Background: Endoscopic extraction of bile duct stones after sphincterotomy has a success rate of up to 95%. Failures occur in patients with extremely large stones, intrahepatic stones, and bile duct ...strictures. This study examined the efficacy and the safety of extracorporeal shock-wave lithotripsy in a large cohort of patients in whom routine endoscopic measures including mechanical lithotripsy had failed to extract bile duct stones. Methods: Out of 1587 consecutive patients, endoscopic stone extraction including mechanical lithotripsy was unsuccessful in 313 (20%). These 313 patients (64% women, median age, 73 years) underwent high-energy extracorporeal shock-wave lithotripsy. Stone targeting was performed fluoroscopically (99%) or by ultrasonography (1%). Results: Complete clearance of bile duct calculi was achieved in 281 (90%) patients. In 80% of the patients, the fragments were extracted endoscopically after shock-wave therapy; spontaneous passage was observed in 10%. For patients with complete clearance compared with those without there were no differences with regard to size or number of the stones, intrahepatic or extrahepatic stone location, presence or absence of bile duct strictures, or type of lithotripter. Cholangitis (n = 4) and acute cholecystitis (n = 1) were the rare adverse effects. Conclusions: In patients with bile duct calculi that are difficult to extract endoscopically, high-energy extracorporeal shock-wave lithotripsy is a safe and effective therapy regardless of stone size, stone location, or the presence of bile duct stricture. (Gastrointest Endosc 2001;53:27-32.)
Bile acid malabsorption has been supposed to play a major pathogenetic role in postcholecystectomy diarrhea. Therefore, the aim of this study was to define the effect of cholecystectomy (CHE) on ...bowel habits and bile acid absorption.
Fifty-one patients were prospectively studied before, at 4 wk, and 12 wk after elective CHE for changes of bowel habits, occurrence of diarrhea, and signs of bile acid malabsorption. Bowel habits were assessed by interview. Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one were used as a marker of bile acid malabsorption. Statistics were performed with the McNemar chi2 test for discrete values and Student's paired t test for continuous values.
After CHE, there was an increase of patients reporting more than one bowel movement per day (from 22% before CHE to 51% p < 0.001 and 45% p < 0.005 at 1 month and 3 months after CHE, respectively) and of patients reporting loose stools (from 2% to 47% p < 0.001 and 33% p < 0.001, respectively). Three months after CHE, three patients (6%) reported intermittent diarrhea. Serum levels of 7alpha-hydroxy-4-cholesten-3-one increased from 25.4+/-14.5 ng/ml to 46.5+/-29.5 ng/ml (p < 0.001) and 52.5+/-33.0 ng/ml (p < 0.001), respectively. Unexpectedly, changes of 7alpha-hydroxy-4-cholesten-3-one in serum were unrelated to changes of bowel habits.
CHE results in considerable changes of bowel habits and an increased loss of bile acids from the intestine in some patients. Bile acid malabsorption, however, may not explain changes of bowel habits after CHE.
Twenty years ago, in January 1985, extracorporeal shock wave lithotripsy (ESWL) was first applied successfully in a patient with gallbladder stones. In the following years, the conditions which ...influence the success rate of ESWL have been extensively investigated. It was shown that the characteristics of the stones, gallbladder emptying and the degree of stone fragmentation are the most important factors which determine the clearance of all fragments from the gallbladder after ESWL. Severe side effects, such as biliary pancreatitis and liver haematoma, were found to be rare and no deaths related to the procedure have been reported. One or more episodes of biliary pain were observed in about one third of patients within the first 3-4 months after ESWL. Follow-up studies after successful treatment, however, have shown that stone recurrence is considerable, limiting the use of ESWL as a non-invasive therapeutic option. Stone recurrence varies between different subgroups of patients indicating that gallbladder motor function and other less well defined factors may be of importance. The recurrence of stones after ESWL is one of the reasons why laparoscopic cholecystectomy has become the standard treatment of symptomatic gallbladder stones today. ESWL has kept its role only in the treatment of bile duct stones resistant to endoscopic extraction. Unless stone recurrence can be decreased by better patient selection and/or other measures to prevent gallstone recurrence, ESWL of gallbladder stones has little chance of surviving.
Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary ...cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding.
UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis.
Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment (p < 0.05).
UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.
To evaluate the usefulness of 7a-hydroxy-4-cholesten-3-one (HCO) serum concentrations as a diagnostic marker of bile acid malabsorption, we determined the reference range of HCO in 106 normal ...subjects (age 40.2+/-16.8 years; 55 women, 51 men) and conducted a utility study in 23 patients with chronic diarrhea of unknown origin (age 49.4+/-15.3 years, 13 women, 10 men). The diagnosis of bile acid malabsorption was made on the basis of a decreased retention of 75Sehomocholyltaurine after oral application (75SeHCAT test). HCO (reference range: 6-48 ng/ml) and the 75SeHCAT test yielded the same results in 19/23 (83%) patients. Bile acid malabsorption was identified by an increase of HCO in serum with a sensitivity of 90% and a specificity of 79%. Analysis of HCO in serum may serve as a novel, simple, and sensitive method for the detection of bile acid malabsorption in patients with chronic diarrhea of unknown origin.
The interaction of the muscarinic agonist carbachol and of dibutyryl cAMP on acid secretion and phosphoinositide second messenger metabolism were studied in rat gastric parietal cells. Compared to ...the added effects of each agonist alone aminopyrine uptake, a measure of acid secretion, was enhanced 2-4-fold by the combination of both compounds. In addition the ED50 for carbachol was left shifted in the presence of dibutyryl-cAMP. The cholinergic stimulation of inositol phosphate production was slightly inhibited by dibutyryl-cAMP while levels of diacylglycerol were not affected. Thus the interaction of the cAMP and the phosphoinositide systems involve potentiation and positive sensitivity modulation of the cholinergic response by cAMP which is mediated by events distal to the generation of phosphoinositide second messengers.
It has been suggested that chenodeoxycholic acid is preferentially formed by the alternative or ‘acidic’ pathway of bile acid biosynthesis starting with 27-hydroxylation of cholesterol, while cholic ...acid is derived from 7α-hydroxycholesterol which initiates the ‘neutral’ pathway. We have studied bile acid formation from each of these precursors using human hepatocytes cultured in a novel sandwich collagen configuration. Culture supernatants were analyzed using capillary gas chromatography and gas chromatography-mass spectrometry. 27-Hydroxycholesterol and 7α-hydroxycholesterol were both found to be efficiently converted to cholic acid as well as chenodeoxycholic acid. Analysis of acidic intermediates after addition of 7α-hydroxycholesterol to the cultures revealed a significant increase of side-chain oxygenated C
24- and C
27-steroids with a 3-oxo-7α-hydroxy-Δ4-ring structure. These data indicate that (i) the ‘neutral’ pathway is connected to the ‘acidic’ pathway by side-chain oxidation of C
27-steroids with a 3-oxo-7α-hydroxy-Δ4-ring structure and that (ii) the relative formation of cholic acid and chenodeoxycholic acid is regulated by metabolic events distal to the initial hydroxylation at either position 7 or position 27 of the cholesterol molecule.
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