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Goals and Background: Long-term outcomes of symptomatic gallbladder (GB) sludge are not fully established. This study aimed to determine whether patients with symptomatic GB sludge could experience subsequent biliary events., Study: This study investigated consecutive patients who presented with typical biliary pain and underwent abdominal ultrasonography from March 2003 to December 2012. A prospectively maintained database of these patients, excluding those with gallstones, was reviewed retrospectively. We compared the development of biliary events such as acute cholecystitis, acute cholangitis, and acute pancreatitis between both GB sludge and non-GB sludge cohorts., Results: In all, 58 and 70 patients were diagnosed with and without GB sludge, respectively. The 5-year cumulative biliary event rate was significantly higher in the GB sludge (33.9% vs. 15.8%, P=0.021) and the hazard ratio of subsequent biliary events was 2.573 (95% confidence interval, 1.124-5.889; P=0.025) in patients with GB sludge. The 5-year cumulative rate of each biliary event was higher in the GB sludge cohort (15.6% vs. 5.3% in acute cholecystitis, 15.5% vs. 5.3% in acute cholangitis, 18.4% vs. 11.1% in acute pancreatitis, respectively), although it was not statistically significant. Among the GB sludge cohort, subsequent biliary events were less frequent in patients who underwent cholecystectomy compared with those who did not (2/16, 12.5% vs. 17/42, 40.4%; P=0.067)., Conclusions: GB sludge accompanying typical biliary pain can cause subsequent biliary events and cholecystectomy may prevent subsequent biliary events. Therefore, GB sludge would be considered as a culprit of biliary events.

Inverse estimation of biomechanical parameters of soft tissues from non-invasive measurements has clinical significance in patient-specific modelling and disease diagnosis. In this paper, we propose a fully nonlinear approach to estimate the mechanical properties of the human gallbladder wall muscles from in vivo ultrasound images. The iteration method consists of a forward approach, in which the constitutive equation is based on a modified Hozapfel-Gasser-Ogden law initially developed for arteries. Five constitutive parameters describing the two orthogonal families of fibres and the matrix material are determined by comparing the computed displacements with medical images. The optimisation process is carried out using the MATLAB toolbox, a Python code, and the ABAQUS solver. The proposed method is validated with published artery data and subsequently applied to ten human gallbladder samples. Results show that the human gallbladder wall is anisotropic during the passive refilling phase, and that the peak stress is 1.6 times greater than that calculated using linear mechanics. This discrepancy arises because the wall thickness reduces by 1.6 times during the deformation, which is not predicted by conventional linear elasticity. If the change of wall thickness is accounted for, then the linear model can used to predict the gallbladder stress and its correlation with pain. This work provides further understanding of the nonlinear characteristics of human gallbladder., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Aim: To investigate the effects of gallbladder stones on motor functions of the gallbladder and the dynamics of bile flow in asymptomatic gallstone disease., Methods: Quantitative hepatobiliary scintigraphy was performed to detect the parameters of gallbladder motor function [gallbladder ejection fraction (GBEF), gallbladder visualization time (GBVT), gallbladder time to peak activity (GBT(max)), gallbladder half emptying time (GBT(1/2)), and transit time of bile to duodenum (TTBD)] in 24 patients with asymptomatic cholelithiasis who were diagnosed incidentally during routine abdominal ultrasonographic examination and 20 healthy subjects with normal gallbladder., Results: Even though there was no significant difference in the clinical and laboratory parameters between the patient and control groups, all parameters of gallbladder function except TTBD were found to differ significantly between the two groups. GBEF in the patient group was decreased (P = 0.000) and GBVT, GBT(max), GBT(1/2) in the patient group were longer (P = 0.000, P = 0.015, P = 0.001, respectively)., Conclusion: Our results showed that even if there were not any clinical and laboratory findings, gallbladder filling and emptying could be impaired in patients with gallstone disease.

Background: Gallstones have been frequently diagnosed after Roux-en-Y gastric bypass (RYGBP). Gallbladder stasis associated with duodenal exclusion may play a role in their pathogenesis., Methods: Gallbladder emptying was studied before and on the 30th and 31st postoperative days (POD) after RYGBP in 20 morbidly obese patients. Gallbladder volume after fasting and every 15 min during a 2-h period following administration of a standard liquid meal was determined by sonography. On the 31st POD, the meal was administered through the gastrostomy in order to promote its transit through the duodenum. Fasting volume (FV), maximum ejection fraction (Max EF), and residual volume (RV) were determined. Biliary sludge and calculi were investigated after 1 and 6 months, respectively., Results: FV was 39.4 +/- 20.2 ml, 50.1 +/- 22.7 ml, and 47.9 +/- 23.4 ml, respectively, for the preoperative and two postoperative assessments (P = 0.09). RV was 7.6 +/- 8.7 ml, 25.1 +/- 20.0 ml, and 24.6 +/- 20.9 ml; and Max EF was 80.5 +/- 20.9%, 54.3 +/- 21.4%, and 50.5 +/- 29.0%, respectively, for the pre-, postoral, and postgastrostomy infusion measurements. There was only a significant difference between the preoperative value and the two postoperative values (P < 0.001). Biliary sludge was detected in 65% of the patients and 46% of them subsequently developed gallstones., Conclusions: Gallbladder emptying became significantly compromised after RYGBP. This impairment was unrelated to duodenal exclusion but it was associated with biliary sludge and stone formation.

Background/aims: Increased viscosity and supersaturation of cholesterol in gallbladder bile, as well as an impaired motility of the gallbladder, are considered to be important factors in the pathogenesis of cholesterol gallstones. However, the relation of these parameters has not yet been determined., Material and Methods: Bile viscosity (mPa s) was measured by rotation viscosimetry and the composition of gallbladder bile was determined using standard methodology. Gallbladder motility was calculated as ejection fraction in percent of total volume 45 min after a test meal using ultrasonography in patients with gallstones prior to elective cholecystectomy., Results: The study included 35 patients with cholesterol gallstones. Viscosity of gallbladder bile ranged between 0.9 and 12.5 mPa s (median 2.2 mPa s) and an ejection fraction of the gallbladder of 55.4 +/- 18.3% (mean +/- SD) was determined. No significant correlation (r = 0.19, p < 0.2) between the 2 parameters could be calculated. Analysis of the composition of gallbladder bile revealed a positive correlation of all components to biliary viscosity but not to the motility of the gallbladder, with the exceptions of a negative correlation (r = 0.39, p < 0.02) between mucin concentration and the ejection fraction at 45 min after the test meal., Conclusions: The motility of the gallbladder appears to be unrelated to the viscosity of gallbladder bile or gallbladder bile composition. The negative correlation between the ejection fraction of the gallbladder and mucin concentration of gallbladder bile suggests that chronic inflammation of the gallbladder wall is associated with both an impaired motility of the gallbladder and increased mucin release into gallbladder bile., (Copyright 2009 S. Karger AG, Basel.)

The biliary clearance (Cl(biliary)) of three compounds was estimated using sandwich-cultured human hepatocytes (SCHH) and compared with Cl(biliary) values measured in vivo. Tc-99m sestamibi (MIBI) Cl(biliary) was determined in seven healthy volunteers using an oroenteric catheter to aspirate duodenal secretions, and gamma scintigraphy to determine gallbladder contraction; this technique was used previously to determine Tc-99m mebrofenin (MEB) and piperacillin (PIP) in vivo Cl(biliary). In vitro Cl(biliary) of MEB, MIBI, and PIP was quantified in SCHH as the ratio of mass excreted into bile canaliculi and area under the blood concentration-time curve (AUC) in medium. MIBI Cl(biliary) in vivo was 5.5+/-1.2 mL/min/kg (mean+/-SD). The rank order of Cl(biliary) predicted from SCHH corresponded well with the in vivo Cl(biliary) values in mL/min/kg for MEB (7.44 vs 16.1), MIBI (1.20 vs 5.51), and PIP (0.028 vs 0.032). In conclusion, the methods developed allowed for reproducible quantification of Cl(biliary) of drugs in healthy humans and prediction of Cl(biliary) from in vitro data.

Aim: To define the risk factors in gallstone and sludge formation, and to investigate the incidence of gallstone and biliary sludge formation during pregnancy in a group of healthy pregnant women., Methods: Sixty-nine healthy pregnant women in early gestation and 28 nulliparous healthy controls were enrolled. Gallbladder volumes, gallbladder ejection fraction (GBEF), serum triglyceride and cholesterol levels were determined in both groups. In the pregnant group, repeated measurements were performed immediately after delivery and compared with initial levels. Risk factors, which are associated with gallstone and biliary sludge development during pregnancy, were determined by linear regression analysis., Results: No statistically significant difference was observed in the assessed parameters of pregnant women in early gestation and controls (both P > 0.05). In the pregnant group, gallstone and biliary sludge development during pregnancy were detected in 6.3% and 10.9% of cases, respectively. The detected parameters were significantly higher early after delivery than in early gestation, while GBEF was lower (both P < 0.001). Lower GBEF was the most significant factor (P < 0.001) associated with gallstone and sludge formation during pregnancy, while multiple childbirths was the other (P = 0.04)., Conclusion: Decrease in GBEF is the most significant risk factor for newly developed gallstone and sludge in pregnant women, while multiple childbirths is the other but less important risk factor.

Gallstone disease in the Western world has an estimated prevalence of 10-15% and more than 75% are cholesterol-enriched gallstones. Defective gallbladder motility has been identified as an important pathogenic factor for cholesterol gallstone disease. Various agents may enhance or impair postprandial gallbladder motility, and their effects on interdigestive gallbladder and intestinal motility should also be taken into account. Patients in high-risk situations for gallstone disease, and those chronically treated with drugs inhibiting gallbladder motility (e.g. somatostatin analogues) may benefit from improving gallbladder motility with prokinetic agents. Whether such a strategy can really prevent gallstone formation is still unknown, long-term studies are lacking so far. The efficacy of bile acid therapy with UDCA for gallstone dissolution or for prevention in high risk patients is limited and hampered by high recurrence rates. The efficacy of UDCA in prevention of colics or gallstone related complications in symptomatic patients with gallbladder stones with contraindications for operation or on the waiting list should be explored further, since several retrospective studies showed favourable outcomes with this strategy.

Diabetes and obesity are strongly associated and are risk factors for cholesterol gallstone disease. Leptin-deficient and leptin-resistant diabetic obese mice have enlarged, hypomotile gallbladders. In addition, bile from gallbladders of leptin-deficient mice has enhanced cholesterol crystal formation, whereas bile from gallbladders of leptin-resistant mice has delayed crystal observation time. To determine the effect of diabetes alone, we hypothesized that leptin-normal, nonobese diabetic (NOD) mice would have reduced biliary motility and rapid crystal formation. Twenty control and 9 prediabetic and 11 diabetic NOD, 12- to 26-week-old mice underwent glucose measurement and cholecystectomy for muscle bath stimulation with neurotransmitters. An additional group of 200 control and 78 NOD 12-week-old mice underwent microscopic bile examination for cholesterol crystal formation. Compared with control mice, prediabetic NOD mice had similar glucose levels and gallbladder volumes. Diabetic NOD mice had higher sugar levels and larger gallbladder volumes (P < 0.001) than control mice. Prediabetic NOD gallbladders had less contractility (P < 0.01) than control gallbladders, and contractility worsened (P < 0.01) in diabetic NOD mice. NOD mice formed cholesterol crystals earlier than did control mice (P < 0.05). Nonobese diabetic NOD mice have (1) decreased gallbladder contraction to neurotransmitters, which worsens with development of diabetes, and (2) rapid crystal formation. We conclude that diabetes alone alters gallbladder motility and cholesterol crystal formation.

The role of female sex hormones in the pathogenesis of gallstones is well established. Pregnancy, contraceptive use, estrogen replacement therapy in postmenopausal women, and estrogen therapy in men for the treatment of prostatic carcinoma have been found to be associated with increased risk of cholesterol gallstones. Alterations in gallbladder emptying and in bile lithogenicity in postmenopausal women receiving hormone replacement therapy (HRT) have not been studied to date. The present study was undertaken to study the effect of HRT on gallbladder emptying and bile lithogenicity. Sixteen postmenopausal women were included in the study. None of the patients had gallstone disease and none had received prokinetic drugs, such as, erythromycin, metoclopramide, domperidone or cisapride, aspirin, and nonsteroidal antiinflammatory drugs. Gallbladder emptying (n = 16), bile microscopy (n = 7), cholesterol saturation index (CSI) (n = 7), and nucleation time (n = 7) were studied before and 3 months after HRT (conjugated estrogen, 0.625 mg, + medroxyprogesterone acetate, 2.5 mg, everyday). Fasting and residual volumes increased (fasting volume, 18.2 +/- 2.2 mL pre-HRT vs 27.6 +/- 3.2 mL post-HRT, P = 0.0003; residual volume, 3.9 +/- 0.6 mL pre-HRT vs 10.3 +/- 2.0 mL post-HRT, P = 0.00009) and ejection fraction decreased (78.2 +/- 2.5% pre-HRT vs 62.2 +/- 3.8% post-HRT; P = 0.0017) after 3 months of HRT. There was no change in CSI (2.32 +/- 0.36 pre-HRT vs 2.60 +/- 0.51 post-HRT; P = NS) or in nucleation time (19.0 +/- 1.2 days pre-HRT vs 17.6 +/- 1.3 days post-HRT; P = NS). None of the bile samples either pre-HRT or post-HRT showed cholesterol monohydrate crystals. Though impairment of gallbladder emptying occurs in the short term with HRT in postmenopausal women, there is no change in CSI and nucleation time.

Biliary sludge is a mixture of particulate matter which has precipitated from bile. It generally consists of cholesterol monohydrate crystals, calcium bilirubinate or other calcium salts. In a clinical setting, biliary sludge is almost always an ultrasonographic diagnosis. Although it is less clinically applicable, direct microscopic examination of gallbladder bile is far more sensitive than ultrasonography into sludge detection, and has to be regarded as the diagnostic gold standard. The overall prevalence of sludge in the general population is relatively low. However, several clinical conditions are associated with a particularly high prevalence of biliary sludge, including pregnancy, rapid weight loss, total parenteral nutrition, octreotide therapy, bone marrow or solid organ transplantation. The clinical course of biliary sludge varies, and complete resolution, a waxing and waning course, and progression to gallstones are all possible outcomes. It may cause complications usually associated with gallstones, such as biliary colic, acute cholecystitis, and acute pancreatitis. The main pathogenic mechanism involved in sludge formation is probably gallbladder dismotility, and in selected patients measures aimed to maintain adequate gallbladder contractions has been shown to effectively prevent sludge development.

Unlabelled: The aim of the project was to study hepatic bile entry into and the transit pattern within the gallbladder lumen during fasting and to introduce a new quantitative scintigraphic test for measurement of its concentration function., Methods: Each of 10 control subjects and 10 chronic acalculous cholecystitis (CAC) patients received 111-185 MBq 99mTc-mebrofenin as a hepatic bile marker. Gamma-camera image data were collected in the anterior view on a 128 x 128 x 16 computer matrix at 1 frame per minute for 60 min for the hepatic phase and 30 min for the gallbladder phase. The radiolabeled hepatic bile area within the gallbladder lumen was traced, and the net transit area and transit time were noted. The hepatic bile transit rate was calculated (as mm2/min) and normalized to 1,000 mm2 of the anterior gallbladder area. The cholecystokinin-8-induced ejection fraction was calculated nongeometrically using counts., Results: Hepatic bile entered the gallbladder continuously during fasting with a mean +/- SD of 71% +/- 20% in control subjects and 59% +/- 27% in CAC patients, which were not significantly different (P > 0.05). The maximum frontal gallbladder area was 1,699 mm2 in control subjects and 1,610 mm2 in CAC patients (P > 0.05). Radiolabeled hepatic bile entered the gallbladder first along its central long axis in both groups, at a mean of 15 min and 16 min, respectively, and traveled toward the periphery in a lamellar fashion at a normalized mean rate of 38 mm2/min and 40 mm2/min in control subjects and CAC patients, respectively. The mean ejection fraction of 17% in CAC patients was significantly lower than the mean value of 56% in control patients (P < 0.00001)., Conclusion: Hepatic bile enters the gallbladder continuously during fasting. In patients with CAC, the gallbladder maintains the normal concentration function but the contraction and emptying are reduced significantly. This new cholescintigraphic technique enables measurement of both functions sequentially with a single dose of 99mTc-mebrofenin.

Bile analysis is performed on duodenal bile obtained after stimulation of the gallbladder (GB) with cholecystokinin or its analog. Rapid amino acids (AA) infusion contracts the GB. Our objective was to assess qualitatively the adequacy of duodenal bile obtained following AA infusion. We prospectively studied 15 patients each with non ulcer dyspepsia (NUD) and gallstones (GS), and 17 patients with acute idiopathic pancreatitis (AIP). Duodenal bile was obtained after duodenal intubation and stimulation of GB by rapid AA infusion. The GB contractile response to AA infusion was assessed by functional ultrasonography. Bile was analyzed for lipids, nucleation time, cholesterol saturation index (CSI), and biliary crystals. Adequate duodenal bile could be collected in all but one patient with AIP and one with GS. The mean +/- SD percent ejection fraction of GB following AA infusion in patients with NUD, GS and AIP was 53.41 +/- 16.23, 52.06 +/- 16.07, and 43.37 +/- 14.16, respectively. Biliary microscopy showed the presence of cholesterol monohydrate crystals (CMC) in 7 of 16 patients with AIP, 12 of 14 patients with GS, and 1 of 15 patients with NUD. Mean CSIs in patients with NUD, GS, CMC-positive AIP, and CMC-negative AIP were 0.78, 1.97, 1.85, and 1.00, respectively. Nucleation time in patients with NUD and gallstones was 21.1 and 8.42 days. respectively. In conclusion, qualitatively adequate bile can be obtained for chemical and microscopic examination following rapid intravenous infusion of AA to stimulate the GB.

Previous studies on the effects of vagotomy on gallbladder (GB) motility have yielded conflicting results. The aim of this study was to evaluate the effects of vagotomy on GB motility and bile kinetics using a new method. Twelve dogs were divided into two groups of six (control and pyloroplasty) and, 4 weeks later, underwent truncal vagotomy. A catheter secured in the GB fundus was used to monitor GB volume. After injecting polyethylene glycol (PEG) into the GB, combined measurements of GB volume and PEG concentration enabled GB emptying and bile kinetics to be estimated. Seven and five of the 12 vagotomized dogs were classified as having large and normal fasting GB volumes, respectively. Postprandial GB emptying was impaired when the fasting GB volume was enlarged. In the fasting state, bile kinetics of vagotomized dogs were significantly smaller than the control values. The emptying ability of the GB of vagotomized dogs with large fasting GB volumes was reduced considerably both in the postprandial and the fasting states. Such retention of bile in the GB after vagotomy may facilitate cholesterol crystal nucleation and stone growth.

Objective: The aim of this study was to assess whether a single noninvasive technique, ultrasonography, is able in vivo: 1) to evaluate the time-related patterns of gallbladder bile storage and emptying, and 2) to quantitate the amount of bile flux through the gallbladder (GB)., Methods: Healthy volunteers were submitted to the simultaneous assessment of gallbladder volume variations by frequent serial ultrasonographic (US) measurements and of hepatic bile flow through the GB by quantitative cholescintigraphy (QC) during continuous i.v. infusion of 99 mTc-HIDA. An ad hoc mathematical analysis of US GB volume measurements was used to estimate the amount of bile flux through the GB. The QC-derived measurements of the flux of hepatic bile through the GB was used to substantiate the US-derived estimates., Results: The curves expressing the time-related GB handling of hepatic bile obtained independently from US and QC measurements were statistically equivalent, and both techniques showed that the patterns and the amount of hepatic bile handled by the gallbladder after meal ingestion is remarkably different during three successive phases. After meals, hepatic bile was mainly 1) stored in the GB in the first phase; 2) emptied from the GB in a second phase; and 3) stored in the GB in the third phase. The ultrasonographic analysis estimated that 1) 23.8+/-12.5 ml (0.44+/-0.11 ml/min), 5.1+/-3.9 ml (0.15+/-0.10 ml/min), and 33.2+/-10.5 ml (0.53+/-0.16 ml/min) of hepatic bile entered into the GB during the three successive postprandial phases, and 2) the entire amount of bile flowing bidirectionally through the cystic duct, during the observation period (132.6+/-23.3 ml) was about five-fold greater than that estimated by the usually employed variables., Conclusion: The proposed mathematical analysis of frequent ultrasonographic measurements of the GB volumes enables one to estimate noninvasively the flux of bile through the gallbladder in humans.

Bile excretion changes the physiological milieu of the duodenum, possibly resulting in enhanced absorption of a drug due to increased solubilisation. This possible influence of bile salts following stimulation of gallbladder emptying by the release of cholecystokinin on the pharmacokinetics of a sustained release theophylline (CAS 58-55-9) preparation (Bronchoretard) was evaluated in this study. An open, randomised, 3-way crossover study in 12 healthy, non-smoking volunteers was selected to prove or reject this hypothesis. All subjects received 500 mg of the sustained release theophylline formulation under two different cholagogia stimulating test conditions compared with a fasting reference condition. A standard breakfast and i.m. administration of cholecystokinin enabled a reproducible modulation of bile flow: a moderate and extreme contraction of the gallbladder could be induced after a standard breakfast and after i.m. administration of cholecystokinin, respectively. Following a standard breakfast, gallbladder volumes were approximately halved (50.6%) compared to the baseline volume after 79 min. Injection of 0.3 microgram/kg body weight cholecystokinin resulted in fast and complete gallbladder evacuation (94.6%) 36 min after the application of this cholagogue stimulus. Gallbladder volumes remained more or less constant under fasting conditions. This manipulation of bile flow did not influence concentration/time profiles of the sustained release theophylline preparation compared to the fasting condition. Even almost complete evacuation of the gallbladder after administration of cholecystokinin did not modify the concentration/time profile of theophylline in a relevant way. An unintentional rapid release of theophylline could be excluded for this sustained release formulation for all three treatments, as not a single case of dose dumping was observed. Furthermore, in vitro dissolution investigations using synthetic surfactants can predict neither food effects nor bile influence on the in vivo absorption at least for the sustained release formulation tested.

Substance P containing nerves are widely distributed throughout the gastrointestinal tract. The aims of this study were to determine the distribution of substance P containing nerves in the extrahepatic biliary tree of the Australian brush-tailed possum and to characterize the effect of exogenous substance P on the sphincter of Oddi (SO) motility and transphincteric flow in vivo. Immunohistochemical staining of fixed specimens (n = 8) found moderate numbers of substance P containing nerve cell bodies and fibres throughout the neural plexuses of the SO, in particular in the serosal and intraluminal nerve trunks of the SO and gallbladder. Synthetic porcine substance P (1-2000 ng kg-1), administered by close intra-arterial injection (i.a.; n = 7), produced a dose-dependent elevation in basal pressure [P < 0.01] and an associated dose-dependent reduction in trans-sphincteric flow [P < 0.0001]. Substance P had no significant dose-dependent effect on SO phasic contraction amplitude or frequency. Tetrodotoxin (9 micrograms kg-1, i.a.) did not inhibit the effect of substance P on SO motility and trans-sphincteric flow (n = 5). In conclusion, substance P containing nerves are found throughout the possum extrahepatic biliary tree. Exogenous substance P stimulates SO motility and reduces trans-sphincteric flow in vivo by acting directly on the sphincter smooth muscle.

Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, interdigestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 +/- 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.

Interdigestive phasic motility of the gallbladder and bile excretion into the duodenum were studied in 100 patients with duodenal ulcer (DU) and 20 healthy subjects. Gall bladder motility and bile excretion in both healthy and DU subjects directly depended on interdigestive phasic activity of the duodenum and gastric antrum. In health, gallbladder volume reached its maximum within termination of phase II, minimum in the end of phase III-beginning of phase I. Maximal bile production occurred at phase II-III and coincided with pH decline in the stomach. The mixture of the vesicular and duct bile flowed out in the end phase III-beginning of phase I. The range of volumetric bladder contraction made up 33% of its capacity. In DU patients this reached 35%, the bladder capacity was reduced, the maximum bile production occurred at phase II, bile flowed out intermittently, its color changed from achromatic to dark yellow. The latter fact suggests hypertensive and hypermotor dyskinesia of the gallbladder as well as its sphincter system and bile duct functional impairment. This requires adequate therapeutic correction with consideration of relevant motor and secretory disturbances.

Background: The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet., Methods: Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK)., Results: Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups., Conclusions: Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.

In a prospective trial to determine whether gastric surgery induces gallbladder sludge and stone formation, 48 patients with gastric cancer were ultrasonographically examined with simultaneous observation on changes in gallbladder contractile function before and serially for 5 years after gastrectomy. Gallbladder sludge formation was induced with a high frequency of 42% 1 month after gastrectomy, with corresponding significant lowering of gallbladder contractile function. Most of gallbladder sludges, however, disappeared within 12 months in relation to the gradual recovery of gallbladder contractile function. Conversely, gallstone developed in nine patients (18.8%), mostly more than 6 months after gastrectomy. Interestingly, gallstone formation was induced in seven patients who were sludge negative. An evolvement of gallbladder sludge into stone was observed in only two patients, who were, however, treated with intravenous hyperalimentation. This study first provides evidence for the relationship between gastrectomy and a considerably high frequency of incidence of gallbladder sludge and stone in relation to changes in gallbladder kinetics after gastrectomy.