Zimmermann / Perilongo Pediatric Liver Tumors

1. Auflage 2011
ISBN: 978-3-642-14504-9
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 232 Seiten

Reihe: Pediatric Oncology

The field of liver tumors in children has seen tremendous therapeutic advances over recent years. This has been achieved through a much better understanding of the biology of disease, improved diagnostic procedures, refined methods of pretreatment tumor staging, the implementation of highly efficient chemotherapy and surgery, detailed monitoring of toxicity, and careful follow-up strategies. International controlled trials have played a key role in these advances, and many leading figures in the trials are among the editors and authors of this book. Their principal goal in Hepatic Tumors in Children is to provide the reader with a complete update on this complex and rapidly evolving field. All aspects of an impressive success story are covered, disclosing how the outcome of a previously devastating disease has been so dramatically improved. This book will prove essential reading for all who are involved in the care of children with liver tumors.

Autoren/Hrsg.

Zimmermann, Arthur

Perilongo, Giorgio

Inhaltsverzeichnis

1;Pediatric Oncology;1
1.1;Copyright Page ;3
1.2;Foreword;4
1.3;Contents;7
1.4;Contributors;9
1.5;1: Introduction;11
1.6;2: Historical Background;12
1.6.1;2.1 Introduction;12
1.6.2;2.2 The Dark Ages;13
1.6.3;2.3 Advent of Printing;13
1.6.4;2.4 Early Children’s Hospital;13
1.6.5;2.5 Pioneer Pathologists and/or Their Textbooks;14
1.6.6;2.6 Pioneers in Surgical Anatomy and Liver Surgery;14
1.6.7;2.7 Liver Transplantation;14
1.6.8;2.8 International Oncology Groups;15
1.6.8.1;2.8.1 COG;15
1.6.8.2;2.8.2 SIOP;15
1.6.8.3;2.8.3 SIOPEL (SIOP Epithelial Liver tumors);15
1.6.8.4;2.8.4 IPSO;16
1.6.8.5;2.8.5 SIOP ASIA;16
1.6.8.6;2.8.6 PODC (Pediatric Oncology in Developing Countries);16
1.6.8.7;2.8.7 EONS (European Oncology Nursing Specialists);16
1.6.9;2.9 National Pediatric Oncology Societies;16
1.6.10;2.10 Clinical Liver Trials;17
1.6.11;2.11 Conclusions and Future Outlook;17
1.6.12;References;21
1.7;3: Epidemiology of Pediatric Liver Tumors;24
1.7.1;3.1 Introduction;24
1.7.2;3.2 Descriptive Epidemiology of Pediatric Liver Tumors;25
1.7.2.1;3.2.1 Spectrum and Frequency of Liver Tumors in Children;25
1.7.2.2;3.2.2 International Variations in Incidence;25
1.7.2.3;3.2.3 Time Trends in Incidence;27
1.7.3;3.3 Analytical Epidemiology of Hepatoblastoma and Hepatocellular Carcinoma in Children;27
1.7.3.1;3.3.1 Overview of Environmental Risk Factors;27
1.7.3.2;3.3.2 Very Low Birth Weight and Hepatoblastoma;28
1.7.3.3;3.3.3 Parental Tobacco Smoking and Hepatoblastoma;29
1.7.3.4;3.3.4 Associations with Heritable Cancer Predisposition, Congenital Malformation Syndromes, and Anomalies;29
1.7.3.5;3.3.5 Etiology of Hepatocellular Carcinoma in Children;30
1.7.4;3.4 Implications of Findings from Analytical Studies of Pediatric Liver Tumors;31
1.7.5;3.5 Conclusions;32
1.7.6;References;33
1.8;4: Molecular Aspects of Hepatoblastoma;36
1.8.1;4.1 Introduction;36
1.8.2;4.2 Basics of Hepatoblastoma;36
1.8.3;4.3 Familial Forms of Hepatoblastoma;37
1.8.4;4.5 Altered Developmental Signaling Pathways in Hepatoblastoma;40
1.8.4.1;4.5.1 The Wnt Signaling Pathway;40
1.8.4.2;4.5.2 The Hedgehog Signaling Pathway;42
1.8.4.3;4.5.3 The Insulin-Like Growth Factor Axis;43
1.8.4.4;4.5.4 The Hepatocyte Growth Factor/c-Met Pathway;44
1.8.5;4.6 Epigenetically Altered Tumor Suppressor Genes in Hepatoblastoma;45
1.8.6;4.7 Gene Signatures as Predictors of Outcome;46
1.8.7;References;47
1.9;5: Ontogenetic Aspects of Liver Tumors;52
1.9.1;5.1 Introduction;52
1.9.2;5.2 Liver Ontogenesis: Pathways from Endoderm to Liver;52
1.9.2.1;5.2.1 Generation of the Hepatoblast and Hepatocyte Lineages;52
1.9.2.2;5.2.2 Development of the Cholangiocyte Lineage and the Bile Duct System;53
1.9.3;5.3 Stem Cells in the Pathogenesis of Hepatoblastomas;54
1.9.4;5.4 Undifferentiated Epithelial Hepatoblastomas and the Rhabdoid Cell/INI1 Connection;55
1.9.5;5.5 Beyond Hepatoblasts: Tumors with More Differentiated Liver Cell Lineages;56
1.9.6;5.6 Bimodal Differentiation: Cholangioblastic Hepatoblastomas and Ductal Plate Tumors May Recapitulate Early Steps of Hepato;56
1.9.7;5.7 Epithelial-Mesenchymal Transition as a Pathogenic Mechanism in Mixed Hepatoblastomas and Related Tumors;57
1.9.8;5.8 Conclusion;58
1.9.9;References;58
1.10;6: Translational Investigations of Liver Tumors: Sampling Strategies and Banking;61
1.10.1;6.1 Introduction;61
1.10.2;6.2 SIOPEL Liver Tumour Storage Programme;62
1.10.2.1;6.2.1 Tumor Tissue Collection;62
1.10.2.2;6.2.2 Tumor Tissue Storing;63
1.10.2.3;6.2.3 Tumor Tissue Distribution;64
1.10.3;6.3 Discussion;65
1.10.4;References;65
1.11;7: Clinical Presentation and Diagnosis;67
1.11.1;7.1 Malignant Liver Tumors;67
1.11.1.1;7.1.1 Age at Diagnosis;67
1.11.1.2;7.1.2 Clinical Symptoms;68
1.11.1.3;7.1.3 Laboratory Investigations;68
1.11.1.4;7.1.4 Imaging;70
1.11.1.5;7.1.5 Biopsy;70
1.11.2;7.2 Benign Tumors;70
1.11.2.1;7.2.1 Vascular Tumors;70
1.11.2.2;7.2.2 Mesenchymal Hamartomas;71
1.11.2.3;7.2.3 Focal Nodular Hyperplasia;71
1.11.2.4;7.2.4 Adenoma;71
1.11.3;7.3 Conclusion;71
1.11.4;References;71
1.12;8: Imaging and Staging of Pediatric Liver Tumors;73
1.12.1;8.1 Imaging Techniques;73
1.12.1.1;8.1.1 Ultrasound (US);73
1.12.1.2;8.1.2 Computed tomography (CT);75
1.12.1.3;8.1.3 Magnetic Resonance Imaging (MRI);77
1.12.1.4;8.1.4 Nuclear Medicine;77
1.12.1.5;8.1.5 Obsolete Imaging Techniques;77
1.12.2;8.2 Approach to Differential Diagnosis;78
1.12.2.1;8.2.1 Benign Tumors;78
1.12.2.2;8.2.2 Malignant Tumors;78
1.12.3;8.3 Staging Systems;80
1.12.4;8.4 Local Staging;80
1.12.4.1;8.4.1 PRETEXT;80
1.12.4.1.1;8.4.1.1 PRETEXT I (Fig. 8.6);81
1.12.4.1.2;8.4.1.2 PRETEXT II (Fig. 8.7);81
1.12.4.1.3;8.4.1.3 PRETEXT III (Fig. 8.8);82
1.12.4.1.4;8.4.1.4 PRETEXT IV (Fig. 8.9);82
1.12.4.2;8.4.2 Imaging of Segmental and Vascular Anatomy;82
1.12.4.3;8.4.3 Multifocal Tumor (F);83
1.12.5;8.5 Vascular Involvement (P, V);83
1.12.6;8.6 Extrahepatic Spread in the Abdomen (E, H);86
1.12.7;8.7 Metastatic Disease (M, N);87
1.12.8;References;89
1.13;9: Pathology of Pediatric Liver Tumors;91
1.13.1;9.1 Hepatoblastoma and Related Tumors;91
1.13.1.1;9.1.1 Introduction;91
1.13.1.2;9.1.2 Classification of Hepatoblastoma;91
1.13.1.3;9.1.3 Macroscopy;92
1.13.1.4;9.1.4 Histopathology of Hepatoblastomas;92
1.13.1.4.1;9.1.4.1 Fetal Hepatoblastoma: The Differentiated Phenotype with a Favorable Histology;93
1.13.1.4.2;9.1.4.2 Embryonal Histology: A Common Partner of Fetal Tissue Components;94
1.13.1.4.3;9.1.4.3 Macrotrabecular Hepatoblastoma: A Distinct Growth Pattern;95
1.13.1.4.4;9.1.4.4 Undifferentiated Epithelial Hepatoblastomas;96
1.13.1.4.4.1;Small Cell Undifferentiated Hepatoblastoma (HB-SCUD);96
1.13.1.4.4.2;Other Phenotypes of Undifferentiated Hepatoblastoma;99
1.13.1.4.4.3;Undifferentiated Hepatoblastoma with Rhabdoid Features and Malignant Rhabdoid Tumor;99
1.13.1.4.5;9.1.4.5 Grading of Epithelial Types of Hepatoblastoma;100
1.13.1.4.6;9.1.4.6 Mixed Epithelial and Mesenchymal Hepatoblastomas;100
1.13.1.4.6.1;Mixed Epithelial and Mesenchymal Hepatoblastoma Without Teratoid Features;100
1.13.1.4.6.2;Mixed Epithelial and Mesenchymal Hepatoblastoma with Teratoid Features;100
1.13.1.5;9.1.5 Immunohistochemistry of Hepatoblastomas;102
1.13.1.6;9.1.6 Growth Patterns, Proliferation, and Differentiation Characteristics in Hepatoblastomas;103
1.13.1.7;9.1.7 Chemotherapy Effects in Hepatoblastomas;105
1.13.1.8;9.1.8 Cholangioblastic Hepatoblastoma (Hepatoblastomas with Cholangioblastic Features) and “Ductal Plate Tumors”;107
1.13.1.9;9.1.9 Transitional Liver Cell Tumor (TLCT);107
1.13.1.10;9.1.10 Tumors Possibly Related to the Hepatoblastoma Tumor Family;109
1.13.2;9.2 Pediatric Hepatocellular Carcinoma;110
1.13.2.1;9.2.1 Definition and Epidemiology;110
1.13.2.2;9.2.2 Etiology;110
1.13.2.3;9.2.3 Pathology of Adult-Type Hepatocellular Carcinoma;111
1.13.2.3.1;9.2.3.1 Gross Presentation;111
1.13.2.3.2;9.2.3.2 Histology of Adult-Type Hepatocellular Carcinoma;112
1.13.2.4;9.2.4 Fibrolamellar Hepatocellular Carcinoma;113
1.13.2.5;9.2.5 Differential Diagnoses;114
1.13.2.6;9.2.6 New Knowledge on Pathogenic/Molecular Pathways;115
1.13.2.7;9.2.7 Conclusion;115
1.13.3;References;116
1.14;10: Surgical Treatment;121
1.14.1;10.1 Introduction;121
1.14.2;10.2 Biopsy;121
1.14.3;10.3 Liver Resections;123
1.14.3.1;10.3.1 Liver Anatomy and Resectability Assessment;124
1.14.3.1.1;10.3.1.1 Hepatic Anatomy;124
1.14.3.1.2;10.3.1.2 Resectability;125
1.14.3.2;10.3.2 Technical Aspects;129
1.14.3.2.1;10.3.2.1 Typical Liver Resections;131
1.14.3.2.2;10.3.2.2 Atypical Liver Resections;132
1.14.3.2.3;10.3.2.3 Special Surgical Techniques;132
1.14.3.3;10.3.3 Tumor Residuum;133
1.14.3.4;10.3.4 Complications and Their Management;134
1.14.3.4.1;10.3.4.1 Bleeding;134
1.14.3.4.2;10.3.4.2 Bile Leak and Stricture;134
1.14.3.4.3;10.3.4.3 Others;134
1.14.4;10.4 Surgery for Metastases;135
1.14.4.1;10.4.1 Pulmonary Metastases;135
1.14.5;10.5 Surgery for Recurrent Disease;136
1.14.6;References;137
1.15;11: Liver Transplantation for Unresectable Liver Tumors in Children;140
1.15.1;11.1 Introduction;140
1.15.2;11.2 Hepatoblastoma;141
1.15.2.1;11.2.1 PRETEXT and Liver Transplantation for HB in SIOPEL;141
1.15.2.2;11.2.2 Outcomes of Transplantation for HB Reported in Literature;143
1.15.2.3;11.2.3 Guiding Principles to Consider for Transplant in HB;145
1.15.2.4;11.2.4 Recommendations for Liver Transplantation in Current Multicenter HB Studies;148
1.15.2.5;11.2.5 Post-Transplant Immunosuppression;149
1.15.3;11.3 Hepatocellular Carcinoma;149
1.15.3.1;11.3.1 Outcomes of Transplantation for HCC Reported in Literature;150
1.15.3.2;11.3.2 Guiding Principles to Consider for Liver Transplant in HCC;151
1.15.3.3;11.3.3 Contemporary Recommendations for Liver Transplantation in HCC in Children;152
1.15.4;11.4 Transplant for Other Pediatric Liver Tumors;153
1.15.4.1;11.4.1 Infantile Hepatic Hemangioma, Infantile Hemangioendothelioma of the Liver (IHHE), and Angiosarcoma;153
1.15.4.2;11.4.2 Malignant Epithelioid Hemangioendothelioma;154
1.15.4.3;11.4.3 Mesenchymal Hamartoma;154
1.15.4.4;11.4.4 Inflammatory Myofibroblastic Tumor;154
1.15.4.5;11.4.5 Undifferentiated (Embryonal) Sarcoma;155
1.15.5;11.5 Pediatric Liver Unresectable Tumor Observatory (Pluto);155
1.15.6;11.6 Conclusion;155
1.15.7;References;156
1.16;12: Chemotherapy for Childhood Hepatoblastoma and Hepatocellular Carcinoma;160
1.16.1;12.1 Hepatoblastoma;160
1.16.1.1;12.1.1 Why Chemotherapy?;160
1.16.1.2;12.1.2 When Chemotherapy?;161
1.16.1.3;12.1.3 Which Chemotherapy?;162
1.16.2;12.2 The North American Experience (Table 12.1);163
1.16.3;12.3 The SIOPEL Experience (Table 12.2);165
1.16.4;12.4 Other Regimens;166
1.16.5;12.5 Hepatocellular Carcinoma;167
1.16.5.1;12.5.1 The North American Experience;167
1.16.5.2;12.5.2 The SIOPEL Experience;167
1.16.6;12.6 The German Experience;168
1.16.6.1;12.6.1 Other Experiencees;168
1.16.6.2;12.6.2 Overall Conclusive Remarks;168
1.16.7;References;168
1.17;13: Salvage Strategies;171
1.17.1;13.1 Failures in Hepatoblastoma;171
1.17.2;13.2 Salvage Modalities;173
1.17.3;13.3 Chemotherapeutic Agents in Salvage Treatment;173
1.17.4;13.4 High-Dose Chemotherapy;176
1.17.5;13.5 Conclusions;179
1.17.6;References;180
1.18;14: Alternative Approaches for Treatment;183
1.18.1;14.1 Introduction;183
1.18.2;14.2 Theoretical Aspects of Intraarterial Chemotherapy;183
1.18.3;14.3 Technical Aspects of Hepatic Artery Chemoembolization;185
1.18.3.1;14.3.1 Complications;187
1.18.4;14.4 Results of Hepatic Artery Chemoembolization;187
1.18.5;14.5 Other Transarterial Techniques;189
1.18.6;14.6 Percutaneous Tumor Ablation;191
1.18.7;14.7 Portal Vein Embolization;191
1.18.8;References;193
1.19;15: Supportive Therapy and Toxicity;195
1.19.1;15.1 Introduction;195
1.19.2;15.2 Supportive Care;195
1.19.2.1;15.2.1 Safer Blood Products;195
1.19.2.2;15.2.2 Central Intravenous Catheters;196
1.19.2.3;15.2.3 Improved Nutritional Support and Antiemetic Therapy;196
1.19.2.4;15.2.4 Management of Infection and Prophylaxis;197
1.19.3;15.3 Toxicity;197
1.19.3.1;15.3.1 Platinum-Containing Agents;197
1.19.3.1.1;15.3.1.1 Administration;197
1.19.3.1.2;15.3.1.2 Acute Toxicity;197
1.19.3.1.2.1;Nausea and Vomiting;197
1.19.3.1.2.2;Allergic Reactions;198
1.19.3.1.2.3;Bone Marrow Toxicity;198
1.19.3.1.3;15.3.1.3 Late Toxicity;198
1.19.3.1.3.1;Renal Toxicity;198
1.19.3.1.3.2;Hearing Loss;198
1.19.3.1.3.3;Neurological Toxicity;201
1.19.3.2;15.3.2 Doxorubicin;201
1.19.3.2.1;15.3.2.1 Administration;201
1.19.3.2.2;15.3.2.2 Acute Toxicity;201
1.19.3.2.2.1;Nausea and Vomiting;201
1.19.3.2.2.2;Bone Marrow Toxicity;201
1.19.3.2.2.3;Mucositis;201
1.19.3.2.3;15.3.2.3 Late Toxicity;201
1.19.3.2.3.1;Cardiotoxicity;201
1.19.3.3;15.3.3 Vincristine;203
1.19.3.3.1;15.3.3.1 Administration;203
1.19.3.3.2;15.3.3.2 Side Effects;203
1.19.4;15.4 Conclusion;203
1.19.5;References;203
1.20;16: Challenges and Opportunities of International Therapeutic Trials;206
1.20.1;16.1 Introduction;206
1.20.2;16.2 Challenges;207
1.20.2.1;16.2.1 Clinical Trials in Very Rare Diseases;207
1.20.2.2;16.2.2 Staging Systems;207
1.20.3;16.3 Trial Designs;208
1.20.3.1;16.3.1 The Hypothesis Dictates the Trial Design;208
1.20.3.2;16.3.2 Biomolecular Investigations;209
1.20.3.3;16.3.3 Case Report Forms;209
1.20.4;16.4 Trial Conduct;209
1.20.4.1;16.4.1 Why Bother to Treat Patients in Clinical Trials?;209
1.20.4.2;16.4.2 Complete Documentation of All Included Patients;210
1.20.4.3;16.4.3 Interim Monitoring;210
1.20.5;16.5 Presentation and Interpretation of Results;211
1.20.5.1;16.5.1 Intention to Treat Analysis;211
1.20.6;16.6 Opportunities;212
1.20.7;References;212
1.21;17: Tumors Other than Hepatoblastoma and Hepatocellular Carcinoma;213
1.21.1;17.1 Introduction;213
1.21.2;17.2 Undifferentiated (Embryonal) Sarcoma of the Liver;213
1.21.2.1;17.2.1 Introduction;213
1.21.2.2;17.2.2 Epidemiology and Etiology;214
1.21.2.3;17.2.3 Clinical Presentation and Diagnosis;214
1.21.2.4;17.2.4 Pathology;215
1.21.2.5;17.2.5 Treatment;215
1.21.2.5.1;17.2.5.1 Therapy of Non-ruptured Solitary Hepatic Lesions with or Without Metastases;215
1.21.2.5.2;17.2.5.2 Therapy in Case of Tumor Rupture;218
1.21.2.5.3;17.2.5.3 Therapy of Multifocal Tumors;218
1.21.2.5.4;17.2.5.4 Relapsing Tumor;218
1.21.3;17.3 Hepatobiliary Rhabdomyosarcoma;218
1.21.3.1;17.3.1 Introduction;218
1.21.3.2;17.3.2 Clinical Presentation and Diagnosis;218
1.21.3.3;17.3.3 Pathology;219
1.21.3.4;17.3.4 Treatment;219
1.21.4;17.4 Malignant Rhabdoid Tumor of the Liver;220
1.21.5;17.5 Angiosarcoma of the Liver;220
1.21.5.1;17.5.1 Introduction;220
1.21.5.2;17.5.2 Clinical Presentation and Diagnosis;220
1.21.5.3;17.5.3 Pathology;220
1.21.5.4;17.5.4 Treatment;221
1.21.6;17.6 Other Hepatic Vascular Tumors;221
1.21.6.1;17.6.1 Infantile Hepatic Hemangioendothelioma;221
1.21.6.2;17.6.2 Epithelioid Hemangioendothelioma of the Liver;222
1.21.7;17.7 Mesenchymal Hamartoma;222
1.21.7.1;17.7.1 Introduction;222
1.21.7.2;17.7.2 Clinical Presentation and Diagnosis;223
1.21.7.3;17.7.3 Treatment;223
1.21.8;17.8 Conclusion;223
1.21.9;References;223
1.22;18: Future Prospective;226
1.22.1;References;228
1.23;Index;229