Complete Gallstone Dissolution Research Articles

A Study of Ursodeoxycholic Acid for Dissolution of Gallstones

Background: Gallstone disease one of the major health problems and causes of morbidity in Bangladesh as well as worldwide. Ursodeoxycholic acid is a bile acid which is used for dissolving gallstones.Objectives: To observe dissolution of gallstones among the patients of gallstone disease by use of ursodeoxycholic acid. Methods: It was a cross-sectional observational study carried out in the Department of Medicine, Rajshahi Medical College Hospital, Rajshahi from July, 2014 to June, 2016. According to inclusion and exclusion criteria 12 people having gallstone disease were selected whose stone size were <10mm and were treated withUrsodeoxycholic acid (Dosage of 8-12mg/kg/day). Thorough history, physical examination along with Ultrasonographical assessment were done for this study.Results: Complete gallstonedissolution with Ursodeoxycholic acid occurred in 08(66.67%) cases whereas dissolution did not occur in 04(33.33%) cases among the patients of gallstone diseases.Conclusion: In this study, complete dissolution of Gallstones (<10mm) occurred in 66.67% patients.TAJ 2014; 27(2): 27-29

Effect of β-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice

This study investigated whether beta-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.

Dissolution of gallstones with simvastatin, an HMG CoA reductase inhibitor.

The aim of this study was to determine whether 12 months of therapy with Simvastatin, an HMG CoA reductase inhibitor, would dissolve gallstones. Twenty-seven subjects entered the study, all had a fasting oral cholecystogram, ultrasound examination, and fasting serum lipids prior to therapy. In addition, 22 subjects had their gallbladder ejection fraction, after CCK, determined by radionucleotide scanning. Eleven subjects had the cholesterol saturation index (CSI) of bile calculated before and at the end of 12 months of therapy. Of the 27 subjects, 26 completed 12 months of treatment with Simvastatin 20 mg daily. There was a significant fall in the total serum cholesterol (27%, P < 0.0001), LDL cholesterol (31%, P < 0.0001), triglyceride (34%, P < 0.0001) but no change in HDL after 12 months of therapy. Simvastatin treatment resulted in a 28% fall in the CSI of bile at the end of therapy (P < 0.01). The concentrations of individual bile acids did not change with therapy, and apart from a slight but significant increase in arachidonate, there were no other significant changes in the fatty acid composition of the biliary phospholipids. After 12 months of Simvastatin therapy there was a small decrease in the gallstone diameter but complete dissolution of gallstones was not achieved in any subjects. In conclusion 12 months of therapy with Simvastatin was effective in lowering the serum lipids and the CSI of bile but was not effective in dissolving gallstones.

Effect of Lactulose and Fiber-rich Diets on Bile in Relation to Gallstone Disease: an Update

The primum movens in cholesterol gallstone formation is hepatic cholesterol hypersecretion and chronic supersaturation of bile. From this event a cascade of contributing factors can be differentiated: (i) Motility defects with impaired gallbladder contractility and gallbladder stasis, but also with small and large intestinal hypomotility. (ii) Multiple biochemical defects in gallbladder bile with increased biliary proteins, increased deoxycholic acid and rapid crystallization of biliary cholesterol from supersaturated unstable vesicles. There is considerable evidence that slow intestinal and colonic transit can increase the deoxycholic acid pool size and biliary cholesterol saturation. Changes in intestinal transit influence the anaerobic bacterial enzymatic biotransformation of conjugated cholate to more hydrophobic deoxycholate. This leads to biliary cholesterol hypersecretion and gallstone formation. Prokinetic drugs or administration of lactulose or fiber products like bran can change the slow intestinal transit favourably with subsequent reduction in deoxycholic acid formation and cholesterol saturation of bile. Whether these applications are indeed of value in the long-term prevention of gallstone disease, however, is doubtful, since fiber-rich diet in prevention of gallstone recurrence after complete gallstone dissolution was not successful.

Repeated bile acid therapy for the long-term management of cholesterol gallstones

Background/Aims: Following non-surgical treatment, cholesterol gallstones recur in a high proportion of patients, and recurrence cannot be predicted nor effectively prevented. Our aim was to test prospectively the viability and the efficacy of repeated bile acid therapy, in which recurrent stones are diagnosed at an early stage by regular ultrasound monitoring and promptly retreated, as a strategy for the management of these patients in clinical practice. Methods: One hundred and seventy-two consecutive patients were recruited upon achieving complete gallstone dissolution using non-surgical therapy (bile acids or lithotripsy plus bile acids), and followed up at 6-monthly intervals by ultrasound scan. Gallstone recurrence was promptly treated by a combination of ursodeoxycholic acid plus chenodeoxycholic acid (5 mg/kg per day each) for a period of 2 years, or less if complete redissolution was achieved. Median follow-up period was 34 months (range 6–70). Results: Forty-five patients had gallstone recurrence; of these, 39 underwent one or more repeated courses of bile acid therapy (follow-up data available in 27). Gallstone recurrence rate was 15% at 1 year and 47% at 5 years. Average annual redissolution rate of recurrent gallstones (intention to treat) was 41%. The proportion of gallstone-free patients in the whole population was 88%, 84%, 77%, 78%, 75% at 1–5 years, respectively, and rose to > 90% at 3 years onwards in patients with single primary stones. Conclusions: We conclude that repeated bile acid therapy maintains the majority of patients gallstone free, and is there fore an effective long-term management strategy, especially in patients with primary single gallstones.

Dissolution of Cholesterol Gallstones by Taurohyodeoxycholic Acid in Carefully Selected Patients

The aim of this controlled, randomised, parallel-group, double-blind study was to determine the efficacy and safety of taurohyodeoxycholic acid (THDCA) compared with another commonly used bile acid, ursodeoxycholic acid (UDCA), in 50 non-obese patients with a diagnosis of symptomatic gallstones. Patients admitted to the trial complained of biliary pain and experienced recurrent biliary colic. The patients, monitored by radiography, oral cholecystography and ultrasonography, were only admitted if they had ≤ 3 radiolucent floatable cholesterol stones with a diameter ≤ 16mm in radiographically well-visualised gallbladders. THDCA and the reference drug were administered at 250mg doses twice a day for 6 months (about 7.5 mg/kg/day). The percentage of patients achieving complete gallstone dissolution was 52.2% in the group treated with THDCA and 19% in the group treated with UDCA (statistically significant difference, p = 0.0225) after 6 months of therapy. In the group treated with THDCA, 8% of patients showed complete gallstone dissolution after only 3 months. Stone diameter was significantly reduced in both groups, but stone number was significantly reduced only in the THDCA group. However, these differences between the 2 groups were not statistically significant. In the UDCA group about 14% of patients (none in the THDCA group) acquired calcification rims. Symptoms were reduced or completely disappeared in about 70% of patients treated with THDCA (62% in the UDCA-treated group). Statistical analysis revealed significant differences in total clinical judgement in the activity of the 2 drugs but not in tolerability judgement or drop-out incidence. Adverse effects were reported in 13% of THDCA-treated patients and in 28% of patients in the UDCA group, without any statistically significant difference between the 2 groups. Although the data from our study suggest that, at a good level of statistical confidence, THDCA could be considered a safe and effective litholytic treatment for gallstones in selected patients, further investigations must be carried out in larger numbers of patients in order to examine closely the therapeutic action and clinical differences between THDCA and other bile acids.

Gallstone recurrence after successful dissolution therapy

After successful dissolution therapy of cholesterol gallbladder stones bile again becomes supersaturated and recurrent gallstones may develop. Three different postdissolution treatments [500 mg ursodeoxycholic acid (UDCA) per day (N = 14, group I), 100 mg aspirin per day (N = 14, group II) and diet (N = 15, group III) versus a control group (no treatment, N = 15, group IV) aimed at preventing recurrence of gallstones were investigated in a prospective, randomized study in 58 gallstone patients (33 female, 25 male) after complete stone clearance. Bile samples (prior to dissolution therapy and at stone recurrence) were investigated for biliary cholesterol (C), phospholipids (PL), total bile acid concentration (BA), cholesterol saturation index (CSI), total lipid concentration (TLC), total biliary protein concentration (TP), and nucleation time (NT). In group IV multiple gallstones tended to recur more often than solitary stones (66.7% vs 16.7%) whereas in groups I-III only solitary stones recurred. Recurrent gallbladder stones were detectable in 10 patients (eight patients in group IV and one each in groups I and II, respectively) within one year after dissolution and in two patients (one each in groups III and IV, respectively) after 15 months. Furthermore, the probability of stone recurrence was significantly higher in untreated patients as compared to treated patients. In nine (group IV) of 12 patients with recurrent stones NT, C, CSI, PL, BA, TLC, TP, and bile acid spectrum remained nearly unchanged as compared to their pretreatment values, whereas in three (groups I-III) of 12 cases a decrease in C, CSI, and TP was observed during therapy. However, in each of these three patients, initial and after-treatment TP was significantly higher and NT shorter as compared to groups I-IV. Furthermore, in these cases (N = 3) NT was prolonged, whereas no significant changes were found in PL, BA, TLC, and bile acid spectrum. Recurrence of gallstones, which seems to occur more likely in patients with multiple stones as compared to solitary stones, will happen in the early stage after stone clearance, again causing biliary pain. UDCA, aspirin or diet will reduce the probability for recurrent stones after complete gallstone dissolution.

Failure of ursodeoxycholic acid to dissolve radiolucent gallstones in patients with cystic fibrosis.

Ursodeoxycholic acid has been used widely to dissolve cholesterol gallstones and more recently was shown to improve clinical symptoms and biochemical indices in different chronic liver diseases, including that associated with cystic fibrosis. We treated 10 cystic fibrosis patients (5 males, 5 females, age range 2-22 years) with pancreatic insufficiency and normal liver function with ursodeoxycholic acid 15-20 mg/kg/day. Seven patients had radiolucent gallstones (in 3 cases associated with biliary sludge) and 3 had sludge; all were asymptomatic. Before treatment, the gallbladder was well opacified in oral cholecystogram. The gallbladder was scanned by ultrasound in similar conditions and by the same operator before administration of ursodeoxycholic acid and after a median period of treatment of 16 months (range 11-32 months). During treatment, all patients remained asymptomatic and the relative proportion of ursodeoxycholic acid in duodenal bile increased from 4.7 +/- 3.2% at baseline to 34.7 +/- 8.6%. Complete or partial dissolution of gallstones was never observed and the maximum diameter of stones increased from a mean of 6.1 +/- 3.4 to 8.0 +/- 5.3 mm; in one case the development of biliary sludge occurred during bile acid therapy. Sludge disappeared in 1 of the 6 patients who initially had it, while in 2 cases its volume increased. We conclude that ursodeoxycholic acid is not effective in most CF patients with gallstones, probably because cholesterol is not the main component of stone or sludge.

Successful dissolution of cholesterol gallstone during treatment with pravastatin

This case report describes a 51-year-old hypercholesterolemic male patient who had a large solitary cholesterol gallstone. The patient was treated with the 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin, 40 mg/day. After 3 months of therapy, serum cholesterol level normalized (7.7 mmol/L before and 5.2 mmol/L during treatment), and biliary cholesterol saturation index decreased from 1.3 before to 0.8 during treatment. Repeatedly performed ultrasonography showed complete gallstone dissolution. Pravastatin may be valuable in the nonsurgical treatment of cholesterol gallstone disease particularly when there is an additional indication for HMG-CoA reductase inhibitors because of hypercholesterolemia.

Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy.

In a five year study, 55 patients with radiolucent gall stones were treated with the combination of 7.5 mg chenodeoxycholic acid (CDCA) and 5.0 mg ursodeoxycholic acid (UDCA)/kg/day--that is, half the monotherapeutic doses. Side effects were few but four patients could not tolerate the prescribed bile acids because of diarrhoea or nausea. Analysis of fasting duodenal bile confirmed that CDCA+UDCA converted supersaturated into unsaturated bile but the saturation indices did not predict the dissolution response. By actuarial analysis, the confirmed (by ultrasound x2) complete gall stone dissolution rates in all 55 patients were mean (SEM) 29 (7)% at 12 and 44 (8)% at 24 months. The advent of routine computed tomography before treatment enabled comparison of dissolution efficacy in those screened by computed tomography (n = 24), whose maximum gall stone attenuation was less than 100 Hounsfield units, with that in those not screened (n = 29). Although stone size and number were comparable, patients screened by computed tomography had significantly better dissolution rates (p less than 0.025) than those not screened in this way. At 12 months, partial or complete gall stone dissolution rates were 93 (7)% in the screened and 55 (11)% in the non-screened patients. At 18 months, complete dissolution rates were 64 (12%) and 20 (9)% respectively. Computed tomography before treatment is cost effective in selecting those patients likely to achieve gall stone dissolution on treatment with UDCA+CDCA.

A Practical Guide to the Nonsurgical Treatment of Gallstones

Until recently, cholecystectomy was the only treatment available for symptomatic gallstone disease. During the past 20 years, better understanding of the pathogenesis of cholesterol gallstone disease has led to alternative nonsurgical methods for treating gallstones in selected groups of patients. Use of 2 naturally occurring bile acids, chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), was reported in 1972 and 1975, respectively, for successful dissolution of cholesterol gallstones in humans. Both these bile acids act by reducing cholesterol secretion in bile, thus enabling it to solubilise more cholesterol from the stone surface. Micellar solubilisation is involved, together with liquid crystal formation in the case of UDCA. Having been extensively studied in clinical trials to assess efficacy and safety, both these compounds are now available for general use. The efficacy of CDCA can be enhanced by single bedtime dose administration and by taking a low cholesterol diet. Bedtime administration also enhances the effect of a suboptimal dose of UDCA. CDCA induces dose-related diarrhoea and hypertransaminaemia, and UDCA can induce calcification of gallstones, thus rendering them resistant to medical dissolution. A combination of the 2 bile acids at half the recommended dose for each has become an accepted practice for reducing adverse effects, and this may also enhance efficacy. One of the main problems of bile acid therapy is that dissolution of gallstones is a very slow process. Use of extracorporeal shockwave lithotripsy (ESWL) to break the stones into smaller fragments, with concurrent use of bile acids, has been shown to speed dissolution rate and to achieve complete gallstone dissolution in 78% of selected cases within 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Nucleation Time, Cholesterol Saturation Index, and Biliary Bile Acid Pattern:A Comparison in Responders and Nonresponders to Systemic Litholysis with Bile Acids

In a 24-month trial of a combination therapy with ursodeoxycholic acid and chenodeoxycholic acid complete dissolution of radiolucent gallstones was achieved in 15 of 55 patients (27.3%). A decrease of stone volume of greater than 35% was achieved in a further 28 patients (50.9%). In 12 patients (21.8%) inadequate compliance (3.6%), a nonfunctioning gallbladder (3.6%), absence of size decrease (10.9%), or acute cholecystitis (3.6%) required interruption of therapy. Determination of the cholesterol saturation index (CSI) did not facilitate patient selection, nor was there a statistically significant difference between responders and nonresponders to dissolution therapy. In the course of treatment the average CSI showed a statistically significant decrease from 1.54 +/- 0.12 to 0.82 +/- 0.06 (p less than 0.001). Patients in whom complete dissolution was achieved and those in whom no improvement was observed differed significantly in nucleation time (4.7 +/- 0.8 versus 15.0 +/- 2.2 days; p less than 0.001) and initial gallstone volume (274 +/- 78 versus 1045 +/- 180 mm3). The nucleation time increased statistically significantly during the therapy in the successfully treated group. The percentages of glycocholic acid (8.1 +/- 1.13 versus 4.1 +/- 0.55%; p less than 0.01), taurocholic acid (2.2 +/- 0.45 versus 0.8 +/- 0.23%; p less than 0.05), and glycodeoxycholic acid (4.9 +/- 0.70 versus 1.4 +/- 0.37%; p less than 0.001) were statistically significantly different after the treatment. There were no statistically significant differences between patients with complete and incomplete stone dissolution with regard to age, mean body weight, or laboratory variables.

Final Outcome of Ursodeoxycholic Acid Treatment in 126 Patients with Radiolucent Gallstones

One hundred and twenty-six patients with radiolucent gallstones in 'functioning' gallbladders were treated with 8-10 mg ursodeoxycholic acid (UDCA) kg/day and followed to a treatment conclusion. Complete or partial gallstone dissolution was achieved in 74 (59 per cent). However, only 22 achieved complete gallstone dissolution, as judged by two normal oral cholecystograms; ultrasonograms were performed in 16 of these patients, and all were normal. UDCA was stopped in 76 patients: because of cystic duct obstruction (n = 12), severe biliary pain (n = 13), non-response (n = 25) or partial stone dissolution with arrested progress (n = 26). Life-table analysis showed that complete gallstone dissolution rates at four years were 25-30 per cent (two normal oral cholecystograms) and 17-19 per cent (two normal oral cholecystograms plus one ultrasonogram). All patients with complete gallstone dissolution had shown partial stone dissolution at 6-12 months; of those with partial stone dissolution at six months, only 25 per cent went on to complete gallstone dissolution, and then always within two years. Efficacy correlated inversely with stone size but not with age, sex, obesity or on-treatment saturation indices. Acquired surface gallstone calcification developed in 13 patients (life-table analysis 22 +/- 7 per cent at four years); none of these patients achieved complete gallstone dissolution and only five achieved partial stone dissolution. Thus, despite relatively high partial gallstone dissolution rates, the ultimate efficacy of UDCA in achieving complete gallstone dissolution is low.

Addition of N-acetylcysteine to aqueous model bile systems accelerates dissolution of cholesterol gallstones

The organic matrix of cholesterol gallstones contains a macromolecular complex of mucin and bilirubin that may inhibit stone dissolution by limiting contact of desaturated bile with crystalline cholesterol. The goal of this study was to determine if the mucolytic agent N-acetylcysteine could accelerate gallstone dissolution in vitro. Paired gallstones were dissolved in either pure taurocholate (140 mM) or ursodeoxycholate (100 mM), or in bovine bile supplemented with either taurocholate or ursodeoxycholate to achieve the same respective bile-salt concentrations. N-acetylcysteine was added to 1 stone from each pair at a concentration of 500 mM in pure bile salts and 100 mM in supplemented bile. Gallstones dissolved significantly faster in bovine bile supplemented with taurocholate or ursodeoxycholate than in pure solutions of the respective bile salts (n = 30, p < 0.001). N-acetylcysteine significantly accelerated gallstone dissolution in pure solutions of bile acids (n = 30, p < 0.001 for each) and in supplemented bovine biles (n = 30, p < 0.001). N-acetylcysteine also significantly increased the frequency of complete gallstone dissolution in taurocholate-supplemented (66.6% vs. 40.0%) and ursodeoxycholate-supplemented (76.6% vs. 50.0%) bile. These results indicate that the mucolytic agent N-acetylcysteine significantly accelerates in vitro gallstone dissolution. We speculate that adjuvant therapy with an appropriate mucolytic agent may potentially increase the efficacy of clinical gallstone dissolution.

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.

Gallstone disease without gallstones: A partial answer

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 < 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.

Utility of biliary microscopy for the prediction of the chemical composition of gallstones and the outcome of dissolution therapy with ursodeoxycholic acid

To learn whether microcrystalline solids in bile could predict gallstone composition, the findings determined by polarizing microscopy of gallbladder bile were related to stone type at cholecystectomy in 53 patients. Cholesterol crystals were present in 36 of 39 cholesterol stone biles and absent in 12 of 14 biles from noncholesterol stones. Fifteen cholesterol stones (eight radiopaque) contained calcium carbonate, and characteristic vaterite microspheroliths were observed in 53% of their biles. In another study, crystals in basal duodenal bile were related to the outcome of gallstone dissolution treatment with ursodeoxycholic acid, 10 mg/kg · day. In 39 patients treated for 1 yr, efficacy (complete gallstone dissolution) was 41% overall and 52% in patients with stones ≤ 10 mm in diameter. In connection with the findings of biliary microscopy, efficacy was 93% in 14 patients with cholesterol crystals in bile, and 27% in 11 patients with microspheroliths in bile. Cholecystectomies in 9 patients with dissolution failure revealed 4 cases of noncholesterol stones and 5 cases (including 3 with on-therapy calcification) of calcium carbonate-rich cholesterol stones with a surface/interior mineral ratio >3. The results confirm that cholesterol crystals in bile are a sensitive measure of cholesterol gallstones. They also show that vaterite microspheroliths in bile indicate the presence of calcium carbonate in gallstones. Both findings suggest that biliary crystals reflect gallstone composition, and it is demonstrated that this information is useful in predicting the success or failure of cholelitholysis with ursodeoxycholic acid. Finally, the data show that radiologically undetectable stone calcification reduces the probability of dissolution, and that the calcified structures appearing in some stones during treatment are composed of calcium carbonate.

Chemical and morphologic characteristics of cholesterol gallstones that failed to dissolve on chenodiol: The National Cooperative Gallstone Study

During the National Cooperative Gallstone Study, chenodiol (chenodeoxycholate), 750 or 375 mg/day, resulted in complete gallstone dissolution in only 13.5% and 5.2% of patients, respectively. The purpose of this study was to analyze the composition and morphology of gallstones from patients who underwent cholecystectomy during the National Cooperative Gallstone Study to determine if calcium salts on the gallstone surface could have been responsible for failure of dissolution. Total gallstone calcium content was not different between the treated and placebo groups; however, surface calcium levels were different, being >1.0% in 47.6% of stones from chenodiol-treated patients (n = 63) but in only 16.7% of those from placebo-treated patients (n = 18), p < 0.02. Pigmented outer rims were found in 52.4% of the stones from the chenodiol-treated group compared with only 16.7% of stones from the placebo group, p < 0.01. The rim calcium content of 36 stones with pigmented outer rims was 3.7% ± 1.0%, whereas that of 45 stones with nonpigmented outer rims was only 1.0% ± 0.3%, p < 0.01. We conclude that the presence of rings of increased concentrations of calcium salts on the gallstone surface may impair dissolution by chenodiol.

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.

Medical management of cholesterol gallstones.

Cholesterol gallstones are a significant cause of morbidity in the U.S. Methods used to treat gallstones include cholecystectomy or medical dissolution. The primary drugs used for the dissolution of cholesterol gallstones are two bile acids, chenodeoxycholic acid and ursodeoxycholic acid. Complete or partial gallstone dissolution rates using chenodeoxycholic acid have ranged from 30 to 80 percent. Factors affecting gallstone dissolution using the bile acids include the dosage and administration schedule, obesity, the stone characteristics, diet, and the duration of therapy. The adverse effects of chenodeoxycholic acid include gastrointestinal complaints, hepatotoxicity, and increased serum cholesterol. Ursodeoxycholic acid, which is investigational, differs from chenodeoxycholic acid in its mechanism of action. Ursodeoxycholic acid has similar efficacy with chenodeoxycholic acid, at a lower daily dosage, with less gastrointestinal and hepatic adverse effects. If appropriate patient selection is used, the response rate to medical therapy can range from 50 to 80 percent.