Clinical Ophthalmic Oncology : Basic Principles

✍ Scribed by Bertil E. Damato; Arun D. Singh

• Publisher: Springer
• Year: 2019
• Tongue: English
• Leaves: 328
• Edition: 3
• Category: Library

✦ Table of Contents

Preface
Acknowledgments
Contents
Contributors
1: Principles of Cancer Epidemiology
Introduction
Research Question
Outcome Measures
Prevalence
Incidence
Mortality
Time to Event
Surrogate Endpoints
Quality of Life
Measures of Association
Relative Risk
Hazard Ratio
Odds Ratio
Differences in Risk
Differences in Mean Score
Precision of the Estimate
Bias
Confounding
Selection Bias
Information Bias
Study Designs
Case Series
Cross-Sectional Study
Cohort Study
Randomized Controlled Trial
Case-Control Study
Pilot Study
Systematic Review
Conclusions
References
Further Readings
2: Etiology of Cancer
Introduction
Carcinogenic Agents
Chemical Carcinogens
Environmental Exposure
Behavioral Exposure
Tobacco
Alcohol
Electromagnetic Radiation
Ultraviolet Light
Ionizing Radiation (X-Rays and Gamma Rays)
Infections Agents
Viruses
Human Papillomavirus (HPV)
Epstein-Barr Virus
Kaposi Sarcoma Herpes Virus
Human T-Cell Lymphotropic Virus-1
Hepatitis B and C Virus
Bacteria
Helicobacter pylori
Chlamydia psittaci
Fungus
Parasites
Immune Evasion
Dietary Factors
Genetic Susceptibility
Iatrogenic Cancers
Immunosuppression
Chemotherapy
Radiation Therapy
Summary
References
3: Cancer Pathology
Introduction
Classification of Neoplasia
Benign Tumors
Malignant Tumors
Tumorigenesis
Genomic Instability and Mutations
Evading Immune Destruction
Proliferative Signaling and Reprogramming Energy Metabolism
Resisting Growth Suppressors
Escaping Cell Death
Replicative Immortality
Angiogenesis
Invasion and Metastasis
Box 3.1 Steps in Metastatic Process
The Tumor Microenvironment
Microscopic Features of Neoplasia
Cellular Proliferation
Cellular Pleomorphism
Cellular Differentiation
Nuclear Cytoplasmic Ratio
Invasion of Surrounding Tissues
Tumor Infiltration by Normal Cells
Tissue Sampling and Processing
Cytological Sampling
Exfoliative Cytology
Aspiration Cytology
Histopathologic Sampling and Processing
Diagnostic Techniques
Light Microscopy
Immunohistochemistry
Additional Techniques
References
4: Pathology Specimen: Handling Techniques
Introduction
Pathological Specimen Handling in Theatre Before Fixation
Multiple Biopsies from a Surgical Procedure
Orientation of Specimens
Conjunctival Mapping Biopsies
Tissue Handling for Frozen Sections
Sampling Fresh Tissue Prior to Fixation
Fixation of Ocular Pathology Specimens [1–7]
Surgical Tumour Specimens
Fine-Needle Aspiration (FNA) Specimens [8–13]
Vitrectomy Specimens [8–13]
Impression Cytology Samples
Specimens Requiring Electron Microscopy
The Ophthalmic Pathology Request Form [14]
Transporting Specimens to the Pathology Laboratory
Handling Ophthalmic Surgical Specimens in the Pathology Laboratory [1–7]
Eyelid Skin Tumour Resections
Mapping Biopsies
Frozen Tissue Handling
Local Resection of Intraocular Tumours
Enucleation Specimens for Intraocular Tumours
Exenteration Specimens for Tumours
Cytology Handling [8–13]
Impression Cytology
FNAs
Vitreous Samples
References
5: Cancer Angiogenesis
Introduction
Tumor Angiogenesis
Cooption
Angiogenic Switch
Steps in Angiogenesis
Tumor Vessels
Metastatic Cascade
Promotors of Angiogenesis
Vascular Endothelial Growth Factor
Functions
Subtypes (VEGF A)
VEGF Receptors
Regulation of VEGF
Hypoxia
Other Factors
Fibroblast Growth Factor
Angiopoietins
Matrix Metalloproteinases (MMPs)
Inhibitors of Angiogenesis
Endogenous
Thrombospondin
Angiostatin
Endostatin
Pharmaceutical
Anti-VEGF Agents
Bevacizumab (Avastin®)
Ranibizumab (Lucentis®)
Pegabtanib (Macugen®)
Aflibercept (Eylea®)
SU5416, Semaxanib
Cox-2 Inhibitors (Celecoxib, Nepafenac/Amfenac)
Trastuzumab (Herceptin®)
Interferon-α2a
Antiangiogenic Therapy in Clinical Practice
Angiogenic Aspects of Specific Ophthalmic Tumors
Retinoblastoma
Treatment
Uveal Melanoma
Pseudovascular Channels (Vasculogenic Mimicry)
Microvessel Density
Tumor Ingrowth into Blood Vessels
Indocyanine Green Angiographic Patterns
VEGF Expression
Metastatic Uveal Melanoma
Treatment
Radiation Retinopathy
Metastatic Uveal Melanoma
Von Hippel-Lindau Disease
Treatment
Hemangioma of the Eyelid
Treatment
Conjunctival Squamous Cell Carcinoma (SSC)
Treatment
Conclusions
References
6: Immunology of Ocular Tumors
Introduction
Innate and Specific Immune Responses
Immunological Escape
Immunological Aspects of Uveal Melanoma
Immune Responses Against UM in Humans
HLA Antigen Expression
Leukocyte Infiltrate
Previously Irradiated Tumors
Immunotherapy
Ipilimumab
Programmed Death-Ligand 1
Interferon Alpha-2b
Dendritic Cell Therapy
Immune-Related Response to Therapy
Conclusions
References
7: Cancer Genetics
Introduction
Proliferation and the Cell Cycle
Growth Factor Signaling Pathways
Rb-p16Ink4a-Cyclin D Pathway
MYC Family of Oncogenes
Apoptosis and Senescence
p53 and MDM2
Bcl-2
Telomere Maintenance
BRCA and BAP1
Splicing Factor Mutations
Angiogenesis
VEGF
HIF/VHL
Epigenetics
Conclusions
References
8: Cancer Staging
Introduction
History
Purposes of Staging
Prognostic Relevance
Therapeutic Relevance
Research Relevance
Summary
References
9: Principles of Cryotherapy
Introduction
Mechanism of Tissue Injury
Direct Effects
Indirect Effects
Technical Aspects
Tissue Temperature
Cooling Rate
Freeze-Thaw Cycle
Number of Repetitions
Indications
Eyelid Tumors
Conjunctival Tumors
Intraocular Tumors
Orbital Tumors
Techniques of Cryotherapy
Eyelid Tumors
Conjunctival Tumors
Intraocular Tumors
Complications
Conclusions
References
10: Principles of Laser Therapy
Introduction
Laser Effects on Tissues
Photothermal Effects
Photochemical Effects
Photomechanical Effects
Types of Ophthalmic Lasers
Treatment Variables
Laser Delivery Systems
Techniques of Ophthalmic Laser Therapy
Summary
References
11: Principles of Radiation Therapy
Introduction
Basic Principles
Dual Nature of Radiation
Electromagnetic Radiation
Particle Radiation
Radioactive Decay
Ionizing and Nonionizing Radiation
Teletherapy Sources
Cobalt-60 Unit
Linear Accelerator
Cyclotron
Radiation Parameters
Radiation Dose
Relative Biological Effectiveness
Cobalt Gray Equivalents
Treatment Parameters
Target Volume
Total Dose
Fractionation
Tissue Tolerance
Teletherapy Techniques
External Beam Therapy
Conformal Radiation Therapy
Three-Dimensional Conformal Therapy
Intensity-Modulated Radiation Therapy
Stereotactic Radiosurgery
Linac-Based Stereotactic Radiosurgery
Treatment Delivery
Gamma Knife Radiosurgery
Charged Particle Therapy
Brachytherapy
Summary
References
12: Ocular Complications of Radiotherapy
Introduction
Periorbital Skin
Conjunctiva
Cornea
Radiation-Induced Dry Eye and Keratitis
Treatment
Scleral Necrosis
Extraocular Muscles
Dose Relationship
Treatment
Iris
Radiation-Induced Iris Neovascularization and Neovascular Glaucoma
Treatment
Lens
Clinical Features
Dose Relationship
Treatment
Radiation Retinopathy
Clinical Features
Dose Relationship
Treatment
Preventive Strategies
Radiation Optic Neuropathy
Clinical Features
Dose Relationship
Treatment
Toxic Tumor Syndrome
Conclusions
Box 12.1. Salient Features of Radiation Retinopathy
References
13: Principles and Complications of Chemotherapy
Introduction
Basic Principles of Chemotherapy
The Cell Cycle
Mechanisms of Action
Dose Intensification of Chemotherapy
Clinical Pharmacology of Chemotherapeutic Agents
Pharmacokinetics
Drug-Drug Interactions
Chemotherapy Resistance
Multimodal Therapy
Adjuvant Chemotherapy
Neoadjuvant Chemotherapy
Commonly Used Chemotherapeutic Agents in Ophthalmologic Cancers
Systemic Treatment of Orbital Lymphoma
Systemic Treatment of Orbital Melanoma
Systemic Treatment of Retinoblastoma
Systemic Treatment of Orbital Rhabdomyosarcoma
Toxicities of Cytotoxic Chemotherapy
Summary
References
14: Ocular Complications of Targeted Therapy
Introduction
Specific Agents
Tyrosine Kinase Inhibitors
Epidermal Growth Factor Receptor Inhibitors
Inhibitors of Angiogenesis
mTOR Pathway Inhibitors
Anaplastic Lymphoma Kinase (ALK) Inhibitors
Mitogen-Activated Protein Kinase RAS-RAF Signaling Pathway
Immunotherapy
Conclusions
References
15: Counseling Patients with Cancer
Introduction
Challenges Faced by Patients with Eye Cancer
Emotions and Fears
Box 15.1 Patients’ Emotions and Fears When Informed of Their Diagnosis and Treatment
Coping Mechanisms
Patients’ Needs
Box 15.2 Patients’ Emotional Needs
Eliciting and Addressing Patients’ Emotional Needs
Communication
Box 15.3 Requirements for Effective Communication
Decision-Making
Psychological Support
Patient-Reported Outcome Measures (PROMs)
Self-Help
Family Support
Support from Patient Organisations
Children with Cancer: What Should They Be Told?
Conclusion
References
16: Tumor-Associated Cataract
Introduction
Surgical Treatment-Induced Cataract
Radiation-Induced Cataract
Chemotherapy- and Hormonal Therapy-Induced Cataract
Specific Entities
Medulloepithelioma
Retinal Lymphoma
Retinoblastoma
Uveal Melanoma
Uveal Metastases
Perioperative and Intraoperative Considerations
Summary
References
17: Tumor-Associated Glaucoma
Introduction
Pathogenesis
Open-Angle Glaucoma
Angle-Closure Glaucoma
Clinical Features
Diagnostic Evaluation
Specific Entities
Childhood Glaucoma
Sturge-Weber Syndrome
Neurofibromatosis Type 1
Von Hippel-Lindau Disease
Juvenile Xanthogranuloma
Medulloepithelioma
Adult Glaucoma
Iris Stromal Cysts
Melanocytoma
Fuchs Adenoma
Uveal Melanoma
Metastatic Tumors
Leukemia/Lymphoma
Myelodysplastic Syndrome/Multiple Myeloma
Treatment
Summary
References
18: Graft-Versus-Host Disease
Introduction
Etiology
Pathogenesis
Classification of GVHD
Acute GVHD
Chronic GVHD
Clinical Ophthalmic Features
Ocular Surface Manifestations
Symptoms and Signs
Target Tissues
Lacrimal Glands
Meibomian Glands
Conjunctiva
Cornea
Diagnostic Evaluation
Differential Diagnosis
Treatment of Systemic GVHD
Biomarkers in Serum and Tears
Prevention of Systemic GVHD
Treatment of Established Systemic GVHD
Treatment of Ocular GVHD
Topical Lubricants
Topical Corticosteroids
Topical Cyclosporine A
Tacrolimus
Autologous Serum Eye Drops
Contact Lenses
Cataract Surgery in cGVHD
Follow-Up
Prognosis of GVHD
Systemic GVHD
Ocular GVHD
References
19: Diagnostic Techniques: Angiography
Introduction
Basic Principles
Anterior Segment Tumors
Iris Tumors
Iris Hemangioma
Retinal Tumors
Retinoblastoma
Retinal Vascular Tumors
Retinal Hemangioblastoma (Retinal Capillary Hemangioma)
Retinal Vasoproliferative Tumor
Cavernous Hemangioma
Racemose Hemangioma (Retinal Arteriovenous Malformation)
Retinal Astrocytic Hamartoma
Retinal Pigment Epithelial Tumors
Choroidal Tumors
Choroidal Nevus
Choroidal Melanoma
Melanocytoma
Choroidal Hemangioma
Choroidal Osteoma
Choroidal Granuloma
Choroidal Metastatic Tumors
Choroidal Lymphoma and Vitreoretinal Lymphoma
Simulating Conditions
Coats’ Disease
Persistent Hyperplastic Primary Vitreous/Persistent Fetal Vasculature
Scleritis
Central Serous Chorioretinopathy (CSCR)
Polypoidal Choroidal Vasculopathy (PCV)
Uveal Effusion Syndrome
Paraneoplastic Disorders
Radiation Retinopathy
References
20: Diagnostic Techniques: OCT
Introduction
Enhanced Depth Imaging
Swept-Source OCT (SS-OCT)
Optical Coherence Tomography Angiography
Conjunctival and Corneal Tumors
Scleral Lesions
Anterior Uveal Tumors
Intraocular Tumors
Retinal Pigment Epithelial Tumors
Retinal Tumors
Retinal Astrocytic Hamartoma
Retinoblastoma
Primary Vitreoretinal Lymphoma
Retinal Cavernous Hemangioma
Retinal Capillary Hemangioma
Retinal Vasoproliferative Tumor
Wyburn-Mason Syndrome
Optic Disc Melanocytoma
Choroidal Tumors
Choroidal Nevus
Choroidal Melanoma
Choroidal Osteoma
Choroidal Metastasis
Choroidal Hemangioma
Conclusions
References
21: Diagnostic Techniques: Autofluorescence
Introduction
The Origin of Autofluorescence
Types of Autofluorescence
Short-Wavelength AF
Near-Infrared AF
Choroidal Melanocytic Tumors
Choroidal Nevus
Indeterminate Choroidal Melanocytic Tumor (Small Choroidal Melanoma)
Choroidal Melanoma
Choroidal Hemangioma
Choroidal Metastasis
Congenital Hypertrophy of the Retinal Pigment Epithelium
Neurofibromatosis Type 1 (NF1)
Vitreoretinal Lymphoma
Conclusions
References
22: Diagnostic Techniques: Ultrasonography
Introduction
Basic Physics
Instrumentation
Diagnostic A-Scan
B-Scan
Ultrasound Biomicroscopy (UBM)
Methods for Differentiation of Intraocular Tumors
Topographic Ultrasonography
Quantitative Ultrasonography
Reflectivity
Internal Structure
Sound Attenuation
Kinetic Ultrasonography
Mobility
Vascularity
Convection
Differentiation of Anterior Segment Tumors
Iridociliary Pigment Epithelial Cyst (IPE Cyst)
Iris and Ciliary Body Melanoma
Ciliary Body Melanocytoma
Differentiation of Retinal Tumors
Retinoblastoma
Topographic
Quantitative and Kinetic
Persistent Fetal Vasculature (PFV)
Retinopathy of Prematurity (ROP)
Coats’ Disease
Differentiation of Choroidal Tumors
Choroidal Nevus
Choroidal Melanoma
Topographic
Quantitative and Kinetic
Special Cases
Associated Hemorrhage
Extraocular Extension
Episcleral Brachytherapy
Choroidal Hemangioma
Topographic
Quantitative and Kinetic
Choroidal Metastasis
Topographic
Quantitative and Kinetic
Hemorrhagic Disciform Lesion
References
23: Diagnostic Techniques: FNAB
Introduction
Box 23.1 Intraocular biopsy
Surgical Technique
Iris Tumors
Ciliary Body and Pre-equatorial Tumors
Post-equatorial Tumors
Vitrectomy-Assisted Aspiration Biopsy
Sample Handling
Indications
Melanoma: Prognostic
Amelanotic Uveal Tumor (Primary Versus Metastasis)
Nevus Versus Melanoma (Indeterminate Melanocytic Lesions)
Melanoma: Diagnostic
Intraocular Lymphoma
Retinoblastoma and  Other Retinal Tumors
Orbital Tumors
Complications
False-Negative Biopsy
False-Positive Biopsy
Needle Tract Seeding
Hemorrhage
Retinal Detachment
Endophthalmitis
Conclusions
References
24: Diagnostic Techniques: Other Biopsy Techniques
Introduction
Box 24.1 Other Biopsy Techniques
Vitreous Cutter Aspiration Biopsy
Indications and Contraindications
Surgical Technique
Results and Complications
Incisional Biopsy
Indications and Contraindications
Surgical Technique
Results and Complications
Excisional Biopsy
Indications and Contraindications
Surgical Technique
Results and Complications
Laboratory Techniques
Transport
Laboratory Investigations
Discussion
References
Index