Cholelithiasis and the risk of intrahepatic cholangiocarcinoma: a meta-analysis of observational studies

Abstract

BackgroundThe 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.MethodsPubMed, 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.ResultsSeven 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 %).ConclusionsBile duct stones including choledocholithiasis are important risk factors for ICC. Careful surveillance of patients with extrahepatic biliary tree stone should be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1870-0) contains supplementary material, which is available to authorized users.

Epidemiology and Risk Factors of Cholangiocarcinoma

“…To date, there is no consensus on whether choledocholithiasis or cholecystolithiasis also contribute to IH-CCA development. However, a recent meta-analysis of seven case-control studies including altogether 123,771 participants suggests that the presence of choledocholithiasis alone in the absence of hepatolithiasis is associated with a high risk of IH-CCA, whereas the evidence for cholecystolithiasis was less clear and pronounced [43]. Subgroup analysis indicates that the cancer risk was lower for choledocholithiasis alone than for choledocholithiasis accompanied by hepatolithiasis.…”

A novel nomogram for the prediction of intrahepatic cholangiocarcinoma in patients with intrahepatic lithiasis complicated by imagiologically diagnosed mass

“…Until now, the reason underlying this higher incidence has remained unclear; however, a contributing factor to this difference appears to be intrahepatic lithiasis (IHL), which has been reported to be more frequently observed in Southeast Asia than in Western countries. 6 , 7 The incidence of IHL in Western countries has also increased with the continuous influx of Asian immigrants to these countries. In fact, IHL has been well documented as a high-risk state for ICC.…”

Liver transplantation for hepatolithiasis: Is terminal hepatolithiasis suitable for liver transplantation?

“…However, the coexistence of hepatolithiasis and cholangiocarcinoma makes a correct preoperative diagnosis particularly difficult. The early diagnosis may be delayed so easily because the symptoms related to cholangiocarcinoma are vague and uncharacteristic and are almost similar to those of hepatolithiasis . Some studies proved that preoperative detection of CA199 and/or serum CEA (carcino‐embryonic antigen) might be valuable in survey of ongoing cholangiocarcinoma in patients with hepatolithiasis , , .…”