojejunostomy in the palliation of malignant GOO are summarized in Table 10-2.

Clinical and Technical Success: Self-Expanding Metal Stents Versus Surgery Enteral stents have been shown to have a higher clinical and technical success rate compared to surgery for palliation of malignant GOO.17,45,48,54,55 Del Piano showed that while the technical success was similar in both groups, clinical success was lower in patients undergoing surgery.17 Similarly, a systematic review of the 44 published studies revealed that the technical success for stent placement was 96% compared to surgery (99%). The main reasons for technical failure of stent placement were dislocation of the stent during the procedure and failure to deploy or release the stent from the delivery system. Technical failure in surgery was most commonly due to the finding of peritoneal carcinomatosis during the procedure.8 Even though the technical success for stents and surgery are comparable in most studies, the clinical success in patients undergoing stent placement is higher compared to surgery (89% versus 72%, respectively).8,10,11,13,15,44,45,49,50,53,56

Morbidity and Mortality: Self-Expanding Metal Stents Versus Surgery Past clinical trials have demonstrated very high mortality and morbidity rates (~30%) following a gastrojejunostomy to palliate for malignant GOO. These numbers have remained elevated even in recent studies.17,53 It has now been clearly demonstrated that patients who underwent surgical palliation of the obstruction had significantly more complications than those who underwent stenting (see Table 10-2). While the overall complication rate for patients undergoing SEMS placement ranges from 11% to 43%, the majority of these are minor complications that can be treated conservatively, with others treated via further endoscopy. The incidence of delayed gastric emptying was significantly less frequent after SEMS than surgery. In addition, the 30-day mortality after SEMS placement (range 0% to 28%) has consistently been shown to be significantly lower than that of the surgery group.

Survival Data: Self-Expanding Metal Stents Versus Surgery Survival of patients with malignant GOO seems to be dependent on their comorbidities and performance status. It has been clearly demonstrated that palliative gastrojejunostomy does not prolong survival in patients who have malignant GOO and peritoneal dissemination.57 Enteral stents have not been shown to improve survival in patients with malignant GOO. The reported median survival in different trials after stent placement ranges from 49 to 195 days.7,9,13,19,22 Mittal et al showed that endoscopic palliation resulted in a shorter length of hospital stay compared with surgery (especially when one considers that most

100/90

80/84

100/87

100/100

100/100

Johnsson56

Fiori59

Maetani10

—/100

100/—

Lillemoe47

Adler7

E = endoscopic SEMS placement, G = surgical gastrojejunostomy

97/—

2/5

100/100

Espinel54

100/82

1/—

96/100

Del Piano17

92/56

1/8

1/9

2/6

3

—/9

7/11

3/24

2/10

15/30

3/10

7/15

4/15

4/14

22/—

—/32

4/18

17/61

0/31

40/32

11/11

16/41

7/—

—/0

16/29

0/30

25/16

0/0

28/26

0/18

8/—

Tolerance of 30-Day Hospital Stay Complications Oral Intake Mortality (%) (days) E/G (%) E/G (days) E/G E/G

Mittal11

100/81

100/—

100/—

Wong48

80.6/—

94/—

Clinical Success (%) E/G

Yim55

Technical Success (%) E/G

Table 10-2. Results of Technical and Clinical Success, Hospital Stay, Complications, and Mortality

83

249

140/151

96/70

56/119

54/79

76/99

110/64

94/92

Survival (days) E/G

5736/13256

7215/10190

9921/28173

Costs ($) E/G

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enteral SEMS placements are currently performed on an outpatient basis), although with a decreased length of survival (56 and 119 days, respectively).11 The systemic review by Jeurnink et al revealed that mean survival after stent placement was 105 days and after surgery was 164 days.8 Ongoing improvements in stent technology may reduce long-term stent failures, therefore challenging any potential benefits for surgery in patients who may have a longer expected survival (>6 months) from their malignancy.44,46,58

Cost-Effectiveness of Malignant Gastric Outlet Obstruction Therapy: Self-Expanding Metal Stents Versus Surgery With the increased use of endoscopic SEMS as palliation for malignant GOO, costs of SEMS have been compared with those of open gastrojejunostomy.55 One analysis that focused on cost issues revealed that endoscopic treatment was significantly more cost effective when compared to surgery ($9921 versus $28,173, respectively, p < 0.005). This is mainly a reflection that the length of hospital stay after endoscopic intervention was significantly shorter when compared to patients who underwent surgery. Patients who received an enteral SEMS had a mean hospital stay of 4 days compared to 14 days for patients who underwent surgery (p < 0.005). Siddiqui et al evaluated costs and clinical outcomes in a decision analysis model comparing open gastrojejunostomy, laparoscopic gastrojejunostomy, and endoscopic stenting.45 After evaluating the literature, they showed that endoscopic SEMS had overall superior clinical outcomes compared to both open and laparoscopic gastrojejunostomy. In addition, the costs for endoscopic therapy were $8213 versus $12,191 for open gastrojejunostomy and $10,340 for laparoscopic gastrojejunostomy. Jeurnink et al undertook a randomized, prospective trial comparing stent placement with gastrojejunostomy for malignant GOO.13 In this trial, costs were higher for gastrojejunostomy compared to endoscopy (€12,433 versus €8819; p = 0.049).

CONCLUSION The endoscopic deployment of SEMS for palliation of malignant GOO has now become the therapy of choice, almost completely replacing surgical palliation. Multiple retrospective and prospective trials have shown that endoscopic placement of a SEMS achieved better results than open surgical gastrojejunostomy in terms of better clinical and technical success, reduced costs and hospital stay, and low procedure-related morbidity and mortality. In addition, almost all patients with malignant GOO will be candidates for endoscopic palliation despite multiple comorbidities. Surgery can still play a role depending on local expertise and is of value in patients who cannot undergo endoscopic treatment. Endoscopic placement of SEMS rapidly restores the ability to eat in these patients, as shown by the GOOSS scale, thus significantly improving quality of life in these preterminal patients. Endoscopic stent for malignant GOO should be considered in patients with unresectable disease who have a short life expectancy (90%) than complex fluid collections such as WOPN.39 Potential causes for failure include occlusion of small-caliber plastic stents, stent migration, inability for necrotic debris to flow freely through or between plastic stents and through the cystenterostomy, and difficulty gaining direct endoscopic access through fistula tracts that have been maintained by small plastic stents. To combat these limitations, endoscopists have tried substituting multiple small plastic stents with larger diameter (up to 25 mm) uncovered or fully covered (hence removable) SES that allow drainage of complex fluid and debris. These devices can also serve as a direct conduit through which endoscopic débridement can be performed. Technical and clinical success rates with this technique reach 78% to 100%.39-41

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A recently described alternative approach to management of complex pancreatic collections involves placement of both percutaneous drainage/irrigation catheters and endoscopically placed transgastric or transduodenal plastic stents, establishing the ability to irrigate the WOPN and providing dual routes of drainage (percutaneous and transenteric). This strategy has been associated with low procedure-related morbidity and mortality, shorter hospital length of stay, and a reduction in resource utilization,42,43 without causing chronic percutaneous fistula, which can occur when only percutaneous drainage is attempted.44,45 The use of SES for the transenteric aspect of this combination therapy, rather than small-caliber plastic stents, would make for an interesting clinical study. Regardless of the indication, transgastric or transduodenal SES placement can be challenging given the many technical considerations that must be addressed, such as the multistep nature of these types of procedures, the need for skills in interventional EUS procedures, dependence on assistants who are facile with fluoroscopy and long-wire exchanges, and the difficulty creating a secure fistula across the GI tract wall prior to SES placement. There are also postprocedure complications that can arise, such as inward or outward migration of the stent. Several biotechnology companies are actively working on developing specialty devices, accessories, and SES configurations that should significantly simplify these procedures and reduce the incidence of stent migration (Figure 14-1).

IS THERE A ROLE FOR NOVEL STENT DESIGNS, SUCH AS DRUG-ELUTING, BIODEGRADABLE, OR R ADIOACTIVE STENTS IN THE GASTROINTESTINAL TRACT? Biotechnology companies frequently make modifications and adjustments to existing SES designs in hopes of providing stents that are better suited for a particular clinical application. One example of a SES that was developed from existing materials and technologies is the ComVi Pyloric stent (TaeWoong Medical, Seoul, Korea). In an effort to minimize 2 stent-related problems—ingrowth and migration—the engineers sandwiched a polytetrafluoroethylene membrane (to inhibit ingrowth) between 2 layers of nitinol mesh stent. The external surface of the stent remains uncovered, allowing tissue to anchor into its interstices, reducing the risk of stent migration. Although stent modifications such as these can prove to be quite clinically useful, their overall impact on GI stenting is typically relatively modest, rarely leading to major paradigm shifts in the field of GI endoscopy. On the other hand, what if engineers developed GI tract stents that, in addition to their mechanical properties, could influence the underlying disease of the patient in which they are deployed? Stents with cytotoxic properties could kill adjacent tumor cells, while others could release (elute) drugs (steroids, chemotherapeutic agents, etc) or biologic agents that could reduce stent ingrowth or overgrowth by inhibiting tumor growth or the hyperplastic tissue reaction commonly seen after SES placement. Biodegradable stents (BDS) could eliminate the need to endoscopically remove SES that have migrated or those that were placed for temporary indications (eg, for treatment of leaks and perforations or benign strictures). What follows is a description of what we currently know about drug-eluting, biodegradable, and radioactive stents in the GI tract.

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A

C

D

E

F

Figure 14-1. Traditional and novel approaches to endoscopic pseudocyst drainage. (A) Standard application of double pigtail plastic stents for transluminal endoscopic drainage of a pancreatic pseudocyst. (Reprinted with permission of Douglas G. Adler, MD.) (B) Schematic representation of an AXIOS SEMS for pseudocyst drainage. (C) Fluoroscopic image of an AXIOS stent (arrow) being deployed across a cystgastrostomy and over a guidewire. (D,E) Endoscopic images of an AXIOS stent placed across endoscopically created cystgastrostomy sites to drain a pseudocyst. (F) Endoscopic image of an AXIOS stent being removed using a polypectomy snare. (Images B through F reprinted with permission of Dr. Ken Binmoeller.)

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Drug-Eluting Stents A variety of drugs and biologically active agents (eg, antineoplastic agents, antithrombins, immunosuppressants, tissue growth factors) can be incorporated into a drug-eluting stent (DES). When the drug/agent elutes from the stent over time, it imparts a desired physiologic effect on the surrounding or downstream tissues.46,47 In general, DES are composed of 3 main elements: a stent platform, a drug carrier, and an active drug.48 The platform provides the mechanical and radial strength of the stent and is influenced by the stent material, strut thickness, and configuration (eg, closed versus open cell design).49 Conventional platforms are manufactured with stainless steel, cobalt chromium, nickeltitanium, or various other metal alloys or composites, but as mentioned previously, there is increasing interest in developing stents made from biocompatible polymeric materials (biodegradable and nonbiodegradable polymers are being explored). Drugs or biologically active agents are incorporated into stents using various drug carrier mechanisms, such as direct attachment of the drug to the stent platform (eg, via dip coating), covalent linkers, novel reservoir technologies wherein the stent material contains reservoirs for drug storage, or application of a nanothin microporous hydroxyapatite surface coating that is preimpregnated with the desired drug.48-50 Drug-impregnated sleeves or coverings can also be applied to the surfaces of the stent. There are several areas of active DES research in an attempt to improve their drug-storage capacity, develop methods to affix bioactive surface technologies (bioactive antibodies, peptides, growth factors, nucleotides, genetic modifiers), and develop methods for controlled directional release of drug such that the drug’s physiologic effect can be directed lumenally (toward the hollow lumen so that its impact can be directed downstream from the stent) or ablumenally (toward the wall of the target organ, resulting in direct local impact on the wall of the target organ) depending on the clinical indication.49,50 Although several DES are commercially available for cardiac and vascular use, there are none currently approved for use in the GI tract. It is conceivable that DES in the GI tract could offer novel treatment options for a wide range of disorders. For example, DES that elute chemotherapeutic agents, biologics, or radiosensitizing drugs could play a therapeutic role in patients with GI malignancies. DES that release mediators of fibrosis, inflammation, or proliferation could potentially help treat, or even prevent, benign GI tract stenoses (eg, anastomotic stenoses, stenoses following extensive endoscopic mucosal resection and endoscopic submucosal dissection). Evidence from both in vitro and in vivo animal studies (the latter using drug-coated SEMS) has demonstrated that local exposure to paclitaxel, 5-fluorouracil, and gemcitabine can induce local tissue responses when placed in contact with benign and malignant GI tract tissues.51-58 In 1998, Manifold et al reported the first human use of a metal (tantalum) stent with a paclitaxel-impregnated coating in 11 patients with unresectable esophageal adenocarcinoma. They were deployed safely, but when compared to a group of patients (n = 10) treated with a comparable stent without paclitaxel, no convincing reduction in stent ingrowth or overgrowth was demonstrated.59 In a subsequent study, 3 of 5 cholangiocarcinoma patients experienced a partial response and favorable toxicity profile after placement of carboplatin-coated percutaneous biliary tubes.60 Nearly a decade later, Suk et al reported their experience treating 21 patients with presumed cholangiocarcinoma with endoscopically placed paclitaxel-coated biliary SEMS; the mean follow-up was 329 days. There were no paclitaxel-specific toxicities, and systemic concentrations resulting from paclitaxel

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absorption were relatively low. When compared to a historic control group of patients treated with standard SEMS, paclitaxel appeared to improve mean stent patency rates and overall patient survival.61 Recently, 52 patients with unresectable distal bile duct obstruction (suspected to be malignant) were randomized to receive a conventional-covered SEMS (cSEMS) or a paclitaxel-covered SEMS (pcSEMS).62 All SEMS had a double-covering design, including a protective silicone inner covering and an outer polyurethane covering (impregnated with 20% paclitaxel in the pcSEMS group). The incidence of local or systemic paclitaxelspecific complications was low. However, pcSEMS did not appear to significantly improve stent patency or overall patient survival compared to cSEMS. Therefore, the application of drugs into the GI tract using stents does not seem to be associated with high systemic drug concentrations or significant systemic side effects. However, additional research with different drugs/agents is clearly needed to define whether DES are of any clinical benefit in this setting and to better understand several key factors, including dosimetry, bioavailability, pharmacokinetics, drug-drug interactions, drug-host interactions, safety, and toxicity.

Biodegradable Stents Fully BDS for cardiovascular use have been made from materials such as bioabsorbable magnesium or ferrous sulfate alloys, nanoporous materials such as hydroxyapatite, or biodegradable polymers. Efforts to develop BDS for GI use have focused on various biodegradable polymers, such as poly-L-lactic acid, polyglycolic acid, poly-DL-lactic acid, and polydioxanone (ie, PDS, a polymer used in biodegradable surgical sutures for decades). These polymers degrade via hydrolysis into carbon dioxide and water,63 and biodegradation is influenced by many factors, such as pH. For example, degradation of a polymer-based esophageal stent would be faster in the distal esophagus (lower pH) than in the proximal esophagus.64-66 In the GI tract, BDS could have several potential advantages over conventional SEMS or self-expanding plastic stents (SEPS). They do not require endoscopic removal, even if they migrate, and thus could be more desirable for the management of problems including refractory benign GI stenoses and leaks in patients undergoing neoadjuvant chemoradiation for esophageal or pancreaticobiliary malignancies, in cases where uncertainty exists about an individual’s surgical resectability or uncertainty about the diagnosis (eg, indeterminate bile duct strictures), and prophylactic placement to prevent iatrogenic GI tract stenosis (eg, anastomotic or postmucosectomy stenosis). However, there are numerous challenges regarding BDS, including (but not limited to) the following: • When constrained onto a delivery system, polymer-based stent platforms tend to “set” in their constrained conformation and optimal “self-expansion,” as is typically seen with a conventional SEMS, is less likely to occur. Thus, self-expanding polymer-based stents must be mounted on the delivery device just before use, similar to commercially available SEPS. Easy-mounting strategies for BDS are currently being developed. • Degradation over time can lead to a gradual loss of the stent’s mechanical properties, significantly sooner than the mass of the stent has completely degraded, resulting in piecemeal fragmentation of the stent. These fragments continue to degrade during their journey down the GI tract, and there is an inherent risk of complications due to the

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presence of portions of nondegraded stent in the GI tract. Existing data suggest that these complications are uncommon, but the data are limited. • Bioabsorbable polymers lack radiopacity, which can be compensated by compounding the polymer with a radio-opaque substance, such as gold, tantalum, or barium sulfate. However, these substances could potentially be retained in the body as the stent degrades. • Humidity promotes degradation of polymers. This property impacts packaging requirements and shelf life and makes the sterilization process for biodegradable medical devices more complicated than for biostable devices.

Biodegradable Stents in the Esophagus In the mid-1990s, 2 small human case reports demonstrated feasibility of inserting a SES made of a single wire of poly-L-lactide twisted into a coil-spring configuration (Medtronic InStent Inc, Eden Prairie, MN).67,68 Subsequent case series have confirmed the feasibility of placing polymer-based BDS in the GI tract.69-71 In one cohort, 6 patients underwent treatment for benign caustic or anastomotic stenoses, and 7 patients underwent prophylactic stenting following endoscopic submucosal dissection in an effort to prevent iatrogenic strictures. Although the stent was deemed successful based on the absence of symptoms or need for further dilations in all of the study patients, the majority (77%) of the stents had migrated out of the esophagus within 10 to 21 days of insertion, and in only a minority (3 patients) did the stents remain in position for more than 21 days. Thus, the natural history of stent degradation within the esophagus and the tolerability of the degradation process were not adequately assessed. In 2007, the first (and currently the only) BDS with regulatory clearance for use in the GI tract became available (in Europe only). This device, the SX-ELLA-BD stent (ELLA-CS Ltd, Hradec Kralove, Czech Republic), is self-expanding and is composed of polydioxanone fiber, which is a semicrystalline biodegradable polymer belonging to the polyester family (Figure 14-2). It is officially indicated for treatment of benign refractory esophageal strictures (peptic, anastomotic, caustic) and achalasia and does not currently have clearance for the palliation of malignant dysphagia. Several sizes are available; stent body diameters range from 18 to 25 mm and stent lengths range from 60 to 135 mm (final length when fully expanded). It requires compression and assembly onto a 9.4-mm (28 Fr) delivery system immediately prior to use. According to unpublished in vitro and animal testing studies performed by the manufacturer, the radial force of the SX-ELLA-BD stent is supposed to remain intact for approximately 4 to 6 weeks, then decrease to 50% by week 9. In the esophagus, the earliest signs of degradation are discoloration and single breaks of the stent mesh. The average time to complete degradation of the stent is reported to be 11 to 12 weeks. Initial human experience using the SX-ELLA-BD stent has been reported in multiple case series from Europe. The indications for use varied, but included achalasia72 and a variety of esophageal strictures including etiologies such as caustic,66,73,74 peptic,66,72,75 malignant,72,75,76 anastomotic,66,76,77 and radiation induced.66 Clinical responses and outcomes varied. In a cohort of 21 patients with refractory benign esophageal strictures with mean dysphagia scores of 3 who had required an average of 2.2 endoscopic dilations per month, a 25-mm SC-ELLA-BD stent was deployed with 100% technical success and no intraprocedural complications. Complications included severe thoracic pain (14%),

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Figure 14-2. SX-ELLA-BD biodegradable esophageal stent. (Reprinted with permission of Dr. Pohl, ELLA-CS.)

migration 4 to 7 weeks after placement (9.4%), and one case of significant tissue hyperplasia resulting in occlusion of the stent. In 19 patients, vestiges of the fragmented stent persisted in the esophagus at 3 months; the stents were completely eliminated by 6 months in all patients. After a median follow up of 53 months, 45% of patients had significant relief of dysphagia and required no further therapy while 55% failed to respond and required resumption of serial endoscopic dilations, albeit at less frequent intervals than they required before stenting. Other than the patient with hyperplasia-related stent occlusion, there were no long-term stent-related complications.66 The same investigators recently published a comparison of temporary SEPS versus the biodegradable ELLA stent in 38 patients with refractory benign esophageal strictures, demonstrating comparable rates of long-term palliation of dysphagia (30% versus 33%), with comparable complication rates and fewer reintervention procedures in the ELLA stent group (15 versus 21). However, recurrent dysphagia occurred frequently in both treatment arms (50% versus 67%).78 An SX-ELLA-BD stent modified with the addition of a nonbiodegradable covering made from polyurethane was used in 5 patients with esophageal leaks or perforations (4 anastomotic dehiscence, 1 iatrogenic perforation).79 Initial clinical success was achieved in 4 of 5 (80%). The single treatment failure was caused by the polyurethane coating, which deformed as the stent degraded and caused acute aphagia requiring endoscopic extraction. Stent migration occurred in 3 patients within 5 to 7 days, but only one required placement of additional BDS and successful closure of the leak was achieved. Due to the biodegradable nature, retrieval of the migrated stents was not required. The value of the ELLA stent with a nonbiodegradable covering versus standard covered stents remains unknown. Combined, the published trials on use of the SX-ELLA-BD stent encourage additional investigations into their use, but demonstrate that this stent, not unlike commercially available SEMS and SEPS, can induce significant hyperplastic tissue responses.66,72,76,77,80 Efforts to define ways to prevent and treat this troublesome complication are ongoing.

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Biodegradable Stents in the Pancreaticobiliary Tract Data suggest that endoscopic removal of covered biliary SEMS is feasible,81,82 but to date, none of the commercially available SEMS have been granted a “removability indication” by the US Food and Drug Administration (although this is often performed in an off-label manner). BDS have been explored in the pancreas and biliary tree as a means of providing temporary mechanical support without requiring subsequent removal. Animal trials of braided, woven, or helically configured biodegradable biliary stents have demonstrated feasibility of implantation, relative safety, and potential efficacy in a variety of experimental settings. They have been studied in several preclinical scenarios, including feasibility of endoscopic83 or surgical84 placement into a normal canine bile duct, for reinforcement of either hepaticojejunal85,86 or common bile duct surgical anastomoses,87,88 for maintaining patency and the growth of biliary epithelium within jugular vein grafts that are inserted between 2 bile duct segments in order to form a “neobile duct”89,90 and for management of cystic duct leaks following cholecystectomy.91 There is limited information about BDS use in human bile ducts or pancreatic ducts. In 2001, Haber et al published (in abstract form) interim results from a prospective, multicenter study of a prototype bioabsorbable biliary Wallstent (Boston Scientific, Natick, MA) made of poly-L-lactic acid monofilaments woven into a tubular mesh stent configuration (stent diameter, 10 mm; delivery system diameter, 11 Fr) in 50 patients with inoperable malignant extrahepatic bile duct obstruction. The stents were deployed safely in the majority of patients, but data regarding overall complications, patency, and survival are not available since the study was never subsequently published in full form.92 The SX-ELLA-BD esophageal stent has been modified for treatment of refractory intrahepatic bile duct stenoses (centrally located) in 2 patients who had previously undergone surgical bilioenteric reconstructions.93 Durable clinical resolution of the biliary strictures was reported with up to 2 years of follow up. To date, no human studies of pancreatic duct stenting with SES have been reported.

Self-Expanding Stents in the Small Intestine and Colon Although an area of clinical interest, limited published information regarding biodegradable enteral stents exists. In one case report, 3 Crohn’s disease patients with stenosing complications (2 anastomotic strictures and 1 primary colonic Crohn’s stricture) underwent endoscopy with balloon dilation of the stenoses followed by placement of an SX-ELLA-BD stent.94 The stents degraded over a mean of 4 months. Despite one mechanical complication requiring endoscopic modification of the stent, no stent migrations or major complications occurred. However, long-term efficacy and safety data remain unknown.

Radioactive Stents High-dose rate intraluminal brachytherapy (ILBT) and interstitial implantation of radioactive seeds, techniques that locally expose target tissue to various radioisotopes, are clinically effective in a variety of clinical scenarios. There are numerous reports of brachytherapy in the esophagus,95-100 bile ducts,101-107 and pancreas.101,104,108,109 In fact, brachytherapy may provide better long-term palliation for malignant dysphagia than SES in patients with advanced esophageal cancer.100 In the bile ducts, ILBT might enhance patency of metal biliary stents, but ILBT is rarely performed in this setting because the procedure requires repetitive sessions over several weeks via percutaneous or nasobiliary

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catheters.103 Conceptually, combining the cytoreduction and tumor inhibitory properties that radiotherapy offers with the mechanical properties of SES might improve stent patency, quality of life, and overall survival by reducing the incidence of stent ingrowth/overgrowth and by reducing tumor bulk. In vitro and animal studies demonstrate feasibility of use and a range of histological changes in the GI tract (esophagus, bile duct, pancreas) associated with specially designed metal or plastic stents to which different radioisotope seeds (eg, holmium-166, iodine-125) are affixed.110-114 In 2008, Guo et al published the first human trial of radioactive SEMS in unresectable esophageal cancer patients. In this prospective, single-blinded study (the interventional radiologists placing the stents were not blinded to the treatment arm), 60 patients with esophageal cancer were randomized to receive either a cSEMS or either a covered or uncovered radioactive SEMS (rSEMS). Seven patients were lost to follow-up. Of the remaining evaluable patients, 11 had adenocarcinoma and 42 had squamous cell carcinoma. The rSEMS were created by affixing I-125 seeds to the outside of a cSEMS. Mean follow up in the cSEMS and rSEMS groups were 3.3 months and 7.2 months, respectively. There were no severe procedural complications. In addition, although the majority of patients died during follow up (range, 1 to 18 months), placement of rSEMS was associated with statistically greater median (7 versus 4 months) and mean (8.3 versus 3.5 months) survival. Dysphagia scores improved immediately in both cSEMS and rSEMS groups, and palliation of dysphagia was similar after 1 month. Thereafter, each group experienced gradual worsening of dysphagia, but the change in dysphagia scores was more substantial in patients treated with cSEMS. A partial tumor response, based on radiological criteria, was reported in 7 of the 9 rSEMS patients that survived to the 8-month follow-up visit. Chest pain following stent placement was common, but there was no significant difference between the 2 groups. A high frequency of hemorrhage was a major, albeit unexplained, complication in both stent groups (30%). Fatal bleeding (usually an extremely rare occurrence with esophageal stents) occurred in 21% of patients and is of major concern, but there was no significant difference between the cSEMS and rSEMS.115 The other human trial of radioactive stents in the GI tract involved endoscopic placement of I-125 seeds into a small peripheral lumen (“seed channel”) of specially created plastic stents. The seed channel contained small “irradiance windows” to permit transmission of the emitted radioactivity into the adjacent pancreatic duct or bile duct. In this nonrandomized trial, 11 patients (6 with pancreatic head carcinoma, 2 with extrahepatic bile duct cholangiocarcinoma, and 3 with ampullary carcinoma) underwent radioactive stent placement with no significant procedural complications, no lifethreatening or persistent stent-related complications, and minimal radiation hazard to the endoscopist. The inhomogeneous patient population, small study size, and absence of a control arm limit our ability to extrapolate whether radioactive pancreaticobiliary stent placement will translate into clinical benefit, but the study does demonstrate feasibility in humans.116 As with DES, we do not yet know the answers to many relevant questions—which radioisotopes and energies are best for specific GI indications? What are the local and systemic toxicities? What happens if a radioactive stent migrates? What are the implications for the endoscopy unit staff? Are radioactive stents clinically effective? How are these devices to be stored given that the isotopes degrade over time? Until these issues are better understood, radioactive stents are unlikely to be introduced into clinical practice.

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CONCLUSION The future of SES in the GI tract is promising. Already, endoscopists have begun to think “outside the lumen” and have begun placing these devices across the GI tract wall to facilitate drainage and endoscopic access to extraluminal tissue compartments. Our colleagues in the biotechnology industry will continue to make modifications of SES design and materials in response to the clinical demand, ultimately improving the effectiveness of SES for a variety of challenging clinical situations. Endoscopists will likely begin hearing more about DES, BDS, or radioactive stents in the GI tract. While these novel stent designs hold promise, significant clinical and translational research is warranted to define the role they will play in clinical practice.

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Financial Disclosures

Dr. Douglas G. Adler is a consultant for Boston Scientific, Merit Endotek, and Beacon Endoscopy. Dr. Michelle A. Anderson has no financial or proprietary interest in the materials presented herein. Dr. Tyler M. Berzin has no financial or proprietary interest in the materials presented herein. Dr. Kathryn R. Byrne has no financial or proprietary interest in the materials presented herein. Ms. Jessica I. Chan has no financial or proprietary interest in the materials presented herein. Dr. Ram Chuttani is a consultant for Olympus. Dr. Peter Darwin has no financial or proprietary interest in the materials presented herein. Dr. Christopher J. DiMaio is a consultant for Boston Scientific Corp. Dr. Kulwinder S. Dua is the inventor of the antireflux valve, assigned to Cook Medicals, and is a consultant for Boston Scientific Inc. Dr. John C. Fang is affiliated with Merit Endotek and Kimberly Clark Health Care.

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Financial Disclosures

Dr. Andres Gelrud has no financial or proprietary interest in the materials presented herein. Dr. Eric Goldberg has no financial or proprietary interest in the materials presented herein. Dr. Sonia Gosain has no financial or proprietary interest in the materials presented herein. Dr. Kevin Halsey has no financial or proprietary interest in the materials presented herein. Dr. Sanjay R. Hegde has no financial or proprietary interest in the materials presented herein. Dr. Sergey V. Kantsevoy has no financial or proprietary interest in the materials presented herein. Dr. Richard S. Kwon has no financial or proprietary interest in the materials presented herein. Dr. John Y. Nasr has no financial or proprietary interest in the materials presented herein. Dr. Gulshan Parasher is a paid consultant for Olympus America, is part of the speakers’ bureau for Takeda Pharmaceuticals, and is part of the speakers’ program for Wilson-Cook Medical. Dr. Douglas K. Pleskow is a consultant for Boston Scientific and is a member of the Advisory Board and a stockholder in Beacon Endoscopic. Dr. Waqar Qureshi has no financial or proprietary interest in the materials presented herein. Dr. Jess D. Schwartz has no financial or proprietary interest in the materials presented herein. Dr. Ali A. Siddiqui has no financial or proprietary interest in the materials presented herein. Dr. Jeffrey L. Tokar has no financial or proprietary interest in the materials presented herein.