Gallstone Formation Research Articles

Risk Factors Associated with Cholelithiasis during Pregnancy and Postpartum

Gallbladder disease is the most common non-obstetrical cause of maternal hospitalization in the first year postpartum. Many risk factors have been associated with gallbladder disease in pregnancy including body mass index, prenatal weight gain, prenatal physical activity, dietary fat, age, parity, a history of gallbladder disease and the number of previous pregnancies were significant factors related to new gallstones and biliary sludge formation in the pregnant group. The aim of this study is to evaluate the risk factors for gallstones formation in pregnancy and one year after labour. The study included 328 female patients (pregnant or postpartum) divided into two groups; patient group (164 patient) that are pregnant or postpartum patient have gallstones and control group (164 patient) that are pregnant or postpartum patient does not have gallstones. All patients were subjected to full history taking; especially about risk factors predisposing for gallstones, physical examination and pre-operative routine laboratory investigations and imaging as abdominal ultrasound study (U/S). Obesity, young age, history of gallbladder disease and use of estrogen and progesterone are the main risk factors that increase incidence of gallstones during pregnancy or one year postpartum. Use of vit C, iron, drinking coffee and practicing regular physical activity are considered protective factors.

Stimulation Of Neutrophil Oxidative Burst By Calcium Phosphate Particles With Adsorbed Mucin

Objective — Mucin can promote formation of gallstones via precipitation with calcium phosphate. The proinflammatory effect of mucin-coated particles is still unclear, and our aim was to study the role of mucin sorption in activation of neutrophil respiratory burst. Material and Methods — Polydisperse calcium phosphate nanowires (CP) were prepared from hot gelatin solution and according to scanning electron microscopy (SEM) had the length 1-10 μm and thickness 50-450 nm. CP were incubated in mucin or human serum albumin (HSA) giving CP-Muc and CP-HSA. Their hemolytic activity towards human erythrocytes was assayed, and neutrophil lucigenin- and luminol- chemiluminescence (Luc-CL and Lum-CL) response to CP, CP-HSA and CP-Muc was measured. Cytokine RNA was detected in neutrophils by means of reverse transcription with subsequent real-time PCR. Cytokines (IL-1β, IL-6, IL-8, IL-10) were assessed in cell medium by ELISA. Results and Conclusion — Hemolytic activity of CP was 3.0±0.5%, mucin sorption (0.019 mg/mg) reduced it to 0.24±0.04% (p<0.05) as well as HSA. CP and CP-HSA stimulated neutrophil Lum-CL and Luc-Cl by 2-3 times vs. spontaneous values while for CP-Muc the effect was 10-fold and higher. No increased cytokine gene expression or cytokine secretion was detected after 1h incubation of neutrophils with samples. Obviously, sorption of mucin but not that of HSA stimulated generation of reactive oxygen and halogen species with no increase in cytokine production. Thus, the mucin-coated CP has the potential to contribute to gallstone-associated cholecystitis via oxidative damage of mucosa and epithelium.

Prevalence of undiagnosed hypothyroidism in patients with gall bladder stones in Belagavi

Background: Contribution of hypothyroidism to gallstone formation is debated over years. With this background, the study intended to analyze the prevalence of undiagnosed hypothyroidism in patients with cholelithiasis. The aim is to understand the prevalence of hypothyroidism in patients with gallstones.Methods: A prospective, hospital-based study was done on 100 patients admitted for the management of gall stone disease in Belagavi. After initial screening, a detailed history was obtained with special reference to symptomatology and the risk factors as per proforma from patients meeting selection criteria. Thyroid function test was done on all eligible patients. Patients were divided into three groups of Euthyroid, Subclinical hypothyroid and clinical hypothyroidism. Statistical analysis used. Percentage of gall stones in different age groups and gender of the study population was calculated followed by prevalence of hypothyroidism and subclinical hypothyroidism in all the patients included.Results: Among the study population, 40% were male and 60% were female. 23 of them have subclinical hypothyroidism and 6 of them were diagnosed with hypothyroidism. Majority of subclinical hypothyroid patients (39.13%) were aged 41-60 years. Hypothyroid symptoms were shown by the study population with unknown thyroid status.Conclusions: The prevalence of hypothyroidism in cholelithiasis is 29% in the study and is significant. The study demands further studies to consider hypothyroidism as a cause /risk factor for biliary calculus.

A Study of Gallstones Disease incidence in Babylon's Province population

Background :There are multiple disorders affecting the biliary system . Malignancies,congenital anomalies, dysfunctional disorders, infections, strictures and gallstones formation are some of the spectrum of diseases affecting the biliary system. Yet, gallstones formation with its associated complications is a commonest disorder occupying the top in the spectrum of the biliary system diseases. Objectives :This study tries to assess and analyse the incidence of gallstones disease in Babylon's Province population. It also attempts to identify and evaluate the predisposing risk factors associated with this disease. Comparison of local results with those from other parts of the world had been reviewed and investigated. Methods :Medical records of (257) patients who underwent laparoscopic and/or open cholecystectomy for their symptomatic gallstones proved by abdominal ultrasonography and/or computer assisted tomography over a period of three years in Al-Hilla General Teaching Hospital had been reviewed and analysed. All cases of gallstones disease which had been managed medically had been excluded from this study. Results :An incidence of (12%) of gallstones disease among Babylon's Province population had been disclosed according to this study. The female to male ratio revealed to be of (6:1). The peak incidence of the disease was in the fourth decade of life. An increasing incidence of the disease among patients less than (30) years old had been demonstrated.

O-B01 Role of Ursodeoxycholic acid in prevention of gallstones formation in bariatric patients: need to amend recent BOMSS guidelines

Abstract Background During rapid weight-loss phase following bariatric procedures, biliary cholesterol homeostasis is altered leading to increased propensity to gallstone formation. Incidence of gallstone formation following bariatric procedures is shown to be 10-38%. There is no consensus regarding its prevention and current BOMSS guidelines do not address this issue. This meta-analysis aims to pool high level evidence (RCTs) to assess efficacy of Ursodeoxycholic acid (UDCA) in reducing risk of gallstone formation in this cohort of patients and the need for revision of current guidelines. Methods A systematic literature search was performed using electronic databases (Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PROSPERO and Google Scholar) in line with PRISMA guidelines. Only randomised controlled trials were included without restrictions on study language, year, status of publication and patient’s age. Meta-analysis was performed using Review Manager Software to calculate pooled risk ratios (RR) using random-effects model. Results Fifteen trials were included (3952 patients analysed, 2487 in UDCA and 1465 in placebo group). The overall rate of gallstone formation was 16.0% (6.4% in UDCA vs 31.4% in placebo group). Trials included various bariatric procedures (SG/RYGB/OAGB/AGB/Gastroplasty). UDCA dose ranged from 300 to 1200mg per day. UDCA significantly reduced the risk of post-operative gallstone formation (3952 patients, RR 0.24, 95% CI 0.16-0.37, p < 0.0001). The absolute risk reduction and number needed to treat (NNT) were 25% and 4 respectively. Conclusions Oral Ursodeoxycholic acid treatment following restrictive bariatric surgical procedures significantly reduces the risks of gallstone formation. As such, its regular use in first 6 months (rapid weight-loss phase) can significantly reduce the risk of complications associated with gallstones. Such treatment would be cost effective and benefit 1 in 4 patients. There is significant evidence available on benefits of using UDCA in post-operative bariatric patients and that this should be added to the recent BOMSS guidelines.

Genome-wide analysis identifies gallstone-susceptibility loci including genes regulating gastrointestinal motility.

Genome-wide association studies (GWAS) have identified several risk loci for gallstone disease. As with most polygenic traits, it is likely that many genetic determinants are undiscovered. The aim of this study was to identify genetic variants that represent new targets for gallstone research and treatment. We performed a GWAS of 28,627 gallstone cases and 348,373 controls in the UK Biobank, replicated findings in a Scottish cohort (1089 cases, 5228 controls), and conducted a GWA meta-analysis (43,639 cases, 506,798 controls) with the FinnGen cohort. We assessed pathway enrichment using gene-based then gene-set analysis and tissue expression of identified genes in Genotype-Tissue Expression project data. We constructed a polygenic risk score (PRS) and evaluated phenotypic traits associated with the score. Seventy-five risk loci were identified (p<5 ×10-8 ), of which 46 were new. Pathway enrichment revealed associations with lipid homeostasis, glucuronidation, phospholipid metabolism, and gastrointestinal motility. Anoctamin 1 (ANO1) and transmembrane Protein 147 (TMEM147), both in novel, replicated loci, are expressed in the gallbladder and gastrointestinal tract. Both regulate gastrointestinal motility. The gallstone risk allele rs7599-A leads to suppression of hepatic TMEM147 expression, suggesting that the protein protects against gallstone formation. The highest decile of the PRS demonstrated a 6-fold increased odds of gallstones compared with the lowest decile. The PRS was strongly associated with increased body mass index, serum liver enzymes, and C-reactive protein concentrations, and decreased lipoprotein cholesterol concentrations. This GWAS demonstrates the polygenic nature of gallstone risk and identifies 46 novel susceptibility loci. We implicate genes influencing gastrointestinal motility in the pathogenesis of gallstones.

Postoperative Incidence of Iatrogenic Gallbladder Perforation During Laparoscopic Cholecystectomy in Sulaimaniyah Teaching Hospital

Background and Objective: Iatrogenic perforation of the gallbladder has been reported in 28% of those patients who undergo laparoscopic cholecystectomy. It has been pointed out that gallbladder perforation can result in formation of gallstones and spillage of bile. The present study was carried out in order to investigate the postoperative incidence of iatrogenic gallbladder perforation during laparoscopic cholecystectomy in SulaimaniTeaching Hospital.Patients and Methods: The present investigation was a single center, retrospective observational study that was carried out in Sulaimani Teaching Hospital in 2018-2019. The study sample included 99 patients who had undergone elective cholecystectomy. Required data on the possible risk factors and early outcomes and the patients’ demographics including age, BMI, and gender were collected. The collected data were analyzed through the Statistical Package for the Social Sciences (version 22.0).Results: The results revealed that 80% of the patients were females. Also, 42.4% had no chronic diseases, while diabetes mellitus (DM), DM along with hypertension (HT), and HT were found to be the most prevalent chronic diseases among them with 18.2%, 16.2%, and 10.1% of prevalence, respectively. Only 17.2% of the patients had abdominal operation before, and acute cholecystitis and chronic cholecystitis were seen respectivelyin 13% and 17% of them. The most common causes of gallbladder perforation (GP) were found to be electrocautery(16.2%) and grasper (7.1%). Moreover, 33.3% of the patients were overweight (BMI between 25 and 29.9), 45.5% were obese (BMI between 30 and 34.9), and 20.2% had BMI of over 35. Most of the patients aged 30 to 49 (62.6%). A majority of the patients (94.9%) were found to have gallstones.Conclusion: Iatrogenic gallbladder perforation is prevalent among patients who undergo laparoscopic cholecystectomy. However, laparoscopic cholecystectomy is still a better choice and associated with fewer complications compared to open cholecystectomy. Required measures need to be adopted for patients with perforated gallbladder in order to minimize spillage and remove as much spilled gallbladder content as possible.

Current management of choledocholithiasis after bariatric surgery

The increasing prevalence of obesity all over world has led to a growing number of metabolic and bariatric surgeries. Bariatric surgery is more effective for weight loss than medical therapy, with Roux-en-Y gastric bypass (RYGB) being considered the gold standard of care over the past decade. Bariatric surgery and the subsequent weight loss are associated with an increased risk for the development of gallstone formation. Common bile duct stones prevalence around 10% among patients with symptomatic gallbladder stones. Choledocholithiasis can be technically challenging problem to treat in patients post-laparoscopic RYGB (LRYGB) or a biliopancreatic diversion (BPD/DS) due to the altered upper gastrointestinal anatomy. This review describes the different treatment options of common bile duct stones after malabsorptive bariatric surgery, success rate, and adverse effects of each treatment modality including enteroscopy-assisted endoscopic retrograde cholangiopancreatography (EA-ERCP), percutaneous transhepatic cholangiography (PTC), endoscopic ultrasound-directed transgastric retrograde cholangiopancreatography (EDGE), and laparoscopic-assisted ERCP (LAERCP).

Predictive Factors of Cholelithiasis After Prophylactic Administration of Ursodeoxycholic Acid Following Laparoscopic Bariatric Surgery: Tehran Obesity Treatment Study.

Cholelithiasis is a well-known consequence of obesity as well as rapid weight loss especially after bariatric surgery. A routine postoperative course of ursodeoxycholic acid (UDCA) is recommended as a prophylactic measure against gallstone formation. However, the efficacy of UDCA after bariatric surgery and predictors of cholelithiasis despite prophylaxis are not well understood. We assessed the incidence and predictors of de novo cholelithiasis after bariatric surgery in patients who received UDCA prophylaxis. Uniform data from 2629 consecutive patients who underwent either sleeve gastrectomy or gastric bypass between March 2013 and 2018 were collected prospectively. All patients received a 6-month course of UDCA 300mg twice daily. Cholelithiasis was assessed with abdominal ultrasound at baseline as well as 6, 9, 12, 18, and 24months postoperatively. The association between cholelithiasis and its predictors was examined by Cox proportional hazards models and restricted cubic spline regression. The cumulative rate of cholelithiasis in 24months after surgery was 10.8% (n = 283) with the greatest incidence within the first year. After multivariate analysis, 6-month body mass index (BMI) loss was found to be the only independent predictor for postoperative cholelithiasis (HR = 1.10 [95% CI: 1.04-1.16]). The concordance index for predicting cholelithiasis was 0.60 (0.56-0.64) for 6-month BMI loss. Early postoperative rapid weight loss as represented by 6-month BMI loss is the main predictor of de novo cholelithiasis after bariatric surgery, although this parameter does not have enough power for discrimination of postoperative cholelithiasis.

Concomitant Cholecystectomy for Asymptomatic Gallstones in Bariatric Surgery-Safety Profile and Feasibility in a Large Tertiary Referral Bariatric Center.

Obesity is a risk factor for gallstone formation, which can be exacerbated by bariatric surgery-induced rapid weight loss. Current guidelines do not recommend concomitant cholecystectomy (CC) for asymptomatic gallstones during the bariatric surgery procedure. However, long-term follow-up studies have shown that the incidence of post-bariatric surgery symptomatic gallstones necessitating therapeutic cholecystectomy increases to 40%. Therefore, some surgeons advocate simultaneous cholecystectomy during the bariatric surgery for asymptomatic individuals. This study aims to evaluate the safety of performing cholecystectomy for asymptomatic gallstones during the bariatric procedure. Data from a consecutive series of patients that underwent primary laparoscopic sleeve gastrectomy (LSG), laparoscopic Roux-en-Y gastric bypass (LRYGB) or conversion of LSG to a LRYGB with or without concomitant cholecystectomy for asymptomatic gallstones between Jan 2010 and Dec 2017 were retrieved from the database. The primary endpoint was the complication rate. Secondary endpoints were the surgical operating room time (ORT) and the length of hospital stay (LOS). Out of the 2828 patients who were included, 120 patients underwent a concomitant cholecystectomy during their bariatric procedure (LSG or LRYGB) for asymptomatic gallbladder stones and were compared to the 2708 remaining patients who only had bariatric surgery. None of the concomitant cholecystectomy patients developed a gallbladder-related complication. There was no significant increase in the rate of minor or major complications between the CC groups and the non-CC groups (LSG: 6.7% vs. 3.2%, p=0.132; LRYGB: 0% vs. 2.3%, p =0.55; and conversion of LSG to LRYGB: 20% vs. 7.1%, p = 0.125, respectively). In addition, there was no significant increase in the length of hospital stay (1.85 ±4.19 days vs. 2.24 ±1.82, p=0.404) for LSG group and (1.75 ±2.0 vs. 2.3 ±2.1, p=0.179) for LRYGB group. Adding the cholecystectomy to the bariatric procedure only added an average of 23 min (min) (27 min when added to LSG and 18 min when added to LRYGB). As one of the largest series reviewing concomitant cholecystectomy in bariatric surgery, this study showed that in skilled laparoscopic bariatric surgical hands, concomitant cholecystectomy during bariatric surgery is safe and prevents potential future gallstone-related complications. Long-term large prospective randomized trials are needed to further clarify the recommendation of prophylactic concomitant cholecystectomy during bariatric surgery.

Antihypertriglyceridemia activities of naturally fermented green tea, Heukcha, extract through modulation of lipid metabolism in rats fed a high-fructose diet.

Hypertriglyceridemia, a symptom of elevated triglyceride level in the blood, is a potent risk factor for cardiovascular and metabolic disorders. Among the numerous treatments to regulate circulating triglyceride levels, fibrates are widely used to treat hypertriglyceridemia, although they also have side effects such as hepatotoxicity and gallstone formation. In the present study, we aimed to investigate the blood triglyceride-lowering effects of a naturally fermented green tea extract (NFGT) and the underlying mechanisms on hypertriglyceridemia in vitro and in vivo models. NFGT suppressed the expression of lipogenic genes, while augmented expression of fatty acid oxidation-related genes in cultured cells, leading to the significant decrease of intracellular triglyceride content. NFGT treated group in fructose-induced hypertriglyceridemic rat model significantly decreased plasma and hepatic triglyceride, which was accompanied by an increase in excretion of fecal fat. Taken together, we propose that NFGT could be potentially a novel functional ingredient to prevent or treat hypertriglyceridemia.

Assessment of Cholelithiasis in Obese Patients on Grayscale Ultrasonography

Background: Gallstones are concretions that can develop in any section of the biliary system, and cholelithiasis is when they affect the gall bladder. Gallstones are made up of bile that has built up in the gallbladder. Gallstones are one of the most common and costly gastroenterological disorders, posing a significant financial burden. Obesity and gallstone formation have been linked. The gold standard for cholelithiasis diagnosis is ultrasonography. Aim: To assess the cholelithiasis in obese patients on grayscale ultrasonography. Method: A prospective cross-sectional study sample of 151 patients, visited the hospital, during the research data collection period in Aziz Bhatti Shaheed Teaching Hospital, Gujrat. The results were evaluated by Ultrasound. Results: By performing ultrasound it has been evaluated that 89 patients had gall stones. In total, 25 patients had single G.B stone, 64 patients had multiple G.B stones, and 62 patients showed negative findings of G.B stone. 90 were females and 61 were male patients. The mean value of the age was calculated 49.64 ± 12.24 with a minimum age of 30 years and 80 years as a maximum of age. The mean value of the Height was calculated as 1.66 ± 0.07 in meters with minimum height of 1.55 meters and 1.85 meters as maximum height. The mean value of the weight was calculated as 86.3 ± 8.70 in kg with minimum weight of 73 kg and 110 kg as maximum weight. The mean value of the BMI was calculated as 30.85 ± 0.96 with minimum BMI of 30 and 34 as maximum BMI. In total, 5 patients had positive findings of sludge. Conclusion: In current study, feminine gender, a high BMI, and advanced age may all be risk factors for gallstone development. Females were spotted in greater numbers. The severity of cholelithiasis was exacerbated by a lack of awareness, information, and dietary education, as well as ignorance of the symptoms. If left untreated, it can lead to a variety of problems, including gallbladder cancer and other serious ...........

Magnitude of hypothyroidism among patients of cholelithiasis in a tertiary care centre in rural West Bengal: a prospective study

Background: Cholelithiasis is a common pathology of the gall bladder affecting about 10 to 15% of the adults in western countries and 2 to 29% in India. More than 80% of the patients with cholelithiasis are asymptomatic. Hypothyroidism may cause gall stone formation due to the hyperlipidemia, motility disorders affecting the bile duct and sphincter of Oddi.Methods: This was a descriptive cross-sectional study conducted at Department of Surgery, Bankura Sammilani Medical College and Hospital, Bankura from March 2019 to February 2020 for duration of one and half year. The sample size was 54 and consecutive non-probability sampling technique was used for the sampling. All the collected data were recorded in a pre-designed proforma and analyzed in MS excel.Results: Out of 54-patients with cholelithiasis, 28% patients were from the age group 45-54 years.40% patients were hypothyroid pre-dominantly females. Among 30-female patients 11 (26.82%) were hypothyroid and among 11-male patients 2 (15.38%) were hypothyroid. Hypothyroidism in male and female was statistically significant.Conclusions: This study was introduced to determine the relationship between hypothyroidism and cholelithiasis. It was concluded that hypothyroidism was more common in female, obese and elder patients. The gender distribution of the hypothyroidism in patients with cholelithiasis was statistically significant while all other variables were statistically not significant.

Bariatric surgery and prophylaxis against symptomatic gallstone disease

Obesity and gallstones are two common diseases with increasing prevalence. Gallstone formation is associated with obesity, but conversely, rapid weight loss can also increase the likelihood of gallstones forming.1 Thus, around a third of patients develop gallstones in the first 6 months after bariatric surgery. As more patients seeking treatment for their obesity undergo bariatric surgery or medical or endoscopic therapies, the incidence of gallstones will increase, with some becoming symptomatic and leading to cholecystectomy.

Ursodeoxycholic acid for the prevention of symptomatic gallstone disease after bariatric surgery (UPGRADE): a multicentre, double-blind, randomised, placebo-controlled superiority trial

Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.

Circadian Rhythm Disruption Influenced Hepatic Lipid Metabolism, Gut Microbiota and Promoted Cholesterol Gallstone Formation in Mice.

BackgroundHepatic lipid metabolism regulates biliary composition and influences the formation of cholesterol gallstones. The genes Hmgcr and Cyp7a1, which encode key liver enzymes, are regulated by circadian rhythm-related transcription factors. We aimed to investigate the effect of circadian rhythm disruption on hepatic cholesterol and bile acid metabolism and the incidence of cholesterol stone formation.MethodsAdult male C57BL/6J mice were fed either a lithogenic diet (LD) only during the sleep phase (time-restricted lithogenic diet feeding, TRF) or an LD ad libitum (non-time-restricted lithogenic diet feeding, nTRF) for 4 weeks. Food consumption, body mass gain, and the incidence of gallstones were assessed. Circulating metabolic parameters, lipid accumulation in the liver, the circadian expression of hepatic clock and metabolic genes, and the gut microbiota were analyzed.ResultsTRF caused a dysregulation of the circadian rhythm in the mice, characterized by significant differences in the circadian expression patterns of clock-related genes. In TRF mice, the circadian rhythms in the expression of genes involved in bile acid and cholesterol metabolism were disrupted, as was the circadian rhythm of the gut microbiota. These changes were associated with high biliary cholesterol content, which promoted gallstone formation in the TRF mice.ConclusionDisordered circadian rhythm is associated with abnormal hepatic bile acid and cholesterol metabolism in mice, which promotes gallstone formation.

1163 Genome-wide Association Study Reveals 55 Loci Associated with Gallstone Disease

Abstract Aim Gallstones have a prevalence of 20-40% in European populations and cause significant morbidity. Gallstones form from cholesterol and calcium bilirubinate and knowledge of genetic determinants remains incomplete. A genome-wide association study (GWAS) was performed to identify determinants of gallstones. Method A GWAS of 16,356,211 single nucleotide polymorphisms (SNPs) for 28,627 cases and 348,373 controls of European ancestry in the UK Biobank was undertaken. A logistic regression with additive allelic dosage was performed (significance: P &amp;lt; 5*10-8). Functional annotation and linkage disequilibrium clumping were performed to reveal distinct loci. Lead SNPs were investigated by linear regression for association with plasma lipids, liver enzymes and blood count markers. Results 55 lithogenic loci were identified of which 27 are novel. Functional annotation revealed genes involved in metabolism of cholesterol, glucose, bile acids and bilirubin with corresponding changes in serum biomarkers caused by those lithogenic alleles. Several novel variants did not alter cholesterol or other biomarkers. Lithogenic variants within genes controlling intra- and paracellular transport may govern biliary composition (PCDHB4, NUP153, CLDN7) and promote lithogenic bile. Variants within genes which may influence gallbladder motility (ANO1, TMEM147) and cholangiocyte ciliogenesis (TBC1D32, ADAMTS20, DYNC2LI1, HNF1B) may promote gallstone formation through reduced biliary flow. Conclusions We identified 27 novel associations with gallstones. Impact of lithogenic alleles on serum biomarkers was highly variable demonstrating that gallstone formation is partially driven by pathways which do not influence cholesterol, glucose or bilirubin metabolism. Variants within genes that may influence biliary composition, bile flow and gallbladder motility represent new targets for research into gallstones.

477 Surgical Solutions and Problems in An Adult Patient with VACTERL Association

Abstract Background We report an adult patient with features of VACTERL - oesophageal and anal atresia, with cardiac malformation. In infancy he underwent colonic interposition for oesophageal atresia using the transverse colon as a conduit. As a teenager he underwent formation of a Koch continent ileostomy after previous stoma formation for anal atresia. Eventual failure of the Koch pouch nipple valve necessitated a laparotomy for attempted refashioning. Unfortunately, this operation was beset by life-threatening complications and a protracted post-operative course. He presented to our hospital with a laparostomy, high output enterocutaneous fistulae (ECF) necessitating home total parenteral nutrition (TPN), severe cachexia and deconditioning. Method Conservative therapy was utilised to improve the nutritional and physiological status of the patient. Simultaneously, attempts were made to define the anatomy of his abdomen in relation to previous surgery. However, operation notes for the original procedures (oesophageal reconstruction and Koch pouch formation) were lost due to closure of the hospital which he attended at the time. A laparotomy was subsequently performed to manage the ECFs. Most of the small intestine was unsalvageable due to multiple fistulae and adhesions, leaving 35cm of small bowel terminating in an end ileostomy. A cholecystectomy was performed to mitigate gallstone formation. Conclusions Efficient communication is imperative in the management of complex patients. The loss of original operation notes made interpretation of subsequent imaging and planning of surgery troublesome. In contrast, efficient communication between teams involved in his peri-operative care, particularly the respiratory and intensive care teams facilitated a smooth post-operative course and successful discharge from hospital.

Gallstone Formation Follows a Different Trajectory in Bariatric Patients Compared to Nonbariatric Patients.

Since obese patients form cholesterol gallstones very rapidly after bariatric surgery, in patients who did not form gallstones during preceding years, we hypothesized that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. We therefore analyzed the lipid composition of gallbladder bile derived from 18 bariatric gallstone patients and 17 nonbariatric gallstone patients (median (IQR) age, 46.0 (28.0–54.0) years; 33 (94%) female) during laparoscopic cholecystectomy using an enzymatic and lipidomics approach. We observed a higher concentration of total lipids (9.9 vs. 5.8 g/dL), bile acids (157.7 vs. 81.5 mM), cholesterol (10.6 vs. 5.4 mM), and phospholipids (30.4 vs. 21.8 mM) in bariatric gallstone patients compared to nonbariatric gallstone patients. The cholesterol saturation index did not significantly differ between the two groups. Lipidomics analysis revealed an interesting pattern. Enhanced amounts of a number of lipid species were found in the gallbladder bile of nonbariatric gallstone patients. Most striking was a fivefold higher amount of triglyceride. A concomitant ninefold increase of apolipoprotein B was found, suggesting secretion of triglyceride-rich lipoproteins (TRLs) at the canalicular pole of the hepatocyte in livers from nonbariatric gallstone patients. These findings suggest that gallstone formation follows a different trajectory in bariatric patients compared to nonbariatric patients. Impaired gallbladder emptying might explain the rapid gallstone formation after bariatric surgery, while biliary TRL secretion might contribute to gallstone formation in nonbariatric patients.

Gall Bladder Calculus in reproductive age group females attending the ultrasound clinic at a tertiary care hospital: A comparative Cross-sectional study

Background: Pregnant females are at risk for cholelithiasis' progress, and the obstruction in the bile duct produced by gallstones is responsible for jaundice and abdominal pain. Objective: The objectives of the present study were to see the burden of gall stones, relation with parity, and trimester among reproductive age group females. Methodology: A cross-sectional study was conducted on 467 females of age between 15 to 45 years. The gall bladder was thoroughly examined by an ultrasound probe of frequency 2-5 MHz in all planes. Results: In most females who had gallstones, single (68.8 percent) gall stone was common as compared to multiple (31.2 percent). More nonpregnant women had gall bladder stones than pregnant women (p-value &lt;0.005). Among the current nonpregnant group, the percentage of presence of gallbladder stones was greater in the female having parity of two or more (27.4 percent) than the females having parity of less than two (8.2 percent) with p-value &lt;0.05. Conclusion: Since Gallstones can further complicate the situation in the form of gallbladder carcinoma, and females with higher parity have more chances of developing gallstones. Therefore, it becomes necessary to know the trimester of gallstone formation and its role in the progression of symptoms.