Photodynamic therapy with topical metatetrahydroxychlorin (Fosgel) is ineffective for the treatment of anal intraepithelial neoplasia, grade III.
*Department of Dermatology, daggerDepartment of Radiation Oncology, Center for Optical Diagnostics and Therapy, double daggerDepartment of Internal Medicine, section signDepartment of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands, ||Department of Internal Medicine, MCRZ, Rotterdam, The Netherlands, paragraph signDepartment of Infectious Diseases, Leiden University Medical Center, The Netherlands, #Department of Internal Medicine, Haaglanden MC, The Hague, The Netherlands.JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.39). 10/2009; 52(1):141-3. DOI: 10.1097/QAI.0b013e3181b05f93
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ABSTRACT: Anal canal intraepithelial neoplasia (AIN) is a pre-malignant condition of the anal canal transitional epithelium that is associated with human papillomavirus (HPV) infection. The incidence and prevalence of AIN and anal cancer are increasing rapidly in HIV-positive men who have sex with men (MSM). Other groups like HIV-negative MSM, immunosuppressed patients and people affected by other HPV diseases like genital warts and cervical intraepithelial neoplasia (CIN) may also develop AIN. The condition is complicated by its multicentric and multifocal nature and high rates of relapse and morbidity. Targeted excisions using ablative treatments such as cautery, infrared coagulation (IRC) and cryotherapy have been used as first-line therapeutic strategies, and there are many other options. There is no consensus about the optimal management of AIN. To evaluate the effects of therapeutic interventions for anal canal intraepithelial neoplasia (AIN). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4), MEDLINE and EMBASE (to October 2011). We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies, and contacted experts in the field and manufacturers of any AIN and HPV-specific treatments. Randomized controlled trials (RCTs) that assessed any type of intervention for AIN. Two review authors independently abstracted data and assessed risk of bias. If it was possible, the data were synthesised in a meta-analysis. We found only one RCT, which included 53 patients, that met our inclusion criteria. This trial reported data on imiquimod versus placebo. There was no statistically significant difference in the risk of disease cure but there was a trend for imiquimod to downgrade the AIN to a low-risk stage. The lack of statistical power of the trial may be due to the small number of patients in each group. The risk of bias was estimated as moderate. The included trial failed to demonstrate any statistically significant efficacy of imiquimod in the management of anal intraepithelial neoplasia (AIN). The absence of reliable evidence for any of the interventions used in AIN precludes any definitive guidance or recommendations for clinical practice. Prospective cohort studies and retrospective studies have not been included in this review as they are considered to provide lower quality evidence. Well designed RCTs are needed.Cochrane database of systematic reviews (Online) 01/2012; 12(12):CD009244. DOI:10.1002/14651858.CD009244.pub2 · 5.94 Impact Factor
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ABSTRACT: There is a growing range of treatment options for anal intraepithelial neoplasia (AIN). In HIV-positive patients, sustained treatment is often required to achieve clearance. The treatments considered are topically applied fluorouracil, imiquimod, cidofovir and trichloroacetic acid, the potential treatments of topical lopinavir and photodynamic therapy with aminolevulenic acid, and the surgical methods of electrosurgery, infrared coagulation and laser. Destructive treatment methods, possibly including TCA, are more effective than self applied topical treatments. Combining or alternating different treatments should be considered.Sexual Health 08/2012; 9(6). DOI:10.1071/SH11157 · 1.58 Impact Factor
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ABSTRACT: Photosensitizers for photodynamic therapy (PDT) are most commonly delivered to patients or experimental animals via intravenous injection. After initial distribution throughout the body, there can be some preferential accumulation within tumors or other abnormal tissue in comparison to the surrounding normal tissue. In contrast, the photosensitizer precursor, 5-aminolevulinic acid (ALA) or one of its esters, is routinely administered topically, and more specifically, to target skin lesions. Following metabolic conversion to protoporphyrin IX, the target area is photoilluminated, limiting peripheral damage and targeting the effective agent to the desired region. However, not all skin lesions are responsive to ALA-PDT. Topical administration of fully formed photosensitizers is less common but is receiving increased attention, and some notable advances with selected approved and experimental photosensitizers have been published. Our team has examined topical administration of the phthalocyanine photosensitizer Pc 4 to mammalian (human, mouse, pig) skin. Pc 4 in a desired formulation and concentration was applied to the skin surface at a rate of 5-10 μL/cm2 and kept under occlusion. After various times, skin biopsies were examined by confocal microscopy, and fluorescence within regions of interest was quantified. Early after application, images show the majority of the Pc 4 fluorescence within the stratum corneum and upper epidermis. As a function of time and concentration, penetration of Pc 4 across the stratum corneum and into the epidermis and dermis was observed. The data indicate that Pc 4 can be delivered to skin for photodynamic activation and treatment of skin pathologies.Proceedings of SPIE - The International Society for Optical Engineering 02/2012; DOI:10.1117/12.909029 · 0.20 Impact Factor
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