Basics of Oncology

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Preface Who Should Read This Book What This Book Is About Objective of This Book Acknowledgements Contents Contributors Part I: The Cancer Problem 1: What Is Malignancy? 1.1 Nature of a Malignancy 1.2 What Is the Prevalence of Cancer? 1.3 Tumours: Benign and Malignant? 1.4 Dangers of Malignant Tumours 1.5 What Causes Cancer 1.5.1 Is There a Single Cause or a Single Common Pathway? 1.5.2 Apoptosis 1.5.3 Carcinogens 1.5.4 Tobacco Smoking 1.5.5 Alcohol 1.5.6 Betel Nut 1.5.7 Sunshine 1.5.8 Other Forms of Irradiation: X-Rays and Atomic Irradiation 1.5.9 Industrial Irritants and Carcinogens 1.5.10 Chemical Carcinogens 1.5.11 Hormones 1.5.12 Viruses 1.5.12.1 Recent Studies of Viruses at a Molecular Level 1.5.13 Bacteria 1.5.14 Pre-existing Abnormalities 1.5.15 Nutritional Deficiencies and Food Habits 1.5.16 Estimate of Known Risk Factors and Associations with Cancer 2: Epidemiology 2.1 Comparative Cancer Incidence 2.2 People Most at Risk 2.3 Viral and Other Infection Associations 2.4 Heredity and Genetic Factors 2.4.1 Tumour Suppressors, Proto-Oncogenes and  Cancer Oncogenes 2.4.2 Tumour Suppressor Genes 2.4.3 Cell Cycle Regulatory Genes 2.5 Molecular Biological Changes in Controlling Cell Division 2.5.1 Inherited Cancer Genes: Inherited and Familial Cancers 2.6 Age 2.6.1 Infants 2.6.2 Children, Adolescents and Young Adults 2.6.3 Increasing Age 2.7 Predisposing and Pre-malignant Risk Factors 2.7.1 Skin 2.7.2 Oesophagus 2.7.3 Stomach 2.7.4 Bowel 2.7.5 Mouth and Throat 2.7.6 Stones: Gallstones and Kidney and Bladder Stones 2.7.7 Chronic Inflammation 2.7.8 Acute Injury 2.7.9 Pre-existing Lumps and Benign Tumours 2.7.10 Congenitally Abnormal Tissues 2.7.11 Gender 2.8 Diet and Cancer: Special Dietary Preventive Ingredients 2.9 Stomach Cancer 2.10 Bowel Cancer: Cancers of the Colon and Rectum 2.11 Other Cancers 2.12 Vegetarian Diets 2.13 Special Dietary Ingredients: Phytoestrogens and Lycopene 2.14 Vitamins, Anti-oxidants and Trace Elements 2.15 Race 2.16 Geographic Associations 2.17 Environment 2.17.1 Sunshine 2.17.2 Air Pollution 2.17.3 Ionising Irradiation 2.17.4 Goitre Belts 2.18 Occupation 2.19 Habits and Lifestyle 2.19.1 Smoking 2.19.2 Alcohol 2.19.3 Sun Exposure 2.19.4 Betel Nut 2.19.5 Pregnancies and Breast Cancer 2.19.6 Cultural and Social Customs 2.20 Psychological Factors: The Possible Role of Stress or Emotion in Cancer Development 2.21 Cancer Registries 3: Summary of Practical Measures to Prevent Cancer 3.1 Smoking 3.2 Viral and Bacterial Protection 3.3 Genetic Protection 3.4 Skin Cancers 3.5 Diets: Stomach and Bowel Cancer, Breast Cancer 3.5.1 Prostate Cancer 3.5.2 Thyroid Cancer 3.5.3 Dioxins 3.5.4 Breast Cancer 3.6 Industrial Cancers 3.7 Ionising Irradiation 3.8 Treatment of Pre-malignant and Potentially 3.8.1 Pre-malignant Conditions Part II: General Features of Cancer-Presentation and Management 4: Symptoms of Cancer: Local and General 4.1 Lump 4.2 Ulcer 4.3 Pain 4.4 Bleeding 4.5 Weight Loss 4.6 Interference with Tissue or Organ Function 4.7 Symptoms of Metastatic Spread 4.7.1 Lymph Nodes 4.7.2 Liver 4.7.3 Lungs 4.7.4 Bones 4.7.5 Fat and Muscles 4.7.6 Bowel 4.7.7 The Brain 4.7.8 The Unknown Primary Syndrome 5: Signs of Cancer: Local and General 5.1 Lump 5.2 Ulcer 5.3 Bleeding and Evidence of Blood Loss 5.4 Lymph Node Enlargement 5.5 Other Swellings 5.6 Findings of a General Examination Including the Mouth,Throat, Abdomen, Rectum and Anus 5.7 Rare and Seemingly Unrelated Indications of Cancer 6: Clinico-Pathology of Cancers 6.1 Typing, Grading and Staging of Cancer 6.2 Cancer Typing 6.3 Cancer Grading 6.4 Clinico-Pathological Staging of Cancer 6.5 Clinical Decisions Based on Pathology Information 7: Investigations That May Be Useful in Detecting Cancer 7.1 Screening Programmes 7.2 Screening Tests 7.2.1 The Cervical Smear or “Pap” (Papanicolaou) Test 7.2.2 Occult Blood Tests 7.2.3 Gastro-Oesophageal Screening 7.2.4 Breast Screenings: Mammography 7.2.5 Skin Cancer Screening: Especially the “Mole Check” 7.2.6 PSA Screening Test 7.2.7 Genetic Testing 7.3 Organ Imaging 7.3.1 X-Rays 7.3.2 Barium (Baryum) and Iodine Contrast X-Rays 7.3.3 Radiographic Screening 7.3.4 Mammography 7.3.5 Chest X-Ray 7.3.6 Skeletal X-Rays 7.3.7 Angiography 7.3.8 Isotope Scans (Nuclear Scintigraphy) 7.3.9 CT Scan or CAT Scan (Computerised Axial Tomography) 7.3.10 Ultrasound Scans 7.3.11 MRI (Magnetic Resonance Imaging) 7.3.12 PET (Positron Emission Tomography) Scan 7.4 Endoscopic Examinations: Rigid and Flexible Scopes 7.4.1 Rigid Scopes 7.4.2 Sigmoidoscopy 7.4.3 Proctoscopy 7.4.4 Vaginal Speculum 7.4.5 Laryngoscopy and Bronchoscopy 7.4.6 Oesophagoscopy 7.4.7 Cystoscopy 7.4.8 Echo-Endoscopy 7.4.9 Flexible Scopes 7.4.10 Gastroscopy or Endoscopy 7.4.11 Colonoscopy 7.4.12 Laparoscopy (Peritoneoscopy) and Thoracoscopy 7.4.13 Culdoscopy 7.5 Indirect Evidence of Cancer 7.5.1 Blood and Serum Tests 7.5.2 White Cell Count (WCC) 7.5.3 Erythrocyte Sedimentation Rate (ESR) 7.5.4 Serum Biochemistry 7.5.5 Tumour Markers 7.5.6 The Future 7.6 Direct Evidence of Cancer 7.6.1 Biopsy 7.6.2 Needle Aspiration or “Punch-Out” Biopsy 7.6.3 Aspiration Cytology 7.6.4 Bone Marrow Biopsy 7.6.5 Standard Paraffin Section Biopsy and Frozen Section Biopsy 8: Treating Cancer 8.1 Can Cancer Be Cured? An Outline of Prognosis 8.2 In Western Societies More Cancers Are Cured than Not Cured 8.3 Methods of Treatment 8.3.1 Principles of Treatment of Potentially Curable Regional Cancers 8.3.2 Surgery 8.3.3 Radiotherapy 8.3.3.1 Brachytherapy 8.3.4 Chemotherapy (Cytotoxic Drug Treatment) 8.3.4.1 Anti-cancer Drugs 8.3.4.2 Using Combined Anti-cancer Agents 8.3.4.3 Time and Concentration of Anti-cancer Cytotoxic Drugs on Different Cancer Cell Types 8.3.4.4 Palliative Chemotherapy 8.3.4.5 Adjuvant Chemotherapy 8.3.4.6 Systemic and Regional (Intra-arterial) Chemotherapy Intra-arterial Infusion Isolated Perfusion Chemoembolisation (Trans-arterial Chemoembolisation TACE) Stopflow Infusion Aim of Regional Chemotherapy Reduction of Side Effects 8.3.4.7 Other Regional Chemotherapy 8.3.4.8 Combined Integrated Treatment 8.3.4.9 Induction Chemotherapy 8.3.4.10 Side Effects of Chemotherapy 8.3.4.11 Concomitant Chemotherapy and Radiotherapy: The So-Called Sandwich Treatment 8.4 Other Important Treatments 8.4.1 Hormone Therapy 8.4.1.1 Breast Cancer Anti-oestrogens: Tamoxifen Cortisone Hormone Side Effects Long-Term Hormone Therapy New Agents 8.4.1.2 Prostate Cancer 8.4.1.3 Other Possible Hormone-Sensitive Cancers 8.4.2 Immunotherapy 8.4.2.1 Monoclonal Antibodies 8.4.2.2 Interferon 8.4.2.3 The Interleukins 8.4.2.4 Tumour Necrosis Factor (TNF) Small-Molecule Target Inhibitors 8.4.2.5 Cell-Mediated Anti-cancer Activity 8.5 Some Further Treatments Under Study 8.5.1 Heat Therapy 8.5.1.1 Cryosurgery 8.5.1.2 Laser Surgery 8.5.1.3 Photodynamic Therapy 8.5.2 Gene Therapy 8.5.2.1 Matching Treatment to Cancer-Associated Genes and Molecular Characterisation of Cancers 8.5.2.2 Anti-angiogenesis 8.6 General Care 8.6.1 Care of General Health 8.6.2 Treatment of Complications 8.6.3 Supportive Care and Supportive Care Teams 8.6.4 Pain Relief 8.6.5 Psychological and Spiritual Help 8.6.6 Follow-Up Care 8.6.7 The Specialty of Palliative Care 8.6.8 Alternative Medicine 8.6.8.1 Ranging from Unproven Naturopathic and Herbal Medicine Remedies to Unscrupulous “Quack” Practices 9: Relationship Between Patients, Their Doctors and the Healthcare Team Part III: Most Common Cancers 10: Skin Cancers 10.1 Skin Cancer Prevention 10.2 Basal Cell Carcinoma (BCC) 10.2.1 Treatment 10.3 Squamous Cell Carcinoma (SCC) 10.3.1 Treatment 10.4 Melanoma 10.4.1 Pathology 10.4.2 Causes and Incidence 10.4.3 Early Features of Melanoma 10.4.4 Treatments of Melanoma 10.4.4.1 Surgical Treatment 10.4.5 Investigations to Guide Surgical Treatment 10.4.5.1 Skin Penetration 10.4.5.2 Sentinel Node Biopsy 10.4.6 Other Treatments 10.4.7 Vaccine Studies 11: Lung Cancer (Bronchogenic Carcinoma) 11.1 Symptoms 11.2 Investigations 11.3 Significance of Histological Findings 11.4 Treatments 11.5 Mesothelioma 11.6 Metastatic Cancer in the Lung 12: Cancer of the Breast: An Overview 12.1 Introduction 12.1.1 Epidemiology 12.1.2 Workup 12.1.3 Breast Biopsy 12.1.4 Histological Types and Molecular Subtypes 12.1.5 Triple-Negative Breast Cancer 12.1.6 Staging 12.2 Breast Cancer Treatment: Concepts 12.2.1 Lobular Carcinoma In Situ 12.2.2 Ductal Carcinoma In Situ 12.2.3 Invasive Breast Cancer: Stages I, IIA and IIB or T3, N1, M0 12.2.3.1 Locoregional Treatment 12.2.4 Pre-operative (Induction or Neoadjuvant) Chemotherapy for Large Clinical Stage IIA and IIB Tumours and T3, N1, M0 Tumours 12.2.4.1 Induction Chemotherapy 12.2.4.2 Induction Endocrine Therapy 12.2.4.3 Induction Therapy in Patients with HER2-Positive Tumours 12.2.4.4 Induction Therapy in Patients with TNBC 12.2.4.5 Surgical Treatment After Induction Chemotherapy 12.2.5 Radiation Therapy 12.2.5.1 Post-lumpectomy Radiation Therapy 12.2.5.2 Postmastectomy Radiation Therapy 12.2.6 Breast Reconstruction 12.2.7 Systemic Adjuvant Therapy 12.2.7.1 Axillary Lymph Node-Negative Tumours 12.2.7.2 Axillary Lymph Node-Positive Tumours 12.2.7.3 Adjuvant Endocrine Therapy 12.2.7.4 Adjuvant Cytotoxic Chemotherapy 12.2.7.5 Targeting HER2/neu in Adjuvant Setting 12.2.8 Stage III, Locally Advanced, Inflammatory Breast Cancer 12.2.8.1 Operable LABC: Clinical Stage T3, N1, M0 12.2.8.2 Inoperable LABC: Non-T3, N1, M0 Clinical Stage IIIA, Clinical Stage IIIB or Clinical Stage IIIC 12.2.9 Inflammatory Breast Cancer (IBC) 12.2.10 Advanced Breast Cancer (ABC): Recurrent or Metastatic 12.2.10.1 Advanced Breast Cancer ABC (Stage IV, Recurrent or Metastatic Disease), HER2 Negative 12.2.10.2 Chemotherapy for Stage IV or Recurrent Metastatic Disease 12.2.10.3 Single Agents 12.2.10.4 Combination Regimens 12.2.11 First-Line Regimens for HER2-Positive Tumours 12.2.12 Tumours Previously Exposed to Trastuzumab 12.2.13 Endocrine Therapy 12.3 Breast Cancer and Bone-Modifying Drugs References 13: Cancers of the Digestive System (Alimentary Tract) 13.1 Cancer of the Oesophagus 13.1.1 Pathology 13.1.2 Symptoms 13.1.3 Signs 13.1.4 Investigations 13.1.5 Treatment 13.2 Cancer of the Stomach 13.2.1 Pathology 13.2.2 Symptoms 13.2.3 Signs 13.2.4 Investigations 13.2.5 Treatment 13.3 Cancers of the Liver 13.3.1 Primary Liver Cancer (Hepatoma or Hepatocellular Carcinoma) 13.3.1.1 Features of Primary Liver Cancer 13.3.1.2 Investigations 13.3.1.3 Treatment 13.3.2 Secondary (Metastatic) Liver Cancer 13.3.2.1 Investigations 13.3.2.2 Treatments 13.4 Cancer of the Gall Bladder and Bile Ducts 13.4.1 Symptoms 13.4.2 Signs 13.4.3 Pathology and Treatment 13.5 Cancer of the Pancreas 13.5.1 Presentation 13.5.2 Investigations 13.5.3 Treatment 13.6 Cancers of the Small Intestine 13.6.1 Carcinoid Tumour 13.7 Cancer of the Large Bowel (Colon and Rectum) 13.7.1 Clinical Features 13.7.2 Investigations 13.7.3 Treatment 13.7.4 Follow-Up Care 13.8 Cancer of the Anus 13.8.1 Presentation and Pathology 13.8.2 Treatment 14: Head and Neck Cancers 14.1 Cancers of the Lips 14.2 Cancers of the Floor of the Mouth (Under the Tongue), Anterior Two-Thirds of the Tongue and Buccal Mucosa (Inside the Cheek) 14.3 Cancer in the Posterior Third of Tongue, Tonsillar Region and Pharynx 14.4 Cancers of the Post-nasal Space (the Air Passage at the Back of the Nose) 14.4.1 Presentation 14.4.2 Treatment 14.5 Cancer of the Larynx 14.5.1 The Lost Chord Club 14.6 Salivary Gland Cancers 14.7 Cancers of the Thyroid Gland 14.7.1 Causes and Presentation 14.7.2 Accidental Irradiation 14.7.3 Investigations 14.7.4 Types of Thyroid Cancer 14.7.5 Papillary Cancer 14.7.6 Follicular Cancer 14.7.7 Medullary Cancer 14.7.8 Anaplastic Cancer 14.7.9 Other Types 15: Cancers of Female Genital Organs 15.1 Cancers of the Uterus 15.2 Cancer of the Cervix 15.2.1 Presentation and Risk Factors 15.2.2 Investigations 15.2.3 Treatment 15.2.4 Prevention 15.3 Cancer of the Body of the Uterus (Endometrial Cancer) 15.3.1 Presentation 15.3.2 Investigations 15.3.3 Treatment 15.4 Choriocarcinoma 15.5 Cancer of the Ovary 15.5.1 Presentation 15.5.2 Investigations 15.5.3 Treatment 15.5.4 Prevention 15.5.5 Metastatic Cancer of the Ovary 15.6 Cancer of the Vagina 15.7 Cancer of the Vulva 16: Cancers of the Male Genital Organs 16.1 Cancer of the Penis 16.2 Cancer of the Testis 16.2.1 Presentation 16.2.2 Investigations 16.2.3 Pathology 16.2.4 Treatment 16.3 Cancer of the Prostate Gland 16.3.1 Presentation 16.3.2 Investigations 16.3.3 Screening Tests: The PSA (Prostate-Specific Antigens) and the DRE (Digital Rectal Examination) 16.3.4 Controversies in Management of Men with  Prostate Cancer 16.3.5 Treatments 16.3.6 Treatment of Bone Metastases 17: Cancers of Bladder and Kidneys 17.1 Bladder Cancer 17.1.1 Investigations 17.1.2 Types of Bladder Cancer (Pathology) 17.1.3 Treatment 17.2 Kidney Cancers 17.2.1 Wilm’s Tumour (Nephroblastoma) 17.2.2 Adenocarcinoma (Hypernephroma or Grawitz Tumour) 17.2.3 Carcinoma of the Renal Pelvis or Ureter (Transitional Cell Carcinoma) 17.2.4 Investigations 17.2.5 Treatment 18: Cancers of the Brain and Nervous System 18.1 Brain Cancers 18.1.1 Clinical Features (Symptoms and Signs) 18.1.1.1 General Features 18.1.1.2 Focal Features 18.1.2 Pathology Types 18.1.3 Investigations 18.1.4 Treatment 18.2 Secondary Cancers in the Brain 18.3 Nerve Cell Cancers 18.3.1 Neuroblastoma 18.3.2 Presentation 18.4 Retinoblastoma 18.4.1 Presentation 19: The Leukaemias and Lymphomas 19.1 The Leukaemias 19.1.1 Incidence and Prevalence of Leukaemias 19.2 The Acute Leukaemias 19.2.1 Clinical Presentation 19.2.1.1 Acute Lymphatic (Lymphoblastic) Leukaemia (ALL) 19.2.1.2 Acute Myeloid Leukaemia 19.2.2 Investigations 19.2.3 Treatment 19.3 Chronic Lymphocytic (Lymphatic) Leukaemia 19.3.1 Clinical Presentation 19.3.2 Investigations 19.3.3 Treatment 19.4 Chronic Myeloid Leukaemia (CML) 19.4.1 Clinical Presentation 19.4.2 Investigations 19.4.3 Treatment 19.4.4 Hairy Cell Leukaemia 19.5 The Lymphomas 19.5.1 Causes of Lymphoma 19.6 Hodgkin Lymphoma 19.6.1 Presentation 19.6.2 Investigations 19.6.3 Staging and the Staging Laparotomy 19.6.4 Treatment 19.7 Non-Hodgkin Lymphomas 19.7.1 Presentation 19.7.2 Investigations 19.7.3 Treatment 19.8 Multiple Myeloma 19.8.1 Investigations 19.8.2 Treatment 20: Soft Tissue Sarcomas 20.1 Classification: Pathological Types 20.1.1 Fibrosarcoma 20.1.2 Liposarcoma 20.1.3 Rhabdomyosarcoma 20.1.4 Leiomyosarcoma 20.1.5 Neurosarcoma 20.1.6 Malignant Fibrous Histiocytoma (MFH) 20.1.7 Angiosarcoma 20.1.8 Synovial Sarcoma (Synoviosarcoma or Malignant Synovioma) 20.1.9 Presentation 20.1.10 Investigations 20.1.11 Treatment 21: Malignant Tumours of Bone and Cartilage 21.1 Osteosarcoma 21.1.1 Presentation 21.1.2 Investigations 21.1.3 Treatment 21.1.4 Intra-operative Irradiation 21.2 Osteoclastoma (Central Giant Cell Tumour of Bone) 21.2.1 Presentation 21.2.2 Investigations 21.2.3 Treatment 21.3 Ewing’s Tumour 21.3.1 Presentation 21.3.2 Investigations 21.3.3 Treatment 21.4 Chondrosarcoma 21.4.1 Presentation 21.4.2 Investigations 21.4.3 Treatment 22: Metastatic (Secondary) Cancer Part IV: Making Progress 23: Techniques and Evidence of Progress 23.1 Evidence-Based Medicine 23.1.1 Randomised Trials 23.1.2 Other Historic Methods of Gathering Evidence 23.2 Clinical Trials 23.2.1 Ethics Approval 24: Future Directions 24.1 Prevention (See Chap. 3) 24.2 Improved Cancer Screening and Diagnostic Techniques (See Chap. 7) 24.2.1 MRS (Magnetic Resonance Spectroscopy) 24.2.2 Combined Imaging Using PET and CT or PET and MRI 24.2.3 Magnetic Resonance-Guided Focused Ultrasound Surgery 24.3 Vaccines 24.4 Improved Treatment Agents 24.5 Self-Rescuing Concept (SRC) 24.6 New Agents 24.7 Therapeutic Viruses 24.8 Targeted Therapies 24.9 Improvements in Radiotherapy 24.9.1 Improvements in Focusing Radiotherapy 24.10 More Effective Use of Chemotherapy and Radiotherapy Integrated with Surgery 24.11 Prevention of Metastases 24.12 Heat Therapy 24.13 Other Physical Treatments 24.14 Immunotherapy 24.15 Stem Cell Research 24.16 Studies in Cell-Mediated Anti-cancer Activity 24.17 Genetic Engineering and Gene Therapy 24.18 Developments in Antibody Treatment 24.19 Molecular Characterisation in Future Cancer Treatment 24.20 Gene Expression Profiling for Prediction of Response to Chemotherapy 24.21 Molecular Heterogeneity 24.22 Learning from Alternative and Naturopathic Practices 24.23 Improved Palliative Care and Supportive Care 24.24 Personalised Medicine 24.24.1 Background: The Variety of Tumours 24.24.2 Rapid Improvement of Diagnostic Methods 24.24.3 Biomarker 24.24.4 Heterogeneity: The Evolution of Cancer 24.24.5 Immune Therapy 24.24.6 Immune Therapy: Checkpoints and Their Inhibitors 24.24.7 Immune Therapy: Adoptive Therapies 24.24.8 Immune Therapy: Tumour-Specific Antibodies 24.24.9 Outlook 24.25 Hope for the Future Literature Appendix A: Further Reading Appendix B: Appendix Glossary