Tannapfel Malignant Mesothelioma

1. Auflage 2011
ISBN: 978-3-642-10862-4
Verlag: Springer
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 189, 196 Seiten

Reihe: Recent Results in Cancer Research

Malignant mesothelioma is an aggressive and fatal neoplasm of serous membranes that still shows a rising incidence worldwide. This book covers all the important aspects of the disease by bringing together contributions from selected experts in the fields of epidemiology, imaging, pathological diagnosis, therapy, genetics, and screening. Special emphasis is placed on the latest diagnostic techniques and current therapy standards. In addition, the mineralogy of asbestos is reviewed and clear advice is included on the analysis of tissue mineral fiber content. By providing a compact, scientifically based, and up-to-date overview of the management of malignant mesothelioma, this volume will be invaluable for all clinicians and pathologists who are engaged in the diagnosis and treatment of the disease or in related research.

Autoren/Hrsg.

Tannapfel, Andrea

Inhaltsverzeichnis

1;Copyright Page;5
2;Preface;6
3;Contents;8
4;1: Mineralogy of Asbestos;14
4.1;1.1 Introduction and Historical Background;14
4.2;1.2 Geologic and Mineralogic Features;15
4.3;1.3 Distribution and Physicochemical Properties of Chrysotile;17
4.4;1.4 Distribution and Physicochemical Properties of the Amphibole Species;20
4.5;1.5 Identification and Characterization of Asbestos;22
4.6;References;23
5;2: Epidemiology of Mesothelioma and Historical Background;25
5.1;References;35
6;3: Imaging of Mesothelioma;38
6.1;3.1 Introduction;38
6.2;3.2 Patterns of Presentation and Imaging Features;39
6.3;3.3 Preoperative Evaluation of MPM;40
6.4;3.4 Postoperative Evaluation;47
6.5;3.5 Unresectable Disease;47
6.6;3.6 Future Directions;49
6.7;3.7 Summary;52
6.8;References;52
7;4: Biopsy Techniques for the Diagnosis of Mesothelioma;55
7.1;4.1 Introduction;55
7.2;4.2 Clinical Presentation;56
7.3;4.3 Investigation of Pleural Effusion;56
7.3.1;4.3.1 Cytology;56
7.4;4.4 Investigation of Pleural Thickening with No Effusion;57
7.5;4.5 Percutaneous Pleural Biopsy Techniques;57
7.5.1;4.5.1 Abrams Needle;57
7.5.2;4.5.2 Radiologically Guided Percutaneous Pleural Biopsy;58
7.5.3;4.5.3 Positron Emission Tomography (PET) CT;59
7.6;4.6 Thoracoscopy;59
7.6.1;4.6.1 Local Anaesthetic Thoracoscopy;60
7.6.2;4.6.2 Video-Assisted Thoracoscopic Surgery;61
7.7;4.7 Open Biopsy;62
7.8;4.8 Prophylactic Radiotherapy;62
7.9;References;63
8;5: Pathohistological Diagnosis and Differential Diagnosis;66
8.1;5.1 Introduction;67
8.2;5.2 Malignant Mesothelioma of the Pleura;67
8.2.1;5.2.1 Morphology;67
8.2.1.1;5.2.1.1 Macroscopy and Tumour Spread;67
8.2.1.2;5.2.1.2 Histological Patterns;68
8.2.1.2.1;Epithelioid Mesothelioma;68
8.2.1.2.2;Sarcomatoid Mesothelioma;69
8.2.1.2.3;Biphasic Mesothelioma;69
8.2.1.2.4;Rare Forms of Mesothelioma;69
8.3;5.3 Differential Diagnosis of Malignant Mesothelioma and Pleural Metastases;70
8.3.1;5.3.1 Morphological Differences;70
8.3.2;5.3.2 Immunohistochemistry;71
8.3.2.1;5.3.2.1 Important Markers for Differential Diagnosis;71
8.3.2.1.1;Pancytokeratin;71
8.3.2.1.2;CK 5/6;71
8.3.2.1.3;Calretinin;72
8.3.2.1.4;WT-1;72
8.3.2.1.5;D2-40;72
8.3.2.1.6;TTF-1;73
8.3.2.1.7;BerEP4;73
8.3.2.1.8;MOC-31;73
8.3.2.1.9;BG8;73
8.3.2.1.10;Claudin;73
8.3.2.2;5.3.2.2 Conclusions Immunohistochemistry;73
8.4;5.4 Reactive Versus Neoplastic Mesothelial Proliferation;74
8.5;5.5 Primary Pleural Tumours Other than Malignant Mesothelioma;75
8.5.1;5.5.1 Peritoneal Mesothelioma;76
8.5.1.1;5.5.1.1 Pathohistological Diagnosis;76
8.5.1.1.1;Macroscopy;76
8.5.1.1.2;Microscopy;77
8.5.2;5.5.2 Malignant Mesothelioma of Tunica Vaginalis Testis;78
8.5.3;5.5.3 Well-Differentiated Papillary Mesothelioma;78
8.5.4;5.5.4 Prognosis and Predictive Factors;79
8.5.5;5.5.5 Differential Diagnosis;80
8.5.6;5.5.6 Benign Lesions;80
8.5.6.1;5.5.6.1 Benign Multicystic Peritoneal Mesothelioma;80
8.5.6.2;5.5.6.2 Adenomatoid Tumour;80
8.5.7;5.5.7 Malignant Lesions;81
8.5.7.1;5.5.7.1 Peritoneal Metastases;81
8.5.7.2;5.5.7.2 Carcinoma of Unknown Primary (CUP);81
8.5.7.3;5.5.7.3 Primary Peritoneal Carcinoma;81
8.5.7.4;5.5.7.4 Primary Peritoneal Borderline Tumour;82
8.5.8;5.5.8 Immunohistochemistry;82
8.6;5.6 Primary Peritoneal Carcinoma/Metastases of Serous Ovarian Cancer Versus Malignant Peritoneal Mesothelioma;83
8.7;References;84
9;6: Mesothelioma and Analysis of Tissue Fiber Content;88
9.1;6.1 Introduction;89
9.2;6.2 Techniques for Analysis of Pulmonary Mineral-Fiber Content;91
9.2.1;6.2.1 Lung Tissue Digests;91
9.3;6.3 Methods for Mineral Fiber Analysis;92
9.3.1;6.3.1 Light Microscopy (LM);92
9.3.2;6.3.2 Electron Microscopy;92
9.3.3;6.3.3 Comparability of Results Generated by Light or Electron Microscopy;93
9.3.4;6.3.4 Reference Population and Background Lung Asbestos Burden;93
9.3.5;6.3.5 Asbestos Bodies and Fiber Counting;93
9.4;6.4 Asbestos Lung Tissue Content in Patients with Mesothelioma;94
9.4.1;6.4.1 Light Microscopy;94
9.4.2;6.4.2 Electron Microscopy;95
9.4.3;6.4.3 Asbestos Content and Fiber Dimensions in Pleural Samples;95
9.5;6.5 Discussion;96
9.5.1;6.5.1 Asbestos Bodies and Fiber Burden of the Lung;96
9.5.2;6.5.2 Latency Period and Mean Age at Diagnosis of Mesothelioma;97
9.5.3;6.5.3 Clearance and Biopersistence of Asbestos Fibers;97
9.5.4;6.5.4 Carcinogenic Potency of Asbestos Fibers;98
9.5.5;6.5.5 Peritoneal Mesothelioma;98
9.5.6;6.5.6 Asbestos-Associated Mesothelioma and Other Possible Causes of Malignant Mesothelioma;98
9.5.7;6.5.7 Threshold or Cut-off Level;99
9.6;6.6 Conclusion;99
9.7;References;99
10;7: Surgical Therapy of Mesothelioma;105
10.1;7.1 Introduction;105
10.2;7.2 Natural History;106
10.3;7.3 Diagnosis;106
10.3.1;7.3.1 Video-Assisted Thoracoscopy;106
10.4;7.4 Staging;108
10.4.1;7.4.1 Laparoscopy;108
10.4.2;7.4.2 Mediastinoscopy;109
10.4.3;7.4.3 Thoracoscopy;110
10.4.4;7.4.4 Endoscopic Staging;110
10.5;7.5 Palliative Surgery;111
10.5.1;7.5.1 Pleural Drainage;111
10.5.2;7.5.2 Pleurectomy;111
10.6;7.6 Cytoreductive Surgery;113
10.6.1;7.6.1 Extrapleural Pneumonectomy (EPP);113
10.6.1.1;7.6.1.1 Technique;113
10.6.1.2;7.6.1.2 Postoperative Care;117
10.6.1.3;7.6.1.3 Adjuvant Therapy;117
10.6.2;7.6.2 Pleurectomy/Decortication (P/D);121
10.6.2.1;7.6.2.1 Technique;121
10.6.2.2;7.6.2.2 Postoperative Care;123
10.6.2.3;7.6.2.3 Adjuvant Therapy;123
10.6.3;7.6.3 Intrapleural Therapies;123
10.6.4;7.6.4 Extrapleural Pneumonectomy Versus Pleurectomy/Decortication;127
10.6.5;7.6.5 Does Cytoreductive Surgery Improve Survival?;128
10.7;7.7 Summary;129
10.8;References;129
11;8: Chemotherapy and Radiotherapy for Mesothelioma;134
11.1;8.1 Introduction;134
11.2;8.2 Radiotherapy;135
11.2.1;8.2.1 Radical Radiotherapy;135
11.2.1.1;8.2.1.1 Radical Radiotherapy as a Single Treatment;135
11.2.1.2;8.2.1.2 Radical Radiotherapy as Part of a Multimodal Treatment;135
11.2.1.2.1;Radiotherapy Following P/D;136
11.2.1.2.2;Radical Radiotherapy After EPP;136
11.2.1.2.3;Intensity Modulated Radiotherapy (IMRT);138
11.2.2;8.2.2 Prophylactic Radiotherapy;139
11.3;8.3 Systemic Therapies for Malignant Pleural Mesothelioma;140
11.3.1;8.3.1 Systemic Chemotherapy;140
11.3.1.1;8.3.1.1 First Line Chemotherapy;140
11.3.1.2;8.3.1.2 Optimal Time to Start the Treatment and Duration of Chemotherapy;142
11.3.1.3;8.3.1.3 Second-Line Treatment;143
11.3.2;8.3.2 Targeted Therapies;145
11.3.2.1;8.3.2.1 Epidermal Growth Factor Receptor (EGFR);145
11.3.2.2;8.3.2.2 Vascular Endothelial Growth Factor (VEGF) Inhibitors and Other Anti-angiogenic Drugs;146
11.3.2.3;8.3.2.3 Ribonuclease Inhibitors;147
11.3.2.4;8.3.2.4 Histone Deacetylase Inhibitors (HDACi);147
11.3.3;8.3.3 Immunomodulators, Gene Therapy and Cell Therapy;148
11.3.3.1;8.3.3.1 Immunomodulators;148
11.3.3.2;8.3.3.2 Gene Therapy;148
11.3.3.3;8.3.3.3 Cell Therapy;148
11.4;8.4 Conclusion;149
11.5;References;149
12;9: Genetics and Molecular Biology of Mesothelioma;155
12.1;9.1 Apoptosis as a Tumor Suppressor Mechanism;155
12.2;9.2 Key Alterations in the Core Apoptosis Signaling in Mesothelioma;155
12.2.1;9.2.1 Regulation of the Intrinsic (Mitochondrial) Apoptosis Pathway in Mesothelioma;155
12.2.2;9.2.2 Extrinsic Apoptosis Pathway Regulation in Mesothelioma;158
12.2.3;9.2.3 Inhibitors of Apoptosis in Mesothelioma;158
12.3;9.3 Tumor Suppressor Loss in Mesothelioma;158
12.3.1;9.3.1 Loss of nf2 Is Frequent in Mesothelioma;158
12.3.2;9.3.2 NF2 Encodes the Tumor Suppressor Merlin;159
12.3.3;9.3.3 PLZF Is a Novel Tumor Suppressor in Mesothelioma;160
12.4;9.4 Therapeutic Inhibition of Survival Pathways;160
12.4.1;9.4.1 PI3K/AKT/mTOR Axis in Mesothelioma;160
12.4.2;9.4.2 HGF/cMET Pathway Is Activated in Mesothelioma;160
12.4.3;9.4.3 WNT Pathway Activation in Mesothelioma;161
12.4.4;9.4.4 Estrogen Receptor Beta;162
12.5;9.5 Therapeutic Reactivation of Tumor Suppressors;162
12.5.1;9.5.1 Epigenomic Dysregulation in Mesothelioma;162
12.5.2;9.5.2 Targeting the Mesothelioma Epigenome via Inhibition of Histone Deacetylases;163
12.5.3;9.5.3 Targeting the Ubiquitin Proteasome Pathway;164
12.6;9.6 Synthetic Lethal Strategies;164
12.7;9.7 Summary;165
12.8;References;165
13;10: Early Stages of Mesothelioma, Screening and Biomarkers;174
13.1;10.1 Early-Stage Malignant Mesothelioma, Including the Concept of Mesothelioma In Situ and the Distinction from Reactive Me;174
13.2;10.2 Biomarkers for Early-Stage Epithelioid Malignant Mesothelioma Versus Reactive Mesothelial Hyperplasia;179
13.2.1;10.2.1 Epithelial Membrane Antigen (EMA);179
13.2.2;10.2.2 GLUT-1;180
13.2.3;10.2.3 Bcl-2;181
13.2.4;10.2.4 p53;181
13.2.5;10.2.5 X-Linked Inhibitor of Apoptosis Proteins (XIAP);182
13.2.6;10.2.6 P-Glycoprotein (P-170);182
13.2.7;10.2.7 Neural Cell Adhesion Molecules (NCAMs): CD56;182
13.3;10.3 Screening for Malignant Mesothelioma and Prognostic Biomarkers: Serum Levels of Soluble Mesothelin-Related Proteins (;183
13.3.1;10.3.1 Introductory Remarks on Screening for Malignant Mesothelioma;183
13.3.2;10.3.2 Radiological Screening for MM;184
13.3.3;10.3.3 Soluble Mesothelin-Related Proteins (SMRPs);184
13.3.4;10.3.4 Serum Osteopontin (OPN) Levels;186
13.3.5;10.3.5 Megakaryocyte Potentiating Factor (MKPF);187
13.3.6;10.3.6 CA125;187
13.3.7;10.3.7 Summary;187
13.4;10.4 Aquaporins and Malignant Mesothelioma;188
13.5;References;190