title: Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up.
  
  
  METHODS
  A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs).
  
  
  RESULTS
  Among the 192,960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345,251 people and 4,854,969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively).
  
  
  CONCLUSIONS
  Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy.
authors.affiliation: Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. helena.nordenstedt@ki.se
authors.forename: H
authors.initials: H
authors.lastname: Nordenstedt
authors.forename: F
authors.initials: F
authors.lastname: Mattsson
authors.forename: H
authors.initials: H
authors.lastname: El-Serag
authors.forename: J
authors.initials: J
authors.lastname: Lagergren
mesh_terms: D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D017734:Bile Ducts, Extrahepatic; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D002763:Cholecystectomy; D015331:Cohort Studies; D005260:Female; D042882:Gallstones / Q000150:complications* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology