The aim of the study was to evaluate the metabolism of individual bile acids in patients with cholesterol gallstone disease. Therefore, we determined pool size and turnover of deoxycholic (DCA), cholic (CA), and chenodeoxycholic acid (CDCA) in 23 female gallstone patients classified according to their gallbladder function and in 15 healthy female controls. Gallstone patients had normal hepatic bile acid synthesis, but, depending on gallbladder function, differed with respect to turnover and size of the bile acid pools: Patients with well-emptying gallbladder (group A, n = 9) had enhanced turnover and reduced pools of CA (-46%; P < 0.01 vs. controls) and CDCA (-24%; P < 0.05), but normal input and size of the DCA pool. With reduced gallbladder emptying (< 50% of volume; group B, n = 6), turnover and pools of CA, CDCA, and DCA were similar as in controls. Patients with loss ofgallbladder reservoir (group C, n = 8) had increased input (+100%; P < 0.01) and pool size of DCA (+45%; P = 0.07) caused by rapid conversion of CA to DCA, while the pools of CA (-71%; P < 0.001 vs. controls) and CDCA (-36%; P < 0.05) were reduced by enhanced turnover. Thus, in patients with cholesterol gallstones, the pools of primary bile acids are diminished, unless gallbladder emptying is reduced. Furthermore, in a subgroup of gallstone patients, who had completely lost gallbladder function, the CA pool is largely replaced by DCA owing to rapid transfer of CA to the DCA pool. This probably contributes to supersaturation of bile with cholesterol. (J. Clin. Invest. 1992. 90:859-868.) Key words: bile acid metabolism * cholesterol gallstone disease * deoxycholic acid -gallbladder emptying . cholesterol saturation of bile IntroductionIn most nonobese patients with cholesterol gallstones, the pools of cholic acid (CA)' and chenodeoxycholic (CDCA) are reduced ( 1-6), and deoxycholic acid (DCA) is often increased in bile (7). Both changes could contribute to supersaturation of bile with cholesterol ( 1, 7, 1. Abbreviations used in this paper: CA, cholic acid; CCK, cholecystokinin; CDCA, chenodeoxycholic acid; DCA, deoxycholic acid; FTR, fractional turnover rate. circulation (9), the increase ofDCA by raising biliary secretion of cholesterol ( 10).The small pools ofCA and CDCA may be caused by a small gallbladder reservoir ( 1 1), by enhanced turnover (2, 5), or by inhibition of bile acid synthesis by an oversensitive feedback mechanism ( 1 2) or by elevated levels of DCA ( 13,14). An increased fraction ofDCA in bile could be caused by high input and large pool size of DCA. CA is nearly completely 7a-dehydroxylated to DCA by anaerobic bacteria in the colon (7,15,16), but only 30-40% of this DCA is absorbed from the intestine ( 17 ). The DCA pool could be expanded by increased input of DCA owing to increased synthesis ofthe precursor CA or to an increased fraction of CA transferred to the DCA pool.It is still unclear which of the above factors account(s) for the reduction in CA and CDCA pool size and which for an increase in biliary DCA. ...

Removal of the gallbladder is thought to increase formation and pool size of secondary bile acids, mainly deoxycholic acid (DCA), by increased exposure of primary bile acids (cholic acid ICA], chenodeoxycholic acid [CDCAJ) to bacterial dehydroxylation in the intestine. We have tested this hypothesis by simultaneous determination of pool size and turnover of DCA, CA, and CDCA in nine women before and at various intervals after removal of a functioning gallbladder. An isotope dilution technique using marker bile acids labeled with stable isotopes (2H4Dl)CA, 13C-CA, 13C-CDCA) was used. After cholecystectomy, concentration and output of bile acids relative to bilirubin increased (P < 0.02) in fasting duodenal bile and cholesterol saturation decreased by 27% (P < 0.05) consistent with enhanced enterohepatic cycling of bile acids. Three months after removal of the gallbladder bile acid kinetics were in a new steady state: pool size and turnover of CDCA were unchanged. Synthesis of CA, the precursor of DCA, was diminished by 37% (P = 0.05), probably resulting from feedback inhibition by continuous transhepatic flux of bile acids. The fraction of CA transferred after 7a-dehydroxylation to the DCA pool increased from 46±16 to 66±32% (P < 0.05). However, this enhanced transfer did not lead to increased input or size of the DCA pool, because synthesis of the precursor CA had decreased.

Aneurysms of the extracranial carotid artery represent a serious disease because of possible cerebral embolism and aneurysm rupture. Between 1960 and 1979, 28 aneurysms of the extracranial carotid artery were seen in 27 patients at our institution. Twenty-six of these patients noticed a pulsating tumor, 12 patients had neurological symptoms; 2 aneurysms were ruptured. Five times the external carotid artery, and 3 times the internal carotid artery were ligated without neurological symptoms. After aneurysm resection, the carotid artery was reconstructed in 4 cases by direct suture, and in 2 cases by patch angioplasty. Reconstruction was accomplished with a tube-graft in 9 instances, once an extra-intracranial shunt had to be performed in advance. Two patients developed neurological deficiencies after the operation (8.7%), in one of them these were permanent. In the follow-up, 20 patients were without symptoms (87%), 3 patients died after the operation (peri-operative mortality 13%). Out of the 5 non-operated patients 2 died after a short time: one of an acute myocardial infarction and one of an extensive cerebro-vascular infarction. Two patients with asymptomatic internal carotid aneurysm refused the operation and are without symptoms for 2 and 40 years respectively. Because of the potential risks of cerebro-vascular infarction and aneurysm rupture, good results of operative treatment call for an aggressive surgical approach in dealing with extracranial carotid aneurysms.

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined.The cholesterol nucleation time was significantly (p < 0.01) longer in the bile from patients with solitary stones ( < 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones ( < 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal ( > 4 days) nucleation time.However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 2 0.65 vs. 1.54 -+ 0.59, mean 2 S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones. (HEPATOLOGY 1992; 15:804-808.)The recurrence of cholesterol gallstones, like primary gallbladder stone formation, probably involves a triple defect with cholesterol supersaturation, abnormally

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