Gastrointestinal defects in gallstone and cholecystectomized patients.

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.

Ultrasound Assessment of Hepatobiliary and Splenic Changes in Patients With Dengue and Warning Signs During the Acute and Recovery Phases.

OBJECTIVES: To evaluate whether abdominal ultrasound (US) with a gallbladder (GB) contractility study or motor function test can be used as a diagnostic tool in patients with dengue and warning signs in acute and recovery phases. METHODS: Fifty-one individuals in the acute phase of dengue presenting with warning signs (dengue group) and 49 healthy individuals without a history of dengue or hepatobiliary disease (control group) were studied with abdominal US and a GB contractility study. RESULTS: Statistical differences in US measurements of the liver (right lobe, P = .012; left lobe, P = .001) and spleen (P = .008) dimensions, GB wall thickness (P < .001), and the GB emptying fraction (P < .001) were observed in dengue during the acute phase compared with the control group. After 60 days, abdominal US of the dengue group showed a statistical difference in liver (right lobe, P < .001; left lobe, P = .078) and spleen (P < .001) dimensions, GB wall thickness, and the GB emptying fraction (P < .001) compared with the results obtained during the acute phase. Furthermore, a statistical difference in the spleen volume and GB emptying fraction (P < .001) was observed when comparing dengue after clinical recovery and the control group. Abdominal pain in patients with dengue was positively associated with hepatomegaly (P = .031), splenomegaly (P = .008), increased GB wall thickness (P = .016), and a reduced GB emptying fraction (P = .038) during the acute phase and with splenomegaly (P = .001) and a reduced GB emptying fraction (P = .003) after clinical recovery. CONCLUSIONS: Abdominal US with a GB motor function test can be used as a diagnostic tool in patients with dengue during acute and recovery phases.

Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity.

AIMS: Treatment with liraglutide 3.0 mg has been associated with gallbladder-related adverse events. To conduct a single-centre, double-blind, 12-week trial comparing the effect of 0.6 mg liraglutide and steady-state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes. METHODS: Participants were randomized 1:1 to once-daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6-mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600-kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12-week maximum postprandial gallbladder ejection fraction (GBEFmax ), measured over 240 minutes after starting the meal. RESULTS: Baseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2 , 50% women). Mean 12-week GBEFmax (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% × min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11-240) minutes with liraglutide 3.0 mg and 77 (22-212) minutes with placebo. Similar findings were noted after the first 0.6-mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events. CONCLUSIONS: Treatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax .

The bile acid-sequestering resin sevelamer eliminates the acute GLP-1 stimulatory effect of endogenously released bile acids in patients with type 2 diabetes.

AIMS: Discovery of the specific bile acid receptors farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) in enteroendocrine L cells has prompted research focusing on the impact of bile acids on glucagon-like peptide-1 (GLP-1) secretion and glucose metabolism. The aim of the present study was to assess the GLP-1 secretory and gluco-metabolic effects of endogenously released bile, with and without concomitant administration of the bile acid-sequestering resin, sevelamer, in patients with type 2 diabetes. MATERIALS AND METHODS: We performed a randomized, placebo-controlled, double-blinded cross-over study including 15 metformin-treated patients with type 2 diabetes. During 4 experimental study days, either sevelamer 3200 mg or placebo in combination with intravenous infusion of cholecystokinin (CCK) (0.4 pmol sulfated CCK-8/kg/min) or saline was administered in randomized order. The primary endpoint was plasma GLP-1 excursions as measured by incremental area under the curve. Secondary endpoints included plasma responses of glucose, triglycerides, insulin, CCK, fibroblast growth factor-19 and 7α-hydroxy-4-cholesten-3-one (C4). In addition, gallbladder dynamics, gastric emptying, resting energy expenditure, appetite and ad libitum food intake were assessed. RESULTS: CCK-mediated gallbladder emptying was demonstrated to elicit a significant induction of GLP-1 secretion compared to saline, whereas concomitant single-dose administration of the bile acid sequestrant sevelamer was shown to eliminate the acute bile acid-induced increase in plasma GLP-1 excursions. CONCLUSIONS: Single-dose administration of sevelamer eliminated bile acid-mediated GLP-1 secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally localized TGR5 on enteroendocrine L cells.

Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs.

OBJECTIVE: Recent randomized and controlled trials of drugs derived from the gut hormone glucagon-like peptide-1 (GLP-1) show that the most frequent adverse symptoms are gastrointestinal, including gallbladder-related side effects such as cholithiasis and cholecystitis. Since the gut hormone cholecystokinin (CCK) stimulates bile secretion and regulates gallbladder motility and emptying, we examined the effect of GLP-1 on the secretion of CCK in normal subjects and patients with type 1 diabetes mellitus. MATERIALS AND METHODS: Plasma was sampled from 10 healthy subjects and 10 patients with diabetes. With plasma glucose concentrations clamped between 6 and 9 nmol/l, GLP-1 or saline was infused for 240 min during and after a meal. The plasma concentrations of CCK were measured with a highly specific radioimmunoassay. RESULTS: Basal plasma concentrations of CCK were similar in the normal subjects and in the diabetes patients. During the meal, the CCK concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of CCK significantly in both normal subjects and in the diabetes patients. CONCLUSIONS: The results show that GLP-1 suppresses the secretion of CCK after a meal in normal and diabetic subjects. The suppression attenuates the gallbladder contractility. Our data, therefore, offer an explanation for the increased risk of adverse gallbladder events during treatment with GLP-1-derived drugs.

Ursodeoxycholic acid protects interstitial Cajal-like cells in the gallbladder from undergoing apoptosis by inhibiting TNF-α expression.

Hypomotility is a common symptom of gallstone disease, which is accompanied by a loss of interstitial Cajal-like cells (ICLCs) in the gallbladder. Ursodeoxycholic acid (UDCA) is widely used in treating gallstone disease, and has shown anti-apoptotic and anti-inflammatory effects apart from its ability to dissolve gallstones. In this study, we investigated the anti-apoptotic and anti-inflammatory effects of UDCA on ICLCs in guinea pigs with gallstones. Guinea pigs were fed a high-cholesterol diet for 8 weeks to induce the formation of gallstones. A group of animals was administered UDCA (50 mg·kg-1·d-1, ig) simultaneously. At the end of 8 weeks, the animals were euthanized with anesthesia, cholecystectomy was performed immediately and gallbladder was collected for further analysis. We showed that in the model group the contractility of gallbladder muscle strips in response to both acetylcholine (ACh) and CCK-8 was severely impaired, which was significantly improved by UDCA administration. Furthermore, UDCA administration significantly reduced the apoptotic ratio of ICLCs, based on the observation of co-localization imaging of apoptotic cells and c-kit-positive cells. Western blotting analysis and real-time PCR results revealed that the TNF-α/Caspase8/Caspase3 pathway was suppressed in the UDCA-treated animals, confirming the anti-apoptotic effect of UDCA in the gallbladder. The H&E staining showed that UDCA administration significantly attenuated inflammatory cell infiltration in the gallbladder wall. In conclusion, UDCA can protect ICLCs in the gallbladder from undergoing apoptosis by inhibiting the TNF-α/Caspase8/caspase3 pathway.

Impaired intestinal cholecystokinin secretion, a fascinating but overlooked link between coeliac disease and cholesterol gallstone disease.

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.

The impact of EndoBarrier gastrointestinal liner in obese patients with normal glucose tolerance and in patients with type 2 diabetes.

AIMS: The duodenal-jejunal bypass sleeve ((DJBS) or EndoBarrier Gastrointestinal Liner) induces weight loss in obese subjects and may improve glucose homeostasis in patients with type 2 diabetes (T2D). To explore the underlying mechanisms, we evaluated postprandial physiology including glucose metabolism, gut hormone secretion, gallbladder emptying, appetite and food intake in patients undergoing DJBS treatment. MATERIAL AND METHODS: A total of 10 normal glucose-tolerant (NGT) obese subjects and 9 age-, body weight- and body mass index-matched metformin-treated T2D patients underwent a liquid mixed meal test and a subsequent ad libitum meal test before implantation with DJBS and 1 week (1w) and 26 weeks (26w) after implantation. RESULTS: At 26w, both groups had achieved a weight loss of 6 to 7 kg. Postprandial glucagon-like peptide-1 (GLP-1) and peptide YY responses increased at 1w and 26w, but only in T2D subjects. In contrast, glucose-dependent insulinotropic polypeptide responses were reduced only by DJBS in the NGT group. Postprandial glucose, insulin, C-peptide, glucagon, cholecystokinin and gastrin responses were unaffected by DJBS in both groups. Satiety and fullness sensations were stronger and food intake was reduced at 1w in NGT subjects; no changes in appetite measures or food intake were observed in the T2D group. No effect of DJBS on postprandial gallbladder emptying was observed, and gastric emptying was not delayed. CONCLUSIONS: DJBS-induced weight loss was associated with only marginal changes in postprandial physiology, which may explain the absence of effect on postprandial glucose metabolism.

Evaluation of anti-diabetic effect and gall bladder function with 2-thio-5-thiomethyl substituted imidazoles as TGR5 receptor agonists.

A novel series of 2-thio-5-thiomethyl substituted imidazoles was discovered to be potent TGR5 agonists that possessed glucose-lowering effects while inhibiting gall bladder emptying in mice.

Critical Illness Is Associated With Impaired Gallbladder Emptying as Assessed by 3D Ultrasound.

OBJECTIVE: To quantify gallbladder dysfunction during critical illness. DESIGN: Prospective observational comparison study of nutrient-stimulated gallbladder emptying in health and critical illness. SETTING: Single-centre mixed medical/surgical ICU. PATIENTS: Twenty-four mechanically ventilated critically ill patients suitable to receive enteral nutrition were compared with 12 healthy subjects. INTERVENTIONS: Participants were studied after an 8-hour fast. Between 0 and 120 minutes, high-fat nutrient (20% intralipid) was infused via a postpyloric catheter into the duodenum at 2 kcal/min. MEASUREMENTS AND MAIN RESULTS: Three-dimensional images of the gallbladder were acquired at 30-minute intervals from -30 to 180 minutes. Ejection fraction (%) was calculated as changes between 0 and 120 minutes. Blood samples were obtained at 30-minute intervals for plasma cholecystokinin. Data are mean (SD) or median [interquartile range]. In the critically ill, fasting gallbladder volumes (critically ill, 61 mL [36-100 mL] vs healthy, 22 mL [15-25] mL; p < 0.001] and wall thickness (0.45 mm [0.15 mm] vs 0.26 mm [0.08 mm]; p < 0.001] were substantially greater, and sludge was evident in the majority of patients (71% vs 0%). Nutrient-stimulated emptying was incomplete in the critically ill after 120 minutes but was essentially complete in the healthy individuals (22 mL [9-66 mL] vs 4 mL [3-5 mL]; p < 0.01]. In five critically ill patients (21%), there was no change in gallbladder volume in response to nutrient, and overall ejection fraction was reduced in the critically ill (50% [8-83%] vs 77 [72-84%]; p = 0.01]. There were no differences in fasting or incremental cholecystokinin concentrations. CONCLUSIONS: Fasted critically ill patients have larger, thicker-walled gallbladders than healthy subjects and nutrient-stimulated gallbladder emptying is impaired with "gallbladder paresis" occurring in approximately 20%.

The cholecystokinin-1 receptor antagonist devazepide increases cholesterol cholelithogenesis in mice.

BACKGROUND: A defect in gallbladder contraction function plays a key role in the pathogenesis of gallstones. The cholecystokinin-1 receptor (CCK-1R) antagonists have been extensively investigated for their therapeutic effects on gastrointestinal and metabolic diseases in animal studies and clinical trials. However, it is still unknown whether they have a potential effect on gallstone formation. DESIGN: To study whether the CCK-1R antagonists enhance cholelithogenesis, we investigated cholesterol crystallization, gallstone formation, hepatic lipid secretion, gallbladder emptying function and intestinal cholesterol absorption in male C57BL/6J mice treated by gavage with devazepide (4 mg/day/kg) or vehicle (as controls) twice per day and fed the lithogenic diet for 21 days. RESULTS: During 21 days of feeding, oral administration of devazepide significantly accelerated cholesterol crystallization and crystal growth to microlithiasis, with 40% of mice forming gallstones, whereas only agglomerated cholesterol monohydrate crystals were found in mice receiving vehicle. Compared to the vehicle group, fasting and postprandial residual gallbladder volumes in response to the high-fat meal were significantly larger in the devazepide group during cholelithogenesis, showing reduced gallbladder emptying and bile stasis. Moreover, devazepide significantly increased hepatic secretion of biliary cholesterol, but not phospholipids or bile salts. The percentage of intestinal cholesterol absorption was higher in devazepide-treated mice, increasing the bioavailability of chylomicron-derived cholesterol in the liver for biliary hypersecretion into bile. These abnormalities induced supersaturated bile and rapid cholesterol crystallization. CONCLUSIONS: The potent CCK-1R antagonist devazepide increases susceptibility to gallstone formation by impairing gallbladder emptying function, disrupting biliary cholesterol metabolism and enhancing intestinal cholesterol absorption in mice.

Gallbladder Ejection Fraction Is Unrelated to Gallbladder Pathology in Children and Adolescents.

OBJECTIVES: Biliary dyskinesia is a common diagnosis that frequently results in cholecystectomy. In adults, most clinicians use a cut off value for the gallbladder ejection fraction (GBEF) of <35% to define the disease. This disorder is not well characterized in children. Our aim was to determine the relation between GBEF and gallbladder pathology using a large statewide medical record repository. METHODS: We obtained records from all patients of 21 years and younger who underwent hepatic iminodiacetic acid (HIDA) testing within the Indiana Network for Patient Care from 2004 to 2013. GBEF results were obtained from radiology reports using data mining techniques. Age, sex, race, and insurance status were obtained for each patient. Any gallbladder pathology obtained subsequent to an HIDA scan was also obtained and parsed for mention of cholecystitis, cholelithiasis, or cholesterolosis. We performed mixed effects logistic regression analysis to determine the influence of age, sex, race, insurance status, pathologist, and GBEF on the presence of these histologic findings. RESULTS: Two thousand eight hundred forty-one HIDA scans on 2558 patients were found. Of these, 310 patients had a full-text gallbladder pathology report paired with the HIDA scan. GBEF did not correlate with the presence of gallbladder pathology (cholecystitis, cholelithiasis, or cholesterolosis) when controlling for age, sex, race, insurance status, and pathologist using a mixed effects model. CONCLUSIONS: Hypokinetic gallbladders are no more likely to have gallbladder pathology than normal or hyperkinetic gallbladders in the setting of a patient with both a HIDA scan and a cholecystectomy. Care should be used when interpreting the results of HIDA scans in children and adolescents.

Gallbladder Volume in Sikkimese Population.

Background Gall bladder volume can have clinical and therapeutic implications and possibly affect certain pathophysiological mechanisms of many diseases affecting the gallbladder including gall stones. Objective The objective of the study was to establish baseline indices of gallbladder volume for the Sikkimese population and determine its correlation with age, sex and Body Mass Index. Method A prospective epidemiologic study on selected 100 patients (equal male to female ratio) over the age of 36 years, undergoing ultrasound scan of abdomen, was undertaken. Age, Sex, Body Mass Index and gall bladder volume for each subject were collected and analysed statistically. Spearman's correlation test was performed to look for significant variables. Result The overall mean gallbladder volume in the present study was 15.47±7.9 ml with 17.2±8.9 ml and 13.74±6.4 ml being average volumes in males and females respectively, which gives the baseline indices for the Sikkimese population. Gall bladder volume was strikingly increased in obese subjects. There was a positive correlation between gall bladder volume and age (r=0.114), gender (r=0.182) and BMI (r= 0.175) but the strength of correlation was weak and not statistically significant (p <0.001). Conclusion Ultrasonography is an easy and effective method for evaluation of gall bladder volume. Sikkimese males have a larger fasting gall bladder volume which is directly correlated with higher body mass index. Fasting gall bladder volume has a weak correlation with advancing age.

[NERVOUS REGULATION OF BILIARY TRACT MOTILITY].

Aim: The study of mechanisms of regulation of biliary tract motility by divisions of autonomic nervous system (ANS). Material and methods: Experiments were carried out on rabbits, chinchillas weighing 3.5-4 kg using gentle methods of treatment of experimental animals. Electromotor activity of electromotor (EMA) of the gallbladder and sphincter of Oddi was recorded. Irritation of the nerve produces an electrical pulse duration of 2 ms, the amplitude of 1.5-15 V, frequency of 10 Hz. Results: The mechanism of vagal inhibition of sphincter of Oddi motility and unidirectional stimulatory influence of ANS divisions on the motility of the gallbladder and sphincter of Oddi was studied. It was established that in the mechanism of vagal inhibition of sphincter of Oddi motility involved intramural adrenergic neurons synaptically connected with preganglionic parasympathetic fibers. At the stimulatory effect of vagus on biliary tract motility serotonergic intramural neurons are involved transmitting excitation to serotonin receptors of effector tissue.

Cholesterol gallstone disease: focusing on the role of gallbladder.

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.

Endogenous elevation of plasma cholecystokinin does not prevent gallstones.

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.

Prediction of symptom improvement in children with biliary dyskinesia.

BACKGROUND: Rates of cholecystectomy for biliary dyskinesia are rising. Our objective was to identify clinical determinants of symptom improvement in children undergoing cholecystectomy for biliary dyskinesia. METHODS: This retrospective cohort study included patients undergoing cholecystectomy for biliary dyskinesia from 2006-2013 who had their gallbladder ejection fraction (EF) measured by either cholecystokinin-stimulated hepatobiliary iminodiacetic acid scan and/or fatty meal ultrasound. Patients presenting from 2010-2013 were interviewed >1 y after cholecystectomy to determine symptom improvement, complete symptom resolution, and any postoperative clinical interventions related to biliary dyskinesia. Sensitivity and positive predictive values for the diagnostic tests for symptom improvement were calculated. Multivariable logistic regression models were used to identify preoperative characteristics associated with symptom improvement. RESULTS: Of the 153 included patients, 76% were female, 89% were Caucasian, and 39% were obese. At postoperative evaluation, symptom improvement was reported by 82% of the patients and complete symptom resolution in 56%. For both the hepatobiliary iminodiacetic acid and fatty meal ultrasound, the sensitivity of the test to predict symptom improvement increased with higher EF, whereas the positive predictive values remained around 80%. Of the 41 patients who participated in phone interview for long-term follow-up, 85% reported symptom improvement and 44% reported complete symptom resolution. Factors associated with symptom improvement included a shorter duration of pain, a history of vomiting, and a history of epigastric pain. CONCLUSIONS: Despite not identifying an EF level that predicted symptom improvement, over 80% of patients undergoing cholecystectomy for biliary dyskinesia reported symptom improvement. These results support continuing to offer cholecystectomy to treat biliary dyskinesia in children.

Long-term Outcomes of Symptomatic Gallbladder Sludge.

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.

Long-term follow-up of non-operated patients with symptomatic gallbladder stones: a retrospective study evaluating the role of Hepatobiliary scanning.

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.

Vitamin-D Deficiency Is Associated with Gallbladder Stasis Among Pregnant Women.

BACKGROUND: Pregnant women are at increased risk of gallbladder (GB) stasis, an important risk factor for gallstones (GS). In non-pregnant women, Vitamin-D deficiency (VDD) is associated with GB stasis, which improves on supplementation. Relationship of VDD with GB stasis among pregnant women is not known. METHODS: This is a prospective study in tertiary care centre. Consecutive healthy pregnant women (12-16 weeks gestation) were enrolled. Serum 25(OH) vitamin-D was estimated, and levels <20 ng ml(-1) were considered as VDD. Risk factors and clinical features of VDD were assessed. Gallbladder ejection fraction (GBEF) was assessed by ultrasound after a standard fatty meal, and <40 % was defined as stasis. Statistical analysis was performed to assess relationship of GB stasis and vitamin-D levels and identify factors associated with VDD. KEY RESULTS: Median serum vitamin-D in 304 women was 7.9 ng ml(-1) (IQR 5.7, 12). VDD afflicted 92 % of them. Women with VDD more often had GB stasis (20 % vs 0 %; p = 0.015) and had lower GBEF [53.7 ± 17 % vs 59 ± 10 %; p = 0.026] compared to those with normal vitamin-D. GBEF showed positive correlation with vitamin-D levels (r = 0.117; p = 0.042). Risk factors for low vitamin-D levels were urban residence (p = 0.001), lower sun-exposure time (p = 0.005), limited skin exposure (p < 0.001), higher BMI (p = 0.05) and higher socioeconomic status (p = 0.02). Vitamin-D deficiency was associated with low serum calcium (ρ = 0.457; p < 0.001). CONCLUSIONS: Vitamin D deficiency is highly prevalent among pregnant Indian women. It is associated with GB stasis and lower GBEF. The risk factors for VDD were reduced sun exposure, inadequate dietary intake and urban lifestyle.