Mucin in gall bladder bile of gall stone patients: influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid.

The concentration of hexosamine, a marker for mucin, was determined and related to the degree of cholesterol saturation and to the occurrence of cholesterol crystals in gall bladder bile of gall stone patients (n = 40) and gall stone free subjects (n = 25). Ten of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and eight with ursodeoxycholic acid (UDCA) three to four weeks before cholecystectomy. The hexosamine content was significantly higher in gall stone patients (137 (19) ng/ml, mean (SE) than in gall stone free subjects (83 (9) ng/ml, p less than 0.02). Treatment with CDCA or UDCA decreased cholesterol saturation, but did not significantly affect the hexosamine concentration. There was no difference in hexosamine concentration between gall stone patients with and without cholesterol crystals. The results do not support the hypothesis that the degree of cholesterol saturation is important for the mucin content of gall bladder bile in man. Neither do the data indicate that the formation and occurrence of cholesterol crystals in gall bladder bile from gall stone patients is caused by an increased concentration of mucin. As the studies were conducted on patients who had already had gall stones for several years, however, an effect of mucin in the very early stage of gall stone formation cannot be completely excluded.     

Nucleation time of gall bladder bile in gall stone patients: influence of bile acid treatment.

The time required for precipitation of cholesterol crystals (nucleation time, NT) was determined and related to the cholesterol saturation in gall bladder bile of gall stone free subjects (n = 11), patients with pigment stones (n = 3), and patients with cholesterol gall stones (n = 30) undergoing cholecystectomy. Seven of the gall stone patients had been treated with chenodeoxycholic acid (CDCA) and nine with ursodeoxycholic acid (UDCA), 15 mg/kg/day for three weeks before operation. NT was longer in gall stone free subjects (mean, 20 days), patients with pigment stones (14 days) and patients treated with CDCA (24 days) and UDCA (17 days) compared with untreated patients with cholesterol gall stones (1.5 days). In spite of low cholesterol saturation and prolonged NT, and in contrast to those treated with CDCA, four of the nine patients treated with UDCA had cholesterol crystals in their bile. These observations give further support to the concept that the mechanism for inducing gall stone dissolution may be different for CDCA and UDCA.     

Hepatic biliary lipid secretion and gall bladder biliary lipid mass in gall stone patients: effect of ursodeoxycholic acid.

We have carried out overnight measurements of hepatic secretion rate and duodenal output of biliary lipids using a duodenal perfusion technique. We correlated these measurements with the fasting state mass of biliary lipids within the gall bladder on the following morning using a combined nasoduodenal intubation and isotope scanning technique. We studied six gall stone subjects before and during treatment with ursodeoxycholic acid 675 mg/day. Lipid mass within the gall bladder correlated with the corresponding overnight hepatic secretion rate for all three biliary lipids. During ursodeoxycholic acid treatment, there was an increase in gall bladder bile acid mass without significant change in cholesterol or phospholipid mass. We conclude that the mass of individual biliary lipids within the fasting gall bladder is influenced by overnight hepatic biliary lipid secretion rate; and that the effect of ursodeoxycholic acid (675 mg/day) on cholesterol saturation index of fasting gall bladder bile is mediated via an increase in bile acid mass rather than through a decrease in cholesterol mass within the gall bladder.     

Reduced cholesterol metastability of hepatic bile and its further decline in gall bladder bile in patients with cholesterol gall stones.

The reduced metastability of biliary cholesterol in the gall bladder bile of patients with cholesterol gall stones has been well shown. The purpose of this study was to examine the hypothesis that such a difference in metastability already exists in hepatic bile. Paired hepatic and gall bladder bile samples were collected from 10 patients with cholesterol gall stones and six patients without gall stones. Cholesterol nucleation time, biliary lipid concentration, vesicular cholesterol distribution, and biliary protein concentration were measured and compared. The nucleation time in the hepatic bile of patients with cholesterol gall stones was significantly shorter than the gall stone free patients (8.2 (7.2) v 15.7 (5.8) days, p < 0.05), and was associated with a greater concentration of biliary lipid despite the lack of a difference in the cholesterol saturation index (CSI) and total protein concentration. During the storage of bile in the gall bladder, the nucleation time became quicker in the patients with cholesterol gall stone (2.9 (1.7) days) while it was similar in the gall stone free patients (17.3 (5.7) days) compared with that of the corresponding hepatic bile. These differences were associated with a higher CSI (1.44 (0.33) v 1.13 (0.14), p < 0.05) and a greater vesicular cholesterol distribution (19.7 (11.9) v 4.4 (1.4)%, p < 0.01) in the patients with cholesterol gall stones than the gall stone free patients. The concentrations of total lipid and protein in gall bladder bile were not significantly different between the two groups. In conclusion, patients with cholesterol gall stones produce less metastable hepatic bile by the evidence of shorter nucleation time. During the storage of the bile in the gall bladder, the metastability is reduced further only in the cholesterol gall stone patients but not in the gall stone free patients.     

Deoxycholic acid in gall bladder bile does not account for the shortened nucleation time in patients with cholesterol gall stones.

The relations between the concentration of deoxycholic acid (DCA), the cholesterol saturation index, and the nucleation time in gall bladder bile were measured to determine the role of DCA in bile in the pathogenesis of cholesterol gall stone disease. Bile was obtained from patients with cholesterol gall stones (n = 30), subjects without gall stones (n = 35), and patients with pigment gall stones (n = 9). Three of 30 cholesterol gall stone patients and 10 of 35 gall stone free subjects were treated with antibiotics by mouth to decrease the concentration of bile DCA and determine the effect of DCA on biliary lithogenecity. Both the percentage and concentration of DCA in bile were similar in patients with and without cholesterol gall stones despite significant differences in their cholesterol saturation indices and nucleation times. Neither the percentage nor the concentration of DCA in bile correlated with either the cholesterol saturation index or the nucleation time. Analysis of subgroups with matching cholesterol saturation indices showed no correlation between the proportion of DCA in the bile and the cholesterol nucleation time. The proportion of DCA in bile was decreased by antibiotic treatment, but this had no effect on the cholesterol saturation index or nucleation time. These results suggest that DCA in bile is not responsible for biliary cholesterol saturation or cholesterol nucleation time.     

Quantitative and qualitative comparison of gall bladder mucus glycoprotein from patients with and without gall stones.

Human gall bladder mucus glycoprotein was isolated by Sepharose 4B gel filtration followed by caesium chloride density gradient ultracentrifugation from four groups: patients with cholesterol gall stones, patients with pigmented stones, patients with complete obstruction of the cystic duct and patients with no biliary tract abnormalities (controls). Mucus glycoprotein concentrations in cholesterol gall stone bile (203 micrograms/ml +/- 199 SD, n = 17), pigment gall stone bile (110 micrograms/ml +/- 77 SD, n = 6) and control gall bladder bile (96 micrograms/ml +/- 98 SD, n = 11) were not significantly different. While bile from patients with complete obstruction of the cystic duct contained significantly higher concentrations of mucus glycoprotein (6220 micrograms/ml +/- 4130, n = 4). In vitro cholesterol nucleation time was not correlated to gall bladder mucus glycoprotein concentrations. Qualitative analysis of the carbohydrate and amino acid composition showed a basic structure typical of mucus glycoproteins in general. It is unlikely that either quantitative or qualitative differences in mucus glycoproteins are responsible for the rapid in vitro nucleation time characteristic of cholesterol gall stone patients.     

Correlation between gall bladder fasting volume and postprandial emptying in patients with gall stones and healthy controls.

To evaluate whether the extent of postprandial gall bladder emptying is correlated with gall bladder fasting volume, gall bladder motility was studied in 56 patients with cholesterol gall stone and 19 control patients. Gall bladder volumes were determined sonographically, while cholecystokinin plasma values were measured radioimmunologically. Twenty three per cent of gall stone patients were classified as pathological contractors (residual fraction > mean +2SD of controls) and 77% as normal contractors. Normal but not pathological contractor patients exhibited larger gall bladder fasting volumes (mean (SEM)) (24.7 (1.7) ml) than controls (15.3 (1.2) ml, p < 0.001). In normal contractor patients and controls fasting volume was closely related with ejection volume (r = 0.97, p < 0.001) and residual volume (r = 0.80, p < 0.001). Although ejection volume was enlarged in normal contractor patients it did not compensate the increase in fasting volume. Thus, residual volumes were considerably increased not only in pathological contractors (12.7 (2.5) ml, p < 0.001) but also in normal contractor patients (7.0 (0.5) v 4.6 (0.6) ml, p < 0.001). Postprandial cholecystokinin secretion did not differ between patients and controls. It is concluded, that in normal contractor patients gall bladder fasting volume is closely correlated with ejection and residual volume. Thus, fasting volume may be an essential factor affecting postprandial gall bladder emptying. Large fasting volumes in cholesterol gall stone disease could thereby contribute to bile retention, which facilitates gall stone growth.     

Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly.

Octreotide therapy in acromegaly is associated with an increased prevalence of gall stones, which may be the result of an inhibition of gall bladder motility. Gall stone prevalence in untreated acromegalic patients relative to the general population is unknown, however, and the presence of gall stones and gall bladder motility in these patients and in acromegalic patients receiving octreotide was therefore examined. Thirty four percent of 39 patients who had taken octreotide for a mean of 20 months had gall stones compared with 16% of 38 patients who had not been treated with octreotide (p < 0.005). In a subgroup of 21 patients studied prospectively over 4 to 18 months, two patients developed stones. No patient had symptoms referrable to their gall stones. In 31 untreated acromegalic patients, the mean fasting gall bladder volume was similar to that in normal subjects. Maximal percentage emptying, however, was impaired (34 v 64%, p < 0.001) and the mean postprandial residual gall bladder volume increased (21.7 v 9.0 ml, p < 0.001). Treatment with octreotide increased the mean postprandial residual volume further to 36.8 ml (p < 0.001). Gall bladder emptying in untreated acromegalic subjects is impaired. Octreotide further increases postprandial residual gall bladder volume and this may be a factor in the increased gall stone prevalence seen in these patients.     

Mucus glycoprotein biosynthesis in the human gall bladder: inhibition by aspirin.

Aspirin, which inhibits mucin secretion in the gastrointestinal tract prevents gall stone formation in animals and may reduce gall stone recurrence in man. This study examines the effect of aspirin on mucin synthesis in human gall bladder explants. Two hundred explants were cultured with 3H-glucosamine (74 kBq/ml) for 24 hours at 37 degrees C. Mucin and other glycoproteins were isolated by papain digestion (72 hours) and exhaustive dialysis (144 hours) to remove non-incorporated radioactivity and digested protein. 3H-glucosamine was readily incorporated into glycoprotein. Pooled gall bladder explants were fractionated on a CsCl density gradient and by gel filtration on Sepharose 2B and 4B to confirm that >90% radioactivity was incorporated into mucin. Acetylsalicylic acid (230-666 micrograms/ml) significantly reduced total 3H-glucosamine incorporation (43-89%), p<0.01 (unpaired t test). Diclofenac (125-1250 micrograms/ml), similarly reduced incorporation by 45-97% p<0.001 (unpaired t test). Inhibition of mucin glycoprotein biosynthesis was irreversible with both drugs. Analysis of pooled samples on Sepharose 4B showed abolition of radioactive incorporation into mucin but no effect on incorporation into low molecular weight glycoprotein material (10% of total incorporation). This study provides a method for measuring human gall bladder mucin synthesis and shows its irreversible inhibition by acetylsalicylic acid and diclofenac at concentrations compatible with a therapeutic dose.     

Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.

Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.     

Inhibition of human gall bladder mucus synthesis in patients undergoing cholecystectomy.

Hypersection of gall bladder mucus is associated with gall stone formation in animal models. Aspirin inhibits both mucus synthesis and secretion, prevents gall stone formation in animals and reduces gall stone recurrence in man after dissolution therapy. Mucus biosynthesis in human gall bladder mucosal explants is inhibited by aspirin in vitro. We have studied the effects of aspirin in vivo. Fifty five patients with functioning gall bladder and stones have been randomised, 27 to group 1 (aspirin EC 300 mg once daily for seven days before cholecystectomy) and 28 to group 2 (controls). Gall bladder bile composition was analysed and mucus synthesis rates measured using 3H-glucosamine incorporation into mucosal explants cultured for 24 hours. Patient age, sex, and gall bladder histology were similar in both groups. There were no differences in stone composition, gall bladder bile calcium concentration, cholesterol saturation and cholesterol nucleation time. The mean 3H-glucosamine incorporation in aspirin treated patients was 1347 fmol/g wet weight as compared with 2008 fmol/g wet weight in controls (95% confidence interval 222-1100, p<0.005, unpaired t test). This reduction in biosynthesis was associated with gall bladder bile mucus concentrations of 7.6 mg/ml in patients and 7.1 mg/ml in controls (ns). Treatment with aspirin led to a significant reduction in mucus biosynthesis by the gall bladder mucosa. This action is consistent with a role for aspirin in the prevention of gall stones.     

Effects of simvastatin and cholestyramine on bile lipid composition and gall bladder motility in patients with hypercholesterolaemia.

Although the effects of 3-hydroxy, 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and bile acid sequestrants on bile lipid composition have been studied separately, no data are available on combination therapy of these drugs. Moreover, the effects of prolonged (four weeks) administration of these drugs on gall bladder motility, an important determinant of cholesterol gall stone formation, have not been studied so far. A prospective study was therefore performed with eight patients who had hypercholesterolaemia (age 53 (5) (SEM), body mass index 27.4 (1.1) kg m-2, low density lipoprotein cholesterol 5.9 (0.3) mmol/l). They received treatment during three periods of four weeks with simvastatin 20 mg/day, cholestyramine 4 g twice daily, and a combination of both in random order, each treatment period separated by a two week wash out period. Before treatment and after each treatment period, postprandial gall bladder motility was studied with ultrasound, followed by duodenal bile sampling. Serum cholesterol decreased in all subjects in any treatment period illustrating good compliance. Molar percentages in duodenal bile of cholesterol, phospholipids, and bile salts were unchanged during simvastatin and cholestyramine treatment. During combined therapy percentage bile salts was lower (72.5 (2.9)% v 77.8 (1.7)% at baseline, p < 0.05) whereas phospholipids were higher (21.2 (2.4)% v 16.4 (1.3)% at baseline, p < 0.05). As a result cholesterol saturation index (CSI) did not change in any treatment period. No cholesterol crystals were detected in any bile sample, taken at baseline and after each treatment period. Bile salt hydrophobicity index during cholestyramine (0.19 (0.02)) and combined treatment (0.22 (0.01)) decreased strongly compared with baseline (0.34 (0.01), p < 0.001, p < 0.01, respectively), resulting from increased proportions of glycocholate (59.4 (3.9)% (cholestyramine), 55.6 (2.4)% (combination), and 28.2 (2.2) (baseline), p < 0.001)) and decreased proportions of deoxycholic acid and chenodeoxycholic acid. Fasting gall bladder volume was increased during simvastatin (28.7 (2.8) ml) v baseline (23.2 (2.3) ml, p < 0.01) whereas, residual volume did not differ (5.7 (0.9) ml (simvastatin) v 5.9 (0.7) (baseline). During cholestyramine and combined treatment, no significant differences in gall bladder motility were seen. In conclusion, this study suggests that HMG-CoA reductase inhibitors alone and combined with cholestyramine do not affect major determinants of cholesterol gall stone formation, for example, CSI and gall bladder emptying. In addition cholestyramine alone and combined with simvastatin leads to a strong decrease of bile salt hydrophobicity, which may be beneficial in the prevention of nucleation of cholesterol crystals.     

Roles of gall bladder emptying and intestinal transit in the pathogenesis of octreotide induced gall bladder stones.

BACKGROUND--Octreotide treatment of acromegalic patients increases the % deoxycholic acid conjugates and the cholesterol saturation of gall bladder bile, and induces gall stone formation. AIMS--To study the roles of gall bladder emptying and intestinal transit in these phenomena. METHODS AND PATIENTS--Gall bladder emptying and mouth to caecum transit was measured in (a) control subjects and acromegalic patients given saline or 50 micrograms of octreotide, and (b) acromegalic patients taking long term octreotide. In the second group, large bowel transit was also measured. RESULTS--A single dose of octreotide inhibited meal stimulated gall bladder emptying, the ejection fraction falling from mean (SEM) 66.0 (2.3)% to 7.0 (5.3)% in controls (p < 0.001); from 72.5 (2.1) to 16.6 (5.1)% in untreated acromegalic patients (p < 0.001), and to 30.4 (9.5)% in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic group). Octreotide prolonged mouth to caecum transit time, from 112 (15) min to 237 (13) min in controls (p < 0.001), from 170 (13) min to 282 (11) min in untreated acromegalic patients (p < 0.001), and to 247 (10) min in acromegalic patients taking long term octreotide (p < 0.001 v untreated acromegalic patients). The mean large bowel transit in octreotide untreated compared with treated acromegalic patients remained unchanged (40 (6) h v 47 (6) h). CONCLUSIONS--Prolongation of intestinal transit and impaired gall bladder emptying may contribute to lithogenic changes in bile composition and gall stone formation in patients receiving long term octreotide.     

Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn''s disease.

Biliary lipid composition, cholesterol saturation, and bile acid pattern were determined in fasting duodenal bile of 10 patients (four men and six women, mean age 41 years) with Crohn's disease and a history of ileal resection (mean 64 cm). The data were compared with corresponding values in a group of healthy subjects. None of the patients with Crohn's disease had supersaturated bile. Cholesterol saturation was significantly lower in the patients with Crohn's disease than in the healthy subjects. The molar percentage of cholesterol was also lower among the patients but there was no significant difference. The molar percentages of phospholipids and bile acids were normal. Bile acid composition in the patients with ileal resection was characterised by a significant decrease in the deoxycholic acid fraction and a pronounced increase in the ursodeoxycholic acid fraction compared with the healthy subjects. The surprisingly high percentage of ursodeoxycholic acid may contribute to the low degree of cholesterol saturation in bile. Based on these results patients with Crohn's disease should not have an increased risk of cholesterol gall stone formation.     

Influence of pregnancy, oophorectomy and contraceptive steroids on gall bladder concentrating function and hepatic bile flow in the cat.

Pregnancy and contraceptive steroids are associated with a raised incidence of cholesterol gall stone disease. In pregnancy there is an increase in the size of the gall bladder. Investigation of hepatobiliary function in man and mammals has not established if the enlarged gall bladder is simply dilated, or if the absorptive capacity of the mucosa has changed. In the present study the concentrating function of the gall bladder and bile secretion from the liver were studied in pregnant animals, oophorectomised animals and animals treated for three months with contraceptive steroids. The effects of intravenous administration of prolactin, progesterone and oestrogen were studied in oophorectomised animals. It was found that the net rate of water absorption in the gall bladder of pregnant animals was doubled, while oophorectomy and contraceptive steroids did not affect this variable. The volume outflow of bile was enhanced in pregnant animals and in animals treated with contraceptive steroids. Intravenous infusions of prolactin, oestrogen or progesterone were found not to influence gall bladder concentrating function, nor hepatic bile secretion in oophorectomised animals.     

Expression and regulation of scavenger receptor class B type I (SR-BI) in gall bladder epithelium

BACKGROUND AND AIMS: Biliary lipid absorption by the gall bladder mucosa and the cholesterol content of the gall bladder wall appear to play a role in cholesterol gall stone formation. As the scavenger receptor class B type I (SR- BI) regulates cellular cholesterol uptake, we studied its expression in human and murine gall bladders, its regulation by increased biliary lipid content, and its role in gall stone formation. METHODS AND RESULTS: Using immunohistochemistry, SR-BI was found in the apical domain of human gall bladder epithelial cells. Immunoblotting of isolated membranes from gall bladder epithelial cells showed a specific signal for the 82 kDa SR-BI protein. In C57BL/6 mice, SR-BI was also found in the gall bladder epithelium. Using western blot analysis, an inverse relationship was observed between biliary cholesterol concentration and SR-BI expression in murine gall bladder mucosa. By comparing lithogenic diet fed wild-type and SR-BI deficient mice, gall bladder wall cholesterol content and gall stone formation were not found to be dependent on SR-BI expression. CONCLUSIONS: (i) SR-BI is expressed in both human and murine gall bladder epithelium; (ii) biliary cholesterol hypersecretion is associated with decreased gall bladder SR-BI expression in mice; and (iii) murine SR-BI is not essential in controlling gall bladder wall cholesterol content and gall stone formation during diet induced cholelithiasis.     

Optimum bile acid treatment for rapid gall stone dissolution.

To determine the optimum bile acid regimen for rapid gall stone dissolution, 48 gall stone patients were divided into four groups of 12 according to stone diameter and were randomly allocated to receive one of four treatment regimens: bedtime or mealtime chenodeoxycholic acid (CDCA, 12 mg/kg/day) and bedtime or mealtime ursodeoxycholic acid (UDCA, 12 mg/kg/day). An additional 10 patients treated with a combination of CDCA plus UDCA (each 6 mg/kg/day) at bedtime were matched with the 10 patients on bedtime CDCA and the 10 on bedtime UDCA. The gall stone dissolution rates at six and 12 months were determined by standardised oral cholecystography and expressed as the percentage reduction in the gall stone volume after treatment. The gall stone dissolution rate at six months was higher for UDCA than CDCA treatment (median 78% v 48%, p less than 0.01), and for bedtime than mealtime administration (69% v 39%, p less than 0.02). Both differences were greater for stones less than 8 mm diameter. The dissolution rate was faster for combination therapy than for CDCA alone at both six (82% v 36%, p less than 0.05) and 12 months (100% v 54%, p less than 0.05), but was not different from UDCA alone. We conclude that bile acid treatment should be confined to patients with small gall stones and that bedtime administration of combined UDCA and CDCA is likely to provide the most effective and safe combination.     

Pulverisation of calcified and non-calcified gall bladder stones: extracorporeal shock wave lithotripsy used alone.

Using a modified electromagnetic lithotripter (Siemens), extracorporeal shock wave lithotripsy (ESWL) was performed in 260 patients with gall bladder stones. Exclusion criteria for treatment were a non-functioning gall bladder, subcostal gall bladder location, and multiple stones occupying more than three quarters of the gall bladder volume. Stone pulverisation was the end point of ESWL. The number of shock wave discharges and sessions was not limited. Pulverisation was achieved in 250 patients (96.1%) after a median of three ESWL sessions (range 1-21). The number of sessions required depended upon stone composition and burden. More than three sessions were required in 60.2% of patients with calcified stones compared with 35.9% of patients with non-calcified stones (p < 0.001). 65.8% of patients with stones measuring more than 30 mm in total diameter required more than three sessions compared with 42.9% of patients with a stone burden less than 30 mm (p < 0.01). At 18-24 (8-12) months follow up, stone clearance was achieved in 94.3% (80.4%) of patients with non-calcified stones, compared with 89.5% (76.8%) in patients with calcified stones and in 75% (71.4%) of patients with a total stone diameter more than 30 mm compared with 95.7% (80.4%) for patients with a total stone diameter less than 30 mm (p < 0.05). ESWL related complications (gross haematuria) occurred in three patients. Thirty six (13.8%) patients experienced biliary colic; four had cholecystectomy, and five endoscopic papillotomy because of common bile duct obstruction. Stone recurrence was seen in 5.3% of patients over a follow up period of up to two years (median 16.6 months).     

Longterm effects of endoscopic sphincterotomy on gall bladder motility.

BACKGROUND: Some of patients with an intact gall bladder develop acute cholecystitis or have gall bladder stone formation after endoscopic sphincterotomy. Endoscopic sphincterotomy may affect gall bladder motility. AIMS: To prospectively evaluate longterm effect of endoscopic sphincterotomy on gall bladder motility. PATIENTS: Thirty two patients with an intact gall bladder (15 with and 17 without gall bladder stones) who underwent endoscopic sphincterotomy for choledocholithiasis. METHODS: Gall bladder function was examined before and at from seven days to five years after sphincterotomy. Gall bladder volume, at fasting and after caerulein administration, was determined by ultrasonography. RESULTS: After endoscopic sphincterotomy, the enlarged orifice remained patent during a five year follow up period. One patient with gall bladder stones subsequently developed acute cholecystitis, the remaining being asymptomatic. In the patients before sphincterotomy, particularly in those with gall bladder stones, the gall bladder showed larger fasting volume and lower caerulein stimulated maximum contraction than normal controls. Throughout five years after sphincterotomy, fasting volume of the gall bladder decreased and its maximum contraction increased, regardless of gall bladder stones; significantly different from the values before sphincterotomy (p < 0.05). CONCLUSIONS: Endoscopic sphincterotomy decreases fasting volume of the gall bladder and increases its contraction ability for a long period. These changes may rather decrease the risk of future acute cholecystitis or gall stone formation.     

Computed tomography in predicting gall stone solubility: a prospective trial.

This prospective study was undertaken to evaluate the correlation between densitometric values of gall stones assessed by computed tomography and the success rate of litholytic therapy in 28 patients eligible for oral treatment. A densitometric study of the stones was performed in all patients before treatment. A cut off point of 60 Hounsfield units (HU) was chosen to divide the subjects into two groups--group 1, 14 patients with low density stones (less than 60 HU) and group 2, 14 patients with high density stones (greater than 60 HU). All patients were treated with ursodeoxycholic acid (8-10 mg/kg/day) for 12 months and followed up by ultrasound. In group 1, dissolution was complete in 50% of the patients and partial in a further 20%. In group 2 patients, complete dissolution was not observed but 33% showed partial dissolution. The number of patients with total dissolution at 12 months was significantly higher in group 1 compared with group 2 (p less than 0.02). These results suggest that computed tomography can be used to select patients with a better likelihood of successful stone dissolution after bile acid therapy.