Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma

Abstract

Background and Aim: Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones. Methods: Patients with gallstone disease (n = 958 677) and age-matched and sex-matched controls (n = 9 586 770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones. Results: Patients with gallstones showed increased risks of CCA (1.80, 1.67-1.93) and HCC (1.03, 1.00-1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76-2.14) and HCC (0.93, 0.87-0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89-6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43-4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls. Conclusion:The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.

Cholecystectomy and risk of liver disease: a systematic review and meta-analysis of 27 million individuals

“…After examining the full text of these 33 potentially eligible studies, 13 studies were excluded because of the following reasons: no outcome of interest was reported ( n =3), the risk of cancer was shown with a standardized incidence ratio (SIR) instead of OR, HR, or RR ( n =4), or study populations overlapped ( n =6). Finally, 20 studies 17 – 36 were included in the meta-analysis consisting of 13 cohort studies 17 – 20 , 22 , 24 – 26 , 28 , 29 , 32 , 33 , 36 , 3 matched case–control studies 30 , 31 , 34 , and 4 cross-section studies 21 , 23 , 27 , 35 . The results of the literature research and study selection are detailed in Figure 1 .…”

“…Half of the studies included in this meta-analysis were conducted in Asia ( n = 10), whereas 8 studies were carried out in the United States, and two studies were carried out in Europe. Of the 20 studies, 7 studies 18 , 21 – 24 , 27 , 33 evaluated the association between cholecystectomy and NAFLD, 3 studies evaluated cirrhosis 26 , 29 , 35 , and 11 studies 17 , 19 , 20 , 25 , 28 – 32 , 34 , 36 evaluated PLC [3 studies 17 , 29 , 30 evaluated the hepatocellular carcinoma (HCC), 3 studies 17 , 31 , 34 evaluated the intrahepatic cholangiocarcinoma (ICC), and 6 studies 19 , 20 , 25 , 28 , 32 , 36 did not distinguish HCC and ICC]. The majority of studies 17 – 20 , 22 , 24 – 26 , 28 – 34 , 36 included in this meta-analysis were of high quality.…”

“…Twenty studies 17 – 36 provided data suitable for the pooled primary analysis, involving a total of 27 320 709 individuals with 282 670 liver disease cases. The cholecystectomy was associated with a moderately increased risk of liver disease (OR: 1.63, 95% CI: 1.34–1.98) with considerable heterogeneity ( I 2 =96.7%, P <0.0001) (Fig.…”

“…Eleven studies 17 , 19 , 20 , 25 , 28 – 32 , 34 , 36 provided data suitable for the pooled primary analysis, involving a total of 12 722 890 individuals with 48 736 PLC cases. The cholecystectomy was associated with a 46% increased risk of PLC (OR: 1.46, 95% CI: 1.18–1.82, I ²=88.9%, P <0.0001) (Fig.…”

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management

“…A recent systemic review [ 41 ] showed that CCY was associated with a significant 54% increase in the risk of cholangiocarcinoma, especially in the ECC, in comparison with healthy controls. The updated study, which focused on complicated gallstone disease patients, showed that CCY slightly decreased cholangiocarcinoma risk [ 42 ], but this study still used age-matched and sex-matched controls without further detailed confounding factors adjustments. The problems of heterogenous disease severity and inflammatory conditions due to cholelithiasis in the CCY group and in the pure gallstone disease group/normal population existed in almost all previous articles.…”