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Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity., (© 2019 World Obesity Federation.)

Context: Several cases of cholelithiasis and cholecystitis have been reported in patients treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) and GLP-2 receptor agonists (GLP-2RAs), respectively. Thus, the effects of GLP-1 and GLP-2 on gallbladder motility have been investigated. We have provided an overview of the mechanisms regulating gallbladder motility and highlight novel findings on the effects of bile acids and glucagon-like peptides on gallbladder motility., Evidence Acquisition: The articles included in the present review were identified using electronic literature searches. The search results were narrowed to data reporting the effects of bile acids and GLPs on gallbladder motility., Evidence Synthesis: Bile acids negate the effect of postprandial cholecystokinin-mediated gallbladder contraction. Two bile acid receptors seem to be involved in this feedback mechanism, the transmembrane Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor. Furthermore, activation of TGR5 in enteroendocrine L cells leads to release of GLP-1 and, possibly, GLP-2. Recent findings have pointed to the existence of a bile acid-TGR5-L cell-GLP-2 axis that serves to terminate meal-induced gallbladder contraction and thereby initiate gallbladder refilling. GLP-2 might play a dominant role in this axis by directly relaxing the gallbladder. Moreover, recent findings have suggested GLP-1RA treatment prolongs the refilling phase of the gallbladder., Conclusions: GLP-2 receptor activation in rodents acutely increases the volume of the gallbladder, which might explain the risk of gallbladder diseases associated with GLP-2RA treatment observed in humans. GLP-1RA-induced prolongation of human gallbladder refilling may explain the gallbladder events observed in GLP-1RA clinical trials., (Copyright © 2019 Endocrine Society.)

This study aimed to evaluate the association between cholelithiasis and sialolithiasis using a national sample cohort in Korea.The Korean National Health Insurance Service-National Sample Cohort (patients ≥20 years old) was collected from 2002 to 2013. In study I, we extracted cholelithiasis patients (n = 21,170) and 1:4 matched control I subjects (n = 84,680) and analyzed the occurrence of sialolithiasis. In study II, we extracted sialolithiasis patients (n = 761) and 1:4 matched control II subjects (n = 3044) and analyzed the occurrence of cholelithiasis. Hazard ratios (HRs) were determined using the stratified Cox proportional hazard model.The HR for sialolithiasis was 1.49 (95% CI = 0.88-2.52) in the cholelithiasis group (P = .14), and the HR for cholelithiasis was 1.18 (95% CI = 0.53-2.59) in the sialolithiasis group (P = .69).We did not find an association between cholelithiasis and sialolithiasis.

Cholelithiasis affects approximately 15% of the US population. Rising trends in obesity and metabolic syndrome have contributed to an increase in diagnosis of cholelithiasis. There are several risk factors for cholelithiasis, both modifiable and nonmodifiable. Women are more likely to experience cholelithiasis than are men. Pregnancy, increasing parity, and obesity during pregnancy further increase the risk that a woman will develop cholelithiasis. The classic presentation of persons experiencing cholelithiasis, specifically when gallstones obstruct the common bile duct, is right upper quadrant pain of the abdomen that is often elicited upon palpation during physical examination and documented as a positive Murphy's sign. Referred pain to the right supraclavicular region and/or shoulder, nausea, and vomiting are also frequently reported by persons with cholelithiasis. Cholelithiasis can result in complications, including cholecystitis (inflammation of the gallbladder) and cholangitis (inflammation of the bile duct). Lack of physical examination findings does not rule out a diagnosis of cholelithiasis. Laboratory tests such as white blood cell count, liver enzymes, amylase, and lipase may assist the clinician in diagnosing cholelithiasis; however, ultrasonography is the gold standard for diagnosis. Management is dependent on severity and frequency of symptoms. Lifestyle and dietary modifications combined with medication management, such as use of gallstone dissolution agents, may be recommended for persons who have a single symptomatic episode. If symptoms become severe and/or are recurrent, laparoscopic cholecystectomy is recommended. It is recommended that individuals with an established diagnosis of cholelithiasis be referred to a surgeon and/or gastroenterologist within 2 weeks of initial presentation regardless of severity or frequency of symptoms., (© 2019 by the American College of Nurse-Midwives.)

Background: In inflammatory bowel disease (IBD) patients there are reports of the occurrence of hepatobiliary manifestations, so the aim of this study was to evaluate the hepatobiliary manifestations in patients with Crohn's disease (CD) and ulcerative colitis (UC) from an IBD reference center., Methods: Cross-sectional study in an IBD reference center, with interviews and review of medical charts, between July 2015 and August 2016. A questionnaire addressing epidemiological and clinical characteristics was used., Results: We interviewed 306 patients, and the majority had UC (53.9%) and were female (61.8%). Hepatobiliary manifestations were observed in 60 (19.6%) patients with IBD. In the greater part of the patients (56.7%) hepatobiliary disorders were detected after the diagnosis of IBD. In UC (18.2%) patients, the hepatobiliary disorders identified were 11 (6.7%) non-alcoholic fatty liver disease, 9 (5.5%) cholelithiasis, 6 (3.6%) primary sclerosing cholangitis (PSC), 3 (1.8%) hepatotoxicity associated with azathioprine, 1 (0.6%) hepatitis B, and 1 (0.6%) hepatic fibrosis. In CD (21.3%) patients, 11 (7.8%) had cholelithiasis, 11 (7.8%) non-alcoholic fatty liver disease, 4 (2.8%) PSC, 3 (2.1%) hepatotoxicity, 1 (0.7%) hepatitis B, (0.7%) hepatitis C, 1 (0.7%) alcoholic liver disease, and 1 (0.7%) autoimmune hepatitis (AIH). There was one case of PSC/AIH overlap syndrome., Conclusion: The frequency of hepatobiliary disorders was similar in both forms of IBD in patients evaluated. The most common nonspecific hepatobiliary manifestations in IBD patients were non-alcoholic liver disease and cholelithiasis. The most common specific hepatobiliary disorder was PSC in patients with extensive UC or ileocolonic CD involvement; this was seen more frequently in male patients.

Introduction: A reduced number of interstitial Cajal-like cells (ICLCs) in the gallbladder have been proposed to play a role in the pathogenesis of cholelithiasis. Therefore, this prospective study was conducted to investigate the relationship between gallbladder contractility and the number of gallbladder ICLCs in patients with cholelithiasis., Material and Methods: Patients admitted to the Department of Hepatobiliary Surgery for cholecystectomy were divided into the cholelithiasis (n = 18) and non-cholelithiasis (n = 8) groups based on their clinical data. Patients' clinical data were collected on admission, and B-mode ultrasonography was performed to assess their gallbladder contractility. The resected gallbladder specimens were fixed, paraffin sections mounted on slides, and the immunofluorescence staining with the anti-human CD-117 and anti-human tryptase antibodies was performed to identify ICLSs and mast cells, respectively. The number of ICLCs was counted in 10 high-power fields (HPFs) randomly., Results: Independent sample t-tests revealed differences between the cholelithiasis and non-cholelithiasis groups in the number of ICLCs (mean ± standard deviation: 88.61 ± 28.22 vs. 115.89 ± 27.87 per HPFs, P = 0.032) and gallbladder contractility (43.94% ± 18.50% vs. 61.00% ± 20.50%, P = 0.046). Pearson and Spearman cor-relation analyses revealed no significant correlation between the number of ICLCs and gallbladder contractility., Conclusion: The results suggest that the number of gallbladder ICLCs in the wall of the gallbladder of patients with or without cholelithiasis is not a decisive factor affecting gallbladder contractility.

Background: Physical inactivity puts the populations at risk of several health problems, while regular physical activity brings beneficial effects on cardiovascular disease, mortality and other health outcomes, including obesity, glycaemic control and insulin resistance. The hepatobiliary tract is greatly involved in several metabolic aspects which include digestion and absorption of nutrients in concert with intestinal motility, bile acid secretion and flow across the enterohepatic circulation and intestinal microbiota. Several metabolic abnormalities, including nonalcoholic fatty liver as well as cholesterol cholelithiasis, represent two conditions explained by changes of the aforementioned pathways., Materials and Methods: This review defines different training modalities and discusses the effects of physical activity in two metabolic disorders, that is nonalcoholic fatty liver disease (NAFLD) and cholelithiasis. Emphasis is given to pathogenic mechanisms involving intestinal bile acids, microbiota and inflammatory status., Results: A full definition of physical activity includes the knowledge of aerobic and endurance exercise, metabolic equivalent tasks, duration, frequency and intensity, beneficial and harmful effects. Physical activity influences the hepatobiliary-gut axis at different levels and brings benefits to fat distribution, liver fat and gallbladder disease while interacting with bile acids as signalling molecules, intestinal microbiota and inflammatory changes in the body., Conclusions: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes., (© 2018 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Bariatric surgery predisposes patients to development of cholelithiasis, and therefore the need of a subsequent cholecystectomy; however, the incidence of cholecystectomy after bariatric surgery is debated., Objective: The purpose of our study is to assess the incidence of cholecystectomy after 3 of the most common bariatric procedures., Setting: University Hospital, involving a large database in New York State., Methods: The Statewide Planning and Research Cooperative System administrative longitudinal database was used to identify all patients undergoing Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and laparoscopic adjustable gastric banding (LAGB) between 2004 and 2010. Through the use of a unique identifier patients were followed to evaluate for the need of a subsequent cholecystectomy over at least 5 years. Cox proportional hazard regression analysis was used to identify risk factors for subsequent cholecystectomy., Results: During this time period, there were 15,301 LAGB procedures, 19,996 RYGB, and 1650 SG. There were 989 (6.5%) patients who underwent cholecystectomy after LAGB, 1931 (9.7%) patients after RYGB, and 167 (10.1%) after SG. Approximately one quarter of follow-up cholecystectomies were performed at the same institutions. LAGB and RYGB were less likely to have a subsequent cholecystectomy compared with SG (hazard ratio .5, 95% confidence interval .4-.6 for LAGB; and hazard ratio .7, 95% confidence interval .6-.9 for RYGB). Risk factors for a subsequent cholecystectomy included age, sex, race, and some co-morbidities and complications (P<.05) based on a multivariable Cox proportional hazard model., Conclusion: The rate of cholecystectomy after LAGB, RYGB, and SG was 6.5%, 9.7% and 10.1%, respectively. Patients should be counseled preoperatively about this risk and biliary prophylaxis should be contemplated., (Published by Elsevier Inc.)

Purpose of Review: Gallstone disease is a major epidemiologic and economic burden worldwide, and the most frequent form is cholesterol gallstone disease., Recent Findings: Major pathogenetic factors for cholesterol gallstones include a genetic background, hepatic hypersecretion of cholesterol, and supersaturated bile which give life to precipitating cholesterol crystals that accumulate and grow in a sluggish gallbladder. Additional factors include mucin and inflammatory changes in the gallbladder, slow intestinal motility, increased intestinal absorption of cholesterol, and altered gut microbiota. Mechanisms of disease are linked with insulin resistance, obesity, the metabolic syndrome, and type 2 diabetes. The role of nuclear receptors, signaling pathways, gut microbiota, and epigenome are being actively investigated., Summary: Ongoing research on cholesterol gallstone disease is intensively investigating several pathogenic mechanisms, associated metabolic disorders, new therapeutic approaches, and novel strategies for primary prevention, including lifestyles.

Purpose of Review: The establishment of mouse models of gallstones, and the contribution of mouse models to genetic studies of gallstone disease, as well as the latest advances in the pathophysiology of gallstones from mouse experiments are summarized., Recent Findings: The combined uses of genomic strategies and phenotypic studies in mice have successfully led to the identification of many Lith genes, which pave the way for the discovery of human LITH genes. The physical-chemical, genetic, and molecular biological studies of gallstone disease in mice with knockout or transgene of specific target genes have provided many novel insights into the complex pathophysiological mechanisms of this very common hepatobiliary disease worldwide, showing that interactions of five primary defects play a critical role in the pathogenesis of cholesterol gallstones. Based on mouse studies, a new concept has been proposed that hepatic hypersecretion of biliary cholesterol is induced by multiple Lith genes, with insulin resistance as part of the metabolic syndrome interacting with cholelithogenic environmental factors to cause the phenotype., Summary: The mouse model of gallstones is crucial for elucidating the physical-chemical and genetic mechanisms of cholesterol crystallization and gallstone formation, which greatly increase our understanding of the pathogenesis of this disease in humans.

Cholecystectomy has long been regarded as a safe procedure with no deleterious influence on the body. However, recent studies provide clues that link cholecystectomy to a high risk for metabolic syndrome (MetS). In the present review, we describe the epidemiologic evidence that links cholecystectomy to MetS. Various components of MetS are investigated, including visceral obesity, dyslipidemia, elevated blood pressure, impaired fasting glucose, and insulin resistance. The possible mechanisms that associate cholecystectomy with MetS are discussed on the basis of experimental studies.

We report a 3-month-old male with Down syndrome (DS), prolonged jaundice and poor weight gain, that showed biliary lithiasis and undiagnosed congenital hypothyroidism (CH).CH should be considered in DS, especially in presence of gastrointestinal symptoms or malformations. Clinicians should be aware of the increased risk of gallstones in hypothyroid children with DS, even in neonatal age.

Competing Interests: Competing interests: None

Competing Interests: Competing interests: Michel Kahaleh MD has received grant support from Boston Scientific, Fujinon, EMcison, Xlumena Inc., W.L. Gore, MaunaKea, Apollo Endosurgery, Cook Endoscopy, ASPIRE Bariatrics, GI Dynamics, NinePoint Medical, Merit Medical, Olympus and MI Tech. He is a consultant for Boston Scientific, Xlumena Inc., Concordia Laboratories Inc, ABBvie, and MaunaKea Tech. All other authors have no conflicts of interest to report.

Background: Cholesterol cholelithiasis is a multifactorial hepatobiliary disease., Methods: Interactions between genetic and environmental factors play a critical role in biliary cholesterol homeostasis and its imbalance enhances cholelithogenesis., Results: In patients developing symptoms or complications of gallstone disease, laparoscopic cholecystectomy is recommended for treatment of gallstones. In a subgroup of patients with small, radiolucent pure cholesterol gallstones, the hydrophilic bile acid, ursodeoxycholic acid (UDCA) is still considered the only pharmacological therapy able to induce oral litholysis. Identifying novel and effective pharmacological therapies is being investigated., Conclusions: We propose that the specific intestinal Niemann-Pick C1-like 1 protein inhibitor ezetimibe is a potential agent for preventing gallstone formation by reducing bioavailability of intestine- derived cholesterol to the liver for biliary secretion and desaturating bile through the inhibition of intestinal absorption of cholesterol., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

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.

Background: Bile duct microenvironment plays several key roles in cholangiolithiasis occurrence. Sphincter of Oddi laxity (SOL) is associated with cholangiolithiasis, probably due to enhanced reflux of intestinal contents that changes the microenvironment. However, the microenvironment has not been investigated comprehensively., Study Design: Patients with cholangiolithiasis were consecutively recruited and their bile was collected intraoperatively for high-throughput experiments. Pyrosequencing of 16S ribosomal RNA gene was performed to characterize the microbiota in the bile. A liquid chromatography mass spectrometry-based method was used to profile bile composition. Clinical manifestation, microbiome, and bile composition were compared between patients with and without SOL., Results: Eighteen patients with SOL and 27 patients without SOL were finally included. Patients with SOL showed more severe inflammation. Bacteria in the bile duct were overwhelmingly aerobes and facultative anaerobes. Proteobacteria and Firmicutes were the most widespread phylotypes, especially Enterobacteriaceae. Compared with those without SOL, patients with SOL possessed more varied microbiota. In the SOL group, pathobionts, such as Bilophila and Shewanella algae had richer communities, and harmless bacteria were reduced. Metabolomics analysis showed the differences in bile composition between groups were mainly distributed in lipids and bile acids. Particularly, the increased abundance of Bilophila involved in taurine metabolism was associated with reduced contents of taurine derivatives in the bile of patients with SOL., Conclusions: A bile duct microenvironment with more severe bacterial infection and stronger lithogenicity was found in patients with SOL. The findings suggest a possible mechanism of cholangiolithiasis and provide the basis for future strategies for prevention of cholangiolithiasis recurrence., (Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Liraglutide is a glucagon-like peptide-1 analog and recently started to be using as an incretin-based treatment for diabetes mellitus. Liraglutide causes some adverse affects including nausea, vomiting, acute nasopharyngitis and acute pancreatitis. However, development of liraglutide-dependent cholelithiasis has not been reported in the literature. A 75-year-old female patient had been diagnosed with type 2 diabetes mellitus for 10 years and she has been treated by liraglutide for 6 months. The patient was admitted to the emergency service due to sudden onset of abdominal pain. After laboratory and imaging studies, she was diagnosed with acute cholecystitis and cholelithiasis. And then patient's oral intake was stopped, intravenous fluid and ceftriaxone 2 g/day were started. Furthermore, liraglutide treatment discontinued and ursodeoxycholic acid (UDCA) was started to treat cholelithiasis. During follow-up, abdominal pain completely relieved. Hepatobiliary ultrasonography in sixth month follow-up showed entirely regression of cholelithiasis. Any liraglutide-related cholelithiasis case has not been reported in the literature previously. Therefore, our case is the first case. Especially, elderly diabetic patients who are started to liraglutide treatment should be monitored closely for the formation of cholelithiasis. UDCA treatment would be an alternative prior to surgical treatment for liraglutide-related cholelithiasis.

Objective: The aim of this study was to investigate the daily energy expenditure; resting metabolic rate (RMR); health-related physical fitness parameters such as maximal aerobic capacity, muscle strength, and flexibility; pulmonary function tests (PFTs); and body composition and body fat distribution changes in patients with cholelithiasis, and to compare them with healthy controls., Materials and Methods: Thirty female patients with cholelithiasis and 30 controls were included in this study. Daily physical activity was monitored using a metabolic Holter and the maximal aerobic capacity was estimated using the Astrand submaximal exercise protocol. The body composition was established with a bioelectrical impedance analyzer. RMR, PFTs, strength, flexibility, circumference, and skinfold measurements were also carried out., Results: Maximal aerobic capacity, trunk flexibility, daily moderate activity duration, daily vigorous activity duration, total energy expenditure, RMR, PFT, lean body mass, adiposity, and body fat distribution values were not significantly different between the patients and the controls. The cholelithiasis patients had lower daily step numbers, handgrip strength, and back-leg strength values, whereas their higher daily sleep duration values were comparable with those of the controls., Conclusion: Our results suggest that daily physical activity and muscle strength were impaired in female cholelithiasis patients when compared with the healthy controls. We suggest that using daily exercises, including not only aerobic but also strength training as lifestyle modifications in cholelithiasis patients, might be helpful for the development of more beneficial illness management strategies.

Introduction: The ketogenic diet is a treatment modality used for patients with refractory epilepsy. Development of cholelithiasis while on the ketogenic diet is a potential side effect that has been described in the literature. There however have not been any reports on the outcomes of continuing the diet after cholecystectomy., Patient: We present a 5-year-old boy with history of pharmacologically intractable epilepsy that was well controlled on the ketogenic diet. He underwent laparoscopic cholecystectomy for the development of symptomatic cholelithiasis 12 months after the initiation of ketogenic diet for seizure control., Results: Patient tolerated the surgery well and was able to continue the ketogenic diet postoperatively., Discussion: There have been no reports describing the continuation of ketogenic diet after cholecystectomy. This child demonstrates the safety of the procedure and the ability to continue the ketogenic diet without further biliary or surgical complications., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Statins can modify bile cholesterol and, thus, the formation of gallstones. We examined whether statin use also modifies the severity of symptomatic gallstone disease and its treatment., Methods: A total of 1,140 consecutive patients with symptomatic gallstone disease were recruited during 2008-2010 at Kuopio university hospital, Finland. Case-control analysis matched the patients using (n = 272) or not using (n = 272) statins by age and sex. The baseline characteristics of the patients, need and type of surgical treatment, duration of operation, perioperative bleeding, postoperative complications and overall mortality rate were compared statistically between the study groups., Results: Morbidity and subsequent polypharmacy occurred more frequently among the patients with statins compared to the patients without statins. There were no significant differences between the statin users and non-users regarding surgical treatment (open vs. laparoscopic cholecystectomy). The mean operation time for laparoscopic cholecystectomy was 10% shorter for the patients with statin use than for the patients without. In addition, there was a non-significant tendency for statin users to bleed less during laparoscopic operations than the non-users. There were no differences in other procedure-related parameters (e.g., operation urgency, conversions, choledochotomies, complications and mortality) in patients with or without statins., Conclusions: Compared to no treatment, statin treatment was associated with a shorter operation time for laparoscopy cholecystectomy. Other surgical outcome parameters were similar in patients with or without statins, although statin users had more polypharmacy and circulatory illnesses than non-users.

Introduction: Gallstone ileus is an uncommon disease and accounts for 1-4 % of all cases of mechanical intestinal obstruction. The physiopathology is related to the presence of a bilioenteric fistula., Method: We report two cases of gallstone ileus in patients operated on biliointestinal bypass for morbid obesity. The anastomosis of the gallbladder to the proximal end of the bypassed jejunum allowed the transit of gallstones in the excluded ileum and its impaction in anti-reflux valvular system., Results: Preoperative exams were unable to solve the diagnostic query, and the diagnosis was achieved only at laparotomy. One-stage combined enterolithotomy and cholecystectomy were performed., Conclusion: The two patients had an uneventful recovery. To our knowledge, this is the first report of gallstone ileus after biliointestinal bypass.

Unlabelled: BACKGROUND; Decreased gallbladder smooth muscle (GBSM) contractility is a hallmark of cholesterol gallstone disease, but the interrelationship between lithogenicity, biliary stasis, and inflammation are poorly understood. We studied a mouse model of gallstone disease to evaluate the development of GBSM dysfunction relative to changes in bile composition and the onset of sterile cholecystitis., Methods: BALB/cJ mice were fed a lithogenic diet for up to 8 weeks, and tension generated by gallbladder muscle strips was measured. Smooth muscle Ca(2+) transients were imaged in intact gallbladder., Key Results: Lipid composition of bile was altered lithogenically as early as 1 week, with increased hydrophobicity and cholesterol saturation indexes; however, inflammation was not detectable until the fourth week. Agonist-induced contractility was reduced from weeks 2 through 8. GBSM normally exhibits rhythmic synchronized Ca(2+) flashes, and their frequency is increased by carbachol (3 μm). After 1 week, lithogenic diet-fed mice exhibited disrupted Ca(2+) flash activity, manifesting as clustered flashes, asynchronous flashes, or prolonged quiescent periods. These changes could lead to a depletion of intracellular Ca(2+) stores, which are required for agonist-induced contraction, and diminished basal tone of the organ. Responsiveness of Ca(2+) transients to carbachol was reduced in mice on the lithogenic diet, particularly after 4-8 weeks, concomitant with appearance of mucosal inflammatory changes., Conclusions & Inferences: These observations demonstrate that GBSM dysfunction is an early event in the progression of cholesterol gallstone disease and that it precedes mucosal inflammation., (© 2012 Blackwell Publishing Ltd.)

Objectives: This study aimed to identify the prevalences of and risk factors associated with the development of gallbladder stones and polyps in a large Chinese population., Methods: Prevalences of and risk factors for biliary stones and gallbladder polyps were retrospectively investigated among subjects who underwent a general check-up at the Health Screening Centres of Peking Union Medical College Hospital and Beijing Charity Hospital between January 2007 and June 2010., Results: A total of 60,064 people were enrolled in the study. Overall prevalences of biliary stones and gallbladder polyps were 4.2% (n= 2527) and 6.9% (n= 4119), respectively. Risk factors associated with increased odds ratios (ORs) for the development of biliary stones were female gender (OR = 1.51), age ≥ 50 years (OR = 2.09), history of hypertension (OR = 1.37), thickened gallbladder wall (cholecystitis) (OR = 1.98), fasting blood glucose ≥ 6.10 mmol/l (OR = 1.27), body mass index ≥ 25 kg/m(2) (OR = 1.25), systolic blood pressure ≥ 140 mmHg (OR = 1.31) and diastolic blood pressure ≥ 90 mmHg (OR = 1.44). Factors associated with gallbladder polyps were female gender (OR = 0.66), thickened gallbladder wall (OR = 2.09), negativity for hepatitis B surface antigen (HBsAg) and positivity for hepatitis B core antibody (anti-HBc) (OR = 2.61), and positivity for both HBsAg and anti-HBc (OR = 3.21)., Conclusions:   Prevalences of biliary stones and gallbladder polyps among Chinese people are similar to those reported for other populations. Biliary stones appear to be associated with female gender, age, obesity, blood glucose, blood pressure and cholecystitis. Male gender, hepatitis B virus infection and cholecystitis were strong risk factors for the formation of gallbladder polyps., (© 2012 International Hepato-Pancreato-Biliary Association.)

Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Purpose: The objective of this study was to investigate the association of quality-of-life status with baseline laboratory findings among Taiwanese adults having symptomatic gallstone disease., Methods: A prospective quality-of-life survey was administered at a tertiary referral medical center among 102 consecutive adults with symptomatic gallstone disease. Patients underwent regular laboratory testing at admission and were evaluated using the 36-Item Short-Form Health Survey (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI). Correlation and regression models were used to investigate quality-of-life predictors., Results: Compared with the general Taiwanese adult population, patients having symptomatic gallstone disease had significantly poorer performance on all eight SF-36 subscales (P < 0.001). Total GIQLI showed moderate to strong correlation with all eight SF-36 subscale scores (gamma = 0.29 ~ 0.62, P < 0.05). In multivariate analysis, serum levels of direct bilirubin (beta = -32.6, P = 0.001) and alkaline phosphatase (beta = -13.6, P = 0.032) were predictive of worse total GIQLI (adjusted R (2) = 0.183)., Conclusions: Symptomatic gallstone disease may considerably affect patient quality of life in terms of general health status and gastrointestinal-specific measures. Before gallstone surgery, serum levels of direct bilirubin and alkaline phosphatase significantly correlated with quality-of-life measures and can be used to evaluate patient well-being at admission.

Gallstones are frequent in patients with cystic fibrosis (CF). These stones are generally "black" pigment (i.e., Ca bilirubinate) with an appreciable cholesterol admixture. The pathophysiology and molecular mechanisms for this "mixed" gallstone in CF are unknown. Here we investigate in a CF mouse model with no overt liver or gallbladder disease whether pathophysiological changes in the physical chemistry of gallbladder bile might predict the occurrence of "mixed" cholelithiasis. Employing a DeltaF508 mouse model with documented increased fecal bile acid loss and induced enterohepatic cycling of bilirubin (Am J Physiol Gastrointest Liver Physiol 294: G1411-G1420, 2008), we assessed gallbladder bile chemistry, morphology, and microscopy in CF and wild-type mice, with focus on the concentrations and compositions of the common biliary lipids, bilirubins, Ca(2+), and pH. Our results demonstrate that gallbladder bile of CF mice contains significantly higher levels of all bilirubin conjugates and unconjugated bilirubin with lower gallbladder bile pH values. Significant elevations in Ca bilirubinate ion products in bile of CF mice increase the likelihood of supersaturating bile and forming black pigment gallstones. The risk of potential pigment cholelithogenesis is coupled with higher cholesterol saturations and bile salt hydrophobicity indexes, consistent with a proclivity to cholesterol phase separation during pigment gallstone formation. This is an initial step toward unraveling the molecular basis of CF gallstone disease and constitutes a framework for investigating animal models of CF with more severe biliary disease, as well as the human disease.

Juxtapapillary duodenal diverticula (JPD) are observed in around 10-20% of patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). They are acquired extraluminal outpouchings of the duodenal wall through 'locus minoris resistance' and their incidence increases with age. They have been studied mainly with regard to their association with pancreatobiliary disease. Choledocholithiasis is considered to be strongly associated with JPD, but the role of JPD in the development of cholecystolithiasis and pancreatitis is still disputable. Since JPD are located in the vicinity of the papilla of Vater, they not only cause mechanical compression of the bile duct but also induce dysfunction of the sphincter of Oddi. They are considered to lead to bile stasis and to allow reflux from the duodenum into the bile duct, which results in an ascending infection of beta-glucuronidase-producing bacteria. The ERCP procedure can be hampered by JPD, although recent papers have reported no difference in the successful cannulation rate or complications between patients with JPD and those without JPD. Disorders caused by JPD are amenable to appropriate therapy, e.g. endoscopic sphincterotomy and surgical intervention., ((c) 2010 S. Karger AG, Basel.)

Introduction: We used ultrasonography to detect the presence of biliary sludge or gallstones in Greek patients with complete high spinal cord injury (SCI) above the seventh thoracic segment (T7), within the first six months from injury onset, in order to evaluate the effects of neurological instability and dysfunction of the sympathetic nervous system (SNS) on the gallbladder function in the early post-SCI phase., Methods: We evaluated 78 asymptomatic patients (57 males, 21 females; mean age 34.8 (range 19-56) years) with complete high SCI located above the T7 segment, and 78 healthy subjects (59 males, 19 females; mean age 35.2 (range 21-59) years) matched for age, gender and race, for a total period of 39 months. All the participants underwent ultrasonographical examination of the gallbladder and common bile duct within the first six months from the injury, in order to investigate the development of biliary sludge and gallstones., Results: The incidence of biliary sludge was significantly higher in patients with SCI compared with the control group. The incidence of biliary sludge and gallstones was also significantly higher in patients with SCI patients in comparison with the healthy subjects. In male SCI patients, the incidence of biliary sludge was significantly increased in comparison with healthy subjects. No significant difference was revealed between the two groups in detection of gallstones., Conclusion: Our study indicates that the detection of gallbladder sludge and gallstones are significantly higher in Greek patients with complete high SCI above the T7 segment, as compared with healthy control subjects within the first six months of the injury onset. The complete disruption of the SNS and the neurological instability in the early post-SCI phase is probably responsible for the biliary sludge and gallstone formation. Our results suggest that ultrasonography should be performed in these patients at the first 3-6 months from the injury for the early diagnosis of the lithogenic bile.

Aim: To investigate acute transient hepatocellular injury in patients with cholelithiasis and cholecystitis but no evidence of choledocholithiasis., Methods: The medical records of patients with cholelithiasis who underwent cholecystectomy between July 2003 and June 2007 were retrospectively reviewed. Imaging studies to detect common bile duct (CBD) stones were performed in 186 patients, who constituted the study population. Biochemical liver tests before and after surgery, and with the presence or absence of CBD stones were analyzed., Results: In 96 patients with cholelithiasis and cholecystitis without evidence of CBD stones, 49 (51.0%) had an alanine aminotransferase level elevated to 2-3 times the upper limit of normal, and 40 (41.2%) had an elevated aspartate aminotransferase level. Similar manifestations of hepatocellular injury were, as would be expected, even more obvious in the 90 patients with CBD stones. These markers of hepatocellular injury resolved almost completely within 2 wk to 1 mo after cholecystectomy. Compared to 59 patients with histologically less severe cholecystitis in the group undergoing urgent surgery (total 74 patients), the 15 patients with a gangrenous gallbladder had a higher mean level of total bilirubin (1.14 +/- 1.27 mg/dL vs 2.66 +/- 1.97 mg/dL, P < 0.001) and white cell count (9480 +/- 4681/microL vs 12840 +/- 5273/microL, P = 0.018)., Conclusion: Acute hepatocellular injury in cholelithiasis and cholecystitis without choledocholithiasis is mild and transient. Hyperbilirubinemia and leukocytosis may predict severe inflammatory changes in the gallbladder.

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: Rapid weight loss increases risk for gallstone formation. Prophylactic cholecystectomy is difficult. Several small trials have shown that ursodeoxycholic acid (UDCA) may prevent gallstone formation after bariatric surgery. The aim of this study is to assess the efficacy and safety of UDCA in the prevention of gallstone formation after bariatric surgery., Methods: Electronic databases, including the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Australasian Medical Index, LILACS, and HERDIN, were searched. Reference lists of trials selected by the above electronic searching were also searched. Authors of the retrieved trials and pharmaceutical companies were also contacted for other trials, published and unpublished. A meta-analysis of all randomized, double-blind, placebo-controlled prospective trials comparing UDCA and placebo was performed., Results: Five RCTs including 521 patients were assessed. Random effects meta-analysis showed a significant reduction of gallstone formation (RR 0.43, 95% confidence interval 0.22-0.83), with 8.8% of those taking UDCA developing gallstones compared to 27.7% for placebo. Although this meta-analysis is heterogeneous with I(2) of 61.9%, the directions of the effect are all consistently in favor of UDCA (p=0.01). A meta-analysis on the adverse effects could not be performed because the studies did not report them in a way to make the analysis possible., Conclusions: UDCA can prevent gallstone formation after bariatric surgery.

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.

This study aimed to examine the effects of differing intra-abdominal pressures on pulmonary function test results in laparoscopic cholecystectomy. Forty-five patients were operated on under 3 different intra-abdominal pressures: group A (8 mm Hg), group B (12 mm Hg), and group C (15 mm Hg). On the first day before and after the operation, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC rate, peak expiratory flow speed (PEF), and maximal middle expiration speed (FEF25-75) values were measured using Vmax 229 spirometry. No significant differences were observed among the 3 groups regarding preoperative and postoperative FVC, FEV1, FEV1/FVC, PEF, and FEF25-75 values (P=0.96, P=0.73, P=0.48, P=0.34, and P=0.33, respectively). When the groups' preoperative and postoperative values were compared, FVC, FEV1, and PEF values significantly decreased in each group. The FEF25-75 values statistically significantly decreased in groups B and C when compared with their preoperative values; however, the decrease in group A was not significant. In conclusion, different intra-abdominal pressures during laparoscopic cholecystectomy had similar effects on pulmonary function test results. However, lower intra-abdominal pressures were associated with slightly more negative effects on FEF25-75 values.

Background and Aim: To examine associations between lifestyle risk factors and intrahepatic stone (IHS), we conducted a case-control study in Taiwan, which has the highest incidence of IHS in the world., Methods: Study subjects were 151 patients newly diagnosed with IHS at Chang Gung Memorial Hospital between January 1999 and December 2001. Two control subjects per case were selected randomly from patients who underwent minor surgery at the same hospital and from family members or neighbors of the hospital staff. Controls were matched to each case by age and gender. Information on lifestyle factors was collected using a self-administered questionnaire. Strength of associations was assessed using odds ratios derived from conditional logistic models., Results: Female patients were significantly shorter than female controls. Compared to subjects with two or fewer children, odds ratios for those with six or more children were 20.4 in men (95% confidence interval, 1.89-221) and 2.82 (0.97-8.22) in women. Increasing level of education lowered the risk of intrahepatic stone (trend P = 0.004 for men and < 0.0001 for women). Women who had consumed ground-surface water for a long period had a somewhat increased risk (trend P = 0.05)., Conclusion: Lower socioeconomic status and poor hygiene may be involved in the development of intrahepatic stones.

Background & Aims: Cholesterol cholelithiasis is one of the most prevalent and most costly digestive diseases in developed countries and its incidence has increased markedly in Asian countries owing to the adoption of Western-type dietary habits. Because animal experiments showed that high efficiency of intestinal cholesterol absorption contributes to gallstone formation, we explored whether the potent cholesterol absorption inhibitor ezetimibe could prevent gallstones and promote gallstone dissolution in mice and reduce biliary cholesterol content in human beings., Methods: Male gallstone-susceptible C57L mice were fed a lithogenic diet and concomitantly administered with ezetimibe at 0, 0.8, 4, or 8 mg/kg/day for 8 or 12 weeks. Gallbladder biles and gallstones were examined by microscopy. Gallbladder emptying in response to cholecystokinin octapeptide was measured gravimetrically. Biliary lipid outputs were analyzed by physical-chemical methods. Cholesterol absorption efficiency was determined by fecal dual-isotope ratio and mass balance methods. Lipid changes in gallbladder biles of gallstone patients vs overweight subjects without gallstones were examined before (day 0) and at 30 days after ezetimibe treatment (20 mg/day)., Results: Ezetimibe prevented gallstones by effectively reducing intestinal cholesterol absorption and biliary cholesterol secretion, and protected gallbladder motility function by desaturating bile in mice. Treatment with ezetimibe promoted the dissolution of gallstones by forming an abundance of unsaturated micelles. Furthermore, ezetimibe significantly reduced biliary cholesterol saturation and retarded cholesterol crystallization in biles of patients with gallstones., Conclusions: Ezetimibe is a novel approach to reduce biliary cholesterol content and a promising strategy for preventing or treating cholesterol gallstones by inhibiting intestinal cholesterol absorption.

Background: It has been noted that following a laparoscopic cholecystectomy (LC), liver function parameters were disturbed. The causes of this disturbance are still controversial., Patients and Methods: The serum levels of eight parameters of liver function were measured both before and 24 hours after surgery in 142 consecutive patients who underwent LC, 23 patients who underwent open cholecystectomy (OC), and in 25 patients who underwent a conventional hernial repair. The same anesthetic protocol was applied to all patients in the various groups and in the case of LC; the intra-abdominal pressure was maintained at 12 mmHg of CO2., Results: Twenty-four (24) hours after surgery, there was a statistically significant change of all the eight parameters studied, except alkaline phosphatase in patients who underwent LC, whereas there were only 3 patients from the OC group who had changes of alanine aminotransferase and aspartite aminotransferase and 2 patients who had raised levels of direct bilirubin, and no changes were observed among those who had conventional hernial repair. We found that 83% of the patients showed more than a 100% increase in at least one parameter, 43% showed an increase in two or more parameters, and 23% showed an increase in three or more parameters. We also observed a significant drop of total proteins and albumin levels in all patients who had LC., Conclusions: It appears that the pneumoperitoneum plays a major role in these changes. Although these changes of liver function were of no clinical relevance in healthy patients, the safety of the procedure must nonetheless be assessed in those with underlying liver diseases.

Asymptomatic cholelithiasis is increasingly diagnosed today, mainly as a result of the widespread use of abdominal ultrasonography for the evaluation of patients for unrelated or vague abdominal complaints. About 10-20% of people in most western countries have gallstones, and among them 50-70% are asymptomatic at the time of diagnosis. Asymptomatic gallstone disease has a benign natural course; the progression of asymptomatic to symptomatic disease is relatively low, ranging from 10-25%. The majority of patients rarely develop gallstone-related complications without first having at least one episode of biliary pain ("colic"). In the prelaparoscopy era, (open) cholecystectomy was generally performed for symptomatic disease. The minimally invasive laparoscopic cholecystectomy refueled the discussion about the optimal management of asymptomatic cholelithiasis. Despite some controversy, most authors agree that the vast majority of subjects should be managed by observation alone (expectant management). Selective cholecystectomy is indicated in defined subgroups of subjects, with an increased risk for the development of gallstone-related symptoms and complications. Concomitant cholecystectomy is a reasonable option for good-risk patients with asymptomatic cholelithiasis undergoing abdominal surgery for unrelated conditions. Routine cholecystectomy for all subjects with silent gallstones is a too aggressive management option, not indicated for most subjects with asymptomatic cholelithiasis. An in-depth knowledge of the natural history of gallstone disease is required to select the optimal management option for the individual subject with silent gallstones. Management options should be extensively discussed with the patient; he or she should be actively involved in the process of therapeutic decision making.

Bariatric surgery is an effective treatment for patients with clinically severe obesity. In addition to significant weight loss, it is also associated with improvements in comorbidities. Unfortunately, bariatric surgery also has the potential to cause a variety of nutritional and metabolic complications. These complications are mostly due to the extensive surgically induced anatomical changes incurred by the patient's gastrointestinal tract, particularly with roux-en-Y gastric bypass and biliopancreatic diversion. Complications associated with vertical banded gastroplasty are mostly due to decreased intake amounts of specific nutrients. Macronutrient deficiencies can include severe protein-calorie malnutrition and fat malabsorption. The most common micronutrient deficiencies are of vitamin B12, iron, calcium, and vitamin D. Other micronutrient deficiencies that can lead to serious complications include thiamine, folate, and the fat-soluble vitamins. Counseling, monitoring, and nutrient and mineral supplementation are essential for the treatment and prevention of nutritional and metabolic complications after bariatric surgery.

Cholelithiasis is the most common form of benign gallbladder disease that results in major heath expenditure. Female sex hormones are causally related to cholesterol gallstone disease, which are more common in women than in men. The risk of development of cholelithiasis is further enhanced by the use of exogenous female sex hormones and by pregnancy. Oestrogens are used in oral contraceptives and in hormone replacement therapy (HRT). Oral contraceptives do not pose a greater risk for gallbladder disease. The findings from two randomised, controlled trials, the Heart and Oestrogen/Progestin Replacement Study and the Women's Health Initiative postmenopausal hormone trial, unequivocally confirm that oral oestrogen use in postmenopausal women is causally associated with gallbladder disease, and the magnitude of the effect is not influenced greatly by the presence or absence of progestins. A cautious approach should be observed when prescribing HRT. Women must be informed about the effect of oestrogen use on increased risk of benign gallbladder disease. HRT should be used in the lowest possible dose for the shortest possible time. Women harbouring asymptomatic gallstones should not receive oestrogens because of the possibility of developing cholecystitis.

'Sludge' is the solid material which results from the slow settling of particles dispersed in a liquid medium. Biliary sludge in the gallbladder can be detected by transabdominal ultrasonography, and the typical echoes derive mainly from pigment precipitates mixed with cholesterol crystals. A portion of biliary sludge contains comparatively large particles (1-3 mm) called microliths, the formation of which is an obligatory intermediate step in the development of all types of gallstone. Microlithiasis and sludge in bile may cause colicky pain, cholecystitis, cholangitis, and acute pancreatitis, and are thus of clinical relevance. In these patients treatment follows the guidelines of symptomatic gallstone disease, and strategies include long-term application of ursodeoxycholic acid, endoscopic papillotomy, or preferably laparoscopic cholecystectomy.

The clinical and laboratory indices of cholelithiasis in adult Nigerians with homozygous sickle-cell disease (SCD) were studied in 100 consecutive patients attending the adult SS clinic of the University of Ilorin Teaching Hospital, Ilorin, Nigeria. The study examined the role of clinical (sickle cell (SS) crises, body mass indices [BMIs]), haematological (reticulocyte count, haemoglobin) and biochemical (serum bilirubin, serum alkaline phosphatase and serum amino transaminases) indices in predicting the likelihood of finding cholelithiasis in patients with SS anaemia. A positive correlation was found between the BMI, SS crises, reticulocyte count, serum bilirubin, serum alanine and asparate transferases on one hand and the development of cholelithiasis (at P values of 0.04, 0.03, 0.05, 0.01 and 0.04, respectively) on the other. No such association was found between the other indices studied and cholelithiasis.

Cholelithiasis is one of the most prevalent gastroenterological diseases, imposing a huge economic burden on health-care systems. Gallbladder stones form when the concentration of cholesterol or bilirubin exceeds the solubility in the bile salt and phospholipid-rich bile. The physiology of biliary lipid secretion by a number of specialized transport proteins has recently been elucidated, and underlying genetic defects in these proteins have been identified as susceptibility factors for gallstone disease. Recent studies of identical twins and family strongly support the idea of a genetic component to gallstone disease. Epidemiological studies in high-risk populations indicate that gallstone formation is caused by multiple environmental influences and common genetic factors and their interactions. Monogenic subtypes of cholelithiasis, such as biliary lipid transporter deficiencies, appear to be rare. The characterization of lithogenic genes in knockout and transgenic mice, and the identification of many gallstone susceptibility loci in inbred mice, provide the basis for studies of the corresponding genes in patients with gallstones. The transfer of findings from mouse genetics to the bedside might lead to new strategies for individual risk assessment and reveal molecular targets for the development of new treatment strategies.

Objective: To determine the proportion and timing for suspecting the diagnosis of gall bladder carcinoma in patients undergoing cholecystectomy for cholelithiasis., Methods: A retrospective study conducted at the Aga Khan University Hospital, Karachi over a period of six years, included medical records of patients, with cholecystectomy for cholelithiasis and a histopathological diagnosis of gall bladder carcinoma. An extensive review was done with special reference to the features of suspected or unsuspected gall bladder carcinoma. Timing of suspicion was categorized on the basis of clinical features, investigations, operative and histopathological findings., Results: Out of 1396 cholecystectomies performed during the period of study, sixteen patients (1.15%) were diagnosed as gall bladder carcinoma. Only three patients had pre-operative ultrasonographic features to raise suspicion for gall bladder malignancy whereas eight patients were suspected to have a malignant lesion, on the operative findings. Five patients were missed and the diagnosis was established after histopathological examination., Conclusion: The ultrasonography can miss a significant number of malignant lesions of the gall bladder and every cholecystectomy specimen should be examined histologically.

Aim: To investigate those associations using data of the population-based Study of Health in Pomerania., Methods: A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis., Results: There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L). The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; P<0.05). Also among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified., Conclusion: There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.