Acute diarrhea during azathioprine treatment of type I autoimmune hepatitis.

Sporadic descriptions of acute onset of watery diarrhea within a few hours to a few weeks azathioprine administration beginning have been reported, particularly in inflammatory bowel disease patients. This article reports the case of a woman treated with azathioprine because of type I autoimmune hepatitis, who developed acute watery diarrhea after more than two months of therapy. In two occasions the patient reassumed the drug and in a few hours diarrhea recurred. Subsequent 6-mercaptopurine treatment was well tolerated, suggesting that the previous side-effect could be due to the nitroimidazole moiety of azathioprine.

Diagnostic accuracy of portal-phase CT and MRI with mangafodipir trisodium in detecting liver metastases from colorectal carcinoma.

AIM: To compare the diagnostic accuracy of single section spiral computed tomography (CT) and magnetic resonance imaging (MRI) with tissue-specific contrast agent mangafodipir trisodium (MnDPDP) in the detection of colorectal liver metastases. MATERIAL AND METHODS: One hundred and twenty-five consecutive patients undergoing surgery for primary and/or metastatic disease were evaluated using CT (5 mm collimation and reconstruction interval, pitch 2), two-dimensional fast spoiled gradient echo (2D FSPGR) T1 and single shot fast-spin echo (SSFSE) T2 weighted breath-hold MRI sequences, performed before and after intravenous administration of MnDPDP. The reference standards were intraoperative ultrasound and histology. RESULTS: The per-patient accuracy of CT was 72.8 versus 78.4% for unenhanced MRI (p = 0.071) and 82.4% for MnDPDP-enhanced MRI (p = 0.005). MnDPDP-enhanced MRI appeared to be more accurate than unenhanced MRI but this was not significant (p = 0.059). The sensitivity of CT was 48.4% versus 58.1% for unenhanced MRI (p = 0.083) and 66.1% for MnDPDP-enhanced MRI (p = 0.004). The difference in specificity between procedures was not significant. The per-lesion sensitivity was 71.7, 74.9 and 82.7% for CT, unenhanced MRI, and MnDPDP-enhanced MRI, respectively; the positive predictive value of the procedures was respectively 84.0, 96.0 and 95.8%. MnDPDP-enhanced MRI provided a high level diagnostic confidence in 92.5% of the cases versus 82.5% for both unenhanced MRI and CT. The kappa value for inter-observer variability was >0.75 for all procedures. CONCLUSIONS: The diagnostic accuracy and sensitivity of MnDPDP-enhanced MRI is significantly higher than single section spiral CT in the detection of colorectal cancer liver metastases; no significant difference in diagnostic accuracy was observed between unenhanced MRI and MnDPDP-enhanced MRI.

CT colonography: screening in individuals at high risk for colorectal cancer.

The use of computed tomographic colonography (CTC) as a screening test for colorectal cancer is being advocated with growing enthusiasm by physicians and the public as stronger evidence of its validity and limited invasiveness emerges from the literature. Because the approach to surveillance of colorectal cancer depends on an individual's degree of risk category, which depends on familial and personal histories, it seems logical that the diagnostic performance and cost efficacy of screening CTC may differ according to the characteristics of the target population. Although CTC seems a valid option in low- to average-risk populations, pending a careful assessment of its cost and estimates of its cost efficacy, there are some important issues that should be addressed when it comes to considering its use in high-risk patients. The expected larger number of induced colonoscopies and higher false-positive rates are likely to have a great influence on CTC costs, but if its implementation causes a dramatic increase in the number of patients willing to undergo screening, thanks to its acceptability, then the cost efficacy ratio may ultimately become competitive with all other screening strategies for colorectal cancer. We strongly feel that large and well-conducted trials are needed to clarify the role of CTC in screening patients at increased risk of developing colorectal cancer.

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas.

BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.

Ileocecal valve imaging on computed tomographic colonography.

BACKGROUND: The aim of our study was to describe the visualization, normal anatomy, and variations of the ileocecal valve with computed tomographic (CT) colonography to provide information about its optimal imaging. METHODS: We analyzed data in two- and three-dimensional rendering mode in 71 consecutive patients who underwent routine CT colonoscopy followed by conventional colonoscopy for confirmation of the radiologic findings. RESULTS: Complete visualization of the ileocecal valve was better achieved in the supine than in the prone position (82% vs. 62%, respectively); the ileocecal valve appeared in 64% of cases in the supine position when it was invisible in prone position (p < 0.0001). Partial visualization of the ileocecal valve was possible in 94% of cases. The ileocecal valve was of labial type in 76%, papillary type in 21%, and lipomatous in 3% of cases. The orifice was identified in 53% of ileocecal valves; in two cases of cecal carcinoma, the normal ileocecal valve morphology was grossly disrupted. CONCLUSION: The ileocecal valve was at least partly visualized by CT colonoscopy in 94% of cases, more frequently in the supine position. Its most common normal morphology is the labial type. The absence of orifice visualization alone is not a specific sign for neoplasia, but its presence helps distinguish physiologic bulging from neoplasia.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

Treatment of primary sclerosing cholangitis with low-dose ursodeoxycholic acid: results of a retrospective Italian multicentre survey.

BACKGROUND: Data concerning the usefulness and type of drugs employed to treat patients with primary sclerosing cholangitis are controversial. Ursodeoxycholic acid has been shown to be a useful agent, however the drug dosage and its effect on the clinical course are still under debate. AIM: To evaluate the efficacy of low-dose ursodeoxycholic acid in the treatment of primary sclerosing cholangitis. METHODS: We retrospectively analysed data from 86 patients with primary sclerosing cholangitis from eight centres in Italy between 1987 and 1997: 69 were treated with ursodeoxycholic acid (8-13 mg/kg/day), while 17 received symptomatic treatment and served as controls. The effect of therapy was evaluated by standard liver function tests and symptom analysis. RESULTS: Ursodeoxycholic acid treatment was associated with significant improvement in serum alkaline phosphatase (735+/-833 vs. 519+/-448 U/l, p<0.001), gamma-glutamyl transpeptidase (401+/-352 vs. 234+/-235 U/l, p<0.001), aspartate aminotransferase (87+/-70 vs. 56+/-42 U/l, p=0.001), alanine aminotransferase (146+/-139 vs. 76+/-73 U/l, p<0.001), and total bilirubin (1.88+/-2.44 vs. 1.76+/-4.12 U/l, p=0.01); there was also amelioration of fatigue (p=0.007), jaundice (p=0.002), and body weight loss (p=0.002). CONCLUSIONS: Ursodeoxycholic acid, at a dose of 8-13 mg/kg/day was beneficial for the general condition and liver biochemistry of patients with primary sclerosing cholangitis; high-dose ursodeoxycholic acid treatment requires further evaluation.

Alcohol abstinence does not offset the strong negative effect of lifetime alcohol consumption on the outcome of interferon therapy.

Heavy alcohol consumption has been reported to negatively affect the outcome of interferon therapy. We studied the impact of lifetime alcohol consumption in patients with chronic hepatitis C treated with interferon after 6 months of alcohol withdrawal. Alcohol intake was measured when patients with chronic hepatitis C were referred to us for the first time, and from that moment complete abstinence was recommended. After 6 months of abstinence, 150 patients with persistent elevated serum alanine aminotransferase (ALT) have been treated with interferon (IFN)-alpha, 3 or 6 microU three times per week for 12 months. Univariate and multivariate analysis were performed to identify the predictors of treatment response. Carbohydrate-deficient transferrin was employed to assess alcoholic abstinence. The sustained response rate felt from 33% in nondrinkers to 20% of mild-drinkers and to only 9% in heavy drinkers. Drinker patients showed a relapse rate twice as high as that of nondrinkers. According to the multivariate analysis, the strongest independent predictors of nonresponse were genotype 1b infection, age of the patients and their lifetime alcohol intake. Carbohydrate-deficient transferrin detected at baseline, at 3 months of therapy and at the end of follow-up gave a positive result only in eight determinations (1.77%), confirming the compliance of patients to our recommendation of alcohol abstinence. Lifetime alcohol consumption has a strong negative effect on the outcome of interferon treatment, mainly in heavy drinkers. A 6-month period of abstinence may not be sufficient to offset this negative effect on treatment outcome.

Outcome of surgical treatment for chronic calcifying pancreatitis.

OBJECTIVE: To evaluate the short and long-term results of surgical treatment of calcifying chronic pancreatitis in our center. PATIENTS AND METHODS: We studied 55 consecutive patients operated on for chronic calcifying pancreatitis during a period of 12 years. The mean follow-up period was 6.2 years. Main outcome measures were operative mortality and morbidity, degree of pain control, diabetes onset, survival, and causes of death. RESULTS: The etiology was alcoholic in 48 patients and idiopathic in seven patients. A resection was performed in 78% of cases and a by-pass procedure was performed in 22%. Operative mortality was 3.6%; morbidity was 21.8%. A ductal adenocarcinoma was found in 3.6% of cases. The alcohol withdrawal rate was 78%. Complete pain control was achieved in 71.4% of the patients. Among diabetes, cirrhosis, type of surgery, smoking and alcohol abuse history, only alcohol withdrawal was associated with pain control (p < 0.03). A late reintervention was needed in only one patient in the by-pass group. Five and 10-year survival rates for the entire population were 80% and 61%, respectively. Among alcohol, cirrhosis, diabetes, and type of surgery, only the former was associated with survival (p < 0.003). Five-year actuarial survival was 55.6% for patients who continued drinking compared with 86.3% for ex-alcoholics. CONCLUSIONS: Surgical resection should be performed when required by the anatomical conditions because it was associated with good long-term pain control and low postoperative and late morbidity. Alcohol withdrawal has a key role for effective control of pain and prolonged survival.

Biliary lipid composition in cholesterol microlithiasis.

BACKGROUND: Little information is available on the pathogenesis of cholesterol microlithiasis, and it is not clear if biliary lipid composition in these patients is similar to changes seen in cholesterol gall stone patients. AIMS: To measure biliary lipid composition in patients with cholesterol microlithiasis. PATIENTS: Eleven patients with cholesterol microlithiasis, 20 cholesterol gall stone patients, and 17 healthy controls. METHODS: Duodenal bile was collected in the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids, and total bile acids were analysed by enzymatic assays, and conjugated bile acids by high pressure liquid chromatography. RESULTS: Patients with microlithiasis had a cholesterol saturation index significantly higher than controls (mean value 1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6)) and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8), respectively) but was significantly increased in gall stone patients (10.9% (9.3-12.4)). Bile acid composition in patients with microlithiasis was similar to controls whereas in gall stone patients deoxycholic acid was significantly increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9-26.2) in patients with microlithiasis. CONCLUSION: Patients with cholesterol microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol gall stone patients. Whereas in the latter this is due to increased per cent cholesterol, in patients with microlithiasis this is caused by phospholipid deficiency, with normal per cent cholesterol and normal biliary bile acid composition.

Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.

BACKGROUND: Combination therapy using ursodeoxycholic acid plus chenodeoxycholic acid has been advocated for dissolution of cholesterol gallstones because the two bile acids have complementary effects on biliary lipid metabolism and cholesterol solubilization. AIM: To compare the clinical efficacy of combination therapy with ursodeoxycholic acid monotherapy. PATIENTS AND METHODS: A total of 154 symptomatic patients with radiolucent stones (< or = 15 mm) in functioning gallbladders were enrolled from six centres in England and Italy. They were randomized to either a combination of chenodeoxycholic acid plus ursodeoxycholic acid (5 mg.day/kg each) or to ursodeoxycholic acid alone (10 mg.day/kg). Dissolution was assessed by 6-monthly oral cholecystography and ultrasonography for up to 24 months. RESULTS: Both regimens reduced the frequency of biliary pain and there was no significant difference between them in terms of side-effects or dropout rate. Complete gallstone dissolution on an intention-to-treat basis was similar at all time intervals. At 24 months this was 28% with ursodeoxycholic acid alone and 30% with combination therapy. The mean dissolution rates at 6 and 12 months were 47% and 59% with ursodeoxycholic acid, and 44% and 59% with combination therapy, respectively. CONCLUSION: There is no substantial difference in the efficacy of combined ursodeoxycholic acid and chenodeoxycholic acid and that of ursodeoxycholic acid alone in terms of gallstone dissolution rate, complete gallstone dissolution, or relief of biliary pain.

Spontaneous rupture of hepatocelluar carcinoma: surgical resection and long-term survival.

AIMS: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening event, particularly in patients with associated cirrhosis. We present our experience of hepatic resection of ruptured HCC. METHODS: We performed 199 resections of hepatocellular carcinoma between January 1984 and December 1999. Six (3%) of these patients were operated on as an emergency because of haemoperitoneum: in five the liver was cirrhotic. RESULTS: The mean duration of the operation was 195+/-101 min; all the patients received blood transfusions. The overall morbidity was 50%, with a mortality rate of 16.5%. Three patients were alive at 50, 80 and 116 months respectively; two had an intrahepatic recurrence treated by chemoembolization. CONCLUSIONS: Non-surgical treatment of spontaneously ruptured hepatocarcinoma should be performed only in patients with contraindication to surgery. Hepatic resection should be the treatment of choice since, according to our experience, long-term results are similar to those of elective surgery.

Liver function and encephalopathy after partial vs direct side-to-side portacaval shunt: a prospective randomized clinical trial.

BACKGROUND: The aim of this study was to determine, in a prospective randomized clinical trial, whether the partial portacaval shunt offers any advantage in terms of liver function and encephalopathy rate when compared with direct side-to-side direct portacaval shunt. METHODS: Forty-six "good risk" patients with cirrhosis and with documented variceal hemorrhage were randomly assigned to either a partial shunt procedure (achieved by 10-mm diameter interposition portacaval H-graft) or direct small-diameter side-to-side portacaval anastomosis. RESULTS: Operative mortality was zero in both groups. During the follow-up period, encephalopathy developed in 3 patients in the partial shunt group and 9 in the direct shunt group (P =.04). Kaplan-Meier analysis demonstrated that encephalopathy-free survival was significantly longer in the partial shunt group (P =.025). Direct shunt patients had significant hepatic functional deterioration postoperatively compared with the partial shunt group. CONCLUSIONS: The partial portacaval shunt effectively controls variceal hemorrhage. Compared with direct side-to-side portacaval shunt, partial shunt preserves long-term hepatic function and minimizes postoperative encephalopathy. We conclude that the partial portacaval shunt is the preferred approach over direct shunts for patients with cirrhosis and with variceal bleeding.

Serum interferon gamma in primary biliary cirrhosis: effect of ursodeoxycholic acid and prednisone therapy alone and in combination.

BACKGROUND: Interferon-gamma may have immunopathogenic importance in primary biliary cirrhosis, stimulating aberrant expression on biliary epithelium of class II major histocompatibility molecules and inter-cellular adhesion molecule-1. Liver transcripts for interferon-gamma are found in primary biliary cirrhosis. Its serum level is increased in pretransplantation stages and decreases after transplantation. OBJECTIVES: (1) To verify whether serum interferon-gamma levels are increased in non-cirrhotic stages of primary biliary cirrhosis. (2) To evaluate the effect of ursodeoxycholic acid and prednisone alone and in combination on serum levels of interferon-gamma and soluble inter-cellular adhesion molecule-1. METHODS: Nine non-cirrhotic, anicteric patients with primary biliary cirrhosis (patient test group), 14 healthy, negative controls and 14 positive controls, with chronic hepatitis related to hepatitis C virus were studied in basal condition. Primary biliary cirrhosis patients were treated with ursodeoxycholic acid, prednisone and the association of the two drugs for three 4-week periods, each period separated by a 4-week wash-out. Interferon-gamma and soluble inter-cellular adhesion molecule-1 were measured in serum by commercially available immuno-enzymatic kits. RESULTS: Median interferon-gamma levels were increased in patients with primary biliary cirrhosis compared with healthy controls (44 vs 19 pg/ml; P < 0.01) but similar to those in chronic hepatitis patients (47 pg/ml). Serum soluble inter-cellular adhesion molecule-1 was significantly reduced by ursodeoxycholic acid, and an even greater reduction was obtained on addition of prednisone. No treatment affected interferon-gamma levels. CONCLUSION: Serum interferon-gamma is increased in noncirrhotic patients with primary biliary cirrhosis, but this is not disease-specific. Neither ursodeoxycholic acid, nor prednisone, nor the combination of the two drugs influenced this immunological pathway of primary biliary cirrhosis.

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients]. / Impiego dell'endoscopia virtuale con Tomografia Computerizzata nell'identificazione delle neoplasie colorettali. Studio prospettico in pazienti sintomatici.

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

Biliary bile acid composition in gastric cancer.

Bile reflux into the stomach has been considered carcinogenic. Secondary bile acids, and in particular deoxycholic acid, have been shown to act experimentally as co-carcinogens in the colon and are increased in patients with colorectal adenocarcinoma. No information is available with respect to biliary bile acid composition in patients with gastric cancer. We studied biliary bile acid composition in 11 patients with gastric cancer and 23 healthy controls. Bile acids were measured using high-performance liquid chromatography. The site of gastric cancer was the antrum in 6 patients and body in 5. There were 6 intestinal-type and 5 diffuse adenocarcinomas. Only 2 patients had Helicobacter pylori infection. Deoxycholic acid constituted 24% +/- 2% of biliary bile acid in gastric cancer patients versus 22% +/- 2% in healthy controls (NS). Similarly, no differences were found between the two groups for all other bile acids. Deoxycholic acid constituted 23% +/- 3% of biliary bile acid (NS vs. controls) in patients with antral adenocarcinoma and 25% +/- 2% (NS vs. controls) in patients with intestinal-type gastric adenocarcinoma. Gastric adenocarcinoma is not associated with an increase in the more-toxic secondary bile acids, and deoxycholic acid in particular. This reduces the importance of bile acid composition as a promotor in gastric carcinogenesis.

Biliary lipid composition in idiopathic bile acid malabsorption.

BACKGROUND: Chronic diarrhoea is the clinical hallmark of patients presenting with idiopathic bile acid malabsorption. Its pathogenesis is unknown; colonic water secretion can be induced by dihydroxy bile acids, but it is not known whether enrichment of the bile acid pool with these bile acids occurs in such patients. Furthermore, bile acid malabsorption is known to affect biliary lipid composition, but no information is available for the idiopathic type. AIMS: To verify: (a) whether diarrhoea in patients with idiopathic bile acid malabsorption is associated with enrichment of the bile acid pool with dihydroxy bile acids; and (b) whether supersaturation with cholesterol of duodenal bile occurs in such patients as a result of chronic bile acid depletion. PATIENTS: Thirteen patients with idiopathic bile acid malabsorption diagnosed according to abnormal 75SeHCAT test and absence of other organic diseases, and 23 control subjects. METHODS: Bile rich duodenal fluid was collected during intravenous ceruletide infusion in the fasting state. Biliary lipids were analysed by enzymatic assays and bile acids by high performance liquid chromatography. RESULTS: Patients with idiopathic bile acid malabsorption had a cholesterol saturation index similar to controls. Bile acid composition showed only a decrease in percentage cholic acid (29 (2)% versus 36 (2)%; p<0.05); the dihydroxy:trihydroxy bile acid ratio was similar to controls. CONCLUSIONS: Patients with idiopathic bile acid malabsorption do not have an increased risk of forming cholesterol gallstones. The mechanism of diarrhoea does not seem to depend on an enrichment of the bile acid pool with dihydroxy bile acids.

Minimal change nephropathy presenting in a patient with primary sclerosing cholangitis.

The association of primary sclerosing cholangitis and renal disease is not frequent, and is limited to a few reported cases of immune complex glomerulonephritis. We report the case of a 34-year-old patient with sclerosing cholangitis diagnosed 5 years earlier, with well preserved liver function and no clinical manifestations of cholestasis, who developed minimal change nephropathy. During the nephrotic phase of the disease, the peripheral blood lymphocyte count was normal, with a relative increase in percent CD4+ and an increase in the CD4+: CD8+ ratio. CD4+ cells showed immunoactivation. The HLA-DR expression on T-cells was 59%, and 16.5% of CD3+ cells were CD25+. A course of prednisone therapy induced long-lasting remission of the nephrotic syndrome. Peripheral blood lymphocyte count and subtyping were normal 7 months after prednisone withdrawal. We conclude that primary sclerosing cholangitis can be associated with minimal change nephropathy; underlying cell-mediated immunity may be the common pathogenic mechanism.

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 therefore an effective long-term management strategy, especially in patients with primary single gallstones.

Determination of gallbladder bile lithogenicity in patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis have a higher prevalence of gallstone disease. Aim of this study was to determine whether gallbladder bile of these patients is lithogenic. We studied 11 patients with early stage primary biliary cirrhosis, and compared them with 16 control subjects. We combined a cholescintigraphic method with nasoduodenal bile sampling to measure the mass of lipids within the gallbladder. Cholesterol saturation index, as measured by standard techniques, was similar in patients with primary biliary cirrhosis and controls (medians: 0.85 vs 0.90). Primary biliary cirrhosis patients showed a significant reduction in the masses of cholesterol, phospholipids and bile acids, as well as in percent biliary deoxycholic acid, as measured by high pressure liquid chromatography (medians 8.6% vs 17.4% in controls; p < 0.05). Percent deoxycholic acid directly correlated with cholesterol mass in all subjects (r = 0.48; p < 0.05). Biliary lipid coupling were similar in the two groups. We conclude that, in patients with early stage primary biliary cirrhosis, gallbladder bile is not lithogenic and biliary lipid coupling is normal, due to a parallel reduction in the masses of cholesterol, phospholipids and bile acids. The significant reduction in percent deoxycholic acid, characteristic of cholestasis, may help explain this biliary lipid mass pattern, that differs from that of cholesterol gallstone patients.