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Cholelithiasis following peptic ulcer surgery: a prospective controlled study.

An association between gastric surgery and gallstones has been suggested but conflicting conclusions are found in the literature. A prospective study of 118 patients with proved duodenal ulcer disease has been undertaken to determine the true incidence of gallbladder disease. Sixty-one patients undergoing surgery and 57 patients treated medically were matched for age, sex and weight. All patients had oral cholecystography at entry into the study and at 18 months and 109 were reviewed radiologically at 3 years. Three patients in the surgical group developed asymptomatic gallstones whereas none were detected in the medical group. This gives an incidence of gallstones of 4.9 per cent 3 years after gastric surgery. These findings are discussed.

Adult↗

Extracorporeal shockwave lithotripsy and litholytic therapy in cholelithiasis.

Extracorporeal shockwave lithotripsy (ESWL) and litholytic therapy were used in 100 patients over a period of 16 months. ESWL was carried out with a Lithostar Plus and chenodeoxycholic acid was used as the lytic agent, given until 3 months after complete disappearance of stones. Within a period of 8-12 months, stones disappeared completely in 82 per cent of the patients who had a single stone less than or equal to 20 mm in diameter and in 50 per cent of those with a single stone greater than 20 mm in size or with multiple stones. Complications requiring surgery developed in five patients: three had acute cholecystitis and two developed acute pancreatitis. Of the patients in whom complete stone clearance was achieved, two of 11 followed up developed recurrence of stones 4 months after cessation of lytic therapy.

Adolescent↗

Cholelithiasis and bile acid absorption after truncal vagotomy and gastroenterostomy.

Gallbladder disease in the form of gallstones demonstrated by ultrasonography or previous cholecystectomy was found in 15 of 26 women of median age 69 (range 52-82) years who had had truncal vagotomy and gastroenterostomy performed a median of 27 (range 11-30) years previously, compared with eight of 31 healthy age- and sex-matched controls drawn from the community (P < 0.02). Bile acid malabsorption identified by retention of 23-selena, 25-homotaurocholate (75SeHCAT) occurred in only two of the 26 patients after vagotomy and there was no relationship between retention and the presence or absence of gallbladder disease. The serum concentration of 7 alpha-hydroxycholestenone, an indicator of bile acid turnover, was significantly lower in patients with gallbladder disease after vagotomy than in controls (mean(s.e.m.) 19.1(3.7) versus 31.4(4.4) ng/ml, P < 0.05). Bile acid malabsorption does not play a significant role in the pathogenesis of gallstones after vagotomy but decreased bile acid synthesis may be important. There is no correlation between retention of 75SeHCAT and 7 alpha-hydroxycholestenone levels in patients after vagotomy, indicating that bile acid synthesis and absorption are uncoupled in this situation.

Absorption↗

Analysis of bilirubins in biological fluids by extraction and thin-layer chromatography of the intact tetrapyrroles: application to bile of patients with Gilbert's syndrome, hemolysis, or cholelithiasis.

A method was developed to extract quantitatively the bilirubins from bile, urine, serum, stool, and preparations from liver with a chloroform-ethanol mixture at pH 1.8 in the presence of ascorbic acid and NaCl. Extracted pigment was submitted to thin-layer chromatography, and the separated bilirubins were either immediately eluted and determined spectrophotometrically or individually converted to ethyl anthranilate azo derivatives for thin-layer chromatographic analysis of each isolated pigment band. Bilirubins in duodenal bile of eight healthy adults comprised 1.5 +/- 1.3% unconjugated bilirubin-IX alpha, 69 +/- 6% bilirubin diglucuronide, and 16 +/- 4% bilirubin monoglucuronides. Mixed diconjugates containing one glucuronosyl moiety and either one xylosyl or one glucosyl group amounted to 10 +/- 3%. Most samples (6 of 8) contained trace amounts (0.6 +/- 0.6%) of unconjugated bilirubin-IX beta, in agreement with nearly exclusive cleavage of heme at the alpha-meso position. The composition of the bilirubins in bile was normal in 6 patients with cholesterol gallstones, 4 with chronic hepatitis, and 3 with hemolysis. In duodenal bile of individuals with Gilbert's syndrome (n = 10), the concentration of bilirubin conjugates was comparable to that in healthy adults, but the proportion of bilirubin diglucuronides (52 +/- 8%) was decreased. The concentration of unconjugated bilirubin-IX alpha showed a fair positive correlation with that of bilirubin monoglucuronide and was increased in half of the patients with Gilbert's syndrome.

Bile↗

Oleic acid-induced cholelithiasis in the rabbit: conversion of dietary oleic acid to cholestanol as a cause of calcium-bile salt gallstones.

Rabbits fed a diet rich in oleic acid develop gallstones consisting of calcium salts of (5 alpha)-glyco-allodeoxycholic acid. To study the metabolic pathway of oleic acid, we followed the changes in plasma, hepatic and biliary lipids in this animal model. In addition, to also determine the role played by intestinal microflora on biliary lipid metabolism, we added kanamycin to the oleic acid diet. Oleic acid-fed rabbits rapidly developed hypercholesterolemia. This was associated with an increase in liver 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, accumulation of cholesterol as well as cholestanol in the liver and progressive saturation of cholesterol in bile. [14C]oleic acid fed orally to rabbits was recovered in liver extracts as both cholesterol and cholestanol. With oleic acid feeding, there was a progressive increase in glyco-allodeoxycholic acid culminating in the formation of gallstones. Kanamycin supplement to the oleic acid diet resulted in the same changes in plasma and hepatic sterol metabolism compared with oleic acid-fed rabbits. There was, however, a striking difference in the biliary bile acid profile. Kanamycin supplementation dramatically reduced the proportion of 5 alpha-dihydroxy bile acids, increased the proportion of 5 beta-trihydroxy bile acids and completely abolished gallstone formation. We postulate that, in the rabbit, oleic acid is used as a carbon source for cholesterol synthesis, and a high oleic acid diet increases hepatic cholesterogenesis. Hepatic cholesterol is then metabolized to form cholestanol, followed by (5 alpha)-glyco-allocholic acid which is secreted into bile and transformed by gut bacteria to form (5 alpha)-allodeoxycholic acid. Kanamycin abolished gallstone formation by inhibiting intestinal bacterial dehydroxylation.

Animals↗

Factors associated with gallstone disease in the MICOL experience. Multicenter Italian Study on Epidemiology of Cholelithiasis.

The epidemiological associations of gallstone disease were evaluated in a general population sample of 29,584 individuals (15,910 men and 13,674 women; age range, 30-39 years) belonging to 14 cohorts examined between December 1984 and April 1987. Subjects were screened for the presence of gallstones by gallbladder ultrasonography, completed a questionnaire, and underwent a physical examination and blood chemistry tests. Participants were considered to have gallstone disease if they had already had cholecystectomy or gallstones. Statistical associations were established by univariate analysis of the age-standardized data and by stepwise multiple logistic regression. Increasing age and body mass index and a maternal family history of gallstone disease were the most consistent associations (both at univariate and multivariate analysis and in both sexes) found in this study. Personal history of dieting was associated with gallstone disease in men, and at univariate analysis, in women. Decreasing serum total cholesterol levels and increasing serum triglycerides were associated with gallstone disease in both sexes in the multivariate analysis. In women, associations were also found with a number of pregnancies and paternal family history of gallstone disease. A slight but negative association with contraceptive pill use was identified only at multivariate analysis. Associations (investigated at univariate analysis) were also found with diabetes, cirrhosis, angina or myocardial infarction, and peptic ulcer. There was no association with smoking habits and use of aspirin or antirheumatic drugs.

Adult↗

Clinical manifestations of gallstone disease: evidence from the multicenter Italian study on cholelithiasis (MICOL).

Despite the many efforts to delineate the clinical manifestations of gallbladder disease, the precise symptom complex associated with gallstones is still a matter of debate, and even the existence of gallstone-specific symptoms has been questioned. We carried out a large population-based cross-sectional study (MICOL) to identify symptoms significantly related to gallstones. Fourteen centers throughout Italy enrolled 29,504 subjects aged 30 to 69 years. All subjects were administered an ultrasonographic examination of the upper abdomen and a precoded questionnaire. All subjects were divided into 4 groups: 25,374 (86.0%) gallstone-free subjects (GF), 1,832 (6.2%) patients with gallstones not previously diagnosed (GNPD), 638 (2.2%) patients with gallstones previously diagnosed (GPD), 1,660 (5.6%) patients with a history of cholecystectomy for gallstones (CC). In logistic regression analysis, pain at epigastrium and, even more, pain at right hypocondrium were significantly associated with gallstones. For pain at right hypocondrium, this association progressively increased from GNPD (OR = 1.60, 95% CI = 0.97-2.65) to GPD (OR = 8.77, 95% CI = 5.27-14.61) to CC (OR = 59.40, 95% CI = 43.87-80.42). Absence of heartburn combined with right hypocondrium or epigastrium pain and intolerance to fried or fatty food were also significantly related to gallstones. We also found some pain characteristics significantly associated with gallstones, i.e., pain radiated to the right shoulder, forcing the patient to rest, occurring soon after meals or unrelated to meals, not relieved by bowel movements, and frequently accompanied by gallstone-related morbidities. We developed a probability tree reporting the cumulative probability of having gallstones for each combination of those symptoms and characteristics of pain significantly associated with gallstones. In conclusion, we have identified symptoms and signs significantly associated with gallstones. We have shown that there is an increase in frequency and severity of these symptoms and signs across the different stages of gallstone disease. We have proposed a complex of symptoms and signs significantly associated with gallstones that might help physicians in clinical decision making.

Adult↗