Endoscopic Ultrasonography [4 ed.] 1119697913, 9781119697916

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Endoscopic Ultrasonography

Endoscopic Ultrasonography Edited by

Frank G. Gress MD Professor of Medicine Icahn School of Medicine at Mount Sinai, NY, USA and Chief, Division of Gastroenterology & Hepatology Mount Sinai Hospital South Nassau, NY, USA

Thomas J. Savides MD Distinguished Professor of Clinical Medicine University of California, San Diego School of Medicine La Jolla, CA, USA

Fourth Edition

This edition first published 2024 © 2024 JohnWiley & Sons Ltd. Edition History Blackwell Publishing Ltd (1e, 2001); Blackwell Publishing Ltd (2e, 2009); Blackwell Publishing Ltd (3e, 2016) All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions. The right of Frank G. Gress and Thomas J. Savides to be identified as the authors of the editorial material in this work has been asserted in accordance with law. Registered Offices John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, USA John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK For details of our global editorial offices, customer services, and more information about Wiley products visit us at www.wiley.com. Wiley also publishes its books in a variety of electronic formats and by print-on-demand. Some content that appears in standard print versions of this book may not be available in other formats. Trademarks: Wiley and the Wiley logo are trademarks or registered trademarks of John Wiley & Sons, Inc. and/or its affiliates in the United States and other countries and may not be used without written permission. All other trademarks are the property of their respective owners. John Wiley & Sons, Inc. is not associated with any product or vendor mentioned in this book. Limit of Liability/Disclaimer of Warranty The contents of this work are intended to further general scientific research, understanding, and discussion only and are not intended and should not be relied upon as recommending or promoting scientific method, diagnosis, or treatment by physicians for any particular patient. In view of ongoing research, equipment modifications, changes in governmental regulations, and the constant flow of information relating to the use of medicines, equipment, and devices, the reader is urged to review and evaluate the information provided in the package insert or instructions for each medicine, equipment, or device for, among other things, any changes in the instructions or indication of usage and for added warnings and precautions. While the publisher and authors have used their best efforts in preparing this work, they make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives, written sales materials or promotional statements for this work. This work is sold with the understanding that the publisher is not engaged in rendering professional services. The advice and strategies contained herein may not be suitable for your situation. You should consult with a specialist where appropriate. The fact that an organization, website, or product is referred to in this work as a citation and/or potential source of further information does not mean that the publisher and authors endorse the information or services the organization, website, or product may provide or recommendations it may make. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Library of Congress Cataloging-in-Publication Data Names: Gress, Frank G., editor. | Savides, Thomas J., editor. Title: Endoscopic ultrasonography / edited by Frank G. Gress, Thomas J. Savides. Other titles: Endoscopic ultrasonography (Gress) Description: Fourth edition. | Hoboken, NJ : Wiley-Blackwell, 2024. | Includes bibliographical references and index. Identifiers: LCCN 2023050536 (print) | LCCN 2023050537 (ebook) | ISBN 9781119697916 (cloth) | ISBN 9781119697909 (adobe pdf) | ISBN 9781119697930 (epub) Subjects: MESH: Endosonography | Digestive System Diseases–diagnostic imaging | Ultrasonography Classification: LCC RC804.E59 (print) | LCC RC804.E59 (ebook) | NLM WN 208 | DDC 616.07/543–dc23/eng/20231213 LC record available at https://lccn.loc.gov/2023050536 LC ebook record available at https://lccn.loc.gov/2023050537 Cover Design: Wiley Cover Images: Courtesy of Thomas J. Savides Set in 9/11pt, MinionPro by Straive, Chennai, India.

Contents

List of contributors, vii Preface, ix Acknowledgments, xi 1 A history of endoscopic ultrasonography, 1

Michael B. Wallace MD MPH 2 Basic principles and fundamentals of EUS imaging, 5

Joo Ha Hwang & Michael B. Kimmey 3 Learning EUS anatomy, 15

John C. Deutsch 4 EUS instruments, room setup, and assistants, 27

Brian C. Jacobson 5 EUS procedure: consent and sedation, 32

Michael G. Daniel & Michael L. Kochman 6 The EUS report, 38

Jose G. de la Mora-Levy & Michael J. Levy 7 Endosonography of the mediastinum, 45

Kondal R. Kyanam Kabir Baig & Michael B. Wallace 8 Linear-array EUS: normal anatomy, 52

James T. Sing, Jr. 9 High-frequency ultrasound probes, 61

Nidhi Singh, Alberto Herreros-Tejada & Irving Waxman 10 EUS elastography, 68

Julio I. Garcia, Jose Lariño-Noia & Juan Enrique Dominguez Muñoz 11 Fundamentals of EUS FNA, 81

Larissa Fujii-Lau, Michael J. Levy & Maurits J. Wiersema 12 EUS FNA cytology: material preparation and

interpretation, 91 Cynthia Behling 13 EUS: applications in the mediastinum, 98

David H. Robbins 14 EUS for esophageal cancer, 105

Syed M. Abbas Fehmi & Aws Hasan 15 EUS of the stomach and duodenum, 111

Sarah A. Rodriguez & Douglas O. Faigel

17 EUS and its emerging modalities for the diagnosis and

staging of pancreatic tumors, 141 Muhddesa Lakhana & Iman Andalib 18 EUS for pancreatic cysts, 150

Jacob Lipkin & Kevin McGrath 19 The role of diagnostic EUS in inflammatory diseases

of the pancreas, 161 Amy Tyberg & Shireen Pais 20 Autoimmune pancreatitis, 172

Larissa Fujii-Lau, Suresh T. Chari, Thomas C. Smyrk, Naoki Takahashi & Michael J. Levy 21 EUS for biliary diseases, 183

Mihai Rimba¸s & Alberto Larghi 22 EUS in liver disease, 197

Mark Hanscom, Emmanuel C. Gorospe & Ferga C. Gleeson 23 Colorectal EUS, 207

Sarakshi Mahajan, Brian R. Weston, Pradermchai Kongkam & Manoop S. Bhutani 24 Therapeutic EUS for cancer treatment, 223

Christopher Paiji & V. Raman Muthusamy 25 EUS-guided biliary access, 234

Khaled Elfert & Michel Kahaleh 26 Pancreatic fluid collections, 242

Daniella Mikhail, Michel Kahaleh & Amy Tyberg 27 EUS-guided enteric anastomoses, 251

Edoardo Troncone & Manuel Perez-Miranda 28 EUS-guided drainage of pelvic fluid collections, 261

Philippe Willems, Ji Young Bang & Shyam Varadarajulu 29 EUS hemostasis, 267

Everson L.A. Artifon & Marcio Roberto Facanali Junior 30 Training in EUS, 275

Sam Serouya & Adam J. Goodman 31 The future of EUS, 287

Sahin Coban, Kamran S. Zahid & William R. Brugge Index, 295

16 EUS for gastrointestinal subepithelial masses, 127

Raymond S. Tang & Thomas J. Savides

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List of contributors

Iman Andalib

John C. Deutsch

Mark Hanscom

Department of Gastroenterology and Hepatology Icahn School of Medicine at Mount Sinai New York, NY, USA

Essentia Health Systems Duluth, MN, USA

Division of Gastroenterology & Hepatology Mayo Clinic Rochester, MN, USA

Khaled Elfert Everson L.A. Artifon

Department of Medicine SBH Health System Bronx, NY, USA

Aws Hasan

University of São Paulo São Paulo, Brazil

Ji Young Bang

Douglas O. Faigel

Alberto Herreros-Tejada

Center for Advanced Endoscopy, Research & Education Orlando Health Digestive Health Institute Orlando, FL, USA

Mayo Clinic Department of Gastroenterology and Hepatology Scottsdale, AZ, USA

Center for Endoscopic Research and Therapeutics (CERT) University of Chicago Chicago, IL, USA

Cynthia Behling

Abbas Fehmi

Pacific Rim Pathology Group Sharp Memorial Hospital 7901 Frost Street San Diego, CA, USA

University of California San Diego, CA, USA

Manoop S. Bhutani Department of Gastroenterology Hepatology and Nutrition-Unit 1466 UT MD Anderson Cancer Center Houston, TX, USA

William R. Brugge Department of Gastroenterology Harvard University School of Medicine Mount Auburn Hospital Cambridge, MA, USA

Suresh T. Chari Division of Gastroenterology and Hepatology Mayo Clinic Rochester, MN, USA

Sahin Coban Division of Gastroenterology Charleston Area Medical Center West Virginia University Charleston, WV, USA

Michael G. Daniel Gastroenterology Division Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA, USA

Jose G. de la Mora-Levy Endoscopy Unit Gastroenterology Department Instituto Nacional de Cancerologia Mexico City, Mexico

Larissa L. Fujii Division of Gastroenterology and Hepatology Mayo Clinic Rochester, MN, USA University of Hawaii Honolulu, HI, USA

Julio I. Garcia Department of Gastroenterology and Hepatology Health Research Institute of Santiago de Compostela (IDIS) University Hospital of Santiago de Compostela Santiago de Compostela, Spain

Ferga C. Gleeson Division of Gastroenterology & Hepatology Mayo Clinic Rochester, MN, USA

Huron Gastroenterology Associates USA

Joo Ha Hwang Division of Gastroenterology University of Washington School of Medicine Seattle, WA, USA

Brian C. Jacobson Harvard Medical School Massachusetts General Hospital Boston, MA, USA

Marcio Roberto Facanali Junior University of São Paulo São Paulo, Brazil

Michel Kahaleh Gastroenterology Division Department of Medicine Robert Wood Johnson University Hospital New Brunswick, NJ, USA Rutgers Robert Wood Johnson Medical School New Brunswick, NJ, USA

Adam J. Goodman

Michael B. Kimmey

Division of Gastroenterology and Hepatology New York University Langone Medical Center New York, NY, USA

Franciscan Digestive Care Associates Tacoma, WA, USA

Emmanuel C. Gorospe Las Palmas Medical Center El Paso, TX, USA

Michael L. Kochman Gastroenterology Division Department of Medicine Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA, USA

Frank G. Gress Icahn School of Medicine at Mount Sinai New York, NY, USA Division of Gastroenterology & Hepatology Mount Sinai South Nassau Hospital New York, NY, USA

Pradermchai Kongkam Division of Gastroenterology Chulalongkorn University and King Chulalongkorn Memorial, Hospital Thai Red Cross Society Bangkok, Thailand

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List of contributors

Kondal R. Kyanam Kabir Baig

Shireen Pais

Raymond S. Tang

The Basil I. Hirschowitz Endoscopic Center of Excellence University of Alabama Birmingham UAB School of Medicine Birmingham, AL, USA

Division of Gastrointestinal and Hepatobiliary Diseases New York Medical College Westchester Medical Center Valhalla, NY, USA

Division of Gastroenterology and Hepatology Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong, China

Manuel Perez-Miranda Muhddesa Lakhana Department of Gastroenterology and Hepatology Mount Sinai South Nassau Oceanside, NY, USA

Department of Gastroenterology and Hepatology Hospital Universitario Rio Hortega Valladolid, Spain

V. Raman Muthusamy Alberto Larghi Digestive Endoscopy Unit Catholic University Rome, Italy

Vatche and Tamar Manoukian Division of Digestive Diseases University of California Los Angeles, CA, USA

Mihai Rimba¸s Jose Lariño-Noia Department of Gastroenterology and Hepatology Health Research Institute of Santiago de Compostela (IDIS) University Hospital of Santiago de Compostela Santiago de Compostela, Spain

Michael J. Levy Division of Gastroenterology and Hepatology Mayo Clinic Rochester, MN, USA

Jacob Lipkin Division of Gastroenterology, Hepatology, and Nutrition University of Pittsburgh Medical Center Pittsburgh, PA, USA

Sarakshi Mahajan Department of Internal Medicine Washington University at Saint Louis Saint Louis, MO, USA

Kevin McGrath Division of Gastroenterology, Hepatology, and Nutrition University of Pittsburgh Medical Center Pittsburgh, PA, USA

Gastroenterology and Internal Medicine Departments Colentina Clinical Hospital Carol Davila University of Medicine Bucharest, Romania

Juan Enrique Dominguez Muñoz Department of Gastroenterology and Hepatology Health Research Institute of Santiago de Compostela (IDIS) University Hospital of Santiago de Compostela Santiago de Compostela, Spain

Department of Systems Medicine University of Rome Tor Vergata Rome, Italy

Amy Tyberg Division of Gastroenterology and Hepatology Rutgers Robert Wood Johnson Medical School New Brunswick, NJ, USA Rutgers Robert Wood Johnson Medical School New Brunswick, NJ, USA

Shyam Varadarajulu

Lenox Hill Hospital North Shore-Long Island Jewish Health Care System New York, NY, USA

Center for Advanced Endoscopy, Research & Education Orlando Health Digestive Health Institute Orlando, FL, USA

Sarah A. Rodriguez

Michael B. Wallace

The Oregon Clinic Gastroenterology Portland, OR, USA

Mayo Clinic College of Medicine Jacksonville, FL, USA

Thomas J. Savides Distinguished Professor of Clinical Medicine University of California San Diego School of Medicine La Jolla, CA, USA

Sam Serouya Division of Gastroenterology and Hepatology New York University Langone Medical Center New York, NY, USA

James T. Sing, Jr. Division of Gastroenterology Baylor Scott & White Clinic and Hospital Temple, TX, USA

Nidhi Singh Center for Endoscopic Research and Therapeutics (CERT) University of Chicago Chicago, IL, USA

Thomas C. Smyrk Division of Anatomical Pathology Mayo Clinic Rochester, MN, USA

Christopher Paiji Vatche and Tamar Manoukian Division of Digestive Diseases University of California Los Angeles, CA, USA

Department of Gastroenterology and Hepatology Hospital Universitario Rio Hortega Valladolid, Spain

David H. Robbins

Daniella Mikhail Rutgers Robert Wood Johnson Medical School New Brunswick, NJ, USA

Edoardo Troncone

Naoki Takahashi Division of Radiology Mayo Clinic Rochester, MN, USA

John C Andersen Professor of Medicine Mayo Clinic Jacksonville, FL, USA

Irving Waxman Center for Endoscopic Research and Therapeutics (CERT) University of Chicago Chicago, IL, USA

Brian R. Weston Department of Gastroenterology Hepatology and Nutrition UT MD Anderson Cancer Center Houston, TX, USA

Maurits J. Wiersema Indiana University School of Medicine Terre Haute, IN, USA

Philippe Willems Center for Advanced Endoscopy, Research & Education Orlando Health Digestive Health Institute Orlando, FL, USA

Kamran S. Zahid Division of Gastroenterology Charleston Area Medical Center West Virginia University Charleston, WV, USA

Preface

Endoscopic ultrasonography (EUS) was first conceptualized more than 30 years ago, during the early years of endoscopy, and was developed in an attempt to improve ultrasound imaging of the pancreas. Since the first prototype EUS scopes were released in the early 1980s, EUS has evolved into the “standard of care” for the diagnosis and staging of a variety of gastrointestinal (GI) pathologies. In the last few years, it has become an important therapeutic tool for performing complex interventional endoscopic procedures. EUS is now widely available at community hospitals throughout the world and is no longer confined only to academic medical centers. Our hope is that Endoscopic Ultrasonography improves the training and dissemination of EUS by providing interested GI endoscopists with an authoritative and practical approach to the role of EUS in the management of specific digestive disorders. This text allows the learner to understand the history of EUS, the fundamentals of ultrasound, important references in EUS research, and how best to utilize EUS in diagnostic and interventional

procedures. Experienced endosonographers can improve their therapeutic endoscopic skills. This fourth edition brings many new and exciting changes and additions to the book, especially new chapters dedicated to therapeutic procedures using lumen-apposing metal stents. We have continued to emphasize a practical “how-to” approach to learning EUS. Many of our contributors are either the “first-generation” pioneers of endosonography or the proteges of those pioneers. They have contributed significantly to clinical practice, research, and training in GI endosonography. Their collective experience in applying EUS to the management of GI diseases is unsurpassed. A tremendous amount of effort on the part of each individual author has led to this new fourth edition. They are the true masters of EUS. We are deeply grateful to them for their outstanding contribution. We hope you enjoy the fourth edition of Endoscopic Ultrasonography.

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Acknowledgments

We give our thanks and love to our parents, Francis and Evelyn Gress and John and Anita Savides, for their guidance, support, and love that created the opportunities we are fortunate to have had in life. We cannot thank enough our wives, Debra Gress and Wendy Buchi, for their unending support, understanding, and sacrifice during the many years spent learning, practicing, and teaching EUS and other GI endoscopic procedures and the many hours spent completing this text. We dedicate this book to our parents, wives, and especially children, Travis, Erin, Morgan, and Abby Gress, and Michael Savides, for their love, kindness, and patience, which sustain us every day.

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CHAPTER 1

A history of endoscopic ultrasonography Michael B. Wallace MD MPH John C Andersen Professor of Medicine, Mayo Clinic, Jacksonville, FL, USA

The first report of endoscopic ultrasonography (EUS), to my knowledge, is that of DiMagno et al., published in 1980 [1]. These investigators described a prototype echoendoscope assembled by attaching a transducer to a duodenoscope. Although images were obtained only in dogs, this work established the feasibility of EUS. As with nearly all seminal advances in endoscopy, EUS was basically an amalgamation of existing technologies. But in 1980, the potential of this hybrid technology was scarcely apparent to anyone, probably including these first endosonographers, who did not expand on their demonstration of the feasibility of EUS. For practical purposes, the inception of EUS as a clinical entity in the United States can be traced to a meeting between Dr. Michael Sivak and Mr. Hiroshi Ichikawa of the Olympus Optical Company, most likely around 1981. Olympus was developing several new technologies and sought advice on priorities for the development of EUS, or enteroscopy. Dr. Sivak advised Olympus to focus on EUS, largely because the idea of endosonography seemed especially intriguing; it offered a greater challenge but also the promise of a much wider range of prospective applications. At the time, there was little thought or appreciation of the formidable obstacles to the clinical realization of this potential or the investment of time and effort needed to reach this goal. Mr. Ichikawa did, in fact, lay emphasis on the obstacles, warning that the instrumentation was in the early stages of development. Because of the scope and difficulty of the project, Olympus proposed to work with two investigators in the United States (actually, the western hemisphere), the other being Dr. Charles Lightdale in New York City, as well as a few individuals in other countries. As it turned out, this was the beginning of a long and rewarding professional association, for which EUS became the basis. Thus, EUS in the United States began with Michael Sivak and Charlie Lightdale. Given the technical sophistication of present-day EUS systems, it is important to recognize that during the early years, the viability of endosonography was far from certain. Until about 1985, there was substantial skepticism concerning the future of EUS, even among those most closely involved with and committed to its development. The ample tribulations facing the very small cadre of nascent endosonographers became strikingly evident with the arrival of the first EUS system, a prototype in the truest sense. Despite the obvious problems, however, early pioneers remained encouraged;

the best description of their mindset during these formative years might be “doggedly enthusiastic.” An early all-encompassing protocol written by Dr. Sivak allowed the use of the instrument as an investigational device in patients. The protocol, essentially, had no hypothesis other than the assertion that EUS was going to be a good thing. It listed almost every possible indication conceivable and minimized the risks, which were unknown in any case. By today’s standards, it is doubtful it would be approved by any institutional research committee. The major problems that had to be addressed in the beginning can be divided into four categories: the technical limitations and deficiencies of the equipment; the development of efficient and safe techniques for the use of the echoendoscope in patients; the interpretation of the ultrasound images; and the need to define and establish indications for EUS in clinical practice. More issues, some even more complicated, became evident over time. The prototype echoendoscope itself was, by modern standards, incredibly cumbersome. The electronic (video) endoscope had not been introduced into clinical practice, so the prototype echoendoscope was a fiberoptic instrument; the optical (endoscopic) component consisted of an ocular lens and focusing ring, coupled to a coherent fiberoptic bundle, with another lens at the distal end of the insertion tube to focus an image on the bundle. The latter provided a limited, 80∘ field of view, oriented obliquely at an angle of 70∘ to the insertion tube. Of these two parameters, the narrow field of view was more of a limitation than the oblique orientation, which was not especially problematic for endoscopists accustomed to the side-viewing duodenoscope. The ultrasound component of early echoendoscopes consisted of a transducer coupled to a rotating acoustic mirror at the distal tip of the insertion tube. The mirror was turned by means of an electric motor within a motor housing situated between a standard design control section and the insertion tube; thus the designation, “mechanical, sector-scanning echoendoscope.” Because the mirror turned around the long axis of the insertion tube, the ultrasound scanning plane was oriented perpendicular to the insertion tube. In retrospect, this was the best choice because it seemed to simplify the problems of image interpretation. But this arrangement also had its limitations, mainly that it was unsuitable for guiding a needle to a target. Needle aspiration was, in fact, attempted with the

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Endoscopic Ultrasonography

sector-scanning (now called “radial”) instrument, albeit unsuccessfully, because the width of the tissue within the circular scan was much too narrow. Unfortunately, the ultrasound imaging sector provided by the first instruments was not a full 360∘ but only 180∘ . To obtain a complete, circumferential sector scan of the surrounding tissue – a circumferential esophageal tumor, for example – it was necessary to rotate the insertion tube 180∘ while maintaining the same scanning plane. This was a considerable feat, especially with the instrument deeply inserted, for example, in the third part of the duodenum. In truth, it was largely impossible because any application of torque to the insertion tube invariably altered the scanning plane. This was but one among many difficulties. Owing to the mechanical components, principally the motor and its housing, the instrument was much heavier than a standard endoscope. Because EUS had no established clinical purpose, the first procedures can only be described as exploratory. Consequently, procedure length was determined largely by patient endurance, and with an especially tolerant patient, the weight of the instrument seemingly increased exponentially. After two or three examinations, it was often difficult (and painful) to straighten your left arm. The combination of optical and acoustical components at the distal end of the insertion tube conferred other penalties, including some potential hazards. The outer diameter of the insertion tube was 13 mm, which is substantially greater than that of the upper endoscopes of the time. To make matters worse, the distal end was rigid over a length of 4.5 cm, that is, the distance from the tip to the bending section. Together with the limited field of view, this increased the difficulty of inserting the instrument through the mouth and pharynx and into the esophagus. Although we assumed that the risk of complications with EUS was no greater than that with upper endoscopy, and informed our patients the same, in reality, the risk of perforating the pyriform sinus was probably greater – a fact subsequently substantiated. Moreover, attempts at insertion of the large-diameter echoendoscope through a constricting tumor in the esophagus were no doubt associated with an appreciable risk of perforation. In addition to developing techniques for the safe insertion of the echoendoscope, the learning curve for EUS imaging can only be described as long and steep, like a line with a slope approaching straight up. According to Yogi Bera, “ninety percent of everything is half mental,” and this was definitely true of EUS. The first quandary was the need to uncouple endoscopic imaging from ultrasonography. This relates to the need for acoustic coupling, that is, the creation of a suitable interface between the tissue and the transducer (in this case, the acoustic mirror). We discovered in short order that ultrasound images cannot be obtained through the air. The obvious solution is to remove the air. But this proved impractical for several reasons. The alternative was to interpose water between tissue and “transducer,” which could be accomplished in two ways: by placing a balloon over the transducer section of the instrument and filling it with water, or by filling the gut with water. However, it was not simply a matter of choosing between these two options. Depending on the circumstances, including location within the gastrointestinal tract, one or the other is usually a better choice. With the balloon method in particular, the endoscopic view was lost as the balloon was brought into contact with the gut wall, meaning that ultrasound imaging could only proceed by abandoning the endoscopic view. For technical reasons, therefore, EUS imaging was, of necessity, endoscopically blind. Although this decoupling might seem inconsequential today, it was a mental leap of faith in

the early days, inasmuch as endoscopic dogma deemed “blind” use of an endoscope hazardous. The use of the balloon with early-model echoendoscopes was so exasperating that it deserves a digressive paragraph of its own. The latex material that constituted the balloon was not of uniform quality, which made it nearly impossible to place the balloon on the echoendoscope without tearing it. When expanded, the balloon had an asymmetric bulge, and according to the instructions, the bulge was to be placed over the transducer on the same side as the optical component; this was never accomplished. Assuming that the balloon could be maneuvered intact into the correct position, it was next necessary to tie it in place with small sutures. The design of the instrument was such that the proximal end of the balloon sometimes occluded the opening of the channel for air insufflation and water irrigation, which would not be evident until it was securely tied in place and tested. Subsequent attempts to nudge the balloon into the proper position usually result in tearing. Since the objective was to create a water–tissue interface, it was necessary to remove all the air from the balloon (without breaking it). The balloon, if not placed exactly, could occlude the tiny-diameter channel provided for this purpose. Once all of the delicate parameters were attained and the balloon was in gloriously correct position and functioning properly, the most maddening occurrence was the rupture of the ill-fated bag in the middle of an examination, usually at the most inopportune moment. Early adopters dealt with some of these frustrations by persuading support staff from the biomedical engineering department (designated the “balloon man”) to take on the task of balloon placement prior to each procedure. During the examination, the balloon was filled with water via a Luer lock fitting located between the control section and the motor housing. Unfortunately, this design meant that the attached syringe protruded in a perpendicular fashion. Accordingly, as the endosonographer moved his right hand from the control section to the insertion tube, he invariably broke the syringe. In order to fill the balloon, it was necessary to set a small lever on the motor housing to the balloon-filling position, clearly labeled as “B.” The other choice was “G,” which, when selected, channeled the water into the gut. Since it was not possible to see this lever, it was advisable to remember which position it was in. Otherwise, the balloon might be filled with water beyond its capacity. One of the most gratifying aspects of endosonography, readily apparent at the very first examination, was the ability to obtain a structured image of the gut wall. Believe me, all of us knew intuitively and immediately that this was going to be very big. But the interpretation of these images was something else again. There was a natural tendency to assume and hope that the five-layer structure corresponded in exact fashion to the actual layers of the gut wall as seen microscopically in a histological section. This betrays a near total ignorance of the principles of ultrasound imaging, and over time, it became evident that the physical basis for the endosonographic representation of the bowel wall is much more complex. For reasons unknown to me, the main ultrasound frequency selected for the first EUS systems was 7.5 MHz, a frequency that happens, under the usual conditions, to render the wall structure of the stomach as five layers. I suspect that this choice of frequency was based on technical considerations rather than experimental data. In any case, it took some time to work out the actual physical basis for the ultrasound images of the gut wall. During the initial discussions with Dr. Sivak and Hiroshi Ichikawa, they soon realized that EUS might have a positive impact on the problem of pancreatic cancer. By 1980, it was clear that

Chapter 1: A history of endoscopic ultrasonography

endoscopic retrograde cholangiopancreatography (ERCP) could never alter the natural history of this disease, but perhaps EUS might provide an opportunity, under certain circumstances, for earlier detection and therefore improved survival. In retrospect, this was a worthy but naïve notion. Nevertheless, they resolved to pursue EUS of the pancreas. Dr. Charlie Lightdale, on the other hand, took a more sensible and practical path by studying the applications of EUS in staging esophageal cancer. Imaging the pancreas presented many challenges to early endosongraphers, and it was soon obvious that the only way to move forward was to seek the partnership of a radiologist with expertise in ultrasonography. Many of the first endosonographers adopted a similar approach. And so, a radiologist by the name of Craig George joined the team at University Hospitals Cleveland. Dr. George would look over Dr. Sivak’s shoulder during the EUS procedure and essentially interpret the images. By this time, a second-generation prototype EUS system was available. In contrast to the first prototype, the second system included an extremely bulky image processor with a tiny display screen, probably no more than 8 inches on the diagonal. Moreover, the quality of the image was poor, which made it necessary to get close to the screen to see anything. Furthermore, the screen was placed in the box so that it was only about 4 feet above the floor. Although this arrangement was cumbersome, the endosonographer and sonographer soon mastered pancreatic imaging and the principles of ultrasonography and gradually returned to independent imaging by the GI physician. Until June 1982, the struggle to develop EUS was a lonely one; only a handful of endoscopists had any practical experience with EUS, and all were working essentially alone. This changed that June, when Olympus sponsored the first “International Workshop on Endoscopic Ultrasonography” at the Grand Hotel in Stockholm, Sweden – a time and venue selected to coincide with the World Congress of Gastroenterology. They met in a very small room, as there were, according to timely notes, only about 15 active participants, including two invited guests with expertise in areas of digestive ultrasonography other than EUS and excluding about a half dozen representatives from Olympus. Compared to the many subsequent EUS meetings, this first gathering was by far the most important. By the time of the meeting, each participant had discovered many things about EUS, but none had a complete picture of its limitations or true potential. Thus, there was a remarkable and exhilarating exchange of information and ideas that, in retrospect, amounted by aggregation to a significant advance. Dr. Sivak led a long discussion on EUS of the pancreas that solidified the concept of stationed withdrawal of the echoendoscope from the duodenum. Essentially, they made a list of the organs and structures that should be imaged at each station. But, most importantly, each of the dozen participants left the meeting with a revitalized sense of purpose as well as a stronger sense of confidence in the future of EUS. Another aspect of EUS that was clarified by the 1982 meeting was the incredible value of cooperation in the effort to establish EUS as a clinically useful technology. In many ways, the meeting revealed more about what we did not know than what we did, and it showed how much had to be done before EUS could be considered clinically relevant. Shortly thereafter, and in response to the lessons learned at the meeting, Mr. Mark Donohue of Olympus and Dr. Sivak helped organize a small group of investigators that would meet two or three times each year. Our purpose was to grapple collectively with the problems of EUS and, in general, find ways to advance

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its development. In addition to Dr. Sivak, the original membership included Charlie Lightdale and Drs. H. Worth Boyce and Lok Tio. Over the eight or so years of its existence, the membership changed somewhat, but it was always strictly limited to no more than six (usually five). Together with two or three people from Olympus, the total number attending each meeting was never more than eight or nine. Naturally, when the existence of this group became known, albeit not widely, Olympus was besieged by individuals who felt they had the qualifications for membership. But, to the credit of Olympus, Mr. Donohue resisted all requests in order to preserve the small-group dynamic. The group was aptly named the “EUS Users Group.” These EUS Users Group meeting topics covered much of the developmental history of EUS from about 1982 to 1989. The subject matter was divided into two major areas: technical development and the application of the technology to clinical practice and training. As interest in EUS increased, it became glaringly evident that training constituted a formidable problem, all the more so inasmuch as clinical relevance would never be achieved if EUS were performed by a small number of experts. This issue was further compounded by the high cost of the equipment (relative to that of standard endoscopes) and the absence of reimbursement. In those days, echoendoscopes were also fragile and as expensive. The need for frequent maintenance and repairs substantially increased the cost of operation. In the hands of an inexperienced operator, this fragility frequently pushed repair costs well beyond those normally anticipated by an endoscopy unit. All of these factors constituted a significant “cost barrier” to involvement with EUS. There was a certain division within the “Users Group” as to the best approach to the problem of training. There was unanimity concerning the value of didactic teaching, resulting in a number of short symposia. However, it was clearly recognized that this was no substitute for so-called “hands-on” instruction. With respect to the latter, one viewpoint held that short periods of training, ranging from a few days for an accomplished endoscopist to 6 months for the less experienced, would be adequate to “get started.” Some others felt that a “quick and dirty” approach was doomed to failure and advocated more formal and prolonged training. The caveat to this approach, however, was that EUS might never become established. As late as 1988, the programs with the capability for training numbered only five; that is, the members of the group. Even if the group trained 10 endosonographers per year, it would take many years before EUS became widely available. It was fortunate that EUS was introduced during the decade of the 1980s, a period when endoscopists were under less pressure to be ultra-efficient and financially productive. The commitment to screening colonoscopy, for example, had not yet arisen, even as a concept. Had the introduction of EUS been attempted 10 years later, the probability that it would become an established procedure would have been substantially reduced. The establishment of EUS as a clinical procedural entity stands as a tribute to the perseverance of a relatively small group of people as well as to the resolve of the Olympus company. Although this was not generally known, EUS also constituted a substantial cost barrier for the company; in fact, it was a financial loss for more than a decade. That any company would invest so much time and talent for so long, despite an uncertain prospect of financial gain, is remarkable. There is a story, admittedly apocryphal, that Mr. Ichizo Kawahara, then the director of the Medical Instrument Division of Olympus, was once asked why the company persisted in its efforts to develop EUS despite the obstacles and the uncertain chance for

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success. He is said to have replied, “Because the doctors want it.” This, I believe, also reveals the different nature of those times. By 1986, EUS was here to stay with the introduction of the Olympus/Aloka UM2 system. The GF-UM2 echoendoscope was still a fiberoptic instrument, but the EU-M2 display unit was markedly improved. In particular, it offered a 360-sector display, a gigantic improvement with respect to pancreatic imaging. This was followed by a gradual but steady flow of technical improvements. This, together with the continuing addition of more and better data, solidified a lasting place for EUS in clinical practice. It took a lot longer than I had imagined, but it was gratifying to have played a part.

PART 1. Early history (edited by Michael Wallace) The next phase of EUS is characterized by increasing interventional applications of EUS, beginning with the ability to extend a needle through the endoscopic into tissue, cysts, or ducts, initially for cytological sampling and then later with therapeutic applications. I entered the EUS world as a 2nd-year GI fellow at the Brigham and Women’s Hospital, Boston, MA, in 1996 under the mentorship of Jacques Van Dam and David Carr-Locke. I was fascinated by the GI application to cancer detection, staging, and treatment and found myself pulled to the EUS room. In 1998, as a 3rd-year fellow, I became aware of the first EUS needles becoming available in Boston, and Dr. Bill Brugge came to the Brigham to do the first case with us. A key technological development that enabled EUS-guided fine-needle aspiration, as well as many subsequent innovations, was the curved linear array (CLA) EUS scope, where the ultrasound axis sector aligned with the scope and needle, thus allowing full visualization of the target and needle. EUS-FNA (Fine Needle Aspiration) applications rapidly expanded, starting with pancreatic tumors, cysts, lymph nodes, other metastatic sites, the mediastinum, and virtually any site within 6–8 cm reach of the gut lumen. I soon completed my standard fellowship and received an ASGE-Olympus scholarship to train in EUS with Dr. Robert Hawes and Peter Cotton in South Carolina, where I stayed as faculty for four more years. During those years, the first therapeutic interventions, celiac plexus block/neurolysis, were reported.

The past 20 years of EUS have largely been characterized by luminal access procedures, initially through needle puncture-guidewirestandard stents from the gut lumen to any number of sites (pseudocyst/walled-off necrosis, bile duct, pancreatic duct, gallbladder, other gut lumen). The most important advance of this time was the invention and commercialization by Dr. Ken Binmoeller of the first lumen-apposing metal stent (LAMS). This device revolutionized EUS by allowing the safe, reliable anastomosis of two hollow lumens. Twenty years ago, many skeptics of EUS predicted it would be replaced by better imaging (CT, MRI) and minimally invasive or even natural orifice (NOTES) surgery. Quite the opposite, EUS has continued to grow and thrive through innovation and scientific discovery. The need for neoadjuvant therapy for many EUS-relevant cancers (pancreas, esophagus, rectum, and lung) implies that tissue is needed before surgery. Classical NOTES was neither less invasive nor safer than laparoscopic surgery, but EUS-guided lumen apposition outperformed both. Training options rapidly increased. The first 5 founders trained 5 more per year, and then those 10 trained 10, and then 20 trained 20, and so on, leading to 1000s now trained. Thanks to the foresight and stamina of those early pioneers, EUS is now a mainstream and, in fact, essential tool for GI care.

Acknowledgments The first section of this chapter was written by Dr. Michael Sivak of University Hospitals, Case Medical Center, Cleveland, OH, USA. I am deeply grateful for his work in describing the early history of EUS. I have adapted Dr. Sivak’s section to the third person, and have personally contributed to some of the more recent history, but much of the chapter remains the work of Dr. Sivak.

Reference 1 DiMagno EP, Buxton JL, Regan PT, et al. Ultrasonic endoscope. Lancet 1980;I:629–631.

CHAPTER 2

Basic principles and fundamentals of EUS imaging Joo Ha Hwang 1 & Michael B. Kimmey 2 1 Division

of Gastroenterology, University of Washington School of Medicine, Seattle, WA, USA Digestive Care Associates, Tacoma, WA, USA

2 Franciscan

An understanding of the fundamental mechanisms of ultrasound (US) is useful to both the new and the experienced endosonographer. It is not necessary to be a physicist or an engineer to appreciate some basic principles of US imaging and Doppler US. These principles can guide the endosonographer in both obtaining the best representation of a tissue structure with endoscopic ultrasounography (EUS) and interpreting the images thus produced. Knowing these fundamental concepts also aids in the recognition and avoidance of artifacts. In this chapter, the principles of US imaging will be reviewed. An emphasis will be placed on their practical application to endosonography, rather than on the derivation of formulas and equations, which will soon be forgotten.

How US images are made Sound is mechanical energy that is transmitted as a wave through a fluid or solid medium [1, 2]. Unlike electromagnetic waves (e.g., radio, light, and X-ray), sound waves cannot be transmitted through a vacuum. The energy must be transmitted via its impact on the molecules of the transmitting medium. The periodicity or frequency of sound waves per unit of time varies widely and is measured in the number of cycles of the wave that are formed in 1 second, termed a hertz (Hz). Each wave cycle has both a positive and a negative pressure component. US is higher in frequency than can be heard by the human ear (Figure 2.1). The frequencies of waves commonly used in medical imaging are between 3.5 and 20 million Hz, usually abbreviated as 3.5–20 MHz. Even higher-frequency waves can be used in microscopy to define tissue ultrastructure. The high-frequency sound waves used in imaging have some interesting properties that affect how they are used. Unlike lower-frequency audible sound waves, which travel well through air, high-frequency sound is more readily absorbed and attenuated by air, and is strongly reflected at the boundary between tissue and air. This is why gas-filled lungs and bowel limit the use of transcutaneous US in imaging of mediastinal and retroperitoneal structures.

How US waves are made Sound waves are made by applying an oscillating pressure to a medium. A radio speaker vibrates at variable speeds or frequencies to create sound waves in air, which we hear as sound. Higher-frequency US waves are made by crystals that vibrate to transmit a US pulse within a body fluid or tissue. These crystals are made from a special ceramic material, because this can be made to vibrate at a high frequency when a high-frequency alternating polarity charge is applied to it. This property is termed piezoelectric and is also responsible for the crystal’s ability to detect sound waves returning from the tissue and convert them back into an electrical signal. US transducers are composed of either one large crystal or, more commonly, multiple crystals aligned in an array. These transducers change an electrical signal to a sound wave and also receive the reflected sound wave back from the tissue. US transducers typically emit a series of waves or a pulse, and then stop transmitting while they wait to detect the returning echo. What happens when US waves encounter tissue US waves propagate through tissue at a speed that is determined by the physical properties of the tissue [3, 4]. The speed of transmission is largely determined by the stiffness of the tissue: the stiffer it is, the faster the speed. For soft tissue, the variation in speed is only approximately 10%, ranging from 1460 m/s in fat to 1630 m/s in muscle [5–7]. US waves are reflected back to the transducer when the sound wave encounters a tissue that is difficult to pass through. For example, water easily transmits US, but air and bone do not. A sound wave that travels through a water-filled structure like the gallbladder is likely to reach the opposite gallbladder wall unless it encounters a gallstone, which will it back to the transducer. Other solid tissues reflect sound waves to a variable extent, depending on the tissue properties. Fat and collagen are more reflective to US than are muscle and lean solid organs. Sound waves are also reflected when they encounter a boundary or interface between two tissues with different acoustical properties (see next section).

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Audible sound

Medical ultrasound

Transducer element A mode

ULTRASOUND 20

20,000

2,000,000 20,000,000

1,000,000,000

Time (A )

B mode

Amplitude

How images are made from reflected US waves Sound waves that are reflected by tissue components back to the transducer are detected by the same piezoelectric crystals that created them. These crystals then translate the waves back into electrical signals for processing into an image. The transducer detects the returning echo as a function of the time that passed from when the sound pulse was emitted. The amount of time it takes for an echo to return is a function of the speed of sound in the tissue and the distance from the transducer of the part of the tissue from which the sound wave is being returned. Because the speed of sound in lean tissue varies only by approximately 10%, the time between transmission and return of an echo is a good marker for the distance the sound wave has traveled. Thus, for medical imaging, distance or the location of a reflector within a tissue can be approximated by the delay observed in the return of a US pulse. The returning waves or echoes can be displayed in a number of ways or modes. The simplest display plots the intensity or amplitude of echoes according to the time at which they are detected. This is termed A-mode and is infrequently used for medical imaging. If the amplitude of the returning signals is displayed as the brightness of a dot on the image, a B-mode image is created. If the transducer is moved across the tissue or if the transducer contains numerous crystals, a two-dimensional image is created out of the dots, which reflect echo amplitude; one dimension is the location or depth of the reflector causing the echo, while the other is the span of tissue being imaged (Figure 2.2). The precise time at which a returning echo is detected is also a function of the orientation of the target tissue and the transducer. A more accurate representation of tissue structure is obtained when the US wave propagates in a direction that is perpendicular to the target. The reflected wave is then perpendicular to the transducer as well. If the US wave encounters the target from another angle or tangentially, then the returning wave is detected later and is thus displayed on the image at a distance that overestimates its actual position (see section on Imaging Artifacts).

Time (B)

Compound B mode

Distance

Figure 2.1 Frequencies of audible sound and US.

Amplitude

Sound frequency (Hz)

How transducer properties affect the image US frequency and axial resolution When high US frequencies are used, more waves can be transmitted per unit of time and the duration of the pulse of US energy can be proportionately reduced. This allows the US transducer to receive returning echoes more often. The result is a better ability to discriminate between two points in the target tissue that are within the direction of the US beam. This distance between distinguishable points in the direction of the US beam is termed “axial” or “range” resolution (Figure 2.3). In general, the higher the US frequency, the better the axial resolution. Most endoscopic US systems have axial resolutions that are approximately 0.2 mm. However, tissue penetration is also reduced with higher US frequencies (Table 2.1).

Time (C) Figure 2.2 The basic types of US image. (A) An A-mode image plots the

amplitude of a returning echo versus the time at which it returns relative to the transmitted US wave. Because the velocity of sound through soft tissue is relatively constant, the time taken for an echo to return can be converted into the distance or depth within the tissue at which the echo originated. (B) A B-mode image displays the amplitude of an echo as the brightness of a dot. (C) When multiple transducers are used or when a single transducer is moved over an area, the multiple single-line B-mode images can be converted into a rectilinear or compound scan.

Chapter 2: Basic principles and fundamentals of EUS imaging

Resolution cell Range

Rectangular transducer

f2 > f1

f1

7

f1

Azimuth

w Lateral h

Figure 2.4 Effects of US frequency (f) on the beam pattern of a transducer.

dff

t1

t2

t3

For the same size transducer, a beam (solid lines) with a higher US frequency (f2 ) produces a near–far field transition point that is further from the transducer and causes a narrower beam width in the far field. A beam (dashed lines) with a “lower frequency” (f1 ) is illustrated for comparison. Source: Kimmey MB, Martin RW 1992 [4]. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 2:561, WB Saunders. Reproduced with permission of Elsevier.

Figure 2.3 The resolution in three dimensions (resolution cell) for a pulse of

US energy as it propagates from a rectangular-shaped transducer of defined width (w) and height (h). The duration of the pulse, defining the axial or range resolution, stays the same as the wave propagates and is illustrated at three times: t1 , t2 , and t3 . Changes in the beam pattern produce changes in the lateral and azimuthal resolutions at the three time points. The near–far field transition point (dff ) is the point with the smallest-resolution cell (in this case, illustrated at time t2 ) and offers the best overall resolution. Source: Kimmey MB, Martin RW 1992 [4]. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 2:560, WB Saunders. Reproduced with permission of Elsevier.

Table 2.1 Effect of US frequency on axial resolution and tissue penetration. US frequency (MHz)

Axial resolution (mm)

Tissue penetration (cm)

5 10 20

0.8 0.4 0.2

8 4 2

Transducer size and lateral resolution The lateral resolution makes it possible to distinguish between two points in the lateral dimension (see Figure 2.3). The magnitude of this resolution is dependent on the diameter of the transducer. In general, larger transducers have poorer lateral resolution. The lateral resolution is not constant, but varies according to the distance of the target reflector from the transducer. The location of the best lateral resolution is often referred to as the focal zone of the transducer, and is the point at which the beam is focused and the lateral resolution is optimized. With most US endoscopes, this distance is between 2 and 3 cm from the transducer. The frequency of a US transducer also affects the lateral resolution. Small-diameter transducers used on catheter probes are especially vulnerable to this effect. With other variables being equal, higher-frequency small-diameter transducers have a narrower focal zone over a broader distance from the transducer than do lower-frequency transducers of the same diameter (Figure 2.4). This is the primary reason why catheter probes are made with higher-frequency (12–20 MHz) transducers.

Attenuation and tissue penetration “Attenuation” refers to the loss of strength of the US beam over time or distance traveled. The degree of attenuation is dependent on the properties of both the US transducer and the tissue, but the most

Figure 2.5 A duodenal lipoma (L) strongly attenuates the 12.5 MHz US

beam, producing an acoustic shadow (arrows) in the tissue deep to the lipoma.

important factor is the US frequency. Higher US frequencies are maximally attenuated and hence do not penetrate as far into the tissue. Higher frequencies are also attenuated to a greater degree by specific tissue components, such as fat. For example, a lipoma within the gastrointestinal (GI) wall can attenuate a 12 or 20 MHz US beam so effectively that no US energy reaches the deep aspect of the lesion (Figure 2.5). The entire lipoma therefore may not be represented on the US image. In such situations, a lower-frequency US transducer might be preferable. Since all tissue attenuates US to some degree, returning echoes from deeper tissue structures will have lower amplitude than those from more superficial structures. This is due to attenuation of both the transmitting US wave and the returning echo. Medical US imaging systems compensate for this effect by amplifying the echoes that return to the transducer later (Figure 2.6). Amplification of these echoes from deeper tissue structures is called time gain compensation (TGC). TGC can be controlled by the sonographer by changing settings on the US processor. The goal is to make similar tissue have the same US appearance, irrespective of location within the tissue.

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Echoes attenuate with distance

(A)

Distance or time

Time varying amplification control signal

Time (B)

Knowledge of attenuation can also be useful in image interpretation. Most bodily fluids (blood, urine, and bile) attenuate a US beam very little. Thus, when imaging a fluid-filled structure, more US energy is transmitted to the tissue deep to the structure than to the tissue deep to the adjacent solid tissue. There are then more returning echoes from the tissue deep to the fluid-containing structure, making this tissue brighter on the image. This through-transmission enhancement can be used to help distinguish between fluid-filled and solid structures. For example, images of a cyst will show brighter echoes in the area of tissue deep to the cyst (Figure 2.7).

How tissue properties affect images: the GI wall The composite image of a tissue depends on the properties of the tissue and on the US transducer and system used. US imaging of the GI tract wall is a good example of how these various factors interact.

Electronic compensation for attenuation

Distance (C) Figure 2.6 Time-varying gain (TVG) compensation. The vertical axis repre-

sents the amplitude of the received echoes (A, C) and the control signal (B). (A) US echoes with the same amplitude at the reflection site are received by the transducer as lower-amplitude signals according to how far the reflector is from the transducer, because of attenuation of both the transmitted and the reflected US waves. (B) The received echo can be electronically amplified according to when it is received. As shown by the linear increase, echoes from similar reflectors have the same amplitude at all distances from the transducer. Source: Kimmey MB, Martin RW 1992 [4]. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 2:563, WB Saunders. Reproduced with permission of Elsevier.

Frequency dependence Early reports of imaging of the GI wall with transcutaneous US transducers described a three-layered structure. The layers represented luminal contents (echo rich), the wall itself (echo poor), and the surrounding tissues (echo rich). The axial resolution of these low-frequency (3–5 MHz) systems was too poor to detect the different components of the wall itself. With the development of endoscopic US systems with higher frequency (7.5–12 MHz) and better-resolution transducers, the GI wall was usually imaged as a five-layered structure, due to the different US properties of the mucosa, submucosa, and muscularis propria [8]. Most recently, 20 MHz catheter-based EUS systems routinely image the GI wall as a seven- or nine-layer structure, due to their better resolution, which allows the muscularis mucosae and the intermuscular connective tissue of the muscularis propria to be distinguished [9, 10]. Higher US frequencies also produce brighter echoes from specular reflectors (see next section). This also contributes to the improved resolution seen with higher-frequency US systems. Specular and nonspecular reflectors There are two types of tissue reflector that are sources of echoes on US images. These are termed “nonspecular” and “specular” reflectors. Echoes from nonspecular reflectors are produced by tissue components that scatter the US wave. Echoes from specular reflectors are produced when the US wave encounters two adjacent tissues with different acoustical properties. The US image is a composite of echoes from both types of reflector. For example, the US image of a mixture of oil and water is homogeneous and echo-rich. Echoes are reflected from nonspecular reflectors caused by the small oil droplets mixed in the water. After separation of the oil and water, however, only a thin echoic line is seen from the specular reflector at the interface between the oil and the water.

Nonspecular reflectors (scatterers)

Figure 2.7 Fluid within this small pancreatic cyst (C) does not reflect much

of the US beam, leading to more echoes being seen in the tissue deep to the cyst (between arrows). This is the through-transmission artifact.

Fat and collagen are the most reflective tissue components of the GI wall. These tissue components are responsible for the bright layer seen in the center of the GI wall on EUS images. The submucosa is a dense network of collagen fibrils that provide structural support and allow for sliding of the overlying mucosa during motility. There is sometimes fat present in the submucosa, as well. The other bright layer on EUS images of the bowel wall comes from tissue just deep to the muscularis propria. In most areas of the body, this is from fat

Chapter 2: Basic principles and fundamentals of EUS imaging

in the subserosa. In the esophagus, which is not covered by serosa, the bright layer is caused by fat in the mediastinum. In the rectum, fat and collagen in the pelvis create the bright layer.

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1 2 3

Specular reflectors (interface echoes) Early interpretations of US images of the GI wall associated the echo-poor second layer with the muscularis mucosae. However, careful measurements later demonstrated that this US layer was much too thick to be the muscularis mucosae [8]. Further measurements also suggested that the central echoic layer was too thick to be the submucosa and the deep, echo-poor (or fourth) layer was too thin to represent the muscularis propria. These observations were reconciled by considering the contribution to the image of specular reflectors produced at the interface between tissue layers of the bowel wall [8]. The thickness of an interface echo is determined by the pulse length or axial resolution of the US transducer. The beginning of an interface echo corresponds with the location of the interface, so that the thickness of the interface echo itself will co-locate with the most superficial aspect of the deeper tissue layer. Thus, an interface echo will add thickness to a more superficial echo-rich layer like the submucosa, but subtract from the apparent thickness of a deeper echo-poor layer like the muscularis propria. When layer measurements are corrected for the presence of interface echoes, an accurate interpretation of the images is possible (Figure 2.8). These principles can also be applied to the interpretation of the seven- or nine-layered images of the GI wall that are obtained with higher US frequencies. Better axial resolution and thinner interface echoes allow the muscularis mucosae to be visualized as a thin echo-poor layer superficial to the submucosa. The interface echo between the lamina propria and the muscularis mucosae divides the mucosa into four layers: an interface echo at the mucosal surface, the lamina propria, an interface echo between the lamina propria and muscularis mucosae, and the remainder of the muscularis

4 5

6 7 8 9 Figure 2.9 High-frequency US transducers may image the GI wall as a

nine-layered structure. From the mucosal surface at the top, layer 1 is produced by the interface between luminal fluid and the mucosal surface. Layer 2 is from the remainder of the lamina propria. Layer 3 is from the interface of the lamina propria and the muscularis mucosae. The remainder of the muscularis mucosae is visualized as a hypoechoic fourth layer only if the muscularis mucosae is thicker than the pulse length or axial resolution of the US transducer used. Layer 5 is from the submucosa and its interface with the muscularis propria. Layer 6 is the remainder of the inner circular component of the muscularis propria. The intermuscular connective tissue produces a thin echoic layer 7. The outer longitudinal component of the muscularis propria is responsible for layer 8. Layer 9 is from subserosal fat and connective tissue.

mucosae that was not obscured by the interface echo [9, 10]. The additional three layers in a nine-layered GI wall are caused by the division of the muscularis propria into inner circular and outer longitudinal components by a line of nonspecular echoes from a thin layer of connective tissue (Figure 2.9).

1 2

3

4

5

Figure 2.8 The five layers of the normal GI wall, as imaged with most endo-

scopic ultrasound equipment. From the mucosal surface at the top, layer 1 is produced by the interface between luminal fluid and the mucosal surface. Layer 2 is from the remainder of the mucosa. Layer 3 is from the submucosa and its interface with the muscularis propria. Layer 4 is the remainder of the muscularis propria. Layer 5 is from subserosal fat and connective tissue.

Detection of tissue movement: doppler imaging When a US wave encounters a moving object, its US frequency is shifted. This frequency change is termed the Doppler shift, and the use of this principle in detecting tissue movement is called Doppler imaging. Movement of red blood cells within blood vessels is the most common application of Doppler imaging. The direction of the frequency shift can also be used to determine the direction of the movement (i.e., toward or away from the transducer). A few special principles of Doppler physics need to be recalled to optimize use of this technique. First, the Doppler frequency shift is maximal when the US wave encounters the moving objects at a tangential rather than a perpendicular angle. This is contrary to the principle of US imaging that tissue structure is reproduced most faithfully by a US wave that is perpendicular to the tissue. It is therefore often necessary to move the transducer in real time to simultaneously obtain optimal imaging and Doppler information. There are two basic methods for performing Doppler measurements: pulsed Doppler and continuous-wave Doppler. Continuous-wave Doppler requires two transducers: a transmitting transducer and a receiving transducer. The transmitting transducer delivers a continuous fixed-frequency US wave into the tissue. The receiving transducer then receives the signal. If there is movement

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in the tissue, the transmitted and received signals will differ, and when the two signals are summed together, the result will be a waveform that contains a beat frequency that is equivalent to the Doppler shift frequency. Continuous-wave Doppler is unable to give information regarding the location at which the Doppler shift is detected; therefore, pulsed Doppler was developed to obtain depth information regarding where the motion causing the Doppler shift is occurring. In pulsed Doppler, a single transducer is used to send a US pulse intermittently, so that detection of the returning Doppler wave is not limited by further transmitting waves. This leads to a more reliable detection of the depth of the moving object. For example, pulsed-wave Doppler probes have been shown to reliably detect the location of blood vessels in the GI wall [11]. Doppler information can be displayed in a number of ways. The Doppler shift of moving blood is approximately 15 000 Hz. Because this is within the range of human hearing, the signal can be amplified into an audible signal. The Doppler signal can also be superimposed on a B-mode scan so that the location of the moving objects can be determined by looking at the B-mode image. This is called duplex scanning and is commonly used in EUS. The presence of a Doppler signal is good evidence that a cystic anechoic structure on B-mode imaging is a blood vessel. The direction of the Doppler shift can also be codified with color, in a technique called color Doppler. Red is commonly used to represent flow toward the transducer, and blue to represent flow away from the transducer. Power Doppler is the most recent advancement in Doppler US imaging and is the most sensitive method for detecting blood flow. For power Doppler imaging, pulsed Doppler is used to obtain the Doppler signal. However, power Doppler evaluates the strength of the Doppler signal and discards any information regarding the velocity or direction of motion.

New techniques in EUS imaging Contrast-enhanced EUS imaging Intravenous injection of a US contrast agent (UCA) – gas-filled microbubbles that are 2–5 μm in diameter – results in enhancement of vascular structures on US imaging if an appropriate imaging technique and processing are used. This is a relatively well developed imaging technology for cardiac imaging and transabdominal applications; however, the technology for EUS imaging is still in development [12]. The use of UCAs has enhanced the diagnostic capabilities of US imaging by improving the ability to image smaller-caliber blood vessels, improving identification of tumors, and enhancing visualization of the cardiac wall [13–15]. Potential applications in EUS include evaluation of vascular invasion for tumor staging, differentiating benign and malignant lymph nodes [16], discriminating between focal pancreatitis and pancreatic carcinoma [17, 18], and localizing vascular tumors such as insulinomas [19]. Elastography Elastrography is a method used to assess the stiffness of tissue in response to compression, by comparing the backscattered US signal from tissue in a compressed and a noncompressed state [20]. This method is being evaluated for use in diagnosing disease processes that cause the stiffness of tissue to change, such as cirrhosis, inflammation, and malignancy. It is analogous to the physical examination technique of palpation. For example, malignant tumors are often firm when palpated on physical examination. Elastography is a form of palpation that uses US to detect regions that have different stiffness relative to the surrounding tissue.

With external compression, the US signal that is received from the region of interest will be different than the signal received when the region of interest is not compressed. The two signals are compared using image processing algorithms to produce an elastrogram. For external imaging applications, the US transducer can be used to apply compression to the region of interest, typically in a repetitive motion (compression–relaxation). For endoscopic applications, it can be difficult to apply compression to a region of interest using the EUS transducer; therefore, the compressions to the region of interest can be made by vascular pulsation or respiratory motion. EUS elastography should improve the diagnostic capabilities of EUS and help to improve localization of lesions and diagnostic yields on biopsy [21].

Imaging artifacts There are a number of artifacts that should be recognized when performing EUS imaging. Artifacts are echoes seen on an image that do not reliably reproduce the actual tissue structure. Failure to recognize artifacts can lead to image misinterpretation and errors in patient management. This section will highlight some common artifacts and discuss how to recognize or, if possible, avoid them. Reverberation artifacts Strong echoes are produced when a US wave encounters solid nontissue objects. The most common example of this is reverberation of the US beam from the casing of the transducer. This produces a characteristic series of echoes at equal intervals, radiating out from the transducer – the ring artifact (Figure 2.10). It is seen more commonly with the radial scanning echoendoscope than with the curvilinear array (CLA) instrument, and in some situations can interfere with the near-field image. Reducing overall and near-field gain helps to minimize this artifact. Moving the transducer away from the area

Figure 2.10 The plastic casing (C) around the US transducer produces a

strong reverberation of the US beam between the transducer and the casing. This results in a series of circular rings (arrows) of equal spacing and diminishing amplitude around the transducer.

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between water and air (Figure 2.11). This is typically seen when imaging within a partially water-filled organ such as the stomach or rectum. The US waves bounce back and forth between the transducer and the air–water interface, creating a mirror image of the transducer on the opposite side of the air–water interface (Figure 2.12). This effect is similar to observing both a mountain and its inverted reflection in a lake. The artifact is easily recognized and can be avoided by removing air and adding more water into the lumen.

(B), produced by reverberation between the transducer and the air–water interface (arrow) within the gastric lumen.

Tangential scanning As previously discussed, distances, and therefore tissue thicknesses, are most accurate when the US wave is perpendicular to the area of interest. When the US wave is tangential, tissue layers appear artificially thickened (Figure 2.13). This artifact can result in tumor “overstaging,” especially in the esophagus and gastroesophageal (GE) junction, and particularly when the radial scanning US endoscope is used (Figure 2.14). To avoid this problem, the endoscope should be carefully maneuvered so that the US wave is perpendicular to the tissue. The normal wall layers should appear symmetric and of uniform thickness. When imaging abnormal tissue, care must be taken that the findings are reproducible and are not altered by small deflections of the endoscope tip.

of interest by filling the balloon or bowel lumen with water may help move the artifact away from the area of interest. Another problem created by reverberation is the mirror-image artifact [22]. In this situation, US waves bounce off of an interface

Attenuation artifacts Other artifacts are caused by attenuation of the US wave, but attenuation artifacts facilitate image interpretation in some cases. For example, lack of transmission of US through a

Figure 2.11 Mirror image (M) of the US transducer and water-filled balloon

Ultrasound image

0

Ultrasound probe in the stomach

0

Mirror image from water-air reflection

Water

0

0

0

d2 d1

0

d2

Air

d1

Em2 Direct image

Em1 Ed1

Ed2

Balloon

Stomach wall Figure 2.12 Production of a mirror-image artifact by reverberation of echoes from an air–water interface. The air–water interface reflects so strongly that

US energy is redirected back to the transducer, just like light is redirected by a mirror. In the illustration at the left, the echoes Em1 and Em2 result from a double reflection, from the air–water interface and the stomach wall or balloon (or transducer case), respectively. The US processor records the position of the echo according to the time it receives the signal; the double reflection path takes longer and therefore causes the echo to appear further away from the transducer, as if it were a reflection in a mirror (diagram at left). The echoes received by the transducer directly (e.g., Ed1 and Ed2 ) are displayed on the image in the expected location. The distance from the transducer to the air–water interface (d) and the distance from the balloon or transducer case to the interface (d2 ) are also illustrated. (Reproduced from Kimmey MB, Martin RW. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 1992;2:570, with permission from WB Saunders.)

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Echoes amplitude

Distance

(A)

es ho e Ec litud p am

Figure 2.14 EUS image of an esophageal cancer (Tj), appearing to show

invasion of the descending aorta (Ao) at the arrow. This is an artifact caused by nonperpendicular or tangential scanning. A clue to this is the location of the water-filled balloon (B): the transducer and balloon should be positioned in the center of the esophagus, with the transducer in the center of the balloon to avoid this artifact and avoid tumor over-staging.

Distance

(B) Figure 2.13 Why artifactual layer thickness increases with tangential scan-

ning. (A) Amplitude and spatial duration of the echoes from the interfaces and specular reflectors in the normal GI wall when the US beam is at right angles to the wall. The diagonally-hatched region represents a tissue type with nonspecular echoes (e.g., the submucosa); the remaining echoes are produced by interfaces between tissue layers (specular echoes). The duration of the interface echoes is the same as the duration of the US pulse or the range resolution of the system (illustrated as a black rectangle in the beam). The echoes (displayed at the right) are spatially separated and distinguishable from one another. (B) When the US beam is not perpendicular to the wall, both the lateral and range resolution affect the duration of the echoes from each layer. In the extreme situation illustrated here, echoes from each layer overlap and cannot be distinguished individually. (Reproduced from Kimmey MB, Martin RW. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 1992;2:572, with permission from WB Saunders.)

gallstone or pancreatic duct stone is a key feature of cholelithiasis, choledocholithiasis, and pancreaticolithiasis. Soft tissue can also attenuate US waves, making it difficult to image deep into the tissue, especially when high-frequency transducers such as those on catheter probes are used. This can limit the ability to image the deep aspects of tissue masses. Another common artifact is caused by attenuation by air bubbles. Bubbles develop in several unwanted locations, including the oil surrounding the transducer within the transducer housing, the water in the balloon on the outside of the transducer housing, water placed into the GI lumen, and air within the lumen itself. The transducer casing should be inspected for air bubbles prior to each procedure; removing these bubbles requires a minor repair by the manufacturer. Air bubbles in the balloon can be avoided by using degassed water and by repetitive filling and suctioning of the balloon prior to use. Air in water placed into the lumen can be avoided by using degassed water and by having the patient drink a simethicone “cocktail” before the procedure [23]. Side-lobe artifacts These artifacts are characterized as nonshadowing echoes within an otherwise anechoic or fluid-filled structure [24]. They can be confused with biliary sludge in the gallbladder or with a mass within a pancreatic cyst (Figure 2.15). Side-lobe artifacts are caused by low-amplitude components of the transmitted US beam that are not perpendicular to the target. If these echoes are reflected by solid tissue outside the fluid-containing target, they may be displayed by the US processor as having come from the fluid-filled structure. When imaging solid tissue, low-amplitude side-lobe echoes are obscured by the echoes from the solid tissue and do not pose a problem in image interpretation. However, when an anechoic structure is being imaged, these echoes become visible and can artifactually suggest the presence of a solid component.

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improperly set. This filter is meant to reduce noise from vessel wall motion, but can sometimes indiscriminately delete clinically important low-frequency echoes.

Conclusion The principles of US discussed in this chapter can be used to facilitate better endosonographic scanning and produce images that more accurately reproduce tissue structure. The importance of a standardized pre-procedure checklist and consistent procedure technique cannot be overemphasized. The basic steps in achieving an optimal examination, based on the principles discussed in this chapter, are summarized in Table 2.2.

References

Figure 2.15 Pancreatic cyst (C) with apparent echoes (arrows), suggesting

a solid component. These echoes are caused by side-lobe artifacts and are recognized because they are not consistently imaged when the transducer is maneuvered into another imaging plane.

They are easily recognized because they disappear with transducer movement and are eliminated by scanning from other angles. Doppler artifacts Artifacts associated with Doppler imaging can lead to signals being detected when no flow is present and, conversely, a lack of signal when flow is present. Flow can be artifactually seen when the Doppler gain is set too high. Under those conditions, bowel wall and transmitted cardiac and respiratory motion can be amplified and give the appearance of flow. However, this false signal is usually easy to recognize, because the Doppler signal is diffuse and is not localized to a specific structure. False-negative Doppler signals can occur if the US beam is perpendicular to the target. Doppler shift is best detected with a US beam that is less than 60∘ incident to the target. Doppler can also miss low levels of venous flow if the US processor’s wall filter is

Table 2.2 Use of US principles to optimize image quality. Principle

Practice

US frequency affects penetration depth US frequency affects axial resolution

Use lower US frequency for distant targets Use the highest US frequency that provides adequate penetration Position the transducer so that the target is in the optimal focal zone Use lower frequencies for fatty and fibrous structures Adjust the TGC on the US processor

Lateral resolution varies with distance from the transducer Attenuation is greater with higher US frequencies The same tissue type should appear the same throughout the US image Air transmits high-frequency US poorly Images are more reliable if the US beam is perpendicular to the tissue Doppler shift is greatest with a tangential US beam

Eliminate air bubbles in the water-filled balloon and in the lumen Recognize and avoid tangential scanning artifacts Adjust the transducer position to optimize the Doppler signal

1 Curry TS, Dowdey JE, Murry RC Jr., Ultrasound. In: Christensen’s Introduction to the Physics of Diagnostic Radiology, 4th edn. Philadelphia: Lea & Febiger, 1990. 2 Powis RL, Powis WJ. A thinker’s guide to ultrasonic imaging. Baltimore: Urban & Schwarzenberg, 1984. 3 Kimmey NO, Silverstein FE, Martin RW. Ultrasound interaction with the intestinal wall: esophagus, stomach, and colon. In: Kawai K (ed.) Endoscopic Ultrasonography in Gastroenterology. Tokyo: Igaku-Shoin, 1988: 35-43. 4 Kimmey MB, Martin RW. Fundamentals of endosonography. Gastrointest Endosc Clin North Am 1992;2:557–573. 5 Fields S, Dunn F. Correlation of echographic visualizability of tissue with biological composition and physiological state. J Acoust Soc Am 1973;54:809–812. 6 Goss SA, Johnston RL, Dunn F. Comprehensive compilation of empirical ultrasonic properties of mammalian tissues. J Acoust Soc Am 1978;64:423–457. 7 Goss SA, Johnston RL, Dunn F. Compilation of empirical ultrasonic properties of mammalian tissues II. J Acoust Soc Am 1980;68:93–108. 8 Kimmey MB, Martin RW, Haggitt RC, et al. Histological correlates of gastrointestinal endoscopic ultrasound images. Gastroenterology 1989;96:433–441. 9 Wiersema MJ, Wiersema LM. High resolution 25megahertz ultrasonography of the gastrointestinal wall: histologic correlates. Gastrointest Endosc 1993;39:499–504. 10 Odegaard S, Kimmey M. Localization of the muscularis mucosae in gastric tissue specimens using high frequency ultrasound. Eur J Ultrasound 1994;1:39–50. 11 Matre K, Odegaard S, Hausken T. Endoscopic ultrasound Doppler probes for velocity measurements in vessels in the upper gastrointestinal tract using a multifrequency pulsed Doppler meter. Endoscopy 1990;22:268–270. 12 Feinstein SB, Cheirif J, Ten Cate FJ, et al. Safety and efficacy of a new transpulmonary ultrasound contrast agent: initial multicenter clinical results. J Am Coll Cardiol 1990;16:316–324. 13 Keller MW, Feinstein SB, Watson DD. Successful left ventricular opacification following peripheral venous injection of sonicated contrast agent: an experimental evaluation. Am Heart J 1987;114: 570–575. 14 Kitzman DW, Goldman ME, Gillam LD, et al. Efficacy and safety of the novel ultrasound contrast agent perflutren (definity) in patients with suboptimal baseline left ventricular echocardiographic images. Am J Cardiol 2000;86:669–674.

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15 Dietrich CF, Ignee A, Frey H. Contrast-enhanced endoscopic ultrasound with low mechanical index: a new technique. Z Gastroenterol 2005;43:1219–1223. 16 Hocke M, Menges M, Topalidis T, et al. Contrast-enhanced endoscopic ultrasound in discrimination between benign and malignant mediastinal and abdominal lymph nodes. J Cancer Res Clin Oncol 2008;134:473–480. 17 Hocke M, Schulze E, Gottschalk P, et al. Contrast-enhanced endoscopic ultrasound in discrimination between focal pancreatitis and pancreatic cancer. World J Gastroenterol 2006;12:246–250. 18 Becker D, Strobel D, Bernatik T, Hahn EG. Echo-enhanced color- and power-Doppler EUS for the discrimination between focal pancreatitis and pancreatic carcinoma. Gastrointest Endosc 2001;53:784–789. 19 Kasono K, Hyodo T, Suminaga Y, et al. Contrast-enhanced endoscopic ultrasonography improves the preoperative localization of insulinomas. Endocr J 2002;49:517–522.

20 Gao L, Parker KJ, Lerner RM, Levinson SF. Imaging of the elastic properties of tissue – a review. Ultrasound Med Biol 1996;22: 959–977. 21 Giovannini M, Hookey LC, Bories E, et al. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy 2006;38:344–348. 22 Grech P. Mirror-image artifact with endoscopic ultrasonography and reappraisal of the fluid-air interface. Gastrointest Endosc 1993;39:700–703. 23 Yiengpruksawan A, Lightdale CJ, Gerdes H, Botet JF. Mucolyticantifoam solution for reduction of artifacts during endoscopic ultrasonography: a randomized controlled trial. Gastrointest Endosc 1991;37:543–546. 24 Laing FC, Kurtz AB. The importance of ultrasonic side-lobe artifacts. Radiology 1982;145:763–776.

CHAPTER 3

Learning EUS anatomy John C. Deutsch Essentia Health Systems, Duluth, MN, USA

Endoscopic Ultrasonography (EUS) is different than regular endoscopy in that it is a planar anatomy-based procedure. However, EUS anatomy is somewhat difficult to learn, as the planes generated are not often described in traditional anatomy learning material. Beyond this, there are other factors which increase the difficulty of becoming proficient at EUS anatomy. First, the images are generated by ultrasound, so one must be able to interpret an ultrasound image. Next, there are often patient features (obesity, hiatal hernias, variant anatomy) that can complicate placing an echoendoscope into a position in which it can generate the desired images.

General principles of EUS EUS anatomy is easier to interpret if one considers a few basic concepts. The first has to do with understanding the nature of ultrasonography. The transducer on the tip of the echoendoscope makes the sound waves and receives the echoes. The transducer has quartz (piezoelectric) crystals. An electric current applied to these crystals causes the crystals to vibrate and produce sound waves that travel outward. These waves are reflected back at various intensities, depending on what is in their path, and when they return to hit the crystals, the crystals emit electrical currents. The probe has an acoustic lens to help focus the emitted sound waves. Fat and air tend to strongly reflect sound waves, leading to bright (hyperechoic) images. Fluid tends to conduct sound waves, leading to dark (hypoechoic) images. Fluid-filled structures (arteries, veins, ducts) can generally be well seen and can be used as guides to finding organs and lesions of interest. Endosonography is facilitated if one has a general knowledge of vascular and ductal anatomy, as these fluid-filled structures provide a “roadmap” of the regional anatomy. Figure 3.1 shows the major vascular and ductal structures of interest during an EUS exam. Familiarity with these structures simplifies EUS procedures.

Another important concept is that the echo endoscope may not go where the endoscopist thinks it is going. One can get lost while pushing in an endoscope, assuming that it is moving in a caudal direction when it is actually moving in a cephalad, anterior, or lateral direction. Rather than trying to figure out where one is by assuming a course, it is often better to trace a known structure (particularly a vessel or duct) to the desired location. Finally, personal evaluation of computed tomography (CT) and abdominal ultrasound images helps one become better at endosonographic anatomy. One becomes better at EUS by becoming better at reading CT scans and transabdominal ultrasounds.

Echo endoscopes There are two basic arrays of piezoelectric crystals on an echo endoscope: the radial array, which encircles the tip of the endoscope, and the linear array, which is parallel to the endoscope. The anatomic planes generated during EUS are quite different when one uses a radial versus a linear array probe. Although the early echo endoscopes were primarily radial array, the majority of EUS applications (such as fine-needle aspiration) currently use linear-array technology.

Regional anatomy The esophagus and extraesophageal spaces Esophageal EUS tends to follow traditional cross-section CT anatomy (radial-array exams approximate transaxial views (Figure 3.2), while linear-array images follow coronal and sagittal planes (Figure 3.3)). Extraesophageal EUS anatomy is the easiest to learn. The esophagus runs a relatively straight course and is partially bordered by vascular structures, which provide excellent endosonographic images. If one is familiar with the aorta, the branches on the

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Figure 3.1 The major vascular and ductal structures of interest during an EUS exam. Touch of Life Technologies, Inc.

aortic arch, the azygos vein, and the heart, the other regional structures fall into place. Esophageal radial array anatomy is very similar to routine transaxial CT anatomy from the thyroid to the diaphragm, and placing the aorta at 5 or 6 o’clock will approximate transaxial CT images (Figure 3.2). The thyroid, mediastinal nodes, vertebral column, and cardiac structures are usually clearly evident. Linear-array exams are easiest after identification of the aorta. The mediastinum can be fully evaluated as the instrument is rotated. From the level of the aortic arch, the left subclavian and left carotid arteries are seen. Moving towards the stomach reveals the aortopulmonary window, subcarina space, azygos arch, and cardiac structures such as the great pulmonary vessels, left atrium, mitral valve, and left ventricle (Figure 3.3). The aorta can then be followed into the abdomen, down to the celiac artery.

Knowing the vascular anatomy allows one to use vessels to guide one’s way to lesions. Figure 3.4 shows the major vessels of the chest and their relation to the esophagus. The stomach and the extragastric spaces The extragastric spaces can be a challenge to examine in full detail. There are many factors that can alter images, including hiatal hernias, different amounts of intraabdominal fat, and various orientations of the stomach within the abdomen. EUS anatomy reference material will usually show ideal images from ideal patients, but in practice most patients will not be ideal. In addition, the stomach does not confine the echo endoscope to any specific path. It is important to be able to find landmarks and work outwards from them, tracing known structures.

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Figure 3.2 (A1, B1) Thoracic transaxial CT images and (A2, B2) corresponding extraesophageal radial-array EUS images taken at the level of (A1, A2) the

azygos arch and (B1, B2) the carina. The red circles show the esophagus and the location of an EUS probe. A, aorta; T, trachea; z, Azygos; B, bronchus.

Figure 3.3 (A1) Sagittal CT image of the chest. (A2) The same image, rotated and flipped to put it into an orientation seen during linear-array EUS.

(A3) Corresponding EUS image. LA, left atrium; LV, left ventricle; PA, pulmonary artery. The location of the EUS probe is shown by a red spot.

There are a limited number of structures that one looks at during a gastric EUS. Beyond the gastric wall, the primary organ of interest is generally the pancreas body and tail. One also commonly evaluates the liver, the left (and sometimes right) adrenal gland, periaortic lymph nodes, the spleen, and various arteries and veins. The gallbladder can be seen from both the stomach and the duodenum, but is often better visualized from the duodenum. The majority of

extragastric EUS evaluation can be carried out by tracing the splenic artery and vein to the left, and then the hepatic artery and portal vein to the right. Figure 3.5 shows three-dimentional reconstructed anatomy of the stomach and its relation to the pancreas, major arteries, and veins. On entering the stomach, it is best to find the aorta near the gastroesophageal (GE) junction and follow it distally. The first

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Figure 3.4 Vascular structures of the chest and their relation to the esophagus. Touch of Life Technologies, Inc. (A1) The aortic arch and the proximal

branches, as viewed from the left. (A2) The addition of the pulmonary truck and pulmonary arteries, as viewed from the left. (A3) The cavity of the left ventricle and left atrium, separated by the mitral valve, with the pulmonary veins, from the left. (A4) A posterior right view showing the azygos vein, superior vena cava, trachea, and main stem bronchi.

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Figure 3.5 Three-dimensional anatomy of the stomach, viewed from the left and right. Touch of Life Technologies, Inc. HA, hepatic artery; SA, splenic

artery; Celiac, celiac artery; SMA, superior mesenteric artery; PV, portal vein; SV, splenic vein.

Figure 3.6 Comparison of CT images and correlated EUS images. A: Sagittal CT (1) and linear-array EUS (2) at the level of the celiac artery insertion in the

aorta. B: Transaxial CT (1) and radial-array EUS (2) at the level of the celiac artery insertion in the aorta. SMA, superior mesenteric artery.

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Figure 3.7 Cross-sections from the University of Colorado Visible Human project, approximating EUS examinations going left from the aorta. (A1–4)

Sagittal views, similar to linear-array EUS. (B1–4) Transaxial views, similar to radial-array EUS. (A1) Aorta at celiac and superior mesenteric origins. (A2) Slightly left. (A3) Further left, at the level of the left adrenal gland. (A4) Further left, at the splenic hilum. (B1) Aorta at the level of the celiac artery. (B2) Portal confluence. (B3) Slightly left, at the level of the left adrenal gland. (B4) Slightly left, at the level of the splenic hilum. A, aorta; AD, left adrenal gland; C, celiac artery; P, pancreas; PV, portal vein; SA, splenic artery; SMA, superior mesenteric artery; SV, splenic vein.

Figure 3.8 Cross-sections from the University of Colorado Visible Human project, approximating EUS examinations going right from the aorta. (A1–3)

Sagittal views, similar to linear-array EUS. (B1–3) Transaxial views, similar to radial-array EUS. CBD, common bile duct; CYS, cystic duct; GB gallbladder; GDA, gastroduodenal artery; HA, hepatic artery; IVC, inferior vena cava; PD, pancreatic duct; PV, portal vein; SMA, superior mesenteric artery; SV, splenic vein.

artery to branch off the aorta in the abdomen is the celiac artery, and the second is the superior mesenteric artery (Figure 3.6). The celiac/superior mesenteric artery origin in the aorta is the main starting point for extragastric EUS evaluation. Using either radial or linear echoendoscopes, one can usually find the pancreas, pancreas duct, and splenic vein from that location. The splenic vein is easier to follow left than the splenic artery, as it runs a straighter course and is on the inferior margin of the pancreas. The pancreas duct runs through the pancreas. Lymph nodes are generally obvious in

this region. The adrenal gland is at the level of the celiac artery and just to the left. The spleen is at the termination of the splenic artery and at the origin of the splenic vein. Figure 3.7 shows cross-sectional images generated from the University of Colorado Visible Human database similar to those obtained during EUS moving leftward from the aorta with either linear- or radial-array instruments. Returning to midline, the pancreas and splenic vein can be traced to the right past the pancreas genu and the portal confluence. The

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Figure 3.9 Three-dimensional anatomy of the duodenum, showing major vessels and ducts. Touch of Life Technologies, Inc. CBD, common bile duct; GDA,

gastroduodenal artery; HA, hepatic artery; IVC, inferior vena cava; PD, pancreatic duct; PV, portal vein; SMA, superior mesenteric artery; SV, superior mesenteric vein.

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portal vein can be traced to the liver, and the common bile duct can often be seen from this location (Figure 3.8). One primarily sees images of the liver and gallbladder when moving further right. The duodenum and extraduodenal spaces The duodenum is a confined space but can run a variable course in the abdomen. However, it always wraps around the pancreas head. There are five major blood vessels that run in roughly the same direction (cephalad to caudad) in the periduodenal region (the aorta, the vena cava, the portal vein/superior mesenteric vein, the superior mesenteric artery, and the gastroduodenal/superior

pancreaticoduodenal artery). The superior mesenteric vein has many branches, which can sometimes complicate imaging. The common bile duct takes a somewhat parallel course to these vessels and is often similar in size and orientation to the gastroduodenal artery. The hepatic artery and pancreatic duct run a more perpendicular course. Figure 3.9 shows the relation of these structures to the duodenum. Endosonography of the duodenum can start at the bulb and work forwards, start somewhere in the third duodenum and work backwards, or start by finding the ampulla and working from that level. Starting from the ampulla is often the easiest option.

Figure 3.10 Touch of Life Technologies, Inc. Visible Human data Oblique Maker program, showing (A1,B1) planes placed into three-dimensional models and (A2,B2) the cross-sectional anatomy generated within them. CBD, common bile duct; IVC, inferior vena cava; PD, pancreatic duct; PV, portal vein; SV, splenic vein; SMV, superior mesenteric vein. A is similar to a linear array exam of the ampulla from the proximal duodenum. B is similar to a radial array exam of the ampulla from the proximal duodenum bulb.

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Figure 3.11 Cross-sections from the University of Colorado Visible Human project, showing (A1,2) periampullary images and (B1) correlated linear-array

and (B2) radial-array EUS. CBD, common bile duct; PD, pancreatic duct; PV, portal vein.

The images from a linear array exam go from a coronal to a transaxial orientation, where the radial exam is primarily coronal, but in a posterior-to-anterior orientation, so that all anatomy is backwards. Figure 3.10 shows respective images planes and relative orientations of echoendoscopes when visualizing the ampullary region. Figure 3.11 shows EUS images and cross-sectional visible human anatomy from the region of the ampulla. Anatomic orientation is helped by identification of the common bile duct and the pancreatic duct; one can then look for the main vascular structures. The proximal part of the duodenum probably has the most complex extraluminal anatomy. This is partially because endoscopes pass through a curved area and imaging takes place from a variety of orientations. Most of the structures in this region are visualized when the common bile duct is traced from the ampulla. The portal vein and the common bile duct are together proximally. The right hepatic artery is adjacent to the common bile duct proximally, but the gastroduodenal artery is closer distally (Figure 3.12) The most distal part of the EUS exam is usually around the third to fourth portion of the duodenum. Good extraduodenal landmarks include the aorta and the superior mesenteric artery. This

provides evidence that the uncinated process of the pancreas has been passed and examined. The planar anatomy provided by echo endoscope changes as one goes around the c-loop of the duodenum. The linear-array instrument goes from showing approximate coronal anatomy to transaxial anatomy, whereas the radial-array exam goes from approximate transaxial to sagittal images (Figure 3.13). However, with rotation of the endoscope, other orientations can be seen with either instrument. The rectum and the extrarectosigmoid spaces The rectum is relatively straight and the anatomy is relatively easy to learn. The bladder, prostate, and seminal vesicles are anterior in the male. The bladder, vagina, and uterus are anterior in the female. The coccyx and sacrum are posterior (Figure 3.14). In the more proximal areas, the sigmoid colon is quite variable. The iliac vessels and branches provide landmarks that can be used as guides to pelvic structures. In general, the right internal iliac artery and vein are crossed in the distal sigmoid colon, but it is often possible to find the bifurcation of the right and left internal and external iliac arteries and veins. In some patients, it is possible to trace the vessels to the iliac bifurcation at the aorta (Figure 3.15).

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Figure 3.12 Three-dimensional models made from the TolTech dissector program using University of Colorado Visible Human data. The vasculature and

ductal structures around the proximal duodenum are shown. CBD, common bile duct; GB, gallbladder; GDA, gastroduodenal artery and superior pancreaticoduodenal artery; HA, common hepatic artery; LHA, left hepatic artery; RHA, right hepatic artery; SA, splenic artery; SMV, superior mesenteric artery. Source: Touch of Life Technologies, Inc.

Approach to understanding EUS anatomy Know the names of the important structures in the region to be evaluated, particularly the arteries and veins. Review CT and ultrasound images whenever possible. During EUS, it is often best to go to a specific location (the “stations” approach; this has been taught over the years and summarized in various textbooks and monographs [1]) or to an easily identifiable anatomic structure, and then work out from there. For instance: 1 From the esophagus, after identifying the aortic arch, one can look for the left subclavian artery, the left carotid artery,

and the left pulmonary artery, then push in to find the left atrium. 2 From the stomach, after identifying the celiac artery and the superior mesenteric artery, one can follow the splenic vessels left to see the pancreas tail, the left adrenal gland, and the spleen, and then go right to follow the hepatic artery, and find the portal confluence, pancreas genu, and liver. 3 From the duodenum, after identifying the ampulla, one can trace the common bile duct and identify the pancreas duct, pancreas head, cystic duct, gallbladder, and portal vein, and then go distal to evaluate the aorta, vena cava, and superior mesenteric artery and vein.

Chapter 3: Learning EUS anatomy

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Figure 3.13 EUS and CT images taken where the duodenum crosses over the vertebral column. This is generally the distal extent of an EUS examination.

(A1) Linear-array image, which provides a transaxial view, similar to (A2) a standard transaxial CT. An enlarged lymph node is shown between the aorta and the inferior vena cava. (B1) Radial array image, similar to (B2) a sagittal CT image rotated 90∘ counterclockwise. IVC, inferior vena cava; RV, left renal vein; SMA, superior mesenteric vein.

Figure 3.14 Sagittal cross-sections from the University of Colorado Visible Human project, showing the (A1) male and (A2) female pelvis. SV, seminal

vesicles.

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Endoscopic Ultrasonography

Figure 3.15 (A1, A2, A3) Three-dimensional models made from the TolTech dissector program using University of Colorado Visible Human data and (A4)

an EUS image taken from the sigmoid colon showing a sagittal view of the aortic bifurcation over a mass lesion. The internal iliac vessels drape over the rectosigmoid juncture (A1), and the right-sided vessels are generally easier to see than the left-sided, as shown in the posterior anterior image (A3). (A4) Linear-array image taken while doing a guided biopsy of a mass lesion that was found at the iliac bifurcation on CT scan (insert). RI, right iliac artery; LI, left iliac artery; M, mass. Source: Touch of Life Technologies, Inc.

Conclusion

Reference

EUS anatomy can be a challenge to learn. Doing so can be accomplished by obtaining a working knowledge of normal anatomy and then reviewing images and tracing structures while performing an examination.

1 Topazian M, Deutsch J. Station approach to endoscopic ultrasound anatomy of the abdomen. In: MS Bhutani, JC Deutsch (eds.) Digital Human Anatomy and Endoscopic Ultrasonography. London: Decker Hamilton, 2005: 170–198.

CHAPTER 4

EUS instruments, room setup, and assistants Brian C. Jacobson Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA

Endoscopic ultrasonography (EUS), like endoscopic retrograde cholangiopancreatography (ERCP), utilizes specialized instruments and accessories. Furthermore, just as an endosonographer obtains additional endoscopic training to ensure competency in EUS, nurses and other assistants also require a specialized skill set. Attention to these issues is important when establishing an EUS practice. This chapter will review the equipment required to perform EUS, provide tips for setting up an EUS examination room, and address issues concerning the assistants who will be helping you with EUS. Spending some extra time thinking about what equipment you will need and how to build an EUS team will make procedures run more efficiently and help you provide the best possible care for your patients.

EUS instruments and other equipment There are essentially two forms of echoendoscope, denoted “radial” and “linear,” based upon the arrangement of the piezoelectric crystals that generate the EUS image. In a linear-array echoendoscope (sometimes referred to as a curvilinear echoendoscope), the crystals are arranged along one side of the endoscope’s tip, generating an image parallel to the long axis of the instrument (Figure 4.1). In a radial-array echoendoscope (sometimes referred to as a transverse array echoendoscope), these crystals are arranged in a band around the shaft of the endoscope, generating an image plane perpendicular to the long axis of the instrument (Figure 4.1). Only the linear-array echoendoscope can be used to guide a needle for tissue sampling or to aid in therapeutic maneuvers like EUS-guided stent placement. A needle viewed with a radial-array echoendoscope would be seen in cross section, and therefore would appear only as a dot in the image, making it impossible to guide safely into the tissue. Deciding on appropriate equipment for an EUS practice requires consideration of several factors. What types of echoendoscopes are you familiar with from your training? If you have trained predominantly with linear echoendoscopes, you may feel a radial echoendoscope is not necessary. Studies have demonstrated that radial and linear echoendoscopes perform similarly in appropriate hands for the staging of upper gastrointestinal (GI) malignancies [1]. While radial-array instruments may detect more lymph nodes per patient [2], linear-array instruments allow for both identification and immediate sampling of nodes, making more efficient use of

time. Moreover, linear instruments detect more pancreatic lesions compared to radial instruments [3]. Ultimately, your choice of ratio of radial to linear echoendoscopes in your purchasing decisions will not be an evidence-based decision so much as one based on your likely case-mix and indications. Those expecting to perform a greater percentage of EUS procedures for tissue acquisition and therapeutic maneuvers than simple image-based diagnostics or luminal cancer staging (e.g., esophageal, rectal) would best opt for a greater number of linear instruments. Table 4.1 lists the instruments currently available for purchase as well as their technical specifications. Pentax, Olympus, and Fujinon each offer both radial and linear echoendoscopes, with minor differences between them. For example, the Olympus instruments have an oblique viewing angle, as the video camera lens is located behind the ultrasound transducer. The Pentax and Fujinon radial instruments have the camera lens in the endoscope’s tip, as in standard forward-viewing endoscopes. Additionally, depending on your choice of echoendoscope, you will need the appropriate processor, as detailed in Table 4.1. The next decision is the total number of echoendoscopes to purchase. There are several factors to consider. How many procedures do you expect to perform in a given year? Will that number grow rapidly once you introduce EUS into your practice? How rapidly can your endoscopes be appropriately disinfected and processed between procedures? How many physicians in your practice will be performing EUS? If you plan to perform EUS cases sporadically throughout the day, sandwiched between screening colonoscopies and routine upper endoscopies, you could consider purchasing one radial and one linear echoendoscope. In this case, the careful spacing of non-EUS cases between endosonography would provide an appropriate turnaround time for reprocessing. Linear echoendoscopes, because of the elevator mechanism, may be best cleaned with two cycles of high-level disinfection [4] and will therefore not return to use for considerably longer than a standard endoscope. If you prefer to cluster several EUS cases into a single half-day or full-day session, you will need at least two instruments and ideally four (one radial and three linear, or just four linear). This will provide greater flexibility while also permitting the scheduling of back to back EUS cases. What about high-resolution ultrasound mini probes? These fragile probes are helpful when evaluating small, subepithelial

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Endoscopic Ultrasonography

Figure 4.1 A

linear-array echoendoscope (top) and an electronic radial-array (or transverse array) echoendoscope (bottom). The piezoelectric crystals on the linear-array echoendoscope are arranged along a single curved surface (arrows). On the electronic radial-array echoendoscope, the crystals are arranged as a band around the side of the instrument’s tip.

lesions in the esophagus, stomach, colon, and rectum, and when staging early cancers, such as T1 esophageal cancers. However, with the availability of higher ultrasound frequencies built into newer generation standard echoendoscopes and the widespread availability of endoscopic mucosal resection or endoscopic submucosal dissection for small lesions, mini probes are not commonly called into use. One exception may be probes used to image the biliary tree, some of which come as a wire-guided system for passage during ERCP [5]. Intra-ductal ultrasound with mini probes may also be helpful in pregnant patients to document clearance of choledocholithiasis during ERCP, thereby limiting the use of fluoroscopy [6]. If you do purchase the probes, be aware of their compatible probe drivers and processors. Table 4.2 includes information about the catheter probe systems offered by Olympus and Fujinon. Pentax does not currently offer a probe system. Echoendoscopes are disinfected and reprocessed using similar equipment as other endoscope reprocessing devices. However, the equipment you purchase may lead to important considerations in

this regard. For instance, if you have other endoscope equipment made by Fujinon and choose to buy EUS equipment from Olympus, you must be sure to have a reprocessor that will accommodate the Olympus echoendoscopes. Be sure to address this issue with your sales representatives when formulating a purchase plan. Finally, give considerable thought to the other accessories and equipment you will use during EUS, such as needles, stents, and microforceps [7]. The number and size of needles you’ll need for both fine needle aspiration (FNA) and fine needle biopsy (FNB) will be based on the types of cases in your practice. Both FNA and FNB can provide adequate tissue for diagnosing solid lesions. In the setting of rapid onsite evaluation (ROSE) of procured specimens, FNA has proven comparable to FNB without the use of ROSE [8]. FNA needles will also be needed for diagnostic aspiration of cystic lesions, so even if you plan to perform FNB exclusively for solid masses, having some FNA needles will be necessary. EUS-guided liver biopsy is typically performed with 19 g needles [9], so even if you prefer 22 or 25 g needles for most diagnostic indications, it is helpful to stock a few 19 g needles as well. When selecting which FNB needle to stock, keep in mind that Franseen and fork-tip needles appear superior in terms of tissue acquisition and diagnostic accuracy, especially 22 g needles, compared with reverse-bevel and Manghini needle designs [10]. However, when ROSE is available, all needle types appear comparable. FNB technique, particularly how the stylet is handled (e.g., “slow pull” method), may need to be considered depending on the needle type you choose to stock [11]. For therapeutic EUS, such as EUS-guided cystgastrostomies, you have a choice of stent sizes in terms of both width and length. Many endosonographers rely on the hot AXIOS system from Boston Scientific for a variety of indications, but keeping a large number of all stent sizes in stock would take up considerable room and would be quite costly. You may want to consider stocking stents with a mix of widths but just one length (e.g., 10 mm). Additional stents, such as plastic double pigtail stents, are also frequently used, so be sure to account for their use if drawing from the supply used for ERCP. It is also important to consider the balloons attached to the echoendoscope tip to achieve acoustic coupling. These balloons are typically made of latex, which can be problematic for patients with a latex allergy. There are latex-free balloons available, so consider stocking a small supply of these as well.

™

Table 4.1 Echoendoscopes currently available. Manufacturer

Model

Ultrasound type

Ultrasound frequencies (MHz)

Ultrasound field of view (degrees)

Insertion tube length (mm)/ diameter (mm)/ accessory channel diameter (mm)

Angulation: up/down; right/left

Video image viewing orientation and angle (degrees)

Compatible ultrasound processor

Pentax

EG-36-J10UR

Radial

5–13

360

1566/12.1/2.4

Linear

5–13

150

1250/11.6/2.8

Linear

5–13

150

1250/12.8/4.0

Forward viewing (0) Oblique viewing (45) Oblique viewing (45)

ARIETTA 850 PX or 65 PX ARIETTA 850 PX or 65 PX ARIETTA 850 PX or 65 PX

Olympus

Slim Linear EG-34-J10U Therapeutic Linear EG-38-J10UT GF-UE160-AL5

150/70 70/70 160/130 120/120 160/130 120/120

Radial

5/6/7.5/10

360

1250/11.8/2.2

GF-UCT180

Linear

5/6/7.5/10

180

1250/12.6/3.7

EG-580UR

Radial

5/7.5/10/12

360

1250/11.4/2.8

Linear

5/7.5/10/12

150

1250/13.9/3.8

Oblique viewing (55) Oblique viewing (55) Forward viewing (0) Oblique viewing (40)

ALOKA ARIETTA 850 ALOKA ARIETTA 850 SonartSU-1

EG-580UT

130/90 90/90 130/90 90/90 190/90 100/100 150/150 120/120

Fujinon

SonartSU-1

Chapter 4: EUS instruments, room setup, and assistants

29

Table 4.2 Ultrasound catheter probes currently available. Manufacturer

Model

Frequency (MHz)

Minimum endoscope working channel diameter (mm)

Working length (cm)

Insertion tube diameter (mm)

Probe driver/ processor

Olympus

UM-3R-3 UM-S20-17S UM-S20-20R-3 UM-G20-29R-3 PB2020-M

20 20 20 20 20

2.8 2.0 2.2 3.2 2.2

205 215 205 205 215

2.5 1.7 2.0 2.9 2.0

MAJ-1720 MAJ-1720 MAJ-1720 MAJ-1720 SP-900

Fujinon

Comments

Compatible with an introducer guide sheath Compatible with an introducer guide sheath Wire-guided for use within ductal structures

Figure 4.2 Telecytology allows for a cytotechnologist to prepare slides and

Figure 4.3 The EUS image is fed from the processor to the room’s primary

identify suspicious findings within the endoscopy unit. The microscopic images can then be shared electronically with an offsite cytopathologist (see inset image on the computer monitor), who can render a diagnosis remotely. (Source: Brian Jacobson)

monitor to increase viewing options. Note that the EUS processor is to the right of the endosonographer to improve access to the instrument panel and keyboard.

If you anticipate having a cytopathologist available for ROSE, consider purchasing a microscope to keep in, or near, the EUS room. Otherwise, the cytopathologist will have to bring one with them each time they are called to assist in a case, a potential disincentive for voluntary participation. If you are purchasing a microscope for this purpose, video microscopes can be connected to in-room monitors and the internet for telecytology (Figure 4.2) [12]. The microscopic images can therefore be displayed on a video monitor in the EUS room for others to view. Microscope video output can also be captured with recording equipment, either for incorporation of still images into a report or for brief video clips used for teaching purposes.

Room setup There are several things to consider when setting up a room for EUS. First, unlike standard endoscopy, which may be performed in several rooms within a single endoscopy unit, EUS requires at least one additional processor, which you may not want to move from room to room. Therefore, if you have several rooms in your endoscopy unit, you must first determine which one(s) will be used for EUS. This is not to say other endoscopic procedures can’t take place in the room; rather, you are simply “setting up shop” in one location to permit the centralization of various EUS equipment and accessories. If your endoscopy unit has a dedicated fluoroscopy room for ERCP, you will need to be able to move the EUS processor in and out of the room as necessary.

There are several reasons not to perform all your EUS cases in a fluoroscopy room. First and foremost, the fluoroscopy unit generally consumes a large amount of space, making it difficult to accommodate all the requirements for EUS. With EUS separated from fluoroscopy, an endoscopy unit can accommodate both ERCP cases and EUS cases simultaneously, providing more scheduling freedom for providers in a multi-person practice. In addition, while most ERCPs can be accomplished in a reasonable amount of time, the occasional procedure may run quite long for technical reasons (e.g., a difficult bile duct cannulation or multiple large stones). Likewise, fluoroscopy may be suddenly required for an unanticipated emergent ERCP. These situations can dramatically hamper your ability to provide timely service for scheduled EUS cases as you wait for your room to become available. The placement of the EUS processor within the endoscopy room also requires some thought. Unlike standard endoscopy, you will need easy access to the processor’s keyboard and instrument panel during the procedure. For standard endoscopy, the processor is usually located behind the endoscopist. During EUS, it is very helpful to have the processor placed to the right of the endoscopist, keeping the instrument’s keypads within easy reach of their right hand. Left-handed endoscopists may want to modify this arrangement (Figure 4.3). An imaging monitor for EUS may be incorporated into the processor itself. In this case, you will want to connect the EUS processor’s video output to your endoscope processor to allow for projection of the EUS images on the room monitor and for

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Endoscopic Ultrasonography

Figure 4.4 A small worktable in the EUS room provides a dedicated

workspace for the processing of cytology samples. Keeping a microscope and cytology reagents in or near the EUS room makes it easier for cytopathology staff to simply stop in to help with a case.

still photo capture of EUS images in the same way you capture endoscopic images. Most systems allow for toggling between the standard endoscopic view, the EUS view, and a combination of the two as a picture-in-picture on the room monitor. If you are able to establish a ROSE protocol in your unit, you will need dedicated space with a video microscope and the equipment required to perform rapid staining of slides (Figure 4.4). When the endosonographer can view the microscopic images at the same time as the cytopathologist, there can be more informed discussion about specimen adequacy and a possible diagnosis. Over time, the endosonographer can also learn the appearance of malignant cells and develop a sense of when an aspirate is likely inadequate. The endosonographer thus becomes more efficient, as they can decide fairly quickly on their own that another FNA/FNB pass will be required, even before hearing it from the cytopathologist.

EUS assistants Like any complicated endoscopic procedure, EUS is best viewed as a team effort, with the endosonographer providing clear, concise instructions to assistants who help complete the procedure safely and efficiently. The endosonographer, for example, will be holding the echoendoscope during tissue sampling, relying on the assistants to prepare the needle and cytological material from the needle after the aspiration/biopsy, and perhaps even to help the cytotechnologist prepare slides for preliminary review. This means additional effort on your part to prepare endoscopy personnel for the tasks required during EUS. Some units may find it more efficient to train only a few nurses and technicians among a larger staff to assist with EUS, ensuring frequent exposure to the techniques used. This will be especially helpful if you perform EUS infrequently. Otherwise, any individual nurse or assistant among a large group may not have sufficient practice to keep their skills honed. Many national and international EUS courses are held each year, and some of these have sessions devoted specifically to nursing and technician roles. These courses often have a “hands-on” component that enables attendees to practice using needles and other devices. Unless you are going to prepare your own echoendoscopes for use, someone

else will need to know how to affix a balloon to the tip and perhaps how to clear air bubbles from the balloon prior to use. Beyond the specialized technical skills required of your EUS nurses and technicians, there are other patient care aspects that should be reviewed as you introduce EUS into your practice. Your EUS team should be aware that patients are often much more anxious about their EUS than standard endoscopic procedures. This is because many are aware of a newly diagnosed or suspected cancer and know that the EUS will be providing information about that cancer’s diagnosis and stage. Many patients have already had an endoscopy or colonoscopy that has led to the EUS and therefore may have fewer concerns about the technical aspects of what they are about to undergo. Rather, they may be looking to the staff for information about cancer management and prognosis or just for someone to help them feel less frightened during a harrowing time. Likewise, as nurses complete the necessary intake questions, there are often anxious family members present, who may have cancer-related questions and concerns. Nurses should be prepared for these issues and have appropriate responses to questions that may arise. Nurses should also be reminded to check for latex allergies, as the detachable balloons used on the tips of echoendoscopes are made of natural rubber latex and can result in severe allergic reactions in susceptible patients. Other important members of the EUS team are the assistants who clean and process your equipment. The fragility of EUS instruments, especially catheter probes, must be stressed to ensure safe handling and maximum instrument life. These assistants must also know how to carefully remove balloons from the echoendoscope tip and be aware of any cleaning steps particular to your specialized instruments. At the same time, the endosonographer with back-to-back cases must be attentive to turnover demands placed on these assistants by physicians performing standard endoscopy simultaneously in a busy unit. It is helpful to communicate with endoscope reprocessing personnel when a particular instrument will be needed in short order. For example, if you know your next case will require the use of an instrument you just used, you should have a mechanism in place for moving that endoscope to the head of the line for cleaning. Proper cleaning of the elevator mechanism of linear echoendoscopes is also vital to ensuring compliance with infection control protocols. Those persons who schedule your EUS cases should also be considered part of your specialized team. EUS, particularly when done for cancer diagnosis or staging, should be scheduled in a timely manner. Patients and referring physicians should not wait more than a few weeks at most. Therefore, schedulers need to know the importance of accommodating these cases. However, when FNA or dilation may be part of the procedure, schedulers must pay careful attention to any anticoagulation issues, especially when cases are booked within a few days of referral. For example, patients should have enough time to discontinue antithrombotic or antiplatelet therapy if necessary. As many EUS referrals can come from outside your institution, your EUS schedulers may also be the ones who request and assemble pertinent patient information, such as office notes and imaging reports, from referring physicians. In this case, schedulers will need guidance about what information you require, including copies of computed tomography (CT) or magnetic resonance imaging (MRI) images, prior to the patient’s EUS appointment. You may also want to establish guidelines about who can direct-book an EUS with you or what types of EUS procedures can be arranged without your prior consideration. For example, you may be comfortable with the direct booking of

Chapter 4: EUS instruments, room setup, and assistants

an EUS for anal sphincter evaluation in the setting of incontinence but may want to personally review the case of someone referred for pancreatic head “fullness” on CT. A discussion of EUS assistants would not be complete without mention of your cytopathology colleagues. First, if you are purchasing a microscope, you may want to seek their advice about what to buy. In addition, if you want someone to help with onsite evaluation of FNA/FNB samples, it is important to discuss this with your pathology department and find out exactly what services are possible. For instance, your pathology department may make a cytopathology fellow available to assist with slide preparation and assessment for sample adequacy but may not provide an attending cytopathologist for an interpretation of results during the procedure. Likewise, you must establish a system for notifying cytology personnel when their assistance will be needed. Some cytopathologists may want to be booked days in advance; others may be able to respond to a page shortly before your case begins. This will undoubtedly depend on specific factors within your institution and may require some negotiations on your part. Cytopathologists interpreting EUS samples may not be accustomed to evaluating this type of material. If EUS is new to your institution, it is a good idea to make a formal presentation about it to your pathology colleagues. Without your clarification of the technical aspects of the procedure, they may not necessarily understand why columnar mucosa is present in your pancreatic aspirates or why squamous cells appear in your mediastinal lymph node aspirates. Review the special stains available to you, such as when looking for glycogen-rich cells or mucin in pancreatic cyst aspirates.

Conclusion EUS is one of the most important advances in GI endoscopy to date and often yields fascinating findings. But establishing an EUS practice requires careful decision-making about what equipment to purchase, how to set up an endoscopy room for efficient EUS, and even how to assemble a specialized team to help perform timely, safe, and accurate procedures. Hopefully, this chapter has provided some insight into that process. The instruments and accessories available for EUS may change from year to year, so this chapter should serve as a starting point but not necessarily a comprehensive source. Other places to look for information about new EUS devices, techniques, and technology include endoscopy-oriented journals, your local endoscope equipment vendors, and national and international endoscopy societies.

31

The American Society for Gastrointestinal Endoscopy (ASGE), for instance, has a special-interest group devoted specifically to EUS. Also, never be shy about asking colleagues in the field for advice. As you build or expand your EUS practice, it is your attention to this initial foundation that will provide your biggest return on investment.

References 1 Siemsen M, Svendsen LB, Kingge U, et al. A prospective randomized comparison of curved array and radial echoendoscopy in patients with esophageal cancer. Gastrointest Endosc 2003;58:671–676. 2 Mattes K, Bounds BC, Collier K, et al. EUS staging of upper GI malignancies: results of a prospective randomized trial. Gastrointest Endosc 2006;64:496–502. 3 Shin EJ, Topazian M, Goggins, MG, et al. Linear-array EUS improves detection of pancreatic lesions in high-risk individuals: a randomized tandem study. Gastrointest Endosc 2015;82:812–818. 4 Day LW, Muthusamy R, Collins J, et al. Multisociety guideline on reprocessing flexible GI endoscopes and accessories. Gastrointest Endosc 2021;93:11–33. 5 Levy MJ, Vazquez-Sequeiros E, Wiersema MJ. Evaluation of the pancreaticobiliary ductal systems by intraductal US. Gastrointest Endosc 2002;55:397–408. 6 Friedel D, Stavropoulos S, Iqbal S, Cappell MS. Gastrointestinal endoscopy in the pregnant woman. World J Gastrointest Endosc 2014;6:156–167. 7 Hwang JH, Aslanian HR, Thosani N, et al. Devices for use with EUS. VideoGIE 2017;3:35–45. 8 Jacobson BC, Bhatt A, Greer KB, et al. ACG Clinical Guideline: diagnosis and management of gastrointestinal subepithelial lesions. Am J Gastroenterol 2023;118:46–58. 9 Diehl DL. Top tips regarding EUS-guided liver biopsy. Gastrointest Endosc 2022;95:368–371. 10 Gkolfakis P, Crinò SF, Tziatzios G, et al. Comparative diagnostic performance of end-cutting fine-needle biopsy needles for EUS tissue sampling of solid pancreatic masses: a network meta-analysis. Gastrointest Endosc 2022;95:1067–1077. 11 Bang JY, Kraill K, Jhala N, et al. Comparing needles and methods of endoscopic ultrasound-guided fine-needle biopsy to optimize specimen quality and diagnostic accuracy for patients with pancreatic masses in a randomized trial. Clin Gastroenterol Hepatol 2021;19:825–835. 12 Yao K, Li Z. Review of different platforms to perform rapid onsite evaluation via telecytology. Cytopathology 2020;5:379–384.

CHAPTER 5

EUS procedure: consent and sedation Michael G. Daniel & Michael L. Kochman Gastroenterology Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

Endoscopic ultrasonography (EUS), endoscopic ultrasonographyguided fine-needle aspiration (EUS FNA), and EUS-guided drainage procedures have potential adverse events and anticipated and unanticipated issues with procedural sedation that do not commonly occur with non-interventional upper endoscopic procedures. This chapter will review the consent process and sedation involved when performing EUS.

Consent The consent process is a continuum of the patient’s understanding of the disease and pathological processes that they have or are suspected of having. It is important that patients scheduled for an EUS examination understand the indications for the procedure and are aware of the risks and benefits of the alternatives, if any exist. The possible complications and potential adverse outcomes should be reviewed and/or discussed at the time of consent. Complications that are specific to or more frequent with EUS will be discussed in this section. Infection There does not appear to be an increased risk of infection after EUS or EUS FNA of solid upper gastrointestinal (GI) tract lesions when compared to regular diagnostic upper endoscopy. Three prospective studies addressing this issue to date have reported a 0–5.8% incidence of bacteremia after EUS FNA; none of the patients with bacteremia had clinical signs of illness [1–3]. This is in comparison to bacteremia rates of 12–22%, and up to 31% after esophageal dilation and esophageal variceal sclerotherapy, which are also not associated with an increased risk of clinical infection in the absence of other risk factors [4–7]. Infection, bacteremia, and sepsis after EUS FNA of mediastinal and pancreatic cystic lesions have been reported in the literature [3, 8–12]. Despite the administration of prophylactic antibiotics, a case of streptococcal sepsis was reported after EUS FNA of a pancreatic cystadenoma, which resolved with additional antibiotic therapy [11]. Wildi et al. reported infection of a mediastinal cyst with beta-hemolytic Streptococcus C after EUS FNA was performed

without prior antibiotic administration; in contrast, infection was not reported in the three other patients in this series, who received antibiotics both before and after EUS FNA of mediastinal cysts [8]. Candidal infection has also been described after EUS FNA of a mediastinal foregut cyst [9]. A large retrospective analysis from our own institution of 266 cases of EUS FNA of pancreatic cystic lesions (antibiotics were not used in 178 of the cases) showed a very low incidence of infectious complications and no protective effect from periprocedural prophylactic antibiotic administration [13]. However, a separate retrospective study at a single large tertiary center demonstrated that a single dose of intra-procedural ceftriaxone in 146 out of 204 patients undergoing EUS FNA of pancreatic cysts was safe and effective at preventing infection [14]. A meta-analysis of EUS FNA adverse events reported one case of perirectal abscess, which resolved with antibiotics, among 193 patients undergoing EUS FNA of perirectal lesions [15]. We have had experience with a febrile episode after FNA of a perirectal cyst, which resolved with 7 days of oral antibiotics. A prospective study of 100 patients who underwent EUS FNAs of solid lesions of the lower GI tract showed low rates of bacteremia but no clinical evidence of infectious complications in any patient [16]. Therapeutic EUS procedures, such as endoscopic ultrasonography-guided biliary drainage (EUS-BD), have also demonstrated low rates of infection. A meta-analysis of the safety of EUS-BD demonstrated a post-procedure infection rate of 3.8% [17]. The American Society for Gastrointestinal Endoscopy (ASGE) recommends the administration of prophylactic antibiotics prior to EUS FNA of pancreatic cystic lesions, although there have been no randomized controlled trials to support this approach [18]. The ASGE guidelines also recommend antibiotic prophylaxis before EUS FNA for mediastinal cysts [18]. A reasonable approach is to administer a fluoroquinolone prior to the procedure and continue for 3 days after the procedure. The American Heart Association (AHA) does not recommend the administration of prophylactic antibiotics solely to prevent infective endocarditis in patients undergoing GI-tract procedures [19]. Antibiotics prior to GI endoscopic procedures to prevent septic arthritis in patients with prosthetic joints are also not recommended, given the extremely low risk of infection and minimal data to support their use [18].

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Chapter 5: EUS procedure: consent and sedation

Bleeding There have been a few reports of bleeding after EUS FNA. Mild intraluminal bleeding occurred in 4% of cases in one study, while another reported a 1.3% rate of extraluminal bleeding after EUS FNA of various lesions [20, 21]. In both studies, no clinically significant symptoms were noted when bleeding occurred. A retrospective study of EUS puncture of solid and cystic pancreatic masses in two tertiary care centers demonstrated a risk of minor bleeding of 15.6% in solid lesions and 8.2% in cystic lesions. The risk of bleeding increased with the use of FNB needles and anticoagulation [22]. However, serious intraluminal and extraluminal bleeding has been reported, with one resulting in death [23]. We tend not to perform EUS FNA in patients with acute pancreatitis (AP) because there appears to be an increased risk of hemorrhage in this setting, and the endoscopic appearance of the pancreas may be misleading as to the size and location of a neoplastic mass lesion. The ASGE guidelines recommend holding thienopyridine and anticoagulation therapy prior to performing EUS FNA, whereas diagnostic EUS may be performed without interruption of antithrombotic therapy [24]. Perforation There are limited data regarding perforation during EUS. A published survey reported a 0.03% rate of perforation during 43 852 upper EUS exams, with one resulting in death [25]. Interestingly, it appears that perforation most often occurs prior to the introduction of the echoendoscope into the esophagus proper and rarely within the GI lumen. A prospective study of 4894 patients undergoing EUS reported a 0.06% rate of cervical esophageal perforation [26]. Perforations occurred using the curvilinear echoendoscope, and all patients with perforations were octogenarians. All perforations were suspected at the time of intubation and were treated surgically. Duodenal perforation has been reported in the literature and anecdotally in other instances [27]. It appears that distorted anatomy due to pancreaticobiliary malignancy or prior surgery may be a predisposing factor. It has been suggested that partially inflating the balloon may facilitate the passage of the echoendoscope and lessen the likelihood of perforation [28]. A meta-analysis of a total of 10 941 patients reported an overall perforation rate of 0.02% [15]. Based on these data, perforation appears to occur at a similar rate as in upper endoscopy, which has a 0.03% perforation rate [29]. It is important to remember that air may track along the needle track when a biopsy is taken and that intraperitoneal air may not reflect true perforation. FNA needle-track seeding EUS FNA resulting in needle-track implantation of malignant cells has been reported in multiple case reports since the first in 2003. A review of 33 cases of needle tract seeding following EUS-FNA or EUS-FNB demonstrated that 27 cases were from pancreatic cancer. The remainder were intrabdominal or intrathoracic tumors. Notably, 29 of the needle-track implantation cases were pancreatic body and tail lesions. No pancreatic head lesions were reported. This is likely due to the removal of the primary foci and pancreatico-duodenal tract with surgical resection [30]. Conversely, surgical resection of body and tail lesions is unlikely to excise the track used for sampling. Needle track implantation occurs outside of the pancreatic lesions. Seeding of the transgastric tract occurred after EUS FNA of a malignant perigastric lymph node in a patient with metastatic melanoma [31]. This was detected 6 months after EUS FNA at the time of laparotomy for excision of the malignant node. Needle-tract implantation of the esophageal

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wall occurred after EUS FNA of a malignant mediastinal lymph node in a patient with gastric cancer [32]. Despite these reports, needle-track implantation of malignant cells resulting in clinically significant metastases is extremely rare. Esophageal dilation for facilitation of EUS evaluation A compromise of the esophageal lumen from esophageal cancer may prevent advancement of the echoendoscope through the lesion into the stomach, which also precludes visualization of the celiac axis and distant lymph nodes. Early studies reported esophageal perforation rates of up to 24% upon aggressive dilation of high-grade malignant strictures to allow passage of the echoendoscope [33, 34]. However, more recent studies have shown that less aggressive dilation is safe and effective [35, 36]. Pfau et al. reported no perforations after dilation of malignant esophageal strictures using three 1mm sequentially larger balloons or Savary dilators under the site of first resistance; using this technique, the echoendoscope was able to cross the stricture in 85% of patients studied [35]. In the era of neoadjuvant chemoradiotherapy and computed tomography–positron emission tomography (CT-PET), there is less need for dilation of an esophageal tumor solely for staging purposes. Pancreatitis There is a risk of pancreatitis if EUS FNA of the pancreas is performed. Scant data exist, and almost all are retrospective, most likely underestimating the overall risk. Rates of pancreatitis after pancreatic EUS FNA have ranged from 0 to 2% [11, 23, 37–39]. In a survey of centers offering training in EUS, pancreatitis was reported in 0.29% of cases (range 0–2.35%) after EUS FNA of solid pancreatic masses [40]. A meta-analysis of 8246 cases found a pancreatitis rate of 0.44%, with most cases being mild (75%), but with one case of severe pancreatitis leading to death [15]. Anecdotally, it appears that the risk is increased in those who have normal pancreatic tissue traversed to sample benign lesions or neuroendocrine tumors. Bile peritonitis Bile peritonitis is a rare complication of EUS FNA, although it is difficult to confidently estimate its true incidence. It has been reported in case series after inadvertent puncture of the common bile duct following EUS FNA of a pancreatic head mass or after puncture of the gallbladder in an attempt to identify patients with microlithiasis [41, 42]. A meta-analysis that included 383 patients in 11 studies evaluated patients undergoing EUS FNA for biliary stricture and gallbladder tumors and demonstrated one case of biliary peritonitis that resulted in death [43]. Specific issues related to celiac plexus neurolysis Celiac plexus neurolysis (CPN) can be performed for palliation of pain in pancreatic cancer patients by injecting absolute alcohol and a local anesthetic through an FNA needle under EUS guidance. Celiac plexus blockade (CPB) is employed in the management of pain from benign pancreatic diseases and involves the delivery of a combination of a steroid and a local anesthetic under EUS guidance. Percutaneous and surgical CPN for pain control have been associated with serious complications, such as lower-extremity weakness, paresthesia, and paraplegia [44, 45]. Adverse events associated with EUS-guided CPN and CPB include transient diarrhea, transient orthostasis, a transient increase in pain, and abscess formation [46, 47]. A retrospective analysis

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of 189 cases of CPB and 31 cases of CPN reported one patient with asymptomatic hypotension after CPN, one patient with a retroperitoneal abscess after CPB, and two patients with severe, self-limited post-procedural pain after CPB [48]. One prospective study in patients with inoperable pancreatic cancer undergoing transgastric EUS-guided CPN reported minor complications, such as postural hypotension (20%), diarrhea (17%), and exacerbation of pain (9%) [49]. Two prospective studies have demonstrated a rare risk of neurologic impairment with lower limb weakness as well as a patient who developed severe irreversible paralysis related to spinal cord infarction [50, 51]. Intravenous volume loading and pharmacological therapy appear to decrease the incidence of adverse events. There have been case reports of severe ischemia-related complications, including injury to and perforation of the gastric wall and even complete thrombosis of the celiac axis with resultant extensive visceral infarcts [52, 53]. Specific issues related to EUS-guided biliary and pancreatic access EUS-guided biliary and pancreatic access has evolved as a salvage technique used to access the biliary and pancreatic ducts in order to perform a variety of therapeutic interventions, ranging from transgastric or transduodenal drainage for biliary obstruction to rendezvous procedures to aid with transpapillary access to the biliary or pancreatic ducts when conventional methods fail. Complications associated with EUS-guided interventions range from 3.4 to 21% in the largest series and include bile leak, peritonitis, cholangitis, pneumoperitoneum, bleeding, and stent migration [54–57].

Sedation Sedation plays an important role in the performance of EUS, as it does in regular endoscopic procedures. The possible adverse effects of sedation need to be discussed with the patient at the time of consent since, overall, these account for nearly half of all endoscopic complications [58]. Moderate sedation used to be the most common sedation method for EUS procedures. This paradigm is changing in favor of monitored anesthesia care (MAC). Prospective studies have demonstrated that MAC results in shorter recovery times, increased patient satisfaction, and reduces the risk of oversedation [59]. The most commonly used sedative for moderate sedation is a benzodiazepine with or without an opiate for EUS procedures. Adjunctive medications such as diphenhydramine, droperidol, ketamine, and promethazine have also been utilized. For deep sedation, propofol is often used during EUS. Regardless of what type of sedation is used, a greater amount of medication may be required for EUS due to the often-increased length of the procedure compared to regular upper endoscopy. Pre-procedure assessment The goal of the pre-procedure assessment is to identify aspects of the patient’s medical history and physical examination that could have a deleterious impact on the outcome of administering sedation. The presence of conditions such as neurological disorders and cardiopulmonary diseases, including sleep apnea, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD), should be noted as part of this assessment. Prior adverse reactions to anesthesia, medication allergies, and a history of drug or alcohol

abuse should also be ascertained. In addition, each patient should be risk stratified based on the American Society of Anesthesiologists (ASA) physical status classification system. Consideration should be given to employing anesthesia assistance in sedating ASA class IV or V patients, those who have previously failed conscious sedation, and those who have had an adverse reaction to sedation. Benzodiazepines Benzodiazepines bind to the gamma-aminobutyric acid (GABAA ) receptor within the cerebral cortex. They have several pharmacological effects, including sedation, amnesia, and anxiolysis. Their side effects are generally dose-dependent, and include respiratory depression and hypopnea, which may lead to apnea, hypoxia, hypotension, and paradoxical reactions such as agitation. Midazolam is currently the preferred benzodiazepine for sedation during endoscopic procedures because of its short onset and duration of action. It undergoes both hepatic and renal metabolism. The typical starting dose is 1 mg intravenously over 1–2 minutes. Additional doses of 1–2 mg can be given every 2 minutes until adequate sedation is achieved. Lower doses of midazolam may be necessary with concurrent opioid use due to the synergistic interaction between the two. Diazepam, which is available in intravenous and oral forms, undergoes hepatic metabolism to a metabolite with slow clearance. This accounts for its longer duration of effect compared to midazolam. The initial dose is 5–10 mg over 1 minute. Additional doses can be given at 5-minute intervals. Injection-site discomfort is common after intravenous diazepam administration; this, along with its slower onset of action and longer duration of effect, makes it less desirable than midazolam. Flumazenil, a GABA-A receptor blocker, reverses the central effects of benzodiazepines and should be used in cases of oversedation. It is less effective in reversing benzodiazepine-induced respiratory depression. It is usually administered as incremental intravenous boluses of 0.1–0.3 mg, but it can also be given as an infusion of 0.3–0.5 mg per hour if prolonged usage is anticipated. The occurrence of resedation should be carefully looked for since its effects have a shorter duration than those of midazolam, and it has a half-life of only approximately 1 hour. Opiates Meperidine and fentanyl are the most commonly used opioids for endoscopic procedures. Both bind to opioid receptors in the central nervous system (CNS), thereby altering pain perception. Both can lead to sedation and respiratory depression if given in larger amounts. Meperidine is an opioid that is converted by the liver to normeperidine, a metabolite that is several times more potent. Meperidine has an onset of action of 3–6 minutes and is administered in doses of 25–50 mg slowly over 1–2 minutes. The combination of meperidine and monoamine oxidase inhibitors should be avoided due to the increased risk of developing serotonin syndrome, which can manifest as mental status changes, autonomic instability, and neuromuscular hyperactivity. Meperidine should also be prescribed with caution in patients with renal insufficiency, due to the accumulation of metabolites associated with seizures, and it is rarely used currently. Fentanyl is an entirely synthetic opioid that is structurally similar to meperidine. Allergic reactions and cross-reactivity with reactions to other opiates should not occur. The initial dose given for endoscopic procedures is 50–100 mcg; supplemental doses of 25 mcg can

Chapter 5: EUS procedure: consent and sedation

be given every 2–5 minutes until the desired effect is achieved. Large doses of fentanyl have been reported to cause chest wall rigidity from skeletal muscle hypertonicity. Fentanyl is considered the preferred opiate for conscious sedation, given its rapid onset of action and lack of toxic metabolites. Naloxone is an opioid antagonist that can be given to reverse the CNS effects of opiate overdose, including respiratory depression and analgesia. It has an onset of action in 1–2 minutes and a half-life of 30–45 minutes. The recommended dose is 0.2–0.4 mg intravenously every 2–3 minutes, as needed. Additional doses may be necessary since both meperidine and fentanyl have a longer half-life than naloxone. Adjuncts to benzodiazepines and opiates Several agents have been studied to potentiate the effects of benzodiazepines and opiates. Diphenhydramine, a histamine-1 antagonist, has CNS depressive effects at higher doses, theoretically making it a useful adjunct to benzodiazepines and opiates. Although it has not been formally studied in the setting of EUS, one trial using either 50 mg of diphenhydramine intravenously or placebo in addition to midazolam and meperidine for colonoscopy showed improved patient sedation and amnesia in the diphenhydramine group [60]. Droperidol is a butyrophenone neuroleptic with antiemetic and antianxiety effects that can be used for conscious sedation in addition to benzodiazepines and opioids. It has been shown to be a useful adjunct for difficult-to-sedate patients [61]. However, its use has been tempered more recently by a black box warning following reports of cardiac events, specifically QT prolongation and torsade de pointes [62]. Ketamine is a phencyclidine derivative that inhibits the N-methyl D-aspartate (NMDA) receptor. It possesses both analgesic and sedative properties and generally does not result in cardiovascular or respiratory depression. Ketamine has a very short onset of action of less than 1 minute and a short duration of action of 15–30 minutes [63]. A dose-dependent stimulation of the sympathetic nervous system manifesting as elevated heart rate and blood pressure is seen with ketamine. An emergence reaction, consisting of dreams, hallucinations, and delirium, can occur in adults. The use of ketamine in adults is limited, and most studies of this agent for endoscopic sedation have been in the pediatric population. Promethazine is a phenothiazine that is often used for its antiemetic effects. It has α1-adrenergic inhibitory effects and competitively inhibits the histamine-1 receptor. Promethazine has been studied to a limited extent as a possible adjunct for sedation in endoscopic procedures [64]. Its onset of action is typically around 5 minutes, and it has a half-life of 9–16 hours. The typical dose is 12.5–25.0 mg intravenously. Side effects include hypotension, respiratory depression, neuroleptic malignant syndrome, and extrapyramidal effects. Propofol The use of propofol, an ultra-short-acting hypnotic and amnestic agent with minimal analgesic properties, has grown in popularity in recent years. Propofol is lipophilic and rapidly crosses the blood–brain barrier (BBB) to cause depression in consciousness, likely via potentiation of GABA-A receptors in the brain [65]. Although published studies on the use of propofol for standard upper and lower endoscopic procedures have not consistently demonstrated clinical benefits, propofol has been shown to be beneficial in prolonged procedures such as endoscopic retrograde cholangiopancreatography (ERCP) and EUS. A study of patients

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undergoing ERCP or EUS found that, compared to midazolam and meperidine, propofol produced significantly shorter recovery times and a good quality of sedation [66]. A prospective, randomized study comparing the use of propofol and meperidine/midazolam for sedation in ERCP or EUS showed significantly faster induction, faster recovery, and higher post-procedure satisfaction with propofol [67]. Complication rates with propofol and the meperidine/midazolam combination for EUS have not been shown to significantly differ [68]. Propofol has no reversal agent. Procedural monitoring All patients receiving sedation for EUS must have monitoring of their vital signs throughout the procedure. Blood pressure, oxygen saturation, pulse, and respiratory rate should be monitored during the procedure and recovery period. Capnography, used to monitor end-tidal carbon dioxide, can be employed as a superior way of evaluating respiration and improving patient safety. The use of capnography has been shown to reduce the frequency of severe hypoxemia and apnea in patients undergoing EUS [69]. Bispectral index monitoring, which quantifies the depth of sedation by measuring electroencephalographic (EEG) waveforms, has been used in some centers but does not appear to correlate well with mixed analgesic and sedative regimens. Post-procedural monitoring Sedated patients need to be observed after EUS for adverse effects from the sedation or the procedure itself. Blood pressure, oxygenation, pain, and level of consciousness need to be assessed at regular intervals during the recovery period. Patients receiving naloxone or flumazenil should be monitored for an extended period in the event that resedation develops, since the half-life of these reversal agents is shorter than that of opioids and benzodiazepines. Several systems for assessing a patient’s suitability for discharge have been described. One is the Aldrete scoring system, which evaluates the patient’s activity, respiration, oxygen saturation, blood pressure, and level of consciousness [70]. Patients should be instructed not to drive, operate heavy machinery, or sign important documents.

Conclusion The use of FNA and injection techniques has expanded the armamentarium of diagnostic and therapeutic EUS. As a result, the role of EUS has expanded for both GI and non-GI disease processes. The consent process for EUS is a multistep process, similar in nature to that of other endoscopic procedures, with FNA and therapeutic EUS potentially carrying additional risks to the patient. FNA may increase the risk of bleeding, infection, and pancreatitis, and when the performance of injection therapy or drainage procedures is anticipated, there are specific additional risks that merit discussion with the patient before the procedure.

References 1 Levy MJ, Norton ID, Wiersema MJ, et al. Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNA. Gastrointest Endosc 2003;57(6):672–678. 2 Barawi M, Gottlieb K, Cunha B, et al. A prospective evaluation of the incidence of bacteremia associated with EUS-guided fine-needle aspiration. Gastrointest Endosc 2001;53(2):189–192.

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3 Janssen J, Konig K, Knop-Hammad V, et al. Frequency of bacteremia after linear EUS of the upper GI tract with and without FNA. Gastrointest Endosc 2004;59(3):339–344. 4 Zuccaro G Jr., Richter JE, Rice TW, et al. Viridans streptococcal bacteremia after esophageal stricture dilation. Gastrointest Endosc 1998;48(6):568–573. 5 Nelson DB, Sanderson SJ, Azar MM. Bacteremia with esophageal dilation. Gastrointest Endosc 1998;48(6):563–567. 6 Hirota WK, Wortmann GW, Maydonovitch CL, et al. The effect of oral decontamination with clindamycin palmitate on the incidence of bacteremia after esophageal dilation: a prospective trial. Gastrointest Endosc 1999;50(4):475–479. 7 Botoman VA, Surawicz CM. Bacteremia with gastrointestinal endoscopic procedures. Gastrointest Endosc 1986;32(5):342–346. 8 Wildi SM, Hoda RS, Fickling W, et al. Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA. Gastrointest Endosc 2003;58(3):362–368. 9 Ryan AG, Zamvar V, Roberts SA. Iatrogenic candidal infection of a mediastinal foregut cyst following endoscopic ultrasound-guided fine-needle aspiration. Endoscopy 2002;34(10):838–839. 10 Wiersema MJ, Vilmann P, Giovannini M, et al. Endosonographyguided fine-needle aspiration biopsy: diagnostic accuracy and complication assessment. Gastroenterology 1997;112(4):1087–1095. 11 Williams DB, Sahai AV, Aabakken L, et al. Endoscopic ultrasound guided fine needle aspiration biopsy: a large single centre experience. Gut 1999;44(5):720–726. 12 Diehl DL, Cheruvattath R, Facktor MA, Go BD. Infection after endoscopic ultrasound-guided aspiration of mediastinal cysts. Interact Cardiovasc Thorac Surg 2010;10(2):338–340. 13 Guarner-Argente C, Shah P, Buchner A, et al. Use of antimicrobials for EUS-guided FNA of pancreatic cysts: a retrospective, comparative analysis. Gastrointest Endosc 2011;74(1):81–86. 14 Klein A, Rose Q, Nagubandi S, et al. Single-dose intra-procedural ceftriaxone during endoscopic ultrasound fine-needle aspiration of pancreatic cysts is safe and effective: results from a single tertiary center. Ann Gastroenterol 2017;30(1):1–5 15 Wang KX, Ben QW, Jin ZD, et al. Assessment of morbidity and mortality associated with EUS-guided FNA: a systematic review. Gastrointest Endosc 2011;73(2):283–290. 16 Levy MJ, Norton ID, Clain JE, et al. Prospective study of bacteremia and complications with EUS FNA of rectal and perirectal lesions. Clin Gastroenterol Hepatol 2007;5(6):684–689. 17 Dhindsa BS, Mashiana HS, Dhaliwal A, et al. EUS-guided biliary drainage: a systemic review and meta-analysis. Endosc Ultrasound 2020;9(2):101–109. 18 ASGE Standards of Practice Committee, Khashab M, Chithadi KV, Acosta R, et al. Antibiotic prophylaxis for GI endoscopy. Gastrointest Endosc 2015;81(1):81–89. 19 Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis: guidelines from the American Heart Association: a guideline from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Circulation 2007;116(15):1736–1754. 20 Voss M, Hammel P, Molas G, et al. Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses. Gut 2000;46(2):244–249. 21 Affi A, Vazquez-Sequeiros E, Norton ID, et al. Acute extraluminal hemorrhage associated with EUS-guided fine needle aspiration:

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

frequency and clinical significance. Gastrointest Endosc 2001; 53(2):221–225. Razpotnik M, Bota S, Kutilek M, et al. The bleeding risk after endoscopic ultrasound-guided puncture of pancreatic masses. Scand J Gastroenterol 2021;56(2):205–210. Gress FG, Hawes RH, Savides TJ, et al. Endoscopic ultrasoundguided fine-needle aspiration biopsy using linear array and radial scanning endosonography. Gastrointest Endosc 1997;45(3): 243–250. ASGE Standards of Practice Committee, Acosta RD, Abraham NS, Chandrasekhara V, et al. The management of antithrombotic agents for patients undergoing GI endoscopy. Gastrointest Endosc 2016;83(1):3–16. Das A, Sivak MV Jr., Chak A. Cervical esophageal perforation during EUS: a national survey. Gastrointest Endosc 2001; 53(6):599–602. Eloubeidi MA, Tamhane A, Lopes TL, et al. Cervical esophageal perforations at the time of endoscopic ultrasound: a prospective evaluation of frequency, outcomes, and patient management. Am J Gastroenterol 2009;104(1):53–56. Raut CP, Grau AM, Staerkel GA, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration in patients with presumed pancreatic cancer. J Gastrointest Surg 2003;7(1):118–126; discussion 127–128. Kadish SL, Ginsberg GG, Kochman ML. Safe maneuvering of echoendoscopes in patients with distorted duodenal anatomy. Gastrointest Endosc 1995;42(3):278. Silvis SE, Nebel O, Rogers G, et al. Endoscopic complications: results of the 1974 American Society for Gastrointestinal Endoscopy Survey. JAMA 1976;235(9):928–930. Gao RY, Wu BH, Shen XY, et al. Overlooked risk for needle tract seeding following endoscopic ultrasound-guided minimally invasive tissue acquisition. World J Gastroenterol 2020 26(40): 6182–6194 Shah JN, Fraker D, Guerry D, et al. Melanoma seeding of an EUS-guided fine needle track. Gastrointest Endosc 2004;59(7): 923–924. Doi S, Yasuda I, Iwashita T, et al. Needle tract implantation on the esophageal wall after EUS-guided FNA of metastatic mediastinal lymphadenopathy. Gastrointest Endosc 2008;67(6):988–990. Catalano MF, Van Dam J, Sivak MV Jr., Malignant esophageal strictures: staging accuracy of endoscopic ultrasonography. Gastrointest Endosc 1995;41(6):535–539. Van Dam J, Rice TW, Catalano MF, et al. High-grade malignant stricture is predictive of esophageal tumor stage: risks of endosonographic evaluation. Cancer 1993;71(10):2910–2917. Pfau PR, Ginsberg GG, Lew RJ, et al. Esophageal dilation for endosonographic evaluation of malignant esophageal strictures is safe and effective. Am J Gastroenterol 2000;95(10):2813–2815. Wallace MB, Hawes RH, Sahai AV, et al. Dilation of malignant esophageal stenosis to allow EUS guided fine-needle aspiration: safety and effect on patient management. Gastrointest Endosc 2000;51(3):309–313. O’Toole D, Palazzo L, Arotçarena R, et al. Assessment of complications of EUS-guided fine-needle aspiration. Gastrointest Endosc 2001;53(4):470–474. Gress F, Michael H, Gelrud D, et al. EUS-guided fine-needle aspiration of the pancreas: evaluation of pancreatitis as a complication. Gastrointest Endosc 2002;56(6):864–867. Eloubeidi MA, Chen VK, Eltoum IA, et al. Endoscopic ultrasoundguided fine needle aspiration biopsy of patients with suspected

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40

41 42

43

44

45 46

47 48

49

50

51

52

53

54

55

pancreatic cancer: diagnostic accuracy and acute and 30-day complications. Am J Gastroenterol 2003;98(12):2663–2668. Eloubeidi MA, Gress FG, Savides TJ, et al. Acute pancreatitis after EUS-guided FNA of solid pancreatic masses: a pooled analysis from EUS centers in the United States. Gastrointest Endosc 2004;60(3):385–389. Chen HY, Lee CH, Hsieh CH. Bile peritonitis after EUS-guided fine-needle aspiration. Gastrointest Endosc 2002;56(4):594–596. Jacobson BC, Waxman I, Parmar K, et al. Endoscopic ultrasoundguided gallbladder bile aspiration in idiopathic pancreatitis carries a significant risk of bile peritonitis. Pancreatology 2002;2(1):26–29. Sadeghi A, Mohamadnejad M, Islami F, et al. Diagnostic yield of EUS-guided FNA for malignant biliary stricture: a systemic review and meta-analysis. J Gastrointest Endosc 2016 83(2):290–298. Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg 1995;80(2):290–295. Hayakawa J, Kobayashi O, Murayama H. Paraplegia after intraoperative celiac plexus block. Anesth Analg 1997;84(2):447–448. Gress F, Schmitt C, Sherman S, et al. Endoscopic ultrasound-guided celiac plexus block for managing abdominal pain associated with chronic pancreatitis: a prospective single center experience. Am J Gastroenterol 2001;96(2):409–416. Hoffman BJ. EUS-guided celiac plexus block/neurolysis. Gastrointest Endosc 2002;56(Suppl 4):S26–S28. O’Toole TM, Schmulewitz N. Complication rates of EUS-guided celiac plexus blockade and neurolysis: results of a large case series. Endoscopy 2009;41(7):593–597. Gunaratnam NT, Sarma AV, Norton ID, Wiersema MJ. A prospective study of EUS-guided celiac plexus neurolysis for pancreatic cancer pain. Gastrointest Endosc 2001;54(3):316–324. Kamata K, Kinoshita M, Kinoshita I, et al. Efficacy of EUS-guided celiac plexus neurolysis in combination with EUS-guided celiac ganglia neurolysis for pancreatic cancer-associated pain: a multicenter prospective trial. Int J Clin Oncol 2022;27:1196–1201. Levy MJ, Gleeson FC, Topazian MD, et al. Combined celiac ganglia and plexus neurolysis shortens survival, without benefit, vs plexus neurolysis alone. CGH. 2019;17(4):728–738. Loeve US, Mortensen MB. Lethal necrosis and perforation of the stomach and the aorta after multiple EUS-guided celiac plexus neurolysis procedures in a patient with chronic pancreatitis. Gastrointest Endosc 2013;77(1):151–152. Gimeno-Garcia AZ, Elwassief A, Paquin SC, Sahai AV. Fatal complication after endoscopic ultrasound-guided celiac plexus neurolysis. Endoscopy 2012;44(Suppl 2):E267–E267. UCTN:E267-00321309709. Park Do H, Jang JW, Lee SS, et al. EUS-guided biliary drainage with transluminal stenting after failed ERCP: predictors of adverse events and long-term results. Gastrointest Endosc 2011;74(6):1276–1284. Maranki J, Hernandez AJ, Arslan B, et al. Interventional endoscopic ultrasound-guided cholangiography: long-term experience of an emerging alternative to percutaneous transhepatic cholangiography. Endoscopy 2009;41(6):532–538.

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56 Khashab MA, Valeshabad AK, Modayil R, et al. EUS-guided biliary drainage by using a standardized approach for malignant biliary obstruction: rendezvous versus direct transluminal techniques (with videos). Gastrointest Endosc 2013;78(5):734–741. 57 Dhir V, Bhandari S, Bapat M, Maydeo A. Comparison of EUS-guided rendezvous and precut papillotomy techniques for biliary access (with videos). Gastrointest Endosc 2012;75(2):354–359. 58 Waring JP, Baron TH, Hirota WK, et al. Guidelines for conscious sedation and monitoring during gastrointestinal endoscopy. Gastrointest Endosc 2003;58(3):317–322. 59 Early DS, Lightdale JR, Vargo JJ, et al. Guidelines for sedation and anesthesia in GI endoscopy. Gastrointest Endosc 2018;87(2):327–337. 60 Tu RH, Grewall P, Leung JW, et al. Diphenhydramine as an adjunct to sedation for colonoscopy: a double-blind randomized, placebo-controlled study. Gastrointest Endosc 2006;63(1):87–94. 61 Cohen J, Haber GB, Dorais JA, et al. A randomized, double-blind study of the use of droperidol for conscious sedation during therapeutic endoscopy in difficult to sedate patients. Gastrointest Endosc 2000;51(5):546–551. 62 Faigel DO, Metz DC, Kochman ML. Torsade de pointes complicating the treatment of bleeding esophageal varices: association with neuroleptics, vasopressin, and electrolyte imbalance. Am J Gastroenterol 1995;90(5):822–824. 63 Green SM, Li J. Ketamine in adults: what emergency physicians need to know about patient selection and emergence reactions. Acad Emerg Med 2000;7(3):278–281. 64 Findlay CW Jr., The value of promethazine hydrochloride in preparing patients for peroral endoscopy. Am Rev Respir Dis 1962;86:272–274. 65 Trapani G, Altomare C, Liso G, et al. Propofol in anesthesia: mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem 2000;7(2):249–271. 66 Vargo JJ, Zuccaro G Jr., Dumot JA, et al. Gastroenterologistadministered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial. Gastroenterology 2002;123(1):8–16. 67 Dewitt J, McGreevy K, Sherman S, Imperiale TF. Nurseadministered propofol sedation compared with midazolam and meperidine for EUS: a prospective, randomized trial. Gastrointest Endosc 2008;68(3):499–509. 68 Nayar DS, Guthrie WG, Goodman A, et al. Comparison of propofol deep sedation versus moderate sedation during endosonography. Dig Dis Sci 2010;55(9):2537–2544. 69 Qadeer MA, Vargo JJ, Dumot JA, et al. Capnographic monitoring of respiratory activity improves safety of sedation for endoscopic cholangiopancreatography and ultrasonography. Gastroenterology 2009;136(5):1568–1576; quiz 1819–1820. 70 Chung F, Chan VW, Ong D. A post-anesthetic discharge scoring system for home readiness after ambulatory surgery. J Clin Anesth 1995;7(6):500–506.

CHAPTER 6

The EUS report Jose G. de la Mora-Levy 1 & Michael J. Levy 2 1 Endoscopy 2 Division

Unit, Gastroenterology Department, Instituto Nacional de Cancerologia, Mexico City, Mexico of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

Reports form the essential link in medical practice. They are used by health care providers as a tool to convey patient information. Clear and accurate reporting is essential to providing appropriate care and minimizing medico-legal risk. According to Merriam-Webster, a report is a document: “an original or official paper relied on as the basis, proof, or support of something” (www.merriam-webster .com). To report is “to give a formal or official account or statement of; to return or present a matter referred for consideration with conclusions or recommendation” (www.merriam-webster.com). While these terms and the intent of the report are clear, they are often overlooked, rendering reports inadequate in terms of clarity, detail, or completeness. Professional societies are increasingly recognizing the importance of establishing minimal reporting standards, including the American Society for Gastrointestinal Endoscopy (ASGE), which has published its recommendations for the minimal elements that an endoscopy report should include (Table 6.1). While alternative versions exist, most follow a similar structure and convey the same general information.

Roles of the endoscopic report While the main function of the report is to serve as a clinical decision-making tool, it plays other roles in health care, too. It is often used to assess quality control efforts, to facilitate clinical research, and for administrative and legal purposes. Accordingly, various aspects of the report have different significance depending on the particular interest of the reviewer. Clinical care When considering which details to include in an endoscopic ultrasonography (EUS) report, one must be mindful of the medical specialists and subspecialists who are likely to participate in the patient’s care. While certain information is germane to all providers, there are specific details that may have variable importance depending on one’s area of expertise – whether primary care physician, gastroenterologist, pulmonologist, radiotherapist, surgeon, radiologist, or oncologist.

Quality control Quality is measured in a number of ways. Patient-derived measures include quality of life, cost-effectiveness, patient satisfaction, morbidity, and mortality. Some of these are derived directly from the information contained in reports and related databases. In this setting, details pertaining to outcomes, such as procedure-related morbidity, might be more important than patient demographics or findings. Specific quality indicators for EUS have been established, and these rely heavily on proper reporting. Procedure findings that are used as quality indicators vary based on the specific context and goals of the examination (e.g., identification of key structures, such as celiac lymph nodes during esophageal cancer staging [1]), and as the role of EUS evolves, other indicators are used, such as the diagnostic accuracy of EUS-guided fine-needle aspiration (FNA) [2] or ancillary procedures such as cytologic diagnoses using defined criteria [3]. Clinical research Clinical research largely depends on the information contained within reports. Accurate and detailed reporting is necessary, but this takes time and dedication. Prospectively conducted studies allow for complete and accurate reporting and avoid the need for subjective interpretation of findings. For example, when reporting the T stage for an esophageal cancer, one may cite uncertainty around whether the tumor is T2 or T3 and so make no clear designation. As such, retrospectively collected data from established databases may be incomplete or inaccurate. Prospective study and reporting usually require specific designation of the T stage, thereby facilitating data retrieval. In essence, the information obtained from a database is only as good as the reports it comes from. As EUS is a rapidly evolving procedure, with new technology such as elastography [4] appearing and new techniques being developed [5], the need for quality reports that can facilitate research is very high. Administrative and legal issues Administrative and management decisions are frequently guided by data derived from reports. Among other activities, patient,

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Table 6.1 ASGE recommendations for elements of an endoscopy report. Source: Jacobson BC, Chak A, Hoffman B, et al. 2006 [2]. Quality indicators for endoscopic ultrasonography. 101:808–901. Reproduced with permission of Am J Gastroenterol.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

Date of procedure Patient identification data Endoscopist(s) Assistant(s) Documentation of relevant patient history and physical examination Indication of informed consent Endoscopic procedure Indication(s) Types of endoscopic instrument Medication (anesthesia, analgesia, sedation) Anatomic extent of examination Limitation(s) of examination Tissue or fluid samples obtained Findings Diagnostic impression Results of therapeutic intervention (if any) Complications (if any) Disposition Recommendations for subsequent care

personnel, and procedure scheduling, supply purchasing, and planned instrument repairs are impacted by key elements in a report. Many of the newer generations of instruments incorporate software that keeps track of some of these variables, including patient demographics, instrument use, and procedure type and duration. From a legal perspective, a detailed and comprehensive procedure report is a vital risk-management tool that can be used to defend or prosecute a malpractice suit. The legal system takes the stance that, “If it isn’t documented, it didn’t happen,” and, “If it is documented, then it must have happened.” Detailed, precise, and accurate reporting is critical to avoiding misrepresentation. Inaccuracy or lack of completeness in this regard can be used against hospitals or physicians confronting a lawsuit. It is imperative that a report, whether written or dictated, not be modified, unless typing or clerical errors are noted. Reporting software should stamp the date and time at which the report is initially prepared, subsequently edited, and signed.

Evolution of the medical report Medical reports, including endoscopic reports, have evolved from a somewhat anecdotal account of events to an objective set of data. Handwritten reports have given way to dictated notes and, more recently, to computer software-generated electronic reports. However, as of 1999, a survey discovered that 80% of gastroenterologists in the United States were still using handwritten or dictated reports [5]. In 2001, an international survey of distinguished endoscopists from Latin America, the Middle East, Asia, Africa, and Europe found that most still wrote or dictated reports, or utilized custom software adapted from commercial databases (e.g., Excel or Access) and maintained their data in local databases [6]. Although undocumented, most hospitals and ambulatory care centers in the United States now use some type of electronic medical record.

Standard terminology and structured reporting Radiologists and pathologists were pioneers in the use of standardized terminology and structured reporting. SNOMED

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(Systematized Nomenclature of Medicine) is used worldwide in a variety of settings and includes language associated with Health Level 7 (HL7) and the Digital Imaging and Communications in Medicine (DICOM) standards commonly used in gastroenterology. Currently, this system provides insufficient detail to be used for EUS reporting. The first dedicated effort to design a universally accepted language for gastrointestinal (GI) endoscopy emerged from Europe in 1989, and was published as the OMED (Organization Mundial D’Endoscopie Digestif) terminology [7]. The idea was to create a widely accepted list of terms with broad applicability in reporting the majority of cases (present in >1% of endoscopic examinations). Terminology was arranged in hierarchical order: headings, terms, attributes, values, and sites. Preliminary use of the OMED system showed that it applied to 95% of routine upper endoscopies, colonoscopies, and cholangiopancreatographies [8]. In a retrospective analysis of >10 000 cases from six European centers, this system accurately described 87% of procedure indications, 94% of findings, and 91% of diagnoses [9]. The remaining findings required use of free text (5%). After further revision, the Minimal Standard Terminology (MST) system was validated [10], but, despite some use in Europe, it has not gained wide acceptance in the United States. However, some newer software systems are using modifications of the MST. Standard terminology Most of the findings and descriptors associated with EUS differ from those used in other endoscopic procedures. Therefore, a panel of expert endosonographers from Europe, Japan, and the United States attempted in 1997 to introduce MST for EUS (MST EUS Version 1.0) [11]. Their first step was to identify widely accepted terms that allowed accurate description of most EUS examinations. This was achieved by reviewing 350 EUS reports from the Medical University of South Carolina. One goal was to avoid excessive detail and seldom-used terms. The EUS MST was divided based on reasons for performing EUS (with qualifiers), equipment, EUS anatomic terms (with modifiers), findings (with attributes and attribute value options), interventions, and diagnoses (with qualifiers). After several iterations, the EUS MST was published as part of the OMED terminology. The latest iteration is the MST 3.0 [12], published in January 2009, which is available from the OMED Web site (www .omed.org). A spreadsheet database in xls format is also available from the same source. Some changes introduced in this version include: the inclusion of EUS and enteroscopy (including capsule endoscopy), the reorganization of the lists of findings (with one generic list for each main category – luminal, ERCP, EUS – coupled with a table indicating which findings are relevant for which organ), the extension and revision of lists of indications and diagnoses, the provision of new sections on therapy and adverse events (including FNA and celiac plexus neurolysis (CPN), pseudocysts, and ductal drainage), and an update to the classifications included as attributes, wherever relevant (none for EUS). Structured reporting Although use of structured reporting may limit expressivity, it offers advantages over free text by reducing error, suppressing duplication, and minimizing oversight. In addition, along with the use of MST, structure reporting forms the basis for automation of electronic reports. Other potential advantages of structured reporting include speed and completeness.

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Speed

Databases

Structured reports can often be completed more quickly than can dictated or transcribed notes. In one study [13], in which ∼30% of routine upper endoscopies were normal, allowing use of the phrase “normal findings,” only ∼10% required extensive and detailed reporting. The remaining ∼60% of reports could be completed with structured reporting. It is likely that the percentage of normal or negative EUS examinations would be much lower, since most are performed to assess known pathology. However, faster reporting may not always be realized when using systems that incorporate too many variables and choices, which can lead to confusion and to one’s becoming lost within the network of options. Similarly, delays may occur when attempting to locate a variable within the MST framework, due to a lack of similarity or accuracy in describing a finding. Furthermore, dissimilarity between the sequence of data acquisition and data entry may slow reporting and lead to inaccuracy.

One of the most important advantages of electronic versus handwritten or dictated reports is the ability to construct databases. Merriam-Webster defines a database as “a usually large collection of data, organized especially for rapid search and retrieval” (www .merriam-webster.com). Database construction requires the use of a common language and “structured reporting” using fields distinguished by clear headings with pulldown menus that incorporate preset terms derived from a standard language. Data are incorporated and organized by several models, including hierarchical, network, and relational models. The most suitable structure depends on the application, transaction rate, number of inquiries made, and advantages and limitations unique to each model.

Completeness When structured systems are used for reporting, a reminder effect has been noted. Studies show that use of electronic reporting software leads to more complete and accurate reporting. In contrast, studies comparing free text to a desired list of reported items have commonly found relevant information to be missing. In a series of colonoscopies performed in patients with ulcerative colitis, important details were absent in the majority of reports, and individual endoscopic signs of inflammation were mentioned in only 27–77% [14]. Acceptance of MST systems requires a careful balance so that there is sufficient structure and function to allow thorough and accurate reporting, but not so much as to slow the process and restrict effective expression of findings. The limitations of restrictive formats may be partially overcome by allowing use of free text entry.

Free text and conventional reports Reporting is optimized by systems that allow the addition of free text to explain terms or items that are vague or insufficiently detailed. However, when used for clinical (and other scientific) purposes, these are often inadequate. Terms such as “likely,” “possible,” and “probable” have different meanings and carry different weight for patients and physicians [15, 16]. Other limitations of free text include omission of findings, redundancy, and the use of different styles and terminologies to express the same finding. For instance, review of chest radiography reports in 8426 Medicare patients with cardiac disease found as many as 23 terms to report a single finding [17]. One can only speculate about the finding of a similar study reviewing EUS reports. In addition, free text does not lend itself to systematic computer searches, thereby hampering research efforts. Finally, use of conventional reporting requires transcription, which is associated with additional cost, delays in availability, and inaccuracy due to errors of communication and typing. A study of 4871 radiology reports from the Brigham and Women’s Hospital found that 33.8% required editing by the radiologists and nearly 6% were substantive, leading to unnecessary treatment or testing [18]. Optimized free text capability also requires sufficient space, copy-and-paste capability, and the ability to customize text features, including font size, type, and color.

Hierarchical With this model, data are entered into a network or tree (parent) containing a number of increasingly smaller branches (children). Data entry must follow a strict order, with all information within a given branch being entered before any can be inserted into a parallel branch. Use is limited by the difficulty of adding new terms and of searching for information located deep within a distal branch. This model was often used by older databases. Network Whereas hierarchical models structure data as a tree of records, with each record having one parent and many children, the network model allows each record to have multiple parent and child records, forming a lattice structure. This structure facilitates rapid simultaneous data retrieval. This model can be useful when input from different sources comes together to form one body, such as the final report. However, it lacks flexibility and is no longer employed in medical record keeping. Relational In this model, each term or attribute is chosen from a list that is independent of prior and subsequent lists. Advantages include the ease of adding new terms and the enhanced search function at all levels of data entry. This is the most common design currently in use in most commercially available databases. In GI endoscopy, the Clinical Outcomes Research Initiative (CORI) database is an excellent example (www.cori.org). Now in version 4, the CORI project began in 1995 under the auspices of the ASGE as the National Endoscopy Database. In 2005, it was receiving 21 000 reports monthly from 107 practice sites and more than 750 physicians in the United States. It currently includes more than 2.7 million procedures, including EUS. It is easy to submit data, including images and pathology results, through the CORI Endoscopic Reporting Software v4.2.2.0, which is also compliant with the Certification Commission for Health Information Technology (CCHIT). The Commission has been certifying electronic health record (EHR) technology since 2006 and is authorized by the Office of the National Coordinator for Health Information Technology (ONC) of the US Department of Health and Human Services (HHS) as a certification body (ONC-ACB). CCHIT is accredited by the American National Standards Institute (ANSI) as a certification body for the ONC HIT Certification Program for EHR technology and is accredited by the National Voluntary Laboratory Accreditation Program (NVLAP) of the National Institute of Standards and Technology (NIST) as

Chapter 6: The EUS report

an Accredited Testing Laboratory (ATL) for the testing of EHRs. It is also involved in the GI Quality Improvement Consortium (GIQuIC) registry.

Commercial software for EUS reporting There are a few practical points to consider when purchasing a commercial software product. Table 6.2 lists the Web sites of some companies that offer EUS reporting capabilities. When selecting software, the needs of a particular EUS department should be identified (administrative, research, clinical), as well as the interface potential and available budget. Most hospital-based information management systems (administrative, billing) are HL7 standard compatible. Automatic labeling of CPT codes should be sought, as should ICD-9 and ICD-10 coding. Some options also provide for coding using SNOMED. Minimal hardware requirements should be clear, although most commercial software products can be used with the average personal computer and are compatible with Windows XP and higher. It is important to know whether the report format can be customized, and to what degree. For instance, does the system allow modification, addition, and deletion of fields and/or terms within a specified field? Use is greatly aided by the ability to insert free text. Search capabilities using any of the terms and fields are required for research purposes . Some provision for secure access should also be available, and the software should be HIPAA compliant. Depending on preference or institutional practice, images can be incorporated within the report. Compatible formats and the number of images that can be added should be verified. A simple cut-and-paste option works best, but is not always available. Commonly used image formats include .jpg and .tif. Although some options support the addition of video clips, this feature is not essential; in some countries, the procedure is recorded and a CD is given to the patient. Other nonessential features include barcode reading and voice recognition capabilities. Instrument tracking, automated coding, and billing are also available. Finally, software products should be scalable to meet growth demands as EUS volumes increase. With the relatively recent explosion in information technology, software (apps), and electronic instruments, it is possible to manage complete medical records, including pictures, coding, and billing, using personal tools such as iPads and even iPhones (at least in small practice or ambulatory centers). One product that allows this is drchrono, available for Apple and Android-based tablets (www.drchrono.com). Information can also be easily sent out, printed, and stored in iCloud or similar systems. However, HIPPA compatibility remains an issue. Similar and more complete EHRs exist for hospital use, such as Microsoft’s Windows Embedded Health Care solutions.

The EUS report No universally accepted set of criteria has been published concerning essential data or findings that should be included in an EUS report (save for the MST3.0). In the absence of a consensus, we offer opinion regarding the key elements that most EUS reports should contain. Our recommendations are not intended to represent a formal mandate, but instead to serve as a template for one’s

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Table 6.2 Web sites of companies offering software for endoscopic reporting. www.endosoft.com www.pentaxmedical.com (endoPRO IQ) www.gmed.com www.novosolutions.com (MediTrac) www.endoworks.com (Olympus, version 7) www.provationmedical.com www.md-reports.com www.cori.org

practice. Modifications can be made based on individual procedure indications and goals. Similarly, the extent, detail, and granularity of EUS reports should be tailored to a particular practice setting. Although certain information should be standard in all settings, specific details may have lesser or greater importance based on clinical and research activities within a particular center. In addition, our recommendations do not address which procedures or techniques should be employed at the time of EUS. Instead, we offer opinion as to the need to document the various findings, procedures, and techniques when performed. The same is true when findings or procedures are not performed, which is relevant, because omission of a particular finding may indicate that the finding was not present or that no effort was made to search for it. Non-EUS information Key non-EUS information that might appear in the referring physician, nurse, cytopathology, or EUS report should be documented for most patients undergoing EUS. Such information includes relevant personal history, physical examination findings, the names of health care providers participating in the procedure, and verification that informed consent has been obtained. An increasing number of centers are performing a “pre-procedure pause” in order to verify they have the correct patient, procedure site, and procedure intent and goals. This process should be documented. The procedure date, time, and location, as well as patient identifying information such as name and medical record number, should be specified. It may be necessary to substitute a de-identifying code in place of the patient’s name in order to comply with HIPAA regulations. The report should include the title and IRB number of EUS studies that the patient is participating in. It is important to clearly and accurately list the primary and secondary procedure indications in order to provide a framework that the examination should logically follow, set the key elements that the report should contain, and facilitate data retrieval for research and administrative purposes. The names and dosages of all medications administered should be specified, including those employed to induce and reverse sedation, to inhibit motility, and as part of EUS guided therapy. It often helps to document patient tolerance, along with advice regarding the need for anesthesia support during subsequent examinations. The report should include information regarding prophylactic administration of oxygen and flow rate versus use following desaturation. Vital signs must be recorded during and after the procedure. As appropriate, the physician should convey to the staff and document the need for prolonged post-procedure observation (e.g., following CPN), guidelines for patient discharge whenever they differ from standard practice, instructions for dietary restriction, and patient education regarding alarm symptoms and measures to take in the event of their occurrence.

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General EUS information It is important to list all EUS equipment used (radial, linear, probes) and its serial numbers. We also recommend that the findings for each instrument be noted separately, given the various advantages and limitations of each. This provides greater perspective in terms of the findings and complications, and in guiding instrument selection for future examinations. While the technique for performing EUS varies, most authorities recommend that a structured and uniform approach be adopted in order to ensure a complete and thorough examination. The same is true when documenting EUS findings. We suggest describing pertinent positive, negative, and incidental findings. Key elements of the report are likely to evolve over time based on future research (e.g., whether one should report an esophageal tumor as T3 or specify “superficial” versus “deep” T3 as emerging data suggest a difference in prognosis and outcomes) [19]. It is important to note the precise location of all pathology, as well as the anatomic extent of the examination. This can be achieved by relating the findings to key anatomic landmarks (e.g., stating that a 6.0 × 5.0 mm pancreatic islet cell tumor is located in the caudal aspect of the pancreatic neck 1.0 cm from the portal vein confluence). This level of detail is necessary to guide screening and plan therapeutic intervention. Factors that limited the completeness of the examination should also be noted, including retained gastric contents, any obstructing tumor, the presence of a stent, air and/or shadowing stones within the bile duct or gallbladder, inadequate sedation, and poor colon preparation. Incomplete examination may result in failure to identify pathology, reduce staging accuracy, and impact billing and reimbursement. EUS interventions (diagnostic and therapeutic) Whenever tissue sampling is performed via FNA or Trucut biopsy (TCB), the site, number of passes, and needle gauge should be noted. Although we discourage obtaining biopsies that require traversal of the primary luminal cancer, if such a biopsy is obtained, this should be noted. Reasons for failed or difficult tissue sampling should also be noted. When performing therapeutic interventions, it is important to indicate the instruments and accessories used and to outline key technical aspects of the procedure. Other pertinent information varies based on the specific procedure, but may include the medications administered as part of EUS therapy, along with the dose and route of injection. The specific site of intervention and the short-term effect should also be noted. With the expansion of therapeutic interventions, such as fiducial placement and ductal drainage [20], new terminology and more precise descriptions should be employed, including the reason for performance, route, accessories used, immediate results, and complications. Likewise, with the use of other EUS-associated technologies, such as confocal endomicroscopy [21], future reports will likely include additional terms. Complications It is important to carefully document all complications and to specify whether they developed secondary to sedation, during routine imaging, or as a result of therapeutic intervention. Include details regarding intraprocedural monitoring and efforts to manage complications. Consider providing initial guidance to those reading the note as to the suggested post-procedure management, although most aspects of patient care following a complication will be conveyed within the hospital chart and through immediate and direct physician communication.

Procedure summary It is important to summarize the findings, to provide perspective as to their significance, and to suggest a differential diagnosis. Some measure of certainty or confidence in one’s findings is often helpful. In addition, a statement of the need for further evaluation, monitoring, and/or therapeutic management, based on information acquired during the EUS examination, as well as a suggested approach to carrying these out, may assist referring and consulting physicians. This should be given in a general and qualified manner, so as not to force or mandate a particular course of action, which might have potential legal implications if not acted on. The report should state which medications to administer (e.g., antibiotics following cyst aspiration) after the procedure and offer suggestions regarding the specific antibiotic, dose, and duration of therapy. The need for and timing of resumption of long-term medications, such as anticoagulants, should also be addressed. When these issues are handled by the endosonographer, the report may serve as a means of documenting their care, rather than of suggesting a course of action to other physicians. Quality of EUS reports There is a paucity of information regarding the quality of EUS reports. One effort analyzed 100 different EUS procedural reports from six hospitals in Israel and one in the United States. It showed several strongly reported areas, including indication for the procedure (97%), administration of anesthesia (94%), periprocedural evaluation (87%), and overall summary of the EUS examination (82%). Intermediately reported areas included relevant past medical history (71.7%), evaluation of the biliary tree (63%), and informed consent (52%). Very importantly, 50% of reports analyzed did not include a systematic organ evaluation. Other areas, such as screened organs (36%), details of FNA (15%), use of the tumor–node–metastases (TNM) system for staging (5%), and adverse events (0%) were seldom reported [22],

Disease-specific information Luminal cancer (esophageal, gastric, rectal) An upper endoscopy or flexible sigmoidoscopy is usually performed to assess the tumor site, traversibility, and need to dilate, and to acquire mucosal biopsies. The proximal and distal tumor extent should be measured relative to landmarks including the incisors and gastroesophageal (GE) junction for esophageal and gastric cancer, and including the anal verge for rectal cancer. The report should include details concerning dilatation, when performed, and the number and sites of mucosal biopsies. The morphology (exophytic, ulcerated, or sessile) and degree of circumferential involvement should be reported. The presence or absence of a hiatal hernia, Barrett’s esophagus, and esophagitis should be mentioned for patients with esophageal or gastric cancer. Tumor mobility (fixed or tethered) should be noted for rectal cancers. Current treatment protocols are guided by TNM staging as part of the American Joint Committee on Cancer (AJCC) staging criteria. A primary aim of EUS is to establish the tumor (T) stage and nodal (N) stage, and, when possible, to detect metastasis (M). The specific T stage should be noted, and for patients with a T4 tumor, the report should specify which tissue is infiltrated to signify this advanced stage. Consider recording the greatest depth of primary tumor extension, as this finding roughly correlates with T stage. One should indicate whether the N stage was determined by imaging characteristic alone or by onsite FNA results. It is necessary to

Chapter 6: The EUS report

document the exact location of nodal metastasis, given the impact on prognosis and therapy. For example, one should separately note the presence of celiac, perigastric, and mediastinal lymphadenopathy for patients with esophageal cancer [23]. Similarly, in patients with rectal cancer, it is important to distinguish iliac nodes (M1) from rectal nodes (N1) [24]. Consider listing each nodal feature (size, echodensity, shape, and border, including qualitative and/or quantitative elastography, if used). The site of distant (M stage) metastasis, when present, should be reported, including the sites examined to make this determination. Mention of ascites, omental thickening, and/or a pleural effusion should be included. In addition, whether the EUS is performed at the time of initial diagnosis, after chemoradiation, or to evaluate recurrent disease should be specified. Subepithelial lesions Findings of initial endoscopy that should be included in the EUS report include the lesion site, size, and color, the presence of a pillow sign, and whether the lesion is mobile or fixed. The aim of EUS is to characterize the lesion and, often, to obtain a tissue diagnosis. Since a tentative diagnosis is based on the layer of origin, this is essential information to include. Other important features include lesion size, echogenicity, homogeneity, the presence or absence of calcification, cystic spaces, necrosis, and border appearance. Some of these features have been variably mentioned as predictors of malignancy for certain types of subepithelial lesion [25]. Similarly, the presence or absence of direct infiltration of surrounding structures and malignant lymphadenopathy should be reported. The presence of internal blood vessels or proximity to the papilla and other key structures should be noted, as these features may influence the surgical approach. Solid pancreatic tumor Endoscopic evidence of tumor infiltration into the duodenum, papilla, or stomach should be reported, as should the presence of an obstructing mass. The role of EUS in this context is to identify or exclude the presence of a suspected mass not otherwise seen, establish resectability, and, often, to obtain a tissue diagnosis. The report should describe the primary lesion in terms of echodensity, homogeneity, border features, the presence of cystic spaces, and the number of lesions, as these features often correlate with the underlying pathology. As with luminal cancer, current treatment protocols for patients with pancreatic cancer are guided by the TNM stage. T4 tumors are considered locally unresectable via involvement of major vascular structures such as the celiac trunk, hepatic artery, and/or superior mesenteric artery. Involvement of these vessels should be noted in the EUS report. Additionally, while T1 to T3 tumors are generally deemed resectable, patients with significant involvement of the portal and/or superior mesenteric vein are often not taken to surgery. Therefore, the report should indicate the perceived extent of involvement. Use of terms and criteria such as infiltration, abutment, invasion, percent encasement, length of involvement, tumor thrombus, and presence of collateral vessels varies among centers. However, their use is encouraged, if appropriate, even though they have only moderate sensitivity, specificity, and interobserver variability [26, 27]. Although tumor size influences T stage (T1 < 2 cm vs. T2 > 2.0 cm), distinction of T1 and T2 does not influence therapy. Omental thickening and ascites should be reported, as these findings may suggest omental seeding. While the presence of

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regional nodes does not alter therapy, distant lymphadenopathy and evidence of metastatic disease (M1) should be reported, along with the specific site(s). Findings suggestive of acute pancreatitis (AP) and/or chronic pancreatitis (CP) should be noted, as they may explain the failure to discern an underlying malignancy and impact the timing of repeat imaging. In addition, consider reporting additional information, such as bile duct caliber, the presence of sludge or stones, and post-obstructive pancreatic features. If elastography is used, the strain ratio should be mentioned [4]. Pancreatic cystic lesions The goals of EUS in this context are to further characterize the cystic lesion(s), in order to narrow the differential, and to search for malignant transformation. The EUS report should describe the appearance of the papilla and specify the location, number, and size of the cysts. The report should also mention the presence or absence of internal echogenic material, a wall (presence, thickness, regularity), septations (presence, thickness, regularity), a focal solid component, and evidence of local invasion. The report should note whether the cyst communicates, abuts, and/or deforms the pancreatic duct, and should characterize the main pancreatic duct. The presence of an associated solid pancreatic mass or CP should be reported. For patients with a large and complex cyst, it is important to note each feature of the cyst as a whole, as well as of the smaller cystic components. Koito’s morphologic classification of cystic lesions could be useful, but it is not frequently used [28]. Details of cyst fluid aspiration should include the needle used, fluid appearance, viscosity, volume and completeness of aspiration, and string sign results. One should also indicate which tests were ordered for cystic fluid analysis (e.g., carcinoembryonic antigen, amylase, cytology). The report should specify the desired sequence of testing, based on perceived priority and volume aspirated. The antibiotic, dose, and route of administration should be included, as should the need for therapy following the examination. Pancreatitis While pancreatitis is typically thought of as acute (AP), acute recurrent (ARP), chronic (CP), or autoimmune (AIP), there is frequent overlap of clinical and imaging findings. For the purpose of the EUS note, they are considered together, since we favor reporting each feature regardless of the presumed “state” of pancreatitis. The presence and location of each established ductal and parenchymal feature that suggests CP should be specified individually. Also, for the benefit of those reading the report, in particular nongastroenterologists, we suggest an interpretive comment, as some may mistake the presence of any feature as diagnostic of CP. In this case, the Rosemont Criteria are reproducible enough, and we strongly support their use to guide clinicians unfamiliar with their interpretation and as a tool for quality assessment [29, 30]. In addition, findings that suggest pancreatic or peripancreatic acute inflammation should be reported. Finally, EUS findings that might suggest the underlying pathology or an alternate diagnosis should be recorded, including evidence of microlithiasis, bile duct stones, pancreas divisum, anomalous pancreatobiliary junction, or a benign or malignant tumor.

Conclusion Key elements to include within an EUS report vary based on many factors, including the procedure indications and goals, and the

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particular practice setting. However, there is increasing recognition of the importance of providing clarity, detail, and completeness in reporting. While our suggested minimal criteria may not be ideal for all settings, they can serve as a template for a particular practice, allowing modifications as necessary.

References 1 Jacobson BC, Chak A, Hoffman B, et al. Quality indicators for endoscopic ultrasonography. Am J Gastroenterol 2006;101:808–901. 2 Bluen BE, Lachter J, Khamaysi I, Kamal Y, et al. Accuracy and quality assessment of EUS-FNA: a single-center large cohort of biopsies. Diagn Ther Endosc 2012:139563. 3 Layfield LJ, Dodd L, Factor R, Schmidt RL. Malignancy risk associated with diagnostic categories defined by the Papanicolaou Society of Cytopathology pancreaticobiliary guidelines. Cancer Cytopathol 2014;122:420–427. 4 Dietrich CF, S˘aftoiu A, Jenssen C. Real time elastography endoscopic ultrasound (RTE-EUS), a comprehensive review. Eur J Radiol 2014;83:405–414. 5 ASGE Technology Committee. Computerized endoscopic medical record systems. Gastrointest Endosc 1999;51:793–796. 6 Waye J, Aabakken L, Alvarez S, et al. Endoscopy reports, databases, and computers in 2001. Gastrointest Endosc 2001;53:838–839. 7 Maratka Z. Terminology, Definition and Diagnostic Criteria in Digestive Endoscopy. Bad-Homburg: Normed Verlag, 1989. 8 Delvaux M, Korman LY, Armengol-Miro JR, et al. The minimal standard terminology for digestive endoscopy: introduction to structured reporting. Int J Med Inform 1998;48:217–225. 9 Crespi M, Delvaux M, Shapiro M, et al. Working party report by the Committee for Minimal Standards of Terminology and Documentation in Digestive Endoscopy of the European Society of Gastrointestinal Endoscopy. Minimal standard terminology for a computerized endoscopic database. Am J Gastroenterol 1996;91: 191–216. 10 Delvaux M, Crespi M, Armengol-Miro JR, et al. Minimal standard terminology for digestive endoscopy: results of prospective testing and validation in the GASTER project. Endoscopy 2000;232: 345–55. 11 Aabakken L. Standardized terminology in endoscopic ultrasound. Eur J Ultrasound 1999;10:179–183. 12 Aabaken L, Rembacken B, LeMoine O, et al. Minimal standard terminology for gastrointestinal endoscopy – MST 3.0. Endoscopy 2009;41:727–728. 13 Groenen MJ, Kuipers EJ, van Berge Henegouwen GP, et al. Computerisation of endoscopy reports using standard reports and text blocks. Neth J Med 2006;64:78–83. 14 de Lange T, Moum BA, Tholfsen JK, et al. Standardization and quality of endoscopy text reports in ulcerative colitis. Endoscopy 2003;35:835–840.

15 Kong A, Barnett Go, Mosteller F, Youtz C. How medical professionals evaluate expressions of probability. N Engl J Med 1986;315: 740–744. 16 Ohnishi M, Fukui T, Matsui K, et al. Interpretation of and preference for probability expressions among Japanese patients and physicians. Family Practice 2002;19:7–11. 17 Sobel JL, Pearson ML, Gross K, et al. Information content and clarity of radiologists’ report of chest radiography. Acad Radiol 1996;3:709–717. 18 Holman BL, Aliabadi P, Silverman SG, et al. Medical impact of unedited preliminary radiology reports. Radiology 1994;191: 519–521. 19 Yusuf TF, Harewood GC, Clain JC, et al. Clinical implications of the extent of invasion of T3 esophageal cancer by endoscopic ultrasound. J Gastroenterol Hepatol 2005;20:1880–1885. 20 Alvarez-Sánchez MV, Jenssen C, Faiss S, Napoléon B. Interventional endoscopic ultrasonography: an overview of safety and complications. Surg Endosc 2014;28:712–734. 21 Konda VJ, Meining A, Jamil LH, et al. A pilot study of in vivo identification of pancreatic cystic neoplasms with needle-based confocal laser endomicroscopy under endosonographic guidance. Endoscopy 2013;45:1006–1013. 22 Jesse Lachter J, Bluen B, Waxman I, Bellan W. Establishing a quality indicator format for endoscopic ultrasound. World J Gastrointest Endosc 2013;5:574–580. 23 Vazquez-Sequeiros E. Nodal staging: number or site of nodes? How to improve accuracy? Is FNA always necessary? Junctional tumors – what’s N and what’s M? Endoscopy 2006;38:S4–S8. 24 Gleeson FC, Clain JE, Rajan E, et al. EUS-FNA assessment of extramesenteric lymph node status in primary rectal cancer. Gastrointest Endosc 2011;74:897–905. 25 Nickl NJ. Gastrointestinal stromal tumors: new progress, new questions. Curr Opin Gastroenterol 2004;20:482–487. 26 Rosch T, Dittler HJ, Strobel K, et al. Endoscopic ultrasound criteria for vascular invasion in the staging of cancer of the head of the pancreas: a blind reevaluation of videotapes. Gastrointest Endosc 2000;52:469–477. 27 Aslanian H, Salem R, Lee J, et al. EUS diagnosis of vascular invasion in pancreatic cancer: surgical and histologic correlates. Am J Gastroenterol 2005;100:1381–1385. 28 Koito K, Namieno T, Nagakawa T, et al. Solitary cystic tumor of the pancreas: EUS-pathologic correlation. Gastrointest Endosc 1997;45:268–276. 29 Catalano MF, Sahai A, Levy M, et al. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc 2009;69:1251–1261 30 Gardner TB, Taylor DJ, Gordon SR. Reported findings on endoscopic ultrasound examinations for chronic pancreatitis: toward establishing an endoscopic ultrasound quality benchmark. Pancreas 2014;43:37–40.

CHAPTER 7

Endosonography of the mediastinum Kondal R. Kyanam Kabir Baig 1 & Michael B. Wallace 2 1 The

Basil I. Hirschowitz Endoscopic Center of Excellence, University of Alabama Birmingham, UAB School of Medicine, Birmingham, AL, USA Clinic College of Medicine, Jacksonville, FL, USA

2 Mayo

Case A 62-year-old male presented with dyspnea and an abnormal chest X-ray showing hilar fullness. A CT chest revealed significant mediastinal lymphadenopathy. Cultures and skin testing for tuberculosis were negative. Endosonography was performed to evaluate the lymph nodes, and a transesophageal biopsy revealed granulomas consistent with sarcoidosis.

Introduction Endosonography is a highly effective method of evaluating patients with lung cancer, malignant lymphadenopathy, and other mediastinal conditions such as cysts and masses. Due to the central location of the esophagus within the chest, transesophageal EUS offers reliable access to the posterior and inferior mediastinum [1]. Endosonography can also be used to assess non-specific generalized lymphadenopathy in the absence of a known primary. Interventional endosonography in the mediastinum with transesophageal drainage of mediastinal fluid collections has also been reported [2–4]. Another complementary tool available for the evaluation of mediastinal lymphadenopathy and cancer staging is endobronchial ultrasound (EBUS), which is typically performed during bronchoscopy. The combination of the two modalities allows near-complete access to all mediastinal lymph node stations. Due to the more anterior location of the trachea, EBUS is preferred for evaluating upper anterior pathology, particularly when the air-filled trachea obscures the view from the esophagus. The procedure and its indications are discussed in this topic review. In addition, the advantages, disadvantages, and complications of EUS are reviewed. What are the techniques for performing EUS/EUS-FNA in the mediastinum? As described previously in the textbook, endosonography can be performed with a radial or linear array echoendoscope. The radial echoendoscope provides cross-sectional images perpendicular to the axis of the endoscope (Figures 7.1 and 7.2). However, tissue or

fluid sampling is not possible. The curvilinear array echoendoscope provides images parallel to the echoendoscope. It has an accessory channel for a biopsy needle that can be visualized as a biopsy is being done and can be manipulated with an elevator to target lesions of interest (Figures 7.3–7.6). The Doppler feature can help not only in identifying vascular and other structures in the path of the needle but also in defining vascular abnormalities and cystic lesions (Figures 7.7–7.9). Structures ranging from a few millimeters up to 5–10 cm from the transducer can be visualized. Due to artifacts from air, ultrasound imaging of the lung parenchyma and structures opposite the air-filled trachea/bronchi is limited. Most endosonography for routine indications can be performed safely under moderate or deep sedation. The choice of echoendoscope often depends on the indication and whether biopsy or aspiration is necessary. The sonography settings for visualization of the mediastinum are different depending on the indication. Typically, moderate frequencies (5–10 MHz) are used to achieve a balance of high resolution and penetration depth. An examination of the esophagus wall is best performed at a higher frequency (10–20 MHz). The mediastinal tissue, lymph nodes, pleura, heart, spine, and vascular structures in the mediastinum can be easily identified. The superior mediastinum, above the level of the carina, can be difficult to visualize effectively because of the anterior air containing the trachea. The posterior part of the mediastinum in this region can still be visualized effectively. Mediastinal lymph nodes can also be seen in the subcarina, paraesophageal, and aortopulmonary regions (Figures 7.1B, 7.2, and 7.3). Pre-tracheal and paratracheal lymph nodes are more challenging to visualize unless they are large or located lateral to the trachea. However, the esophagus can sometimes be mobilized laterally with the endoscope to allow access even to pre-tracheal structures. Careful evaluation of the mediastinum may require evaluation with both radial and linear echoendoscopes to better localize the lymph nodes to be targeted for FNA. Lymph nodes lateral to large arteries such as the aorta can be visualized, but FNA through the vessel should generally be avoided, although case reports suggest it can be done safely in specific circumstances [5] (Figure 7.10).

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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(A)

(B)

(C)

Figure 7.1 (A) Endoscopic image of a circumferential esophageal mass. (B) Peritumoral lymph node. (C) Circumferential esophageal mass-radial view.

Figure 7.2 Radial view of the subcarinal lymph node.

Figure 7.4 Linear view of the subcarinal node.

Figure 7.3 Linear view of the aortopulmonary node.

Figure 7.5 Linear view of the peri-aortic node.

Chapter 7: Endosonography of the mediastinum

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Figure 7.8 Doppler of an aneurysm.

Figure 7.6 Linear view of lung mass encasing the aorta.

Figure 7.9 Doppler waveform of aneurysm.

Figure 7.7 A 1.5-cm vascular aneurysm of a branch from the aorta.

Fine needle aspiration: endosonography with a linear echoendoscope enables FNA under direct visualization and rapid on-site cytological evaluation. This ability gives endosonography a unique advantage over other invasive methods such as mediastinoscopy and can provide information that can prevent thoracoscopy and surgery [6–8]. Needles are available in 25-, 22-, and 19-gauge sizes. Core biopsy needles are also available that enable histologic samples, which may be helpful in lymphoma or granulomatous disease [9]. When is EUS/EUS-FNA of the mediastinum indicated? The indications for endosonography of the mediastinum are listed in Table 7.1. Endosonography for Barrett’s dysplasia, esophageal cancer and staging, and esophageal mural lesions are addressed elsewhere. Diagnostic sampling of mediastinal abnormalities: When the lesion of interest is paraesophageal and in the posterior or inferior

mediastinum, endosonography and FNA should be the first sampling methods [1]. Endobronchial ultrasound is a complementary modality that is more suitable for lesions in the anterior or superior mediastinum. Our center has conducted a prospective blinded study that demonstrates that the combination of EUS and EBUS with FNA is superior to bronchoscopic FNA and has a high positive and negative predictive value for lymph node sampling in lung cancer [10].

Diagnosis Benign lymphadenopathy can be seen in inflammatory conditions such as sarcoidosis and in infections such as tuberculosis and histoplasmosis. EUS-FNA is a safe and minimally invasive method of obtaining tissue and has a robust yield when the index of suspicion is high [11–14]. A retrospective study of 127 patients with mediastinal lymphadenopathy of unclear etiology demonstrated a sensitivity and specificity of 89 and 96%, respectively, for sarcoidosis [14]. In another retrospective study of patients who had a mediastinal mass, benign diseases were detected in about half the patients [15]. A diagnosis was established in 82% of patients in a prospective cohort study of EUS-FNA for suspected sarcoidosis [12].

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Evaluation of lymph nodes by CT/PET

Normal CT/PET but high suspicion for nodal involvement

Abnormal lymph nodes on CT scan or PET scan

Paraesophageal, inferior or posterior location– endosonography +/– FNA

and/ or

Anterior or superior location– endobronchial ultrasound +/– FNA

Successful and accurate staging/restaging Figure 7.10 Transaortic FNA.

Table 7.1 Indications for endosonography/FNA/B of mediastinum. Common indications – Lymphadenopathy – Lung cancer nodal staging – Esophageal cancer tumor and nodal staging – Mediastinal mass Uncommon indications – Mediastinal vascular abnormalities – Mediastinal cystic lesions – Thyroid mass/lesion – Mediastinal collections

Malignant diseases EUS-FNA is an excellent tool for detecting malignant disease in the mediastinum. Lung cancer: Bronchoscopy with or without EBUS is often the first diagnostic test for lung cancer. EUS-FNA is an excellent adjunct tool when a diagnosis has not been made by bronchoscopy, particularly when inferior or posterior lymphadenopathy is present. EUS detected lung cancer in 25/35 patients suspected of having lung cancer with a negative bronchoscopy and missed the diagnosis in 1/35 [16]. EUS-FNA showed lymph nodes in the high paratracheal, aortopulmonary, subcarinal, paraesophageal, and hilar regions. The ability of EUS to sample subcentimeter nodes makes it superior to CT and PET [17]. Other malignancies: In a retrospective study on patients with non-lung cancer malignant mediastinal disease, EUS-FNA detected colon cancer, breast cancer, laryngeal cancer, renal cell cancer, lung cancer, and metastatic disease from an unknown site in 22 of 49 patients. The accuracy of EUS-FNA for malignant and benign diagnoses was over 90% [15]. Lung cancer staging is based on the tumor–node–metastasis (TNM) system, which is also used to inform prognosis and management. Multiple studies have shown that the treatment algorithm for

lung cancer is altered in up to 95% of patients when endosonography is utilized in staging [7, 17–19]. In a prospective cohort study of endosonography/FNA of mediastinal lymph nodes, thoracoscopy/ mediastinoscopy or surgery was avoided in half the patients [20]. Endosonography was highly cost-effective compared to surgical staging. Endosonography has the ability to contribute to each component of TNM staging. T stage: EUS can define the primary tumor and its relationship to surrounding structures, particularly invasion in the vasculature and other mediastinal structures, establishing T4 disease with a sensitivity and specificity of 87 and 98%, precluding surgery [21]. N stage: mediastinal lymph node evaluation is its primary role. Patients with abnormal mediastinal lymph nodes detected by conventional cross-sectional imaging (CT scan) or PET scan should undergo lymph node sampling [22]. The sensitivity and specificity of diagnosing metastatic disease by imaging alone are inadequate. EUS-FNA is effective at detecting metastatic disease in lymph nodes with an accuracy of 83–97% and a sensitivity of 84–92% [11, 18, 20, 23–28]. A prospective study demonstrated a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 92, 100, 100, 94, and 97%, respectively, in a series of 104 patients who underwent mediastinal lymph node FNA [24]. As previously described, EUS-FNA and EBUS-TBNA can be used together for incremental benefit. EBUS provides access to the anterior and superior mediastinal lymph nodes. Endosonography allows access to the posterior and inferior mediastinal lymph nodes. Endosonography may be uniquely useful in identifying and sampling lymph nodes based on EUS criteria in the absence of lympadenopathy by cross-sectional imaging [29, 30]. In two studies, EUS was able to detect metastatic disease in 25% of patients with no nodal enlargement by CT scan and also advanced local disease in 12%, thus preventing unnecessary surgery. The lesions detected included invasion of mediastinal structures, contralateral and distant lymph node involvement, esophageal involvement, and adrenal metastases [31, 32].

Chapter 7: Endosonography of the mediastinum

A few small studies have demonstrated the benefit of analyzing the cytology samples for genes that may predict micrometastases in up to one in five cytologically negative lymph nodes [33–35]. M stage: While distant metastatic disease is generally detected by cross-sectional imaging, EUS provides a unique opportunity to evaluate and sample abdominal metastatic disease such as celiac lymph nodes, liver, and adrenal metastasis at the same time as mediastinal EUS [8, 24, 31]. Endosonography identified celiac lymphadenopathy in 11% of patients [36].

Although adherence to the European NSCLC mediastinal staging guideline on the initial use of endosonography was good, 30% of endosonography procedures were performed insufficiently. Confirmatory mediastinoscopy following negative endosonography was frequently omitted. Significant variability was found among participating centers regarding staging strategies and the systematic performance of procedures. However, unforeseen N2 rates after mediastinal staging by endosonography with and without confirmatory mediastinoscopy were comparable [37]. The MEDIASTrial will study whether mediastinoscopy can be omitted after negative endosonography in mediastinal staging in patients with NSCLC. Since debate exists on the additional value of mediastinoscopy, this trial will provide definite evidence on this topic. The current literature suggests that diagnostic strategies with or without mediastinoscopy may be equivalent concerning efficacy and that abandoning mediastinoscopy appears favorable concerning morbidity and speed of the diagnostic process, but a formal comparison of cost-effectiveness and cost-utility has never been performed, and no ongoing studies comparing these two strategies have been registered in trial registers so far. The results of such a trial will have an immediate impact on international guidelines [38]. A significant increase in invasive mediastinal nodal staging in patients with resectable NSCLC was found between 2011 and 2017 in the Netherlands. Increasing use of less invasive endosonography prior to (or substituting for) surgical staging did not lead to more cases of uN2. Performance of invasive staging indicated a possible overall survival benefit in patients with cN1–3 disease [39]. Combined endosonographic lymph node staging should be considered in the pretreatment staging of high-risk patients with non-small-cell lung cancer in the presence of radiologically normal mediastinal lymph nodes due to the significant rate of radiologically occult lymph nodes [40]. The accuracy of PET-CT and mediastinal endosonography is lower for mediastinal restaging than it is for surgical techniques; their false positive and false negative (FN) rates are high, and so they require histological confirmation. Here we explain and revise the results from the most recent studies and current international guidelines [41].

Restaging is often done after neoadjuvant therapy to assess response to therapy and surgical resectability. In a prospective study, EUS-FNA was able to diagnose post treatment lung cancer in mediastinal lymph nodes with a sensitivity and specificity of 75 and 100% [37]. Our study looking at combined EUS and EBUS with FNA in similar patients with a normal CT scan series demonstrated a high negative predictive value and changed therapy in 10% of patients [27]. Mediastinal cysts can be assessed by endosonography for vascular involvement and the presence of solid or mixed components. The differential includes duplication and bronchogenic cysts. Fluid aspiration in anechoic patients carries a high risk of serious infectious complications [42, 43]. However, one series has demonstrated that aspiration may be safe with antibiotic prophylaxis and the use of a smaller gauge needle [40]. Comparative and randomized trials have not been done to address the concern of mediastinal cyst infection.

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Endosonographic assessment of thyroid lesions has been reported in case series for posterior and lateral thyroid lesions. Its utility in documenting the local stage of thyroid cancer and its ability to biopsy certain lesions have also been described [44, 45].

Interventional endoscopy Endosonography has been utilized and studied extensively for transgastric interventions and drainage of collections, particularly pancreatic collections such as pseudocysts and necroses [46]. Multiple case reports and series have been reported of transesophageal drainage of mediastinal pancreatic collections, showing feasibility and safety [2, 4]. However, prospective studies or comparative trials have not been done, and the role of EUS in this setting remains to be defined.

Summary From a patient perspective, endosonography-guided fine needle aspiration (EUS-FNA) is preferred because it is minimally invasive and can be performed on an outpatient basis under moderate sedation. Technically, EUS-FNA has the ability to access posterior mediastinal nodes, which are often a site of metastases from lung cancer and are not easily evaluated by other invasive staging modalities. The real-time evaluation facilitated by endosonography allows the assessment and biopsy of small lesions and decreases the risk of complications associated with other invasive alternatives. It is also the only modality that allows for concurrent visualization and sampling of extramediastinal regions such as the liver, adrenal glands, and abdominal lymph nodes [24, 31, 47, 48]. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) also has specific drawbacks. It is not useful for evaluating the mediastinum completely because the air-filled trachea interferes with ultrasound imaging. There is a finite occurrence of FN biopsies due to sampling error; however, this is also seen with other methods [49]. False-positive results are rare and can occur due to sampling of peri-tumoral nodes or contamination from intraluminal cancer cells. The specific expertise required is not available everywhere, but the capability is expanding rapidly. The few contraindications to endoscopic ultrasound-guided fine needle aspiration are similar to those for general endoscopy, such as difficulty with sedation, serious cardiac or pulmonary comorbidities, and uncorrectable bleeding diathesis.

Complications Endosonography is a very safe procedure. A review by the American Society for Gastrointestinal Endoscopy states that the perforation rates are comparable to upper endoscopy and are less than 0.1% in two large series [50]. Esophageal strictures, obstructive esophageal malignancy, and multiple attempts at esophageal intubation are independently associated with perforation. The complication rate of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is related to the kind of lesion sampled. There is a higher chance of infectious complications with cystic lesions, but this is exceedingly rare in FNA of solid lesions. Other rare complications include infection, hemorrhage, drug reaction, bowel wall perforation, and posterior pharyngeal perforation [50]. Though there is a concern for pneumothorax, it has not been reported thus far. One

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case of severe mediastinitis needing thoracotomy and one case of esophago-mediastinal fistula formation have been reported [51, 52].

Conclusion Endosonography is a safe and effective modality for the evaluation of mediastinal lesions and tissue acquisition. It has been shown to provide valuable information in lung cancer staging that alters treatment algorithms, prevents unnecessary and invasive surgery, and is cost-effective in this context. Endosonography is also the most effective and least invasive method for the diagnosis and evaluation of benign lymphadenopathy such as sarcoidosis and infectious adenopathy.

References 1 ASGE Standards of Practice Committee, Jue TL, Sharaf RN, Appalaneni V, et al. Role of EUS for the evaluation of mediastinal adenopathy. Gastrointest Endosc 2011;74(2):239–245. 2 Piraka C, Shah RJ, Fukami N, et al. EUS-guided transesophageal, transgastric, and transcolonic drainage of intra-abdominal fluid collections and abscesses. Gastrointest Endosc 2009;70(4): 786–792. 3 Wehrmann T, Stergiou N, Vogel B, et al. Endoscopic debridement of paraesophageal, mediastinal abscesses: a prospective case series. Gastrointest Endosc 2005;62(3):344–349. 4 Gornals JB, Loras C, Mast R, et al. Endoscopic ultrasound-guided transesophageal drainage of a mediastinal pancreatic pseudocyst using a novel lumen-apposing metal stent. Endoscopy 2012;44(Suppl 2). UCTN:E211-2. 5 Wallace MB, Woodward TA, Raimondo M, et al. Transaortic fine-needle aspiration of centrally located lung cancer under endoscopic ultrasound guidance: the final frontier. Ann Thorac Surg 2007;84(3):1019–1021. 6 Varadarajulu S, Hoffman BJ, Hawes RH, Eloubeidi MA. EUS-guided FNA of lung masses adjacent to or abutting the esophagus after unrevealing CT-guided biopsy or bronchoscopy. Gastrointest Endosc 2004;60(2):293–297. 7 Savides TJ, Perricone A. Impact of EUS-guided FNA of enlarged mediastinal lymph nodes on subsequent thoracic surgery rates. Gastrointest Endosc 2004;60(3):340–346. 8 Kramer H, Groen HJ. Diagnosis of mediastinal and left adrenal abnormalities with endoscopic ultrasonography. Respir Med 2005;99(7):926–928. 9 Varadarajulu S, Fraig M, Schmulewitz N, et al. Comparison of EUS-guided 19-gauge Trucut needle biopsy with EUS-guided fine-needle aspiration. Endoscopy 2004;36(5):397–401. 10 Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA 2008;299(5): 540–546. 11 Fritscher-Ravens A, Sriram PV, Topalidis T, et al. Diagnosing sarcoidosis using endosonography-guided fine-needle aspiration. Chest 2000;118(4):928–935. 12 Annema JT, Veselic M, Rabe KF. Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of sarcoidosis. Eur Respir J 2005;25(3):405–409. 13 Tournoy KG, Praet MM, Van Maele G, Van Meerbeeck JP. Esophageal endoscopic ultrasound with fine-needle aspiration with an on-site cytopathologist: high accuracy for the diagnosis of mediastinal lymphadenopathy. Chest 2005;128(4):3004–3009.

14 Wildi SM, Judson MA, Fraig M, et al. Is endosonography guided fine needle aspiration (EUS-FNA) for sarcoidosis as good as we think? Thorax 2004;59(9):794–799. 15 Devereaux BM, Leblanc JK, Yousif E, et al. Clinical utility of EUS-guided fine-needle aspiration of mediastinal masses in the absence of known pulmonary malignancy. Gastrointest Endosc 2002;56(3):397–401. 16 Fritscher-Ravens A, Soehendra N, Schirrow L, et al. Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer. Chest 2000;117(2):339–345. 17 Annema JT, Veselic M, Rabe KF. EUS-guided FNA of centrally located lung tumours following a non-diagnostic bronchoscopy. Lung Cancer 2005;48(3):357–361; discussion 63–64. 18 Fritscher-Ravens A, Davidson BL, Hauber HP, et al. Endoscopic ultrasound, positron emission tomography, and computerized tomography for lung cancer. Am J Respir Crit Care Med 2003; 168(11):1293–1297. 19 Larsen SS, Vilmann P, Krasnik M, et al. Endoscopic ultrasound guided biopsy performed routinely in lung cancer staging spares futile thoracotomies: preliminary results from a randomised clinical trial. Lung Cancer 2005;49(3):377–385. 20 Larsen SS, Krasnik M, Vilmann P, et al. Endoscopic ultrasound guided biopsy of mediastinal lesions has a major impact on patient management. Thorax 2002;57(2):98–103. 21 Varadarajulu S, Schmulewitz N, Wildi SM, et al. Accuracy of EUS in staging of T4 lung cancer. Gastrointest Endosc 2004;59(3):345–348. 22 Detterbeck FC, Jantz MA, Wallace M, American College of Chest Physicians, et al. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl):202S–220S. 23 Wallace MB, Silvestri GA, Sahai AV, et al. Endoscopic ultrasoundguided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg 2001;72(6):1861–1867. 24 Eloubeidi MA, Cerfolio RJ, Chen VK, et al. Endoscopic ultrasoundguided fine needle aspiration of mediastinal lymph node in patients with suspected lung cancer after positron emission tomography and computed tomography scans. Ann Thorac Surg 2005;79(1):263–268. 25 Giovannini M, Seitz JF, Monges G, et al. Fine-needle aspiration cytology guided by endoscopic ultrasonography: results in 141 patients. Endoscopy 1995;27(2):171–177. 26 Wiersema MJ, Vazquez-Sequeiros E, Wiersema LM. Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle aspiration biopsy. Radiology 2001;219(1):252–257. 27 Wallace MB, Fritscher-Ravens A, Savides TJ. Endoscopic ultrasound for the staging of non-small-cell lung cancer. Endoscopy 2003;35(7):606–610. 28 Yasuda I, Kato T, Asano F, et al. Mediastinal lymph node staging in potentially resectable non-small cell lung cancer: a prospective comparison of CT and EUS/EUS-FNA. Respiration 2009;78(4): 423–431. 29 Kondo D, Imaizumi M, Abe T, et al. Endoscopic ultrasound examination for mediastinal lymph node metastases of lung cancer. Chest 1990;98(3):586–593. 30 Arita T, Kuramitsu T, Kawamura M, et al. Bronchogenic carcinoma: incidence of metastases to normal sized lymph nodes. Thorax 1995;50(12):1267–1269. 31 LeBlanc JK, Devereaux BM, Imperiale TF, et al. Endoscopic ultrasound in non-small cell lung cancer and negative mediastinum on computed tomography. Am J Respir Crit Care Med 2005;171(2): 177–182.

Chapter 7: Endosonography of the mediastinum

32 Wallace MB, Ravenel J, Block MI, et al. Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography. Ann Thorac Surg 2004;77(5):1763–1768. 33 Wallace MB, Block MI, Gillanders W, et al. Accurate molecular detection of non-small cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration. Chest 2005;127(2):430–437. 34 Pellise M, Castells A, Gines A, et al. Detection of lymph node micrometastases by gene promoter hypermethylation in samples obtained by endosonography- guided fine-needle aspiration biopsy. Clin Cancer Res 2004;10(13):4444–4449. 35 Ulivi P, Romagnoli M, Chiadini E, et al. Assessment of EGFR and K-ras mutations in fixed and fresh specimens from transesophageal ultrasound-guided fine needle aspiration in non-small cell lung cancer patients. Int J Oncol 2012;41(1):147–152. 36 Singh P, Camazine B, Jadhav Y, et al. Endoscopic ultrasound as a first test for diagnosis and staging of lung cancer: a prospective study. Am J Respir Crit Care Med 2007;175(4):345–354. 37 Bousema JE, van Dorp M, Hoeijmakers F, et al. Guideline adherence of mediastinal staging of non-small cell lung cancer: a multicentre retrospective analysis. Lung Cancer 2019;134:52–58. 38 Bousema JE, Dijkgraaf MGW, Papen-Botterhuis NE, et al. MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): study protocol of a multicenter randomised controlled trial. BMC Surg 2018;18(1):1–11. 39 Bousema, JE, Aarts MJ, Dijkgraaf MGW, et al. Trends in mediastinal nodal staging and its impact on unforeseen N2 and survival in lung cancer Eur Respir J 2021;57(4). European Respiratory Society. 40 Hegde P, Molina JC, Thivierge-Southidara M, et al. Combined endosonographic mediastinal lymph node staging in positron emission tomography and computed tomography node-negative non–small-cell lung cancer in high-risk patients Semin Thorac Cardiovasc Surg 2020;32(1):162–168. 41 Leiro-Fernández V, Fernández-Villar A. Mediastinal staging for non-small cell lung cancer Transl Lung Cancer Res 2021;10(1):496. AME Publications.

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42 Diehl DL, Cheruvattath R, Facktor MA, Go BD. Infection after endoscopic ultrasound-guided aspiration of mediastinal cysts. Interact Cardiovasc Thorac Surg 2010;10(2):338–340. 43 Wildi SM, Hoda RS, Fickling W, et al. Diagnosis of benign cysts of the mediastinum: the role and risks of EUS and FNA. Gastrointest Endosc 2003;58(3):362–368. 44 Koike E, Yamashita H, Noguchi S, et al. Endoscopic ultrasonography in patients with thyroid cancer: its usefulness and limitations for evaluating esophagopharyngeal invasion. Endoscopy 2002;34(6): 457–460. 45 Sawhney MS, Nelson DB, Debol S. The ever-expanding spectrum of GI endoscopy: EUS-guided FNA of thyroid cancer. Gastrointest Endosc 2007;65(2):319–320; discussion 20. 46 Puli SR, Graumlich JF, Pamulaparthy SR, Kalva NR. Endoscopic transmural necrosectomy for walled-off pancreatic necrosis: a systematic review and meta-analysis Can J Gastroenterol 2013;28: 50–53. 47 Ringbaek TJ, Krasnik M, Clementsen P, et al. Transesophageal endoscopic ultrasound/fine-needle aspiration diagnosis of a malignant adrenal gland in a patient with non-small cell lung cancer and a negative CT scan. Lung Cancer 2005;48(2):247–249. 48 DeWitt J, LeBlanc J, McHenry L, et al. Endoscopic ultrasoundguided fine needle aspiration cytology of solid liver lesions: a large single-center experience. Am J Gastroenterol 2003;98(9): 1976–1981. 49 Muehlstaedt M, Bruening R, Diebold J, et al. CT/fluoroscopy-guided transthoracic needle biopsy: sensitivity and complication rate in 98 procedures. J Comput Assisted Tomogr 2002;26(2):191–196. 50 Adler DG, Jacobson BC, Davila RE, et al. ASGE guideline: complications of EUS. Gastrointest Endosc 2005;61(1):8–12. 51 Ryan AG, Zamvar V, Roberts SA. Iatrogenic candidal infection of a mediastinal foregut cyst following endoscopic ultrasound-guided fine-needle aspiration. Endoscopy 2002;34(10):838–839. 52 von Bartheld MB, van Kralingen KW, Veenendaal RA, et al. Mediastinal-esophageal fistulae after EUS-FNA of tuberculosis of the mediastinum. Gastrointest Endosc 2010;71(1):210–212.

CHAPTER 8

Linear-array EUS: normal anatomy James T. Sing, Jr. Division of Gastroenterology, Baylor Scott & White Clinic and Hospital, Temple, TX, USA

With the advent of interventional endosonography, led by endoscopic ultrasonography (EUS)-guided fine-needle aspiration (FNA), there has been continued, rapidly growing interest in linear endosonography. This technology has been shown to be an effective modality for establishing a histologic diagnosis of primary malignant lesions within and adjacent to the gastrointestinal (GI) tract, documenting the spread of malignancy to lymph nodes and the liver, and evaluating fluid collections. The essentials of learning both radial and linear EUS are well described [1, 2]. A thorough review of mediastinal, upper abdominal, and pelvic anatomy is essential to navigating through a successful endosonographic examination. It is also important to understand the normal major anatomic variations, as this will give the endoscopist the awareness needed to identify abnormal structures and lesions. Thus, a well-illustrated anatomic atlas is foundational to any endosonographic library. Radiology texts on computed tomography (CT) or magnetic resonance imaging (MRI) can be very helpful to understanding the normal, anatomic variations, and pathological appearances of the mediastinum, abdomen, and pelvis in transverse, sagittal, and coronal planes. The basic principles of ultrasound also need to be mastered, including ultrasound physics, instrumentation, and artifacts (see Chapters 2 and 4). The specific resources for training in EUS are fortunately now very extensive; they include a large body of medical literature, many excellent monographs and textbooks, and multiple online learning videos and DVDs, available from organizations such as the American Society for Gastrointestinal Endoscopy (ASGE) (www.asge.org). A variety of monographs, atlases, and CD- and DVD-based learning tools are available from endoscopic industrial educational resources.

Performing the examination Training in endosonography has focused mainly on the use of radial echoendoscopes. However, soon after linear instruments became available, it was demonstrated that a complete upper and lower endosonographic examination could be just as easily carried out using linear instrumentation [3]. Most endosonographers, equally experienced in both techniques, find a linear examination a little more cumbersome for rapid survey of the mostly radially oriented gut; however, multiple studies have demonstrated that

diagnostic EUS for almost all indications can be performed equally well with either radial or linear instrumentation in the hands of an experienced endosonographer. There are four basic approaches to performing a complete upper endosonographic linear examination. The first, and probably most common, approach involves using radial endosonography as the primary diagnostic modality and then, if pathology requiring endosonographic intervention is found (e.g., a mass for FNA), proceeding directly to a focused linear endosonographic examination. With this approach, the endosonographer has the unique challenge of rapidly relocating any pathology noted on the radial examination with the following linear study. This requires a very thorough understanding of normal linear anatomy, especially the ability to place lesions relative to the surrounding vascular structures and organs so as to find those same anatomic structures with the linear echoendoscope. In the other three approaches, the linear echoendoscope is used for the whole examination. In the second approach, the scope is placed deep into the duodenum, and the organs around the duodenum, stomach, and esophagus are systematically examined on its withdrawal. This approach is especially practical when also using a video echoendoscope to perform a visual endoscopic examination prior to endosonography. Once the endoscopic portion is completed in the duodenum, the endosonographic examination can proceed on withdrawal. The third approach, also involving complete linear endosonographic examination, is to systematically interrogate sections as the scope is passed from the esophagus to the stomach and on to the duodenum. The fourth approach is to begin the endosonographic examination by focusing on the area of clinical interest and then examine other structures after the primary pathology has been interrogated. This approach may optimize time usage, but it runs the risk of missing unexpected pathology: it is easy to forget to examine all anatomic areas in the excitement of finding significant pathology at one location. The first, third, and fourth approaches may or may not be preceded by a survey upper endoscopy examination using either a standard endoscope or a forward endoscopically viewing radial echoendoscope. Personally, I often use the fourth approach because

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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it allows me to most efficiently plan out the remainder of the procedure. For example, if I am examining a patient with a potential mass that may need FNA, then, by proceeding directly to the anatomic area of interest, I can quickly decide whether an FNA is going to be needed, allowing me to get the appropriate equipment set up and the necessary personnel mobilized from cytopathology while I finish up the diagnostic examination of the remaining endosonographic stations. Alternatively, if I am ruling out a common duct stone and I find one, then the appropriate facilities and time for a subsequent endoscopic retrograde cholangiopancreatography (ERCP) under the same sedation can be arranged while I finish the examination. Any of the four approaches is reasonable as long as the examination consistently covers all the structures accessible to routine endosonographic interrogation so that unexpected pathology is not missed. An essential key to not missing pathology is including all the anatomic stations so as to be sure that all anatomy areas are interrogated. The specific stations used in linear endosonography and their numbering have not been standardized, and they vary from author to author and institution to institution. Although the numbering and sequences may vary, the stations uniformly include viewing from the deep duodenum, mid duodenum, and duodenal bulb, the mid-stomach, gastric cardia, and the mid- and distal esophagus. Another helpful concept that is somewhat similar to anatomic stations is that of “home base” views. Home base views are locations that can be found easily in the major anatomic regions (esophagus, stomach, duodenum, and rectum) where the anatomy varies little and the endosonographic structures are usually obvious and are similar from patient to patient. Whenever one gets lost (which happens even to the most experienced endosonographer), the scope can be quickly repositioned to the easily found and anatomically uniform home base structure for the given region. From there, uncertain structures can be systematically located or followed to determine their identification. The linear home base locations and structures for the esophagus, stomach, duodenum, and rectum are detailed in Table 8.1. There is variation in the conventions for displaying linear endoscopic images around the world. The agreed upon convention in radiology is to display longitudinal images, with cranial to the left and caudal to the right. However, most endosonographers in the United States, the United Kingdom, and France display linear endosonographic images with the scope tip oriented to the left of the image, which is usually caudal with an upper endosonographic examination. Images from Japan and Germany typically display the tip of the echoendoscope, usually caudal, to the right of their images. For this chapter, I will follow the former convention of displaying the tip of the endoscope to the left. Orientation at the tip location makes more sense than whether the scope is viewing in a cranial or caudal orientation, since this can change rapidly when passing beyond the proximal stomach. Like many experienced endosonographers, I do not usually use a balloon on the tip of a linear-array echoendoscope, as this is not needed for excellent imaging. Balloons can occasionally be useful Table 8.1 Home base structures for linear endosonographic anatomy. Esophagus Stomach Duodenum Rectum

Descending aorta at 30–35 cm (Figure 8.1A) Abdominal aorta just below GE junction (Figure 8.5A) Endoscopic and endosonographic ampulla (Figure 8.8A) Male: prostate at 7–9 cm (Figure 8.10B) Female: vagina at 6–9 cm (Figure 8.10D)

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when trying to “lock” the scope in position in the second portion of the duodenum.

The linear esophagus On initial deep intubation of the esophagus (i.e., 30–35 cm from the incisors; Figure 8.1A), the linear echoendoscope most naturally orients pointing down toward the patient’s left anterior region. The home base structure throughout the esophagus is the descending aorta, which is located by rotating the shaft of the echoendoscope a little to the right (clockwise) or left (counterclockwise). Rotation of the echoendoscope shaft is done by either grabbing the shaft with one’s hand and rotating or rotating one’s body toward the right, producing clockwise rotation, or the left, producing counterclockwise rotation. The descending aorta is easily recognized as a large, echolucent, longitudinal structure with a very bright, deep wall secondary to the air interface from the adjacent left lung. From the descending aorta, rotating the shaft of the echoendoscope about 90∘ clockwise will bring the easily identified left atrium into view (Figure 8.1B). The left atrium will appear as a contracting, thin-walled echolucent chamber, with the mitral valve opening into the deeper left ventricle. With a little further clockwise rotation and withdrawal (Figure 8.1C), the aortic outflow tract, aortic valve, and ascending aorta can be visualized through the left atrium. Further withdrawal of the echoendoscope will follow the ascending aorta proximally and bring the right pulmonary artery into view. This is a very important view for localizing subcarinal lymph nodes (thoracic nodal station 7; Figure 8.2) for FNA. Further rightward (clockwise) rotation at this level will reveal the superior vena cava, which can be followed distally to where it drains into the right atrium (Figure 8.1D). The inferior vena cava may also be seen draining into the right atrium. Further withdrawal of the echoendoscope from the subcarinal view will result in a blind spot as the scope is pulled over the air-filled left main stem bronchus. Just proximal to the bronchus-caused blind spot and with some minor left-right rotation, the arch of the aorta comes into view as a large circular structure adjacent to the esophagus (Figure 8.3A). Just distal to the arch is the cross-sectional view of the right pulmonary artery. Between the aortic arch and the right pulmonary artery is the aortopulmonary window, the medial portion of thoracic nodal station 5 (Figure 8.2), which is another important area for FNA of pathological mediastinal lymph nodes. By rotating the scope slightly right and left and withdrawing, the takeoffs of the left common carotid and, more rarely, the subclavian arteries can be seen (Figure 8.3C). Deep into the arch is the occasionally visible left innominate (brachiocephalic) vein. Along the path of the left common carotid is thoracic nodal station 2L (Figure 8.2). On withdrawing the echoendoscope into the neck, the esophagus is wedged between the impenetrable air-filled trachea anteriorly and the spine posteriorly. Rotating further clockwise from the left common carotid in the very proximal esophagus may reveal views of the right common carotid artery and the deeper internal jugular veins, along which is thoracic nodal station 2R (Figure 8.2). Returning back to the linear esophageal home base of the distal esophageal descending aorta (Figure 8.1A), rotation to the left (counterclockwise) from the descending aorta for most of the distal half of the esophagus will promptly bring the azygous vein into view as a thin, longitudinal echolucency close to the wall of the esophagus (Figure 8.3B). Withdrawing the scope while following the azygous vein will bring the arch of the azygous into view as it courses into the deeper superior vena cava. Rotation of the echoendoscope leftward

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(A)

(B)

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Figure 8.1 (A) Home base view of the descending aorta (da) in the mid-esophagus. (B) View of the left atrium (la), with the deeper mitral valve (mv),

left ventricle, and the main pulmonary artery (pa). (C) A view of the subcarinal region (arrow), with the deeper right pulmonary artery (rpa), ascending aorta (aa), and aortic valve (av). (D) View of the right atrium (ra), with the inferior vena cava (ivc) and superior vena cava (svc) running into it. Unless otherwise stated, all endosonographic images were made using the Olympus GF-UC240P-AL5 ultrasound gastrovideoscope with an Aloka Pro Sound Alpha 5 ultrasound processor at 7.5 MHz.

2R

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10R

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Figure 8.2 Locations of thoracic nodal groups used in lung cancer staging.

from the aorta at the level of the gastroesophageal (GE) junction will usually show the liver with its hepatic veins draining into the inferior vena cava, which itself runs into the right atrium (Figure 8.3D).

The linear stomach As in the radial examination, home base in the linear stomach is the abdominal aorta at the level of the GE junction (station 1 in

Figure 8.4). This posterior structure is always easy to locate by positioning the echoendoscope at the GE junction and rotating it right or left until the aorta comes into view. This is also a nice window through which to aspirate peritoneal fluid, if necessary. Since the retroperitoneal structures are all posterior to the stomach, clockwise (rightward) rotation of the echoendoscope will point the echoendoscope toward the patient’s left side, while counterclockwise (leftward) rotation will point it toward their right (Figure 8.4). Unlike the descending aorta in the mediastinum, the abdominal aorta at the level of the GE junction will have the crus of the diaphragm interposed between the gastric wall and the aorta. The crus can occasionally appear quite mass-like, especially in muscular individuals and on radial viewing. It can be mistaken by novices for a celiac node or the left adrenal. From the GE junction, rotating the echoendoscope slightly to the right (clockwise) with a few centimeters of insertion will bring into view the left adrenal (Figure 8.5B), with its echolucent cortex and more echogenic medullary portion. However, the linear left adrenal tends to be a more longitudinally flat organ, and it can be more difficult to identify by this method than by radial EUS. Rotating left (counterclockwise) from the abdominal aorta at the GE junction brings into view the liver, the dome of the diaphragm, and the hepatic veins draining into the inferior vena cava (Figure 8.3D). Further rotation points the ultrasonic view anteriorly, so that the left lobe of the liver can be systematically interrogated. With the patient lying on their left side, this is a region where it is often easy to find and aspirate small amounts of ascites by EUS-guided FNA. From the stomach’s home base at the abdominal aorta near the GE junction, the echoendoscope can then be inserted deeper into the stomach, following the course of the aorta (station 2 in Figure 8.4). Soon, the takeoff of the celiac artery is visible (Figure 8.5C), with the more oblique takeoff of the superior mesenteric artery usually apparent just distal to this.

Chapter 8: Linear-array EUS: normal anatomy

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Figure 8.3 (A) View of the aortopulmonary window, with thoracic nodal station 5A nestled between cross-sectional views of the arch of the aorta (aa) and

the right pulmonary artery (rpa). (B) View of the azygous vein (az) from the mid-esophagus level. (C) View of the left common carotid artery (lcc) arising out of the arch of the aorta. (D) View of the hepatic veins (hv) draining into the inferior vena cava at the dome of the diaphragm (dia).

1 5

2

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Figure 8.4 Endosonographic stations in the stomach.

This view is important because it localizes the celiac axis region for EUS-guided FNA of celiac nodes and for celiac plexus neurolysis. To view the celiac, the scope tip may need to be bent downward with the control knobs, as the aorta appears to be moving deep away from the posterior wall of the stomach as the scope is inserted. It is actually the stomach moving anteriorly that causes this effect. From the celiac artery, the scope is inserted a little farther (station 3 in Figure 8.4), bringing the pancreas neck or body into view within the triangle made by the celiac and superior mesenteric arteries and the gastric wall (Figure 8.5D). Note that the splenic artery can course tortuously in and out of the pancreas, but the splenic vein usually has a straight course and is the larger and deeper of the two vessels. Both vessels tend to appear at the caudad border of the pancreas neck, body, and tail. The pancreas is interrogated from

the neck to the body (Figure 8.6A) and tail through the stomach at this level by rotating the echoendoscope to the right (clockwise), with slight withdrawal (station 5 in Figure 8.4), which follows the splenic vein and splenic artery as they run into the hilum of the spleen (Figure 8.6D). The pancreas neck, body, and tail will appear between the splenic vein and the posterior gastric wall. The pancreatic duct is usually seen in cross section using linear EUS through the stomach; thus, it will normally appear as just a small, sometimes difficult-to-see, echolucent dot in the middle of the pancreatic parenchyma. Rotation to the left at the level of the celiac axis and body of the pancreas (station 4 in Figure 8.4) brings into view the pancreatic neck, with the portal vein confluence deep to it (Figure 8.6B). The splenic vein merges into the confluence from the patient’s left, and the superior mesenteric vein runs caudad from the portal vein confluence. Although it may take a little fine positioning of the echoendoscope tip, portions of the superior mesenteric artery can usually be seen deep to the portal vein confluence. A little further leftward rotation of the echoendoscope may produce views of the right border of the pancreatic neck looking down toward the pancreatic head (Figure 8.6C). Sometimes, longitudinal views of the pancreatic duct can be obtained from this view. Further leftward rotation brings the left lobe of the liver back into view. Liver metastases are most easily aspirated between this level and the GE junction. On moving the echoendoscope into the antrum, little more than the surrounding bowel, liver, and omentum is usually seen; however, some of the structures of the porta hepatis, such as the gallbladder, can be viewed through the prepyloric antrum.

The linear duodenum As with radial endosonography, the linear duodenum presents the endosonographer with the most variability and, at times, frustration in the endosonographic anatomical relationships of vessels, ducts,

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Figure 8.5 (A) Home base view for the stomach (station 1 in Figure 8.4), with the abdominal aorta (aa) seen in longitudinal section and the crus of the left

diaphragm overlying it. (B) View of the left adrenal, made using a Pentax FG36-UX echoendoscope with a Hitachi EUB-525 processor at 7.5 MHz. (C) View of the celiac artery (ca) arising from the abdominal aorta, with the more distal and oblique superior mesenteric artery (sma) (station 2 in Figure 8.4). (D) View of the pancreas body in cross section, with the splenic artery (sa) and vein (sv) typically seen caudad to it (station 3 in Figure 8.4). Note the very small normal pancreatic duct (pd), also seen in cross section.

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Figure 8.6 (A) Linear view across the midbody of the pancreas (p) (station 3 in Figure 8.4), showing the splenic artery (sa) weaving around the pancreas,

with the larger and straighter splenic vein (sv) deep to it. Also in view are the left adrenal (la) and the left renal vein (lrv). (B) View of the neck of the pancreas at the level of the portal vein (pv) confluence (station 4 in Figure 8.4). The superior mesenteric vein (smv) merges into the portal vein, with glimpses of the superior mesenteric artery (sma) deep to this. (C) View of the right lateral margin of the pancreatic neck, looking down toward the pancreatic head (arrow). (D) View of the spleen and its hilar vessels (station 5 in Figure 8.4).

and periduodenal organs. In addition, there is a confusing array of linear structures very close to one another, where just slight changes in orientation of the echoendoscope tip produce totally new views (Figure 8.7). Finally, there is a marked transition in the direction of the scope tip and therefore in anatomic views between

entering the duodenal bulb in a “long position” (Figure 8.7A,B), where the scope tip is pointing cephalad and posterior, and a “short position” (Figure 8.7C,D), where the scope tip is pointing caudad, when withdrawing from the second portion of the duodenum. Adding to this complexity, an endosonographic home base is not

Chapter 8: Linear-array EUS: normal anatomy

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Figure 8.7 Fluoroscopic views of a linear echoendoscope maneuvering around the duodenum. (A) On first entering into the duodenal bulb, the scope is

typically in a long position, with the tip pointing posteriorly and caudad. (B) View from this first duodenal station, looking down on to the pancreatic head intercepting the gastroduodenal artery (gda), bile duct, hepatic artery (ha), portal vein (pv), and superior mesenteric vein confluence (smv). Also shown are the gallbladder (gb), common hepatic artery (cha), and splenic artery (sa). (C) Second duodenal station, the home base location of the echoendoscope over the ampulla in a short position. Here, the common bile duct (cbd) and pancreatic duct appear within the pancreatic head, with the smv and superior mesenteric artery (sma) deep to them. (D) In the third station of the duodenum, the echoendoscope is deep at the junction between the second and third portions, looking up toward the ventral pancreas and mesenteric root vessels.

as easily defined as for the linear esophagus or stomach – or for the radial duodenum, for that matter. I find that the most reliable starting point is to place the echoendoscope in a short position in the second portion of the duodenum, then endoscopically visualize the region of the ampulla of Vater with the partially side-viewing optics characteristic of all linear echoendoscopes. The tip can then be deflected, and air sucked from and/or water added to the duodenum (or balloon, if one is used), to allow direct endosonographic evaluation of the region directly over the ampulla itself (Figure 8.8A). On slightly rotating the scope right or left with very gentle withdrawal, the pancreatic duct will usually be seen first, traveling relatively perpendicularly away from the transducer (Figure 8.8B). The common bile duct will be seen to originate from the ampulla between the duodenal lumen and the pancreatic duct. Like the pancreatic duct in the stomach, the common bile duct in the duodenum will be seen primarily in cross section when using this maneuver. Although a markedly dilated common bile duct is easy to identify, this cross-sectional view means that a normal, 2–3 mm common bile duct will be just a black dot nestled within the pancreatic parenchyma (Figure 8.8B). The use of color-flow Doppler to differentiate vascular from ductal structures can be very helpful in this region. The pancreatic parenchyma seen at the level of the ampulla represents primarily the ventral pancreas. The echolucency of the ventral anlage commonly seen by radial endosonography [4] may be less apparent by linear EUS (Figure 8.8B). At this level, if vessels are seen deep into the pancreatic head, they are usually the superior mesenteric vein and artery. If the echoendoscope is placed deeper into the duodenum, a linear view of the aorta or inferior

vena cava may appear in either a transverse section, as seen radially (Figure 8.8C), or longitudinally. If one inserts the echoendoscope into the third portion of the duodenum, one may see the uncinate portion of the pancreas nestled among the vessels of the mesenteric root (Figure 8.8D). Because this is a difficult view to obtain with a radial instrument, the same view using a linear instrument is sometimes the only way in which deep uncinate tumors may be seen. Anywhere in the second portion of the duodenum, views of the right kidney may appear. With its characteristic appearance, this is usually easy to pick out (Figure 8.9C), but sometimes the right renal vein or artery may be confused for a mesenteric vessel or duct. If there is any doubt, it can be resolved by following the vessel to its origin in the renal hilum or using pulse Doppler to determine that the structures are systemic veins or arteries. From the home base of the ampullary region, further gradual withdrawal and rotation to the left (counterclockwise) will follow the course of the tubular structures of the porta hepatis (Figure 8.9B). The largest structure seen in cross section will usually be the portal vein, which can be followed arising smoothly from the superior mesenteric vein. Sometimes, the splenic vein will be seen coursing into the portal vein/superior mesenteric vein from deep within these vessels (Figure 8.9A). This view is usually easier to obtain when the scope is first inserted into the duodenal bulb and its tip is oriented more cephalad (Figure 8.7B). Again, color-flow Doppler or pulse-wave analysis can help clear up any confusion about this. The pancreatic head can also be viewed at this level as the tissue between the superior mesenteric vein/portal vein and the duodenal wall.

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(A)

(B)

(C)

(D)

Figure 8.8 (A) Linear view from the second duodenal station (Figure 8.7C), where the echoendoscope is placed directly over the ampulla (amp). Usually, the pancreatic duct (pd) is seen first at this level. (B) A slightly more caudad view from above, with the common bile duct (cbd) now seen between the duodenal wall and pancreatic duct. (C) In the third duodenal station (Figure 8.7D), the abdominal aorta (aa) and inferior vena cava (ivc) come into view, either in cross section or longitudinally. (D) View of mesenteric root vessels (mv) from the proximal third portion of the duodenum (third duodenal station), showing some uncinate pancreatic tissue (p).

(A)

(B)

(C)

(D)

Figure 8.9 (A) Linear view from the first duodenal station (Figure 8.7A,B), where the echoendoscope is in a long position inserted deep into the duodenal

bulb. From here, the bulk of the pancreatic head is visible, with the pancreatic duct (pd) running deep toward the neck. The common bile duct (cbd) is seen in cross section, as is the potentially confusing gastroduodenal artery (gda). The portal vein (pv), superior mesenteric vein (smv), and splenic vein (sv) confluence is the prominent deep structure. Deep in the portal vein is the hepatic artery (ha). (B) Further counterclockwise rotation from above brings the porta hepatis into view, with the triad of the portal vein, common bile duct, and hepatic artery in cross section. Notice the large gastroduodenal artery coming off the hepatic artery, which can be mistaken for the common bile duct. (C) Anywhere in the second portion of the duodenum, the right kidney (K) may be seen. (D) Rotation 180∘ in the duodenal bulb or antrum usually results in views of the gallbladder (gb).

Chapter 8: Linear-array EUS: normal anatomy

(A)

(B)

(C)

(D)

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Figure 8.10 (A) Linear view of the male rectum at about 9 cm from the anal verge. The seminal vesicles (sv) are caudad to the prostate (pr). Deep to this is

the bladder (B). (B) At the distal end of the prostate, the membranous urethra (mu) and perineal membrane (pm) mark the end of the male pelvis. (C) Linear view of the female rectum at about 9 cm, showing the uterus (ut) and the deeper bladder. (D) At 5–9 cm from the anal verge, the vagina (V) is easy to detect due to the small amount of air within it, producing a bright stripe.

Further leftward rotation and withdrawal into the duodenal bulb (Figure 8.9B) follow the course of the common bile duct up to the level of the common hepatic duct. The common bile duct will be seen between the duodenal wall and the portal vein, but it can sometimes be difficult to distinguish from vascular structures such as the gastroduodenal artery. As the echoendoscope is rotated up and down the porta hepatis, the hepatic artery (ha) will usually be seen above or deep into the portal vein. The gastroduodenal artery comes off the hepatic artery, then travels toward the duodenal wall, where it can run near the common bile duct. The rotation of the linear-array echoendoscope almost 180∘ counterclockwise from the pancreas in the duodenum or duodenal bulb should produce images of the gallbladder (Figure 8.9D). The right adrenal may also be seen from the bulb, deep into the inferior vena cava or near the upper pole of the right kidney.

The linear rectum Male Linear evaluation of the rectum is usually reserved for therapeutic purposes, such as EUS-guided FNA. I find that negotiating the tortuous rectosigmoid is much easier to accomplish with a radial echoendoscope under ultrasonic guidance than with a linear echoendoscope. As with the radial rectal examination, the echoendoscope is usually inserted into the mid-sigmoid colon and then withdrawn. The first structures to come into view in both sexes will be cross-sectional images of the iliac vessels. These can be seen anywhere from 15 to 25 cm from the anus, depending on the orientation of the sigmoid colon. Withdrawal of the echoendoscope to approximately 7–11 cm in the rectum, with rotation to the right or left, will bring into view the easily identified home base structure in the male rectum, the prostate (Figure 8.10A). Just proximal to the prostate lie the seminal vesicles, arising to the right and

left of the prostate, with the bladder seen more proximally and deeper into the seminal vesicles. In older men, the prostate often contains bright echoes from small calcifications. Withdrawal of the echoendoscope distally from the prostate reveals a short portion of the membranous urethra diving away from the lumen of the rectum toward the root of the penis (Figure 8.10B). The muscular peroneal membrane may also be visible, distal to the membranous urethra. Female In females, withdrawal of the echoendoscope from the sigmoid colon will bring the uterus into view with the deeper bladder (Figure 8.10C). Sometimes the left adnexal structures can also be seen on deep insertion near the pelvic rim vessels. Withdrawal from the level of the uterus will show a home base view of the air stripe of the vagina anteriorly, with portions of the urethra seen deep to it (Figure 8.10D). The anal sphincters are more difficult to assess with linear than with radial endosonography, and most anal sphincter studies are carried out using radial systems. If linear endosonography is used, the internal sphincter is seen as an echolucent layer just deep to the bright anal mucosal layer. Deep into the internal sphincter, the external sphincter blends into the other muscle layers of the levator ani complex.

Conclusion Although most endosonographers look at linear EUS anatomy as more difficult than radial, it can be mastered through dedicated focus on the anatomic relationships of the organs and vessels around the gut. Once knowledge of these relationships becomes “second nature,” remembering the ever-changing direction of the tip of the linear echoendoscope in various locations will allow the endosonographer to put them into clinical practice.

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References 1 Boyce HW. Training in endoscopic ultrasonography. Gastrointest Endosc 1996;43:S12–S15. 2 Eisen GM, Dominitz JA, Faigel DO. et al., American Society for Gastrointestinal Endoscopy. Guidelines for credentialing and granting privileges for endoscopic ultrasound. Gastrointest Endosc 2001; 54:811–814.

3 Villman P, Hancke S. Endoscopic ultrasound scanning of the upper gastrointestinal tract using a curved linear array transducer: the linear anatomy. Gastrointest Endosc Clinics N Am 1995;5:507–521. 4 Savides TJ, Gress FG, Zaidi SA, et al. Detection of embryologic ventral pancreatic parenchyma with endoscopic ultrasound. Gastrointest Endosc 1996;43:14–19.

CHAPTER 9

High-frequency ultrasound probes Nidhi Singh, Alberto Herreros-Tejada & Irving Waxman Center for Endoscopic Research and Therapeutics (CERT), University of Chicago, Chicago, IL, USA

Endoscopic ultrasonography (EUS) was developed to use radial and linear array to evaluate the luminal wall and adjacent tissues in the gastrointestinal (GI) tract. One of the most important roles of EUS has been in the evaluation and local staging of GI malignancies [1]. Standard echoendoscopes operate with frequencies between 5 and 20 MHz; the higher the frequency, the better the resolution of the image, but the lower the penetration of the ultrasound [2].

High-frequency ultrasonography The high-frequency ultrasound (HFUS) device is a small-caliber ultrasound probe (less than 2.6 mm), first introduced in 1989 [3] (Figure 9.1). It operates at higher frequencies (12–30 MHz) and obtains a significantly higher resolution than conventional EUS [4, 5]. Compared to the standard EUS, the HFUS probe is inserted into the accessory channel of an endoscope, allowing its use with standard upper or lower endoscopy. The higher resolution of the HFUS probe provides a better definition of the GI wall layers, and therefore yields a better accuracy in the study of small or superficial lesions of the GI tract [4]. Another potential benefit is its ability to pass through tight strictures. Technical features HFUS probes are divided into mechanical and electronic types. The mechanical type is based on a single ultrasound transducer in the tip of the probe, rotated by a central wire and thus producing a 360∘ image perpendicular to the axis of the probe. The transducer cap is filled with oil, which serves as an acoustic interface. The electronic type consists of fixed transducers, and is mainly used in cardiovascular procedures [6]. Standard HFUS mechanical probes are available in different diameters (2.0–2.9 mm), different frequencies (12–30 MHz), and different lengths (1700–2200 mm) [6, 7] (Table 9.1). Reportedly, the mean imaging depths based on the 12, 20, and 30 MHz probes are 29, 18, and 10 mm, respectively [4, 8]. Currently available HFUS probes generate high-resolution radial images, and can be used with upper endoscopy, enteroscopy, sigmoidoscopy, colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP). Prior to the procedure, the tip of the HFUS probe should be rotated outside the body to allow even distribution of the immersion oil around the

tip, and the image quality should be assessed. During preparation, the patient may be given intravenous glucagon or atropine to decrease peristalsis and facilitate the procedure. Some endoscopists advocate the administration of mucolytics to remove superficial mucus and thus enhance the quality of the image. If a biopsy of the lesion is needed, it is highly recommended to perform it after the HFUS probe is used, to prevent artifact imaging. Once the tip of the endoscope is placed near the target lesion, the inactivated probe is passed through the biopsy channel and set out approximately 1 cm from the endoscope tip, close to the lesion. Acoustic coupling between the probe and the tissue can be improved by careful aspiration of the air in the lumen, instilling water into the lumen (taking precautions to reduce the risk of aspiration), and applying jelly transuding medium. Some reports have shown that a condom or a balloon sheath may be affixed over the tip of the endoscope to improve acoustic coupling, particularly when using it in the esophagus and rectum [9, 10]. Some endosonographers have utilized submucosal injection below a lesion to enhance the image of esophageal and colorectal lesions and thus improve accuracy when staging the depth of tumor invasion [11]. When an HFUS probe is used in the bile duct, the bile itself reduces the need for additional balloon or water immersion. Anatomical correlation The image obtained with an HFUS probe is smaller than that of the standard EUS, due to the higher frequency applied. The depth of penetration is limited to 2–3 cm. On the other hand, the superior definition provides an ultrasonographic image of the wall structure layers resembling those seen on histology [12]. Whereas conventional EUS is able to discern only five layers of the wall structure, HFUS probe (20–30 MHz) imaging has been able to identify nine to eleven layers in the stomach and five layers in the colon [11, 13]. The normal stomach wall anatomy under high-frequency ultrasonography may include nine layers (Figure 9.2): • The first (hyperechoic) and second (hypoechoic) layers correspond to the interface with the probe surface and the mucosa. • The third (hyperechoic) layer corresponds to the muscularis mucosae. • The fourth (hypoechoic) layer corresponds to the interface between mucosa and submucosa. • The fifth (hyperechoic) layer represents the submucosa.

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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• The sixth (hypoechoic) layer corresponds to the inner circular muscle layer, the seventh (hyperechoic) to the intermuscular connective tissue interface, and the eighth (hypoechoic) to the outer longitudinal muscle layer. • The ninth (hyperechoic) layer represents the subserosal and serosal. In the colon, the three layers of the muscularis propria may also be visualized: • Inner hypoechoic 5 circular muscle. • Middle hyperechoic interface 5 connective tissue. • Outer hypoechoic longitudinal 5 muscle layer. The superior resolution yield of the HFUS probe allows a detailed evaluation of the muscularis mucosa and muscularis propria. This capability is very useful in the diagnosis of motility disorders and local evaluation of early cancers, prior to endoscopic mucosal/submucosal resection. Applications of high-frequency ultrasonography HFUS probes can be used in tumor staging in nonbulky lesions and depth evaluation of superficial early cancer prior to endoscopic therapy [14]. The accuracy of staging of superficial tumors of the esophagus, stomach, and colon may be as high as 90% [8, 15–20]. However, due to the inability to correctly discern inflammation and malignancy on ultrasonographic imaging, some limitations have been observed [19]. Moreover, the reduced visualization of distant lymph nodes due to the high frequency may prevent complete tumor–node–metastases (TNM) staging.

Table 9.2 Results of HFUS in esophageal carcinoma staging. Series

N

T-stage accuracy

N-stage accuracy

Yanai et al. [24] Akahoshi et al. [25] Hunerbein et al. [26] Kida et al. [27]

52 78 30 302

71% 67% 82% 79%

– 80% 80% –

Esophagus

Esophageal cancer In comparison to the standard EUS, T-staging accuracy of esophageal cancer with high-frequency ultrasonography may be superior, due to both improved resolution and the ability of the probe to traverse tight strictures [8]. It can reach an accuracy of up to 85% [15, 21–23] (Table 9.2). This characteristic makes it particularly useful in the evaluation of superficial or early carcinomas eligible for endoscopic resection [21]. One of the main limitations of high-frequency ultrasonography is regional node staging, which should be attempted with standard EUS [15].

Barrett esophagus The HFUS probe has limited accuracy in identifying invasive cancer in patients found to have high-grade dysplasia or intramucosal carcinoma, even in the setting of Barrett esophagus with endoscopically visible lesions [13].

Other indications

Figure 9.1 HFUS probe through the working channel of a side-view

endoscope.

Table 9.1 HFUS probes. Designer Model

Fujinon

Olympus

PL 2220 PL 1726–1926 PL 2226 UM-S20-20R UM-S30-20R UM-2R UM-3R UM-S30-25R UM-DP12-25R UM-DP20-25R UM-BS20-26R-3 UM-G20-29R

High-frequency ultrasonography can be used in the evaluation of esophageal varices, measuring variceal radius and wall thickness [28–30]. The probe has the advantages of not requiring passage of the entire scope to the level of variceal lesions and not resulting in variceal compression. In achalasia, an HFUS probe has been used to identify the lower esophageal sphincter, in order to properly localize the injection site of botulinum toxin [31], and to help in the evaluation of esophageal motor and sensory function. Hypertrophy or incoordination of the circular and longitudinal muscle layers could appear in achalasia, diffuse esophageal spasm, or nutcracker esophagus [32, 33]. High-frequency ultrasonography may allow early identification and diagnosis of eosinophilic esophagitis, by identifying significant expansion of the esophageal wall and individual tissue layers (mucosa, submucosa, and muscularis propria) [34]. Stomach

Diameter (mm)

Length (mm)

Mode

2.0 2.6 2.6 2.0 2.0 2.5 2.5 2.5 2.5 2.5 2.6 2.9

2200 1700–1900 2200 2140 2140 2140 2140 2140 2200 2200 2140 2140

Radial/linear Radial/linear Radial/linear Radial Radial Radial Radial Radial Radial/linear Radial/linear Radial Radial

Frequency (MHz) 12–15–20 12–15–20 7.5 20 30 12 20 30 12 20 20 20

Early gastric cancer High-frequency ultrasonography can be quite accurate for T-staging, which seems to be facilitated when the gastric cancer lesions are elevated and well differentiated [16, 35, 36]. Accuracy has been described as up to 80%, compared with 63% for conventional EUS [23, 24, 26, 27, 36]. One of the main concerns in the use of HFUS is the risk of overstaging, related to local inflammation, edema, or fibrosis [36]. On the other hand, the T-staging accuracy of high-frequency ultrasonography decreases when the lesions invade deeper than 10 mm [25]. Even with these limitations, HFUS can be very useful in decision-making for endoscopic mucosal resection (EMR) therapy of superficial/early gastric carcinoma [37, 38].

Chapter 9: High-frequency ultrasound probes

1. Superficial mucosa 2. Interface Sum/mm

hyperechoic hypoechoic

3. Muscularis mucosae 4. Interface Mm/Sm 5. Submucosa

hyperechoic hypoechoic hyperechoic

6. Circular muscle layer 7. Interface Cml/Lml

hypoechoic hyperechoic

8. Longitudinal muscle 9. Adventitia/serosa

hypoechoic hyperechoic

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1 2 Mucosal layer 3 4 Interface Mm/Sm 5 Submucosal layer 6 Inner circular muscle layer 7 Intermuscularis propria layer 8 Outer logitudinal muscle layer 9 Subserosa and serosa

Figure 9.2 Sonographic correlation with wall structure of the gastric wall (HFUS 20 MHz).

Other indications Reports have shown that HFUS probes aid in the diagnosis of gastric lymphoma, linitis plastica, Menetrier gastropathy, and gastric varices [39]. Lymphoma may appear to have thickened mucosa or submucosa, with hypertrophic folds. Linitis plastica may present with marked thickening of the mucosa, submucosa, and muscularis propria. Sonogoraphically, Menetrier gastropathy may appear to have mucosal thickening, with cyst formation. Small bowel and colon

Technical features The technique of probe insertion is similar to that used with the stiffer occlusion balloon catheter (Figure 9.3). Cannulation with the miniprobe can be difficult without sphincterotomy or the use of a guide-wire. Although most probes are semiflexible, excessive elevator use during cannulation can result in damage to the transducer. Some probes of small diameter and long length may be advanced to the distal main hepatic ducts. The exploration of the pancreatic duct may be especially tricky if it is not dilated or if the anatomical duct is tortuous.

Colorectal cancer The HFUS probe has the ability to be used through a standard colonoscope, thus allowing easy access from the colon to the cecum. T-staging accuracy appears to be similar to that of standard EUS [17, 18]. The ideal target for the HFUS probe may be flat and superficial invasive tumors, where it can reach nearly 100% accuracy for small lesions [7]. High-frequency ultrasonography has also been compared with magnification colonoscopy for T-staging, obtaining superior results [20, 40].

Anatomical correlation Under IDUS, the sphincter of Oddi will appear as a hypoechoic circular thickening within the duodenal wall. The bile duct appears to have two or three layers: an inner hyperechoic layer, corresponding to the interface between the duct mucosa and bile; a middle discontinuous hypoechoic liner, correlate with the fibromuscular layer; and the outer hyperechoic layer, which corresponds to the

Other applications The HFUS probe has been used to aid in the preoperative diagnosis of bowel tumors, including leiomyoma, leiomyosarcoma, lipoma, lymphoma, and neuroendocrine tumors. Studies have also shown the usefulness of the HFUS probe in measuring the colonic wall thickness and layer structure to identify lesions and to try to determine severity in active inflammatory bowel disease [41, 42].

Intraductal ultrasonography The development of intraductal ultrasonography (IDUS) based on special miniprobes has advanced the study of the pancreatico-biliary tree and the duodenal ampulla. These wire-guided miniprobes (5–10 F in diameter, with frequencies ranging from 12.5 to 30 MHz) can be advanced through the biliary and pancreatic ducts in a transampullary fashion, either by free cannulation or over a wire-guide. IDUS creates radial images from within the duct lumen, centering on the scanner unit; the tubular anatomy and the presence of bile or pancreatic fluid facilitates the acquisition of high-resolution images. These miniprobes can be used through a standard side-viewing endoscope, or else percutaneously.

Figure 9.3 Radiologic images of an IDUS probe in the common bile duct

during ERCP.

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Figure 9.4 HFUS of (A) normal pancreas and (B)

correspondent histopathology.

subserosal fat tissue layer (Figure 9.4). When the IDUS miniprobe is placed in the intrahepatic duct, some vascular structures, such as the portal vein and the right hepatic artery, can be identified, although with significant limitation due to the higher frequencies. The pancreas, with its usual homogenous echogenicity, can be best viewed when within the intrapancreatic common bile duct. The main pancreatic duct can be seen traveling alongside the distal common bile duct. The inferior vena cava may also be visualized posterior to the pancreas.

(A)

(B)

diagnosis between (under) stage III and (over) stage IVA, as well as in assessing portal and right hepatic artery involvement [56]. IDUS has also been used in the assessment of response to radiation therapy, by measuring the bile duct thickness before and after treatment [57]. This proves its usefulness for predicting the patency of metallic stents in bile duct cancer. Drawbacks include the inability to demonstrate lymph node involvement, distant metastases, or vessel invasion beyond the hepatoduodenal ligament.

Ampullary tumors Applications of IDUS

Choledocholithiasis Several studies have demonstrated that IDUS is superior to ERCP or EUS alone in identifying stones [43, 44]. A study by Ohashi et al. showed that IDUS was able to detect up to 33% of small stones not seen on ERCP [45]. Despite these advantages, its use is still limited due to its cost and a lack of data.

Bile duct strictures Various preliminary studies suggested that a hypoechoic mass, heterogeneity of the internal echo, irregular surface, and wall thickening or disruption of the normal bile duct stricture can indicate underlying malignancy [46–48]. One retrospective study reported that IDUS images were able to correctly identify benign from malignant strictures with up to 90% accuracy [47]. Similar studies have shown that IDUS could be more accurate than EUS or ECRP in determining the nature and potential resectability of bile duct strictures [49, 50]. An additional study found that HFUS probes used in conjunction with ERCP could increase the accuracy of characterizing bile duct strictures from 58 to 90% [51].

Some studies have found that IDUS probes are superior to standard EUS and computed tomography (CT) for the visualization and diagnosis of ampullary tumors [50, 58].

Pancreatic adenocarcinoma and pancreatic strictures IDUS has been used in the detection of pancreatic tumors in early stages [59, 60], and for the evaluation of pancreatic strictures [46, 47, 61]. An echo-rich area surrounded by an echo-poor margin should be considered characteristic for pancreatic cancer [59]. On the other hand, a ring-like echolucent band surrounded by a fine reticular pattern is distinctive of chronic pancreatitis (CP), and the degree of heterogenicity is considered to be in proportion to the degree of fibrosis [46, 47].

Mucin-producing tumors IDUS has been helpful in the evaluation of mucin-producing pancreatic tumors, where clear images of the cystic lesions and surface changes of the pancreatic duct may be identified.

Complications Cholangiocarcinoma Management of cholangiocarcinoma depends largely on the location of the tumor, tumor stage (TNM), and resectability. Preliminary data on IDUS indicate that it is useful in assessing the extension of bile duct carcinoma into the portal vein and right hepatic artery. IDUS is significantly superior to conventional EUS for T-staging (77 vs. 54%), with a reported accuracy and sensitivity of 89 vs. 76% and 91 vs. 76%, respectively [52–54]. The IDUS miniprobe allows further access to proximal cholangiocarcinomas at the hilum compared with standard EUS [52]. IDUS has also been shown to be more accurate than cholangiography in assessing for intraductal spread (86 vs. 43%) [52, 55]. This modality proved useful for the differential

To date, there have been no serious complications reported with the use of ultrasound probes, and no increased risks when compared with standard EUS have been described. Caution should be maintained when lumen irrigation is required, above all in the esophagus, due to the risk of aspiration. When using IDUS, the usual risks of pancreatic and biliary instrumentation apply, including the risk of pancreatitis, with an incidence between 0.4 and 1.5% [49, 62, 63].

The future Some endoscopy manufacturers are developing three-dimensional scanning probes capable of obtaining up to 120 slices of radial

Chapter 9: High-frequency ultrasound probes

Figure 9.5 HFUS 3D imaging: reconstructed images.

images per minute and then producing 3D figures by computer processing (Figure 9.5). Some preliminary studies in 3D EUS have shown a promising accuracy in evaluation of tumor volume and accurate diagnosis of local invasion, with a good explorer agreement and low interobserver variability [64–67]. Recent reports of new 3D IDUS suggest this technology might be good at assessing the extension of bile duct tumors and their relationship with surrounding organs [68, 69]. Tamada et al. compared 3D IDUS to 2D imaging in assessing tumor extension of bile duct carcinoma [68]. 3D reconstructions of the primary tumor and its relationship to surrounding structures allowed for better recognition of tumor involvement into the pancreas and portal vein [68].

Conclusion HFUS is a new technology that provides detailed imaging of the GI wall for the evaluation and staging of mucosal and submucosal lesions of the GI tract and pancreatic biliary tree. It operates at higher frequency than standard EUS, resulting in higher-resolution images with limited depth penetration. HFUS is relatively easy to perform, involving inserting the probe through an upper or lower standard endoscope (or side-view scope, in the case of IDUS). The accuracy of HFUS for superficial GI neoplasms (early carcinoma confined to mucosa or submucosa layers) exceeds conventional EUS in T-staging, providing useful information that alters therapeutic strategies in patients with superficial lesions. One of the main limitations is the poor lymph node staging, due to the lower ultrasound penetration. IDUS is the modality applied in biliopancreatic diseases. It can be safely performed during ERCP and can achieve accurate evaluation of bile and pancreatic stenosis, local staging of carcinoma, and diagnosis of choledocolithiasis. Ongoing developments will continue to expand probe ultrasound technology and therapeutic capability.

References 1 Gan SI, Rajan E, Adler DG, et al. Role of EUS. Gastrointest Endosc 2007;66(3):425–434. 2 Bhutani MS. Interventional endoscopic ultrasonography: state of the art at the new millenium. Endoscopy 2000;32(1):62–71.

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3 Silverstein FE, Martin RW, Kimmey MB, et al. Experimental evaluation of an endoscopic ultrasound probe: in vitro and in vivo canine studies. Gastroenterology 1989;96(4):1058–1062. 4 Kimmey MB, Martin RW, Silverstein FE. Endoscopic ultrasound probes. Gastrointest Endosc 1990;36(2 Suppl.):S40–S46. 5 Schembre D, Ayub K, Jiranek G. High-frequency mini-probe ultrasound: the Rodney Dangerfield of endoscopy? J Clin Gastroenterol 2005;39(7):555–556. 6 Liu J, Carpenter S, Chuttani R, et al. Endoscopic ultrasound probes. Gastrointest Endosc 2006;63(6):751–754. 7 Hurlstone DP, Cross SS, Sanders DS. 20-MHz high-frequency endoscopic ultrasound-assisted endoscopic mucosal resection for colorectal submucosal lesions: a prospective analysis. J Clin Gastroenterol 2005;39(7):596–599. 8 Chak A, Canto M, Stevens PD, et al. Clinical applications of a new through-the-scope ultrasound probe: prospective comparison with an ultrasound endoscope. Gastrointest Endosc 1997;45(3):291–295. 9 Wallace MB, Hoffman BJ, Sahai AS, et al. Imaging of esophageal tumors with a water-filled condom and a catheter US probe. Gastrointest Endosc 2000;51(5):597–600. 10 Schembre D, Chak A, Stevens P, et al. Prospective evaluation of balloon-sheathed catheter US system. Gastrointest Endosc 2001;53(7):758–763. 11 Watanabe H, Miwa H, Terai T, et al. Endoscopic ultrasonography for colorectal cancer using submucosal saline solution injection. Gastrointest Endosc 1997;45(6):508–511. 12 Odegaard S, Nesje LB, Ohm IM, Kimmey MB. Endosonography in gastrointestinal diseases. Acta Radiol 1999;40(2):119–134. 13 Waxman I, Raju GS, Critchlow J, et al. High-frequency probe ultrasonography has limited accuracy for detecting invasive adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia or intramucosal carcinoma: a case series. Am J Gastroenterol 2006;101(8):1773–1779. 14 Waxman I, Saitoh Y, Raju GS, et al. High-frequency probe EUS-assisted endoscopic mucosal resection: a therapeutic strategy for submucosal tumors of the GI tract. Gastrointest Endosc 2002;55(1):44–49. 15 Hasegawa N, Niwa Y, Arisawa T, et al. Preoperative staging of superficial esophageal carcinoma: comparison of an ultrasound probe and standard endoscopic ultrasonography. Gastrointest Endosc 1996;44(4):388–393. 16 Takemoto T, Yanai H, Tada M, et al. Application of ultrasonic probes prior to endoscopic resection of early gastric cancer. Endoscopy 1992;24(Suppl. 1):329–333. 17 May A, Gunter E, Roth F, et al. Accuracy of staging in early oesophageal cancer using high resolution endoscopy and high resolution endosonography: a comparative, prospective, and blinded trial. Gut 2004;53(5):634–640. 18 Saitoh Y, Obara T, Einami K, et al. Efficacy of high-frequency ultrasound probes for the preoperative staging of invasion depth in flat and depressed colorectal tumors. Gastrointest Endosc 1996;44(1):34–39. 19 Yanai H, Yoshida T, Harada T, et al. Endoscopic ultrasonography of superficial esophageal cancers using a thin ultrasound probe system equipped with switchable radial and linear scanning modes. Gastrointest Endosc 1996;44(5):578–582. 20 Yoshida M, Tsukamoto Y, Niwa Y, et al. Endoscopic assessment of invasion of colorectal tumors with a new high-frequency ultrasound probe. Gastrointest Endosc 1995;41(6):587–592.

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21 Murata Y, Suzuki S, Ohta M, et al. Small ultrasonic probes for determination of the depth of superficial esophageal cancer. Gastrointest Endosc 1996;44(1):23–28. 22 Murata Y, Suzuki S, Mitsunaga A, et al. Endoscopic ultrasonography in diagnosis and mucosal resection for early esophageal cancer. Endoscopy 1998;30(Suppl 1):A44–A46. 23 Hunerbein M, Ulmer C, Handke T, Schlag PM. Endosonography of upper gastrointestinal tract cancer on demand using miniprobes or endoscopic ultrasound. Surg Endosc 2003;17(4):615–619. 24 Yanai H, Noguchi T, Mizumachi S, et al. A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer. Gut 1999;44(3):361–365. 25 Akahoshi K, Chijiiwa Y, Tanaka M, et al. Endosonography probe-guided endoscopic mucosal resection of gastric neoplasms. Gastrointest Endosc 1995;42(3):248–252. 26 Hunerbein M, Ghadimi BM, Haensch W, Schlag PM. Transendoscopic ultrasound of esophageal and gastric cancer using miniaturized ultrasound catheter probes. Gastrointest Endosc 1998;48(4): 371–375. 27 Kida M, Tanabe S, Watanabe M, et al. Staging of gastric cancer with endoscopic ultrasonography and endoscopic mucosal resection. Endoscopy 1998;30(Suppl 1):A64–A68. 28 Kane L, Kahaleh M, Shami VM, et al. Comparison of the grading of esophageal varices by transnasal endoluminal ultrasound and esophagogastroduodenoscopy. Clin Gastroenterol Hepatol 2005;3(8):806–812. 29 Schiano TD, Adrain AL, Cassidy MJ, et al. Use of high-resolution endoluminal sonography to measure the radius and wall thickness of esophageal varices. Gastrointest Endosc 1996;44(4):425–428. 30 Kishimoto H, Sakai M, Kajiyama T, et al. Miniature ultrasonic probe evaluation of esophageal varices after endoscopic variceal ligation. Gastrointest Endosc 1995;42(3):256–260. 31 Hoffman BJ, Knapple WL, Bhutani MS, et al. Treatment of achalasia by injection of botulinum toxin under endoscopic ultrasound guidance. Gastrointest Endosc 1997;45(1):77–79. 32 Dogan I, Mittal RK. Esophageal motor disorders: recent advances. Curr Opin Gastroenterol 2006;22(4):417–422. 33 Mittal RK. Motor and sensory function of the esophagus: revelations through ultrasound imaging. J Clin Gastroenterol 2005;39(4 Suppl. 2):S42–S48. 34 Fox VL, Nurko S, Teitelbaum JE, et al. High-resolution EUS in children with eosinophilic “allergic” esophagitis. Gastrointest Endosc 2003;57(1):30–36. 35 Yanai H, Fujimura H, Suzumi M, et al. Delineation of the gastric muscularis mucosae and assessment of depth of invasion of early gastric cancer using a 20-megahertz endoscopic ultrasound probe. Gastrointest Endosc 1993;39(4):505–512. 36 Akahoshi K, Chijiwa Y, Hamada S, et al. Pretreatment staging of endoscopically early gastric cancer with a 15 MHz ultrasound catheter probe. Gastrointest Endosc 1998;48(5):470–476. 37 Waxman I, Saitoh Y. Clinical outcome of endoscopic mucosal resection for superficial GI lesions and the role of high-frequency US probe sonography in an American population. Gastrointest Endosc 2000;52(3):322–327. 38 Ohashi S, Segawa K, Okamura S, et al. The utility of endoscopic ultrasonography and endoscopy in the endoscopic mucosal resection of early gastric cancer. Gut 1999;45(4):599–604. 39 Buscarini E, Stasi MD, Rossi S, et al. Endosonographic diagnosis of submucosal upper gastrointestinal tract lesions and large fold gastropathies by catheter ultrasound probe. Gastrointest Endosc 1999;49(2):184–191.

40 Matsumoto T, Hizawa K, Esaki M, et al. Comparison of EUS and magnifying colonoscopy for assessment of small colorectal cancers. Gastrointest Endosc 2002;56(3):354–360. 41 Soweid AM, Chak A, Katz JA, Sivak MV Jr., Catheter probe assisted endoluminal US in inflammatory bowel disease. Gastrointest Endosc 1999;50(1):41–46. 42 Watanabe F, Honda S, Kubota H, et al. Preoperative diagnosis of ileal lipoma by endoscopic ultrasonography probe. J Clin Gastroenterol 2000;31(3):245–247. 43 Catanzaro A, Pfau P, Isenberg GA, et al. Clinical utility of intraductal US for evaluation of choledocholithiasis. Gastrointest Endosc 2003;57(6):648–652. 44 Tseng LJ, Jao YT, Mo LR, Lin RC. Over-the-wire US catheter probe as an adjunct to ERCP in the detection of choledocholithiasis. Gastrointest Endosc 2001;54(6):720–723. 45 Ohashi A, Ueno N, Tamada K, et al. Assessment of residual bile duct stones with use of intraductal US during endoscopic balloon sphincteroplasty: comparison with balloon cholangiography. Gastrointest Endosc 1999;49(3 Pt. 1):328–333. 46 Furukawa T, Tsukamoto Y, Naitoh Y, et al. Differential diagnosis of pancreatic diseases with an intraductal ultrasound system. Gastrointest Endosc 1994;40(2 Pt. 1):213–219. 47 Furukawa T, Tsukamoto Y, Naitoh Y, et al. Differential diagnosis between benign and malignant localized stenosis of the main pancreatic duct by intraductal ultrasound of the pancreas. Am J Gastroenterol 1994;89(11):2038–2041. 48 Waxman I. Characterization of a malignant bile duct obstruction by intraductal ultrasonography. Am J Gastroenterol 1995;90(7): 1073–1075. 49 Menzel J, Domschke W. Intraductal ultrasonography (IDUS) of the pancreato-biliary duct system. Personal experience and review of literature. Eur J Ultrasound 1999;10(2–3):105–115. 50 Vazquez-Sequeiros E, Baron TH, Clain JE, et al. Evaluation of indeterminate bile duct strictures by intraductal US. Gastrointest Endosc 2002;56(3):372–379. 51 Stavropoulos S, Larghi A, Verna E, et al. Intraductal ultrasound for the evaluation of patients with biliary strictures and no abdominal mass on computed tomography. Endoscopy 2005;37(8):715–721. 52 Tamada K, Ido K, Ueno N, et al. Preoperative staging of extrahepatic bile duct cancer with intraductal ultrasonography. Am J Gastroenterol 1995;90(2):239–246. 53 Menzel J, Domschke W, Brambs HJ, et al. Miniprobe ultrasonography in the upper gastrointestinal tract: state of the art 1995, and prospects. Endoscopy 1996;28(6):508–513. 54 Kuroiwa M, Tsukamoto Y, Naitoh Y, et al. New technique using intraductal ultrasonography for the diagnosis of bile duct cancer. J Ultrasound Med 1994;13(3):189–195. 55 Tamada K, Ueno N, Ichiyama M, et al. Assessment of pancreatic parenchymal invasion by bile duct cancer using intraductal ultrasonography. Endoscopy 1996;28(6):492–496. 56 Tamada K, Ido K, Ueno N, et al. Assessment of portal vein invasion by bile duct cancer using intraductal ultrasonography. Endoscopy 1995;27(8):573–578. 57 Tamada K, Wada S, Ohashi A, et al. Intraductal US in assessing the effects of radiation therapy and prediction of patency of metallic stents in extrahepatic bile duct carcinoma. Gastrointest Endosc 2000;51(4 Pt 1):405–411. 58 Itoh A, Goto H, Naitoh Y, et al. Intraductal ultrasonography in diagnosing tumor extension of cancer of the papilla of Vater. Gastrointest Endosc 1997;45(3):251–260.

Chapter 9: High-frequency ultrasound probes

59 Ariyama J, Suyama M, Satoh K, Wakabayashi K. Endoscopic ultrasound and intraductal ultrasound in the diagnosis of small pancreatic tumors. Abdom Imaging 1998;23(4):380–386. 60 Itoh A, Goto H, Hirooka Y, et al. Endoscopic diagnosis of pancreatic cancer using intraductal ultrasonography. Hepatogastroenterology 2001;48(40):928–932. 61 Inui K, Nakazawa S, Yoshino J, et al. Endoluminal ultrasonography for pancreatic diseases. Gastroenterol Clin North Am 1999;28(3):771–781. 62 Furukawa T, Oohashi K, Yamao K, et al. Intraductal ultrasonography of the pancreas: development and clinical potential. Endoscopy 1997;29(6):561–569. 63 Gress F, Chen YK, Sherman S, et al. Experience with a catheterbased ultrasound probe in the bile duct and pancreas. Endoscopy 1995;27(2):178–184. 64 Vegesna A, Raju R, Asfari W, et al. Three-dimensional US volume analysis of gastric pseudotumors in a porcine model. Gastrointest Endosc 2006;64(4):635–640.

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65 Fritscher-Ravens A, Knoefel WT, Krause C, et al. Threedimensional linear endoscopic ultrasound: feasibility of a novel technique applied for the detection of vessel involvement of pancreatic masses. Am J Gastroenterol 2005;100(6):1296–1302. 66 Kikuchi S, Kida M, Kobayashi K, et al. New diagnostic imaging of gastrointestinal tumors: a preliminary study of three-dimensional tumor structure and volumetry. Anticancer Res 2005;25(4): 2935–2941. 67 Tsutsui A, Okamura S, Muguruma N, et al. Three-dimensional reconstruction of endosonographic images of gastric lesions: preliminary experience. J Clin Ultrasound 2005;33(3):112–118. 68 Tamada K, Tomiyama T, Ohashi A, et al. Preoperative assessment of extrahepatic bile duct carcinoma using three-dimensional intraductal US. Gastrointest Endosc 1999;50(4):548–554. 69 Kanemaki N, Nakazawa S, Inui K, et al. Three-dimensional intraductal ultrasonography: preliminary results of a new technique for the diagnosis of diseases of the pancreatobiliary system. Endoscopy 1997;29(8):726–731.

C H A P T E R 10

EUS elastography Julio I. Garcia, Jose Lariño-Noia & Juan Enrique Dominguez Muñoz Department of Gastroenterology and Hepatology, Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela, Santiago de Compostela, Spain

Introduction The introduction of endoscopic ultrasonography (EUS) into clinical practice was an important advancement in the management of a wide variety of diseases. EUS has been demonstrated to have significantly changed the diagnosis and/or management of up to 50% of cases [1–6]. Nevertheless, an accurate diagnosis cannot always be determined using only conventional B-mode EUS imaging. In many cases, EUS-guided sampling is needed. The accuracy of EUS-guided sampling has been demonstrated to be very high, with sensitivities between 80 and 85% and specificities approaching 100%, mainly related to the development of EUS-specific devices [7, 8]. In this setting, histological needles have made a great advance with the ability to provide real core samples. In fact, we have the option to obtain not only a cyto-histological diagnosis but also specific information on lesion type based on immunohistochemistry and molecular profiling [9–12]. However, EUS-guided sampling is still technically demanding, and on certain occasions, multiple punctures may be necessary to obtain the diagnosis; even after repeated sampling, cytohistologic assessment can be falsely negative, especially in the case of solid pancreatic masses in patients with advanced chronic pancreatitis and in the evaluation of enlarged lymph nodes [13–15]. Furthermore, EUS-guided sampling is associated with small but not insignificant morbidity rates [16–18]. Hence, new methods such as contrast-enhanced EUS and EUS-guided elastography have emerged, which can allow for a more accurate but still noninvasive characterization of different types of lesions from multiple locations, limiting the need for EUS-guided tissue acquisition and guiding biopsies of areas with the highest suspicion for malignancy. Elastography is a real-time method for the evaluation of tissue stiffness. Several different pathologies, including cancer, can induce alterations in tissue stiffness. Elastography was initially developed for the evaluation of lesions accessible from the body surface [19, 20]. Today, elastographic evaluation can be performed from inside the gastrointestinal (GI) tract in combination with conventional EUS. Several studies have shown its high accuracy in differentiating benign from malignant lesions from many different locations, mostly in the pancreas and lymph nodes. We will review the technical aspects and clinical applications of EUS elastography.

Technical aspects and methodology of elastography Nowadays, two different systems to perform an elastographic evaluation are available: strain elastography and shear wave elastography (SWE). Strain elastography Strain elastography is based on the knowledge that certain diseases (among them, cancer) lead to a change in tissue hardness (elasticity modulus). Elastography can be regarded as a development from the well-known fremitus technique in breast ultrasonography, which demonstrates that healthy breast tissue vibrates more than solid malignant lesions, despite its isoechoic appearance under B-mode ultrasound [19]. The technology is based on the detection of small structure deformations within the B-mode image caused by compression, and the degree of deformation is used as an indicator of the stiffness of the tissue [21]. This noninvasive technique measures elasticity in real time by registering differences in distortion of the EUS image after application of slight pressure by the EUS probe, together with physiologic vascular pulsations and respiratory movements, which provide the vibrations and compressions necessary for the recording. The elasticity modulus can be calculated from the strain and stress of the evaluated structures. An extended combined autocorrelation method has been designed, allowing the reconstruction of the tissue elasticity of the different structures based on a 3-dimensional finite element model. This allows a highly accurate estimation of tissue elasticity distribution and adequate compensation of sideslips. The basis for elastography is that different pathologic processes, including inflammation, fibrosis, and cancer, all induce alterations in tissue stiffness, so that the strain is smaller in hard tissues than in soft tissues [21–23]. Strain elastography analysis can be evaluated in a qualitative manner, based on color map distribution, or quantitatively by evaluating the strain ratio and strain histogram (SH).

Qualitative strain elastography Qualitative elastography relies on the quantification of the compression-induced deformation of the structures in the B-mode image, using the degree of deformation as an indicator of tissue

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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Figure 10.1 Qualitative EUS elastography of the normal pancreas, showing a specific color distribution.

stiffness [21]. When performing the evaluation, the probe needs to be attached to the wall, exerting sufficient pressure for an optimal and stable B-mode image. For the elastographic analysis, a region of interest (ROI) is manually selected to include the whole targeted lesion, when possible, as well as surrounding tissues. Maximal sensitivity for elastographic registration is recommended. Elasticity (on a scale of 1–255) is depicted using a color map (red–green–blue), wherein hard tissue is shown in dark blue, medium hard tissue in cyan, tissue with intermediate hardness in green, medium soft tissue in yellow, and soft tissue in red. The elastography pattern is demonstrated by superimposing the color pattern on a conventional B-mode picture. Usually, a two-panel image is used for presentation, with the conventional grey-scale B-mode image on the right side and the elastographic image on the left (Figure 10.1). Elastographic software, to avoid bias on manual selection of the image, allows performing a frame average evaluation. The system also selects the optimal frames to analyze [21, 23]. Table 10.1 summarizes the elastographic patterns and their significance.

Table 10.1 EUS-guided elastographic classification and/or significance. Stiffness

Homogenous blue is predominant Heterogeneous blue predominant Heterogeneous green predominant Homogenous green predominant Heterogeneous green and blue without predominance SR>10 SR150 SH 50–150 SH35 mm), in which including the entire lesion and sufficient surrounding tissue in the analyzed ROI could be problematic; lesions distant from the transducer; and the presence of fluid (vessels, cysts, ducts, etc.) in the ROI. Importantly, the latest advances in elastography software are helping to overcome these problems. Another important fact coming from some key studies is related to the very good interobserver agreement for determining the

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Figure 10.4 Qualitative EUS elastography of a pancreatic adenocarcinoma, showing a heterogeneous, blue-predominant pattern, with some green areas

corresponding to necrotic component.

malignant potential of lesions evaluated, with kappa scores around 0.7 [33–35]. Regarding quantitative elastography, malignant pancreatic masses and neuroendocrine tumors produce a higher strain ratio and a lower strain histogram than inflammatory masses and normal parenchyma. It has been suggested that a strain ratio >10 or a mean strain histogram value 10 or a strain histogram level 155, sensitivity and specificity for malignancy were 90.9% and 95.2%, respectively [54]. However, not all studies presented good results. Larsen et al. reported their experience on the usefulness of strain ratio evaluation of lymph nodes in patients with upper GI cancer. The sensitivity of EUS for differentiation between malignant and benign LN was 86%, compared with 55–59% for the different elastographic modalities. The specificity of EUS was 71%, which was inferior to that of EUS-guided elastography (82–85%) [68]. Studies of the accuracy of EUS-guided elastography in determining the malignancy of lymph nodes are summarized in Table 10.3. The differentiation between benign and malignant lymph nodes has been investigated in one meta-analysis, which included 7 studies with 368 patients and 431 LN in total. The pooled sensitivity of EUS elastography for the differential diagnosis of benign and malignant LN was 88%, and the specificity was 85%. The area under the summary ROC curve was 0.9456. The authors concluded that EUS-guided elastography is a promising, noninvasive method for the differential diagnosis of malignant LN and may become a valuable supplemental method to EUS-guided sampling [71].

Gastrointestinal lesions When facing subepithelial lesions, differentiation between gastrointestinal stromal tumors (GIST) and other mesenchymal tumors such as leiomyoma or Schwannoma is essential. EUS-guided

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sampling has shown good accuracy; however, accessing small lesions is highly complex [72]. Therefore, differentiation by imaging is valuable for the management of these lesions. Tsuji et al. used the elastic score to classify patterns in 25 gastric subepithelial lesions. Their findings indicate that GISTs are depicted as “hard” tissues compared with other subepithelial lesions [73]. In contrast, Ignee et al. reported difficulty in differentiating GIST from benign leiomyoma by pattern diagnosis using an elastic score [74]. The eventual usefulness of EUS-guided elastography in this field remains a matter that deserves further investigation. Another potential and promising role of elastography is on the staging of esophageal and gastric cancer. Elastographic imagens might help to determine the degree of infiltration of the tumor, mostly to differentiate T3 from T4 lesions.

Transrectal EUS elastography The value of transrectal EUS elastography has been investigated for the diagnosis and evaluation of prostate cancer, rectal cancer, inflammatory bowel disease, and fecal incontinence. In prostate cancer, elastography has been demonstrated to be superior to transrectal EUS alone, and it improves the specificity of prostate biopsies by highlighting areas highly suspected of malignancy. The sensitivity of transrectal elastography in the diagnosis of prostate cancer ranges from 68 to 92% and its specificity from 62 to 87% in patients clinically suspected of prostate cancer [75–78]. Transrectal elastography for differentiating between benign and malignant rectal tumors has been evaluated in one study, which involved 69 patients with rectal tumors. Quantitative elastography using the strain ratio differentiated between adenomas and adenocarcinomas with a sensitivity of 0.93, a specificity of 0.96, and an accuracy of 0.94 [79, 80]. In a pilot study, the strain ratio of the EUS evaluation of rectal wall thickness was investigated for the diagnosis of inflammatory bowel disease and the differentiation of Crohn’s disease from ulcerative colitis. Patients with Crohn’s disease had significantly higher strain ratios than both controls and patients with ulcerative colitis, but there was no difference between the strain ratios of patients with ulcerative colitis and controls [81]. Allgayer et al. evaluated the elastography of anal sphincters in 50 patients with fecal incontinence, finding no correlation between the elastographic appearance of sphincters and the functional and clinical parameters of the patients [82].

Table 10.3 Studies analyzing the accuracy of EUS-guided elastography in the differential diagnosis of lymph nodes.

Other indications Study

n

Sensitivity (%)

Specificity (%)

Giovannini et al. [30] Giovannini et al. [34] Jansen et al. [65] Saftoiu et al. [69] Saftoiu et al. [69] Saftoiu et al. [66] Knabe et al. [70] Paterson et al. [67] Larsen et al. [68] Puga-Tejada et al. [54]

31 101 66 42 42 78 40 53 56 121

100 91.8 84 91.7 95.8 85.4 88.9 83 59 90.9

50 82.5 85 94.4 94.4 91.9 86.7 96 85 95.2

Given the current indications for conventional EUS, EUS elastography may be useful in evaluating solid lesions in the left suprarenal glands by differentiating between adenomas and metastases. Our preliminary, unpublished data support this hypothesis. Another possible indication for EUS elastography is the evaluation of liver diseases [83] and the differentiation between benign and malignant solid liver lesions (Figure 10.11) [84]. We believe that EUS elastography will be an integral part of the EUS evaluation of any pathology that can alter tissue stiffness, including inflammation, fibrosis, and cancer.

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Figure 10.11 Qualitative EUS elastography of a solid liver lesion corresponding to a metastasis from a colon cancer. The lesions present the typical heterogeneous blue-predominant pattern, clearly differentiated from surrounding tissue.

Conclusion EUS-guided elastography is considered today as an excellent tool capable of differentiating fibrotic/inflammatory tissues from malignant lesions. It has been demonstrated that it can differentiate between benign and malignant solid pancreatic masses and lymph nodes with high accuracy, as well as normal pancreatic tissues from early CP. EUS-guided sampling will still be needed in most situations. However, EUS elastography is useful for identifying cases in which biopsies are unnecessary and for directing biopsies to optimal areas in cases where histologic diagnosis is required. Future research will keep updating and defining the role of EUS elastography in clinical practice.

References 1 Wani S, Wallace MB, Cohen J, et al. Quality indicators for EUS. Gastrointest Endosc 2015;81(1):67–80. 2 Dye CE, Waxman I. Endoscopic ultrasound. Gastroenterol Clin North Am 2002;31(3):863–879. 3 Byrne MF, Jowell PS. Gastrointestinal imaging: endoscopic ultrasound. Gastroenterology 2002;122(6):1631–1648. 4 Tamerisa R, Irisawa A, Bhutani MS. Endoscopic ultrasound in the diagnosis, staging, and management of gastrointestinal and adjacent malignancies. Med Clin North Am 2005;89(1):139–518, viii. 5 Simons-Linares CR, Wander P, Vargo J, Chahal P. Endoscopic ultrasonography: an inside view. Cleve Clin J Med 2020;87(3):175–183. 6 Giannone F, Crippa S, Aleotti F, et al. Improving diagnostic accuracy and appropriate indications for surgery in pancreatic cystic neoplasms: the role of EUS. Gastrointest Endosc 2022;96(4):648–656.e2.

7 Dumonceau JM, Deprez PH, Jenssen C, et al. Indications, results, and clinical impact of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline - Updated January 2017. Endoscopy 2017;49(7):695–714. 8 Pouw RE, Barret M, Biermann K, et al. Endoscopic tissue sampling – Part 1: Upper gastrointestinal and hepatopancreatobiliary tracts. European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2021;53(11):1174–1188. 9 Mohan BP, Madhu D, Reddy N, et al. Diagnostic accuracy of EUS-guided fine-needle biopsy sampling by macroscopic on-site evaluation: a systematic review and meta-analysis. Gastrointest Endosc 2022;96(6):909–917.e11. 10 Tanaka H, Matsusaki S. The utility of endoscopic-ultrasonographyguided tissue acquisition for solid pancreatic lesions. Diagn Basel Switz 2022;12(3):753. 11 Facciorusso A, Crinò SF, Gkolfakis P, et al. Endoscopic ultrasound fine-needle biopsy vs fine-needle aspiration for lymph nodes tissue acquisition: a systematic review and meta-analysis. Gastroenterol Rep 2022;10:goac062. 12 Gkolfakis P, Crinò SF, Tziatzios G, et al. Comparative diagnostic performance of end-cutting fine-needle biopsy needles for EUS tissue sampling of solid pancreatic masses: a network meta-analysis. Gastrointest Endosc 2022;95(6):1067–1077.e15. 13 Polkowski M, Jenssen C, Kaye P, et al. Technical aspects of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline – March 2017. Endoscopy 2017;49(10): 989–1006.

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14 Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc 2005;62(5):728–736; quiz 751, 753. 15 Iglesias-García J, Lindkvist B, Lariño-Noia J, Domínguez-Muñoz JE. The role of EUS in relation to other imaging modalities in the differential diagnosis between mass forming chronic pancreatitis, autoimmune pancreatitis and ductal pancreatic adenocarcinoma. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig 2012;104(6):315–321. 16 Micames C, Jowell PS, White R, et al. Lower frequency of peritoneal carcinomatosis in patients with pancreatic cancer diagnosed by EUS-guided FNA vs. percutaneous FNA. Gastrointest Endosc 2003;58(5):690–695. 17 Eloubeidi MA, Tamhane A, Varadarajulu S, Wilcox CM. Frequency of major complications after EUS-guided FNA of solid pancreatic masses: a prospective evaluation. Gastrointest Endosc 2006;63(4):622–629. 18 Eloubeidi MA, Tamhane A. Prospective assessment of diagnostic utility and complications of endoscopic ultrasound-guided fine needle aspiration. Results from a newly developed academic endoscopic ultrasound program. Dig Dis Basel Switz 2008;26(4): 356–363. 19 Itoh A, Ueno E, Tohno E, et al. Breast disease: clinical application of US elastography for diagnosis. Radiology 2006;239(2):341–350. 20 Cochlin DL, Ganatra RH, Griffiths DFR. Elastography in the detection of prostatic cancer. Clin Radiol 2002;57(11):1014–1020. 21 Dietrich CF, Bibby E, Jenssen C, et al. EUS elastography: how to do it? Endosc Ultrasound 2018;7(1):20–28. 22 Dietrich CF, Burmeister S, Hollerbach S, et al. Do we need elastography for EUS? Endosc Ultrasound 2020;9(5):284–290. 23 Iglesias-García J, Lariño-Noia J, Domínguez-Muñoz JE. New imaging techniques: endoscopic ultrasound-guided elastography. Gastrointest Endosc Clin N Am 2017;27(4):551–567. 24 Ferraioli G, Barr RG, Farrokh A, et al. How to perform shear wave elastography. Part II. Med Ultrason 2022;24(2):196–210. 25 Yamashita Y, Kitano M. Benefits and limitations of each type of endoscopic ultrasonography elastography technology for diagnosis of pancreatic diseases. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 2021;33(4):554–556. 26 Ohno E, Hirooka Y, Kawashima H, Ishikawa T. Feasibility of EUS-guided shear-wave measurement: a preliminary clinical study. Endosc Ultrasound 2019;8(3):215–216. 27 van Huijgevoort NCM, Del Chiaro M, Wolfgang CL, et al. Diagnosis and management of pancreatic cystic neoplasms: current evidence and guidelines. Nat Rev Gastroenterol Hepatol 2019; 16(11):676–689. 28 Rana SS. Evaluating the role of endoscopic ultrasound in pancreatitis. Expert Rev Gastroenterol Hepatol 2022;16(10):953–965. 29 Salom F, Prat F. Current role of endoscopic ultrasound in the diagnosis and management of pancreatic cancer. World J Gastrointest Endosc 2022;14(1):35–48. 30 Giovannini M, Hookey LC, Bories E, et al. Endoscopic ultrasound elastography: the first step towards virtual biopsy? Preliminary results in 49 patients. Endoscopy 2006;38(4):344–348. 31 Dietrich CF, Hirche TO, Ott M, Ignee A. Real-time tissue elastography in the diagnosis of autoimmune pancreatitis. Endoscopy 2009;41(8):718–720. 32 Dong Y, D’Onofrio M, Hocke M, et al. Autoimmune pancreatitis: imaging features. Endosc Ultrasound 2018;7(3):196–203.

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33 Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. EUS elastography for the characterization of solid pancreatic masses. Gastrointest Endosc 2009;70(6):1101–1108. 34 Giovannini M, Thomas B, Erwan B, et al. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: a multicenter study. World J Gastroenterol 2009;15(13):1587–1593. 35 Soares JB, Iglesias-Garcia J, Goncalves B, et al. Interobserver agreement of EUS elastography in the evaluation of solid pancreatic lesions. Endosc Ultrasound 2015;4(3):244–249. 36 Iglesias-Garcia J, Larino-Noia J, Abdulkader I, et al. Quantitative endoscopic ultrasound elastography: an accurate method for the differentiation of solid pancreatic masses. Gastroenterology 2010;139(4):1172–1180. 37 Iglesias-Garcia J, Lindkvist B, Lariño-Noia J, et al. Differential diagnosis of solid pancreatic masses: contrast-enhanced harmonic (CEH-EUS), quantitative-elastography (QE-EUS), or both? United Eur Gastroenterol J 2017;5(2):236–246. 38 Ignee A, Jenssen C, Arcidiacono PG, et al. Endoscopic ultrasound elastography of small solid pancreatic lesions: a multicenter study. Endoscopy 2018;50(11):1071–1079. 39 Hu DM, Gong TT, Zhu Q. Endoscopic ultrasound elastography for differential diagnosis of pancreatic masses: a meta-analysis. Dig Dis Sci 2013;58(4):1125–1131. 40 Lu Y, Chen L, Li C, et al. Diagnostic utility of endoscopic ultrasonography-elastography in the evaluation of solid pancreatic masses: a meta-analysis and systematic review. Med Ultrason 2017;19(2):150–158. 41 Mei M, Ni J, Liu D, et al. EUS elastography for diagnosis of solid pancreatic masses: a meta-analysis. Gastrointest Endosc 2013;77(4):578–589. 42 Zhang B, Zhu F, Li P, et al. Endoscopic ultrasound elastography in the diagnosis of pancreatic masses: a meta-analysis. Pancreatol Off J Int Assoc Pancreatol IAP Al 2018;18(7):833–840. 43 Ohno E, Kawashima H, Ishikawa T, et al. Diagnostic performance of endoscopic ultrasonography-guided elastography for solid pancreatic lesions: shear-wave measurements versus strain elastography with histogram analysis. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 2021;33(4):629–638. 44 S˘aftoiu A, Vilmann P, Gorunescu F, et al. Neural network analysis of dynamic sequences of EUS elastography used for the differential diagnosis of chronic pancreatitis and pancreatic cancer. Gastrointest Endosc 2008;68(6):1086–1094. 45 S˘aftoiu A, Vilmann P, Gorunescu F, et al. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy 2011;43(7):596–603. 46 Figueiredo FAF, da Silva PM, Monges G, et al. Yield of contrastenhanced power doppler endoscopic ultrasonography and strain ratio obtained by eus-elastography in the diagnosis of focal pancreatic solid lesions. Endosc Ultrasound 2012;1(3):143–149. 47 Dawwas MF, Taha H, Leeds JS, et al. Diagnostic accuracy of quantitative EUS elastography for discriminating malignant from benign solid pancreatic masses: a prospective, single-center study. Gastrointest Endosc 2012;76(5):953–961. 48 Havre RF, Ødegaard S, Gilja OH, Nesje LB. Characterization of solid focal pancreatic lesions using endoscopic ultrasonography with real-time elastography. Scand J Gastroenterol. 2014;49(6):742–751. 49 Opaˇci´c D, Rustemovi´c N, Kalauz M, et al. Endoscopic ultrasound elastography strain histograms in the evaluation of patients with pancreatic masses. World J Gastroenterol 2015;21(13):4014–4019. 50 Mayerle J, Beyer G, Simon P, et al. Prospective cohort study comparing transient EUS guided elastography to EUS-FNA for the

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diagnosis of solid pancreatic mass lesions. Pancreatol Off J Int Assoc Pancreatol IAP Al 2016;16(1):110–114. Okasha H, Elkholy S, El-Sayed R, et al. Real time endoscopic ultrasound elastography and strain ratio in the diagnosis of solid pancreatic lesions. World J Gastroenterol 2017;23(32):5962–5968. Rustemovi´c N, Kalauz M, Grubeli´c Ravi´c K, et al. Differentiation of pancreatic masses via endoscopic ultrasound strain ratio elastography using adjacent pancreatic tissue as the reference. Pancreas 2017;46(3):347–351. Kataoka K, Ishikawa T, Ohno E, et al. Endoscopic ultrasound elastography for small solid pancreatic lesions with or without main pancreatic duct dilatation. Pancreatol Off J Int Assoc Pancreatol IAP Al 2021;21(2):451–458. Puga-Tejada M, Del Valle R, Oleas R, et al. Endoscopic ultrasound elastography for malignant pancreatic masses and associated lymph nodes: critical evaluation of strain ratio cutoff value. World J Gastrointest Endosc 2022;14(9):524–535. Yamada K, Kawashima H, Ohno E, et al. Diagnosis of vascular invasion in pancreatic ductal adenocarcinoma using endoscopic ultrasound elastography. BMC Gastroenterol 2020;20(1):81. Iglesias-Garcia J, Domínguez-Muñoz JE, Castiñeira-Alvariño M, et al. Quantitative elastography associated with endoscopic ultrasound for the diagnosis of chronic pancreatitis. Endoscopy 2013;45(10):781–788. Itoh Y, Itoh A, Kawashima H, et al. Quantitative analysis of diagnosing pancreatic fibrosis using EUS-elastography (comparison with surgical specimens). J Gastroenterol 2014;49(7):1183–1192. Dominguez-Muñoz JE, Iglesias-Garcia J, Castiñeira Alvariño M, et al. EUS elastography to predict pancreatic exocrine insufficiency in patients with chronic pancreatitis. Gastrointest Endosc 2015;81(1):136–142. Domínguez-Muñoz JE, Lariño-Noia J, Alvarez-Castro A, et al. Endoscopic ultrasound-based multimodal evaluation of the pancreas in patients with suspected early chronic pancreatitis. United Eur Gastroenterol J 2020;8(7):790–797. Iglesias-Garcia J, Lariño-Noia J, Nieto Bsn L, et al. Pancreatic elastography predicts endoscopic secretin-pancreatic function test result in patients with early changes of chronic pancreatitis: a prospective, cross-sectional, observational study, Am J Gastroenterol 2022;117(8):1264–1268. Yamashita Y, Tanioka K, Kawaji Y, et al. Utility of elastography with endoscopic ultrasonography shear-wave measurement for diagnosing chronic pancreatitis. Gut Liver 2020;14(5):659–664. Yamashita Y, Yamazaki H, Shimokawa T, et al. Shear-wave versus strain elastography in endoscopic ultrasound for the diagnosis of chronic pancreatitis. Pancreatol Off J Int Assoc Pancreatol IAP Al 2022;S1424-3903(22):00817-1. Janssen J, Papavassiliou I. Effect of aging and diffuse chronic pancreatitis on pancreas elasticity evaluated using semiquantitative EUS elastography. Ultraschall Med Stuttg Ger 2014;35(3):253–258. Dietrich CF, Jenssen C, Arcidiacono PG, et al. Endoscopic ultrasound: elastographic lymph node evaluation. Endosc Ultrasound 2015;4(3):176–190. Janssen J, Dietrich CF, Will U, Greiner L. Endosonographic elastography in the diagnosis of mediastinal lymph nodes. Endoscopy 2007;39(11):952–957. S˘aftoiu A, Vilmann P, Ciurea T, et al. Dynamic analysis of EUS used for the differentiation of benign and malignant lymph nodes. Gastrointest Endosc 2007;66(2):291–300.

67 Paterson S, Duthie F, Stanley AJ. Endoscopic ultrasound-guided elastography in the nodal staging of oesophageal cancer. World J Gastroenterol 2012;18(9):889–895. 68 Larsen MH, Fristrup C, Hansen TP, et al. Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard. Endoscopy 2012;44(8):759–766. 69 S˘aftoiu A, Vilmann P, Hassan H, Gorunescu F. Analysis of endoscopic ultrasound elastography used for characterisation and differentiation of benign and malignant lymph nodes. Ultraschall Med Stuttg Ger 2006;27(6):535–542. 70 Knabe M, Günter E, Ell C, Pech O. Can EUS elastography improve lymph node staging in esophageal cancer? Surg Endosc 2013;27(4):1196–1202. 71 Xu W, Shi J, Zeng X, et al. EUS elastography for the differentiation of benign and malignant lymph nodes: a meta-analysis. Gastrointest Endosc 2011;74(5):1001–1009; quiz 1115.e1-4. 72 Akahoshi K, Oya M, Koga T, et al. Clinical usefulness of endoscopic ultrasound-guided fine needle aspiration for gastric subepithelial lesions smaller than 2 cm. J Gastrointest Liver Dis JGLD 2014;23(4):405–412. 73 Tsuji Y, Kusano C, Gotoda T, et al. Diagnostic potential of endoscopic ultrasonography-elastography for gastric submucosal tumors: a pilot study. Dig Endosc Off J Jpn Gastroenterol Endosc Soc 2016;28(2):173–178. 74 Ignee A, Jenssen C, Hocke M, et al. Contrast-enhanced (endoscopic) ultrasound and endoscopic ultrasound elastography in gastrointestinal stromal tumors. Endosc Ultrasound 2017;6(1):55–60. 75 Kamoi K, Okihara K, Ochiai A, et al. The utility of transrectal real-time elastography in the diagnosis of prostate cancer. Ultrasound Med Biol 2008;34(7):1025–1032. 76 Kapoor A, Kapoor A, Mahajan G, Sidhu BS. Real-time elastography in the detection of prostate cancer in patients with raised PSA level. Ultrasound Med Biol 2011;37(9):1374–1381. 77 Giurgiu CR, Manea C, Cri¸san N, et al. Real-time sonoelastography in the diagnosis of prostate cancer. Med Ultrason 2011;13(1):5–9. 78 Miyagawa T, Tsutsumi M, Matsumura T, et al. Real-time elastography for the diagnosis of prostate cancer: evaluation of elastographic moving images. Jpn J Clin Oncol 2009;39(6):394–398. 79 Waage JER, Rafaelsen SR, Borley NR, et al. Strain elastography evaluation of rectal tumors: inter- and intraobserver reproducibility. Ultraschall Med Stuttg Ger 2015;36(6):611–617. 80 Waage JER, Leh S, Røsler C, et al. Endorectal ultrasonography, strain elastography and MRI differentiation of rectal adenomas and adenocarcinomas. Colorectal Dis Off J Assoc Coloproctology G B Irel 2015;17(2):124–131. 81 Rustemovic N, Cukovic-Cavka S, Brinar M, et al. A pilot study of transrectal endoscopic ultrasound elastography in inflammatory bowel disease. BMC Gastroenterol 2011;11:113. 82 Allgayer H, Ignee A, Dietrich CF. Endosonographic elastography of the anal sphincter in patients with fecal incontinence. Scand J Gastroenterol 2010;45(1):30–38. 83 Rimba¸s M, Gheonea DI, S˘andulescu L, et al. EUS elastography in evaluating chronic liver disease. Why not from Inside? Curr Health Sci J 2009;35(4):225–227. 84 Iglesias García J, Lariño Noia J, Souto R, et al. Endoscopic ultrasound (EUS) elastography of the liver. Rev Espanola Enfermedades Dig Organo Of Soc Espanola Patol Dig 2009;101(10): 717–719.

C H A P T E R 11

Fundamentals of EUS FNA Larissa Fujii-Lau 1 , Michael J. Levy 2 & Maurits J. Wiersema 3 1 University

of Hawaii, Honolulu, HI, USA of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA 3 Indiana University School of Medicine, Terre Haute, IN, USA 2 Division

Since it was first introduced in the early 1990s, endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) has emerged as the preferred method for tissue acquisition when staging gastrointestinal (GI) malignancies [1, 2]. Essentially, any organ or abnormality that lies in close proximity to the GI tract is accessible for EUS FNA or fine needle biopsy (FNB). As EUS FNA is increasingly being performed, it is important to understand the basics concerning the procedure. This chapter focuses on the fundamentals of EUS FNA before, during, and after the procedure to ensure a safe and efficient evaluation.

Pre-procedural fundamentals Indications and contraindications of EUS FNA The first step in the application of any test is to understand its indications and contraindications. EUS FNA should only be performed when the cytology, or FNB when the histologic results will guide patient management and when the benefits of the procedure outweigh its risks. At present, the most common indications for EUS FNA include [3, 4]: (1) Staging of GI luminal, pancreatic, and intrathoracic/mediastinal malignancies (Figure 11.1). (2) Primary diagnosis of subepithelial tumors (e.g., GI stromal tumor, leiomyoma). (3) Evaluation of mediastinal, retroperitoneal, and/or abdominal lymphadenopathy of unknown etiology (Figures 11.2 and 11.3). (4) Diagnostic aspiration of cystic pancreatic tumors. (5) Diagnosis of extraluminal recurrence of GI cancers. (6) Diagnostic sampling of peritoneal and pleural fluid. Historically recognized absolute contraindications for EUS FNA included an uncorrectable coagulopathy (INR > 1.5) or thrombocytopenia (platelets 4 mm) [73]. The cystic spaces seen in stromal cell tumors of high malignant potential may correspond to cystic degeneration and liquefaction necrosis [74, 75]. When two or more of these criteria are present, the lesion is likely to have high malignant potential [73]. Stromal cell tumors of low malignant potential often demonstrate none of these criteria [73]. However, when using these criteria, expert endosonographers

Chapter 16: EUS for gastrointestinal subepithelial masses

MUCOSA MASS SUBMUCOSA MUSCULARIS

Figure 16.7 Stromal cell tumor of the stomach. Note that this lesion is dif-

fusely hypoechoic and located in the submucosa. This tumor probably developed as a bud from either the muscularis propria or the muscularis mucosa, and grew within the submucosa.

only have fair agreement, and thus conventional EUS features cannot accurately predict malignant versus benign GISTs with certainty [73]. Contrast-enhanced harmonic (CEH) EUS can be helpful in differentiating high-grade GIST from low-grade GIST. In a Japanese study of 29 surgically resected GISTs (16 high-grade and 13 low-grade GISTs), the finding of regular fine tumor vessels and a homogeneous enhancement pattern on CEH EUS was associated with low-grade GISTs, while the presence of irregular tumor vessels flowing from the periphery to the center of the tumor and a heterogeneous enhancement pattern on CEH EUS was more commonly observed in high-grade GISTs [76]. Figure 16.8 demonstrates a conventional EUS and CEH EUS examination of a gastric GIST. Deep mucosal biopsies and FNA may not yield enough tissue for an accurate pathological assessment of the malignant potential of these lesions in terms of the number of mitotic fields. Devices designed to obtain “tissue cores” for histological examination are available and will be further discussed in the section on endoscopic tissue sampling. Tissue acquisition of suspected stromal cell tumors should only be performed if there is doubt regarding the diagnosis of the submucosal mass and if the tissue diagnosis will change clinical management. If tissue sampling is performed, then material should be sent for c-Kit analysis, as a c-Kit-positive lesion represents a true GIST with some malignant potential, while a c-Kit-negative lesion often represents a leiomyoma with little or no malignant potential. The management options for submucosal masses that are suspected to be GISTs, according to EUS, continue to evolve. In general, surgical resection should be considered for all lesions that are causing symptoms (i.e., bleeding, obstruction, and pain), lesions ≥2 cm in diameter, lesions with suspicious EUS findings, and lesions that increase in size on serial EUS examination. For lesions that are 40 ng/mL) and the two-hit sequence of KRAS mutation followed by allelic loss [14]. Over the last decade, DNA sequencing technology has advanced considerably. With the development of Next Generation Sequencing (NGS) techniques, genetic mutations are able to be detected with greater sensitivity and on smaller samples than was previously achievable. Small surgical studies found a mutation in the guanine nucleotide binding protein alpha stimulating complex locus (GNAS) to be highly specific for intraductal papillary mucinous neoplasms (IPMNs) [15, 16]. Application of NGS techniques to pancreatic cyst fluid naturally followed. Early pilot and retrospective studies not only confirmed genetic hallmarks of various cyst types (e.g., KRAS in mucinous cysts and GNAS in IPMN) but also identified markers of advanced neoplasia [17, 18]. In a single-center study of 637 cyst fluid specimens using an 11-gene NGS panel, genomic alterations were identified in 57% of specimens. Surgical pathology was available from 17% of specimens for correlation. The presence of KRAS and/or GNAS mutations was highly sensitive and specific for IPMN (100 and 96%) and mucinous cysts (89 and 100%), confirming findings from previous studies. NGS outperformed CEA level and fluid viscosity in the identification of mucinous cysts, and NGS was more sensitive than Sanger sequencing in the identification of KRAS and GNAS mutations. The presence of TP53, PIK3CA, and/or PTEN mutations was sensitive and specific for the identification of advanced neoplasia (high-grade dysplasia or adenocarcinoma) in mucinous

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cysts (79 and 95%, respectively), outperforming high-risk imaging features and cytology [19]. A subsequent, larger prospective multicenter study was conducted to evaluate the diagnostic capabilities of pancreatic fluid NGS. In this study, 1933 EUS-FNA samples from 1889 patients were evaluated using an expanded 22-gene NGS molecular analysis panel, with surgical pathology available in 251 (22%) and longitudinal clinical follow-up in 1216 (66%, median 23 months) cases. Mucinous cysts were readily identified by the presence of KRAS, GNAS, BRAF, and/or RNF43 mutations (90% sensitivity, 100% specificity). NGS was 88% sensitive and 98% specific in the identification of mucinous cysts with advanced neoplasia based on the presence of TP53, SMAD4, PIK3CA, PTEN, and/or AKT1 mutations. NGS alone outperformed conventional cyst fluid analysis (cytology and CEA) as well as radiographic criteria for the identification of advanced neoplasia. Furthermore, NGS aided in the classification of non-mucinous cysts, namely serous cystadenomas and cystic pancreatic neuroendocrine tumors (PanNETs), through the identification of the highly specific von-Hippel-Lindau (VHL) and multiple endocrine neoplasia type 1 (MEN-1) mutations, respectively. Current data highlight the excellent performance characteristics of NGS in cyst classification and the identification of advanced neoplasia within mucinous cysts. Furthermore, the identification of benign cysts (such as serous cystadenomas) may provide cost-savings in the form of reducing unnecessary surveillance. Recognition of the genetic signatures of pancreatic cyst subtypes has improved the diagnostic capabilities of EUS-FNA, thus leading to the incorporation of NGS into our routine clinical practice. Histologic analysis Histologic samples of the cyst wall can now be reliably obtained using microforceps passed through a 19-g EUS needle. This through-the-needle biopsy (TTNB) technique utilizing the Moray microforceps (U.S. Endoscopy, Mentor, Ohio, USA) has demonstrated higher diagnostic yield for mucinous cysts compared to FNA cytology and CEA analysis [20, 21]. A meta-analysis of 426 patients revealed a pooled sensitivity and specificity of 90 and 94%, respectively, for the diagnosis of mucinous cysts [22]. When performing TTNB, single bites should be obtained only when the “tent sign” is observed, visualizing the microforceps “tenting” the cyst wall or septation under EUS guidance and thereby ensuring that the microforceps have grasped the cyst epithelium. Two macroscopically visible tissue samples should be obtained, which maximizes histologic adequacy [23]. We currently reserve TTNB for select larger indeterminant cysts where diagnostic FNA (to include NGS) has failed and where a definitive histologic diagnosis would alter management. As TTNB requires cyst puncture with a 19-g needle, the complication rate is higher than FNA using 22 or 25-g needles. Pancreatitis and intracystic hemorrhage are the most common complications and are typically mild and self-limited. Complication rates as high as 23% have been reported [24], with a 7% pooled rate in the aforementioned meta-analysis. Cyst wall fine needle biopsy (FNB) is another technique aimed at obtaining a cyst wall histologic core sample. After aspirating fluid with resultant cyst collapse, a 22- or 19-g FNB needle is used to traverse septations and/or the cyst wall. A diagnostic yield of 87% was obtained in a small 47-patient study. The mean cyst size was 38 mm, and the complication rate was 8.5% [25]. Confocal laser endomicroscopy (nCLE) allows visualization of the cyst wall epithelium, with certain imaging patterns being

associated with specific cyst types. In a single-center prospective study of 144 consecutive patients, nCLE was more sensitive (98% vs. 74%), specific (94% vs. 61%), and accurate (97% vs. 71%; p < 0.001) for the identification of mucinous versus non-mucinous cysts compared to CEA and cytology [26]. However, this platform also requires puncture with a 19-gauge needle and therefore may be best suited for use in large, indeterminate cysts. Additionally, the interpretation of imaging patterns is subjective and likely influenced by operator experience.

Characteristics of pancreatic cystic lesions Despite the inaccuracy of cyst morphology for diagnosis, certain pancreatic cystic lesions have some characteristic features (Table 18.2), and their recognition may aid in diagnosis and help direct FNA. Characteristics of the more frequently encountered pancreatic cystic lesions will be discussed in this section. Pancreatic cystic neoplasms PCNs include MCNs, IPMNs, serous tumors, and solid pseudopapillary neoplasms (SPNs).

Mucinous cystic neoplasms These tumors are diagnosed exclusively in women, with a peak incidence in the fifth to sixth decade [27–32]. The vast majority (∼75%) are located in the pancreatic body and tail [27, 28, 30, 33]. MCNs appear as thinly septated cystic lesions, comprising several fluid-filled compartments, or as unilocular cysts (Figure 18.1). The wall is typically thin; “eggshell” or eccentric calcifications can occur (∼15%) and are considered pathognomonic [29, 34–36]. The presence of an associated mass or mural nodule is a harbinger of malignant transformation. The cyst aspirate is generally slightly viscous to thick and mucoid [32], but a thin, watery aspirate does not exclude MCN. CEA is generally elevated, with marked elevation more frequently seen in malignant lesions [8, 9, 37]. Specific for mucinous cystic lesions, KRAS mutations are increasingly detected in MCNs using NGS techniques, albeit with suboptimal sensitivity; a recent study identified KRAS mutations in 47% of MCNs that underwent surgical resection [38]. The cyst cavity is lined by tall columnar mucin-producing cells; agitating the cyst wall or septa with the FNA needle may increase the cytology yield. From a histologic perspective, the presence of ovarian-type stroma is required to render a diagnosis of MCN [39, 40]. Although premalignant, the natural history of MCNs is largely unknown. In a surgical series of 851 consecutive resected pancreatic cysts, 199 were MCNs (23%, mean size 4.4 cm); 10% were malignant [3]. In another large surgical series of 163 resected MCNs, 17% were malignant, of which 12% were invasive [41]. All malignant MCNs were either ≥4 cm or harbored mural nodules. For noninvasive MCNs, 5-year disease-specific survival was 100%; for invasive cancer, it was 57%. Thus, international consensus guidelines recommend that MCNs, regardless of size, be resected in all surgically fit patients [42]. However, previous literature suggests that surveillance of small presumed MCNs without worrisome or high-risk features may be appropriate, depending on the clinical setting [40].

Intraductal papillary mucinous neoplasms IPMNs are a neoplastic disorder of varying degree and extent that affects the pancreatic ductal epithelium. An IPMN is defined as “an intraductal papillary mucin-producing neoplasm, arising

Chapter 18: EUS for pancreatic cysts

153

Table 18.2 Pancreatic cyst characteristics. Serous cystadenoma

Mucinous cystic neoplasm

IPMN

Solid pseudopapillary neoplasm

Cystic pancreatic NET

Lymphoepithelial Cyst

Pseudocyst

Imaging/EUS characteristics

Microcystic/ honeycomb appearance Oligocystic appearance less common

Unilocular cyst occupies most of the neoplasm; can have a thick wall with a “bullseye” appearance

Microcystic, multilocular, or solid-appearing

Anechoic, thick-walled, rare septations; may have fine layering debris

Thin, often bloody

Dilated main or pancreatic duct branch or branches A solid component, if present, may suggest malignancy Viscous in majority

Solid and cystic masses ± calcifications

Aspirate appearance

Unilocular or septated cyst ± wall calcifications A solid component, if present, may suggest malignancy Viscous in majority

Bloody

Typically clear and thin, or serosanguinous

Thick milky, gray, or frothy

Cytology

Cuboidal cells that stain positive for glycogen; yield 3 MINOR features 1 MAJOR A feature plus 1 MAJOR B feature 2 MAJOR A features

Indeterminate for CP

Normal 4 EUS criteria were present

Lees et al. [75] Zimmerman et al. [76]

7 34

Furukawa et al. [77]

15

Varadarajulu et al. [78]

42

Patients underwent EUS Patients underwent EUS, followed by pancreatic resection or biopsy Intraductal ultrasonography (IDUS) was compared to histology in excised pancreatic tissue Patients underwent EUS, followed by surgery

Chong et al. [79]

71

Patients underwent EUS, followed by surgery

Bhutani et al. [80]

18

Albashir et al. [81] Sahia et al. [52] Catalano et al. [2]

25 126 80

Nattermann et al. [82]

114

Patients dying of all-cause mortality underwent EUS vs. post-mortem pancreatic tissue Patients underwent EUS within 12 months of wedge resection Patients underwent EUS and ERCP Patients underwent EUS, followed by ERCP and a secretin-stimulation test 94 patients with suspected CP vs. 20 control patients underwent EUS and ERCP 69 patients with suspected CP vs. 20 asymptomatic volunteers underwent EUS and ERCP; 16 underwent secretin-stimulated pancreatic juice collection Patients underwent EUS, ERCP, and secretin pancreatic function tests Patients underwent EUS within 12 months of pancreatic resection Patients underwent EUS, TUS, and CT; 55 underwent ERCP Patients with suspected CP underwent EUS and MRCP; 40 were diagnosed with CP, and 59 were controls

Wiersema et al. [49]

20

Stevens et al. [83]

83

Albashir et al. [84]

25

Buscail et al. [85] Pungpapong et al. [86]

81 99

the diagnosis of CP. Furukawa et al. [77] compared intraductal ultrasonography (IDUS) to histology in freshly excised pancreatic tissue in 15 patients with CP. IDUS detected CP changes in 11 of the 15 cases. Several more recent studies have reexamined the correlation of EUS findings with histology specimens. In a small, prospective cohort of patients who underwent pancreatic resection after EUS examination, four or more EUS criteria optimized the diagnosis of noncalcific CP [78]. A larger retrospective study evaluated 71 patients with a median histologic fibrosis score of seven who underwent EUS followed by surgery [79]. This study, which included patients with calcific CP, concluded that more than three EUS criteria optimized sensitivity and specificity for the diagnosis of CP. In addition, the same authors found that EUS may identify calcifications missed by other imaging studies. Bhutani et al. [80] looked at patients dying of all-cause mortality and compared their post-mortem pancreatic histology to EUS findings performed in vitro. Of these patients, 10 showed histologic evidence of CP, and all 10 had more than three criteria for CP on EUS. Another retrospective review of patients who underwent EUS within 12 months of pancreatic wedge resection found a significant correlation between EUS criteria and histological fibrosis [81]. EUS was found to have a sensitivity of 86% and a specificity of 100% when compared to histology. Overall, there seems to be a good correlation between EUS findings of CP and histologic confirmation when more than three EUS criteria for CP are identified.

IDUS detected CP in 11 of 15 patients EUS sensitivity is 91% and specificity is 86% when >4 EUS criteria are present EUS sensitivity is 83% and specificity is 80% for CP when >3 EUS criteria are present All patients with >3 EUS criteria for CP showed CP on histology EUS sensitivity is 86% and specificity is 100% EUS sensitivity 85% when >5 criteria present >5 EUS criteria confirmed diagnosis; normal EUS excluded diagnosis EUS showed CP in all patients with abnormal ERCP; EUS showed CP in some patients with normal ERCP EUS sensitivity is 80% and specificity is 86% when >3 EUS criteria are present No significant difference in sensitivity or specificity between EUS and ERCP when compared with pancreatic function tests EUS sensitivity is 84% and specificity is 67% compared to pancreatic function tests EUS sensitivity is 88% and specificity is 100% EUS sensitivity is 93% and specificity is 93% when >4 criteria are present

of EUS for the diagnosis of CP was greater than 85% when fewer than three criteria were required, and the specificity was greater than 85% when more than five criteria were used. Catalano et al. [2] reviewed consecutive patients with recurrent pancreatitis who underwent EUS followed by ERP and a secretin-stimulation test at least 6 weeks after the last episode of pancreatitis. The authors concluded that a normal EUS excludes CP and that more than five EUS criteria for CP confirm the diagnosis. Nattermann et al. [82] correlated parenchymal and ductal changes on EUS to ERP and found that EUS showed inflammatory changes in almost all patients in whom ERP suggested CP. EUS was also abnormal in a considerable number of cases that had a normal ERP but clinical evidence of pancreatic inflammation (Figure 19.6). Wiersema et al. [49] studied EUS versus ERP in asymptomatic

Comparison to ERCP and secretin-stimulated duodenal aspiration EUS has been compared to ERP and secretin-stimulated duodenal aspiration. Sahai et al. [52] conducted a double-blinded, prospective trial to evaluate the accuracy of EUS in diagnosing, ruling out, and establishing the severity of CP as compared to ERP. The sensitivity

Figure 19.6 EUS image of mild CP using radial endosonography in a patient

with a normal pancreatogram on ERP: hyperechoic pancreatic duct walls, hyperechoic foci, and stranding.

Chapter 19: The role of diagnostic EUS in inflammatory diseases of the pancreas

volunteers versus patients with chronic abdominal pain of suspected pancreaticobiliary origin. For all patients, the sensitivity, specificity, and accuracy of EUS in diagnosing CP were 80%, 86%, and 84%, respectively. ROC curves demonstrated that optimal sensitivity and specificity were obtained when there were more than three parenchymal and/or ductular features. These studies suggest that EUS is not only not inferior to ERP in diagnosing CP but may actually be more sensitive in early cases. A recent study compared EUS and ERP to secretin ePFTs and found no significant difference in sensitivity (72% vs. 68%) or specificity (76% vs. 79%) between EUS and ERP [83]. Albashir et al. [84] compared EUS and ePFT to histology and found that EUS had a sensitivity of 84% and a specificity of 67%, compared with a sensitivity of 86% and a specificity of 67% for ePFT. When both modalities were combined, the sensitivity increased to 100%.

Comparison to CT and TUS EUS has proven superior to CT and TUS for the diagnosis of CP. In a prospective study of patients who underwent ERP, EUS, TUS, and CT, sensitivity for the diagnosis of CP was 88% for EUS, 58% for TUS, 74% for ERP, and 75% for CT, while specificity was 100% for ERCP and EUS, 95% for CT, and 75% for TUS [85]. Limitations include a lack of standardized EUS criteria and the fact that an unknown number of criteria were used to diagnose CP. However, EUS was more sensitive and specific than CT and TUS for diagnosing CP.

Comparison to MRCP One randomized study compared MRCP to EUS in diagnosing CP and compared both to ERP [86]. EUS had a higher sensitivity (93% vs. 65%) and similar specificity (93% vs. 90%) when compared with MRCP. EUS-guided tissue sampling for diagnosis of CP It has been postulated that the addition of tissue sampling might improve the diagnosis of patients with EUS findings suggestive of CP. Hollerbach et al. [87] found that the addition of EUS-guided fine-needle aspiration (EUS FNA) to diagnostic EUS was relatively safe and increased the NPV but not the specificity for the diagnosis of CP. However, cytology provides only cellular material for microscopic examination, and its exact correlation with histopathology is unknown. Newer needle designs, such as the reverse bevel and the Franseen or fork-tip geometry, have allowed the emergence of EUS-guided fine needle biopsy (EUS-FNB). This allows for visualization of histological architecture and to perform immunohistochemical analysis and molecular profiling. DeWitt et al. [88] found that EUS FNB may permit histologic sampling of the pancreas in suspected nonfocal CP. This study demonstrated histologic evidence of CP in only one of nine patients with clinically suspected disease in whom pancreatic core biopsy specimens were obtained. Nondiagnostic biopsy specimens were found in 6 of 15 patients with retrievable tissue. Due to the potential complications and limited diagnostic yield, the authors concluded that this technique is not currently recommended for use in the routine evaluation of these patients. Differentiating CP and pancreatic cancer EUS FNA and EUS-FNB are useful for the diagnosis of pancreatic cancer, with a sensitivity of 92–96% and a specificity of nearly 100% [89–92]. However, in the presence of CP, the sensitivity of EUS FNA

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for the diagnosis of cancer decreased to 54–74%, without a decrease in specificity [93, 94]. Findings in CP can mimic those seen in pancreatic cancer, making distinguishing these two conditions difficult. As a result, more FNA/FNB passes may be required to obtain the diagnosis of malignancy. New technologies are emerging that may provide additional means to distinguish between these conditions (see the next section). Developing EUS technologies for the diagnosis of CP

Elastography Elastography is a technology that uses variations in sound waves transmitted through tissues to measure tissue elasticity. EUS elastography can be classified into two categories: shear-wave elastography (EUS-SWE) and strain elastography (EUS-SE). In EUS-SE, the strain ratio is calculated based on the ratio of stiffness between the lesion and the unaffected, adjacent pancreatic tissue [95]. EUS-SWE uses absolute values to objectively calculate tissue elasticity [96]. Elastography can differentiate pancreatic tumors and chronic pancreatitis from normal tissue based on the hypothesis that solid tumors and pancreatic fibrosis would have a loss of elasticity and a subsequent high strain ratio. In a study that compared elastography images in controls, patients with CP, and patients with pancreatic masses, a “honeycombed” elastography pattern was apparent in most of the CP patients and the patients with pancreatic masses but was absent in most of the control patients [97]. Several studies have looked at EUS elastography specifically as a diagnostic tool for CP. In a prospective trial of 191 patients undergoing EUS-SE for epigastric pain or known CP who underwent EUS elastography in addition to standard EUS with Rosemont classification, a linear correlation was found between the number of EUS criteria for CP and the strain ratio measured on elastography (p < 0.0001). The accuracy of EUS elastography for diagnosing CP was 91.1% [98]. A study of 52 patients with indeterminate or suggestive CP by Rosemont criteria also found that EUS-SWE significantly positively correlated with the Rosemont criteria and the number of EUS features. The sensitivity and specificity of EUS-SWE for CP were 100% and 94%, respectively [99]. Elastography may also be useful for establishing the severity of CP. A study of 115 patients with CP, including 35 with pancreatic insufficiency, showed a direct relationship between the strain ratio and the probability of exocrine insufficiency [100]. Another study showed that elastography might decrease interobserver variation because it provides a quantitative measure of tissue strain [101]. This study found a good correlation between endosonographers, with κ = 0.72 and a sensitivity and specificity of 93.4% and 66.0%, respectively.

Contrast-enhanced EUS The concept that pancreatic malignancies and inflammatory pancreatitis would have different vascularity patterns was first proven by Kato et al. in 1995 [102]. These researchers used EUS angiography in 40 patients with suspected pancreatic lesions and found that pancreatic adenocarcinomas showed slight or negative enhancement compared to inflammatory pancreatitis, which showed isoenhancement. Contrast-enhanced endoscopic ultrasonography (CEUS) uses contrast-enhanced diffusion-EUS imaging and gas-filled microbubbles that are injected intravenously peri-procedurally to clearly differentiate vessel-rich areas from hypovascular areas in real time [103].

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While predominantly evaluated for pancreatic masses, CEUS has also proven effective in diagnosing CP. Both mass-forming chronic pancreatitis and autoimmune pancreatitis present as hyperenhanced pseudotumors as opposed to the hypoenhanced lesions associated with pancreatic adenocarcinoma [103]. In a study by Hocke et al. [104], 194 patients with CP (n = 73) or pancreatic cancer (n = 121) underwent EUS alone and CEUS. The sensitivities for pancreatic malignancy and for inflammatory pancreatitis using CEUS were 92% and 96%, respectively, compared with 80% and 82%, respectively, with EUS alone. These findings were replicated in a study of 51 patients, which documented a sensitivity and specificity of 93% and 89%, respectively, in differentiating pancreatic malignancy from inflammatory pancreatitis with CEUS [105].

Digital image analysis Digital image analysis (DIA) is a technique that creates a digital image by computing mathematical and statistical parameters based on the distribution of the pixels that compose a standard EUS image. This technique was first applied to EUS in 2001. In a study by Norton et al. [106], EUS images from 21 patients with pancreatic cancer and 14 with pancreatitis were used to create a computer analysis that differentiated pancreatic cancer from CP with 89% sensitivity but only 50% specificity. Das et al. [107] applied DIA to EUS images of pancreatic tissue from patients with CP (n = 12) and pancreatic malignancy (n = 22) and controls (n = 22). Using their model, they reported a sensitivity and specificity of 93% and 92%, respectively, in distinguishing pancreatic tissue among the three groups and 100% sensitivity and specificity when comparing normal pancreas and CP. However, they concluded that this high sensitivity was expected since all of the patients in the study had severe CP confirmed by other modalities. S˘aftoiu et al. [108] created a neural network analysis using images from 258 patients who underwent EUS elastography for CP (n = 47) or pancreatic malignancy (n = 211) and documented a sensitivity of 87.6% and a specificity of 82.94% in differentiating the two conditions. Overall, this technology seems to be a promising modality to help distinguish CP from pancreatic malignancy, and it may help in differentiating CP from a normal pancreas.

Conclusion EUS is a valuable tool in the diagnosis of patients with pancreatitis. In patients with AP and RAP, EUS can identify small biliary stones and sludge that are missed by other diagnostic modalities. EUS can also increase sensitivity for microlithiasis as an etiology in these patients. EUS is also a critical component in the diagnosis of CP. The development of the Rosemont classification identifies major and minor EUS features for diagnosis and labels patients as “most consistent with CP,” “suggestive of CP,” “indeterminate for CP,” or “normal” according to the number of visualized major and minor features. Yet despite this standardization, concerns over interobserver reliability and the specificity of EUS remain. Factors such as smoking, male sex, age, obesity, diabetes, and alcoholism can cause similar endosonographic changes in the pancreas as those seen in CP, leading to concerns about false-positive tests. The interpretation of images in these subsets needs to be undertaken with reference to the clinical scenario and supporting imaging. New technology within the field of EUS, such as elastography and contrast-enhanced EUS, may overcome these limitations.

References 1 Savides TJ, Gress FG, Zaidi SA, et al. Detection of embryologic ventral pancreatic parenchyma with endoscopic ultrasound. Gastrointest Endosc 1996;43(1):14–19. 2 Catalano MF, Lahoti S, Geenen JE, Hogan WJ. Prospective evaluation of endoscopic ultrasonography, endoscopic retrograde pancreatography, and secretin test in the diagnosis of chronic pancreatitis. Gastrointest Endosc 1998;48(1):11–17. 3 Sugiyama M, Wada N, Atomi Y, et al. Diagnosis of acute pancreatitis: value of endoscopic sonography. Am J Roentgenol 1995;165(4): 867–872. 4 Cho JH, Jeon TJ, Choi JS, Kim HM, et al. EUS finding of geographic hyperechoic area is an early predictor for severe acute pancreatitis. Pancreatology 2012;12(6):495–501. 5 Sotoudehmanesh R, Hooshyar A, Kolahdoozan S, et al. Prognostic value of endoscopic ultrasound in acute pancreatitis. Pancreatology 2010;10(6):702–706. 6 Fogel EL, Sherman S. Acute biliary pancreatitis: when should the endoscopist intervene? Gastroenterol 2003;125:229–235. 7 Sharma VK, Howden CW. Metaanalysis of randomized controlled trials of endoscopic retrograde cholangiography and endoscopic sphincterotomy for the treatment of acute biliary pancreatitis. Am J Gastroenterol 1999;94:3211–3214. 8 Dong B, Chen M. Improved sonographic visualization of choledocholithiasis. J Clin Ultrasound 1987;15:185–190. 9 Stott MA, Farrands PA, Guyer PB, et al. Ultrasound of the common bile ducts in patients undergoing cholecystectomy. J Clin Ultrasound 1991;19(2);73–76. 10 Pedersen OM, Nordgard K, Kvinnsland S. Value of sonography in obstructive jaundice: limitations of bile duct caliber as an index of obstruction. Scand J Gastroenterol 1987;22:975–981. 11 Neitlich JD, Topazian M, Smith RC, et al. Detection of choledocholithiasis: comparison of unenhanced helical CT and endoscopic retrograde cholangiopancreatography. Radiology 1997;203(3): 753–757. 12 Griffin N, Wastle ML, Dunn WK, et al. Magnetic resonance cholangiopancreatography versus endoscopic retrograde cholangiopancreatography in the diagnosis of choledocholithiasis. Eur J Gastroenterol Hepatol 2003;15(7):809–813. 13 Mendler MH, Bouillet P, Sautereau P, et al. Value of MR cholangiography in the diagnosis of obstructive disease of the biliary tree: a study of 58 cases. Am J Gastroenterol 1998;93(12):2482–2490. 14 Menon K, Barkun AN, Romagnuolo J, et al. Patient satisfaction after MRCP and ERCP. Am J Gastroenterol 2001;96(9):2646–2650. 15 Chan WL, Chan AC, Lam WW, et al. Choledocholithiasis comparison of MR cholangiography and endoscopic retrograde cholangiography. Radiology 1996;200(1):85–89. 16 Amouyal P, Amouyal G, Levy P, et al. Diagnosis of choledocholithiasis by endoscopic ultrasonography. Gastroenterol 1994; 106(4):1062–1067. 17 Prat F, Amouyal P, Amouyal G, et al. Prospective controlled study of endoscopic ultrasonography and endoscopic retrograde cholangiography in patients with suspected bile duct lithiasis. Lancet 1996;347(8994):75–79. 18 Norton SA, Alderson D. Prospective comparison of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in the detection of bile duct stones. Br J Surg 1997;84:1366–1369. 19 Kohut M, Nowakowska-Duława E, Marek T, et al. Accuracy of linear endoscopic ultrasonography in the evaluation of patients

Chapter 19: The role of diagnostic EUS in inflammatory diseases of the pancreas

20

21

22

23

24

25

26

27

28

29

30

31

32 33

34

35

36

37

with suspected common bile duct stones. Endoscopy 2002;34(4): 299–303. Canto MI, Chak A, Stellato T, Sivak MV Jr., Endoscopic ultrasonography versus cholangiography for the diagnosis of choledocholithiasis. Gastrointest Endosc 1998;47(6):439–448. Buscarini E, Tansini P, Vallisa D, et al. EUS for suspected choledolithiasis: do benefits outweigh costs? A prospective, controlled study. Gastrointest Endosc 2003;57(4):510–518. Verma D, Kapadia A, Eisen GM, Adler DG. EUS vs. MRCP for detection of choledocholithiasis. Gastrointest Endosc 2006; 64:248–254. de Lédinghen V, Lecesne R, Raymond JM, et al. Diagnosis of choledocholithiasis: EUS or magnetic resonance cholangiography? A prospective controlled study. Gastrointest Endosc 1999; 49(1):26–31. Kondo S, Isayama H, Akahane M, et al. Detection of common bile duct stones: comparison between endoscopic ultrasonography, magnetic resonance cholangiography, and helical-computedtomographic cholangiography. Eur J Radiol 2005;54(2):271–275. Block MA, Priest RJ. Acute pancreatitis related to grossly minute stones in a radiographically normal gallbladder. Am J Dig Dis 1967;12:934–938. Freund H, Pfeffermann R, Durst AL, Rabinovici N. Gallstone pancreatitis. Exploration of the biliary system in acute and recurrent pancreatitis. Arch Surg 1976;111(10):1106–1107. Sherman S, Jamidar P, Reber H. Idiopathic acute pancreatitis: endoscopic approach to diagnosis and treatment [abstract]. Am J Gastroenterol 1993;88:1541. Catalano MF, Sivak MV, Falk GW, et al. Idiopathic pancreatitis: diagnostic role of sphincter of Oddi manometry and response to endoscopic sphincterotomy [abstract]. Gastrointest Endosc 1993;39:310A. Zhan X, Guo X, Chen Y, et al. EUS in exploring the etiology of mild acute biliary pancreatitis with a negative finding of biliary origin by conventional radiological methods. J Gastro Hep 2011;26(10): 1500–1503. Yusoff IF, Raymond G, Sahai AV. A prospective comparison of the yield of EUS in primary vs. recurrent idiopathic acute pancreatitis. Gastrointest Endosc 2004;60:673–678. Frossard JL, Sosa-Valencia L, Amouyal G, et al. Usefulness of endoscopic ultrasonography in patients with “idiopathic” acute pancreatitis. Am J Med 2000;109:196–200. Norton SA, Alderson D. Endoscopic ultrasonography in the evaluation of idiopathic acute pancreatitis. Br J Surg 2000;87:1650–1655. Liu CL, Lo CM, Chan JK, et al. EUS for detection of occult cholelithiasis in patients with idiopathic pancreatitis. Gastrointest Endosc 2000;51(1):28–32. Coyle WJ, Pineau BC, Tarnasky PR, et al. Evaluation of unexplained acute and acute recurrent pancreatitis using endoscopic retrograde cholangiopancreatography, sphincter of Oddimanometry and endoscopic ultrasound. Endoscopy 2002;34(8):617–623. Ballinger AB, Barnes E, Alstead EM, Fairclough PD. Is intervention necessary after first episode of idiopathic acute pancreatitis? Gut 1996;38(2):293–295. Gislason H, Horn A, Hoem D, et al. Acute pancreatitis in Bergen, Norway. A study on incidence, etiology and severity. Scand J Surg 2004;93(1):29–33. Andersson R, Andersson B, Haraldsen P, et al. Incidence, management and recurrence rate of acute pancreatitis. Scand J Gastroenterol 2004;39(9):891–894.

169

38 Gullo L, Migliori M, Pezzilli R, et al. An update on recurrent acute pancreatitis: data from five European countries. Am J Gastroenterol 2002;97:1959–1962. 39 Wilcox CM, Varadarajulu S, Eloubeidi M. Role of endoscopic evaluation in idiopathic pancreatitis: a systematic review. Gastrointest Endosc 2006;63:1037–1045. 40 Kloppel G, Maillet B. The morphological basis for the evolution of acute pancreatitis into chronic pancreatitis. Virchows Arch A Pathol Anat Histopathol 1992;420:1–4. 41 Bolondi L, Li Bassi S, Gaiani S, Barbara L. Sonography of chronic pancreatitis. Radiol Clin North Am 1989;27(4):815–833. 42 Luetmer PH, Stephens DH, Ward EM. Chronic pancreatitis: reassessment with current CT. Radiology 1989;171:353–357. 43 Clain JE, Pearson RK. Diagnosis of chronic pancreatitis. Is a gold standard necessary? Surg Clin North Am 1999;79:829–845. 44 Conwell DL, Zuccaro G, Vargo JJ, et al. An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis. Gastrointest Endosc 2003;57(1):37–40. 45 Stevens T, Conwell DL, Zuccaro G Jr,., et al. A randomized crossover study of secretin-stimulated endoscopic and Dreiling tube pancreatic function test methods in healthy subjects. Am J Gastroenterol 2006;101(2):351–355. 46 Stevens T, Conwell DL, Zuccaro G Jr,., et al. The efficiency of endoscopic pancreatic function testing is optimized using duodenal aspirates at 30 and 45 minutes after intravenous secretin. Am J Gastroenterol 2006;102(2):297–301. 47 Axon AT, Classen M, Cotton PB, et al. Pancreatography in chronic pancreatitis: international definitions. Gut 1984;25(10):1107–1112. 48 Gardner TB, Purich ED, Gordon SR. Pancreatic ductal compliance following secretin stimulation: a novel EUS diagnostic tool for chronic pancreatitis. Pancreas 2012;41(2):290–294. 49 Wiersema MJ, Hawes RH, Lehman GA, et al. Prospective evaluation of endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography in patients with chronic abdominal pain of suspected pancreatic origin. Endoscopy 1993;25(9): 555–564. 50 Jones SN, Lees WR, Frost RA. Diagnosis and grading of chronic pancreatitis by morphological criteria derived by ultrasound and pancreatography. Clin Radiol 1988;39:43–48. 51 International Working Group for Minimum Standard Terminology for Gastrointestinal Endosonography. Reproduction of minimal standard terminology in gastrointestinal endosonography. Dig Endosc 1998;10:158–188. 52 Sahai AV, Zimmerman M, Aabakken L, et al. Prospective assessment of the ability of endoscopic ultrasound to diagnose, exclude, or establish the severity of chronic pancreatitis found by endoscopic retrograde cholangiopancreatography. Gastrointest Endosc 1998;48(1):18–25. 53 Rajan E, Clain E, Levy MJ, et al. Age-related changes in the pancreas identified by EUS: a prospective evaluation. Gastrointest Endosc 2005;61(3):401–406. 54 Stevens T, Dumot J, Zuccaro G Jr., Vargo J et al. Evaluation of duct-cell and acinar-cell function and endosonographic abnormalities in patients with suspected chronic pancreatitis. Clin Gasto Hepatol 2009;7(1):114–119 55 Conwell DL, Zuccaro G, Purich E, et al. Comparions on endoscopic ultrasound chronic pancreatitis criteria to the endoscopic secretin-stimulated pancreatic function test. Dig Dis Sci 207;52(5): 1206–1210.

170

Endoscopic Ultrasonography

56 Gordon S, Gardner T. Interobserver agreement for pancreatic EUS determined by back-to-back examinations. Gastrointest Endoscp 2010;71(5):AB278. 57 Wallace MB, Hawes RH, Durkalski V, et al. The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers. Gastrointest Endosc 2001;53:294–299. 58 Mainie I, Faias S, Vaughan R, et al. Endoscopic ultrasonography for the diagnosis of chronic pancreatitis. Endoscopy 2006;39:WE20. 59 Lieb JG 2nd, Palma DT, Garwan CW, et al. Intraobserver agreement among endosonographers for endoscopic ultrasound features of chronic pancreatitis: a blinded multicenter study. Pancreas 2011;40(2):177–180. 60 Hernandez LV, Sahai A, Brugge WR, et al. Standardized weighted criteria for EUS features of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc 2008;67:AB96. 61 Catalano M, Sahai A, Levy M, et al. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. GIE 2007;69(7):1251–1261 62 Del Pozo D, Poves E, Tabernero S, et al. Conventional versus Rosemont endoscopic ultrasound criteria for chronic pancreatitis: interobserver agreement in same day back-to-back procedures. Pancreatology 2012;12:284–287. 63 Klamin B, Hoffman B, Hawes R, Romagnuolo J. Conventional versus Rosemont endoscopic ultrasound criteria for chronic pancreatitis: comparing interobserver reliability and intertest agreement. Can J Gastroenterol 2011;25(5):261–264. 64 Stevens T, Lopez R, Adler DG, et al. Multicenter study of interobserver agreement of standard endoscopic ultrasound scoring and Rosemont classification for diagnosis of chronic pancreatitis. Gastrointest Endosc 2010;71(3):519–526. 65 Yusoff IF, Sahai AV. A prospective, quantitative assessment of the effect of ethanol and other variables on the endosonographic appearance of the pancreas. Clin Gast Hepatol 2004;2(5):405–409 66 Thuler FP, Costa PP, Paulo GA et al. Endoscopic ultrasonography and alcoholic patients: can one predict early pancreatic tissue abnormalities? JOP 2005;10(6):568–574. 67 Conwell DL, Lee L, Yadav D, et al. American pancreatic association practice guidelines in chronic pancreatitis: evidence-based report on diagnostic guidelines. Pancreas 2014;43(8):1143–1162 68 Catalano MF, Kaul V, Hernandez LV, et al. Diagnosis of chronic pancreatitis (CP) by endoscopic ultrasound (EUS) – radial vs. linear endosonography [abstract]. Gastrointest Endosc 2008;67(5): AB208. 69 Stevens T, Zuccaro G Jr., Dumot JA, et al. Prospective comparison of radial and linear endosonographic ultrasound for diagnosis of chronic pancreatitis. Endoscopy 2009;41(10):836–841. 70 Walsh TN, Rode J, Theis BA, Russell RC. Minimal change chronic pancreatitis. Gut 1992;33(11):1566–1571. 71 Hayakawa T, Kondo T, Shibata T, et al. Relationship between pancreatic exocrine function and histological changes in chronic pancreatitis. Am J Gastroenterol 1992;87(9):1170–1174. 72 Kahl S, Glasbrenner B, Leodolter A, et al. EUS in the diagnosis of early chronic pancreatitis: a prospective follow-up study. Gastrointest Endosc 2002;55(4):507–511. 73 Morris-Stiff G, Webster P, Frost B, et al. Endoscopic ultrasound reliably identifies chronic pancreatitis when other imaging modalities have been non-diagnostic. JOP2009;10:280–283. 74 Hastier P, Buckley MJ, Francois E, et al. A prospective study of pancreatic disease in patients with alcoholic cirrhosis: comparative diagnostic value of ERCP and EUS and long-term significance

75

76

77

78

79

80

81

82

83

84

85

86

87

88

89

90

91

of isolated parenchymal abnormalities. Gastrointest Endosc 1999;49(6):705–709. Lees WR. Endoscopic ultrasonography of chronic pancreatitis and pancreatic pseudocysts. Scand J Gastroenterol 1986; 21 (Suppl. 123):123–129. Zimmerman MJ, Mishra G, Lewin DN, et al. Comparison of EUS findings with histopathology in chronic pancreatitis [abstract]. Gastrointest Endosc 1997;45:AB185. Furukawa T, Tsukamoto Y, Naitoh Y, et al. Differential diagnosis of pancreatic diseases with an intraductal ultrasound system. Gastrointest Endosc 1994;40 (2 Pt. 1):213–219. Varadarajulu S, Eltoum I, Tamhane A, Eloubeidi MA. Histopathologic correlates of noncalcific chronic pancreatitis by EUS: a prospective tissue characterization study. Gastrointest Endosc 2007;66(3):501–509. Chong AK, Hawes RH, Hoffman BJ, et al. Diagnostic performance of EUS for chronic pancreatitis: a comparison with histopathology. Gastrointest Endosc 2007;65(6):808–814. Bhutani MS, Arantes VN, Verma D, et al. Histopathologic correlation of endoscopic ultrasound findings of chronic pancreatitis in human autopsies. Pancreas 2009;38(7):820–824. Albashir S, Bronner MP, Parsi MA, et al. Endoscopic ultrasound, secretin endoscopic pancreatic function test, and histology: correlation in chronic pancreatitis. Gastroenterol 2010;105(11): 2498–2503. Nattermann C, Goldschmidt AJ, Dancygier H. Endosonography in chronic pancreatitis: a comparison between endoscopic retrograde pancreatography and endoscopic ultrasonography. Endoscopy 1993;25:565–570. Stevens T, Conwell DL, Zuccaro G Jr., et al. Comparison of endoscopic ultrasound and endoscopic retrograde pancreatography for the prediction of pancreatic exocrine insufficiency. Dig Dis Sci 2008;53(4):1146–1151. Albashir S, Bronner M, Parsi M, et al. Endoscopic ultrasound, secretin endoscopic pancreatic function test, and histology: correlation in chronic pancratitis. Am J Gastroenterol2010;105(11): 2498–2503. Buscail L, Escourrou J, Moreau J, et al. Endoscopic ultrasonography in chronic pancreatitis: a comparative prospective study with conventional ultrasonography, computed tomography, and ERCP. Pancreas 1995;10(3):251–257. Pungpapong S, Wallace M, Woodward T, et al. Accuracy of endoscopic ultrasonography and magnetic resonance cholangiopancreatography for the diangosis of chronic pancreatitis: a prospective comparison study. J Clin Gastroenterol 2007;41(1):88–93. Hollerbach S, Klamann A, Topalidis T, Schmiegel WH. Endoscopic ultrasonography (EUS) and fine-needle aspiration cytology for diagnosis of chronic pancreatitis. Endoscopy 2001;33:824–831. DeWitt J, McGreevy K, LeBlanc J, et al. EUS-guided Trucut biopsy of suspected nonfocal chronic pancreatitis. Gastrointest Endosc 2005;62(1):76–84. Eloubeidi MA, Jhala D, Chhieng C, et al. Yield of endoscopic ultrasound-guided fine-needle aspiration biopsy in patients with suspected pancreatic carcinoma. Cancer 2003;99(5):285–292. Gress F, Gottlieb K, Sherman S, Lehman G. Endoscopic ultrasonography guided fine-needle aspiration biopsy of suspected pancreatic cancer. Ann Intern Med 2001;134(6):459–464. Harewood GC, Wiersema MJ. Endosonography-guided fine needle aspiration biopsy in the evaluation of pancreatic masses. Am J Gastroenterol 2002;97:1386–1391.

Chapter 19: The role of diagnostic EUS in inflammatory diseases of the pancreas

92 Chen YI, Chatterjee A, Berger R, et al. Endoscopic ultrasound (EUS)-guided fine needle biopsy alone vs. EUS-guided fine needle aspiration with rapid onsite evaluation in pancreatic lesions: a multicenter randomized trial. Endoscopy 2022;54(1):4–12 93 Fritscher-Ravens A, Brand L, Knofel T, et al. Comparison of endoscopic ultrasound-guided fine needle aspiration of focal pancreatic lesions in patients with normal parenchyma and chronic pancreatitis. Am J Gastroenterol 2002;97(11):2768–2775. 94 Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc 2005;62:728–736. 95 Cote G, Smith J, Sherman S, Kelly K. Technologies for imaging the normal and diseased pancreas. Gastroenterology 2013;144: 1262–1271. 96 Iglesias-Garcia J, Lariño-Noia J, de la Iglesia-García D, DominguezMuñoz JE. Endoscopic ultrasonography: enhancing diagnostic accuracy. Best Pract Res Clin Gastroenterol 2022;60-61:101808 97 Janssen J, Schlorer E, Greiner L. EUS elastography of the pancreas: feasibility and pattern description of the normal pancreas, chronic pancreatitis, and focal pancreatic lesions. Gastrontest Endosc 2007;65:971–978 98 Iglesias-Garcia J, Dominguez-Muñoz JE, Castiñeira-Alvariño M, et al. Quantitative elastography associated with endoscopic ultrasound for the diagnosis of chronic pancreatitis. Endoscopy 2013;45(10):781–788. 99 Yamashita Y, Tanioka K, Kawaji Y, et al. Utility of elastography with endoscopic ultrasound shear wave measurement for diagnosing chronic pancreatitis. Gut Liver 2020;14:659e64.) 100 Dominguez-Muñoz, J.E., Iglesias-Garcia, J., Alvariño, M.C., et al. EUS elastography to predict pancreatic exocrine insufficiency

101

102

103 104

105

106

107

108

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in patients with chronic pancreatitis. Gastrointest Endosc, 2015; 81(1):136–142. S˘aftoiu A, Vilman P, Gorunescu F, et al. Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study. Endoscopy 2011;43(7):596–603. Kato T, Tsukamoto Y, Naitoh Y, et al. Ultrasonographic and endoscopic ultrasonographic angiography in pancreatic mass lesions. Acta Radiol 1995;36(4):381–387. Saftoiu, et al. Do we need contrast agents for EUS? 364 Endosc Ultrasound 2020;9(6) Hocke M, Schmidt C, Zimmer B, et al. Contrast enhanced endosonography for improving differential diagnosis between chronic pancreatitis and pancreatic cancer. Dtsch Med Wochenschr 2008;133(38):1888–1892. Gheonea D, Streba CT, Ciurea T, S˘aftoiu A. Quantitative low mechanical index contrast-enhanced ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. BMC Gastro 2013;13(2). Norton ID, Zheng Y, Wiersema MS, et al. Neural network analysis of EUS images to differentiate between pancreatic malignancy and pancreatitits. Gastrointest Endosc 2001;54(5):625–629. Das A, Nguyen C, Li F, Li B. Digistal image analysis of EUS images accurately differentiates pancreatic cancer from chronic pancreatitis and normal tissue. Capsule summary. Gastrointest Endoscop 2008;67(6):861–867. S˘aftoiu A, Vilmann P, Gorunescu F, et al. Efficacy of an artificial neural network-based approach to endoscopic ultrasound elastography in diagnosis of focal pancreatic masses. Clin Gastro Hepatol 2012;10(1):84–90.

C H A P T E R 20

Autoimmune pancreatitis Larissa Fujii-Lau 1 , Suresh T. Chari 2 , Thomas C. Smyrk 3 , Naoki Takahashi 4 & Michael J. Levy 5 1 University

of Hawaii, Honolulu, HI, USA Anderson, Houston, TX, USA 3 Division of Anatomical Pathology, Mayo Clinic, Rochester, MN, USA 4 Division of Radiology, Mayo Clinic, Rochester, MN, USA 5 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA 2 MD

Autoimmune pancreatitis (AIP) is a rare entity, but it is becoming increasingly recognized due to an improved understanding of its diverse nature and clearer criteria for its diagnosis. Current International Consensus Diagnostic Criteria (ICDC) for the diagnosis of AIP require a positive finding in at least one of five categories: characteristic imaging findings of the pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histopathology, and response to steroids [1]. Despite consensus diagnostic criteria, the diagnosis of AIP often remains elusive [2–4]. Furthermore, the current diagnostic criteria incorporate imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP), but not endoscopic ultrasonography (EUS). Therefore, further refinement of the diagnostic criteria is warranted. In this chapter, we focus on a review of AIP and the potential utility of EUS in the diagnosis of this disorder, particularly in its ability to provide not only high-quality imaging of the pancreas but also tissue acquisition through fine-needle aspiration (FNA), Trucut biopsy (TCB), and ProCore biopsy [5–9].

Classification of AIP Two distinct subtypes of AIP have been established: type 1 and type 2. Worldwide, type 1 AIP is more common than type 2, and it is the exclusive subtype found in Asian countries [10]. The two subtypes have different clinical presentations, histopathologic features, and outcomes, as outlined in Table 20.1. Type 1 is also referred to as “lymphoplasmacytic sclerosing pancreatitis” (LPSP) and is the pancreatic manifestation of IgG4 -related disease (IgG4 -RD); type 2 has been termed “idiopathic duct-centric pancreatitis” (IDCP).

Clinical presentation of AIP The most common acute presentation of AIP is obstructive jaundice and/or a pancreatic mass. Less commonly, AIP may present with acute pancreatitis or abdominal pain; these symptoms are more often associated with type 2 AIP [10]. When patients present with

acute pancreatitis, they also commonly have obstructive jaundice [11]. If present, the abdominal pain is characteristically mild in nature. If there is significant weight loss, severe pain requiring narcotics, or anorexia, then AIP is less likely and a diagnosis of pancreatic cancer must be entertained [1]. AIP may also present similarly to chronic pancreatitis, but pain is a less dominant feature. Although AIP is considered to be an uncommon cause of pancreatitis (4%), acute or chronic pancreatitis was the initial presentation in 24 and 11% of patients eventually diagnosed with AIP, respectively, in one series [12]. Endocrine dysfunction (diabetes mellitus) and exocrine dysfunction (abnormal fecal elastase, BT-PABA testing) can be seen in 70 and 80% of patients with AIP [13].

Diagnosis of AIP AIP often presents a diagnostic challenge for the gastroenterologist. Its uncommon incidence, heterogeneous manifestations, and ability to mimic the clinical presentation and imaging characteristics of pancreatic cancer make AIP a difficult diagnosis. Furthermore, worldwide variations in the clinical approach further complicate the diagnosis of AIP. To help overcome these limitations, the ICDC was formed to create a uniform approach to diagnosing AIP [1]. Diagnosis of type 1 AIP The ICDC incorporates five cardinal criteria for the diagnosis of type I AIP: pancreatic imaging of either the parenchyma (P) or duct (D), serology (S), other organ involvement (OOI), pancreatic histology (H), and response to steroid therapy (Rt) [1]. A classic imaging feature of the pancreatic parenchyma (P) as seen on CT or MRI is diffuse pancreatic enlargement with a delayed or rim-like enhancement. Less common appearances include segmental enlargement and enhancement, low-density mass, main pancreatic duct dilation, and distal pancreatic atrophy. On ERP, the pancreatic duct (D) characteristically contains a long (>1/3 the length of the duct) or multiple strictures without marked upstream dilation (duct diameter 1/3 the length of the main pancreatic duct), narrow stricture; lack of upstream dilatation (1 mm) in a nonstenotic bile duct, symmetrical wall thickness, homogeneous internal foci, and lateral mucosal lesions continuous to the hilum are more common in patients with IgG4 -SC than with PSC or cholangiocarcinoma [9, 35].

Ampullary biopsy IgG4 staining of biopsies taken from the ampulla may provide additional diagnostic support for the diagnosis of AIP. Several studies have found that the presence of >10 IgG4 -positive cells per high-power field correlates with IgG4 staining of pancreatic head biopsies, even in the absence of serological IgG4 elevation [36–39]. Ampullary biopsies may have a role in the diagnostic algorithm in patients with pancreatic head involvement who have a high clinical suspicion of AIP despite a normal serum IgG4 and an unsuccessful pancreatic biopsy.

EUS imaging features of AIP EUS imaging of the pancreas There are no pathognomonic EUS imaging characteristics of AIP. However, there are classic EUS findings that include diffuse pancreatic enlargement with parenchyma that is hypoechoic, patchy, and

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(A)

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(B)

Figure 20.8 Extrapancreatic biliary stricture in IgG4 -SC seen during ERC (A) before and (B) after treatment with steroids.

Figure 20.9 Classic AIP features on EUS with diffuse pancreatic enlarge-

Figure 20.10 AIP presenting as a focal hypoechoic mass on EUS.

ment featuring hypoechoic, heterogeneous parenchyma.

heterogenous (Figure 20.9) [5, 40, 41]. In our experience, a patient has a high probability of AIP when all these EUS features are present, which may be in up to 57% of cases [5, 41]. While patients often do not have all of the features, the EUS findings can still suggest the diagnosis, even in the absence of other non-EUS criteria, including a negative CT or MRI. EUS may also demonstrate a focal solitary mass which is typically visualized as a hypoechoic lesion, commonly located in the head of the pancreas (Figure 20.10). As with advanced pancreatic adenocarcinoma, the mass may appear to involve peripancreatic vessels (Figure 20.11), to cause main pancreatic duct narrowing with duct wall thickening and upstream dilation of the duct, and to be associated with enlarged peripancreatic lymph nodes [5, 40, 41]. Further, EUS findings of the pancreatic parenchyma may mimic those of chronic pancreatitis, including the presence

of hyperechoic foci, hyperechoic strands, and lobularity. In a case series of AIP patients treated with corticosteroids, the parenchymal enlargement, lobularity, and lobular outer margins decreased with treatment, while the hyperechoic foci and strands persisted [42]. Finally, EUS may demonstrate a normal-appearing pancreas (Figure 20.12). It is important to differentiate focal AIP from pancreatic cancer. The presence of diffuse hypoechoic areas, diffuse pancreatic enlargement, thickened bile duct walls, and peripancreatic hypoechoic margins is more commonly seen in patients ultimately diagnosed with AIP than with pancreatic cancer [43]. On the other hand, focal hyperechoic areas and focal enlargement are more common in patients with pancreatic cancer. Although they all reach statistical significance, each characteristic (other than peripancreatic hypoechoic margins) may be seen in both diseases.

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Figure 20.11 Focal mass with suggestion of peripancreatic vessel involvement, confirmed by EUS TCB as AIP.

Figure 20.13 Classic appearance on EUS of IgG4 -SC.

duct and gallbladder. Although they do not exclude IgG4 -SC, findings of short, band-like strictures, beading, pruning, biliary diverticula, proximal ductal dilatation, pancreatic duct dilation, pancreatic atrophy, or evidence of malignancy elsewhere either indicate or suggest an alternative diagnosis. However, there may be considerable overlap between these findings for various disease processes, which may be impacted by the timing of imaging relative to disease onset, therapies provided, the presence of an indwelling stent, and the disease course.

Figure 20.12 Normal-appearing pancreas on EUS in a patient with type 1

AIP.

EUS imaging of other organs As the biliary tree is the most common extrapancreatic organ involved in AIP, it is important to evaluate the bile ducts during an EUS examination in patients suspected of having type 1 AIP. In one study, in 38% of patients who underwent EUS for AIP, the extrahepatic bile duct and gallbladder wall were thickened (Figure 20.13) [44]. There were two types of bile duct wall thickening: (i) a “three-layer type,” with a high–low–high echo appearance; and (ii) a “parenchymal-echo type,” with a thickened wall throughout the entire bile lumen and a parenchymal echo present within the bile duct itself. A similar appearance to the three-layer type, with a regular homogenous thickening with a hyper–hypo–hyperechoic series of layers of the ductal wall (termed “sandwich pattern”), was seen on EUS in a different series [41]. The authors also described bile duct dilatation in those with biliary involvement from AIP. This EUS appearance was different than that often seen with pancreaticobiliary malignancies, in which the biliary tree is frequently more irregular. We similarly find that patients with IgG4 -SC most often demonstrate profound, homogenous, symmetric bile duct wall thickening with smooth inner and outer margins. The involvement and strictures of the bileduct wall are typically segmental or long and often extend into the cystic

Image enhancement techniques in EUS With the lack of pathognomonic features and the variety of EUS findings in patients with AIP, several image enhancement techniques have been investigated to determine their diagnostic utility. Each of these image enhancement techniques is in the experimental phase, and routine use in evaluating possible AIP cannot be recommended at this time. Furthermore, the results from the following studies must be interpreted with caution, as additional investigation is needed for confirmation. While slightly compressing an area that encompasses both abnormal and normal tissue, the use of EUS elastography distinguishes tissues based on their stiffness by measuring tissue strain [45]. Five patients with focal AIP were found to have a homogenous stiff (blue) pattern in the mass and throughout the entire pancreas, which differed from the intermediate stiffness (green) of the pancreatic parenchyma seen in pancreatic cancer or normal pancreas [46]. Contrast-enhanced EUS uses intravenously administered ultrasound contrast agents (Sonovue (sulfur hexafluoride MBs; Bracco Interventional BV, Amsterdam, The Netherlands), Levovist (Bayer AG, Leverkusen, Germany), or Sonazoid (perfluorobutane; GE Healthcare, Little Chalfont, UK)) to produce microbubbles that allow visualization of the vascular pattern within a structure [45]. In 10 patients who received Sonovue contrast during EUS imaging in the bicolor Doppler mode, AIP was associated with hypervascularity within the involved region of the pancreas and surrounding pancreatic parenchyma [47]. This was compared to pancreatic cancer, in which the mass was hypovascular compared to its surrounding pancreatic parenchyma. Similarly, contrast-enhanced harmonic EUS uses ultrasound contrast agents, but instead of visualizing in Doppler mode, it uses a dedicated contrast harmonic mode. The use of contrast-enhanced

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harmonic imaging allows for decreased artifact (e.g., ballooning and overpainting) by the Doppler [45]. In one study, 8 patients with focal AIP and 22 patients with pancreatic cancer were administered Sonazoid contrast [48]. The ultrasonographic contrast uptake and distribution were isoenhanced and homogenous, respectively, in all patients with AIP compared to only 1 patient with pancreatic cancer. In comparison, the majority of patients with pancreatic cancer had hypoenhanced uptake in a heterogeneous pattern of distribution. Furthermore, the optimal maximum intensity gain (MIG) cutoff value for differentiating between AIP and pancreatic cancer with 100% specificity and sensitivity using a receiver operating characteristic (ROC) curve was 12.5. More data are needed to clarify the potential utility and role of each of these newer imaging modalities before they can be incorporated into the diagnostic algorithm.

EUS-guided tissue acquisition EUS-FNA In addition to providing pancreatic imaging, EUS may confirm the diagnosis of AIP through the collection of tissue samples. EUS-guided tissue acquisition is important, particularly in the diagnosis of type 2 AIP, because pancreatic histology (H) is one of the diagnostic criteria of the ICDC. FNA samples, usually obtained with a 22-gauge needle, commonly yield small specimens for cytological review, most of which have a loss of tissue architecture. There are a few reports on the ability to diagnose AIP using FNA only, but there is no broadly accepted consensus around the cytological diagnosis of AIP, and most pathologists are reluctant to rely solely on FNA specimens [49–53]. Even EUS-FNA using a 19-gauge needle was able to achieve a histological diagnosis of AIP in only 43% of patients [54]. Some suggest that the role of EUS-FNA is predominately to exclude pancreatic cancer rather than to diagnose AIP [9, 55, 56]. However, with a 10–40% false-negative rate, the assumption that a negative EUS excludes an underlying pancreatic malignancy is not recommended [57–61]. EUS-FNB In order to overcome the limitations of EUS-FNA, larger-caliber cutting biopsy needles have been developed that preserve tissue architecture during tissue acquisition, allowing for histological evaluation [62–69]. An EUS TCB device (Quick-Core, Wilson-Cook, Winston-Salem, NC, USA) uses a 19-gauge needle with a tissue tray and sliding sheath that is designed to capture a core tissue sample. This device has been shown to be useful for the diagnosis of neoplasms that are difficult to diagnose based on cytopathology alone (e.g., stromal tumors and lymphomas in which immunohistochemical analysis is useful, or desmoplastic tumors in which aspiration is difficult) [70–77]. Furthermore, with the larger specimen size and the ability to preserve tissue architecture, TCB has been shown to help differentiate AIP from classic chronic pancreatitis and pancreatic cancer [4, 78]. The diagnostic sensitivity and safety of EUS TCB were evaluated in 48 patients diagnosed with AIP at the Mayo Clinic in Rochester. Only 23% of patients had a serum IgG4 >2× ULN. Histologic examination of the EUS TCB specimens provided a diagnosis in 35 patients (73%). Diagnostic sensitivity varied among five endosonographers, ranging from 33% to 90%. Nondiagnostic cases were found to have chronic pancreatitis (n = 8), failed tissue acquisition (n = 3), or nondiagnostic histology (n = 2). Complications included mild transient abdominal pain (n = 3) and self-limited intraprocedural

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bleeding (n = 1). No patient required hospitalization or therapeutic intervention. Over a mean follow-up of 2.6 years, no false-negative diagnoses of pancreatic cancer were identified in the patients diagnosed with AIP by EUS TCB. Prior to EUS, the diagnosis of AIP was strongly suspected in only 14 patients based on clinical, laboratory, or imaging findings. Therefore, the potential utility of EUS imaging for the initial suspicion of AIP was seen in 12 patients, initiating TCB. More recently, the use of EUS TCB in pediatric patients with a suspected diagnosis of AIP has been studied [79]. The diagnostic yield of EUS TCB in this patient population was 87%; all patients who were eventually diagnosed with AIP had the type 2 subset. A meta-analysis compared EUS-FNA with EUS-FNB in the diagnosis of AIP [80]. The pooled diagnostic yield for EUS-FNB [87.2% (95% CI 68.8–98.1%)] was higher than EUS-FNA [55.8% (95% CI 37–73.9%), p = 0.03]. In this analysis, the pooled histological procurement rates and adverse event rates were similar between EUS-FNA and EUS-FNB. EUS-FNB appears to be safe and may provide a sufficient histological specimen to aid in the diagnosis of AIP, thereby guiding treatment and avoiding surgical intervention. Some suggest the use of EUS-FNB as a “rescue” technique to obtain adequate tissue samples if EUS-FNA fails [7, 52]. The current ICDC guidelines recommend a pancreatic core biopsy in patients presenting with a focal mass and/or obstructive jaundice once cancer has been excluded if the diagnosis remains elusive [1]. We perform EUS-FNB in patients with a compatible clinical presentation but an uncertain diagnosis when the findings are likely to alter management. By performing EUS-FNB, pancreatic cancer may be excluded and unnecessary surgical intervention averted.

Treatment and outcomes of AIP Corticosteroids remain the mainstay of therapy for AIP. Typically, a dose of 40 mg (0.6–1 mg/kg/day) of prednisone for 4 weeks is started for symptomatic AIP and weaned by 5–10 mg every 1–2 weeks [81, 82]. As steroid response is included in the diagnostic criteria, the majority of patients with AIP should quickly respond to steroids, both clinically and radiographically. It is recommended that cross-sectional imaging and serology be performed within 1–2 weeks after starting treatment to evaluate response to treatment [83]. The lack of response to steroids should prompt a reevaluation of the diagnosis, and pancreatic cancer should be considered. Rituximab can be considered for remission induction in patients who have a contraindication to steroids [83]. Relapse occurs in 25–47% of patients with type 1 AIP initially treated with steroids [14, 81, 82]. Most of the relapse occurs after steroid discontinuation and involves the pancreas and/or extrahepatic biliary system. Although not consistently reported, some risk factors for relapse include high serum IgG4 levels, abdominal pain as the presenting symptoms (vs. acute pancreatitis), presence of other organ involvement (particularly IgG4 -SC involving the distal extrahepatic bile duct), presence of pancreatic endocrine or exocrine insufficiency at diagnosis, and diffuse pancreatic swelling on imaging. Patients with low risk of relapse (disease confined to the pancreas with only a focal lesion and complete serological and radiologic response) can have their steroids tapered within 3 months [83]. Maintenance therapy with either low-dose steroids, immunomodulators, or rituximab is recommended for patients with diffuse pancreatic involvement, delayed radiographic or serologic response, 2 or more OOIs, or proximal IgG4-SC before treatment.

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Relapse is generally treated with reinitiation of steroids, with a good clinical response. However, some patients require the initiation of immunomodulator medications such as azathioprine for steroid resistance or dependence [81]. Rituximab is increasingly being used for patients with new onset of severe disease (typically with OOI), disease flare after steroids, and/or steroid intolerance [84]. In this meta-analysis, ritixumab was associated with high remission rates, with a complete response of 88.9% (95% CI 80.5–93.9%) at 6 months. There was an overall relapse rate of 21% (95% CI 10.5–40.3%), with a higher rate in the presence of OOI of 35.9% (95% CI 17.3–60.1%), at a median time to relapse of 10 months. Less commonly, other immunomodulators such as mycophenolate mofetil, cyclosporine, methotrexate, or cyclophosphamide are used [82]. Long-term sequelae of chronic pancreatitis, including pancreatic duct stones and diabetes, are seen in 7 and 39% of patients, respectively. Risk factors for the development of pancreatic endocrine insufficiency include female gender, older age, pancreatic imaging abnormalities, and type 1 AIP [81]. The majority of patients (>75%) diagnosed with type 2 AIP do not have relapse of their disease [14, 81, 82]. Therefore, maintenance treatment is not required in patients with type 2 AIP [83]. As in the initial disease, if relapse occurs, it is limited to the pancreas.

Conclusion AIP is increasingly being recognized and diagnosed after pancreatic cancer has been excluded. The two subsets are clinically distinct, with different diagnostic criteria and outcomes. EUS is not currently included within the diagnostic algorithm for AIP, but with its ability to provide both high-quality imaging and tissue acquisition via either FNA or TCB, it has a promising complementary role to play in the diagnosis of this disorder. The utility and role of image enhancement techniques such as elastography and contrast-enhanced EUS remain to be determined.

References 1 Shimosegawa T, Chari ST, Frulloni L, et al. International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology. Pancreas 2011; 40(3):352–358. 2 Kamisawa T, Egawa N, Nakajima H, et al. Clinical difficulties in the differentiation of autoimmune pancreatitis and pancreatic carcinoma. Am J Gastroenterol 2003;98(12):2694–2699. 3 Taniguchi T, Tanio H, Seko S, et al. Autoimmune pancreatitis detected as a mass in the head of the pancreas without hypergammaglobulinemia, which relapsed after surgery: case report and review of the literature. Dig Dis Sci 2003;48(8):1465–1471. 4 Yadav D, Notahara K, Smyrk TC, et al. Idiopathic tumefactive chronic pancreatitis: clinical profile, histology, and natural history after resection. Clin Gastroenterol Hepatol 2003;1(2):129–135. 5 Farrell JJ, Garber J, Sahani D, Brugge WR. EUS findings in patients with autoimmune pancreatitis. Gastrointest Endosc 2004;60(6):927–936. 6 Finkelberg DL, Sahani D, Deshpande V, Brugge WR. Autoimmune pancreatitis. N Engl J Med 2006;355(25):2670–2676. 7 Levy MJ, Reddy RP, Wiersema MJ, et al. EUS-guided trucut biopsy in establishing autoimmune pancreatitis as the cause of obstructive jaundice. Gastrointest Endosc 2005;61(3):467–472.

8 Levy MJ, Wiersema MJ, Chari ST. Chronic pancreatitis: focal pancreatitis or cancer? Is there a role for FNA/biopsy? Autoimmune pancreatitis. Endoscopy 2006;38(Suppl 1):S30–S35. 9 Moon SH, Kim MH. The role of endoscopy in the diagnosis of autoimmune pancreatitis. Gastrointest Endosc 2012;76(3):645–656. 10 Kamisawa T, Chari ST, Giday SA, et al. Clinical profile of autoimmune pancreatitis and its histological subtypes: an international multicenter survey. Pancreas 2011;40(6):809–814. 11 Sah RP, Chari ST. Autoimmune pancreatitis: an update on classification, diagnosis, natural history andmanagement. Curr Gastroenterol Rep 2012;14(2):95–105. 12 Sah RP, Pannala R, Chari ST, et al. Prevalence, diagnosis, and profile of autoimmune pancreatitis presenting with features of acute or chronic pancreatitis. Clin Gastroenterol Hepatol 2010;8(1):91–96. 13 Okazaki K, Kawa S, Kamisawa T, et al. Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020. J Gastroenterol 2022;57:225–245. 14 Sah RP, Chari ST, Pannala R, et al. Differences in clinical profile and relapse rate of type 1 versus type 2 autoimmune pancreatitis. Gastroenterology 2010;139(1):140–148, quiz e12–e13. 15 Chari ST. Diagnosis of autoimmune pancreatitis using its five cardinal features: introducing the Mayo Clinic’s HISORt criteria. J Gastroenterol 2007;42(Suppl 18):39–41. 16 Chari ST, Smyrk TC, Levy MJ, et al. Diagnosis of autoimmune pancreatitis: the Mayo Clinic experience. Clin Gastroenterol Hepatol 2006;4(8):1010–1016, quiz 934. 17 Chari ST, Takahashi N, Levy MJ, et al. A diagnostic strategy to distinguish autoimmune pancreatitis from pancreatic cancer. Clin Gastroenterol Hepatol 2009;7(10):1097–1103. 18 Irie H, Honda H, Baba S, et al. Autoimmune pancreatitis: CT and MR characteristics. AJR Am J Roentgenol 1998;170(5):1323–1327. 19 Sahani DV, Kalva SP, Farrell J, et al. Autoimmune pancreatitis: imaging features. Radiology 2004;233(2):345–352. 20 Church NI, Pereira SP, Deheragoda MG, et al. Autoimmune pancreatitis: clinical and radiological features and objective response to steroid therapy in a UK series. Am J Gastroenterol 2007;102(11): 2417–2425. 21 Takahashi N, Fletcher JG, Fidler JL, et al. Dual-phase CT of autoimmune pancreatitis: a multireader study. AJR Am J Roentgenol 2008;190(2):280–286. 22 Suzuki K, Itoh S, Nagasaka T, et al. CT findings in autoimmune pancreatitis: assessment using multiphase contrast-enhanced multisection CT. Clin Radiol 2010;65(9):735–743. 23 Wakabayashi T, Kawaura Y, Satomura Y, et al. Clinical and imaging features of autoimmune pancreatitis with focal pancreatic swelling or mass formation: comparison with so-called tumor-forming pancreatitis and pancreatic carcinoma. Am J Gastroenterol 2003;98(12): 2679–2687. 24 Van Hoe L, Gryspeerdt S, Ectors N, et al. Nonalcoholic ductdestructive chronic pancreatitis: imaging findings. AJR Am J Roentgenol 1998;170(3):643–647. 25 Kamisawa T, Chen PY, Tu Y, et al. MRCP and MRI findings in 9 patients with autoimmune pancreatitis. World J Gastroenterol 2006;12(18):2919–2922. 26 Kamisawa T, Tu Y, Egawa N, et al. Can MRCP replace ERCP for the diagnosis of autoimmune pancreatitis? Abdom Imaging 2009;34(3):381–384. 27 Park SH, Kim MH, Kim SY, et al. Magnetic resonance cholangiopancreatography for the diagnostic evaluation of autoimmune pancreatitis. Pancreas 2010;39(8):1191–1198.

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28 Ichikawa T, Sou H, Araki T, et al. Duct-penetrating sign at MRCP: usefulness for differentiating inflammatory pancreatic mass from pancreatic carcinomas. Radiology 2001;221(1):107–116. 29 Muhi A, Ichikawa T, Motosugi U, et al. Mass-forming autoimmune pancreatitis and pancreatic carcinoma: differential diagnosis on the basis of computed tomography and magnetic resonance cholangiopancreatography, and diffusion-weighted imaging findings. J Magn Reson Imaging 2012;35(4):827–836. 30 Sugumar A, Levy MJ, Kamisawa T, et al. Endoscopic retrograde pancreatography criteria to diagnose autoimmune pancreatitis: an international multicentre study. Gut 2011;60(5):666–670. 31 Kim JH, Kim MH, Byun JH, et al. Diagnostic strategy for differentiating autoimmune pancreatitis from pancreatic cancer: is an endoscopic retrograde pancreatography essential? Pancreas 2012. Epub ahead of print. PMID: 22228050. 32 Nakazawa T, Ohara H, Sano H, et al. Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis. Gastrointest Endosc 2004;60(6): 937–944. 33 Kim JH, Byun JH, Kim SY, et al. Sclerosing cholangitis with autoimmune pancreatitis versus primary sclerosing cholangitis: comparison on endoscopic retrograde cholangiography, MR cholangiography, CT, and MRI. Acta Radiol 2013;54(6):601–607. 34 Kim JH, Byun JH, Lee SJ, et al. Differential diagnosis of sclerosing cholangitis with autoimmune pancreatitis and periductal infiltrating cancer in the common bile duct at dynamic CT, endoscopic retrograde cholangiography and MR cholangiography. Eur Radiol 2012;22(11):2502–2513. 35 Kubota K, Kato S, Uchiyama T, et al. Discrimination between sclerosing cholangitis-associated autoimmune pancreatitis and primary sclerosing cholangitis, cancer using intraductal ultrasonography. Dig Endosc 2011;23(1):10–16. 36 Moon SH, Kim MH, Park do H, et al. IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis. Gastrointest Endosc 2010;71(6):960–966. 37 Kamisawa T, Tu Y, Egawa N, et al. A new diagnostic endoscopic tool for autoimmune pancreatitis. Gastrointest Endosc 2008;68(2):358–361. 38 Kamisawa T, Tu Y, Nakajima H, et al. Usefulness of biopsying the major duodenal papilla to diagnose autoimmune pancreatitis: a prospective study using IgG4 -immunostaining. World J Gastroenterol 2006;12(13):2031–2033. 39 Sepehr A, Mino-Kenudson M, Ogawa F, et al. IgG4 + to IgG+ plasma cells ratio of ampulla can help differentiate autoimmune pancreatitis from other “mass forming” pancreatic lesions. Am J Surg Pathol 2008;32(12):1770–1779. 40 Buscarini E, Lisi SD, Arcidiacono PG, et al. Endoscopic ultrasonography findings in autoimmune pancreatitis. World J Gastroenterol 2011;17(16):2080–2085. 41 De Lisi S, Buscarini E, Arcidiacono PG, et al. Endoscopic ultrasonography findings in autoimmune pancreatitis: be aware of the ambiguous features and look for the pivotal ones. JOP 2010;11(1): 78–84. 42 Okabe Y, Ishida Y, Kaji R, et al. Endoscopic ultrasonographic study of autoimmune pancreatitis and the effect of steroid therapy. J Hepatobiliary Pancreat Sci 2012;19(3):266–273. 43 Hoki N, Mizuno N, Sawaki A, et al. Diagnosis of autoimmune pancreatitis using endoscopic ultrasonography. J Gastroenterol 2009; 44(2):154–159.

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44 Koyama R, Imamura T, Okuda C, et al. Ultrasonographic imaging of bile duct lesions in autoimmune pancreatitis. Pancreas 2008;37(3):259–264. 45 Fusaroli P, S˘aftoiu A, Mancino MG, et al. Techniques of image enhancement in EUS (with videos). Gastrointest Endosc 2011;74(3): 645–655. 46 Dietrich CF, Hirche TO, Ott M, Ignee A. Real-time tissue elastography in the diagnosis of autoimmune pancreatitis. Endoscopy 2009;41(8):718–720. 47 Hocke M, Ignee A, Dietrich CF. Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis. Endoscopy 2011;43(2):163–165. 48 Imazu H, Kanazawa K, Mori N, et al. Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma. Scand J Gastroenterol 2012;47(7):853–860. 49 Chari ST, Kloeppel G, Zhang L, et al. Histopathologic and clinical subtypes of autoimmune pancreatitis: the Honolulu consensus document. Pancreas 2010;39(5):549–554. 50 Deshpande V, Mino-Kenudson M, Brugge WR, et al. Endoscopic ultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis: diagnostic criteria and pitfalls. Am J Surg Pathol 2005;29(11):1464–1471. 51 Kanno A, Ishida K, Hamada S, et al. Diagnosis of autoimmune pancreatitis by EUS-FNA by using a 22-gauge needle based on the International Consensus Diagnostic Criteria. Gastrointest Endosc 2012;76(3):594–602. 52 Mizuno N, Bhatia V, Hosoda W, et al. Histological diagnosis of autoimmune pancreatitis using EUS-guided trucut biopsy: a comparison study with EUS-FNA. J Gastroenterol 2009;44(7): 742–750. 53 Ishikawa T, Itoh A, Kawashima H, et al. Endoscopic ultrasoundguided fine needle aspiration in the differentiation of type 1 and type 2 autoimmune pancreatitis. World J Gastroenterol 2012;18(29): 3883–3888. 54 Iwashita T, Yasuda I, Doi S, et al. Use of samples from endoscopic ultrasound-guided 19-gauge fine-needle aspiration in diagnosis of autoimmune pancreatitis. Clin Gastroenterol Hepatol 2012;10(3): 316–322. 55 Naitoh I, Nakazawa T, Hayashi K, et al. Clinical differences between mass-forming autoimmune pancreatitis and pancreatic cancer. Scand J Gastroenterol 2012;47(5):607–613. 56 Takuma K, Kamisawa T, Gopalakrishna R, et al. Strategy to differentiate autoimmune pancreatitis from pancreas cancer. World J Gastroenterol 2012;18(10):1015–1020. 57 Chen J, Yang R, Lu Y, et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol 2012;138(9): 1433–1441. 58 Eloubeidi MA, Tamhane A. EUS-guided FNA of solid pancreatic masses: a learning curve with 300 consecutive procedures. Gastrointest Endosc 2005;61(6):700–708. 59 Mitsuhashi T, Ghafari S, Chang CY, Gu M. Endoscopic ultrasoundguided fine needle aspiration of the pancreas: cytomorphological evaluation with emphasis on adequacy assessment, diagnostic criteria and contamination from the gastrointestinal tract. Cytopathology 2006;17(1):34–41. 60 Turner BG, Cizginer S, Agarwal D, et al. Diagnosis of pancreatic neoplasia with EUS and FNA: a report of accuracy. Gastrointest Endosc 2010;71(1):91–98.

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61 Voss M, Hammel P, Molas G, et al. Value of endoscopic ultrasound guided fine needle aspiration biopsy in the diagnosis of solid pancreatic masses. Gut 2000;46(2):244–249. 62 Ball AB, Fisher C, Pittam M, et al. Diagnosis of soft tissue tumours by Tru-Cut biopsy. Br J Surg 1990;77(7):756–758. 63 Brandt KR, Charboneau JW, Stephens DH, et al. CT- and US-guided biopsy of the pancreas. Radiology 1993;187(1):99–104. 64 Harrison BD, Thorpe RS, Kitchener PG, et al. Percutaneous Trucut lung biopsy in the diagnosis of localised pulmonary lesions. Thorax 1984;39(7):493–499. 65 Ingram DM, Sheiner HJ, Shilkin KB. Operative biopsy of the pancreas using the Trucut needle. Aust N Z J Surg 1978;48(2):203–206. 66 Kovalik EC, Schwab SJ, Gunnells JC, et al. No change in complication rate using spring-loaded gun compared to traditional percutaneous renal allograft biopsy techniques. Clin Nephrol 1996; 45(6):383–385. 67 Lavelle MA, O’Toole A. Trucut biopsy of the prostate. Br J Urol 1994;73(5):600. 68 Piccinino F, Sagnelli E, Pasquale G, Giusti G. Complications following percutaneous liver biopsy. A multicentre retrospective study on 68 276 biopsies. J Hepatol 1986;2(2):165–173. 69 Welch TJ, Sheedy PF 2nd, Johnson CD, et al. CT-guided biopsy: prospective analysis of 1000 procedures. Radiology 1989;171(2): 493–496. 70 DeWitt J, Emerson RE, Sherman S, et al. Endoscopic ultrasoundguided Trucut biopsy of gastrointestinal mesenchymal tumor. Surg Endosc 2011;25(7):2192–2202. 71 Gines A, Wiersema MJ, Clain JE, et al. Prospective study of a Trucut needle for performing EUS-guided biopsy with EUS-guided FNA rescue. Gastrointest Endosc 2005;62(4):597–601. 72 Lee JH, Choi KD, Kim MY, et al. Clinical impact of EUS-guided Trucut biopsy results on decision making for patients with gastric subepithelial tumors ≥2 cm in diameter. Gastrointest Endosc 2011;74(5):1010–1018. 73 Levy MJ, Jondal ML, Clain J, Wiersema MJ. Preliminary experience with an EUS-guided trucut biopsy needle compared with EUS-guided FNA. Gastrointest Endosc 2003;57(1):101–106.

74 Levy MJ, Smyrk TC, Reddy RP, et al. Endoscopic ultrasound-guided trucut biopsy of the cyst wall for diagnosing cystic pancreatic tumors. Clin Gastroenterol Hepatol 2005;3(10):974–979. 75 Levy MJ, Wiersema MJ. EUS-guided Trucut biopsy. Gastrointest Endosc 2005;62(3):417–426. 76 Wiersema MJ, Levy MJ, Harewood GC, et al. Initial experience with EUS-guided trucut needle biopsies of perigastric organs. Gastrointest Endosc 2002;56(2):275–278. 77 S˘aftoiu A, Vilmann P, Guldhammer Skov B, Georgescu CV. Endoscopic ultrasound (EUS)-guided Trucut biopsy adds significant information to EUS-guided fine-needle aspiration in selected patients: a prospective study. Scand J Gastroenterol 2007;42(1): 117–125. 78 Suda K, Takase M, Fukumura Y, et al. Histopathologic characteristics of autoimmune pancreatitis based on comparison with chronic pancreatitis. Pancreas 2005;30(4):355–358. 79 Fujii LL, Chari ST, El-Youssef M, et al. Pediatric pancreatic EUS-guided trucut biopsy for evaluation of autoimmune pancreatitis. Gastrointest Endosc 2013;77(5):824–828. 80 Yoon SB, Moon SH, Song TJ, et al. Endoscopic ultrasound-guided fine needle aspiration versus biopsy for diagnosis of autoimmune pancreatitis: Systematic review and comparative meta-analysis. Dig Endosc 2021;33:1024–1033. 81 Maire F, Le Baleur Y, Rebours V, et al. Outcome of patients with type 1 or 2 autoimmune pancreatitis. Am J Gastroenterol 2011;106(1):151–156. 82 Hart PA, Kamisawa T, Brugge WR, et al. Long-term outcomes of autoimmune pancreatitis: amulticentre, international analysis. Gut 2013;62(12):1771–1776. 83 Okazaki K, Chari ST, Frulloni L, et al. International consensus for the treatment of autoimmune pancreatitis. Pancreatology 2017;17:1–6. 84 Lanzillotta M, Della-Torre E, Wallace ZS, et al. Efficacy and safety of rituximab for IgG4-related pancreato-biliary disease: A systematic review and meta-analysis. Pancreatology 2021;21:1395–1401.

C H A P T E R 21

EUS for biliary diseases Mihai Rimba¸s 1 & Alberto Larghi 2 1 Gastroenterology 2 Digestive

and Internal Medicine Departments, Colentina Clinical Hospital, Carol Davila University of Medicine, Bucharest, Romania Endoscopy Unit, Catholic University, Rome, Italy

Since its introduction in the early 1980s, endoscopic ultrasonography (EUS) has become an irreplaceable tool for the diagnostic evaluation of the biliary system. Together with the widespread availability of magnetic resonance cholangiopancreatography (MRCP), EUS has contributed to the disappearance of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). The subsequent advent of real-time EUS-guided fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB) has further expanded the role of EUS for this indication, providing the capability to reach a definitive diagnosis and proper lymph nodal staging, which are crucial for management decisions concerning diseases of the biliary system. In the last few years, the ability of EUS to target adjacent organs and insert a needle into them has naturally stimulated investigators to consider EUS not only for tissue acquisition but also for more interventional and therapeutic indications. EUS-guided drainage of the biliary system is now becoming an attractive, less invasive alternative after an unsuccessful ERCP and may soon replace percutaneous drainage due to its quality-of-life advantages, especially in patients with very advanced disease and a short life expectancy. Equally, EUS-guided drainage of the gallbladder in patients with acute cholecystitis has been successfully attempted and may become the definitive treatment for those unfit for surgery. In this chapter, we will review the clinical applications and the results of EUS for biliary diseases, with emphasis on both well-established and novel indications, and then provide a look into future developments.

Common bile duct stones EUS is a safe and minimally invasive procedure to evaluate for the presence of common bile duct stones [1–3] and to differentiate common bile duct obstruction due to choledocholithiasis from other causes, such as cholangiocarcinomas, ampullary tumors, cholangitis, and congenital malformations. Two meta-analyses published up to 2007 reported the sensitivity and specificity of EUS for common bile duct stone detection to be 85–94% and 94–95%, respectively [4, 5]. These results were subsequently confirmed

in more recent studies (Table 21.1) [6–22]. Interestingly, in one of these studies, Karakan et al. [9] reported that EUS was more sensitive than ERCP in detecting common bile duct stones (91% vs. 75%), mainly due to the significantly higher capability of EUS in diagnosing common bile duct stones 10 mm [76]. However, since polyps 10 mm have been found to be benign [77], there is a need for a more sensitive diagnostic tool for the evaluation of these lesions. EUS has been reported in two studies to be superior to transabdominal ultrasonography (TUS) in distinguishing benign from

malignant gallbladder polyps [78, 79] and in staging gallbladder cancer [80]. In many cases of gallbladder polyps 3 mm in 134 patients. They identified gallbladder wall thickening >10 mm and hypoechoic internal echogenicity as independent predictive factors for neoplasia, with an overall EUS sensitivity of 84.6%. Contrast-enhanced EUS (CEUS) represents a novel technology that can assess both the microvasculature and parenchymal perfusion by selectively depicting the signals derived from the ultrasound contrast agent [89]. The perfusion and vascularity assessment capabilities of CEUS could be useful in distinguishing malignant from benign gallbladder lesions. A study from Korea reported the sensitivity and specificity of CEUS for the differential diagnosis

Table 21.5 Studies addressing the performance of EUS in detecting gallbladder polyps. References

n

Study population

EUS type

Sensitivity of EUS for neoplastic lesions (%)

Sensitivity of EUS for malignancy (%)

Sensitivity of EUS-FNA for malignancy (%)

Cheon et al. [81]

94

Radial

66.7

NA

NA

Cho et al. [82]

88

Radial

90c

85d

NA

Jang et al. [83] Hijioka et al. [84]

144 16

Radial Linear

NA NA

86 NA

NA 90

Hijioka et al. [85] Park et al. [86] Kim et al. [87]

50 34 134

Linear Radial Radial

NA

NA

96d

NA

84f

NA

Choi et al. [88]

93

94 surgical cases of gallbladder polyps 3 mm) Patients with gallbladder polyps >10 mm in diameter

Radial

NA

93.5

NA

a

Using the presence of hyperechoic spots as a positive and hypoechoic foci as a negative predictive factor. Using the presence of microcysts as a positive predictive factor. c Using the presence of hypoechoic foci as a positive predictive factor. d Using the presence of hypoechoic foci and size >15 mm as a positive predictive factor. e Biopsies of gallbladder masses were carried out when lymph node biopsies were inconclusive or lymph nodes could not be assessed. f For diagnosing neoplastic gallbladder wall thickening. b

Chapter 21: EUS for biliary diseases

Figure 21.6 EUS-FNA of a mass completely occupying the entire gallblad-

der bed.

of gallbladder adenomas from cholesterol polyps based on the enhancement pattern to be 75.0 and 66.6%, respectively [86]. More recently, Choi et al. [88] found no significant difference between CEUS and EUS in the differentiation of benign from malignant gallbladder polyps, with CEUS findings able to change the therapeutic strategy in only 8.6% of cases. Regarding the possibility of performing EUS-FNA-TA of gallbladder masses, pivotal studies on a small number of patients reported the sampling procedure to be safe, feasible, and useful in reaching a definitive diagnosis (Figure 21.6) [90, 91]. These findings were confirmed by Kim et al. [92], who analyzed 28 patients with gallbladder masses. EUS-FNA of a gallbladder mass was performed in 13 patients, while in the remaining 15, suspicious metastatic lymph nodes were sampled. Overall, of the 13 gallbladder lesions sampled by EUS-FNA, 10 were diagnosed as malignant and 3 were negative for malignant cells. Of the latter 3, 2 were false negatives for malignancy. All 14 metastatic lymphadenopathy cases were diagnosed with EUS-FNA of lymph nodes. Cholecystitis occurred after EUS-FNA in one patient [92]. The Japanese group from Nagoya examined the usefulness of EUS-FNA in diagnosing gallbladder lesions in two different studies [84, 85]. In the first one, on 15 patients with a gallbladder mass, the diagnostic accuracy of EUS-FNA was 93.3%, with a sensitivity and specificity of 90 and 100%, respectively [84]. In the second study, conducted on 88 patients, EUS-FNA was performed with a sampling protocol in which enlarged regional intraabdominal lymph nodes were targeted first, and the gallbladder mass was targeted only if there were no visible or inaccessible lymph nodes or there was a negative on-site evaluation of the lymph node samplings. EUS-FNA results were then compared with those obtained at ERCP [85]. EUS-FNA was found to be significantly more sensitive than ERCP in obtaining a definitive diagnosis of malignancy (96.0% vs. 47.4%) and to have fewer complications as compared to ERCP (0.0% vs. 6.7%) [85].

EUS-guided biliary drainage EUS-guided biliary drainage (EUS-BD) can be performed with 3 different approaches: rendezvous, antegrade, and transmural stenting [93]. EUS-guided rendezvous and antegrade stenting follow the principles of ERCP with the placement of a transpapillary drainage. EUS-guided transmural stenting is a technique in

189

evolution, with new devices being continuously developed and refined to improve safety and outcomes. Transmural EUS-BD can be performed via a transgastric–transhepatic (hepaticogastrostomy) or a transduodenal-transcholedochal approach (choledochoduodenostomy). Initially, drainage was performed using biliary self-expanding metal stents (SEMS) borrowed from the ERCP armamentarium. Recently, small (6–8 mm in diameter) self-expandable lumen-apposing metal stents (LAMS) specifically designed for EUS-guided choledochoduodenostomy have been developed and are now equipped with a cystotome capability on the tip of the device, which permits a single-step procedure without accessory exchange [94]. Moreover, partially covered tubular metal stents or those with antimigration features designed for EUS-guided hepatico-gastrostomy have also become available [95] (Figure 21.7). EUS-guided biliary drainage represents an attractive, less invasive alternative to percutaneous transhepatic biliary drainage (PTBD) or surgery after unsuccessful ERCP, which can occur in up to 10% of cases due to altered anatomy, periampullary diverticula, tortuous ducts, impacted stones, or tumor infiltration [96]. Two meta-analyses have compared PTBD and EUS-BD after failed ERCP. In the first study by Sharaiha et al. [97], including 9 studies with 483 patients, despite identical technical success rates, EUS-BD was found to be associated with better clinical success (OR, 0.45), fewer post-procedural adverse events (OR, 0.23), and a lower rate of re-intervention (OR, 0.13). In addition, EUS-BD was found to be more cost-effective than PTBD. In the second meta-analysis by Hayat et al. [98], including 10 studies and 1131 patients (EUS-BD n = 567; and PTBD n = 564), EUS-BD was associated with significantly fewer acute (p = 0.03) and total (p = 0.01) AEs. Based on these results, the ESGE guideline on therapeutic EUS recommended EUS-BD over PTBD after failed ERCP in malignant biliary obstruction (strong recommendation, moderate quality evidence) [99]. In the last few years, EUS-BD has also been utilized as a primary drainage procedure instead of ERCP. So far, 4 RCTs have been published comparing EUS-BD versus ERCP in patients with distal malignant biliary obstruction (Table 21.6) [100–103]. The first study by Park et al. [100] involved 30 patients (15 in each arm) and EUS-BD was performed using a biliary SEMS, the Hanarostent. After a follow-up of less than 6 months, no differences in technical, clinical, or AE rates were observed. In the second study by Bang et al. [101], 67 patients were enrolled (ERCP = 34 vs. EUS-BD = 33), and EUS-BD was performed with a biliary SEMS (Viabil, Conmed). Similarly, after a mean follow-up of 6 months, no differences in technical, clinical, or AE rates were detected. In the third study from Korea by Paik et al. [102], a one-step dedicated stent introducer was used (DEUS; Standard Sci Tech Inc., Seoul, South Korea) preloaded with a SEMS featuring an uncovered portion (8 mm in diameter and 15 mm in length) to allow for better anchoring and prevent occlusion of side branches in the biliary tree when placed in the liver, and a covered portion (6 mm in diameter and 35–85 mm in length) extending transmurally to prevent intraperitoneal bile leakage. This stent could be used to perform both choledochoduodenostomy and hepatico-gastrostomy. Among the 125 studied patients (ERCP = 61 vs. EUS-BD = 64) after a median follow-up of 155 days, no differences in technical and clinical success rates were found, while EUS-BD was associated with a significant reduction in adverse event (19.7% vs. 6.3%, p = 0.03) and re-intervention (42.6% vs. 15.6%; p = 0.001) rates. Importantly, 6-month stent patency was significantly higher in the EUS-BD group as compared to the ERCP group (85.1% vs. 48.9%;

190

Endoscopic Ultrasonography

(A)

(B)

(C)

(D)

(E)

(F)

Figure 21.7 EUS-guided biliary drainage using the forward-viewing echoendoscope and the Axios fully covered metal stent in a patient with an inaccessible

papilla due to malignant duodenal obstruction. (A) EUS view from the duodenal bulb of a dilated common bile duct (17 mm). (B) Puncture of the dilated common bile duct using a 19-gauge needle, which provides evidence of the presence of bile. (C) Contrast injection showing a dilated common bile duct with a distal stricture. (D) Fluoroscopic view of 0.035 guidewire inside the common bile duct. (E) EUS view of the distal flange of the 6–8 mm AXIOS stent opened inside the dilated common bile duct. (F) Endoscopic view of the proximal flange of the AXIOS stent placed in the duodenal bulb.

Chapter 21: EUS for biliary diseases

191

Table 21.6 Comparative studies between ERCP and EUS-guided biliary drainage. Author (year)

No. of patients ERCP/EUS

Type of stent

Follow-up (months)

Results

Park (2018) [100] Bang (2018) [101] Paik (2018) [102]

30 15/15 67 34/33 125 61/64

Hanarostent Viabil (Conmed) DEUS

200 000

images was able to identify FLL 92% of the time and classify them as malignant with a 90% sensitivity and 71% specificity [40]. Together, EUS-EG and AI have the potential to introduce a new, non-invasive form of “virtual biopsy.”

Malignant lesions in the liver Hepatocellular carcinoma and other primary liver tumors HCC is a primary neoplasm of the liver. It makes up more than 80% of all primary liver malignancies [41]. Its major risk factors are cirrhosis, alcohol, and chronic viral hepatitis. The diagnosis of HCC can be made based on radiologic hallmarks of arterial hypervascularity and late venous washout, and only if the imaging is inconclusive do current guidelines recommend performing a liver biopsy [42]. The diagnostic yield of a liver biopsy should be weighed against the risk of bleeding and tumor seeding. The incidence of needle-tract tumor seeding following a liver biopsy for HCC is 2.7% [43]. EUS serves as a complementary test to TUS and other established imaging modalities for HCC. Endosonographically, HCC appears as an intrahepatic lesion with a hypoechoic border and heterogenous echotexture. Occasionally, HCC can present as either a hyperechoic or isoechoic lesion [44]. There can also be mixed echogenicity due to hypervascularity and tumor necrosis. This makes detection of HCC difficult in the setting of cirrhosis and regenerative nodules. The advantage of EUS has been shown in only a small number of studies [45–47]. In a single-center prospective study of 17 patients, EUS-FNA detected significantly higher numbers of nodular lesions than TUS, CT, or MRI [47]. The sensitivity and specificity of EUS-FNA in predicting the nonresectability of liver tumors based on tumor location are summarized in Table 22.3. EUS-FNA may be useful in HCC patients who meet criteria for transplantation but have suspicious lymph nodes. In these cases, confirmation of extrahepatic lesions or lymph node involvement by FNA results in exclusion from liver transplantation [44]. EUS also has a role in the Table 22.3 EUS test performance in assessing nonresectability in liver tumors. Location

Sensitivity (range)

Specificity (range)

Left liver lobe Right liver lobe Both liver lobes

50% (22–78) 24% (9–48) 60% (31–83)

100% (63–100) 94% (72–100) 67% (20–94)

Chapter 22: EUS in liver disease

evaluation of portal vein thrombosis (PVT) [48, 49]. Malignant PVT occurs in 35% of patients with HCC, the presence of which excludes a patient from transplant consideration [50]. In these cases, a positive diagnosis in patients without evidence of distant disease can lead to an upstaging that alters treatment strategy. For example, in one cohort study, EUS-FNA of PVT was positive for malignancy in 8.8% of patients, of whom only one was previously diagnosed with HCC [51]. In a separate case series of patients with chronic liver disease, FNA of PVT led to upstaging of disease in six out of seven patients (85.7%) [52]. EUS-FNA of PVT is safe, effective, and should be considered in patients with HCC and without other evidence of metastatic disease [53]. Other, less common primary liver neoplasms include fibrolamellar HCC, primary liver lymphoma, epithelioid hemangioendothelioma, and hemangiosarcoma [54]. As with HCC, EUS is not the principal imaging modality for the diagnosis of these rare liver tumors. Often, these lesions are found incidentally during EUS intended for other indications. Primary liver lymphoma can present as a well-defined hypoechoic mass or multiple subcentimeter lesions [55]. Fibrolamellar HCC is a slow-growing tumor that develops in noncirrhotic livers. It can appear as a large, solitary, well-defined mass with variable echotexture and associated lymphadenopathy [55, 56]. Epithelioid hemangioendothelioma and hemangiosarcoma are rare malignant vascular tumors. They are hypoechoic and difficult to differentiate from other neoplasms. The recommended imaging for these lesions is either a multiphasic CT or an MRI. Liver metastases In North America and Europe, metastatic liver disease is more common than primary liver cancer [57]. Liver metastases represent 25% of all metastatic lesions from other solid organs and include adenocarcinomas, squamous cell carcinomas, and neuroendocrine tumors [57, 58]. Melanomas, lymphomas, and sarcomas also metastasize to the liver, to a lesser extent. Common primary organ sources of metastases to the liver include the lungs, colon, pancreas, breasts, and stomach, which make up 25, 16, 11, 9, and 6% of all metastatic disease, respectively [57]. It has been more than a decade since a seminal study at the University of California at Irvine reported the prevalence of liver lesions in patients undergoing EUS for suspected gastrointestinal (GI) malignancies. Only 14 (2.4%) of the 574 participants were found to have liver metastases with EUS-FNA, and CT failed to detect metastatic lesions in 11 (78.5%) of these [59]. Other prospective studies comparing CT scans and EUS with FNA soon followed, with results that support comparable or even better detection rates with EUS-FNA for liver metastases [60, 61]. FLL that are less than 1 cm could remain undetected by CT [60]. For example, EUS can detect occult liver metastases in up to 7% of patients with esophageal or gastric cancer [45, 62, 63]. In a larger study of 730 patients who underwent EUS for staging or sampling of malignancy, EUS detected FLL in 150 patients (20.5%) and metastases in 118 (16.2%), compared to CT/MRI, which detected FLL in 99 patients (13.6%) and metastases in 82 (11.2%). EUS missed lesions in 7 patients (1%), while CT/MRI missed lesions in 58 patients (7.9%) [64]. EUS-FNA is also comparable to CT FNA in terms of diagnostic utility for hepatic lesions and can be considered over CT FNA when a lesion is difficult to target with CT FNA or the patient is at increased risk for complications during percutaneous biopsy due to coagulopathy, cirrhosis, or ascites [61, 65]. As a result, while EUS is not the primary imaging modality for evaluating metastatic

201

Figure 22.9 Metastatic liver mass with necrosis, seen as intratumoral mixed

echogenicity.

Figure 22.10 Subtle liver lesion arising in the left lobe of the liver in a patient with metastatic pancreatic adenocarcinoma.

disease, evaluation of the liver during EUS is now an important part of the standard EUS examination for cancer staging [66]. Liver metastases have similar sonographic features in both EUS and TUS [67]. Metastatic liver lesions are usually hypoechoic with poorly defined borders. Often, they are multiple, with variable morphology and echogenicity secondary to tumor necrosis (Figure 22.9). Sometimes, metastatic disease can present as a solitary lesion (Figures 22.10 and 22.11). Levy et al. developed an EUS scoring system that could distinguish benign from malignant liver masses with a positive predictive value of 88%. Features consistent with a malignant lesion included an isoechoic/slightly hyperechoic center, post-acoustic enhancement, distortion of adjacent structures, and a size >10 mm. Features favoring a benign lesion included a hyperechoic mass with a distinct shape [68]. In cases of indeterminate lesions, the diagnosis can be confirmed with EUS-FNA (Figure 22.9B).

Benign lesions in the liver Hepatic adenomas Hepatic adenomas are benign epithelial tumors. They are observed more frequently in women than in men and are associated with anabolic steroid use and contraceptives [69, 70]. Multiphasic, helical CT is more accurate in detecting and characterizing hepatic adenomas than is ultrasonography [70]. Sonographically, hepatic adenomas are difficult to differentiate from malignant tumors. Hepatic adenomas appear hyperechoic due to their high lipid content [71]. Occasionally, they can appear with variable echogenicity due to bleeding and calcifications. EUS-FNA has limited utility in the

202

Endoscopic Ultrasonography

Figure 22.11 FNA cytology showing metastatic pancreatic adenocarcinoma. Cytologic findings include irregular size, marked nuclear pleomorphism, and irregular mucin production.

diagnosis of hepatic adenomas, and FNA is not usually performed due to the risk of bleeding. Focal nodular hyperplasia Focal nodular hyperplasia (FNH) is the most common benign nodular liver lesion of nonvascular origin. It represents up to 20% of all benign liver tumors [72]. The diagnosis of FNH is made by characteristic features on a helical, dynamic CT scan demonstrating a hypo- or isodense lesion with a central scar. FNH becomes hyperdense during the hepatic arterial phase because of the arterial origin of its blood supply [73]. The fibrous septae that radiate from the central scar can only be seen in 20% of cases [74]. EUS-FNA is of limited use, as FNA biopsies will usually contain normal hepatocytes and ductular cells [75].

demonstrated by color Doppler in 50% of patients [77]. EUS-FNA has limited application in the diagnosis of hemangiomas. FNA is not recommended because of the risk of bleeding and low diagnostic yield. Instead, MRI is the preferred imaging modality, with a sensitivity and specificity of >90% [78].

Cystic liver lesions

Hemangiomas Hemangiomas are the most common of all benign liver tumors. They comprise blood-filled vascular spaces. Sonographically, hemangiomas are well demarcated, hyperechoic, and round (Figure 22.12). They are mostly homogenous, except in large hemangiomas with variable echogenicity from intratumoral fibrosis or thrombosis [76]. They vary in size from subcentimeter lesions to giant hemangiomas that can occupy most of the liver. Although hemangiomas are vascular, intratumoral blood flow can only be

Liver cysts can be broadly classified as either acquired or congenital. Acquired cystic lesions are either benign or malignant. The most common liver cysts are simple cysts, which are found incidentally. They are mostly unilocular, with fluid-filled spaces. Sonographically, they appear as anechoic round structures with posterior acoustic enhancement (Figure 22.13) [79]. FNA is seldom required to establish the diagnosis. Acquired neoplastic cysts include noninvasive mucinous cystic neoplasms (MCN) and MCN with invasive carcinoma, which were previously referred to as “cystadenoma” and “cystadenocarcinoma,” respectively. Both are rare and are better diagnosed with the aid of a TUS or CT scan [80]. Noninvasive MCN mostly occurs in women. Sonographically, they appear as hypoechoic lesions with worrisome features such as thickened, irregular walls, intracystic debris, or cystic wall nodules. MCN with invasive carcinoma are usually multilocular, with thickened walls and associated masses extending

Figure 22.12 Small hyperechoic liver hemangioma.

Figure 22.13 Anechoic, Doppler-negative liver cyst.

Chapter 22: EUS in liver disease

from the internal cyst wall [81]. Due to their high risk of malignant transformation, liver resection is the recommended treatment [82]. Acquired cystic lesions of infectious etiology include abscesses and hydatid cysts. EUS-guided drainage of abscesses is safe and feasible, especially for abscesses in the left liver lobe [83, 84]. However, TUS and CT-guided percutaneous drainage still remain the most available and least invasive therapeutic modalities [85].

Intrahepatic biliary disorders Intrahepatic cholangiocarcinoma Cholangiocarcinomas (CCA) are a heterogeneous group of tumors that originate from the bile duct epithelium [86]. Based on location, CCA can be classified as intrahepatic, perihilar, or distal [87]. Intrahepatic CCA arises from the intrahepatic biliary tract and is the second most common primary hepatic malignancy [88]. It can progress either as a periductal, intraductal, or mass-forming tumor [89]. The diagnosis and staging of intrahepatic CCA rely heavily on CT and MRI [90]. In contrast, endoscopic retrograde cholangiopancreatography (ERCP) with intraductal biopsy and brush cytology is an important diagnostic test for perihilar and distal CCA. Data on the utility of EUS for intrahepatic CCA are very limited. Most of the recommendations are extrapolated from retrospective studies on patients with perihilar or distal CCA. Sonographically, intrahepatic CCA can present with mixed echogenicity and associated intrahepatic biliary dilatation. Although EUS might assist in the diagnosis of CCA, carelessly obtaining an EUS-guided biopsy can result in iatrogenic upstaging and the exclusion of a patient from liver resection or transplantation [91]. The advantage of obtaining a diagnosis should be evaluated against the risk of tumor seeding. In a retrospective analysis of patients who underwent operative staging to assess candidacy for liver transplantation, peritoneal metastases were found in five out of six patients (83%) who had positive preoperative FNA, as compared to only 14 out of 175 patients (8%) who did not undergo FNA [92]. However, a more recent single-center retrospective analysis of 150 CCA patients did not show any significant difference in either overall or progression-free survival between those with and without preoperative FNA [93]. Overall, the role of EUS in CCA is likely limited to the evaluation of lymphadenopathy in patients being assessed for liver transplantation [94]. In a series of patients with unresectable hilar CCA who underwent evaluation for liver transplantation, 8 out of 47 (17%) patients were confirmed by FNA to have malignant lymphadenopathy before a staging laparotomy was performed [95]. In addition, EUS-FNA detected 12 more patients with previously undetected lymph nodes by CT or MRI. The detection of a positive FNA precludes the need for unnecessary staging laparotomies, neoadjuvant therapy, or liver transplantation. Although the use of EUS-FNA in CCA is controversial, its application in this setting may alter the treatment plan and quality of life for this cohort of patients. Primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a chronic, progressive disease of unclear etiology. The diagnosis requires clinical, laboratory, cholangiographic, and histologic testing. Cholangiography is mostly acquired with magnetic resonance cholangiopancreatography (MRCP). ERCP with biliary sampling is required in cases with dominant strictures to rule out concomitant CCA. The role of EUS in the diagnosis of PSC is limited. EUS may detect thickening of the common bile duct wall. In a cross-sectional study

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comparing bile duct thickness, patients with PSC had bile duct wall thickening of more than 1.5 mm as compared to patients with choledocholithiasis or normal biliary anatomy [96]. This feature was assessed in a prospective study of 138 patients in conjunction with other parameters such as irregular wall structure, changes in bile duct caliber, and the presence of perihilar lymphadenopathy during endosonography. When two features were present, the sensitivity and specificity of EUS in diagnosing PSC were 76 and 100%, respectively [97]. These findings have yet to be replicated, and as such, EUS is not recommended as a substitute for either ERCP or MRCP [98].

Biliary adenomas Biliary adenomas are usually seen as incidental findings and are mostly asymptomatic [99]. The MRCP is the recommended diagnostic test. Sonographically, biliary adenomas present as hyperechoic lesions near the liver capsule. They remain stable in size on surveillance imaging [100]. The role of EUS-FNA is in tissue acquisition in cases where metastatic liver disease needs to be ruled out.

Conclusions EUS assessment of the liver has advanced rapidly over the past decade. With new technology and techniques, EUS imaging of the liver has improved, and novel interventional procedures, such as EUS-LB and EUS-PPG, have been introduced. Together, these advancements have led to the debut of a new clinical niche, referred to as endohepatology. In the future, the importance of EUS in the field is likely to continue to grow, reinforcing the growing integration between interventional endoscopy, interventional radiology, and hepatology.

References 1 Patel KD, Abeysekera KWM, Marlais M, et al. Recent advances in imaging hepatic fibrosis and steatosis. Expert Rev Gastroenterol Hepatol 2011;5:91–104. 2 DeWitt J, LeBlanc J, McHenry L, et al. Endoscopic ultrasoundguided fine-needle aspiration of ascites. Clin Gastroenterol Hepatol 2007;5:609–615. 3 Nguyen PT, Chang KJ. EUS in the detection of ascites and EUS-guided paracentesis. Gastrointest Endosc 2001;54:336–339. 4 Lee YT, Ng EK, Hung LC, et al. Accuracy of endoscopic ultrasonography in diagnosing ascites and predicting peritoneal metastases in gastric cancer patients. Gut 2005;54(11):1541–1545. 5 Oberti F, Burtin P, Maiga M, et al. Gastroesophageal endoscopic signs of cirrhosis: independent diagnostic accuracy, interassociation, and relationship to etiology and hepatic dysfunction. Gastrointest Endosc 1998;48:148–157. 6 Gonzalez JM, Giacino C, Pioche M, et al. Endoscopic ultrasoundguided vascular therapy: is it safe and effective? Endoscopy 2012;44:539–542. 7 Sharma M, Vashishtha C. Role of endoscopic ultrasound in portal hypertension. J Gastroenterol Hepatol 2013;28:619. 8 Mohan BP, Chandan S, Khan SR, et al. Efficacy and safety of endoscopic ultrasound-guided therapy versus direct endoscopic glue injection therapy for gastric varices: systematic review and meta-analysis. Endoscopy 2020;52(4):259–267. doi: 10.1055/a1098-1817.

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Endoscopic Ultrasonography

9 McCarty T, Bazarbashi A, Hathorn K, et al. Combination therapy versus monotherapy for EUS-guided management of gastric varices: a systematic review and meta-analysis. Endosc Ultrasound 2020;9(1):6. doi: 10.4103/eus.eusTh37Th19. 10 Qiao W, Ren Y, Bai Y, et al. Cyanoacrylate injection versus band ligation in the endoscopic management of acute gastric variceal bleeding: meta-analysis of randomized, controlled studies based on the PRISMA statement Medicine (Baltimore) 2015;94(41):e1725. 11 Chirapongsathorn S, Manatsathit W, Farrell A, Suksamai A. Safety and efficacy of endoscopic cyanoacrylate injection in the management of gastric varices: a systematic review and meta-analysis. JGH Open 2021;5(9):1047–1055. 12 Gralnek IM, Camus Duboc M, Garcia-Pagan JC, et al. Endoscopic diagnosis and management of esophagogastric variceal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2022;54(11):1094–1120. 13 Henry Z, Patel K, Patton H, Saad W. AGA clinical practice update on management of bleeding gastric varices: expert review. Clin Gastroenterol Hepatol 2021;19(6):1098–1107.e1. doi: 10.1016/j.cgh.2021.01.027. 14 Cheng L, Wang Z, Li C, et al. Low incidence of complications from endoscopic gastric variceal obturation with butyl cyanoacrylate. Clin Gastroenterol Hepatol 2010;8(9):760–766. 15 Maruyama H, Yoshikawa M, Yokosuka O. Current role of ultrasound for the management of hepatocellular carcinoma. World J Gastroenterol 2008;14:1710–1719. 16 Kagansky N, Levy S, Keter D, et al. Non-alcoholic fatty liver disease – a common and benign finding in octogenarian patients. Liver Int 2004;24(6):588–594. 17 Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006;43:S99–S112. 18 Kemmer N, Neff G, Parkinson E, et al. Non-alcoholic fatty liver disease (NAFLD) epidemic and its implications for liver transplantation. Am J Transplant 2013;13:223–224. 19 Lazo M, Hernaez R, Bonekamp S, et al. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study. BMJ 2011;343:d6891. 20 Silva-Santisteban A, Agnihotri A, Cruz-Romero C, et al. EUS imaging for the diagnosis of nonalcoholic fatty liver disease. Gastrointest Endosc 2022;95(4):711–716. doi: 10.1016/j.gie.2021.11.048 21 Mansour S, Hou D, Rattan R, Wan A. Non-alcoholic steatohepatitis mimicking liver metastasis in obesity surgery. Dig Endosc 2011;23:316–318. 22 Meng K, Lee CH, Saremi F. Metabolic syndrome and ectopic fat deposition: what can CT and MR provide? Acad Radiol 2010;17:1302–1312. 23 Tobari M, Hashimoto E, Yatsuji S, et al. Imaging of nonalcoholic steatohepatitis: advantages and pitfalls of ultrasonography and computed tomography. Intern Med 2009;48:739–746. 24 Gleeson FC, Clayton AC, Zhang L, et al. Adequacy of endoscopic ultrasound core needle biopsy specimen of nonmalignant hepatic parenchymal disease. Clin Gastroenterol Hepatol 2008; 6:1437–1440. 25 Rockey DC, Caldwell SH, Goodman ZD, et al. Liver biopsy. Hepatology 2009;49(3):1017–1044. doi: 10.1002/hep.22742. 26 Diehl DL. Endoscopic ultrasound-guided liver biopsy. Gastrointest Endosc Clin N Am 2019;29(2):173–186. doi: 10.1016/j.giec.2018.11 .002.

27 Diehl D, Mok S, Khara H, et al. Heparin priming of EUS-FNA needles does not adversely affect tissue cytology or immunohistochemical staining. Endosc Int Open 2018;06(03):E356–E362. doi: 10.1055/s-0043-121880. 28 Mok SRS, Diehl DL, Johal AS, et al. Endoscopic ultrasound-guided biopsy in chronic liver disease: a randomized comparison of 19-G FNA and 22-G FNB needles. Endosc Int Open 2019;7(1):E62–E71. doi: 10.1055/a-0655-7462. 29 Mok SRS, Diehl DL, Johal AS, et al. A prospective pilot comparison of wet and dry heparinized suction for EUS-guided liver biopsy (with videos). Gastrointest Endosc 2018;88(6):919–925. doi: 10.1016/j.gie.2018.07.036. 30 Khurana S, Butt W, Khara HS, et al. Bi-lobar liver biopsy via EUS enhances the assessment of disease severity in patients with non-alcoholic steatohepatitis. Hepatol Int 2019;13(3):323–329. doi: 10.1007/s12072-019-09945-4. 31 Lai L, Poneros J, Santilli J, Brugge W. EUS-guided portal vein catheterization and pressure measurement in an animal model: a pilot study of feasibility. Gastrointest Endosc 2004;59(2):280–283. doi: 10.1016/S0016-5107(03)02544-6. 32 Huang JY, Samarasena JB, Tsujino T, et al. EUS-guided portal pressure gradient measurement with a simple novel device: a human pilot study. Gastrointest Endosc 2017;85(5):996–1001. doi: 10.1016/j.gie.2016.09.026. 33 Choi AY, Kolb J, Shah S, et al. Endoscopic ultrasound-guided portal pressure gradient with liver biopsy: 6 years of endo-hepatology in practice. J Gastroenterol Hepatol 2022;37(7):1373–1379. doi: 10.1111/jgh.15875. 34 Hajifathalian K, Westerveld D, Kaplan A, et al. Simultaneous EUS-guided portosystemic pressure measurement and liver biopsy sampling correlate with clinically meaningful outcomes. Gastrointest Endosc 2022;95(4):703–710. doi: 10.1016/j.gie.2021.11.037. 35 Zhang W, Peng C, Zhang S, et al. EUS-guided portal pressure gradient measurement in patients with acute or subacute portal hypertension. Gastrointest Endosc 2021;93(3):565–572. doi: 10.1016/j.gie.2020.06.065. 36 Levy MJ, Bendel EC, Bjarnason H, et al. Endoscopic ultrasoundguided dual ultrasound hepatic cyst aspiration and sclerotherapy to ameliorate portal hypertension. Am J Gastroenterol 2022;117(5):715–716. 37 Schulman AR, Lin MV, Rutherford A, et al. A prospective blinded study of endoscopic ultrasound elastography in liver disease: towards a virtual biopsy. Clin Endosc 2018;51(2):181–185. doi: 10.5946/ce.2017.095. 38 Sandulescu L, Padureanu V, Dumitrescu C, Braia N et al. A pilot study of real time elastography in the differentiation of focal liver lesions. Curr Health Sci J 2012;38(1):32–5. 39 Robles-Medranda C, Oleas R, Puga-Tejada M, et al. Results of liver and spleen endoscopic ultrasonographic elastography predict portal hypertension secondary to chronic liver disease. Endosc Int Open 2020;08(11):E1623–E1632. doi: 10.1055/a-1233-1934. 40 Marya NB, Powers PD, Fujii-Lau L, et al. Application of artificial intelligence using a novel EUS-based convolutional neural network model to identify and distinguish benign and malignant hepatic masses. Gastrointest Endosc 2021;93(5):1121–1130 41 Goodman ZD. Neoplasms of the liver. Mod Pathol 2007; 20(Suppl. 1):S49–S60. 42 Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011;53:1020–1022.

Chapter 22: EUS in liver disease

43 Silva MA, Hegab B, Hyde C, et al. Needle track seeding following biopsy of liver lesions in the diagnosis of hepatocellular cancer: a systematic review and meta-analysis. Gut 2008;57:1592–1596. 44 Thuluvath PJ. EUS-guided FNA could be another important tool for the early diagnosis of hepatocellular carcinoma. Gastrointest Endosc 2007;66:274–276. 45 Awad SS, Fagan S, Abudayyeh S, et al. Preoperative evaluation of hepatic lesions for the staging of hepatocellular and metastatic liver carcinoma using endoscopic ultrasonography. Am J Surg 2002;184:601–604, disc. 604–605. 46 Storch I, Gomez C, Contreras F, et al. Hepatocellular carcinoma (HCC) with portal vein invasion, masquerading as pancreatic mass, diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Dig Dis Sci 2007;52:789–791. 47 Singh P, Erickson RA, Mukhopadhyay P, et al. EUS for detection of the hepatocellular carcinoma: results of a prospective study. Gastrointest Endosc 2007;66(2):265–273. 48 Gan L, Houser F, Di Bernardo T, et al. EUS-FNA of portal venous tumoral thrombosis for diagnosis of hepatocellular carcinoma without primary hepatic mass (with video). Endosc Ultrasound 2021;10(1):71. doi: 10.4103/eus.eusTh64Th20 49 Levy MJ, Zhang L, Gleeson FC. Electronic clinical challenges and images in GI. Portal vein tumor thrombosis in a patient with previously unconfirmed hepatocellular carcinoma. Gastroenterology 2009;136(5):e1–3. doi: 10.1053/j.gastro.2008.12.036. 50 Nonami T, Yokoyama I, Iwatsuki S, Starzl TE. The incidence of portal vein thrombosis at liver transplantation. Hepatology 1992;16(5):1195–8. PMID: 1427658; PMCID: PMC2989675. 51 Eskandere D, Hakim H, Attwa M, et al. Role of endoscopic ultrasound-guided fine-needle aspiration of portal vein thrombus in the diagnosis and staging of hepatocellular carcinoma. Clin Endosc 2021;54(5):745–753. doi: 10.5946/ce.2020.240 52 Gimeno Garcia AZ, Aparicio JR, Barturen A, et al. Short article: endoscopic ultrasound-guided fine-needle aspiration of portal vein thrombosis in patients with chronic liver disease and suspicion of hepatocellular carcinoma. Eur J Gastroenterol Hepatol 2018;30(4):418–423. doi: 10.1097/MEG.0000000000001094. 53 Lange A, Muniraj T, Aslanian HR. Endoscopic ultrasound for the diagnosis and staging of liver tumors. Gastrointest Endosc Clin N Am 2019;29(2):339–350. doi: 10.1016/j.giec.2018.12.005. PMID: 30846157. 54 Weinman MD, Chopra S. Tumors of the liver, other than primary hepatocellular carcinoma. Gastroenterol Clin N Am 1987; 16:627–650. 55 Federle MP, Jeffrey RB, Tublin ME, Borhani AA. Specialty Imaging: Hepatobiliary and Pancreas. Manitoba: Amirys, 2013. 56 Crowe A, Knight CS, Jhala D, et al. Diagnosis of metastatic fibrolamellar hepatocellular carcinoma by endoscopic ultrasoundguided fine needle aspiration. CytoJournal 2011;8:2. 57 Centeno BA. Pathology of liver metastases. Cancer Control 2006;13:13–26. 58 Abbruzzese JL, Abbruzzese MC, Lenzi R, et al. Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin. J Clin Oncol 1995;13:2094–2103. 59 Nguyen P, Feng JC, Chang KJ. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions. Gastrointest Endosc 1999;50:357–361. 60 Singh P, Mukhopadhyay P, Bhatt B, et al. Endoscopic ultrasound versus CT scan for detection of the metastases to the liver results of a prospective comparative study. J Clin Gastroenterol 2009;43: 367–373.

205

61 Crowe DR, Eloubeidi MA, Chhieng DC, et al. Fine-needle aspiration biopsy of hepatic lesions – computerized tomographic-guided versus endoscopic ultrasound-guided FNA. Cancer Cytopathol 2006;108:180–185. 62 Prasad P, Schmulewitz N, Patel A, et al. Detection of occult liver metastases during EUS for staging of malignancies. Gastrointest Endosc 2004;59(1):49–53. 63 McGrath K, Brody D, Luketich J, Khalid A. Detection of unsuspected left hepatic lobe metastases during EUS staging of cancer of the esophagus and cardia. Am J Gastroenterol 2006; 101:1742–1746. 64 Okasha H, Wifi MN, Awad A, et al. Role of EUS in detection of liver metastasis not seen by computed tomography or magnetic resonance imaging during staging of pancreatic, gastrointestinal, and thoracic malignancies. Endosc Ultrasound 2021;10(5):344. doi: 10.4103/EUS-D-20-00178 65 Hollerbach S, Willert J, Topalidis T, et al. Endoscopic ultrasoundguided fine-needle aspiration biopsy of liver lesions: histological and cytological assessment. Endoscopy 2003;35:743–749. 66 Schwartz DA, Wiersema MJ. The role of endoscopic ultrasound in hepatobiliary disease. Curr Gastroenterol Rep 2002;4:72–78. 67 Harvey CJ, Albrecht T. Ultrasound of focal liver lesions. Eur Radiol 2001;11:1578–1593. 68 Fujii-Lau LL, Abu Dayyeh BK, Bruno MJ, et al. EUS-derived criteria for distinguishing benign from malignant metastatic solid hepatic masses. Gastrointest Endosc 2015;81(5):1188–1196.e7. 69 Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology 1977;73:386–394. 70 Nakao A, Sakagami K, Nakata Y, et al. Multiple hepatic adenomas caused by long-term administration of androgenic steroids for aplastic anemia in association with familial adenomatous polyposis. J Gastroenterol 2000;35(7):557–562. 71 Sandler MA, Petrocelli RD, Marks DS, Lopez R. Ultrasonic features and radionuclide correlation in liver cell adenomaand focal nodular hyperlasia. Radiology 1980;135:393–397. 72 John TG, Greig JD, Crosbie JL, et al. Superior staging of liver tumors with laparoscopy and laparoscopic ultrasound. Ann Surg 1994;220:711–719. 73 Carlson SK, Johnson CD, Bender CE, Welch TJ. CT of focal nodular hyperplasia of the liver. AJR Am J Roentgenol 2000; 174:705–712. 74 Shamsi K, De Schepper A, Degryse H, Deckers F. Focal nodular hyperplasia of the liver: radiologic findings. Abdom Imaging 1993;18:32–38. 75 Bioulac-Sage P, Balabaud C, Bedossa P, et al. Pathological diagnosis of liver cell adenoma and focal nodular hyperplasia: Bordeaux update. J Hepatol 2007;46(3):521–527. 76 Gandolfi L, Leo P, Solmi L, et al. Natural history of hepatic haemangiomas: clinical and ultrasound study. Gut 1991;32:677–680. 77 Perkins AB, Imam K, Smith WJ, Cronan JJ. Color and power Doppler sonography of liver hemangiomas: a dream unfulfilled? J Clin Ultrasound 2000;28:159–165. 78 McFarland EG, Mayo-Smith WW, Saini S, et al. Hepatic hemangiomas and malignant tumors: improved differentiation with heavily T2-weighted conventional spin-echo MR imaging. Radiology 1994;193:43–47. 79 Nisenbaum HL, Rowling SE. Ultrasound of focal hepatic lesions. Semin Roentgenol 1995;30:324–346. 80 Regev A, Reddy KR, Berho M, et al. Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center. J Am Coll Surg 2001;193(1):36–45.

206

Endoscopic Ultrasonography

81 Ishak KG, Willis GW, Cummins SD, Bullock AA. Biliary cystadenoma and cystadenocarcinoma: report of 14 cases and review of the literature. Cancer 1977;39:322–338. 82 Hai S, Hirohashi K, Uenishi T, et al. Surgical management of cystic hepatic neoplasms. J Gastroenterol 2003;38:759–764. 83 Seewald S, Imazu H, Omar S, et al. EUS-guided drainage of hepatic abscess. Gastrointest Endosc 2005;61(3):495–498. 84 Itoi T, Ang TL, Seewald S, et al. Endoscopic ultrasonographyguided drainage for tuberculous liver abscess. Dig Endosc 2011; 23(Suppl 1):158–161. 85 Yu SC, Lo RH, Kan PS, Metreweli C. Pyogenic liver abscess: treatment with needle aspiration. Clin Radiol 1997;52:912–916. 86 Razumilava N, Gores GJ. Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol 2013;11(1):13–21. 87 Blechacz B, Komuta M, Roskams T, Gores GJ. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol 2011;8:512–522. 88 Everhart JE, Ruhl CE. Burden of digestive diseases in the United States. Part III: liver, biliary tract, and pancreas. Gastroenterology 2009;136:1134–1144. 89 Yamasaki S. Intrahepatic cholangiocarcinoma: macroscopic type and stage classification. J Hepato-Biliary-Pancreat Surg 2003; 10:288–291. 90 Vilgrain V. Staging cholangiocarcinoma by imaging studies. HPB (Oxford) 2008;10:106–109. 91 Levy MJ, Heimbach JK, Gores GJ. Endoscopic ultrasound staging of cholangiocarcinoma. Curr Opin Gastroenterol 2012; 28:244–252.

92 Heimbach JK, Sanchez W, Rosen CB, Gores GJ. Trans-peritoneal fine needle aspiration biopsy of hilar cholangiocarcinoma is associated with disease dissemination. HPB (Oxford) 2011;13: 356–360. 93 El Chafic AH, Dewitt J, LeBlanc JK, et al. Impact of preoperative endoscopic ultrasound-guided fine needle aspiration on postoperative recurrence and survival in cholangiocarcinoma patients. Endoscopy 2013;45(11):883–889. 94 Pollack MJ, Gholam PM, Chak A. EUS-FNA in unresectable cholangiocarcinoma: a novel indication. Gastrointest Endosc 2008; 67:444–445. 95 Gleeson FC, Rajan E, Levy MJ, et al. EUS-guided FNA of regional lymph nodes in patients with unresectable hilar cholangiocarcinoma. Gastrointest Endosc 2008;67(3):438–443. 96 Mesenas S, Vu C, Doig L, Meenan J. Duodenal EUS to identify thickening of the extrahepatic biliary tree wall in primary sclerosing cholangitis. Gastrointest Endosc 2006;63:403–408. 97 Lutz HH, Wasmuth HE, Streetz K, et al. Endoscopic ultrasound as an early diagnostic tool for primary sclerosing cholangitis: a prospective pilot study. Endoscopy 2012;44(10):934–939. 98 European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol 2009;51(2):237–267. 99 Lev-Toaff AS, Bach AM, Wechsler RJ, et al. The radiologic and pathologic spectrum of biliary hamartomas. AJR Am J Roentgenol 1995;165:309–313. 100 Zheng RQ, Zhang B, Kudo M, et al. Imaging findings of biliary hamartomas. World J Gastroenterol 2005;11:6354–6359.

C H A P T E R 23

Colorectal EUS Sarakshi Mahajan 1 , Brian R. Weston 2 , Pradermchai Kongkam 3 & Manoop S. Bhutani 4 1 Department

of Internal Medicine, Washington University at Saint Louis, Saint Louis, MO, USA of Gastroenterology, Hepatology and Nutrition, UT MD Anderson Cancer Center, Houston, TX, USA 3 Department of Internal Medicine, Chulalongkorn University and King Chulalongkorn Memorial, Hospital, Thai Red Cross Society, Bangkok, Thailand 4 Deparment of Gastroenterology, Hepatology and Nutrition-Unit 1466, UT MD Anderson Cancer Center, Houston, TX, USA 2 Department

Introduction Applications for endoscopic ultrasound (EUS) in the colon and rectum have continued to expand since introduced in the early 1980s. Innovation and refinements in the technology have considerably improved over time. Availability has become increasingly widespread, and EUS has evolved to play an integral role in the diagnosis, therapeutic applications, and staging of rectal cancer as well as the evaluation of other lesions involving the rectum, perirectal space, colon, and anal canal.

Instruments for colorectal endosonography Rigid probes The use of rigid probes is limited to evaluation of the distal rectum and anal canal. Rigid probes do not incorporate fiberoptic bundles or video chips and thus do not provide a simultaneous endoscopic and ultrasound image. The most frequently used rigid probe is an instrument with a single-element 7.5 MHz transducer that provides a 360∘ radial image at right angles to the long axis of the probe (Bruel and Kjaer; Naerum, Denmark; Marlborough, MA). A balloon around the transducer provides acoustic coupling with the gut wall. Rigid probes with linear array imaging are also available. Echoendoscopes EUS endoscopes are flexible and may be used in the rectum and accessible proximal colon. A standard upper radial or linear echoendoscope or a miniprobe (catheter-based EUS probe passed through the working channel of a regular endoscope) may be used. The frequencies available for these instruments range from 5 to 10 or 12 MHz for echoendoscopes and 12 to 20 MHz for miniprobes. The lower frequencies in this 5–20 MHz spectrum have greater penetration and are suitable to image lesions larger than 1 cm and those structures beyond the gut wall. The higher frequencies have limited penetration, but they provide superior resolution of various layers of the gastrointestinal wall and are ideal for lesions 10 mm, round, with distinct margins, and hypoechoic have been considered to have a much greater chance of malignant invasion in upper gastrointestinal cancers such as the esophagus [24]. However, there is no universal agreement among endosonographers about the features most predictive of malignant invasion [25]. In rectal cancer, the size cut-off for lymph nodes considered suspicious for malignant invasion is 5 mm instead of 10 mm. Lymph node metastasis increases with T-stage (T1 = 10%, T2 = 25%, and T3/T4 = 50%) [26]. Malignant perirectal lymph nodes are usually associated with higher T3 or greater-stage disease. The presence of tumoral stenosis is a predictive factor for poor N-staging in EUS. Up to 15% of rectal cancers cannot be completely evaluated due to tumor stenosis [27]. In retrospective study conducted on 42 CRC patients, comparison was made between the perfusion patterns using contrast-enhanced EUS and markers of angiogenesis obtained through immunohistochemical and genetic analysis. The samples were taken from patients prior to any treatment. Specialized software was used to analyze contrast-enhanced EUS video data and extract ten parameters and was compared to expression of vascular endothelial growth factor receptor (VEGFR) 1 and VEGFR 2 genes from biopsy samples collected during colonoscopy. Furthermore, microvascular density and vascular area were calculated through immunostaining of CD 31 and CD 105 markers. The results of the study showed positive correlation between contrast-enhanced EUS parameters and cancer stage indicating that they could potentially provide insights into LN invasion by assessing the angiogenesis in CRC.

Chapter 23: Colorectal EUS

Fine-needle aspiration (FNA) The application of EUS-guided FNA may be used as an adjunct to accurate lymph node assessment during EUS [25], and it has been applied in patients with rectal cancer [28] (Figure 23.4). Perirectal lymph nodes are also frequently peritumoral and thus not amenable for FNA. EUS-guided FNA of lymph nodes is not an option for lymph nodes that are in the immediate vicinity of the primary tumor since passage of the needle through the tumor will lead to false positive results and potential seeding [29, 30]. FNA of perirectal LNs has been shown in at least one prospective study to have no impact on staging or clinical management compared to EUS alone [27, 31]. FNA may nonetheless improve staging in a subset of patients such as those with early or recurrent disease. Gleeson et al. showed that the addition of EUS-FNA may enhance extramesenteric lymph node metastases detection outside of standard radiation fields (M1 disease); 41 of 316 patients (13%) with primary rectal cancer had M1 disease by EUS-FNA [32]. Chafic et al. demonstrated that EUS-FNB using SharkCore needle for suspected GI stromal tumors was technically similar and equally safe, with better acquisition of tissue seen with fewer needle passes [9]. A study by Facciorusso et al. [33] aimed to compare the effectiveness of endoscopic ultrasound (EUS), fine-needle biopsy (FNB), and fine-needle aspiration (FNA) for sampling lymph nodes (LNs) in patients with abdominal tumors. Among 502 patients who underwent EUS sampling, 105 patients received EUS-FNB, and 105 received EUS-FNA. The main focus was on diagnostic accuracy, with secondary outcomes including diagnostic sensitivity, specificity, sample adequacy, optimal histological core procurement, number of passes, and adverse events. The final diagnosis indicated LN metastasis, mainly from colorectal cancer, in around 70.4% of the EUS-FNB group and 66.6% of the EUS-FNA group. The study found that EUS-FNB exhibited superior performance compared to EUS-FNA in terms of diagnostic accuracy (87.62% vs. 75.24%), diagnostic sensitivity (84.71% vs. 70.11%), and histological core procurement rate (94.2% vs. 51.4%). Both approaches had a specificity of 100%. Sample adequacy also trended better with EUS-FNB (96.1% vs. 89.5%) [33].

Interobserver variability in rectal cancer staging by EUS The quality of the results of EUS is operator dependent [34–38]. Special training and a learning curve are acknowledged [38]. How

Figure 23.4 EUS-guided fine-needle aspiration of a perirectal lymph node.

The tip of the needle is within the lymph node (arrowhead).

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well-published results translate in clinical practice is a concern. Marusch et al. [34] suggested that EUS for rectal cancer in clinical practice does not achieve the good results achieved in the literature in a very large multicenter prospective evaluation from Germany. Of 29 206 patients included, 27 458 were treated by surgical resection and 12 235 (44.6%) underwent EUS. Of these, 7096 did not receive neoadjuvant radiochemotherapy, allowing an uT-pT comparison. The uT-pT correspondence was 64.7% (95% confidence interval (CI) 63.6–65.8%); the frequencies of understaging and overstaging were 18% and 17.3%, respectively. The kappa coefficient was greatest for T1 tumors (𝜅 = 0.591). For T3 tumors, 𝜅 was 0.468. The poorest correspondence was found for T2 and T4 tumors (𝜅 = 0.367 and 0.321, respectively). A breakdown by hospital volume showed that the uT-pT correspondence was 63.2% (95%CI 61.5–64.9%) for hospitals undertaking ≤10 EUS/year, 64.6% (95%CI 62.9–66.2%) for doing 11–30 EUS/year, and 73.1% (95%CI 69.4–76.5%) for those hospitals performing >30 EUS/year. Most still agree that colorectal EUS is best done in high-volume centers by experienced operators.

EUS compared to CT and MRI By comparison, CT and MRI accuracies in staging of rectal cancer have been estimated to be 65–75% and 75–85%, respectively [14, 28, 39–48]. CT is most useful for evaluation of advanced disease and distant metastases. Parallel improvements in high-resolution MRI have shown similar accuracy for T- and N-staging when compared to EUS. A meta-analysis was recently performed on the diagnostic accuracy of MRI for the assessment of T-stage, lymph node metastasis, and circumferential resection margin (CRM) involvement in patients with rectal cancer. Twenty-one studies were included in the analysis. There was notable heterogeneity among studies. MRI specificity was significantly higher for CRM involvement (94–95% CI: 88–97) than for T-category (75%, 95% CI: 68–80) and lymph nodes (71%, 95% CI: 59–81). There was no significant difference in sensitivity between the three elements as a result of wide overlapping CIs. Diagnostic odds ratio was significantly higher for CRM (56.1, 95% CI: 15.3–205.8) than for lymph nodes (8.3, 95% CI: 4.6–14.7) but did not differ significantly from T-category (20.4, 95% CI: 11.1–37.3). Bipat [45] also conducted a meta-analysis comparing EUS, CT, and MRI for rectal cancer staging and found that EUS was the most accurate modality when compared with CT and MRI for the evaluation of T-stage in rectal cancer. For lymph node involvement, the results of EUS, CT, and MRI were comparable. However, the T-staging system does not discriminate between T3 tumors with close or involved circumferential resection clearance. The distance of the tumor from the rectal fascia or the anticipated circumferential resection clearance was not evaluated. Lahaye et al. [46] conducted another meta-analysis regarding the accuracy of preoperative imaging for predicting the two most important risk factors that they recognized for local recurrence in rectal cancer: the circumferential resection clearance and the lymph node status. For nodal status, EUS was slightly, but not significantly, better than MRI. Major progress has been made in the preoperative staging of rectal tumors by MRI, and several authors have indicated that a tumor-free circumferential clearance of more than 1 mm can be predicted using this method [49]. Factors that may negatively influence EUS and MRI are tumor stenosis and polypoid morphology, respectively [27]. Polypoid morphology of the tumor was shown to be inversely associated with the accuracy of T-stage in MRI, whereas tumoral stenosis was

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a predictive factor for poor N-staging in EUS. EUS may perform better than MRI for early cancers as well as the ability to perform FNA. However, FNA of perirectal lymph nodes has been shown to have little impact on clinical management [27, 31, 41]. MRI may be better for advanced cancers including the ability to identify the mesorectum and mesorectal fascia which is critical for predicting tumoral involvement of the circumferential resection margin as well as anal sphincter assessment [27, 50, 51]. The best choice of staging evaluation modality for rectal cancer will depend on local availability and expertise. The combination of EUS and CT or MRI may well be the best approach depending on the individual case with the understanding that all tests can be complementary and have limitations. At least one study has shown the combination of abdominal CT plus rectal EUS to be the most cost-effective [52]. Others suggest that MRI seems to be cost-effective in selecting appropriate patients for neoadjuvant therapy, and its use is justified for local staging [50, 52]. The study conducted by Malmstrom et al. aimed to compare the accuracy of preoperative tumor (T) and nodal (N) staging in left-sided colon cancer using endoscopic ultrasonography (EUS) and computed tomography (CT) against postoperative histology. They enrolled 44 patients between November 2014 and January 2016, with 35 included in the final analysis. Patients underwent EUS, CT, and surgery within two weeks. The diagnostic performance was assessed for “low-risk” (T1 + T2 + T3 with ≤5 mm extramural invasion) and “high-risk” (T3 with >5 mm extramural spread or T4) colonic cancer. Results showed that EUS had a sensitivity of 0.90 and specificity of 0.75 for “low-risk” cancer, while CT had a sensitivity of 0.96 and specificity of 0.25. Both methods were poor at predicting the presence or absence of nodal involvement (N0 or N+ disease). It was concluded that EUS and CT demonstrated comparable and good sensitivity for evaluating T-stage in left-sided colon cancer. However, EUS exhibited significantly higher specificity in assessing “low-risk” tumors [53]. In another study by Chan et al., although EUS and MRI were both deemed reasonable diagnostic accuracy in the staging of nonmetastatic rectal cancer, EUS was superior to MRI in overall T-staging and overall T- and N-staging after adjusting for MRI technology [54]. On the contrary, a systemic review published by Li et al. deemed MRI at field strength of 3.0 T was better at evaluating lymph node (LN) metastasis for rectal cancer when compared to CT or EUS [55]. Practitioners should be aware of advantages and disadvantages of all three modalities and choose appropriate methods while considering diagnostic accuracy of each test and institutional practices and limitations [56].

Three-dimensional EUS for rectal cancer staging Three-dimensional (3D) EUS image reconstruction may improve the accuracy of EUS and may help decrease errors in staging. Potential advantages of 3D reconstruction in EUS include better spatial assessment of the location of tumors and their relationships with adjacent organs and blood vessels [57–59]. Kim et al. have published significant work on the efficacy of 3D endorectal ultrasonography in rectal cancer [58, 59]. Thirty-three patients were studied using both 3D and conventional EUS for staging rectal cancer. Accuracy of 3D EUS was 90.9% for T2 and 84.8% for T3 tumors, whereas that of conventional EUS was 84.8% and 75.8%, respectively. Lymph node metastasis was accurately predicted by 3D EUS in 28 patients (84.8%) and in 22 patients (66.7%) by conventional EUS [57]. 3D

EUS has shown greater accuracy than 2D EUS or CT for evaluation in rectal cancer staging and lymph node metastasis. Eighty-six consecutive rectal cancer patients undergoing curative surgery were evaluated by 2D EUS, 3D EUS, and CT scan. The accuracy in T-staging was 78% for 3D EUS, 69% for 2D EUS, and 57% for CT (P < 0.001–0.002), whereas the accuracy in evaluating lymph node metastases was 65%, 56%, and 53%, respectively (P < 0.001–0.006). Examiner errors were the most frequent cause of misinterpretation, occurring in 47% of 2D EUS examinations and in 65% of 3D EUS examinations [58]. Giovannini studied a software program [59] in 35 patients for staging of rectal cancer by three-dimensional EUS that can be used with electronic radial or linear rectal probes. In six of 15 patients classified as having T3N0 lesions, three-dimensional EUS revealed malignant lymph nodes, a finding that was confirmed surgically in five of the six cases. Three-dimensional EUS also made it possible to assess the degree of infiltration of the mesorectum precisely in all cases, demonstrating complete invasion of the mesorectum in eight cases. These findings were confirmed in all cases by surgery. Two-dimensional EUS accuracy for T- and N-staging was correct in 25 of 35 rectal tumors (71.4%), while the accuracy with three-dimensional EUS was 31 of 35 (88.6%). However, availability and expertise with this technology have not been utilized on a widespread basis to date [59].

Contrast-enhanced EUS for rectal cancer staging Contrast-enhanced Doppler EUS (CD-EUS) enhances Doppler signals from vessels and is useful for characterizing lesions detected by EUS. Contrast-enhanced harmonic EUS (CH-EUS) with second-generation ultrasound contrast agents and a broadband transducer allows microvessels and parenchymal perfusion to be visualized. Vascularity can also be quantitatively analyzed during CH-EUS and is superior to multiple detector CT in terms of the differential diagnosis of small lesions that are ≤2 cm. CH-EUS complements EUS-guided fine-needle aspiration (EUS-FNA) as it identifies the EUS-FNA target and lesions with false-negative EUS-FNA findings. CH-EUS is also used to estimate the malignant potential of gastrointestinal stromal tumors and may help to differentiate between malignant and benign lymphadenopathy [60].

Clinical impact of EUS staging in rectal cancer EUS is a highly useful technique for local staging of rectal cancer as preoperative staging determines the type of surgery performed and whether preoperative neoadjuvant chemoradiation is needed. EUS may alter patient management in relation to surgical candidacy, extent of resection, and/or radiation therapy field. Savides et al. [29] summarized the indications for EUS in rectal cancer after review of the literature and potential impact based on tumor stage. Indications for EUS in rectal cancer include the following: (a) in a large polyp or small rectal cancer to determine suitability for endoscopic mucosal resection or transanal excision (if the lesion is T1 by EUS); (b) in a large, rectal cancer to determine whether preoperative chemotherapy and radiation is needed or not (T2: radical resection, T3–4 or N1: preoperative chemoradiation followed by radical resection); (c) surveillance after surgery for rectal cancer. Harewood and colleagues [30, 50, 60–62] have published multiple studies on the clinical impact of EUS in rectal cancer. The authors concluded that preoperative staging with EUS results in

Chapter 23: Colorectal EUS

more frequent use of preoperative neoadjuvant therapy than if staging was performed with CT alone. An evidence-based consensus statement on the role and application of endosonography for rectal cancer staging in clinical practice has been published [6]. Most rectal cancers present at an advanced stage T3 and/or N1 stage ∼75% [63–68]. Accurate assessment of these groups is important for those patients eligible for preoperative chemotherapy and radiation protocols. EUS can assess the circumferential resection margin (CRM) for anteriorly located tumors by assessing the extent of tumor involvement in the mesorectal fascia. The distance from the tumor to the CRM is an important predictor for recurrence of rectal cancer after surgery [68]. The relation of tumor edge to the circumferential margin is an important factor in deciding the need for neoadjuvant treatment and prognosis [48]. Sphincter-saving transanal excision of an early (T1 No) lesion can be performed rather than an abdominoperineal resection which can be reserved for more advanced lesions that have penetrated into the muscularis propria or beyond [68, 69]. However, determination of malignancy within a large adenoma at the level of the anal sphincters may be technically very difficult due to artifacts [70]. In another study on clinical impact in rectal cancer, EUS staging information changed the surgeon’s original treatment plan based on CT alone in 31% of patients [31]. The role of EUS staging in colon cancers throughout the rest of the colon is less clear as these patients would undergo laparotomy and resection anyway, if there are no distant metastases. However, EUS may be a helpful staging modality for proximal colon cancers with the advent of minimally invasive laparoscopic and endoscopic mucosal resection [71–74] for early lesions, and also if neoadjuvant chemotherapy of locally advanced proximal colon cancers becomes more common [11, 12].

EUS for local recurrence of colorectal carcinoma Local recurrence of colorectal cancer after attempted curative resection is variable in the published literature depending on surgical technique, involvement of the circumferential resection margin (tumors within 1 mm of the mesorectal fascia), neoadjuvant therapy, etc. [48]. Recurrence may recur in 2.6–32% of patients although rates have generally improved. Endosonography may be useful in the diagnosis of suspected local recurrence especially for intra- or extraluminal lesions. EUS in such cases may reveal hypoechoic areas (or areas of mixed echogenicity) inside or outside the colorectal wall. Endosonographic alterations due to the primary surgery need to be kept in mind. Fibrosis at the site of surgery appears hyperechoic. Surgical anastomosis is seen as an interruption of the five-layer echo structure [74, 75]. If staples were used during surgery, they create a very bright localized echo [75]. The risk of recurrence for rectal cancer is greatest in the first 2 years after surgery. Detection of local recurrence in a resectable stage provides an opportunity for repeat surgery with curative intent. A number of studies have shown EUS to be accurate in detecting recurrent rectal cancer at or near the anastomotic site with EUS-guided FNA being able to provide tissue confirmation [76–80]. Lohnert et al. [76] performed a prospective study to assess the role of endorectal and endovaginal ultrasound to detect asymptomatic resectable local recurrence in 338 patients. Local recurrence was found in 116 patients (34.3%) which was suggested by EUS and proven by EUS-guided needle biopsy in all cases of unclear pararectal structures that could not be verified by endoscopic biopsy. In the study by Rotondano et al., 62 patients operated

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on for rectal cancer were prospectively enrolled in a follow-up study including endorectal ultrasound (EUS), serial CEA levels, digital examination, colonoscopy, and pelvic CT. Local recurrence occurred in 11 patients; in all cases, this was suggested by EUS. In two patients (18%), other techniques had failed to detect recurrent disease, which was identified only by EUS [77]. Hunerbein et al. [78] prospectively investigated the role of EUS with biopsy in the postoperative follow-up of rectal cancer in 312 patients. Local recurrence was found in 36 patients. Intraluminal recurrence was diagnosed by proctoscopy in 12. Transrectal EUS-guided biopsy showed pelvic recurrence in 22 of 68 patients with perirectal masses. There was a strong agreement between EUS-guided transrectal biopsy results and the final diagnosis (𝜅 = 0.84), the sensitivity and specificity being 91% and 93%, respectively. In comparison, clinical examination (𝜅 = 0.27), computed tomography (𝜅 = 0.47), or EUS imaging alone (𝜅 = 0.42) showed only a moderate level of agreement with the histopathologic diagnosis. Although many studies have shown the value of EUS in detecting local recurrence in rectosigmoid cancer, the optimal interval for repeating EUS after surgical treatment of rectal cancer is unclear.

Restaging after chemotherapy and radiation Neoadjuvant chemoradiation is often utilized for down-staging of rectal cancer prior to surgical resection [81–85]. A complete pathologic response may be seen in up to 30% of cases and is associated with low rates of recurrence [51]. The most commonly used tests to restage rectal cancer after chemoradiation therapy are CT, MRI, and rectal EUS. Although EUS is very accurate in T- and N-staging for rectal cancer prior to initiating any treatment, restaging after chemoradiation is inaccurate. Neoadjuvant therapy may produce deep modifications in cancer tissue and on surrounding structures such as overgrowth fibrosis, deep stroma alteration, wall thickness, muscle disarrangement, tumor necrosis, calcification, and inflammatory infiltration [52]. These changes appear hypoechoic and may be indistinguishable from malignant tissue. This results in the obvious problem of overstaging by EUS after radiation and chemotherapy [85–89]. The diagnostic accuracy of clinical examination and all imaging techniques such as rectal ultrasound, CT, MRI, and PET when used for restaging is far less accurate with less than 60% in most studies for both rectal wall invasion and lymph node involvement [40, 63, 89–91]. The accuracy in T-restaging by EUS ranges between 27% and 72%, with overstaging occurring between 16% and 53%. In the majority of the studies, T1–2 stages are more misdiagnosed than T3 [49, 51, 57, 90–95]. When examining the accuracy to correctly diagnose T0, the figure drops from 0% to 60% [57, 93, 94]. In some cases of complete pathological response, the fibrosis caused persistent interruption of the five layers leading to misinterpretation of the examination. The accuracy of N restaging by EUS is somewhat higher, ranging between 39% and 83% and with most studies 70%. Lymph nodes visualized prior to treatment may still be present but commenting on whether they are benign or malignant may not be accurate. When compared with other imaging techniques, namely CT and standard MRI, restaging by ultrasound was variable [51, 91–94]. The diagnostic accuracy of clinical examination, rectal ultrasound, CT, MRI, and PET ranged between 25% and 75% being less than 60% in most studies, both for rectal wall invasion and for lymph node involvement. Mezzi et al. compared EUS and MRI for restaging rectal cancer after radiotherapy. After neoadjuvant

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chemoradiation, EUS and MRI correctly classified 46% (18/39) and 44% (17/39) of patients, respectively, in line with their histological T-stage (P > 0.05). These proportions were higher for both techniques when nodal involvement was considered: 69% (27/39) and 62% (24/39). When patients were sorted into T and N subgroups, the diagnostic accuracy of EUS was better than MRI for patients with T0–T2 (44% vs. 33%, P > 0.05) and N0 disease (87% vs. 52%, P = 0.013) [49]. However, MRI was more accurate than EUS in T- and N-staging for patients with more advanced disease after radiotherapy, though these differences did not reach statistical significance. In another study comparing digital rectal examination, computed tomography, endorectal ultrasound, and magnetic resonance imaging for predicting T1N0 disease after irradiation of rectal cancers, digital exam had the highest negative predictive value which still detected only 24% of patients to be free of disease. Endoscopic ultrasound failed to detect the absence of disease in 83% of patients [86]. Vanagunas et al. [52] studied the accuracy of EUS in staging rectal cancer after neoadjuvant chemoradiation in a large cohort of patients. EUS staging was performed before and after concurrent 5-fluorouracil and radiotherapy in 82 patients with recently diagnosed locally advanced rectal cancer. All patients underwent subsequent surgical resection and complete pathologic staging. After chemoradiation, 16 patients (20%) had no residual disease at pathologic staging (T0N0). Overall accuracy of EUS post-chemoradiation for pathologic T-stage was only 48%. Fourteen percent were understaged, and 38% overstaged. EUS accuracy for N-stage was 77%. The T-category was correctly staged before surgery in 23 of the 56 responders (41%) and in 16 of 24 nonresponders (67%). EUS was unable to accurately distinguish postradiation changes from residual tumor. Similarly, another recent study [25] tried to compare the accuracy of EUS staging for rectal cancer before (group I) and following chemoradiation (group II). The accuracy of the T-staging for group I was 86% (57/66). Inaccurate staging was mainly associated with overstaging EUS T2 tumors. In group II, following chemoradiation, overstaging EUS T3 tumors accounted for most inaccurate staging. The EUS staging predicted post-chemoradiation T0N0 stage correctly in only 50% of cases. Restaging with EUS after chemoradiation, if attempted should be done with caution with an understanding of limitations/pitfalls as well as communication with oncologists and surgeons using the EUS information for possible therapeutic decisions. The ability to predict complete pathological response, in order to tailor the surgical approach, remains low. Due to the post-treatment change, combined with imaging technical aspects, low rate accuracy is achieved, making modern imaging techniques still unreliable in restaging rectal cancer after chemotherapy. CT, EUS, and MRI might still be useful to demonstrate tumor shrinkage and down-staging in responsive tumors, which might occasionally disappear completely [15, 23, 49, 95, 96]. It is not possible to exclude the persistence of tumor cells within fibrosis [49]. The recent development of elastosonography, a new real-time EUS modality that gives a qualitative image of tissue elasticity, might improve the accuracy and sensitivity of EUS in this setting. Adding elastosonography to real-time EUS enhanced the accuracy in T-staging of the disease. The ability of elastosonography to distinguish tissues with different levels of elasticity means it can detect inflammatory (soft) tissues and tumor (hard) separately, particularly when the real-time modality does not exclude the suspicion of perirectal invasion [97].

Linitis plastica of the rectum Linitis plastica of the rectum is a rare phenomenon. It may be a primary rectal carcinoma or metastases from another primary such as gastric linitis plastica, breast carcinoma, or prostate carcinoma. Endoscopy generally reveals rectal stenosis with induration and thickening of the rectal wall. Endoscopic mucosal biopsy is positive in only a small number of these cases. EUS classically reveals circumferential thickening of the rectal wall with a mean thickness of 12 mm, with either a thickening of the submucosa/muscularis propria or disruption of the normal five-layer wall pattern [98–101]. Perirectal fat infiltration, ascites, or lymph nodes may also be seen. EUS-FNA and or tru-cut biopsy can confirm the diagnosis of linitis plastica of the rectum [101]. However, EUS cannot differentiate between primary and secondary rectal linitis plastica. If these patients undergo chemotherapy, EUS may be used to monitor treatment [98].

Anal cancer Squamous cell carcinoma is the most common type of anal cancer. Staging in anal cancer is based on size of the tumor to define T-stage rather than depth of invasion. TNM classification is outlined as per the post recent American Joint Committee on Cancer (AJCC) Cancer Staging Manual 9th edition [102]. Radiation therapy alone may be definitive. EUS can be used to help stage anal cancer and may help in determining the extent of radiation, especially if lymph nodes are involved [66, 103].

Anal sphincter defects Transrectal ultrasound has provided a unique method to image the external and internal anal sphincters [104]. The internal anal sphincter is seen as a thin hypoechoic zone surrounding the anal canal. The external anal sphincter is seen as a heterogeneous echogenic area lateral to the internal anal sphincter. Defects in the continuity of the external and internal anal sphincters can be visualized by transrectal sonography. Imaging of these defects is useful in evaluation of patients with fecal incontinence problems to anatomically define defects in their anal sphincter mechanism [105]. These sphincter defects visualized during anal sonography correlate with physiologic defects by anal needle electromyography [106–108]. Patients with anorectal inflammatory conditions such as Crohn’s disease, ileoanal pouch with infectious complications, and radiation proctitis have increased thickness of anal wall dimensions when studied by anal sonography [109–111].

Subepithelial lesions and compression of the colorectal wall It is difficult to predict the cause of an endoscopically visible bulge in the gastrointestinal lumen when the overlying mucosa is normal. Such subepithelial compression can be due to an intramural lesion arising from the deeper layers of the gastrointestinal wall or due to an extramural compression by an intrinsic lesion or anatomic structure. Similar to subepithelial compressions of the upper gastrointestinal tract, EUS is extremely useful in evaluating lower gastrointestinal subepithelial lesions. In the American Endosonography Club Study on the Clinical Utility of EUS, the subgroup where EUS had the greatest impact was patients with submucosal (subepithelial) lesions [110]. A lipoma is characterized by

Chapter 23: Colorectal EUS

(A)

(B) Figure 23.5 (A) A subepithelial bulge in the rectum from a large intramural,

subepithelial mass. (B) EUS of the mass in Figure 23.5A shows it to be to be a hypoechoic mass that is contiguous with the muscularis propria (MP). EUS-FNA revealed it to be a GIST (gastrointestinal stromal tumor).

a homogeneous, echogenic lesion that is contiguous with the third echo layer corresponding with the submucosa. Most lipomas are benign, and malignant transformation is a rare phenomenon. Thus, there is controversy about the need for endoscopic removal once a lipoma is diagnosed by EUS. However, EUS would be a prerequisite prior to contemplating an endoscopic removal of a lipoma. EUS may also help in monitoring this lesion if it is not removed. A myogenic tumor appears as a hypoechoic mass that is contiguous with the fourth echo layer representing the muscularis propria (Figure 23.5A,B). The differential diagnosis of a myogenic tumor includes a leiomyoma, leiomyosarcoma, leiomyoblastoma, or a GIST (gastrointestinal stromal tumor). A myogenic tumor, which is >4 cm in diameter, has an irregular margin, with cystic or echogenic foci, and is more likely to be a malignant lesion [111]. However, there is overlap between benign and malignant myogenic or GIST lesions, and resection of the entire lesion is the surest way to ensure absence of malignancy [111–113]. If, however, a decision is made to monitor a myogenic lesion that appears benign, EUS may be useful. Any change in echo features such as size, echogenicity, margins, or appearance of lymphadenopathy may then warrant a surgical resection. Myogenic lesions and GISTs may also arise superficially to the muscularis propria from the muscularis mucosa of the colorectal mucosa. Such lesions, if limited to the second and third EUS layer

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and if small ( 1.5 and/or platelets < 50 000/L), inadequate sedation, and inadequate visualization or access to the region of the celiac artery takeoff. Some investigators recommend patient hydration with up to 1 L of normal saline to minimize the risk of postural hypotension that frequently results from performing CN [68]. The procedure is performed with the patent in the left lateral decubitus position, often under deep sedation. Continuous monitoring for 2 hours after the procedure is recommended to assess for postural hypotension. Technique EUS-guided techniques for performing CN may be categorized as those which involve diffuse injection into the CPN and those in which the celiac ganglia are directly targeted (celiac ganglia neurolysis, CGN). The initially described and most commonly used approach to EUS CN has been CPN. The aorta, which appears in a longitudinal plane on linear-array imaging from the posterior lesser curve of the gastric fundus, is identified and followed distally to the celiac trunk (the first major branch below the diaphragm). Most reports to date have performed these injections using standard EUS-FNA needles. A needle specifically designed for EUS-guided celiac plexus blockade and neurolysis (EchoTip CPN needle, Cook, Bloomington, IN) has been developed. This 20-gauge device has a solid, sharp, conical tip (without a removable stylet) and an array of side holes for radial delivery of the injectate into the celiac plexus. The authors prefer to use a 22-gauge needle with the stylet slightly retracted. The needle is inserted under EUS guidance, with the tip placed approximately 1 cm from the origin of the celiac trunk, and the stylet is then advanced to clear the tip and then completely withdrawn. A syringe containing the injectate is attached to the needle, and aspiration is performed to rule out inadvertent blood vessel penetration prior to any injection. In our practice, for patients with pancreatic cancer, we use a mixture of 30% by volume of 0.25% bupivacaine with 70% by volume of 98% dehydrated alcohol, although data to guide the optimal injectate type, volume, and mixing ratio are lacking. Before withdrawing the needle, it is flushed with a small amount of normal saline solution to fully clear the medication. Some clinicians deliver the entire volume at a single central site (central), while others prefer to inject half the volume on one side and the remainder on the opposite side of the aorta (bilateral). There are limited and conflicting data regarding the efficacy of single versus bilateral injections. Sahai et al. [69] compared central

Chapter 24: Therapeutic EUS for cancer treatment

and bilateral injections in a nonrandomized mixed population of patients with pancreatic cancer or chronic pancreatitis. They determined bilateral CN to be more effective than a single injection (mean pain reduction of 70% vs. 46%, p = 0.0016). These findings were supported by the results of a recent meta-analysis, in which the proportions of patients with pain relief were 85 and 46% after bilateral versus central EUS-guided CPN [70]. LeBlanc et al. [71] reported on a randomized prospective comparison of the central versus bilateral injection in patients with pancreatic cancer. They randomized 50 patients to one-injection (n = 29) versus two injections (n = 21). Overall pain relief was not significantly different between the approaches (69% in the one-injection group versus 81% in the two-injection group, p = 0.34). There were also no significant differences in the median onset or duration of pain relief between the groups. More recently, a meta-analysis of six randomized controlled trials (437 patients) found no significant difference in short-term pain relief or response to treatment between bilateral and unilateral CN [72]. However, analgesic usage reduced significantly more after bilateral CN compared with unilateral CN (RR = 0.66, p = 0.02). While EUS-guided CPN has had an excellent safety profile, it has provided limited efficacy and durability, especially in benign diseases. This may partly be explained by the diffuse nature of the injection, which does not specifically target the ganglia. Subsequent recognition of the capability of the EUS to visualize the celiac ganglia has led to the ability to perform direct celiac intraganglionic injection, or CGN [73–75]. On EUS, ganglia are typically located adjacent to the celiac artery and anterior to the aorta and are commonly hypoechoic, oval-shaped structures with irregular margins, ranging in size from 0.2 to 2.0 cm. Central hyperechoic strands, or foci, are commonly present. Reported studies suggest that celiac ganglia can be visualized on EUS in 79–89% of patients [76, 77]. The technique for celiac ganglia injection (Figure 24.2) has not been standardized; however, Levy et al. [78] outlined their approach in the first published report of EUS-guided CGN: for ganglia smaller than 1 cm, they position the needle tip within the central point of the ganglia, while for ganglia 1 cm or larger (in the needle plane axis), they advance the needle tip into the deepest point within the ganglia. Injection is performed as the needle is slowly withdrawn. All identified ganglia are targeted. The number of injections and precise volume of the injectate were not controlled in their original report; however, the mean number of ganglia injected was 2.7 (range 1–6), with a mean bupivacaine volume injected of

(A)

229

Table 24.1 Summary of published prospective studies on the efficacy of EUS-guided CN techniques. References

n

Technique

Follow-up (weeks)

Efficacy (%)

Gunaratnam et al. [79] Levy et al. [78] Sahai et al. [69] Iwata et al. [80] LeBlanc et al. [71] Doi et al. [81] Levy et al. [82]

58

Bilateral CPN

24

78

17 160a 47 50

CGN CPN (bilateral vs. central) CPN (central) CPN (central vs. bilateral)

2–4 1 1 14

94 70 vs. 46 68 69 vs. 81

68 110

CGN vs. central CPN CGN vs. CPN

1 12

74 vs. 46 46 vs. 40

a

Mixed population of patients with pancreatic cancer and chronic pancreatitis.

8.3 mL (range 1–17) and a mean alcohol volume injected of 12.7 mL (range 2–20). Results A number of published reports have examined the efficacy of EUS-guided CN (Table 24.1). Wiersema and Wiersema [83] published an initial study of 58 patients evaluating EUS-guided CPN for pain secondary to inoperable pancreatic cancer and updated their findings in a later prospective report [79]. Neurolysis was performed by injecting 3–6 mL (0.25%) bupivacaine and 10 mL (98%) alcohol into both sides of the celiac trunk. A standardized 11-point visual analog scale (VAS) was used to assess pain scores. Of the 58 patients in the study, 49 (78%) experienced a decrease in pain score (of at least 1 point) after EUS-guided CPN. Significant pain score reduction was observed 2 weeks after the procedure, and sustained pain relief was observed for 24 weeks. On multivariate analysis, this pain reduction was independent of opioid use or adjuvant therapy. No major complications were reported, and minor complications were mild and transient. These included postural hypotension (20%), diarrhea (17%), and pain exacerbation (9%). Preliminary data from this study suggested the efficacy and safety of EUS-guided CPN. However, the study was limited by the small number of patients, the absence of a placebo control, and the lack of blinding. Despite 78% of patients experiencing a drop in pain score, only 31 (54%) experienced a 3 or more point decline in the VAS score – a threshold measure considered necessary to signify efficacy [68]. The benefit of EUS-guided CPN diminished after 8–12 weeks, highlighting a relatively short-duration efficacy for this technique.

(B)

Figure 24.2 Celiac ganglion neurolysis. (A) A 22-gauge needle is advanced into the celiac ganglion (white arrows), which is subsequently injected with

a mixture of alcohol and bupivacaine. (B) The depot injection produces an anechoic region with focal hyperechoic foci – c/w fluid containing small air bubbles – within the celiac ganglion (white arrows).

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Recently, Iwata et al. [80] published their retrospective experience after EUS-guided CPN among 47 patients. Central CPN was performed with a median of 2 (range 2–4) needles, and the median total volume of alcohol injected was 20 mL (range 15–20). Successful pain relief was defined as a stable dose of narcotics and a VAS pain score of 3 or less. At 1 week, 32 of 47 (68%) patients had achieved these criteria. Few published studies have evaluated EUS-guided CGN in patients with pancreatic cancer [78, 81, 84]. Levy et al. [78] used EUS-guided CGN to target as many ganglia as possible (median 2.7, range 1–6). Partial pain relief was reported in 16 of 17 (94%) patients at 2–4 weeks after CGN. Narcotic use decreased in only 3 (18%) patients. Transient postural hypotension was observed in a third of treated patients. Overall, 36% experienced transient initial pain exacerbations (lasting 30 after paralysis, gastric and rectal decompression Figure 26.5 Multidisciplinary algorithm for management of complex PFCs. Source: Adapted from Sameera et al. [30].

to deliver feeding distal to that region, as stimulation of CCK and secretin may lead to worsening of the pancreatitis [67].

Pancreatic ductal evaluation PFCs are commonly associated with injuries to the pancreatic duct. This is important to recognize and assess because damage to the pancreatic duct can lead to long-term complications for the patient, including a more severe course of pancreatitis, a higher risk for pancreatic necrosis, and an increased rate of PFC recurrence after drainage. In the Jang et al. study [68], 84 patients with acute necrotizing pancreatitis who underwent MR cholangiopancreatography and/or ERCP to assess the prevalence of main pancreatic duct disruption showed that 38% of patients were found to have damage to their pancreatic duct. Nealon et al. [69] followed 563 patients with pseudocysts who had their pancreatic ducts evaluated. They noted that pancreatic ductal changes were able to predict the resolution of pancreatitis and the success of non-operative measures. ERCP with pancreatic duct exploration or MRCP evaluation of the pancreatic duct should be considered concurrently with PFC drainage when a pancreatic duct leak is suspected [60, 70].

Tailored multidisciplinary approach based on the creation of an algorithm Complicated PFCs often fall at the intersection of several service lines, from their admission via the emergency room to the intensive care unit to the interaction between surgeons, radiologists, and interventional endoscopists. With the literature clearly leading

toward an endoscopic approach as the main modality, having a dedicated algorithm focusing on integrating all possible interventions based on patients’ symptoms and cross-sectional imaging is critical [71]. Figure 26.5 is an adapted algorithm from Sameera et al. created after multi-disciplinary discussions between all involved service lines that permits uniformity and safety when offering therapy to this patient population [30].

Conclusion PFCs are a dreaded complication of pancreatitis. They are classified according to the Atlanta classification as acute PFCs, acute necrotic collections, pseudocysts, or WOPN based on their time to development after the initial insult as well as the presence or absence of necrotic debris. Enteral feeding is typically offered for poorly organized PFCs, while drainage is the mainstay of therapy for symptomatic PFCs or those causing complications. Surgical, percutaneous, and endoscopic drainage are efficacious in drainage PFCs, though recent literature has confirmed proceeding with an endoscopic approach whenever possible, reserving percutaneous drainage for collections that are inaccessible endoscopically and surgery as a last resort.

References 1 Vanek P, Falt P, Vitek P, et al. EUS-guided transluminal drainage using lumen-apposing metal stents with or without coaxial plastic stents for treatment of walled-off necrotizing pancreatitis: a prospective bicentric randomized controlled trial. Gastrointest Endosc 2023;97(6):1070–1080. doi: 10.1016/j.gie.2022.12.026.

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2 Guo Y, Hu S, Wang S, et al. Laparoscopic intervention to pancreatic pseudocyst confers short-term benefits: a meta-analysis. Emerg Med Int 2021;2021:7586338. doi: 10.1155/2021/7586338. 3 Banks PA, Bollen TL, Dervenis C, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut 2013;62(1):102–111. doi: 10.1136/gutjnl-2012-302779. 4 Quinlan JD. Acute pancreatitis. Am Fam Physician 2014;90(9): 632–639. 5 Poornachandra KS, Bhasin DK, Nagi B, et al. Clinical, biochemical, and radiologic parameters at admission predicting formation of a pseudocyst in acute pancreatitis. J Clin Gastroenterol 2011;45(2): 159–163. doi: 10.1097/MCG.0b013e3181dd9d14. 6 Habashi S, Draganov PV. Pancreatic pseudocyst. World J Gastroenterol 2009;15(1):38–47. doi: 10.3748/wjg.15.38. 7 American Gastroenterological Association Institute on “Management of Acute Pancreatits” Clinical Practice and Economics Committee, Board AGAIG. AGA Institute medical position statement on acute pancreatitis. Gastroenterology 2007;132(5):2019–2021. doi: 10.1053/j.gastro.2007.03.066. 8 Khaled YS, Malde DJ, Packer J, et al. Laparoscopic versus open cystgastrostomy for pancreatic pseudocysts: a case-matched comparative study. J Hepatobiliary Pancreat Sci 2014;21(11):818–823. doi: 10.1002/jhbp.138. 9 van Santvoort HC, Besselink MG, Bakker OJ, et al. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010;362(16):1491–1502. doi: 10.1056/NEJMoa0908821. 10 Baron TH, Thaggard WG, Morgan DE, Stanley RJ. Endoscopic therapy for organized pancreatic necrosis. Gastroenterology 1996;111(3):755–764. doi: 10.1053/gast.1996.v111.pm8780582. 11 van Baal MC, van Santvoort HC, Bollen TL, et al. Systematic review of percutaneous catheter drainage as primary treatment for necrotizing pancreatitis. Br J Surg 2011;98(1):18–27. doi: 10.1002/bjs.7304. 12 Lang EK, Paolini RM, Pottmeyer A. The efficacy of palliative and definitive percutaneous versus surgical drainage of pancreatic abscesses and pseudocysts: a prospective study of 85 patients. South Med J 1991;84(1):55–64. doi: 10.1097/00007611-199101000-00014. 13 Adams DB, Anderson MC. Percutaneous catheter drainage compared with internal drainage in the management of pancreatic pseudocyst. Ann Surg 1992;215(6):571–576; discussion 576–8. doi: 10.1097/00000658-199206000-00003. 14 Cremer M, Deviere J, Engelholm L. Endoscopic management of cysts and pseudocysts in chronic pancreatitis: long-term follow-up after 7 years of experience. Gastrointest Endosc 1989;35(1):1–9. doi: 10.1016/s0016-5107(89)72677-8. 15 Binmoeller KF, Seifert H, Walter A, Soehendra N. Transpapillary and transmural drainage of pancreatic pseudocysts. Gastrointest Endosc 1995;42(3):219–224. doi: 10.1016/s0016-5107(95)70095-1. 16 Park DH, Lee SS, Moon SH, et al. Endoscopic ultrasound-guided versus conventional transmural drainage for pancreatic pseudocysts: a prospective randomized trial. Endoscopy 2009;41(10): 842–848. doi: 10.1055/s-0029-1215133. 17 Kahaleh M, Shami VM, Conaway MR, et al. Endoscopic ultrasound drainage of pancreatic pseudocyst: a prospective comparison with conventional endoscopic drainage. Endoscopy 2006;38(4):355–359. doi: 10.1055/s-2006-925249. 18 Varadarajulu S, Christein JD, Tamhane A, et al. Prospective randomized trial comparing EUS and EGD for transmural drainage of pancreatic pseudocysts (with videos). Gastrointest Endosc 2008; 68(6):1102–1111. doi: 10.1016/j.gie.2008.04.028.

19 Ramouz A, Shafiei S, Ali-Hasan-Al-Saegh S, et al. Systematic review and meta-analysis of endoscopic ultrasound drainage for the management of fluid collections after pancreas surgery. Surg Endosc 2022;36(6):3708–3720. doi: 10.1007/s00464-022-09137-6. 20 Conrad CC, Ellrichmann M. Stent placement in pancreatic disease, when, which, and why? – a current perspective. Front Gastroenterol 2023;1:1–11. 21 Sousa GB, Machado RS, Nakao FS, Libera ED. Efficacy and safety of endoscopic ultrasound-guided drainage of pancreatic pseudocysts using double-pigtail plastic stents: a single tertiary center experience. Clinics (Sao Paulo) 2021;76:e2701. doi: 10.6061/clinics/2021/e2701. 22 Chen YI, Khashab MA, Adam V, et al. Plastic stents are more cost-effective than lumen-apposing metal stents in management of pancreatic pseudocysts. Endosc Int Open 2018;6(7):E780–E788. doi: 10.1055/a-0611-5082. 23 Achanta CR, Kinhal SV. A wolf in LAMS clothing: the expansion of off-label indications for lumen-apposing metal stents. Dig Dis Sci 2022;67(6):1917–1919. doi: 10.1007/s10620-021-07271-0. 24 Bang JY, Hasan MK, Navaneethan U, et al. Lumen-apposing metal stents for drainage of pancreatic fluid collections: when and for whom? Dig Endosc 2017;29(1):83–90. doi: 10.1111/den.12681. 25 Parihar V, Basir Y, Nally D, et al. A novel value-based scoring system for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a single-centre comparative study of plastic and lumen-apposing metal stents (NOVA study). Eur J Gastroenterol Hepatol. 2021;32(2):157–162. doi: 10.1097/MEG. 0000000000001891. 26 Akshintala VS, Saxena P, Zaheer A, et al. A comparative evaluation of outcomes of endoscopic versus percutaneous drainage for symptomatic pancreatic pseudocysts. Gastrointest Endosc. 2014;79(6):921–928; quiz 983 e2, 983 e5. doi: 10.1016/j.gie.2013. 10.032. 27 Khizar H, Zhicheng H, Chenyu L, et al. Efficacy and safety of endoscopic drainage versus percutaneous drainage for pancreatic fluid collection; a systematic review and meta-analysis. Ann Med 2023;55(1):2213898. doi: 10.1080/07853890.2023.2213898. 28 Varadarajulu S, Bang JY, Sutton BS, et al. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology 2013;145(3): 583–590.e1. doi: 10.1053/j.gastro.2013.05.046. 29 Zhao X, Feng T, Ji W. Endoscopic versus surgical treatment for pancreatic pseudocyst. Dig Endosc 2016;28(1):83–91. doi: 10.1111/ den.12542. 30 Sameera S, Mohammad T, Liao K, et al. Management of pancreatic fluid collections: an evidence-based approach. J Clin Gastroenterol. 2023;57(4):346–361. doi: 10.1097/MCG.0000000000001750. 31 Voermans RP, Veldkamp MC, Rauws EA, et al. Endoscopic transmural debridement of symptomatic organized pancreatic necrosis (with videos). Gastrointest Endosc 2007;66(5):909–916. doi: 10.1016/j.gie.2007.05.043. 32 Papachristou GI, Takahashi N, Chahal P, et al. Peroral endoscopic drainage/debridement of walled-off pancreatic necrosis. Ann Surg 2007;245(6):943–951. doi: 10.1097/01.sla.0000254366.19366.69. 33 Gardner TB, Coelho-Prabhu N, Gordon SR, et al. Direct endoscopic necrosectomy for the treatment of walled-off pancreatic necrosis: results from a multicenter U.S. series. Gastrointest Endosc 2011;73(4):718–726. doi: 10.1016/j.gie.2010.10.053. 34 Seewald S, Groth S, Omar S, et al. Aggressive endoscopic therapy for pancreatic necrosis and pancreatic abscess: a new safe

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and effective treatment algorithm (videos). Gastrointest Endosc 2005;62(1):92–100. doi: 10.1016/s0016-5107(05)00541-9. Charnley RM, Lochan R, Gray H, et al. Endoscopic necrosectomy as primary therapy in the management of infected pancreatic necrosis. Endoscopy 2006;38(9):925–928. doi: 10.1055/s-2006-944731. Escourrou J, Shehab H, Buscail L, et al. Peroral transgastric/ transduodenal necrosectomy: success in the treatment of infected pancreatic necrosis. Ann Surg 2008;248(6):1074–1080. doi: 10.1097/SLA.0b013e31818b728b. Seifert H, Biermer M, Schmitt W, et al. Transluminal endoscopic necrosectomy after acute pancreatitis: a multicentre study with long-term follow-up (the GEPARD Study). Gut 2009;58(9): 1260–1266. doi: 10.1136/gut.2008.163733. Gluck M, Ross A, Irani S, et al. Endoscopic and percutaneous drainage of symptomatic walled-off pancreatic necrosis reduces hospital stay and radiographic resources. Clin Gastroenterol Hepatol 2010;8(12):1083–1088. doi: 10.1016/j.cgh.2010.09.010. Varadarajulu S, Phadnis MA, Christein JD, Wilcox CM. Multiple transluminal gateway technique for EUS-guided drainage of symptomatic walled-off pancreatic necrosis. Gastrointest Endosc 2011;74(1):74–80. doi: 10.1016/j.gie.2011.03.1122. Bang JY, Wilcox CM, Trevino J, et al. Factors impacting treatment outcomes in the endoscopic management of walled-off pancreatic necrosis. J Gastroenterol Hepatol 2013;28(11):1725–1732. doi: 10.1111/jgh.12328. Attam R, Trikudanathan G, Arain M, et al. Endoscopic transluminal drainage and necrosectomy by using a novel, through-the-scope, fully covered, large-bore esophageal metal stent: preliminary experience in 10 patients. Gastrointest Endosc 2014;80(2):312–318. doi: 10.1016/j.gie.2014.02.013. Smoczynski M, Marek I, Dubowik M, et al. Endoscopic drainage/ debridement of walled-off pancreatic necrosis--single center experience of 112 cases. Pancreatology 2014;14(2):137–142. doi: 10.1016/j.pan.2013.11.005. Sarkaria S, Sethi A, Rondon C, et al. Pancreatic necrosectomy using covered esophageal stents: a novel approach. J Clin Gastroenterol 2014;48(2):145–152. doi: 10.1097/MCG.0b013e3182972219. Mukai S, Itoi T, Sofuni A, et al. Clinical evaluation of endoscopic ultrasonography-guided drainage using a novel flared-type biflanged metal stent for pancreatic fluid collection. Endosc Ultrasound 2015;4(2):120–125. doi: 10.4103/2303-9027.156738. Siddiqui AA, Adler DG, Nieto J, et al. EUS-guided drainage of peripancreatic fluid collections and necrosis by using a novel lumen-apposing stent: a large retrospective, multicenter U.S. experience (with videos). Gastrointest Endosc 2016;83(4):699–707. doi: 10.1016/j.gie.2015.10.020. Bansal RK, Puri R, Choudhary NS, et al. Endoscopic pancreatic necrosectomy: why scuff when you can flush the muck – make it an easy row to hoe. Endosc Int Open 2017;5(9):E847–E853. doi: 10.1055/s-0043-112854. Bang JY, Arnoletti JP, Holt BA, et al. An endoscopic transluminal approach, compared with minimally invasive surgery, reduces complications and costs for patients with necrotizing pancreatitis. Gastroenterology 2019;156(4):1027–1040.e3. doi: 10.1053/j.gastro.2018.11.031. Rinninella E, Kunda R, Dollhopf M, et al. EUS-guided drainage of pancreatic fluid collections using a novel lumen-apposing metal stent on an electrocautery-enhanced delivery system: a large retrospective study (with video). Gastrointest Endosc 2015;82(6): 1039–1046. doi: 10.1016/j.gie.2015.04.006.

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49 Walter D, Will U, Sanchez-Yague A, et al. A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study. Endoscopy 2015;47(1):63–67. doi: 10.1055/s-0034-1378113. 50 Albers D, Toermer T, Charton JP, et al. Endoscopic therapy for infected pancreatic necrosis using fully covered self-expandable metal stents: combination of transluminal necrosectomy, transluminal and percutaneous drainage. Z Gastroenterol 2016;54(1):26–30. doi: 10.1055/s-0041-104228. 51 Shah RJ, Shah JN, Waxman I, et al. Safety and efficacy of endoscopic ultrasound-guided drainage of pancreatic fluid collections with lumen-apposing covered self-expanding metal stents. Clin Gastroenterol Hepatol 2015;13(4):747–752. doi: 10.1016/j.cgh. 2014.09.047. 52 Vazquez-Sequeiros E, Baron TH, Perez-Miranda M, et al. Evaluation of the short- and long-term effectiveness and safety of fully covered self-expandable metal stents for drainage of pancreatic fluid collections: results of a Spanish nationwide registry. Gastrointest Endosc 2016;84(3):450–457.e2. doi: 10.1016/j.gie.2016.02.044. 53 Gornals JB, Consiglieri CF, Busquets J, et al. Endoscopic necrosectomy of walled-off pancreatic necrosis using a lumen-apposing metal stent and irrigation technique. Surg Endosc 2016;30(6): 2592–2602. doi: 10.1007/s00464-015-4505-2. 54 Teoh AYB, Bapaye A, Lakhtakia S, et al. Prospective multicenter international study on the outcomes of a newly developed self-approximating lumen-apposing metallic stent for drainage of pancreatic fluid collections and endoscopic necrosectomy. Dig Endosc 2020;32(3):391–398. doi: 10.1111/den.13494. 55 Karstensen JG, Novovic S, Hansen EF, et al. EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: a single-centre randomised controlled trial. Gut 2023;72(6):1167–1173. doi: 10.1136/gutjnl-2022-328225. 56 Raraty MG, Halloran CM, Dodd S, et al. Minimal access retroperitoneal pancreatic necrosectomy: improvement in morbidity and mortality with a less invasive approach. Ann Surg 2010;251(5):787–793. doi: 10.1097/SLA.0b013e3181d96c53. 57 Bakker OJ, van Santvoort HC, van Brunschot S, et al. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012;307(10):1053–1061. doi: 10.1001/jama.2012.276. 58 Thompson CC, Kumar N, Slattery J, et al. A standardized method for endoscopic necrosectomy improves complication and mortality rates. Pancreatology 2016;16(1):66–72. doi: 10.1016/ j.pan.2015.12.001. 59 Kumar N, Conwell DL, Thompson CC. Direct endoscopic necrosectomy versus step-up approach for walled-off pancreatic necrosis: comparison of clinical outcome and health care utilization. Pancreas 2014;43(8):1334–1339. doi: 10.1097/MPA.0000000000000213. 60 Boumitri C, Brown E, Kahaleh M. Necrotizing pancreatitis: current management and therapies. Clin Endosc 2017;50(4):357–365. doi: 10.5946/ce.2016.152. 61 Werner J, Feuerbach S, Uhl W, Buchler MW. Management of acute pancreatitis: from surgery to interventional intensive care. Gut 2005;54(3):426–436. doi: 10.1136/gut.2003.035907. 62 Hochman D, Louie B, Bailey R. Determination of patient quality of life following severe acute pancreatitis. Can J Surg 2006;49(2): 101–106. 63 Petrov MS, van Santvoort HC, Besselink MG, et al. Enteral nutrition and the risk of mortality and infectious complications in patients with severe acute pancreatitis: a meta-analysis of randomized

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64

65

66

67

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trials. Arch Surg 2008;143(11):1111–1117. doi: 10.1001/archsurg. 143.11.1111. Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev 2010;2010(1):CD002837. doi: 10.1002/ 14651858.CD002837.pub2. Pagliari D, Rinninella E, Cianci R, et al. Early oral vs parenteral nutrition in acute pancreatitis: a retrospective analysis of clinical outcomes and hospital costs from a tertiary care referral center. Intern Emerg Med 2020;15(4):613–619. doi: 10.1007/ s11739-019-02210-4. Makola D, Krenitsky J, Parrish C, et al. Efficacy of enteral nutrition for the treatment of pancreatitis using standard enteral formula. Am J Gastroenterol 2006;101(10):2347–2355. doi: 10.1111/j.1572-0241.2006.00779.x. Spanier BW, Bruno MJ, Mathus-Vliegen EM. Enteral nutrition and acute pancreatitis: a review. Gastroenterol Res Pract 2011;2011 doi: 10.1155/2011/857949.

68 Jang JW, Kim MH, Oh D, et al. Factors and outcomes associated with pancreatic duct disruption in patients with acute necrotizing pancreatitis. Pancreatology 2016;16(6):958–965. doi: 10.1016/j.pan.2016.09.009. 69 Nealon WH, Bhutani M, Riall TS, et al. A unifying concept: pancreatic ductal anatomy both predicts and determines the major complications resulting from pancreatitis. J Am Coll Surg 2009;208(5):790–799; discussion 799–801. doi: 10.1016/ j.jamcollsurg.2008.12.027. 70 Tyberg A, Karia K, Gabr M, et al. Management of pancreatic fluid collections: a comprehensive review of the literature. World J Gastroenterol. 2016;22(7):2256–2270. doi: 10.3748/wjg.v22.i7.2256. 71 Xu MM, Andalib I, Novikov A, et al. Endoscopic therapy for pancreatic fluid collections: a definitive management using a dedicated algorithm. Clin Endosc 2020;53(3):355–360. doi: 10.5946/ce.2019.113.

C H A P T E R 27

EUS-guided enteric anastomoses Edoardo Troncone 1,2 & Manuel Perez-Miranda 1 1 Department 2 Department

of Gastroenterology and Hepatology, Hospital Universitario Rio Hortega, Valladolid, Spain of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

Introduction The continuous expansion of EUS-guided transluminal interventions has stretched the limits of therapeutic endoscopy across traditional surgical boundaries, such as enteric anastomoses. The first EUS-guided entero-anastomosis (EUS-EA) technique to make its way into clinical practice was originally reported in 2012 by Binmoeller and Shah in a landmark porcine model by using a lumen-apposing metal stent (LAMS) [1]. The unique design of LAMS, which is a fully covered, “dumb-bell”-shaped braided nitinol metal stent with wide anti-migratory flanges, provides effective lumen-to-lumen apposition, facilitating EUS-guided drainage and anastomosis procedures. In this experimental series, the placement of a LAMS resulted in a stable fistula between the stomach and a small bowel loop adjacent to the gastric wall; this anastomosis could be passed with a slim gastroscope [1]. Since this landmark study, the widespread dissemination of LAMS, the evolution of the delivery system to incorporate a cautery tip (“hot” LAMS), and increased operator familiarity with the device have all transformed EUS-EA into a viable option for the management of several conditions with unmet clinical needs. The main indication for EUS-EA is gastric outlet obstruction (GOO), for which an anastomosis between the stomach and the distal duodenum (gastroduodenostomy) or the proximal jejunum (gastrojejunostomy (GJ)) is created. The term EUS-guided gastroenterostomy (EUS-GE) encompasses both approaches. EUS-EA has also been performed to create a conduit for endoscope passage in surgically altered anatomy patients with bilio-pancreatic disease requiring ERCP. This newly created EUS-guided gastro-gastrostomy or entero-enterostomy allows the passage of a duodenoscope or gastroscope to reach the major papilla or bilio-digestive anastomosis for retrograde interventions, avoiding time-consuming procedures such as enteroscopy or invasive percutaneous/surgical approaches. These procedures are known as EUS-Directed Transgastric ERCP (EDGE) in the case of transgastric anastomoses in patients with Roux-en-Y gastric bypass (RYGB) or EUS-Directed Transenteric ERCP (EDEE) in the case of transjejunal anastomoses to the afferent limb of various non-RYGB surgically altered anatomy situations. Finally, EUS-guided entero-enterostomy can provide minimally

invasive treatment of afferent limb syndrome, a relatively infrequent condition generally occurring in frail patients with advanced malignancies and prior gastric and/or pancreatic surgical resection. In this chapter, we will describe the technical and clinical aspects of EUS-EA applied to these three indications and discuss unresolved issues related to these innovative procedures.

EUS-guided gastroenterostomy for gastric outlet obstruction GOO is defined as the mechanical obstruction of the pylorus or duodenum secondary to benign or malignant stenosis, whether arising primarily from the GI tract wall or from compression by extraluminal disease. These stenoses hamper the passage of food and/or fluids, and thus prevent oral feeding [2]. GOO generally results in vomiting, weight loss, malnutrition/dehydration secondary to poor oral intake, and reflux esophagitis, all of which impact negatively on patient quality of life and limit survival in malignant disease [2, 3]. The most frequent causes of malignant GOO are pancreatic and gastric cancer [2]. Independent of the etiology, effective management of malignant GOO is crucial for patients who need chemotherapy as well as for those who only require supportive care and symptom palliation. For many years, the only therapeutic possibility was surgical gastroenterostomy, initially performed as open surgery and then refined with the laparoscopic approach. However, the complexity and frailty of patients with malignant GOO, many of whom cannot bear the invasiveness of surgery, prompted the development of less invasive approaches to GOO. In the last two decades, enteral stenting has become the mainstay of management of malignant GOO, particularly in compromised patients with limited life expectancy [4]. Placement of a duodenal self-expandable metal stent (SEMS) results in rapid symptom relief and shorter hospitalization compared to a surgical GJ. The downside of duodenal SEMS placement is a high rate of recurrent obstructive symptoms requiring reintervention due to stent dysfunction caused by ingrowth, angulation, or overgrowth [5, 6]. EUS-GE could theoretically offer the advantages of a minimally invasive approach to GOO, with prompt symptom relief

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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and hospital discharge, together with a long-lasting effect as the anastomosis is created away from the malignant stricture, just like in the surgical procedure. EUS-gastroenterostomy: technical aspects and clinical outcomes From a technical point of view, the target small bowel loop in proximity of the Treitz’s ligament is imaged with a linear-array EUS scope from the stomach, usually from the posterior wall of the gastric body. The target loop is better visualized and punctured if previously distended with fluid. Fluid can be delivered into the target loop either by direct instillation of water/normal saline through the endoscope working channel across the stenosis or through a previously placed catheter (e.g., a naso-biliary tube) alongside the echoendoscope in real time during EUS imaging, the so-called PET (parallel enteric tube) method [7] (Table 27.1). Anti-peristaltic drugs are customarily administered intravenously prior to fluid instillation. A balloon-assisted technique was also described in earlier series using non-cautery LAMS; a retrieval or dilating balloon was advanced through the stenosis and subsequently used as a reference to localize the target bowel for EUS-guided puncture [8]. In some of the earlier series, the target bowel loop was first punctured under EUS with a 19-gauge FNA needle, and a guidewire was passed into the balloon. Then, the tract was dilated with a cystotome or a balloon, to allow passage of the stent delivery system. Finally, the LAMS flanges were opened under a combined EUS, fluoroscopic, and endoscopic view. LAMS deployment results in tight luminal apposition and effective sealing of the puncture tract. A major drawback of this “classic” technique of EUS-GE is the multiple steps requiring several over-the-wire exchanges. It was recognized early on that the guidewire itself may push away the highly mobile bowel loop, which in turn could lead to stent misdeployment and the attendant risks of leakage and perforation [9]. With the advent of cautery-enabled LAMS delivery systems, direct puncture of the small bowel using the “freehand” technique became gradually adopted by most operators. The freehand technique

Table 27.1 Schematic description of the main techniques used to target and distend the bowel loop before LAMS placement during EUS-guided enteroanastomosis. Technique

Description

- Unassisted approach

Direct puncture and distension of the bowel loop with a FNA needle Direct infusion of saline/contrast across the luminal stricture or after canalization with a catheter or an ultra-slim endoscope A stone retrieval or dilating balloon is inserted across the stricture and inflated with contrast fluid; EUS-guided puncture and bursting of the balloon confirm the correct site for LAMS placement. A catheter (e.g., naso-biliary drainage, feeding tube) is advanced over the wire across the stricture through the endoscope, and the endoscope is removed, leaving the tube in the jejunum. The EUS scope is advanced in parallel to the tube, and the target loop is visualized after saline/contrast real-time injection through the tube. A specialized double-balloon enteric tube is advanced over the wire across the stricture; saline/contrast is injected between the two balloons to distend and stabilize the target loop.

- Direct approach

- Balloon-assisted

- PET method

- EPASS

FNA, fine-needle aspiration; LAMS, lumen-apposing metal stent; EPASS, EUS-guided double balloon-occluded gastrojejunostomy bypass; PET, parallel enteric tube.

avoids the risks associated with the multiple exchanges required with the legacy “cold” delivery systems and the nuances involved whenever transmural access into the GI tract involves a guidewire. As a consequence, the cumbersome balloon-assisted approach to EUS-GE was superseded. To date, the PET-method, by which small bowel distension is achieved through a previously placed tube, followed by direct puncture with a cautery-enabled LAMS, appears to be the most expedient and reproducible technique to perform EUS-GE [10–12] (Figure 27.1). An alternative technique utilizing a dedicated device to distend the target loop is the so-called EPASS, or EUS-guided double balloon-occluded GJ bypass [13, 14]. In the EPASS technique, a dedicated double-balloon enteric tube (Tokyo Medical University type; Create Medic Co., Ltd. Yokohama, Japan) is inserted over a guidewire placed distal to the stenosis. Both balloons are filled with saline, and then saline mixed with contrast is delivered into the space between the two balloons to distend the target bowel segment. This allows sufficient distention and stabilization of the small bowel so that the subsequent EUS-guided LAMS placement can be easily performed in a freehand fashion. The EPASS technique appears to optimize the safety and reproducibility of EUS-GE. However, the double-balloon tube is not available worldwide, which helps explain why the EPASS technique has undergone limited dissemination. The first clinical study on EUS-GE was a retrospective case series reporting technical and clinical outcomes in 10 patients with either benign (n = 7) or malignant (n = 3) GOO, including both direct and balloon-assisted EUS-GE [8]. A 15-mm LAMS was used, the technical success was 90%, and there were no adverse events (AE). Clinical success with the resumption of solid oral intake was achieved in all 9 patients (100%) who underwent a technically successful procedure. The Gastric Outlet Obstruction Scoring System (GOOSS) was used to gauge clinical outcomes. The GOSS is based on a 4-point scale with 0 for no oral intake, 1 for liquids only, 2 for soft solids only, and 3 for a low-residue or full diet (Table 27.2). Usually, clinical success is defined as GOOSS ≥ 2, although there is some heterogeneity in the definition across studies. Several subsequent studies have confirmed the favorable outcomes of EUS-GE in terms of technical and clinical success, safety, and a low reintervention rate [14–20]. A meta-analysis including 245 patients reported pooled technical and clinical success rates of 95.3 and 89%, respectively, a reintervention rate of 11.2%, and an overall AE rate of 21.9% [21]. Of note, EUS-GE significantly improves the quality of life in patients with malignant GOO, as demonstrated in a recent multicenter prospective study [11]. Good clinical outcomes have also been confirmed during long-term follow-up. A multicenter retrospective study including 232 EUS-GE (191 malignant and 41 benign GOO) reported an extremely low reintervention rate for stent dysfunction of 0.9% after a median follow-up of 233 days (IQR 95.3–498.5 days) [22]. This large cohort study highlights the durability of the clinical effects afforded by EUS-GE while confirming excellent results in terms of technical and clinical success, both above 98%. The initial studies on EUS-GE were performed using 15-mm-diameter LAMS. Subsequently, 20-mm-diameter LAMS became available. An international multicenter retrospective study on 267 patients with malignant GOO specifically evaluated the outcomes of EUS-GE with 15 mm LAMS (148 patients) versus 20 mm LAMS (119 patients) [23]. The overall technical success (96% [92.3–99.1%] vs. 95% [91–98.9%]), clinical success (89.2% [84.2–94.2%] vs. 84.1% [77.4–90.6%]), and AE rates (12.8% [7.5–18.2%] vs. 11.8% [6–17.6%]) were comparable between the 15 and 20-mm groups. Clinical success was defined as an improvement

Chapter 27: EUS-guided enteric anastomoses

(A)

(C)

(E)

(B)

(D)

(F)

253

Figure 27.1 (A) Fluoroscopic view of the oro-jejunal catheter placement; (B) endosonographic view of the distended bowel loop after enteroclysis; fluoro-

scopic (C) and endosonographic (D) view of the opening of the first LAMS flange in the bowel loop; final fluoroscopic (E) and endosonographic (F) view of the deployed LAMS. Table 27.2 Gastric Outlet Obstruction Scoring System (GOOSS) Score

Tolerated diet

0 1 2 3

No oral intake Liquids only Soft solids Low-residue or full diet

of at least 1 point in GOOSS. Interestingly, a higher proportion of patients with 20 mm LAMS were able to tolerate a soft, solid, or complete diet, corresponding to a GOOSS ≥ 2 (91.2% [84.4–95.7%] vs. 81.2% [73.9–87.2%], p = 0.04). Moreover, a trend towards fewer reinterventions was found in the 20-mm group (4.1% vs. 8.2%), although this trend did not reach statistical significance. These findings suggest that a 20-mm LAMS should be preferred over a smaller diameter LAMS for EUS-GE. Current evidence on EUS-GE largely pertains to malignant GOO, with benign indications representing only a small percentage of the reported cases. The technical and immediate clinical success rates of EUS-GE in benign GOO are equally high; however, long-term relief of symptoms is particularly relevant in benign disease. Indefinite LAMS placement is not recommended for other indications, such as drainage of peripancreatic fluid collections, due to the risks of bleeding and buried stent. The risks associated with LAMS placement for peripancreatic fluid collections raise concerns about the long-term management of LAMS placed for enteral anastomoses. Clinical strategies for long-term LAMS management following EUS-GE in benign GOO are still evolving. James and colleagues reported 22 cases of EUS-GE for benign GOO. Following initial

technical and clinical success, 5 patients (23.8%) developed GOO symptom recurrence after a mean LAMS dwell time of 228 days. Among these, one patient eventually underwent surgery. Following definitive resolution of various underlying causes of GOO, LAMS were removed electively in 18 patients (85.7%) after a mean dwell time of 270 ± 273 days, with 3 patients subsequently experiencing GOO recurrence. These findings highlight EUS-GE as a temporary therapeutic option in difficult-to-manage benign GOO, either until resolution of the underlying disease or as a bridge to definitive surgical treatment. Depending on the underlying disease, patient status and overall prognosis, EUS-GE could be used in benign GOO to either avoid surgery in potentially reversible causes of GOO or to improve the patient’s nutritional status before elective surgery. Other reports confirmed the feasibility and long-term success of EUS-GE in benign disease; however, larger prospective studies are still awaited [24, 25]. Currently, European guidelines recommend EUS-GE for benign disease only in refractory GOO and poor surgical candidates [26]. Safety of EUS-gastroenterostomy for gastric outlet obstruction The most serious AE of EUS-GE is LAMS misdeployment, which could potentially result in a free perforation and the attendant risks of peritonitis and fatal abdominal sepsis. Stent misdeployment is the main cause of technical failure in EUS-GE and has been reported to occur between 7% and 36% of attempts, more frequently at the beginning of the learning curve [9, 14–19]. A retrospective study including 467 patients with EUS-GE for GOO addressed the incidence and outcomes of LAMS misdeployment and proposed a novel classification for stent misdeployment [27]. The overall rate

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of stent misdeployment was 9.85% (46/467); stent misdeployment was graded as mild or moderate in most cases (60.9 and 23.9%, respectively), whereas it was severe in 13% and fatal in one case (2.2%). Only 5 patients (10.9%) eventually required surgery, with the remaining cases successfully managed endoscopically through a variety of approaches, including placement of another LAMS, a bridging SEMS through the misdeployed LAMS, simple gastrotomy closure, natural orifice transluminal endoscopic surgery (NOTES), salvage of the anastomosis, or different combinations of the above. Interestingly, almost three-quarters of LAMS misdeployments (73.2%) occurred in the first 13 cases of the endoscopists’ learning curves, which highlights both the critical role of adequate operator expertise and the need for further procedural standardization for the safe performance and wider dissemination of EUS-GE. Concerns have been raised about the influence of anatomical variations of the duodenum and proximal jejunum on the success of EUS-GE by a Japanese study based on barium upper GI series [26]. The proposed optimal cut-off value for the distance between the stomach and the target loop predicting the technical success of EUS-GE is 10 mm [28]. In the above-mentioned study on more than 1000 barium upper GI radiography series, three main morphologies for the small bowel at the Treitz’s angle were found: in type 1 and type 3 morphology (78% of all cases), the fourth portion of the duodenum runs towards the stomach; in type 2 (22% of cases), however, the fourth portion of the duodenum runs away from the stomach [29]. Given the dynamic nature of anatomical relationships between the stomach and duodenum during endoscopy, the relevance of these observations to the actual performance of EUS-GE is uncertain. Nonetheless, these findings would suggest that technical difficulties due to duodenal anatomy variations might potentially arise in up to 20–25% of EUS-GE. Other possible AEs of EUS-GE include bleeding, stent migration, stent obstruction, and infection. Bleeding and stent migration have been rarely reported in the published studies. It is probable that the wide flanges of the LAMS used in most studies, together with the fully covered design and the use of Doppler when performing the puncture, minimize the risks for these AEs. Stent obstruction is also a relatively rare event, which represents one of the major advantages of EUS-GE over duodenal SEMS. The silicon coating of the LAMS may gradually disappear over time, resulting in tissue ingrowth and, eventually, stent obstruction [22]. This relatively uncommon late AE can be easily managed endoscopically by either LAMS removal and replacement or by the LAMS-in-LAMS technique, depending on the degree of ingrowth. Patients with malignant GOO may present with ascites and peritoneal carcinomatosis secondary to advanced disease. EUS-GE has also been reported in the presence of ascites; however, the safety and reproducibility of this patient subgroup are a matter of debate. The presence of abundant ascites would make EUS-GE more challenging due to the increased distance and mobility of the target bowel loop. Moreover, ascites in the setting of malignant disease is often a sign of widespread disease, which may reduce the clinical efficacy of EUS-GE due to the possibility of additional sites of obstruction more distally. Even if ascites is not an absolute contraindication to EUS-GE [30, 31], an increased risk of peritonitis and sepsis has been reported in patients with ascites who underwent EUS-GE [15, 18, 22, 30]. A careful assessment of the risks and benefits should be carried out in GOO patients with ascites before EUS-GE, with mandatory antibiotic prophylaxis and paracentesis whenever possible.

EUS-gastroenterostomy versus enteral stenting versus surgical gastrojejunostomy As a minimally invasive endoscopic procedure, EUS-GE was initially viewed as an alternative to duodenal SEMS placement for the management of malignant GOO. However, its favorable preliminary clinical results soon suggested that EUS-GE could also become an alternative to surgical GJ in operative patients. The early retrospective cohort studies comparing EUS-GE to traditional alternative options for GOO reported slightly inferior technical success for EUS-GE (86.7–100%), likely a reflection of a learning curve effect [2, 17]. Even if the technical success rates of duodenal SEMS placement and open/laparoscopic GJ were close to 100%, their respective clinical success rates were fairly comparable to those of EUS-GE. In addition, the incidence of stent dysfunction was significantly lower for EUS-GE than for duodenal SEMS placement; similarly, the safety profile favored EUS-GE over surgical GJ. More recent comparative studies reported similar technical success for EUS-GE, duodenal stenting, and surgical GJ [22, 32] (Table 27.3). A propensity score-matched retrospective study showed that EUS-GE outperformed duodenal SEMS placement in terms of clinical success (91% vs. 75%; p = 0.008), stent dysfunction (1% vs. 26%; p < 0.001), and AE rate (10% vs. 21%; p = 0.09) [32]. Compared to surgical GJ, EUS-GE resulted in shorter hospital stays and a lower AE rate; these favorable outcomes apply even to patients with peritoneal carcinomatosis [22, 35]. A recent meta-analysis confirmed a higher reintervention rate for duodenal SEMS compared to EUS-GE; data on surgical GJ were, however, more heterogeneous. Surgical GJ is typically burdened with a higher AE rate, including gastroparesis and ileus, which may negatively impact patient quality of life in the short term, delay the initiation of chemotherapy, and increase overall costs [17, 33]. Definitive evidence about the superiority of EUS-GE over duodenal SEMS placement or surgical GJ is awaited shortly, once the results of the randomized trials currently under way become available. EUS-GE is considered by international guidelines to be a valid therapeutic option for patients with GOO. Guideline endorsement signals a successful transition from the experimental setting to clinical practice in just a decade; however, the major lingering caveats of operator expertise and procedural standardization require further assessment [7, 26, 36].

EUS-directed transgastric interventions ERCP in post-surgical anatomy patients may be extremely challenging. Indeed, the papilla or bilio-enteric anastomosis may not be reachable with conventional endoscopes. Enteroscopy-assisted ERCP (EA-ERCP) is available in some expert centers, but the relatively narrow endoscope working channel and the limited range of dedicated accessories lead to suboptimal technical success rates. RYGB and other surgical procedures that limit endoscopic biliary access are increasingly being performed worldwide with bariatric intent, leaving patients at increased risk for biliary stone formation [37]. In RYGB anatomy, a small gastric pouch is anastomosed to a jejunal loop, leaving the excluded remnant stomach and duodenum out of reach for the endoscopist. Traditionally, these patients have been managed with ERCP performed through a surgical gastrotomy to access the excluded stomach and the duodenum by means of laparoscopy-assisted ERCP (LA-ERCP), a more invasive alternative than EA-ERCP [38]. Alternatively, percutaneous transhepatic biliary drainage (PTBD) or surgical stone clearance can be performed in this patient population; both of these approaches carry

Table 27.3 Summary of studies comparing EUS-guided gastroenterostomy with enteral stenting and surgical gastrojejunostomy. Author, year (Reference)

Study design

EUS-GE technique

LAMS size

Comparison group

Number of patients

Technical success

Clinical success

Hospitalization length (median)

Symptom recurrence/ reintervention

Adverse events

Chen et al. 2017 [14]

Retrospective

15 mm

Duodenal SEMS

EUS-GE: 30 SEMS: 52

26/30 (86.7%) 49/52 (94.2%)

25/30 (83.3%) 35/52 (67.3%)

11.3 ± 6.6a d 9.5 ± 8.3 d

1/30 (4.3%) 10/52 (28.6%)

5/30 (16.7%) 6/52 (11.5%)

Khashab et al. 2017 [16]

Retrospective

NR

Open GJ

EUS-GE: 30 Open GJ: 63

26/30 (87%) 63/63 (100%)

26/30 (87%) 57/63 (90%)

11.6 ± 6.6a d 12 ± 8.2 d

1/30 (3%) 9/63 (14%)

5/30 (16.7%) 16/63 (25%)

Pérez-Miranda et al. 2017 [17] Ge et al. 2019 [15]

Retrospective

NR

Laparoscopic GJ (LGJ)

Retrospective

Direct, balloon-assisted, EPASS Direct, balloon-assisted, EPASS PET method, Balloon-assisted Direct

15 mm

Duodenal SEMS

Kouanda et al. 2019 [33]

Retrospective

PET method

15 mm

Open GJ

EUS-GE: 25 LGJ: 29 EUS-GE: 22 SEMS: 78 EUS-GE: 40

23/25 (88%) 29/29 (100%) 22/22 (100%) 78/78 (100%) 37/40 (92.5%)

21/25 (90%) 28/29 (90%) 21/22 (95.5%) 60/78 (76.3%) 34 (85.0)

9.4a d 8.9 d 7.4 ± 9.1a d 7.9 ± 8.2 d 5 (2–7)b d

NR NR 2/22 (8.3%) 31/78 (32%) 8/40 (20%) 3/26 (11.5%)

3/25 (12%) 12/29 (41%) 5/22 (20.8%) 39/78 (40.2%) 9/40 (22.5%)

Bronswijk et al. 2021 [12]

Retrospective (propensity score–matched comparison) Retrospective

PET method

15 and 20 mm

Laparoscopic GJ (LGJ)

Open GJ: 26 EUS-GE: 37 LGJ: 37

26/26 (100%) 35/37 (94.6%) 37/37 (100%)

22 (84) 34/37 (91.9%) 33/37 (89.2%)

14.5 (8–18) d 4 (2.0-8.0)b d 8 (5.5-19.5) d

0/37 (0%) 5/37 (13.5%)

23/26 (88.5%) 1/37 (2.7%) 10/37 (27.0%)

PET method PET method

15 and 20 mm 15 and 20 mm

Duodenal SEMS

Retrospective (propensity score–matched comparison) Retrospective

EUS-GE: 79 SEMS: 97 EUS-GE: 88 SEMS: 88

74/79 (93.7%) 90/97 (92.8%) 83/88 (94%) 86/88 (98%)

73/79 (92.4%) 81/97 (83.5%) 80/88 (91%) 66/88 (75%)

NR NR 4 (2–10.8)b d 4 (1–9.5) d

72/79 (91.1%) 72/97 (74.2%) 1/80 (1%) 17/66 (26%)

8/79 (10.1%) 10/97 (10.3%) 9/88 (10.2%) 18/88 (20.5%)

15 and 20 mm

Duodenal SEMS and surgical GJ (open and laparoscopic)

EUS-GE: 232 SEMS: 131 GJ: 73

228/232 (98.3%) 130/131 (99.2%) 73/73 (100.0%)

228/232 (98.3%) 120/131 (91.6%) 66/73 (90.4%)

2 (1–3)b d 3 (1–10) d 5 (2–9) d

2 (0.9%) 16 (12.2%) 10 (13.7%)

20 (8.6%) 51 (38.9%) 20 (27.4%)

Sanchez-Aldehuelo et al. 2022 [34] van Wanrooij et al. 2022 [32]

Jaruvongvanich et al. 2023 [22]

Direct, balloon-assisted, EPASS, and PET methods

Duodenal SEMS

EUS-GE, endoscopic ultrasound-guided gastroenterostomy; LAMS, lumen-apposing metal stent; EPASS, EUS-guided double balloon-occluded gastrojejunostomy bypass; PET, parallel enteric tube; SEMS, self-expanding metal stent; NR, not reported; GJ, gastrojejunostomy. a Mean ± standard deviation. b Median (interquartile range).

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their respective sets of drawbacks [39]. In LA-ERCP, a sterilized duodenoscope is passed percutaneously into the stomach in the operating room, allowing standard ERCP accessories to be passed through a large-diameter working channel with the advantage of an elevator. When combined with cholecystectomy, LA-ERCP allows treatment of both choledocholithiasis and cholelithiasis in the same surgical session, with technical success rates comparable to those of standard ERCP. However, LA-ERCP is burdened with the invasiveness of surgery, making it a less appealing choice for patients with previous cholecystectomy. Moreover, LA-ERCP needs the coordination of the endoscopic and surgical teams, adding an extra layer of logistical complexity. On the other hand, EA-ERCP is a relatively long and tedious procedure in which failure to reach the papilla occurs in up to 30% of cases. In EA-ERCP, failure to reach the papilla is only realized after a significant amount of time and effort has been spent; even when the papilla is reached by enteroscopy, the range of therapeutic interventions is limited by the small working channel, the forward view, and the lack of an elevator. The development of EUS-guided anastomoses represents a significant innovation for the practice of ERCP in RYGB patients over the traditional approaches of LA-ERCP and EA-ERCP. During EDGE, a gastro-gastrostomy or jejuno-gastrostomy is created under EUS guidance in patients with RYGB, allowing access to the excluded stomach and the descending duodenum with a standard duodenoscope. First, the excluded stomach is visualized with a linear-array echoendoscope from the gastric pouch, then punctured with a 19G FNA needle, and distended with normal saline and contrast. Second, a large caliber LAMS (15 or 20 mm diameter) is placed under EUS guidance across the gastric wall from either the pouch, to create a gastro-gastrostomy, or the proximal jejunum next to the surgical GJ, to create a jejuno-gastrostomy. In the earlier EDGE series, the LAMS was placed through the multistep technique after guidewire placement and tract dilation; however, hot LAMS are increasingly being placed lately by using the freehand technique instead [40]. To facilitate the subsequent through-the-LAMS intervention, care should be taken to sufficiently dilate the LAMS prior to endoscope passage, to align on fluoroscopy the axis of the endoscope with the LAMS during passage, and to prevent traction on the LAMS when approaching the pylorus after passage. Post-LAMS passage traction is typically caused by the looping of the duodenoscope in the excluded stomach before traversing the pylorus, which typically happens when a LAMS is placed too far distally, resulting in an acute angulation of the duodenoscope shaft. A LAMS placed too distally into the excluded stomach may impair smooth pyloric passage of the duodenoscope into the descending duodenum, leading to excessive traction on the LAMS with the attendant risk of LAMS dislodgement. It is still unclear which is the best strategy to prevent LAMS dislodgment during EDGE, despite abundant and strong recommendations in the literature, which are characteristically based on limited evidence. The options range from careful adherence to the technical tips mentioned above to converting EDGE into a two-stage procedure where ERCP is performed 2–4 weeks after LAMS placement. LAMS suturing techniques represent a compromise between the simpler and logistically more convenient single-session EDGE and the purportedly safer two-stage EDGE. Even if the recommendation is frequently made to postpone ERCP for 2–4 weeks to allow fistula maturation and reduce the risk of a free perforation in the event of LAMS dislodgement, free perforation of a mature fistula during two-stage EDGE still remains a possibility [41]. The drawback of single-session EDGE is the increased risk of acute stent dislodgement. Similar to

stent misdeployment during EUS-GE, endoscopic salvage strategies for LAMS dislodgement can effectively be applied [41]. Excellent technical and clinical outcomes have been reported for EDGE. A meta-analysis including 16 studies and 470 patients showed technical and clinical success of 96 and 91%, respectively [42]. The overall AE rate was 17% and included both ERCP-related AE, such as pancreatitis and post-sphincterotomy bleeding, and fistula-related AE, such as failure of fistula closure (17%), stent migration (7%), post-EDGE weight gain (4%), and perforation (4%). As mentioned above, single-session EDGE is widely perceived to increase the risk of stent dislodgement and perforation. In a retrospective study including 128 EDGE procedures and 11 stent dislodgements, a larger LAMS diameter (20 vs. 15 mm), LAMS dilation, and suturing were identified as possible factors associated with dislodgment, even though only a 15-mm LAMS diameter was found to be a significant predictor in logistic-regression analysis [43]. A subsequent study evaluating 37 single-session EDGE procedures with a 20-mm LAMS sutured to the gastric wall reported no dislodgement events [44]. Notably, stent dislodgement during EDGE can be managed endoscopically with the placement of a new LAMS or a tubular SEMS in most cases; a surgical intervention is rarely needed [41, 45]. The persistence of a fistula into the excluded stomach after LAMS removal is considered a late AE. Such fistulas may result in weight gain in about 4% of EDGE procedures. A factor associated with persistent fistulas is the time of LAMS indwelling with a significantly increased risk after 40 days [46]. The odds of developing a persistent fistula have been demonstrated to increase by 9.5% for every 7 days that the LAMS is left in situ, which would argue in favor of single-session EDGE. Interestingly, primary closure of the fistula or argon plasma coagulation treatment during LAMS removal appears not to be protective against fistula persistence, despite claims to the contrary. Persistent fistulas can nonetheless be successfully managed through endoscopic closure in about 75% of cases [46]. A comparative study found similar technical success rates between EDGE and LA-ERCP (100% vs. 94%). Both EDGE and LA-ERCP outperformed EA-ERCP, which showed a technical success of just 75% [47]. Furthermore, the time to complete the EDGE procedure was significantly shorter (79 ± 31 min) compared with LA-ERCP (158 ± 50 min) and EA-ERCP (102 ± 43 min; p < 0.001). These results have been confirmed in a meta-analysis including 1268 patients, which reported a similar safety profile of EDGE compared to LA-ERCP with a lower pooled AE rate for EA-ERCP (21.9% vs. 17.4% vs. 8.4%, respectively) [48]. In addition, the shorter hospital stay of EDGE compared to LA-ERCP and EA-ERCP noted in some studies may favor EDGE from a cost-effectiveness perspective [42, 49]. Once an EUS-directed transgastric access has been created, several different endoscopic interventions other than ERCP can be performed. Ghandour et al. reported 54 EUS-directed transgastric interventions (EDGI) in 47 patients, which included diagnostic evaluation of pancreatic lesions with EUS-FNA/FNB, pancreatic collection drainage, and management of other gastroduodenal luminal conditions [50]. The overall technical success was 96%, with an AE rate of 10.6%, mainly consisting of stent dislodgement, with surgery required in only one case.

EUS-directed transenteric ERCP The relatively high frequency with which ERCP is considered in clinical practice in patients with RYGB anatomy allowed

Chapter 27: EUS-guided enteric anastomoses

standardization of the EDGE procedure, with the accrual of convincing evidence about its safety and efficacy. In contrast, limited evidence is available about EUS-EA in non-RYGB post-surgical anatomy, such as total gastrectomy, Whipple, or bilio-enteric anastomoses. Ironically, biliary access in non-RYGB anatomy was the first application of EUS-EA reported in clinical practice [51]. As in EDGE, EUS-guided GJ, duodeno-jejunostomy, or jejuno-jejunostomy creates “faster” access to the biliary limb, closer to the papilla, or bilio-enteric anastomosis in non-RYGB altered anatomy patients (Figure 27.2). This procedural approach has been termed “EUS-directed transenteric ERCP” (or EDEE). EDEE may represent an alternative to the long and cumbersome EA-ERCP or the invasive percutaneous/surgical approaches [51]. The technical steps are similar to other EUS-EA and include the following: identification of the target bowel loop by EUS and fluoroscopy; fluid distension with normal saline alone or in combination with methylene-blue/contrast solutions prior to EUS-guided access; and LAMS placement using either the over-the-wire or the freehand techniques. The relative anatomical variability in non-RYGB patients makes identification and distension of the target bowel during EDEE more challenging than identifying and distending the duodenojejunal flexure during EUS-GE or the excluded stomach during EDGE. The biliary limb can be opacified and distended through a previously placed percutaneous biliary catheter, can be directly accessed through EUS-guided puncture, or, alternatively, can be located with enteroscopy, through which a nasobiliary tube can be placed endoscopically and fluoroscopically to facilitate fluid instillation into the afferent limb [51]. Another option to help identify the afferent limb next to the bilio-enteric anastomosis (or the duodenum in patients with Roux-en-Y gastrectomy) is EUS-guided biliary drainage. The left hepatic duct can be targeted under EUS, and transmural biliary access and drainage can be achieved through a hepaticogastrostomy. The afferent limb can be identified by contrast injection through the hepaticogastrostomy, or even by antegrade transhepatic placement of a nasobiliary tube through which fluid can be instilled under EUS. After EUS-EA, the

257

subsequent trans-LAMS intervention can be performed in the same session or postponed to allow fistula maturation. Mutignani et al. reported 32 patients with surgical hepaticojejunostomy treated with EDEE [52]. Most patients had strictures (n = 29); biliary stones (n = 2) or postoperative leaks (n = 1) were also present. The biliary limb was identified after distension and opacification through percutaneous drainage or endoscopic catheters, and the EUS-EA was created using a biflanged fully covered LAMS (Nagi stent, 16-mm diameter, 20-mm long; Taewoong Medical, South Korea) or a standard cautery-enabled LAMS (Hot-Axios, 15-mm diameter, 10-mm long; Boston Scientific, Marlborough, Mass, USA) in just one case. After a successful EUS-EA in 31 patients (technical success 96.9%), subsequent ERCP became possible in all technically successful EUS-EA. Of note, the trans-enteric ERCP was performed in the same session if the axis of the anastomosis was deemed favorable to access the bilio-digestive anastomosis; if otherwise, the procedure was postponed for a week to allow for fistula maturation. One post-procedural (mild bleeding) and five long-term mild AEs (mainly stent displacement) were reported. The entero-anastomosis allowed successful ERCP with the placement of biliary SEMS or plastic stents, with the added benefit of easy repeated access for stent exchanges. In this series, EDEE successfully avoided the need for enteroscopy and the inconvenience of prolonged external PTBD tubes. Similar results have been reported by Ichkhanian et al., which described 18 cases of EDEE performed with LAMS (“hot” or “cold” Axios; Boston Scientific, Marlborough, Mass, USA) in Whipple and Roux-en-Y hepaticojejunostomy anatomy [53]. All cases of EUS-EA were technically successful, and subsequent ERCP was feasible in 17/18 (94.4%). Only one mild AE was reported (abdominal pain), further confirming the safety of EDEE when performed by experienced operators. The best timing to remove the LAMS after treatment completion remains to be defined. In contrast to EDGE, where the burden of biliary disease is typically lighter, EDEE patients often exhibit complex biliary disease and are prone to recurrences (e.g., recurrent biliary anastomotic strictures) [54]. The currently available evidence on EDEE is limited. Further studies are warranted before results can be generalized.

EUS-guided enteroanastomosis for the management of afferent limb syndrome

Figure 27.2 Transenteric ERCP through a LAMS in a Roux-en-Y hepatico-

jejunostomy.

Afferent limb or loop syndrome (ALS) is a rare condition that patients after Whipple surgery or after gastric resection with gastrojejunal reconstruction (Billroth II, gastrectomy with Y-en-Roux) may experience. The afferent limb, also named the pancreatobiliary loop, is the duodenojejunal segment that drains biliary and pancreatic secretions toward the gastrojejunal anastomosis. In ALS, the obstruction of such a limb determines the accumulation of pancreatobiliary secretions and the increase of intraluminal pressure frequently resulting in reflux cholangitis, pancreatitis, abdominal pain, vomiting, and, rarely, even loop perforation [55]. Potential causes include benign conditions, such as internal herniation, kinking secondary to adhesions, gastrojejunal anastomosis, fibrotic stricture, or, more commonly, malignant recurrence. Given the invasiveness and complexity of surgical management, particularly in patients with advanced malignancy, minimally invasive approaches are generally preferred. Traditionally, percutaneous decompression via PTBD has been used. More recently, endoscopic management, including nasoenteric tube placement or enteral stenting, either with SEMS or plastic stents, has also been reported [56–58]. EUS-EA is the most recent alternative option

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to manage ALS. The obstructed limb can usually be visualized endosonographically from the gastric remnant or the efferent limb, and a gastrojejunal or jejuno-jejunal EUS-EA can be created for decompression by placing a LAMS either over a guidewire or, more commonly, freehand. Retrospective studies reported higher rates of technical and clinical success of EUS-EA for ALS, together with lower rates of AE and reintervention, compared to enteral stenting [59, 60]. A recent international multicenter analysis of EUS-EA for malignant ALS, including 45 patients, reported technical and clinical success rates of 95.6 and 91.1%, respectively [61]. Typically, the anastomoses were created with the freehand technique; different types of LAMS were used. Only two (4.4%) mild AEs (stent misdeployment) were noted, both successfully managed by endoscopy. Six patients (14.6%) experienced recurrent cholangitis, caused by buried LAMS in 3 cases. These events were easily treated endoscopically. Occasionally, an appropriate window for the enteric anastomosis may not be found on EUS in ALS patients, for example, due to excessive interluminal distance. In those rare instances, ALS can also be successfully managed through an EUS-guided hepaticogastrostomy, which also provides effective decompression into the stomach. This procedure can be performed by the same operator in the same session of the failed EUS-EA and appears to be preferable to PTBD in the clinical setting of ALS [62]. Despite coming from relatively small retrospective studies, these findings convincingly demonstrate EUS-EA as a safe and effective strategy to treat malignant ALS, provided the requisite expertise in therapeutic EUS is available.

5 Jeurnink SM, Steyerberg EW, van Hooft JE, et al. Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointest Endosc 2010;71(3):490–499. 6 Mehta S, Hindmarsh A, Cheong E, et al. Prospective randomized trial of laparoscopic gastrojejunostomy versus duodenal stenting for malignant gastric outflow obstruction. Surg Endosc 2006; 20(2):239–242. 7 Chavarría C, Martín-Álvarez V Aparicio JR, et al. OP108 EUS-guided gastroenterostomy (EUS-GE) for gastric outlet obstruction (GOO) with a lumen-apposing metal stent (LAMS): prospective multicenter procedural standardization of the parallel enteral catheter (PEC) method. Endoscopy 2021;53:S45. 8 Khashab MA, Kumbhari V, Grimm IS, et al. EUS-guided gastroenterostomy: the first U.S. clinical experience (with video). Gastrointest Endosc 2015;82(5):932–938. 9 Itoi T, Ishii K, Ikeuchi N, et al. Prospective evaluation of endoscopic ultrasonography-guided double-balloon-occluded gastrojejunostomy bypass (EPASS) for malignant gastric outlet obstruction. Gut 2016;65(2):193–195. 10 Nguyen NQ, Hamerski CM, Nett A, et al. Endoscopic ultrasoundguided gastroenterostomy using an oroenteric catheter-assisted technique: a retrospective analysis. Endoscopy 2021;53(12): 1246–1249. 11 Garcia-Alonso FJ, Chavarria C, Subtil JC, et al. Prospective multicenter assessment of the impact of EUS-guided gastroenterostomy on patient quality of life in unresectable malignant gastric outlet obstruction. Gastrointest Endosc 2023. 12 Bronswijk M, Vanella G, van Malenstein H, et al. Laparoscopic versus EUS-guided gastroenterostomy for gastric outlet obstruction: Conclusion an international multicenter propensity score-matched comparison The widespread dissemination of interventional EUS, including the (with video). Gastrointest Endosc 2021;94(3):526–536.e2. advent of dedicated devices and the availability of trained operators, prompted the expansion of EUS toward indications that were the 13 Itoi T, Itokawa F, Uraoka T, et al. Novel EUS-guided gastrojejunostomy technique using a new double-balloon enteric tube and prerogative of surgery until recently. The data presented show that lumen-apposing metal stent (with videos). Gastrointest Endosc EUS-GE and EDGE are already a reality in clinical practice for 2013;78(6):934–939. the management of GOO and for ERCP in patients with RYGB anastomosis, respectively, in many centers across the world. Other 14 Chen YI, Itoi T, Baron TH, et al. EUS-guided gastroenterostomy is comparable to enteral stenting with fewer re-interventions in maligEUS-EA indications have shown promising preliminary results. nant gastric outlet obstruction. Surg Endosc 2017;31(7):2946–2952. Further study is needed to better define the role of these novel procedures within current therapeutic algorithms relative to com- 15 Ge PS, Young JY, Dong W, Thompson CC. EUS-guided gastroenterostomy versus enteral stent placement for palliation of malignant peting alternatives. Results from recently completed or currently gastric outlet obstruction. Surg Endosc 2019;33(10):3404–3411. under way randomized controlled trials comparing EUS-GE with 16 Khashab MA, Bukhari M, Baron TH, et al. International multiduodenal SEMS placement or with surgical GJ are eagerly awaited. center comparative trial of endoscopic ultrasonography-guided Procedural standardization, together with optimization of training gastroenterostomy versus surgical gastrojejunostomy for the treatstrategies, still warrants further evaluation. ment of malignant gastric outlet obstruction. Endosc Int Open 2017;5(4):E275–E281. References 17 Perez-Miranda M, Tyberg A, Poletto D, et al. EUS-guided gastrojejunostomy versus laparoscopic gastrojejunostomy: an international 1 Binmoeller KF, Shah JN. Endoscopic ultrasound-guided gastroencollaborative study. J Clin Gastroenterol 2017;51(10):896–899. terostomy using novel tools designed for transluminal therapy: a 18 Tyberg A, Perez-Miranda M, Sanchez-Ocana R, et al. Endoscopic porcine study. Endoscopy 2012;44(5):499–503. ultrasound-guided gastrojejunostomy with a lumen-apposing 2 Troncone E, Fugazza A, Cappello A, et al. Malignant gastric outlet metal stent: a multicenter, international experience. Endosc Int obstruction: which is the best therapeutic option? World J GastroenOpen 2016;4(3):E276–E281. terol 2020;26(16):1847–1860. 3 Brimhall B, Adler DG. Enteral stents for malignant gastric outlet 19 Chen YI, Kunda R, Storm AC, et al. EUS-guided gastroenterostomy: a multicenter study comparing the direct and balloon-assisted techobstruction. Gastrointest Endosc Clin N Am 2011;21(3):389–403, niques. Gastrointest Endosc 2018;87(5):1215–1221. vii–viii. 4 van Halsema EE, Rauws EA, Fockens P, van Hooft JE. Self-expandable 20 Kerdsirichairat T, Irani S, Yang J, et al. Durability and long-term outcomes of direct EUS-guided gastroenterostomy using lumenmetal stents for malignant gastric outlet obstruction: a pooled analapposing metal stents for gastric outlet obstruction. Endosc Int ysis of prospective literature. World J Gastroenterol 2015;21(43): 12468–12481. Open 2019;7(2):E144–E150.

Chapter 27: EUS-guided enteric anastomoses

21 Krishnamoorthi R, Bomman S, Benias P, et al. Efficacy and safety of endoscopic duodenal stent versus endoscopic or surgical gastrojejunostomy to treat malignant gastric outlet obstruction: systematic review and meta-analysis. Endosc Int Open 2022;10(6):E874–E897. 22 Jaruvongvanich V, Mahmoud T, Abu Dayyeh BK, et al. Endoscopic ultrasound-guided gastroenterostomy for the management of gastric outlet obstruction: a large comparative study with long-term follow-up. Endosc Int Open 2023;11(1):E60–E66. 23 Bejjani M, Ghandour B, Subtil JC, et al. Clinical and technical outcomes of patients undergoing endoscopic ultrasound-guided gastroenterostomy using 20-mm vs. 15-mm lumen-apposing metal stents. Endoscopy 2022;54(7):680–687. 24 Chen YI, James TW, Agarwal A, et al. EUS-guided gastroenterostomy in management of benign gastric outlet obstruction. Endosc Int Open 2018;6(3):E363–E368. 25 Tsuchiya T, Sofuni A, Itoi T. Successful EUS-guided gastrojejunostomy with very long-term patency for duodenal obstruction after severe acute pancreatitis. J Hepatobiliary Pancreat Sci 2022;29(6):e59–e60. 26 van der Merwe SW, van Wanrooij RLJ, Bronswijk M, et al. Therapeutic endoscopic ultrasound: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2022;54(2):185–205. 27 Ghandour B, Bejjani M, Irani SS, et al. Classification, outcomes, and management of misdeployed stents during EUS-guided gastroenterostomy. Gastrointest Endosc 2022;95(1):80–89. 28 Wannhoff A, Ruh N, Meier B, et al. Endoscopic gastrointestinal anastomoses with lumen-apposing metal stents: predictors of technical success. Surg Endosc 2021;35(5):1997–2004. 29 Nutahara D, Nagai K, Sofuni A, et al. Morphological study of the gastrointestinal tract around the ligament of Treitz using upper gastrointestinal radiography: fundamental data for EUS-guided gastrojejunostomy. J Hepatobiliary Pancreat Sci 2021;28(11):1023–1029. 30 Mahmoud T, Storm AC, Law RJ, et al. Efficacy and safety of endoscopic ultrasound-guided gastrojejunostomy in patients with malignant gastric outlet obstruction and ascites. Endosc Int Open 2022;10(5):E670–E678. 31 Basha J, Lakhtakia S, Yarlagadda R, et al. Gastric outlet obstruction with ascites: EUS-guided gastro-enterostomy is feasible. Endosc Int Open 2021;9(12):E1918–E1923. 32 van Wanrooij RLJ, Vanella G, Bronswijk M, et al. Endoscopic ultrasound-guided gastroenterostomy versus duodenal stenting for malignant gastric outlet obstruction: an international, multicenter, propensity score-matched comparison. Endoscopy 2022;54(11): 1023–1031. 33 Kouanda A, Binmoeller K, Hamerski C, et al. Endoscopic ultrasound-guided gastroenterostomy versus open surgical gastrojejunostomy: clinical outcomes and cost effectiveness analysis. Surg Endosc 2021;35(12):7058–7067. 34 Sanchez-Aldehuelo R, Subtil Inigo JC, Martinez Moreno B, et al. EUS-guided gastroenterostomy versus duodenal self-expandable metal stent for malignant gastric outlet obstruction: results from a nationwide multicenter retrospective study (with video). Gastrointest Endosc 2022;96(6):1012–20.e3. 35 Abbas A, Dolan RD, Bazarbashi AN, Thompson CC. Endoscopic ultrasound-guided gastroenterostomy versus surgical gastrojejunostomy for the palliation of gastric outlet obstruction in patients with peritoneal carcinomatosis. Endoscopy 2022;54(7):671–679. 36 Ahmed O, Lee JH, Thompson CC, Faulx A. AGA clinical practice update on the optimal management of the malignant alimentary tract obstruction: expert review. Clin Gastroenterol Hepatol 2021;19(9):1780–1788.

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37 Hamdan K, Somers S, Chand M. Management of late postoperative complications of bariatric surgery. Br J Surg 2011;98(10):1345–1355. 38 Ayoub F, Brar TS, Banerjee D, et al. Laparoscopy-assisted versus enteroscopy-assisted endoscopic retrograde cholangiopancreatography (ERCP) in Roux-en-Y gastric bypass: a meta-analysis. Endosc Int Open 2020;8(3):E423–E436. 39 Connell M, Sun WYL, Mocanu V, et al. Management of choledocholithiasis after Roux-en-Y gastric bypass: a systematic review and pooled proportion meta-analysis. Surg Endosc 2022;36(9): 6868–6877. 40 Kahaleh M. EUS-directed transgastric ERCP: a step-by-step approach (with video). Gastrointest Endosc 2022;95(4):787–789. 41 de Benito Sanz M, Carbajo AY, Sanchez-Ocana Hernandez R, et al. Endoscopic ultrasound-directed transgastric ERCP in patients with Roux-en-Y gastric bypass using lumen-apposing metal stents or duodenal self-expandable metal stents. A European single-center experience. Rev Esp Enferm Dig 2020;112(3):211–215. 42 Deliwala SS, Mohan BP, Yarra P, et al. Efficacy & safety of EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) in Roux-en-Y gastric bypass anatomy: a systematic review & meta-analysis. Surg Endosc 2023. 43 Shinn B, Boortalary T, Raijman I, et al. Maximizing success in single-session EUS-directed transgastric ERCP: a retrospective cohort study to identify predictive factors of stent migration. Gastrointest Endosc 2021;94(4):727–732. 44 Keane MG, Higa JT, La Selva D, et al. Suturing a 20-mm lumen-apposing metal stent allows for safe same-session EUSdirected transgastric intervention in patients with Roux-en-Y gastric bypass anatomy: a multicenter study (with video). Gastrointest Endosc 2023;97(2):291–299. 45 Ichkhanian Y, Runge T, Jovani M, et al. Management of adverse events of EUS-directed transgastric ERCP procedure. VideoGIE 2020;5(6):260–263. 46 Ghandour B, Keane MG, Shinn B, et al. Factors predictive of persistent fistulas in EUS-directed transgastric ERCP: a multicenter matched case-control study. Gastrointest Endosc 2023;97(2): 260–267. 47 Kochhar GS, Mohy-Ud-Din N, Grover A, et al. EUS-directed transgastric endoscopic retrograde cholangiopancreatography versus laparoscopic-assisted ERCP versus deep enteroscopy-assisted ERCP for patients with RYGB. Endosc Int Open 2020;8(7):E877–E882. 48 Dhindsa BS, Dhaliwal A, Mohan BP, et al. EDGE in Roux-en-Y gastric bypass: how does it compare to laparoscopy-assisted and balloon enteroscopy ERCP: a systematic review and meta-analysis. Endosc Int Open 2020;8(2):E163–E171. 49 James HJ, James TW, Wheeler SB, et al. Cost-effectiveness of endoscopic ultrasound-directed transgastric ERCP compared with device-assisted and laparoscopic-assisted ERCP in patients with Roux-en-Y anatomy. Endoscopy 2019;51(11):1051–1058. 50 Ghandour B, Shinn B, Dawod QM, et al. EUS-directed transgastric interventions in Roux-en-Y gastric bypass anatomy: a multicenter experience. Gastrointest Endosc 2022;96(4):630–638. 51 Perez-Miranda M, Sanchez-Ocana R, de la Serna Higuera C, et al. Transenteric anastomosis with lumen-apposing metal stent as a conduit for iterative endotherapy of malignant biliary obstruction in altered anatomy. Gastrointest Endosc 2014;80(2):339. 52 Mutignani M, Forti E, Larghi A, et al. Endoscopic entero-enteral bypass: an effective new approach to the treatment of postsurgical complications of hepaticojejunostomy. Endoscopy 2019;51(12): 1146–1150.

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53 Ichkhanian Y, Yang J, James TW, et al. EUS-directed transenteric ERCP in non-Roux-en-Y gastric bypass surgical anatomy patients (with video). Gastrointest Endosc 2020;91(5):1188–94.e2. 54 Donatelli G, Cereatti F, Spota A, et al. Long-term placement of lumen-apposing metal stent after endoscopic ultrasound-guided duodeno- and jejunojejunal anastomosis for direct access to excluded jejunal limb. Endoscopy 2021;53(3):293–297. 55 Wu CCH, Brindise E, Abiad RE, Khashab MA. The role of endoscopic management in afferent loop syndrome. Gut Liver 2022 17, 351–359. 56 Cao Y, Kong X, Yang D, Li S. Endoscopic nasogastric tube insertion for treatment of benign afferent loop obstruction after radical gastrectomy for gastric cancer: a 16-year retrospective single-center study. Medicine (Baltimore) 2019;98(28):e16475. 57 Pannala R, Brandabur JJ, Gan SI, et al. Afferent limb syndrome and delayed GI problems after pancreaticoduodenectomy for pancreatic cancer: single-center, 14-year experience. Gastrointest Endosc 2011;74(2):295–302. 58 Sakai A, Shiomi H, Iemoto T, et al. Endoscopic self-expandable metal stent placement for malignant afferent loop obstruction after

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61

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pancreaticoduodenectomy: a case series and review. Clin Endosc 2020;53(4):491–496. Brewer Gutierrez OI, Irani SS, Ngamruengphong S, et al. Endoscopic ultrasound-guided entero-enterostomy for the treatment of afferent loop syndrome: a multicenter experience. Endoscopy 2018;50(9):891–895. Rodrigues-Pinto E, Grimm IS, Baron TH. Efficacy of endoscopically created bypass anastomosis in treatment of afferent limb syndrome: a single-center study. Clin Gastroenterol Hepatol 2016;14(4): 633–637. Perez-Cuadrado-Robles E, Bronswijk M, Prat F, et al. Endoscopic ultrasound-guided drainage using lumen-apposing metal stent of malignant afferent limb syndrome in patients with previous Whipple surgery: multicenter study (with video). Dig Endosc 2022;34(7): 1433–1439. De Bie C, Bronswijk M, Vanella G, et al. EUS-guided hepaticogastrostomy for patients with afferent loop syndrome: a comparison with EUS-guided gastroenterostomy or percutaneous drainage. Surg Endosc 2022;36(4):2393–4200.

C H A P T E R 28

EUS-guided drainage of pelvic fluid collections Philippe Willems, Ji Young Bang & Shyam Varadarajulu Center for Advanced Endoscopy, Research & Education, Orlando Health Digestive Health Institute, Orlando, FL, USA

Pelvic fluid collections are classified into two categories: postsurgical and medical. Pelvic fluid collection is an infrequent complication of abdominal surgery, especially anterior resection, and occurs in 0.5–30.0% of cases [1, 2]. Medical causes include diverticulitis, ischemic colitis, Crohn’s disease, appendicitis, and sexually transmitted infections [3]. Although rare, they are associated with considerable morbidity and mortality [4]; hence, emphasis is placed on timely diagnosis and management for improved outcomes. While small collections ( 1.5) or thrombocytopenic (PLT < 50). An enema should be administered to clean the rectum and sigmoid colon. It is also prudent to place a Foley catheter into the bladder to ensure it is not mistaken for the pelvic fluid collection. Prophylactic antibiotics with broad gram-negative coverage (ciprofloxacin, for example) are administered IV immediately prior to the procedure and continued PO for 3 days after the procedure.

Procedure After obtaining informed consent, the patient is placed in the left lateral decubitus position, and the procedure is performed under conscious sedation or anesthesia. Fluoroscopic guidance is recommended. A radial echoendoscope can be used to survey the collection size, location, and relationship with adjacent structures. A curvilinear array (CLA) echoendoscope with at least a 3 mm working channel is then advanced slowly up to the splenic flexure and withdrawn in a torqueing motion to identify the pelvic fluid collection. The point of access is chosen based on the proximity of the collection to the colonic lumen. The collection must be less than 2 cm from the lumen of the colon; Doppler should be used to screen for potential vascular structures. A 19-gauge fine-needle aspiration (FNA) needle is then advanced into the collection, and fluid is aspirated and sent for Gram stain and culture. Saline (10 mL) is flushed down the needle into the collection to ensure that any residual material is expelled. A 0.035-in. guidewire with a hydrophilic tip is then advanced and coiled. The fluoroscopic view of the coiled guidewire may provide a clue as to the complexity of the collection; the guidewire appears irregularly coiled in complex collections (Figure 28.1A), but takes a smooth oval configuration in simple ones (Figure 28.1B). Plastic stent A 4.5-Fr endoscopic retrograde cholangiopancreatography (ERCP) cannula or needle-knife catheter is then used to dilate the transmural tract and create a fistula. Sequential dilation of the tract is subsequently performed using a 6–8 mm biliary balloon until the waist disappears (Figure 28.1C,D). Once the dilation is complete, the discharge of purulent material is evident on endoscopic view. One or two double-pigtail plastic stents are deployed, depending on the density and size of the collection being drained (Figure 28.2A–D). Lumen-apposing metal stent (LAMS) The collection should be no more than 1 cm from the colonic lumen. Using the electrocautery-enhanced LAMS delivery system,

Endoscopic Ultrasonography, Fourth Edition. Edited by Frank G. Gress and Thomas J. Savides. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.

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(A)

(B)

(C)

(D)

Figure 28.1 (A) Fluoroscopic image of the echoendoscope with a coiled guidewire in a complex collection. Note the disorganized configuration of the

guidewire. (B) Fluoroscopic image of the echoendoscope with a well-coiled guidewire in an uncomplicated collection. (C) Fluoroscopic image at transluminal balloon dilation with demonstration of the “waist.” (D) Fluoroscopic image with balloon dilation revealing obliteration of the “waist.”

a fistula is created, and the stent is deployed in the collection. A 15 × 10 mm stent is preferred if the collection contains pus or an infected hematoma; otherwise, a 10 × 10 mm stent is usually sufficient. Purulent discharge into the colonic lumen denotes appropriate stent placement. There is no need for balloon dilation of the fistula tract. When the density of the collection is high and the cavity is larger than 8 cm, a 10 Fr transrectal drainage catheter may be deployed with irrigation of 200 mL of normal saline every 4 hours until the

aspirate is clear. Unless there is the placement of a transrectal drain, the patient can be discharged the same day.

Post-procedure care and follow-up Symptomatic, radiological, and biochemical parameters are monitored post-drainage, and the patient is discharged when stable. A CT scan is obtained at 2 weeks post-procedure to ensure resolution of the collection, followed by endoscopic removal of the

Chapter 28: EUS-guided drainage of pelvic fluid collections

(A)

(C)

263

(B)

(D)

Figure 28.2 (A) Endoscopic view of a 0.035-in. guidewire entering through the mucosa into the collection, with discharge of purulent material. (B) Endo-

scopic image of balloon dilation revealing copious discharge of pus. (C) Endoscopic view of the fistula. (D) Endoscopic image of a transcolonic pigtail in the colonic lumen.

transluminal stents (Figures 28.3A,B). LAMS should be removed within 3–4 weeks to avoid complications. If the initial EUS-guided drainage is unsuccessful, repeat EUS-guided drainage or surgical drainage can be attempted.

Current evidence Since the first report of EUS-guided abdominopelvic abcess drainage in 2003, 20 other case series have been published. A recent meta-analysis including 135 procedures reported a pooled technical success of 100% and a pooled clinical success of 92% [7]. There is only one study comparing endoscopic drainage to other drainage modalities [8]. EUS was more efficient than transrectal surgical drainage after a single treatment (83.0% vs. 48.0%) while offering similar abscess resolution rates (78.0% vs. 74.0%) and hospital

length of stay (24 vs. 20 days). The main series are presented in Table 28.1. Giovannini et al. [9] published their experience in 12 patients undergoing EUS-guided drainage and reported a 75% treatment success rate, with failure in collections larger than 8 cm. The deployed stents were straight and 8.5 or 10.0 Fr in diameter; adverse events included stent clogging or dislodgement and pelvic discomfort. The drainage technique was improved by Varadarajulu and Drelichman with the placement of double-pigtail stents in conjunction with a transrectal catheter [17]. The aim of this technique was to maintain the fistula open until resolution of the abscess and use short-term irrigation to evacuate the cavity of infected debris. This approach was associated with 100% technical and clinical success rates and no complications. Importantly, it shortened the length of the hospital stay. In a later study from the same group, 10 patients

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(A)

(B)

Figure 28.3 CT images of a pelvic fluid collection (A) before and (B) after transluminal stent placement.

Table 28.1 Published series on EUS-guided transluminal pelvic abscess drainage. References

Country

n

Route of access

Mean size (mm)

Drainage modality

Technical success (%)

Treatment success (%)

Complication

Giovannini 2003 [9]

France

12

Transrectal

48.9

100

88

None

Varadarajulu [10]

United States

25

Transrectal/ transcolonic

68

100

96

None

Puri [11]

India

14

65

100

93

None

Ramesh [12]

United States

38

Transcolonic/ Transrectal 11 Transcolonic

9 straight plastic stents 3 aspirations only 15 double-pigtail 10 double-pigtail and drainage catheters 9 double-pigtail 5 aspirations only Double-pigtail and drainage catheter

100

70

None

Poincloux [13]

France

37

27 Transrectal 3 Transcolonic 34 Transrectal

70 60

100 100

96 91.9

Mudireddy [14] Guingand [15]

United States France

8 73

Transrectal 3 Transcolonic 70 Transrectal

N/A 48.9

100 100

87.5 96

None 1 perforation1 stent migration 1 rectal discomfort N/A None

Al Khaldi [16]

Canada

60

N/A

65

97

72.7

75

with fluid collections >8 cm in size had both a catheter and a stent placed, while patients with smaller fluid collections underwent stent placement alone [10]. This study highlighted that in carefully selected patients (i.e., those with a fluid collection size