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The cholecystokinin A receptor (CCKAR) is expressed predominantly in the gallbladder and small intestine in the digestive system, where it is responsible for CCK's regulation of gallbladder and small intestinal motility. The effect of CCKAR on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. The Cckar gene has been identified to be an important gallstone gene, Lith13 , in inbred mice by a powerful quantitative trait locus analysis. Knockout of the Cckar gene in mice enhances cholesterol cholelithogenesis by impairing gallbladder contraction and emptying, promoting cholesterol crystallization and crystal growth, and increasing intestinal cholesterol absorption. Clinical and epidemiological studies have demonstrated that several variants in the CCKAR gene are associated with increased prevalence of cholesterol cholelithiasis in humans. Dysfunctional gallbladder emptying in response to exogenously administered CCK-8 is often found in patients with cholesterol gallstones, and patients with pigment gallstones display an intermediate degree of gallbladder motility defect. Gallbladder hypomotility is also revealed in some subjects without gallstones under several conditions: pregnancy, total parenteral nutrition, celiac disease, oral contraceptives and conjugated estrogens, obesity, diabetes, the metabolic syndrome, and administration of CCKAR antagonists. The physical-chemical, genetic, and molecular studies of Lith13 show that dysfunctional CCKAR enhances susceptibility to cholesterol gallstones through two primary mechanisms: impaired gallbladder emptying is a key risk factor for the development of gallbladder hypomotility, biliary sludge (the precursor of gallstones), and microlithiasis, as well as delayed small intestinal transit augments cholesterol absorption as a major source for the hepatic hypersecretion of biliary cholesterol and for the accumulation of excess cholesterol in the gallbladder wall that further worsens impaired gallbladder motor function. If these two defects in the gallbladder and small intestine could be prevented by the potent CCKAR agonists, the risk of developing cholesterol gallstones could be dramatically reduced.

Background and Aim: Several gallstone patients complain of dyspeptic symptoms, irrespective of the presence of typical colicky pain. Symptoms often persist after a cholecystectomy. Systematic studies on dyspepsia and dynamic gastrointestinal motor function are missing in gallstone patients with preserved gallbladder or after a cholecystectomy., Materials and Methods: Forty-six gallstone patients (age 55 ± 2 years; 15M, 31F) and 24 cholecystectomized patients (age 57 ± 2 years; 6M, 18F) (no difference in type and volume of gallstones between the two groups) were compared against a group of 65 healthy controls (age 51 ± 2 years; 30M, 35F). Dyspepsia occurring in the prior months was assessed by a questionnaire, gastric and gallbladder emptying by functional ultrasonography and orocecal transit time by a hydrogen breath test using a lactulose-enriched standard liquid meal., Results: Gallstone patients had significantly greater dyspepsia, fasting and residual gallbladder volumes, and slower gallbladder emptying, gastric emptying and small intestinal transit time than controls. In cholecystectomized patients, gastric emptying further delayed, compared to gallstone patients and controls., Conclusion: Gallstone patients with the gallbladder "in situ" or after a cholecystectomy display dyspeptic symptoms. Symptoms are associated with multiple gastrointestinal motility defects involving the gallbladder, stomach and small intestine. After cholecystectomy, gastric emptying worsens., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Cholecystokinin (CCK) is an important neuro-intestinal peptide hormone produced by the enteroendocrine I-cells in the upper part of small intestine. Protein- and fat-enriched food plays an important role in triggering CCK secretion from the intestine. Carbohydrates stimulate only small amounts of CCK release. The CCK-1 receptor (CCK-1R) is largely localized in the gallbladder, sphincter of Oddi, pancreas, small intestine, gastric mucosa, and pyloric sphincter, where it is responsible for CCK to regulate multiple digestive processes including gallbladder contraction, pancreatic secretion, small intestinal transit, and gastric emptying. Accumulated evidence clearly demonstrates that CCK regulates gallbladder and small intestinal motility through CCK-1R signaling cascade and the effect of CCK-1R on small intestinal transit is a physiological response for regulating intestinal cholesterol absorption. Disruption of the Cck or the Cck-1r gene in mice significantly increases the formation of cholesterol gallstones by disrupting gallbladder emptying and biliary cholesterol metabolism, as well as promoting intestinal absorption of cholesterol. Abnormalities in gallbladder motility function in response to exogenously administered CCK are found primarily in patients with cholesterol gallstones. Patients with pigment gallstones display an intermediate degree of gallbladder motility defect without gallbladder inflammation and enlarged fasting gallbladder. Dysfunctional gallbladder contractility has been found under several conditions such as pregnancy, obesity, diabetes, celiac disease, and total parenteral nutrition although gallstones are not observed. The gallbladder-specific CCK-1R-selective agonist may lead to an efficacious novel way for preventing gallstone formation by promoting gallbladder emptying, particularly for pregnant women and subjects with dysfunctional gallbladder motility function such as celiac patients, as well as patients with total parenteral nutrition., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Coeliac disease is a chronic, small intestinal, immune-mediated enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Clinical studies have found that intestinal cholecystokinin secretion and gallbladder emptying in response to a fatty meal are impaired before coeliac patients start the gluten-free diet (GFD)., Design: However, it was never really appreciated whether coeliac disease is associated with gallstones because there were very few studies investigating the mechanism underlying the impact of coeliac disease on the pathogenesis of gallstones., Results: We summarize recent progress on the relationship between coeliac disease and gallstones and propose that coeliac disease is an important risk factor for gallstone formation because defective intestinal cholecystokinin secretion markedly increases susceptibility to cholesterol gallstones via a mechanism involving dysmotility of both the gallbladder and the small intestine. Because GFD can significantly improve the coeliac enteropathy, early diagnosis and therapy in coeliac patients is crucial for preventing the long-term impact of cholecystokinin deficiency on the biliary and intestinal consequences. When gluten is reintroduced, clinical and histologic relapse often occurs in coeliac patients. Moreover, some of the coeliac patients do not respond well to GFD., Conclusions: It is imperative to routinely examine by ultrasonography whether gallbladder motility function is preserved in coeliac patients and monitor whether biliary sludge (a precursor of gallstones) appears in the gallbladder, regardless of whether they are under the GFD programme. To prevent gallstones in coeliac patients, it is urgently needed to investigate the prevalence and pathogenesis of gallstones in these patients., (© 2017 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to dietary gluten in genetically predisposed individuals. Cholecystokinin (CCK) release from the proximal small intestine and gallbladder emptying in response to a fatty meal are greatly reduced in celiac patients before they start the gluten-free diet, showing a genetic predisposition to gallstones., Methods: To elucidate the complex pathophysiological mechanisms determining the biliary characteristic of celiac disease, we investigated the effect of the absence of endogenous CCK on cholesterol crystallization and gallstone formation in mice fed a lithogenic diet for 28 days., Key Results: Fasting gallbladder volumes were increased and the response of gallbladder emptying to the high-fat diet was impaired in CCK knockout (KO) mice compared to wild-type mice. Because of the absence of CCK, small intestinal transit time was prolonged and intestinal cholesterol absorption was increased. During 28 days of feeding, elevated biliary cholesterol concentrations and gallbladder stasis promoted the growth and agglomeration of solid cholesterol crystals into microlithiasis and stones. Thus, cholesterol crystallization and gallstone formation were accelerated in CCK KO mice. In contrast, daily intraperitoneal administration of CCK-8 reduced gallstone formation in CCK KO mice even on the lithogenic diet., Conclusions & Inferences: The lack of endogenous CCK enhances susceptibility to gallstones by impairing gallbladder contractile function and small intestinal motility function. These findings show that celiac disease is an important risk factor for gallstone formation and the gallbladder motility function should be routinely examined by ultrasonography and gallbladder stasis should be prevented in celiac patients., (© 2015 John Wiley & Sons Ltd.)

Background: To assess hepatobiliary (HB) scans for predicting recurrent symptoms in nonoperated patients with mild or vague symptomatic gallstones., Methods: Data of 170 patients with symptomatic gallstone and who had not undergone cholecystectomy were retrospectively enrolled. These patients were divided into two groups according to whether or not operations were performed due to recurrent symptoms during the follow-up period. The demographic factors and gallbladder ejection fraction (GBEF) of HB scans were compared between the groups. Additionally, symptom-free rate was obtained beginning from the date of the HB scan to the date of surgery, and analyzed based on the level of GBEF., Results: Among the 170 enrolled patients, two patients who underwent cholecystectomy for other disease were excluded. Thirty-four patients underwent cholecystectomy due to recurrent symptoms (OP group), and the remaining 136 patients did not experience recurrent symptoms and therefore did not undergo cholecystectomy (non-OP group). In the OP group, the mean GBEF was significantly lower than that of the non-OP group (28.8 ± 29.9 vs. 66.3 ± 20.0; P < 0.001). The rate of lower GBEF (<30 %, including non-visualization of the gallbladder) was significantly higher in the OP group than the non-OP group (54.9 vs. 5.1 %; P < 0.001). In patients with non-visualization of the gallbladder or GBEF <30 %, the 10-year symptom-free rate was significantly lower than those with a GBEF ≥ 30 % (19.8 % vs. 81.9 %; P < 0.001)., Conclusion: HB scanning is a useful objective modality to differentiate gallstone-related symptoms from other etiologies and predict recurrent symptoms.

Objective: To discuss the hazards of cholecystolithiasis recrudesce after cholecystolithotomy with gallbladder reservation; To provide a theoretical basis for reducing the recurrence rate of gallstone., Patients and Methods: The patients who were followed up for at least one year after minimally-invasive operation with gallbladder reservation because of cholecystolithiasis were selected. In this population, the patients with recurrence after surgery were as the case group, those patients with no recurrence after surgery were as the control group. Through collection of general data of selected cases, relevant information of Ultrasound Examinations of gallbladder and history data of the patients questionnaires were completed. Relevant factors of gallstone recurrence of patients, were observed through statistic analysis. Main factors go as follows: gender, age, nation, career, BMI, whether or not the patient had the history of chronic superficial gastritis, and regulation of gallbladder emptying function, family history, etc. The information of selected cases is complete., Results and Conclusions: The main hazards of cholecystolithiasis recurrence were BMI, family history of gallstone disease, and emptying function of gallbladder.

Background: Regular gall bladder contraction reduces bile stasis and prevents gallstone formation. Intraduodenal administration of exogenous pancreatic secretory trypsin inhibitor-I (PSTI-I, also known as monitor peptide) causes cholecystokinin (CCK) secretion., Design: We proposed that stimulation of CCK release by PSTI would produce gall bladder contraction and prevent gallstones in mice fed a lithogenic diet. Therefore, we tested the effect of overexpression of rat PSTI-I in pancreatic acinar cells on plasma CCK levels and gall bladder function in a transgenic mouse line (TgN[Psti1]; known hereafter as PSTI-I tg)., Results: Importantly, PSTI tg mice had elevated fasting and fed plasma CCK levels compared to wild-type (WT) mice. Only mice fed the lithogenic diet developed gallstones. Both fasting and stimulated plasma CCK levels were substantially reduced in both WT and PSTI-I tg mice on the lithogenic diet. Moreover, despite higher CCK levels PSTI-I tg animals developed more gallstones than WT animals., Conclusions: Together with the previously observed decrease in CCK-stimulated gall bladder emptying in mice fed a lithogenic diet, our findings suggest that a lithogenic diet causes gallstone formation by impaired CCK secretion in addition to reduced gall bladder sensitivity to CCK., (© 2015 Stichting European Society for Clinical Investigation Journal Foundation.)

Gallstone disease (GSD) is one of the most common biliary tract diseases worldwide in which both genetic and environmental factors have roles in its pathogenesis. Biliary cholesterol supersaturation from metabolic defects in the liver is traditionally seen as the main pathogenic factor. Recently, there have been renewed investigative interests in the downstream events that occur in gallbladder lithogenesis. This article focuses on the role of the gallbladder in the pathogenesis of cholesterol GSD (CGD). Various conditions affecting the crystallization process are discussed, such as gallbladder motility, concentrating function, lipid transport, and an imbalance between pro-nucleating and nucleation inhibiting proteins.

Cholesterol gallstone formation is a complex process and involves phase separation of cholesterol crystals from supersaturated bile. In most cases, cholesterol hypersecretion is considered the primary event in gallstone formation. The sterol is transported through the hepatocytic canalicular membrane by ABCG5-G8. Expression of this transport protein is regulated by transcription factor Liver X Receptor-alpha, which may be responsible for biliary hypersecretion. Hydrophobic bile salt pool, bile concentration, excess pronucleating mucin, and impaired gallbladder and intestinal motility are secondary phenomena in most cases but nevertheless may contribute to gallstone formation., (Copyright 2010 Elsevier Inc. 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.

We studied gall bladder contractility in 61 children with beta-thalassaemia who were asymptomatic for gall bladder disease and 51 sex- and age-matched controls in Cairo, Egypt, using, andreal-time ultrasonography. Multiple gall bladder stones were present in 18.0% of thalassaemia patients and sludge in 6.6%. There were statistically significant differences between thalassaemia patients controls in gall bladder fasting volume, residual volume, emptying time and contraction index. There was significant positive correlation between fasting and residual volumes and age, weight and height, and between fasting volume and body mass index and serum ferritin level. Contraction index was negatively correlated with serum total bilirubin. Impaired gall bladder motility was evident in patients with beta-thalassaemia and it may be related to disease duration, serum ferritin and total serum bilirubin level.

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.)

Free radical-mediated damage of the gall bladder epithelium predisposes to the development of both gall bladder inflammation and gallstone formation, which often coexist. Melatonin, a pineal and gut secretory product, due to its antioxidant activity along with its effect on the aging gall bladder myocytes, inhibits gallstone formation. Melatonin reduces the biliary levels of cholesterol by inhibiting cholesterol absorption across the intestinal epithelium and by increasing the conversion of cholesterol to bile acids. The incidence of gallstones is increasing and is expected to rise dramatically with the increase in the longevity and the risk factors such as obesity. The change in the prevalence of cholelithiasis is associated with a proportionate rise in the incidence of cholangiocarcinoma. In an attempt to improve the quality of life of the rapidly increasing aging population, this article reviews up-to-date information on the pathophysiology of the gall bladder function and discusses the development of new therapies with potential good patient compliance and lower cost than the current treatments.

Aim: To analyze gallbladder contractility in patients with black pigment stones (BPSs) and to compare this with patients with cholesterol stones (CSs) and healthy volunteers., Methods: The pattern of bile evacuation from the gallbladder was quantified by computer cholescintigraphy in 28 normal subjects, 22 patients with CSs and 14 with BPSs. The parameters of gallbladder contractility included ejection period (EP), ejection fraction (EF) and ejection rate (ER)., Results: A significantly shorter EP was observed in patients with BPSs in comparison to those with CSs (t = 2.4, P < 0.05). EF in BPS patients significantly decreased in comparison to that in CS and normal subjects (t = 6.4, P < 0.0001; t = 2.1, P < 0.05). EF in CS patients also significantly decreased in comparison to that in normal subjects (t = -3.0, P < 0.005). Consequently, ER in patients with BPSs and CSs was significantly smaller than that in normal subjects (t = 3.1, P < 0.005; t = -3.5, P < 0.001). Moreover, in cases where postprandial reflux of a radioisotope into the common hepatic duct from the gallbladder was observed, EF and ER of either CS or BPS patients showed a significant reduction., Conclusion: Bile evacuation from the gallbladder is reduced in patients with BPSs, in comparison to those with CSs and to healthy volunteers. Bile stagnation due to impaired gallbladder kinetics seems to be one of the predisposing factors for the development of BPSs.

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.

Objective: In this study, we determined the frequency of gallbladder stone (GBS) in rheumatoid arthritis (RA) patients and evaluated factors which could affect the formation of GBS--such as lipids and the GB motilities of the patients., Methods: One hundred and thirteen RA patients (92F, 21M, mean disease duration: 8.9 years) and 117 healthy controls (94F, 23M) were included. In all RA patients, the clinical findings were recorded down; biochemical parameters and body mass index (BMI) were determined; and, abdominal ultrasonography was performed. In addition, 16 RA patients and 20 controls who were age-matched were randomly chosen for GB emptying monitored by ultrasound at 30-minute intervals for 2 hours after a mixed meal. Fasting volume (FV), residual volume (RV) and ejection fraction (EF) for all GBs were assessed., Results: There was a tendency towards a higher frequency of GBS including cholecystectomy (11 GBS, 11 cholecystectomy, 19.5%) in RA patients when compared to controls (8 GBS, 5 cholecystectomy, 11.1%) (p = 0.08). The frequency of GBS plus cholecyctectomy in female RA patients (22.8%) was significantly higher than the control group (11.7%, p = 0.044). Logistic regression analysis showed that only older age was significantly associated with the presence of GBS in RA (OR:1.05, p = 0.048). There was no difference between the 2 groups in FV (p > 0.05). RV, PRV and EF were significantly higher in RA patients than in the control group (p < 0.05)., Conclusion: We diagnosed a higher frequency of GBS in female RA patients when compared to controls. Impaired GB motility in RA patients might contribute to an increased incidence of GBS development.

Hepatobiliary problems are not uncommon in general practice. Many cases can be solved on the basis of a thorough history, clinical examination, blood tests and abdominal ultrasound. The focus of this tutorial paper lies on a number of possible pitfalls in the workup of such problems, based on brief case histories. Atypical presentations of lithogenic biliary obstruction, with or without cholangitis, are discussed as a relatively frequent cause of management difficulties. Furthermore, certain caveats in the interpretation of tumor marker CA19-9, prothrombin time/INR, and ferritin are highlighted.

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.

Background: The incidence of gallstone is higher in patients with diabetes mellitus than in general population because of hypomotility and lowered emptying function. The aim of this study was to investigate the gene expression of cholecystokinin-A (CCK-A) receptor in patients with gallstones and diabetes mellitus and its correlation with the hypomotility of the gallbladder., Methods: Smooth muscle was taken from the gallbladder after cholecystectomy and total RNA was extracted from it by Trizol reagent to compose cDNA. CCK-A receptor was enlarged by reverse transcription-polymerase chain reaction (RT-PCR) and identified by electrophoresis. Based on the analysis of images, the relative expression of the CCK-A receptor was obtained after comparison of the CCK-A receptor and beta-action. The emptying function of the gallbladder was measured with B ultrasound before operation., Results: Gallbladder ejection fraction (GBEF2) (%) (24.9+/-12.7) decreased more significantly in patients with gallstones and diabetes mellitus than in those with simple gallstone (61.5+/-8.5) (P<0.01). In the two groups, a fraction of 540bp of CCK-A receptor could be testified respectively, but the relative expression was different. Compared to the expression of beta-action, it was 0.400+/-0.068 in patients with gallstones and diabetes mellitus, but 0.622+/-0.070 in those with gallstone only (F=7.169, Pu0.01). The result was consistent with the decreased contractility., Conclusions: The gene expression of CCK-A receptor on the smooth muscle of the gallbladder may decrease more significantly in patients with gallstone and diabetes mellitus than in those with gallstone only; this result is consistent with the decreased motility. Thus the lowered expression of CCK-A receptor is probably the cause of hypomotility in patients with gallstones and diabetes mellitus.

Aim: It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility., Methods: We measured gallbladder volume changes in response to gastric distension (saline 500 mL) and fatty meal in 10 normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group II). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups., Results: In group I, there were significant decreases in gallbladder volumes 5-25 min after gastric distension, compared to fasting volumes. Compared to normal volunteers and group II, group I had significantly decreased gallbladder volumes 10-20 min after drinking 500 mL of normal saline and 10 to 50 min after eating fatty meal., Conclusion: Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.

Purpose: Gallbladder hypomotility could play a significant role in the process of lithogenesis, but this role has yet to be defined in black African populations. This role was assessed by measuring gallbladder emptying after stimulation by a fat meal in a group of black African subjects with and without cholelithiasis., Materials and Methods: Fifteen subjects with cholelithiasis and thirty controls divided in two pools were studied. Gallbladder emptying was stimulated by fat meals of 610 and 740 Kcal, and was measured with ultrasound for a period of 120 min., Results: The mean fasting gallbladder Volume of the subjects with lithiasis was significantly superior to that of the controls. Compared to what has been previously published in Caucasian subjects, gallbladder emptying was generally more rapid in our study. Further more, gallbladder emptying was significantly better in the control group than in the group of subjects with cholelithiasis. Two groups of subjects with cholelithiasis were isolated. The first group had poor gallbladder emptying and normal fasting gallbladder Volume; the second had normal gallbladder emptying but significantly increased fasting gallbladder Volume., Conclusion: Impaired gallbladder emptying and/or increased fasting gallbladder Volume probably play a role in lithogenesis. Hypomotility seems to play a significant role only for those subjects with normal fasting gallbladder Volume.

In experimental animals, sphincterotomy facilitates passage of solids from the gallbladder and inhibits gallstone formation apparently by improvement in gallbladder emptying. In humans, however, gallbladder emptying has not been studied following endoscopic sphincterotomy (ES) in patients with gallstones. We therefore prospectively studied resting and cerulin-stimulated gallbladder volumes by real time ultrasonography in 15 patients of choledocholithiasis with gallbladder in situ (eight with and seven without gallbladder calculi) before and after (after bile duct clearance) ES. ES significantly lowered resting gallbladder volume (21.2 +/- 10.6 vs 11.1 +/- 5.0; P < 0.0001) and cerulin-stimulated residual gallbladder volume (10.8 +/- 5.6 vs 4.4 +/- 2.1; P < 0.0001). ES also significantly increased the gallbladder ejection fraction (47.3 +/- 12.1% vs 58.8 +/- 11.1%; P < 0.0001). The rate constant for gallbladder emptying after cerulin infusion also increased significantly after ES (-0.022/min vs -0.031/ min; P < 0.0001). Significant improvement in gallbladder motility was observed in both groups of patients with and without gallbladder calculi. ES significantly improves gallbladder motility in humans.

Background: Change in gallbladder function may occur in patients with an intact gallbladder after endoscopic sphincterotomy (EST). This study was designed to evaluate the factors influencing gallbladder filling after EST and the correlation between gallbladder function and stone recurrence., Methods: Sixty Chinese patients with symptomatic choledocholithiasis and an intact gallbladder received EST to clear the bile ducts. They were further investigated with sphincter of Oddi manometry (SOM), quantitative cholescintigraphy (QC), and long-term clinical follow-up., Results: Fifty-six of the 60 patients in the study group were confirmed to have a loss of sphincteric function by SOM. QC showed normal gallbladder filling in 35 of these patients and delayed or non-filling in 21 patients. A significantly higher incidence of normal gallbladder filling occurred in patients with juxtapapillary diverticulum than in those without (P < 0.02), but preexisting cholecystolithiasis had no effect on it. During the follow-up period (median, 32 months: range, 9-54 months) 10 of 56 patients developed recurrent choledocholithiasis. There was no correlation between the status of gallbladder filling, preexisting cholecystolithiasis, and recurrent stones, but 9 of the 10 patients with recurrent stones had a juxtapapillary diverticulum. Repeated endoscopic treatment was satisfactory in eight patients, and only two patients received cholecystectomy., Conclusions: EST does not alter gallbladder function in most patients. Juxtapapillary diverticulum may facilitate gallbladder filling after EST, but it is also a possible factor for recurrent choledocholithiasis.