Cholesterol nucleation time in gallbladder bile of patients with solitary or multiple cholesterol gallstones.

Patients with multiple cholesterol gallbladder stones have been found to be at a higher risk for the recurrence of gallstones after successful nonsurgical treatment than those with a solitary stone. Cholesterol gallstone recurrence, like primary gallstone formation, probably involves a triple defect with supersaturation, abnormally rapid nucleation of cholesterol in bile and altered gallbladder motor function. We investigated whether the increased recurrence rate of patients with multiple stones might be caused by more rapid nucleation. Therefore the time required for cholesterol monohydrate crystals to appear in ultracentrifuged bile of patients with solitary (n = 71) or multiple (n = 42) cholesterol gallstones was determined. The cholesterol nucleation time was significantly (p less than 0.01) longer in the bile from patients with solitary stones (less than 1 to 16 days, median = 2.0 days) than in the bile from patients with multiple stones (less than 1 to 8 days, median = 1.0 days). Moreover, 15 of 71 (21.1%) patients with solitary cholesterol stones but only 1 of 42 (2.4%) patients with multiple cholesterol stones showed a normal (greater than 4 days) nucleation time. However, no difference in the cholesterol saturation index was found between the bile samples from patients with solitary stones and the bile samples from patients with multiple stones (1.55 +/- 0.65 vs. 1.54 +/- 0.59, mean +/- S.D., respectively). The more rapid cholesterol nucleation in gallbladder bile may, therefore, be the major risk factor causing the higher percentage of stone recurrence in patients with multiple cholesterol stones as compared with patients with solitary cholesterol stones.     

The Relation between Biliary Lipids,Nucleation Time,and Number of Gallbladder Stones after Percutaneous Gallbladder Puncture

Tudyka J, Kratzer W, Maier C, Mason R, Wechsler JG. The relation between biliary lipids, nucleation time, and number of gallbladder stones after percutaneous gallbladder puncture. Scand J Gastroenterol 1994;29:844-848.

Background: Biliary lipids and nucleation time are increasingly of importance in the understanding of the cholesterol nucleation process in gallstone patients. Methods: Biliary lipids, total lipid concentration (TLC), cholesterol saturation index (CSI) and nucleation time (NT) were studied in 221 bile samples from patients with solitary (n equals; 120) and multiple (n equals; 101) gallbladder stones. Results: Biliary cholesterol concentration and CSI did not differ between patients with solitary or multiple stones; however, it was positively correlated with the CSI (r equals; 0.93; p < 0.01). We found a negative correlation between CSI and TLC (r equals; ? 0.77 for solitary stones and r equals; ? 0.79 for multiple stones; p < 0.01). Furthermore, levels of total bile acids and phospholipids were similar in cases with solitary and multiple gallbladder stones. TLC did not correlate with single or multiple stones, whereas NT was determined to be negatively correlated with the number of gallstones (r= ?0.39; p<0.01). Patients with solitary stones had a significantly (p < 0.01) longer NT than those with multiple gallbladder stones (7.5 ± 4.2 days versus 2.3 ± 1.5 days). Conclusions: Our findings suggest that there exists a nucleation-promoting activity, which seems to be more pronounced in patients with multiple gallbladder stones than in those with solitary stones, indicating a major risk factor for the higher recurrence rate seen in these patients.     

The Effect of Ursodeoxycholic Acid on Nucleation Time in Patients with Solitary or Multiple Gallbladder Stones

Objective: The objective of this study was to determine the effect of ursodeoxycholic acid (UDCA), lOOO mg/day, on nucleation time and cholesterol saturation index (CSI) in human gallbladder bile. Methods and Results: In 48 patients with cholesterol gallbladder stones undergoing extracorporeal Shockwave lithotripsy. bile samples exhibited a significant longer median nucleation time in the case of solitary stones (7.9 ± 5.1 days) than in patients with multiple stones (1.7 ± 1.0 days; p < 0.0001). Stone number and nucleation time were correlated inversely (r =−0.79). UDCA led to a significant prolongation of nucleation time (solitary stones 17.9 ± 5.8 days, multiple stones 18.0 ± 5.7 days; p < 0.01) with a concomitant disappearance of cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile. Initially, there was no difference in the CSI between patients with solitary stones or multiple gallbladder stones (1.4 ± 0.3 vs . 1.4 ± 0.4, respectively). UDCA caused a significant decrease in CSI by 64.3% ( P < 0.01). Conclusions: We conclude that UDCA prolongs the nucleation time by decreasing the cholesterol saturation index, as well as by diminishing cholesterol liquid crystals and cholesterol monohydrate crystals in gallbladder bile from patients with cholesterol gallstones. Second, recurrent stones essentially occur in patients with multiple cholesterol gallstones, reflected by a concomitant short nucleation time.     

Cholecystectomy or gallbladder in situ after endoscopic sphincterotomy and bile duct stone removal in Chinese patients

BACKGROUND & AIMS: In patients with stones in their bile ducts and gallbladders, cholecystectomy is generally recommended after endoscopic sphincterotomy and clearance of bile duct stones. However, only approximately 10% of patients with gallbladders left in situ will return with further biliary complications. Expectant management is alternately advocated. In this study, we compared the treatment strategies of laparoscopic cholecystectomy and gallbladders left in situ. METHODS: We randomized patients (>60 years of age) after endoscopic sphincterotomy and clearance of their bile duct stones to receive early laparoscopic cholecystectomy or expectant management. The primary outcome was further biliary complications. Other outcome measures included adverse events after cholecystectomy and late deaths from all causes. RESULTS: One hundred seventy-eight patients entered into the trial (89 in each group); 82 of 89 patients who were randomized to receive laparoscopic cholecystectomy underwent the procedure. Conversion to open surgery was needed in 16 of 82 patients (20%). Postoperative complications occurred in 8 patients (9%). Analysis was by intention to treat. With a median follow-up of approximately 5 years, 6 patients (7%) in the cholecystectomy group returned with further biliary events (cholangitis, n = 5; biliary pain, n = 1). Among those with gallbladders in situ, 21 (24%) returned with further biliary events (cholangitis, n = 13; acute cholecystitis, n = 5; biliary pain, n = 2; and jaundice, n = 1; log rank, P = .001). Late deaths were similar between groups (cholecystectomy, n = 19; gallbladder in situ, n = 11; P = .12). CONCLUSIONS: In the Chinese, cholecystectomy after endoscopic treatment of bile duct stones reduces recurrent biliary events and should be recommended.     

Gallbladder function, cholesterol stones, and bile composition.

Gallbladder bile obtained at operation from five patients with no symptoms of biliary disease was undersaturated with cholesterol in every case. However, gallbladder bile from patients with stones composed of 97-100% crystalline cholesterol was on average just saturated with cholesterol when the gallbladder was functioning and undersaturated when it was not. Regardless of gallbladder function, the patients with stones had on average significantly more cholesterol in their bile than in the control group, but the differences between the mean composition of bile from functioning and non-functioning gallbladders were not significant. Common duct bile from patients with non-functioning and functioning gallbladders was on average supersaturated with cholesterol, but there was significantly more bile salt and significantly less cholesterol in the bile from patients with non-functioning gallbladders. Only in the case of patients with functioning gallbladders did the mean composition of the common duct and gallbladder biles differ significantly. The former contained significantly more cholesterol and less bile salt than the latter. It is suggested that patients with non-functioning gallbladders may be 'autocholecystectomised' with the duct bile reverting to a more 'normal' composition.     

The anionic peptide fraction is present on the gallbladder apical epithelium and favours biliary cholesterol absorption

BACKGROUND/AIMS: We investigated (a) in vitro and in vivo the changes of biliary mass of the anionic peptide fraction, apolipoproteinA-I, immunoglobulin-A, albumin and cholesterol over time in the excluded gallbladder and (b) in vivo the localization in the gallbladder epithelium of the anionic peptide fraction and cholesterol absorbed from bile. METHODS: Native bile was substituted with pig bile containing radiolabeled cholesterol in the in vitro isolated intra-arterially perfused pig gallbladder (n=9) and in vivo in anestethized pigs with excluded gallbladders (n=6). The amount of cholesterol (scintillation counting) and proteins (enzyme-linked immunosorbent assay) in gallbladder bile were measured over time. The localization of the anionic peptide fraction and cholesterol absorbed from bile in the gallbladder epithelium was studied in vivo by immunohistochemistry and fluoro-phospho-imager analysis. RESULTS: The rate of biliary cholesterol disappeared from bile was a function of the initial concentration and of the biliary mass changes over time of the anionic peptide fraction, but not of that of the other biliary proteins. The anionic peptide fraction colocalized with biliary cholesterol absorbed by the gallbladder on the apical side of gallbladder epithelial cells. CONCLUSIONS: These data indirectly suggest that biliary anionic peptide fraction could favour biliary cholesterol absorption by the gallbladder epithelium.     

Combination therapy of gallbladder stones using extracorporeal shock waves and bile acids: results in relation to stone diameter and stone number]

420 patients were referred to our center for gallstone lithotripsy. 97 patients (23%) with radiolucent gallbladder stones (total diameter less than or equal to 3 cm) and intact gallbladder function were found suitable for extracorporal shock-wave lithotripsy. Disintegration of gallbladder stones was achieved in 92 of the 97 patients (95%). Chenodeoxycholic acid and ursodeoxycholic acid were used as adjuvant litholytic therapy. The therapeutic results were evaluated cumulatively in 90 patients after a follow-up of 10 months. 80% of patients with solitary stones (less than or equal to 20 mm in diameter (n = 46) had a stone-free gallbladder, whereas patients with solitary stones greater than 2 cm, less than or equal to 3 cm in diameter (n = 20) and multiple stones (n = 22) became stone-free in only 28% (p less than 0.01). During the observation period 21 patients (23%) experienced biliary colics, 2 (2%) mild pancreatitis, 2 (2%) showed fragment impaction in the common bile duct, and 17 (19%) displayed transient microscopic hematuria. Our results confirm previous studies showing that solitary stones sized up to 2 cm in diameter represent the best suited subgroup for extracorporeal shock-wave lithotripsy.     

人体胆囊结石时胆囊组织PGE、PGI2、LTC4的含量

本文测定非结石组（ｎ＝１６）与结石组（ｎ＝４７）人体胆囊粘膜内前列腺素Ｅ（ＰＧＥ）、前列环素（ＰＧＩ２）白三烯０４（ＬＴＣ４）的含量及磷脂酶Ａ２（ＰＬＡ２）的活性，发现结石组四者的水平均非常显著地高于非结石组。提示可能由于脂类代谢紊乱，胆囊组织的ＰＬＡ２活性增加．致使ＰＧｓ、ＬＴｓ水平增高，引起胆囊上皮细胞活化，合成分泌粘蛋白功能亢进，从而参与促进结石的形成。     

Sensitivity and specificity of microscopic examination of gallbladder bile for gallstone recognition and identification

During cholecystectomy, gallbladder bile and gallstones were obtained from 77 patients and gallbladder bile was obtained from 39 patients free of stones (11 patients had biliary stenosis). According to their chemical composition, gallstones were classified as cholesterol (n = 46) or pigment (n = 31) stones. In patients with gallstones (a) cholesterol crystals better helped to identify cholesterol gallstones (sensitivity, 87%; specificity, 97%; positive predictive value, 97%) than did an abnormal cholesterol saturation index of bile (sensitivity, 93%; specificity, 48%; positive predictive value, 73%); (b) the presence of cholesterol crystals was significantly related to the cholesterol content of gallstones and the bile cholesterol saturation index; and (c) bilirubinate crystals, when present alone (without cholesterol crystals), were good predictors of pigment gallstones (sensitivity, 71%; specificity, 93%; positive predictive value, 88%). In the absence of stones, bilirubinate crystals were present in 9 of 28 patients without biliary stenosis (4 with alcoholic cirrhosis and 2 with alcoholic pancreatitis) and 8 of 11 patients with biliary stenosis. In the absence of stones, cholesterol crystals were present in 2 of 28 patients without biliary stenosis and in 4 of 11 patients with biliary stenosis, suggesting that bile stasis can induce cholesterol crystal formation.     

Cholesterol crystals, cholesterol saturation of bile and biliary lithiasis

It has been repeatedly shown that normal human gallbladder bile is commonly supersaturated wih cholesterol. It has been therefore suggested that the crucial step of the formation of cholesterol gallstones might be the nucleation and growth of cholesterol monohydrate crystals. Consequently this work was aimed at determining: 1) if cholesterol crystal formation is really a typical feature of gallbladder bile with cholesterol gallstones; 2) the influence of the degree of cholesterol saturation of bile on the formation of cholesterol crystals. Gallbladder bile from 89 patients (23 from patients with cholesterol gallstones, 7 from patients with non-cholesterol gallstones and 59 from patients free of gallstones) and hepatic bile from 17 previously cholecystectomized patients were studied. Four of these patients had cholesterol stones of the common bile duct. Results: (a) gallbladder bile: cholesterol crystals were present on immediate examination in 19 of the 23 bile samples with cholesterol stones, in 2 of the 7 bile samples with non-cholesterol stones and in 1 of the 59 bile samples without stones. Only 1 bile sample with cholesterol stone developed crystals. Cholesterol saturation of bile with or without crystals did not differ significantly; (b) hepatic bile: cholesterol crystals were detected on immediate examination in one of the 17 bile samples and subsequently appeared in one of the remaining samples. Cholesterol saturation of hepatic bile (2.10 +/- 0.43) was significantly higher (p less than 0.01) than that of gallbladder bile containing cholesterol stones (1.32 +/- 0.43).(ABSTRACT TRUNCATED AT 250 WORDS)     

Gallbladder mucosal blood flow increases during early cholesterol gallstone formation.

Gallbladder absorption increases during early cholesterol gallstone formation and is influenced by the intraluminal presence of lithogenic bile. The effect of lithogenic bile on gallbladder mucosal blood flow is unknown. The current study tested the hypothesis that the presence of lithogenic gallbladder and hepatic bile enhances gallbladder mucosal blood flow in cholesterol-fed (0.4%) prairie dogs, as determined by hydrogen gas clearance. Gallbladder mucosal blood flow in control animals was 35.57 +/- 3.9 mL.min-1.100 g-1. In contrast, basal gallbladder mucosal blood flow in cholesterol-fed animals was significantly (P less than 0.01) increased to 64.94 +/- 8.7 mL.min-1.100 g-1. In crossover studies, the addition of lithogenic gallbladder bile to control animals (n = 6) resulted in a significant (P less than 0.025) 26% increase in gallbladder mucosal blood flow, whereas the addition of nonlithogenic gallbladder bile into gallbladders of cholesterol-fed prairie dogs resulted in a significant (P less than 0.025) 58% decrease in gallbladder mucosal blood flow. Similarly, hepatic bile crossover studies showed that the addition of lithogenic hepatic bile to control gallbladders significantly increased (P less than 0.025) gallbladder blood flow by 30%, whereas instillation of nonlithogenic hepatic bile in gallbladders of cholesterol-fed animals significantly (P less than 0.025) decreased gallbladder mucosal blood flow by 29%. These results suggest that alterations in gallbladder mucosal blood flow, influenced by the presence and absence of lithogenic bile, may play a role in cholesterol gallstone formation.     

Impaired human gallbladder lipid absorption in cholesterol gallstone disease and its effect on cholesterol solubility in bile

BACKGROUND & AIMS: The role of the gallbladder in gallstone pathogenesis is still unclear. We examined the effects of gallbladder mucosal lipid absorption on lipid composition and cholesterol crystallization in bile. METHODS: The in vitro-isolated, intra-arterially perfused gallbladder model was used (1) to compare the absorption rates of lipids from standard bile by gallbladders obtained from 7 patients with cholesterol gallstones and 6 controls; and (2) to measure the microscopic cholesterol crystal detection time in cholesterol-enriched pig bile before and after lipid absorption by the pig gallbladder. RESULTS: Control gallbladders, but not cholesterol gallstone gallbladders, significantly reduced cholesterol (P < 0.02) and phospholipid (P < 0.01) and increased bile salt (P < 0.01) molar percentages in bile over a 5-hour period by efficient and selective cholesterol and phospholipid absorption. A histomorphometric study of the epithelial cells showed significantly higher values for nuclear density (P < 0.01) and nuclear (P < 0.05) and cytoplasmic (P < 0.05) areas in the cholesterol gallstone than the control group. Sequential microscopy of cholesterol-enriched pig bile showed significantly shorter cholesterol filament (P < 0.01) and typical cholesterol plate (P < 0. 02) detection times before than after exposure of bile to the gallbladder lipid absorption. CONCLUSIONS: In cholesterol gallstone disease, the human gallbladder epithelium loses its capacity to selectively and efficiently absorb cholesterol and phospholipids from bile, even if it is hyperplastic and hypertrophic. This epithelial dysfunction eliminates the positive effect that the normal gallbladder exerts on cholesterol solubility in bile and might be a pathogenetic cofactor for cholesterol gallstone formation.     

Effect of gallbladder mucin on the crystallization of cholesterol in bile

OBJECTIVES: Mucin is supposed to accelerate the crystallization of cholesterol in model bile while studies in native human gallbladder bile revealed conflicting results. METHODS: Therefore, we determined the relation of mucin concentration and cholesterol crystal observation time in gallbladder bile of 73 patients with cholesterol and mixed and 21 patients with pigment stones. In addition, bile samples of 20 patients with cholesterol gallstones were supplemented with either 0 (control) or 0.5-4.0 mg/ml purified bovine mucin or human mucin isolated from gallbladder bile, to study the effect of variable mucin concentrations on the crystallization of cholesterol. RESULTS: Rapid nucleating biles ( 4 days, n = 35) cholesterol crystal observation times (P < 0.05), but no correlation between mucin concentration and cholesterol crystal observation time was observed. Supplementation experiments with bovine purified mucin (up to 4.0 mg/ml) showed no significant effect on the total amount of newly formed cholesterol crystals within 21 days. However, higher amounts of newly formed cholesterol crystals were seen in bile samples supplemented with human mucin in comparison to negative controls. CONCLUSIONS: Our results demonstrate a dose-dependent effect of human but not of bovine gallbladder mucin on the formation of cholesterol monohydrate crystals in gallbladder bile of patients with cholesterol stones. Therefore, studies of cholesterol crystallization in model bile systems may be valuable but should always be confirmed in native gallbladder bile as the more physiological effector system.     

Small gallstones, preserved gallbladder motility, and fast crystallization are associated with pancreatitis

Acute pancreatitis is a severe complication of gallstones with considerable mortality. We sought to explore the potential risk factors for biliary pancreatitis. We compared postprandial gallbladder motility (via ultrasonography) and, after subsequent cholecystectomy, numbers, sizes, and types of gallstones; gallbladder bile composition; and cholesterol crystallization in 21 gallstone patients with previous pancreatitis and 30 patients with uncomplicated symptomatic gallstones. Gallbladder motility was stronger in pancreatitis patients than in patients with uncomplicated symptomatic gallstones (minimum postprandial gallbladder volumes: 5.8 +/- 1.0 vs. 8.1 +/- 0.7 mL; P = .005). Pancreatitis patients had more often sludge (41% vs. 13%; P = .03) and smaller and more gallstones than patients with symptomatic gallstones (smallest stone diameters: 2 +/- 1 vs. 8 +/- 2 mm; P = .001). Also, crystallization occurred much faster in the bile of pancreatitis patients (1.0 +/- 0.0 vs. 2.5 +/- 0.4 days; P < .001), possibly because of higher mucin concentrations (3.3 +/- 1.9 vs. 0.8 +/- 0.2 mg/mL; P = .04). No significant differences were found in types of gallstones, relative biliary lipid contents, cholesterol saturation indexes, bile salt species composition, phospholipid classes, total protein or immunoglobulin (G, M, and A), haptoglobin, and alpha-1 acid glycoprotein concentrations. In conclusion, patients with small gallbladder stones and/or preserved gallbladder motility are at increased risk of pancreatitis. The potential benefit of prophylactic cholecystectomy in this patient category has yet to be explored.     

Human gallbladder mucin accelerates nucleation of cholesterol in artificial bile

The gallbladder bile of patients with cholesterol gallstones is characterized by two abnormalities: (a) supersaturation with cholesterol and (b) accelerated nucleation of cholesterol monohydrate crystals. We studied the ability of purified human gallbladder mucin to nucleate artificial bile in vitro. Human gallbladder mucin at concentrations of 2 and 4 mg/ml accelerated the nucleation time of cholesterol crystals in model bile. The mean number of cholesterol crystals in artificial bile incubated for 10 days with 4 mg/ml of human gallbladder mucin was 2327/mm3 (p less than 0.01) vs. control of 51/mm3. The number of crystals found in model bile was dependent on the concentration of human gallbladder mucin (2-16 mg/ml) and the time of incubation (4-14 days). Human gallbladder mucin was associated with an increase in the number of liquid crystals after 4 days of incubation, which then decreased in number as solid cholesterol monohydrate crystals formed. Nucleation by human gallbladder mucin was significantly increased only with cholesterol saturation indices greater than 1.0, and in biles containing 10% but not 3% total lipid by weight. Pooled human gallbladder mucin from gallbladders with and without stones both increased nucleation significantly when compared with controls. Increased nucleation of saturated model bile was also observed with purified monkey cervical and bovine gallbladder mucin, but not with porcine gastric mucin. These observations provide further evidence that human gallbladder mucin may contribute to cholesterol gallstone formation in humans by accelerating nucleation of cholesterol monohydrate crystals from supersaturated gallbladder bile.     

Ursodeoxycholic acid therapy and biliary lipids--a dose-response study.

The effects of four different doses of ursodeoxycholic acid (250, 500, 750, and 1000 mg daily) on biliary lipids were studied in 24 patients with radiolucent gallbladder stones. There was a significant increase in the proportion of ursodeoxycholic acid in bile after all doses, being greatest with 750 and 1000 mg daily. Unsulphated lithocholic acid was also increased in the bile after therapy, while the other major bile acids were reduced. The cholesterol content of bile was reduced by all doses, and this change was most marked after 1000 mg (from 10.9 +/- 1.4 to 5.6 +/- 0.5 mol%, P < 0.01). Biliary cholesterol saturation improved significantly only after 750 and 1000 mg daily.     

Symptomatic versus silent gallstones

It is unknown whether demography, gallbladder function, or the radiographic appearance of gallstones predispose them to cause symptoms. We investigated these features in a consecutive series of 260 patients with newly diagnosed, uncomplicated gallstone disease, of whom 146 had experienced biliary pain and 114 were asymptomatic. All patients underwent double-dose oral cholecystography and cholecystosonography, and the combined data of these examinations were used to assess gallbladder function and stone number, size, and radiopacity. The gallstones were multiple in 68%, radiolucent in 73%, and in visualized gallbladders in 79% of the 260 patients. The comparison of different variables in patients with and without biliary pain showed that the female gender (P=0.030; odds ratio 1.86), a family history of gallbladder disease (P=0.022; odds ratio 1.89), a nonvisualized gallbladder (P<0.001; odds ratio 3.14), multiple stones (P=0.036; odds ratio 1.89), and those which were small (P=0.009; odds ratio 2.08) or of dissimilar size (P=0.041; odds ratio 1.91) were associated with biliary pain. Women with silent stones had been pregnant more often (P<0.001, difference between means 1) than those with biliary pain. Gallbladder function and the radiologic characteristics of stones were unrelated to age and gender. Estimates of eligibility for nonsurgical therapies among the 146 symptomatic patients were 44% for bile acid therapy, 16% for lithotripsy, and 56% for methyltert-butyl ether. In conclusion, some inherent features of gallstones are associated with biliary pain. Whether they have predictive value of future symptom development in subjects with silent stones can be determined by prospective follow up.     

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6 +/- 0.6 mg/ml, mean +/- SD, n = 10), calcium bilirubinate gallstone bile (4.2 +/- 1.1 mg/ml, n = 10), black pigment gallstone bile (1.9 +/- 0.6 mg/ml, n = 4) and control gallbladder bile (2.3 +/- 0.5 mg/ml, n = 9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of controls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins proteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.     

Correlation between biliaryα 1-acid glycoprotein concentration and cholesterol crystal nucleation time in gallstone disease

A biliary form of theα ₁-acid glycoprotein (AAG) promotes cholesterol crystallization in the lower-molecular-weight, concanavalin A-bound fraction of gallbladder bile. In addition, bile AAG concentration is higher in cholesterol gallstone patients with multiple stones than in control patients without gallstone disease. In this study we sought to determine whether the increased biliary concentration of AAG in cholesterol gallstone patients is accompanied by a more rapid nucleation time in patients with multiple stones. AAG concentration in native biles was measured by ELISA. Nucleation time was measured using a standard microscopy method. The concentration of biliary AAG was then related to nucleation time in biles from the same patients. Nucleation times were significantly shorter (≤5 days) in cholesterol gallstone patients with raised AAG concentrations (P<0.03). There was a significant (P=0.004) negative correlation (r=?0.53) between nucleation time and the AAG concentration in cholesterol gallstone patients with multiple stones. The concentration of biliary AAG appears to exert an important influence on the speed of cholesterol nucleation in bile in many patients with cholesterol gallstone disease.     

Periampullary diverticula cause pancreatobiliary reflux

BACKGROUND: Periampullary diverticula are associated with dysfunction of the sphincter of Oddi. Papillary dysfunction may allow reflux of pancreatic juice as well as intestinal contents into the common bile duct. We prospectively investigated pancreatobiliary reflux in patients with and without periampullary diverticula. METHODS: The ductal bile was sampled for amylase concentration during endoscopic retrograde cholangiopancreatography in 47 patients with choledocholithiasis (n = 29; with (n = 14) or without (n = 15) periampullary diverticula) or gallbladder cholesterol polyps (n = 18; with (n = 6) or without (n = 12) diverticula). RESULTS: The amylase concentration within the ductal bile was significantly higher in choledocholithiasis patients with periampullary diverticula (1621 +/- 587 IU/l) than in those without diverticula (1155 +/- 418 IU/l). The amylase concentration tended to be higher in gallbladder polyp patients with diverticula (1087 +/- 275 IU/l) than in those without diverticula (833 +/- 272 IU/l). Irrespective of the presence or absence of diverticula, patients with bile duct stones had significantly higher amylase concentrations than those with gallbladder polyps. CONCLUSIONS: Periampullary diverticula cause pancreatobiliary reflux. Further investigation is required to determine the clinical implication of pancreatobiliary reflux.