Hamster Model of an Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas
The reflux of pancreatic juice into the biliary tract is a well-known risk factor for the development of biliary carcinoma. In this study, we investigated the role of bile-reflux into the pancreatic ducts in pancreatic carcinogenesis, especially in the development of carcinoma in the main pancreatic duct, in hamsters. Syrian hamsters were subjected to one of three surgical procedures: cholecystoduodenostomy with dissection of the extrahepatic bile duct on the distal end of the common duct (Model A); cholecystoduodenostomy with dissection of the common bile duct (Model B); or simple laparotomy (Model C). Four weeks after the surgery, the animals received weekly subcutaneous injections of N-nitrosobis(2-oxopropyl) amine (BOP), for 9 weeks. They were killed for pathological investigation 16 weeks after the initial BOP injection. Pancreatic carcinomas developed in 95%, 88%, and 90% of the Model A (n = 22), Model B (n = 24), and Model C (n = 21) hamsters, respectively. The induced pancreatic tumors were classified into four histological types: papillary; tubular; cystic adenocarcinoma; and intraductal carcinoma of the main pancreatic duct, consisting of intraductal papillary carcinoma (IPC) and intraductal tubular carcinoma (ITC). The number and incidence of IPCs induced in the Model A hamsters were 24 lesions and 77%, which were significantly higher than those in the Model B (7 lesions and 29%) and C hamsters (7 lesions and 33%) (P < 0.01). Bile-reflux into the pancreatic ducts was seen only in the Model A hamsters, after an indocyanine green injection via the portal vein. Proliferative cell nuclear antigen labeling indices of the epithelial cells in the main pancreatic duct, with no BOP treatment, were 3.8%, 0.8%, and 1.1% in Models A (n = 10), B (n = 10), and C (n = 10), respectively. These differences were significant (P < 0.01). Our findings suggest that bile-reflux into the pancreatic ducts is a significant factor predisposing to the development of IPC of the pancreas through the acceleration of epithelial cell kinetics of the main pancreatic duct.
KeywordsPancreatic Duct Main Pancreatic Duct Choledochal Cyst Extrahepatic Bile Duct Tubular Adenocarcinoma
Unable to display preview. Download preview PDF.
- 3.Miyazaki M, Takada T, Miyakawa S, Tsukada K, Nagino M, Kondo S, Furuse J, Saito H, Tsuyuguchi T, Chijiiwa K, Kimura F, Yoshitomi H, Nozawa S, Yoshida M, Wada K, Amano H, Miura F. Risk factors for biliary tract and ampullary carcinomas and prophylactic surgery for these factors. J Hepatobiliary Pancreat Surg 2008 15:15–24.PubMedCrossRefGoogle Scholar