Wilms’ Tumor

Description

This book covers all aspects of Wilms’ tumor, the second most typical solid tumor in children. Its potential for complete cure underscores correct management of this tumor. To achieve this goal, the book aims to provide all necessary details for practicing Pediatric surgeons, Oncologists, Pediatricians, Urologists, and Medical students. Topics ranging from epidemiology, etiology, pathology, clinical features, diagnostic methods, surgery, chemotherapy, radiotherapy to cutting-edge inventions are described in great detail.Detailed descriptions of surgical techniques and their nuances will greatly benefit surgeons and surgical residents. Importantly, all the chapters are written by authors who have first-hand experience with clinical management. Thus the text ensures the practical application of theoretical details.   Foreword Preface Contents Editor and Contributors About the Editor Contributors 1: The History of Renal Tumors in Children 1.1 Introduction 1.2 Prehistoric Era 1.2.1 The Parshve Gulma of Sushruta 1.2.2 Ayurvedic Treatment of Gulma 1.3 Era of Pathological Understanding 1.3.1 Phase of Morphological Descriptions 1.3.2 Interest in Histological Studies 1.3.3 American Scenario 1.3.4 Unified Nomenclature 1.3.5 Etiologic Theories 1.3.6 Arrival of Max Wilms 1.3.7 The Erroneous Eponym 1.4 Era of Therapeutic Discoveries 1.4.1 Surgical Remedy 1.4.2 Radiotherapy 1.4.3 Chemotherapy 1.5 Era of Cooperative Groups 1.5.1 The North American Cooperative Groups and NWTSG 1.5.2 Societe International d’Oncologie Pediatrique (SIOP) 1.6 A Century of Wilms’ Tumor References 2: Epidemiology 2.1 Introduction 2.2 Incidence and Geographical Variation 2.3 Age and Sex Predisposition 2.4 Causative Hypothesis and Role of Environmental Factors 2.5 Syndromic and Non-syndromic Associations 2.6 WT in Low-Income Countries 2.7 Role of Tumor Registries References 3: Genetics and Molecular Biology 3.1 Introduction 3.2 Genetic Events in Normal and Abnormal Nephrogenesis 3.2.1 Nephrogenesis Pathways 3.3 Multistep Model for Sporadic WT Development 3.4 Genetic Changes and WT 3.4.1 WT1 and WT2 3.4.2 CTNNβ1 3.4.3 WTX 3.4.4 MYCN, 16q and 1P, and TP53 3.5 Newer Genes 3.6 Other Forms of WT and Associated Genetic Changes 3.7 Syndromes Associated with WT 3.8 Epigenetic Changes and WT 3.8.1 Epigenetic Changes at 11p15 3.8.2 Epigenetic Changes at 11p13 References 4: Tumor Microenvironment and Inflammatory Markers 4.1 Tumor Microenvironment 4.2 TME and Genesis of WT 4.3 Immune cells, Inflammation, and Their Effect on Tumor Progression 4.3.1 WT and Immune Cells 4.3.2 WT and B Lymphocytes 4.3.3 WT and T Lymphocytes 4.3.4 WT and Macrophages 4.3.5 WT and Tumor-Infiltrating Neutrophils (TIN) 4.3.6 WT and Mast Cells 4.3.7 Tumor Cell-Immune Cell Interaction and Expression of Inflammatory Mediators in WT 4.3.8 WT and COX2 4.3.9 WT and Phosphorylated Extracellular Signal-Regulated Kinase 1 and 2 4.3.10 WT and HIF-1α 4.3.11 WT and VEGF 4.3.12 WT and Phosphorylated STAT 3 4.3.13 WT and Inducible Nitric Oxide Synthase (iNOS) 4.3.14 WT and Nitrotyrosine (NT) 4.3.15 WT and Chemokines/Cytokines 4.3.16 WT and CBP/p300 Interacting Transactivators with Glutamic Acid [E]/Aspartic Acid [D]-rich Carboxy-Terminal Domain (CITED1) 4.3.17 WT and B7 Homolog 1 4.3.18 WT and CD44 4.3.19 WT and Carbonic Anhydrase 9 4.3.20 WT and PDGF 4.4 Future Directions References 5: Syndromic Wilms’ Tumor 5.1 Introduction 5.2 Incidence and Genetic Penetrance 5.3 Syndromes and Clinical Conditions 5.4 WT1-Associated Phenotypes 5.4.1 WAGR Syndrome 5.4.2 WAGRO Syndrome 5.4.3 Denys-Drash Syndrome 5.4.4 Frasier Syndrome 5.4.5 Other WT1 Phenotypes 5.5 Overgrowth Syndromes 5.5.1 Beckwith-Wiedemann Syndrome 5.5.2 Simpson-Golabi-Behmel Syndrome 5.5.3 Perlman Syndrome 5.5.4 Sotos Syndrome 5.6 Familial Wilms’ Tumor 5.7 Other Tumor Predisposition Syndromes 5.7.1 Bloom Syndrome 5.7.2 Mosaic Variegated Aneuploidy 5.7.3 Fanconi Anemia 5.7.4 Other Syndromes 5.8 Constitutional Chromosomal Disorders 5.9 Conditions with Uncertain Association with WT 5.10 Evaluation and Surveillance in Predisposed Children 5.10.1 Evaluation 5.10.2 Molecular Genetic Testing 5.10.3 Surveillance 5.11 Surgical and Medical Management in Syndromic Patient 5.11.1 Oncological Management 5.11.2 Nephron-Sparing Surgery (NSS) in Syndromic WT 5.12 Future Directions References 6: Familial Non-syndromic Wilms’ Tumor 6.1 Introduction 6.2 Epidemiology of FWT 6.3 Risk of WT in Kindreds of WT Families 6.4 Pathology of Familial WT 6.5 Genetics and Molecular Biology 6.5.1 WT1 Gene 6.5.2 Familial Predisposition Gene 6.5.3 Novel Predisposition Genes for Familial WT 6.6 Genetic Counseling and Surveillance References 7: Pathology 7.1 Introduction 7.2 Gross Features 7.3 Microscopy 7.3.1 Blastemal Component 7.3.2 Epithelial Component 7.3.3 Stromal Component 7.4 Anaplasia 7.5 Nuclear Unrest 7.6 Chemotherapy-Induced Changes 7.7 Role of Pre-Therapy Biopsy/Fine Needle Aspiration Cytology 7.8 Immunohistochemistry (IHC) 7.9 Differential Diagnosis 7.10 Cystic Nephroma (CN) and Cystic Partially Differentiated Nephroblastoma (CPDN) 7.11 Handling of Nephrectomy Specimen 7.11.1 Frozen Section 7.11.2 Sample Handling 7.12 Nephrogenic Rests and Nephroblastomatosis 7.13 Adult Wilms’ Tumor 7.14 Extrarenal Wilms’ Tumor 7.15 Conclusions References 8: Clinical Presentation 8.1 Clinical Presentation 8.2 Examination 8.3 Associated Syndromes References 9: Laboratory Workup 9.1 Panel of Biochemical Investigations 9.1.1 Complete Hemogram 9.1.2 Renal Function Tests 9.1.3 Serum Electrolyte Panel 9.1.4 Urine Examination 9.1.5 Clotting Screen 9.1.6 Novel Tumor Markers 9.1.7 Investigations to Exclude Other Differentials 9.1.8 Pre and Post Chemotherapy Investigations References 10: Imaging Studies 10.1 Imaging Modalities 10.1.1 Conventional Radiography 10.1.2 Ultrasonography 10.1.3 Magnetic Resonance Imaging (MRI) 10.1.4 Computed Tomography 10.2 Tumor Staging 10.2.1 Local Extent 10.2.2 Size of the Tumor 10.2.3 Distant Metastases 10.2.3.1 Pulmonary Metastases 10.2.3.2 Other Metastatic Sites 10.3 SIOP Post Chemotherapy Evaluation 10.4 Evaluation of Contralateral Kidney 10.5 Nephrogenic Rests 10.6 Role of Imaging in Nephron-Sparing Surgery 10.7 Role of PET/PET-CT Imaging 10.8 Pretreatment Biopsy 10.9 Differential Diagnosis 10.10 Posttreatment Imaging Surveillance and Screening 10.11 Conclusion References 11: Diagnostic Biopsy 11.1 Introduction 11.2 Fallacies of Imaging Alone 11.3 Children Cancer and Leukemia Group Guidelines–UK [11] 11.4 Limitations 11.5 The Technique 11.6 Complications 11.6.1 Tract Recurrence 11.6.2 Others 11.7 The Future References 12: General Surgical Guidelines 12.1 Introduction 12.2 General Surgical Guidelines for Nephroureterectomy for Unilateral Wilms’ Tumor 12.2.1 Access 12.2.2 Inspection of the Abdominal Cavity 12.2.3 The Procedure 12.2.4 Tumor Thrombus in the Renal Vein and Inferior Vena Cava 12.2.5 Adrenal Gland 12.2.6 Lymph Nodes 12.2.7 Translocation of Ovary References 13: Nephron-Sparing Surgery 13.1 Introduction 13.2 Historical Background 13.3 Neoadjuvant Chemotherapy 13.4 Operative Technique [22, 26] 13.5 NSS and MIS 13.6 New Classification System for NSS 13.7 NSS in Non-syndromic Unilateral Tumors 13.7.1 Rationale and Selection Criteria 13.7.2 Follow-Up 13.7.3 Prognosis After NSS in uWT References 14: Lymph Node Sampling 14.1 Introduction 14.2 Lymphatic Drainage of Kidneys 14.3 Pattern of Lymphatic Spread in WT 14.4 Role of Imaging for Assessment of LN Involvement 14.4.1 PET Scan 14.5 Method of LN Sampling 14.6 Processing and Reporting of Lymph Nodes 14.7 Adverse Events of LN Sampling 14.8 Outcomes of LN Positive FH WT 14.9 Future Directions 14.9.1 Reducing Toxicity of Treatment 14.9.2 Rapid Central Pathology and Radiology Review 14.9.3 Lymph Node Sampling During Surgery References 15: Minimally Invasive Surgery 15.1 Introduction 15.2 Laparoscopic Surgery 15.3 Indications and Contraindications 15.4 Transperitoneal Approach 15.4.1 Patient and Team Positioning 15.4.2 Surgical Technique 15.5 Retroperitoneal Approach 15.5.1 Patient Positioning 15.5.2 Surgical Technique 15.6 Nephron Sparing Surgery 15.7 Robotic Surgery 15.8 Complications of MIS 15.9 Postoperative Care 15.10 Conclusions References 16: Bench Surgery and Auto-Transplantation 16.1 Introduction 16.2 Advantages 16.3 Technique 16.4 Outcomes References 17: Anesthesia 17.1 Introduction 17.2 Preoperative Concerns and Optimization 17.3 Intraoperative Management 17.4 Anesthesia for Special Circumstances 17.4.1 Anesthesia in a Case of Tumor Extension to the Right Atrium 17.4.2 Anesthesia in Bench Surgery 17.4.3 Anesthesia for Laparoscopic Nephrectomy 17.5 Postoperative Concerns 17.6 Conclusions References 18: Staging 18.1 Introduction 18.2 COG and SIOP Staging 18.3 Salient Differences Between the SIOP and COG Staging System 18.4 Role of Surgeon in Appropriate Staging References 19: Chemotherapy 19.1 Introduction 19.2 NWTSG/COG vs. SIOP Philosophy of Management 19.3 National Wilms’ Tumor Study Group (NWTSG)/Children’s Oncology Group (COG) 19.3.1 Role of Neoadjuvant ChT in COG 19.3.2 Treatment Overview of Unilateral WT 19.3.3 Current COG Protocols 19.3.3.1 AREN0532 19.3.3.2 AREN0533 19.3.3.3 AREN05321 19.3.4 Treatment Overview of Bilateral WT/Solitary Kidney with WT 19.3.4.1 AREN0534 Initial Therapy Therapy at the End of 6 Weeks Complete Response (CR) PR or Greater and Feasible for Bilateral NSS Partial Response or Greater, But Not Feasible for Surgery Less than Partial Response Therapy at the End of 12 Weeks 19.3.5 Treatment Overview of Patients with High Risk of Developing Metachronous Tumors 19.3.5.1 Initial Therapy 19.3.5.2 Therapy at the End of 6 Weeks 19.3.5.3 Therapy at the End of 12 Weeks 19.3.6 Treatment Overview of Diffuse Hyperplastic Perilobar Nephroblastomatosis (DHPLNB) 19.4 Société Internationale D’Oncologie Pédiatrique (SIOP) 19.4.1 Therapy for Unilateral WT in SIOP 19.4.1.1 Preoperative ChT 19.4.1.2 Postoperative ChT Regimen for Localized WT in SIOP [10] AV1 Regimen AV2 AVD Regimen Regimen HR-1 Postoperative ChT for Metastatic Disease (Stage IV) in SIOP [10] 19.4.2 Bilateral WT Management (SIOP) [10] 19.4.3 Management of Patients with Unilateral Tumor and Predisposition Syndromes/ Contralateral Nephroblastomatosis References 20: Radiotherapy 20.1 Introduction 20.2 Technical Considerations of Radiotherapy 20.2.1 Pediatric Radiation Oncology 20.2.2 Target Volume Definition 20.2.3 Equipment and Treatment Techniques 20.2.4 Simulation and Shielding 20.2.5 Radiation Dose and Fractionation 20.2.6 Sequelae of Radiation 20.3 Indications for Radiation 20.3.1 Locoregional Disease 20.3.2 Metastatic Disease 20.3.3 Recurrent Disease 20.4 Comparison of Radiotherapy Schedules in COG and SIOP-RTSG (Umbrella Protocol) 20.5 Conclusions References 21: Novel Tumor Directed Interventions 21.1 Intra-tumoral Chemotherapy for Wilms’ Tumor 21.1.1 Indications for IT-ChT 21.1.2 Mode of Action 21.1.3 Administration of IT-ChT 21.1.4 Results 21.2 Trans-arterial Chemo-embolization (TACE) 21.2.1 Technique 21.2.2 Post-procedural Care 21.3 TACE in WT 21.3.1 Contraindications 21.3.2 Adverse Events 21.4 Ablation Techniques 21.4.1 Radiofrequency Ablation (RFA) 21.4.2 Microwave Ablation (MWA) 21.4.3 MR-Guided High-Intensity Focused Ultrasound Ablation (MR-HIFU) References 22: Wilms’ Tumor in Resource-Challenged Nations 22.1 Introduction 22.2 Challenges to WT Care in LMIC 22.2.1 Late Presentations 22.2.2 Abandonment of Therapy 22.2.3 Malnutrition 22.2.4 Socioeconomic Factors 22.2.5 Cultural Issues 22.2.6 Biology 22.3 SIOP PODC and Adapted Regimens 22.4 Suggested Management for LMIC 22.5 SIOP PODC Clinical Guidelines for LIC [18] 22.6 Post-treatment Surveillance in LMIC References 23: Management of Resected Wilms’ Tumor with Unknown Staging Status 23.1 Background to the Vexed Problem 23.2 Management 23.2.1 Management of Favorable Histology Tumors 23.2.2 Management of Anaplastic Tumors 23.2.3 Management of Metastatic Tumors 23.2.4 Management of Small-Sized Favorable Histology Tumors in Young Children (