In the progression of chronic gastritis, gastric mucosal cells deviate from the normal pathway of gastric differentiation to an intestinal phenotype. Many epidemiologic studies have found an association between the formation of intestinal metaplasia and the development of gastric carcinoma. However, there is no direct evidence that shows intestinal metaplasia is a precursor lesion of gastric carcinoma, to date. We periodically examined the intestinal metaplastic mucosa of Cdx2-transgenic mice we have previously generated. Gastric polyps developed from intestinal metaplastic mucosa in all stomachs of Cdx2-transgenic mice examined. These gastric polyps consisted of intestinal-type adenocarcinoma that invaded the submucosa and muscularis propria and occasionally spread into the subserosa. p53 and APC gene mutations were recognized in the adenocarcinomas. The participation of APC and p53 gene mutations in gastric carcinogenesis from the intestinal metaplasia was verified by the Cdx2-transgenic mice, carrying Apc Min mutation or p53 deficiency, that developed gastric polyps much earlier than Cdx2 alone. We successfully showed that long-term intestinal metaplasia induces invasive gastric carcinoma. These results indicate that intestinal metaplasia itself plays a significant role in the genesis and progression of gastric carcinoma.

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Background: When endoscopic retrograde cholangiopancreatography (ERCP) guided bile duct biopsy fails to demonstrate malignancy, it remains unclear how to manage patients with presumably malignant strictures. Aims: To evaluate the value of intraductal ultrasonography (IDUS) when bile duct biopsy is negative. Methods: Sixty two patients with strictures of the bile duct were studied prospectively. During ERCP, IDUS was performed using an ultrasonic probe (diameter 2.0 mm; frequency 20 MHz). Following IDUS, a bile duct biopsy was performed using forceps (diameter 1.8 mm). The IDUS images of the tumour were classified as polypoid lesions, localised wall thickening, intraductal sessile tumours, sessile tumour outside of the bile duct, or absence of apparent lesion. The bile duct wall structures at the site of the tumour as well as the maximum diameter of the tumour were also analysed. The IDUS findings were compared with the histological findings or clinical course. Results: When the IDUS images showed a polypoid lesion (n=19), localised wall thickening (n=8), intraductal sessile tumour (n=13), and sessile tumour outside of the bile duct (n = 20), the sensitivities of the biopsy were 80%, 50%, 92%, and 53%, respectively. Multiple regression analysis showed that the presence of sessile tumour (intraductal or outside of the bile duct: p<0.05), tumour size greater than 10.0 mm (p<0.001), and interrupted wall structure (p<0.05) were independent variables that predicted malignancy. Conclusion:When biopsy fails to demonstrate evidence of malignancy, the presence of sessile tumour (intraductal or outside of the bile duct), tumour size greater than 10.0 mm, and interrupted wall structure on IDUS images are factors that can predict malignancy.

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