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;Ref