Effects of epidermal growth factor receptor inhibitor on proliferative cholangitis in hepatolithiasis  

作　　者：Qin Yang Yong Zhou Fu-Yu Li Hui Mao Anuj Shrestha Wen-Jie Ma Nan-Sheng Cheng Wei Zhang 

机构地区：[1]Department of Hepatobiliary Surgery, West China Hospital of Sichuan University [2]Department of Medicine, The George Washington University

出　　处：《Hepatobiliary & Pancreatic Diseases International》2015年第5期509-515,共7页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the National Nature Science Foundation of China(30801111 and 30972923);Science&Technology Support Project of Sichuan Province(10SZ0166,14ZC1337 and 14ZC1335)

摘　　要：BACKGROUND： There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis（PC）, which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor（EGFR） inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.METHODS： After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.RESULTS： The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and β-glucuronidase activity.CONCLUSION： Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.BACKGROUND： There is currently no effective medication to prevent stone recurrence after choledochoscopic lithotomy or to treat proliferative cholangitis（PC）, which is the pathologic basis of hepatolithiasis. This study aimed to investigate whether gefitinib, an epidermal growth factor receptor（EGFR） inhibitor, inhibited cholangio hyperplasia and lithogenesis in PC.METHODS： After cholangioscopic lithotomy, indwelling catheters were placed in the diseased bile duct lumens in 94 patients with hepatolithiasis. Subsequently, 49 of the 94 patients were treated with 250 mg gefitinib solution via a catheter twice a week, and they were subjected to choledochoscopic biopsy at 6 and 12 weeks. The rest 45 hepatolithiasis patients without gefitinib treatment served as controls.RESULTS： The expressions of EGFR, PCNA and procollagen I were significantly reduced in the patients treated with gefitinib in 12 weeks compared with those in the control group. Patients in the gefitinib group had a much lower degree of hyperplasia of the biliary epithelium, submucosal glands and collagen fibers compared with those in the control group. Gefitinib treatment significantly decreased mucin 3 expression and β-glucuronidase activity.CONCLUSION： Postoperative gefitinib treatment could significantly inhibit PC-mediated hyperplasia and lithogenesis, which might provide a novel strategy for the prevention of biliary restenosis and stone recurrence in patients with hepatolithiasis.

关 键 词：hepatolithiasis proliferative cholangitis epidermal growth factor receptor blockade recurrence restenosis prevention 

分 类 号：R575.7[医药卫生—消化系统]