title: Safe ablation of the anal mucosa and perianal skin in rats using Photodynamic Therapy--a promising approach for treating Anal Intraepithelial Neoplasia.
abstract: 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 200mg/kg 5-aminolaevulinic acid (ALA) and killed 1-8h 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: 50-150 J/cm using 1cm diffuser fibre; for peri-anal skin, 50-200 J/cm(2), using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28 days later and the anal region removed for histological examination.
  
  
  RESULTS
  Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50 J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200 J/cm(2); complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy.
  
  
  CONCLUSIONS
  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 undergo clinical trials.
authors.affiliation: Department of Surgery, Division of Surgery and Interventional Science, UCL, London WC1E 6BT, United Kingdom. Electronic address: vgeneve@cliniquedarne.com.
authors.forename: F
authors.initials: F
authors.lastname: Abbasakoor
authors.forename: J
authors.initials: J
authors.lastname: Woodhams
authors.forename: N
authors.initials: N
authors.lastname: Farooqui
authors.forename: M
authors.initials: M
authors.lastname: Novelli
authors.forename: S
authors.initials: S
authors.lastname: Bown
authors.forename: A
authors.initials: A
authors.lastname: MacRobert
authors.forename: P
authors.initials: P
authors.lastname: Boulos
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D001005:Anus Neoplasms / Q000188:drug therapy*; D002278:Carcinoma in Situ / Q000188:drug therapy*; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects*; D010778:Photochemotherapy / Q000009:adverse effects / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000293:injuries / Q000528:radiation effects*; D016896:Treatment Outcome
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid
keywords: 5-Aminolaevulinic acid (ALA); Anal Intraepithelial Neoplasia (AIN); Photodynamic Therapy (PDT)