BOOK
Abeloff's Clinical Oncology E-Book
John E. Niederhuber | James O. Armitage | James H Doroshow | Michael B. Kastan | Joel E. Tepper
(2013)
Additional Information
Book Details
Abstract
Practical and clinically focused, Abeloff’s Clinical Oncology is a trusted medical reference book designed to capture the latest scientific discoveries and their implications for cancer diagnosis and management of cancer in the most accessible manner possible. Abeloff’s equips everyone involved - from radiologists and oncologists to surgeons and nurses - to collaborate effectively and provide the best possible cancer care.
- Consult this title on your favorite e-reader, conduct rapid searches, and adjust font sizes for optimal readability.
- Enhance your understanding of complex concepts with a color art program that highlights key points and illustrates relevant scientific and clinical problems.
- Stay at the forefront of the latest developments in cancer pharmacology, oncology and healthcare policy, survivorship in cancer, and many other timely topics.
- See how the most recent cancer research applies to practice through an increased emphasis on the relevance of new scientific discoveries and modalities within disease chapters.
- Streamline clinical decision making with abundant new treatment and diagnostic algorithms as well as concrete management recommendations.
- Take advantage of the collective wisdom of preeminent multidisciplinary experts in the field of oncology, including previous Abeloff’s editors John E. Niederhuber, James O. Armitage, and Michael B. Kastan as well as new editors James H. Doroshow from the National Cancer Institute and Joel E. Tepper of Gunderson & Tepper: Clinical Radiation Oncology.
- Quickly and effortlessly access the key information you need with the help of an even more user-friendly, streamlined format.
- Access the complete contents anytime, anywhere at Expert Consult, and test your mastery of the latest knowledge with 500 online multiple-choice review questions.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front cover | cover | ||
| Inside front cover | ifc1 | ||
| Abeloff's Clinical Oncology, 5/e | i | ||
| Copyright page | iv | ||
| Dedication | v | ||
| Memoriam | vii | ||
| Preface | ix | ||
| Acknowledgments | ix | ||
| Contributors | xi | ||
| Table of Contents | xxxi | ||
| I Science of Clinical Oncology | 1 | ||
| A Biology and Cancer | 2 | ||
| 1 Molecular Tools in Cancer Research | 2 | ||
| Summary of Key Points | 2 | ||
| Introduction | 2 | ||
| Our Unstable Heredity | 2 | ||
| Detecting Cancer Mutations | 2 | ||
| Generating Diversity with Alternate Splicing | 3 | ||
| The Genomics of Cancer | 4 | ||
| Building Gene Libraries | 5 | ||
| Losing Control of the Genome | 7 | ||
| Epigenetics and Cancer | 7 | ||
| Profiling Tumors | 7 | ||
| The Cancer Proteome | 13 | ||
| Modeling Cancer in Vivo | 15 | ||
| Transgenic Models of Cancer | 16 | ||
| Conditional Control of Oncogene Activation | 16 | ||
| Models of Recessive Gene Mutations in Cancer | 18 | ||
| Future View | 18 | ||
| Recommended Texts | 21 | ||
| Further Selected Reading | 21 | ||
| 2 Intracellular Signaling | 22 | ||
| Summary of Key Points | 22 | ||
| Introduction | 22 | ||
| Receptor Tyrosine Kinase Signaling | 22 | ||
| Epidermal Growth Factor Receptor Signaling | 23 | ||
| Insulin and Insulin-Like Growth Factor–1 Receptor Signaling | 25 | ||
| Platelet-Derived Growth Factor Receptor Signaling | 27 | ||
| Fibroblast Growth Factor Receptor Signaling | 27 | ||
| RET Signaling | 28 | ||
| Vascular Endothelial Growth Factor Signaling | 28 | ||
| Hepatocyte Growth Factor Receptor Signaling | 29 | ||
| SRC Signaling | 34 | ||
| BCR-ABL Signaling | 34 | ||
| G-Protein Coupled Receptors Signaling | 29 | ||
| Cytokine Receptor Signaling | 31 | ||
| Serine/Threonine Receptor Signaling | 32 | ||
| Notch Receptor Signaling | 33 | ||
| Nuclear Hormone Receptor Signaling | 33 | ||
| Integrin Receptor Signaling | 33 | ||
| Non-receptor Tyrosine Kinase Signaling SRC Signaling The SRC family of intracellular, non-receptor tyrosine kinase proteins is composed of 11 members (Src, Fyn, Yes, Blk, Yrk, Frk/Rak, Fgr, Hck, Lck, Srm, and Lyn).296 They share common structural features, including the so-called SH domains 1 to 4. The SH1 domain includes the kinase domain. Only Src, Fyn, and Yes are expressed ubiquitously, whereas the tissue distribution of the latter six is more restricted.297 Together, Src family kinases have pleiotropic roles in cellular proliferation, apoptosis, differentiation, motility, adhesion, angiogenesis, and immunity.298,299 SRC is by far the most intensively studied family member and was the first gene observed to have oncogenic potential. Peyton Rous was awarded the Nobel Prize for a series of experiments showing that a transmissible factor was present in avian sarcomas that was capable of initiating tumors in recipient birds. Five decades later the viral oncogene v-Src was identified as the oncogenic factor in the Rous sarcoma virus.300-302 Bishop and Varmus later showed that v-Src was a mutant form of the cellular protooncogene c-SRC, and Hunter and colleagues showed that its transformative capacity was dependent on its tyrosine kinase activity.13,14,303 c-SRC, hereafter called SRC, is regulated in a number of ways. First, Src has a myristoylation site in its N-terminus that is necessary for membrane localization and that promotes its interaction with nearby membrane-bound effectors.304 The SH2 and SH3 domains facilitate protein-protein interactions and conformational changes in the protein. Inactive SRC is maintained in a closed conformation, with phosphorylated Y530 (mediated by CSK, C-terminal SRC, and CSK homology kinases) interacting with the folded over SH2 domain.305 The closed, inactive confirmation of SRC is further stabilized by proline-rich segments of the kinase domain associating with the SH3 domain.306 SRC activation requires dephosphorylation of Y530, likely by PTPα/γ/1β (protein tyrosine phosphatase α/γ/1β) or SHP1/2, which allows the kinase to assume an open conformation.296,307 Autophosphorylation of Y419 in the activation loop of the kinase domain also promotes full activity,308 whereas binding of focal adhesion kinase and CRK-associated substrate to the SH2 domain induce SRC activation and link SRC signaling to the regulation of focal adhesion, actin reorganization, and migratory phenotypes.309,310 SRC is a downstream mediator of numerous receptor families including receptor tyrosine kinases, integrin receptors, hormone receptors, cytokines receptors, and GCPRs and promotes signaling through the PI3K/AKT, RAS/MAP kinase, and JAK/STAT cascades, among others.296,297,299,307,311-315 Although SRC mutations are rare in human cancers, SRC is frequently activated as a consequence of other mutational events in colorectal, breast, esophageal, gastric, pancreatic, hepatocellular, ovarian, and lung cancers.296 In colorectal and hepatocellular carcinomas, SRC activation occurs in the setting of concomitant loss of CSK.316-318 The tyrosine kinase inhibitor dasatinib, which is used in the treatment of chronic myelogenous leukemia and Philadelphia-chromosome–positive acute lymphoid leukemia, inhibits Src family kinases, as well as BCR-ABL, KIT, Ephrin A2 receptor, and PDGFR (Table 2-1).319-321 Additional dual SRC/ABL and SRC selective inhibitors that are in early clinical testing include bosutinib (SKI-606), saracatinib (AZD0530), ponatinib (AP24534), XL-228, KX2-391, AZM475271, XL99, TG100435/100855, and DCC2036. Most have shown limited single-agent activity and are being developed as combination therapies.299,307,313-315 BCR-ABL Signaling The ABL tyrosine kinase is found in both the cytoplasm and the nucleus, and its functions vary based on subcellular localization.322 Cytoplasmic ABL has been implicated in G1/S checkpoint regulation,323 whereas nuclear ABL inhibits binding of the DNA repair protein RAD51 to sites of DNA damage.324 ABL contains an SH3 domain, an SH2 domain, and a kinase domain followed by a C terminal region that contains actin binding sites, suggesting that when localized to the cytoplasm, the protein interacts with components of the cytoskeleton.325 Although chronic myelogenous leukemia (CML) is the disease most associated with derangements in ABL signaling, a number of neurodegenerative disorders, including Alzheimer and Parkinson disease, have also been shown to have aberrant activation of ABL.322 Translocation of the ABL gene on chromosome 9 with the breakpoint cluster region (BCR) gene on chromosome 22 results in the expression of a BCR-ABL fusion protein.326 This translocation, the Philadelphia chromosome, is found in almost all CML patients and represents the pathognomonic molecular lesion in this disease. BCR-ABL translocations are also found in approximately one third of acute lymphoblastic leukemias.327,328 The realization that the proliferation and survival of CML cells is dependent on the fusion protein encoded by the 9;22 translocation led to the development of imatinib, an inhibitor of the ABL tyrosine kinase (Table 2-1).328 Essentially all patients with CML respond to this agent, and the development of imatinib established selective inhibitors of oncogenic kinases as a viable therapeutic strategy. 329 | 34 | ||
| RAS/MAP Kinase Pathway Signaling | 35 | ||
| The PI3K/Akt/mTOR Pathway Signaling | 36 | ||
| Translational Implications | 37 | ||
| References | 38 | ||
| References | 39.e1 | ||
| 3 The Cellular Microenvironment and Metastases | 40 | ||
| Summary of Key Points | 40 | ||
| Introduction | 40 | ||
| Mechanisms of Metastasis | 40 | ||
| Hematogenous Metastasis | 40 | ||
| Invasion | 40 | ||
| Changes in Cell Adhesion | 40 | ||
| Cell Motility | 42 | ||
| Disruption of the Basement Membrane | 42 | ||
| Intravasation | 42 | ||
| Survival in the Circulatory System | 42 | ||
| Arrest and Extravasation | 42 | ||
| Proliferation | 43 | ||
| Angiogenesis | 43 | ||
| Lymphatic Metastasis | 43 | ||
| Transcoelomic Metastasis | 43 | ||
| Adhesion | 43 | ||
| Anoikis | 44 | ||
| Immune Evasion | 44 | ||
| Peritoneal Implantation and Metastatic Growth | 44 | ||
| Metastasis and Tumor Reseeding | 44 | ||
| Tumor Microenvironment and Metastasis | 44 | ||
| Cancer Stem Cells | 44 | ||
| Endothelial Cells and Pericytes | 45 | ||
| Immune Cells | 45 | ||
| Fibroblasts | 45 | ||
| Hypoxia | 46 | ||
| Patterns of Metastasis | 47 | ||
| Seed and Soil Hypothesis | 47 | ||
| Premetastatic Niche | 47 | ||
| Organ Specificity | 48 | ||
| Metastases to the Bone | 48 | ||
| Metastases to the Brain | 48 | ||
| Metastases to the Lung | 48 | ||
| Metastases to the Liver | 49 | ||
| Clinical Relevance and Applications | 49 | ||
| Conclusion | 49 | ||
| References | 50 | ||
| References | 51.e1 | ||
| 4 Control of the Cell Cycle | 52 | ||
| Summary of Key Points | 52 | ||
| Introduction | 52 | ||
| The Cell Division Cycle | 53 | ||
| Overview of the Cell Cycle Machinery | 53 | ||
| Cyclin-Dependent Kinases and Their Regulators | 53 | ||
| Retinoblastoma Proteins and E2F Transcription Factors | 55 | ||
| Cell Cycle Phosphatases | 55 | ||
| Ubiquitin-Dependent Protein Degradation | 55 | ||
| The Mitotic Spindle and Mitotic Kinases and Kinesins | 55 | ||
| Entry into the Cell Cycle | 56 | ||
| DNA Replication | 56 | ||
| Mitosis | 58 | ||
| Cell Cycle Checkpoints | 60 | ||
| G1/S Checkpoint | 60 | ||
| Intra-S Phase Checkpoint | 62 | ||
| G2 Checkpoint | 62 | ||
| Spindle Assembly Checkpoint | 62 | ||
| Cell Cycle Deregulation in Human Cancers | 63 | ||
| Unscheduled Cell Cycle Entry in Cancer | 63 | ||
| Mutations in p53 and Checkpoint Regulators | 65 | ||
| Aneuploidy and Chromosomal Instability | 65 | ||
| Therapeutic Manipulation of Cell Cycle Controls | 65 | ||
| Targeting Cyclin-Dependent Kinase Activity | 66 | ||
| Targeting DNA Damage Response Proteins | 66 | ||
| Targeting the Mitotic Spindle and the SAC | 67 | ||
| Targeting Mitotic Entry and Exit | 67 | ||
| Targeting Aneuploidy | 67 | ||
| Summary | 67 | ||
| References | 68 | ||
| References | 68.e1 | ||
| Additional Resources | 68.e6 | ||
| 5 Pathophysiology of Cancer Cell Death | 69 | ||
| Summary of Key Points | 69 | ||
| Introduction | 69 | ||
| Fundamental Science—Mechanisms of Cell Death | 69 | ||
| Apoptosis | 69 | ||
| Extrinsic Apoptosis | 70 | ||
| Intrinsic Apoptosis | 70 | ||
| Necrosis | 71 | ||
| Autophagy | 72 | ||
| Fundamental Science—Cell Death and Cancer | 72 | ||
| Oncogenes and Cell Death Regulation | 73 | ||
| Oncosuppressors and Cell Death Regulation | 74 | ||
| Clinical Relevance and Applications | 76 | ||
| What the Future Holds | 76 | ||
| References | 77 | ||
| References | 77.e1 | ||
| 6 Cancer Immunology | 78 | ||
| Summary of Key Points | 78 | ||
| Overview | 78 | ||
| The Antigenic Profile That Distinguished Tumors From Normal Tissues | 79 | ||
| Evidence Pro and Con for Immune Surveillance of Cancer | 80 | ||
| Innate Mechanisms of Tumor Immune Surveillance | 81 | ||
| Immune Tolerance and Immune Evasion—the Immune Hallmarks of Cancer | 82 | ||
| Immunologic Characteristics of the Tumor Microenvironment | 84 | ||
| Regulatory T Cells and Cancer | 84 | ||
| Immature Myeloid Cells/Myeloid-Derived Suppressor Cells in Cancer | 86 | ||
| Immune Inhibitory Molecules Expressed in the Tumor Microenvironment | 86 | ||
| TGF-β—A Major Inhibitory Cytokine in the Tumor Microenvironment | 87 | ||
| Co-Inhibitory Ligands and Receptors That Downmodulate Tumor Immunity | 87 | ||
| The CTLA4 Checkpoint—A Global Regulator of T-Cell Activation | 87 | ||
| Biology of the PD1 Checkpoint—A Pathway That Functions Within the Tumor Microenvironment | 88 | ||
| Additional Checkpoints Participate in Tumor Immune Resistance and Tolerance | 89 | ||
| Inhibition of Antitumor Responses Versus Induction of Tumor Antigen–Specific Tolerance | 92 | ||
| The Nature of Immune Responses That Promote Cancer Formation | 92 | ||
| Tumor Promotion Via the IL-23/Th17 Axis | 93 | ||
| Implications for Cancer Immunotherapy | 94 | ||
| References | 95 | ||
| References | 97.e1 | ||
| 7 Stem Cells, Cell Differentiation, and Cancer | 98 | ||
| Summary of Key Points | 98 | ||
| Introduction | 98 | ||
| Properties of Normal Stem Cells | 98 | ||
| Genetic Regulation of Self-Renewal | 99 | ||
| Target Cells for Malignant Transformation | 100 | ||
| Evidence for Cancer Stem Cells | 102 | ||
| Clinical Implications of CSCs | 104 | ||
| Future Implications of CSCs | 106 | ||
| Acknowledgments | 106 | ||
| References | 106 | ||
| References | 107.e1 | ||
| 8 Vascular and Interstitial Biology of Tumors | 108 | ||
| Summary of Key Points | 108 | ||
| Introduction | 108 | ||
| Vascular Compartment | 108 | ||
| New Vessel Formation | 109 | ||
| Cellular Mechanisms | 109 | ||
| Molecular Mechanisms | 110 | ||
| Vascular Architecture | 111 | ||
| Blood Flow and Microcirculation | 112 | ||
| Vascular Permeability | 112 | ||
| Movement of Cells Across Vessel Walls | 114 | ||
| Extravascular Compartment | 116 | ||
| Composition and Origin | 116 | ||
| Interstitial Transport | 116 | ||
| Lymphangiogenesis and Lymphatic Transport | 116 | ||
| Interstitial Hypertension | 119 | ||
| Metabolic Environment | 120 | ||
| Hypoxia | 120 | ||
| Low pH | 121 | ||
| Molecular, Cellular, and Therapeutic Consequences | 121 | ||
| Antiangiogenic Agents in the Clinic | 122 | ||
| Mechanisms of Action | 122 | ||
| Biomarkers | 124 | ||
| Toxicity | 124 | ||
| Perspective | 124 | ||
| Conclusion | 124 | ||
| Acknowledgments | 125 | ||
| References | 125 | ||
| References | 126.e1 | ||
| B Genesis of Cancer | 127 | ||
| 9 Environmental Factors | 127 | ||
| Summary of Key Points | 127 | ||
| Introduction | 127 | ||
| Role of Environmental Agents in the Etiology of Human Cancers | 128 | ||
| Chemicals | 128 | ||
| Polycyclic Aromatic Hydrocarbons | 128 | ||
| Aromatic Amines | 130 | ||
| Benzene | 130 | ||
| Aflatoxins | 130 | ||
| Tobacco Chemicals | 131 | ||
| Chemotherapeutic Agents | 131 | ||
| Radiation | 132 | ||
| Ultraviolet | 132 | ||
| Ionizing | 133 | ||
| Radon | 133 | ||
| Metals | 133 | ||
| Arsenic | 133 | ||
| Nickel | 134 | ||
| Cadmium | 134 | ||
| Chromates | 134 | ||
| Fibers and Dusts | 135 | ||
| Asbestos | 135 | ||
| Silica | 135 | ||
| Wood Dust | 135 | ||
| Dietary Factors in Human Carcinogenesis: Naturally Occurring Carcinogens and Anticarcinogens | 135 | ||
| Exposure Biomarkers and Susceptibility Factors | 136 | ||
| Assessing Human Exposure: Role for Intermediate Biomarkers | 136 | ||
| Genetic Polymorphisms and Human Susceptibility | 137 | ||
| Public Health Approaches to Cancer Prevention | 138 | ||
| Geographic Distribution of Cancer | 138 | ||
| Identifying Human Carcinogens | 139 | ||
| Cancer Chemoprevention | 139 | ||
| Summary | 140 | ||
| References | 140 | ||
| 10 DNA Damage Response Pathways and Cancer | 142 | ||
| Summary of Key Points | 142 | ||
| Introduction | 142 | ||
| Types of DNA Damage | 143 | ||
| Consequences of DNA Damage | 143 | ||
| DNA Damage Response Pathways | 143 | ||
| Types of DNA Repair and Their Contribution to Cancer | 145 | ||
| Nucleotide Excision Repair | 145 | ||
| Human Nucleotide Excision Repair Deficient Syndromes and Cancer | 146 | ||
| Base Excision Repair | 147 | ||
| Mismatch Repair | 148 | ||
| Human MMR Deficiency and Cancer | 148 | ||
| Double-Strand Break Repair | 149 | ||
| Ataxia Telangiectasia | 150 | ||
| Other Cancer-Prone Disorders Associated with Genomic Instability | 151 | ||
| Diseases Involving Homologues of RecQ | 151 | ||
| p53 Gene and Li-Fraumeni Syndrome | 151 | ||
| BRCA1, BRCA2, and Breast-Ovarian Cancer Susceptibility | 151 | ||
| Fanconi Anemia, Cancer, and Interstrand Cross-link Repair | 152 | ||
| Conclusions and Future Directions | 153 | ||
| References | 153.e1 | ||
| References | 153 | ||
| 11 Viruses and Human Cancer | 154 | ||
| Summary of Key Points | 154 | ||
| Introduction | 154 | ||
| Epstein-Barr Virus | 154 | ||
| Hepatitis B Virus | 157 | ||
| Human Papillomaviruses | 159 | ||
| Human T-Cell Leukemia Virus-I | 161 | ||
| Human Hepatitis C Virus | 162 | ||
| Kaposi Sarcoma Herpesvirus | 163 | ||
| Merkel Cell Polyomavirus | 165 | ||
| Treatment and Prevention of Viral Tumors | 166 | ||
| HBV Vaccine | 166 | ||
| Human Papillomavirus Vaccine | 166 | ||
| References | 168.e1 | ||
| References | 167 | ||
| 12 Genetic Factors: | 169 | ||
| Summary of Key Points | 169 | ||
| Common Syndromes of Cancer Predisposition | 173 | ||
| Breast and Ovarian Cancer Syndromes | 174 | ||
| Clinical Features | 174 | ||
| Genetics | 176 | ||
| Clinical Management | 177 | ||
| Cowden Syndrome | 177 | ||
| Clinical Features | 177 | ||
| Genetics | 177 | ||
| Risk Management Recommendations | 178 | ||
| Common Colon Cancer Predisposition Syndromes | 178 | ||
| Lynch Syndrome | 178 | ||
| Clinical Features | 178 | ||
| Genetics | 178 | ||
| Clinical Management | 179 | ||
| Polyposis Syndromes | 179 | ||
| Familial Adenomatous Polyposis | 179 | ||
| II Problems Common to Cancer and its Therapy | 531 | ||
| A Hematologic Problems and Infections | 532 | ||
| 34 Disorders of Blood Cell Production in Clinical Oncology | 532 | ||
| Summary of Key Points | 532 | ||
| Introduction | 532 | ||
| Disorders of Red Cells | 532 | ||
| Anemia | 532 | ||
| Pathophysiology | 532 | ||
| Management | 533 | ||
| Increasing Importance of Iron and Iron Metabolism | 534 | ||
| Safety of Erythropoiesis-Stimulating Agents | 534 | ||
| Polycythemia | 536 | ||
| Disorders of White Cells | 536 | ||
| Neutropenia | 536 | ||
| Pathophysiology | 536 | ||
| Management | 536 | ||
| Prevention of Infection | 536 | ||
| Treatment of Established Neutropenia or Neutropenic Infection | 537 | ||
| Use of Myeloid Growth Factors to Maintain Chemotherapy Dose Intensity | 537 | ||
| Leukocytosis | 538 | ||
| Disorders of Platelets | 538 | ||
| Thrombocytopenia | 538 | ||
| Pathophysiology | 538 | ||
| Management | 538 | ||
| Thrombocytosis | 538 | ||
| Acquired Marrow Failure States | 539 | ||
| Myelodysplastic Syndrome | 539 | ||
| Acute Nonlymphocytic Leukemia | 539 | ||
| Congenital Marrow Failure States | 539 | ||
| Congenital and Cyclic Neutropenia | 539 | ||
| Cellular Treatment of Cytopenias | 539 | ||
| References | 540 | ||
| References | 541.e1 | ||
| 35 Diagnosis, Treatment, and Prevention of Cancer-Associated Venous Thromboembolism | 542 | ||
| Summary of Key Points | 542 | ||
| Introduction | 543 | ||
| Epidemiology of Cancer-Associated VTE | 543 | ||
| Cancer-Associated VTE Is Common | 543 | ||
| The Bidirectional Relationship Between Cancer and VTE | 544 | ||
| VTE is Associated with Worse Outcomes in Patients with Cancer | 544 | ||
| Pathogenesis of Cancer-Associated VTE | 544 | ||
| Tumor-Specific Factors | 545 | ||
| Host-Specific Factors | 546 | ||
| Environmental Factors | 547 | ||
| Surgery, Radiation Therapy, and Cancer-Associated VTE | 547 | ||
| Chemotherapy, Hormonal Therapy, and Cancer-Associated VTE | 547 | ||
| Immunomodulatory Agents and Cancer-Associated VTE | 548 | ||
| Molecularly Targeted Therapies and Cancer-Associated VTE | 548 | ||
| Hematopoietic Growth Factors and Cancer-Associated VTE | 548 | ||
| Indwelling Venous Catheters and Cancer-Associated VTE | 548 | ||
| Prevention of Cancer-Associated VTE | 548 | ||
| Prevention of VTE in Hospitalized Medical Oncology Patients | 548 | ||
| Prevention of VTE in Ambulatory Medical Patients with Cancer | 549 | ||
| Assessment of Risk of Cancer-Associated VTE | 551 | ||
| Prevention of VTE in Hospitalized Surgical Patients with Cancer | 552 | ||
| Prevention of Central Venous Catheter Thrombosis | 552 | ||
| Diagnosis of VTE in Patients with Cancer | 553 | ||
| Diagnosis of Cancer-Associated VTE | 553 | ||
| D-Dimer Testing in the Diagnosis of VTE | 553 | ||
| Imaging | 553 | ||
| Duplex Ultrasonography | 553 | ||
| Contrast Venography | 554 | ||
| Computed Tomographic Venography | 554 | ||
| Magnetic Resonance Venography | 554 | ||
| Diagnosis of Cancer-Associated PE | 554 | ||
| Pulmonary Angiography | 554 | ||
| Ventilation/Perfusion Scanning | 554 | ||
| Computed Tomography Pulmonary Angiography | 554 | ||
| Management of Cancer-Associated VTE | 555 | ||
| Acute Management of Cancer-Associated VTE | 555 | ||
| Anticoagulation | 555 | ||
| Thrombolysis | 555 | ||
| Vena Cava Filters | 556 | ||
| Chronic Management of Cancer-Associated VTE | 556 | ||
| Management of Recurrent Cancer-Associated VTE | 556 | ||
| Management of Cancer-Associated VTE in Special Situations | 557 | ||
| Central Venous Catheter–Associated VTE | 557 | ||
| Cancer-Associated VTE in Patients with Thrombocytopenia | 557 | ||
| Cancer-Associated VTE in Patients with Central Nervous System Lesions | 558 | ||
| Hematopoietic Stem Cell Transplant and VTE | 558 | ||
| Outpatient Management of Cancer-Associated VTE | 558 | ||
| Management of Unsuspected VTE | 559 | ||
| Use of Anticoagulants to Improve Survival in Patients with Cancer | 559 | ||
| Reversal of Anticoagulation | 559 | ||
| References | 560 | ||
| References | 561.e1 | ||
| 36 Infection in the Patient with Cancer | 562 | ||
| Summary of Key Points | 562 | ||
| Introduction | 562 | ||
| Infection Risk Factors | 562 | ||
| Neutropenia as a Risk Factor for Infection | 562 | ||
| Other Risk Factors for Infection | 563 | ||
| Sources of Infection | 563 | ||
| Approach to Fever in the Neutropenic Patient | 564 | ||
| Definitions | 564 | ||
| Initial Evaluation | 565 | ||
| Risk Assessment | 565 | ||
| Empiric Antibiotic Therapy | 566 | ||
| Use of Vancomycin or Other Gram-Positive Agents | 567 | ||
| Initial Empirical Therapy for Patients Who Are Clinically Unstable | 567 | ||
| Subsequent Modifications of Empiric Antibiotic Regimens | 568 | ||
| Empiric Antifungal Therapy | 568 | ||
| Duration of Antibiotic Therapy | 569 | ||
| Adjunctive Therapies | 569 | ||
| Hematopoietic Growth Factors | 569 | ||
| Granulocyte Transfusions | 569 | ||
| Infections in the Patient with Cancer | 569 | ||
| Bacteremia | 569 | ||
| Pulmonary Infections | 569 | ||
| Fungal Infections | 570 | ||
| Gastrointestinal Infections | 571 | ||
| Upper Gastrointestinal Tract | 571 | ||
| Lower Gastrointestinal Tract | 571 | ||
| Central Nervous System Infections | 572 | ||
| Vascular Access Devices | 572 | ||
| Viral Infections | 573 | ||
| Prevention of Infections in Selected Risk Groups | 574 | ||
| Low-Risk Patients | 574 | ||
| Patients with Acute Leukemia | 574 | ||
| Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation | 575 | ||
| Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation | 575 | ||
| Patients with Graft-versus-Host Disease | 577 | ||
| Prophylaxis with Other Immunosuppressive Therapies | 577 | ||
| Pretransplantation Measures to Prevent Infection | 578 | ||
| Pretransplantation Serostatus Blood Work | 578 | ||
| Environmental Measures to Prevent Infection during and after Transplantation | 578 | ||
| Review of Commonsense Measures That Will Assist in the Prevention of Infection | 579 | ||
| References | 579 | ||
| References | 580.e1 | ||
| B Metabolic and Paraneoplastic Syndromes | 581 | ||
| 37 Hypercalcemia | 581 | ||
| Summary of Key Points | 581 | ||
| Introduction | 581 | ||
| Etiology | 581 | ||
| Types of Hypercalcemia of Malignancy | 582 | ||
| Humoral Hypercalcemia of Malignancy | 582 | ||
| Parathyroid Hormone–Related Protein | 583 | ||
| Vitamin D–Linked Hypercalcemia | 583 | ||
| Local Osteolytic Hypercalcemia | 583 | ||
| Multiple Myeloma | 583 | ||
| Carcinoma of the Breast | 583 | ||
| Special Cases | 584 | ||
| Pseudohypercalcemia | 584 | ||
| Multiple Endocrine Neoplasia | 584 | ||
| Tamoxifen-Linked Hypercalcemia | 584 | ||
| Evaluation of the Patient | 584 | ||
| Clinical Findings | 584 | ||
| Laboratory Investigations | 585 | ||
| Grading the Complication | 585 | ||
| Mild Hypercalcemia | 585 | ||
| Moderate Hypercalcemia | 585 | ||
| Severe Hypercalcemia | 585 | ||
| Treatment | 585 | ||
| Ethical Considerations | 585 | ||
| General Considerations | 586 | ||
| Extracellular Fluid Volume Expansion | 586 | ||
| Calciuretic Therapy | 586 | ||
| Furosemide | 586 | ||
| Calcitonin | 586 | ||
| Antiresorptive Therapy | 586 | ||
| Bisphosphonates | 586 | ||
| Gallium Nitrate | 587 | ||
| Therapy Directed against Humoral Factors | 587 | ||
| Calcimimetics | 587 | ||
| Humanized Antibodies to PTHrP | 588 | ||
| Osteoprotegerin and Denosumab | 588 | ||
| Other Therapies | 588 | ||
| Long-Term Treatment | 588 | ||
| References | 589 | ||
| 38 Tumor Lysis Syndrome | 591 | ||
| Summary of Key Points | 591 | ||
| Epidemiology and Definition | 591 | ||
| Etiology and Pathogenesis | 591 | ||
| Risk Factors and Incidence of Tumor Lysis Syndrome | 591 | ||
| Prevention and Management of Tumor Lysis Syndrome | 593 | ||
| Allopurinol | 593 | ||
| Rasburicase | 593 | ||
| Conclusions | 595 | ||
| References | 596 | ||
| 39 Paraneoplastic Neurologic Syndromes | 597 | ||
| Summary of Key Points | 597 | ||
| Introduction | 597 | ||
| Paraneoplastic Syndromes of the Central Nervous System | 598 | ||
| Paraneoplastic Encephalomyelitis | 598 | ||
| Limbic Encephalitis | 598 | ||
| Anti–N-methyl-d-aspartate Receptor Encephalitis | 600 | ||
| Paraneoplastic Cerebellar Degeneration | 601 | ||
| Motor Neuron Syndromes | 601 | ||
| Stiff Man Syndrome | 602 | ||
| Peripheral Nerve Hyperexcitability (Neuromyotonia) | 602 | ||
| Paraneoplastic Opsoclonus-Myoclonus | 602 | ||
| Paraneoplastic Syndromes of the Visual System | 603 | ||
| Paraneoplastic Syndromes of the Peripheral Nervous System | 603 | ||
| Paraneoplastic Sensory Neuronopathy | 603 | ||
| Sensorimotor Neuropathies | 604 | ||
| Vasculitic Neuropathy | 604 | ||
| Autonomic Neuropathy | 604 | ||
| Paraneoplastic Syndromes of the Neuromuscular Junction | 605 | ||
| Myasthenia Gravis | 605 | ||
| Lambert-Eaton Myasthenic Syndrome | 605 | ||
| Paraneoplastic Myopathic Syndromes | 605 | ||
| Polymyositis–Dermatomyositis | 605 | ||
| Acute Necrotizing Myopathy | 606 | ||
| Treatment and Prognosis | 606 | ||
| References | 606 | ||
| References | 607.e1 | ||
| 40 Cancer-Related Pain | 608 | ||
| Summary of Key Points | 608 | ||
| Incidence | 608 | ||
| Facts | 608 | ||
| Etiology | 608 | ||
| Current Status of Cancer Pain Management | 609 | ||
| Barriers to the Provision of Adequate Analgesia | 609 | ||
| Evaluation of the Patient with Pain | 610 | ||
| Management of Cancer Pain | 612 | ||
| Pharmacologic Therapy | 612 | ||
| Antineoplastic Therapy | 614 | ||
| Nonpharmacologic Therapy | 614 | ||
| Invasive Therapy | 614 | ||
| Regional Analgesia | 615 | ||
| Neuroablative Procedures | 616 | ||
| Difficult-to-Manage Pain Problems | 616 | ||
| Patients with Pain of Neuropathic Origin | 616 | ||
| Patients with Episodic or Incidental Pain | 617 | ||
| Patients with Impaired Cognitive or Communicative Function | 617 | ||
| Patients with a History of Substance Abuse | 618 | ||
| Conclusion | 618 | ||
| References | 618 | ||
| 41 Cancer Cachexia | 620 | ||
| Summary of Key Points | 620 | ||
| Introduction | 620 | ||
| Definitions and Epidemiology | 620 | ||
| Biological Characteristics and Pathophysiology | 621 | ||
| Patient Evaluation and Staging | 622 | ||
| Treatment | 622 | ||
| Future Possibilities and Clinical Trials | 624 | ||
| References | 624 | ||
| 42 Nausea and Vomiting | 626 | ||
| Summary of Key Points | 626 | ||
| Introduction | 626 | ||
| Physiology of the Vomiting Reflex | 626 | ||
| Clinical Features of Chemotherapy-Induced Emesis | 627 | ||
| Clinical Syndromes | 627 | ||
| Acute Nausea and Vomiting | 627 | ||
| Delayed Nausea and Vomiting | 628 | ||
| Anticipatory Nausea and Vomiting | 628 | ||
| Prognostic Factors | 628 | ||
| Chemotherapeutic Agents | 628 | ||
| Patient Characteristics | 628 | ||
| Age | 628 | ||
| Gender | 628 | ||
| History of Alcohol Intake | 629 | ||
| Previous Chemotherapy | 629 | ||
| Conduct and Interpretation of Clinical Antiemetic Trials | 629 | ||
| Treatment of Chemotherapy-Induced Nausea and Vomiting | 630 | ||
| Acute Nausea and Vomiting | 630 | ||
| 5-HT3 Receptor Antagonists | 630 | ||
| NK1 Receptor Antagonists | 631 | ||
| Corticosteroids | 631 | ||
| Substituted Benzamides | 631 | ||
| Phenothiazines | 632 | ||
| Benzodiazepines | 632 | ||
| Butyrophenones | 632 | ||
| Cannabinoids | 632 | ||
| Combination Antiemetic Therapy | 632 | ||
| Anticipatory Nausea and Vomiting | 632 | ||
| Delayed Nausea and Vomiting | 632 | ||
| Radiation-Induced Nausea and Vomiting | 633 | ||
| Summary of Recommendations for Combination Antiemetic Therapy | 633 | ||
| References | 634 | ||
| References | 634.e1 | ||
| 43 Oral Complications | 635 | ||
| Summary of Key Points | 635 | ||
| Introduction | 635 | ||
| Pathophysiology of Mucosal Injury and Clinical Manifestations | 635 | ||
| Mucositis Assessment | 636 | ||
| Oral Complications From Chemotherapy, Including Myeloablative Chemotherapy | 636 | ||
| Incidence and Risk Factors | 636 | ||
| Biological Therapies | 637 | ||
| Prevention of Chemotherapy-Induced Oral Complications | 638 | ||
| Oral Care Protocols and Oral Hygiene | 638 | ||
| Antimicrobial and Antiseptic Interventions | 638 | ||
| Cryotherapy | 638 | ||
| 5-FU–Based Chemotherapy | 638 | ||
| Edatrexate | 638 | ||
| High-Dose Melphalan | 638 | ||
| Antioxidants, Anticholinergics, and Coating Agents | 639 | ||
| Antiinflammatory Agents | 639 | ||
| Amino Acids | 639 | ||
| Growth Factors | 639 | ||
| Low-Level Laser Therapy | 639 | ||
| Other Interventions | 639 | ||
| Treatment of Chemotherapy-Induced Oral Mucositis | 640 | ||
| Mouthwashes and Coating Agents | 640 | ||
| Antiinflammatory Agents | 640 | ||
| Growth Factors | 640 | ||
| Systemic Analgesics | 640 | ||
| Laser Therapy | 640 | ||
| Other Therapies | 640 | ||
| Treatment For Biological Therapy–Induced Mucositis | 640 | ||
| Oral Complications From Radiation Therapy | 641 | ||
| Mucositis | 641 | ||
| Etiology of Mucositis | 641 | ||
| Prevention of Mucositis | 641 | ||
| Radiotherapy Technique | 641 | ||
| Oral Hygiene | 641 | ||
| Growth Factors | 642 | ||
| Low-Level Laser Therapy | 642 | ||
| Antibiotics and Probiotics | 642 | ||
| Benzydamine Hydrochloride | 642 | ||
| Sucralfate | 642 | ||
| Amifostine | 642 | ||
| Other Interventions | 642 | ||
| Treatment of Established Mucositis | 643 | ||
| Concurrent Oral Mucosa Infection | 643 | ||
| Analgesics | 643 | ||
| Daily Nursing Evaluation | 643 | ||
| Other Interventions | 643 | ||
| Xerostomia | 643 | ||
| Etiology of Xerostomia | 643 | ||
| Prevention of Xerostomia | 644 | ||
| Radiotherapy Technique | 644 | ||
| Amifostine | 644 | ||
| Pilocarpine | 644 | ||
| Salivary Gland Transfer | 644 | ||
| Acupuncture | 644 | ||
| Treatment of Xerostomia | 644 | ||
| Dietary Modification | 644 | ||
| Oral Lubricants | 644 | ||
| Muscarinic Receptor Agonists | 645 | ||
| Acupuncture | 645 | ||
| Dental Caries | 645 | ||
| Etiology of Dental Caries | 645 | ||
| Prevention and Treatment of Dental Caries | 645 | ||
| Soft Tissue Necrosis | 645 | ||
| Etiology of Soft Tissue Necrosis | 645 | ||
| Treatment of Soft Tissue Necrosis | 645 | ||
| Osteoradionecrosis | 646 | ||
| Etiology of Osteoradionecrosis | 646 | ||
| Treatment of Osteoradionecrosis | 646 | ||
| Taste Alterations | 646 | ||
| Trismus | 646 | ||
| Etiology of Trismus | 646 | ||
| Prevention and Treatment of Trismus | 646 | ||
| Malignancy | 646 | ||
| References | 647 | ||
| References | 647.e1 | ||
| 44 Dermatologic Toxicities of Anticancer Therapy | 648 | ||
| Summary of Key Points | 648 | ||
| Introduction | 650 | ||
| Cutaneous Complications of Cytotoxic Chemotherapy | 650 | ||
| Chemotherapy-Induced Alopecia | 650 | ||
| Etiology and Biocharacteristics | 650 | ||
| Epidemiology | 651 | ||
| Clinical Manifestations | 651 | ||
| Workup | 652 | ||
| Differential Diagnosis | 652 | ||
| Treatment | 652 | ||
| Preemptive Counseling | 652 | ||
| Preventive Treatment | 653 | ||
| Treatments for Acceleration of Hair Growth After Chemotherapy | 653 | ||
| Prognosis | 653 | ||
| Cutaneous Extravasation Injury | 653 | ||
| Etiology and Biocharacteristics | 653 | ||
| Epidemiology | 653 | ||
| Clinical Manifestations | 653 | ||
| Workup | 654 | ||
| Treatment | 654 | ||
| Prevention | 654 | ||
| Pharmacologic and Surgical Treatment | 654 | ||
| Prognosis | 655 | ||
| Chemotherapy-Induced Hyperpigmentation | 655 | ||
| Etiology and Biocharacteristics | 655 | ||
| Epidemiology | 655 | ||
| Clinical Manifestations | 656 | ||
| Workup | 656 | ||
| Differential Diagnosis | 656 | ||
| Generalized Hyperpigmentation | 656 | ||
| Localized Hyperpigmentation | 656 | ||
| Treatment | 656 | ||
| Prognosis | 656 | ||
| Toxic Erythema of Chemotherapy | 656 | ||
| Hand-Foot Syndrome | 657 | ||
| Etiology and Biocharacteristics | 657 | ||
| Epidemiology | 658 | ||
| Clinical Manifestations | 658 | ||
| Workup | 659 | ||
| Differential Diagnosis | 659 | ||
| Hand-Foot Skin Reaction | 659 | ||
| Acute Graft-Versus-Host Disease | 659 | ||
| Erythema Multiforme | 659 | ||
| Treatment | 659 | ||
| Dose Reductions | 660 | ||
| Prevention | 660 | ||
| Reactive/Symptomatic Treatment | 661 | ||
| Prognosis | 661 | ||
| Neutrophilic Eccrine Hidradenitis | 661 | ||
| Etiology and Biocharacteristics | 661 | ||
| Epidemiology | 661 | ||
| Clinical Manifestations | 661 | ||
| Workup | 661 | ||
| Differential Diagnosis | 661 | ||
| Clinical | 661 | ||
| Histological | 661 | ||
| Treatment | 661 | ||
| Prognosis | 662 | ||
| Cutaneous Complications of Radiation Therapy | 662 | ||
| Radiation Dermatitis | 662 | ||
| Etiology and Biocharacteristics | 662 | ||
| Epidemiology | 662 | ||
| Clinical Manifestations | 662 | ||
| Differential Diagnosis | 663 | ||
| Acute | 663 | ||
| Chronic | 663 | ||
| Diagnosis/Workup | 663 | ||
| Treatment | 663 | ||
| Prognosis | 664 | ||
| Radiation Recall | 664 | ||
| Etiology and Biocharacteristics | 664 | ||
| Epidemiology | 664 | ||
| Clinical Manifestations | 664 | ||
| Differential Diagnosis | 664 | ||
| Cytostatic Drug Recall | 664 | ||
| Radiosensitization | 664 | ||
| III Specific Malignancies | 937 | ||
| 66 Cancer of the Central Nervous System | 938 | ||
| Summary of Key Points | 938 | ||
| Introduction | 939 | ||
| Epidemiology | 939 | ||
| Tumor Biology | 942 | ||
| Cell Proliferation | 942 | ||
| Invasion | 943 | ||
| Angiogenesis and Hypoxia | 943 | ||
| Stem Cells | 943 | ||
| Clinical Presentation | 944 | ||
| Pathophysiology of Signs and Symptoms | 944 | ||
| General Signs and Symptoms | 945 | ||
| Localizing Signs of Intracranial Tumors | 945 | ||
| Treatment of Brain Tumor Symptoms | 946 | ||
| Acute Raised ICP | 946 | ||
| Chronically Increased ICP | 946 | ||
| Seizures | 946 | ||
| Deep Venous Thrombosis | 947 | ||
| Diagnostic Imaging | 947 | ||
| Magnetic Resonance Imaging | 947 | ||
| Computed Tomography | 949 | ||
| Positron Emission Tomography | 949 | ||
| Lumbar Puncture | 950 | ||
| Skull Radiograph Studies | 950 | ||
| Intraoperative Ultrasound Examination | 950 | ||
| Surgery: General Considerations | 950 | ||
| Radiation Therapy: General Considerations | 951 | ||
| Radiation Therapy: Technical Details | 951 | ||
| Stereotactic Radiotherapy | 951 | ||
| Intensity-Modulated Radiation Therapy | 952 | ||
| Heavy Charged Particle Radiation Therapy | 952 | ||
| Adverse Effects after Irradiation of the Brain or Spine | 952 | ||
| Acute and Early Delayed Effects after Cranial Irradiation | 952 | ||
| Late Effects | 952 | ||
| Radiation Necrosis of the Brain | 952 | ||
| Neurocognitive Deficits after Cranial Irradiation | 953 | ||
| Endocrine Deficits after Cranial or Spinal Irradiation | 954 | ||
| Optic Neuropathy after Cranial Irradiation | 954 | ||
| Second Malignant Neoplasms Developing after Cranial Irradiation | 954 | ||
| Myelopathy after Spinal Irradiation | 954 | ||
| General Principles of Chemotherapy | 955 | ||
| Supratentorial Gliomas | 956 | ||
| Clinical Considerations | 956 | ||
| Pathological Classification of Supratentorial Gliomas | 957 | ||
| Imaging of Supratentorial Gliomas | 959 | ||
| Genetics of Supratentorial Gliomas | 959 | ||
| Genetic Changes in Astrocytomas | 959 | ||
| Genetic Changes in Glioblastomas | 960 | ||
| Genetic Changes in Oligodendrogliomas and Oligoastrocytomas | 962 | ||
| Isocitrate Dehydrogenase Mutations | 963 | ||
| Surgery for Supratentorial Gliomas: Extent of Surgical Resection | 965 | ||
| Navigation during Surgery | 965 | ||
| Complications of Surgery | 965 | ||
| Radiation Therapy for Supratentorial Gliomas | 966 | ||
| Radiation Therapy for Low-Grade Gliomas | 966 | ||
| Radiation Therapy for High-Grade Gliomas | 967 | ||
| Chemotherapy for Gliomas | 969 | ||
| Chemotherapy for Newly Diagnosed High-Grade Astrocytomas | 969 | ||
| Chemotherapy for Recurrent High-Grade Astrocytomas | 969 | ||
| Chemotherapy for Low-Grade Astrocytomas | 971 | ||
| Chemotherapy for Newly Diagnosed Anaplastic Oligodendrogliomas | 972 | ||
| Chemotherapy for Recurrent Anaplastic Oligodendroglioma and Oligoastrocytoma | 972 | ||
| Chemotherapy for Low-Grade Oligodendrogliomas and Oligoastrocytomas | 973 | ||
| Therapy for Elderly Patients with Malignant Gliomas | 973 | ||
| Quality of Life after Therapy for Gliomas | 973 | ||
| New Approaches to Therapy of Gliomas | 973 | ||
| Adult Brainstem Gliomas | 974 | ||
| Primary CNS Lymphoma | 975 | ||
| Histopathological Features | 975 | ||
| Tumor Biology | 975 | ||
| Clinical Diagnosis and Staging | 975 | ||
| Treatment | 977 | ||
| Meningioma | 979 | ||
| Clinical and Pathological Considerations | 979 | ||
| Surgery and Conventional Radiation Therapy for Meningiomas | 980 | ||
| Stereotactic Radiation Techniques for Meningiomas | 981 | ||
| Medical Therapy for Meningiomas | 981 | ||
| Pituitary Adenoma | 981 | ||
| Clinical and Pathological Considerations | 981 | ||
| Surgery for Pituitary Adenomas | 982 | ||
| Medical Therapy for Pituitary Adenomas | 983 | ||
| Radiation Therapy for Pituitary Adenomas | 983 | ||
| Late Effects after Pituitary Irradiation | 984 | ||
| Stereotactic Radiation Techniques for Pituitary Adenomas | 984 | ||
| Acoustic Neuroma | 984 | ||
| Clinical and Pathological Considerations | 984 | ||
| Surgery for Acoustic Neuromas | 985 | ||
| Radiotherapy for Acoustic Neuromas | 985 | ||
| Cerebellar Hemangioblastomas | 986 | ||
| Index | 2093 | ||
| A | 2093 | ||
| B | 2099 | ||
| C | 2105 | ||
| D | 2118 | ||
| E | 2121 | ||
| F | 2125 | ||
| G | 2126 | ||
| H | 2130 | ||
| I | 2135 | ||
| J | 2138 | ||
| K | 2139 | ||
| L | 2139 | ||
| M | 2144 | ||
| N | 2151 | ||
| O | 2155 | ||
| P | 2158 | ||
| Q | 2167 | ||
| R | 2167 | ||
| S | 2173 | ||
| T | 2179 | ||
| U | 2183 | ||
| V | 2184 | ||
| W | 2185 | ||
| X | 2186 | ||
| Y | 2186 | ||
| Z | 2186 | ||
| Inside back cover | ibc1 |