Gastrointestinal Interventional

Endoscopy: Advanced Techniques

Mihir S. Wagh
Visit to download the full and correct content document:
https://textbookfull.com/product/gastrointestinal-interventional-endoscopy-advanced-t
echniques-mihir-s-wagh/
More products digital (pdf, epub, mobi) instant
download maybe you interests ...

Clinical Gastrointestinal Endoscopy Vinay

Chandrasekhara

https://textbookfull.com/product/clinical-gastrointestinal-
endoscopy-vinay-chandrasekhara/

Therapeutic Endoscopy in the Gastrointestinal Tract 1st

Edition Georg Kähler

https://textbookfull.com/product/therapeutic-endoscopy-in-the-
gastrointestinal-tract-1st-edition-georg-kahler/

Gastrointestinal Malignancies: A Practical Guide on

Treatment Techniques 1st Edition Suzanne Russo

https://textbookfull.com/product/gastrointestinal-malignancies-a-
practical-guide-on-treatment-techniques-1st-edition-suzanne-
russo/

Chemically Bonded Phosphate Ceramics. Twenty-First

Century Materials with Diverse Applications 2nd Edition
Arun S. Wagh

https://textbookfull.com/product/chemically-bonded-phosphate-
ceramics-twenty-first-century-materials-with-diverse-
applications-2nd-edition-arun-s-wagh/
Advanced Techniques in Diagnostic Microbiology Volume 1
Techniques Yi-Wei Tang

https://textbookfull.com/product/advanced-techniques-in-
diagnostic-microbiology-volume-1-techniques-yi-wei-tang/

Minimally Invasive Surgical Techniques for Cancers of

the Gastrointestinal Tract: A Step-by-Step Approach
Joseph Kim

https://textbookfull.com/product/minimally-invasive-surgical-
techniques-for-cancers-of-the-gastrointestinal-tract-a-step-by-
step-approach-joseph-kim/

GPU Zen Advanced Rendering Techniques Wolfgang Engel

(Editor)

https://textbookfull.com/product/gpu-zen-advanced-rendering-
techniques-wolfgang-engel-editor/

Advanced Techniques in Shoulder Arthroscopy Peter J.

Millett

https://textbookfull.com/product/advanced-techniques-in-shoulder-
arthroscopy-peter-j-millett/

Endoscopy in liver disease First Edition Hayes

https://textbookfull.com/product/endoscopy-in-liver-disease-
first-edition-hayes/
Gastrointestinal
Interventional
Endoscopy
Advanced Techniques
Mihir S. Wagh
Sachin B. Wani
Editors

123
Gastrointestinal Interventional
Endoscopy
Mihir S. Wagh • Sachin B. Wani
Editors

Gastrointestinal
Interventional
Endoscopy
Advanced Techniques
Editors
Mihir S. Wagh Sachin B. Wani
Interventional Endoscopy, Division of Interventional Endoscopy, Division of
Gastroenterology Gastroenterology
University of Colorado-Denver University of Colorado-Denver
Aurora, CO Aurora, CO
USA USA

Additional material to this book can be downloaded from

https://link.springer.com/book/10.1007/978-3-030-21695-5

ISBN 978-3-030-21694-8    ISBN 978-3-030-21695-5 (eBook)

https://doi.org/10.1007/978-3-030-21695-5

© Springer Nature Switzerland AG 2020

This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifically the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specific statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
The publisher, the authors, and the editors are safe to assume that the advice and information in
this book are believed to be true and accurate at the date of publication. Neither the publisher nor
the authors or the editors give a warranty, expressed or implied, with respect to the material
contained herein or for any errors or omissions that may have been made. The publisher remains
neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This Springer imprint is published by the registered company Springer Nature Switzerland AG
The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland
To my parents, Maya and Suhas Wagh, for giving me
everything.
—Mihir S. Wagh

I dedicate this book to my parents, Balkrishna and Sudha Wani,

who have always inspired me to follow my own path, giving me
all the opportunities I have had in my life and to whom I owe
everything. To my entire family, I am grateful for all your love,
encouragement, and support. To my colleagues, trainees,
nurses, and mentors, I continue to learn from you every single
day. Finally, to my wife, Anuja, and our twins, Kaahan and
Krish, who have allowed me to pursue my dreams. I thank you
for all of your sacrifices, patience, compassion, and motivation
to dream big.
—Sachin B. Wani
Foreword I

Interventional endoscopy has expanded far beyond the techniques of ERCP

and EUS. This outstanding text focuses on the newer procedures in interven-
tional endoscopy that have been developed and evolved in the spaces of endo-
scopic resection, endoscopic bariatric therapies, per oral endoscopic
myotomies, endoscopic antireflux therapies, tissue apposition, and interven-
tional endoscopic ultrasound. My colleagues and partners, Mihir S. Wagh and
Sachin B. Wani, have developed this text, with a dedication to the practice
and teaching of interventional endoscopy. I have had the good fortune to
directly observe their enthusiasm, teaching, and practice over the past years.
For this work, they have recruited outstanding experts in this space to describe
the innovations that have occurred in the past decade that have changed our
approaches and expanded the minimally invasive therapies we offer our
patients. While some of these techniques are being optimized, others have
been established in prospective clinical trials as viable alternatives in the
management of gastrointestinal disorders. Most of us enthusiastically entered
this subspecialty with the intent of helping our patients with new, minimally
invasive procedures. This enthusiasm continues with the development of
these newer techniques and our expansion into areas that were previously not
approached endoscopically. The innovation and thoughtfulness of our col-
leagues that practice and continue to push the boundaries of this space are
impressive. The collective drive to continue to advance minimally invasive
solutions to the clinical problems that we all face guarantees that some, if not
all, of these techniques will be supplanted by even more novel and innovative
approaches in the future. We are fortunate to view this current snapshot as the
continuum of minimally invasive endoscopic care advances. The authors and
editors of this text are to be commended for marking our progress to date in
this comprehensive and timely work. It is a resource for practitioners and
trainees alike as it nicely summarizes our current state of the practice of the
newer techniques in this broadening field of interventional endoscopy.


Aurora, CO, USA Steven A. Edmundowicz, MD, FASGE

vii
Foreword II

Gastrointestinal (GI) endoscopy has a relatively recent history, starting in

1932 with the development of the flexible gastroscope by Schindler. Only
after the introduction of the gastrocamera in 1950 by Uji and colleagues,
Hischowitz invented in 1957 the first fiberscope for the upper GI tract and
colon. The use of endoscopy further increased in popularity with the intro-
duction of video endoscopes. At the same time, the first prototypes of endo-
scopic ultrasound (EUS) were introduced in the 1980s. EUS was initially
used as a diagnostic adjunct but rapidly evolved to a therapeutic tool for vari-
ous GI disorders.
In the past 10 years, GI endoscopy has seen various remarkable develop-
ments. In the following, four major developments will be highlighted.
One of these developments include endoscopic resection. It originally
started with endoscopic polypectomy but soon thereafter developed further to
endoscopic mucosal resection (EMR) for the removal of larger superficial
lesions, followed by endoscopic submucosal dissection (ESD) for en bloc
resections, and recently to endoscopic full-thickness resection (EFTR),
allowing the resection of lesions that are located in the deeper layers of the GI
tract.
Due to the dramatic increase in overweight and obesity in the last 10–15
years, especially in the Western world, endoscopic bariatric treatments were
introduced. This initially started with minimally invasive treatments, i.e.,
intragastric balloon placement and aspiration therapy. Later, when endo-
scopic suturing devices became available, endoscopic sleeve gastroplasty was
introduced.
The third development which can be considered as one of the most appeal-
ing in the last 10 years is endoscopic myotomy. It first started with a proce-
dure developed by Dr. Haruhiro Inoue, named peroral endoscopic myotomy
(POEM). This initiated several other procedures which are likewise charac-
terized by restoring continuity in the GI tract, such as endoscopic myotomy
for Zenker’s diverticulum (Z-POEM), endoscopic pyloromyotomy for gas-
troparesis (G-POEM), and endoscopic per rectal endoscopic myotomy for
Hirschsprung’s disease (PREM). The technique of myotomy has also set the
stage for other third-space endoscopic procedures, for example, submucosal
tunneling endoscopic resection (STER).
Finally, in the mid-1990s, EUS-guided cyst gastrostomy and EUS-guided
celiac plexus neurolysis shifted the perception of EUS from a purely diagnos-
tic examination to a modality capable of performing therapeutic ­interventions.

ix
x Foreword II

Numerous advances have since been made, including EUS-directed biliary

and pancreatic drainage, treatment of neoplasia, anastomosis creation, and
treatment of bleeding. Most of these technologies will most likely shift sev-
eral therapeutic approaches in the near future.
The editors of this book, entitled Gastrointestinal Interventional
Endoscopy: Advanced Techniques, Drs. Mihir S. Wagh and Sachin B. Wani,
are to be congratulated for their initiative to bring together a superb list of
authors. This book offers an overview of therapeutic gastrointestinal endos-
copy for upper and lower gastrointestinal diseases. New therapeutic tech-
niques using advanced endoscopic devices are extensively covered. The
authors are without exception experts in the field with a great store of knowl-
edge on a wide variety of therapeutic endoscopic procedures. The book will
provide a clear guidance for practicing clinicians when performing therapeu-
tic gastrointestinal endoscopy.


Nijmegen, The Netherlands Peter D. Siersema, MD, PhD, FASGE
Preface

It is our great pleasure to present to you this book on newer techniques in

gastrointestinal interventional endoscopy. At the outset, let us start by men-
tioning the main reason for this endeavor. The field of interventional endos-
copy is moving at a dramatically rapid pace with newer endoscopic devices
and techniques emerging in the last decade. Traditionally, interventional
endoscopy has included endoscopic retrograde cholangiopancreatography
(ERCP) and endoscopic ultrasonography (EUS). However, the field has now
expanded to more than just these procedures with the development of a new
domain in endoscopy, often called “flexible endoscopic surgery.” This book
specifically focuses on these components of interventional endoscopy beyond
ERCP and EUS. We hope that this would be the “go to” book or “textbook”
for all interested in interventional endoscopy since it contains a thorough
description and analysis of these newer topics.
This book is divided into six parts – Endoscopic Resection, Bariatric
Endoscopy, Endoscopic Myotomy, Endoscopic Antireflux Therapies,
Endoscopic Tissue Apposition, and Advances in Interventional EUS – with
chapters authored by world-renowned experts in each field. We highlight
indications and technical details, assess safety and efficacy, and suggest qual-
ity metrics and training pathways for these endoscopic procedures. We have
included multiple illustrations, tables, and endoscopic photos and videos
highlighting these topics to help the reader clearly understand key concepts
and procedural details. The book is geared towards all endoscopists – gastro-
enterologists and surgeons, trainees, as well as seasoned practitioners – inter-
ested in this ever-evolving minimally invasive discipline.
We are grateful to our panel of distinguished contributors, national and
international endoscopists from across the globe, for sharing their knowledge
and experience with us. We would like to extend a special thanks to Andy
Kwan and Smitha Diveshan at Springer for patiently guiding us through the
publishing process.

Aurora, CO, USA Mihir S. Wagh MD, FACG, FASGE

 Sachin B. Wani MD

xi
Contents

Part I Endoscopic Resection

1 Endoscopic Lesion Recognition and Advanced

Imaging Modalities��������������������������������������������������������������������������   3
Jorge D. Machicado, Jennifer M. Kolb, and Sachin B. Wani
2 Endoscopic Mucosal Resection of the Esophagus ������������������������ 25
Samuel Han and Hazem Hammad
3 Gastric and Duodenal Endoscopic Mucosal Resection���������������� 41
Rommel Romano and Pradermchai Kongkam
4 A Pragmatic Approach to Complex Colon Polyps������������������������ 45
Michael X. Ma and Michael J. Bourke
5 Endoscopic Tools and Accessories for ESD������������������������������������ 67
Calvin Jianyi Koh, Dennis Yang, and Peter V. Draganov
6 Esophageal ESD ������������������������������������������������������������������������������ 83
Lady Katherine Mejía Pérez, Seiichiro Abe, Raja Siva,
John Vargo, and Amit Bhatt
7 Gastric ESD�������������������������������������������������������������������������������������� 97
Takuji Gotoda
8 Colonic ESD�������������������������������������������������������������������������������������� 107
Vikneswaran Namasivayam and Yutaka Saito
9 Endoscopic Full-Thickness Resection (EFTR)
and Submucosal Tunneling Endoscopic Resection (STER) �������� 127
Mingyan Cai, Marie Ooi, and Pinghong Zhou
10 EMR Versus ESD: Pros and Cons�������������������������������������������������� 153
Fayez Sarkis, Vijay Kanakadandi, Mojtaba S. Olyaee,
and Amit Rastogi
11 Training and Competency in Endoscopic Resection�������������������� 163
Daniel S. Strand and Andrew Y. Wang

xiii
xiv Contents

Part II Bariatric Endoscopy

12 Intragastric Balloons and Aspiration Therapy ���������������������������� 181

Chetan Mittal and Shelby Sullivan
13 Endoscopic Sleeve Gastroplasty (ESG)������������������������������������������ 193
Gontrand Lopez-Nava and Inmaculada Bautista-Castaño
14 Emerging Endoscopic Therapies for Weight Loss������������������������ 199
Thomas J. Wang and Marvin Ryou
15 Endoscopic Therapy of Post-­Bariatric Surgery
Strictures, Leaks, and Fistulas�������������������������������������������������������� 211
Filippo Filicori and Lee L. Swanström
16 Endoscopic Management of Weight Regain���������������������������������� 223
Eric J. Vargas, Andrew C. Storm, Fateh Bazerbachi,
and Barham K. Abu Dayyeh

Part III Endoscopic Myotomy

17 POEM: Pre-procedural Work-Up and Indications���������������������� 235

Joseph Rayfield Triggs and John E. Pandolfino
18 Per-Oral Endoscopic Myotomy: Endoscopic Techniques������������ 251
Chetan Mittal and Mihir S. Wagh
19 POEM: Efficacy, Safety, Training, and Competency�������������������� 263
Juergen Hochberger and Volker Meves
20 Endoscopic Myotomy for Zenker’s Diverticulum
(Z-POEM)���������������������������������������������������������������������������������������� 283
Alessandro Fugazza, Roberta Maselli, and Alessandro Repici
21 Per-Oral Endoscopic Pyloromyotomy (G-POEM) and
Per-Rectal Endoscopic Myotomy (PREM)������������������������������������ 291
Amol Bapaye and Amit Maydeo

Part IV Endoscopic Anti-reflux Therapies

22 History of Endoscopic Anti-Reflux Therapies:

Lessons Learned������������������������������������������������������������������������������ 315
Zaheer Nabi and D. Nageshwar Reddy
23 Transoral Incisionless Fundoplication (TIF) for
Treatment of Gastroesophageal Reflux Disease���������������������������� 325
Pier Alberto Testoni, Sabrina Gloria Giulia Testoni,
Giorgia Mazzoleni, and Lorella Fanti
24 Radiofrequency Ablation (RFA) and Anti-Reflux
MucoSectomy (ARMS) for Gastroesophageal
Reflux Disease���������������������������������������������������������������������������������� 339
Bryan Brimhall, Amit Maydeo, Mihir S. Wagh,
and Hazem Hammad
Contents xv

Part V Endoscopic Tissue Apposition

25 Techniques for Endoscopic Suturing���������������������������������������������� 347

Olaya I. Brewer Gutierrez and Stuart K. Amateau
26 Endoscopic Clips and Glues������������������������������������������������������������ 363
Roupen Djinbachian and Daniel von Renteln

Part VI Advances in Interventional EUS

27 Interventional EUS: Pancreas�������������������������������������������������������� 385

Vinay Dhir, Ankit Dalal, and Carmen Chu
28 Interventional EUS: Bile Duct and Gallbladder �������������������������� 401
Anthony Yuen Bun Teoh, Kenjiro Yamamoto,
and Takao Itoi
29 Interventional Vascular EUS���������������������������������������������������������� 415
Jason B. Samarasena, Kyle J. Fortinsky,
and Kenneth J. Chang
Index���������������������������������������������������������������������������������������������������������� 429
Contributors

Seiichiro Abe Endoscopy Division, National Cancer Center Hospital,

Tokyo, Japan
Barham K. Abu Dayyeh Mayo Clinic, Rochester, MN, USA
Stuart K. Amateau University of Minnesota Medical Center, Department
of Medicine, Division of Gastroenterology and Hepatology, Minneapolis,
MN, USA
Amol Bapaye Shivanand Desai Center for Digestive Disorders, Deenanath
Mangeshkar Hospital and Research Center, Pune, India
Inmaculada Bautista-Castaño Bariatric Endoscopy Unit, Madrid
Sanchinarro University Hospital, Madrid, Spain
Ciber of Obesity and Nutrition Pathophysiology (CIBEROBN), Instituto de
Salud Carlos III, Madrid, Spain
Fateh Bazerbachi Department of Gastroenterology and Hepatology, Mayo
Clinic, Rochester, MN, USA
Amit Bhatt Department of Gastroenterology and Hepatology, Digestive
Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Michael J. Bourke Department of Gastroenterology and Hepatology,
Westmead Hospital, Sydney, NSW, Australia
University of Sydney, Sydney, NSW, Australia
Olaya I. Brewer Gutierrez Johns Hopkins Medical Institution, Department of
Medicine, Division of Gasroenerology and Hepatology, Baltimore, MD, USA
Bryan Brimhall Division of Gastroenterology, University of Colorado,
Boulder, CO, USA
Mingyan Cai Endoscopy Center, Zhongshan Hospital of Fudan University,
Shanghai, China
Kenneth J. Chang Department of Medicine, H.H. Chao Comprehensive
Digestive Disease Center, University of California, Irvine Medical Center,
Orange, CA, USA
Carmen Chu Division of Pancreatic-biliary Endoscopy, Institute of
Digestive and Liver Care, SL Raheja Hospital, Mumbai, India

xvii
xviii Contributors

Ankit Dalal Division of Pancreatic-biliary Endoscopy, Institute of Digestive

and Liver Care, SL Raheja Hospital, Mumbai, India
Division of Gastroenterology, Baldota Institute of Digestive Sciences, Mumbai,
India
Vinay Dhir Division of Pancreatic-biliary Endoscopy, Institute of Digestive
and Liver Care, SL Raheja Hospital, Mumbai, India
Roupen Djinbachian Division of Internal Medicine, Montreal University
Hospital Center (CHUM), Montreal, Canada
Montreal University Research Center (CRCHUM), Montreal, Canada
Peter V. Draganov Division of Gastroenterology, Hepatology and Nutrition,
University of Florida Health, Gainesville, FL, USA
Lorella Fanti IRCCS San Raffaele Scientific Institute, Vita-Salute San
Raffaele University, Division of Gastroenterology and Gastrointestinal
Endoscopy, Milano (MI), Italy
Filippo Filicori Lenox Hill Hospital-Hofstra Northwell School of Medcine,
New York, NY, USA
Kyle J. Fortinsky Department of Medicine, H.H. Chao Comprehensive
Digestive Disease Center, University of California, Irvine Medical Center,
Orange, CA, USA
Alessandro Fugazza Digestive Endoscopy Unit, Division of
Gastroenterology, Humanitas Research Hospital, Rozzano, MI, Italy
Takuji Gotoda Division of Gastroenterology and Hepatology, Department
of Medicine, Nihon University School of Medicine, Tokyo, Japan
Hazem Hammad Division of Gastroenterology and Hepatology, Section of
Therapeutic Endoscopy, University of Colorado Anschutz Medical Center
and Veterans Affairs Eastern Colorado Health Care System, Aurora, CO,
USA
Samuel Han Division of Gastroenterology and Hepatology, University of
Colorado Anschutz Medical Center, Aurora, CO, USA
Juergen Hochberger Gastroenterology, GI Oncology, Interventional
Endoscopy, Vivantes Klinikum im Friedrichshain, Berlin, Germany
Takao Itoi Department of Gastroenterology, The University of Tokyo,
Tokyo, Japan
Vijay Kanakadandi Department of Gastroenterology and Hepatology, The
University of Kansas Hospital, Kansas City, KS, USA
Calvin Jianyi Koh Division of Gastroenterology and Hepatology, National
University Hospital, Singapore, Singapore
Contributors xix

Jennifer M. Kolb Division of Gastroenterology and Hepatology, University

of Colorado Anschutz Medical Center, Aurora, CO, USA
Pradermchai Kongkam Pancreas Research Unit, Department of Medicine,
Chulalongkorn University, Bangkok, Thailand
Gontrand Lopez-Nava Bariatric Endoscopy Unit, Madrid Sanchinarro
University Hospital, Madrid, Spain
Michael X. Ma Department of Gastroenterology and Hepatology, Westmead
Hospital, Sydney, NSW, Australia
Jorge D. Machicado Division of Gastroenterology and Hepatology, Mayo
Clinic Health System, Eau Claire, WI, USA
Roberta Maselli Digestive Endoscopy Unit, Division of Gastroenterology,
Humanitas Research Hospital, Rozzano, MI, Italy
Amit Maydeo Baldota Institute of Digestive Sciences, Global Hospital,
Mumbai, India
Giorgia Mazzoleni IRCCS San Raffaele Scientific Institute, Vita-Salute San
Raffaele University, Division of Gastroenterology and Gastrointestinal
Endoscopy, Milano (MI), Italy
Volker Meves Gastroenterology, Klinikum Oldenburg AöR, Oldenburg,
Germany
Chetan Mittal Division of Gastroenterology, University of Colorado-
Denver, Aurora, CO, USA
Zaheer Nabi Department of Gastroenterology, Asian Institute of
Gastroenterology, Hyderabad, India
Vikneswaran Namasivayam Department of Gastroenterology and
Hepatology, Singapore General Hospital, Singapore, Singapore
Duke NUS Medical School, Singapore, Singapore
Yong Loo Lin School of Medicine, National University of Singapore,
Singapore, Singapore
Mojtaba S. Olyaee Department of Gastroenterology and Hepatology, The
University of Kansas Hospital, Kansas City, KS, USA
Marie Ooi Department of Gastroenterology, Royal Adelaide Hospital,
Adelaide, SA, Australia
John E. Pandolfino Division of Gastroenterology, Department of Medicine,
Northwestern University’s Feinberg School of Medicine, Chicago, IL, USA
Lady Katherine Mejía Pérez Department of Internal Medicine, Cleveland
Clinic, Cleveland, OH, USA
xx Contributors

Amit Rastogi Department of Gastroenterology and Hepatology, The

University of Kansas Hospital, Kansas City, KS, USA
D. Nageshwar Reddy Asian Institute of Gastroenterology, Hyderabad, India
Alessandro Repici Digestive Endoscopy Unit, Division of Gastroenterology,
Humanitas Research Hospital, Rozzano, MI, Italy
Humanitas University, Rozzano, MI, Italy
Rommel Romano Department of Medicine, University of Santo Tomas
Hospital, Manila, Philippines
Marvin Ryou Harvard Medical School, Boston, MA, USA
Brigham and Women’s Hospital, Division of Gastroenterology, Hepatology,
and Endoscopy, Boston, MA, USA
Yutaka Saito National Cancer Center Hospital, Endoscopy Division,
Endoscopy Center, Tokyo, Japan
Jason B. Samarasena Department of Medicine – Gastroenterology,
University of California, Irvine Medical Center, Orange, CA, USA
Fayez Sarkis Department of Gastroenterology and Hepatology, The
University of Kansas Hospital, Kansas City, KS, USA
Raja Siva Department of Thoracic and Cardiovascular Surgery, Cleveland
Clinic Foundation, Cleveland, OH, USA
Andrew C. Storm Department of Gastroenterology and Hepatology, Mayo
Clinic, Rochester, MN, USA
Daniel S. Strand Division of Gastroenterology and Hepatology, University
of Virginia Health System, Charlottesville, VA, USA
Shelby Sullivan University of Colorado School of Medicine, Aurora, CO,
USA
Lee L. Swanström Division of Gastrointestinal and Minimally Invasive
Surgery, The Oregon Clinic, Portland, OR, USA
Anthony Yuen Bun Teoh Department of Surgery, Prince of Wales Hospital,
The Chinese University of Hong Kong, Shatin, Hong Kong SAR
Pier Alberto Testoni IRCCS San Raffaele Scientific Institute, Vita-Salute
San Raffaele University, Division of Gastroenterology and Gastrointestinal
Endoscopy, Milano (MI), Italy
Sabrina Gloria Giulia Testoni IRCCS San Raffaele Scientific Institute,
Vita-Salute San Raffaele University, Division of Gastroenterology and
Gastrointestinal Endoscopy, Milano (MI), Italy
Joseph Rayfield Triggs Section of Gastroenterology and Hepatology in the
Department of Medicine, Northwestern Feinberg School of Medicine,
Chicago, IL, USA
Contributors xxi

Eric J. Vargas Department of Gastroenterology and Hepatology, Mayo

Clinic, Rochester, MN, USA
John Vargo Department of Gastroenterology and Hepatology, Digestive
Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
Daniel von Renteln Montreal University Research Center (CRCHUM),
Montreal, Canada
Division of Gastroenterology, Montreal University Hospital Center (CHUM),
Montreal, Canada
Mihir S. Wagh Interventional Endoscopy, Division of Gastroenterology,
University of Colorado-Denver, Aurora, CO, USA
Andrew Y. Wang Section of Interventional Endoscopy, Division of
Gastroenterology and Hepatology, University of Virginia Health System,
Charlottesville, VA, USA
Thomas J. Wang Massachusetts General Hospital, Department of Medicine,
Boston, MA, USA
Harvard Medical School, Boston, MA, USA
Sachin B. Wani Interventional Endoscopy, Division of Gastroenterology,
University of Colorado-Denver, Aurora, CO, USA
Kenjiro Yamamoto Department of Gastroenterology, The University of
Tokyo, Tokyo, Japan
Dennis Yang Division of Gastroenterology, Hepatology and Nutrition,
University of Florida, Gainesville, FL, USA
Pinghong Zhou Endoscopy Center, Zhongshan Hospital of Fudan
University, Shanghai, China
 Part I
Endoscopic Resection
 Endoscopic Lesion Recognition
and Advanced Imaging Modalities
Jorge D. Machicado, Jennifer M. Kolb,
and Sachin B. Wani
Introduction
The field of gastrointestinal endoscopy has
evolved in the last 50 years as a consequence of
significant advances in engineering, physics,
chemistry, and molecular biology among oth-
ers. One of the most important goals of endos-
copy is in detecting and characterizing
premalignant or early neoplastic lesions that
may be suitable for curative therapies. The
explosive growth of optical, cross-sectional,
and molecular methods allows us to recognize
subtle lesions that may have been missed, in
addition to predicting histology and guiding
endoscopic therapy.
The development of fiber-optic technology
was a determinant step that permitted the intro-
duction of flexible gastrointestinal endoscopes
in 1957, which replaced the old, rigid, and
semiflexible endoscopes [1]. Conventional
J. D. Machicado
Division of Gastroenterology and Hepatology,
Mayo Clinic Health System, Eau Claire, WI, USA
J. M. Kolb
Division of Gastroenterology and Hepatology,
University of Colorado Anschutz Medical Center,
Aurora, CO, USA
S. B. Wani (*)
Interventional Endoscopy, Division of
Gastroenterology,
University of Colorado-Denver, Aurora, CO, USA
© Springer Nature Switzerland AG 2020
M. S. Wagh, S. B. Wani (eds.), Gastrointestinal Interventional Endoscopy,
https://doi.org/10.1007/978-3-030-21695-5_1
1
video endoscopy was then developed in 1993
by using charge-coupled devices (CCDs),
which enabled visualization of real-time imag-
ing on a monitor [2]. During the last decade,
developments in video endoscopy resolution
and monitor definition have led to the introduc-
tion of high-­definition white light endoscopy
(HDWLE), which is now considered as the
standard of care [3].
Despite these tremendous advancements in
video endoscopy, subtle lesions can still be
missed. Thus, other optical, cross-sectional, and
molecular methods have rapidly evolved as an
adjunct to HDWLE. Optical technologies such
as conventional and virtual chromoendoscopy
have been available in clinical practice for sev-
eral years. In contrast, cross-sectional m
­ ethods
with the ability to provide real-time histology
images such as confocal laser e­ ndomicroscopy
(CLE), optical coherence ­tomography (OCT),
and volumetric laser endomicroscopy (VLE) are
still being evaluated, not yet available to most
endoscopists, and hence not ready for routine
clinical use. Most recently, molecular imaging
has emerged to detect specific targets and guide
individualized treatments, but it is at early
stages and only available for research purposes.
In this chapter, we will review each of these
advanced imaging modalities (AIMs) and their
applicability in recognizing different gastroin-
testinal lesions in clinical practice.
3
4 J. D. Machicado et al.

Table 1.1 Pros and cons of different advanced imaging modalities

Advanced imaging modality
Conventional
chromoendoscopy
Virtual chromoendoscopy
Autofluorescence imaging
(AFI)
Confocal laser
endomicroscopy (CLE)
Optical coherence tomography
(OCT)/ volumetric laser
endomicroscopy (VLE)
Molecular imaging
Pros
Detailed surface pit pattern
Useful for dysplasia detection in IBD
Detailed surface pit and vascular
pattern
Easy and cheap on/off button
Validated classification systems
Useful for neoplasia detection in
Barrett’s esophagus, stomach lesions,
and colon polyps
Useful for colon polyp
characterization
Imaging at greater depth
High resolution
Visualization of mucosa at cellular
level, allows in vivo histology
Visualization of mucosa and
submucosa at cellular level
VLE can mark abnormal area
High specificity
Cons
Adds time and cost (dyes)
Potential risks with vital stains
Lack of validated classification systems
Evaluation limited to the mucosa
Evaluation limited to the mucosa
Interpretation requires training
Low specificity, high false positive rates
Low resolution
Requires special equipment
Time consuming, costly
Typically requires probes (pCLE)
Requires IV contrast agents
Evaluation limited to the mucosa
Low resolution
Requires special equipment, costly
Requires training
Adds time and cost
Requires special equipment
Not available for routine clinical use

Description of Technologies with 410,000 pixel CCD that provided a digital

Table 1.1 summarizes the pros and cons related to
the use of each advanced imaging technology in
clinical practice.
 hite Light Endoscopy (WLE):
W pixels and that are displayed in monitors with
Standard vs. High Definition
Equipment required for video endoscopy includes
a video processor, a light source, the endoscope,
and a monitor. An external xenon light source pro-
vides the full spectrum of visible white light which
travels through fiber-optic glass bundles and is
emitted through a lens at the end of the endoscope
[4]. Light is reflected off the mucosa, through the
objective lens of the endoscope, and reaches the
photosensitive surface of the CCD – a small chip
in the endoscope tip that senses an image. The
CCD captures the image and transmits the charge
through electrical wires to the video processor,
where a digital image is produced. The initial stan-
dard-definition (SD) endoscopes were equipped
image that was 640 (width) by 480 (height) [5].
Soon after came the realization that image quality
was largely dependent on resolution, which is a
function of CCD pixel density.
HDWLE uses smaller chips that produce
images with a resolution of more than a million
either 4:3 or 5:4 aspect ratios and at least 650
pixels in height [6]. In order to truly capture
HD images, all of the endoscopy equipment
must be HD compatible (endoscope, CCD, pro-
cessor, monitor, and transmission cables). HD
monitors can display progressive images where
lines are scanned consecutively and the images
painted 60 times per second, which produces
fewer artifacts for moving objects. Optical
magnification with HD endoscopy can provide
images up to 150 times the original size with
preserved resolution. This function can be acti-
vated with a button in newer endoscopes
through a system called near focus, which mod-
ifies a mechanical movable lens at the tip of the
endoscope [7].
1 Endoscopic Lesion Recognition and Advanced Imaging Modalities
Conventional Chromoendoscopy
This type of AIM enhances the GI mucosa with
topically applied dyes to outline lesion borders,
highlight surface changes, and delineate mucosal
depth. Several methods of dye application are
employed depending on the target surface area.
For focal suspicious lesions, a 60 mL syringe of
diluted dye can be pushed through the instrument
channel of the endoscope, and the target area is
then examined closely. In cases targeting a larger
area of tissue, such as patients with inflammatory
bowel disease, a more efficient method for deliv-
ering dye is through the water jet irrigation sys-
tem after mixing 250 mL of normal saline with
dye in various concentrations [8]. Each dye has
distinct chemical properties designed for differ-
ent clinical applications.
Methylene blue is a vital dye that is absorbed
by the epithelial cells of the small intestine (e.g.,
intestinal metaplasia, IM) and colonic crypts.
Absorption generally occurs within 1 minute of
topical application, and the effect remains for up
to 20 minutes. Whereas “normal” mucosa will
soak up the dye color, neoplastic or inflamed
mucosa will absorb little or no dye. Thus, a
brighter and unstained area is a clue for pathol-
ogy. Lugol’s solution is another vital dye used
mostly for screening of esophageal squamous
cell cancer in high-risk populations. Suspicious
areas more likely to harbor high-grade intraepi-
thelial neoplasia appear as well-demarcated
unstained regions of >5 mm, often termed the
“pink color sign” as these areas retain a pink
mucosal hue in contrast to the iodine-stained sur-
rounding mucosa (Fig. 1.1) [9]. Other but less
used vital dyes include crystal violet and cresyl
violet.
Non-vital dyes are applied to the surface and
provide contrast but without being absorbed by
the epithelial cells. Indigo carmine is one of the
most commonly used non-vital dyes. It collects in
the pits and grooves of the mucosa, thereby
enhancing visualization of mucosal structures,
surface topography, lesion depth, and borders.
Acetic acid is a weak acid that induces a chemical
reaction in the mucosa with a goal of delineating
epithelial structures. Endoscopic delivery of ace-
5
Fig. 1.1 Squamous cell dysplasia with chromoendos-
copy using Lugol’s solution (unstained areas representing
areas of dysplasia)
tic acid through a spray catheter temporarily alters
the structure of surface epithelial glycoproteins,
which lasts for 2–3 minutes [10]. The unbuffered
acid facilitates disruption of disulfide and hydro-
gen bonds, provokes deacetylation, and in turn
denatures the proteins. Repeat application of ace-
tic acid may be necessary to sustain the effect.
Virtual Chromoendoscopy
Virtual chromoendoscopy uses optical lenses and
digital processing programs to achieve similar
results as conventional chromoendoscopy but
with the ease of only pressing a button. The most
widely used of these systems is narrow band
imaging (NBI, Olympus), which is based on the
optical phenomenon that the depth of light pene-
tration into tissue depends on the wavelength; the
shorter the wavelength, the more superficial
the penetration. In WLE, light at wavelengths
400–700 nm illuminates the surface mucosa and
reproduces all images in their natural color. NBI
applies an optical filter in real time using a red-­
green-­blue illumination system at a narrower
range of 400–540 nm designed to match hemo-
globin absorption [11]. This allows structures
with high hemoglobin content to appear dark
(surface capillaries, brown; submucosal vessels,
cyan) which provides a contrast to the surround-
ing mucosa that reflects the light.
6 J. D. Machicado et al.
Other systems use the full spectrum of white
light to capture images and then perform post-­
imaging processing. The Fujinon Intelligent
Chromoendoscopy (FICE) (Fujinon Inc., Japan)
system applies software-based technology to
modify images captured through the standard
endoscopic video processor [12]. The algorithm
selectively enhances specific light wavelengths
and creates a reconstructed FICE image. A simi-
lar technology is iScan (Pentax, Japan), which
uses a digital post-processing system to reconsti-
tute an image [13]. The endoscopist can switch
between surface, color, or tone enhancement
modes by pressing a button to improve visualiza-
tion of specific features. Another modality is
called blue laser imaging (BLI) or Lasero
(Fujinon), which uses a two-laser system. BLI
was created in response to the limitations of FICE
and NBI as a way to combine the strengths of
each individual technology [14]. The limited-­
wavelength blue laser highlights the mucosal
vasculature (similar to NBI), while the second
laser induces fluorescent light to illuminate the
target.
Autofluorescence Imaging (AFI)
This is a technology dependent on endogenous
fluorophores within the GI mucosa, the most
important of which is collagen. Fluorophores
are naturally occurring substances that absorb
energy from short-wavelength light (blue) and
in turn emit longer-wavelength light (fluores-
cent). The patterns of fluorescence vary based
on the metabolic activity, blood flow, and bio-
chemical characteristics of the tissue, which can
be abnormal with neoplasia and inflammation.
Endoscopes with AFI capability have a rotating
filter in front of the light source that delivers
narrow-spectrum blue light (390–470 nm) alter-
nating with green light (540–560 nm) [15].
There is an additional interference filter whereby
only fluorescent and green light are filtered
through the CCD to be processed. In the result-
ing image, normal tissue appears green, and
abnormal mucosa appears dark reddish purple
in color.
Confocal Laser Endomicroscopy (CLE)
This technology is based on light microscopy, but
requires contrast agents administered intravenously
(fluorescein) or topically (fluorescein or acriflavine
hydrochloride). A laser is then focused by an objec-
tive lens to illuminate a single point in the focal
plane. Light reflected back from that focal point
will converge through a pinhole to the detector
[16]. Light that comes from outside the focal point
will be scattered and not collected. When the detec-
tor processes the light, a high-­resolution image at a
gray scale will be created showing cellular struc-
tures from the mucosal layer (250 um), but not
deeper structures. Confocal imaging can be endos-
copy based (eCLE) or probe based (pCLE) [17].
Probes are designed to pass through the endoscope
working channel toward the target tissue in the bili-
ary tree, upper GI tract, or lower GI tract.
 ptical Coherence Tomography (OCT)
O
and Volumetric Laser
Endomicroscopy (VLE)
OCT is a disposable probe-based system where
long wavelengths of light are used to penetrate into
areas of interest and create cross-sectional images
[18]. This is similar to endoscopic u­ ltrasound, but
infrared light is used instead of acoustic waves to
create high-resolution images. A single light
source emits two beams, one that is directed at the
target tissue and the other to a reference mirror.
Light is reflected from both sources and then com-
bined again at a detector to produce interference,
which is measured and translated into an image.
VLE uses technology similar to OCT, where
rapid scanning facilitates capture of images at a
depth of 3 mm with resolution to 10 mm [19]. It
is designed for use within a circumferential
lumen such as the esophagus. A balloon is passed
through the instrument channel and inflated.
Then an optical probe is passed through the bal-
loon. The balloon is rotated 360 degrees as the
probe is pulled back slightly. The probe VLE has
the potential to quickly and effectively image
large areas in short periods of time (the entire
6 cm length of the balloon in 90 seconds).
1 Endoscopic Lesion Recognition and Advanced Imaging Modalities 7

Molecular Imaging grade dysplasia (HGD), and finally EAC [26].

Thus, endoscopic surveillance with targeted biop-
Molecular imaging is an innovative technology sies of visible lesions and four-quadrant random
where targeted probes are directed to specific biopsies every 1–2 cm (Seattle biopsy protocol) is
molecules in the GI tract. A molecular probe can endorsed by international society guidelines to
be designed using a peptide, antibody, nanopar- detect dysplasia or EAC at earlier stages, receive
ticle, or other molecules [20]. Peptides are the curative therapy, and enhance survival [25, 27–
most commonly described probes in molecular 30]. Moreover, this approach can help identify
endoscopy as they offer certain advantages. patients with neoplastic lesions who are amenable
They are small for mucosal penetration, are to endoscopic eradication therapies (EETs) in lieu
safe, have low immunogenicity, and are rela- of surgery or chemoradiation. However, this
tively easy and inexpensive to mass-produce. approach has several limitations including sam-
The peptide is isolated using a bacteriophage pling errors (focal distribution of neoplasia and
library and then labeled to a fluorophore to be surveillance biopsies sample only 5% of the
applied topically during endoscopy using a Barrett’s segment), limited reliability of histo-
spray catheter. Use of a multimodal video endo- logic interpretation of dysplasia, and the associ-
scope provides images using a special fluores- ated costs, time, and labor, which may explain
cent and reflectance filter [21]. This technology why community endoscopists do not adhere to the
has the potential for more accurate in vivo diag- Seattle biopsy protocol [31, 32]. In addition, visi-
nosis and prediction of patients with higher risk ble lesions can be easily missed because they are
of progression into neoplasia before morpho- often small and focally distributed.
logic changes even develop.
 ndoscopic Inspection of BE
E
The endoscopist should inspect the Barrett’s seg-
Endoscopic Evaluation of the Upper ment in a systematic fashion to maximize detec-
GI Tract tion of visible lesions which can harbor dysplasia
or early cancer. Careful evaluation of BE with
Barrett’s Esophagus, Dysplasia, HDWLE is recommended as the minimum stan-
and Esophageal Adenocarcinoma dard to maximize detection of visible lesions [27,
33]. However, there are no randomized clinical tri-
Rationale and Limitations als directly comparing HDWLE with standard
of Surveillance Endoscopy WLE for detection of visible lesions in BE, and
The global incidence of esophageal adenocarci- this recommendation is inferred from several other
noma (EAC) is 0.7/100,000 person years and has studies [34, 35]. Longer inspection time, along
significantly increased in Europe, Australia, and with careful and organized BE inspection, may be
the United States in the last four decades [22, 23]. associated with higher number of lesions detected
Most cases of EAC are diagnosed at advanced and increased diagnosis of HGD/EAC [33].
stages, which is associated with dismal survival Careful endoscopic examination can reassure
and poor quality of life [24]. Barrett’s esophagus detection of >80% of lesions with HGD/EAC [36].
(BE) or intestinal metaplasia (IM) of the esopha- The following recommendations can be con-
gus is the precursor lesion for EAC and can be sidered to ensure high-quality care. First, con-
detected endoscopically in the presence of sider the use of a transparent distal attachment
salmon-colored mucosa extending more than cap on the tip of the endoscope to facilitate endo-
1 cm proximal to the gastroesophageal junction scopic view especially in patients with BE-related
with confirmed IM on biopsies [25]. neoplasia. Second, clean the mucosa by using the
Progression of BE to EAC involves a series of water jet channel and carefully suctioning the
pathologic changes from non-dysplastic BE fluid with minimal mucosal trauma. Third,
(NDBE) to low-grade dysplasia (LGD), high-­ inspect the suspected BE by varying insufflation
8 J. D. Machicado et al.

and desufflation to detect subtle surface irregu-

a
larities. Fourth, inspect the distal Barrett’s seg-
ment in a retrograde view. Fifth, describe the
location of the diaphragmatic hiatus, gastro-
esophageal junction, and squamocolumnar junc-
tion, as well as the extent of BE including
circumferential and maximal segment length
using the Prague classification [37]. After ade-
quate inspection of BE, biopsies can then be per-
formed. Biopsies should be avoided in normal or
irregular Z line to avoid overdiagnosis of BE in
patients who in fact have IM of the cardia which
is not associated with EAC and in areas of erosive
esophagitis until optimizing antireflux therapy, as b
reparative changes from active esophagitis can be
difficult to distinguish from dysplasia.

 niform Evaluation of Visible Lesions

U
Subtle mucosal abnormalities, such as ulceration,
erosion, plaque, nodule, stricture, or other luminal
irregularities in the Barrett’s segment, should be
sampled separately, as there is an association of
such lesions with underlying dysplasia and cancer
[38]. These mucosal abnormalities should undergo
endoscopic mucosal resection (EMR), as this pro-
vides a better sample for pathologic review and
changes the histopathologic diagnosis in approxi-
mately 30–50% of patients, compared with biopsies
[39, 40]. Moreover, EMR of suspicious esophageal
lesions represents a quality indicator of EET of BE, c
both as a diagnostic (to determine the T-stage and/or
grade of dysplasia) and therapeutic maneuver [35].
Chapter 3 of this book offers further details regard-
ing esophageal EMR techniques.
The Paris classification provides a grading
system for visible mucosal lesions, which facili-
tates uniform communication among clinicians
[41]. Visible lesions are described as follows:
protruded lesions, 0-Ip (pedunculated) or 0-Is
(sessile); and flat lesions, 0-IIa (superficially ele-
vated), 0-IIb (flat), 0-IIc (superficially depressed),
and 0-III (excavated). Lesions classified as 0-Is,
0-IIc, and 0-III are most likely to harbor invasive Fig. 1.2 Description of visible lesions in Barrett’s esoph-
cancer, whereas 0-IIa and 0-IIb are likely associ- agus using the Paris classification. (a) Flat Barrett’s
ated with early neoplasia (Fig. 1.2) [27]. The esophagus without visible lesions. (b) Paris IIa diffuse
nodularity within Barrett’s segment. (c) Paris IIa and IIc
length of the lesion should be reported using the lesion within Barrett’s segment
1 Endoscopic Lesion Recognition and Advanced Imaging Modalities 9

Table 1.2 Quality indicators for endoscopic eradication therapy (EET) in Barrett’s esophagus (BE) and suggested
median threshold benchmark
Type Metric Threshold
Pre-­procedure The rate at which the reading is made by a GI pathologist or confirmed by a 90%
second pathologist before EET is begun for patients in whom a diagnosis of
dysplasia has been made
Centers in which EET is performed should have available HDWLE and NA
expertise in mucosal ablation and EMR techniques
The rate at which documentation of a discussion of the risks, benefits, and >98%
alternatives to EET is obtained from the patient prior to treatment
Intra-­procedure The rate at which landmarks and length of BE are documented (e.g., Prague 90%
grading system) in patients with BE before EET
The rate at which the presence or absence of visible lesions is reported in 90%
patients with BE referred for EET
The rate at which the BE segment is inspected by using HDWLE 95%
The rate at which complete endoscopic resection (en bloc resection or 90%
piecemeal) is performed in patients with BE with visible lesions
The rate at which a defined interval for subsequent EET is documented for 90%
patients undergoing EET who have not yet achieved complete eradication of
intestinal metaplasia
The rate at which complete eradication of dysplasia is achieved by 18 months in 80%
patients with BE-related dysplasia or intramucosal cancer referred for EET
The rate at which complete eradication of intestinal metaplasia is achieved by 70%
18 months in patients with BE-related dysplasia and intramucosal cancer
referred for EET
Post-­procedure The rate at which a recommendation is documented for endoscopic surveillance 90%
at a defined interval for patients who achieve complete eradication of intestinal
metaplasia
The rate at which biopsies of any visible mucosal abnormalities are performed 95%
during endoscopic surveillance after EET
The rate at which an antireflux regimen is recommended after EET 90%
The rate at which adverse events are being tracked and documented in 90%
individuals after EET

proximal and distal margin of the lesion in rela- procedure quality indicators. The performance
tion to the endoscope distance from the incisors. threshold for each of these metrics can be found
The circumferential involvement should be in Table 1.2.
reported using the lateral margins of the lesion
relative to the clock position and with the endo-  dvanced Imaging Modalities (AIMs)
A
scope in the neutral position. to Enhance Surveillance
Several AIMs have been investigated to over-
Quality Indicators of Endoscopic come some of the limitations of current
Surveillance surveillance practices of BE with WLE. A
­
Defining quality indicators may help to ensure Preservation and Incorporation of Valuable
the delivery of high-quality care. In this era of Endoscopic Innovations (PIVI) statement from
value-based and quality-based healthcare, the the American Society of Gastrointestinal
development of quality indicators that bench- Endoscopy (ASGE) has outlined thresholds for
mark performance is critical. Thus, a recent study performing AIMs during endoscopic surveillance
used a methodologically rigorous process to of BE [42]. To eliminate random biopsies, an
develop valid quality indicators for EET in the AIM with target biopsies should have the follow-
management of patients with BE-related neopla- ing characteristics: (1) per-patient sensitivity of
sia. The valid quality indicators were categorized ≥90% and a negative predictive value of ≥98%
into pre-procedure, intra-procedure, and post-­ for detecting HGD/EAC, compared with the
10 J. D. Machicado et al.

c­ urrent standard protocol, and (2) specificity of

a
≥80% to allow a reduction in the number of biop-
sies compared with biopsies obtained using the
Seattle protocol. A recent meta-analysis demon-
strated that only experts in the field of BE meet
these thresholds with acetic acid chromoendos-
copy, NBI, and eCLE [43]. Thus, AIMs should
not yet replace surveillance endoscopy with ran-
dom biopsies in non-expert hands. However,
AIMs can increase the diagnostic yield for iden-
tification of HGD/EAC if added to the Seattle
protocol, as recently demonstrated in a meta-
analysis with 34% and 35% incremental yield of
HGD/EAC with virtual and conventional chro- b
moendoscopy, respectively [44]. In head-to-head
studies, both chromoendoscopy modalities have
demonstrated comparable detection of HGD/
EAC [34, 45].

Virtual Chromoendoscopy
The majority of studies evaluating virtual chro-
moendoscopy in BE have used NBI. In the largest
international crossover RCT to date comparing
NBI with HDWLE, there was significantly higher
detection of dysplasia (30 vs. 21%) with NBI
[46]. Several classification patterns (Kansas [47],
Amsterdam [48], Nottingham [49]) have been
proposed to predict histopathology based on NBI
surface patterns, but the proposed criteria are
complex, and validation studies had disappointing
results. An international working group recently
developed a simple and internally validated sys-
tem to identify dysplasia and EAC in patients with
BE based on NBI results [50]. This system, known
as the BING criteria, can classify BE with >90%
accuracy and a high inter-observer agreement.
Regular mucosal patterns were defined as circu-
lar, ridged/villous, or tubular patterns; and irregu-
lar mucosa was marked by absent or irregular
surface patterns. Regular vascular patterns were
defined by blood vessels situated regularly along
or between mucosal ridges and/or those showing
normal, long, branching patterns; irregular vascu-
lar patterns were marked by focally or diffusely
distributed vessels not following the normal archi-
tecture of the mucosa (Fig. 1.3). Additional stud-
ies are needed with BLI, FICE, and iScan to
assess their utility and interpretation.
Fig. 1.3 Abnormal NBI pattern of visible lesions in
Barrett’s esophagus. (a) Paris IIa and IIc lesion with
abnormal NBI pattern from 9 to 1 o’clock position and
with normal NBI pattern from 1 to 9 o’clock position. (b)
Paris Is lesion in the GE junction with abnormal NBI
pattern
Conventional Chromoendoscopy
The dyes most commonly used for conventional
chromoendoscopy in BE are acetic acid and
methylene blue. No standardized classification
criteria have been established for any dye. In the
meta-analysis by Thosani et al., acetic acid chro-
moendoscopy was found to meet the thresholds
established by the ASGE PIVI (sensitivity, 97%;
negative predictive value, 98%; and specificity,
85%) and can be used in clinical practice at least
by experts [43]. In contrast, methylene blue chro-
moendoscopy fails to meet these thresholds (sen-
sitivity, 64%; negative predictive value, 70%; and
specificity, 96%) and does not increase the diag-
nostic yield over random biopsies for the detec-
1 Endoscopic Lesion Recognition and Advanced Imaging Modalities
tion of HGD/cancer [43, 51]. Furthermore, the
safety of methylene blue has been questioned as
one study suggested that it can cause induce oxi-
dative damage to DNA when photosensitized
with light [52]. Acetic acid causes disruption of
the columnar mucosal barrier in minutes, leading
to whitening of the tissue with vascular conges-
tion and accentuation of the villi and mucosal
pattern when the acid reaches the stroma. The
whitening effect in dysplastic areas is lost earlier
than in the surrounding mucosa, which helps
identify neoplastic areas.
 ole of AFI, CLE, VLE, and OCT
R Compared with noninvasive tests, endoscopy
Other AIMs have been investigated, but none
appear to be ready for clinical application at the
present time [53]. AFI is limited by its high false
positive rate, fair to moderate inter-observer
agreement, and minimal incremental diagnostic
yield over the Seattle protocol [54]. CLE has the
potential to confirm a real-time diagnosis of neo-
plasia without the need for histology, which
could lead to immediate endoscopic therapy
without biopsies, such as same-session EMR or
ablative therapy. Use of eCLE meets the ASGE
PIVI thresholds but is no longer commercially
available, while pCLE does not meet these
thresholds [43]. A meta-analysis recently showed
that VLE is associated with a marginal increase
in detection of HGD/cancer and has very high
rates of false positive results [55]. However, OCT
and VLE can evaluate epithelial thickness and
buried glands, which can predict prolonged or
failed ablation, and be useful in post-endoscopic
ablation surveillance [56, 57]. The clinical appli-
cability of these AIMs needs to be better defined
before recommending their routine use in sur-
veillance of BE.
 astric Intestinal Metaplasia,
G lesions such as light changes in color (redness or
Dysplasia, and Cancer
Rationale of Screening
and Surveillance
Gastric cancer (GC) is one of the most frequent
and lethal malignancies worldwide. The intro-
duction of universal screening in Korea and
11
Japan is associated with earlier GC diagnosis
and lower cancer-related mortality [58–60].
Thus, universal screening is warranted in indi-
viduals from high-­incidence countries, but is
more selective in low-­incidence countries based
on demographic data and Helicobacter pylori
status [61]. This translates in higher rates of
early GC diagnosis – lesion confined to the
mucosa or submucosa – in countries with
national screening programs compared to
Western countries (60 vs. 20%), which can be
safely treated by mucosal or submucosal endo-
scopic resection [62, 63].
is the best and most cost-effective screening
modality to detect precancerous lesions and GC
[64]. The development of intestinal-type GC is
preceded by a cascade of several precancerous
events that range from non-atrophic gastritis,
multifocal atrophic gastritis (AG), IM, dysplasia,
and ultimately GC [65]. Management and sur-
veillance intervals are determined based on the
individual histologic risk of progression into
GC. A population study from the Netherlands
illustrated this by showing an annual incidence
of GC of 0.2% for AG, 0.3% for IM, 0.6% for
mild-­moderate dysplasia, and 6% for severe dys-
plasia [66]. The risk of GC with AG and IM can
then be further stratified based upon location,
severity, and extension of the lesion. Patients
with widespread atrophy or IM pose high risk of
cancer and require endoscopic surveillance
every 3 years. Patients with LGD should be fol-
lowed every 12 months, while those with HGD
should be followed every 6 months or have the
lesion resected [67].
 ndoscopic Evaluation of Stomach
E
Lesions
Endoscopic findings suggestive of superficial
pale faded), irregularities of mucosal folds,
absence of submucosal vessel pattern, and spon-
taneous bleeding should be carefully examined
(Fig. 1.4a) [68]. Well-demarcated border or irreg-
ularity in color/surface pattern is more suggestive
of malignant lesions. However, the sensitivity of
WLE for identifying GC is ~80% and can miss
12
a
b Diagnostic accuracy of NBI is maximized with
c Further research is needed to establish a stan-
Fig. 1.4 Representative endoscopic images of gastric
neoplasia. (a) Paris Is and IIc friable gastric mass. (b)
Ulcerated gastric mass with abnormal NBI pattern. (c)
Chromoendoscopy with methylene blue determining outer
margins of early gastric cancer that was ultimately resected
small or flat lesions [68]. If endoscopic examina-
tion is normal, at least five nontargeted biopsies
should be obtained according to the Sydney
system in the antrum (×2), incisura angularis
­ cancer [74].
J. D. Machicado et al.
(×1), and body (×2) [69]. Biopsy specimens
should be submitted in separate jars labeled by
region of the stomach sampled. This protocol is
sensitive for detection of atrophic gastritis and
intestinal metaplasia when performed in high-
risk populations [70].
 ole of Virtual and Conventional
R
Chromoendoscopy
After recognition of suspicious lesions with
WLE, virtual and conventional chromoendos-
copy help in lesion characterization and high-
light lesion outer margins (Fig. 1.4b, c).
magnifying endoscopy, by analyzing the micro-
vascular and microsurface patterns separately.
In a recent meta-analysis of 14 studies, magni-
fying NBI showed high sensitivity (86%) and
specificity (96%) for detection of early GC [71].
This showed to be especially helpful for
depressed or small lesions ≤10 mm in size,
which can be more accurate than with conven-
tional chromoendoscopy [71, 72]. Magnifying
NBI can also delineate the lateral margins of a
lesion even when conventional chromoendos-
copy is not able to determine the margins [73].
dard NBI classification system to reduce various
biases and improve its diagnostic accuracy in
the assessment of gastric lesions. For example,
fine network patterns with abundant microves-
sels connected one to another are characteristic
of adenocarcinoma, and a corkscrew pattern
with tortuous isolated microvessels is character-
istic of poorly differentiated adenocarcinoma.
Conventional chromoendoscopy with indigo
carmine and acetic acid has been used in clinical
practice for evaluation of gastric lesions, but
delineation of margins is not superior to NBI.
 ole of AFI and CLE
R
The role of other AIMs has not been fully estab-
lished in the screening or surveillance of
GC. AFI has limited clinical value due to its high
false positive rate and low specificity. CLE has
shown encouraging results for the in vivo diag-
nosis of premalignant lesions and early gastric
1 Endoscopic Lesion Recognition and Advanced Imaging Modalities 13

Duodenal Adenomas and Cancer

a
Rationale for Screening
and Surveillance
Duodenal cancer is rare among all GI malignan-
cies. For several years, it has been recognized
that this malignancy arises from an adenoma-to-­
carcinoma pathway similar to colorectal cancer
(CRC) [75]. Duodenal adenomas should be cate-
gorized as being ampullary or non-ampullary and
as sporadic or arising in the context of familial
adenomatous polyposis (FAP). The lifetime risk
of duodenal cancer in patients with FAP is
5–10%, while in the general population, it ranges
from 0.01% to 0.04% [76]. In addition, duodenal b
adenomas are diagnosed in up to 90% of FAP
patients, can be multiple, and involve the ampulla.
Thus, endoscopic screening and surveillance are
recommended in FAP patients [77].

Endoscopic Evaluation
Endoscopic evaluation should be performed
using a distal attachment cap and often requires a
duodenoscope to definitively determine lesion
relationship to the major and minor papilla.
Morphologic features including the size of the
lesion, number of folds affected, percent of cir-
cumference involved, and Paris classification c
should be determined to decide on management
(surveillance, endoscopic resection, or surgery)
(Fig. 1.5a, b).
The Spigelman staging system is widely used
to evaluate the severity of duodenal polyposis
and consists of a five-grade scale (0 to IV) based
on polyp burden (number, size, histologic type,
and degree of dysplasia) [78]. The 10-year risk
of cancer can be as high as 36% for Spigelman
stage IV disease, but much lower (≤2%) for
lower stages [79]. Thus, endoscopic staging
helps to determine the surveillance and treat-
ment strategies for FAP patients with duodenal Fig. 1.5 Duodenal lesions. (a) Ampullary adenoma
adenomas [77]. examined with duodenoscope. (b) Large duodenal ade-
noma in the second portion of the duodenum using for-
Diagnosis of adenoma with HDWLE and for- ward view endoscope and a distal attachment cap. (c)
ceps biopsies is highly sensitive (>90%), but the Representative image of duodenal adenoma using NBI
sensitivity for detection of adenocarcinoma is
lower, and biopsies can miss up to 30% of ulceration, friability, or induration. Polyps larger
ampullary cancers [80, 81]. Cancer should be than 1 cm have also been associated with
suspected in the presence of irregular margins, advanced histology.
Another random document with
no related content on Scribd:
 One other thing, the oysters at Kurrachee are not bad, particularly
when you know you won’t get any for five years to come.
We were much struck with the beauty and cheapness of the black-
wood furniture here. This beautiful carved furniture is now, so they
told us, out of fashion in India, and may be had for a song; the worst
of it is, it is brittle and bulky. We went to one of the dealers and
bought a hundred pounds’ worth, and for this sum our Persian home
would have been sumptuously furnished; we made a contract with
the seller, in writing, to pay him ten per cent. extra for the whole to be
delivered free on board, in cases not weighing over three hundred
pounds each, and not measuring more than four by three feet; if
otherwise as to size and weight, the bargain to be off. The afternoon
before the Arcot left, we, on our return from our drive, found the
dealer on board, and he smilingly informed us that the furniture was
all in the hold; he then presented his bill. I smelt a rat, as I had told
him I must see the cases and weigh them before shipment. Luckily I
did not trust the fellow, for some of the cases weighed eight hundred
pounds, and of course could not have gone up country in Persia. I
refused to take delivery, and was threatened with the law. But it
appears that the dealer, on showing his contract to a solicitor, was
told he had no case, and reluctantly removed his packages. I was
sorry the man lost by the affair, but packages of huge size and
weight were useless for mule carriage. So we lost our black-wood
furniture.
We had ten days of the coast of Belūchistan and the Persian Gulf,
stopping at Linga, Bunder Abbas, etc., though we did not go ashore,
having no desire for some hours’ pull, in the sun, in an open native
boat on a very rough sea.
At length Bushire was reached, and after a seven weeks’ voyage
from the time we left London, we landed in Persia; and were
hospitably entertained at the Residency, where Colonel Prideaux,
one of the whilom captives of King Theodore, was Acting Political
Resident in the Persian Gulf; Colonel Ross being at home on leave.
I was anxious to draw pay again, which I could only do on
reaching my station, Shiraz; and to escape the rains: so I engaged a
muleteer, and finding two of my old servants and a boy in Bushire,
we started with thirty mules, ourselves riding muleteers’ ponies.
Our stay in Bushire lasted only four days, and at some personal
discomfort we started, hoping to avoid the rains which were due in a
fortnight.
 CHAPTER XXXII.
FROM THE PERSIAN GULF TO ISPAHAN.

Our start for Shiraz—Camp out—Borasjūn—Spring at Dalliké—Kotuls—Kazerūn—

Buy a horse—A tough climb—Place of Collins’s murder—Arrive in Shiraz—
Hire a house—Settle down—Breaking horses—Night marching—Difficulties of
start—Mūrghab—Find our muleteer and loads—Abadeh—Yezdikhast—
Koomishah—Mayar—Marg—Arrive in Julfa.

We ourselves, our small dog “Pip” in a cage, and our canaries—

almost unknown in Persia—and seventy-two tiny “avadavats”
(bought at Kurrachee for three rupees), left in a boat for Sheif, on an
estuary of the gulf, thus avoiding the Macheelah plain, a dreadful
march of mud and water, and shortening the journey to Shiraz by two
stages.
After four hours’ pull and sail in the burning sun we reached Sheif.
This appeared simply a mud hut on the beach. There may have
been a village, but we saw nothing of it. Here we mounted our sorry
steeds.
Some three hours after we caught up with the rest of our loads,
which had struggled out through the Macheelah the day before. All
the mules were knocked up, and my wife was fatigued with the
unwonted exertion of riding a muleteer’s pony. This is at any time
hard work for a man, for the beast does not answer the bit, bores
continually on it, and strokes with a light-cutting whip are quite unfelt.
There is also a struggle among the riding ponies, more used to loads
than riders, as to who shall be last of all; in which a lady’s pony is
generally the victor.
It had been impossible to buy a hack suited to a lady in Bushire. I
had been asked English prices for the ghosts of steeds—quite
honestly, however, for Bushire prices are much higher than Shiraz
ones. So after my wife’s trying my pony, the cook’s, and the head
muleteer’s, I got one of our escort, a good-natured fellow, clad in
rags and smiles, to lend her his. This “yabū” (common pony) was at
all events easy, and had a canter in him at need.
At sunset the muleteer informed me that we were twenty miles
from our halting-place, Borasjūn, and that the mules could do no
more. It was hopeless to attempt to go on, as my wife was as tired
as the mules. Night (happily a warm one) was coming on; there was
no sign of any shelter for miles, the only thing visible on the sandy
plain being the distant date-groves, and these are of course no
protection. The road was dry, which was something, and we had
plenty of food with us; so we halted, spread our carpets, had tea,
and later on dinner, and camped out—rather a dreadful first day’s
travelling in Persia for a lady, to sleep without shelter, and in her
clothes, in the middle of the road, after travelling since ten a.m.
However, there was nothing else for it. The Sheif road is a very
unfrequented one, and the country was safe and undisturbed. It was
a lovely night, not a breath of wind. At four a.m. we had tea, and
started at five, getting into Borasjūn at ten.
For the time of year the luxuriant vegetation near the village was
extraordinary; it was now late in October, the heat was great, and the
amount of moisture in the air somewhat oppressive. We found
capital rooms in the caravanserai, and the clerk at the telegraph-
station made us welcome to high tea, being rather indignant that we
had not come straight to the office. After that we started again, and
reached our halting-place at midnight.
At Dalliké is a rest-house maintained by the Department for the
use of the employés. A short distance from the rest-house at Dalliké
is a hot spring of clearest water; the temperature is about one
hundred degrees, and being in a circular natural basin, some four
feet deep in the centre, and in a place where no warm bath can be
had, it is a favourite halting-place for travellers. Besides giving a
comfortable bath, there is a peculiarity that I have seen nowhere
else; the basin is full of myriads of fish about the size of whitebait.
On dipping the hand in, they at once cover it, and in a minute it is
quite hid from sight by crowds of tiny fish: they have no fear, and can
be removed in handfuls. On stripping and entering the basin a
curious effect is produced by one’s limbs becoming black with the
fish, which nibble at the skin, and only leave it when you plunge
violently. On becoming still, one’s body is again entirely covered with
fish.
From thence we travelled by day only. At each village I tried to get
a pony for my wife, but nowhere could I succeed, though I was ready
to buy anything not absolutely vicious.
Mr. M⸺ kindly gave us quarters at the telegraph-office at
Kazerūn, and here we rested a day.
The kotuls, or passes (literally ladders), well known throughout the
country, had astonished my wife: they are terrible places to ride up,
and nearly impossible to ride down: she, however, was determined
not to be beaten, and had ridden them all. We had been especially
fortunate in our weather; no rain, though we saw many clouds, and it
was imminent.
As I was looking out of window at the Kazerūn telegraph-office, I
saw a man mounted on a handsome grey mare. I hallooed, and he
stopped. I went down and parleyed. The mare was sound, and six
years old, fast, light-mouthed. I felt that, if free from vice, she was
what my wife wanted. I rode her, and succeeded in getting the man
to close for seven hundred and fifty kerans, about thirty pounds. I
gave him fifty kerans in cash, and a bill on Shiraz for the remainder. I
never regretted the purchase. The mare was all that a lady’s horse
should be. She was tall for Persia, being fourteen three in height, no
goose rump, and very handsome. Her mouth soon got very light, and
her only fault, a very trifling one, was that she carried her ears badly.
My wife and I constantly rode her for four years, and after marching
twenty-eight stages from Ispahan to the Caspian on her with a side-
saddle on, I handed her over in good condition, having sold her for a
fair price.
Of course the journey to my wife became now a pleasure. She had
a horse of her own that did not jolt, and who at a word or a shake of
the rein would canter or gallop, instead of the thwack, thwack of the
muleteer’s yabū. By fancying the troubles of a lady compelled to
cross the Rocky Mountains on a small Hampstead donkey, with a
tendency to fall, one might form some faint ideas of my wife’s trials in
getting over her five days’ climb from the coast to Kazerūn. We here
left the date-groves, which had been numerous till now.
Two more passes remained to us—the Kotul Dokter and Kotul Peri
Zun (the Passes of the Virgin and the Old Woman). That of the Old
Woman is very bad indeed, and it is a wonder how loaded mules do
get up it—miles of awful road among loose rocks and stones, and
then steep zigzags of paved road up a perpendicular cliff. Awful
work! We did it, however, and did it in the night; for we had been
stopped by a great firing of guns and alarm of thieves in the beautiful
Oak Valley, and so lost the daylight. We avoided a great part of the
pass by scrambling up “Walker’s Road,” a straight path under the
telegraph-line, well enough to walk down, but almost impossible to
ride up, particularly at night; fortunately, we had a moon, and the
weather was fine. My wife, however, was compelled to dismount
twice, and we lugged, shoved, and dragged the horses up, the
mules, of course, going by the high-road: at last we did get in, but all
tired out.
Next day a longish march brought us to the hill leading down into
the plain of Desht-i-arjeen. It was on this hill, some eleven years
before, that Major St. John[33] was riding, when a lion suddenly
sprang upon his horse’s hind-quarters. St. John had only a very
small Colt’s revolver with him at the time, when suddenly he saw a
lioness some thirty yards in front; he cracked his whip and shouted
at her, thinking that she would bolt. She charged; sprang, and came
down under his foot. With so small a pistol it would have been
useless to fire, so he spurred his horse, which, however, would not
move. The lioness now attacked from the rear, standing on her hind-
legs, and clawing the horse’s hind-quarters; he then jumped off,
getting, however, one slight scratch.
The horse now plunged and reared, knocking over the lioness on
one side, and the man on the other. The horse now was moving
away. The lioness stared at the horse, the man at her; then St. John
fired a couple of shots over her head to frighten her, but without
effect; she sprang again on the horse’s hind-quarters, and both were
lost to view. After an hour St. John found his horse, who, however,
would not let him mount. He drove the animal to the little hamlet,
where he found a single family, but the fear of beasts would not let
the head of it come out to search for the horse; however, next
morning he was found quietly grazing; his quarters and flanks were
scored in every direction with claw-marks, and one wound had
penetrated the flesh, which St. John sewed up. In a week the horse
was as well as ever, but bore the marks for the rest of his life.
I have taken the liberty of abridging Major St. John’s own account
of this real lion story from his note to the article “Leo,” in the work on
the ‘Zoology of Persia,’ volume ii., edited by Mr. W. Blandford, the
well-known naturalist. At the time the affair took place, Major St.
John was superintendent of the Persian Telegraph Department;
shortly after, I had the honour of serving under him in Shiraz for
some time, and was indebted to him for many kindnesses. I saw the
horse some two years after the affair, and the scars were very
apparent. I did not tell my wife this story till we had passed the stage,
and there was no more lion country.
Our next march brought us to Khana Zinyun, where a handsome
caravanserai has been built by the Muschir, the great man of Shiraz.
Before reaching it we passed a pole, marking the place where the
body of Sergeant Collins was found, after his murder by highway
robbers in the famine time.
The next morning we rode into Shiraz, and had no sooner reached
our house than the expected rain, which had happily held off during
our journey, began to fall, the sky was overcast, and continuous
storms took place, which lasted for a fortnight. Thanking our lucky
stars, we prepared to make ourselves as comfortable as possible,
and set to to unpack and arrange our quarters.
When we arrived at Shiraz, the superintendent’s house, which was
in a garden just out of the town, was kindly placed at our disposal. In
a few days I succeeded in hiring a good new brick-built house. We
bought a few carpets, and moved into it.
My colleague, Dr. Odling, kindly gave us the loan of his furniture
for the six months he expected to be away on leave, which was a
good thing, as one cannot get furniture made in Shiraz, and
everything has to be ordered in India or Ispahan. In the latter place
there are fairly good carpenters.
Our house was the property of the superintendent of the
Government powder mills, and for ten tomans, or four pounds a
month, we hired it for the six months that we should have to stop in
Shiraz during my colleague’s leave of absence. On his return it had
been arranged that we were to go to Ispahan, where we were to be
permanently stationed.
The house was formed of a quadrangle, having rooms on three
sides, and a dead wall at the end.
The greater portion of our kit being in tin-lined cases, and intended
for our permanent abode, we did not unpack. After about a week we
had settled down into working order, obtained a fair cook, and old
and respectable servants; put our little “Crescent” car together, a
small low dog-cart, built by McMullen, of Hertford, which has the
great advantage of taking to pieces, being easily put together, easily
packed in small and light parcels, and was thoroughly seasoned; and
stood the extraordinary dryness of the climate without cracking or
warping, which is saying a great deal.
The next thing was to get a trap-horse. The roads are mere tracks,
and very rough and heavy, and a strong animal was required. I
managed for twelve pounds to pick up a cobby pony of thirteen two. I
had him gelded, as even in Persia it is considered unsafe to drive an
entire horse; and he with another animal I gave seven pounds for,
were handed over to the coachman of the Muschir to be broken. I
had vainly attempted to break them myself with a gun-carriage, for
my little dog-cart was too light and pretty to risk a smash with. After a
fortnight the Muschir’s coachman informed me that both were quite
broken. I suggested that he should drive them in his master’s trap, a
big brougham; but he evidently feared an accident, and gave up the
job in despair. Another fellow, however, took it in hand, and after a
few days I rode out some five miles, and was delighted to find that
one of the ponies was fairly broken, the little grey one. The other one
was hopeless; he, however, answered well as a servant’s drudge.
 We were able now to take frequent drives, though a long one, from
the heavy state of the roads, generally kept the pony in the stable for
a couple of days. Still it was nice driving over the plain, when once
outside Shiraz and its environs.
My wife found the life amusing from its novelty; and as we were
not to remain in Shiraz during the summer, which is the unhealthy
time, our stay was enjoyable enough.
As Shiraz has been previously described, there is nothing more to
be said than that the winter soon slipped away, and the spring, the
most enjoyable part of the year in Shiraz, arrived, bringing the jaunts
to gardens so usual there.
My colleague, anxiously expected, did not, however, arrive till July,
and the weather had then got so hot as to necessitate our marching
up to Ispahan by night. As I have not noticed this mode of travelling
before, I cannot do better than quote my wife’s diary, which gives her
experience of the matter.
“On Tuesday, July the 17th, 1877, everything being ready, we
were informed that our muleteer was unable to start, his mules being
a hundred miles off; so after much delay we found another, and
engaged with him for forty mules, each carrying three hundred and
fifty pounds, at the rate of seven hundred pounds, from Shiraz to
Ispahan, for two pounds eight. Besides this, our cook had three
mules for himself and his family, and with our own three horses, we
shall form quite a respectable cavalcade.
“Shiraz to Zergūn, 24 miles.—On Wednesday the 18th, after
weighing all our cases and tying them up with the charwardar’s
ropes, at six p.m. we rode out, accompanied by Mirza Hassan Ali
Khan (our friend the British Agent here); having started all our
servants, bedding, and road-kit, on six mules. We kept one servant
with us, and a gholam (or irregular cavalry man), having an order
from the Governor of Fars on all the chiefs of villages to vacate their
houses if needed, and to find us with food and forage, of course
being paid for them. No sooner had we cleared the town, than, to our
disgust, we found our pantry-man surrounded by his weeping
relatives, his wife and our cook’s lady being unable to tear
themselves from their sympathising friends. This, of course, did not
matter, but, alas! the mule-load with our bedding was with them.
“My husband, by a free use of threats, compelled Abdul Hamid
(the pantry-man) to start, the gholam following in charge of the mule
which carried Hamid’s wife and the cook’s wife and daughter, a girl of
nine; all closely veiled, and weeping copiously.
“On getting about a mile out, the cage containing eight canaries,
two goldfinches, and eighteen avadavats, which we had got at
Kurrachee, was given to Hamid to carry in front of him; but as it was
his first journey and attempt at riding, after about a couple of
hundred yards he and the cage came crash to the ground, some
avadavats escaping; so we gave the cage to a villager to carry on his
head; we then bid good-bye to Mirza Hassan Ali Khan; and my
husband now was occupied in whipping on the mule of helpless
Abdul Hamid, to get him up to the other servants, in which he
succeeded after we had gone twelve miles. From the packing, and
excitement about getting mules, and not having had anything since
breakfast at one p.m., we were very tired; as were the horses, which
we had been from peculiar circumstances obliged to keep on grass
for the last three weeks.
“The road was a good one, but the moon gave very little light, and
we could not canter on that account, and for fear of the servants
lagging. This stage was formerly a very bad one, but the road was
made good last year, when the king was expected in Shiraz.
“At last, at eleven p.m., we reached the chupper-khana (or post-
house) at Zergūn, where we took the bala-khana (or upper room);
we drank some milk, and lay down till our dinner—a roast fowl and
potatoes, and custard pudding—was ready, which was not till nearly
one hour after midnight.
“After that we slept heavily till seven a.m., when we were glad of
our tea and devilled fowl. We had breakfast at twelve, and vainly
expected the mules all day; and after seeing our horses groomed
and fed, we dined at seven on soup, boiled fowl, and caper sauce,
Irish stew, custard pudding, figs, and grapes; ice, of course, was not
procurable; our wine we brought with us, and we always have a flask
full of it for the road.
“Just before starting, at half-past two a.m., in the dark, we had a
basin of soup; and having got all our servants off, started for our
second stage.
“At three we got off, and after nearly missing the road, we
marched along with our mules till dawn, when we cantered over a
good and level road, and feeling tired at sunrise, got down and had
some cold fowl and wine. Another hour brought us to Hadjiabad,
where we found two comfortable rooms occupied by some small
official, of whose carpets and water-skin we took possession (by
means of a few kerans), and slept till breakfast. We again rested till
five p.m., when we had soup, and started, reaching Sivend at nine
p.m., seven hours’ journey, thirty-two miles from Zergūn.
“To our disgust we found that the inspector had locked every room
in the telegraph-office, he being on leave; so we took up our quarters
on the verandah, which was fairly cool. In the morning still no mules,
so we moved over to the best house in the village, where we are
very comfortable. We were glad to give our horses a rest, for the
sudden exertion after grass had done them no good. We passed our
day in seeing our saddles cleaned, the washing of ‘Pip,’ and writing
letters.
“At night, the place being full of cats, who attacked the birds, C⸺
shot two and missed two more. They, however, ate one canary, and
the wires being broken, C⸺ had to pursue another bird over many
roofs, catching him at last unhurt.
“Sunday.—Still no news of mules; sent a ‘kossid’ (or foot-
messenger) with a letter to Shiraz asking for steps to be taken to get
them out. The man is to get half-a-crown for walking the fifty-six
miles in eighteen hours, and to bring back an answer!
“Monday.—Venison for breakfast. We got a welcome present of
snow last night, and by laying the top of the table on the bird-cage,
succeeded in defying the cats.
 “At twelve p.m., Wednesday, having no news of our mules, we
engaged two muleteers, started, and in two hours marched to
Kawamabad, eight miles, fording the river Bendamir half-way. A fair
road. The weather changed here; it was very chilly on arrival, and
cool and windy all day.
“Left Kawamabad at six p.m., Thursday, and reached the tomb of
Cyrus at twelve, where we rested a little, and ate some fowl, and
found the night very cold. The monument is like a huge dog-kennel,
of great squared stones, on a stone platform. Ussher states the tomb
itself to be forty-three feet by thirty-seven. There are seven stone
steps, which diminish in thickness as one ascends. The kennel-like
edifice at the top is twenty-one feet by sixteen only; the thickness is
five feet. The interior dimensions are ten feet long, seven wide, and
eight high. There are no inscriptions. The door is four feet high only.
There are the remains of twenty-four columns, six on each side.[34]
“Got to Murghāb, twenty-eight miles, at two a.m. A very long and
fatiguing march; several passes. This place is celebrated for carpets,
but we failed to obtain any. In the centre of the village there is a large
piece of turf like a cricket field—the only piece of turf I have seen as
yet.
“Left at six p.m. A bad road, with several passes, till half way, when
it became a sort of steppe; here we came on a number of mules
grazing: we fortunately sent a man to ask whose they were, and they
turned out to be our loads and the missing charwardar,[35] who had
passed us when we halted at Sivend.
“Our difficulties will now be much less, as with lots of muleteers we
shall get loaded and off quickly, and our bedding mule (which at
present carries my fortnightly box, C⸺’s portmanteau, a carpet,
two heavy chairs, and a table, a champagne box full of wine, an
india-rubber sack full of odds and ends, my little black bag, a heavy
cage for Pip, and the birds’ cage a yard long, besides our bedding;
and its pack-saddle weighing thirty pounds) will go much lighter: we
shall also get our bath, which had gone on with the loads.
 “We reached Dehbeed, twenty-six miles, at two; we had soup and
fowl on the road, and were very glad to get in. There is nothing here
but a chupper-khana, a caravanserai (in ruins), and a telegraph-
office. It is delightfully cool and windy, the water, too, is like ice, and
very good. Nothing to be got but bread; but we had supplies with us.
Left at nine p.m., and over a fair road with two small passes to Konar
Khora, twenty-four miles. This is a more lonely place than the last;
water only and cucumbers to be got; a post-house and caravanserai
(in ruins) the only houses, and nothing nearer than twenty-four miles.
The flies so hungry here that they bite and hurt.
“Left at six p.m., over a level plain and splendid road; stopped at
Faizabad, twenty-four miles, at twelve midnight, and taking the best
house, a very good one with two rooms overlooking a garden, slept
again in the open air; much warmer here; meat to be got again; we
are now out of the wilderness; had a really comfortable rest here; left
at ten p.m.
“Reached Abadeh, sixteen miles, at two a.m. Our groom had
lagged behind with the horse-clothing, and the other two men had
lost their way; so we, the cook and the bedding, arrived alone. C⸺
had to tie up the horses as best he could, and we took an hour to get
to bed. The road was good, and in the morning we got a fair mutton
steak, but no fruit was to be had. Left at ten p.m. Abadeh is a large
place enclosed in a mud wall, the post-house being outside; it is
celebrated for spoons carved in wood in a wonderful manner, but
they are useless and dear. Here Mr. Carapet, of the Department,
hospitably entertained us and gave us a capital dinner, and a leg of
mutton for the road.
“Over a long plain, twenty-four miles to Shūrgistan; put up in the
guest-house of the shrine; arrived at half-past three. Nothing to be
got here; so hot that we had to go downstairs—the lower rooms are
cooler. Left at half-past eight p.m., and over a long plain to
Yezdikhast, twenty miles, where we arrived at one. A fine
caravanserai; got a good room on the roof. People here report the
king’s death, and there is a panic. The place is peculiar, being built
on a high cliff which is in the middle of a deep gorge nearly a mile
wide, a small river running down the middle. Our gholam left us here,
this being the frontier of Fars.
“Left at six p.m. with three guards on horseback, the road reported
to be not safe. This stage is where C⸺ was robbed, and where the
Bakhtiaris make their incursions. Twenty-six miles to Maxsud Beg: a
long road. Arrived at two a.m. Took the guards the whole way, or we
should never have found the chupper-khana, which is off the road.
Got some good bread here at a small village. Found a load of ice
sent us from Kūmishah; a welcome present from the inspector there.
A good room twice the usual size, very cool; a high wind all day and
night. Left at half-past seven for Kūmishah, sixteen miles, a fair road,
wind very high and cold. Arrived at half-past eleven, after much
trouble in a rocky valley, servants losing themselves and coming to
grief. The brown horse went lame (from a projecting nail) and had to
be led. Were hospitably entertained by the inspector, Sergeant
McIntyre, who gave us a breakfast of many dishes. A large place,
but in ruins; very cool; a fine shrine and resting-place for pilgrims,
accommodating some thousands.
“Left at half-past five; twenty miles over a dreary plain to Mayar, a
large caravanserai, and a village which is the Shah’s personal
property (in ruins); arrived at half-past eleven. No beds, as we had
got in two hours before the loads. I was so tired, I lay down and slept
in my habit. We were all too tired to eat, and the servants were dead
beat; so we went without dinner, ordering a good breakfast to be
served as soon as we should wake. Being determined to try and get
into Ispahan (or rather Julfa) to-morrow, an early move was
necessary; we started at five p.m., and reached Marg caravanserai,
twenty-eight long miles, at two a.m.; here my husband determined to
halt for a few hours, and I slept till dawn in a wretched hole. There
were good quarters in the chupper-khana (post-house), and the
post-house and caravanserai are all that Marg consists of; but we
were told that glanders had been rife there, and we were afraid to
trust our horses in the place.
“At dawn our caravan arrived; the muleteers and servants swore
they could do no more, but a little persuasion and a promise of a
present got them off, after feeding their mules, and we cantered on,
reaching our quarters at ten a.m., after a hot ride in the sun. By this
forced march we escaped the meeting with new friends, who
otherwise, had we arrived the next day, as was calculated, would
have ridden out to meet us. I lay down at once, and the mules and
their riders dropped in one by one, each man on his arrival seeming
to shout louder than his predecessor.
“But our journey was over, and I trust I may never again have to
march three hundred miles at night.”
 CHAPTER XXXIII.
JULFA.

Hire a house—Coolness of streets—Idleness of men—Industry of women—Stone

mortars—Arrack—Hire a vineyard—A wily Armenian—Treasure-trove—The
“Shaking Minarets”—A hereditary functionary—A permanent miracle—Its
probable explanation—Vaccination—Julfa priests—Arrack as an anæsthetic—
Road-making—Crops of firewood—Fire temple—Huge trees—The racecourse
—Disappearance of ancient brick buildings—Donkeys—Healthiness of Julfa—
Zil-es-Sultan—His armoury—Prospects of the succession to the throne—Bull-
terriers—Mastiffs—Politeness and rudeness of the prince.

After a considerable amount of diplomacy, we managed to secure

a fine large house with a good garden and stabling, in the principal
and best street of Julfa. My wife was pleased with the cool climate of
Ispahan, the abundance of water, and the rows of trees with which
each street is planted.
The Armenian is a thrifty fellow, and plants the Zoban-i-gūngishk,
or sparrow-tongue, a kind of willow, on either side of the small ditch
which runs down the side or centre of the streets; this ditch brings
the water for the irrigation of the gardens, and by planting the trees
he obtains shade and fire-wood; for the “Zoban-i-gūngishk” is the
best of all woods for fuel, and the roots keep the ditch-bank solid and
in good repair. Cool and pretty as the streets look from the
unaccustomed masses of foliage, one soon finds that one is in a
Christian village. Sheep and oxen are slaughtered all down the
principal street, in the most public manner; and on Saturday night
especially drunkards are common, while swarms of loafers, generally
men who live on small pensions from relatives in India, lean with
their backs against the wall, basking in the early sun, or sprawl in the
shade during the heat.
In each doorway sit or lounge the women, but their hands and
tongues are busily employed; they knit socks as long as daylight
lasts; some widows even maintain a family by this industry. With
nose and mouth hidden, poorly fed, but well and warmly clad, the
Armenian woman makes up by her industry for the laziness of her
husband; she sweeps the house and yard, cooks the food, makes
the clothes, bakes the bread, makes wine, arrack, flour—for this is
generally ground in a hand-mill by the poor; and the rest of her time
is filled up by knitting. These Armenian women are notable
housekeepers, and though generally ignorant and ungraceful—a girl
is never even fairly good-looking after seventeen—they are hard-
working and very virtuous.
In most of the quarters of Julfa may be seen at the roadside huge
stone mortars for the pounding of rice, by which means it is extracted
from the husk; these are the remains of the teeming Julfa of other
days, when it was a large city with twenty-four crowded parishes,
each with its church, the ruins of most of which are now all that
remain of the parishes. You seldom see a Julfa man pounding at one
of the huge mortars; he prefers to hire a Mussulman or villager to do
the heavy work for him, and as he does not care to part with his
money—“Thrift, thrift, Horatio!”—the payment is generally a glass of
spirits. These spirits cost nothing, as each man makes his own wine,
which he sells, and from the refuse his arrack, which he drinks.
Armenians seldom drink wine; it is not strong enough for them, and
arrack is much more to their taste. All the refuse, after clearing the
wine, is put in a big pot, a head and worm is fixed on with mud, and
distillation by means of a very slow fire of big logs is proceeded with.
The product is redistilled once, and even a third time. A strong rough
spirit is the result; it is generally coloured green, and flavoured by
thrusting a handful of leaves of anise (rasianah) into the receiver. Of
course the spirit is quite pure, being after a third distillation simply
strong spirits of wine. What the Armenians sell, however, is much
adulterated and drugged; it is known as “fixed bayonets,” and is
simply made to produce intoxication.
I secured a fine house in Julfa for forty-eight pounds a year. One
side of this house—it formed two of the four enclosing sides of a big
garden—is shown in the illustration. The immense window indicates
the great size of the huge T-shaped summer room, or Orūssee, the
floor of which was tiled. The fountain is seen playing in the hauz, or
ornamental tank, in front of the Orūssee.

DR. WILLS’S HOUSE IN JULFA.

My landlord had a fine vineyard at the side of my house, and for a

yearly payment of one hundred kerans I secured the right of entry,
and the privilege of eating as many grapes as we pleased. The
landlord, however, made mud bricks, and covered over all the paths
with the freshly-made bricks laid to dry; it was only, finding
remonstrance ineffectual, by calling our five dogs in with us, and
letting them run over the soft bricks, that I could get him to clear the
paths. I found, too, that I was waterless directly water became
scarce and dear, the man having sold our water. Fortunately the
lease specified the water, so I took the water, and referred the
purchasers to my landlord. They beat him, and got back their money.
I saw the three arguing and fighting for several days; how the matter
ended I did not inquire. I got my water.
Twice in my house concealed treasure had been discovered; once
to a large amount by the grandfather of my landlord, and a second
time to a smaller value by his father.
On this second occasion, the well running dry, men were sent
down to deepen it; a door was found in the wall, and a quantity of
arms and clothing were discovered in a small chamber in the wall,
but no money or jewels. I found a secret chamber in this house, but it
was empty.
Of course my wife had to be taken to that terrible fraud, the
Shaking Minarets. Why, no one knows, but every one has heard of
the Shaking Minarets. “You went to Ispahan. What did you think of
the Shaking Minarets?” is constantly asked by those who have not
been there. Even those who have, much on the principle of the
bumpkin, who, on paying his penny, is triumphantly shown the
biggest donkey in the fair, in a looking-glass, and urges his friends to
go and see that show: so does a feeling of having been defrauded
cause people to advise their friends to see the Shaking Minarets.
The mere name is poetical and mysterious.
Upon a gentleman high in the diplomatic service being asked what
was the use of the British Agent at Ispahan, he replied:
“Oh, it is an hereditary office; he shows British travellers the
Shaking Minarets.”
But then that “excellency” was a humorous man. He it was who,
on being troubled by a pertinacious clergyman with many
grievances, and told by him (the parson) that “he was but a humble
member of the Church Militant,” replied, “Church Pugnacious, you
mean.”
Dearly did the British Agent love to perform his “hereditary
function.” The new-comer, full of desire to see the Shaking Minarets,
and really pleased with his visit to the town of Ispahan, would make
the appointment for the sight, and, seeing the “hereditary
functionary’s” enthusiasm, not liking to damp it, would acknowledge
that he had seen the eighth wonder of the world.
An hour’s sharp canter through bridle-paths and shady lanes, after
crossing the river by the old Marnūn bridge, would bring one to the
little shrine, through the power of whose “Pir,” or saint, there interred,
the miracle of the Shaking Minarets is daily on view. As one
approached the village where the shrine is, the labourers in the field
would begin to run towards it, each eager to be the holder of a
European’s horse, and their shouts would bring a crowd to the
scene.
There is nothing particularly wonderful about the shrine; it is under
a lofty arch of modern construction, and is the usual rectangular
chest, under which reposes the body of the saint. On the whole lies
an open Koran and reading-stand. The chest is covered by a ragged
pall of cotton cloth; and a few strings of copper “kendils,” or votive
offerings, in the shape of small copper cylinders constricted in the
middle, attest the popularity of the saint with the villagers. The
guardian, also the village schoolmaster, is a Syud, or holy man; no
information can be obtained from him, save that the dead saint has
great power, and that the shaking is a miracle. Proceeding to the top
of the shrine, a good view of the Ispahan valley is obtained, and here
one sees the celebrated Shaking Minarets. A lusty villager ascends
each, and by dint of strong shaking, both vibrate considerably. The
“hereditary functionary” used to do this himself with great gusto, but,
having visited England, has become too important for the personal
exercise of his “functions.” When one man ceases to shake the
vibration continues in both, and a peculiar sensation of insecurity is
felt when one is inside the minaret.
The minarets are some twelve or fourteen feet high above the
roof. They are of brick; and the fact is, that being continuous with a
long thin wall which connects the two at the base, the vibration
caused in one is communicated to the other. This is the miracle,
which will probably some day cease by the vibrator being propelled
into space, and then the office of the “hereditary functionary” will be
really a sinecure. The place, however, has been repaired, and the
minarets rebuilt, within the last thirty years, so the guardian says. I