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P172. Photodynamic surveillance of colitis-associated dysplasia in patients with ulcerative colitis and in mouse model, by visualization following oral 5-amino-levulinic acid sensitization

T. Iwasaki1, T. Kato2, N. Komoike1, H. Saijo1, R. Sawada1, M. Saruta1, S. Arihiro1, M. Matsuoka1, S. Koido1, M. Ito3, S. Homma3, H. Tajiri1,2, 1The Jikei University School of Medicine, Gastroenterology and Hepatology, Tokyo, Japan, 2The Jikei University School of Medicine, Endoscopy, Tokyo, Japan, 3The Jikei University School of Medicine, Institute of DNA Medicine, Tokyo, Japan

Background

An important issue in the clinical management of patients with long-standing ulcerative colitis (UC) is the early and accurate detection of dysplastic lesions. Although many endoscopic procedures have been suggested for more efficient detection of dysplastic lesions, reliable methods remain uncertain. Recently, photodynamic diagnosis has been used clinically, especially in neurosurgery and urology, to detect the extent of neoplasms. 5-Aminolevulinic acid (5-ALA) is converted intracellularly into the sensitizer protoporphyrin IX (PpIX), which selectively accumulates in neoplastic tissue, allowing their detection. As there are very few reports regarding photodynamic surveillance, its utility is still unclear and controversial. Our aim was to evaluate this efficacy for endoscopic detection of dysplastic lesions in patients with UC, using autofluorescent endoscopy (AFE) following sensitization by orally administered 5-ALA. In addition, to evaluate the potential of this procedure for UC surveillance, we investigated the expression of PpIX in dysplastic lesions induced in a model of colitis-associated dysplasia in mice.

Methods

13 patients with long-standing UC were enrolled from Oct. 2010 to Oct. 2012. 5-ALA was administered orally, and followed by conventional colon lavage. Endoscopic examination, including AFE, was performed six hours after oral 5-ALA administration. Target biopsies were performed and the histopathological findings were compared. The localization of fluorescent signals after oral administration of 5-ALA was also determined in the mouse model. Inflammatory carcinogenesis was induced in Apcmin/+ mice by oral administration of 2% dextran sulfate sodium for seven days and then water for the following 28 days. Six hours after administration of oral 5-ALA, the colon containing induced colonic polypoid lesions was resected and observed by autofluorescent stereoscopy and histopathological examination.

Results

During AFE, three flat protruding lesions with bright fluorescent signals on their borders were detected in three patients, revealing low grade dysplasia (LGD) on pathological examination. In the mouse model, strong fluorescent signals of PpIX were observed only in the LGD that were confirmed histopathologically. Interestingly, strong PpIX fluorescent signals observed macroscopically on the borders of the LGD in mice, corresponded to the AFE observation of human LGD.

Conclusion

Photodynamic surveillance with AFE after 5-ALA sensitization offers the possibility of detecting LGD in UC by characteristic fluorescent enhancement. Our data suggest this procedure is a promising surveillance method for detecting dysplastic lesions that can be useful in detecting precancerous lesion during UC surveillance.