Low-dose ursodeoxycholic acid prolongs cholesterol nucleation time in gallbladder bile of patients with cholesterol gallstones

The high rate of stone recurrence represents a drawback of non-surgical therapy of cholesterol gallstone disease. Although most studies report that long-term bile acid treatment does not have protective effects, preliminary results suggest that low-dose ursodeoxycholic acid decreases the rate of gallstone recurrence in a subgroup of younger patients. To clarify the underlying mechanism we investigated whether low-dose ursodeoxycholic acid treatment influences biliary cholesterol saturation and/or nucleation time of cholesterol. Ten patients with cholesterol gallstones and functioning gallbladder received 250 mg ursodeoxycholic acid/day at bedtime 6–10 days prior to cholecystectomy. Eleven patients with cholesterol gallstones without treatment served as controls. Cholesterol crystals were present in the gallbladder bile of 7 out of the 10 patients receiving ursodeoxycholic acid and in all control biles. Ursodeoxycholic acid treatment significantly (P < 0.02) decreased the cholesterol saturation index (mean ± S.E.: 0.94 ± 0.05 vs. 1.43 ± 0.18) and led to an approximately 5-fold prolongation (P < 0.005) of the cholesterol nucleation time (mean ± S.E.: 12.0 ± 2,4 vs. 2.3 ± 0.7 days). We conclude that lowdose ursodeoxycholic acid might be effective in the prevention of post-dissolution gallstone recurrence by both decreasing cholesterol saturation and prolonging cholesterol nucieation tim

Effect of phospholipids and bile acids on cholesterol nucleation time and vesicular/micellar cholesterol in gallbladder bile of patients with cholesterol stones

Supersaturation and rapid nucleation of cholesterol in bile are of key importance in the pathogenesis of cholesterol gallstones. While the effects of bile acids and phospholipids on cholesterol saturation of bile have been extensively studied, their influence on the cholesterol nucleation time has not been compared. We, therefore, investigated whether increases of bile acid or phospholipid concentrations in bile by in vitro supplementation affect the cholesterol nucleation time. Bile samples were obtained at surgery from patients with cholesterol gallstones. Prior to the nucleation assay the bile samples were divided into 0.5-ml aliquots and supplemented with 1.25, 2.5, 5.0, and 10.0 mumol/ml of different phosphatidylcholines (PC-dimyristoyl, PC- dipalmitoyl, PC-distearoyl, and extracted biliary PCs) or with 5.0, 10.0, and 20.0 mumol/ml of bile acids (glycine or taurine conjugates of cholic acid, deoxycholic acid, or chenodeoxycholic acid). The increase of phosphatidylcholine or bile acid concentration decreased the mean cholesterol saturation index to a similar extent (PC: 0.1-0.3; BA: 0.1- 0.2). Supplementations of bile with increasing amounts of synthetic or biliary PCs caused a marked prolongation of the nucleation time in bile from 1.5 +/- 0.2 up to > or = 21 days or 2.5 +/- 0.7 up to > or = 21 days. Concurrently, biliary cholesterol was shifted from vesicles to mixed micelles and the cholesterol/phospholipid ratio of the remaining vesicles was progressively lowered. In contrast, the addition of bile acids to gallbladder bile did not affect the cholesterol nucleation time (2.2 +/- 0.3 days), the percentage of vesicular cholesterol, or the cholesterol/phospholipid ratio of vesicles and micelles

Ascitic fluid analysis for the differentiation of malignancy related and nonmalignant ascites

The authors tried to differentiate malignancy-related from nonmalignant ascites with a sequence of sensitive followed by specific ascitic-fluid parameters. There were four results of this study. First, of nine parameters investigated in a first series of 48 patients, 28 with nonmalignant and 20 with malignancy-related ascites, ascitic-fluid cholesterol and fibronectin yielded the best negative predictive value of 92% each. Carcinoembryonic antigen (CEA) and cytologic examination both showed a positive predictive value of 100%. Second, combining cytologic examination (sensitivity, 70%) and CEA determination (sensitivity, 45%) increased the sensitivity to 80%. Third, cytologic findings were negative in all ascitic-fluid samples with a cholesterol concentration below the cutoff value of 45 mg/100 ml. Fourth, based on the results of the first series of 48 patients, the diagnostic sequence with cholesterol as a sensitive parameter, followed by the combination of cytologic examination and CEA determination as specific parameters, was tested in a second series of 71 patients, 37 with nonmalignant and 34 with malignancy-related ascites. Again cytologic examination was negative in all samples with cholesterol levels below 45 mg/100 ml. In the total of 119 patients, this diagnostic sequence did not identify 9% of patients with malignancy-related ascites, and 82% of samples classified as malignancy related by cholesterol levels above 45 mg/100 ml were confirmed by positive cytologic examination and/or CEA level above 2.5 ng/ml. Thus, a diagnostic sequence with ascitic-fluid cholesterol determination, followed by cytologic examination and CEA determination, in samples with cholesterol levels above 45 mg/100 ml should permit a cost-efficient routine differentiation of malignancy-related from nonmalignant ascites