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Background: The relationship of hypoglycemic drugs, inflammatory proteins and gallbladder diseases remain unknown., Methods: Four hypoglycemic drugs were selected as exposure: glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and metformin. The outcome were two gallbladder diseases: cholecystitis and cholelithiasis. Mendelian Randomization (MR) was employed to determine the association between hypoglycemic drugs and gallbladder diseases., Results: DPP-4i and SGLT-2i had no effect on cholecystitis and cholelithiasis. However, a causal relationship was found between inhibition of ETFDH gene, a target of metformin expressed in cultured fibroblasts, and cholelithiasis (OR: 0.84, 95 %CI: (0.72,0.97), p = 0.021), as well as between GLP1R expression in the brain caudate basal ganglia and cholecystitis (OR: 1.29, 95 %CI: (1.11,1.49), p = 0.001). The effect of ETFDH inhibition on cholelithiasis through Interleukin-10 receptor subunit beta (IL-10RB) levels and Neurotrophin-3 (NT-3) levels, with a mediated proportion of 8 % and 8 %, respectively., Conclusion: Metformin plays a protective role in cholelithiasis, while GLP-1RA have a harmful effect on the risk of cholecystitis. Metformin may reduce the risk of cholelithiasis by modulating the levels of Neurotrophin-3 (NT-3) and Interleukin-10 receptor subunit beta (IL-10RB). Further clinical and mechanistic studies are required to confirm these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial., Methods: Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers., Results: The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR] = 1.04, 95% confidence interval [CI]: 1.01-1.06, p = 0.002) and endometrial cancer (EC) (RR = 1.26, 95% CI: 1.02-1.56, p = 0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p = 0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p = 0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p > 0.05)., Conclusion: This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC., (© 2024 University College London (UCL) and John Wiley & Sons Ltd.)

Background and Aim: Helicobacter pylori (H. pylori) infection is a bacterial disease of the stomach that has been associated with an increased incidence of cholelithiasis. While the updated German guideline emphasizes the relevance of H. pylori as a pathogen and recommends eradication therapy, systematic data on the association between H. pylori infection, its eradication, and the subsequent diagnosis of cholelithiasis in Germany are missing., Methods: A total of 25 416 patients with and 25 416 propensity score-matched individuals without H. pylori infection were identified from the Disease Analyzer database (IQVIA) between 2005 and 2021. A subsequent diagnosis of cholelithiasis was analyzed as a function of H. pylori infection as well as its eradication using Cox regression models., Results: After 10 years of follow-up, 8.0% versus 5.8% of patients with and without H. pylori infection were diagnosed with cholelithiasis (P < 0.001). Regression analysis revealed a significant association between H. pylori infection and cholelithiasis (hazard ratio [HR]: 1.45; 95% confidence interval [CI]: 1.33-1.58), which was stronger in men (HR: 1.63; 95% CI: 1.41-1.90) than in women (HR: 1.36; 95% CI: 1.22-1.52). In terms of eradication therapy, both an eradicated H. pylori infection (HR: 1.48; 95% CI: 1.31-1.67) and a non-eradicated H. pylori infection (HR: 1.41; 95% CI: 1.25-1.60) were associated with a subsequent diagnosis of cholelithiasis., Conclusion: The present study reveals a strong association between H. pylori infection and a subsequent diagnosis of cholelithiasis in a large real-world cohort from Germany. Eradication therapy was not associated with a reduced incidence of cholelithiasis in our cohort., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Linkage studies have indicated a potential genetic predisposition to cholelithiasis. This study aims to determine the frequency of positive family history of gallstone disease in patients presenting with gallstones in a Pakistani population. A descriptive, cross-sectional study was conducted at the surgical department of the University of Lahore Teaching Hospital from June 30, 2023 to August 30, 2023. A total of 102 radiologically confirmed cholelithiasis patients were enrolled. Out of 102 participants, 75.5% (n = 77) were females, with a mean age at presentation of 42.1 ± 12.1 years. The study found that 32.4% (n = 33) of participants had a single family member with gallstones, 3.9% (n = 4) had 2 family members affected, and 1% (n = 1) had 3 family members affected. The attributable risk of genetics from our study was 37.2%. Additionally, there was no significant association between positive family history and earlier onset of disease. A significant percentage of Pakistani population may have gallstone disease due to genetic factors., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The prevalence rates of hepatosteatosis and gallstones are increasing owing to the multifactorial causes of chronic kidney disease, and the prevalence may change with the availability of different forms of renal replacement therapy. We aimed to determine the incidence or prevalence rates of hepatosteatosis, cholelithiasis, and acute cholecystitis in patients with chronic kidney disease and compare them between renal replacement therapy modalities., Methods: A total of 270 patients (90 with chronic kidney disease stages III-V, 90 undergoing peritoneal dialysis, and 90 undergoing hemodialysis) were included and categorized into the pre-dialysis, hemodialysis, and peritoneal dialysis groups. The patients were questioned about previous gallbladder surgeries and chronic diseases. The results of abdominal ultrasonography, tomography, and magnetic resonance imaging were retrospectively evaluated with respect to the findings on the hepatobiliary system. Hepatosteatosis and cholelithiasis were diagnosed by expert radiologists on the basis of abdominal ultrasonography, tomography, and magnetic resonance imaging findings. The prevalence rates of hepatosteatosis, cholelithiasis, and other liver findings were compared between the groups., Findings: Hepatosteatosis and cholelithiasis were detected in 16.7% and 21.5% of the 270 cases, respectively. Hepatosteatosis was present in 17.8%, 25.6%, and 6.7% of patients in the pre-dialysis, hemodialysis, and peritoneal dialysis groups, respectively. The prevalence of hepatosteatosis was significantly higher in patients undergoing hemodialysis than in patients undergoing peritoneal dialysis (p = 0.002). However, no statistically significant difference was found between the peritoneal dialysis and pre-dialysis groups or between the hemodialysis and pre-dialysis groups (p >0.05). The prevalence rates of cholelithiasis were 15.6%, 28.9%, and 20.0%, in the pre-dialysis, hemodialysis, and peritoneal dialysis groups, respectively, and there were no statistically significant differences among the groups. The incidence of acute cholecystitis was significantly higher in the hemodialysis group than in the pre-dialysis group (p = 0.006)., Discussion: Our study showed that the hepatobiliary system is frequently affected in chronic kidney disease and that the findings may differ depending on the renal replacement therapy modality., (© 2024 International Society for Hemodialysis.)

Introduction: Nutritional exposure is considered the main environmental influence that contributes to gallstone disease (GD)., Aim: The aim of this study was to determine food intakes patters and estimate risk of GD., Methods: A nested case-control study was carried out within the framework of a previous screening study conducted on a representative sample in Rosario, Argentina. Participants underwent a personal interview. Average amount of each food intake and quantity nutrients were estimated applying a food-frequency questionnaire. Food consumption patterns were identified by principal component analysis, and logistic regression analysis was used to estimate risks., Results: The sample was conformed by 51 cases and 69 controls. Two dietary patterns were identified. Cases were characterised by the unhealthy intake pattern (high intakes of animal fats, sugar, cereals, grains, cold cuts, processed meats, chicken with skin, fat beef and low intake of red vegetables and yellows, cabbages, fruits and fish)., Conclusion: Controls were characterised by the healthy intake pattern (high intake of skinless chicken, nuts, lean beef, vitamin A and C rich fruits, and low consumption of chicken with skin, green leaves vegetables and sprouts). The unhealthy pattern showed an increased risk of developing GD while healthy patter behaved as a protective factor., (Universidad Nacional de Córdoba)

This study aimed to examine the association between calcific rotator cuff tendinopathy (RCT) and nephrolithiasis and/or cholelithiasis. A case-control study was conducted on patients diagnosed with RCT between June 2016 and June 2022. RCT was confirmed by ultrasound, and patients were divided into 2 groups: calcific RCT (case) and non-calcific RCT (control). Data were collected retrospectively from electronic medical records and completed by phone calls, looking for a history of nephrolithiasis and/or cholelithiasis; based on clinical features or incidental findings on abdominal and pelvic imaging. A total of 210 patients with RCT were included. Among the 95 cases of calcific RCT, 43 had a history of lithiasis (45.3%) against 23 (20%) from the non-calcific RCT group (P < .001); 21 patients suffered from nephrolithiasis (22.1%) and 26 had cholelithiasis (27.4%) versus 10 (8.7%) (P = .006) and 16 (13.9%) (P = .015) in the non-calcific RCT group, respectively. Logistic regression showed that the independent predictors of calcific RCT included a history of nephrolithiasis (OR, 4.38; 95% CI: 1.61-11.92, P = .004) and a history of cholelithiasis (OR, 3.83; 95% CI: 1.64-8.94, P = .002). In patients with calcific RCT, the occurrence of lithiasis was significantly associated in the bivariate analysis with higher age, body mass index, fasting blood sugar, and HbA1c (all with P < .05), but only with the presence of another site of calcific tendinopathy than the shoulder (OR, 3.11; 95% CI: 1.12-8.65, P = .03) in the multivariate analysis. Nephrolithiasis and/or cholelithiasis are associated with calcific RCT, and their presence predicts calcific RCT at least 3 times. Further research is required to determine the common risk factors and preventive measures against lithogenesis in patients with calcific RCT, nephrolithiasis, and cholelithiasis., Competing Interests: The authors have no funding and no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cholelithiasis is a common digestive disease that drives a myriad of adverse complications. The correlation between sarcopenia and various digestive disorders has been extensively researched, whereas its association with cholelithiasis remains unreported. We aimed to investigate the association through prospective and Mendelian randomization (MR) analyses and establish a quantitative score reflecting the impact of sarcopenia-related markers on cholelithiasis. The prospective study involved 448 627 participants from the UK Biobank. Cox proportional hazard models were employed to investigate the correlation between sarcopenia-related markers and cholelithiasis. To quantitatively assess cholelithiasis risk, the SARCHO score was derived from a multivariable Cox model. Bidirectional two-sample MR analysis was conducted to validate the causal association. A total of 16 738 individuals developed cholelithiasis during a median follow-up of 12 years. Hazard ratios (HRs) of cholelithiasis decreased stepwise over skeletal muscle index tertiles (highest tertile: reference; middle tertile: 1.23, p < .001; lowest tertile: 1.33, p < .001). The tertiles of grip strength showed a similar pattern. Individuals with slow walking pace had a higher risk of cholelithiasis compared to those with normal walking pace (HR 1.23; p < .001). Our SARCHO score better quantifies the risk of cholelithiasis. MR analysis showed a causal relationship between muscle mass and cholelithiasis (OR 0.81; p < .001). No causal effect of cholelithiasis on lean mass was observed. Prospective and MR analyses have consistently demonstrated an increased risk of cholelithiasis in individuals with decreased muscle mass. Additionally, SARCHO score further quantified the cholelithiasis occurrence risk. These findings provide compelling evidence for muscle strengthening in preventing cholelithiasis., (© 2024 Wiley Periodicals LLC.)

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population-based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m 2 ); normal (18.5-22.9 kg/m 2 ); overweight (23-24.9 kg/m 2 ); and obese (25+ kg/m 2 ). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02-1.38] for males, HR 1.30 [1.14-1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis., (© 2023 UICC.)

Background: The prevalence and risk factors of cholelithiasis in individuals with severe or profound intellectual and motor disabilities (SPIMD) are poorly characterised. Thus, we aimed to investigate the prevalence and risk determinants of cholelithiasis in a cohort with SPIMD under medical care in a residential facility., Methods: We categorised 84 patients in a residential hospital for persons with SPIMD into groups: those with (Group CL) and without (Group N) cholelithiasis. Gallstones were detected via computed tomography, ultrasonography or both. We evaluated gastrostomy status, nutritional and respiratory support, constipation, and bladder and kidney stones. Data were significantly analysed using univariate and multivariate logistic regression analyses., Results: The prevalence rate of cholelithiasis in our SPIMD cohort was 27%. There were no significant differences in sex, age, weight, height, or Gross Motor Function Classification System between the two groups. However, more patients received enteral nutrition (39.13% vs. 6.56%; P = 0.000751) and were on ventilator support (56.52% vs. 19.67%; P = 0.00249) in Group CL than in Group N. Enteral nutrition [odds ratio (OR) 10.4, 95% confidence interval (CI) 1.98-54.7] and ventilator support (OR 20.0, 95% CI 1.99-201.0) were identified as independent risk factors for the prevalence of cholelithiasis in patients with SPIMD., Conclusions: Patients with SPIMD demonstrated an increased prevalence of cholelithiasis, with a notable association between nutritional tonic use and respiratory support. Therefore, to emphasise the need for proactive screening, it is crucial to devise diagnostic and therapeutic strategies specific to patients with SPIMD. Further investigation is essential to validate our findings and explore causative factors., (© 2024 John Wiley & Sons and MENCAP.)

Introduction: Radical gastrectomy is associated with significant functional complications. In appropriate patients may be amenable to less invasive resection aimed at preserving the vagal trunks. The aim of this systematic review and meta-analysis was to assess the functional consequences and oncological safety of vagal sparing gastrectomy (VSG) compared to conventional non-vagal sparing gastrectomy (CG)., Methods: A systematic review of four databases in accordance with PRISMA guidelines was undertaken for studies published between January 1, 1990, and December 15, 2021, comparing patients who underwent VSG to CG. We meta-analysed the following outcomes: operative time, blood loss, nodal yield, days to flatus, body weight changes, as well as the incidence of post-operative cholelithiasis, diarrhoea, delayed gastric emptying, and dumping syndrome., Results: Thirty studies were included in the meta-analysis with a selection of studies qualitatively analysed. VSG was associated with a lower rate of cholelithiasis (OR: 0.25, 95% CI: 0.15-0.41, p &lt; 0.010) and early dumping syndrome (OR: 0.42, 95% CI: 0.21-0.86; p = 0.02), less blood loss (mean difference [MD]: -51 mL, 95% CI: -89.11 to -12.81 mL, p = 0.009), less long-term weight loss (MD: 2.03%, 95% CI: 0.31-3.76%, p = 0.02) and a faster time to flatus (MD: -0.42 days, 95% CI: -0.48 to 0.36, p &lt; 0.001). There was no significant difference in nodal harvest, overall survival, and all other endpoints., Conclusion: VSG significantly reduces the incidence of post-operative cholelithiasis and dumping syndrome, decreases weight loss, and facilitates an earlier return of gut motility. Although technically more challenging, VSG should be considered for prophylactic surgery., (© 2024 S. Karger AG, Basel.)

The risk factor for cholelithiasis include low physical activity. With an aging society, the number of bedridden patients who undergo percutaneous endoscopic gastrostomy (PEG) has increased, and cholelithiasis has often been found in these patients. This study aimed to evaluate the risk factors correlated with cholelithiasis in adults who underwent PEG. This retrospective single-center design study reviewed patients who underwent PEG and were confirmed to have cholelithiasis through imaging from March 1996 to December 2021. The investigated variables were age, sex, body mass index (BMI, kg/m 2 ), cause of PEG insertion, initial physical activity status, laboratory findings on PEG insertion day, and incidence of acute cholecystitis. The differences between categorical and continuous variables were analyzed using Student's t test and chi-square test. We enrolled 576 eligible patients who underwent PEG insertion. A total of 161 patients were detected with cholelithiasis (28.0%). The overall independent risk factors for cholelithiasis in patients who underwent PEG insertion were increased C-reactive protein (CRP) levels and decreased physical activity status (bedridden state). The incidence of cholelithiasis was increased by up to 30.7%, especially in patients with bedridden status. However, the incidence of acute cholecystitis among cholelithiasis group was only 5.6%. BMI and total cholesterol were positively correlated with the size of gallbladder (GB) stones. One of the major risk factors for cholelithiasis is decreased physical activity, especially in patients who underwent PEG insertion. Abdominal imaging is recommended to confirm the presence of cholelithiasis and to consider prophylaxis for cholelithiasis, especially in bedridden patients with elevated initial CRP levels at the time of PEG insertion., (© 2023. The Author(s).)

Background: Cholelithiasis is an uncommon and mainly incidental finding in dogs; current literature on this topic is scarce in cats., Hypothesis: Report prevalence, clinical presentation, management, and outcome of cholelithiasis in cats., Animals: Ninety-eight cats with cholelithiasis., Methods: Retrospective multicenter case series. Electronic databases from 3 hospitals were searched for cats diagnosed with cholelithiasis by ultrasonography (US). Cholelithiasis was classified as incidental (IC) or symptomatic (SC) depending on clinicopathological signs, biliary tract US appearance, and presence of another disease potentially explaining the clinical presentation. Multivariate analysis was used to investigate factors associated with clinical expression of cholelithiasis and, within the SC group, survival., Results: The observed prevalence of cholelithiasis was 0.99% (95% confidence interval [CI], 0.79%-1.19%) among cats that underwent abdominal US. Cholelithiasis was classified as IC in 41% and SC in 59%. Choleliths found in multiple locations within the biliary tract (odds ratio [OR], 8.11; 95% CI, 2.32-34.15; P = .001) or associated with US signs of obstruction (OR, 18.47; 95% CI, 2.13-2413.34; P = .004) were significantly associated with SC. Concurrent hepatobiliary diseases were suspected or confirmed in 83% of cases with SC. Forty-three cats (74%) with SC survived to discharge. Biliary tract obstruction (BTO) was negatively associated with survival (OR, 13.87; 95% CI, 1.54-124.76; P = .001). None of the cats with IC that had available follow-up (47%) developed clinicopathological signs related to cholelithiasis., Conclusions and Clinical Importance: Cholelithiasis is uncommon and can be asymptomatic in cats. Symptomatic cholelithiasis frequently is associated with another hepatobiliary disease or BTO or both. Biliary tract obstruction is associated with poorer outcome., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Introduction: Patients with pancreatic cancer can present with a variety of insidious abdominal symptoms, complicating initial diagnosis. Early symptoms of pancreatic cancer often mirror those associated with gallstone disease, which has been demonstrated to be a risk factor for this malignancy. This study aims to compare the incidence of gallstone disease in the year before diagnosis of pancreatic ductal adenocarcinoma (PDAC) as compared to the general population, and evaluate the association of gallstone disease with stage at diagnosis and surgical intervention., Methods: Patients with PDAC were identified from SEER-Medicare (2008-2015). The incidence of gallstone disease (defined as cholelithiasis, cholecystitis and/or cholecystectomy) in the 1 year before cancer diagnosis was compared to the annual incidence in an age-matched, sex-matched, and race-matched noncancer Medicare cohort., Results: Among 14,654 patients with PDAC, 4.4% had gallstone disease in the year before cancer diagnosis. Among the noncancer controls (n = 14,654), 1.9% had gallstone disease. Both cohorts had similar age, sex and race distributions. PDAC patients with gallstone disease were diagnosed at an earlier stage (stage 0/I-II, 45.8% versus 38.1%, P < 0.0001) and a higher proportion underwent resection (22.7% versus 17.4%, P = 0.0004) compared to patients without gallstone disease., Conclusions: In the year before PDAC diagnosis, patients present with gallstone disease more often than the general population. Improving follow-up care and differential diagnosis strategies may help combat the high mortality rate in PDAC by providing an opportunity for earlier stage of diagnosis and earlier intervention., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Observational studies about the association between serum total bilirubin and cholelithiasis are inconsistent. Hence, it is essential to reevaluate the association between serum total bilirubin and cholelithiasis and to verify whether such association is causal or not., Methods: We selected single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure as instrumental variable and conducted a bidirectional two-sample Mendelian randomization (MR) study to explore the causal association between serum total bilirubin and cholelithiasis. We implemented the inverse-variance weighted approach as a primary analysis to combine the Wald ratio estimates. Four additional analyses, namely, MR-Egger regression, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier (PRESSO), were utilized to investigate the causal association and the influence of potential pleiotropy., Results: A total of 116 SNPs were selected as valid instrumental variables to estimate the causal association of serum total bilirubin on cholelithiasis, and causal association between genetically determined serum total bilirubin and cholelithiasis was demonstrated [beta = 0.10; 95% confident interval (CI), 0.07 to 0.14; p < 0.001]. Likewise, the other methods, namely, the weighted median (beta = 0.12; 95% CI, 0.08 to 0.15; p < 0.001), MR-Egger (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), weighted mode (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), and MR-PRESSO approaches, further confirmed that this result (p = 0.054) indicates similar results. In addition, seven SNPs were selected as instrumental variable to estimate causal association of cholelithiasis on serum total bilirubin, and the result supported the causal effect of cholelithiasis to serum total bilirubin (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001). At the same time, the other methods, namely, the weighted median (beta = 0.10; 95% CI, 0.06 to 0.13; p < 0.001), MR-Egger (beta = 0.12; 95% CI, 0.07 to 0.18; p = 0.007), weighted mode (beta = 0.09; 95% CI, 0.03 to 0.14, p = 0.019), and MR-PRESSO methods, further confirmed this result (p < 0.001)., Conclusion: Our MR study revealed that the serum total bilirubin was causally associated with the risk of cholelithiasis, and the genetic predisposition to cholelithiasis was causally associated with the increased serum total bilirubin levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sun, Yang, Dai, Zheng, Zhang, Zheng, Wang, Bi, Duan, Wu and Kong.)

Background: Gallstone disease remains a major health issue. There have been significant changes in the management and demographics of patients with these conditions. We aimed to evaluate trends in hospitalization, management, and post-procedural adverse events for patients with gallstone disease., Methods: The National Inpatient Sample was used to identify discharges for symptomatic cholelithiasis and cholecystitis between 2005 and 2014. Temporal trends were evaluated by calculating annual percent changes (APCs). Joinpoint regression was used to assess inflection points. Multivariable regression models were used to evaluate associations between urban and rural divisions and mortality, use of interventional procedures, and post-procedural adverse events., Results: From 77,394,755 unweighted discharges, there was a decline in discharges for cholelithiasis (APC - 5.5%, 95% confidence intervals, CI, - 7.6 to - 3.4%) and cholecystitis from 2012 to 2014 (APC - 4.5%, 95% CI - 7.2 to - 1.7%). Interventions were more likely at urban hospitals for symptomatic cholelithiasis (odds ratio, OR, 1.49, 95% CI 1.24 to 1.66) and cholecystitis (OR 1.96, 95% CI 1.86 to 2.05). In-hospital mortality significantly decreased annually for patients with cholecystitis (OR 0.92, 95% CI 0.91 to 0.93). In-hospital mortality between rural and urban centers was comparable for symptomatic cholelithiasis (OR 1.27, 95% CI 0.79 to 2.03) and cholecystitis (OR 0.93, 95% CI 0.84 to 1.04)., Conclusions: Hospitalizations for gallstone disease have decreased since the 2010s. In-hospital mortality between urban and rural centers is similar, but urban hospitals utilize a higher rate of procedural interventions. Future studies should evaluate practice trends and costs across inpatient and ambulatory settings between rural and urban divisions., (© 2023. The Society for Surgery of the Alimentary Tract.)

Objective: Although the association between adiposity and gastrointestinal (GI) diseases has been explored, the causal effects of adiposity on GI diseases are largely unknown., Methods: Mendelian randomization was conducted using single-nucleotide polymorphisms associated with BMI and waist circumference (WC) as instrumental variables, and the causal associations of BMI or WC with GI conditions were estimated among >400,000 UK Biobank participants, >170,000 Finnish-descent participants, and numerous consortia participants of predominantly European ancestry., Results: Genetically predicted BMI was robustly associated with increased risk of nonalcoholic fatty liver disease (NAFLD), cholecystitis, cholelithiasis, and primary biliary cholangitis. For the diseases, the odds ratio per 1-SD increase in genetically predicted BMI (4.77 kg/m 2 ) ranged from 1.22 (95% CI: 1.12-1.34; p < 0.0001) for NAFLD to 1.65 (95% CI: 1.31-2.06; p < 0.0001) for cholecystitis. Genetically predicted WC was robustly associated with increased risk of NAFLD, alcoholic liver disease, cholecystitis, cholelithiasis, colon cancer, and gastric cancer. Alcoholic liver disease was consistently associated with WC even after adjusting for alcohol consumption in a multivariable Mendelian randomization analysis. The odds ratio per 1-SD increase in genetically predicted WC (12.52 cm) for such associations ranged from 1.41 (95% CI: 1.17-1.70; p = 0.0015) for gastric cancer to 1.74 (95% CI: 1.21-1.78; p < 0.0001) for cholelithiasis., Conclusions: High genetically predicted adiposity was causally associated with an increased risk of GI abnormalities, particularly of hepatobiliary organs (liver, biliary tract, and gallbladder) that are functionally related to fat metabolism., (© 2023 The Obesity Society.)

Background: Epidemiological characteristics of nonalcoholic fatty liver disease (NAFLD) in Chongqing, a west-central city of China, remain unclear. The objective of this study was to investigate the prevalence of NAFLD and the related risk factors among healthy adults for physical examination in Chongqing., Methods: A total of 110,626 subjects were enrolled in the present study. Each of the participants underwent physical examination, laboratory measurements, and abdominal ultrasonography. The chi-square test was employed to compare differences in the NAFLD prevalence, and logistic regression analysis was used to estimate the odds ratio for risk factors of NAFLD., Results: The prevalence of NAFLD in individuals in the population of Chongqing was 28.5%, and the prevalence in men (38.1%) was significantly higher than that in women (13.6%) (OR = 2.44; 95% CI: 2.31-2.58). NAFLD was more common in men aged 51-60 years and women over 60 years. Approximately 79.1% of the people with obesity and 52.1% of the people with central obesity had NAFLD. The prevalence of NAFLD in people with hypertension and cholelithiasis was 48.9 and 38.4%, respectively. Logistic regression showed that gender, age, body max index (BMI), central obesity, hypertension, impaired fasting glucose/diabetes mellitus (DM), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), hyperuricemia (HUA), alanine transaminase (ALT), and cholelithiasis were independently associated with the presence of NAFLD., Conclusion: The prevalence of NAFLD among healthy adults in Chongqing was high. To improve the prevention and management of NAFLD, special attention should be paid to the factors associated with the presence of NAFLD, including higher BMI, higher waist circumference, higher blood glucose, hypertension, hypertriglyceridemia, hyperuricemia, cholelithiasis, and elevated ALT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kong, Yang, Li, Shan, Wang and Shan.)

Background: The pathogenesis of pancreatitis involves diverse environmental risk factors, some of which have not yet been clearly elucidated. This study systematically investigated the causal effects of genetically predicted modifiable risk factors on pancreatitis using the Mendelian randomization (MR) approach., Methods: Genetic variants associated with 30 exposure factors were obtained from genome-wide association studies. Summary-level statistical data for acute pancreatitis (AP), chronic pancreatitis (CP), alcohol-induced AP (AAP) and alcohol-induced CP (ACP) were obtained from FinnGen consortia. Univariable and multivariable MR analyses were performed to identify causal risk factors for pancreatitis., Results: Genetic predisposition to smoking (OR = 1.314, P = 0.021), cholelithiasis (OR = 1.365, P = 1.307E-19) and inflammatory bowel disease (IBD) (OR = 1.063, P = 0.008) as well as higher triglycerides (OR = 1.189, P = 0.016), body mass index (BMI) (OR = 1.335, P = 3.077E-04), whole body fat mass (OR = 1.291, P = 0.004) and waist circumference (OR = 1.466, P = 0.011) were associated with increased risk of AP. The effect of obesity traits on AP was attenuated after correcting for cholelithiasis. Genetically-driven smoking (OR = 1.595, P = 0.005), alcohol consumption (OR = 3.142, P = 0.020), cholelithiasis (OR = 1.180, P = 0.001), autoimmune diseases (OR = 1.123, P = 0.008), IBD (OR = 1.066, P = 0.042), type 2 diabetes (OR = 1.121, P = 0.029), and higher serum calcium (OR = 1.933, P = 0.018), triglycerides (OR = 1.222, P = 0.021) and waist-to-hip ratio (OR = 1.632, P = 0.023) increased the risk of CP. Cholelithiasis, triglycerides and the waist-to-hip ratio remained significant predictors in the multivariable MR. Genetically predicted alcohol drinking was associated with increased risk of AAP (OR = 15.045, P = 0.001) and ACP (OR = 6.042, P = 0.014). After adjustment of alcohol drinking, genetic liability to IBD had a similar significant causal effect on AAP (OR = 1.137, P = 0.049), while testosterone (OR = 0.270, P = 0.002) a triglyceride (OR = 1.610, P = 0.001) and hip circumference (OR = 0.648, P = 0.040) were significantly associated with ACP. Genetically predicted higher education and household income levels could lower the risk of pancreatitis., Conclusions: This MR study provides evidence of complex causal associations between modifiable risk factors and pancreatitis. These findings provide new insights into potential therapeutic and prevention strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mao, Mao, Sun, Huang, Wang, Zhang, Wang, Li, Zou and Liao.)

Background: Growing evidence indicates an association between NAFLD and gallstone disease (GD), while some does not support this. The aim of this meta-analysis was to evaluate the bidirectional association between NAFLD and GD., Research Design and Methods: Five electronic databases were searched from inception to May 2022. The association was analyzed based on the odds ratio (OR) and 95% confidence interval (CI) with Reviewer Manager 5.3., Results: Ten studies involving 284,512 participants met the criteria for GD predicting the onset of NAFLD. GD patients had a higher incidence of NAFLD (OR:1.48, CI:1.32-1.65, p < 0.00001), especially the incidence of moderate-to-severe NAFLD (OR:1.63; CI:1.40-1.79), with females at a higher risk (OR: 1.84; CI: 1.48-2.29). The inverse association was explored in eight studies involving 326,922 participants. The GD incidence in NAFLD patients was higher (OR:1.71, CI:1.63-1.79, p < 0.00001) and may increase due to female sex (OR: 4.18; CI: 1.21-14.37) and high BMI (OR: 1.80; CI: 1.36-2.56), compared with the non-NAFLD group. Besides, this bidirectional association was also confirmed in the Chinese population., Conclusions: The findings supported positive concurrent and bidirectional relationships between NAFLD and GD. Therefore, clinicians may alert the possibility of NAFLD in patients with GD and vice versa.

Background: Obesity has been identified as an independent risk factor for cholelithiasis. As a treatment for obesity, bariatric surgery may increase the incidence of cholelithiasis. The risk factors for cholelithiasis after bariatric surgery remain uncertain. The purpose of this study was to explore the risk factors for postoperative cholelithiasis after weight-loss surgery and propose suggestions for clinical decision making., Methods: Four databases, PubMed, EMBASE, Web of Science and Cochrane, were systematically searched for all reports about cholelithiasis after bariatric surgery, and literature screening was performed following prespecified inclusion criteria. The included studies were all evaluated for quality according to the NOS scale. Data extraction was followed by analysis using Reviewer Manager 5.4 and StataSE 15., Results: A total of 19 articles were included in this meta-analysis, and all studies were of high quality. A total of 20,553 patients were included in this study. Sex [OR = 0.62, 95% CI (0.55, 0.71), P < 0.00001] and race [OR = 1.62, 95% CI (1.19, 2.19), P = 0.002] were risk factors for cholelithiasis after bariatric surgery. Surgical procedure, preoperative BMI, weight-loss ratio, smoking, hypertension, diabetes mellitus, and dyslipidemia were neither protective nor risk factors for cholelithiasis after bariatric surgery., Conclusion: Caucasian race and female sex are risk factors for developing cholelithiasis after bariatric surgery; surgical procedure, BMI, weight loss ratio, hypertension, diabetes mellitus, dyslipidemia, and smoking are not risk factors for cholelithiasis after bariatric surgery., (© 2023. The Author(s).)

Background: Fatty acids are important dietary factors that have been extensively studied for their implication in health and disease. Evidence from epidemiological studies and randomised controlled trials on their role in cardiovascular, inflammatory, and other diseases remains inconsistent. The objective of this study was to assess whether genetically predicted fatty acid concentrations affect the risk of disease across a wide variety of clinical health outcomes., Methods and Findings: The UK Biobank (UKB) is a large study involving over 500,000 participants aged 40 to 69 years at recruitment from 2006 to 2010. We used summary-level data for 117,143 UKB samples (base dataset), to extract genetic associations of fatty acids, and individual-level data for 322,232 UKB participants (target dataset) to conduct our discovery analysis. We studied potentially causal relationships of circulating fatty acids with 845 clinical diagnoses, using mendelian randomisation (MR) approach, within a phenome-wide association study (PheWAS) framework. Regression models in PheWAS were adjusted for sex, age, and the first 10 genetic principal components. External summary statistics were used for replication. When several fatty acids were associated with a health outcome, multivariable MR and MR-Bayesian method averaging (MR-BMA) was applied to disentangle their causal role. Genetic predisposition to higher docosahexaenoic acid (DHA) was associated with cholelithiasis and cholecystitis (odds ratio per mmol/L: 0.76, 95% confidence interval: 0.66 to 0.87). This was supported in replication analysis (FinnGen study) and by the genetically predicted omega-3 fatty acids analyses. Genetically predicted linoleic acid (LA), omega-6, polyunsaturated fatty acids (PUFAs), and total fatty acids (total FAs) showed positive associations with cardiovascular outcomes with support from replication analysis. Finally, higher genetically predicted levels of DHA (0.83, 0.73 to 0.95) and omega-3 (0.83, 0.75 to 0.92) were found to have a protective effect on obesity, which was supported using body mass index (BMI) in the GIANT consortium as replication analysis. Multivariable MR analysis suggested a direct detrimental effect of LA (1.64, 1.07 to 2.50) and omega-6 fatty acids (1.81, 1.06 to 3.09) on coronary heart disease (CHD). MR-BMA prioritised LA and omega-6 fatty acids as the top risk factors for CHD. Although we present a range of sensitivity analyses to the address MR assumptions, horizontal pleiotropy may still bias the reported associations and further evaluation in clinical trials is needed., Conclusions: Our study suggests potentially protective effects of circulating DHA and omega-3 concentrations on cholelithiasis and cholecystitis and on obesity, highlighting the need to further assess them as prevention treatments in clinical trials. Moreover, our findings do not support the supplementation of unsaturated fatty acids for cardiovascular disease prevention., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: DG is employed part-time by Novo Nordisk. VZ is a paid statistical consultant on PLOS Medicine’s statistical board., (Copyright: © 2022 Zagkos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Symptomatic cholelithiasis is a common surgical disease and accounts for half of the over one million cholecystectomies performed in the USA annually. Despite its prevalence, only one prior systematic review has examined the evidence around treatment strategies and it contained a narrow scope. The goal of this systematic review was to analyze the clinical effectiveness of treatment options for symptomatic cholelithiasis, including surgery, non-surgical therapies, and ED pain management strategies., Methods: Literature search was performed from January 2000 through June 2020, and a narrative analysis was performed as studies were heterogeneous., Results: We identified 12 publications reporting on 10 trials (9 randomized controlled trials and 1 observational study) comparing treatment methods. The studies assessed surgery, observation, lithotripsy, ursodeoxycholic acid, electro-acupuncture, and pain-management strategies in the emergency department. Only one compared surgery to observation., Conclusion: This work presents the existing data and underscores the current gap in knowledge regarding treatment for patients with symptomatic cholelithiasis. We use these results to suggest how future trials may guide comparisons between the timing of surgery and watchful waiting to create a set of standardized guidelines. Providing appropriate and timely treatment for symptomatic cholelithiasis is important to streamline care for a costly and prevalent disease., Trial Registration: PROSPERO Protocol Number: CRD42020153153., (© 2022. The Author(s).)

Background and Aims: Observational and Mendelian randomization (MR) studies have identified several modifiable risk factors of cholelithiasis. However, there is limited evidence about the causal effect of blood metabolites on the cholelithiasis risk., Methods: To have a comprehensive understanding to causal relations between blood metabolites and cholelithiasis, for the primary discovery, we applied two MR methods to explore the associations between 249 circulating metabolites and cholelithiasis. For secondary validations, we replicated the examinations using another metabolic dataset with 123 metabolites. The summary statistics of cholelithiasis were retrieved from FinnGen Consortium Release 5 and UK Biobank. Inverse-variance weighted, weight median and MR-egger methods were used for calculating causal estimates. Furthermore, Bayesian model averaging MR (MR-BMA) method was employed to detect the dominant causal metabolic traits with adjustment for pleiotropy effects., Results: In the primary analysis, sphingomyelin showed consistent protective causal associations with cholelithiasis; while plasma cholesterol-associated traits showed generally inverse correlation with cholelithiasis risk. Notably, large numbers of traits within the (un)saturated fatty acid category demonstrated significant causal effects. Secondary analyses demonstrated similar results, with traits related to the levels of bisallylic groups in fatty acids showing protective effects. Lastly, MR-BMA analyses discovered that the degree of unsaturation plays a predominant role in reducing the risk of cholelithiasis., Conclusion: Our MR study provides a complete atlas of associations between plasma metabolites on cholelithiasis risk. It highlighted that genetically predicted sphingomyelin and degree of unsaturation of fatty acid were causally associated with the reduced risk of cholelithiasis., (© 2022. Asian Pacific Association for the Study of the Liver.)

The incidence of gallstone disease has increased in recent years. The pathogenesis of cholelithiasis is not fully understood. The occurrence of the disease is influenced by both genetic and environmental factors. This article reviews the literature on cholelithiasis in children, with the exception of articles on hematological causes of cholelithiasis and cholelithiasis surgery. The aim of this review is to present the latest research on the pathogenesis of gallstone disease in children. The paper discusses the influence of all factors known so far, such as genetic predisposition, age, infections, medications used, parenteral nutrition, and comorbidities, on the development of gallstone disease. The course of cholelithiasis in the pediatric population is complex, ranging from asymptomatic to life-threatening. Understanding the course of the disease and predisposing factors can result in a faster diagnosis of the disease and administration of appropriate treatment.

Introduction: Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial., Methods: We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case-control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations., Results: Our case-control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06-3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17-1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03-1.51) and Asia (RR = 1.32, 95%CI 1.24-1.41)., Conclusions: The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better., (© 2022. The Author(s).)

Background:  Spinal cord injury (SCI) is a significant medical condition associated with various secondary complications, including cholelithiasis. Cholelithiasis can cause biliary duct obstruction and result in acute cholecystitis. The development of acute cholecystitis in SCI patients has been well studied in the Taiwanese population, showing an increased risk of acute cholecystitis in patients with SCI. The development of cholecystitis has not been well studied in the United States., Materials and Methods:  A retrospective review was performed on 3,939 propensity score-matched patients aged 18 to 85 years who had SCI/surgery from 2000 to 2019. Patients were divided based on the development of postoperative complications, specifically cholecystitis with cholecystectomy., Results:  SCI consisted of quadriplegia (42%), paraplegia (53%), unspecified lesion of cervical spinal cord (3%), and thoracic spinal cord (2%). All groups were comparable regarding age, gender, body mass index, smoking status, and Charlson comorbidity Index. The incidence of acute cholecystitis with subsequent cholecystectomy among patients with SCI was 43.0 per 10,000 person-years (95% confidence interval: 41.51-44.49). Median follow-up was 36 months. The development of cholecystitis was comparable among females (54.5%) and males (45.5%), and among African Americans (52.5%) and Caucasians (47.5%)., Conclusion:  There is an association between SCI and development of acute cholecystitis among U.S., Patients: As SCI patients do not present with the classic signs of biliary colic, risk assessment for the development of acute cholecystitis will guide patient management and allow neurosurgeons to weigh the risks and benefits of prophylactic treatment for gallbladder complications., Competing Interests: None declared., (Thieme. All rights reserved.)

Background and Study Aims: Low phospholipid-associated cholelithiasis (LPAC) syndrome is a form of cholelithiasis associated with the ABCB4 gene mutation. The defects of the protein ABCB4 encoded by this gene promote the formation of biliary cholesterol microcalculations. ABCB4 screening is negative in a significant proportion of patients., Patients and Methods: An analytical study of the epidemiological, clinical, biological, and radiological characteristics of 19 patients was conducted, followed by Sanger-type sequencing of the 27 exons encoding the ABCB4 gene., Results: Our results showed a female predominance, symptomatic vesicular lithiasis predominance, and a high frequency of biliary complications in patients carrying an ABCB4 mutation. Normal ​​ liver enzyme values were found in 84.2% of the cases. Intrahepatic hyperechoic foci were present in 68.4%. Molecular analysis detected a pathogenic mutation of the ABCB4 gene in 31.57% of patients. The mutations found were a nonsense mutation and three missense mutations, including two new mutations., Conclusion: Our epidemiological, clinical, and genetic results concord with previous studies of LPAC syndrome. Two of the mutations we found have never been detected in patients with LPAC. The low percentage of ABCB4 gene mutations can be explained by the absence of studies of other genes involved in bile acid homeostasis besides the ABCB4 gene and by the inclusion criteria used in this study., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.)

Purpose: This study analyzed the effectiveness of minimizing surgical trauma, reducing the severity of the stress reaction, and restoring the normal functioning of the body after planned gallbladder operations under an enhanced recovery program., Materials and Methods: This prospective comparison study included 30 patients from the surgical department of Irkutsk Clinical Hospital No. 1 who had been diagnosed with cholelithiasis in 2019-2020. All 30 patients completed the study and were randomly assigned to one of two groups: the FTS group (group I, n = 15) and the standard group (group II, n = 15). The comparison groups were statistically homogeneous in terms of preoperative parameters. All patients underwent prescribed surgeries. In the early and late postoperative period, there were no cases of mortality or significant complications., Results: A comparison of the groups with respect to the effectiveness of treatment according to established criteria showed good treatment results for 13 (86.6%) patients in group I and 2 (13.3%) patients in group II (p = 0.016). The FTS treatment protocol was a significant predictor of treatment success (OR 3.1; 95% CI 0.2; 6.0; p = 0.033)., Conclusion: The fast track surgery protocol gave superior results for surgical treatment in comparison with the standard protocol in patients with cholelithiasis.

Introduction: In the current era, laparoscopic cholecystectomy is the treatment of choice for symptomatic gallstone disease. The aim of this study is to find out the prevalence of open cholecystectomy among patients undergoing laparoscopic cholecystectomy in a tertiary care centre., Methods: It is a descriptive cross-sectional study done among 345 patients at the Department of Surgery of a tertiary care centre from June, 2020 to May, 2021 after receiving ethical clearance from the Institutional Review Committee (Reference number: CMC-IRC/0770798-271). Convenience sampling was done. Successive patients who underwent elective laparoscopic cholecystectomy during the study period were included. Standard 4 port laparoscopic technique was used for the laparoscopic cholecystectomy and sub-costal Kocher incision was used for the open cholecystectomy respectively. After data collection, entry and analysis were done in Microsoft Excel. Point estimate at a 95% Confidence Interval was calculated along with frequency and percentages for binary data., Results: Out of 345 patients, the prevalence of open cholecystectomy among patients undergoing laparoscopic cholecystectomy was 6 (1.73%) (0.35-3.11 at a 95% Confidence Interval)., Conclusions: This study showed that the prevalence of open cholecystectomy among patients undergoing laparoscopic cholecystectomy was lower when compared to similar studies conducted in similar settings., Keywords: cholecystectomy; cholelithiasis; laparoscopic cholecystectomy.

Background: Obesity and fast weight loss in the postoperative period of bariatric surgery increase significantly the risk of cholelithiasis. Moreover, emerging evidence has pointed out the role of bile acids as possible metabolism and weight loss enhancers. This study aims to analyze the influence of cholecystectomy (CL) concomitant with bariatric surgery on weight loss, metabolic repercussions, and postoperative morbidity., Study Design: Retrospective cohort study. A total of 363 medical records were analyzed between 2002 and 2017, with 255 patients divided into four groups: with concomitant CL: sleeve gastrectomy (SG + CL group) and Roux-en-Y gastric bypass (GB + CL group); without concomitant CL: sleeve gastrectomy (SG group) and RYGB (GB group)., Results: CL concomitant with bariatric surgery is not related to worse long-term metabolic outcomes when compared to isolated bariatric surgery. In the postoperative follow-up of the isolated bariatric surgeries, 18 (16.5%) patients underwent cholecystectomy. There was no statistical difference between the groups regarding post-surgical complications., Conclusion: CL did not lead to worse metabolic outcomes and was also not related to a higher incidence of postoperative complications. Cholelithiasis and cholecystitis are important concerns in the postoperative period of bariatric surgery and a careful evaluation of the concomitant procedure should be performed., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors., Approach and Results: We obtained genetic variants associated with the exposures at the genome-wide significance (p < 5 × 10 -8 ) level from corresponding genome-wide association studies. Summary-level statistical data for cholelithiasis were obtained from FinnGen and UK Biobank (UKB) consortia. Both univariable and multivariable Mendelian randomization (MR) analyses were conducted to identify causal risk factors of cholelithiasis. Results from FinnGen and UKB were combined using the fixed-effect model. In FinnGen, the odds of cholelithiasis increased per 1-SD increase of body mass index (BMI) (OR = 1.631, p = 2.16 × 10 -7 ), together with body fat percentage (OR = 2.108, p = 4.56 × 10 -3 ) and fasting insulin (OR = 2.340, p = 9.09 × 10 -3 ). The odds of cholelithiasis would also increase with lowering of total cholesterol (OR = 0.789, p = 8.34 × 10 -5 ) and low-density lipoprotein-cholesterol (LDL-C) (OR = 0.792, p = 2.45 × 10 -4 ). However, LDL-C was not significant in multivariable MR. In UKB, the results of BMI, body fat percentage, total cholesterol, and LDL-C were replicated. In meta-analysis, the liability to type 2 diabetes mellitus and smoking could also increase the risk of cholelithiasis. Moreover, there were no associations with other predominant risk factors., Conclusions: Our MR study corroborated the risk factors of cholelithiasis from previous MR studies. Furthermore, lower total cholesterol level could be an independent risk factor., (© 2021 The Authors. Hepatology published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)

Introduction: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis., Objective: To determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis., Materials and Methods: Observational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology., Results: 80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m 2 . Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed., Conclusion: Because cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found., Competing Interests: Conflicts of interest Itzayana Rodríguez-Antonio, Guillermo N. López-Sánchez, Víctor A. Reyes-Gómez, Ericka H. Contreras-Flores, Fernanda Farías-García, Mariana Espejel-Deloiza, Marco A. Durán-Padilla, Fredy Chablé-Montero, Misael Uribe, Norberto C. Chávez-Tapia, Eduardo E. Montalvo-Javé and Natalia Nuño-Lámbarri have no related conflicts of interest to declare., (Copyright © 2021 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Cholelithiasis is an issue in bariatric surgery patients. The incidence of cholelithiasis is increased in morbidly obese patients. After bariatric surgery, the management maybe sometimes challenging. There is no consensus about how to deal with cholelithiasis prior to bariatric surgery., Materials and Methods: A retrospective review from our prospectively collected bariatric surgery database. Primary bariatric procedures from 2009 to 2020 were included. Prevalence of cholelithiasis and its management prior to bariatric surgery and the incidence and management of postoperative biliary events were analyzed., Results: Over 1445 patients analyzed, preoperatively cholelithiasis was found in 153 (10.58%), and 68 out of them (44.44%) were symptomatic. Seventy-six patients had a concomitant cholecystectomy. In those cases, the bariatric procedure did not show increased operative time, length of stay, morbidity, or mortality compared to the rest of primary bariatric procedures. Twelve patients (15.58%) with previous cholelithiasis and no concomitant cholecystectomy presented any kind of biliary event and required cholecystectomy. De novo cholelithiasis rate requiring cholecystectomy was 3.86%. Postoperative biliary events both in de novo and persistent cholelithiasis population did not show any difference between the type of surgery, weight loss, and other characteristics., Conclusions: Cholelithiasis was present in 10.58% of our primary bariatric surgery population. Concomitant cholecystectomy was safe in our series. Non-surgical management of asymptomatic cholelithiasis did not lead to a higher risk of postoperative biliary events. The global postoperative cholecystectomy rate was equivalent to the general population., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To establish the role of the main risk factors and endocrine cells of the antrum of the stomach producing motilin (M-cells) in the occurrence of cholelithiasis., Materials and Methods: The first group included 122 patients with cholelithiasis. The second group consisted of 30 healthy individuals who underwent medical examination. The groups were matched for gender and age. The work analyzed anamnestic, biochemical and anthropometric data. All patients underwent esophagogastroduodenoscopy with targeted biopsy of the mucous membrane from the antrum. Biopsies were subjected to cytological and immunohistochemical studies in order to verify Helicobacter pylori and estimate the number of M-cells., Results: Patients with cholelithiasis more often belonged to the group of people of mental labor, had low physical activity, were committed to inappropriate nutrition and more often indicated the presence of aggravated heredity for cholelithiasis. Patients with gallstone disease had higher body mass index, waist volume, total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, lower high-density lipoprotein cholesterol, H. pylori infection was more often verified and M-cell hypoplasia in the mucous membrane was established. stomach in comparison with the representatives of the second group., Conclusion: Our results suggest that certain external factors, nutritional characteristics of the metabolic syndrome components, hypoplasia of M-cells in the gastric mucosa are important factors in the formation of calculi in the gallbladder.

Objective: Alpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the 'Pi*Z' variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous 'Pi*Z' carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common 'Pi*S' variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD., Design: Baseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption., Results: Among UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8-53.7)) and primary liver cancer (aOR=44.5 (10.8-183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2-2.2)) and cholelithiasis (aOR=1.3 (1.2-1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1-8.2)) and primary liver cancer (aOR=6.6 (1.6-26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis., Conclusion: Our study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sickle cell disease (SCD) remains prevalent in Nigeria and can be complicated by cholelithiasis even in children. There is still a dearth of knowledge about the occurrence of cholelithiasis in these children. The present study is aimed to determine the prevalence of cholelithiasis in pediatric SCD in Lagos and documents relevant socio-demographic and clinical correlates., Subjects and Methods: This was a cross-sectional study of children and adolescents aged 1-19 years with SCD attending the Paediatric Haematology Clinic of the Lagos University Teaching Hospital. One hundred and forty-seven children were consecutively recruited into the study over 3 months and they all had sonographic examination of the gall bladder. The association between cholelithiasis, sociodemographic data, clinical symptoms, laboratory parameters, and the use of hydroxyurea was also documented., Results: The median age (range) of the study participants was 9.0 (1-19) years and majority were males (59.9%). The prevalence of cholelithiasis was 13.6% and the condition was most prevalent in adolescents (21.4%) compared to the younger children (6.5%). All the children with cholelithiasis were asymptomatic. Age and the frequency of crisis were significantly associated with cholelithiasis on multivariate analysis (P = 0.03, 0.045, respectively). The use of hydroxyurea was not significantly related to the occurrence of cholelithiasis., Conclusion: The prevalence of cholelithiasis observed in this study is high. Routine screening of older children and adolescents with SCD, especially with the frequent crisis is suggested. Longitudinal studies to establish the relationship between hydroxyurea and cholelithiasis is also advocated., Competing Interests: None

Background and Aim: Cholelithiasis is one of the most common gastrointestinal diseases worldwide. The metabolic syndrome (MetS), a combination of various metabolic abnormalities, is also common with a continually increasing prevalence. These diseases are associated with several risk factors. However, data on the association between MetS components and cholelithiasis are insufficient. This study aimed to analyze the association of MetS and its components with the incidence of cholelithiasis using national data from the Korean population., Methods: Data were obtained from the National Health Insurance Corporation of Korea, and 207 850 individuals without cholelithiasis in 2009 were enrolled and followed up until 2013. A multivariate Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of cholelithiasis according to the presence of MetS and the number of MetS components. Furthermore, the risk of cholelithiasis was evaluated in individuals with a single metabolic component., Results: The multivariate adjusted HRs and 95% CIs for incident cholelithiasis according to 1, 2, 3, and 4-5 MetS components were 1.08 (0.93-1.24), 1.22 (1.06-1.41), 1.35 (1.17-1.57), and 1.35 (1.15-1.57), respectively (P < 0.001). This increasing trend was observed in both sexes. Compared with participants with no metabolic components, those with low high-density lipoprotein (HDL) cholesterol had a significantly increased risk for cholelithiasis (adjusted HR, 1.39 [95% CI, 1.05-1.85])., Conclusions: Metabolic syndrome is a potential risk factor for cholelithiasis. Low HDL cholesterol level is the most relevant factor among MetS components for incident cholelithiasis., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: 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., Competing Interests: Declaration of interests PF reports a grant from the Netherlands Organization for Health Research and Development, during the conduct of the trial. VEAG reports grants from the Foundation for Clinical Research of the Slotervaart Hospital and the Spaarne Gasthuis Academy, during the conduct of the trial. RPV reports grants from Amsterdam Gastroenterology Endocrinology Metabolism, during the conduct of the trial. Zambon Netherlands BV provided trial materials consisting of all ursodeoxycholic acid tablets and an ultrasonography device. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: We declare no competing interests.

Background: Gallstone disease has been associated with colorectal cancer and some form of polyps, although the findings are inconclusive. It remains unknown whether gallstone disease influences the initiation of colorectal cancer., Methods: We prospectively assessed the association of gallstone disease with risk of colorectal cancer precursors, including conventional adenomas and serrated polyps, in the Nurses' Health Study (1992-2012), the Nurses' Health Study II (1991-2011), and the Health Professionals Follow-up Study (1992-2012). Gallstone diseases were assessed using biennial follow-up questionnaires. Self-reported polyp diagnosis was confirmed by review of medical records. Logistic regression models were used to calculate the ORs with adjustment for smoking and other potential confounders., Results: Among participants who had undergone a total of 323,832 endoscopies, 16.5% had gallstone disease and 11.3% received cholecystectomy. We documented 1,724, 1,212, and 1,943 cases of conventional adenomas and 1,470, 1,090, and 1,643 serrated polyps in patients with gallstones, cholecystectomy, and either of them, respectively. The OR for adenomas was 1.00 [95% confidence interval (CI): 0.95-1.06] for gallstones, 0.99 (95% CI, 0.93-1.06) for cholecystectomy, and 1.00 (95% CI, 0.95-1.05) for either exposure. The corresponding ORs for serrated polyps were 0.98 (95% CI, 0.92-1.04), 0.99 (95% CI, 0.93-1.06), and 0.97 (95% CI, 0.92-1.03), respectively., Conclusions: Gallstone disease is not associated with colorectal polyps., Impact: Patients with gallstones appear to have similar risk of colorectal polyps compared with those without and may therefore follow average-risk colorectal cancer screening guidelines., (©2021 American Association for Cancer Research.)

Introduction: Obesity and rapid weight loss after bariatric surgery (BS) are risk factors for the development of cholelitiasis. The aim of this study is to know the incidence of the de novo symptomatic cholelitiasis (DNSC) after BS and to analyze the risk factors for its development., Methods: Single-centre retrospective observational study of patients undergoing BS between January 2010 and December 2017. The incidence of DNSC has been studied and sex, age, comorbilities, surgical tecnique, initial BMI and percentage of excess BMI lost (%EBMIL) at 6th, 12th and 24th postoperative months have been analyzed., Results: Among the 415 patients who underwent BS, 280 have been studied since they were not previously cholecystectomized and had a preoperative negative abdominal ultrasound. Twenty-nine developed DNSC (10,35%), with a remarkably higher increase in cumulative incidence during the first postoperative year (CI 5%, IC 95% 2,4-7,6). A higher percentage of excess BMI lost at the 6, 12 and 24 postoperative months was statistically significantly correlated with an increased risk of DNSC., Conclusions: Incidence of DNSC and cholecystectomy after BS are relatively high, mainly during rapid weight loss period and even more the higher the percentage of excess BMI lost is. Concomitant cholecystectomy during BS in case of preoperative cholelithiasis regardless of symptoms and the use of ursodeoxycholic acid during the period of greater risk for DNSC development are two therapeutic options to consider., (Copyright © 2020 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To investigate the relationship of cholelithiasis and urolithiasis with Methylenetetrehydrofolate Reductase (MTHFR) polymorphism(s) in patients with poor obstetric history to search whether they are risk factors for adverse pregnancy outcome., Materials and Method: This study is consisted of 94 patients with poor obstetric history. Patients were evaluated in terms of the presence of cholelithiasis and urolithiasis in association with MTHFR polymorphism(s). Additional laboratory tests including homocysteine measurements were also performed. ROC analysis for assessing the performance of blood homocysteine level in predicting the presence of cholelithiasis and urolithiasis were also performed., Results: Patients were divided into three groups such as cholelithiasis group (n = 9, 9.6%), urolithiasis group (n = 18, 19.1%) and control group (n = 67, 71.3%). Groups did not differ in term of age and Beksac obstetrics index (BOI) which is "[living child+(π/10)]/gravidity." The rate of the presence of MTHFR polymorphisms were 88.9% (8/9), 88.9% (16/18) and 43.3% (29/67) in cholelithiasis, urolithiasis and control groups respectively. Median homocysteine levels were found to be 13.1, 11.6 and 7.2 micromol/lt for the groups respectively. Statistically significant differences were found for MTHFR polymorphism rates and homocysteine levels (<0.001 for both). According to ROC analysis, 10.9 mcmol/L (88.9% sensitivity, 89.6% specificity) and 9.25 mcmol/L (83.3% sensitivity, 73.1% specificity) were determined to be cutoff values of homocysteine for cholelithiasis and urolithiasis respectively., Conclusion: More frequent MTHFR polymorphisms are observed in women with a clinical history of gall or renal stones. Thus, screening of these patients may be benefical for the approprate management of their subsequent pregnancies.

Cholelithiasis is one of the most prevalent diseases in the general population. Among kidney transplant (KT) recipients, atypical clinical presentation may delay the diagnosis and proper treatment. This single-center retrospective cohort study compared cholelithiasis clinical presentation and cholecystectomy-associated complications in 230 KT recipients and in 172 members of the general population. KT recipients had a higher proportion of men, comorbidities, biliary pancreatitis, choledocholithiasis, and acute cholecystitis clinical presentations than the general population. KT recipients presented higher American Society of Anesthesiologists scores and higher rates of emergency surgeries (15.7% vs 9.9%, P = .091), conversion (5.7% vs 1.2%, P = .019), drainage (7.8% vs 2.3%, P = .016), postoperative complications (10% vs 4.7%, P = .047), and longer hospital length of stay (1 vs 1 days, interquartile range, 2 vs 0 days; P < .001). There were 5 deaths, all of which occurred in KT recipients. History of diabetes mellitus, renal function, and surgical conversion were independent risk factors associated with postoperative complications. Male sex and level of renal function were independent risk factors associated with postoperative acute cholecystitis. KT was an independent risk factor associated with postoperative choledocholithiasis (adjusted odds ratio, 5.89; 95% confidence interval, 3.03-15.66) and pancreatitis (adjusted odds ratio, 6.89; 95% confidence interval, 2.99-11.61). In conclusion, KT recipients with cholelithiasis have an increased risk for clinical and surgical complications compared with the general population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Elevated systemic levels of soluble cluster of differentiation 14 (sCD14) have been associated with gallbladder cancer (GBC), but the association with sCD14 levels within the gallbladder has not been investigated. Here, we evaluated sCD14 in the bile of 41 GBC cases and 117 gallstone controls with data on 65 bile inflammation markers. We examined the relationship between bile sCD14 levels and GBC using logistic regression and stratified the analysis by stage. We included GBC-associated inflammatory biomarkers in the model to evaluate the influence of local inflammation. Bile sCD14 levels (third versus first tertile) were associated with GBC (adjusted odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.2-8.0). The association was equally strong for stage I/II (OR: 3.3, 95% CI: 0.9-15.6) and stage III/IV (OR: 3.2, 95% CI: 1.0-12.4) cancers. Including the GBC-associated inflammatory markers in the model removed the association between bile sCD14 and GBC (OR: 1.0, 95% CI: 0.3-3.5). The findings suggest that immune activation within the gallbladder may be related to GBC development, and the effect of sCD14 is influenced by inflammation. Similar associations across tumor stages suggest that elevated bile sCD14 levels may reflect changes early in GBC pathogenesis. Associations between GBC and sCD14 levels in both bile and plasma suggest sCD14 could be a potential biomarker for GBC.

Background: Bariatric surgery could increase the risk of cholelithiasis, although it is unclear whether the incidence rates of cholelithiasis are similar after different bariatric procedures., Objectives: To compare the incidence rates of cholelithiasis after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) in people with obesity., Setting: Meta-analysis of cohort studies., Methods: We searched the PubMed and Web of Science databases for relevant studies before December 2020, and estimated the summary odds ratios (OR) and 95% confidence intervals (CI) using a random-effects model or fixed-effects model, according to the heterogeneity., Results: In total, 8 cohort studies were included in this meta-analysis, and 94,855 and 106,844 participants received SG and RYGB, respectively. Compared with those receiving RYGB, the summary results showed that participants receiving SG had a 35% lower rate of cholelithiasis (OR, .65; 95% CI, .49-.86). Also, the participants receiving SG had a significantly lower incidence of cholecystectomy than those receiving RYGB (OR, .54; 95% CI, .30-.99). In a subgroup analysis, SG was associated with a significantly lower incidence of subsequent cholelithiasis than RYGB in both Western and non-Western countries. SG led to a significantly lower incidence of cholelithiasis than RYGB only when the follow-up was <2 years instead of over 2 years., Conclusion: Participants receiving SG had a significantly lower incidence of cholelithiasis than those receiving RYGB, particularly within the first 2 years after the bariatric surgery., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Laparoscopic cholecystectomy (LC) is one of the safest, most commonly performed surgical procedures, but postoperative complications including bile leak, retained stone, cholangitis, and gallstone pancreatitis following LC occur in up to 2.6% of cases and may require readmission with possible endoscopic retrograde cholangiopancreatography (ERCP) intervention. There is a paucity of literature on factors predictive of need for ERCP following LC. The goal of this study is to describe the prevalence and risk factors for readmission with indication for ERCP., Methods: We queried the ACS/NSQIP 2012-2017 Participant User Files for patients who underwent LC. Patient demographics, comorbidities, operative characteristics, and postoperative outcomes were evaluated. Multivariate logistic regression was used to identify risk factors for readmission with indication for ERCP intervention., Results: Of 275,570 patients, 11,010 (4.00%) were readmitted within the 30-day postoperative period. Among these, 930 (8.44%) were admitted with indication for ERCP intervention. On multivariate regression, readmissions were more likely in older patients, inpatients, and patients with baseline comorbidities, acute preoperative morbidity, and those discharged to care facilities. The use of intraoperative cholangiogram was associated with lower odds of readmission. Less than 10% of readmitted patients had an indication for ERCP. Those who were readmitted with an indication for ERCP were more likely to have undergone emergency surgery, experienced longer operative times, and had elevated preoperative LFTs or gallstone pancreatitis prior to surgery. The risk of 30-day mortality was significantly higher among patients who experienced any complications after their surgery (OR 13.03, 95% CI 10.57-16.07, p < 0.001)., Conclusions: Older patients, patients with greater preoperative morbidity, and those discharged to care facilities were more likely to be readmitted for any reason following laparoscopic cholecystectomy, whereas patients with evidence of complicated gallstone disease were more likely to be readmitted with an indication for ERCP, even when controlling for the use of intraoperative cholangiogram. Initiatives aimed at reducing readmission with indication for ERCP should focus on these patient subgroups.

Background: Gallstone disease (GSD) is associated with a higher risk of gastrointestinal (GI) cancer. However, it is unclear whether the associations are causal., Methods: The prospective China Kadoorie Biobank (CKB) recorded 17,598 cases of GI cancer among 510,137 participants without cancer at baseline during 10 years of follow-up. Cox regression was used to estimate hazard ratios (HRs) for specific cancer by GSD status and duration. Mendelian randomisation was conducted to assess the genetic associations of GSD with specific cancer., Results: Overall 6% of participants had symptomatic GSD at baseline. Compared with those without GSD, individuals with symptomatic GSD had adjusted HRs of 1.13 (1.01-1.29) for colorectal, 2.01 (1.78-2.26) for liver, 3.70 (2.88-4.87) for gallbladder, 2.31 (1.78-3.07) for biliary tract, and 1.38 (1.18-1.74) for pancreatic cancer. Compared with participants without GSD, the risks of colorectal, liver, gallbladder, biliary tract, and pancreatic cancer were highest during 0 to <5 years following disease diagnosis. There was evidence of genetic associations of GSD with these cancers, with odds ratios per 1-SD genetic score of 1.08 (1.05-1.11) for colorectal, 1.22 (1.19-1.25) for liver, 1.56 (1.49-1.64) for gallbladder, 1.39 (1.31-1.46) for biliary tract, and 1.16 (1.10-1.22) for pancreatic cancer. When meta-analysing the genetic estimates in CKB and UK Biobank, there was evidence of causal associations of GSD with colon cancer, gallbladder and biliary tract cancer (GBTC), and total GI cancer (RR per 1-SD: 1.05 [0.99-1.11], 2.00 [1.91-2.09], and 1.09 [1.05-1.13])., Conclusions: GSD was associated with higher risks of several GI cancers, warranting future studies on the underlying mechanisms.

Alpha thalassemia and beta-globin haplotype are considered classical genetic disease modifiers in sickle cell anemia (SCA) causing clinical heterogeneity. Nevertheless, their functional impact on SCA disease emergence and progression remains elusive. To better understand the role of alpha thalassemia and beta-globin haplotype in SCA, we performed a retrospective study evaluating the clinical manifestations of 614 patients. The univariate analysis showed that the presence of alpha-thalassemia -3.7-kb mutation (αα/-α and -α/-α) decreased the risk of stroke development (p = 0.046), priapism (p = 0.033), and cholelithiasis (p = 0.021). Furthermore, the cumulative incidence of stroke (p = 0.023) and cholelithiasis (p = 0.006) was also significantly lower for patients carrying the alpha thalassemia -3.7-kb mutation. No clinical effects were associated with the beta-globin haplotype analysis, which could be explained by the relatively homogeneous haplotype composition in our cohort. Our results reinforce that alpha thalassemia can provide protective functions against hemolysis-related symptoms in SCA. Although, several genetic modifiers can impact the inflammatory state of SCA patients, the alpha thalassemia mutation remains one of the most recurrent genetic aberration and should therefore always be considered first.