Autofluorescence imaging colonoscopy for the detection of dysplastic lesions in ulcerative colitis: a pilot study.

AIM: Autofluorescence imaging (AFI) is a novel technology for endoscopy, which enhances neoplastic lesions of the gastrointestinal tract. The aim of this investigation was to examine whether AFI colonoscopy can identify dysplasia in ulcerative colitis. METHOD: We examined 48 patients with ulcerative colitis by AFI colonoscopy. Apparently flat, coarse granular mucosa and visible protruding lesions under conventional colonoscopy were observed by AFI. Those target areas were classified into low AF and high AF according to the colour under AFI colonoscopy. The grade of dysplasia was determined in the specimens obtained from the target areas. RESULTS: About 126 sites (35 protruding lesions and 91 flat areas) were examined by AFI colonoscopy. AF was determined to be high in 42 areas and to be low in 84 areas. The positive rate of dysplasia was higher in protrusions (31%) than in flat mucosa (3.3%, P < 0.0001). The rate of positive dysplasia was not statistically different between lesions determined to be low AF (14%) and those to be high AF (5%, P = 0.09). The positive rate of dysplasia in protruding lesions was significantly higher in low AF than in high AF (45.0%vs 13.3%, P = 0.043), while the value in flat lesions was not different between low AF and high AF (8.2%vs 0%, P = 0.3). CONCLUSIONS: Autofluorescence imaging colonoscopy seems to have a role for the detection of dysplaia in ulcerative colitis.

Genomic and functional analyses of MUTYH in Japanese patients with adenomatous polyposis.

The present study was undertaken to elucidate germ line mutations of the base excision repair gene, MUTYH, in Japanese patients with adenomatous polyposis. We screened germ line mutations of adenomatous polyposis coli (APC) gene and MUTYH in 66 Japanese patients with adenomatous polyposis. APC was screened by the protein truncation test, while MUTYH was screened by polymerase chain reaction-based single-strand conformation polymorphism and direct sequencing. The nicking assay was applied in order to evaluate the DNA glycosylase activity of the identified MUTYH variant. In this study, Seven MUTYH variants were identified in 16 of 21 APC-negative patients. Q324H mutation was the most frequent mutation, with an allele frequency of 49%. Two patients carried biallelic mutations other than Q324H; a patient had biallelic G272E and A359V mutations, while the other had compound heterozygotes of P18L and G25D mutations. Nicking assay for G272E using the corresponding mouse MUTYH mutant with G257E revealed that G272E is a variant to cause an impaired DNA glycosylase activity. Homozygous MUTYH mutation accounts for approximately 10% of Japanese patients with adenomatous polyposis. G272E may be one of the mutations specific to patients with adenomatous polyposis in East Asia.

Flat adenoma-carcinoma sequence with high-malignancy potential as demonstrated by CD10 and beta-catenin expression: a different pathway from the polypoid adenoma-carcinoma sequence.

AIMS: CD10+ colorectal carcinomas have a high risk of giving rise to liver metastasis. The aim was to examine phenotypic expression in colorectal neoplasia and to elucidate changes in such expression through the adenoma-carcinoma sequence. METHODS AND RESULTS: We examined the expression of various proteins immunohistochemically in 111 flat [non-polypoid growth (NPG)] colorectal neoplasms, categorized into 28 low-grade (NPG-LGN), 44 high-grades (NPG-HGN) and 39 cases of invasive neoplasia (NPG-IN), as well as in 96 polypoid [polypoid growth (PG)] neoplasms, categorized into 26 PG-LGN, 39 PG-HGN and 31 PG-IN according to the Vienna classification. CD10 was more frequently expressed in NPG than in PG neoplasia. MUC2 and MUC5AC were more frequently expressed in PG than in NPG neoplasias. Nuclear beta-catenin was more frequently expressed in NPG-LGN than in PG-LGN. No difference in p53 expression was found between NPG and PG neoplasia. CONCLUSIONS: From the viewpoint of the expression of CD10 and beta-catenin, it would appear that NPG-LGN differs significantly from PG-LGN, thereby indicating that NPG-LGN is a precursor of CD10+ carcinoma. It is important to ensure that NPG neoplasia is not overlooked if cases of CD10+ carcinoma are to be detected at an early stage.

Mucosal proinflammatory cytokine and chemokine expression of gastroduodenal lesions in Crohn's disease.

BACKGROUND: The stomach and the duodenum are frequent sites of involvement by diminutive lesions in Crohn's disease (CD). AIM: To assess mucosal proinflammatory cytokines and chemokines in gastroduodenal lesions of CD. METHODS: 13C-Urea breath test and upper endoscopy were performed in 29 CD patients and seven control subjects, and biopsy specimens were obtained from the gastric cardia and the duodenum. Histology and mucosal levels of IL-1beta, IL-8/CXCL8 and RANTES/CCL5 were assessed and compared according to the presence of gastric cardial lesion [bamboo joint-like appearance (BJA)] and duodenal lesion (notched appearance, aphthous erosion and polypoid lesion). In 11 CD patients, these procedures were repeatedly performed after administration of famotidine. RESULTS: H. pylori was less frequently positive in CD patients than in controls (10% vs. 71%, P = 0.003). Prevalence of cardial and duodenal lesion was significantly higher in CD than in controls (59% vs. 0%, P = 0.008 for gastric lesion; 45% vs. 0%, P = 0.034 for duodenal lesion). There were no differences in IL-1beta, IL-8 and RANTES between CD and controls. Duodenal mucosal IL-1beta and IL-8 were significantly higher in positive duodenal lesion than in negative duodenal lesion. However, there were no such differences with respect to cardial lesions. Endoscopic findings remained unchanged after administration of famotidine, while there was a trend towards decreases in IL-1beta and IL-8 in the gastric cardia. CONCLUSIONS: The pathogenesis of diminutive lesions of CD may be different between the stomach and the duodenum. Famotidine may not have a therapeutic effect on duodenal lesion in CD.

Small invasive colonic cancer occurring in a hyperplastic polyp.

We report a case of advanced colon cancer which was supposed to have arisen from a hyperplastic polyp in a 68-year-old man. Colonoscopy revealed a depressed reddish area with a surrounding elevated lesion that was of a faded color compared with the normal mucosa. After the mucosal surface had been sprayed with crystal violet dye, magnifying colonoscopy showed an amorphous area in the central depression and the surrounding, slightly elevated lesion had an asteroid pattern. The depressed area was therefore considered to be a colonic cancer surrounded by a hyperplastic polyp. Endoscopic ultrasonography showed that the lesion was infiltrating further than the deep submucosal layer and it was therefore decided to treat the patient by laparoscopically assisted right hemicolectomy. The depressed lesion was found to be a well-differentiated adenocarcinoma invading the muscularis propria (diagnosed as IIc + IIa-like advanced adenocarcinoma). The surrounding flat elevated lesion was found to be hyperplastic mucosa. No adenomatous lesions were found. There have been few reported cases in which a preoperative diagnosis of carcinoma in a hyperplastic polyp has been made, but the possibility of carcinogenesis from hyperplastic polyps has come under consideration recently. This case was considered to be important because it raises the possibility that nonpolypoid cancer can develop from a hyperplastic polyp.

Multiple microcarcinoids in a patient with long standing ulcerative colitis.

A male patient with a 17 year history of intractable ulcerative colitis of the entire type was treated by total proctocolectomy. Colonoscopy before surgery did not identify dysplasia. Histological examination of the resected colorectum revealed that, in addition to chronic inflammatory infiltrates, there were 21 areas of microcarcinoids located in the muscularis propria and in the superficial layer of the submucosa. Carcinoids may be more common than previously thought, and they may be a reactive phenomenon to a variety of factors in ulcerative colitis.