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BACKGROUND AND AIMS: Pruritus is a debilitating symptom for many people living with primary biliary cholangitis (PBC). In studies with seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, patients with PBC experienced significant improvement in pruritus and reduction of serum bile acids. Interleukin-31 (IL-31) is a cytokine known to mediate pruritus, and blocking IL-31 signaling provides relief in pruritic skin diseases. This study examined the connection between seladelpars antipruritic effects and IL-31 and bile acid levels in patients with PBC. APPROACH AND RESULTS: IL-31 levels were quantified in serum samples from the ENHANCE study of patients with PBC receiving daily oral doses of placebo (n = 55), seladelpar 5 mg (n = 53) or 10 mg (n = 53) for 3 months, and for healthy volunteers (n = 55). IL-31 levels were compared with pruritus using a numerical rating scale (NRS, 0-10) and with bile acid levels. Baseline IL-31 levels closely correlated with pruritus NRS ( r = 0.54, p < 0.0001), and total ( r = 0.54, p < 0.0001) and conjugated bile acids (up to 0.64, p < 0.0001). Decreases in IL-31 were observed with seladelpar 5 mg (-30%, p = 0.0003) and 10 mg (-52%, p < 0.0001) versus placebo (+31%). Patients with clinically meaningful improvement in pruritus (NRS ≥ 2 decrease) demonstrated greater dose-dependent reductions in IL-31 compared to those without pruritus improvement (NRS < 2 decrease). Strong correlations were observed for the changes between levels of IL-31 and total bile acids ( r = 0.63, p < 0.0001) in the seladelpar 10 mg group. CONCLUSIONS: Seladelpar decreased serum IL-31 and bile acids in patients with PBC. The reductions of IL-31 and bile acids correlated closely with each other and pruritus improvement, suggesting a mechanism to explain seladelpars antipruritic effects.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Background and Aim: The association between biliary disorders with weight reduction enhanced by GLP-1RAs was observed frequently, nevertheless, the relative risk of the clinically relevant cholelithiasis was not specified clearly among different GLP-1RAs. Methods: 308 patients with type 2 diabetes mellitus (T2D) were recruited and divided into 4 groups; liraglutide, dulaglutide, semaglutide, versus control group; comprised of 69, 76, 71, and 92, respectively. Clinical history, examination, laboratory, and radiology tests were implemented. Results: Cholelithiasis significantly associates GLP1-RAs (p = 0.033). Overall cholelithiasis was evident in 31.2% of our participants. Symptomatic cholelithiasis prevails in 60.4% of patients with cholelithiasis. Symptomatic complicated cholelithiasis prevailed in 33.3%; distributed in 28.1%, 28.1%, 21.9%, and 21.9% in liraglutide, semaglutide, dulaglutide, and control groups, respectively. Meanwhile, symptomatic uncomplicated cholelithiasis was observed in 27.1%; distributed in 34.6%, 30.8%, 15.4%, and 19.2% in Liraglutide, semaglutide, dulaglutide, and control groups, respectively. Asymptomatic cholelithiasis was noted in 36.8%, 21.1%, 10.5%, and 31.6% of patients with dulaglutide, semaglutide, liraglutide, and control groups, respectively. Specifically, 81.1%, 68%, and 44% of patients with liraglutide, semaglutide, and dulaglutide experienced symptomatic cholelithiasis. The relative risk of cholelithiasis was 1.2, 1.3, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 17.25, 14.69, and 10.96, respectively. The relative risk of symptomatic cholelithiasis was 1.6, 0.9, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 3.14, 16.67, and 5.56, respectively. Conclusion: Liraglutide was associated with the highest risk of clinically relevant cholelithiasis than semaglutide, and dulaglutide in patients with T2D. [ABSTRACT FROM AUTHOR]

A 1‐year‐old, female, spayed dachshund presenting with clinical signs associated with cholangiohepatitis and cholangitis was found to have synthetic linear foreign material causing a common bile duct obstruction. The patient underwent a cholecystectomy, and foreign material was removed from the common bile duct via retrograde flushing into the duodenal papilla and manual retrieval. At the 6‐month post‐operative follow up visit, the patient had an improved cholestatic hepatopathy, with only a mild alkaline phosphatase elevation, moderate dilation of the common bile duct on ultrasonography, and was doing clinically well at home. 8 months post‐operatively, the patient re‐presented for an episode of septic cholangiohepatitis, with linear foreign material visualised within a dilated common bile duct on ultrasound. This episode was medically managed and was resolved with a 2‐week course of antibiotics. 1.5 years post‐operatively, the patient is doing clinically well, but continues to have persistent, moderate elevations of alanine transaminase and alkaline phosphatase. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholangiocarcinoma is a biliary neoplasm usually showing a dismal prognosis. In early stages, surgical resection is the best treatment option, significantly increasing the overall survival. This approach is also recommended in the case of relapsing disease. In this study, we report the case of a patient affected by intrahepatic cholangiocarcinoma with multiple relapses and still alive for over 18 years. We also provide a systematic review regarding long-survivor (> 60 months) of intrahepatic cholangiocarcinoma. Case Presentation: A 41-year-old woman with no pathological history was diagnosed with localized intrahepatic cholangiocarcinoma and surgically treated with left hepatectomy. After the first intervention, the patients underwent three further surgical resections because of locoregional recurrences. Histologically, there were some significant similarities among all neoplasms, including the tubule-glandular architecture, but also morphological heterogeneity. The tumor immune microenvironment remained stable across the different lesions. The molecular analysis with next-generation sequencing demonstrated that all neoplasms shared the same genomic profile, including NBN and NOTCH3 mutations and chromosomes 1 and 3 alterations. Conclusions: This case study highlights the essential role of a stringent follow-up after resection of intrahepatic cholangiocarcinoma for detecting early relapsing tumors. Moreover, it shows the importance of the molecular characterization of multiple tumors for understanding their real nature. The accurate study of long-surviving patients highlights the features that are critical for outcome improvement. [ABSTRACT FROM AUTHOR]

Background: Gallstone pancreatitis (GSP) is common in elderly patients and carries worse outcomes. Laparoscopic cholecystectomy (LC) is recommended for prevention of recurrent GSP. In frail populations, an endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP-s) is an alternative. Management guidelines of GSP in the elderly are lacking. This study aimed to investigate and compare management strategies for GSP in the elderly. Materials and methods: A retrospective comparison of outcome of patients aged ≥65 years with first presentation of GSP treated either with (1) LC only, (2) ERCP-s, (3) ERCP-S followed by LC, or (4) no intervention. Results: 216 patients were included. Median age was 76 years (interquartile range 70-83). Most (80%, n = 172) had mild pancreatitis, whilst 12% (n = 26) had severe disease. 24% (n = 55) were treated with ERCP-s; 40% (n = 87) underwent LC alone; 11% (n = 23) had ERCP-s followed by LC; and 25% (n = 55) received no intervention. Patients without intervention were older (P < .001) and frailer (P < .001). The LC-only group had lower post-procedure re-admission rates of 6% (n = 5) compared to 27% (n = 14) for ERCP-s, 33% (n = 7) for ERCP-S + LC, and 31% (n = 17) for the no intervention group (P = .0001). Biliary cause mortality was highest in the no intervention group (n = 11, 20%). Conclusion: Laparoscopic cholecystectomy represents the gold standard for elderly patients with GSP. [ABSTRACT FROM AUTHOR]

Background: Patients with low socioeconomic status (SES) are disadvantaged in terms of access to health care. A novel metric for SES is the Distressed Communities Index (DCI). This study evaluates the effect of DCI on hospital choice and distance traveled for surgery. Methods: A Florida database was queried for patients with symptomatic cholelithiasis or chronic cholecystitis who underwent an outpatient cholecystectomy between 2016 and 2019. Patients' DCI was compared with hospital ratings, comorbidities, Charlson Comorbidity Index, and distance traveled for surgery. Stepwise logistic regression was used to determine which factors most influenced distance traveled for surgery. Results: There were 54,649 cases-81 open, 52,488 laparoscopic, and 2,080 robotic. There was no difference between surgical approach and patient's DCI group (p = 0.12). Rural patients traveled the farthest for surgery (avg 21.29 miles); urban patients traveled the least (avg 5.84 miles). Patients from distressed areas more often had surgery at one- or two-star hospitals than prosperous patients (61% vs 36.3%). Regression indicated distressed or at-risk areas predicted further travel for rural/small-town patients, while higher hospital ratings predicted further travel for suburban/urban patients. Discussion: Compared to prosperous areas, patients from distressed areas have surgery at lower-rated hospitals, travel further if they live in rural/small-town areas, but travel less if they live in suburban areas. We postulate that farther travel in rural areas may be explained by a lack of health care resources in poor, rural areas, while traveling less in suburban areas may be explained by personal lack of resources for patients with low SES. [ABSTRACT FROM AUTHOR]

Introduction: The role of robotic surgery in the nonelective setting remains poorly defined. Accessibility, patient acuity, and high turn-over may limit its applicability and utilization. The goal is to characterize the role of robotic cholecystectomy (CCY) in a busy acute care surgery (ACS) practice at a quaternary medical center, and compare surgical outcomes and resource utilization between robotic and laparoscopic CCY. Methods: Adult patients who underwent robotic (Da Vinci Xi) or laparoscopic CCY between 01/2021-12/2022 by an ACS attending within 1 week of admission were included. Primary outcomes included time from admission to surgery, off hour (weekend and 6p-6a) cases, operation time, and hospital costs, to reflect "feasibility" of robotic compared to laparoscopic CCY. Secondary outcomes encompassed surgery-related outcomes and complications. Results: The proportion of robotic CCY increased from 5% to 32% within 2 years. In total 361 laparoscopic and 89 robotic CCY were performed. Demographics and gallbladder disease severity were similar. Feasibility measures--operation time, case start time, time from admission to surgery, proportion of off-hour cases, and cost--were comparable between robotic and laparoscopic CCY. There were no differences in surgical complications, common bile duct injury, readmission, or mortality. Conversion to open surgery occurred more often in laparoscopic cases (5% vs 0%, P = .02, OR = 1.05). Discussion: Robotic CCY is associated with fewer open conversions and otherwise similar outcomes compared to laparoscopic CCY in the non-elective setting. Incorporation of robotic CCY in a busy ACS practice model is feasible with available resources. [ABSTRACT FROM AUTHOR]

Introduction: Preoperative Coronavirus Disease 2019 (COVID-19) infections are associated with postoperative adverse outcomes. However, there is limited data on the impact of postoperative COVID-19 infection on postoperative outcomes of common general surgery procedures. Objective: To evaluate the impact of postoperative COVID-19 diagnosis on laparoscopic cholecystectomy outcomes. Methods: Patients with symptomatic cholelithiasis, acute cholecystitis, or gallstone pancreatitis who underwent laparoscopic cholecystectomy with or without intraoperative cholangiogram were identified using the 2021 National Surgical Quality Improvement Program (NSQIP) database. Patients were categorized into two groups: patients with and without a postoperative COVID-19 diagnosis. Coarsened Exact Matching was used to match the groups based on preoperative risk factors, and outcomes were compared. Results: A total of 47,948 patients were included. In the aggregate cohort, 31% were male, and mean age was 50 years. Age, BMI, smoking, COPD, CHF, preoperative sepsis, and ASA class were significantly different between the two groups. After matching, there were no differences in characteristics. 30-day morbidity (OR = 2.7, 95% CI 1.4-5.1), pneumonia (OR = 5.0, 95% CI 1.7-15.0), DVT (OR = 8.22, 95% CI 1.0-66), reoperation (OR = 9.3, 95% CI 1.2-73.8), and readmission (OR = 4.8, 95% CI 2.3-10.1) continued to be significantly worse in the matched cohort. Conclusion: Postoperative COVID-19 infection was associated with worse outcomes after laparoscopic cholecystectomy. These findings suggest that even postoperative COVID-19 diagnosis increases the risk for adverse outcomes in patients recovering from laparoscopic cholecystectomy and may indicate that precautions should be taken and new COVID-19 infections even after surgery should be closely monitored. [ABSTRACT FROM AUTHOR]

Introduction: There is sparse data from India on indications, technical success, safety and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) using standard adult duodenoscope in the pediatric population. Methods: Retrospective analysis of prospectively maintained electronic endoscopy and clinical database was performed to identify pediatric patients (age ≤ 18 years) who underwent ERCP between January 2017 and December 2022. Demographics and procedural details including indications, cholangio-pancreatogram findings, endotherapy type performed, technical and clinical success and complications were noted. Results: As many as 150 pediatric patients were included of whom 88 had pancreatic (mean age-13.7 years) and 62 had biliary disease (mean age- 14.9 years). Common pancreatic ERCP indications were chronic pancreatitis (n = 45 [51.1%]), pancreatic duct disruption fistula (n = 21 [23.9%]) and recurrent acute pancreatitis (n = 16 [18.2%]). Among biliary indications were choledocholithiasis (n = 29 [46.8%]), benign bile duct strictures (n = 13 [21%]), bile duct injury/leak and biliary stent removal (n = 7 [11.3%]) , choledochal cyst (n = 5 [8.1%]) and pancreatic mass causing biliary compression (n = 1 [1.6%]). Technical success in pancreatic and biliary ERCP was 94.3% and 95.2%, respectively, and clinical success was 84.1% and 93.5%, respectively. Most common complications following pancreatic ERCPs were acute pancreatitis (n = 9 [10.2%]) (mild = 5, moderate = 4) patients and post sphincterotomy bleed in one (1.1%). Among biliary ERCPs, post ERCP pancreatitis was seen in (n = 3 [4.8%]) (mild = 2, moderate = 1). Conclusion: ERCP can be safely and effectively performed in children using standard duodenoscope. Chronic pancreatitis, choledocholithiasis and pancreatic divisum are common pediatric ERCP indications. [ABSTRACT FROM AUTHOR]

Background: The detailed mechanisms underlying the development of ischemia‐type biliary lesions (ITBLs) in aged donor grafts remain unclear. In the present study we aimed to investigate the impact of aging on the response of the peribiliary gland (PBG) to ischemia–reperfusion injury (IRI) and its temporal changes. Methods: Experiments were performed using a 90‐min partial warm liver ischemia model in male Wistar rats of two age groups: young (7–8 weeks old) and old (52–60 weeks old). Liver tissues were obtained 24, 72, and 168 h after IRI. Histopathological and immunohistochemical assessments of the perihilar bile duct (PHBD), including the PBG, distal to the clip‐clamped site were performed. Results: Young rats showed little change in the bile duct tissues after IRI. However, old rats showed an increased PBG volume in the PHBD and marked PBG cell proliferation 24 h after IRI. Bile duct wall thickening with narrowing of the lumen peaked 72 h after IRI. Mucus production and oxidative stress in the PBG were significantly higher in old than in young rats after IRI. These findings showed a trend toward improvement 168 h after IRI. Conclusion: Age‐dependent differences in the response of the PBG to IRI may be related to differences in ITBL frequency. [ABSTRACT FROM AUTHOR]

Abstract Background and Aim The association between biliary disorders with weight reduction enhanced by GLP-1RAs was observed frequently, nevertheless, the relative risk of the clinically relevant cholelithiasis was not specified clearly among different GLP-1RAs. Methods 308 patients with type 2 diabetes mellitus (T2D) were recruited and divided into 4 groups; liraglutide, dulaglutide, semaglutide, versus control group; comprised of 69, 76, 71, and 92, respectively. Clinical history, examination, laboratory, and radiology tests were implemented. Results Cholelithiasis significantly associates GLP1-RAs (p = 0.033). Overall cholelithiasis was evident in 31.2% of our participants. Symptomatic cholelithiasis prevails in 60.4% of patients with cholelithiasis. Symptomatic complicated cholelithiasis prevailed in 33.3%; distributed in 28.1%, 28.1%, 21.9%, and 21.9% in liraglutide, semaglutide, dulaglutide, and control groups, respectively. Meanwhile, symptomatic uncomplicated cholelithiasis was observed in 27.1%; distributed in 34.6%, 30.8%, 15.4%, and 19.2% in Liraglutide, semaglutide, dulaglutide, and control groups, respectively. Asymptomatic cholelithiasis was noted in 36.8%, 21.1%, 10.5%, and 31.6% of patients with dulaglutide, semaglutide, liraglutide, and control groups, respectively. Specifically, 81.1%, 68%, and 44% of patients with liraglutide, semaglutide, and dulaglutide experienced symptomatic cholelithiasis. The relative risk of cholelithiasis was 1.2, 1.3, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 17.25, 14.69, and 10.96, respectively. The relative risk of symptomatic cholelithiasis was 1.6, 0.9, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 3.14, 16.67, and 5.56, respectively. Conclusion Liraglutide was associated with the highest risk of clinically relevant cholelithiasis than semaglutide, and dulaglutide in patients with T2D.

Christopher Thom, Justin Yaworsky, Kevin Livingstone, David Han, Jakob Ottenhoff Department of Emergency Medicine, University of Virginia Health System, Charlottesville, Virginia, USACorrespondence: Christopher Thom, University of Virginia Health System, 1215 Lee Street, Charlottesville, Virginia, 22903, USA, Email ct9k@hscmail.mcc.virginia.eduBackground: Biliary ultrasound is often utilized in the evaluation of abdominal pain in the Emergency Department (ED). Common bile duct (CBD) identification is traditionally a standard component of the biliary ultrasound examination but can be challenging to perform for the novice sonographer. Previous work has demonstrated that CBD dilatation is rare in cases of cholecystitis with normal liver function tests (LFTs). We sought to assess the frequency of CBD dilatation in the subset of ED patients undergoing hepatobiliary ultrasound who have normal LFTs and an absence of gallstones or biliary sludge on ultrasound. We also performed an assessment of changes in CBD diameter by age and cholecystectomy status.Methods: This was a retrospective chart review at a single academic ED. Patients were enrolled in the study if they underwent a radiology performed (RP) hepatobiliary ultrasound within the 2 year study period. Records were reviewed for the presence of gallstones or sludge, CBD diameter, age, clinical indication for the ultrasound, and LFTs. Descriptive analyses were performed, and interobserver agreement among data abstractors was assessed by K analysis for the presence of CBD dilatation. The Mann–Whitney test was utilized to assess statistical significance in the comparison of differences between CBD diameters amongst age groups.Results: Of 1929 RP hepatobiliary ultrasounds performed in the study period, 312 were excluded and 1617 met inclusion criteria. Amongst these, there were 506 patients who had normal LFTs and an ultrasound with no stones or sludge. Ten patients within this group had a dilated CBD > 7 mm (1.98%, 95% CI of 1.08% to 3.6%). We also noted a statistically significant increase in CBD size in the older age cohort and in those individuals with a history of cholecystectomy.Conclusion: CBD dilation in ED patients who present with normal LFTs and an absence of gallstones and biliary sludge is rare. Physicians should be reassured that the routine identification of the CBD on ultrasound in this setting is of low yield and need not be pursued.Plain Language Summary: The common bile duct is often taught as part of the biliary point-of-care ultrasound examination. However, it is more challenging to identify than the gallbladder and thus may limit adoption of POCUS by ED physicians. Our study adds to the body of work demonstrating that omitting the common bile duct from an ultrasound evaluation is likely reasonable when both the gallbladder and liver function tests are normal. Our study also adds to the literature regarding the increase in common bile duct size with age and with post-cholecystectomy status.Keywords: biliary, common bile duct, ultrasound, gallstones, cholelithiasis, point-of-care ultrasound

Background: Gallstone is a common problem in patients with sickle cell disease. Prevalence of this problem among sickle cell disease (SCD) children may vary with age, and geographic location. Studies on gallstone prevalence in SCD children are scanty in the South-South zone of Nigeria. Aim: To determine by ultrasonography the prevalence of gallstones among steady state sickle cell disease children attending the Paediatric Outpatient Clinic of the University of Benin Teaching Hospital, Benin-City, south south Nigeria. Methodology: The study was a descriptive cross sectional study. The prevalence of gall stones was studied prospectively on 101 sickle cell disease patients who attended the Paediatric Outpatient clinic of the University of Benin Teaching Hospital by means of ultrasonography. They were aged 1-18 years. All except three patients were Haemoglobin (Hb) SS while the remaining three were bSC. Statistical analysis was done by means, percentages and tests of significance was done using students t- test. Results: Five of the 101 children studied had gallstones and one had biliary sludge. The prevalence of gallstone was 5%. All patients with gallstones were HbSS, none with HbSC had stone although only three were studied.Only one child was symptomatic for the presence of gallstones. One patient had biliary sludge. The male: female ratio was 4:1. Prevalence increased with age; 2.9% 4.5% and 9.1% in patients aged less than 5,6-10 and 11-18 years respectively. Body weight was significantly associated with the presence of gallstones. Conclusion: Gallstone was found in 5% of the SCD children aged 1- 18years. This value is low compared to those from Europe and North America. It however confirmed the relative low prevalence in the general population of Nigerians.The clinical significance of gallstones in these SCD children is that it may contribute significantly to the morbidity and mortality seen in these children. Recommendation: Routine abdominal scan is recommended for sickle cell disease children to detect gallstone whose presence can mimic abdominal crisis. The option of elective cholecystectomy with reduced morbidity compared to emergency cholecystectomy can thus be exploited.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. In recent years, related studies in China and globally have provided some evidence-based medical evidence for the integrated traditional Chinese and Western medicine treatment of PBC. Based on the latest diagnosis and treatment experience and guidelines in China and globally, Expert Committee on Hepatology, Doctor Society of Integrative Medicine, Chinese Medical Doctor Association, organized related experts in China to formulate this consensus, in order to provide guidance and reference for clinicians in the diagnosis, TCM syndrome differentiation, and integrated traditional Chinese and Western medicine treatment of PBC. [ABSTRACT FROM AUTHOR]

Background: The cornerstone treatment for primary biliary cholangitis (PBC) is ursodeoxycholic acid (UDCA), but many patients exhibit an incomplete response, leading to disease progression. Risk prediction models like the GLOBE and UK-PBC scores hold promise for patient stratification and management. We aimed to independently assess the predictive accuracy of these risk scores for UDCA response in a prospective U.S. cohort. Methods: We conducted a prospective cohort study at a U.S. liver center, monitoring UDCA-treated PBC patients over a one-year follow-up. We evaluated the predictive efficacy of the GLOBE and UK-PBC scores for UDCA treatment response, comparing them to the Paris II criteria. Efficacy was assessed using univariate and multivariate analyses, followed by prognostic performance evaluation via receiver operating characteristic (ROC) curve analysis. Results: We evaluated 136 PBC patients undergoing UDCA therapy. Based on the Paris II criteria, patients were categorized into UDCA full-response and non-response groups. The GLOBE score identified a non-responder rate of 18% (p = 0.205), compared to 20% (p = 0.014) with the Paris II criteria. Multivariate analysis, adjusted for age and biochemical markers, showed that both the GLOBE and UK-PBC scores were strongly associated with treatment response (p < 0.001). The area under the ROC curve was 0.87 (95% CI 0.83−0.95) for the GLOBE score and 0.94 (95% CI 0.86−0.99) for the UK-PBC risk score. Conclusions: Our study demonstrates that GLOBE and UK-PBC scores effectively predict UDCA treatment response in PBC patients. The early identification of patients at risk of an incomplete response could improve treatment strategies and identify patients who may need second-line therapies. [ABSTRACT FROM AUTHOR]

Introduction: Fibrosis and cirrhosis are associated with worse outcomes after hepatectomy. Aspartate transaminase to platelet ratio index (APRI) is associated with fibrosis and cirrhosis in hepatitis C patients. However, APRI has not been studied to predict outcomes after hepatectomy in patients without viral hepatitis. Methods: We reviewed the ACS-NSQIP dataset to identify patients who underwent a minor hepatectomy between 2014 and 2021. We excluded patients with viral hepatitis or ascites as well as patients who underwent emergent operations or biliary reconstruction. APRI was calculated using the following equation: (AST/40)/(platelet count) × 100. APRI ≥0.7 was used to identify significant fibrosis. Univariable analysis was performed to identify factors associated with APRI ≥0.7, transfusion, serious morbidity, overall morbidity, and 30-day mortality. Multivariable logistic regression was performed to identify adjusted predictors of these outcomes. Results: Of the 18,069 patients who met inclusion criteria, 1630 (9.0%) patients had an APRI ≥0.7. A perioperative blood transfusion was administered to 2139 (11.8%). Overall morbidity, serious morbidity, and mortality were experienced by 3162 (17.5%), 2475 (13.7%), and 131 (.7%) patients, respectively. APRI ≥0.7 was an independent predictor of transfusion (adjusted OR: 1.48 [1.26-1.74], P <.001), overall morbidity (1.17 [1.02-1.33], P =.022), and mortality (1.97 [1.22-3.06], P =.004). Transfusion was an independent predictor of overall morbidity (3.31 [2.99-3.65], P <.001), serious morbidity (3.70 [3.33-4.11], P <.001), and mortality (5.73 [4.01-8.14], P <.001). Conclusions: APRI ≥0.7 is associated with perioperative transfusion, overall morbidity, and 30-day mortality. APRI may serve as a noninvasive tool to risk stratify patients prior to elective minor hepatectomy. [ABSTRACT FROM AUTHOR]

E. innesii is a recently described Enterococcus species which may be difficult to differentiate from the more common E. casseliflavus. We present the first clinical report of invasive E. innesii infection, featuring two cases of biliary sepsis. Whole genome sequencing confirmed the taxonomic assignment and the presence of vanC-4. Analysis of public genomes identified 13 deposited E. innesii and 13 deposited E. casselifalvus/E.gallinarum genomes which could be reassigned as E. innesii. Improved laboratory diagnosis of E. innesii is expected to generate additional data concerning its clinical relevance and support the future diagnosis and treatment of this uncommon pathogen. [ABSTRACT FROM AUTHOR]

Background and Objectives: Prolonged biliary stenting may lead to complications such as cholangitis, stentolith and stent migration. There is limited data on forgotten biliary stents for more than five years in literature. The aim of this retrospective study was to analyze the complications and outcomes in patients who forgot to get their biliary stents removed or exchanged for more than five years. Methods: The study population included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) and plastic biliary stent placements in a tertiary care center from 1990 to 2022 for benign biliary diseases. Loss to follow-up and subsequent forgotten stent for more than five years were observed in 40 patients who underwent ERCP during this study period. We retrospectively analyzed the indications of stenting, present status of stent, complications and outcomes in the study patients. Results: The mean age of the study patients was 51.5 ± 11.5 years with 27 females. Indications of biliary stent placement were choledocholithiasis (33, 82.5%), bile leak (3, 7.5%), benign biliary stricture (2, 5%) and choledochal cyst (2, 5%). The mean duration of forgotten stent was 5.9 ± 3.6 years. Presenting symptoms were abdominal pain (37, 92.5%), fever (26, 65%) and jaundice (32, 80%). Most commonly placed stent was 7 French double pigtail of 10 cm length. Complications in the study patients were cholangitis (35, 87.5%), internal migration (2, 5%), pancreatitis (1, 2.5%) and portal hypertension (1, 2.5%). The outcomes were stone removal (30, 90.9%), stent removal (31, 77.5%), stent reinsertion (19, 47.5%), broken stent (3, 7.5%) and surgery (2, 5%). Conclusions: Prolonged duration (> 5 years) of forgotten stent is uncommon and is observed most commonly in patients with choledocholithiasis. The most common complication of long duration of forgotten stents was cholangitis followed by internal migration, pancreatitis and portal hypertension. Stone and stent removal was successful in a majority of patents, while surgery was required in less number of patients. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. Methods: Pediatric patients under 18 years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. Results: Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13 years (range 3 years and 5 months–17 years and 9 months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. Conclusions: Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3 years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP. [ABSTRACT FROM AUTHOR]

Artificial Intelligence (AI) is poised or has already begun to influence absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected – that of superior modelling of ADME data to increase its predictive power. It is influencing traditional exhaustive and careful literature research by providing almost perfect summaries of existing information. This will highly influence how people study, graduate and progress in the ADME sciences. The literature contains many flaws (protein binding influence on unbound drug concentration is one of the examples cited) and without direction AI may help to popularise them. ADME science has a relatively small number of key assays and values, but these are produced under widely varying conditions so large data sets, the best substrate for artificial intelligence, are not readily available to produce new more predictive systems. The use of AI to enrich the databases may be a near term goal. AI is already contributing in other areas such as technical skill assimilation, maintenance of complex instruments (combined with virtual reality) and the processing of pharmacovigilance. [ABSTRACT FROM AUTHOR]

Background and aimsENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA).Approach and resultsPatients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events.ConclusionsPatients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated.

The rising incidence combined with pregnancy-related physiological changes make gallbladder and biliary pathology high on the differential for pregnant patients presenting with right upper abdominal pain. Imaging plays a crucial role in determining surgical versus non-surgical management in pregnant patients with biliary or gallbladder pathology. Ultrasound (first-line) and magnetic resonance with magnetic resonance cholangiopancreatography (second-line) are the imaging techniques of choice in pregnant patients with suspected biliary pathology due to their lack of ionizing radiation. MRI/MRCP offers an excellent non-invasive imaging option, providing detailed anatomical detail without known harmful fetal side effects. This article reviews physiological changes in pregnancy that lead to gallstone and biliary pathology, key imaging findings on US and MRI/MRCP, and management pathways.

Introduction. Biliary obstruction is a common manifestation of biliopancreatic malignancies, and its relief is an essential part of the treatment algorithm. Currently, there are three techniques to manage malignant biliary obstruction—endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD). ERCP has been adopted as a first-line treatment modality but EUS-BD is gradually emerging as a viable alternative. The aim of the current article is to assess the clinical outcomes of the three nonsurgical biliary drainage procedures. Materials and methods. A total of 102 consecutive patients with unresectable biliopancreatic malignancy inducing biliary obstruction and subjected to palliative treatment by means of ERCP, EUS-BD, or PTBD were retrospectively included in the study. Results. No difference in clinical and technical success of the procedures was found: ERCP—97.2% technical; 88.9% clinical; PTBD—94.4% technical, 72.2% clinical; EUS-BD—90% technical; 83.3% clinical. Adverse events (AEs) and reinterventions were significantly more common in PTBD (38.9% and 52.8%) and ERCP (27.9% and 25%) compared to EUS-BD (10% and 3.3%). Total duration of hospital stay and number of hospitalizations were lower in the EUS-BD compared to PTBD and ERCP groups. Conclusions. In the presence of adequate expertise, EUS-BD may be superior to PTBD and ERCP in achieving and sustaining biliary drainage in the setting of unresectable malignancy.

BACKGROUND AND AIMS: Patients with primary biliary cholangitis (PBC) often suffer with pruritus. We describe the impact of pruritus on quality of life and how it is managed in a real-world cohort. METHODS: TARGET-PBC is a longitudinal observational cohort of patients with PBC across the USA. Data include information from medical records for three years prior to the date of consent up to 5 years of follow-up. Enrolled patients were asked to complete patient-reported outcome surveys: PBC-40, 5-D itch, and the PROMIS fatigue survey. Kruskal-Wallis tests were used to compare differences in symptoms between groups. RESULTS: A total of 211 patients with completed PRO surveys were included in the current study. PRO respondents were compared with non-respondents in the TARGET-PBC population and were broadly similar. Pruritus was reported in 170 patients (81%), with those reporting clinically significant pruritus (30%) scoring worse across each domain of the PBC-40 and 5-D itch, more frequently having cirrhosis, and having significantly greater levels of fatigue. Patients reporting clinically significant pruritus were more likely to receive treatment, but 33% had never received treatment (no itch = 43.9%, mild itch = 38.3%). CONCLUSIONS: The prevalence of pruritus was high in this population, and those reporting clinically significant pruritus had a higher likelihood of having advanced disease and worse quality of life. However, this study found that pruritus in PBC is under-treated. This may be due in part to ineffectiveness of current treatments, poor tolerance, or the lack of FDA-approved medications for pruritus.

Background and aimsCurrent treatment guidelines recommend ursodeoxycholic acid (UDCA) as the first-line treatment for new-diagnosed primary biliary cholangitis (PBC) patients. However, up to 40% patients are insensitive to UDCA monotherapy, and evaluation of UDCA response at 12 months may result in long period of ineffective treatment. We aimed to develop a new criterion to reliably identify non-response patients much earlier.MethodsFive hundred sixty-nine patients with an average of 59 months (Median: 53; IQR:32-79) follow-up periods were randomly divided into either the training (70%) or the validation cohort (30%). The efficiency of different combinations of total bilirubin (TBIL), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) threshold values to predict outcomes was assessed at 1, 3 or 6 month after the initiation of UDCA therapy. The endpoints were defined as adverse outcomes, including liver-related death, liver transplantation and complications of cirrhosis. Adverse outcome-free survival was compared using various published criteria and a proposed new criterion.ResultsA new criterion of evaluating UDCA responses at 1 month was established as: ALP ≤ 2.5 × upper limit of normal (ULN) and AST ≤ 2 × ULN, and TBIL ≤ 1 × ULN (Xi'an criterion). The 5 year adverse outcome-free survival rate of UDCA responders, defined by Xi'an criterion, was 97%, which was significantly higher than that of those non-responders (64%). An accurate distinguishing high-risk patients' capacity of Xi'an criterion was confirmed in both early and late-stage PBC.ConclusionsXi'an criterion has a similar or even higher ability to distinguish high-risk PBC patients than other published criteria. Xi'an criterion can facilitate early identification of patients requiring new therapeutic approaches.

Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease.

Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC is multifactorial and involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, ultimately leading to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA) and obeticholic acid (OCA) are currently used as first- and second-line treatments, respectively. However, many patients do not respond adequately to UDCA, and the long-term effects of these drugs are limited. Recent research has advanced our understanding the mechanisms of pathogenesis in PBC and greatly facilitated development of novel drugs to target mechanistic checkpoints. Animal studies and clinical trials of pipeline drugs have yielded promising results in slowing disease progression. Targeting immune mediated pathogenesis and anti-inflammatory therapies are focused on the early stage, while anti-cholestatic and anti-fibrotic therapies are emphasized in the late stage of disease, which is characterized by fibrosis and cirrhosis development. Nonetheless, it is worth noting that currently, there exists a dearth of therapeutic options that can effectively impede the progression of the disease to its terminal stages. Hence, there is an urgent need for further research aimed at investigating the underlying pathophysiology mechanisms with potential therapeutic effects. This review highlights our current knowledge of the underlying immunological and cellular mechanisms of pathogenesis in PBC. Further, we also address current mechanism-based target therapies for PBC and potential therapeutic strategies to improve the efficacy of existing treatments.

Genome-wide association studies have identified 19p13.3 locus associated with primary biliary cholangitis (PBC). Here we aim to identify causative variant(s) and initiate efforts to define the mechanism by which the 19p13.3 locus variant(s) contributes to the pathogenesis of PBC. A genome-wide meta-analysis of 1931 PBC subjects and 7852 controls in two Han Chinese cohorts confirms the strong association between 19p13.3 locus and PBC. By integrating functional annotations, luciferase reporter assay and allele-specific chromatin immunoprecipitation, we prioritize rs2238574, an AT-Rich Interaction Domain 3A (ARID3A) intronic variant, as a potential causal variant at 19p13.3 locus. The risk allele of rs2238574 shows higher binding affinity of transcription factors, leading to an increased enhancer activity in myeloid cells. Genome-editing demonstrates the regulatory effect of rs2238574 on ARID3A expression through allele-specific enhancer activity. Furthermore, knock-down of ARID3A inhibits myeloid differentiation and activation pathway, and overexpression of the gene has the opposite effect. Finally, we find ARID3A expression and rs2238574 genotypes linked to disease severity in PBC. Our work provides several lines of evidence that a non-coding variant regulates ARID3A expression, presenting a mechanistic basis for association of 19p13.3 locus with the susceptibility to PBC.

Background and aimsPruritus is associated with multiple liver diseases, particularly those with cholestasis, but the mechanism remains incompletely understood. Our aim was to evaluate serum IL-31 as a putative biomarker of pruritus in clinical trials of an farnesoid X receptor (FXR) agonist, cilofexor, in patients with NASH, primary sclerosing cholangitis (PSC), and primary biliary cholangitis (PBC).Approach and resultsSerum IL-31 was measured in clinical studies of cilofexor in NASH, PSC, and PBC. In patients with PSC or PBC, baseline IL-31 was elevated compared to patients with NASH and healthy volunteers (HVs). IL-31 correlated with serum bile acids among patients with NASH, PBC, and PSC. Baseline IL-31 levels in PSC and PBC were positively correlated with Visual Analog Scale for pruritus and 5-D itch scores. In patients with NASH, cilofexor dose-dependently increased IL-31 from Week (W)1 to W24. In patients with NASH receiving cilofexor 100 mg, IL-31 was higher in those with Grade 2-3 pruritus adverse events (AEs) than those with Grade 0-1 pruritus AEs. IL-31 weakly correlated with C4 at baseline in patients with NASH, and among those receiving cilofexor 100 mg, changes in IL-31 and C4 from baseline to W24 were negatively correlated. IL-31 messenger RNA (mRNA) was elevated in hepatocytes from patients with PSC and NASH compared to HVs. In a humanized liver murine model, obeticholic acid increased IL-31 mRNA expression in human hepatocytes and serum levels of human IL-31.ConclusionsIL-31 levels correlate with pruritus in patients with cholestatic disease and NASH, with FXR agonist therapy resulting in higher serum levels in the latter group. IL-31 appears to derive in part from increased hepatocyte expression. These findings have therapeutic implications for patients with liver disease and pruritus.

Introduction. Biliary obstruction is a common manifestation of biliopancreatic malignancies, and its relief is an essential part of the treatment algorithm. Currently, there are three techniques to manage malignant biliary obstruction—endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic biliary drainage (PTBD), and endoscopic ultrasound-guided biliary drainage (EUS-BD). ERCP has been adopted as a first-line treatment modality but EUS-BD is gradually emerging as a viable alternative. The aim of the current article is to assess the clinical outcomes of the three nonsurgical biliary drainage procedures. Materials and methods. A total of 102 consecutive patients with unresectable biliopancreatic malignancy inducing biliary obstruction and subjected to palliative treatment by means of ERCP, EUS-BD, or PTBD were retrospectively included in the study. Results. No difference in clinical and technical success of the procedures was found: ERCP—97.2% technical; 88.9% clinical; PTBD—94.4% technical, 72.2% clinical; EUS-BD—90% technical; 83.3% clinical. Adverse events (AEs) and reinterventions were significantly more common in PTBD (38.9% and 52.8%) and ERCP (27.9% and 25%) compared to EUS-BD (10% and 3.3%). Total duration of hospital stay and number of hospitalizations were lower in the EUS-BD compared to PTBD and ERCP groups. Conclusions. In the presence of adequate expertise, EUS-BD may be superior to PTBD and ERCP in achieving and sustaining biliary drainage in the setting of unresectable malignancy. [ABSTRACT FROM AUTHOR]

Introduction: Uganda has until recently mostly referred patients for complex hepato‐pancreato‐biliary (HPB) surgery abroad due to lack of local expertize. We report indications and a spectrum of surgeries performed in the first 4 years following the establishment of a routine HPB service at Lubaga Hospital (LH), Kampala, Uganda. We also detailed the challenges encountered in setting up this service. Methods: Demographic, clinical parameters, surgery indications, procedures performed, and outcomes of consecutive patients that underwent HPB surgeries at LH from December 2018 to October 2022 were analyzed. Results: Majority were females 72 (57.6%) with a median age of 50 (6–88) years. Forty‐one (32.8%) underwent surgery on the pancreas (PS), 34 (27.2%) on the liver (LS), and 50 (40.0%) on the bile ducts (CBS). The most common symptom was abdominal pain. Benign disease was present in 37 patients (29.6%) while 88 (70.4%) had malignancy. A total of 34 patients (27.2%) had unresectable pancreatic head cancer and distal cholangiocarcinoma missed at preoperative imaging and discovered intraoperatively thus underwent palliative hepaticojejunostomy. Only 34 (27.2%) patients received postoperative ICU care. In‐hospital mortality for this heterogenous group of patients was 6 (4.8%) for PS, 3 (2.4%) for LS, and 8 (6.4%) for CBS. Conclusion: Despite many challenges like limited access to ERCP accessories, lack of endoscopic ultrasound scans and PET–CT scans in the whole country, late presentation, and low quality imaging especially in preoperative determination of resectability of hepato‐pancreato‐biliary cancers, we managed to establish a functional HPB service. Patient results achieved were good in spite of these limitations. [ABSTRACT FROM AUTHOR]

This article discusses a retrospective study conducted in Kolkata, India, which examined the burden and outcome of acute pancreatitis (AP). The study found that the most common causes of AP were alcohol, gallstones, and post-endoscopic retrograde cholangiopancreatography (ERCP). Local complications such as peripancreatic collections and pseudocysts were observed in many cases, and organ failure, particularly respiratory failure, was the most common complication. The mortality rate was 6.6%, primarily due to respiratory failure in severe AP cases. The study emphasizes the importance of early diagnosis and management of AP to improve outcomes. [Extracted from the article]

Ultrasound (US) is a fundamental and inexpensive tool both for the prompt diagnosis and for the study of diverse medical conditions. Its widespread use is partly due to the availability of US devices in the daily practice of physicians. US can be performed in real-time and is instrumental in the generation of clinical algorithms for the management of situations like trauma. It also constitutes a primary approach for the study of oncological diseases, and a guidance tool for interventions such as percutaneous drainages. In addition, and specifically for HPB surgeons, US is an essential tool in the operating room: intraoperative (either open or laparoscopic) US is necessary for the accurate determination of the stage, location, number, and margins of tumors within the liver, pancreas, or biliary tree. On another note, reading and understanding US images are skills that require time and training, which should be taught during surgical residencies. However, this is not customary in most residencies globally. This chapter offers a concise yet comprehensive elucidation of the basic principles of ultrasonography, the instruments required to perform an ultrasonic assessment of a patient, and the basic ultrasound controls.

Abstract Background Total serum bilirubin concentration (TBIL) can provide useful information on several pathophysiological conditions in cats. Nevertheless, whether the variable severity classification of hyperbilirubinemia can reliably indicate certain disease processes or predict a biliary obstruction (BO) has not been investigated. Hypothesis/Objective Determine if hyperbilirubinemia of variable severity can assist clinicians to identify BO, which often is considered a surgical emergency. Animals Two‐hundred sixteen client‐owned cats. Methods Data were retrospectively collected from all cats (January 2015‐August 2022) with an increased TBIL (>0.58 mg/dL [>10 μmol/L]) presented to 3 referral centers in the United Kingdom (UK). Presenting clinical features and diagnostic outcomes were collected. The predictive ability of TBIL to indicate BO was evaluated by multivariable binary logistic regression modeling and receiver operating characteristic (ROC) curves. Results Median TBIL was 1.73 mg/dL (range, 0.59‐26.15; 29.5 μmol/L; range, 10.1‐447.1) with severity classification of hyperbilirubinemia categorized as mild (>0.58‐2.92 mg/dL; >10‐50 μmol/L; 68.1%), moderate (>2.92‐5.85 mg/dL; >50‐100 μmol/L; 17.6%), severe (>5.85‐11.70 mg/dL; >100‐200 μmol/L; 9.7%) and very severe (>11.70 mg/dL; >200 μmol/L; 4.6%). Biliary obstruction was present in 17 (7.9%) cats, all of which received recommendation for emergency surgery. Median TBIL in cats with BO (9.69 mg/dL; 165.7 μmol/L) differed significantly from those without obstruction (1.51 mg/dL; 25.8 μmol/L; P

Gallbladder cancers are the most common biliary tract malignancies in the world. Adenocarcinoma constitutes the most common histology in gallbladder cancer. Neuroendocrine neoplasms of the gallbladder account for about 0.5% of all neuroendocrine neoplasms and 2.1% of all gallbladder tumors. They are rare tumors and present with non-specific symptoms such as abdominal pain, weight loss, anorexia, and obstructive jaundice, and, therefore, are often challenging to diagnose and treat. Mixed neuroendocrine-non-neuroendocrine neoplasm is a subtype of neuroendocrine neoplasm. To add to the literature, we report a rare case of a patient who presented with pain in the abdomen and non-bilious vomiting and was diagnosed with mixed neuroendocrine-non-neuroendocrine gallbladder cancer, identified by immunohistochemistry, and treated with palliative chemotherapy. Due to non-specific symptoms, patients may present at an advanced stage. Further, immunohistochemistry may assist in clinching the diagnosis.

Left-sided gallbladder positioning, or sinistroposition, is a rare anatomical variation that poses challenges during surgical intervention due to associated vascular and biliary anomalies. While existing literature suggests an incidence of approximately 0.04-1.1%, it remains an underreported phenomenon that falls well outside the realm of "expected" anatomical variation and are rarely identified on preoperative imaging. Here, we present a case of acute cholecystitis in a patient with unexpected left-sided gallbladder, highlighting the associated challenges and outlining both preoperative and intraoperative strategies for managing this rare but consequential anatomical variant. In this case, a 49-year-old woman with a prior history of bilateral ovarian cysts presented with clinical, laboratory, and imaging findings consistent with acute cholecystitis. She underwent laparoscopic cholecystectomy and was found to have a severely inflamed left-sided gallbladder that was obscured by omentum. Her gallbladder was found in the midline immediately beneath the falciform ligament, with most of the gallbladder body and fundus attached to liver segment III, situated to the left of the midline. An additional left-sided mid-abdominal port was required to enhance retraction, and an intraoperative cholangiogram (IOC) was performed given the elevated risk of structural injury. This case underscores the heightened intraoperative risk associated with deviations in vascular and biliary anatomy and provides recommendations for intraoperative adaptations to mitigate these risks. [ABSTRACT FROM AUTHOR]

Background: Total serum bilirubin concentration (TBIL) can provide useful information on several pathophysiological conditions in cats. Nevertheless, whether the variable severity classification of hyperbilirubinemia can reliably indicate certain disease processes or predict a biliary obstruction (BO) has not been investigated. Hypothesis/Objective: Determine if hyperbilirubinemia of variable severity can assist clinicians to identify BO, which often is considered a surgical emergency. Animals: Two‐hundred sixteen client‐owned cats. Methods: Data were retrospectively collected from all cats (January 2015‐August 2022) with an increased TBIL (>0.58 mg/dL [>10 μmol/L]) presented to 3 referral centers in the United Kingdom (UK). Presenting clinical features and diagnostic outcomes were collected. The predictive ability of TBIL to indicate BO was evaluated by multivariable binary logistic regression modeling and receiver operating characteristic (ROC) curves. Results: Median TBIL was 1.73 mg/dL (range, 0.59‐26.15; 29.5 μmol/L; range, 10.1‐447.1) with severity classification of hyperbilirubinemia categorized as mild (>0.58‐2.92 mg/dL; >10‐50 μmol/L; 68.1%), moderate (>2.92‐5.85 mg/dL; >50‐100 μmol/L; 17.6%), severe (>5.85‐11.70 mg/dL; >100‐200 μmol/L; 9.7%) and very severe (>11.70 mg/dL; >200 μmol/L; 4.6%). Biliary obstruction was present in 17 (7.9%) cats, all of which received recommendation for emergency surgery. Median TBIL in cats with BO (9.69 mg/dL; 165.7 μmol/L) differed significantly from those without obstruction (1.51 mg/dL; 25.8 μmol/L; P <.01). The optimal TBIL cut‐off to discriminate between cats with and without BO was ≥3.86 mg/dL (≥66 μmol/L) with a sensitivity of 94.1% and specificity of 82.4%. Using multivariable logistic regression, as age increased, the odds of BO increased significantly (odds ratio, 1.20; 95% confidence interval, 1.01‐1.42; P =.04). Conclusions and Clinical Importance: As part of a thorough clinical assessment, the severity classification of hyperbilirubinemia has the potential to predict the likelihood of a BO and to discriminate between cats that may or may not require surgery for BO at a suggested cut‐off of ≥3.86 mg/dL (≥66 μmol/L). Alongside TBIL, age is also useful when assessing for the likelihood of BO in a cat presented with hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Metastatic gastrointestinal cancer is not an uncommon situation, especially for pancreatic, gastric, and colorectal cancers. In this setting, few data are available on the impact of the treatment of the primary tumour. Oligometastatic disease is associated with longer survival in comparison with more advanced disease. Metastasis-directed therapy, such as stereotactic body radiotherapy, seems related to better outcomes, but the level of evidence is low. In most tumour locations, prospective data are very scarce and inclusion in ongoing trials is strongly recommended. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This case demonstrates an atypical presentation of choledochal cysts (CDCs) and elaborates on the diagnostic challenges encountered when presented with CDCs in adulthood, as it principally presents in children. A choledochal cyst is a rare congenital anomaly characterized by cystic dilations in the extrahepatic and intrahepatic biliary trees. These cysts are classified according to their location and characteristics. This case study aims to demonstrate how nonspecific clinical features can pose a diagnostic dilemma when presented in adults. Additionally, the case report provides an overview of diagnostic methods and treatment options. In this case, we discuss a 50‐year‐old female who presented with a 2‐ to 3‐day history of severe colicky pain in the right upper quadrant of her abdomen without any other symptoms or abnormal laboratory tests. In addition to ultrasonography evidence of CBD dilation and cholelithiasis, MRCP results confirmed the diagnosis. She underwent surgical intervention involving cyst excision, a Roux‐en‐Y hepatojejunostomy, and a cholecystectomy. The postoperative period was without significant complications. The case presented here illustrates the potential outcomes for individuals who present with choledochal cysts during adulthood. Often, these cases present with vague symptoms or as the underlying cause of a more severe condition. This case contributes to the existing knowledge of choledochal cysts by providing insight into the clinical presentation, diagnostic methods, and treatment options. [ABSTRACT FROM AUTHOR]

Acute biliary pancreatitis (ABP) poses significant challenges in determining the optimal timing and approach for cholecystectomy, particularly in mild, moderately severe, and severe forms. This article reviews the existing literature on cholecystectomy timing and its impact on outcomes in ABP. A systematic literature search yielded 41 relevant articles from PubMed and Scopus databases. In mild ABP, early cholecystectomy within 72 hours of onset is increasingly favoured due to reduced technical difficulty and lower risk of recurrent pancreatitis. Conversely, delayed cholecystectomy, although traditionally practiced, may lead to higher recurrence rates and prolonged hospital stays. For moderate severe ABP, evidence remains limited, but early cholecystectomy appears to decrease hospital stay without increasing perioperative complications. In severe ABP, consensus suggests delaying cholecystectomy until peripancreatic collections resolve, typically 6 to 10 weeks post-onset, to minimize surgical morbidity. The role of endoscopic retrograde cholangiopancreatography (ERCP) alongside cholecystectomy remains contentious, with guidelines recommending its use in specific scenarios such as cholangitis or biliary obstruction. However, routine ERCP in mild ABP lacks robust evidence and may increase complications. Challenges persist regarding the management of residual choledocholithiasis post-ABP, highlighting the need for improved diagnostic criteria and management protocols. Overall, this review underscores the evolving landscape of cholecystectomy timing in ABP and provides insights into current best practices and areas for future research. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. The tumor is characterized by insidious onset, high degree of malignancy, poor prognosis, and high recurrence rate. Immortalized cancer cell lines are the best and easiest models for in vitro cancer research. Here, we established a naturally immortalized highly tumorigenic hilar cholangiocarcinoma (hCCA) cell line, CBC3T-1. The CBC3T-1 cell line was cultured for over 60 passages. Thorough analysis showed that CBC3T-1 cells share characteristics similar to original tumor cells from patients with cholangiocarcinoma and display a stable phenotype, including features of epithelial origin, stem cell-like properties, as well as a high invasive and migratory capability and tumorigenicity in mice. Furthermore, this cell line showed the best sensitivity to paclitaxel, followed by gemcitabine. RNA sequencing and whole‑exome sequencing showed that cancer-associated pathways and somatic mutations played a dominant role in the development of CCA. We established and characterized a new hCCA cell line, CBC3T-1, which contributes to a better understanding of bile duct cancer, and can be used to study tumorigenesis and progression and the role of anticancer drugs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Primary biliary cholangitis (PBC) is an autoimmune disease with significant gender difference. X chromosome inactivation (XCI) plays important roles in susceptibility to diseases between genders. This work focuses on the differences of LncRNA XIST in several defined immune cells populations as well as its effects on naive CD4+ T cells proliferation and differentiation in patients with PBC. METHODS: NKs, B cells, CD4+ T, and CD8+ T cells were separated by MicroBeads from peripheral blood mononuclear cells (PBMCs) of PBC patients and healthy control (HC). The expression levels of LncRNA XIST in these immune cells were quantified by qRT-PCR and their subcellular localized analyzed by FISH. Lentivirus were used to interfere the expression of LncRNA XIST, and CCK8 was used to detect the proliferation of naive CD4+ T cells in PBC patients. Finally, naive CD4+ T cells were co-cultured with the bile duct epithelial cells (BECs), and the effects of LncRNA XIST on the typing of naive CD4+ T cells and related cytokines were determined by qRT-PCR and ELISA. RESULTS: The expression levels of LncRNA XIST in NKs and CD4+ T cells in PBC patients were significantly higher than those in HC, and were primarily located at the nucleus. LncRNA XIST could promote the proliferation of naive CD4+ T cells. When naive CD4+ T cells were co-cultured with BECs, the expressions of IFN-γ, IL-17, T-bet and RORγt in naive CD4+ T cells were decreased. CONCLUSION: LncRNA XIST was associated with lymphocyte abnormalities in patients with PBC. The high expression of LncRNA XIST could stimulate proliferation and differentiation of naive CD4+ T cells, which might account for the high occurrence of PBC in female.

Choledochal Cysts (CC), cystic dilatation of biliary tree are an uncommon finding. Generally found in pediatric age group are rarer in adults and commoner in females. They have a relatively greater incidence in a few parts of Asia as compared to the West. Even rarer are Giant Choledochal Cysts (GCC). We successfully treated an adult patient of GCC with an uncommon presentation which is the largest from the Indian subcontinent. [ABSTRACT FROM AUTHOR]