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LIST OF CONTRIBUTORS XI
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Nicholas Holt
Department of Gastroenterology and Hepatology St. George Hospital Sydney New South Wales Australia
Phillip Hopley
Institute of Systems Molecular and Integrative Biology University of Liverpool Liverpool UK
Shakira Hoque
Department of Gastroenterology and Hepatology St. George Hospital Sydney New South Wales Australia
Ta-Chen Huang
Department of Oncology National Taiwan University Hospital Tai pe i Taiwan
Faiz Jabbar
Department of Immunology Oxford University Hospital NHS Foundation Trust Oxford UK
Helena Jankowska
UCL Medical School University College London London UK
Sri Jasti
Department of Medical Oncology St. George Hospital Sydney Australia
Moritz Jesinghaus
Institute of Pathology Phillips University Marburg and University Hospital Marburg Marburg Germany
Robin L. Jones
Institute for Cancer Research Royal Marsden Hospital London UK
Pooja Karukonda
Department of Radiation Oncology Duke University School of Medicine Durham North Carolina USA
Atsuko Kasajima
Institute of Pathology Technical University of Munich Munich Germany
Christy Kim
Department of Gastroenterology and Hepatology St. George Hospital Sydney New South Wales Australia
Izaak Jankowski
Faculty of Medicine Imperial College London South Kensington Campus London UK
Janusz A.Z. Jankowski
Comprehensive Clinical Trials Unit Institute of Clinical Trials & Methodology University College London London UK
Provost’s Office Dubai Medical College United Arab Emirates
Henning Jann
Department of Hepatology and Gastroenterology Campus Virchow Klinikum (CVK) and Campus Charité Mitte (CCM) Charité Universitätsmedizin Berlin Berlin Germany
Günter Klöppel
Institute of Pathology Technical University of Munich Munich Germany
Shahid Khan
St. Mary’s Hospital Imperial College Healthcare NHS Trust London UK
Wolfram Trudo Knoefel
Department of Surgery Heinrich-Heine-University and University Hospital Duesseldorf Duesseldorf Germany
John Kokkinos
Pancreatic Cancer Translational Research Group School of Biomedical Sciences Lowy Cancer Research Centre UNSW Sydney New South Wales Australia
XII LIST OF CONTRIBUTORS
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Björn Konukiewitz
Department of Pathology University Hospital Schleswig-Holstein Campus Kiel Christian-Albrechts-Universität zu Kiel Kiel Germany
Magdalena Krakowska
Department of Chemotherapy Medical University of Lodz Copernicus Memorial Hospital Lodz Poland
Sjoerd Lagarde
Department of Surgery Erasmus MC Cancer Institute Rotterdam the Netherlands
Ngee Soon Lau
Department of Surgery Royal Prince Alfred Hospital and University of Sydney New South Wales Australia
Joanna Lee
Clinical Trials Centre University of Sydney Sydney Australia
Shao-Hsuan Lee
Department of Hematology-Oncology Kaohsiung Chang Gung Memorial Hospital Taiwan
Yasmin Leshem
Oncology Unit Tel Aviv Medical Center Israel Middle East
Winston Liauw
Department of Medical Oncology St. George Hospital Sydney Australia
Translational Medicine Group Pomeranian Medical University Szczecin Poland
Jonathan Lindquist
Department of Interventional Radiology University of Colorado School of Medicine Aurora Colorado
Lisa Liu
Department of Interventional Radiology University of Colorado School of Medicine Aurora Colorado
Suhrid Lodh
Department of Interventional Radiology Prince of Wales Hospital Sydney Australia
Claudio Luchini
Department of Diagnostics and Public Health Section of Pathology University of Verona Vero na Italy
ARC-Net Research Center University of Verona Vero na Italy
Betania Mahler-Araujo
Cambridge Colorectal Unit Department of Pathology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge UK
Ilaria Marinoni
Institute of Tissue Medicine and Pathology University of Bern Bern Switzerland
Katalin Mattes-György
Department of Nuclear Medicine Heinrich-Heine University and University Hospital of Düsseldorf Düsseldorf Germany
Lauren J. McEneaney
St. Mary’s Hospital Imperial College Healthcare NHS Trust London UK
Jeremy Meyer
Cambridge Colorectal Unit Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge UK
LIST OF CONTRIBUTORS XIII
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Piotr Milkiewicz
Liver and Internal Medicine Unit Medical University of Warsaw Wars aw Poland
Claire Mitchell
The Christie Hospital Foundation Trust Manchester UK
Paul Moayyedi
McMaster University Canada
Filippo Montemurro
Candiolo Cancer Institute Italy
Daniel A. Moses
Medical Imaging Department Prince of Wales Hospital Randwick New South Wales Australia
Graduate School of Biomedical Engineering Faculty of Engineering UNSW Sydney New South Wales Australia
Bianca Mostert
Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam the Netherlands
Linda Moxley-Haegert
Department of Psychology Shriners Hospitals for Children Montreal Quebec Canada
Andrzej Mróz
Department of Pathology Center of Postgraduate Medical Education Wars aw Poland
Department of Pathology Maria Sklodowska-Curie Memorial Cancer Hospital and Institute Wars aw Poland
Amrita Sen Mukherjee
Honorary Clinical Research Fellow Imperial College London London UK
Visiting Academic Medicine and Health Sciences Royal College of Surgeons Ireland
Andrea Napolitano
Institute for Cancer Research Royal Marsden Hospital London UK
Yamini Natarajan
Gastroenterology and Hepatology Section Department of Medicine Baylor College of Medicine Houston Texas USA
Khairul Najmi Muhammad Nawawi
Gastroenterology Unit Department of Medicine Faculty of Medicine Universiti Kebangsaan Malaysia Kuala Lumpur Malaysia
GUT Research Group Faculty of Medicine Universiti Kebangsaan Malaysia Kuala Lumpur Malaysia
Alexander Ney
Institute for Liver and Digestive Health University College London London UK
Emil Novruzov
Department of Nuclear Medicine Heinrich-Heine University and University Hospital of Düsseldorf Düsseldorf Germany
Daniel C. Osei-Bordom
Institute for Liver and Digestive Health University College London London UK
Lucy Oldfield
Institute of Systems Molecular and Integrative Biology University of Liverpool Liverpool UK
Sean M. O’Cathail
Senior Research Fellow School of Cancer Sciences University of Glasgow Glasgow UK
XIV LIST OF CONTRIBUTORS
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Chandni Patel
Institute of Systems Molecular and Integrative Biology University of Liverpool Liverpool UK
Antonio Pea
Department of Surgery The Pancreas Institute University of Verona Vero na Italy
,
Aurel Perren
Institute of Tissue Medicine and Pathology University of Bern Bern Switzerland
Stephen P. Pereira
Institute for Liver and Digestive Health University College London London UK
Omali Pitiyarachchi
Pancreatic Cancer Translational Research Group School of Biomedical Sciences Lowy Cancer Research Centre UNSW Sydney New South Wales Australia
Phoebe A. Phillips
Pancreatic Cancer Translational Research Group School of Biomedical Sciences Lowy Cancer Research Centre UNSW Sydney New South Wales Australia
Hans Prenen
University Hospital Antwerp Belgium
Carlo Pulitano
Department of Surgery Royal Prince Alfred Hospital and University of Sydney New South Wales Australia
Alessandra Pulvirenti
Department of Surgery The Pancreas Institute University of Verona Vero na Italy
Mohamed Rabie
Cambridge Colorectal Unit Cambridge University Hospital NHS Foundation Trust Cambridge UK
Praveen Ramakrishnan
UT Southwestern Medical Center Dallas Texas USA
Syed Rizvi
UT Southwestern Medical Center Dallas Texas USA
Christoph Roderburg
Clinic for Gastroenterology Hepatology and Infectious Diseases University Hospital Düsseldorf Medical Faculty of Heinrich Heine University Düsseldorf Düsseldorf Germany
Stefano La Rosa
Unit of Pathology Department of Medicine and Surgery University of Insubria and ASST Sette Laghi Vare se Italy
Iannish Sadien
Cambridge Colorectal Unit Department of Pathology Addenbrooke’s Hospital Cambridge University Hospitals NHS Foundation Trust Cambridge UK
Anna Schneider-Fuchs
Institut für Pathologie Friedrich-Alexander-Universität Erlangen-Nürnberg Klinikum Bayreuth Preuschwitzer Str. 101 Bayreuth Germany
Matthias Schott
Division for Specific Endocrinology Heinrich-Heine-University and University Hospital Duesseldorf Duesseldorf Germany
Johannes Schumacher
Institute of Human Genetics Philipps University of Marburg Marburg Baldingerstraße Germany
Malin Katarina Schumacher
Department of Radiation Oncology Wollongong Hospital and University of New South Wales New South Wales Australia
LIST OF CONTRIBUTORS XV
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Bence Sipos
ENETS Center of Excellence Department of Medical Oncology and Pneumology University Hospital Tuebingen Tuebingen Germany
Private Practice of Pathology and Molecular Pathology Stuttgart Germany
Private Practice of Molecular Pathology Baden-Württemberg Germany
George Sharbeen
Pancreatic Cancer Translational Research Group School of Biomedical Sciences Lowy Cancer Research Centre UNSW Sydney New South Wales Australia
Pram Sirimana
Department of Upper Gastrointestinal and Hepatobiliary Surgery Royal North Shore Hospital Sydney New South Wales Australia
Katrin Sjoquist
Department of Medical Oncology St. George Hospital Sydney and Clinical Trials Centre University of Sydney New South Wales Australia
Myles J. Smith
Institute for Cancer Research Royal Marsden Hospital London UK
Thomas J. Smith
Palliative Medicine Program Johns Hopkins Medical Institutions Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland USA
Manon C.W. Spaander
Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam the Netherlands
Camille Stewart
Department of Surgery University of Colorado School of Medicine Aurora Colorado
Rebecca Strutt
School of Clinical Medicine Faculty of Medicine & Health UNSW Sydney New South Wales Australia
Department of Palliative Medicine Nelune Comprehensive Cancer Centre Prince of Wales Hospital Randwick New South Wales Australia
Martyn Stott
Institute of Systems Molecular and Integrative Biology University of Liverpool Liverpool UK
Luis F. Tapias
Division of Thoracic Surgery Mayo Clinic SW Rochester MN USA
Corey X. Tapper
Division of General Internal Medicine Department of Medicine Palliative Care Program Johns Hopkins Medical Institutions Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland USA
Stephen R. Thompson
School of Clinical Medicine Faculty of Medicine & Health UNSW Sydney New South Wales Australia
Department of Radiation Oncology Nelune Comprehensive Cancer Centre Prince of Wales Hospital Randwick New South Wales Australia
Chen-Kan Tseng
Proton and Radiation Therapy Center Chang Gung Memorial Hospital-Linkou Medical Center Department of Radiation Oncology Chang Gung University Taiwan
XVI LIST OF CONTRIBUTORS
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Yung-Kuan Tsou
Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital Taiwan
Silvia Uccella
Unit of Pathology Department of Medicine and Surgery University of Insubria and ASST Sette Laghi Vare se Italy
Department of Biomedical Sciences Humanitas University and Department of Pathology IRCCS Humanitas Research Hospital Milan Italy
Michael Vieth
Institut für Pathologie Friedrich-Alexander-Universität Erlangen-Nürnberg Klinikum Bayreuth Preuschwitzer Str. 101 Bayreuth Germany
Bavarian Cancer Research Center (BZKF) Bayreuth Germany
Nicolas Villard
Department of Radiology Lausanne University Hospital (CHUV) Lausanne Switzerland
Mathew Vithayathil
St. Mary’s Hospital Imperial College Healthcare NHS Trust London UK
James Wheeler
Cambridge Colorectal Unit Cambridge University Hospital NHS Foundation Trust Cambridge UK
MN USA
Benjamin Chun Yu Wong
Department of Medicine School of Clinical Medicine The University of Hong Kong Queen Mary Hospital Hong Kong China
I-Chen Wu
Department of Gastroenterology Department of Internal Medicine Kaohsiung Medical University Hospital Taiwan
Tsung-Teh Wu
Division of Anatomical Pathology Mayo Clinic SW Rochester MN USA
Jing Xu
UT Southwestern Medical Center Dallas Texas USA
Chi-Ju Yeh
Department of Anatomic Pathology Chang Gung Memorial Hospital-Linkou Chang Gung University Taiwan
Chi Ho Howard Yim
UNSW Microbiome Research Centre St. George and Sutherland Clinical Campuses School of Clinical Medicine Faculty of Medicine and Health University of New South Wales Sydney New South Wales Australia
Christopher Willett
Department of Radiation Oncology Duke University School of Medicine Durham North Carolina USA
Bas P.L. Wijnhoven
Department of Surgery Erasmus MC Cancer Institute Rotterdam the Netherlands
Kenneth K. Wang
Division of Gastroenterology and Hepatology Mayo Clinic SW Rochester
Amany Zekry
Department of Gastroenterology and Hepatology St. George Hospital Sydney New South Wales Australia
Translational Medicine Group Pomeranian Medical University Szczecin Poland
Charlène J. van der Zijden
Department of Surgery Erasmus MC Cancer Institute Rotterdam the Netherlands
Preface
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Why this book, and why now? This invited reference book is aimed at a wide spectrum of readers from patients and carers as well as practitioners, specialists and students.
This new volume is unique and aims to satisfy the immediate needs of each reader, while allowing scope and depth for further learning. The editing process for the contributions also works on the premise that information rapidly progresses, so having links to trusted web sources is key to maintain knowledge in an innovative way.
The first edition of this book was awarded many plaudits and reviews including; “written by the leading international experts in the field, it sets the standard in clinical practice” and “the authorship is a mark of quality, this book is a must read”. In the intervening 15 years so much has changed in cancer management and these advances have been reflected in this invited second edition. Specifically, new sections now include the following: the pathophysiology of cancer including sections on diet, probiotics, carcinogens, and genomics; improvements in cancer screening including non-invasive markers, endo­scopic imaging as well as histopathological biomarkers; sequen­tial use of advanced imaging modalities; surgical, radiotherapy, chemotherapy and advanced targeted/biological therapies; new psychological and palliative care interventions; new chapters such as sarcoma/stromal tumours, liver transplant, and unknown primary and GI lymphomas.
Each chapter has new boxes for ‘key take home messages’, ‘areas where research and the evidence base is weak’ and an extensive’ reading list of trusted websites for further information’.
In summary this book pushes the training envelope and aims to be both comprehensive in the detail as well as holistic in its management of the patient and their carers. Furthermore, the layout is designed to be easy for fast reference and access by phone or bedside devices for immediate impact at the consultation.
I want to thank all the contributors who have worked tire­lessly during the Covid-19 pandemic. They still made time for delivery of uptodate superb contributions, which as so relevant to the post-pandemic world.
So, in ending, I hope you feel purchasing this book, is more of why not?
Prof. Janusz A. Z. Jankowski
JP, MBChB, MSc, MD, PhD, PCME, PGCM, PGCC, AGAF,
FACG, FRCP, SFHEA
Clinical Professor, University College London
Non-Executive Director and Consultant,
National Health Service, UK
Editor in Chief, Gastrointestinal Oncology, Wiley
Former Sir James Black Fellow and Professor,
University of Oxford
xvii
Foreword
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“The paradigm of a journey from observation to hypo­thesis testing and then onward to fulfil Koch’s postulates.”
The discovery 40 years ago of the Helicobacter Pylori organism was a paradigm shift in many ways. Perhaps most importantly as it indicated that the host and the organism have a complex interaction which can lead to disease, not only chronic infec­tion, autoimmunity, but also several forms of cancer. As an adjunctive benefit it showed that we should question any dis­ease causation assumptions which are not evidence based, “Psychiological stress” as a common cause of peptic ulcer dis­ease being the best example.
The journey was long in that it took time to assemble the epi-
demiological, bacteriological, clinical, oncological teams.
The result was, and still is, to provide the only cure for a
condition in gastroenterology, peptic ulcer disease. The
benefits also included alleviation of dyspepsia, cures of low-grade gastric MALTOMAs, and prevention of epithelial tumors of the gastric antrum.
This discovery has spawned new interest in fields of research outside the infection-inflammation-cancer sequence, including probiotics, antibiotic resistance, and modulation of host– bacterial interactions.
As I reflect on my career’s narrative above, I am therefore glad to see such a large array of multidisciplinary experts working together in this endeavor of A Critical Multidisciplinary Team Approach.
Gastrointestinal Oncology:
Barry Marshall, December 2022
Nobel Laureate Medicine
University of Western Australia
xviii
Section I Upper Gastrointestinal Cancer
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1 Epidemiology, Microbiome, and Risk
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Factors Involved in Carcinogenesis of Esophagus, Gastric, and Intestine
Deborah Chia Hsin Chew1, Chi Ho Howard Yim2, Raja A.R. Ali El-Omar
1
Gastroenterology Unit, Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
2
UNSW Microbiome Research Centre, St. George and Sutherland Clinical Campuses, School of Clinical Medicine, Faculty of Medicine and Health,
University of New South Wales, Sydney, New South Wales, Australia
3
School of Medical and Life Sciences, Sunway University, Selangor, Malaysia
4
GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
[Aspects of genomic risk factors are covered in Chapter 2]. [Aspects of relevant colorectal data are covered in Chapter 9].
Introduction
Cancers of the gastrointestinal tract (GIT) encompassing esophagus, stomach, and colorectum make up a significant proportion of cancers diagnosed worldwide and contribute to a considerable burden of disability-adjusted life years and years of life lost. (Kocarnik etal. 2022) The increase of GIT malignancies has been linearly associated with the human development index (HDI), likely due to the adoption of an affluent lifestyle with an increase in the consumption of pro­cessed meat, fast food, sedentary lifestyle, smoking, and increasing alcohol consumption. Obesity has become a world­wide pandemic and has been linked to the development of GIT cancers through multiple genetic and epigenetic micro­environment changes. Excess adipokines in obesity mediate a state of chronic inflammation resulting in the activation of multiple pathways that promote carcinogenesis. The under­standing of the epidemiology and predisposing factors to GIT cancers is crucial in the development of early detection strat­egies. Screening efforts such as colonoscopy has reduced the burden of CRC worldwide. Similarly, screening of gastric can­cers which has been adopted in Japan and Korea has reduced the numbers as well as improved the survival of gastric cancer.
In this chapter, we will discuss the epidemiology, global time trends, burden of disease, risk factors of esophageal, gastric and intestinal cancer, and strategies to reduce the incidence of these malignancies.
Gastrointestinal Oncology: A Critical Multidisciplinary Team Approach,
Second Edition. Edited by Janusz A. Z. Jankowski. © 2024 John Wiley & Sons Ltd. Published 2024 by John Wiley & Sons Ltd.
2
Esophageal Cancer
Epidemiology of Esophageal Cancer
Global Burden and Time Trends of Esophageal Cancer
Esophageal cancer (EC) is the seventh most common cancer glob­ally (Huang et al. 2021) and the sixth leading cause of cancer mortality (Sung et al. 2021). The rates of EC worldwide have increased in the last two decades from 319,969 cases in 1990 to 319,969 cases in 2019 with a relative increase of 67.07% (Li etal.
2021). In 2020 there were 604,100 new cases of EC worldwide with a corresponding age-standardized incidence of 6.3 per 100,000 (Morgan etal. 2022b). The five-year survival of EC remains dismal at less than 20%, owing largely to its late stage of diagnosis (Then etal. 2020). Mortality from EC demonstrated a relative increase of
55.97% from 1990 till 2019 (Li etal. 2021) and resulted in 544,100 deaths in 2020 with a corresponding age-standardized mortality of
5.6 per 100,000 (Morgan etal. 2022b). The highest incidence of EC was observed in East Asia accounting for 59.2% of all EC cases out of which 53.7% occurred in China. EC mortality was observed to be highest in Eastern Asia, accounting for 58.7% of EC-related deaths.
Distribution of Esophageal Adenocarcinoma and Esophageal Squamous Carcinoma
Histologically, EC is divided into adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). The subtype of esophageal cancers varies according to geographic region. ESCC accounts for more than 85% of esophageal cancer cases worldwide (Arnold etal. 2015). There has been a change in the geographic distribu­tion of EC with a rise in EAC, but a reduction in ESCC was noted in Western countries. The incidence rate of ESCC was double in males at 7.8 per 100,000 compared to females at 3.2 per 100,000 (Morgan etal. 2022b). This subtype is commonly seen in regions
1,3,4
& Emad M.
3
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