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.     

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.     

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.     

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.     

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.     

Gall stone disease without gall stones--bile acid and bile lipid metabolism after complete gall stone dissolution.

Although bile acid and bile lipid metabolism have been studied in established cholelithiasis, little is known about them in patients destined to develop gall stones, but in whom the stones have not yet appeared (prestone gall stone disease). After confirmed complete gall stone dissolution and withdrawal of treatment, gall stones recur frequently. Before the stones reappear, these patients have 'poststone gall stone disease'. In 13 such patients we confirmed complete gall stone dissolution with two normal cholecystograms and in 11 of the 13 by normal ultrasonography, measured bile acid and bile lipid composition in fasting duodenal bile, bile acid synthesis from marker corrected three day faecal bile acid excretion, bile acid pool size using an abbreviated isotope dilution technique, 'steady-state' bile lipid secretion using a duodenal amino acid perfusion system and then calculated the enterohepatic cycling frequency of the bile acid pool and the relationship between pool size and body weight. The results confirm that after withdrawal of treatment the biliary cholesterol saturation index reverts to levels (1.6 +/- SEM 0.4) comparable with those before dissolution therapy first began (1.6 +/- 0.2; NS). The mean bile acid pool size in the 13 patients of 4.4 +/- 0.5 mmol was comparable with that in untreated gall stone patients. Pool size was significantly smaller in the nine non-obese patients (3.5 +/- 0.3), than in the four obese (6.0 +/- 0.8; p less than 0.05). It also correlated significantly with body weight (r = 0.72) and with %IBW (r = 0.79). The coefficients of variation for biliary bile acid, phospholipid and cholesterol secretion were high, but the mean hourly secretion rates were of the same order as those seen in untreated gall stone patients studied with the amino acid duodenal perfusion stimulus. These results provide a baseline for assessing the response to postdissolution treatment and may indicate metabolic events leading to gall stone formation.     

Clinical studies on dissolution of gallstones using ursodeoxycholic acid

Ursodeoxycholic acid (UDCA), 7beta hydroxy epimer of chenodeoxycholic acid (CDCA), has been used as a choleretica for 20 years in Japan. Recent report showing increased excretion of UDCA in bile after CDCA administration may suggest the possibility that UDCA has similar effects to CDCA on bile cholesterol unsaturation and on gallstone dissolution. The present paper describes the clinical usefulness of UDCA for gallstone patients during the past two years. Seventy-four gallstone patients with functioning gall-bladders, 19 men and 55 women with a mean age of 48 years, have been treated for 6 months or more. UDCA, supplied in tablets (Ursosan), was given 450 mg per day. The disappearance or the reduction of stone size or number, or both (dissolution effect) was recognized in 32 out of 74 patients (43%). In case of radiolucent stones, the overall effective rate was estimated for 24 of 46 patients (52%). There may be no significant difference in dissolution effect between CDCA and UDCA treatment, however, the merit of UDCA treatment seems to have its few side effects.     

Recurrence and re-recurrence of gall stones after medical dissolution: a longterm follow up.

One hundred patients with radiolucent gall stones less than or equal to 1.5 cm in functioning gall bladders have received oral bile acid dissolution therapy since 1975. Complete data are available on 93 who have received at least six months' treatment. The complete dissolution rate in appropriately selected patients who complied with and tolerated an adequate course of treatment was 55%. By life table analysis the recurrence rates were 13% at one year, 21% at two years, 31% at three years, and 43% at four years. Thereafter the recurrence rate levelled out, being 49% at 11 years. Redissolution was achieved in all seven patients who had a second course of therapy, but was usually followed by re-recurrence. Patients whose gall stones recurred did not differ significantly from those who remained stone free with respect to age, sex, body weight, or time required for dissolution.     

Retrospective comparison of 'Cheno' and 'Urso' in the medical treatment of gallstones.

In two groups of gallstone patients ideally suited for medical treatment, the effect of six to 18 months' therapy was compared retrospectively in 52 given chenodeoxycholic acid (CDCA) and 46 given ursodeoxycholic acid (UDCA). The minimum dose (mg kg-1 day-1) required to desaturate bile consistently was 10.1 for UDCA and 14.3 for CDCA. In patients completing six months' treatment, 23 of 35 (66%) taking a mean of 7.7 (+/- SEM 0.5) mg UDCA and 34 of 42 (81%) taking 14.7 +/- 0.2 mg CDCA showed partial or complete dissolution of gallstones. The mean dose in the UDCA-treated patients, however, was artefactually lowered by previous dose-response studies: in those who had not taken multiple doses, the mean UDCA intake in the 'responders' at six months was 9.1 +/- 0.3 mg kg-1 day-1. At six months, more UDCA (five of 35 or 14.3%) than CDCA (four of 42 or 9.5%)-treated patients showed complete dissolution of gallstones, but, by one year, the situation was reversed, 20 of 41 (49%) CDCA-treated and eight of 30 (27%) UDCA-treated patients showing complete dissolution of gallstones. Cumulative efficacy at one year had risen to 76% for UDCA and 89% for CDCA. Both treatments reduced the frequency of dyspepsia and biliary colic; 37% of CDCA and 2.6% of UDCA-treated patients showed hypertransaminasaemia; diarrhoea developed in 60% of the CDCA group but in none of the UDCA group.     

Dissolution of gall stones with an ursodeoxycholic acid menthol preparation: a controlled prospective double blind trial.

In a controlled prospective double blind trial patients with cholesterol gall bladder stones are treated with ursodeoxy-cholic acid (group A: UDCA 11.1 mg/kg per day; n = 16) and Ursomenth respectively (group B: a mixture of UDCA/menthol: 4.75 mg/kg per day each; n = 17). With same stone number and size (10-12 mm) there is a complete dissolution rate in group A of 38%, and of 53% in group B within 15-16.9 months. The response rate (complete + partial dissolution) amounted to 75% and 76% respectively. In group A there is one case of stone calcification, in group B none. Both preparations are free of unwanted effects. This suggests that the cyclic monoterpene menthol enhances the effect of UDCA and is of comparable effect to a mixture of six different terpenes used in former times.     

Acquired Gallstone Opacification during Cholelitholytic Treatment with Chenodeoscyholic, Ursodeoxycholic, and Tauroursodeoxycholic Acids

Objectives : The appearance of gallstone opacification during oral bile acid administration indicates that stones are no longer susceptible to dissolution and represents, therefore, a definitive treatment failure. Ursodeoxy-cholic acid (UDCA) has been imputed to facilitate gallstone opacification; however, data regarding the comparative occurrence of gallstone opacification during UDCA and chenodeoxycholic acid (CDCA) administration are not yet available. Our objectives were to evaluate the frequency of acquired opacification in gallstone patients taking UDCA and in gallstone patients taking CDCA, to verify whether or not gallstone opacification is a peculiar side effect of UDCA treatment and, further, to evaluate gallstone opacification in gallstone patients receiving tauro-UDCA (TUDCA) to verify whether the administration of the more soluble tauroconjugate might prevent the deposition of calcium salts on the stone surface. Methods : 106 gallstone patients on UDCA, 125 gallstone patients on CDCA, and 31 gallstone patients on TUDCA were evaluated. Before treatment, all patients had radiolucent gallstones as assessed by oral cholecys-tography; further cholecystographic evaluations were performed every 6 months during treatment. Results : The frequency of gallstone opacification was 13.2% (14/ 106) in UDCA patients, 8.8% (11/125) in the CDCA patients, and 12.9% (4/31) in the TUDCA patients. The differences were not statistically significant ( p = NS). Sex, stone size, dose of bile acid, and duration of treatment were not significantly related to an increased frequency of gallstone calcification in any of the treatment groups. The frequency of gallstone opacification appeared to be higher in older patients. Conclusions: 1) UDCA rich bile is not a major predisposing factor for acquired gallstone opacification; 2) the administration of TUDCA does not prevent gallstone opacification; 3) opacification could be related to the natural history of gallstone disease.     

Comparison on Response and Dissolution Rates Between Ursodeoxycholic Acid Alone or in Combination With Chenodeoxycholic Acid for Gallstone Dissolution According to Stone Density on CT Scan: Strobe Compliant Observation Study

Medical dissolution of gallstone is usually performed on radiolucent gallstones in a functioning gallbladder. However, absence of visible gallstone on plain abdominal x-ray does not always preclude calcification. This study aims to compare the response and dissolution rates between ursodeoxycholic acid (UDCA) alone or in combination with chenodeoxycholic acid (CDCA) according to stone density on computed tomography (CT) scan.A total of 126 patients underwent dissolution therapy with either UDCA alone or combination of CDCA and UDCA (CNU) from December 2010 to March 2014 at Korea University Ansan Hospital. In the end, 81 patients (CNU group = 44, UDCA group = 37) completed dissolution therapy for 6 months. Dissolution rate (percentage reduction in the gallstone volume) and response to therapy (complete dissolution or partial dissolution defined as reduction in stone volume of >50%) were compared between the 2 groups. Dissolution and response rates of sludge was also compared between the 2 groups.The overall response rate was 50.6% (CNU group 43.2% vs UDCA group 59.5%, P = 0.14), and the overall dissolution rate was 48.34% (CNU group 41.5% vs UDCA group 56.5%, P = 0.13). When analyzed according to stone density, response rate was 33.3%, 87.1%, 30.0%, and 6.2% for hypodense, isodense, hyperdense, and calcified stones, respectively. Response rate (85.7% vs 88.2%, P = 0.83) and dissolution rate (81.01% vs 85.38%, P = 0.17) of isodense stones were similar between CNU and UDCA group. When only sludge was considered, the overall response rate was 87.5% (CNU group 71.4% vs UDCA group 94.1%, P = 0.19), and the overall dissolution rate was 85.42% (CNU group 67.9% vs UDCA group 92.7%, P = 0.23).Patients with isodense gallstones and sludge showed much better response to dissolution therapy with CNU and UDCA showing comparable efficacy. Therefore, CT scan should be performed before medication therapy if stone dissolution is intended.     

Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial

Background/Aims

Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms.

Methods

A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated.

Results

A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients.

Conclusions

Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.     

Ursocholic acid: bile acid and bile lipid dose response and clinical studies in patients with gall stones.

The biliary bile acid and bile lipid responses to six weeks treatment with approximately 5, 10, and 15 mg/kg/day of ursocholic acid (UCA) were studied in 11 gall stone patients. Maximum enrichment of bile with UCA (24 (SE) 4.9%) occurred with 15 mg UCA/kg/day. The maximum reduction in biliary cholesterol saturation was seen with the 10 mg/kg/day dose when the moles % cholesterol fell from 14 (2.4)% before treatment to 5.6 (0.83)% (p less than 0.02) and the saturation index fell from 1.4 (0.23) to 0.77 (0.13) (p less than 0.05). Clinical studies of the safety and efficacy of UCA in dissolving gall stones were carried out in 13 patients treated for up to two years with a dose of approximately 10 mg/kg/day. Diarrhoea caused withdrawal of treatment in three patients. There were no significant changes in liver function or haematology tests but fasting serum cholesterol tended to rise during treatment. Of nine patients treated for greater than 6 months, only one showed complete gall stone dissolution. As UCA may cause diarrhoea and hypercholesterolaemia, has only a modest effect on biliary cholesterol saturation and low gall stone dissolution efficacy, it is unlikely to replace existing forms of gall stone dissolution therapy.     

Dissolution of cholesterol gall stones using methyltertbutyl ether: a safe effective treatment.

Methyltertbutyl ether (MTBE) administered by percutaneous transhepatic catheter rapidly dissolves radiolucent cholesterol gall bladder stones. However, complete dissolution and clearance of non-cholesterol debris is essential to prevent recurrence. In this study we analysed 25 consecutive patients with reference to efficacy and recurrence based on the presence or absence of non-cholesterol stone fragments after dissolution. Placement of the catheter was successful in 24 patients, one patient requiring cholecystectomy for bile peritonitis. MTBE was infused and aspirated continuously, four to six cycles per minute, resulting in rapid stone dissolution (median six hours; range 4-23 hours for solitary stones and median seven hours, range 4-30 hours for multiple stones). In 18 patients who had complete dissolution, four (22%) had recurrent stones within six to 18 months. Five patients had residual debris which failed to clear completely despite bile acid treatment. One patient with an incomplete rim of calcium in a large stone did not respond to MTBE treatment. A further patient required cholecystectomy for symptomatic recurrence. There were no serious side effects observed. MTBE treatment is a rapid, safe, and effective treatment for patients who refuse surgery or who for medical reasons cannot undergo cholecystectomy. The results of this study confirm that complete dissolution of all fragments is essential and may prevent recurrence.     

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.     

Prolonged administration of bile salts for gallstone dissolution and its effect on rectal epithelial cell proliferation

Bile acids and cholesterol metabolites may play a role in large bowel carcinogenesis. Currently, the bile acids chenodeoxycholic (CDCA) and ursodeoxycholic acid (UDCA) are being used for dissolution of cholesterol gallstones in surgical high-risk patients. The effect of prolonged exogenous bile acid intake on rectal epithelial cell proliferation, as a marker for preneoplasia, was evaluated in 19 patients selected for treatment. They were divided into two groups: nine patients received CDCA, 15 mg/kg/day for a mean duration of 11.0 months, while 11 patients received UDCA, 10 mg/kg/day for a mean duration of 9.2 months. Rectal biopsies taken before treatment and at one, three, six, and 12 months of treatment were analyzed and evaluated by three proliferative parameters including labeling index (LI), distribution of labeled cells, and total cells per crypt column. No significant alterations in epithelial cell proliferation were observed among patients treated with UDCA or CDCA with the exception of the number of cells per crypt column which, in the latter instance, deviated only slightly from the predicted values. The lack of major persistent alterations in the proliferative behavior of rectal epithelial cells does not justify any change in the selection of patients for gallstone therapy, but cannot exclude the potentially deleterious long-term effects of bile acid treatment.     

Intestinal absorption of ursodeoxycholic acid in patients with extrahepatic biliary obstruction and bile drainage.

Ursodeoxycholic acid (UDCA) dissolves cholesterol gallstones and improves liver function test results in patients with cholestatic liver diseases. Its absorption was studied in patients who had complete extrahepatic biliary obstruction caused by pancreatic carcinoma but no intestinal or liver disease. Six patients received 500 mg chenodeoxycholic acid (CDCA) or 250-2000 mg UDCA in capsules in single oral doses in random order, with an interval of 2 days between the different treatment regimens. In the control period the patients excreted into bile 382.3 +/- 108.0 mumol CDCA (mean +/- SD) and 1866.7 +/- 172.6 mumol cholic acid per 24 hours. After administration of 1273.6 mumol (500 mg) CDCA, biliary excretion of this bile acid increased to 1370.9 +/- 185.7 mumol/24 h, indicating an intestinal absorption rate of 77.6% +/- 9.8%. After oral administration of 636.8 mumol (250 mg), 1273.6 mumol (500 mg), 2547.2 mumol (1000 mg), and 5094.4 mumol (2000 mg) of UDCA, the respective absorption rates were 60.3% +/- 7.4%, 47.7% +/- 9.0%, 30.7% +/- 7.5%, and 20.8% +/- 3.9%, and whereas in the control period no UDCA was detected in the bile, the UDCA percentages measured were 14.6% +/- 8.2%, 19.6% +/- 9.1%, 23.1% +/- 11.3%, and 27.4% +/- 12.1%. The coadministration of CDCA did not enhance the absorption of UDCA. The data indicate that absorption of orally administered CDCA is almost complete, whereas UDCA absorption is incomplete. With increasing doses UDCA absorption decreases. To achieve absorption of adequate amounts of UDCA, high and/or multiple doses are needed.     

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.     

Prospective,multicenter study on value of computerized tomography (CT) in gallstone disease in predicting response to bile acid therapy

The aim of the study was to assess the value of quantitative attenuation values (Hounsfield units) and of gallstone pattern by computerized tomography in predicting response to bile acid therapy. We carried out a prospective study in a multicenter setting on 90 consecutive outpatients with radiolucent gallstones. All received bile acid therapy (UDCA 10 mg/kg/day or UDCA+CDCA 5 mg/kg/day of each) up to two years. Hounsfield units for gallstones were recorded using standardized criteria and six categories of patterns were defined: hypodense, isodense, homogenously dense, laminated, rimmed and speckled. We assessed gallstone dissolution rate (percent reduction in volume), response to therapy (>25% reduction in volume), and final outcome of therapy. Eighty-one percent of patients with hypodense/isodense and all four patients with speckled stone pattern responded to therapy, whereas none of the 10 patients with laminated/rimmed and only 45% of patients with homogenously dense stone pattern did. Complete dissolution was achieved by 68%, 50%, 35%, 0% of the hypodense/isodense, speckled, homeogenously dense, rimmed/laminated gallstones, respectively. The use of Hounsfield units did not show an advantage over gallstone pattern for predicting either response or final outcome to bile acid therapy. We conclude that computerized tomography analysis of gallstones is of value in predicting response to bile acid therapy and that gallstone pattern alone predicts response in most cases without the need for quantitative assessment.This study was carried out under the auspices of the British-Italian Gallstone Study Group, which was supported by a grant from Schwarz Pharma Italia.Preliminary results from this work have been presented at the 93rd Annual Meeting of the American Gastroenterological Association in 1992 and published in abstract form (Gastroenterology 102:A329, 1992).