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PubMedDate not supplied

Bacteriological studies of bile from the gallbladder in patients with carcinoma of the gallbladder, cholelithiasis, common bile duct stones and no gallstones disease.

OBJECTIVE: To compare the presence of bacteria of bile from the gallbladder in control subjects, patients with gallstones, and patients with carcinoma of the gallbladder. DESIGN: Prospective open study. SETTING: University department of surgery. SUBJECTS: 372 patients of whom 36 had no signs of gallbladder disease; 211 underwent cholecystectomy for either symptomatic gallstone disease (n = 165) or acute cholecystitis (n = 46); 67 had common bile duct stones and 58 were operated on for carcinoma of the gallbladder. INTERVENTIONS: Aspiration of bile from the gallbladder. MAIN OUTCOME MEASURES: Prevalence of pathogenic bacteria in bile from the gallbladder and correlations between the presence of bacteria, the presence of cancer, and age. RESULTS: No pathogenic bacteria were grown from the bile of the patients who had no signs of gallstones disease. Among the 165 with symptomatic gallstone disease 52 (32%) had pathogens in their bile, and among the 46 with acute cholecystitis the corresponding figure was 19 (41%) while among patients with common bile duct stones this figure was 39 (58%). Among the 58 patients with carcinoma of the gallbladder the bile grew organism in 47 (81%). Patients over the age of 60 years tended to be more likely to have organism in their bile than patients aged 60 or less, and the difference was significant for symptomatic gallstone disease (p < 0.003). Significant differences were also found between patients with symptomatic gallstone disease and those with carcinoma of the gallbladder in both age groups (p < 0.002 in each case). Most of the organism were aerobic or anaerobic Gram negative species, irrespective of type of disease or age. CONCLUSION: Bacteria may have a role in the development of carcinoma of the gallbladder.

Adult↗
PubMed1990

Bile concentration is a key factor for nucleation of cholesterol crystals and cholesterol saturation index in gallbladder bile of gallstone patients.

We investigated whether bile concentration influenced cholesterol saturation index or nucleation time of cholesterol monohydrate crystals in a large number of gallbladder bile samples. Pigment stone patients never had cholesterol crystals in their fresh biles, and nucleation time was always longer than 20 days. Of the cholesterol stone patients 79% had cholesterol crystals in their fresh biles. Long nucleation times were generally found in cholesterol stone patients with dilute biles despite a high cholesterol saturation index. Nucleation time was usually short if bile was well concentrated despite a relatively low saturation index. Serial in vitro dilution of concentrated biles from cholesterol gallstone patients resulted in progressively prolonged nucleation times. Patients with solitary cholesterol stones had longer nucleation times than patients with multiple cholesterol stones. This study indicates that bile concentration is an important factor for nucleation time and cholesterol saturation index. Moreover, solitary and multiple cholesterol stones may have a different pathogenesis.

Adult↗
PubMedDate not supplied

Diagnosis of malignant obstructive jaundice by bile cytology: results improved by dilating the bile duct strictures.

The disruption of malignant biliary strictures by dilation could enhance the results of bile cytology. To test this hypothesis, we studied the results of bile cytology in 64 consecutive patients undergoing endoscopic biliary drainage for malignant biliary strictures. Patients included 36 men and 28 women, ages 29 to 79 years. In the control group (n = 15), bile was obtained by aspiration without dilating the biliary stricture. In the dilated group (n = 49), bile was aspirated after dilating the biliary stricture to 10F gauge. The bile was centrifuged, and smears were prepared, stained, and interpreted as malignant, suggestive of malignancy, or not malignant. The biliary obstruction was caused by gallbladder cancer in 33, primary bile duct cancer in 14, pancreatic cancer in 11, and metastasis in 6 patients. Forty patients had obstruction at the bifurcation of the hepatic duct. Malignancy was confirmed by surgery in 14, fine-needle aspiration cytology in 9, presence of metastasis in 19, and a combination of clinical and radiologic studies, endoscopic cholangiopancreatography findings, elevated tumor markers, and follow-up in 22 patients. Bile cytology was positive for malignancy in 4 (26.6%) and 31 (63.3%), suggestive in 1 (6.7%) and 6 (12.2%), and negative in 10 (66.7%) and 12 (24.5%) patients in the control group and the dilated group, respectively (p = 0.028, 95% CI 1.15 and 21.03). Cytology was positive in 73% of gallbladder cancers, 62.5% of bile duct cancers, 40% of pancreatic cancers, and 60% of metastasized cancers after dilation. Two patients had hemobilia, 8 had cholangitis, and 2 had pancreatitis after biliary drainage.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile↗
PubMed2004

Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice.

BACKGROUND & AIMS: Because the mechanisms leading to bile duct damage in sclerosing cholangitis are unknown, we aimed to determine the pathogenesis of bile duct injury in multidrug resistance gene (Mdr2) (Abcb4) knockout mice (Mdr2(-/-)) as a novel model of the disease. METHODS: Mdr2(-/-) and wild-type controls (Mdr2(+/+)) were studied at 2, 4, and 8 weeks of age. Liver histology, ultrastructure, immunofluorescence microscopy (to study inflammatory cells, tight junction protein ZO-1, basement membrane protein laminin, fluorescence-labeled ursodeoxycholic acid), immunohistochemistry (for alpha-smooth muscle actin, nitrotyrosine), sirius red staining, bacterial cultures of intra-abdominal organs, and polymerase chain reaction (PCR) for Helicobacter bilis DNA were compared between both genotypes. Hepatic cytokine expression was determined by reverse-transcription PCR. RESULTS: Bile ducts of Mdr2(-/-) showed disrupted tight junctions and basement membranes, bile acid leakage into portal tracts, induction of a portal inflammatory (CD11b, CD4-positive) infiltrate, and activation of proinflammatory (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta) and profibrogenic cytokines (transforming growth factor [TGF]-beta1). This resulted in activation of periductal myofibroblasts, leading to periductal fibrosis, separating the peribiliary plexus from bile duct epithelial cells and, finally, causing atrophy and death of the bile duct epithelium. Bacterial translocation was not increased and H. bilis was not detectable in Mdr2(-/-). CONCLUSIONS: Sclerosing cholangitis in Mdr2(-/-) mice is a multistep process with regurgitation of bile from leaky ducts into the portal tracts, leading to induction of periductal inflammation, followed by activation of periductal fibrogenesis, finally causing obliterative cholangitis owing to atrophy and death of bile duct epithelial cells.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2001

Is preventive resection of the extrahepatic bile duct necessary in cases of pancreaticobiliary maljunction without dilatation of the bile duct?

BACKGROUND: No consensus has been reached on whether preventive resection of the extrahepatic bile duct is necessary in cases of pancreaticobiliary maljunction (PBM) without dilatation of the extrahepatic bile duct (undilated type). METHODS: Sixty-eight patients with PBM underwent corrective surgery and several clinical characteristics and pathological findings including K-ras point mutation were evaluated. RESULTS: Unlike dilated bile duct, none of the patients with undilated type duct had clinical symptoms in early childhood. In patients with either cystic or spindle type duct, amylase levels in the bile duct were >10(4) U/l, whereas those in patients with undilated type duct were <10(4) U/l. Postoperative scintigraphy of the biliary system of undilated type revealed no evidence of cholestasis. After surgery, eight patients with undilated type duct, in whom the bile duct had been preserved, had no further clinical symptoms and no evidence of malignancy. Bile duct tissue specimens revealed no hyperplasia, dysplasia or cancerous lesions and they had no K-ras mutation in undilated type. CONCLUSION: The results showed that there was little bile stasis, injury to the mucosa was mild and less genetic changes could be seen in patients with undilated type duct. Therefore, in patients without dilatation of bile duct and advanced cancer, cholecystectomy alone is sufficient.

Adult↗
PubMed2004

Role of farnesoid X receptor in the enhancement of canalicular bile acid output and excretion of unconjugated bile acids: a mechanism for protection against cholic acid-induced liver toxicity.

Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of hepatic bile acid levels are highly sensitive to cholic acid-induced liver toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold after feeding a 0.25% cholic acid diet, whereas only slight increases in serum AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic acid diet, respectively. Bile salt export pump mRNA and protein levels were increased in wild-type mice fed 1% cholic acid diet (2.1- and 3.0-fold) but were decreased in FXR-null mice fed 0.25% cholic acid diet. The bile acid output rate was 2.0- and 3.7-fold higher after feeding of 0.25 and 1.0% cholic acid diet in wild-type mice, respectively. On the other hand, no significant increase in bile acid output rate was observed in FXR-null mice fed 0.25% cholic acid diet in contrast to a significant decrease observed in mice fed a 1.0% cholic acid diet in spite of the markedly higher levels of hepatic tauro-conjugated bile acids. Unconjugated cholic acid was not detected in the bile of wild-type mice fed a control diet, but it was readily detected in wild-type mice fed 1% cholic acid diet. The ratio of biliary unconjugated cholic acid to total cholic acid (unconjugated cholic acid and tauro-conjugated cholic acid) reached 30% under conditions of hepatic taurine depletion. These results suggest that the cholic acid-induced enhancement of canalicular bile acid output rates and excretion of unconjugated bile acids are involved in adaptive responses for prevention of cholic acid-induced toxicity.

Adenosine Triphosphate↗
PubMed1978

Importance of bicarbonate in bile salt independent fraction of bile flow.

The bile salt independent fraction (BSIF) of canalicular bile flow from the isolated rat liver perfused with bicarbonate-free perfusate is 50% of that from the liver perfused with bicarbonate-containing perfusate. HCO3-excretion is nearly eliminated and Na+ and Cl- excretion is reduced 50%. Replacement of HCO3- into perfusate increased bile flow by 0.3 microliter/g.min without changing bile acid excretion rate. 5.5-Dimethyl-2,4-oxazolidinedione (DMO) produced a similar effect. DMO was passively distributed between bile and plasma. The data indicate that a bicarbonate transport mechanism is responsible for production of up to 50% of the BSIF. Another weak acid, N-5[5-(2-methoxyethoxy)-2-pyrimidinyl]sulfamoylbenzene (glymidine), was rapidly excreted into bile and increased bile flow by over 2.0 microliter/g.min. Glymidine is probably excreted by an independent organic anion transport mechanism, and any effect on the bicarbonate transport mechanism is obscured. Canaliculus-enriched hepatocyte membrane fractions contained no HCO3-stimulated ATPase activity. Either this enzyme is unimportant in hepatocyte bicarbonate transport or transport occurs across membranes other than the bile canalicular membrane.

Adenosine Triphosphatases↗
PubMed1985

Nuclear magnetic resonance spectroscopy of bile acids. Development of two-dimensional NMR methods for the elucidation of proton resonance assignments for five common hydroxylated bile acids, and their parent bile acid, 5 beta-cholanoic acid.

The complete 1H nuclear magnetic resonance assignments have been made for the common mono-, di-, and trihydroxy 5 beta-cholanoic acids; lithocholic acid, chenodeoxycholic acid, ursodeoxycholic acid, deoxycholic acid, cholic acid, and the unsubstituted parent compound, 5 beta-cholanoic acid, by heteronuclear-correlated two-dimensional NMR. The known 13C chemical shifts of these compounds were used to make the proton resonance assignments, and consistency of the carbon and proton assignments was verified by expected changes due to substituent effects. This has led to clarification of previously published 13C NMR resonance assignments. Addition of the 3 alpha, 7 alpha, and 12 alpha hydroxyl substituent effects derived from the mono- and dihydroxycholanoic acids yielded predicted values for proton chemical shifts of the trihydroxy-substituted 5 beta-cholanoic acid, cholic acid, that agreed well with experimental values. It is suggested that the individual substituent effects can be used to predict proton chemical shifts for hydroxycholanic acids containing other combinations of 3 alpha, 7 alpha, 7 beta, and 12 alpha hydroxyl groups.

Bile Acids and Salts↗