Detection of dysplastic lesions by fluorescence in a model of colitis in rats after previous photosensitization with 5-aminolaevulinic acid.

Abstract

Endoscopic diagnosis of dysplastic lesions and early cancers in chronic ulcerative colitis is a major problem. Identification of suspicious lesions is influenced by the macroscopic appearance of the colon, but also by the endoscopist's experience. In this study we evaluated the identification of dysplastic lesions by the naked eye in an animal model of colitis after 5-aminoaevulinic acid-induced photosensitization. 80 male Wistar rats were examined. Acute and chronic colitis were induced by oral application of 5% dextrane sulfate sodium (DSS) in 1-7 cycles (1 cycle = seven days DSS and 10 days water). For sensitisation 5-aminolaevulinic acid (5-ALA) at different doses (0, 10, 25, 50, 75, 100, and 200 mg/kg) was used. The colonic fluorescence was examined under a blue light (390-436 nm) for excitation. Histological findings of fluorescent and non-fluorescent biopsy specimens were recorded. Using 100 mg/kg 5-ALA intravenously for photosensitization, all dysplastic lesions (5/5) showed fluorescence (sensitivity 100%). However, at this concentration of 5-ALA, 60 false positive lesions were found out of 76 specimens taken from lesions that were not dysplastic--only 16 specimens of non-dysplastic lesions did not fluoresce (specificity 21%). Using 75 and 50 mg/kg 5-ALA intravenously sensitivity decreased to 92% (36/39) and 42% (5/12), respectively, while specificity increased to 35% (29/82) and 62% (45/73). Using 50 mg/kg 5-ALA intravenously, fluorescence-positive biopsy specimens showed inflammation of the colon in 31% whereas only 12% contained normal mucosa (p < 0.01). The distribution of fluorescence-positive biopsy specimens with histologically confirmed inflammation was similar for different grades of inflammation after sensitisation with 75 and 100 mg/kg 5-ALA, whereas with 50 mg/kg 5-ALA fluorescence-positive biopsy specimens contained significantly (p < 0.05) more moderate, massive, or ulcerative inflammation (79%) than mild inflammation (21%). 5-ALA induced photosensitization gave a high sensitivity, but low specificity in identifying dysplastic lesions in DSS-induced colitis in rats. In this animal model inflammation is a major factor in disturbing the fluorescence localisation of dysplasia after sensitisation with 5-ALA.