Hepatolithiasis is a very common hepatobiliary disease in Asia. Recurrent hepatolithiasis frequently lead to incidence of intrahepatic cholangiocarcinoma. The associated intrahepatic cholangiocarci-noma is generally hidden and often covered up by the related clinical symptoms caused by stones, which can easily lead to missed the best time of diagnosisand treatment. This paper mainly showed the diseases of intra-hepatic cholangiocarcinoma associated with intrahepatic cholelithiasis, and expounded the changes of local microenvironment of bile duct tissue from intrahepatic cholelithiasis to intrahepatic cholangiocarcinoma. The purpose of this study is to look for the risk factors related to the development of intrahepatic cholelithiasis to intrahepatic cholangiocarcinoma and to provide a new research direction for the clinical treatment of intrahe-patic cholangiocarcinoma.

Objective To investigate the expressions and the significance among the three markers TGF β1,Survivin and Caspase-3 in intrahepatic bile duct tissues in patients with intrahepatic bile duct stones.Method Total of 130 paraffin section of intrahepatic bile duct tissue were collected at Department of Pathology,The 904th Hospital of Joint Logistic Support Force of PLA from 2013 to 2018.Total of 50 patients with intrahepatic bile duct stones complicated with bile duct strictures (the stenosis group),40 patients with intrahepatic bile duct stones with chronic inflammation (the inflammation group),and 40 patients with normal liver tissues (the normal control group) were included in this study.The expressions of TGF β1,Survivin and Caspase-3 in liver tissues were detected by immunohistochemistry and compared among the 3 groups to find their correlations with the clinicopathological features of the disease of the patients.Results TGF β1 was expressed in 72.0％ of the patients in the stenosis group,37.5％ in the inflammatory group,and 15.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Survivin was expressed in 78.0％ of the patients in the stenosis group,47.5％ in the inflammatory group,and 25.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05);Caspase-3 was expressed in 10.0％ of the patients in the stenosis group,42.5％ in the inflammatory group,and 75.0％ in the normal control group.The differences among the groups were significant (P ＜ 0.05).Within the stenosis group,TGF β1 was negatively correlated with Caspase-3 (r =-0.882,P ＜ 0.05),and positively correlated with Survivin (r =0.889,P ＜ 0.05).Survivin and Caspase-3 were also negatively correlated (r=-0.923,P＜0.05).Conclusion Abnormal expressions of TGF β1,Survivin and Caspase-3 were involved in the formation of intrahepatic bile duct stones associated with bile duct strictures.