Safe ablation of the anal mucosa and perianal skin in rats using Photodynamic Therapy-A promising approach for treating Anal Intraepithelial Neoplasia

摘要

Background: Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous carcinoma, is increasingly detected in individuals with impaired immune function. However, choices for effective, low morbidity treatment are limited. Photodynamic Therapy (PDT) is promising as it is known to ablate more proximal gastrointestinal mucosa with safe healing, without damage to underlying muscle. It can also ablate skin with safe healing and minimal scarring. Methods: Pharmacokinetics: Normal rats were sensitised with 200 mg/kg 5-aminolaevulinic acid (ALA) and killed 1 -8 h later. Anal tissues were examined by fluorescence microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal rats were sensitised similarly 3h later, laser light (635 nm) was delivered. Anal canal: 50-150J/cm using 1 cm diffuser fibre; for peri-anal skin, 50-200J/cm~2, using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28days later and the anal region removed for histological examination. Results: Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3 h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200 J/cm2; complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy. Conclusion: ALA-PDT can ablate anal mucosa and peri-anal skin with safe healing and no underlying damage. However, over treatment can damage the sphincters. This technique is ready to underao clinical trials.