Plasma campesterol and ABCG5/ABCG8 gene loci on the risk of cholelithiasis and cholecystitis: evidence from Mendelian randomization and colocalization analyses.

The causal relationships between plasma metabolites and cholelithiasis/cholecystitis risks remain elusive. Using two-sample Mendelian randomization, we found that genetic proxied plasma campesterol level showed negative correlation with the risk of both cholelithiasis and cholecystitis. Furthermore, the increased risk of cholelithiasis is correlating with the increased level of plasma campesterol. Lastly, genetic colocalization study showed that the leading SNP, rs4299376, which residing at the ABCG5/ABCG8 gene loci, was shared by plasma campesterol level and cholelithiasis, indicating that the aberrant transportation of plant sterol/cholesterol from the blood stream to the bile duct/gut lumen might be the key in preventing cholesterol gallstone formation.

Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes by PKCα-associated signalling under cholesterol stimulation.

BACKGROUND AND AIMS: The secretion of bile salts transported by the bile salt export pump (BSEP) is the primary driving force for the generation of bile flow; thus, it is closely related to the formation of cholesterol stones. Caveolin-1 (Cav-1), an essential player in cell signalling and endocytosis, is known to co-localize with cholesterol-rich membrane domains. This study illustrates the role of Cav-1 and BSEP in cholesterol stone formation. METHODS: Adult male C57BL/6 mice were used as an animal model. HepG2 cells were cultured under different cholesterol concentrations and BSEP, Cav-1, p-PKCα and Hax-1 expression levels were determined via Western blotting. Expression levels of BSEP and Cav-1 mRNA were detected using real-time PCR. Immunofluorescence and immunoprecipitation assays were performed to study BSEP and Hax-1 distribution. Finally, an ATPase activity assay was performed to detect BSEP transport activity under different cholesterol concentrations in cells. RESULTS: Under low-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels significantly increased, PKCα phosphorylation significantly decreased, BSEP binding capacity to Hax-1 weakened, and BSEP function increased. Under high-concentration stimulation with cholesterol, Cav-1 and BSEP protein and mRNA expression levels decreased, PKCα phosphorylation increased, BSEP binding capacity to Hax-1 rose, and BSEP function decreased. CONCLUSION: Cav-1 regulates the bile salt export pump on the canalicular membrane of hepatocytes via PKCα-associated signalling under cholesterol stimulation.

Association between cholelithiasis, cholecystectomy, and risk of breast and gynecological cancers: Evidence from meta-analysis and Mendelian randomization study.

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.

Safety, efficacy, and feasibility of percutaneous transhepatic endoscopic holmium laser lithotripsy for bile duct stones.

OBJECTIVE: To evaluate the safety and efficacy of percutaneous transhepatic endoscopic holmium laser lithotripsy (PTEHL) for patients with intrahepatic bile duct (IHBD) and common bile duct (CBD) stones. MATERIAL AND METHODS: This retrospective study included 530 patients (mean age: 55.6 ± 8.5; 64.2% female) with IHBD and/or CBD stones at a single institution from January 2019 to December 2021. PTEHL was the chosen treatment for patients with large, complex stones, or those for whom Endoscopic Retrograde Cholangiopancreatography (ERCP) failed or presented difficulties. Patients showing signs of cholangitis required pre-PTEHL drainage. Stone clearance was confirmed by post-procedural cholangiography, and the technique was deemed successful when target stones were removed. Complications were recorded according to the Society of Interventional Radiology adverse event classification. RESULTS: The mean stone size was 20.9 ± 11.9 mm, multiple stones observed in 460 patients (86.8%). A total of 225 patients (42.5%) had stones in both the IHBD and CBD; biliary-enteric anastomosis in 50 patients (9.4%). ERCP for stone removal proved unsuccessful in 18 patients (3.4%). Pre-IHBD drainage was performed in 271 patients (51.1%). The majority (488 patients, 92.1%) underwent a single PTEHL session. The technique was successful in 523 patients (98.7%), with 7 patients requiring surgery due to unsuccessful target stone removal. Complications were noted in 75 patients (14.2%), including 4.7% with severe complications and 9.4% with minor complications. CONCLUSION: PTEHL is a safe and effective method for the treatment of both intrahepatic and extrahepatic bile duct stones. This approach is a valuable option for complex stone cases, particularly when ERCP is unsuccessful or encounters significant challenges. CLINICAL RELEVANCE STATEMENT: Percutaneous Transhepatic Endoscopic Holmium Laser Lithotripsy is a safe and effective treatment method for intrahepatic and extrahepatic biliary stones, particularly in cases of complex stones. KEY POINTS: Percutaneous transhepatic biliary stone removal is difficult for large or intraductal stones. Percutaneous Transhepatic Endoscopic Holmium Laser Lithotripsy (PTEHL) demonstrated a high success rate with few major complications. PTEHL can treat biliary stones, particularly stones that are difficult or have failed ERCP treatment.

Bridging the Gap: Comparison of Outpatient Clinic and Emergency Department Patients Undergoing Cholecystectomy.

INTRODUCTION: Literature shows failure of the outpatient clinic (OC) pathway after emergency department (ED) ultrasound diagnosis of symptomatic cholelithiasis (SC). We hypothesized SC to be more prevalent on final surgical pathology (FSP) in patients who successfully completed OC pathway. METHODS: This retrospective single-institution chart review compared OC and ED patients with right upper quadrant (RUQ) pain and cholelithiasis whom underwent cholecystectomy. Clinical evaluation was considered positive if RUQ pain >4 h, or + Murphy's sign. Ultrasound was positive if two of these three were present: sonographic Murphy's, wall thickness > 4 mm, or pericholecystic fluid. Results were compared with FSP. RESULTS: Six hundred-seven patients underwent cholecystectomy, 299 OC and 308 ED. OC was more likely to SC (23% versus 4.6%) (P < 0.0001) and ED acute cholecystitis (39.3% versus 4.7%). Chronic cholecystitis was the most common FSP in both OC (72%) and ED (56%) populations, of these, 73% of OC denied pain >4 h versus only 10% of ED (P < 0.001). Median time from evaluation to cholecystectomy was 14 d versus 14 h in the OC and ED respectively (P < 0.0001). CONCLUSIONS: While chronic cholecystitis was the most common FSP in both OC and ED, the majority of OC reported RUQ pain <4 h delineating these presentations. Duration of pain should be utilized as algorithm triage. We recommend patients with pain episode <4 h should complete OC algorithm with expedited cholecystectomy within 14 d.

Genetic risk, adherence to healthy lifestyle behaviors, and risk of cholelithiasis: A population-based cohort study.

OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.

Helicobacter pylori infection associated with an increased incidence of cholelithiasis: A retrospective real-world cohort study of 50 832 patients.

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.

Investigating the influence of the gut microbiome on cholelithiasis: unveiling insights through sequencing and predictive modeling.

BACKGROUND: Cholelithiasis is one of the most common disorders of hepatobiliary system. Gut bacteria may be involved in the process of gallstone formation and are, therefore considered as potential targets for cholelithiasis prediction. OBJECTIVE: To reveal the correlation between cholelithiasis and gut bacteria. METHODS: Stool samples were collected from 100 cholelithiasis and 250 healthy individuals from Huzhou Central Hospital; The 16S rRNA of gut bacteria in the stool samples was sequenced using the third-generation Pacbio sequencing platform; Mothur v.1.21.1 was used to analyze the diversity of gut bacteria; Wilcoxon rank-sum test and linear discriminant analysis of effect sizes (LEfSe) were used to analyze differences in gut bacteria between patients suffering from cholelithiasis and healthy individuals; Chord diagram and Plot-related heat maps were used to analyze the correlation between cholelithiasis and gut bacteria; six machine algorithms were used to construct models to predict cholelithiasis. RESULTS: There were differences in the abundance of gut bacteria between cholelithiasis and healthy individuals, but there were no differences in their community diversity. Increased abundance of Costridia, Escherichia flexneri, and Klebsiella pneumonae were found in cholelithiasis, while Bacteroidia, Phocaeicola, and Phocaeicola vulgatus were more abundant in healthy individuals. The top four bacteria that were most closely associated with cholelithiasis were Escherichia flexneri, Escherichia dysenteriae, Streptococcus salivarius, and Phocaeicola vulgatus. The cholelithiasis model based on CatBoost algorithm had the best prediction effect (sensitivity: 90.48%, specificity: 88.32%, and AUC: 0.962). CONCLUSION: The identification of characteristic gut bacteria may provide new predictive targets for gallstone screening. As being screened by the predictive model, people at high risk of cholelithiasis can determine the need for further testing, thus enabling early warning of cholelithiasis.

Digital cholangioscopy-assisted, direct visualization-guided, radiation-free, endoscopic retrograde intervention for cholelithiasis: technical feasibility, efficacy, and safety.

BACKGROUND: Nonradiation, digital cholangioscope (DCS)-assisted endoscopic intervention for cholelithiasis has not been widely performed. For this study, we aimed to report the feasibility, efficacy, and safety of an established DCS-guided lithotomy procedure. METHODS: Data relating to biliary exploration, stone clearance, adverse events, and follow-up were obtained from 289 patients. The choledocholithiasis-related outcomes via the DCS-guided procedure were subsequently compared to those via conventional endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Biliary access was achieved in 285 patients. The technical success rate for the exploration of the common bile duct, the cystic stump, the hilar ducts, and secondary radicals was 100%. Moreover, the success rates were 98.4%, 61.7%, and 20.7%, for the exploration of the cystic duct, complete cystic duct, and gallbladder, respectively. Suspicious or confirmed suppurative cholecystitis, cholesterol polyps, and hyperplastic polyps were detected in 42, 23, and 5 patients, respectively. Stone clearance was achieved in one session in 285 (100%), 11 (100%), 13 (100%), 7 (100%), 6 (100%), and 3 (14.3%) patients with choledocholithiasis and hepatolithiasis, cystic duct stump stones, nondiffuse located intrahepatic lithiasis, a single cystic duct stone, a single gallbladder stone, and diffuse located intrahepatic lithiasis, respectively. Complete stone clearance for diffuse intrahepatic lithiasis was achieved in 19 (90.5%) patients, and fractioned re-lithotomy was performed in 16 (76.2%) patients. One patient developed mild acute cholangitis, and 12 developed mild pancreatitis. Stones recurred in one patient. Compared with conventional ERCP, DCS-guided lithotomy has the advantages of clearing difficult-to-treat choledocholithiasis and revealing concomitant biliary lesions, and this technique has fewer complications and a decreased risk of stone recurrence. CONCLUSIONS: The technical profile, efficacy, and safety of nonradiation-guided and DCS-guided lithotomy are shown in this study. We provide a feasible modality for the endoscopic removal of cholelithiasis.

Therapeutic Potential of Danyankang Capsule in High-Fat Diet-Induced Cholelithiasis and Its Impact on Liver FXR Signaling and Gut Microbiota.

Cholelithiasis, commonly known as gallstones, represents a prevalent hepatobiliary disorder. This study aimed to elucidate the therapeutic role and mechanism of Danyankang capsulein treating cholelithiasis induced by a high-fat diet in C57BL/6 mice. The therapeutical potential of Danyankang was assessed through biochemical analyses, histopathological examinations, protein detection, and 16S rDNA sequencing. A high-fat diet resulted in cholelithiasis manifestation in mice, with discernable abnormal serum biochemical indices and disrupted biliary cholesterol homeostasis. Danyankang treatment notably ameliorated liver inflammation symptoms and rectified serum and liver biochemical abnormalities. Concurrently, it addressed biliary imbalances. Elevated expressions of toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB)/pNF-κB, HMGCR, CYP7A1, and CYP8B1 observed at the inception of cholelithiasis, were notably reduced upon Danyankang administration. Furthermore, 16S rDNA analysis revealed a decline in species number and diversity of the intestinal flora in cholelithiasis-treated mice, while the decline was reversed with Danyankang treatment. Danyankang capsules reduced the abundance of Verrucomicrobiota and increased the abundance of Actinobacteriota and Proteobacteria. In conclusion, the present study demonstrates that Danyankang exerts potent therapeutic efficacy against high-fat diet-induced cholelithiasis. This beneficial outcome is potentially linked to the inhibition of the TLR4/pNF-κB and SHP/CYP7A1/CYP8B1 signaling pathways, as well as the enhancement of intestinal flora species abundance.

Risk of Gallstone Disease in Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

OBJECTIVE: Apart from renal stones, primary hyperparathyroidism (PHPT) has been linked to the occurrence of gallstone disease (GSD). Nevertheless, the association is not consistent across all studies. The present systematic review and meta-analysis aims to collate the hitherto available evidence and provide a pooled estimate of the association between GSD and PHPT. METHODS: PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched from inception till May 10, 2023 for observational studies reporting the prevalence of GSD (in terms of absolute numbers) in patients with PHPT. The pooled prevalence of GSD and odds ratio with 95% CI of the occurrence of GSD in patients with PHPT as compared to age- and sex-matched controls were calculated. Subgroup analysis was performed based on patient ethnicity (Indian/Caucasian). Statistical analysis was carried out using R version 4.2.2. Random-effects model with Hartung-Knapp adjustment was used for analyses. RESULTS: A total of 7 observational studies were included, pooling data from 15 949 patients with PHPT. The pooled prevalence of GSD in patients with PHPT was 16% (95% CI: 7%, 25%, I2 = 99%), being 13% (95% CI: 0%, 66%, I2 = 76%) in Indians, and 17% (95% CI: 4%, 31%, I2 = 99%) in Caucasians. Data consolidated from 3 studies showed that the pooled odds ratio of occurrence of GSD in patients with PHPT compared to controls was 1.77 (95% CI: 1.60, 1.97, P < .001, I2 = 0%). CONCLUSIONS: GSD is more prevalent in patients with PHPT than in the general population. Thus, PHPT may be considered an additional risk factor for GSD.

Higher incidence of cholelithiasis with Roux-en-Y reconstruction compared with Billroth-I after laparoscopic distal gastrectomy for gastric cancer: a retrospective cohort study.

PURPOSE: Cholelithiasis occurs often after gastrectomy. However, no consensus has been established regarding the difference in the incidence of postgastrectomy cholelithiasis with different reconstruction methods. In this study, we examined the frequency of cholelithiasis after two major reconstruction methods, namely Billroth-I (B-I) and Roux-en-Y (R-Y) following laparoscopic distal gastrectomy (LDG) for gastric cancer. METHODS: Among 696 gastric cancer patients who underwent LDG between April 2000 and March 2017, after applying the exclusion criteria, 284 patients who underwent B-I and 310 who underwent R-Y were examined retrospectively. The estimated incidence of cholelithiasis was compared between the methods, and factors associated with the development of cholelithiasis in the gallbladder and/or common bile duct were investigated. RESULTS: During the median follow-up of 61.2 months, 52 patients (8.8%) developed cholelithiasis postgastrectomy; 12 patients (4.2%) after B-I and 40 (12.9%) after R-Y (p = 0.0002). Among them, choledocholithiasis was more frequent in patients who underwent R-Y (n = 11, 27.5%) vs. B-I (n = 1, 8.3%) (p = 0.0056). Univariate and multivariate analyses revealed that male sex, body mass index > 22.5 kg/m2, and R-Y reconstruction were significant predictors of the development of postLDG cholelithiasis. CONCLUSION: Regarding cholelithiasis development, B-I reconstruction should be preferred whenever possible during distal gastrectomy.

Factors associated with postoperative nausea and vomiting after laparoscopic cholecystectomy at the National Referral Hospital, Bhutan: a cross-sectional study.

INTRODUCTION: Postoperative nausea and vomiting (PONV) are common distressing symptoms experienced after laparoscopic cholecystectomy. We report the rate, and the factors associated with postoperative nausea and vomiting, the patterns of prophylactic antiemetic prescription, and the anesthetic techniques used among patients who underwent laparoscopic cholecystectomy at the Jigme Dorji Wangchuck (JDW) National Referral Hospital, Bhutan. METHODS: A cross-sectional study was conducted at the JDW National Referral Hospital, from January to December 2018. All the patients who underwent laparoscopic cholecystectomy under general anesthesia were included in the study. The demographic variables, premedication, induction agents, muscle relaxants, inhalational agents for maintenance, opioid and adjuvant analgesics, the reversal agents used, and the occurrence of PONV within 24 h were recorded. Data were analyzed using SPSS (version 23). Continuous variables were compared using a t-test or Mann-Whitney test, categorical variables were tested using chi-square or Fisher's exact tests. Binary logistic regression analysis was performed to determine the factors associated with postoperative nausea and vomiting. RESULTS: 190 patients underwent laparoscopic cholecystectomy under general anesthesia. The rate of PONV after laparoscopic cholecystectomy was 31.1% (59/190). Over half (53.7%, 102/190) of the study population were within 21-40 years of age, over 80% (157/190) were female, and 2/3rd were overweight and obese. The most frequently used premedication was ranitidine (39%, 34/87) and metoclopramide (31%, 27/87). More than half (57.4%, 109/190) of the patients received morphine as an opioid analgesic before induction. Sodium thiopentone was a commonly used induction agent (65.8%, 125/190). Succinylcholine and atracurium were mostly preferred muscle relaxants. Isoflurane and air were the most used inhalational anesthetic agents for the maintenance of anesthesia. Ondansetron was the most preferred anti-emetics during the intraoperative period. Previous history of motion sickness (OR 5.8, 95%CI 2.9-11.2, p < 0.001), and use of sodium thiopental (OR 4.1, 95%CI 1.9-9.1, p < 0.001) were independent risk factors for PONV. The use of antiemetics (OR 0.1, 95%CI 0.0-0.4, p = 0.002), propofol (OR 0.2, 95%CI 0.1-0.5, p < 0.001), adjuvant analgesic paracetamol (OR 0.4, 95%CI 0.2-0.8, p = 0.026), and adequate hydration with IV fluids (OR 0.9, 95%CI 0.9-1.0, p = 0.042) were preventive factors for PONV. CONCLUSION: The rate of PONV after laparoscopic cholecystectomy was high. History of motion sickness and use of sodium thiopental for induction were independent risk factors of PONV. The use of multimodal prophylactic antiemetics was robust and superior to monotherapy in preventing PONV. This finding re-emphasizes the need for risk stratification and appropriate use of antiemetics and anesthetic agents to prevent PONV.

Causal associations of cytokines and growth factors with cholelithiasis: a bidirectional Mendelian randomization study.

BACKGROUND: It has been reported that patients with cholelithiasis may have changes in levels of cytokines and growth factors, while their causal relationships were still unclear. METHODS: This study was a bidirectional Mendelian randomization (MR) study. Datasets of 41 circulation cytokines and growth factors and the data on cholelithiasis were obtained. Six steps of strict instrumental variable filtration were set, and inverse-variance weighted analysis, MR-Egger regression, and weighted median test were used to identify the causal relationships. Benjamini-Hochberg method was used to adjust the P-values. RESULTS: After adjustments of P-values, four cytokines and growth factors were still causally associated with cholelithiasis significantly: interleukin 2 receptor alpha (adjusted P: 4.59E-02), interleukin 8 (adjusted P: 1.09E-02), monocyte-specific chemokine 3 (adjusted P: 2.73E-04), and stem cell factor (adjusted P: 2.73E-04). In the reverse MR analysis, no significant causal relationship was detected after adjustment. CONCLUSIONS: Four cytokines and growth factors, including interleukin 2 receptor alpha, interleukin 8, monocyte-specific chemokine 3, and stem cell factor, were proven to relate to cholelithiasis causally and unidirectionally.

Association between sarcopenia-related markers and cholelithiasis: A prospective and Mendelian randomization study.

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.

A Comparative Investigation of the Bile Microbiome in Patients with Choledocholithiasis and Cholecystolithiasis through Metagenomic Analysis.

While the precise triggers of gallstone formation remain incompletely understood, it is believed to arise from a complex interplay of genetic and environmental factors. The bile microbiome is being increasingly recognized as a possible contributor to the onset of gallstone disease. The primary objective of this study was to investigate distinctions in the microbial communities within bile specimens from patients with choledocholithiasis (common bile duct stones) and cholecystolithiasis (gallbladder stones). We employed massively parallel sequencing of the 16S rRNA gene to examine the microbial communities within bile samples obtained from 28 patients with choledocholithiasis (group DS) and cholecystolithiasis (group GS). The taxonomic composition of the bile microbial communities displayed significant disparities between the group DS and the group GS. Within the 16 prevalent genera, only Streptococcus, Ralstonia, Lactobacillus, and Enterococcus were predominantly found in the group GS. In contrast, the group DS displayed a more diverse range of genera. The alpha diversity of bile specimens was also notably lower in the group GS compared to the group DS (p = 0.041). Principal coordinate analysis unveiled distinct clustering of bile microbial communities depending on the location of the gallstone. Linear discriminant analysis effect size analysis, with a score threshold of >3 and the Kruskall-Wallis test (α < 0.05), recognized Bacilli and Lactobacillales as potential taxonomic markers for distinguishing patients with cholecystolithiasis limited to the gallbladder. Significant variations were found in the distribution and diversity of bile microbial communities between patients with choledocholithiasis and cholecystolithiasis. This observation suggests that alterations in the bile microbiome may contribute to the development of gallstones in these patients.

[Prognosis of a high risk of non-alcoholic fatty liver disease in the long-term period of laparoscopic cholecystectomy in the elderly and senile.]

After cholecystectomy, elderly patients require special attention, due to the influence of involution processes in the body on the formation of complications. To identify prognostic criteria for the formation of fatty liver degeneration in the long-term period of minimally invasive cholecystectomy, 159 men were examined. Dysregulation of the biliary tract was determined using magnetic resonance cholangiopancreatography, elastography and magnetic resonance imaging of the liver. Microbial markers of the wall microbiome of the intestine were determined using chromatography-mass spectrometry. The relationship between an increase in body mass index and a decrease in the amount of obligate microbiome (r=-0,43, p<0,050), as well as with the formation of fatty liver degeneration in elderly patients, was revealed. The features of vegetative regulation in elderly people with fatty liver degeneration have been determined. It has been proven that in old age, a decrease in the number of obligate anaerobic association of microorganisms of the small intestine (on average from 15 659 to 7 630 in persons of the 2nd age subgroup and from 1 457 to 17 837 in the 3rd) is a predictor of fatty liver degeneration. The prognostic algorithm developed on the basis of the analysis of highly informative signs makes it possible to identify with an accuracy of at least 75% a high risk of fatty liver degeneration in the long-term period of cholecystectomy.

Pediatric gallstone disease-Management difficulties in clinical practice.

BACKGROUND: Gallstone disease (GD) is no longer an exclusive condition of adulthood, and its prevalence is increasing in pediatric age. The management and the extent of the etiological investigation of GD in children and adolescents remains controversial. This study aimed to analyze the difficulties in the work-up and management of pediatric GD patients. METHODS: A retrospective study performed in a single tertiary center enrolled sixty-five patients with GD followed from January 2014 to June 2021. Patients were categorized conveniently according to their age at diagnosis: Group A (<10years, n=35) and Group B (≥10years, n=30). We analyzed demographic, clinical and laboratory data, ultrasonographic findings at presentation, therapeutics and complications. RESULTS: Symptoms were more frequent in patients >10years old (p=0.001). Cholecystectomy was performed in 31 patients (47.7%). A multivariate regression logistic model identified the age >10years (OR=6.440, p=0.005) and underlying entities (OR=6.823, p=0.017) as independent variables to perform surgery. Spontaneous resolution of GD was more common in children <2years old. A multivariate regression logistic model showed a trend for those >10years old to develop more complications. Two out of 18 patients were diagnosed with ABCB4 gene mutations in heterozygosity. CONCLUSIONS: Decision-making on cholecystectomy remains challenging in asymptomatic patients. Identifying predictive factors for the development of complications has proven difficult. However, we found a trend toward the development of complications in individuals older than 10years.

Aetiology, presentation and outcomes of patients presenting with acute pancreatitis in a tertiary care hospital.

Acute pancreatitis (AP) is a multi-causal disease with a high rate of hospita lisation. Only a few cl inical stud ies have i nvestig ated the aetiologic al backgroun d, sever it y, and outcome of AP in Pakistan. Hence, this study was carried out to determine the aforementioned factors and correlate them w ith outcomes in a tert iary care set ting. This was a cros s -sec tional, retrospective study conducted at the Department of Gast roe nterolo gy, Aga Khan University Hospita l, Karachi, from Januar y 1, 2022, to December 31, 2022. Data was analysed using statis tical s oftware SPSS version 25. Vomiting was th e predominant presenting complaint and was seen in 139 (78.5%) patients. Gallstones were the predominant cause in 68 (37%) patients, followed by idiop athic panc reatitis in 22 (12%) p atients. Thirteen (7.1 % ) pat ients expire d. Patients with syst emi c complications were lik ely to suffer fro m severe disease (p=0.0 2), whereas those with lo cal complications were at an increa sed ris k of mor tal it y (p=0.04). Due to lac k of diagnostic facilities, the aetiology of a large number of AP cases remains unknown.

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Cholelithiasis is a common disease of the digestive system. The risk factors for cholelithiasis have been reported and summarized many times in the published literature, which primarily focused on cross-sectional studies. Due to the inherent limitations of the study design, the reported findings still need to be validated in additional longitudinal studies. Moreover, a number of new risk factors for cholelithiasis have been identified in recent years, such as bariatric surgery, hepatitis B virus infection, hepatitis C virus infection, kidney stones, colectomy, osteoporosis, etc. These new findings have not yet been included in published reviews. Herein, we reviewed the 101 cholelithiasis-associated risk factors identified through research based on longitudinal investigations, including cohort studies, randomized controlled trials, and nested case control studies. The risk factors associated with the pathogenesis of cholelithiasis were categorized as unmodifiable and modifiable factors. The unmodifiable factors consist of age, sex, race, and family history, while the modifiable factors include 37 biological environmental factors, 25 socioenvironmental factors, and 35 physiochemical environmental factors. This study provides thorough and comprehensive ideas for research concerning the pathogenesis of cholelithiasis, supplying the basis for identifying high-risk groups and formulating relevant prevention strategies.