To review the evidence for the use of different non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of biliary colic.

A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile, this phenomenon is far less studied, and with this report, we describe the interactions between the BAs and microbiota in this complex biological matrix. Methodology. Thirty-seven gallstone disease patients of which twenty-one with Opisthorchis felineus infection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acid composition was measured by LC-MS/MS. Gallbladder microbiota were previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acid composition and microbiota were analyzed.

Diseases of the gallbladder are common and costly. The best epidemiological screening method to accurately determine point prevalence of gallstone disease is ultrasonography. Many risk factors for cholesterol gallstone formation are not modifiable such as ethnic background, increasing age, female gender and family history or genetics. Conversely, the modifiable risks for cholesterol gallstones are obesity, rapid weight loss and a sedentary lifestyle. The rising epidemic of obesity and the metabolic syndrome predicts an escalation of cholesterol gallstone frequency. Risk factors for biliary sludge include pregnancy, drugs like ceftiaxone, octreotide and thiazide diuretics, and total parenteral nutrition or fasting. Diseases like cirrhosis, chronic hemolysis and ileal Crohn's disease are risk factors for black pigment stones. Gallstone disease in childhood, once considered rare, has become increasingly recognized with similar risk factors as those in adults, particularly obesity. Gallbladder cancer is uncommon in developed countries. In the U.S., it accounts for only ~ 5,000 cases per year. Elsewhere, high incidence rates occur in North and South American Indians. Other than ethnicity and female gender, additional risk factors for gallbladder cancer include cholelithiasis, advancing age, chronic inflammatory conditions affecting the gallbladder, congenital biliary abnormalities, and diagnostic confusion over gallbladder polyps.

The risk factors of cholelithiasis have not been clearly identified, especially for total cholesterol. Here, we try to identify these causal risk factors.

Leptin and its receptor play several physiological roles in the canine gallbladder, and the dysregulation of leptin might play a role in the pathogenesis of gallbladder diseases such as gallbladder mucocele. Previous studies revealed a positive association between hyperlipidemia and gallstones in humans. However, the latter is still unclear in dogs with cholelithiasis. In this study, we examined the differences in leptin, leptin receptor, total cholesterol, and triglyceride levels between healthy dogs and dogs with cholelithiasis, and evaluated the correlation between leptin and hyperlipidemia. Twenty-eight healthy dogs and 34 client-owned dogs with cholelithiasis were enrolled in the study. Leptin concentrations and lipid profiles were determined from sera, and leptin and leptin receptor expression levels were quantified in gallbladder tissue. In dogs with cholelithiasis, serum concentrations of leptin (p < 0.001), total cholesterol (p < 0.001), and triglycerides (p < 0.001) were significantly higher compared with those in healthy dogs. Positive correlations were observed between serum leptin and total cholesterol (95% confidence interval (CI) = 0.61-0.89, r = 0.725, p < 0.001), and between leptin and triglycerides (95% CI = 0.63-0.89, r = 0.782, p < 0.001) in the cholelithiasis group. Hypercholesterolemia (Odds Ratio (OR) = 9.720; 95% CI = 1.148-82.318) and hypertriglyceridemia (OR = 12.913; 95% CI = 1.548-107.722) were shown to be risk factors for gallstone disease. In cholelithiasis patients who underwent cholecystectomy, serum leptin levels were significantly higher than in patients that had not undergone surgery (p < 0.001). Leptin and leptin receptor expression was upregulated in the gallbladder tissues of cholelithiasis patients (p < 0.01 and p < 0.001, respectively). These results indicate that increased serum leptin concentrations and hyperlipidemia (hypercholesterolemia or hypertriglyceridemia) are associated with canine cholelithiasis and that homeostatic imbalance of these parameters might affect the pathogenesis of gallstones.

(1) Background: Disturbances in the sphingolipid profile are observed in many diseases. There are currently no data available on the evaluation of sphingolipids and ceramides in cholelithiasis in children. The aim of this study was to evaluate the concentrations of sphingolipids in the sera of pediatric patients with gallstones. We determined their relationship with anthropometric and biochemical parameters. (2) Methods: The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, ultra-high-performance liquid chromatography-tandem mass spectrometry. (3) Results: The prospective study included 48 children and adolescents diagnosed with gallstones and 38 controls. Serum concentrations of total cholesterol (TC); sphinganine (SPA); ceramides-C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer and C24:1-Cer; and lactosylceramides-C16:0-LacCer, C18:0-LacCer, C18:1-LacCer, C24:0-LacCer and C24:1-LacCer differed significantly between patients with cholelithiasis and without cholelithiasis. After adjusting for age, gender, obesity and TC and TG levels, we found the best differentiating sphingolipids for cholelithiasis in the form of decreased SPA, C14:0-Cer, C16:0-Cer, C24:1-LacCer and C24:0-LacCer concentration and increased C20:0-Cer, C24:1-Cer, C16:0-LacCer and C18:1-LacCer. The highest area under the curve (AUC), specificity and sensitivity were determined for C16:0-Cer with cholelithiasis diagnosis. (4) Conclusions: Our results suggest that serum sphingolipids may be potential biomarkers in pediatric patients with cholelithiasis.

Multidrug resistance 3 (MDR3) is expressed on the canalicular membrane of the hepatocytes and plays an important role in protecting the liver from bile acids. Altered ABCB4 gene expression can lead to a rare hepatic disease, low phospholipid-associated cholelithiasis (LPAC). In this study, we characterized 3 ABCB4 mutations in LPAC patients using various in vitro assay systems. We first measured the ability of each mutant to transport paclitaxel and then the mechanisms by which these mutations might change MDR3 transport activity were determined using immunoblotting, cell surface protein biotinylation, and immunofluorescence. Through a membrane vesicular transport assay, we observed that the uptake of paclitaxel was significantly reduced in membrane vesicles expressing 2 ABCB4 mutations, F165I and S320F. Both mutants showed significantly decreased total and cell surface MDR3 expression. These data suggest two missense mutations of ABCB4 may alter function of MDR3 and ultimately can be determined as LPAC-causing mutations.

Low-phospholipid-associated cholelithiasis (LPAC) syndrome, a rare genetic form of intrahepatic cholelithiasis in adults, is still poorly understood. We report the results of the largest-ever case-control study of patients with LPAC syndrome aiming to assess the prevalence, clinical features, and comorbidities of the disease.

Recent dietary habits and lifestyle could explain the shaping of the gut microbiota composition and, in consequence, the increasing prevalence of certain pathologies. However, little attention has been paid to the influence of diet on microbiotas, other than the gut microbiota. This is important in cholelithiasis, given that changes in the production of bile acids may affect gallbladder microbial communities. Our aim was to assess the association between regular dietary intake and gallbladder microbial composition. Fourteen adults with cholelithiasis and 14 controls, sex‒age-matched and without gastrointestinal pathology, were included. Diet was assessed through a food frequency questionnaire and quantification of gallbladder microbiota sequences by Illumina 16S rRNA gene-based analysis. The cholelithiasic patients showed greater intake of potatoes and lower consumption of vegetables, non-alcoholic drinks, and sauces, which resulted in a lower intake of energy, lipids, digestible polysaccharides, folate, calcium, magnesium, vitamin C, and some phenolic compounds. Regarding the altered bile microorganisms in cholelithiasic patients, dairy product intake was negatively associated with the proportions of Bacteroidaceae and Bacteroides, and several types of fiber, phenolics, and fatty acids were linked to the abundance of Bacteroidaceae, Chitinophagaceae, Propionibacteraceae, Bacteroides, and Escherichia‒Shigella. These results support a link between diet, biliary microbiota, and cholelithiasis.

Cholelithiasis is a common digestive system disease that imposes major burden on patients and society. Investigating the relationship between dietary factors and cholelithiasis risk can provide a basis for disease prevention. Previous studies on milk intake and cholelithiasis incidence have been limited.Therefore, the aim of our study was to assess the association between milk consumption and the incidence of cholelithiasis in males and females.

Locating diseases precisely from medical images, like ultrasonic and CT images, have been one of the most challenging problems in medical image analysis. In recent years, the vigorous development of deep learning models have greatly improved the accuracy in disease location on medical images. However, there are few artificial intelligent methods for identifying cholelithiasis and classifying gallstones on CT images, since no open source CT images dataset of cholelithiasis and gallstones is available for training the models and verifying their performance. In this paper, we build up the first medical image dataset of cholelithiasis by collecting 223846 CT images with gallstone of 1369 patients. With these CT images, a neural network is trained to "pick up" CT images of high quality as training set, and then a novel Yolo neural network, named Yolov3-arch neural network, is proposed to identify cholelithiasis and classify gallstones on CT images. Identification and classification accuracies are obtained by 10-fold cross-validations. It is obtained that our Yolov3-arch model is with average accuracy 92.7% in identifying granular gallstones and average accuracy 80.3% in identifying muddy gallstones. This achieves 3.5% and 8% improvements in identifying granular and muddy gallstones to general Yolo v3 model, respectively. Also, the average cholelithiasis identifying accuracy is improved to 86.50% from 80.75%. Meanwhile, our method can reduce the misdiagnosis rate of negative samples by the object detection model.

The aim of the present study was to investigate the effects and the underlying mechanisms of Yinchenhao Decoction (YCHD), a traditional Chinese medicine formulation, on C57BL/6 mice with lithogenic diet (LD)-induced cholelithiasis. The condition of cholelithiasis was evaluated using a six-level criteria. Levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) in the serum and liver tissue were measured using enzyme colorimetry. Concentrations of TC, phospholipids (PL) and total bile acids (TBA) in the bile were measured to calculate the cholesterol saturation index. Liver histopathology was microscopically observed and mRNA expression levels of ABCG5, ABCG8, SRBI, ABCB4, ABCB11 and NPC1L1 involved in cholesterol metabolism were measured using reverse transcription-quantitative PCR. The results showed that feeding mice the LD induced cholelithiasis, along with abnormal serum biochemical indices and imbalances in biliary cholesterol homeostasis. Increased ALT and ALP levels in the serum and ALT, ALP, TC and LDL-C levels in the serum and liver indicated the existence of hepatocyte injury, which were consistent with the pathological changes. YCHD treatment ameliorated the serum and hepatic biochemical abnormalities and adjusted the biliary imbalance. In addition, elevated expression of ATP-binding cassette subfamily G member 5/8, scavenger receptor class B type I and Niemann-Pick C1 Like 1 in the liver and small intestine were observed at the onset of cholelithiasis but were reversed by YCHD. Taken together, results from the present study suggest that YCHD ameliorated LD-induced cholelithiasis mice, which may be caused by improvements in biliary cholesterol supersaturation and regulation of cholesterol metabolism.

Ursodeoxycholic acid is used in human medicine for litholytic management of choleliths, but the efficacy of medical management in dogs with cholelithiasis is unknown.

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5 × 10(-8)). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08 × 10(-25)). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.

Salmonella typhi and Helicobacter infections have been shown to increase risk of gallbladder cancer (GBC), but findings have been inconsistent. Other bacterial infections may also be associated with GBC. However, information on microbial pathogens in gallbladder bile of GBC patients is scarce. We aimed to investigate the microbial communities in gallbladder bile of patients with GBC and cholelithiasis (CL). Seven GBC patients and 30 CL patients were enrolled in this study. Genomic DNA was extracted from bile and the V3-V4 region of 16S rRNA was amplified. The sequencing results were compared with the 16S database, and the bacteria were identified by homology searches and phylogenetic analysis. DNA was detected in the bile of three GBC (42.9%; Bolivia, 1; Chile, 2) and four CL patients (13.3%; Bolivia, 1; Chile, 3). Of the 37 patients, 30 (81.1%) were negative and unable to analyze. Salmonella typhi and Helicobacter sp. were not detected in bile from any GBC patients. As the predominant species, Fusobacterium nucleatum, Escherichia coli, and Enetrobacter sp. were detected in bile from GBC patients. Those in bile from CL patients were Escherichia coli, Salmonella sp., and Enerococcus gallinarum. Escherichia coli was detected in bile samples from both GBC and CL patients. Whether the bacteria detected in bile from GBC patients would associated with the development of GBC warrant further investigation.

Leptin has been shown to have various physiological and pathological roles in the canine gallbladder. In this study, we performed pre- and postoperative short-term follow-up analyses to confirm changes in serum leptin levels before and after cholecystectomy due to gallbladder mucocele (GBM) or cholelithiasis in dogs.

There are many variations and unclear definitions of the appropriate timing of laparoscopic cholecystectomy (LC) after endoscopic retrograde cholangiopancreatography (ERCP), and there is still a lack of consistency about the appropriate timing. Inappropriate timing can be associated with serious comorbidity and can affect the patients. This meta-analysis was conducted to assess the operative outcomes and morbidity to provide a benefit to the patients based on the best timing of LC after ERCP. Randomized controlled trials (RCTs) and retrospective studies were identified from the PubMed and Scopus databases from inception to July 2021. A meta-analysis was performed to estimate the treatment effects on operative outcomes and morbidity. Four RCTs and four retrospective studies met our inclusion criteria. A meta-analysis indicated that patients who received LC after ERCP on the same day or within 72 hours had about 0.354 days shorter length of hospital stay with a shorter operative time of about 0.111-1.835 minutes and a lower risk of complications around 37%-73%. Our evidence suggests that the appropriate timing of LC after ERCP is either the same day or within 72 hours for treating cholelithiasis patients based on the severity of disease.

The seeds of Macrotyloma uniflorum Lam. (Family Fabaceae) contain extractable total and tannins with reported hepatoprotective, hypocholesterolemic and antioxidant activity. In this study, dietary M. uniflorum seed, methanolic and acetone extracts (ME and AE) were examined for their bile-antilithogenic potential.

Background: Patients with short bowel syndrome (SBS) are at a high risk of cholestasis or cholelithiasis. This study aimed to determine the incidence, risk factors, and clinical consequences of cholelithiasis in adults with SBS over an extended period. Methods: All eligible adults diagnosed with SBS and admitted to a tertiary hospital center between January 2010 and December 2019 were retrospectively identified from the hospital records database. Kaplan-Meier analysis was used to estimate the cumulative incidence of SBS during the 10-year period. For assessment the risk factors for cholelithiasis, we used multivariate Cox proportional hazards model with estimation of hazard ratio (HR) with 95% confidence intervals (95 %CI). Results: This study enrolled 345 eligible patients with SBS. Kaplan-Meier analysis revealed that 72 patients (20.9%) developed cholelithiasis during the 10-year observation period. In multivariate analyses using the Cox proportional hazard model revealed that the remnant jejunum (HR = 2.163; 95% confidence interval [CI]: 1.156-4.047, p = 0.016) and parenteral nutrition dependence (HR = 1.783; 95% CI: 1.077-2.952, p = 0.025) were independent risk factors for cholelithiasis in adults with SBS. Twenty-eight patients developed symptoms and/or complications in the cholelithiasis group. Proportions of acute cholecystitis or cholangitis and acute pancreatitis were significantly increased in the cholelithiasis group compared with the non-cholelithiasis group (31.9 vs. 7.7%, p < 0.01; and 6.9 vs. 1.1%, p = 0.003, respectively). Conclusion: Because of the adverse clinical consequences of cholelithiasis, adult patients with SBS should be closely monitored, and preventive interventions should be considered. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04867538.

Helicobacter pylori (H. pylori) is proved to be the main pathogenic agent of various diseases, including chronic gastritis, gastric ulcer, duodenal ulcer, and gastric cancer. In addition, chronic cholecystitis and cholelithiasis are common worldwide, which are supposed to increase the total mortality of patients. Epidemiologic evidence on the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis still remains unclear. We conducted a systematic review and meta-analysis of overall studies to investigate the relationship between H. pylori infection of the gallbladder and chronic cholecystitis/cholelithiasis. Two researchers searched PubMed, Embase, and Cochrane Library databases to obtain all related and eligible studies published before July 2020. The pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by the random-effects model. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also conducted. Twenty studies were included in the meta-analysis, involving 1735 participants and 1197 patients with chronic cholecystitis/cholelithiasis. Helicobacter species infection of the gallbladder was positively correlated with increased risk of chronic cholecystitis and cholelithiasis, especially H. pylori (OR = 3.05; 95% CI, 1.81-5.14; I 2 = 23.5%). Besides, country-based subgroup analysis also showed a positive correlation between the gallbladder H. pylori positivity and chronic cholecystitis/cholelithiasis risk. For Asian and non-Asian country studies, the ORs were 4.30 (95% CI, 1.76-10.50; I 2 = 37.4%) and 2.13 (95% CI, 1.23-3.70; I 2 = 0.0%), respectively. The association was more obvious using the bile sample and urease gene primer. In conclusion, this meta-analysis provided evidence that there is a positive correlation between H. pylori infection in the gallbladder and increased risk of chronic cholecystitis and cholelithiasis.