Bile Acid Analysis in Biliary Tract Cancer

Abstract

The etiology of biliary tract cancer is obscure, but there are evidences that bile acid plays a role in carcinogenesis. To find the association between biliary tract cancer and bile acid, this study compared the bile acid concentration and composition among patients with biliary cancer, biliary tract stones, and no biliary disease. Bile was compared among patients with biliary tract cancer (n = 26), biliary tract stones (n = 29), and disease free controls (n = 9). Samples were obtained by percutaneous transhepatic biliary drainage, endoscopic nasobiliary drainage, or gallbladder puncture, and analyzed for cholic, deoxycholic, chenodeoxycholic, lithocholic, and ursodeoxycholic acid composition. Total bile acid concentration was lower in the cancer group than the biliary stone and control groups; the proportions of deoxycholic (2.2% vs. 10.2% and 23.6%, p < 0.001 and p < 0.001, respectively) and lithocholic acid (0.3% vs. 0.6% and 1.0%, p = 0.065 and p < 0.001, respectively) were also lower. This result was similar when disease site was limited to bile duct or gallbladder. Analysis of cases with bilirubin ≤ 2.0 mg/dL also showed lower total bile acid concentration and deoxycholic acid composition in the cancer group compared to controls (5.7% vs. 23.6%, p = 0.003). Although the presence of bile duct obstruction explains some of the difference in total concentration and composition of bile acid, there are other contributing mechanisms. We suspect the alteration of bile acid transport might decrease bile acid excretion and cause the accumulation of carcinogenic bile acid in bile duct epithelium.

Ability of Biochemical Parameters to Distinguish between Bile Duct Cancer and Gall Bladder Stones - A Case Control Study in a Tertiary Care Hospital of Pokhara Valley

“…The serum total bilirubin showed a marked difference for bile duct cancer (7.6±3.2 mg/dl) when compared to gall stone formation (2.5±0.8 mg/dl) as there was severe obstruction in cancer cases (p: 0.0001*). The study done by park also showed similar results (Park et al, 2006). In both cancer and stone cases, mildly raised AST and ALT suggested the very less injury to hepatocytes.…”

Increased expression of LXRα, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients

“…The increased levels of deoxycholic acid in the bile of these patients might be related to their disease, because an increase in deoxycholic acid has been described to be associated with an enhanced induction of gallbladder polyps in hamsters (39). However, in Asian subjects, a higher level of deoxycholic acid in healthy liver transplant donors has also been reported, suggesting that differences in biliary bile acid composition may exist between control groups of different ethnicity (40). In the Chilean study (38), the majority of the patients enrolled in the reference group underwent surgical procedures because of gastrointestinal cancer.…”

UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry

“…GDCA was reported to play an important role in the detoxification of lipophilic compounds [49]. Decreased serum bile acids have been related to the accumulation of toxic and even carcinogenic bile acid in liver that may be caused by the alteration in the bile acid transport pathway [50]. GCDCA has been reported as an inducer of apoptosis in human hepatocyte [51].…”