title: Cholelithiasis and the risk of intrahepatic cholangiocarcinoma: a meta-analysis of observational studies.
abstract: BACKGROUND
  The etiological factor for intrahepatic cholangiocarcinoma (ICC) is not clear. Although it has been widely accepted that intrahepatic biliary tree stone is associated with increased risk of ICC, the role of extrahepatic biliary tree stone in the incidence of ICC is controversial. In the present study we aim to evaluate the association between pre-existing choledocholithiasis and cholecystolithiasis and the risk of ICC.
  
  
  METHODS
  PubMed, Embase, and Web of Science were searched to identify cohort and case-control studies on the association between choledocholithiasis or cholecystolithiasis and the risk of ICC. Studies that met the inclusion criteria were subjected to a meta-analysis performed with Stata statistical software. Either a fixed or random effect model was used, depending on the heterogeneity within the studies. Egger's test was performed to assess publication bias.
  
  
  RESULTS
  Seven case-control studies met our inclusion criteria. Of the 123,771 participants, 4763 (3.85 %) were patients with ICC, and 119,008 were tumor-free controls. The presence of pre-existing bile duct stones (choledocholithiasis alone or choledocholithiasis accompanied by hepatolithiasis) was associated with the risk of ICC (odds ratio [OR] 17.64, 95 % confidence interval [CI] 11.14-27.95). Even the presence of choledocholithiasis alone (in the absence of hepatolithiasis) was associated with a high risk of ICC (OR 11.79, 95 % CI 4.17-33.35). Cholecystolithiasis may possibly contributed to the incidence of ICC (OR 2.00, 95 % CI 1.16-3.42), with large heterogeneity within studies (I (2) = 78.5 %).
  
  
  CONCLUSIONS
  Bile duct stones including choledocholithiasis are important risk factors for ICC. Careful surveillance of patients with extrahepatic biliary tree stone should be considered.
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China. doctortsai@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Ultrasound, Zhongshan Hospital Fudan University, Shanghai, 200032, China. breezewen@163.com.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Kong
authors.affiliation: Department of General Surgery, Wuxi Xishan People's Hospital, Wuxi, Jiangsu Province, 214011, China. bobo-chen@163.com.
authors.forename: Chao-Bo
authors.initials: CB
authors.lastname: Chen
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shi.guoming@zs-hospital.sh.cn.
authors.forename: Guo-Ming
authors.initials: GM
authors.lastname: Shi
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China. huang.cheng@zs-hospital.sh.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China. shen.yinghao@zs-hospital.sh.cn.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Shen
authors.affiliation: Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, 200032, China. sun.huichuan@zs-hospital.sh.cn.
authors.forename: Hui-Chuan
authors.initials: HC
authors.lastname: Sun
mesh_terms: D001650:Bile Duct Neoplasms / Q000453:epidemiology / Q000473:pathology*; D001652:Bile Ducts / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000453:epidemiology / Q000209:etiology / Q000473:pathology*; D002769:Cholelithiasis / Q000150:complications / Q000473:pathology*; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000473:pathology; D012307:Risk Factors