Carcinoma of the Gallbladder—Is It a Sequel of Typhoid?

Gallbladder diseases, including carcinoma, are common in the northern part of India and so are Salmonella typhi infection and typhoid carrier state. This study was aimed to find out the association of typhoid carrier state in patients with cholelithiasis, carcinoma of the gallbladder, and controls. The three groups are comparable in age and sex composition. This is the first study of its kind from an area of high endemicity for both typhoid infection and carcinoma of the gallbladder. A case–control study was carried out to detect typhoid carrier state among the patients with biliary diseases and healthy controls, using indirect haemagglutination assay measuring antibodies against highly purified S. typhi Vi polysaccharide antigen. A significantly high Vi positivity was observed in patients with gallbladder carcinoma (29.4%) compared to controls (5%) (² = 6.325, P < 0.004, OR = 7.19) and patients with cholelithiasis (10.7%) (² = 5.066, P < 0.01, OR = 3.86). There is 8.47 times more risk of developing carcinoma of the gallbladder in culture-positive typhoid carriers than the noncarriers. The present study suggests the typhoid carrier state to be one of the possible mechanisms of gallbladder carcinogenesis.     

Cancer of the Gallbladder in Bolivia: Suggestions Concerning Etiology

In order to investigate the very high incidence of gallbladder cancer in Bolivia, a series of patients with gallbladder cancer and/or cholelithiasis from a hospital in La Paz was compared to a series of patients with cholelithiasis from Philadelphia. Each group demonstrated a similar female predilection. Bolivian patients with gallbladder cancer were older than patients with cholelithiasis who, in turn, were older than the general population (p less than 0.001). Racial differences demonstrated previously were confirmed. Bolivian gallstones were uniformly cholesterol in type, in contrast to the US series, in which 27% of patients had black pigment stones. Bile specimens obtained from Bolivian patients with cholelithiasis had a lower concentration of bile salts, phospholipids, and cholesterol than bile specimens from US cholelithiasis patients (p less than 0.01, less than 0.001, and less than 0.001, respectively). These biochemical differences may help to explain the differing incidence of cholelithiasis and gallbladder cancer in the US and Bolivia.     

Gallbladder function during gallstone dissolution. Effect of bile acid therapy in patients with gallstones

Impaired gallbladder emptying has been associated with gallstone disease but any effect on or from bile acid therapy for gallstone dissolution is unknown. We evaluated gallbladder filling and emptying with low-dose cholecystokinin infusion (0.02 U/kg.h) by computer-assisted cholescintigraphy in 52 controls versus 31 gallstone patients: 17 treated with 12-15 mg/kg.day of chenodeoxycholic acid and 14 with 8-10 mg/kg.day of ursodeoxycholic acid. Thirteen of 31 patients with complete dissolution had four scans: before, after 3 mo of therapy, after stone dissolution, and after discontinuation of bile acids. The 18 failures had three scans: before and after 3 and 15-18 mo of therapy. Before therapy, the 31 gallstone patients had significantly impaired gallbladder emptying compared with controls, but filling was not decreased. Bile acids significantly decreased emptying in both treatment groups after 3 mo of therapy. In the dissolution group, emptying improved once the stones had dissolved and increased further upon discontinuing the bile acids. In the failures, impaired emptying persisted for up to 15-18 mo. Gallbladder filling in the 31 gallstone patients was also significantly decreased after 3 mo of bile acid therapy, particularly in the failure patients, 5 of whom exhibited zero filling. No differences were detected between ursodeoxycholic acid and chenodeoxycholic acid for either gallbladder function or efficiency of dissolution. Thus, bile acid therapy impairs gallbladder filling and emptying in gallstone patients. Gallstone dissolution improves emptying, which is further enhanced when bile acids are discontinued.     

Tract microflora in Saudi patients with cholelithiasis

OBJECTIVES: To identify the microflora in the gallbladder of patients undergoing laparoscopic cholecystectomy for gallstones, and the antibiotic susceptibility pattern of the isolates, as well as the usefulness of Gram staining of bile at the time of operation. METHODS: Bile samples were obtained from 112 patients undergoing elective laparoscopic cholecystectomy for gallstones and inoculated directly into aerobic and anaerobic blood culture bottles in the operating theatre. Samples were also collected in sterile universal containers for Gram staining of a centrifuged deposit. Isolates were identified and their in-vitro susceptibilities determined by Kirby Bauer technique. RESULTS: Of 112 bile samples examined, 28 (25%) were culture positive, four of which contained more than one organism. The most common organisms isolated were Escherichia coli 9 (28.1%), Enterococcus faecalis 5 (15.6%) and Pseudomonas aeruginosa 3 (9.4%). In one sample we found Aeromonas hydrophilia and Enterobacter cloacae. No anaerobes were detected but Candida albicans was isolated in one case. In 19 bile samples (67.8%) organisms were identified on Gram stain. Positive bile cultures were found statistically significant (P < 0.05) in patients over the age of 50 (13/32), in patients who developed post-operative fever (6/12) and patients who developed leucocytosis (5/6). CONCLUSION: Age over 50 years was the only significant pre-operative factor associated with positive bile cultures (P < 0.05). In view of the microflora of the gallbladder and the susceptibility pattern of our isolates we would suggest that antibiotic prophylaxis recommended for laparoscopic cholecystectomy for gallstones needs to be reviewed and the role of bacteribilia in the surgical management of cholelithiasis requires further study.     

Quantitative study of metals in bile from patients with cholelithiasis.

OBJECTIVE: Biliary lithiasis is a multifactorial phenomenon that is decisively influenced by the composition of bile. We analyzed the presence of eight metals in bile and compared their concentrations in healthy persons and patients with cholelithiasis. METHODS: We studied bile from 119 patients who underwent cholecystectomy because of symptomatic cholelithiasis, and from 25 control subjects in whom the gallbladder was removed for reasons other than cholelithiasis. Metal concentrations were analyzed by atomic absorption spectrophotometry. The subjects were divided into subgroups according to age, sex and type of stone. RESULTS: Bile from patients with cholelithiasis contained significantly less of the essential element magnesium (Mg) and the toxic element lead (Pb) than bile from control subjects. Calcium (Ca) and strontium (Sr) concentrations were also lower in patients with gallstones than in the control group, although the differences were not significant. CONCLUSIONS: Biliary concentrations of Mg and Pb were significantly lower in patients with cholelithiasis than in the control group. The biliary excretion of Ca and Sr was lower in patients than in controls, although the differences were not statistically significant.     

Activated Pancreatic Enzyme and Pancreatic Stone Protein (PSP/reg) in Bile of Patients with Pancreaticobiliary Maljunction/Choledochal Cysts

Symptoms of pancreaticobiliary maljunction/choledochal cysts are caused by the obstruction of bile and pancreatic ducts due to protein plugs compacted in the common channel. However, the mechanism of protein plug formation remains unknown. Pancreatic stone protein (PSP) is reported to be a key protein to form protein plugs in chronic pancreatitis. Bile from 13 patients with pancreaticobiliary maljunction and bile from two normal controls were analyzed. Activity of pancreatic enzymes and the concentration of PSP were measured. The mean concentrations of PSP were 76.9+/-30.9 ng/mL in the bile-duct bile, and 76.9+/-29.8 ng/mL in the gallbladder bile. PSP was not detected in the controls (P < 0.05). In the bile-duct bile of the patients, trypsin(ogen) was detectable in nine patients, of which seven patients had activated trypsin. In the gallbladder bile, trypsin(ogen) was detectable in 12 patients, of which 9 patients had activated trypsin. Neither activated trypsin nor trypsinogen was detected in the controls. Bile in pancreaticobiliary maljunction patients contained both activated trypsin and PSP. Activated trypsin cleaves soluble PSP and creates insoluble PSP. Protein plugs in pancreaticobiliary maljunction may be formed by assembled insoluble PSP.     

Sensitivity of bile acid breath test in the diagnosis of bacterial overgrowth in the small intestine with and without the stagnant (blind) loop syndrome

The bile acid breath test was studied to examine its sensitivity for establishing the diagnosis of bacterial overgrowth in comparison to that of the Schilling test and small-intestinal cultures in 12 patients with a stagnant (blind) loop syndrome, as well as in 38 patients who had other conditions with suspected bacterial contamination of the small intestine. The presence of bile acid malabsorption was excluded in all 50 patients by studies of fecal excretion of radioactively labeled bile acids. The bile acid breath test was positive in 100% (12/12) of the patients with a stagnant (blind) loop syndrome, whereas 92% (11/12) had a positive Schilling test and 75% (9/12) a positive small-intestinal culture. The abnormal tests improved only in 2 of 4 patients treated with tetracycline. In the group of 38 patients without demonstrable dilated or blind loops of small bowel who were suspected of having bacterial contamination of small bowel, the bile acid breath test was positive in 53% (20/38), the Schilling test in 39% (15/38), and the small-intestinal culture in 45% (17/38). The difference in the incidence of positive results between the tests in the two patient groups was statistically not significant. The findings of these studies have the following diagnostic implications: (1) Bile acid breath test, Schilling test, and cultures of aspirates from the upper small bowel are of comparable sensitivity in the detection of bacterial overgrowth in the small intestine. (2) A negative bile acid breath test makes the diagnosis of a stagnant (blind) loop syndrome very unlikely.     

Extrasecretory liver function disorder in patients with chronic pancreatitis]

Bile production and bile secretion studies in 112 patients with primary chronic pancreatitis have demonstrated. Duodenal intubational chromatic examination can be used in addition to standard laboratory and device methods for early diagnosis of "biliary insuffiency" and cholelithiasis. The analysis of efficacy of Ursofalk was made in 30 patients with chronic pancreatitis. Patients received Ursofalk in a dose 10 mg/kg/day for one month. It was established that Ursofalk stabilizes bile secretion and removes biliary insuffiency.     

Biliary Excretion and Concentration of Cefazolin

The excretion of cefazolin into the human biliary tract in health and disease was investigated in 34 patients undergoing surgical procedures. The patients included: I. Four controls. IIA. Eleven patients with cholelithiasis and/or cholecystitis and a radiological visualized gallbladder. IIB. Nine patients with cholethiasis and cholecystitis and a radiologically nonvisualized gallbladder. III. Five patients with obstructive jaundice. IV. Five patients with a T-tube in the common bile duct. Two dose regimes: 1. A single dose of 500 mg and 2. four doses each of 500 mg. given every six hours, were used. Samples of serum, gallbladder bile, common duct bile and gallbladder tissue were assayed for antibiotic activity by the cylinder plate method with Bacillus subtilis. Following administration of four doses of the antibiotic, the mean level of the drug in the gallbladder bile, in controls was 127.0 mug/ml. In the group with cholelithiasis and cholecystitis and a gallbladder that is visualized, a similar high level was noted (mean = 132.2 mug/ml.). In the presence of a nonvisualized gallbladder or obstructive jaundice, the levels in bile were lower. Two hours following a single injection of the drug, the level in the common duct bile reaches a peak of 10 mug/ml and at eight hours falls to less than one mug/ml. In the absence of obstruction cefazolin reaches a significantly high level in bile and could be valuable in treatment of biliary infections.     

Bile acid malabsorption

Opinion statement Patients with bile acid malabsorption typically present with chronic, watery diarrhea. Bile acids recirculate between the liver and small intestine in the enterohepatic circulation. They are reabsorbed in the distal small intestine, and normally only a small fraction of the bile acid pool is lost to the colon during each cycle. In patients with bile acid malabsorption, a larger amount of bile acids is spilled into the colon, where the acids stimulate electrolyte and water secretion, which results in loose to watery stools. The common causes of bile acid malabsorption are ileal resection and diseases of the terminal ileum (Crohn’s disease and radiation enteritis), which result in a loss of bile acid transporters and, consequently, diminished reabsorption. Bile acid malabsorption also has been documented in a small group of patients with chronic, watery diarrhea who have no demonstrable ileal disease (idiopathic bile acid malabsorption). The amount of bile acid loss to the colon determines the clinical presentation. Patients with mild to moderate bile acid malabsorption present with watery diarrhea and generally respond very well to treatment (with abolishment of diarrhea) with bile acid binders such as cholestyramine. Patients with more severe bile acid malabsorption have both diarrhea and steatorrhea. Treatment with cholestyramine is of no benefit in this group of patients and may, in fact, worsen steatorrhea. These patients are best treated with a low-fat diet supplemented with medium-chain triglycerides.     

Biliary lipid composition in patients with nonoperated Crohn's disease

Lipid composition of fasting duodenal bile was studied in 56 patients with nonoperated Crohn's disease, 21 normals matched for age and sex, 13 patients with cholesterol cholelithiasis, and 9 patients with ileal resections. Crohn's patients had a significantly higher mean saturation index, calculated according to Thomas (0.84±0.51) when compared to normal (0.63±0.25). Patients with ileocolonic Crohn's disease and patients with severe bile acid malabsorption, particularly, showed an increased incidence of cholesterol saturated bile. Saturation in patients with nonoperated Crohn's disease was not increased to the levels found in patients with ileal resection or cholesterol gallstones. Bile acid composition of gallbladder bile was characterized by a significant decrease of thedeoxycholate fractions in patients with Crohn's ileocolitis and colitis as well as in ileal resected patients. These qualitative changes of bile acid composition may influence cholesterol solubility. It is concluded that patients with nonoperated Crohn's disease may have an increased risk of developing cholesterol gallstones.     

Biliary carcinoma risk in patients with pancreaticobiliary maljunction and the degree of extrahepatic bile duct dilatation

BACKGROUND/AIMS: Pancreaticobiliary maljunction (PBM) carries a high risk of biliary carcinoma. This study aimed to examine the biliary complications of patients with PBM in relation to the degree of extra-hepatic bile duct dilatation. METHODOLOGY: Ninety-eight cases of PBM could be divided into 5 groups according to the maximum diameter of the extrahepatic bile duct: < or = 10mm, 11-15mm, 16-20mm, 21-30mm, > or = 31mm. The clinicopathological findings of biliary carcinomas associated with PBM were compared with 232 cases of gallbladder carcinoma and 159 cases of bile duct carcinoma that were not associated with PBM. RESULTS: Gallbladder carcinoma occurred in 36 of 65 patients (55%) with PBM whose maximum diameter of the extrahepatic bile duct was < or = 30mm, but no gallbladder carcinoma occurred in patients with PBM whose diameter was > or = 31mm. Bile duct carcinoma occurred in 6 of 52 patients (12%) with PBM whose diameter was > or = 21mm, but no bile duct carcinoma occurred in patients with PBM whose diameter was < or = 20mm. The age at diagnosis of the patients with gallbladder or bile duct carcinoma associated with PBM was significantly younger than those without PBM (p<0.01). CONCLUSIONS: PBM with an extrahepatic bile duct diameter < or = 30mm is associated with a high risk of gallbladder carcinoma. PBM with an extrahepatic bile duct diameter > or = 21mm is associated with a high risk of bile duct carcinoma. Prophylactic cholecystectomy is recommended for patients with PBM without biliary dilatation.     

免疫球蛋白在胆囊胆固醇结石形成中的作用研究

目的:探讨胆囊胆汁和胆囊组织中免疫球蛋白在胆囊胆固醇结石形成中的作用。方法:采用放射免疫分析(RIA)方法分别测定了56例胆囊胆固醇结石及24例非胆石对照患者胆囊组织和胆囊胆汁中sIgA、IgG、IgM、IgE的含量。结果:胆囊胆固醇结石组胆囊组织和胆囊胆汁中sIgA、IgG、IgM、IgE均与对照组有显著性差异(P<0.01或P<0.05),并且胆囊胆固醇结石组胆囊组织中sIgA、IgM、IgE与胆囊胆汁中的sIgA、IgM、IgE成显著正相关关系。多发结石组胆囊胆汁中IgG与单发结石组有显著性差异(P<0.05),而其sIgA、IgM、IgE及胆囊组织中sIgA、IgG、IgM、IgE与单发结石组虽无显著性差异,但均有升高。结论:本实验结果提示:胆囊组织及胆囊胆汁中免疫球蛋白sIgA、IgG、IgM、IgE与胆囊胆固醇结石的形成密切相关,并在胆囊胆固醇结石的形成过程中起着重要作用,为胆囊胆固醇结石形成过程中的重要促成核因子。     

Effect of ursodeoxycholic acid on the kinetics of the major hydrophobic bile acids in health and in chronic cholestatic liver disease.

Beneficial effects of ursodeoxycholic acid in chronic cholestatic liver diseases have been attributed to displacement of hydrophobic bile acids from the endogenous bile acid pool. To test this hypothesis, we determined pool sizes, fractional turnover rates, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid before and 1 mo after the start of treatment with ursodeoxycholic acid (13 to 15 mg/kg body wt/day) in four healthy volunteers and five patients with chronic cholestatic liver diseases (three with primary biliary cirrhosis and two with primary sclerosing cholangitis). Bile acid kinetics were determined by combined capillary gas chromatography-isotope ratio mass spectrometry in serum samples after administration of [2H4] deoxycholic acid and [13C]chenodeoxycholic acid. In healthy volunteers, deoxycholic acid pool sizes decreased during administration of ursodeoxycholic acid by 72%. In patients with cholestatic liver diseases, deoxycholic acid pool sizes before ursodeoxycholic acid treatment were only 13% of those in healthy volunteers and were unaffected by ursodeoxycholic acid treatment. Chenodeoxycholic acid pool sizes were not different in healthy volunteers and in patients with cholestatic liver disease, and were not altered by ursodeoxycholic acid treatment. In both healthy volunteers and patients with cholestatic liver disease, synthesis/input rates and serum levels of deoxycholic acid and chenodeoxycholic acid were not altered by ursodeoxycholic acid treatment. Because in our patients improvement of serum liver tests during short-term ursodeoxycholic acid treatment was noted without a decrease of the pool sizes of the major hydrophobic bile acids, we conclude that displacement of hydrophobic endogenous bile acids is not the mechanism of action of ursodeoxycholic acid in chronic cholestatic liver disease.     

Biliary carcinoembryonic antigen levels in diagnosis of occult hepatic metastases from colorectal carcinoma

AIM: To prospectively explore the role of carcinoembryonic antigen (CEA) in gallbladder bile in patients with colorectal carcinoma and the morphological and clinical features of neoplasia and the occurrence of hepatic metastases. METHODS: CEA levels in the gallbladder and peripheral blood were studied in 44 patients with colorectal carcinoma and 10 patients with uncomplicated cholelithiasis. CEA samples were collected from the gallbladder bile and peripheral blood during the operation, immediately before extirpating the colorectal neoplasia or cholecystectomy. Values of up to 5 ng/ml were considered normal for bile and serum CEA. RESULTS: In the 44 patients with colorectal carcinoma who underwent operation with curative intent, the average level of serum CEA was 8.5 ng/ml (range: 0.1 to 111.0 ng/ml) and for bile CEA it was 74.5 ng/ml (range: 0.2 to 571.0 ng/ml). In the patients with uncomplicated cholelithiasis who underwent cholecystectomy, the average level of serum CEA was 1.9 ng/ml (range: 1.0 to 3.5 ng/ml) and for bile CEA it was 1.2 ng/ml (range: 0.3 to 2.9 ng/ml). The average duration of follow-up time was 16.5 months (range: 6 to 48 months). Four patients who underwent extirpation of the colorectal carcinoma without evidence of hepatic metastasis and with an average bile CEA value of 213.2 ng/ml presented hepatic metastases between three and seventeen months after removal of the primary colorectal neoplasia. Three of them successfully underwent extirpation of the hepatic lesions. CONCLUSION: High CEA levels in gallbladders of patients undergoing curative operation for colorectal carcinoma may indicate the presence of hepatic metastases. Such patients must be followed up with special attention to the diagnosis of such lesions.     

Changes in gallbladder bile composition following gallstone formation and weight reduction.

Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18-fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile.     

How many cytological examinations should be performed for the diagnosis of malignant biliary stricture via an endoscopic nasobiliary drainage tube?

Background and Aim: The sensitivity of bile cytology is recognized as being low. Repeating cytological sampling is likely to improve the sensitivity. The aim of this study is to determine the optimal number of repeated cytological sampling of bile obtained via an endoscopic nasobiliary drainage (ENBD) tube for the diagnosis of malignant biliary stricture. Methods: Ninety‐eight patients with malignant biliary stricture who underwent ENBD were enrolled. Diagnoses included bile duct carcinoma (n = 53), pancreatic carcinoma (n = 28), carcinoma of the major papilla (n = 8), gallbladder carcinoma (n = 6), and hepatocellular carcinoma (n = 3). Bile was aspirated via an ENBD tube once a day and immediately evaluated cytologically. Results: The median number of cytological samplings via an ENBD tube was 2.8 times (range, 1–10). In 40 of 98 patients with malignant biliary stricture, cytology was positive at the first cytological sampling (sensitivity 40.8%). Cytology was cumulatively positive in 71 of 98 patients (sensitivity 72.4%) from which repeated samples were taken. In 71 patients with positive cytology, correlation of the positive rate and the number of cytological samplings performed was investigated. In 68 of 71 (95.8%) patients with positive cytology, positive results were obtained by or at the sixth examination. Conclusions: Bile cytology via an ENBD tube is an easy method, and has been shown to have relatively high sensitivity. The optimal number of repeated cytological samplings using bile obtained via an ENBD tube for the diagnosis of malignant biliary stricture was concluded to be six.     

Biliary bile acids in cholelithiasis and colon cancer.

The role of biliary deoxycholate as an endogenous colon carcinogen and the possible association between cholelithiasis and/or cholecystectomy and the subsequent development of large bowel cancer is unclear. This paper describes biliary bile acids analysis performed on 13 patients undergoing cholecystectomy for gall stones, 10 patients undergoing colonic resection for colon cancer, and eight control patients. For all 31 patients the total bile acids concentration was highly variable (8.3 mg/ml-106.5 mg/ml). The median ratio of primary to secondary bile acids was 2.7:1. The biliary bile acid ratios were similar in both control patients (3.7:1) and those with colon cancer (3.1:1), whereas patients with gall stones had significantly higher secondary bile acid levels in their biliary bile (ratio 1.9:1, p = less than 0.05). This result indicates that raised biliary deoxycholate concentrations are not present in patients with colon cancer and are therefore unlikely to be a major predisposing factor in the aetiology of this disease. It is unlikely that cholelithiasis and/or cholecystectomy predispose to the subsequent development of colon tumours.     

Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells

BACKGROUND & AIMS: The mechanism by which cholelithiasis increases the risk of acute pancreatitis remains obscure. Because bile acids can enter the pancreas either by luminal diffusion or by interstitial leakage during gallstone impaction and pancreatitis is associated with impaired Ca(2+) signaling, we examined the effect of bile acids on pancreatic acinar cell signaling and the associated intracellular events. METHODS: Rat pancreatic acinar cells were isolated by collagenase digestion and the effects of bile acids on [Ca(2+)](i) signaling, cell survival, inflammatory signals, and the molecular and functional expressions of bile uptake transporters were analyzed. RESULTS: Bile acids specifically inhibited the sarco/endoplasmic reticulum Ca(2+) ATPase pump to chronically deplete part of the Ca(2+) stored in the endoplasmic reticulum. This in turn led to the activation of capacitative Ca(2+) entry and a chronic [Ca(2+)](i) load. The increase in [Ca(2+)](i) and Ca(2+) load activated the inflammation-associated signals of c-Jun amino-terminal kinases and NF-kappaB and led to cell death, which was inhibited by buffering [Ca(2+)](i) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid. A comprehensive molecular analysis of bile acid transporters revealed that pancreatic acinar cells express the bile uptake transporters Na(+)-taurocholate co-transporting polypeptide and organic anion transporting polypeptide in the luminal and basolateral membranes, respectively. Bile acid uptake into acinar cells was in part Na(+)-dependent and in part Na(+)-independent, suggesting that both transporters contribute to bile acid influx into acinar cells. CONCLUSIONS: These results suggest that bile acids can be transported into pancreatic acinar cells through specific membrane transporters and induce cell death by impairing cellular Ca(2+) signaling.