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Wilms’ Tumor Yogesh Kumar Sarin Editor 123 Wilms’ Tumor Yogesh Kumar Sarin Editor Wilms’ Tumor Editor Yogesh Kumar Sarin Department of Pediatric Surgery Lady Hardinge Medical College and Kalawati Saran Children’s Hospital New Delhi, India ISBN 978-981-19-3427-8 ISBN 978-981-19-3428-5 (eBook) https://doi.org/10.1007/978-981-19-3428-5 © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 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. 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The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Dedicated to my patients and my mentors. Foreword There can be little doubt that the management of children with Wilms’ tumor represents one of the great medical advances of the last 50 years. This achieve- ment rests on the twin pillars of cooperative clinical trials and basic science research around the world, and pediatric surgeons and oncologists have been pivotal in driving this progress and can be justly proud of their contributions. Childhood cancer remains uncommon but effective treatment is now available and access to such treatment should be every child’s legitimate expectation. However the benefits of the new management paradigms have not been available to everybody, and progress has exposed the inequities of healthcare provision around the globe. In high-income countries with well-resourced and robust healthcare systems, Wilms’ tumor is no longer a diagnosis to be feared, but most children with cancer do not live in high-income countries! There is still much work to be done to make these advances accessible to the overwhelming majority of children with cancer who live in middle- or low- income countries in Africa, Asia, or South America where comorbidities impact on treatment options and where fragile healthcare systems and lack of resources make compliance with current management protocols difficult or impossible. From time to time in periods of rapid change it is essential to pause and take stock of developments and to assess their relevance to the extant situa- tion on the ground. This is what Director Professor Sarin has achieved with this authoritative book. He has assembled a formidable team of contributors, continuing the tradition of teamwork among pediatric colleagues, to present the current state of play so that treating physicians and surgeons have up-to- date guidelines to aid patient management. He has addressed current contro- versies and included advice on nephron-sparing surgery and minimally invasive techniques, thereby allowing the treatment team to design management plans commensurate with their skills and resources and discuss options available to physicians where facilities are lacking. It will be an invaluable resource to trainees and practicing physicians in oncology and surgery alike. Professor G. P. Hadley, MB,ChB(St And), FRCSEdin, FCS(SA) Professor Emeritus, University of KwaZulu-Natal, Durban, South Africa Past President of the South African Association of Paediatric Surgeons Past President of the International Society of Paediatric Surgical Oncology (IPSO) vii Preface Children are the light of the world. When such pristine innocence and joy get cloaked by a dark veil of any ailment, which sometimes unfortunately turns out to be a malignancy, there can not be anything more satisfying than sailing the child through his/her illness thereby restoring the lost colors of the early years. As physicians, it is our utmost duty to give children diagnosed with Wilms’ tumors a pain-free and unperturbed ride through their treatment journey. Wilms’ tumor is an embryonal malignancy of infancy and early childhood, the management of which is often quoted as an epitome of success in pediatric oncology. Although the overall survival rates for Wilms’ tumor were only about 33% in the 1960s, they jumped to more than 90% in the next three decades. This improvement resulted from better diagnostics and the multi- modal treatment that evolved because of the efforts of clinical trials con- ducted by the cooperative consortia, of which the National Wilms Tumor Study Group/Children’s Oncology Group in the USA and the International Society of Pediatric Oncology (SIOP) are noteworthy. In the twenty-first century, the focus shifted from improved survivals to avoidance of treatment-associated toxicity and long-term effects in the survi- vors. Minimalism is the buzz word with efforts being made to minimize all three limbs of multimodality treatment—the surgery (extension of scope of nephron-sparing surgery to even unilateral nonsyndromic Wilms’ tumors), the chemotherapeutic drugs (avoidance of doxorubicin in pretreated stage III intermediate risk tumors), and the radiotherapy (avoidance of whole lung irradiation to rapid complete responders of pulmonary-alone metastases). Non-contrast computerized tomography of the chest to rule out pulmonary metastases has more or less replaced the chest roentgenograms done earlier. Abdominal magnetic resonance imaging (MRI) would soon be preferentially recommended for cross-sectional imaging of the abdomen in high-income countries. SIOP is attempting to correlate apparent diffusion coefficient map- ping with histopathology prediction after preoperative chemotherapy. However, any attempts to stage tumors on preoperative imaging are fallacious as the perirenal extension and lymph node involvement predicted on imaging have poor correlation to histologic staging; 75% of stage I or II tumors are overstaged and 40% of stage III tumors are understaged by the imaging modalities. The present century also witnessed a steep rise in the knowledge of the genetics and epigenetics in the development of Wilms’ tumor. In 2005, the ix x Preface biological markers (chromosomal abnormalities) were incorporated in the treatment stratification for the first time. The recent advances in liquid biopsy techniques for diagnostics, monitoring of therapy, and detection of minimal residual disease are another value addition in the management of Wilms’ tumor. However, the progress cited above has not been duplicated in the low- and middle-income countries. The factors responsible for the poor outcomes have been detailed in one of the chapters. They mandate prioritization in resource utilization in such settings so as to successfully treat those who have better prognosis and the use of adapted regimens that could give comparable outcomes. I hope that this book with 39 chapters would serve as an authoritative source for the intended readership (students, basic scientists, and clinicians) who want a comprehensive understanding of the basics and management of Wilms’ tumor. I am not aware of any other book that covers the different clinical scenarios that we witness while treating these tumors. I am indebted to my colleagues and collaborators who have contributed their ideas, time, and knowledge to this project. In particular, I would like to thank Drs. Bhaskar N Rao, GP Hadley, and Sushmita Bhatnagar for their friendship, mentorship, and wisdom. Their teachings will continue to be an endless source of passion and inspiration. New Delhi, India Yogesh Kumar Sarin Contents 1 The History of Renal Tumors in Children . . . . . . . . . . . . . . . . . . 1 V. Raveenthiran 2 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Manish Pathak and Dattatray Bhusare 3 Genetics and Molecular Biology . . . . . . . . . . . . . . . . . . . . . . . . . . 27 G. Raghavendra Prasad, Amina Bee, and Nitin James Peters 4 Tumor Microenvironment and Inflammatory Markers . . . . . . . 35 G. Raghavendra Prasad, Wafa Yasmeen, and Mohammed Ikram 5 Syndromic Wilms’ Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Nitin James Peters and Ram Samujh 6 Familial Non-syndromic Wilms’ Tumor . . . . . . . . . . . . . . . . . . . . 55 Rahul Saxena 7 Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Parul Tanwar 8 Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Parveen Kumar and Parthapratim Gupta 9 Laboratory Workup . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Ayushi Vig and Kirtikumar J. Rathod 10 Imaging Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83 Anju Garg and M. Sarthak Swarup 11 Diagnostic Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Khalid Elmalik and Brian Davies 12 General Surgical Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 Yogesh Kumar Sarin and Sushmita N. Bhatnagar 13 Nephron-Sparing Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 Yogesh Kumar Sarin 14 Lymph Node Sampling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129 Kant Shah and Gita Verma xi xii Contents 15 Minimally Invasive Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Kirtikumar J. Rathod and Avinash S. Jadhav 16 Bench Surgery and Auto-Transplantation . . . . . . . . . . . . . . . . . . 143 Yogesh Kumar Sarin, Ilhama Jafarli, and Alexandra Richards 17 Anesthesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 Chandrima Banerjee 18 Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155 Manish Pathak 19 Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Yogesh Kumar Sarin, Pallavi Sachdeva, Manas Kalra, T. K. Jayakumar, and Arvind Sinha 20 Radiotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189 Manur Gururajachar Janaki, Nitin James Peters, and Yogesh Kumar Sarin 21 Novel Tumor Directed Interventions . . . . . . . . . . . . . . . . . . . . . . . 197 Shilpa Sharma, Sachit Anand, and Yogesh Kumar Sarin 22 Wilms’ Tumor in Resource- Challenged Nations . . . . . . . . . . . . . 203 Yogesh Kumar Sarin 23 Management of Resected Wilms’ Tumor with Unknown Staging Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213 Yogesh Kumar Sarin, Manjusha Sailukar, and Shweta Bansal 24 Bilateral Wilms’ Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 S. Kumaravel 25 Wilms’ Tumor in Horseshoe Kidney and Solitary Kidney . . . . . 229 Vikram Khanna 26 Very Large Tumors Not Responding to Chemotherapy/Locally Infiltrating Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Alpana Prasad 27 Intravascular Extension and Tumor Thrombosis . . . . . . . . . . . . 239 Nitin James Peters, Priyanka Garg Mittal, and Ram Samujh 28 Ureteral Extension . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 Vikram Khanna 29 Ruptured Tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247 Alpana Prasad and Nidhi Sugandhi 30 Metastatic Wilms’ Tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 Nidhi Sugandhi 31 Recurrent/Relapsed Wilms’ Tumor . . . . . . . . . . . . . . . . . . . . . . . . 267 Arvind Sinha, T. K. Jayakumar, and Yogesh Kumar Sarin