Withrow and MacEwen's Small Animal Clinical Oncology (eBook)

Front cover 1
Withrow and MacEwen's Small Animal Clinical Oncology 2
Copyright page 5
Contributors 6
Preface 12
Dedication 13
Table of Contents 14
Introduction Why Worry About Cancer in Companion Animals? 16
References 17
I The Biology and Pathogenesis of Cancer 18
1 The Etiology of Cancer 18
n Section A 18
The Genetic Basis of Cancer 18
Genes and Cancer Risk 18
Heritable Cancer Syndromes 18
Genetic Influence in Sporadic Cancers 19
The Hallmarks of Cancer 22
Self-Sufficiency of Growth Signals 22
Insensitivity to Antigrowth Signals 23
Evasion of Cell Death 23
Limitless Replicative Potential 23
Sustained Angiogenesis 23
Invasion and Metastasis 25
Adaptive Evolution and the Tumor Microenvironment 26
Emerging and Enabling Hallmarks 26
Genomic Instability 26
Tumor-Promoting Inflammation 27
Reprogramming Energy Metabolism 27
Evading Immune Destruction 28
Epigenetic Events 28
Cancer Stem Cells 29
Summary 30
References 30
n Section B 32
Chemical, Physical, and Hormonal Factors 32
Chemical Factors 32
Environmental Tobacco Smoke 32
Pesticides, Herbicides, and Insecticides 32
Cyclophosphamide 33
Rural versus Urban Environment 33
Physical Factors 33
Sunlight 33
Trauma/Chronic Inflammation 33
Magnetic Fields 34
Radiation 34
Surgery and Implanted Devices 34
Asbestos 34
Hormonal Factors 34
Estrogen and Progesterone 34
Canine Mammary Cancer 34
Feline Mammary Cancer 35
Lymphoma 35
Androgens/Testosterone 35
Perianal Adenoma 35
Prostate Cancer 35
References 35
n Section C 37
Cancer-Causing Viruses 37
Tumor-Causing Viruses of Dogs 37
Papillomaviruses 37
Pathogenesis 37
Clinical Features 38
Treatment 38
Tumor-Causing Viruses of the Cat 39
Papillomaviruses 39
Pathogenesis 39
Clinical Features 39
Diagnosis 39
Treatment 39
Retroviruses 39
Feline Leukemia Virus 40
Transmission 40
Feline Oncornavirus-Associated Cell Membrane Antigen 41
Neoplastic Diseases Caused by Feline Leukemia Virus 41
Treatment of Feline Leukemia Virus Infections 41
Biologic-Response Modifiers 41
Reverse Transcriptase Inhibitors 41
Prevention and Control 42
Prevention by Vaccination 42
Feline Sarcoma Virus 42
Clinical Features of Feline Sarcoma Virus and Induced Fibrosarcomas 42
Feline Immunodeficiency Virus 43
Transmission 43
Feline Immunodeficiency Virus–Associated Neoplasms 43
Treatment 43
Comparative Aspects 43
References 43
2 Tumor Biology and Metastasis 47
Normal Cell Division 47
The Cell Cycle 47
Cellular Responses to DNA Damage 48
p53 Functions as a Genomic Guardian 48
Cell Death 49
Summary 50
From Normal Cell to Cancer Cell 50
Multistep Carcinogenesis 50
Oncogenes 50
Growth Factors 51
Growth Factor Receptors 51
Protein Kinases 51
Signal Transduction 51
Nuclear Proteins and Transcription Factors 51
Mechanisms by which Oncogenes Become Activated 51
Tumor Suppressor Genes 53
Retinoblastoma Forms the First Clues to the Existence of Tumor Suppressor Genes 53
The p53 Tumor Suppressor Gene 53
Cancer Arises through Multiple Molecular Mechanisms 53
The Hallmarks of Cancer 54
Self-Sufficiency in Growth Signals 54
Insensitivity to Antigrowth Signals or Evading Growth Suppressors 54
Evading Cell Death: The Roles of Apoptosis, Autophagy, and Necrosis 55
Limitless Replicative Capacity 55
Reprogramming Energy Metabolism 56
Metastasis 56
Metastasis-Associated Genes and Metastasis Suppressor Genes 57
Intravasation 57
Epithelial-Mesenchymal Transition 59
Survival in the Circulation (Resisting Anoikis) 59
Evasion of the Immune System 59
Arrest in Target Tissues 59
Early Survival at Distant Sites 60
The Premetastatic Niche and Modulation of the Microenvironment 60
Angiogenesis 60
Metastasis from Metastases 61
Ongoing Controversies and Areas of Research in the Field of Metastasis 61
Does the Metastatic Propensity for Tumors Emerge Early or Late in the Biology of Cancer? 61
Where Is the Inefficiency in Metastatic Inefficiency? 61
What Is Dormancy and Where Do Dormant Cells Reside? 62
The Enabling Characteristics 62
Genome Instability 62
Tumor-Promoting Inflammation 62
The Pathway to Cancer 62
The Tumor Microenvironment 62
Cancer Cells and Cancer Stem Cells 63
Endothelial Cells 63
Pericytes 63
Immune Inflammatory Cells 63
Cancer-Associated Fibroblasts 63
Summary and Future Directions 64
References 64
3 The Pathology of Neoplasia 68
Sample Handling 68
Terminology 69
Histologic Features of Neoplasia 70
Grading and Staging of Neoplasia 72
Assessment of Tumor Margins 73
Assessment of Treatment Response 75
Special Procedures 75
Special Histochemical Stains 76
Immunohistochemistry 76
Electron Microscopy 80
Flow Cytometry and Polymerase Chain Reaction 80
Clinical-Pathologic Correlation and Second Opinions 80
References 81
4 Epidemiology and the Evidence-Based Medicine Approach 85
Measures of Disease Occurrence 85
Incidence 85
Prevalence 87
Sources of Information on Cancer Occurrence 88
Factors Associated with Cancer Risk 89
Highlighted Findings from Observational Studies 95
Environmental Exposures 95
Hormones and Neuter Status 95
Risk Factors in Cats 96
Diagnosis and Screening 96
Therapeutic Interventions 96
Knowledge Gaps and Future Directions 97
References 97
5 Paraneoplastic Syndromes 100
Gastrointestinal Manifestations of Cancer 100
Cancer Cachexia and Anorexia 100
Protein-Losing Enteropathy 100
Gastroduodenal Ulceration 102
Endocrinologic Manifestations of Cancer 102
Hypercalcemia 102
Hypoglycemia 103
Syndrome of Inappropriate Secretion of Antidiuretic Hormone 103
Ectopic Adrenocorticotropic Hormone Syndrome 104
Hypocalcemia/Hyperglycemia 104
Hematologic Manifestations of Cancer 104
Hypergammaglobulinemia 104
Anemia 104
Erythrocytosis 105
Neutrophilic Leukocytosis 105
Thrombocytopenia 105
Coagulopathies and Disseminated Intravascular Coagulation 105
Miscellaneous 106
Cutaneous Manifestations of Cancer 106
Alopecia 106
Cutaneous Flushing 106
Nodular Dermatofibrosis 106
Necrolytic Migratory Erythema/Superficial Necrolytic Dermatitis 107
Miscellaneous Syndromes 107
Renal Manifestations of Cancer 107
Neurologic Manifestations of Cancer 107
Myasthenia Gravis 107
Peripheral Neuropathy 108
Diencephalic Syndrome and Miscellaneous Neuromuscular Syndromes 108
Miscellaneous Manifestations of Cancer 108
Hypertrophic Osteopathy 108
Fever 109
References 109
II Diagnostic Procedure for the Cancer Patient 115
6 Imaging in Oncology 115
Imaging Modalities 115
Radiography 115
Computed Tomography 115
Ultrasonography 117
Magnetic Resonance Imaging 120
Nuclear Medicine 120
Single-Photon Emission Computed Tomography and Positron Emission Tomography 121
Advances 123
References 124
7 Diagnostic Cytopathology in Clinical Oncology 128
Sample Collection 128
Collection Techniques 128
Cytologic Stains 129
Examination and Description of Cytologic Specimens 131
Specimens of Diagnostic Quality 131
Nonneoplastic Cells and Noncellular Material Found in Cytologic Specimens 131
Description of Neoplastic Populations 132
Sending Cytologic Samples to a Diagnostic Laboratory 133
Interpretation of Cytologic Specimens 133
Epithelial, Mesenchymal, and Discrete Round Cell Tumors 134
Tumors of Epithelial Tissues 134
Tumors of Hair Follicles and Sebaceous Glands 134
Tumors of the Epidermis 134
Tumors of Glands 135
Salivary Gland Tumors 135
Mammary Gland Tumors 135
Perianal Gland Tumors 136
Tumors of the Apocrine Gland of the Anal Sac 136
Tumors of the Prostate Gland 136
Tumors of the Urogenital System 136
Transitional Cell Carcinoma 136
Tumors of Organs 136
Hepatocellular Tumors 136
Biliary Tumors 137
Tumors of the Exocrine Pancreas 137
Renal Carcinomas 137
Pulmonary Carcinomas or Adenocarcinomas 137
Thymoma and Thymic Carcinoma 137
Nasal Carcinomas and Adenocarcinomas 137
Gastrointestinal Tumors 137
Endocrine and Neuroendocrine Tumors 138
Thyroid Carcinomas 138
Parathyroid Tumors 138
Chemodectomas 138
Adrenal Cortical and Medullary Tumors 138
Insulinomas 139
Carcinoids of Lung, Liver, Intestine, and Colon 139
Tumors of Mesenchymal Tissues 139
Mesenchymal Tumors Composed of Spindle-Shaped and Stellate Cells 139
Tumors of Fibroblasts 139
Tumors of the Perivascular Wall or Nerve Sheath 140
Tumors of Vascular Endothelium 140
Tumors of Adipose Tissue 141
Mesenchymal Tumors Composed of Thin Elongate Cells 141
Tumors of Smooth Muscle and Stroma 141
Tumors of Striated Muscle 141
Mesenchymal Tumors Composed of Round or Oval Cells 142
Tumors of Bone Origin 142
Tumors of Chondrocytes 142
Tumors of Synovial Cells 142
Tumors of Melanocytes 142
Mesenchymal Tumors Composed of Cells Arranged in Dense Aggregates 143
Mesenchymal Tumors with Frequent Multinucleated Cells 143
Discrete Round Cell Tumors 143
Mast Cell Tumors 143
Plasma Cell Tumors 144
Lymphoma 144
Tumors of Histiocytic Origin 145
Cutaneous Histiocytoma 145
Histiocytic Sarcomas of Dendritic and Macrophage Lineage 145
Transmissible Venereal Tumor 146
Mesenchymal and Epithelial Tumors That May Appear as Discrete Round Cell Tumors 146
Tumor Metastases and Tumors Exfoliating into Cavity Effusions 146
References 147
8 Molecular Diagnostics 148
Goals of Molecular Diagnostic Testing in Oncology 148
Methods for Analyzing Genes 148
Detection of Chromosomal Abnormalities 148
Polymerase Chain Reaction–Based Techniques: Detection of Mutations, Novel Genes, and Assessment of Clonality 149
Detection of Genetic Insertions and Deletions 149
Detection of Single-Base Mutations 150
Detection of Fusion Gene Products by PCR 150
Assessment of Clonality in Lymphoma and Leukemia 150
Single Nucleotide Polymorphism Analysis 152
Quantifying Genes and Gene Expression 152
Real-Time Polymerase Chain Reaction 152
Gene Expression Profiling 154
On the Horizon—Counting Genes 155
Methods for Protein Analysis 155
Western Blots 155
Immunohistochemistry and Flow Cytometry 155
Proteomics 156
Summary 158
References 158
9 Biopsy Principles 160
Biopsy Methods 160
Needle Core Biopsy 160
Punch Biopsy 161
Incisional Biopsy 161
Specialized Biopsy Techniques 162
Endoscopic Biopsies 162
Laparoscopy and Thoracoscopy 162
Image-Guided Biopsy 163
Excisional Biopsy 163
General Guidelines for Tissue Procurement and Fixation 163
Interpretation of Results 164
References 165
III Therapeutic Modalities for the Cancer Patient 166
10 Surgical Oncology 166
Surgery for Diagnosis 166
Surgery for Cure 166
Lymph Node Removal 168
Surgery for Distant Disease 169
Palliative Surgery 169
Cytoreductive Surgery 169
Nonsurgical Locally Ablative Procedures 169
Radiofrequency Ablation 169
Cryoablation 170
Hyperthermia 170
Photodynamic Therapy 170
Surgery and Chemotherapy 170
Surgery and Radiation 170
Prevention of Cancer 171
Miscellaneous Oncologic Surgery 171
Discussion 171
References 171
11 Cancer Chemotherapy 174
General Principles of Cancer Chemotherapy 174
Mechanism of Cancer Therapy 174
Terminology and Concepts 174
Indications and Goals of Therapy 174
Tumor Susceptibility and Resistance 175
Tumor Cell Sensitivity 175
Tumor Cell Resistance 176
Combination Therapies 177
Toxicities Associated with Drug Therapy of Cancer 178
Safety Concerns of Cancer Drug Therapy 180
Pharmacologic Principles in Cancer Therapy 180
Pharmacokinetics 180
Pharmacodynamics 181
Pharmaceutics 181
Specific Chemotherapeutic Agents 182
Alkylating Agents 182
Nitrogen Mustards 182
Mechlorethamine 182
Basic Pharmacology 182
Clinical Pharmacology 182
Clinical Use 182
Melphalan 182
Basic Pharmacology 182
Clinical Pharmacology 182
Clinical Use 182
Cyclophosphamide 183
Basic Pharmacology 183
Clinical Pharmacology 183
Clinical Use 183
Ifosfamide 183
Basic Pharmacology 183
Clinical Pharmacology 183
Clinical Use 183
Chlorambucil 183
Basic Pharmacology 183
Clinical Pharmacology 183
Clinical Use 183
Nitrosoureas 183
Lomustine (Cyclohexylchloroethylnitrosourea) 183
Basic Pharmacology 183
Clinical Pharmacology 183
Clinical Use 184
Streptozotocin 184
Basic Pharmacology 184
Clinical Pharmacology 184
Clinical Use 184
Other Alkylating Agents 184
Dacarbazine 184
Basic Pharmacology 184
Clinical Pharmacology 184
Clinical Use 184
Procarbazine 184
Basic Pharmacology 184
Clinical Pharmacology 184
Clinical Use 184
Antitumor Antibiotics 184
Doxorubicin 184
Basic Pharmacology 184
Clinical Pharmacology 184
Clinical Use 184
Mitoxantrone 185
Basic Pharmacology 185
Clinical Pharmacology 185
Clinical Use 185
Actinomycin D (Dactinomycin) 185
Basic Pharmacology 185
Clinical Pharmacology 185
Clinical Use 185
Antimetabolites 185
Cytosine Arabinoside (Cytarabine) 185
Basic Pharmacology 185
Clinical Pharmacology 185
Clinical Use 185
Methotrexate 186
Basic Pharmacology 186
Clinical Pharmacology 186
Clinical Use 186
Gemcitabine 186
Basic Pharmacology 186
Clinical Pharmacology 186
Clinical Use 186
5-Fluorouracil 186
Basic Pharmacology 186
Clinical Pharmacology 186
Clinical Use 186
Antimicrotubule Agents 187
Taxanes (Paclitaxel and Docetaxel) 187
Basic Pharmacology 187
Clinical Pharmacology 187
Clinical Use 187
Vinca Alkaloids (Vinblastine and Vincristine) 187
Basic Pharmacology 187
Clinical Pharmacology 187
Clinical Use 187
Topoisomerase Inhibitors 187
Epipodophyllotoxins (Etoposide and Teniposide) 188
Basic Pharmacology 188
Clinical Pharmacology 188
Clinical Use 188
Steroids 188
Prednisone 188
Basic Pharmacology 188
Clinical Pharmacology 188
Clinical Use 188
Others 188
Platinum (Carboplatin and Cisplatin) 188
Basic Pharmacology 188
Clinical Pharmacology 188
Clinical Use 188
Hydroxyurea 188
Basic Pharmacology 188
Clinical Pharmacology 188
Clinical Use 189
l-Asparaginase 189
Basic Pharmacology 189
Clinical Pharmacology 189
Clinical Use 189
Future Directions in Drug Therapies for Cancer 189
Individualized Dosing 189
Population Pharmacokinetics 189
Molecular Profiling 189
Tumor Sensitivity 189
Prognostic Evaluation 189
Novel Combinations 190
References 190
12 Radiation Therapy 197
Biologic Principles of Radiation Oncology 197
Repair of Radiation Damage 197
Cell Cycle Effects 197
Oxygen Effects 197
Relative Biologic Effectiveness 197
Time, Dose, and Fractionation 198
Acute and Late Effects 199
Radiation-Induced Neoplasia 199
Cell Survival After Irradiation 200
Alternative Mechanisms of Radiation Injury 200
Chemical Modifiers of Radiation 200
Palliative Radiation Therapy 200
Radiation Therapy Equipment 201
Tumors Commonly Treated with Radiation Therapy 203
Oral Tumors 203
Efficacy of Treatment 203
Radiation Considerations 204
Treatment-Related Toxicities 204
Nasal Tumors 205
Efficacy of Treatment 205
Radiation Considerations 205
Treatment-Related Toxicities 205
Brain Tumors and Pituitary Tumors 206
Efficacy of Treatment 206
Radiation Considerations 206
Treatment-Related Toxicities 206
Superficial Tumors of the Trunk and Extremities 207
Radiation Considerations 207
Treatment-Related Toxicities 208
Bone Tumors 208
Radiation Considerations 208
Treatment-Related Toxicities 208
Other Tumors 208
Lymphoma 210
References 211
13 Cancer Immunotherapy 215
Immune System Control of Tumor Development and Growth 215
Immune Surveillance of Cancer 215
Mechanisms of Immune Evasion by Tumors 215
Active Immune Suppression by Myeloid-Derived Suppressor Cells 216
Induction of Regulatory T-Cells by Tumors 216
Impaired Dendritic Cell Activation and Function 216
Production of Immunosuppressive Cytokines 217
Failure of Tumor Cells to Activate Immune System 217
Strategies to Control Tumor Growth through Immune Activation 219
Depletion of Immunosuppressive Myeloid-Derived Suppressor Cells to Allow for Effective Immunotherapy 219
Nonspecific Immune Activation to Generate Antitumor Activity Using Biologic-Response Modifiers 219
Bacillus Calmette-Guérin and Corynebacterium parvum 219
Salmonella 219
Superantigens 220
Liposome-Encapsulated Muramyl Tripeptide 220
Liposome-DNA Complexes 220
Oncolytic Viruses 221
Nonspecific Tumor Immunotherapy Using Recombinant Cytokine Therapy 221
Interleukin-2 221
Interleukin-12 221
Interleukin-15 221
Interferons 221
Interferon-a, Interferon-ß, and Interferon-. 221
Interferon-. 222
Specific Immunotherapy for Cancer: Tumor Vaccines 222
Tumor Antigen Targets for Immunization 222
Tumor Vaccine Approaches 222
Whole Tumor Cell and Tumor Cell Lysate Vaccines 222
Immunization Against Defined Tumor Antigens Using Plasmid DNA 223
Tumor Vaccination Using Viral Vector Vaccines 223
Vaccination Against Tumor Antigens Using Dendritic Cells 223
Antibody Therapy for Cancer 224
Monoclonal Antibodies 224
Conjugated Monoclonal Antibodies 224
Cancer Immunotherapy Using Adoptive Transfer of T-Cells 224
Transfer of Lymphokine- Activated Killer Cells 224
Transfer of Tumor-Infiltrating Lymphocytes 224
New Approaches to Adoptive T-Cell Transfers 225
The Future of Cancer Immunotherapy 225
References 225
14 Molecular/Targeted Therapy of Cancer 232
n Section A 232
Gene Therapy for Cancer 232
Efficient Gene Delivery: The Major Hurdle to Clinical Benefits 232
Viral Vectors 232
Nonviral Gene Delivery 232
Targeted Gene Delivery 233
Gene Therapy Strategies for Cancer 233
Rescue of the Cancer Cell Through Gene Replacement Technologies 233
Destruction of Cancer Cells Through Delivery of “Suicide Genes” 234
Utilizing Stem Cells to Deliver “Suicide Genes” 235
Gene-Directed Immunotherapy 235
Delivery of Chemoprotective Genes 236
The Use of Replication- Competent Viral Vectors 236
Miscellaneous Approaches to Cancer Gene Therapy 237
Safety Considerations in Gene Therapy 237
New Horizons 237
References 237
. Section B 238
Signal Transduction and Cancer 238
Protein Kinases and Normal Cells 239
Protein Kinases and Cancer Cells 240
Inhibition of Kinases 242
Kinase Inhibitors in Veterinary Medicine 243
Conclusion 244
References 244
. Section C 246
Antiangiogenic and Metronomic Therapy 246
Tumor Angiogenesis 246
Antiangiogenic Therapy 247
Inhibition of Proangiogenic Factors—Receptor Tyrosine Kinase Inhibitors 247
Angiogenic Inhibitor Supplementation 247
Direct Targeting of Tumor Endothelial Cell Surface Markers 247
Other Antiangiogenic Agents 247
Metronomic Chemotherapy 248
Mechanisms of Treatment 248
Clinical Trial Evaluation 248
Veterinary Trials with Cyclophosphamide 249
Other Alkylating Agents 249
Platinum Compounds 249
Biomarkers for Antiangiogenic and Metronomic Therapy 250
Side Effects (Adverse Events) 250
References 250
. Section D 254
Novel and Emerging Therapeutic Targets 254
DNA Methylation 254
Histone Deacetylase 254
The Proteasome 255
Heat Shock Protein 90 255
Poly Adenosine Diphosphate Ribose Polymerase and Poly Adenosine Diphosphate Ribose Glycohydrolase 257
Carbonic Anhydrase 257
References 257
15 Supportive Care for the Cancer Patient 262
. Section A 262
Management of Chronic Cancer Pain 262
How Painful Is Cancer in Animals? 262
General Approach to Cancer Pain Management 262
The Importance of Alleviating Pain in the Cancer Patient 263
Assessment of Cancer Pain 264
Principles of Alleviation of Cancer Pain 265
Pharmacologic Therapy 265
Classification of Cancer Pain 265
Drugs and Strategies Used for Management of Pain in Cancer Patients 266
Nonsteroidal Antiinflammatory Drugs 266
Acetaminophen 266
Opioids 267
N-Methyl d-Aspartate Antagonists 271
Combination Analgesics 271
Anticonvulsant Drugs 271
Tricyclic Antidepressants 271
Sodium Channel Blockade 272
Steroids 272
Bisphosphonates 272
Neuronal Ablation or Exhaustion Therapy 272
Radiation Therapy 273
Acupuncture 273
The Future: Toward a Mechanistic Understanding of Cancer Pain 273
References 273
. Section B 276
Nutritional Management of the Cancer Patient 276
Metabolism of Cancer: Substrate Utilization 276
Cancer Anorexia and Cachexia 277
Epidemiology, Prevention, and Risk Factors 277
Implementing a Nutritional Plan for the Oncology Patient: Nutritional Assessment 278
Feeding the Hospitalized Oncology Patient 280
Coax Feeding and Pharmacologic Appetite Stimulation 280
Assisted Enteral Support 280
Parenteral Support 281
Nutritional Support in the Cancer-Bearing Patient 283
Substrate 283
Amino Acids 284
Polyunsaturated Fats 284
Vitamins and Minerals 285
Antioxidants/Supplements 285
References 286
. Section C 289
Relationship-Centered Approach to Cancer Communication 289
A Paradigm Shift: Paternalism to Partnership 290
Relationship-Centered Care 290
Core Communication Skills for Cancer Communication 291
Gathering Information 291
Identify the Client’s Full Agenda 291
Elicit the Client’s Perspective 291
Explaining and Planning 291
Assess the Client’s Knowledge Level 291
Give Information in Manageable Chunks and Checks 291
Building Relationships 291
Offer Partnership 291
Ask Permission 292
Express Empathy 292
Demonstrate Appropriate Nonverbal Behavior 292
Providing Structure 292
Summarize 292
“I Don’t Have Time for This…” 292
Approaches to Cancer Conversations 293
Delivering Bad News 293
Discussing Prognosis 293
Assessing Quality of Life 293
Transitioning to Palliative Care 294
Preparing Families for Euthanasia 294
Providing Support for Grief and Loss 294
Caring for Yourself 294
Conclusion 294
References 294
16 Complementary and Alternative Medicine for Cancer: 297
Acupuncture 297
What Is Acupuncture? 297
How Does Acupuncture Work? 297
How Might Acupuncture Benefit a Veterinary Patient with Cancer? 298
The Importance of Approaching Acupuncture Scientifically 298
Herbs 298
Do Herbs Have Anticancer Benefits? 298
How Do Herbs Work to Fight Cancer? 298
Additional Issues with Herbs for Cancer Patients 299
Examples of Herbs for Patients with Cancer 300
Asian Mushrooms 300
Curcumin 300
Boswellia 301
Milk Thistle 301
Bloodroot 301
Yunnan Baiyao 302
Massage 302
What Is Massage and How Can It Help Cancer Patients? 302
How Does Massage Work? 303
How Does Massage Benefit Cancer Patients? 303
What Are the Risks of Massage for Cancer Patients? 303
Laser Therapy 303
What Is Laser Therapy? 303
How Does Laser Therapy Work? 303
How Might Laser Therapy Benefit Cancer Patients? 303
How Might Laser Therapy Harm Cancer Patients? 304
Homeopathy 304
What Is Homeopathy? 304
How Does Homeopathy Work? 304
How Might Homeopathy Benefit Patients with Cancer? 304
Can Homeopathy Harm Cancer Patients? 305
Words of Caution 305
General Considerations When Recommending Integrative Care for Oncology Patients 305
References 306
17 Clinical Trials and Developmental Therapeutics 310
Phase I Trials (Dose Finding) 310
Phase II Trials (Activity/Efficacy Trials) 311
Endpoints of Activity/Efficacy 312
Phase III Trials (Pivotal/Confirming Trials) 313
Sample Size and Power 313
Randomization 314
Phase IV Trials (Postregistration Trials) 314
Good Manufacturing Practice/ Good Clinical Practice Criteria 314
Effectiveness versus Efficacy Definitions 315
Regulatory Oversight 315
Veterinary Registration Trials 315
Consortia 315
Comparative Oncology Trials Consortium 315
Animal Clinical Investigation 316
Canine Comparative Oncology and Genomics Consortium 316
Current Challenges and Opportunities in Oncology Drug Development 316
New Trial Designs 316
Adaptive Trial Designs and Stopping Rules 316
Stopping Rules 316
Bayesian (Continuous Learning) Adaptive Designs 317
Randomized Discontinuation Trials 317
Personalized Medicine 318
Clinical Trial Ethics 318
Conclusions 319
References 319
IV Specific Malignancies in the Small Animal 322
18 Tumors of the Skin and Subcutaneous Tissues 322
Incidence 322
Etiology 322
Physical Factors 322
Viral Factors 322
Immune Status 323
Genetic Abnormalities in Skin Cancer 323
Basal Cell Carcinomas 324
Squamous Cell Carcinomas 324
Pathologic Classification of Skin Tumors 324
History and Clinical Signs 324
Diagnostic Techniques and Work-Up 324
Treatment and Prognosis for Specific Tumor Types 325
Epithelial Tumors 326
Tumors of the Primitive Follicular Epithelium 326
Basal Cell Carcinomas 326
Basosquamous Cell Carcinomas 326
Papillomas 327
Squamous Cell Carcinoma in Situ 327
Squamous Cell Carcinomas 327
Tumors with Adnexal Differentiation 329
Infundibular Keratinizing Acanthomas 329
Tricholemmoma 329
Trichoblastoma 329
Trichoepitheliomas 330
Malignant Trichoepithelioma 330
Pilomatricomas 330
Malignant Pilomatricomas 330
Tumors of Glandular Origin 330
Sebaceous Hyperplasia, Sebaceous Adenoma, Sebaceous Ductal Adenoma, and Sebaceous Epithelioma 330
Sebaceous Gland Carcinomas 330
Apocrine Gland Adenomas and Solid-Cystic Apocrine Ductal Adenomas 330
Apocrine Gland Carcinomas 330
Eccrine Adenomas and Carcinomas 331
Neuroendocrine Carcinomas 331
Renal Cystadenocarcinoma and Nodular Dermatofibrosis 331
Tumors of the Ear Canal 331
Ceruminous Gland Adenomas and Cysts 331
Ceruminous Gland Adenocarcinomas 331
Tumors of the Digit 332
References 334
19 Melanoma 338
Pathology and Molecular Biology 338
Biologic Behavior and Prognostic Factors 338
Size and Stage 339
Staging 339
Treatment 339
Surgical Aspects 339
Radiation Therapy 342
Outcomes of Dogs and Cats Treated with Radiation Therapy for Oral Melanoma 342
Combining Chemotherapy with Radiation Therapy 344
Radiation-Associated Prognostic Factors 344
Side Effects of Radiation Therapy 345
Treatments Other than Surgery and Radiation 346
References 347
20 Mast Cell Tumors 352
Canine Mast Cell Tumors 352
Biology of Canine Mast Cells 352
Incidence and Risk Factors 352
History and Clinical Signs 353
Prognostic Factors 354
Diagnostic Technique and Work-Up 357
Treatment 359
Feline Mast Cell Tumors 363
Cutaneous Feline Mast Cell Tumors 363
Splenic/Visceral Feline Mast Cell Tumors 365
Feline Intestinal Mast Cell Tumor 365
Comparative Aspects of Mast Cell Tumors 366
References 366
21 Soft Tissue Sarcomas 373
Incidence and Risk Factors 373
Pathology and Natural History* 373
Specific Tumor Types 373
Tumors of Fibrous Origin 373
Nodular Fasciitis (Fibromatosis, Pseudosarcomatous Fibromatosis) 373
Fibrosarcoma 374
Tumors of the Peripheral Nerves 375
Peripheral Nerve Sheath Tumor (Neurofibrosarcoma, Malignant Schwannoma, Hemangiopericytoma) 375
Histiocytic Disorders 375
Tumors of Adipose Tissue 375
Lipoma 375
Intermuscular Lipoma 375
Infiltrative Lipoma 376
Liposarcoma 376
Tumors of Smooth Muscle 376
Leiomyoma and Leiomyosarcoma 376
Tumors of Skeletal Muscle 377
Rhabdomyosarcoma 377
Tumors of Vascular and Lymphatic Tissue 377
Lymphangiosarcoma 377
Hemangioma 377
Hemangiosarcoma 377
Tumors of Synovial Tissue 378
Synovial Cell Sarcoma 378
Tumors of Uncertain Histogenesis 379
Myxosarcoma 379
Malignant Mesenchymoma 379
History and Clinical Signs 379
Diagnostic Techniques and Work-Up 379
Clinical Staging 380
Treatment 380
Surgery 380
Surgery and Radiation Therapy 382
Radiation Therapy 383
Chemotherapy 384
Prognosis 385
Feline Sarcomas and Vaccine-Associated Sarcomas 386
Epidemiology and Risk Factors 386
Pathology 387
Diagnosis and Work-Up 387
Treatment 387
Surgery 388
Surgery and Radiation Therapy 388
Radiation Therapy 389
Chemotherapy 389
Prognosis 390
Prevention 391
Comparative Aspects 391
References 392
22 Cancer of the Gastrointestinal Tract 398
n Section A 398
Oral Tumors 398
Incidence and Risk Factors 398
Pathology and Natural Behavior 398
Malignant Melanoma 398
Squamous Cell Carcinoma 398
Fibrosarcoma 400
Epulides 400
Peripheral Odontogenic Fibroma 401
Acanthomatous Ameloblastoma 401
History and Clinical Signs 401
Diagnostic Techniques and Work-Up 401
Therapy 402
Surgery 402
Radiation Therapy 404
Chemotherapy 405
Prognosis 405
Malignant Melanoma 406
Squamous Cell Carcinoma 406
Canine Oral Squamous Cell Carcinoma 406
Feline Oral Squamous Cell Carcinoma 407
Fibrosarcoma 407
Osteosarcoma 407
Epulides 408
Peripheral Odontogenic Fibroma 408
Acanthomatous Ameloblastoma 408
Selected Sites or Cancer Conditions in the Oral Cavity 408
Tonsillar Squamous Cell Carcinoma 408
Tongue 408
Undifferentiated Malignancy of Young Dogs 409
Multilobular Osteochondrosarcoma 409
Viral Papillomatosis 410
Odontogenic Tumors 410
Eosinophilic Granulomas 411
Eosinophilic Granulomas in Dogs 411
Eosinophilic Granuloma in the Cat 411
Nasopharyngeal Polyps in Cats 411
Comparative Aspects 411
References 412
. Section B 415
Salivary Gland Cancer 415
Incidence and Risk Factors 415
Pathology 415
History and Clinical Signs 415
Diagnostic Techniques and Work-Up 415
Therapy 415
Prognosis 416
Comparative Aspects 416
References 416
. Section C 416
Esophageal Cancer 416
Incidence and Risk Factors 416
Pathology and Natural Behavior 416
History and Clinical Signs 416
Diagnostic Techniques and Work-Up 417
Therapy 417
Prognosis 417
Comparative Aspects 417
References 417
. Section D 418
Exocrine Pancreatic Cancer 418
Incidence and Risk Factors 418
Pathology and Natural Behavior 418
History and Clinical Signs 418
Diagnostic Techniques and Work-Up 418
Therapy 418
Prognosis 418
Comparative Aspects 418
References 418
. Section E 419
Gastric Cancer 419
Incidence and Risk Factors 419
Pathology and Natural Behavior 419
History and Clinical Signs 419
Diagnostic Techniques and Work-Up 419
Therapy 420
Prognosis 420
Comparative Aspects 421
References 421
. Section F 422
Hepatobiliary Tumors 422
Incidence and Risk Factors 422
Pathology and Natural Behavior 422
Hepatocellular Tumors 422
Bile Duct Tumors 423
Bile Duct Adenoma (Biliary Cystadenoma) 423
Bile Duct Carcinoma (Cholangiocarcinoma) 424
Neuroendocrine Tumors 424
Sarcomas 424
Other Primary Hepatic Tumors 424
History and Clinical Signs 424
Diagnostic Techniques and Work-Up 425
Laboratory Tests 425
Imaging 425
Therapy and Prognosis 426
Hepatocellular Tumors 426
Bile Duct Tumors 427
Neuroendocrine Tumors 427
Sarcomas 427
Other Primary Hepatic Tumors 427
Comparative Aspects 427
References 427
. Section G 429
Intestinal Tumors 429
Incidence and Risk Factors 429
Pathology and Natural Behavior 430
Molecular Aspects 432
History and Clinical Signs 432
Paraneoplastic Syndromes 432
Diagnostic Techniques and Work-Up 432
Physical Examination 432
Clinical Pathology 432
Complete Blood Count 432
Chemistry Profile 432
Cytology and Histopathology 433
Imaging 433
Plain and Contrast Abdominal Radiographs 433
Thoracic Radiographs 433
Abdominal Ultrasound 433
Endoscopy and Laparoscopy 434
Exploratory Laparotomy 434
Therapy and Prognosis 434
Surgery 434
Chemotherapy 436
Radiation Therapy 436
Prognostic Factors 437
Comparative Aspects 437
References 437
. Section H 440
Perianal Tumors 440
Incidence and Risk Factors 440
Pathology and Natural Behavior 442
History and Clinical Signs 442
Diagnostic Techniques and Work-Up 444
Therapy and Prognosis 444
Comparative Aspects 447
References 447
23 Tumors of the Respiratory System 449
. Section A 449
Cancer of the Nasal Planum 449
Incidence and Risk Factors 449
Pathology and Natural Behavior 449
History and Clinical Signs 449
Diagnostic Techniques and Work-Up 449
Therapy 449
Prognosis 451
Comparative Aspects 452
References 452
. Section B 452
Nasosinal Tumors 452
Canine Nasosinal Tumors 452
Incidence and Risk Factors 452
Pathology and Natural Behavior 452
History and Clinical Signs 453
Diagnosis and Staging 453
Treatment and Prognosis 455
Feline Nasosinal Tumors 463
Comparative Aspects 464
References 465
. Section C 468
Cancer of the Larynx and Trachea 468
Incidence and Risk Factors 468
Pathology and Natural Behavior 468
History and Clinical Signs 468
Diagnostic Techniques and Work-Up 468
Therapy 468
Prognosis 469
Comparative Aspects 469
References 469
. Section D 470
Pulmonary Neoplasia 470
Incidence and Risk Factors 470
Pathology and Natural Behavior 470
Clinical Signs and Physical Examination Findings 471
Diagnostic Techniques and Work-Up 471
Clinical Laboratory Findings 471
Fine-Needle Aspiration 472
Treatment 473
Prognosis 475
Comparative Aspects 476
Miscellaneous Lung Conditions 476
Canine Pulmonary Lymphomatoid Granulomatosis 476
Histiocytic Sarcoma 476
References 476
24 Tumors of the Skeletal System 480
Osteosarcoma in Dogs 480
Incidence and Risk Factors 480
Etiology 480
Physical Factors 480
Genetic Factors 481
Molecular Factors 482
Pathology and Natural Behavior 483
History and Clinical Signs 483
Systemic Alterations 484
Diagnostic Techniques and Work-Up 484
Radiology 484
Tissue Biopsy 485
Staging and Patient Assessment 487
Systemic Staging 487
Surgical Staging 487
Patient Assessment 487
Known or Suggested Prognostic Factors 488
Anatomic Location and Signalment 488
Serum Alkaline Phosphatase 488
Molecular, Genetic, and Immunologic Indices of Prognosis 488
Therapy Directed at the Primary Tumor 490
Surgery 490
Amputation 490
Limb-Sparing Surgery 490
Allograft Limb Sparing 491
Metal Endoprosthesis Limb Sparing. 492
Pasteurized Tumoral Autograft. 493
Longitudinal Bone Transport Osteogenesis. 493
Ulna Transposition Limb Sparing. 494
Nonsurgical Alternative Methods of Limb Salvage 495
Intraoperative Radiation Therapy and Extracorporeal Intraoperative Radiation Therapy 495
Stereotactic Radiosurgery 495
Isolation of Limb Circulation and Perfusion 496
Summary of Outcome Following Limb Salvage for Dogs with Osteosarcoma 496
Surgery for Nonappendicular and Less Common Appendicular Sites of OS 497
Radiation 497
Radioisotopes 497
Systemic Adjuvant Therapy for Dogs with Osteosarcoma 498
Chemotherapy 498
Cisplatin: Single Agent 498
Carboplatin: Single Agent 500
Lobaplatin: Single Agent 501
Doxorubicin: Single Agent 501
Doxorubicin/Cisplatin: Concurrent Combination 501
Doxorubicin/Carboplatin: Concurrent Combination 501
Doxorubicin/Cisplatin: Alternating Combination 501
Doxorubicin/Carboplatin: Alternating Combination 501
Carboplatin/Gemcitabine: Concurrent Combination 502
Preliminary Agents 502
Immunotherapy 502
Molecular-Targeted Therapies for Dogs with Osteosarcoma 502
Micrometastatic Adjuvant Setting 502
Treating Gross Metastatic Disease 503
Surgery 503
Chemotherapy and Receptor Tyrosine Kinase Inhibitors for Gross (Macroscopic) Osteosarcoma 503
Investigational Therapies for Gross Metastatic Disease 504
Aerosol Drug Delivery 504
Augmentation of Antitumor Immunity 504
Palliative Treatment: Primary and Metastatic Bone Cancer Pain 504
Bone Cancer Pain Physiology 504
Palliative Radiation Therapy 505
Radiopharmaceuticals 505
Aminobisphosphonates 505
Comparative Aspects 506
Bone Surface Osteosarcoma 507
Other Primary Bone Tumors of Dogs 507
Chondrosarcoma 508
Hemangiosarcoma 508
Fibrosarcoma 509
Multilobular Osteochondrosarcoma 509
Metastatic Tumors of Bone 509
Benign Tumors of Bone 510
Osteomas 510
Multiple Cartilaginous Exostosis 510
Bone Cysts 510
Primary Bone Tumors of Cats 511
Incidence and Risk Factors 511
Pathology and Natural Behavior 512
History and Clinical Signs 512
Diagnostic Work-Up 512
Therapy and Prognosis 512
Fibrosarcoma, Chondrosarcoma, and Hemangiosarcoma 512
References 512
25 Tumors of the Endocrine System 521
Pathogenesis of Endocrine Tumors 521
Pituitary Tumors 521
Pituitary Corticotroph Tumors: Hypercortisolism (Hyperadrenocorticism or Cushing’s Syndrome) 522
Pathogenesis 522
Clinical Findings and Diagnostic Evaluation in Dogs 522
Treatment of Canine Pituitary- Dependent Hypercortisolism 523
Surgery 524
Radiation Therapy 524
Medical Therapy 524
Feline Pituitary-Dependent Hypercortisolism 525
Pituitary Somatotroph Tumors (Feline Acromegaly) 525
Adrenal Gland Neoplasia 527
Adrenocortical Tumors 528
Adrenal Medullary Tumors 529
Surgical Management of Adrenal Tumors 530
Incidental Adrenal Masses 530
Thyroid Gland Neoplasia in Dogs 530
Thyroid Gland Neoplasia in Cats 532
Parathyroid Tumors 534
Pancreatic Beta-Cell Tumors (Insulinomas) 536
Beta-Cell Tumors in Dogs 536
Beta-Cell Tumors in Cats 538
Gastrointestinal Endocrine Tumors 538
Gastrinoma 538
Glucagonoma 538
Intestinal Carcinoid 538
References 539
26 Tumors of the Female Reproductive System 549
Ovarian Tumors 549
Incidence 549
Pathology and Natural Behavior 549
Canine Ovarian Tumors 549
Epithelial Tumors 549
Sex Cord Stomal Tumors 549
Germ Cell Tumors 549
Mesenchymal Tumors 550
Miscellaneous 550
Feline Ovarian Tumors 550
History and Clinical Signs 550
Canine Ovarian Tumors 550
Feline Ovarian Tumors 550
Diagnostic Techniques and Work-Up 550
Therapy 551
Prognosis 551
Comparative Aspects 551
Uterine Tumors 551
Incidence 551
Pathology and Natural Behavior 552
History and Clinical Signs 552
Diagnostic Therapeutics and Work-Up 552
Therapy 552
Prognosis 552
Vaginal and Vulvar Tumors 552
Incidence 552
Pathology and Natural Behavior 552
History and Clinical Signs 553
Diagnostic Techniques and Work-Up 553
Therapy 553
Prognosis 553
References 553
27 Tumors of the Mammary Gland 555
Mammary Gland Tumors in Dogs 555
Epidemiology and Risk Factors 555
Epidemiology 555
Risk Factors 555
Age 555
Hormonal Exposure 555
Breeds and Genetic Susceptibility 556
Other Risk Factors 556
Tumor Biology: Development, Hormones, Growth Factors, and Clinical Implications 556
Tumor Hormone Receptors: Prognostic, Clinical, and Therapeutic Implications 557
History and Clinical Presentation 557
Clinical Assessment, Diagnosis, Work-Up, and Staging 557
Staging System 558
Histopathology 558
Classification Systems 558
Canine Mammary Hyperplasia and Dysplasia 558
Benign Mammary Neoplasms 558
Malignant Canine Mammary Neoplasms 558
Malignant Epithelial Tumors 558
Malignant Mesenchymal Neoplasms: Sarcomas 558
Hyperplasia/Dysplasia/Neoplasia of the Nipple 559
Histopathologic Prognostic Factors and Grading 559
Clinical Prognostic Factors 560
Tumor Size 560
Lymph Node 560
WHO Staging System 560
Therapy 561
Surgical Treatment 561
Systemic Treatment 563
Mammary Tumors in Cats 564
Epidemiology and Risk Factors 564
Epidemiology 564
Risk Factors 564
Age 565
Breed 565
Hormonal Association 565
Tumor Biology: Development, Hormones, Growth Factors, and Prognostic Implications 565
History and Clinical Presentation 565
Clinical Assessment, Diagnosis, Work-Up, and Staging 566
Staging System 566
Histopathology 566
Hyperplasia and Dysplasia 566
Benign Feline Mammary Neoplasms 566
Malignant Feline Mammary Neoplasms 566
Histopathologic Prognostic Factors and Grading 566
Clinical Prognostic Factors 566
Tumor Size and Prognosis 567
Lymph Nodes and Prognosis 567
Breed and Prognosis 567
Age 567
Surgical Treatment 567
Systemic Treatment 568
References 569
28 Tumors of the Male Reproductive System 574
Canine Testicular Tumors 574
Prevalence/Incidence 574
Risk Factors 574
Pathology and Pathogenesis 575
Natural Behavior 576
History and Clinical Signs 576
Diagnostic Techniques and Staging 577
Treatment and Prognosis 578
Comparative Aspects 578
Feline Testicular Tumors 578
Canine Prostate Tumors 578
Incidence/Prevalence 578
Risk Factors 579
Natural Behavior 579
Pathology/Pathogenesis 579
History and Clinical Signs 580
Diagnostic Techniques and Staging 580
Treatment and Prognosis 581
Comparative Aspects 582
Feline Prostate Tumors 582
Canine Penile, Preputial, and Scrotal Tumors 583
Feline Penile, Preputial, and Scrotal Tumors 583
Comparative Aspects 583
References 583
29 Tumors of the Urinary System 589
Canine Urinary Bladder Tumors 589
Etiology and Prevention 589
Diagnosis and Differential Diagnoses 589
Presentation and Clinical Staging 590
Treatment 592
Surgery and Nonsurgical Procedures 592
Radiation Therapy 593
Medical Therapy 593
Systemic Medical Therapy 593
Localized Therapy 595
Supportive Care 595
Prognosis 595
Feline Urinary Bladder Tumors 596
Urethral Tumors 596
Renal Tumors 596
Diagnosis and Clinical Staging 596
Treatment and Prognosis 596
Feline Renal Tumors 596
Comparative Aspects 597
Transitional Cell Carcinoma 597
Renal Cancer 597
References 597
30 Tumors of the Nervous System 600
Brain Tumors 600
Incidence and Risk Factors 600
Pathology 600
History and Clinical Signs 601
Diagnostic Techniques and Work-Up 601
Minimum Database 601
Imaging 601
Cerebrospinal Fluid Analysis 603
Therapy 603
Surgery 603
Radiation Therapy 603
Chemotherapy 604
Other Therapies 604
Prognosis 605
Comparative Aspects 606
Spinal Tumors 606
Incidence and Risk Factors 606
Pathology 606
History and Clinical Signs 607
Diagnostic Techniques and Work-Up 607
Minimum Database 607
Imaging 607
Cerebrospinal Fluid Analysis 607
Therapy 608
Prognosis 608
Comparative Aspects 609
Peripheral Nerve Tumors 609
Incidence and Risk Factors 609
Pathology 609
History and Clinical Signs 609
Diagnostic Techniques and Work-Up 609
Therapy 610
Prognosis 610
Comparative Aspects 610
References 610
31 Ocular Tumors 614
Tumors of the Eyelids, Third Eyelid, Conjunctiva, and Ocular Surface 614
Incidence and Risk Factors 614
Pathology and Natural Behavior 614
History and Clinical Signs 615
Diagnostic Techniques and Work-Up 615
Therapy 616
Prognosis 616
Limbal (Epibulbar) Melanomas 616
Primary Ocular Tumors 617
Canine Anterior Uveal Melanomas 617
Incidence and Risk Factors 617
Pathology and Natural Behavior 617
History and Clinical Signs 617
Diagnostic Techniques and Work-Up 617
Therapy 618
Prognosis 618
Choroidal Melanomas 618
Feline Primary Intraocular Melanomas (Feline Diffuse Iris Melanoma) 618
Incidence and Risk Factors 618
Pathology and Natural Behavior 618
History, Clinical Signs, Diagnostic Techniques, and Work-Up 619
Therapy 619
Prognosis 619
Feline Ocular Posttraumatic Sarcoma 619
Spindle Cell Tumors of Blue-Eyed Dogs 620
Iridociliary Epithelial Tumors 620
Secondary Uveal Neoplasms 620
Tumors of the Orbit and Optic Nerve 620
Incidence and Risk Factors 620
Pathology and Natural Behavior 620
History and Clinical Signs 621
Diagnostic Techniques and Work-Up 621
Therapy 621
Prognosis 622
Ocular Effects of Cancer Therapeutic Modalities 622
Comparative Aspects 622
References 623
32 Hematopoietic Tumors 625
. Section A 625
Canine Lymphoma and Lymphoid Leukemias 625
Lymphoma 625
Etiology 625
Genetic and Molecular Factors 625
Infectious Factors 625
Environmental Factors 625
Immunologic Factors 626
Classification and Pathology 626
Atypical Anatomic Forms of Lymphoma 627
Histologic Classification Systems 627
History and Clinical Signs 629
Diagnostics and Clinical Staging 632
Physical Examination 632
Complete Blood Count, Biochemistry Profile, and Urinalysis 632
Histologic and Cytologic Evaluation of Lymph Nodes 633
Histologic and Cytologic Evaluation of Extranodal Sites 634
Molecular Diagnostic Techniques 634
Immunophenotyping 634
Other Immunohistochemical and Immunocytochemical Assessments 634
Clonality Assays 634
Proteomics 635
Staging 635
Bone Marrow Evaluation 635
Imaging 635
Treatment of Multicentric Lymphoma 636
Multidrug Combination Protocols 636
Single-Agent Chemotherapy with Known Activity for Dogs with Lymphoma 638
Overall Chemotherapy Recommendations for Multicentric Lymphoma (Author Preference) 639
Induction in Treatment-Naïve Patients 639
The Case for Treating T-Cell Lymphoma Differently 640
Treatment Response Evaluation for Lymphoma 640
Reinduction and Rescue Chemotherapy 640
Strategies to Enhance Effectiveness of Therapy in Lymphoma 641
Mechanisms of Drug Resistance 641
Altering Drug Pharmacokinetics 642
Treatment Approaches Using Immunologic or Biologic Agents 642
Monoclonal Antibody Approaches 642
Antitumor Vaccine Approaches 642
Surgery 642
Radiation Therapy 643
Treatment of Extranodal Lymphoma 643
Alimentary Lymphoma 643
Primary Central Nervous System Lymphoma 643
Cutaneous Lymphoma 643
Prognosis 644
Lymphocytic Leukemia 644
Incidence, Risk Factors, and Etiology 644
Pathology and Classification 646
History and Clinical Signs 647
Diagnostics and Clinical Staging 647
Treatment of Chronic Lymphocytic Leukemia 647
Treatment of Acute Lymphoblastic Leukemia 648
Prognosis 648
References 648
. Section B 655
Feline Lymphoma and Leukemia 655
Lymphoma 655
Incidence 655
Etiology 656
Viral Factors 656
Genetic and Molecular Factors 657
Environmental Factors 657
Immunosuppression 657
Chronic Inflammation 657
Diet and Intestinal Lymphoma 657
Pathology and Natural Behavior 657
Alimentary/Gastrointestinal Lymphoma 657
Mediastinal Form 658
Nodal Lymphoma 658
Extranodal Lymphoma 660
History, Clinical Signs, and Physical Examination Findings 660
Nonspecific Signs 662
Diagnosis and Clinical Staging 662
Anatomic Site-Specific Diagnostics 662
Alimentary/Gastrointestinal Lymphoma 662
Mediastinal Lymphoma 663
Nasal Lymphoma 663
Renal Lymphoma 664
Central Nervous System Lymphoma 664
Treatment and Prognosis 664
Anatomic Site-Specific Treatment 665
Alimentary/Gastrointestinal Lymphoma 665
Mediastinal Lymphoma 666
Nodal Lymphoma 666
Nasal Lymphoma 666
Central Nervous System Lymphoma 666
Laryngeal/Tracheal Lymphoma 666
Cutaneous Lymphoma 666
General Summary of Prognosis for Cats with Lymphoma 667
Feline Leukemias, Myeloproliferative Disorders, and Myelodysplasia 667
Lymphoid Leukemia 667
Treatment of Leukemias 667
References 667
. Section C 670
Canine Acute Myeloid Leukemia, Myeloproliferative Neoplasms, and Myelodysplasia 670
Incidence and Risk Factors 671
Pathology and Natural Behavior 671
Acute Myeloid Leukemia 672
Myeloproliferative Neoplasms 674
Polycythemia Vera 674
Chronic Myelogenous Leukemia 674
Basophilic and Eosinophilic Leukemia 675
Essential Thrombocythemia 675
Other Bone Marrow Disorders 675
Myelofibrosis 675
Myelodysplastic Syndrome 675
History and Clinical Signs 676
Diagnostic Techniques and Work-Up 676
Treatment 678
Acute Myeloid Leukemia 678
Polycythemia Vera 678
Chronic Myelogenous Leukemia 678
Essential Thrombocythemia 679
Myelodysplastic Syndrome 679
Prognosis 679
Comparative Aspects 679
References 679
. Section D 682
Myeloma-Related Disorders 682
Multiple Myeloma 682
Incidence and Etiology 682
Pathology and Natural Behavior 682
History and Clinical Signs 685
Diagnosis and Staging 686
Immunohistochemical and Molecular Diagnostics 687
Imaging 687
Differential Diagnosis of MM 687
Treatment 688
Initial Therapy of Multiple Myeloma 688
Evaluation of Response to Therapy 688
Therapy Directed at Complications of Multiple Myeloma 688
Rescue Therapy 690
Investigational Therapies 690
Prognosis 690
Solitary and Extramedullary Plasmacytic Tumors 691
Clinical Signs 691
Diagnosis for Solitary Plasmacytic Tumors 691
Therapy for Solitary Plasmacytic Tumors 692
References 693
33 Miscellaneous Tumors 696
. Section A 696
Hemangiosarcoma 696
Incidence and Risk Factors 696
Pathology and Natural Behavior 696
History and Clinical Signs 697
Diagnostic Techniques and Work-Up 697
Treatment 699
Surgery 699
Chemotherapy 699
Immunotherapy 700
Radiation Therapy 700
Novel Therapies 700
Prognosis 700
Canine 700
Feline 701
Comparative Aspects 701
References 701
. Section B 705
Thymoma 705
Incidence and Risk Factors 705
Pathology and Natural Behavior 705
History and Clinical Signs 705
Diagnostic Techniques and Work-Up 705
Therapy 706
Prognosis 707
Comparative Aspects 707
References 708
. Section C 709
Canine Transmissible Venereal Tumor 709
Incidence and Risk factors 709
Pathology and Natural Behavior 709
History and Clinical Signs 710
Diagnostic Techniques and Work-Up 710
Therapy 711
Prognosis 711
References 712
. Section D 713
Mesothelioma 713
Incidence and Risk Factors 713
Pathology and Natural Behavior 714
History and Clinical Signs 714
Diagnostic Techniques and Work-Up 714
Treatment and Prognosis 715
Comparative Aspects 715
References 716
. Section E 717
Neoplasia of the Heart 717
Incidence and Risk Factors 717
Pathology and Natural Behavior 717
History and Clinical Signs 718
Diagnostic Techniques and Work-Up 719
Therapy 721
Prognosis 721
Comparative Aspects 721
References 721
. Section F 723
Histiocytic Diseases 723
Background 723
Histiocytic Differentiation and Canine Histiocytosis 724
Immunophenotyping 725
Cutaneous Histiocytoma 726
Cutaneous Langerhans Cell Histiocytosis 726
Reactive Histiocytosis 726
Systemic Histiocytosis 727
Histiocytic Sarcoma 727
Pathology and Natural Behavior 727
History and Clinical Signs 728
Diagnosis and Staging 728
Treatment and Prognosis 728
Hemophagocytic Histiocytic Sarcoma 730
Feline Histiocytic Diseases 730
Feline Histiocytic Sarcoma 730
Feline Progressive Histiocytosis 730
Langerhans Cell Histiocytosis 730
Malignant Fibrous Histiocytoma 731
References 731
Index 734
A 734
B 736
C 737
D 743
E 744
F 745
G 747
H 748
I 749
J 751
K 751
L 751
M 752
N 755
O 756
P 757
Q 760
R 760
S 761
T 764
U 766
V 766
W 767
X 767
Y 767
Z 767
End sheet 2 770
End sheet 3 771
Pageburst ad End sheet4 772
End sheet 5-7 773