Carcinogenesis of the Biliary Tract in PBM

  • Yuichi Nagakawa
  • Yatsuka Sahara
  • Chie Takishita
  • Akihiko TsuchidaEmail author


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.


Pancreaticobiliary maljunction Congenital biliary dilatation Carcinogenesis K-ras p53 Cyclooxygenase-2 


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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Yuichi Nagakawa
    • 1
  • Yatsuka Sahara
    • 1
  • Chie Takishita
    • 1
  • Akihiko Tsuchida
    • 1
    Email author
  1. 1.Department of Gastrointestinal and Pediatric SurgeryTokyo Medical UniversityShinjuku-kuJapan

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