Article

Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma

Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
British Journal of Cancer (Impact Factor: 4.84). 02/2012; 106(5):1011-5. DOI: 10.1038/bjc.2011.607
Source: PubMed

ABSTRACT

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.
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).
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).
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.

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Available from: Jesper Lagergren, Jan 24, 2014
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    • "Nordenstedt et al. conducted a cohort study on the association between cholecystolithiasis and the risk of ICC in a Swedish population. However, patients who had both cholecystolithiasis and bile duct stones were not eliminated, so this study was excluded from our analysis [14] . Wu et al. reported a correlation between cholelithiasis and the risk of ICC, but their study was also excluded from our meta-analysis owing to the lack of detailed information on choledocholithiasis or cholecystolithiasis alone [15]. "
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    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 (I2 = 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.
    Full-text · Article · Dec 2015 · BMC Cancer
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    • "Gallstones might induce biliary inflammation and cholecystectomy is typically followed by dilation of the bile ducts (Hussain, 2013), which might also cause inflammation and thereby possibly increase the risk of CCCs. Previous studies addressing gallstones or cholecystectomy in relation to extrahepatic CCCs have revealed contradictory results, and there are potential associations with intrahepatic CCCs (Nordenstedt et al., 2012). "
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    ABSTRACT: Gallstone disease is a major surgical problem in many populations; it is probably related to diet, especially excessive consumption of meat. The objective of this study was to determine the chemical composition of gallstones and their association with neoplastic changes including cholangiocarcinomas in cholecystectomised patients. The chemical composition of gallstones from 40 patients (8 males and 32 females) was analyzed. This is a prospective study performed in Baquba teaching hospital in the period from 1/10/2012 to 1/1/2013 in which we collected the gallstones for the patients who underwent cholecystectomy, whether open or laparoscopic. The stones were classified according to their chemical composition as a mixed stones (MS), and examined using a stone analysis set (chemical qualitative method) for calcium, magnesium, phosphate, uric acid and oxalate which was used reagent for qualitative determination of main individual components of stones. The results of this study showed the highest incidence of gallstones in the age group 40-49 was 13 cases followed by 11, 8 and 4 cases for age groups 30-39, 50-59, 20-29 and 60 and above, respectively. The chemical analysis showed the majority of gallstones were mixed, 38 containing calcium followed by 37 cases with uric acid, 28 with magnesium, and 25 and 22 stones with oxalate and phosphate, respectively. Microscopically, we confirmed neoplastic changes (17.5%) as cholangiocarcinomas (CCCs) (7.55%) and dysplastic cells of carcinoma in situ in 4 (10%), 31 (77.5%) cases were chronic cholecystitis and 2 (5%) cases were acute cholecystitis with empyema out of bile duct disorders patients. In conclusion, majority of cases had mixed gallstones that involved five and four of inorganic chemicals of calcium, magnesium and phosphate, the highest incidence of gallstones in age group 40-49 years old was 13 cases, and neoplastic changes were confirmed (17.5%) including CCCs, (7.5%) and dysplastic cells of carcinoma in situ (10%), while 31 (77.5%) cases were chronic cholecystitis.
    Full-text · Dataset · Apr 2014
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    • "Gallstones might induce biliary inflammation and cholecystectomy is typically followed by dilation of the bile ducts (Hussain, 2013), which might also cause inflammation and thereby possibly increase the risk of CCCs. Previous studies addressing gallstones or cholecystectomy in relation to extrahepatic CCCs have revealed contradictory results, and there are potential associations with intrahepatic CCCs (Nordenstedt et al., 2012). "

    Full-text · Dataset · Mar 2014
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