Clinical and immunohistochemical assessment of vulval intraepithelial neoplasia following photodynamic therapy using a novel bioadhesive patch-type system loaded with 5-aminolevulinic acid.
BACKGROUND
The work in this study appraised photodynamic treatment (PDT) as a treatment method for vulval intraepithelial neoplasia (VIN) using a novel bioadhesive patch to deliver aminolevulinic acid. An analysis of changes in expression of apoptotic and cell cycle proteins (p53, p21, Mdm2, Blc-2, Bax, Ki-67) in response to PDT was evaluated.


METHODS
PDT was performed using non-laser light, either as a one or two-cycle treatment, with clinical and pathological assessment following after 6 weeks. Twenty-three patients with 25 VIN lesions underwent 49 cycles of PDT. Patches were designed to conform to uneven vulval skin and contained 38 mg cm(-2) aminolevulinic acid. Assessment was carried out at 6 weeks post-treatment. Patient-based treatment assessment, along with clinical and pathological changes, were monitored. Immunohistochemical staining was used to elucidate a possible biomolecular basis for induced cellular changes.


RESULTS
Most patients (52%) reported a symptomatic response, with normal pathology restored in 38% of lesions. The patch was easy to apply and remove, causing minimal discomfort. Fluorescence inspection confirmed protoporphyrin accumulation. Pain during implementation of PDT was problematic, necessitating some form of local analgesia. Changes in expression of cell cycle and apoptotic-related proteins suggested involvement of apoptotic pathways. Down regulation of p21 and inverse changes in Bcl-2 and Bax were key findings.


CONCLUSIONS
Treatment of VIN lesions using a novel bioadhesive patch induced changes in cell cycle and apoptotic proteins in response to PDT with possible utilisation of apoptotic pathways. The efficacy of PDT in treating VIN could be improved by a better understanding of these apoptotic mechanisms, the influence of factors, such as HPV status, and of the need for effective pain management.
Zawislak
A
A
Department of Gynaecology, Belfast City Hospital Trust, Lisburn Road, Belfast BT9 7AB, UK.
Donnelly
R F
RF
McCluggage
W G
WG
Price
J H
JH
McClelland
H R
HR
Woolfson
A D
AD
Dobbs
S
S
Maxwell
P
P
McCarron
P A
PA
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017319:Photosensitizing Agents / Q000008:administration & dosage; D014014:Tissue Adhesives / Q000737:chemistry; D016896:Treatment Outcome; D014846:Vulvar Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy* / Q000473:pathology
D004337:Drug Carriers; D017319:Photosensitizing Agents; D014014:Tissue Adhesives; D000622:Aminolevulinic Acid