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Background: Barrett esophagus (BE) is a premalignant condition resulting from chronic acid gastroesophageal reflux and is associated with increased epithelial cell proliferation. Elimination of acid reflux might decrease cancer risk by affecting cell proliferation in BE. The effect of elimination of acid reflux on epithelial cell proliferation in BE was studied. Methods: Forty-five patients with long segment Barrett esophagus were treated in a randomized 2-year follow-up study with either omeprazole 40 mg b.i.d. (OME) or ranitidine 150 mg b.i.d. (RAN) and were compared for the effect on epithelial cell proliferation. Biopsies were taken 3 cm above the GE junction and just below the Z-line, at 0, 3, 9, and 24 months. Epithelial cell proliferation was determined by in vitro labeling with 5-bromo-2-deoxyuridine and immunohistochemistry. Labeling indices (LI) were established for luminal and crypt epithelium separately. Ambulatory 24-h esophageal pH-metry was performed at 0 and 3 months. Comparisons were made for the timeframes 0-3 months, 3-24 months, and 0-24 months. Results: OME reduced mean acid reflux to 0.1%/24 h, RAN to 9.4%. In the distal and the proximal biopsies, change in LI after 3 months was n.s. at either level for both treatments. In the distal biopsies (OME 22, RAN 23 patients) luminal LI increased significantly for RAN from 3 to 24 months (+ 12.64% month, mean area under the curve (AUC)), while that for OME remained stable, RAN versus OME P < 0.05. Crypt LI increased in both groups, only in RAN significantly so (+ 30.75% month), RAN versus OME n.s. In the proximal biopsies luminal LI at 24 months (OME 20, RAN 21 patients) had increased slightly but not significantly in RAN (+ 8.86% month), RAN versus OME n.s., whereas in the crypts LI in OME it had increased significantly (+ 28.80% month), OME versus RAN n.s. Conclusion: Elimination ofacid reflux resulted in a stabilization of luminal cell proliferative activity of Barrett epithelium in the distal esophagus, whereas this activity increased during continued acid reflux. Whether this finding has any implication for the cancer risk in Barrett esophagus remains to be seen. [ABSTRACT FROM AUTHOR]

Background: Fundic gland polyps (FGPs) occur in both syndromic and sporadic form. Syndromic FGPs arise through mutations in the adenomatous polyposis coli (APC) gene, whereas sporadic FGPs are caused by beta-catenin gene mutations. Dysplasia in sporadic FGPs, found less often than in syndromic FGPs, was recently associated with APC rather than beta-catenin mutations. These data suggest different functional consequences of APC and beta-catenin mutations. To investigate this hypothesis, we examined proliferative activity, degree of apoptosis, beta-catenin expression and p53 expression in syndromic and sporadic FGPs., Methods: Syndromic FGPs (n = 9) from familial adenomatous polyposis (FAP) patients and sporadic FGPs (n = 18) were studied. Proliferative activity, apoptotic cell death and expression of beta-catenin and p53 were examined by immunohistochemistry. In FGPs containing dysplasia, areas with and without dysplasia were compared., Results: Syndromic and sporadic FGPs without dysplasia exhibited similar proliferative activity, degree of apoptosis, beta-catenin and p53 expression. Dysplasia was observed more often in syndromic (4/9) than in sporadic FGPs (1/18). Within FGPs containing dysplasia, dysplastic areas showed abnormal nuclear beta-catenin staining in 3/5 cases and higher rates of cell proliferation and apoptosis than non-dysplastic areas. Overexpression of p53 was not observed., Conclusion: The finding of similar rates of proliferation and apoptosis in syndromic and sporadic FGPs does not support the hypothesis that APC and beta-catenin gene mutations have different functional consequences in FGPs. The association of dysplasia with relatively high cell turnover rates and nuclear expression of beta-catenin indicates activation of the Wnt-APC-beta-catenin pathway in dysplasia. The finding of dysplasia in some but not all syndromic FGPs suggests the involvement of other genes in addition to the APC gene in the development of dysplasia in FGPs.