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Background: Gallbladder cancer (GBC) is the most common and lethal malignancy of the biliary tract that lacks effective therapy. In many GBC cases, infiltration into adjacent organs or distant metastasis happened long before the diagnosis, especially the direct liver invasion, which is the most common and unfavorable way of spreading. Methods: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics (ST), proteomics, and multiplexed immunohistochemistry (mIHC) were performed on GBC across multiple tumor stages to characterize the tumor microenvironment (TME), focusing specifically on the preferential enrichment of neutrophils in GBC liver invasion (GBC-LI). Results: Multi-model Analysis reveals the immunosuppressive TME of GBC-LI that was characterized by the enrichment of neutrophils at the invasive front. We identified the context-dependent transcriptional states of neutrophils, with the Tumor-Modifying state being associated with oxidized low-density lipoprotein (oxLDL) metabolism. In vitro assays showed that the direct cell-cell contact between GBC cells and neutrophils led to the drastic increase in oxLDL uptake of neutrophils, which was primarily mediated by the elevated OLR1 on neutrophils. The oxLDL-absorbing neutrophils displayed a higher potential to promote tumor invasion while demonstrating lower cancer cytotoxicity. Finally, we identified a neutrophil-promoting niche at the invasive front of GBC-LI that constituted of KRT17+ GBC cells, neutrophils, and surrounding fibroblasts, which may help cultivate the oxLDL-absorbing neutrophils. Conclusions: Our study reveals the existence of a subset of pro-tumoral neutrophils with a unique ability to absorb oxLDL via OLR1, a phenomenon induced through cell-cell contact with KRT17+ GBC cells in GBC-LI. [ABSTRACT FROM AUTHOR]

The main cause of distal biliary malignant obstructive jaundice (DBMOJ) is the stricture of the extrahepatic biliary tract by malignant tumors, including pancreatic head and uncinate process cancer, low-grade cholangiocarcinoma, duodenal cancer, papillary duodenal cancer and other malignant tumors. The most effective treatment is radical pancreaticoduodenectomy. However, preoperative obstructive jaundice can affect the patient's liver function and blood coagulation function, increase local inflammation and oedema, and make surgery more difficult. Patients with severe obstructive jaundice require preoperative biliary drainage, which can be achieved by various methods, including ultrasound endoscopic biliary drainage (EUS-EBD) and endoscopic retrograde biliary drainage (ERBD). The latter is mainly divided into endoscopic nasobiliary drainage and endoscopic biliary stent. Some patients underwent percutaneous transhepatic biliary drainage (PTBD) when ERBD and EUS-EBD failed. In this study, we aimed to identify PTBD in DBMOJ and to further investigate the role of the puncture pathway in DBMOJ. The relationship between PTBD and bile duct internal diameter was confirmed by analysing and collating clinical data. In this study, DBMOJ was grouped according to bile duct internal diameter and liver function was used as an indicator to examine the improvement in liver function with PTBD in patients undergoing DBMOJ. Analysis of puncture complications showed that PTBD puncture was safe. DBMOJ with different bile duct internal diameters had different rates of liver function improvement after PTBD. The right-side approaches had significantly lower alanine aminotransferase (ALT) and alanine transaminase (AST) than the left-side approaches. This study showed that PTBD for DBMOJ is associated with a low complication rate and good reduction of jaundice. Liver function recovery was faster in patients with DBMOJ treated with PTBD in the right-sided approach compared with the left-sided approach. PTBD is an effective tool to be used in patients who have failed ERBD and EUS-EBD. [ABSTRACT FROM AUTHOR]

Cholecystectomy is indicated for gallbladder mucoceles (GBM). Evaluating the patency of the biliary duct and precise biliary tree visualization is crucial for reducing the risk of compromised bile flow after surgery. Therefore, intraoperative cholangiography (IOC) is recommended during cholecystectomy to prevent biliary tract injury. Although indocyanine green (ICG) cholangiography has been extensively reported in human medicine, only one study has been conducted in veterinary medicine. Therefore, this study aimed to demonstrate the use of ICG for IOC to identify fluorescent biliary tract images and determine the patency of the common bile duct during cholecystectomy in dogs. This study comprised 27 dogs, consisting of 17 with gallbladder mucoceles (GBM) and 10 controls, specifically including dogs that had undergone elective cholecystectomy for GBM. ICG injection (0.25 mg/kg) was administered intravenously at least 45 minutes before surgery. During the operation, fluorescent images from cholangiography were displayed on the monitor and obtained in black-and-white mode for the comparison of fluorescence intensity (FI). The FI values of the gallbladders (GBs) and common bile duct (CBD) were measured using FI analyzing software (MGViewer V1.1.1, MetapleBio Inc.). The results demonstrated successful CBD patency identification in all cases. Mobile GBM showed partial gallbladder visibility, whereas immobile GBM showed limited visibility. Additionally, insights into the adequate visualization of the remaining extrahepatic biliary tree anatomy were provided, extending beyond the assessment of CBD patency and gallbladder intensity. Our study demonstrates the potential of fluorescent IOC using intravenous injection of ICG for assessing the patency of the cystic duct and common bile duct during cholecystectomy in patients with GBM, eliminating the need for surgical catheterization and flushing of the biliary ducts. Further research is warranted to investigate and validate the broader applicability of ICG cholangiography in veterinary medicine. [ABSTRACT FROM AUTHOR]

Introduction: Biliary Infection in patients is a common and important phenomenon resulting in severe complications and high morbidity, while the distributions and drug resistance profiles of biliary bacteria and related risk factors are dynamic. This study explored the characteristics of and risk factors for biliary infection to promote the rational use of antibiotics in clinically. Methods: Bacterial identification and drug susceptibility testing were completed using the Vitek 2 Compact analysis system. The distribution and antibioticresistant characteristics of 3,490 strains of biliary bacteria in patients at Nankai Hospital from 2019 to 2021 were analyzed using Whonet 5.6 and SPSS 26.0 software. We then retrospectively analyzed the clinical data and risk factors associated with 2,340 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (1,508 cases) and non-multidrug-resistant bacteria (832 cases) by a multivariate Cox regression model. Results and discussion: A total of 3,490 pathogenic bacterial strains were isolated from bile samples, including 2,340 (67.05%) Gram-negative strains, 1,029 (29.48%) Gram-positive strains, and 109 (4.56%) fungal strains. The top five pathogenic bacteria were Escherichia coli, Klebsiella pneumoniae, Enterococcus faecium, Enterococcus faecalis, and Pseudomonas aeruginosa. The rate of Escherichia coli resistance to ciprofloxacin increased (p < 0.05), while the resistance to amikacin decreased (p < 0.05). The resistance of Klebsiella pneumoniae to cephalosporins, carbapenems, ß-lactamase inhibitors, cephalases, aminoglycosides, and quinolones increased (p < 0.05), and the resistance of Pseudomonas aeruginosa to piperacillin, piperacillin/tazobactam, ticacillin/clavulanic acid, and amicacin declined significantly (p < 0.05). The resistance of Enterococcus faecium to tetracycline increased by year (p < 0.05), and the resistance of Enterococcus faecalis to erythromycin and highconcentration gentamicin declined (p < 0.05). Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for biliary infection. In summary, Gram-negative bacilli were the most common pathogenic bacteria isolated from biliary infection patients, especially Escherichia coli, and the rates and patterns of drug resistance were high and in constant flux; therefore, rational antimicrobial drug use should be carried out considering risk factors. [ABSTRACT FROM AUTHOR]

Background: Impaired fasting glucose (IFG) is associated with the risk of various cancers, but the cumulative effect of IFG on gastrointestinal cancer risk remains unclear. This study evaluated the association between the cumulative exposure to IFG and gastrointestinal cancer risk. Methods: The authors extracted data from the Korean National Health Insurance Service and health examination data sets. Among individuals =40 years old who were free of diabetes or cancer, 1,430,054 who underwent national health examinations over 4 consecutive years from 2009 to 2012 were selected and followed up until gastrointestinal cancer diagnosis, death, or December 31, 2019. The IFG exposure score (range, 0-4) was based on the number of IFG diagnoses over 4 years. Results: The median follow-up duration was 6.4 years. Consistent normoglycemia for 4 years was found in 44.3% of the population, whereas 5.0% had persistent IFG and 50.7% had intermittent IFG. Compared to the group with an IFG exposure score of 0, groups with IFG exposure scores of 1, 2, 3, and 4 had a 5%, 8%, 9%, and 12% increased risk of gastrointestinal cancer, respectively (score 1: adjusted hazard ratio [aHR], 1.05; 95% confidence interval [CI], 1.01-1.08; score 2: aHR, 1.08; 95% CI, 1.04-1.12; score 3: aHR, 1.09; 95% CI, 1.05-1.14; score 4: aHR, 1.12; 95% CI, 1.06-1.19). Persistent IFG exposure was also associated with higher risks of individual cancer types (colorectum, stomach, pancreas, biliary tract, and esophagus). Conclusions: Cumulative exposure to IFG is associated with an increased risk of developing gastrointestinal cancer, in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review, first, the history of EUS-guided biliary drainage (EUS-BD) is summarized. In the following chapters controversies arising from various approaches and challenges in EUS-BD, EUS-guided gallbladder drainage (EUS-GBD) and alternatively performed procedures are discussed from different points of view on the background of the available evidence. In addition, for all topics arguments in favor and against the techniques are described and reflected. The topics include "Why do we need procedures other than ERCP?"; "Should EUS-BD and ERCP be performed by the same operator?"; rendezvous techniques, including "Should rendezvous be used first?" and "Which rendezvous route should be used?"; percutaneous transhepatic cholangiography and biliary drainage (PTBD); "Should PTBD and EUS-BD be performed by the same physician?"; "Do we need cystotomes?"; "Do we need bougies?"; "Are all EUS needles the same for EUS-BD?"; "Plastic or metal stents?"; and adverse events. In this 14th document in a series of papers entitled "Controversies in Endoscopic Ultrasound" we discuss various aspects of EUS-guided biliary drainage that are debated in the literature and in practice. Endoscopic retrograde cholangiography is still the reference technique for therapeutic biliary access, but EUS-guided techniques for biliary access and drainage have developed into safe and highly effective alternative options. However, EUS-guided biliary drainage techniques are technically demanding procedures for which few training models are currently available. Different access routes require modifications to the basic technique and specific instruments. In experienced hands, percutaneous transhepatic cholangiodrainage is also a good alternative. Therefore, in this paper, we compare arguments for different options of biliary drainage and different technical modifications. [ABSTRACT FROM AUTHOR]

Background: Intraoperative cholangiography (IOC) is a contrast-enhanced X-ray acquired during laparoscopic cholecystectomy. IOC images the biliary tree whereby filling defects, anatomical anomalies and duct injuries can be identified. In Australia, IOC are performed in over 81% of cholecystectomies compared with 20 to 30% internationally (Welfare AIoHa in Australian Atlas of Healthcare Variation, 2017). In this study, we aim to train artificial intelligence (AI) algorithms to interpret anatomy and recognise abnormalities in IOC images. This has potential utility in (a) intraoperative safety mechanisms to limit the risk of missed ductal injury or stone, (b) surgical training and coaching, and (c) auditing of cholangiogram quality. Methodology: Semantic segmentation masks were applied to a dataset of 1000 cholangiograms with 10 classes. Classes corresponded to anatomy, filling defects and the cholangiogram catheter instrument. Segmentation masks were applied by a surgical trainee and reviewed by a radiologist. Two convolutional neural networks (CNNs), DeeplabV3+ and U-Net, were trained and validated using 900 (90%) labelled frames. Testing was conducted on 100 (10%) hold-out frames. CNN generated segmentation class masks were compared with ground truth segmentation masks to evaluate performance according to a pixel-wise comparison. Results: The trained CNNs recognised all classes.. U-Net and DeeplabV3+ achieved a mean F1 of 0.64 and 0.70 respectively in class segmentation, excluding the background class. The presence of individual classes was correctly recognised in over 80% of cases. Given the limited local dataset, these results provide proof of concept in the development of an accurate and clinically useful tool to aid in the interpretation and quality control of intraoperative cholangiograms. Conclusion: Our results demonstrate that a CNN can be trained to identify anatomical structures in IOC images. Future performance can be improved with the use of larger, more diverse training datasets. Implementation of this technology may provide cholangiogram quality control and improve intraoperative detection of ductal injuries or ductal injuries. [ABSTRACT FROM AUTHOR]

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS‐elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self‐expanding metal stents for stent placement for pancreatic duct stenosis and EUS‐guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS‐guided drainage using a double‐pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen‐apposing metal stents have led to advances in the treatment of walled‐off necrosis after acute pancreatitis. EUS‐guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self‐expanding metal stents in difficult‐to‐treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS‐guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case. [ABSTRACT FROM AUTHOR]

This document provides highlights from the European Society for Medical Oncology (ESMO) Annual Meeting in 2023, specifically focusing on pancreatic, hepatic, and biliary tract cancer. The document discusses various clinical trials and studies related to these types of cancer. For localized pancreatic cancer, the PREOPANC-2 trial compared different treatment approaches and found that gemcitabine-based chemoradiotherapy was more effective than neoadjuvant FOLFIRINOX. In advanced pancreatic cancer, the JCOG1611-GENERATE trial showed that nab-paclitaxel plus gemcitabine was more effective than modified FOLFIRINOX or S-IROX. The document also mentions studies on hepatocellular carcinoma and cholangiocellular cancer, highlighting the use of targeted therapies. Overall, the document provides valuable information for researchers and healthcare professionals interested in these areas of oncology. [Extracted from the article]

Cholangiocarcinoma (CCA) is a rare cancer of the bile duct epithelium, and in the last few decades its incidence rate has been increasing. It is associated with a high mortality rate due to late diagnosis and its aggressive nature. Many risk factors have been identified; some are more common in certain regions than others. CCA can be classified according to its anatomical location or macroscopic growth pattern, the latter being most helpful for imaging interpretation. Clinical features can vary from obstructive-like symptoms to nonspecific symptoms, such as weight loss and malaise. Imaging, specifically MRI/ MRCP, is crucial in diagnosing CCA, staging, and treatment planning. Surgery with chemotherapy is the mainstay treatment option, and other palliative treatment options exist for those who have unresectable disease. [ABSTRACT FROM AUTHOR]

Aim: To present a 2-year experience of acute pancreatitis in pregnancy in our institution. Background: Acute pancreatitis during pregnancy is a rare event with incidence, ranging from 1:1,000 to 1:10,000. Biliary tract diseases are the most common cause of acute pancreatitis in pregnancy, with gallstone disease being responsible for more than 70% of cases. Gallstone formation during pregnancy is attributed to the lithogenic effect of pregnancy through estrogen and progesterone. Results: Seven pregnant women with clinical and biochemical diagnosis of acute pancreatitis were studied. The mean gestational age of presentation was 28 weeks, The most common presenting complaint was the upper abdominal pain with vomiting (72%). The maximum amylase level was observed to be 2696 IU/L and the maximum lipase level was 4788 IU/L showing the condition hypertriglyceridemia with the maximum level 757 mg/dL) (28%). One patient had hypocalcemia (5.7 mg/dL) (14%). Six of the seven patients had leukocytosis maximum 22,400/cmm. The corticosteroid-binding globulin (CBG) levels of all patients were normal. The liver function tests (LFTs) of all patients were normal. Three patients had USG features of gallbladder sludge, one patient had gallstones. Three patients required ICU admissions. One patient (14%) had late phase symptoms at 29 weeks gestation requiring UGI Scopy TPN, IV octreotide. Two patients (28%) had moderately severe acute pancreatitis (according to revised Atlanta classification). Clinical significance: It mimics the symptoms of acute fatty liver of pregnancy (AFLP), preeclampsia/hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, and GERD. Hence a thorough understanding of the presentation and differences in management of each condition is required to reduce significant maternal morbidity. Conclusion: Acute pancreatitis in pregnancy is associated with significant maternal morbidity. Early diagnosis, classifying the severity of disease and treatment with multidisciplinary approach was the gold standard treatment. [ABSTRACT FROM AUTHOR]

Introduction: Cholescintigraphy using Tc-99m Mebrofenin is routinely performed as an initial diagnostic test in infants with neonatal cholestasis suspected of having biliary atresia. Demonstration of drainage of bile into the small intestine indicates patency of the biliary tract and thus rules out biliary atresia. Non-excretion of tracer into the small intestine, however, can be caused by obstructive as well as non-obstructive conditions, and it is known that false-positive findings are found with the use of Tc-99m Mebrofenin scintigraphy. Aim: In the present study, we retrospectively calculated the proportion of infants eventually diagnosed to have biliary atresia that were initially ruled to have a non-excreting cholescintigraphy pattern in our institution. We have also attempted a systematic description of the cardinal histological characteristics, haematological and hepatic biochemical variables in infants with non-excreting patterns. Materials and Methods: This retrospective, descriptive study was conducted in Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry. We reviewed data from infants who underwent cholescintigraphy with Tc-99m Mebrofenin between January 2016 through June 2022. We included infants in whom the scan was ruled "non-excreting" i.e. those infants in whom biliary atresia could not be ruled out based on the results of the scan. The difference in mean for haematological parameters and ALP were compared between the two groups i.e., biliary atresia versus other than biliary atresia by using Independent student's t-test; the remaining liver biochemical parameters were compared by using Mann-Whitney U Test and a p value < 0.05 was considered to be statistically significant. Results: A non-excretory pattern on cholescintigraphy was found to be due to biliary atresia in 49% of cases (as confirmed by exploratory surgery) and an additional 19.6 % of cases by trucut biopsy (total 68.6%). The difference in the mean serum GGT levels was found to be statistically significant (<0.001). Conclusion: A non-draining pattern on cholescintigraphy is caused by biliary atresia in the greater percentage of cases presenting with cholestasis. The difference in mean GGT levels was found to be statistically significant between biliary atresia and other causes of non-draining patterns on cholescintigraphy. [ABSTRACT FROM AUTHOR]

The use of indocyanine green for fluorescent cholangiography in patients with cholecystitis initially treated with percutaneous cholecystostomy drainage catheters was described in this two case series. Two patients underwent robotic assisted cholecystectomy with fluorescent cholangiography and indocyanine green through percutaneous cholecystostomy drainage catheters. The patients were diagnosed with acute cholecystitis. Directed injection of indocyanine green allowed for direct visualization of the biliary system allowing for a safe identification of the critical view of safety. Injection of indocyanine green for fluorescent cholangiography through percutaneous cholecystostomy drainage catheters is reliable to assess the critical view of safety and allows for improved identification of the biliary tree anatomy. Administration of indocyanine green through the percutaneous cholecystostomy drainage catheters avoided background hepatic fluorescence and increased contrast between biliary structures. [ABSTRACT FROM AUTHOR]

This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC). Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems). Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055– 0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013– 0.863], P = 0.036). Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤ 6.0). [ABSTRACT FROM AUTHOR]

Biliary stents are used to optimize ductal patency and enable bile flow in the management of obstruction or injury related to biliary tract tumors, strictures, stones, or leaks. Although direct therapeutic applications of biliary stents are less well developed, stents can be used to deliver drugs, radioisotopes, and photodynamic therapy. This report provides an in-depth overview of the clinical indications, and therapeutic utility of biliary stents. Unique considerations for the design of biliary stents are described. The properties and functionalities of materials used for stents such as metal alloys, plastic polymers, or biodegradable materials are described, and opportunities for design of future stents are outlined. Current and potential applications of stents for therapeutic applications for biliary tract diseases are described. Therapeutic biliary stents could be used to minimize inflammation, prevent stricture formation, reduce infections, or provide localized anti-cancer therapy for biliary tract cancers. Stents could be transformed into therapeutic platforms using advanced materials, 3D printing, nanotechnology, and artificial intelligence. Whilst clinical study and validation will be required for adoption, future advances in stent design and materials are expected to expand the use of therapeutic biliary stents for the treatment of biliary tract disorders. [ABSTRACT FROM AUTHOR]

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC‐related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β‐catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence‐free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5‐year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

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Hepatic sparganosis (HS) is extremely rare and has not been previously reported in Eastern China. We report the diagnosis and treatment of a patient with HS from Xuzhou City, Jiangsu Province, China. The patient was admitted due to an acute biliary tract infection, and the symptoms improved after treatment at the Gastroenterology Department. During an ultrasound examination on admission, an abnormal echo was incidentally discovered at the junction of the left and right lobes of the liver. Thereafter, upper abdominal computed tomography (CT) and magnetic resonance imaging (MRI) non-contrast and contrast-enhanced examinations, and serum tumor biomarker examination were completed. After a multidisciplinary treatment (MDT) discussion at the Department of Hepatobiliary Surgery, the patient was diagnosed with intrahepatic mass-type cholangiocarcinoma (IMCC) and surgery was recommended. The patient underwent surgical treatment, and postoperative pathology revealed HS. No signs of intrahepatic recurrence were observed during the 1-year follow-up period. [ABSTRACT FROM AUTHOR]

Bile microecology changes play an important role in the occurrence and development of choledocholithiasis. At present, there is no clear report on the difference of bile microecology between asymptomatic patients with gallbladder polyps and choledocholithiasis. This study compared bile microecology between gallbladder polyp patients and patients with choledocholithiasis to identify risk factors for primary choledocholithiasis. This study was conducted in 3 hospitals in different regions of China. Bile samples from 26 patients with gallbladder polyps and 31 patients with choledocholithiasis were collected by laparoscopic cholecystectomy and endoscopic retrograde choledocholithiasis cholangiography (ERCP), respectively. The collected samples were used for 16S ribosomal RNA sequencing and liquid chromatography mass spectrometry analysis. The α-diversity of bile microecological colonies was similar between gallbladder polyp and choledocholithiasis, but the β-diversity was different. Firmicutes, Proteobacteri, Bacteroidota and Actinobacteriota are the most common phyla in the gallbladder polyp group and choledocholithiasis group. However, compared with the gallbladder polyp patients, the abundance of Actinobacteriota has significantly lower in the choledocholithiasis group. At the genera level, the abundance of a variety of bacteria varies between the two groups, and Enterococcus was significantly elevated in choledocholithiasis group. In addition, bile biofilm formation—Pseudomonas aeruginosa was more metabolically active in the choledocholithiasis group, which was closely related to stone formation. The analysis of metabolites showed that a variety of metabolites decreased in the choledocholithiasis group, and the concentration of beta-muricholic acid decreased most significantly. For the first time, our study compared the bile of gallbladder polyp patients with patients with choledocholithiasis, and suggested that the change in the abundance of Actinobacteriota and Enterococcus were closely related to choledocholithiasis. The role of Pseudomonas aeruginosa biofilm in the formation of choledocholithiasis was discovered for the first time, and some prevention schemes for choledocholithiasis were discussed, which has important biological and medical significance. [ABSTRACT FROM AUTHOR]

Background: Endoscopic sphincterotomy (EST) has been employed for the endoscopic treatment of common bile duct stones (CBDSs) and has been reported to have a high success rate for stone removal. However, EST is associated with a risk of bleeding, perforation, and sphincter of Oddi function disruption. To avoid these risks, endoscopic papillary balloon dilation (EPBD) is an option for CBDS. Sphincter of Oddi function preservation decreases long-term biliary infection and gallstone recurrence. EPBD may have advantages in children who require a long follow up. However, there have been few reports on pediatric cases, particularly in infants. Methods: From September 2017 to December 2023, we performed EPBD for four pediatric CBDSs. The patients were aged from 5 months to 8 years, including two infants aged 5 and 6 months. Furthermore, we reviewed the stone removal rate and complications of 545 ESTs performed at high-volume centers and 13 EPBD-reported cases in children with CBDSs. Results: CBDSs of all patients who underwent EPBD in our institution were successfully removed. No bleeding or perforation was noted; pancreatitis was observed in three patients. In an analysis of 545 ESTs in children, the stone removal rate was high, ranging from 83% to 100% (mean 96%). The incidence of pancreatitis was 0–9.6% (mean 4.4%), and the grade of pancreatitis was almost mild. The bleeding frequency was 1.3–5.4% (mean 2.7%). With regards to the grade of bleeding, seven cases were mild (64%) and four were moderate (36%). Compared with adults who underwent EST, the frequencies of pancreatitis and bleeding were almost equal in children; however, in children, once bleeding occurs, it has a higher risk of leading to blood transfusion. Stone removal via EPBD in children has a 100% success rate. Pancreatitis was responsible for all complications were related; its frequency was 46% (6/13 patients, including five mild cases and one moderate case), which is higher than that of EST and adult cases who underwent EPBD. In most children with pancreatitis, pancreatic enzyme levels returned to normal within 2–3 days following EPBD, and no severe cases caused by EPBD were reported. Conclusions: CBDS removal via EPBD in children has a high success rate with very low risk of bleeding and perforation. Although pancreatitis frequently occurs, most cases are mild. Sphincter of Oddi function preservation via EPBD is expected to prevent long-term stone recurrence and biliary tract infection, and EPBD is considered to be an effective method for CBDS removal in children. [ABSTRACT FROM AUTHOR]

Mirizzi syndrome (MS) is a challenging diagnosis due to its similar presentation with other biliary diseases; thus, the role of endoscopy is sometimes unclear, especially in altered anatomy. Radiological examinations may usually suspect it, but deeper examinations could be necessary to confirm it. Endoscopic retrograde cholangiopancreatography (ERCP) certainly has a therapeutic role in cases of jaundice, cholangitis or concurrent choledocolithiasis, although surgery is without doubt the definitive treatment in most of the cases. Therefore, surgeons may have a clearer picture of the condition of the biliary tree with respect to fistulas thanks to ERCP, particularly in patients with a higher grade of MS (type higher than 2 in the Csendes classification). Therefore, a complete removal of biliary stones is sometimes not possible due to size and location, so biliary stenting becomes the only option, even if transitory. Our brief report is a further demonstration of the fundamental role of ERCP in managing MS, even when it has no long-term therapeutic aim but is performed as bridge-to-surgery, especially in cases with a more difficult biliary anatomy due to the type of fistula. Moreover, we truly suggest discussing patients affected with MS in a multidisciplinary board, preferably in tertiary hepatobiliary centers. [ABSTRACT FROM AUTHOR]

Backgrounds: Radical resection is the most effective treatment for perihilar tumors. Biliary tract reconstruction after resection is one of the key steps in this surgery. Mucosa-to-mucosa cholangiojejunostomy is traditionally performed, in which the bile ducts at the resection margin are separately anastomosed to the jejunum. However, this approach is associated with long operative time and high risk of postoperative complications. The present study presents a modified technique of hepatojejunostomy and its outcomes. Methods: The data of patients who underwent hepatojejunostomy using the modified technique at the Department of Hepatobiliary Surgery, Daping Hospital, Army Medical University, Chongqing, China, from January 2016 to December 2021, were retrospectively analyzed. Results: A total of 13 patients with perihilar tumors underwent R0 resection and bilioenteric reconstruction using the modified hepatojejunostomy technique during the study period. During the operation, the alignment of the bile duct stumps was improved, the posterior wall of the anastomosis was reinforced, internal stents were placed in the smaller bile ducts, external stents were placed in the larger bile ducts, and hepatojejunostomy was performed using 4 − 0 prolene. No serious postoperative complications, such as death or bile leakage, occurred during the hospitalization. Furthermore, there were no cases of biliary stricture or cholangitis after the six-month follow-up period. Conclusion: The modified hepatojejunostomy technique is a safe and effective technique of biliary reconstruction after the resection of perihilar tumors. This can be easily performed for difficult cases with multiple bile ducts that require reconstruction after resection. [ABSTRACT FROM AUTHOR]

Background: To assess the feasibility and tissue response of using a gold nanoparticle (AuNP)-integrated silicone-covered self-expandable metal stent (SEMS) for local hyperthermia in a rat esophageal model. Methods: The study involved 42 Sprague–Dawley rats. Initially, 6 animals were subjected to near-infrared (NIR) laser irradiation (power output from 0.2 to 2.4 W) to assess the in vitro heating characteristics of the AuNP-integrated SEMS immediately after its placement. The surface temperature of the stented esophagus was then measured using an infrared thermal camera before euthanizing the animals. Subsequently, the remaining 36 animals were randomly divided into 4 groups of 9 each. Groups A and B received AuNP-integrated SEMS, while groups C and D received conventional SEMS. On day 14, groups A and C underwent NIR laser irradiation at a power output of 1.6 W for 2 min. By days 15 (3 animals per group) or 28 (6 animals per group), all groups were euthanized for gross, histological, and immunohistochemical analysis. Results: Under NIR laser irradiation, the surface temperature of the stented esophagus quickly increased to a steady-state level. The surface temperature of the stented esophagus increased proportionally with power outputs, being 47.3 ± 1.4 °C (mean ± standard deviation) at 1.6 W. Only group A attained full circumferential heating through all layers, from the epithelium to the muscularis propria, demonstrating marked apoptosis in these layers without noticeable necroptosis. Conclusions: Local hyperthermia using the AuNP-integrated silicone-covered SEMS was feasible and induced cell death through apoptosis in a rat esophageal model. Relevance statement: A gold nanoparticle-integrated silicone-covered self-expanding metal stent has been developed to mediate local hyperthermia. This approach holds potential for irreversibly damaging cancer cells, improving the sensitivity of cancer cells to therapies, and triggering systemic anticancer immune responses. Key points: • A gold nanoparticle-integrated silicone-covered self-expanding metal stent was placed in the rat esophagus. • Upon near-infrared laser irradiation, this stent quickly increased the temperature of the stented esophagus. • Local hyperthermia using this stent was feasible and resulted in cell death through apoptosis. [ABSTRACT FROM AUTHOR]

Common bile duct duplications represent exceptionally rare congenital anomalies of the biliary tract. In this case report we document an unusual variant of common bile duct duplication in a 79-year-old man who underwent a pancreaticoduodenectomy for ampullary cancer. The duplication consisted of two unseparated, completely-layered, common bile ducts which originated above the cystic duct junction and terminated prior to the point of insertion into the pancreas, where the two lumens converged into a single duct. Duplication of the bile duct is rare and often goes undetected. In the present case, the anomaly was found incidentally in a patient who had a pancreaticoduodenectomy for an ampullary carcinoma. However, duplication may be associated with choledocholithiasis, cholangitis, pancreatitis, and pancreaticobiliary malignancies and it is important to be aware of the condition. [ABSTRACT FROM AUTHOR]

Background: Choledochal cysts are rare congenital anomalies of the biliary tree that may lead to obstruction, chronic inflammation, infection, and malignancy. There is wide variation in the timing of resection, operative approach, and reconstructive techniques. Outcomes have rarely been compared on a national level. Methods: We queried the Pediatric National Surgical Quality Improvement Program (NSQIP) to identify patients who underwent choledochal cyst excision from 2015 to 2020. Patients were stratified by hepaticoduodenostomy (HD) versus Roux‐en‐Y hepaticojejunostomy (RNYHJ), use of minimally invasive surgery (MIS), and age at surgery. We collected several outcomes, including length of stay (LOS), reoperation, complications, blood transfusions, and readmission rate. We compared outcomes between cohorts using nonparametric tests and multivariate regression. Results: Altogether, 407 patients met the study criteria, 150 (36.8%) underwent RNYHJ reconstruction, 100 (24.6%) underwent MIS only, and 111 (27.3%) were less than one year old. Patients who underwent open surgery were younger (median age 2.31 vs. 4.25 years, p = 0.002) and more likely underwent RNYHJ reconstruction (42.7% vs. 19%, p = 0.001). On adjusted analysis, the outcomes of LOS, reoperation, transfusion, and complications were similar between the type of reconstruction, operative approach, and age. Patients undergoing RNYHJ had lower rates of readmission than patients undergoing HD (4.0% vs. 10.5%, OR 0.34, CI [0.12, 0.79], p = 0.02). Conclusions: In children with choledochal cysts, most short‐term outcomes were similar between reconstructive techniques, operative approach, and age at resection, although HD reconstruction was associated with a higher readmission rate in this study. Clinical decision‐making should be driven by long‐term and biliary‐specific outcomes. [ABSTRACT FROM AUTHOR]

Background: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. Methods: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. Results: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. Conclusions: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors. [ABSTRACT FROM AUTHOR]

With Currently, Endoscopic retrograde cholangiopancreatography (ERCP) has evolved as a therapeutic intervention for treating disorders related to the biliary system and plays an important role in treating benign and malignant strictures of the biliary system. The placement of biliary stents is a frequent and useful procedure to decompress the biliary system, and endoscopic biliary stenting seems relatively simple. However, in some cases, it can lead to several complications. Distal or proximal migration of endoscopically placed biliary stents is one of the known complications of ERCP and can affect up to 6-10% of patients. Several factors, including those related to the patient, endoscopy, or stent, are involved in stent migration. When migration occurs, it is necessary to remove or replace endoprosthesis to prevent recurrent biliary complications and more severe consequences such as cholangitis and sepsis. This review explores the frequency, etiology, risk factors, complications, and management strategies pertaining to biliary stent migration, consolidating diverse management approaches for informed decision-making. [ABSTRACT FROM AUTHOR]

Background: In the era of laparoscopic procedure, there are innovations in non-surgical management approaches for managing biliary tract disorders, such as therapeutic endoscopic retrograde cholangiopancreatography (ERCP) and interventional endoscopic ultrasound (EUS). There is still no clear consensus yet in step-approach to managing difficult biliary disorders. Therefore, this study was performed to see the impact of endoscopic approach management on the outcomes of complex biliary cases. Method: A retrospective endoscopy database study within two years period was conducted. Characteristics of the study subjects, including demography and clinical data, were presented descriptively. The technical success rate was defined as the completion of the procedure performed on the patients. A bivariate analysis was conducted to evaluate the outcomes of therapy. Results: Sixty-one subjects in this retrospective database study were considered as complex biliary cases. In this study, 16.4% of the subjects underwent a combination of therapeutic ERCP and EUS in one session based on the complexity of the case; and 8.2% of the subjects underwent therapeutic ERCP with additional single operator cholangioscopy procedure. One subject underwent the rendezvous ERCP procedure through a percutaneous approach. Around 4.9% of the subjects underwent EUS-guided biliary drainage procedure. No significant association was observed between all mortality outcomes and baseline characteristics of the patients. There were also no significant associations between re-intervention procedures, as well as post-procedural pain or acute pancreatitis, with mortality outcomes. Conclusion: Complex biliary cases require a good clinical approach algorithm to decide which procedure comes first based on a comprehensive evaluation consisting of the patient's factor, expertise, cost, and the risk of complications. [ABSTRACT FROM AUTHOR]

Background: There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). Aims: This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. Methods: Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. Results: Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17—0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. Conclusions: Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC. [ABSTRACT FROM AUTHOR]

There is an increasing apprehension surrounding the potential health implications associated with prolonged exposure to environmental micro- and nano-plastics (MNPLs) on the human population. Microplastics pose significant threats to both aquatic and terrestrial ecosystems, entering water bodies through various pathways and accumulating in sediments. Additionally, they infiltrate terrestrial environments, spreading contamination through air, water, and soil, impacting soil health and potentially entering the food chain. Likewise, humans encounter microplastics through diverse exposure routes. Studies have demonstrated that multiple substances involved in oncogenetic pathways can trigger carcinogenesis in the human body, leading to various cancers such a colorectal, liver, lung, skin, breast, biliary tract, leukemia, and pancreatic cancers. In this review, we examine the literature highlighting this emerging health issue. [ABSTRACT FROM AUTHOR]

Gender Medicine has had an enormous expansion over the last ten years. Autoimmune liver diseases include several conditions, i.e., autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and conditions involving the liver or biliary tree overlapping with AIH, as well as IgG4-related disease. However, little is known about the impact of sex in the pathogenesis and natural history of these conditions. The purpose of this review is to provide an update of the gender disparities among the autoimmune liver diseases by reviewing the data published from 1999 to 2023. The epidemiology of these diseases has been changing over the last years, due to the amelioration of knowledge in their diagnosis, pathogenesis, and treatment. The clinical data collected so far support the existence of sex differences in the natural history of autoimmune liver diseases. Notably, their history could be longer than that which is now known, with problems being initiated even at a pediatric age. Moreover, gender disparity has been observed during the onset of complications related to end-stage liver disease, including cancer incidence. However, there is still an important debate among researchers about the impact of sex and the pathogenesis of these conditions. With this review, we would like to emphasize the urgency of basic science and clinical research to increase our understanding of the sex differences in autoimmune liver diseases. [ABSTRACT FROM AUTHOR]

Limy bile syndrome (LBS) is a condition in which the biliary tract is filled with radiodense calcium carbonate rich sludge. This rare condition can complicate the management of commonly encountered biliary conditions such as choledocholithiasis. We present a case of a male in his fifties who presented to hospital with a 12-day history of abdominal pain, nausea and jaundice. Imaging and laboratory findings demonstrated a dependent radio-dense substance within the biliary system as well as an obstructing calculus at the duodenal ampulla. Management with endoscopic retrograde cholangiopancreatography alone was insufficient and further surgical management was required. With no clear published guidelines on LBS and associated cholelithiasis, management is variable. We present this case as an addition to the literature on the management of choledocholithiasis complicated by LBS. [ABSTRACT FROM AUTHOR]

Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research. [ABSTRACT FROM AUTHOR]

Background: Despite the approval of tremelimumab in 2022, there is a lack of pharmacovigilance studies investigating its safety profile in real-world settings using the FDA Adverse Event Reporting System (FAERS) database. Aim: This pharmacovigilance study aimed to comprehensively explore the adverse events (AEs) associated with tremelimumab using data mining techniques on the FAERS database. Method: The study utilized data from the FAERS database, covering the period from the first quarter of 2004 to the third quarter of 2022. Disproportionality analysis, the Benjamini Hochberg adjustment method and volcano plots were used to identify and evaluate AE signals associated with tremelimumab. Results: The study uncovered 233 AE cases associated with tremelimumab. Among these cases, pyrexia (n = 39), biliary tract infection (n = 23), and sepsis (n = 21) were the three main AEs associated with tremelimumab use. The study also investigated the system organ classes associated with tremelimumab-related AEs. The top three classes were gastrointestinal disorders (17.9%), infections and infestations (16.6%), and general disorders and administration site infections (11.2%). Several AEs were identified that were not listed on the drug label of tremelimumab. These AEs included pyrexia, biliary tract infection, sepsis, dyspnea, infusion site infection, hiccup, appendicitis, hypotension, dehydration, localised oedema, presyncope, superficial thrombophlebitis and thrombotic microangiopathy. Conclusion: This pharmacovigilance study identified several potential adverse events signals related to tremelimumab including some adverse events not listed on the drug label. However, further basic and clinical research studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

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Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal "C" loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, which is usually associated with long-term alcohol and tobacco misuse, and is more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66-year-old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast-enhanced computed tomography revealed the existence of chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head, and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since endoscopic retrograde cholangiopancreatography was not possible due to the local changes, we decided to perform pancreatoduodenectomy, as surgery appears to be the single effective treatment. [ABSTRACT FROM AUTHOR]

Cholangiopathies include a group of chronic progressive disorders, affecting the cholangiocytes, the epithelial cells that line the biliary tree, leading to liver parenchymal fibrosis and eventually end-stage liver disease necessitating transplantation. Experimental modeling of these multifactorial cholestatic diseases faces challenges due to the lack of adequate experimental in vitro and in vivo models. A novel approach employs three-dimensional organoid systems that offer several advantages for modeling disease and testing drug response in vitro. Organoids mimic intercellular communication, replicate the architecture of organs, and maintain the cell's original phenotype. Cholangiocyte organoids provide an in vitro model to study the pathogenesis and pharmacotherapeutic treatment of cholangiopathies and show great promise for regenerative therapies. In particular, patient-derived organoids allow personalized medicine approaches and the study of individual disease characteristics. This review highlights the significance of cholangiocyte organoid models in advancing our understanding of cholangiopathies and driving advancements in regenerative medicine strategies. [ABSTRACT FROM AUTHOR]

Laparoscopic cholecystectomy is the most common procedure performed for the management of symptomatic gallstone disease. This, however, can be complicated by the formation of fistulous communications between the biliary tree and the gastrointestinal tract. This abnormal communication allows for the flow of bile and bowel contents between two systems (biliary system and intestine), which can cause abdominal pain, nausea, vomiting, and biliary sepsis. We would like to present a rare case of fistulous communication between the cystic duct stump and duodenum and outline possible contributing factors. The literature review describes the most common interventions for the management of fistulas with emphasis on ERCP and stent preferences to eliminate transpapillary pressure gradient, which directly contributes to fistula closure. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Hydatid cysts, primarily found in the liver (70%), are caused by parasitic infections and can lead to severe complications such as cyst rupture. This case report describes a unique instance of a hydatid liver cyst occupying the right lobe with a communicating part with the biliary tree that ruptured showing a concurrent superinfection. Hydatid cysts are a clinical pathology resulting from parasitic infections. They may occur in different organs of the body. However, these are mostly found in the liver (70%). This can cause significant complications including cyst rupture. Several case reports have described various hydatid cyst ruptures; however, only a few have reported an intra‐biliary hydatid cyst rupture. A 24‐year‐old male patient presented with right upper quadrant pain, jaundice, dark urine, and pale stool. Imaging studies, including Magnetic resonance cholangiopancreatography (MRCP) and computed tomography (CT), revealed a beavertail liver, cystobiliary communication and intrahepatic biliary tree‐ruptured hydatid cysts. The cyst was in the right liver lobe, which is the most common site for hydatid cysts. Surgical intervention involving laparoscopic de‐roofing and cyst removal resulted in a smooth recovery without complications. Several case reports have described various hydatid cyst ruptures; however, only a few have reported originally placed intra‐biliary hydatid cyst ruptures. This case report describes a unique instance of a hydatid liver cyst occupying the right lobe with a communicating part with the biliary tree that ruptured showing a concurrent superinfection. [ABSTRACT FROM AUTHOR]

Background/Aims: Peroral cholangioscopy (POC) has been used to assess intrahepatic duct (IHD) lesions but with a limited role. A new multibending (MB) ultraslim endoscope has been designed to improve POC performance. We evaluated the usefulness of POC using the MB ultraslim endoscope for the management of IHD lesions. Methods: Between March 2017 and March 2020, 22 patients underwent direct POC using the MB ultraslim endoscope for IHD lesions documented by previous imaging or cholangiopancreatography. The primary outcome was technical success of POC, and secondary outcomes were technical success of POC-guided interventions, median procedure time, and POC-related adverse events. Results: The technical success rate for POC using the MB ultraslim endoscope for IHD lesions was 95.5% (21/22). Free-hand insertion was successful in 95.2% (20/21). The overall technical success rate for POC-guided intervention was 100% (21/21), including nine diagnostic and 12 therapeutic procedures (eight direct stone removal and four intraductal lithotripsies). The median procedure time was 29 minutes (range, 9 to 79 minutes). There were no procedure-related adverse events. Conclusions: Direct POC using the MB ultraslim endoscope allows direct visualization of IHD lesions and may be useful for diagnosis and therapeutic management in selected patients. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine tumors (NETs) are rare epithelial neoplasms that arise most commonly from the gastrointestinal tract. In pediatrics, the most common site of origin is in the appendix, with the liver being the most common site of metastasis. Neuroendocrine tumors arising from the biliary tract are extremely rare. Methods: We describe a case of a nine‐year‐old girl who presented with obstructive cholestasis and was found to have multiple liver masses identified on biopsy as well‐differentiated neuroendocrine tumor with an unknown primary tumor site. Result: The patient underwent extensive investigation to identify a primary tumor site, including endoscopy, endoscopic ultrasound, and capsule endoscopy. The patient ultimately underwent definitive management with liver transplant, and on explant was discovered to have multiple well‐differentiated neuroendocrine tumors, WHO Grade 1, with extensive infiltration into the submucosa of bile duct, consistent with primary biliary tract neuroendocrine tumor. Conclusion: Identifying the site of the primary tumor in NETs found within the liver can be challenging. To determine if an extrahepatic primary tumor exists, workup should include endoscopy, EUS, and capsule endoscopy. Children with well‐differentiated hepatic NETs, with no identifiable primary tumor, and an unresectable tumor, are considered favorable candidates for liver transplantation. [ABSTRACT FROM AUTHOR]

Background: In patients with advanced biliary tract cancer (BTC), first-line chemotherapy plus immunotherapy has improved outcomes; however, second-line options that reflect the disease's molecular heterogeneity are still needed. One emerging target is MDM2, amplified in ~5– 8% of BTC cases. Methods: This is a subset analysis of two ongoing Phase Ia/Ib trials assessing patients treated with brigimadlin (BI 907828; a highly potent, oral MDM2–p53 antagonist) ± ezabenlimab (PD-1 inhibitor) ± BI 754111 (anti-LAG-3; n = 1). Results: Results from 12 patients with BTC are shown (monotherapy: n = 6/combination: n = 6). Six patients achieved partial response (monotherapy: n = 2/combination: n = 4), four had stable disease; responses were durable. Brigimadlin had a manageable safety profile. Seven patients had dose reductions due to adverse events, but no treatment-related adverse events led to treatment discontinuation. Conclusion: Brigimadlin demonstrated anti-tumor activity in patients with advanced MDM2-amplified BTC, and warrants further investigation. Plain Language Summary: Biliary tract carcinoma (BTC) is a cancer that affects the bile ducts which are part of the digestive system. Usually, the first treatment for advanced BTC (ie cannot be removed surgically and/or has spread) is chemotherapy in combination with immunotherapy. However, if chemotherapy does not work, or stops working, there are few treatment options available in second-line. Accordingly, intensive research is ongoing to try and find effective drugs. One potential medicine, called brigimadlin (or BI 907828), is a tablet that activates a molecule in tumor cells called p53. The normal function of p53 is to kill cells when they first start to become cancerous. However, if p53 is turned off by genetic mutations, or other mechanisms, then cancer can develop. Although p53 is rarely mutated in BTC tumors, it is inactivated by another molecule called MDM2 which is usually present at abnormally high levels in BTC. Brigimadlin prevents interaction between MDM2 and p53. This activates p53 and causes the cancer to die. Two clinical trials are currently assessing brigimadlin in a range of cancers, including BTC, with the aim of identifying a safe dose that can be examined in more detail in larger trials. So far, 12 patients with BTC have been treated. The patients' tumors significantly shrank in six of these patients and remained stable in a further four patients. Side effects were as expected and could be tolerated by pausing treatment or lowering the dose. These results show that brigimadlin should be tested further in patients with advanced BTC. [ABSTRACT FROM AUTHOR]

Background Percutaneous cholangioscopy (PerC) offers an alternative for patients with an inaccessible biliary tree. This systematic review and meta-analysis aimed to evaluate the performance of this technique. Methods A search in Medline, Cochrane and ClinicalTrials.gov databases was performed for studies assessing PerC up to October 2022. The primary outcome was diagnostic success, defined as successful stone identification or stricture workup. Secondary outcomes included therapeutic success (stone extraction, stenting) and complication rate. A subgroup analysis compared previous-generation and modern cholangioscopes. We performed meta-analyses using a randomeffects model and the results were reported as percentages with 95% confidence interval (CI). Results Fourteen studies (682 patients) were eligible for analysis. The rate of diagnostic success was 98.7% (95%CI 97.6-99.8%; I2=31.19%) and therapeutic success was 88.6% (95%CI 82.8-94.3%; I2=74.92%). Adverse events were recorded in 17.1% (95%CI 10.7-23.5%; I2=77.56%), of which 15.9% (95%CI 9.8-21.9%; I2=75.98%) were minor and 0.6% (95%CI 0.1-1.2%; I2=0%) major. The Spyglass system showed null heterogeneity for all outcomes; compared with older-generation endoscopes it offered comparable diagnostic success, but yielded significantly superior therapeutic success (96.1%, 95%CI 90-100%; I2=0% vs. 86.4%, 95%CI 79.2-93.6%; I2=81.41%; P=0.02]. Conclusion PerC, especially using currently available cholangioscopes, is associated with high diagnostic and therapeutic success. [ABSTRACT FROM AUTHOR]

Injury to the Luschka ducts (LDs), also named "subvesicular" ducts, is an under-reported cause of biliary leak following laparoscopic cholecystectomy (LC). A systematic literature search according to PRISMA guidelines was conducted in PubMed, EMBASE and Cochrane Library including all publications that described a bile leak from an LD. A total of 136 articles were retrieved from the searched databases. After the removal of duplicates and non-eligible papers, 48 studies reporting 231 leaks were included: 20 (41.6%) case reports, 2 (4.3%) comparative studies, 7 (14.9%) meeting abstracts and 19 (40.4%) retrospective cohort articles. The rate of LD leak ranges from 0.05% to 1.9%, but injury to a duct of Luschka was the second most common cause of biliary leakage in all the cohort studies (5.5% to 41%). In 21 (43.7%) cases, the leak was successfully treated with a sphincterotomy through Endoscopic Retrograde Cholangiopancreatography (ERCP) plus or minus stenting, and in 12 (25%), re-laparoscopy was necessary. [ABSTRACT FROM AUTHOR]

Simple Summary: The relation between biliary tree diseases and pancreatitis is not well-known in veterinary medicine. Anecdotally, hyperlipemia, pancreatic inflammation, and abnormalities of biliary flow are thought to play a role in the pathogenesis. The aim of the work was to study the frequency and features of pancreatic involvement in dogs with chronic biliary tree disease. We retrospectively included 81 dogs with both laboratory and ultrasound signs of chronic biliary tree disease. Medical records of the included dogs and their pancreatic involvement was recorded considering ultrasonographic features and/or biochemical alterations (Lipase DGGR). Fifty-eight dogs (72%) showed pancreatic involvement, suggesting that pancreatic status should be investigated in canine patients with chronic biliary tree disease. Canine chronic biliary tree disease (CBTD) is a suspected risk factor for pancreatic injury. The aim of this study was to evaluate the frequency and features of pancreatic involvement in canine CBTD, and their relationship with hyperlipemia and its severity. CBTD was defined as the increase in at least two of ALP, GGT, total bilirubin, cholesterol, and a biliary tree abnormal abdominal ultrasound (graded mild to severe). Pancreatic ultrasound appearance was recorded and classified as acute/chronic. Dogs were divided into a PBD group (pancreatic and biliary disease) and BD group (only biliary tree disease). PBD group was subgraded into a "pancreatic injury" and "pancreatitis" group. Eighty-one dogs were retrospectively included: 56 in the PBD group and 25 in the BD group. Of the PBD group, 20 had pancreatitis (15 chronic and 5 dogs acute). US score was mild in 64 dogs and moderate in 17 dogs, and it was not associated with evidence of pancreopathy. Sixty-six dogs had hyperlipemia (mild = 27 dogs; moderate-to-severe = 39 dogs) and no association with pancreopathy was found. Pancreatic injury was more frequent than pancreatitis in CBTD dogs. Although both acute and chronic pancreatic injury may be present, chronic forms were more frequent. Pancreatic injury should be considered in CBTD patients due its possible clinical significance. [ABSTRACT FROM AUTHOR]

Anatomical variations of the biliary tree pose diagnostic and treatment challenges. While most are harmless and often discovered incidentally during procedures, some can lead to clinical issues and biliary complications, making knowledge of these variants crucial to prevent surgical mishaps. Here, we present an unusual and clinically significant case. A 61-year-old man is admitted to the hospital with epigastric pain and diagnosis of pancreatitis of biliary origin and intermediate risk of choledocholithiasis. Magnetic resonance cholangiopancreatography (MRCP) reported hepatolithiasis and choledocholithiasis, whereas endoscopic retrograde cholangiopancreatography showed cystic drain of the right hepatic duct. One month later the patient presented again to the emergency room with increasing abdominal pain and a computed tomography that demonstrated the presence of hepatic abscess and acute cholecystitis. The patient underwent percutaneous drain abscess and a subtotal laparoscopic cholecystectomy. Biliary anatomical variants present challenges on the diagnostic investigations, interventional and surgical procedures, understanding the possible complications is essential. [ABSTRACT FROM AUTHOR]

An abdominal Computed Tomography (CT) scan gives more information about diseases of the liver, gallbladder, and biliary tract. In the image processing approach, liver segmentation is an essential step to be done before liver lesion detection. Liver segmentation removes the unwanted regions from the CT image and makes the task of lesion detection easier. In this paper, a novel Morph-Rec model based on morphological reconstruction operation is proposed for liver segmentation from CT images. The proposed work is focused on segmenting the liver region from the CT slices irrespective of the size and shape of the liver region. The proposed model is validated on 2650 CT slices of 120 and 20 CT scans from the LITS and 3DIRCADb datasets, respectively. The proposed Morph-Rec method is evaluated using metrics such as dice score, accuracy, F1 score, Jaccard index and Matthew's correlation coefficient. To justify the adaptability and efficiency of the proposed model, it is also validated on 50 CT slices of nine CT scans provided by a local scan centre. The proposed method has produced excellent results on all metrics and the obtained results are better than the state-of-the-art conventional methods for liver segmentation. Hence, the proposed technique is an automatic and dataset-generic model that can perform liver segmentation precisely on any CT acquisition of the liver. [ABSTRACT FROM AUTHOR]