Abstract
Pancreaticobiliary maljunction (PBM) complicates biliary tract cancer at a high rate because of continuous biliary reflux of pancreatic juice. Pathological findings suggest a hyperplasia-dysplasia-carcinoma sequence in carcinogenesis of PBM. This appears to be a different mechanism from that of usual gallbladder cancer without PBM, which develops by an adenoma-carcinoma sequence or by de novo carcinogenesis. Molecular biological analysis revealed a high incidence of cellular proliferation-activating factors, such as COX-2, in the hyperplasia stage. In addition, cellular proliferative activity including Ki-67 was significantly higher in normal gallbladder mucosa without PBM. Furthermore, a high incidence of K-ras gene mutation was seen in hyperplasia (13–63%), and microsatellite instability was observed in 60% of cases with dysplasia. In cancerous lesions, a high rate of cyclin D1 and p53 overexpression and p53 gene mutation have been recognized. These results suggest that a multistep carcinogenetic process contributes to the carcinogenesis of PBM. Overexpression of COX-2 is observed in PBM. Therefore, COX-2 inhibitors, such as NSAIDs, may play an important role in preventing carcinogenesis.
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Nagakawa, Y., Sahara, Y., Takishita, C., Tsuchida, A. (2018). Carcinogenesis of the Biliary Tract in PBM. In: Kamisawa, T., Ando, H. (eds) Pancreaticobiliary Maljunction and Congenital Biliary Dilatation. Springer, Singapore. https://doi.org/10.1007/978-981-10-8654-0_20
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DOI: https://doi.org/10.1007/978-981-10-8654-0_20
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