Gallstones

The Japanese Society of Gastroenterology first published evidence-based clinical practice guidelines for cholelithiasis in 2010, followed by a revision in 2016. Currently, the revised third edition was published to reflect recent evidence on the diagnosis, treatment, and prognosis of cholelithiasis conforming to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Following this revision, the present English version of the guidelines was updated and published herein. The clinical questions (CQ) in the previous version were reviewed and rearranged into three newly divided categories: background questions (BQ) dealing with basic background knowledge, CQ, and future research questions (FRQ), which refer to issues that require further accumulation of evidence. Finally, 52 questions (29 BQs, 19 CQs, and 4 FRQs) were adopted to cover the epidemiology, pathogenesis, diagnosis, treatment, complications, and prognosis. Based on a literature search using MEDLINE, Cochrane Library, and Igaku Chuo Zasshi databases for the period between 1983 and August 2019, along with a manual search of new information reported over the past 5 years, the level of evidence was evaluated for each CQ. The strengths of recommendations were determined using the Delphi method by the committee members considering the body of evidence, including benefits and harms, patient preference, and cost-benefit balance. A comprehensive flowchart was prepared for the diagnosis and treatment of gallbladder stones, common bile duct stones, and intrahepatic stones, respectively. The current revised guidelines are expected to be of great assistance to gastroenterologists and general physicians in making decisions on contemporary clinical management for cholelithiasis patients.

About 20% of adults worldwide have gallstones which are solid conglomerates in the biliary tree made of cholesterol monohydrate crystals, mucin, calcium bilirubinate, and protein aggregates. About 20% of gallstone patients will definitively develop gallstone disease, a condition which consists of gallstone-related symptoms and/or complications requiring medical therapy, endoscopic procedures, and/or cholecystectomy. Gallstones represent one of the most prevalent digestive disorders in Western countries and patients with gallstone disease are one of the largest categories admitted to European hospitals. About 80% of gallstones in Western countries are made of cholesterol due to disturbed cholesterol homeostasis which involves the liver, the gallbladder and the intestine on a genetic background. The incidence of cholesterol gallstones is dramatically increasing in parallel with the global epidemic of insulin resistance, type 2 diabetes, expansion of visceral adiposity, obesity, and metabolic syndrome. In this context, gallstones can be largely considered a metabolic dysfunction-associated gallstone disease, a condition prone to specific and systemic preventive measures. In this review we discuss the key pathogenic and clinical aspects of gallstones, as the main clinical consequences of metabolic dysfunction-associated disease.

ImportanceFemale surgeons are still in the minority worldwide, and highlighting gender differences in surgery is important in understanding and reducing inequities within the surgical specialty. Studies on different surgical procedures indicate equal results, or safer outcomes, for female surgeons, but it is still unclear whether surgical outcomes of gallstone surgery differ between female and male surgeons.ObjectiveTo examine the association of the surgeon's gender with surgical outcomes and operating time in elective and acute care cholecystectomies.Design, setting, and participantsA population-based cohort study based on data from the Swedish Registry of Gallstone Surgery was performed from January 1, 2006, to December 31, 2019. The sample included all registered patients undergoing cholecystectomy in Sweden during the study period. The follow-up time was 30 days. Data analysis was performed from September 1 to September 7, 2022, and updated March 24, 2023.ExposureThe surgeon's gender.Main outcome(s) and measure(s)The association between the surgeon's gender and surgical outcomes for elective and acute care cholecystectomies was calculated with generalized estimating equations. Differences in operating time were calculated with mixed linear model analysis.ResultsA total of 150 509 patients, with 97 755 (64.9%) undergoing elective cholecystectomies and 52 754 (35.1%) undergoing acute care cholecystectomies, were operated on by 2553 surgeons, including 849 (33.3%) female surgeons and 1704 (67.7%) male surgeons. Female surgeons performed fewer cholecystectomies per year and were somewhat better represented at universities and private clinics. Patients operated on by male surgeons had more surgical complications (odds ratio [OR], 1.29; 95% CI, 1.19-1.40) and total complications (OR, 1.12; 95% CI, 1.06-1.19). Male surgeons had more bile duct injuries in elective surgery (OR, 1.69; 95% CI, 1.22-2.34), but no significant difference was apparent in acute care operations. Female surgeons had significantly longer operation times. Male surgeons converted to open surgery more often than female surgeons in acute care surgery (OR, 1.22; 95% CI, 1.04-1.43), and their patients had longer hospital stays (OR, 1.21; 95% CI, 1.11-1.31). No significant difference in 30-day mortality could be demonstrated.Conclusions and relevanceThe results of this cohort study indicate that female surgeons have more favorable outcomes and operate more slowly than male surgeons in elective and acute care cholecystectomies. These findings may contribute to an increased understanding of gender differences within this surgical specialty.

BackgroundGallstone disease is a major health burden worldwide, and diabetes is believed to increase the risk of gallstone formation. This study investigates how diabetes promotes gallstone formation and elucidates the underlying mechanism.MethodsData from the National Health and Nutrition Examination Survey and Mendelian randomization analyses were used to identify the causal relationship between diabetes and gallstones. Through the integration of multi-omics sequencing and molecular dynamics simulation, CXCR2 was identified as a molecular bridge linking both diseases. Animal models were established, and Western blotting, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay were employed to explore the relevant mechanisms.ResultsClinical data demonstrated that diabetes is an independent risk factor for gallstones. Animal experiments revealed that diabetes upregulated the expression of CXCR2 in hepatic neutrophils, thereby promoting the formation of neutrophil extracellular traps (NETs). Excessive NETs disrupted the tight junctions between hepatocytes, allowing NETs to enter the bile and accelerate gallstone formation. Moreover, sarcosine inhibited CXCR2 expression, reduced NETs production, and decreased gallstone formation.ConclusionsDiabetes promotes NETs formation through CXCR2 activation, which damages the liver-bile barrier and facilitates gallstone development. Sarcosine may serve as a potential therapeutic agent, providing a theoretical basis for clinical intervention.