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Gallbladder Cancer Current Treatment Options Vijay Kumar Shukla Manoj Pandey Ruhi Dixit Editors 123 Gallbladder Cancer Vijay Kumar Shukla • Manoj Pandey Ruhi Dixit Editors Gallbladder Cancer Current Treatment Options Editors Vijay Kumar Shukla Manoj Pandey Department of General Surgery Department of Surgical Oncology Banaras Hindu University Banaras Hindu University Varanasi, Uttar Pradesh, India Varanasi, Uttar Pradesh, India Ruhi Dixit Department of General Surgery Banaras Hindu University Varanasi, Uttar Pradesh, India ISBN 978-981-19-6441-1 ISBN 978-981-19-6442-8 (eBook) https://doi.org/10.1007/978-981-19-6442-8 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2023 This work is subject to copyright. All rights are solely and exclusively licensed 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Foreword Gallbladder cancer is one of the common neoplasms of the biliary tract, represent- ing 80–95% of biliary tract cancers worldwide. It is among the top five malignan- cies in the gastrointestinal system. A satisfactory outcome depends on an early diagnosis and surgical resection. This tumour is regarded as a highly lethal disease with an overall 5-year survival of less than 5%. Early gallbladder cancer symptoms, however, are typically nonspecific; hence disease has often been diagnosed at an advanced stage and cannot be resected. The methods of treatment are limited to palliative therapies, depending mostly on chemotherapy. ICMR also published a consensus document for the management of gallbladder cancer in 2014. This book focuses on the recent progress in understanding the therapeutic targets for gallbladder cancer, which will provide opportunities for research and for developing innovative strategies that may enhance the benefit of conventional chemotherapy. The book is intended for clinicians, surgeons, scientists and academicians. I congratulate the editors for synchronizing with the global experts in the field to present the most viable options for treatment of gallbladder cancer that will ulti- mately be beneficial to humankind. Department of Health Research Balram Bhargava Ministry of Health and Family welfare Government of India New Delhi, India v Foreword Gallbladder cancer is an aggressive malignancy that disproportionately affects underprivileged populations in South Asia, Latin America and the Far East. Most patients are diagnosed at an advanced, unresectable stage in Asia, whereas incidental finding at cholecystectomy is often the mode of presentation in the Western world for whom cure is feasible with multimodality therapy. Treatment goals in the majority of patients however include palliation of symptoms and prolongation of life, which is possible with systemic chemotherapy. Genetic profiling has identified potential targeted and immunological approaches. The contents of the book focus on the recent progress in understanding the molecular underpinnings of gallbladder cancer, which will provide opportunities for research and innovative strategies that may result in incremental benefit over conventional chemotherapy. Furthermore, surgical and multidisciplinary care are high- lighted throughout the book, stressing their critical role. This book is intended for clinicians, surgeons, scientists and academicians. I congratulate the editors for their efforts and the global experts who have contributed so generously towards this important effort. Department of Medicine, GI Medical Oncology Milind Javle UT MD Anderson Cancer Center Houston, TX, USA vii Preface Gallbladder Cancer (GBC) is characterized by an aggressive and extremely deadly cancer, which ranks fifth among the most common gastrointestinal tract cancers. Global mortality rates for people with gallbladder cancer have risen significantly with poor prognosis in recent decades. With advances in our understanding of the GBC aetiology over the past decade, existing treatment options such as surgery, chemotherapy and radiotherapy are also associated with unacceptably poor survival rates. Even though surgery is the pri- mary treatment available for early-stage GBC, most patients undergoing surgical resection generally suffer from a high risk of recurrence. Currently, the available treatments for GBC seem to be ineffective, as they only work to ease the symptoms but cannot prevent the disease's progression. GBC entails different genetic factors including somatic events and germline pre- disposition. Apparently, the underlying basis for disease development and progression of this malignant tumour remains unclear. Indeed, despite the noteworthy achievements in the understanding of GBC mechanism, there has been little development in formulating new therapeutic strategies. It is important to know the precise molecular or genetic changes occurring in the development of GBC to develop molecular targeted therapy for GBC. This book aims at current treatment options available for GBC and also the recent progress in understanding the therapeutic targets for GBC. Moreover, non-coding RNAs, such as miRNAs and lncRNAs, have also been discussed as potential therapeutic strategies in the regulation of gallbladder cancer development. This volume provides opportunities for advanced research and for developing innovative strategies that may enhance the benefit in gallbladder cancer management. Varanasi, India Vijay Kumar Shukla Varanasi, India Manoj Pandey Varanasi, India Ruhi Dixit ix Contents Part I Introduction 1 Gallbladder Cancer: Current Treatment Options and Therapeutics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Mohammad Taghizadieh, Motahareh Seyedi, Sara Azhdari, Fatemeh Dashti, Sayad Mohammad Ali Mirazimi, Hossein Bannazadeh Baghi, Javid Sadri Nahand, Michael Aschner, and Hamed Mirzaei Part II Surgical Management, Adjuvant Chemotherapy and Palliative Chemotherapy in Gallbladder Cancer 2 Surgical Management of Gallbladder Cancer Patients . . . . . . . . . . . . . 33 Marie Cappelle, Elise de Savornin Lohman, Philip de Reuver, and Bas Groot Koerkamp 3 Conventional Therapy in Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . 59 Xabier de Aretxabala, Luis Manriquez, and Felipe Castillo 4 Adjuvant Therapy of Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . . . 75 Zachary J. Brown, Daniel B. Hewitt, and Timothy M. Pawlik 5 Incidental Gallbladder Cancer: The Role of Routine Versus Selective Histopathological Examination of Gallbladder Specimens After Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Davide Di Mauro, Sarah Saunders, Amira Orabi, Aye Myintmo, Alex Reece-Smith, Shahjehan Wajed, and Antonio Manzelli 6 Minimally Invasive Surgery for Management of Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Marc-Anthony Chouillard, Elie K. Chouillard, and Andrew A. Gumbs 7 Thick-Walled Gallbladder: Differential Diagnosis and Surgical Approach to a Thickened Gallbladder . . . . . . . . . . . . . . . 111 Ashish Gupta xi xii Contents 8 Management of Incidentally Detected Gallbladder Cancer After Cholecystectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 K. Søreide 9 Adjuvant Therapy in Gallbladder Cancers . . . . . . . . . . . . . . . . . . . . . . 145 Divya Khosla and Sushma Agrawal Part III Targeted Therapies in Gallbladder Cancer 10 A Look at Emerging Therapeutic Targets for Gallbladder Cancer: A Multi-Omics Approach . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Pavan Baichan, Previn Naicker, John Devar, Martin Smith, and Ekene Emmanuel Nweke 11 MicroRNA and Their Role in Carcinoma Gallbladder . . . . . . . . . . . . . 177 Anurag Mishra, Adiba Nizam, and Rajdeep Singh 12 Gallbladder Cancer: Epigenetic Landscape, Targeted Therapy, and Prospect of Epitherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 Nivedita Sharma, Anjali Tomar, and P. K. Tiwari 13 Targeted Treatment of Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . . 237 Amol Patel and Vivek Hande 14 Molecular Pathways in Gallbladder Cancer as Potential Therapeutic Target . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 Sameer Gupta, Puneet Prakash, Vijay Kumar, Arun Chaturvedi, and Shashwat Tiwari 15 Targeted Therapy: Molecular Pathology and Targets of Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269 Nilam Bhasker and Faraz Ahmad 16 Targeted Therapies in Gallbladder Cancer: Current Status and Future Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 Manjusha Dixit, Vinay J, and Soham Choudhury 17 Integrative Omics: The Roadmap for Gallbladder Biomarkers Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 Kirti Gondkar, J. R. Parvathi, and Prashant Kumar 18 Anti-EGFR Therapy in Gallbladder Cancer . . . . . . . . . . . . . . . . . . . . . 331 Lovenish Bains and Tanuj Chawla Editors and Contributors About the Editors Vijay Kumar Shukla is Rector, Banaras Hindu University, and Professor in the Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India. Dr. Shukla is internationally known for his research on cancer of the gallbladder and wound healing. He had been visiting professor at reputed international universities/medical schools. He has been honoured with several national and international awards including Life Time Achievement Award at the World Union of Wound Healing Societies at Toronto, Canada, in 2008 for his exemplary work in wound healing and research. He was awarded the Fellow of the College of Wound Care Specialist (FCWCS), Malaysia, in 2017 and fellowship of National Academy of Medical Sciences in 2007. In his illustrious career, Prof. Shukla had been the President of Indian Society of Wound Management, Member of ICMR task force on gallbladder cancer, Examiner and Inspector of National Board of Examination, Vice-president, Hernia Society of India, Executive member, Association of Colon and Rectal Surgeons of India, Governing Council Member of ASI, and Member, Independent Innovators Expert panel of Ministry of Health and Family Welfare, Govt. of India. He has been member of 12 national and international professional bodies and has published 470 papers in International and National Journals. Manoj Pandey is a Professor in the Department of Surgical Oncology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, and Visiting Professor in the Department of Surgical Oncology, AIIMS, Rishikesh, Uttarakhand. He has served as the Director of Bhopal Memorial Hospital and Research Centre and National Institute for Research in Environmental Health, Indian Council of Medical Research. He has expertise in gallbladder cancer research, and his aspiration for quality research can be reflected from his research publications. He has published more than 328 publications. He has been honoured with several awards including Dr. U C Gupta Memorial Award for Excellence in Surgery. Dr. Pandey has also been a member of task force of ICMR on review of cancer management. xiii