Non-Surgical Treatment of Keratinocyte Skin Cancer (eBook)

Non-Surgical Treatment of Keratinocyte Skin Cancer 2
Title Page 3
Copyright page 4
Preface 5
Contents 6
Contributors 9
Chapter 1 12
From Precursor to Cancer: Field Cancerization and the Opportunities for Therapy 12
1.1 Actinic Keratoses and Squamous Cell Carcinoma 13
1.2 Basal Cell Carcinoma 15
1.3 Malignant Melanoma 15
1.4 Treatment of Field Change 16
References 17
Chapter 2 19
When Is a Skin Cancer a Cancer: The Histopathologist’s View 19
2.1 Field Cancerization from the Dermatopathologist’s Point of View 19
2.2 Histologic Diagnosis of Skin Cancers 21
2.3 Advanced Diagnostic Techniques 22
References 23
Chapter 3 25
Epidemiology of Non-Melanoma Skin Cancer 25
3.1 Introduction 25
3.2 Descriptive Epidemiology 25
3.3 Incidence 26
3.3.1 Basal Cell Carcinoma 26
3.3.1.1 Gender and Age Distribution 26
3.3.1.2 Trends in BCC Incidence 26
3.3.1.3 Body-Site Distribution and Histological Classification of BCC 28
3.3.2 Squamous Cell Carcinoma 28
3.3.2.1 Gender and Age Distribution 28
3.3.2.2 Body-Site Distribution 28
3.3.2.3 Trends in SCC Incidence 28
3.4 Methodological Problems in Studying NMSC Incidence 29
3.5 NMSC Prognosis and Mortality 29
3.6 All-Cause Mortality 30
3.7 Risk of De Novo Occurrence of NMSC 30
3.7.1 Risk of Other Malignancy After NMSC 30
3.7.2 Risk of Other Malignancy After BCC 30
3.7.3 Risk of Other Malignancies After SCC 31
3.8 Methodological Problems in Studying Relative Effects of NMSC 31
3.9 Economic and Social Impact 32
3.10 Take Home Pearls 32
References 32
Chapter 4 35
Genetics of Non-Melanoma Skin Cancers and Associated Familial Syndromes 35
4.1 Introduction to Cancer Genetics 35
4.1.1 Genetic Basis of Familial Cancer Syndromes 36
4.2 Genetic Targets in Sporadic Non-Melanoma Skin Cancers (NMSCs) 37
4.2.1 TP53 in NMSCs 37
4.2.1.1 p53 in BCCs 37
4.2.1.2 p53 in SCCs 38
4.2.2 RAS in NMSCs 38
4.2.3 CDKN2A in NMSCs 38
4.3 Cancer Syndromes with Established Genetic Defects 39
4.3.1 Basal Cell Nevus Syndrome (OMIM 109400) 39
4.3.1.1 Cutaneous Findings 39
4.3.1.2 Extracutaneous Findings 40
4.3.1.3 Patched Gene and Sonic Hedgehog 40
4.3.2 Xeroderma Pigmentosum (OMIM 194400, 278700–278800) 40
4.3.2.1 Cutaneous Findings 41
4.3.2.2 Extracutaneous Findings 41
4.3.2.3 Nucleotide Excision Repair Pathways 42
4.3.3 Muir-Torre Syndrome (OMIM 158320) 42
4.3.3.1 Cutaneous Findings 43
4.3.3.2 Extracutaneous Findings 43
4.3.3.3 Mismatch Repair Pathways 44
4.4 Cancer Syndromes Without Established Genetic Defects 44
4.4.1 Syndromes with Basal Cell Carcinomas 44
4.4.1.1 Bazex Syndrome (OMIM 301845) 44
4.4.2 Rombo Syndrome (OMIM 180730) 44
4.4.3 Syndromes with Squamous Cell Carcinomas 44
4.4.3.1 Multiple Self-Healing Squamous Epithelioma (OMIM 132800) 44
4.4.3.2 Epidermodysplasia Verruciformis (OMIM 226400) 45
References 45
Chapter 5 49
Environmental Risk Factors for Non-Melanoma Skin Cancers 49
5.1 Solar Ultraviolet Radiation 49
5.2 Human Papilloma Virus 51
5.3 Immunosuppression 52
5.3.1 Iatrogenic Immunosuppression 52
5.3.2 Acquired Immunodeficiency Syndrome (AIDS) 53
5.4 Phototherapy 53
5.4.1 Psoralen and Ultraviolet-A (PUVA) Therapy 53
5.4.2 Ultraviolet-B Phototherapy 54
5.5 Ionising Radiation 54
5.6 Occupational Factors 55
5.7 Arsenic 56
5.8 Tobacco Smoking and Diet 56
5.8.1 Take Home Messages 56
5.9 Conclusions 56
References 57
Chapter 6 61
Accuracy in the Diagnosis of Non-Melanoma Skin Cancer 61
6.1 Clinical/Physical Examination 62
6.2 Biopsy Techniques 62
6.3 Histopathology and Molecular Markers 64
6.4 High Frequency Ultrasonography and Doppler Sonography 66
6.5 Elastography 68
6.5.1 Optical Diagnostic Technologies 68
6.6 Dermoscopy/Dermatoscopy/Epiluminiscence Microscopy/Incident Light Microscopy/Skin Surface Microscopy 68
6.7 Optical Coherence Tomography 69
6.8 Confocal Microscopy 72
6.9 Near Infrared (NIR), Diffuse Reflectance and Raman Spectroscopy 74
6.10 Fluorescence Spectroscopy 74
6.11 Multiphoton or Two-Photon Microscopy Imaging (MPMI) 75
6.12 Spectrophotometric Intracutaneous Analysis (SIA), SIAscopy 75
6.13 Terahertz Imaging 76
6.14 Electrical Impedance 76
6.15 CT, PET, and MR 76
6.16 Conclusion 77
References 77
Chapter 7 83
Cure Rates Following Surgical Therapy – The Golden Standard 83
7.1 Technical Aspects of MMS 83
7.2 Cure Rates of ‘Gold Standard’ in Special Indications 84
7.2.1 BCCs and SCCs 84
7.2.2 Extramammary Paget’s Disease 86
7.2.3 Merkel Cell Carcinoma 87
7.2.4 Dermatofi brosarcoma Protuberans and Other Spindle Cell Tumours 87
7.3 Conclusions 88
References 89
Chapter 8 91
Pharmacological Therapy: An Introduction 91
References 92
Chapter 9 93
Systemic Chemotherapy of Non-Melanoma Skin Cancer 93
9.1 Overview of Chemotherapeutic Drugs 93
9.2 Chemotherapy Regimens 93
9.2.1 Cisplatin Combination Regimens 93
9.2.2 Paclitaxel or Docetaxel Monotherapy 95
9.2.3 Capecitabine 95
9.3 Anti-Epidermal Growth Factor Receptor (EGFR) Strategies 96
9.4 Experimental Agents 96
9.4.1 Bortezomib 96
9.4.2 Cyclopamine 96
9.5 Role of Systemic Chemotherapy in Skin Cancer 97
9.5.1 Who Is the Candidate for Systemic Chemotherapy? 97
9.5.2 Which Chemotherapy? 97
9.6 Take Home Pearls 98
References 98
Chapter 10 101
Intralesional Agents to Manage Cutaneous Malignancy 101
10.1 Introduction 101
10.2 Basal Cell Carcinoma 101
10.2.1 5-Fluoruracil 101
10.2.2 Bleomycin 102
10.2.3 Aminolevulonic Acid 102
10.2.4 Candida 102
10.3 Squamous Cell Carcinoma 103
10.3.1 5-Fluoruracil 103
10.3.2 Methotrexate 103
10.3.3 Interferon 104
10.3.4 Bleomycin 104
10.6 Conclusion 105
References 105
Chapter 11 107
Topical Chemotherapy 107
11.1 5-Flurouracil 107
11.2 Diclofenac 108
11.3 Colchicine 109
11.4 Retinoids 110
References 110
Chapter 12 112
Immunotherapy: An Introduction 112
12.1 Cancer and the Immune System 112
12.2 NMSC and Immunosuppression 112
12.3 Immunostimulation for the Treatment of NMSC 113
12.4 Conclusion 113
References 114
Chapter 13 115
Intralesional Interferon in the Treatment of Basal Cell Carcinoma 115
13.1 Introduction 115
13.2 Clinical Studies 115
13.3 Patient Selection and Contraindications 116
13.4 Dosing and Injection Technique 117
13.5 Side Effects 118
13.6 Mechanism of Action 118
References 118
Chapter 14 120
Interleukin-2 for Nonmelanoma Skin Cancer 120
14.1 Introduction 120
14.2 Locally Applied IL-2 Immunotherapy for NMSC 121
14.3 Perspectives 125
Take Home Pearls 126
References 126
Chapter 15 129
Topical Imiquimod 129
15.1 Introduction 129
15.2 Mechanism of Action 129
15.3 Pharmacokinetics 130
15.4 Therapeutic Efficacy 131
15.4.1 Imiquimod for the Treatment of AK 131
15.4.2 Imiquimod for the Treatment of BCC 134
15.4.3 Off-Label Use of Imiquimod for the Treatment of Other Skin Malignancies 135
15.5 Adverse Effects 135
15.6 Conclusion and New Innovative TLR Agonist Compounds 135
References 136
Chapter 16 139
Photodynamic Therapy 139
16.1 Photodynamic Therapy 139
16.2 Perspectives 140
References 141
Chapter 17 142
Critical Evidence-Based Review of Current Experience and Possible Future Developments of Topical PDT 142
17.1 Introduction 142
17.2 Mechanism of Action 143
17.3 Procedure 143
17.4 Light Sources 143
17.5 Tumour Indications 144
17.6 Actinic Keratosis 144
17.7 Squamos Cell Carcinoma In Situ (Morbus Bowen) 145
17.8 Basal Cell Carcinoma 145
17.9 Non-Tumour Indications 145
17.10 Acute Side Effects 145
17.11 Chronic Side Effects 146
17.12 Diagnostics 146
17.13 Future Development 146
References 146
Chapter 18 148
Electrochemotherapy in Treatment of Cutaneous Tumors 148
18.1 Introduction 148
18.2 Mechanisms of Action of Electrochemotherapy 149
18.3 How to Perform the Treatment? 150
18.3.1 Drug Selection 151
18.3.2 Timing and Drug Dosage 151
18.3.3 Electric Pulse Parameters 151
18.3.4 Selection of the Electrodes 151
18.4 Clinical Results 151
18.4.1 Malignant Melanoma 152
18.4.2 Basal Cell Carcinoma 153
18.5 Conclusion (Take Home Pearls) 154
References 154
Chapter 19 156
Radiotherapy: At a Glance 156
19.1 Radiation Therapy of Malignant Skin Diseases/Tumors 156
19.1.1 What Is the Ideal Indication for Radiotherapy? 157
19.1.2 What Are the Best Areas to Be Treated by Radiation Therapy? 157
19.1.3 Why Biopsy? 157
19.1.4 Which Radiation Quality? 158
19.1.5 Why Fractionated Doses? 158
19.2 Disseminated Actinic Keratoses 158
19.3 Bowen’s Disease/Queyrat’s Erythroplasia 159
19.4 Lentigo Maligna 159
19.5 Basal Cell Carcinoma, Squamous Cell Carcinoma, Keratoacanthoma 159
19.6 Melanoma of the Lentigo Maligna Type 160
19.7 Paget’s Disease 161
19.8 Merkel Cell Tumor 161
19.9 Cutaneous Lymphomas 161
19.10 Kaposi’s Sarcoma 161
19.11 Other Skin Tumors 162
References 162
Chapter 20 164
Prevention and Adjuvant Therapy 164
20.1 Primary Prevention 165
20.2 Sun Exposure 165
20.3 Primary Prevention Behaviour 165
20.4 Primary Prevention Targets: Location, Age, Period, Environment 165
20.5 Secondary Prevention 167
20.6 Tertiary Prevention 168
20.7 Media Awareness in Prevention 168
20.8 Perspectives 169
References 169
Chapter 21 172
Sunscreens 172
21.1 Introduction 172
21.2 Sunlight 172
21.3 UV-Absorbers 174
21.4 Sun Protection Factor (SPF) 175
21.5 SPF Stability 175
21.6 Amount of Sunscreens Applied 176
21.7 Biological Effect of Sunscreens 176
21.8 Sunscreen and Vitamin-D 177
21.9 Skin Penetration 177
21.10 Endocrine-Disrupting Effect 177
21.11 Allergy and Photoallergy 177
21.12 SPF Level in Photoprotection 178
21.13 Other Protective Measures 178
References 178
Chapter 22 181
Skin Cancer: Antioxidants and Diet 181
22.1 Introduction 181
22.2 Antioxidants and the Oxidative Challenge 181
22.3 Photocarcinogenesis and UV-Induced Immune Suppression 182
22.4 Chemopreventive Efficacy of Dietary Antioxidants in Skin Cancer 183
22.4.1 Vitamin A and the Retinoids 183
22.4.2 Non-Melanoma Skin Cancer 184
22.4.3 Malignant Melanoma, Lentigo Maligna, and Dysplastic Nevi 185
22.4.4 Kaposi Sarcoma 185
22.4.5 Cutaneous T-Cell Lymphoma 185
22.4.6 Carotenoids 185
22.4.7 Vitamin C 186
22.4.8 Vitamin D 186
22.4.9 Vitamin E 186
22.5 Others 187
22.6 Conclusion 187
References 187
Chapter 23 190
Retinoids in the Management of Non-Melanoma Skin Cancer 190
23.1 Retinoids 191
23.1.1 Historical Background and Retinoid Classification 191
23.2 Mechanism of Action of Retinoids in Chemoprevention and Tumor Progression 192
23.3 Indications of Retinoids in Treatment of Non-Melanoma Skin Cancer 192
23.4 Premalignant Cutaneous Diseases 192
23.5 Syndromes with Increased Risk of Cutaneous Malignancy 193
23.6 Malignant Cutaneous Diseases 193
23.7 Organ Transplantation 194
23.8 Selection of Patientsfor Retinoid Chemoprevention and Chemosuppression 194
23.9 Selection of Retinoids 194
23.9.1 Retinoids as Monotherapy 194
23.9.2 Retinoids in Combination Therapies 195
23.10 Adverse Events of Systemic Retinoid Chemoprevention 195
23.11 Take Home Message 196
References 197
Chapter 24 199
PDT for Cancer Prevention 199
24.1 Current Evidence: In Vivo Studies 199
24.2 Evidence for Cancer Prevention: Clinical Studies 200
24.3 Preventive PDT: Mechanism of Action 203
24.4 Conclusion 204
References 204
Chapter 25 206
Dermabrasion, Laser Resurfacing, and Photorejuvenation for Prevention of Non-Melanoma Skin Cancer 206
25.1 Murine Models 207
25.1.1 The Target Cells of Skin Carcinogenesis 207
25.1.2 Dermabrasion, Laser Resurfacing, and Non-Ablative Photorejuvenation for the Prevention of NMSC in Mice 207
25.2 Human Studies 208
25.2.1 Laser Resurfacing 208
25.2.1.1 Controlled Clinical Trials 208
25.2.1.2 Uncontrolled Clinical Trials/Case Reports and Retrospective Studies 209
25.2.2 Dermabrasion 210
25.3 Conclusion 210
25.4 Take Home Pearls 210
References 211
Chapter 26 212
To Cut or Not, That Is the Question 212
26.1 ‘The Objective of the Exercise’ 212
26.2 Recurrence Risk and Invasive Potential 213
26.3 Field Cancerization 213
26.4 Location 213
26.5 General Health 214
26.6 Cosmesis 214
26.7 Combined Treatment 214
26.8 Adjuvant Therapies 214
26.9 Follow-Up 215
26.10 When to Cut and When Not to 215
References 215
Index 216