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Histologic and genetic analysis of the gallbladder in patients with occult pancreatobiliary reflux

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Recent studies have suggested that pancreatobiliary reflux occurs not only in patients with pancreaticobiliary maljunction (PBM), but also in patients without PBM and thereby possibly causes biliary tract disease. In this study, we examined prospectively histological findings and genetic analysis in the non-cancerous epithelium of the gallbladder in patients with high biliary amylase levels and a normal pancreaticobiliary junction. Ki-67 L.I of non-cancerous epithelium was 14.4 and 3.5% in the high biliary amylase levels (HBA) group and the low bliliary amylase levels (LBA) group, respectively (p<0.01). There was no case showing p53 overexpression regardless of amylase levels of bile. COX-2 expression was detected in the cytoplasm of non-cancerous epithelium in 9 cases in the HBA group and 5 cases in the LBA group. The positive rate of COX-2 overexpression was significantly higher in the HBA group than in the LBA group (p<0.05). COX-2 overexpression cases showed higher Ki-67 L.I than COX-2 non-overexpression cases (21.2 vs. 7.9%, p<0.05). Mutations of the K-ras gene were detected in non-cancerous gallbladder epithelium in 3 cases, only in the HBA group. Patterns of K-ras mutation at codon 12 were GAT in two cases and GTT in one case. Three cases showing COX-2 overexpression also showed K-ras mutation. These three cases showing K-ras mutation had comparatively high cellular proliferative activity (28, 26 and 14%). In conclusion, our data suggest that occult pancreaticobiliary reflux, especially with high biliary amylase levels, represents an important risk factor for the development of gallbladder carcinoma as well as PBM, and it may be possible to detect patients with such high biliary amylase levels by ERCP.
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Document Type: Research Article

Affiliations: Fourth Department of Internal Medicine, Tokyo Medical University, Shinjuku-ku, Tokyo 160-0023, Japan., Email: [email protected]

Publication date: March 1, 2005

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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