01.07 Establishment of a Novel Murine Model of Obstructive Jaundice

H. Aoki1,2, M. Aoki1,2, E. Katsuta1,2, J. Yong3, X. Wang3, H. Zhou3, S. Spiegel2, K. Takabe1,2 1Virginia Commonwealth University,Division Of Surgical Oncology, Department Of Surgery,Richmond, VA, USA 2Virginia Commonwealth University,Department Of Biochemistry & Molecular Biology,Richmond, VA, USA 3Virginia Commonwealth University,Department Of Microbiology And Immunology,Richmond, VA, USA

Introduction: Obstructive jaundice is one of the classic signs of pancreatic head mass, or tumor in the biliary tree. Although there are numerous publications on clinical management of obstructive jaundice, there are very few reports regarding the effects of it on cancer biology itself partly due to lack of stable model. The standard murine model for cholestasis is the partial ligation of the common bile duct (pBDL), which is known to have very short survival, usually less than 3-4 days. Recently, a long term survival cholestasis model that totally ligate hepatic bile duct (tHBDL) was reported. Here we compared tHBDL model with standard pBDL model on their characteristics.

Methods: C57Black6 mice were subjected to sham, pBDL and tHBDL operations. For the tHBDL model, total ligation of the hepatic bile duct was performed at the level where left and median lobe bile ducts, as well as the duct from upper right lobe were completely obstructed, whereas right lower lobe bile duct was spared. Of note, cholecystectomy was added to all tHBDL model. For pBDL model, the suture was tied down tightly at the common bile duct with surgical needle placed by the side, and then the needle was removed leaving a defined lumen within the ligation. Survival was determined by humane endpoints and assessed by Kaplan-Meier method. Weights of body, liver and spleen were measured on the indicated days. Intraoperative complications were also recorded.

Results: 24 mice that received pBDL mice died between 3-4 days after operation. On the other hand, mice that underwent tHBDL were observed to survive over 14 days, longest survivor was over 2 months. After 2 days, pBDL model showed the significant body weight loss compared with sham and tHBDL. An increase of liver weight was observed in both pBDL and tHBDL groups, where it was much heavier in tHBDL group than pBDL group. Spleen of tHBDL model was heavier than other groups, on the other hand, weight of spleen in pBDL group was lighter than sham surgery group. In tHBDL model, enlargement of right lobe was observed. Most common complication during the procedure was bleeding from portal vein or liver and technique for tHBDL model was stabilized due to good exposure of procedure field with assistance.

Conclusion: Total hepatic bile duct ligation model was clearly more stable model than standard partial bile duct ligation model, which is most commonly used. Given the longer survival, total hepatic bile duct ligation model provide us tool to investigate the biological impact of obstructive jaundice.