【内容简介】Photodynamic therapy (PDT) is increasingly being used amongst health practitioners in combating a variety of diseases. One common strategy used during this light activated process is to induce the accumulation of significant amounts of a photosensitising agent in the diseased tissue. The naturally occurring amino acid 5-aminovulinic acid (ALA) is used to produce high levels of the photosensitizer, Protoprophyin IX, in the therapy known as ALA-PDT. Written by experts in the field Photodynamic Therapy with ALA outlines a variety of clinical approaches to the topic, outlining current applications. These include the use of ALA-PDT and ALA-FD (fluorescence diagnosis) in the areas of dermatology, urology, brain, otorhinolaryngology, gynaecology and gastroenterology. Also included is a chapter that comprehensively reviews the scientific principles of ALA-PDT. Primarily aimed a clinical audience Photodynamic Therapy with ALA should provide a comprehensive review and useful insight into ALA-PDT.

Table of Contents

          Introduction

                         James Cecil Kennedy

               Outline of the Theory and Technique of ALA-PDT

                    Tissue Specificity

                    Intracellular Targets

                    Fluorescence

                    ALA Administration and Approval

                    ALA/PpIX Clearance

               Factors Affecting Photodynamic Therapy

                    Oxygen

                    Photosensitizer

                    Light

                    Light Dosimetry

               Clinical Applications of ALA-PDT

               Interaction between ALA-PDT and the Immune System

                    Squamous Cell Carcinoma of the Skin

                    Kaposi's Sarcoma

               Conclusions

          Basic Principles

                         B. Krammer

                         Z. Malik

                         R. Pottier

                         H. Stepp

               Introduction

               A Brief History of PDT

               Principles of ALA-Based PDT

                    Phototoxicity

                    ALA Metabolism

                    Underlying Biological Concepts

               Biological Mechanisms

                    Basic Cellular Mechanisms

                    ALA Delivery and Cellular Uptake

                    PpIX Accumulation

                    PpIX Localization

                    Photodynamic Damage

                    Pain During and After ALA-PDT

                    Mechanisms of Cell Death

                    ALA-PDT Induces Apoptotic and Necrotic Cell Death of Tumours

                    Interaction with Tissue

                    Tumour Differentiation and ALA-PDT

                    Hyperthermia, Tissue Oxygenation and ALA-PDT

                    Photobleaching of PpIX, Photoproducts and Light Fractionation Effects

                    Alteration of the Immune Response Following ALA-PDT

                    PpIX Pharmacokinetics

                    Advantages of ALA Versus Pre-Formed Photosensitizer for PDT and FD

                    Compatibility

                    No Overdosing of the Photosensitizer

                    Photobleaching

                    Versatility of Administration

                    Photodetection

                    Rapid Evaluation of Effectiveness of Other Therapies

                    Limitations of ALA for PDT and FD

               Light Sources for PDT

                    Basic Requirements

                    Lasers

                    Lamp Systems

                    LED Sources

                    Fluorescence Sources

                    Applicators

                    Dosimetry

               Principles of ALA-Based FD

                    Physics behind Fluorescence

                    Autofluorescence for FD

                    ALA-Induced PpIX for FD

                    Technical Implementation

                    Clinical Relevance

                    Caveats

               Consideration of PpIX Photobleaching in Light Dosimetry

               Conclusions

                    ALA Versus Other Photosensitizers

                    Clinical Significance of ALA-PDT

                    References

          ALA/MAL-PDT in Dermatology

                         Verena Schleyer

                         Rolf-Markus Szeimies

               Introduction

                    Photosensitizers

                    Light Sources

                    Biological Mechanism

                    Lesion Preparation

                    Contraindications and Drug Interactions

                    Side Effects and Complications

               Oncologic Indications

                    Epithelial Cancers or Precancerous Lesions

                    Basal Cell Carcinoma

                    Different clinical types of basal cell carcinomas

                    Literature

                    Squamous Cell Carcinoma

                    Actinic Keratoses

                    Bowen's Disease

                    Varia

                    Improvement of remission rates and retreatment

                    Follow-up

                    Benefits of PDT

                    Nonepithelial Tumors of the Skin

                    Malignant Melanoma, Kaposi's Sarcoma and Cutaneous Metastases

                    Cutaneous T-Cell Lymphoma

               Non-Oncologic Indications

                    Small Case Series and Initial Trials

                    Inflammatory Dermatoses

                    Scleroderma

                    Darier's disease (keratosis follicularis)

                    Lichen sclerosus

                    Infectious Cutaneous Diseases due to Microorganisms

                    Viral infections: Condylomata acuminata

                    Mycotic infections: Interdigital mycoses of the feet

                    Protozoic infections: Cutaneous leishmaniasis

                    Larger Clinical Trials

                    Psoriasis Vulgaris

                    Acne Vulgaris

                    Recalcitrant Warts

                    Conclusion

               Perspectives

                    Tumor Surveillance

                    Skin Rejuvenation

                    Treatment Algorithm

                    Patient and Lesion Selection

                    Pretreatment

                    Fluorescence Diagnosis and Illumination

                    After Care and Follow-Up

                    Installation of a PDT Business Center (Derived from the Guidelines of the British Photodermatology Group6)

                    References

          ALA-PDT and ALA-FD in Urology

                         Raphaela Waidelich

                         Herbert Stepp

               Introduction

               Fluorescence Cystoscopy: Fluorescence Diagnosis of Bladder Cancer

                    High-Risk Lesions

                    Residual Tumour

                    Recurrence and Progression Rates

                    Therapeutic Strategy

                    Detailed Procedure for Fluorescence Cystoscopy

                    Images

                    Fluorescence Quantification

                    Fluorescence Cytology

               Other Indications for FD in Urology

                    Fluorescence Urethroscopy: FD of Condylomata Acuminata and Urothelial Carcinoma of the Urethra

                    ALA-FD of Penile Cancer

                    ALA-FD of Renal Cell Cancer

               ALA-PDT of Urothelial Carcinoma

               ALA-PDT of Prostate Cancer

               Conclusions

               Future Perspectives

               Materials and Methods for Various Indications

                    ALA-FD of Bladder Cancer

                    ALA-FD of Tumours Within the Urethra

                    ALA-FD of Penile Cancer: Local Treatment of Primary Tumour

                    ALA-FD of Penile Cancer: Detection of Lymph Node Metastases

                    ALA-PDT of Urothelial Carcinoma

                    Photosensitization: ALA Applied Orally

                    Photosensitization: ALA Applied Intravesically

                    Whole Bladder Wall Irradiation Using Coherent Light

                    Whole Bladder Wall Irradiation Using a White Light Source

                    Irradiation of the Upper Urinary Tract

                    References

          ALA-PDT and ALA-FD in the Brain: New Prospects for Treating Malignant Gliomas

                         Walter Stummer

                         Reinhold Baumgartner

               Introduction

                    Background

                    Specificity of Porphyrin-Accumulation in Response to ALA Administration

               Fluorescence-Guided Resections for Malignant Gliomas Using ALA

                    History and Present Status

                    Phase III Drug Approval Trial

                    Practical Aspects of Fluorescence-Guided Resections Using ALA

                    Dosage and Timing of ALA Administration

                    Light Protection

                    Intraoperative Photosensitization

                    Equipment

                    Practical Implementation

                    General Aspects

                    Photobleaching

                    Fluorescence Qualities

                    Optimizing Fluorescence Visualization Intraoperatively

               Photodynamic Therapy of Malignant Gliomas Using ALA

               The Future

                    References

          Otorhinolaryngology

                         C.S. Betz

                         A. Leunig

               Introduction/Motivation

                    Diagnosis

                    Early Detection of (Pre)malignant Lesions

                    Exact Delimitation of Tumor Borders

                    Management of Recurrent Respiratory Papillomatosis (RRP)

                    Therapy

                    Recurrent Respiratory Papillomatosis

                    Precancerous Mucosal Lesions

                    Field Cancerization

                    Tumors not Curatively Resectable

                    Pre- and Early Malignant Lesions of Facial Skin

               Approval Status

                    Diagnosis

                    Therapy

               Procedure

                    Fluorescence Diagnosis

                    Substance, Application, Dosage, and Incubation

                    Fluorescence Imaging

                    Photodynamic Therapy

                    Precancerous Mucosal Lesions of the UADT

                    Cancerous Lesions of the UADT

                    Pre- and Early Malignant Facial Lesions

               ALA-FD

                    Indications

                    Identification of pre- and Early Malignant Mucosal Lesions

                    Superficial Delimitation of SCC of the UADT

                    Screening Method for the Identification of UADT Papillomas

                    Limitations

                    Superficial Staining Following Topical ALA Application

                    General Limitations Following Systemic Administration of ALA

                    Occurrence of False Positives

                    Photobleaching

                    Bacterial Coatings

                    Unwanted Effects

                    Local Symptoms

                    Systemic Symptoms

               ALA-PDT

                    Indications

                    Treatment of pre- and Early Malignant, Unpigmented Facial Lesions

                    Treatment of Precancerous Mucosal Lesions of the UADT

                    Treatment of Cancerous Lesions of the UADT

                    Limitations

                    Superficial Photodynamic Effects

                    The Absence of Tissue Specimens for Histopathological Diagnoses

                    Topical Administration of ALA in the UADT

                    Light Application in the UADT

                    Unwanted Effects

                    Local Symptoms

                    Systemic Symptoms

               Conclusions

               Final Note

                    References

          ALA-PDT in Gynecology

                         Peter Hillemanns

                         Mathias Fehr

                         Rene Hornung

               Photodynamic Therapy (PDT) of Cervical Intraepithelial Neoplasia (CIN)

                    Introduction/Motivation

                    Approval Status

                    Procedure

                    Advantages and Limitations

               Photodynamic Therapy of Vulvar Intraepithelial Neoplasia

                    Introduction/Motivation

                    Approval Status

                    Procedure

                    Advantages and Limitations

               Photodynamic Therapy of Endometrium

                    Introduction/Motivation

                    Approval Status

                    Procedure

               Fluorescence Diagnosis of Endometriosis

                    Introduction/Motivation

                    Approval Status

                    Procedure

               Fluorescence Diagnosis of Ovarian Cancer

                    Introduction/Motivation

                    Approval Status

                    Procedure

               Advantages/Limitations (PDT of Endometrium; FD of Endometriosis, FD of Ovarian Cancer)

                    References

          ALA-PDT in Gastroenterology

                         Hugh Barr

                         Helmut Messmann

                         Esther Endlicher

               Introduction

                    The Clinical Indication

                    Advantages of Photodiagnosis

                    Advantages of Photodynamic Therapy

               Application of ALA-PDT in Gastroenterology

                    Administration of ALA and Subsequent Tissue Distribution and Localization of Protoporphyrin IX

                    Pharmacological Effects

               Endoscopic Fluorescence Diagnosis

                    Technical Background

                    Clinical Results

                    Latest Developments

               Photodynamic Therapy

                    Drug Application

                    Indications and Treatment Procedure

                    Clinical Results

               Conclusions

               Potential Future Trends of ALA-PDT

                    References

          Potential Future Indications

                         Alison Curnow

               Introduction

               Areas of Future Clinical Potential

                    Infectious Diseases

                    Immunological Effects

                    Pneumology

               ALA-PDT Enhancement

               Conclusions

                    References

Appendix

Subject Index