Photodynamic Therapy for Carcinoma In Situ of the Anus
Hypothesis Photodynamic therapy (PDT) for carcinoma in situ of the anus is an alternative to surgical excision in patients who are seropositive for human immunodeficiency virus (HIV).
Design Before-after trial.
Settings Tertiary referral center.
Patients Twelve HIV-seropositive patients who were actively being treated for AIDS with high-grade dysplasia on anal Papanicolaou test results had site-directed biopsies of acetowhitening foci immediately after application of dilute acetic acid. Biopsy results showed that 5 patients had anal carcinoma in situ. These patients were given the photosensitizer δ-aminolevulinic acid orally. Four to 4.25 hours later, the entire anal circumference was treated with PDT. All 5 patients, after being treated with PDT, had repeated Papanicolaou tests at monthly intervals. If acetowhitening occurred at the fifth month, site-directed biopsy was done.
Main Outcome Measures Anal cytologic examination by Papanicolaou test and site-directed biopsy if acetowhitening was found at 5 months in order to determine effectiveness of PDT in downstaging cytologic findings.
Results All patients had a consistent downgrading of cytologic findings during the 5 months of follow-up. Papanicolaou test results showed 2 patients had no dysplasia, 2 had mild dysplasia, and 1 had moderate dysplasia. Moderate dysplasia was confirmed by site-directed biopsy results. No complications of PDT occurred, but all 5 patients developed various abnormalities in liver function test results that returned to baseline values within 2 weeks; this also has been noted in patients ingesting δ-aminolevulinic acid who are presumably HIV seronegative.
Conclusion In a group of patients who are at high risk for recurrence irrespective of initial treatment, PDT can be used as a successful alternative to surgical excision for anal carcinoma in situ.
It is currently believed that the cytologic finding of high-grade squamous intraepithelial lesions (HSIL) in the anus is a precursor of cancer. Now that anal Papanicolaou (Pap) tests are being done more routinely in patients who are positive for human immunodeficiency virus (HIV), HSIL are more frequently found. The prevalence of HSIL is increased in HIV-positive individuals.1 Another important risk factor for anal cytologic abnormalities is human papilloma virus (HPV) infection. Immunosuppression caused by HIV infection increases the likelihood of HPV infection and subsequent anal intraepithelial neoplasia. These observations presumably account for the increasing incidence of anal cancer recognized in patients with AIDS.2,3
There appears to be little argument that high-grade dysplastic lesions of the anus require treatment. The standard approach involves surgical excision, but the problem is that such lesions may be multifocal, requiring removal of large areas of anal epithelium. Furthermore, eradication of HPV infection by excision is unlikely and the chance of recurrent HSIL is estimated to be at least 30% across 5 years.4 There are no known medical therapies at present that effectively treat HSIL. An alternative to surgical excision or gross destruction is photodynamic therapy (PDT), which is associated with a low incidence of complications and can be used for sequential treatments. Photodynamic therapy has been variably successful in eradicating high-grade dysplastic lesions of the lower female genital tract and esophagus.
The purpose of this study was to determine the effectiveness and safety of PDT using the photosensitizing agent δ-aminolevulinic acid (ALA) as an alternative to surgical excision for carcinoma in situ of the anus occurring in patients who were also receiving treatment for HIV infection. Clinically, PDT is based on 2 steps. The first involves the selective accumulation of a photosensitizer in the target tissue. The second involves activation of the photosensitizer with an appropriate wavelength of light. This results in selective tissue destruction via a photochemical reaction. In itself, ALA is not photoreactive but is converted, especially by premalignant and malignant tissues, to its photosensitive end product, protoporphyrin IX.5
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