Qin Yang1,2, Junke Wang1, Fei Liu1, Wenjie Ma1, Haijie Hu1, Congdun Ran1, Fuyu Li3, Qiuwei Pan2. 1. Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, China. 2. Department of Gastroenterology and Hepatology, Postgraduate School Molecular Medicine, Erasmus MC-University Medical Center, Rotterdam, The Netherlands. 3. Department of Hepatobiliary Surgery, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, China. lfy_74@hotmail.com.
Abstract
BACKGROUND: Benign biliary stricture (BBS) is highly refractory. Currently, there is no effective strategy for prevention of BBS recurrence. The aim of this study is to establish a novel BBS rabbit model and to investigate the efficacy of biliary infusion with anti-proliferative medications for treating BBS. METHOD: A BBS model was established via surgical injury and biliary infection. The biliary infusion tube was inserted into the common bile duct via the stump of cystic duct after cholecystectomy. Biliary infusions with Rapamycin, Pirfenidone and Fasudil were performed daily during the 4 weeks following the surgery. The wall thickness and luminal area of the bile duct were assessed. RESULTS: All rabbits formed BBS after surgery. The mortality rate was 13% (8/60) and tube withdrawal rate was 4% (2/48). The thickness of the bile duct wall was significantly reduced; whereas the luminal area of the bile duct was dramatically enlarged in the Rapamycin or the Pirfenidone treated group, compared to the saline treated group. Furthermore, the local treatment significantly decreased the levels of proliferation makers, including PCNA, Collagen I and fibrogenic mediators, including ACTA2 and TGF-beta. CONCLUSION: We have established a novel animal model for BBS formation. We have further demonstrated that biliary infusion with Rapamycin or Pirfenidone limits the biliary strictures through inhibiting the proliferation of the bile duct wall in this model. This may represent a new avenue for preventing biliary restenosis.
BACKGROUND: Benign biliary stricture (BBS) is highly refractory. Currently, there is no effective strategy for prevention of BBS recurrence. The aim of this study is to establish a novel BBSrabbit model and to investigate the efficacy of biliary infusion with anti-proliferative medications for treating BBS. METHOD: A BBS model was established via surgical injury and biliary infection. The biliary infusion tube was inserted into the common bile duct via the stump of cystic duct after cholecystectomy. Biliary infusions with Rapamycin, Pirfenidone and Fasudil were performed daily during the 4 weeks following the surgery. The wall thickness and luminal area of the bile duct were assessed. RESULTS: All rabbits formed BBS after surgery. The mortality rate was 13% (8/60) and tube withdrawal rate was 4% (2/48). The thickness of the bile duct wall was significantly reduced; whereas the luminal area of the bile duct was dramatically enlarged in the Rapamycin or the Pirfenidone treated group, compared to the saline treated group. Furthermore, the local treatment significantly decreased the levels of proliferation makers, including PCNA, Collagen I and fibrogenic mediators, including ACTA2 and TGF-beta. CONCLUSION: We have established a novel animal model for BBS formation. We have further demonstrated that biliary infusion with Rapamycin or Pirfenidone limits the biliary strictures through inhibiting the proliferation of the bile duct wall in this model. This may represent a new avenue for preventing biliary restenosis.
Authors: Jing Du; Katelyn Paz; Ryan Flynn; Ante Vulic; Tara M Robinson; Katie E Lineburg; Kylie A Alexander; Jingjing Meng; Sabita Roy; Angela Panoskaltsis-Mortari; Michael Loschi; Geoffrey R Hill; Jonathan S Serody; Ivan Maillard; David Miklos; John Koreth; Corey S Cutler; Joseph H Antin; Jerome Ritz; Kelli P MacDonald; Timothy W Schacker; Leo Luznik; Bruce R Blazar Journal: Blood Date: 2017-03-02 Impact factor: 22.113