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The article discusses a case study of a 73-year-old man with acute cholecystitis who underwent endoscopic transpapillary gallbladder drainage using a novel cholangioscope due to high surgical risk and Chilaiditi syndrome. The method involved utilizing a cholangioscope with a cytology brush sheath to locate the cystic duct bifurcation and safely advance a guidewire into the gallbladder for drainage. This cost-effective and reliable technique offers a solution for challenging cases where surgery or percutaneous drainage is not feasible, providing a safer alternative for patients. [Extracted from the article]

ABSTRACT Mycotoxins, originating from contaminated raw materials or suboptimal feed storage, are a growing concern in tropical aquaculture. Common fungi such as Aspergillus spp. and Fusarium spp. produce mycotoxins including aflatoxin, fumonisin, deoxynivalenol and zearalenone. High doses or prolonged exposure (weeks) to low doses of these mycotoxins (< 20 μg/kg) can depress growth, immunity, and cause mortality. This study investigated poor growth and low survival in juvenile Asian seabass, Lates calcarifer fed two different diets (FM40 and ABS3) for 5 weeks. Analysis of these diets revealed high peroxide values, multiple mycotoxins and high histamine levels. Fish fed the FM40 diet, which was contaminated with aflatoxin B1 (13.2 μg/kg), aflatoxin B2 (1.9 μg/kg), deoxynivalenol (29.5 μg/kg), alternariol (2.2 μg/kg), elevated peroxide value (45.91 mEq/kg), and histamine (129.51 mg/kg) developed mild bile duct hyperplasia, depressed total serum proteins (50.40 ± 10.06 g/L), markedly elevated blood potassium (8.2 ± 0.18 mmol/L), and heavy iron deposits in splenic melanomacrophage centres (Perl's stain) indicative of increased haemolysis. The presence of multiple cytotoxic mycotoxins in FM40 diet could explain the increased haemolysis and elevated blood potassium. In contrast, fish fed the ABS3 diet, which had high histamine levels (210.05 mg/kg), exhibited protein‐losing nephropathy with multifocal fibrin plugs (Martius scarlet blue stain) indicating acute renal damage, and elevated blood calcium and phosphorus levels. Histamine is metabolised and excreted through the kidneys and known to induce renal arteriolar constriction, disrupt glomerular filtration barrier and increase permeability resulting in protein loss. This study shows that blood biochemistry and histopathology are useful diagnostic tools for assessing the impact of mycotoxins and histamines on fish health. [ABSTRACT FROM AUTHOR]

Background: The anatomy of the biliary tree is complex with anatomical variations which can be found in ~50% of the patients. Purpose: Existing research on these variations primarily stems from studies in developed countries, with uncertain applicability to the Ugandan population due to noted ethnic differences in incidence rates. Objective: The study was aimed at describing the anatomical variations of the gallbladder and bile ducts. Methods: This retrospective cross‐sectional study conducted at Kampala MRI Centre from January 2017 to December 2022 analyzed MRCP images and reports from 231 patients to document gallbladder and bile duct variations. Results: 53.2% of patients exhibited typical cystic duct anatomy, and 51% had Type 1 variations in intrahepatic ducts. Importantly, the study identified a significant correlation between age and common bile duct diameter. Conclusion: The findings showed various anatomical variations that were slightly higher in the study population than those reported in the literature. This study emphasizes the critical need for comprehensive knowledge to enhance surgical safety, minimize iatrogenic trauma, and improve the accuracy of diagnostic imaging and hepatobiliary procedures. [ABSTRACT FROM AUTHOR]

Background: Endoscopic retrograde cholangiopancreaticography (ERCP) is the standard endoscopic procedure for the diagnosis and treatment of diseases of the pancreas and bile ducts. Cholangioscopy provides direct visualization of the bile ducts. It offers the possibility of more detailed diagnostic and therapeutic indications. Today, cholangioscopy is often performed as a single-operator (SOC) procedure. Objectives: We were interested in the clinical efficacy of our SOC procedure in comparison with published studies, and performed this retrospective data analysis of all our consecutive patients from 2016 to 2022 to analyze the feasibility, safety, and efficacy of SOC. Design and Methods: A retrospective single-center analysis of patients undergoing SOC at a tertiary center from 2016 to 2022 (N = 196) was performed. Demographic data, indication for SOC, exam-specific data, efficacy, and complications were included. Sensitivity and specificity for diagnosing indeterminate biliary strictures were calculated. Results: The most common indications for SOC were indeterminate biliary strictures (n = 117; 60%), treatment of biliary stones (n = 45; 23%), and other indications (n = 34; 17%), for example, foreign body removal or intraoperative SOC. In 97% of the SOC (n = 191), the procedure was technically successful. The diagnostic or therapeutic goal was achieved in 91% of SOC (n = 173). In the subgroup where the SOC result was confirmed by subsequent surgery (n = 93), sensitivity was 86%, specificity 99%, and SOC treatment of stones was successful in 89%. Complications occurred in (20%; n = 37). The majority of these patients (n = 18; 10%) had minor bleeding requiring no intervention. Conclusion: SOC is an effective and safe procedure that should be the standard of care when primary diagnostic and/or therapeutic ERCP has failed. The sensitivity and specificity for determining the dignity of biliary strictures and the efficacy for the treatment of difficult-to-treat stones are reproducibly very high. Plain language summary: Feasibility, safety and efficacy of endoscopic biliary endoscopy: a retrospective Single Center study Imaging the bile duct with contrast medium and fluoroscopy as part of endoscopic retrograde cholangiopancreaticography (ERCP) is the gold standard. However, direct visualization of the bile duct using a small camera on a second endoscope (cholangioscope) opens up further diagnostic and therapeutic possibilities. This study is a retrospective study covering the years 2016-2022, with a total of 196 patients. Demographic data, indication for SOC, exam specific data, efficacy, complications were included. The most common indications for direct biliary endoscopy were indeterminate biliary strictures (n=117; 60%), treatment of biliary stones (n=45; 23%) and other indications (n=34; 17%), e.g. foreign body removal or intraoperative biliary endoscopy. In 97% of the direct biliary endoscopy (n=191), the procedure was technically successful. The diagnostic or therapeutic goal was achieved in 91% of direct biliary endoscopy (n=173). In summary, direct biliary endoscopy is an effective and safe procedure that should be the standard of care when primary diagnostic and/or therapeutic ERCP has failed. [ABSTRACT FROM AUTHOR]

The article discusses the advancements in clinical research on biliary drainage, particularly focusing on the criteria for evaluating the outcomes of bile duct stents. It highlights the need for common definitions regarding procedure-related outcomes, stent dysfunction, and adverse events. The new TOKYO criteria, recently revised after a decade, categorize indications into obstructive jaundice and cholangitis, redefine terms related to biliary drainage, and emphasize the importance of clinical success in biliary treatment using stents. The article aims to provide a comprehensive framework for assessing biliary drainage outcomes and encourages further research in this field. [Extracted from the article]

Introduction: Diagnosis of choledocholithiasis, a common manifestation of gallstone disease, is mainly based on advanced endoscopic techniques such as ERCP and EUS. Since the 1970s, ERCP has been a key method in the diagnosis and treatment of choledocholithiasis, allowing direct visualization and therapeutic interventions. However, technological developments have brought the emergence of EUS as a complementary tool, providing high-resolution imaging of the bile ducts. Understanding the diagnostic accuracy, therapeutic options and complications of both modalities is key to optimizing the care of patients with bile duct stones. Aim of the study: The aim of our study is to review and compare various diagnostic methods of bile duct stones, as well as to assess their effectiveness, accuracy, and potential complications. Materials and methods: Electronic sources, particularly PubMed and Google Scholar databases, were searched using keywords such as "endoscopic ultrasonography", "endoscopic retrograde cholangiopancreatography" and "choledocholithiasis". Conclusions: With the use of modern technologies, such as endoscopic ultrasonography (EUS) and retrograde choleangiopancreatography (ERCP), it has become possible to diagnose bile duct stones more accurately and introduce more effective and less invasive therapies. The development of the availability of diagnostic tests, especially those that do not require invasive procedures, has helped reduce the risk of complications. EUS may be the preferred tool of choice for patients with gallstones, as it is associated with a lower risk of complications compared to ERCP alone. Decisions regarding the use of specific diagnostic and therapeutic modalities should be made on a case-by-case basis, taking into account medical and economic considerations. [ABSTRACT FROM AUTHOR]

Background and aims: Relief of cholestasis in hilar cholangiocarcinoma is commonly undertaken in both curative and palliative treatment plans. There are numerous open questions with regard to the ideal biliary drainage strategy – including what constitutes clinical success (CS). In the existing data, curative patients and patients from the Western world are underrepresented. Patients and methods: We performed a retrospective analysis of patients with complex malignant hilar obstruction (Bismuth-Corlette II and higher) due to cholangiocarcinoma who underwent biliary drainage at a German referral center between 2010 and 2020. We aimed to define CS and complication rates and directly compare outcomes in curative and palliative patients. Results: 56 curative and 72 palliative patients underwent biliary drainage. In patients with curative intent, CS was achieved significantly more often regardless of what definition of CS was applied (e.g., total serum bilirubin (TSB) < 2 mg/dl: 66.1% vs. 27.8%, p = < 0.001, > 75% reduction of TSB: 57.1% vs. 29.2%, p = 0.003). This observation held true only when subgroups with the same Bismuth-Corlette stage were compared. Moreover, palliative patients experienced a significantly greater percentage of adverse events (33.3% vs. 12.5%, p = 0.01). Curative intent treatment and TSB at presentation were predictive factors of CS regardless of what definition of CS was applied. The observed CS rates are comparable to published studies involving curative patients, but inferior to reported CS rates in palliative series mostly from Asia. Conclusions: Biliary drainage in complex malignant hilar obstruction due to cholangiocarcinoma is more likely to be successful and less likely to cause adverse events in curative patients compared to palliative patients. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Although turmeric is commonly ingested and well tolerated, there is increasing evidence that over‐the‐counter turmeric supplements can cause drug‐induced liver injury. We sought to thoroughly characterise clinicopathological features of patients for whom liver injury was attributed clinically to turmeric supplements.We identified 11 patients via retrospective pathology archive review: 10 females (91%) and one male, with a median age of 58 years (range = 37–66 years). Six patients (55%) were asymptomatic with abnormal liver function tests, while five patients (45%) presented with malaise and/or jaundice. Ten patients (91%) showed predominant transaminase abnormalities, while one exhibited predominant alkaline phosphatase elevation. Histologically, biopsies showed acute hepatitis (eight cases, 73%, including five pan‐lobular and three zone 3‐predominant inflammation), scattered lobular aggregates of histiocytes (two; 18%) and a chronic hepatitis pattern of injury (one; 9%). Mild bile duct injury was present in five biopsies (45%). All patients stopped ingesting turmeric supplements after presenting with liver injury, and four patients additionally received steroid therapy; liver function tests normalised in all patients. Roussel Uclaf causality assessment method (RUCAM) analysis estimated the likelihood of turmeric supplement‐associated liver injury to be probable (eight cases) and possible (three).Histological features in the ‘possible’ cases were consistent with drug‐induced injury, highlighting the added benefit of histological analysis relative to RUCAM analysis isolation. This study underscores the need to obtain a full history of over‐the‐counter medications and supplements when investigating aetiologies for liver injury, including supplements purportedly containing innocuous compounds such as turmeric. [ABSTRACT FROM AUTHOR]

Hydatid cysts near the porta hepatis present notable medical challenges due to their intricate positioning and potential influence on crucial structures within the liver and its vicinity. While relatively rare, their presence can lead to intricate medical scenarios because of their proximity to vital liver and bile duct structures, but their occurrence can present complex medical situations due to their proximity to critical structures in the liver and bile ducts. We present an unusual case of a 33-year-old male with no known comorbidities presented to the outpatient department of general surgery with pain, insidious in onset and gradually progressive, in the right hypochondrial region for the past 3 months, along with mild fever, reduced appetite, and weight loss of 3 kg. Managing hepatic cysts, especially when near the porta hepatis, poses significant diagnostic challenges. Imaging scans revealed multiple hypodense lesions suggestive of hepatic cysts, with the largest one measuring 5 cm × 8 cm in segment VI. Native post-contrast lesions were also observed in the right lower lobe. Although hepatic duct dilation was not observed, the presence of a cyst near the porta hepatis an atypical site for hydatid cyst, complicated potential PAIR procedures (puncture, aspirate, injection, re-aspirate), raising concerns about the risk of damaging vital structures like the hepatic artery or major bile duct. A multidisciplinary approach engaged interventional radiology to evaluate PAIRS feasibility. PAIRS was performed successfully, except for the cyst near the porta hepatis to avoid complications. Despite this, the patient continued to experience abdominal discomfort post-operation, although liver function tests improved in the postop period. This case underscores the uncommon occurrence of hydatid cysts near the porta hepatis and highlights the need for additional research to comprehend its prevalence and causes. Further investigation is crucial to enhance our understanding of the epidemiology and optimal management strategies involving PAIRS in such challenging cases. [ABSTRACT FROM AUTHOR]

Background: Periampullary diverticulum (PAD) is commonly encountered in endoscopic retrograde cholangiopancreatography (ERCP) procedures. Objectives: We sought to determine whether PADs are associated with a lower success rate of cannulation and an increased risk of adverse events. Design: A retrospective cohort study was conducted using prospectively gathered nationwide registry data. Methods: Using the Swedish registry for gallstone surgery and ERCP, we analyzed a cohort of 66,974 prospectively registered ERCP procedures performed in 2006–2021. The presence of PAD was divided into two groups based on the PAD type: Boix type 1 (the papilla located inside the PAD) and Boix types 2–3 (the papilla located either at the edge of the PAD or immediately adjacent to the PAD). The primary outcomes were the success rate of cannulation and overall adverse events within 30 days. Results: PADs were registered in 8130 (12.1%) of ERCPs included in the study population. In total, 2114 (3.9%) patients had Boix type 1 PAD, while 5035 (8.2%) patients had Boix type 2 or 3 PAD. The chance of successful cannulation was lower in patients with type 1 PAD compared to no PAD (80.1% vs 88.7%; odds ratio: 0.42, 95% confidence interval: 0.38–0.46). No differences were seen in overall adverse events or post-ERCP pancreatitis. Adverse events occurred in 14.6% of patients with PAD type 1 and 16.0% of patients with PAD type 2 or 3, compared to 16.5% of patients without a PAD. Conclusion: Cannulation appears less successful during ERCP when the papilla is located in the PAD (i.e., type 1). Adverse events seem not to increase with the presence of a PAD, but they could theoretically be influenced by the inability to cannulate. Plain language summary: How a pouch in the duodenum affects the difficulty and complications of an endoscopic procedure investigating the bile ducts A duodenal diverticulum (pouch in the duodenum) is a common finding during endoscopic examinations. A diverticulum can make it harder to do an ERCP, which is an endoscopic procedure that examines the bile ducts. The diverticulum might make it harder to do an ERCP because it affects the opening where the bile is released into the intestine. If the bile duct opening is inside the diverticulum, it is classified as type 1. If it is on the edge or outside, it is classified as type 2-3. This study used Swedish registry data to see if these types of diverticula make ERCP harder and cause more problems after the procedure. 47,486 procedures were investigated, and 12.1% had a diverticulum. A type 1 diverticulum makes ERCP harder. There was no difference in complications between the types of diverticula and no diverticulum. This means a diverticulum does not raise the risk of complications during ERCP. However, for a type 1 diverticulum, not being able to perform ERCP may prevent complications. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Objective Materials and Methods Results Conclusions Biliary brushing cytology (BB) to detect cholangiocarcinoma (CCA) is integral in the surveillance of patients with primary sclerosing cholangitis (PSC). Since reactive changes can mimic carcinoma, indeterminant results are frequent. Fluorescence in situ hybridization (FISH) using the UroVysion probe set has been advocated to enhance the detection of CCA. This study evaluates the performance of FISH for detecting CCA in patients with and without PSC.A query of our pathology database for atypical and suspicious BB with concurrent FISH results was performed from 2014 to 2021. FISH (using UroVysion probe set containing centromere enumeration probes to chromosomes 3, 7, and 17) was positive if at least 5 cells demonstrated polysomy. Electronic medical records were reviewed to identify patients with PSC and CCA. CCA was confirmed by pathology or clinical impression.Of the 65 patients (103 BB) in the PSC cohort, 59 patients (94 BB) without CCA and 6 patients (9 BB) with CCA were identified. 33 non‐PSC patients (41 BB) with CCA were included for comparison. Positive FISH was highest in non‐PSC patients with CCA (10/41 BB, 24%). Positive FISH was seen in both PSC with (1/9 BB, 11%) and without (2/94 BB, 2%) CCA.FISH positivity was lower than expected and was positive in PSC patients without CCA. These results question the clinical utility of FISH for CCA surveillance in PSC patients. [ABSTRACT FROM AUTHOR]

Background: Hepatic fibrosis and its associated consequences continue to pose a substantial global health challenge. Developing novel approaches to hepatic fibrosis management and prevention is critically necessary. Radix Paeoniae Alba (RPA) is widely used in Traditional Chinese Medicine (TCM) to treat various diseases. Our earlier research found that a bioactive component of RPA had a dose-dependent effect on anti-allergic asthma. RPA reduces allergic asthma by slowing the hepatic wind, according to "Treatise on Febrile Diseases". However, this bioactive fraction's pharmacological effects and mechanisms on the liver are unknown. Aim: This study examined the bioactive fraction MP-40, the methanol extract of RPA (MRPA), on bile duct ligation (BDL) for its anti-hepatic fibrosis activity and potential mechanisms. Methods: First, the effectiveness of MP-40 in treating BDL-induced hepatic fibrosis in mice and rats was evaluated through survival rates, ALT, AST HYP, and pathological changes. Molecular assays were performed using in vitro cultures of HSC-T6 activation. The expression of a-SMA and Collagen I evaluated fibro-tropic factors with HSC activation. Furthermore, the levels of pyroptosis were assessed by examining the expression of the pyroptosis-related proteins, including NLRP3, Cleaved Caspase-1, GSDMD-N, and 1L-1ß. Additionally, the effective constituents of MP-40 were identified by extraction, separation, and identification. Finally, PF and TGG, as the delegate compounds of MP-40, were tested to confirm their inhibition effects on HSC-T6 activation. Results: The findings demonstrated that MP-40 and MRPA could lower ALT, AST, and HYP levels, boost survival rates, and reduce liver damage in BDL mice and rats. Furthermore, MP-40 outperforms MRPA. MP-40 was proven to drastically diminish fibrotic a-SMA and Collagen I. The expression of pyroptosis-related proteins NLRP3, Cleaved Caspase-1, TGF-ß1, GSDMD-N, and 1L-1ß decreased. MP-40 inhibited the synthesis of pyroptosis-related proteins more effectively than MCC950 (an NLRP3-specific inhibitor). Monoterpene glycosides and tannins were shown to be the most potent MP-40 components. Finally, the delegate compounds MP-40, PF, and TGG were shown to have substantial inhibitory effects on HSC-T6 activation. Conclusion: The results proved that MP-40 alleviates BDL-induced cholestatic hepatic fibrosis by inhibiting NLRP3-mediated pyroptosis. PF and TGG play a role in treating BDL-induced cholestatic hepatic fibrosis in MP-40. [ABSTRACT FROM AUTHOR]

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) facilitates the removal of common bile duct (CBD) calculi by endoscopy. When ERCP fails, exploration of CBD is required for the clearance of CBD calculi. The optimum way for the exploration of CBD is by choledochoscopy. Dedicated flexible or rigid choledochoscopes are expensive and available only in few places in India. Since 1991, we subjected patients with suspected CBD calculi to ERCP, followed by laparoscopic cholecystectomy (LC). Patients in whom ERCP failed to clear CBD were subjected to open exploration of CBD using any easily available, suitable, straight rigid scope for choledochoscopy. Patients and Methods: Since March 1991, out of 8866 patients with cholelithiasis, 862 underwent ERCP. Ninety‑six patients in whom ERCP failed to clear CBD underwent open exploration of CBD. In each case of exploration of CBD, choledochoscopy was performed using a straight rigid scope, either a cystoscope, paediatric cystoscope, hysteroscope or 5‑mm laparoscopy telescope with a 5‑mm cannula. Results: The CBD clearance was complete in 95 patients, and one patient had an impacted calculus at the ampulla. CBD explorations were followed by choledochoduodenostomy, T‑tube placement or suturing of choledochotomy. No residual calculi were observed after such exploration. Conclusion: From our results, we advocate the following algorithm for CBD calculi in resource‑limited settings. Subject patients with CBD calculi to ERCP followed by LC. In case of failed ERCP, open exploration of CBD with choledochoscopy using any suitable rigid scope. Dedicated flexible or rigid choledochoscope is not essential. This approach is cost‑effective and successful. [ABSTRACT FROM AUTHOR]

Background: Precut over a pancreatic duct stent (PPDS) and transpancreatic precut sphincterotomy (TPS) with immediate pancreatic duct stent placement are techniques employed to promote biliary access during endoscopic retrograde cholangiopancreatography (ERCP) in cases of challenging biliary cannulation. However, limited data are available to compare the efficacy of these two pancreatic stent-assisted precut sphincterotomy techniques. Aims: The aim of this study was to compare the efficacy of PPDS versus TPS. Methods: A retrospective analysis was performed on the clinical data of consecutive patients who underwent ERCP between April 1, 2019 and May 31, 2023. According to the selected cannulation approaches, patients were assigned to two groups. In the PPDS group, a pancreatic duct stent was initially placed, followed by needle-knife precut over the stent. In the TPS group, transpancreatic precut sphincterotomy was initially performed, followed by immediate pancreatic stent placement. The success rate of biliary cannulation and the incidence of post-ERCP pancreatitis (PEP) between the two groups were analysed. Results: Among 864 patients who underwent ERCP, 46 patients were equally enrolled in the two groups. Selective bile duct cannulation was successfully achieved in 42 out of 46 (91.3%) cases using the PPDS and in 32 out of 46 (69.6%) cases using TPS technique alone, indicating significantly higher success rate of bile duct cannulation with PPDS compared to TPS (91.3% vs. 69.6%, P = 0.009). The overall success rates for bile duct cannulation were 93.5% and 97.8% in the PPDS and TPS groups, respectively, with no significant difference identified (P = 0.307). PEP occurred in 0 and 4 (8.7%) cases in the PPDS and TPS groups, respectively, with no significant difference between the two groups (8.7% vs. 0%, P = 0.117). There were no cases of bleeding or perforation in either group. Conclusions: Both PPDS and TPS followed by immediate pancreatic duct stent placement are viable options. TPS stands out for its simplicity and cost-effectiveness, while PPDS is more appropriate for patients who are at a high-risk of developing PEP. [ABSTRACT FROM AUTHOR]

Background and Aims: Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disorder without effective medical treatment which is characterized by inflammation and fibrotic structures around the bile ducts. Biliary epithelial cells (cholangiocytes) are the target and potential disease drivers in PSC, yet little is known if cholangiocytes from PSC patients differ from non-PSC controls. To characterize cholangiocytes at early rather than end-stage disease, cholangiocyte organoids (COs) were derived from diseased bile ducts of PSC patients and compared to organoids generated from disease controls. Methods: Cholangiocytes were obtained during endoscopic retrograde cholangiopancreatography (ERCP) brushing of diseased bile duct areas and expanded as organoids using previously established culture methods. Stable CO lines were analyzed for cell type identity, basic cholangiocyte function, and transcriptomic signature. Results: We demonstrate that cholangiocytes, derived from the damaged area within the bile ducts of PSC patients, can be expanded in culture without displaying functional or genetic disease-related features. We further show that COs from patients who later were diagnosed with dysplasia exhibit higher expression of the cancer-associated genes PGC, FXYD2, MIR4435-2HG, and HES1. Conclusions: Our results demonstrate that PSC organoids are largely similar to control organoids after culture and highlight the significance of COs as a tool for regenerative medicine approaches as well as their potential for discovering new potential biomarkers for diagnosing cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized 'adaptive treatment strategy' is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time. [ABSTRACT FROM AUTHOR]

Background: The pancreas is a complex abdominal organ with many anatomical variations, and therefore automated pancreas segmentation from medical images is a challenging application. Purpose: In this paper, we present a framework for segmenting individual pancreatic subregions and the pancreatic duct from three‐dimensional (3D) computed tomography (CT) images. Methods: A multiagent reinforcement learning (RL) network was used to detect landmarks of the head, neck, body, and tail of the pancreas, and landmarks along the pancreatic duct in a selected target CT image. Using the landmark detection results, an atlas of pancreases was nonrigidly registered to the target image, resulting in anatomical probability maps for the pancreatic subregions and duct. The probability maps were augmented with multilabel 3D U‐Net architectures to obtain the final segmentation results. Results: To evaluate the performance of our proposed framework, we computed the Dice similarity coefficient (DSC) between the predicted and ground truth manual segmentations on a database of 82 CT images with manually segmented pancreatic subregions and 37 CT images with manually segmented pancreatic ducts. For the four pancreatic subregions, the mean DSC improved from 0.38, 0.44, and 0.39 with standard 3D U‐Net, Attention U‐Net, and shifted windowing (Swin) U‐Net architectures, to 0.51, 0.47, and 0.49, respectively, when utilizing the proposed RL‐based framework. For the pancreatic duct, the RL‐based framework achieved a mean DSC of 0.70, significantly outperforming the standard approaches and existing methods on different datasets. Conclusions: The resulting accuracy of the proposed RL‐based segmentation framework demonstrates an improvement against segmentation with standard U‐Net architectures. [ABSTRACT FROM AUTHOR]

Background: In ERCP for treatment of Choledocholithiasis, stent insertion after CBD clearance may be beneficial in lowering the pressure in the bile ducts and provide better bile drainage, However, CBD stenting is accused to be of unfavorable outcomes. Aim: To compare between CBD stenting and non-stenting regarding of recurrence rate of CBD stones, complications such as CBD leakage and blockage. Methods: This randomized clinical trial study was conducted at Gastro-Intestinal Endoscopic unit of Internal Medicine Department, Faculty of Medicine, Zagazig University Hospitals, on 60 patients with diagnosis of small CBD stones <15 mm by abdominal ultra-sonography or MRCP. Patients were divided into two groups: group (A): 30 patients who were scheduled for ERCP and underwent CBD clearance and stone retrieval with plastic CBD stent insertion and group (B): 30 patients who were scheduled for ERCP and underwent CBD clearance and stone retrieval without plastic CBD stent insertion. Results: There was significant difference between both groups regarding to recurrence that was higher in group B than group A. Conclusions: Biliary stenting after CBD stone removal reduces the likelihood of stone recurrence. [ABSTRACT FROM AUTHOR]

Background/Objectives: Covered self-expandable metallic stents (CSEMS) are commonly used to treat malignant distal biliary obstructions. A 10-mm CSEMS carries the risk of obstructing the pancreatic and cystic duct orifices by adhering to the bile duct; therefore, postoperative pancreatitis and cholecystitis are reported to occur at a certain frequency. We have adopted a new drainage technique for malignant distal biliary obstruction called "double-slim SEMS stenting" (DSS), where two small-diameter CSEMS are placed side-by-side. We aimed to compare the efficacy and safety of biliary drainage using DSS with those of conventional CSEMS. Methods: In total, 50 patients who underwent endoscopic biliary drainage for malignant distal biliary obstructions between April 2019 and March 2022 at Hyogo Medical University Hospital were enrolled. Patients were divided into DSS and Conventional groups, and the technical success rate, clinical success rate, adverse events, success rate for reintervention, recurrent biliary obstruction (RBO) rate, and time to RBO (TRBO) were evaluated. Results: There were no significant differences in patient characteristics between the DSS (n = 20) and Conventional groups (n = 30). The technical and clinical success rates were 100% in the DSS group. The incidence of adverse events was not significantly different between the two groups (DSS/Conventional: 10.0% [2/20]/20.0% [6/30]) (p = 0.34). No acute cholecystitis was observed in the DSS group. The incidence rates of RBO were 30% (6/20) and 43% (13/30) in the DSS and Conventional groups, respectively (p = 0.92). The median TRBO in the DSS group was 378 days, while the TRBO in the Conventional group was 195 days (p = 0.03), resulting in significantly longer TRBO in the DSS group. Conclusions: DSS emerges as a viable and safe approach for biliary drainage in malignant distal biliary obstruction, demonstrating a lower incidence of adverse events and longer TRBO compared to conventional CSEMS. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a rare, chronic liver disease with no approved therapies. The ursodeoxycholic acid (UDCA) has been widely used, although there is no evidence that the use of UDCA delays the time to liver transplant or increases survival. Several candidate drugs are currently being developed. The largest group of these new agents is represented by FXR agonists, including obeticholic acid, cilofexor, and tropifexor. Other agents that target bile acid metabolism are ASTB/IBAP inhibitors and fibroblasts growth factor (FGF)19 analogues. Cholangiocytes, the epithelial bile duct cells, play a role in PSC development. Recent studies have revealed that these cells undergo a downregulation of GPBAR1 (TGR5), a bile acid receptor involved in bicarbonate secretion and immune regulation. Additional agents under evaluation are PPARs (elafibranor and seladelpar), anti-itching agents such as MAS-related G-protein–coupled receptors antagonists, and anti-fibrotic and immunosuppressive agents. Drugs targeting gut bacteria and bile acid pathways are also under investigation, given the strong link between PSC and gut microbiota. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of our retrospective study was to compare EUS-guided gastroenteroanastomosis (EUS-GE) and enteral stenting (ES) for the palliation of gastric outlet obstruction (GOO) in patients already treated with EUS-guided choledocoduodenostomy (EUS-CDS) for distal malignant biliary obstruction (DMBO). Our results on 77 patients demonstrated that both EUS-GE and ES are safe and effective for palliation of GOO, but EUS-GE is associated with less recurrence of symptoms. Background: EUS-guided gastroenterostomy (EUS-GE) is a novel and effective procedure for the management of malignant gastric outlet obstruction (GOO) with more durable results when compared to enteral stenting (ES). However, data comparing EUS-GE to ES in patients already treated with EUS-guided choledocoduodenostomy (EUS-CDS) for distal malignant biliary obstruction (DMBO) are lacking. We aimed to compare outcomes of EUS-GE and ES for the palliation of GOO in this specific population of patients. Methods: A multicenter, retrospective analysis of patients with DMBO treated by EUS-CDS and subsequent GOO treated by EUS-GE or ES from 2016 to 2021 was conducted. Primary outcomes were overall AEs rate and dysfunction of the EUS-CDS after GOO treatment. Secondary outcomes included clinical success, technical success, procedure duration, length of hospital stay and relapse of GOO symptoms. Results: A total of 77 consecutive patients were included in the study: 25 patients underwent EUS-GE and 52 underwent ES. AEs rate and patency outcomes of the EUS-CDS after GOO treatment were comparable between the two groups (12.5% vs. 17.3%; p = 0.74). No recurrence of GOO symptoms was registered in the EUS-GE group while 11.5% of ES patients had symptoms recurrence, even if not statistically significant (p = 0.16), after a mean follow-up period of 63.5 days. Conclusion: EUS-GE and ES are both effective and safe for the palliation of GOO in patients already treated by EUS-CDS for DMBO with no difference in the biliary stent dysfunction rate and overall AEs. EUS-GE is associated with less recurrence of GOO symptoms. [ABSTRACT FROM AUTHOR]

The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique is a relatively newer method. This randomized trial compares the outcomes of these 2 techniques in patients with benign biliary obstruction. Visual Abstract. Endoscopic Ultrasound-Guided Rendezvous Technique Versus Precut Sphincterotomy as Salvage Technique in Patients With Benign Biliary Disease and Difficult Biliary Cannulation: The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique is a relatively newer method. This randomized trial compares the outcomes of these 2 techniques in patients with benign biliary obstruction. Background: The standard salvage technique used for difficult bile duct cannulation is precut sphincterotomy, whereas endoscopic ultrasound-guided rendezvous technique (EUS-RV) is a relatively newer method. Prospective comparative data between these 2 techniques as salvage for biliary access in patients with benign biliary disease and difficult bile duct cannulation is lacking. Objective: To compare EUS-RV and precut sphincterotomy as salvage technique for difficult bile duct cannulation in benign biliary obstruction. Design: Participant-masked, parallel-group, superiority, randomized controlled trial. (Clinical Trials Registry of India: CTRI/2020/07/026613) Setting: Tertiary care academic institute from July 2020 to May 2021. Participants: All patients with benign biliary disease and difficult bile duct cannulation requiring salvage strategy. Intervention: Patients were randomly assigned by computer-generated randomized blocks sequence in 1:1 fashion to either EUS-RV or precut sphincterotomy. Patients with failure in EUS-RV were crossed over to precut sphincterotomy and vice versa. Measurements: The primary outcome measure was technical success. The other outcome measures included procedure time, radiation dose, and adverse events. Results: In total, 100 patients were randomly assigned to EUS-RV (n = 50) and precut sphincterotomy (n = 50). The technical success rate (92% vs. 90%; P = 1.00; relative risk, 1.02 [95% CI, 0.90 to 1.16]), median procedure time (10.1 vs. 9.75 minutes), and overall complication rate (12% vs. 10%; relative risk, 1.20 [CI, 0.39 to 3.68]) were similar between the 2 groups. Five patients (10%) in the EUS-RV group and 5 patients (10%) in the precut sphincterotomy group had developed post–endoscopic retrograde cholangiopancreatography pancreatitis. All failed cases in either salvage group could be successfully cannulated when crossed over to the other group. Limitation: Single center study done by experts. Conclusion: Endoscopic ultrasound-guided rendezvous technique and precut sphincterotomy have similar success rates as salvage techniques in the technically challenging cohort of difficult bile duct cannulation for benign biliary disease, with acceptable complications rates. Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Robot‐assisted surgery for congenital biliary dilatation has been evolving primarily with the da Vinci® Surgical System. The hinotori™ Surgical Robot System, developed in Japan, received approval for gastroenterological surgery in 2022. We present the inaugural case of congenital biliary dilatation surgery utilizing the hinotori™ system. A 57‐year‐old woman was referred to our institution for evaluation and treatment of common bile duct dilatation classified under Todani Type Ia congenital biliary dilatation. Robotic resection of the extrahepatic bile duct and hepaticojejunostomy with Roux‐en‐Y were performed. The operation lasted 292 min with minimal blood loss (10 mL). The patient had an uneventful postoperative course and was discharged 10 days after surgery. Robotic surgery using the hinotori™ system for congenital biliary dilatation can be safely performed. [ABSTRACT FROM AUTHOR]

Background and Aims: There is increased interest in utilizing dietary interventions to alter the progression of autoimmune diseases. These efforts are driven by associations of gut microbiota/metabolites with levels of short‐chain fatty acids (SCFAs). Propionate is a key SCFA that is commonly used as a food preservative and is endogenously generated by bacterial fermentation of non‐digestible carbohydrates in the gut. A thesis has suggested that a diet rich in propionate and other SCFAs can successfully modulate autoimmunity. Herein, we investigated the effect of long‐term administration of propionylated high‐amylose resistant starches (HAMSP) on the course of murine primary biliary cholangitis. Materials and Methods: Groups of female ARE‐Del mice were fed an HAMSP diet either before or after disease onset. A detailed immunobiological analysis was performed involving autoantibodies and rigorous T‐cell phenotyping, including enumeration of T‐cell subsets in the spleen, liver, intestinal intraepithelial lymphocytes and lamina propria by flow cytometry. Histopathological scores were used to assess the frequency and severity of liver inflammation and damage to hepatocytes and bile ducts. Results: Our results demonstrate that a long‐term propionate‐yielding diet re‐populated the T‐cell pool with decreased naïve and central memory T‐cell subsets and an increase in the effector memory T cells in mice. Similarly, long‐term HAMSP intake reduced CD4+CD8+ double‐positive T cells in intraepithelial lymphocytes and the intestinal lamina propria. Critically, HAMSP consumption led to moderate‐to‐severe hepatocellular steatosis in ARE‐Del mice, independent of the stage of autoimmune cholangitis. Conclusions: Our data suggest that administration of HAMSP induces both regulatory and effector T cells. Furthermore, HAMSP administration resulted in hepatocellular steatosis. Given the interest in dietary modulation of autoimmunity and because propionate is widely used as a food preservative, these data have significant implications. This study also provides new insights into the immunological and pathological effects of chronic propionate exposure. [ABSTRACT FROM AUTHOR]

Background: Patients with acute cholecystitis (AC) presenting with unfavorable systemic or local conditions are often managed with percutaneous cholecystostomy (PC) as a temporary measure. The clinical outcomes of interval cholecystectomy following PC remain unclear. The aim of the study was to identify the association between the timing of cholecystectomy following PC for AC and perioperative complication rates at interval cholecystectomy. We hypothesized that there would be a specific time interval to cholecystectomy associated with lower risk for adverse events. Methods: This was a retrospective (2018–2020) multicenter study at 8 participating hospital systems of adult patients with AC, managed with PC and interval cholecystectomy. Demographics, comorbidities, treatment details, and outcomes were examined. Patients were grouped based on quartiles for timing of surgery after PC (< 7, 7–9, 10–13, > 13 weeks). The primary outcome was a composite endpoint of bile duct injury, reoperation, readmission, image-guided intervention, endoscopic intervention, conversion to open surgery, or death. Results: There were 188 patients with a median age of 66 years with AC classified as mild (41%), moderate (47%), and severe (12%). Median days from PC to surgery were 65 (Q1 = 48, Q3 = 91). Laparoscopic cholecystectomy (89.9%) was the most commonly planned approach (robotic 6.4%, 3.7% open) and 28 (14.9%) were converted to open. The composite endpoint was reported in 51 patients (27.1%). A biliary injury occurred in 7 (3.7%) patients. Time to surgery and intraoperative drain placement were independently associated with the composite outcome. Cholecystectomy within 7 weeks of PC was associated with decreased risk (OR = 0.36, 95% CI 0.13–0.97) of the composite endpoint, compared to patients undergoing surgery > 13 weeks after PC. Conclusion: Timing of surgery following PC was associated with procedural outcomes. Patients undergoing surgery before 7 weeks experienced significantly less morbidity than patients having delayed cholecystectomy. These results should be considered in patient selection and management after PC. [ABSTRACT FROM AUTHOR]

Background: Postoperative pancreatic fistula (POPF) is a critical complication of laparoscopic gastrectomy (LG). However, there are no widely recognized anatomical landmarks to prevent POPF during LG. This study aimed to identify anatomical landmarks related to POPF occurrence during LG for gastric cancer and to develop an artificial intelligence (AI) navigation system for indicating these landmarks. Methods: Dimpling lines (DLs)—depressions formed between the pancreas and surrounding organs—were defined as anatomical landmarks related to POPF. The DLs for the mesogastrium, intestine, and transverse mesocolon were named DMP, DIP, and DTP, respectively. We included 50 LG cases to develop the AI system (45/50 were used for training and 5/50 for adjusting the hyperparameters of the employed system). Regarding the validation of the AI system, DLs were assessed by an external evaluation committee using a Likert scale, and the pancreas was assessed using the Dice coefficient, with 10 prospectively registered cases. Results: Six expert surgeons confirmed the efficacy of DLs as anatomical landmarks related to POPF in LG. An AI system was developed using a semantic segmentation model that indicated DLs in real-time when this system was synchronized during surgery. Additionally, the distribution of scores for DMP was significantly higher than that of the other DLs (p < 0.001), indicating the relatively high accuracy of this landmark. In addition, the Dice coefficient of the pancreas was 0.70. Conclusions: The DLs may be used as anatomical landmarks related to POPF occurrence. The developed AI navigation system can help visualize the DLs in real-time during LG. [ABSTRACT FROM AUTHOR]

[Display omitted] • Fasciola hepatica extracellular vesicles (Hp EVs) induce extracellular matrix secretion. • Hp EVs reduce proliferation of hepatic stellate cells (HSCs) • Dicrocoelium dendriticum EVs (Dd EVs) trigger a global inflammatory response in HSCs and hepatocytes. • Dd EVs have a more potent anti-proliferative effect than Fh EVs. • Fh EVs are taken up faster and in higher amounts than Dd EVs by HSCs and hepatocytes. Fasciola hepatica and Dicrocoelium dendriticum are parasitic trematodes residing in the bile ducts of mammalian hosts, causing, in some cases, impairment of liver function and hepatic fibrosis. Previous studies have shown that extracellular vesicles released by F. hepatica (Fh EVs) and D. dendriticum (Dd EVs) induce a distinct phenotype in human macrophages, but there is limited information on the effect of parasitic EVs on liver cells, which interact directly with the worms in natural infections. In this study, we isolated Fh EVs and Dd EVs by size exclusion chromatography and labeled them with a lipophilic fluorescent dye to analyze their uptake by human hepatic stellate cells (HSC) and hepatocytes, important cell types in liver pathology, using synthetic liposomes as internal labeling and uptake control. We analyzed EV uptake and the proteome profiles after the treatment with EVs for both cell types. Our results reveal that EVs establish unique and specific interactions with stellate cells and hepatocytes, suggesting a different role of EVs derived from each parasite, depending on the migration route to reach their final niche. Fh EVs have a cytostatic effect on HSCs, but induce the extracellular matrix secretion and elicit anti-inflammatory responses in hepatocytes. Dd EVs have a more potent anti-proliferative effect than Fh EVs and trigger a global inflammatory response, increasing the levels of NF-κB and other inflammatory mediators in both cell types. These interactions may have a major influence on the progression of the disease, serving to generate conditions that may favor the establishment of the helminths in the host. [ABSTRACT FROM AUTHOR]

Aim: Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by inflammation of the intra‐ and extrahepatic bile ducts. Pathogenesis of PSC is still enigmatic but is likely to be multifactorial. Recently, we identified an interleukin‐6 (IL‐6)‐dependent signal transducer and activator of transcription 3 (STAT3) activation in CD4+ TH1 and TH17 cells in PSC. The IL‐6/STAT3 pathway was shown to be regulated by protease‐activated receptor 1 (PAR1) contributing to inflammation. The role of the PAR1 −506 deletion/insertion (Del/Ins) polymorphism in PSC has not yet been investigated. Methods: Two hundred eighty four PSC patients (200 patients with inflammatory bowel diseases [IBD] and 84 without IBD) and 309 healthy controls were genotyped for PAR1 rs11267092 (−506 Del/Ins −13 bp). Results were correlated with clinical characteristics and transplant‐free survival. Results: The frequency of PAR1 –506 Ins allele carriers (Del/Ins and Ins/Ins) was significantly higher in PSC patients (57.0%) compared to healthy controls (39.8%). Furthermore, carriers of PAR1 −506 Ins allele were more likely to have PSC than noncarriers (odds ratio 2.01; 95% confidence interval, 1.45–2.79). Patients with PSC carrying the PAR1 −506 Ins allele showed significantly higher alanine aminotransferase serum levels (p = 0.0357) and a trend toward shorter transplant‐free survival time compared to noncarriers (8.9 ± 6.6 years vs. 10.5 ± 7.1 years; p = 0.076). Conclusions: Our study shows that PAR1 −506 Ins is significantly more frequent in people with PSC. As PAR1 −506 Ins allele carriers tended to have a shorter transplant‐free survival, PAR1 might play a role in the development and course of PSC. [ABSTRACT FROM AUTHOR]

Background Disposable digital single-operator cholangioscopy (D-SOC) and direct peroral cholangioscopy (D-POC) using an ultraslim endoscope are established POC modalities for the diagnosis and treatment of various biliary diseases. We compared the usefulness of D-SOC and D-POC for the diagnosis of intraductal superficial lesions of the bile duct (ISL-Bs). Methods 38 consecutive patients with suspected biliary diseases who underwent both D-SOC and D-POC were enrolled. The primary outcome was ISL-B detection rate, and the secondary outcomes were technical success of POC and POC-guided forceps biopsy sampling (POC-FB), procedure time, visualization quality, and tissue adequacy. Results D-SOC had a higher technical success rate than D-POC but the difference was not statistically significant (100% vs. 92.1%, P = 0.25). D-POC had a marginally higher ISL-B detection rate (34.2% vs. 28.9%, P = 0.68) and significantly higher visualization quality (P = 0.03). The mean (SD) procedure time was significantly shorter with D-SOC (11.00 [1.33] vs. 19.03 [2.95] minutes, P<0.001). The technical success rate of POC-FB and tissue adequacy did not differ between the two techniques (D-SOC vs. D-POC: 81.8% vs. 84.6%, P = 0.69 and 77.8% vs. 90.9%, P = 0.57, respectively). Conclusions Both POC systems were safe and useful for the detection, characterization, and diagnosis of minute ISL-Bs. While D-SOC displayed a shorter procedure time and a tendency for higher technical success rate, D-POC provided superior visualization quality, allowing detailed observation of the surface structure and microvascular patterns. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a challenging cholestatic liver disease marked by progressive bile duct inflammation and fibrosis that has no FDA-approved therapy. Although obeticholic acid (OCA) has been sanctioned for PSC, its clinical utility in PSC is constrained by its potential hepatotoxicity. Here, we introduce a novel therapeutic construct consisting of OCA encapsulated within a reactive oxygen species (ROS)-responsive, biodegradable polymer, further cloaked with human placenta-derived mesenchymal stem cell (hP-MSC) membrane (MPPFTU@OCA). Using PSC patient-derived organoid models, we assessed its cellular uptake and cytotoxicity. Moreover, using a PSC mouse model induced by 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC), we demonstrated that intravenous administration of MPPFTU@OCA not only improved cholestasis via the FXR-SHP pathway but also reduced macrophage infiltration and the accumulation of intracellular ROS, and alleviated mitochondria-induced apoptosis. Finally, we verified the ability of MPPFTU@OCA to inhibit mitochondrial ROS thereby alleviating apoptosis by measuring the mitochondrial adenosine triphosphate (ATP) concentration, ROS levels, and membrane potential (ΔΨm) using H 2 O 2 -stimulated PSC-derived organoids. These results illuminate the synergistic benefits of integrating an ROS-responsive biomimetic platform with OCA, offering a promising therapeutic avenue for PSC. ROS-responsive and self-positioning biomimetic nanoparticle delivery of obeticholic acid mitigates primary sclerosing cholangitis via mitochondria-induced apoptosis. [Display omitted] • ROS-responsive PPFTU material loaded with OCA alleviated hepatobiliary damage. • MSC membrane encapsulation enables powerful targeting of the liver and inflammation. • Organoids and animal models reveal that MPPFTU@OCA mitigates disease progression via mitochondrial-induced apoptosis. [ABSTRACT FROM AUTHOR]

Objectives: To describe the MR features and prognosis of patients with an uncommon complication of primary sclerosing cholangitis (PSC) characterized by a spontaneous perforation of the common bile duct (CBD) resulting in a peri-biliary collection and a pseudo-cystic appearance of the CBD. Methods: A single-center cohort of 263 patients with PSC who had at least two MRIs between 2003 and 2022 and a minimum follow-up of 1 year was retrospectively analyzed. MRI data (characteristics of CBD perforation and MR features of PSC) and clinical data were assessed. Analysis of survival without liver transplantation according to type of PSC (classical or CBD spontaneous perforation) was performed according to the Kaplan–Meier method and the curves were compared using the Log-Rank test. Results: A total of nine (3.4%) PSC patients (5 males) had perforation of the CBD with a median age at diagnosis of 18 years compared to 33 years for the control group (p = 0.019). The peri-biliary collections were variable in appearance (fusiform or pedunculated), with a diameter ranging from 5 to 54 mm. All nine patients showed intra- and extra-hepatic bile duct involvement, dysmorphia, and high ANALI scores. The clinical course was characterized by numerous complications in most patients, and five patients (56%) underwent liver transplantation at a median time of 5 years from diagnosis, compared to 40 patients (16%) in the control group (p = 0.02). Conclusion: The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients and is associated with a poor prognosis. Clinical relevance statement: This uncommon complication of primary sclerosing cholangitis with perforation of the common bile duct resulting in a peri-biliary collection and a pseudo-cystic appearance of the common bile duct is characterized by a poor prognosis in younger patients. Key Points: • Among 263 patients with primary sclerosing cholangitis (PSC), nine patients (3.6%) had an uncommon complication characterized on MRI by perforation of the common bile duct (CBD). • This perforation of the CBD was responsible in all nine cases for the formation of a peri-biliary collection, giving a pseudo-cystic appearance to the CBD. • The spontaneous perforation of the common bile duct is an uncommon complication of primary sclerosing cholangitis that affects young patients with a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Bile duct injury (BDI) is one of the most severe complications during cholecystectomy. Early identification of risk factors for BDI may permit risk reduction strategies and inform patient consent. Objective: This study aimed to define patient, provider, and systemic factors associated with BDI; BDI incidence; and short-term outcomes of BDI after urgent cholecystectomy. Methods: Patients who underwent urgent cholecystectomy for acute cholecystitis were retrospectively screened (2020-2022). All patients who sustained BDI were included without exclusions. Demographics, clinical data, and outcomes were collected and compared with descriptive statistics. Results: During the study period, BDI occurred in 4 (0.5%) of 728 patients who underwent urgent cholecystectomy for acute cholecystitis. Most BDI cases (75%) took place overnight or during the weekend. The attending surgeon was almost exclusively (75%) in their first year of practice. BDI was recognized during index operation in 2 cases (50%). Hepatobiliary surgery performed the bile duct repair in all 4 cases. Two complications occurred (50%). All patients were followed by hepatobiliary surgery in the outpatient setting and returned to their baseline level of function within 2 months of hospital discharge. Conclusion: Most BDI occurred in procedures attended by first-year faculty during after hours cholecystectomies, suggesting a role for increased proctorship in early career attendings in addition to in-hours cholecystectomy for acute cholecystitis. The timely return to baseline function experienced by these patients emphasizes the favorable outcomes associated with early recognition of BDI and involvement of hepatobiliary surgery. Further examination with multicenter evaluation would be beneficial to validate these study findings. [ABSTRACT FROM AUTHOR]

Purpose Hepaticojejunostomy anastomosis (HJA) is the most challenging aspect in single-port laparoscopic choledochal cystectomy and Roux-en-Y hepaticojejunostomy (SPCH) in children, especially in small-diameter anastomoses (diameters less than 5 mm), which are more susceptible to anastomotic stricture. We developed the continuous submucosal technique for HJA (CS-HJA) to lessen postoperative complications. The purpose of this study is to introduce our preliminary experiences with CS-HJA. Methods We retrospectively analyzed all available clinical data of children who underwent SPCH surgery between March 2020 and October 2022. We operated with CS-HJA on 10 children who were diagnosed with small-diameter hepaticojejunostomy (diameter less than 5 mm). Data collection mainly included demographic information, imaging data, perioperative details, and postoperative outcomes. Ten patients were included in this study. The average patient age was 55.2 months; the age range was 3 to 120 months, and the average weight was 11.6 kg; male–female ratio was 1:9. The choledocho had fusiform dilatation in five cases and cystic dilatation in five cases. There was no dilatation of the left and right hepatic ducts or intrahepatic bile ducts in all patients. All patients had no dilatation of the left and right hepatic ducts or intrahepatic bile ducts. All patients underwent a single-port laparoscopic bile-intestinal anastomosis using a submucosal jejunal anastomosis technique. Analysis of the duration of the bile-intestinal anastomosis, the length of the child's stay in the hospital after surgery, the intraoperative complications, and the postoperative complications was performed. Results All the 10 patients underwent successful SPCH by CS-HJA technique. The average length of time for hepaticojejunostomy ranged from 22 to 40 minutes, and the postoperative hospital stay was 5.2 to 9.2 days. There were no instances of bile leakage following the operation. At 17 to 30 months of follow-up, there was no abdominal pain or jaundice, and the reexamination of transaminases, bilirubin, and amylase were normal. Ultrasonography showed no bile duct stricture or dilated bile ducts, and the incision is elegant, and the families of the patients were satisfied. Conclusion In SPCH surgery in children, the CS-HJA technique is safe and feasible for small-diameter hepaticojejunostomy. [ABSTRACT FROM AUTHOR]

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Pembrolizumab induced hepatitis has received increasing attention, while pembrolizumab induced cholangitis is poorly understood. This study investigated the clinical features, treatment, and outcome of pembrolizumab induced cholangitis. Case reports, case series and clinical studies of pembrolizumab induced cholangitis were collected by retrieving English and Chinese database from inception until October 30, 2023. Fifty patients with cholecystitis entered our study with a median age of 68 years (range 48, 89). The median time to onset of cholecystitis was 1.1 months (range 0.3, 24), and the median number of cycles was 5 cycles (range 1, 27) after initial administration. Most of the patients had no clinical symptoms and only showed elevated biliary enzymes (24 cases, 48.0%), while some patients showed jaundice (12 cases, 24.0%), abdominal pain (10 cases, 20.0%) and fever (7 cases, 14.0%). The median alkaline phosphatase value was 1111 IU(range 130, 3515) and the median glutamyltransferase value was 649.5 IU(range 159, 3475). The imaging features of gallbladder were bile duct dilatation, stenosis and bile duct wall thickening and irregularity. Bile duct biopsy showed inflammatory infiltration, mainly CD8 + T cell infiltration. Immunosuppression treatment resulted in complete response in 4 cases (8.0%), partial response in 28 cases (56.0%), and poor response in 15 cases (30.0%). Cholangitis is a rare and serious adverse effect of pembrolizumab. Clinicians should be aware of the possibility of cholangitis when administering pembrolizumab. Steroids may not be effective in most patients with cholecystitis, and ursodeoxycholic acid may be an option. [ABSTRACT FROM AUTHOR]

We previously demonstrated that in Ifnar1-/-Ifngr1-/- or Stat1-/- suckling mice lacking intact type I and type II interferon (IFN) signaling, rhesus rotavirus (RRV) infection causes a lethal disease with clinical manifestations similar to biliary atresia, including acholic stools, oily fur, growth retardation, and excess mortality. Elevated levels of viral RNA are detected in the bile ducts and liver of diseased pups together with severe inflammatory responses in these tissues. However, the viral determinants and the molecular mechanisms driving this process remain incompletely understood. Using an optimized rotavirus (RV) reverse genetics system, we generated a panel of recombinant RVs that encode non-structural protein 1 (NSP1) derived from different RV strains. We found that compared to the parental simian SA11 strain that is less biliary pathogenic, SA11 containing an RRV-derived NSP1 resulted in severe biliary obstructive disease comparable to that associated with RRV infection, reflected by high levels of viral RNA and inflammation in the biliary tract, liver, and pancreas. In contrast, RRV containing an SA11-originated NSP1 showed only mild biliary obstruction comparable to what was observed during SA11 infection. Infection with a monoreassortant RRV virus carrying NSP1 from the bovine RV UK strain also showed substantially reduced viral replication in extra-intestinal organs and did not develop clinical biliary diseases. Mechanistically, RRV NSP1 seemed to promote active viral replication in hepatocytes and this expanded tropism led to enhanced infiltration of CD4 and CD8 T cells, causing immunopathology and damage in the hepatobiliary system. These results highlight an unexpectedly important role of RV NSP1 in viral replication and disease progression in extra-intestinal tissues. Author summary: In our research, we investigated how specific proteins from the rotavirus, a virus known for causing gastrointestinal infections, influence the severity of liver diseases in a special mouse model. We found that a protein called NSP1, which varies between different strains of the virus, plays a key role in how severe the liver disease becomes. Mice that lacked certain immune system components developed a serious liver condition similar to biliary atresia—a disease that affects the bile ducts and liver. When these mice were infected with a strain of rotavirus carrying NSP1 from another strain, they showed much more severe liver damage compared to those infected with a different strain. Our findings highlight the significant role of NSP1 in promoting viral replication in the liver and bile ducts. This research may help us understand whether and why some rotavirus strains cause more severe liver disease than others and could guide future studies aiming to develop better treatments for such infections. By uncovering these details, we aim to improve our understanding of rotavirus and its impact on the liver, potentially leading to better strategies for managing and treating related diseases. [ABSTRACT FROM AUTHOR]

Background: The porcine gall bladder and cystic duct gained attention in experimental research aimed at improving human clinical care. While the common bile duct has been investigated before, there is almost no data on the porcine cystic duct. Its relevance for research originates from its potential use in xenotransplantation. Methods: We included 10 consecutive pigs (1♀, 9♂) that had been sacrificed after participation in another study. At necropsy, the distance from the biliary papilla to the gall bladder (gall bladder distance) was measured. The cystic duct was then subjected to linear traction. Ethical approval for the study was granted. Associations between force measurements and anatomical parameters were tested by correlation analysis. Results: The pigs had a mean body weight of 21.9 kg (standard deviation 2 kg), a mean liver weight of 590 g (standard deviation 88 g), and a mean crown rump length of 67.3 cm (standard deviation 3 cm). The gall bladder distance was 8.2 cm (95% confidence interval: 7.6–8.7 cm). The cystic duct withstood mean linear traction forces of 4.8 N (95% confidence interval: 3.7–5.8 N) and could be elongated by a mean of 6 mm (95% confidence interval: 3.9–8 mm). Linear breaking strength was neither correlated to gall bladder distance (R = 0.3, 95% confidence interval: − 0.41 to 0.78, P = 0.406) or crown rump length (R = 0.42, 95% confidence interval: − 0.28 to 0.83, P = 0.222) nor liver weight (R = 0.02, 95% confidence interval: − 0.62 to 0.64, P = 0.954) or body weight (R = 0.36, 95% confidence interval: − 0.35 to 0.81, P = 0.304). This was also true for gall bladder distance. Conclusions: Our study indicates that allometric parameters were not associated with the gall bladder distance or its resistance to traction forces. Consequently, substantial variation of these parameters can be expected in these surgically important parameters, which cannot be derived from easily accessible anatomical parameters. [ABSTRACT FROM AUTHOR]

Background: Liver transplantation in pediatric patients is a crucial intervention for treating end-stage hepatic diseases. Despite significant advances in surgical techniques and postoperative care, complications remain a substantial challenge in this population. Biliary stones, an infrequent complication, present challenges in this context. Given the impossibility of endoscopic treatments, different strategies have been explored to address post-liver transplantation gallstones in children by implementing percutaneous treatment with intraductal lithotripsy. Case presentation: A 7-year-old Latin patient, who had a diagnosis of biliary atresia at the age of 2, underwent a liver transplant from a living donor. However, 4 months after the transplant, the patient experienced recurring episodes of cholangitis. Cholangioresonance revealed intrahepatic lithiasis and anastomotic stenosis. Attempted gallstone removal through percutaneous cholangiography proved unsuccessful, as multiple peripheral stones in all ducts remained immobile. Subsequently, a percutaneous endoscopic cholangioscopy using the SpyGlass Discover system for visual examination of the bile ducts + electrohydraulic lithotripsy was performed, effectively removing the stones without any complications. Conclusions: Percutaneous cholangioscopy with intraductal lithotripsy enables accurate identification and extraction of intrahepatic stones without the need for surgical intervention. This method proves to be a valuable alternative in addressing post-transplant biliary stone. In our case, it was performed on a pediatric patient who underwent liver transplantation, which makes it interesting and relevant as there is currently insufficient literature on this approach in such cases in this population. [ABSTRACT FROM AUTHOR]

Pure laparoscopic donor hepatectomy (PLDH) has become a standard practice for living donor liver transplantation in expert centers. Accurate understanding of biliary structures is crucial during PLDH to minimize the risk of complications. This study aims to develop a deep learning-based segmentation model for real-time identification of biliary structures, assisting surgeons in determining the optimal transection site during PLDH. A single-institution retrospective feasibility analysis was conducted on 30 intraoperative videos of PLDH. All videos were selected for their use of the indocyanine green near-infrared fluorescence technique to identify biliary structure. From the analysis, 10 representative frames were extracted from each video specifically during the bile duct division phase, resulting in 300 frames. These frames underwent pixel-wise annotation to identify biliary structures and the transection site. A segmentation task was then performed using a DeepLabV3+ algorithm, equipped with a ResNet50 encoder, focusing on the bile duct (BD) and anterior wall (AW) for transection. The model's performance was evaluated using the dice similarity coefficient (DSC). The model predicted biliary structures with a mean DSC of 0.728 ± 0.01 for BD and 0.429 ± 0.06 for AW. Inference was performed at a speed of 15.3 frames per second, demonstrating the feasibility of real-time recognition of anatomical structures during surgery. The deep learning-based semantic segmentation model exhibited promising performance in identifying biliary structures during PLDH. Future studies should focus on validating the clinical utility and generalizability of the model and comparing its efficacy with current gold standard practices to better evaluate its potential clinical applications. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore the application value of three-dimensional (3D) visualization technology in the early surgical repair of bile duct injury during laparoscopic cholecystectomy (LC). Methods: A retrospective analysis was conducted on the clinical data of 15 patients who underwent early surgical repair of bile duct injury during LC with the assistance of 3D visualization technology at the Hepatobiliary Surgery Department of Ningxia Hui Autonomous Region People's Hospital from January 2019 to December 2022. Postoperative efficacy and long-term follow-up outcomes were summarized. Results: Before the repair surgery, 15 cases of bile duct injury during LC were evaluated using 3D visualization technology according to the Strasberg-Bismuth classification: 2 cases of type C, 4 of type E1, 3 of type E2, 3 of type E3, and 3 of type E4. Intraoperative findings were consistent with the 3D visualization reconstruction results, and all patients successfully underwent hepaticojejunostomy using Roux-en-Y anastomosis guided by the 3D visualization navigation. The time interval between LC and bile duct repair surgery ranged from 5 to 28 (14.2 ± 9.7) days. The surgical time was between 120 and 190 (156.40 ± 23.92) min, and estimated blood loss ranged from 80 to 250 (119.66 ± 47.60) mL. The length of hospital stay ranged from 12 to 25 days (median: 16 days). One patient experienced mild bile leakage after the operation, which healed with conservative treatment. All patients were followed up for 12–56 months (median: 34 months) without any loss to follow-up. During the follow-up period, no complications, such as anastomotic stricture or stone formation, were observed. Conclusion: The application of 3D visualization technology for preoperative evaluation and intraoperative navigation can accurately and effectively facilitate early surgical repair of bile duct injury during LC and has clinical value for promotion and application. [ABSTRACT FROM AUTHOR]

Biliary complications are still a major cause for morbidity and mortality after liver transplantation (LT). Ischemia/reperfusion injury (IRI) leads to disruption of the biliary epithelium. We introduce a novel model to study the effect of IRI on human cholangiocytes using extrahepatic cholangiocyte organoids (ECOs). Extrahepatic bile duct tissue was collected during LT at static cold storage and after reperfusion (n = 15); gallbladder tissue was used for controls (n = 5). ECOs (n = 9) were cultured from extrahepatic biliary tissue, with IRI induced in an atmosphere of 95% air (nitrogen), 1% O2 and 5% CO2for 48 h, followed by 24 h of reoxygenation. Qualitative and quantitative histology and qRT-PCR were performed to discern phenotype, markers of hypoxia, programmed cell death and proliferation. ECOs self-organized into circular structures resembling biliary architecture containing cholangiocytes that expressed EpCAM, CK19, LGR5 and SOX-9. After hypoxia, ECOs showed increased expression of VEGF A (p < 0.0001), SLC2A1 (p < 0.0001) and ACSL4 (p < 0.0001) to indicate response to hypoxic damage and subsequent programmed cell death. Increase in cyclin D1 (p < 0.0001) after reoxygenation indicated proliferative activity in ECOs. Therefore, ECO structure and response to IRI are comparable to that found in-vivo, providing a suitable model to study IRI of the bile duct in-vitro. [ABSTRACT FROM AUTHOR]

Activation of extracellular matrix–producing hepatic stellate cells (HSCs) is a key event in liver fibrogenesis. We showed that the expression of the heme-thiolate monooxygenase cytochrome P450 1B1 (CYP1B1) was elevated in human and mouse fibrotic livers and activated HSCs. Systemic or HSC-specific ablation and pharmacological inhibition of CYP1B1 attenuated HSC activation and protected male but not female mice from thioacetamide (TAA)–, carbon tetrachloride (CCl4)–, or bile duct ligation (BDL)–induced liver fibrosis. Metabolomic analysis revealed an increase in the disaccharide trehalose in CYP1B1-deficient HSCs resulting from intestinal suppression of the trehalose-metabolizing enzyme trehalase, whose gene we found to be a target of RARα. Trehalose or its hydrolysis-resistant derivative lactotrehalose exhibited potent antifibrotic activity in vitro and in vivo by functioning as an HSC-specific autophagy inhibitor, which may account for the antifibrotic effect of CYP1B1 inhibition. Our study thus reveals an endobiotic function of CYP1B1 in liver fibrosis in males, mediated by liver-intestine cross-talk and trehalose. At the translational level, pharmacological inhibition of CYP1B1 or the use of trehalose/lactotrehalose may represent therapeutic strategies for liver fibrosis. Editor's summary: Hepatic stellate cells (HSCs) are well-known actors in liver fibrosis, and a better understanding of the factors governing their activity could open up therapeutic opportunities. Tung et al. examined the role of the cytochrome P450 analog CYP1B1 in liver fibrosis, finding that its inhibition or depletion reduced liver pathology in multiple mouse models in a sex-dependent manner. The authors tied the observed antifibrotic effect in males to HSC accumulation of trehalose as a result of inhibition of trehalase in the intestine. As a test of therapeutic potential, male mice fed trehalose or nonhydrolyzable lactotrehalose in drinking water showed reduced liver fibrogenesis, with follow-up analysis of similarly treated HSCs demonstrating reduced autophagic degradation. This study suggests that the metabolite trehalose may play a sex-specific role in liver fibrosis. —Catherine Charneski [ABSTRACT FROM AUTHOR]

Background: Acute suppurative cholangitis (ASC) lacks sensitive and specific preoperative diagnostic criteria. Some researchers suggest treating ASC as severe cholangitis. This study aimed to explore the relationship between the Tokyo Guidelines 2018 (TG18) grading system for acute cholangitis (AC) and the diagnosis of acute suppurative cholangitis (ASC), searching for independent risk factors of ASC and develop a nomogram to discriminate ASC from acute nonsuppurative cholangitis (ANSC) accurately. Methods: After applying the inclusion and exclusion criteria, 401 patients with acute cholangitis (AC) were retrospectively analyzed at Nanjing First Hospital between January 2015 and June 2023. SPSS version 27.0 and R studio software were used to analyze data obtained from medical records. The results were validated in a prospective cohort of 82 AC patients diagnosed at Nanjing First Hospital between July 2023 and February 2024. Results: Among the 401 patients, 102 had suppurative bile (the ASC group; AC grade I: 40 [39.2%], AC grade II: 27 [26.5%], AC grade III: 35 [34.3%]), whereas 299 did not have (the ANSC group; AC grade I: 157 [52.5%], AC grade II: 92 [30.8%], AC grade III: 50 [16.7%]). The specificity of ASC for diagnosing moderate-to-severe cholangitis is 79.7%. Multivariate logistic regression analysis identified concurrent cholecystitis, CRP, PCT, TBA, and bile duct diameter as independent risk factors for suppurative bile, and all of these factors were included in the nomogram. The calibration curve exhibited consistency between the nomogram and the actual observation, and the area under the curve was 0.875 (95% confidence interval: 0.835–0.915), sensitivity was 86.6%, and specificity was 75.5%. Conclusion: Suppurative bile is a specific indicator for diagnosing moderate-to-severe cholangitis. However, diagnosing ASC with AC grade II and AC grade III has the risk of missed diagnosis as the sensitivity is only 60.8%. To improve the diagnostic rate of ASC, this study identified concurrent cholecystitis, CRP, PCT, TBA, and preoperative bile duct diameter as independent risk factors for ASC, and a nomogram was developed to help physicians recognize patients with ASC. [ABSTRACT FROM AUTHOR]

Background: Gallbladder cysts are rare diseases with very few reported cases, and no clinical or histological definition has been established. Furthermore, cases of giant cysts outside the gallbladder wall are extremely rare. We report a rare case of giant gallbladder cyst with acute cholecystitis. Case presentation: An 85-year-old woman with appetite loss and right lower abdominal pain lasting 2 days presented to our hospital. At first, the patient's abdominal pain was mild to moderate with no fever. Blood tests revealed a white blood cell count of 10,950/mm3, and the C-reactive protein (CRP) level was 14.35 mg/dl. A contrast-enhanced computed tomography (CT) scan of the abdomen revealed a grossly distended gallbladder (14.5 × 14.5 × 8.7 cm) with an incarcerated stone in the cystic duct. The patient was treated by percutaneous transhepatic gallbladder drainage (PTGBD) with 735 ml of drainage fluid. Oral contrast magnetic resonance cholangiopancreatography (MRCP) revealed that gallbladder swelling remained (14.0 × 6.5 cm) 3 days after PTGBD. We performed laparoscopic cholecystectomy 6 days after PTGBD. Because of the severe adhesion around the junction of the cystic and common bile ducts, we performed open cholecystectomy. The resected specimen was 14 × 11 cm in size and consisted of a gallbladder (6 × 7 cm) with a stone (2.4 × 1.8 cm) in the gallbladder and a large cystic lesion (18 × 18 cm) outside the gallbladder wall. The cystic lesion had a wall thickness of 6 to 12 mm and internal septal structures and contained hemorrhagic and necrotic tissue. Histological examination revealed that the specimens showed a mildly swollen gallbladder and a cystic lesion on the outside of the gallbladder wall, adjacent to the gallbladder wall, with wall thickening and inflammation. The cystic lesion suggested gallbladder duplication, gallbladder diverticulum or extension of the Rokitansky-Aschoff sinus (RAS). There was no malignancy. The patient's postoperative course was uneventful, and she was discharged 5 days after the operation. Conclusion: We present a very rare case of giant gallbladder cyst with acute cholecystitis revealed by cholecystectomy. [ABSTRACT FROM AUTHOR]

Objectives: Although peroral cholangioscopy has improved the endoscopic treatment of difficult stones, the treatment of intrahepatic stones remains challenging. The incidence of cholangitis is high when peroral cholangioscopy is used to treat intrahepatic stones. This study aimed to investigate the efficacy and safety of endoscopic treatment with peroral cholangioscopy for intrahepatic and common bile duct stones. Methods: Patients aged ≥20 years, who underwent endoscopic treatment with peroral cholangioscopy for intrahepatic or common bile duct stones at Tottori University Hospital from January 2016 to December 2022, were retrospectively evaluated to determine the efficacy and safety of the treatment. Results: Overall, 70 patients were included in this study: 22 in the intrahepatic stone group and 48 in the common bile duct stone group. Stones were smaller (8 vs. 17.5 mm, p < 0.001) and more numerous (p = 0.016) in the intrahepatic stone group than in the common bile duct stone group. Although the common bile duct stone group exhibited a higher rate of complete stone clearance in the first session, no significant differences were observed in the final results. The intrahepatic stone group had a higher incidence of cholangitis (36% vs. 8%, p = 0.007); however, all cases were mild. Conclusions: Endoscopic treatment with peroral cholangioscopy for intrahepatic stones may be associated with a higher incidence of cholangitis than that for common bile duct stones. Since saline irrigation may contribute to the development of cholangitis, it is important to be aware of intraductal bile duct pressure when performing peroral cholangioscopy. [ABSTRACT FROM AUTHOR]

Malignant hilar biliary obstruction (MHBO) can cause obstructive jaundice and/or cholangitis necessitating appropriate biliary drainage. Endoscopic biliary stenting is the first-choice treatment, especially in unresectable cases, owing to its minimally invasive nature and utility. However, the hilar region is complex because of the branching and curving of bile ducts, making strictures in this area more complicated. Therefore, MHBO stenting is challenging, and treatment strategies have yet to be established. Furthermore, recent advances in antitumor therapies have altered the background surrounding the development of stenting strategies. Therefore, it is necessary to understand and grasp the current evidence well and to accumulate additional evidence reflecting the current situation. This study reviews the current status, issues, and prospects of endoscopic stenting for MHBO, especially in unresectable cases. [ABSTRACT FROM AUTHOR]

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disorder characterized by progressive cholestatic that, if untreated, can progress to liver fibrosis, cirrhosis and liver decompensation requiring liver transplant. Although the pathogenesis of the disease is multifactorial, there is a consensus that individuals with a genetic predisposition develop the disease in the presence of specific environmental triggers. A dysbiosis of intestinal microbiota is increasingly considered among the potential pathogenic factors. Cholangiocytes, the epithelial cells lining the bile ducts, are the main target of a dysregulated immune response, and cholangiocytes senescence has been recognized as a driving mechanism, leading to impaired bile duct function, in disease progression. Bile acids are also recognized as playing an important role, both in disease development and therapy. Thus, while bile acid-based therapies, specifically ursodeoxycholic acid and obeticholic acid, have been the cornerstone of therapy in PBC, novel therapeutic approaches have been developed in recent years. In this review, we will examine published and ongoing clinical trials in PBC, including the recently approved peroxisome-proliferator-activated receptor (PPAR) agonist, elafibranor and seladelpar. These novel second-line therapies are expected to improve therapy in PBC and the development of personalized approaches. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis (AIP) is identified as an outlier in the clinical practice of chronic pancreatitis caused by autoimmune system dysfunction. AIP is classified into 3 subtypes: AIP type 1 and AIP type 2, which are both sensitive to corticosteroids, and the recently introduced AIP type 3. Case Report: We present a case of a patient who presented with painless obstructive jaundice. Computed tomography (CT) revealed hyperdense gallbladder material, further dilatation of intrahepatic bile ducts, and distention of the bile duct (15 mm). Based on the available clinical data, which were strongly compatible with pancreatic cancer, Whipple surgery was selected as the treatment for this case. The consequent histopathological report revealed areas of pancreatic parenchyma with fibrous connective tissue development and dense inflammatory cell infiltration with lymphocytes and plasmacytes, which showcased IgG4 positivity. The clinical results suggested a diagnosis of AIP type 1, and the patient was referred to his treating physician for further treatment of AIP. Preoperative histological examination of the pancreas, along with evaluation of the radiological and serological features, could have aided in determining the diagnosis of AIP type 1 pancreatitis despite the unique abnormality of this particular case. Conclusions: Given the aforementioned conditions, AIP, even as a rare clinical entity, emerges as a canonical ailment and should be considered a viable possibility in clinical practice since it can exclude the patient from an unnecessary surgery [ABSTRACT FROM AUTHOR]

Background: Biliary dilatation without obvious etiology on cross sectional imaging warrants further investigation. This study aimed to assess yield of endoscopic ultrasound in providing etiologic diagnosis in such situation. Methods: Prospective cohort of consecutive patients with biliary dilatation & non diagnostic computed tomography (CT) and /or magnetic resonance imaging (MRI) underwent endoscopic ultrasound (EUS) with/without fine needle aspiration cytology (FNAC) and were followed clinically, biochemically with/without radiology for up to six months. The findings of EUS were corroborated with histopathology of surgical specimens and endoscopic retrograde cholangiography (ERCP) findings in relevant cases. Results: Median age of 121 patients completing follow up was 55 years. 98.2% patients were symptomatic and median common bile duct (CBD) diameter was 13 mm. EUS was able to identify lesions attributable for biliary dilatation in (67 out of 121) 55.4% cases with ampullary neoplasm being the commonest (29 out of 67 i.e. 43%). Multivariate logistic regression analysis identified jaundice as the predictor of positive diagnosis on EUS, of finding ampullary lesion and pancreatic lesion on EUS. EUS had sensitivity, specificity, positive predictive value and diagnostic accuracy of 95.65%, 94.23%, 95.65% and 95.04% respectively in providing etiologic diagnosis. Threshold value for baseline bilirubin of 10 mg%, for baseline CA 19.9 of 225 u/L and for largest CBD diameter of 16 mm were determined to have specificity of 98%, 95%, 92.5% respectively of finding a positive diagnosis on EUS. Conclusion: EUS provides considerable diagnostic yield with high accuracy in biliary dilatation when cross sectional imaging fails to provide etiologic diagnosis. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions Neuroendocrine tumours (NETs) occurring in the extrahepatic biliary system are exceedingly rare. While NETs typically manifest as mass lesions, the occurrence of microscopic neuroendocrine cell proliferation without a distinct mass remains undocumented at this location. This study aims to characterise the clinicopathological features of a series of well‐differentiated neuroendocrine lesions involving the extrahepatic biliary tree, including mass forming NETs and microscopic non‐mass‐forming neuroendocrine cell proliferation, designated neuroendocrine cell micronests (NCMs).Surgical resections of NETs/NCMs involving the extrahepatic bile ducts and gallbladder were identified from electronic pathology databases among seven institutions spanning from January 2011 to September 2023. Clinical and histological findings were recorded. Ten patients (four female, six male: age range = 34–75 years) were included in the study. Histopathological examination revealed visible mass‐forming lesions in four cases (1.6–14.0 cm in size), identified in the gallbladder (n = two) or extrahepatic bile duct (n = two), all diagnosed as well‐differentiated NETs. The remaining six cases revealed incidental non‐mass‐forming NCMs in either the cystic duct (n = two), common bile duct (n = three) or gallbladder (n = one), ranging from < 0.1 to 0.4 cm; four were associated with biliary lithiasis. No evidence of metastasis or recurrence was seen in the follow‐up period (range = 0.1–11.2 years).This study highlights the spectrum of extrahepatic biliary well‐differentiated neuroendocrine lesions, ranging from incidental microscopic NCMs to grossly apparent mass‐forming NETs, potentially requiring different clinical management. Noteworthy is the frequent association of incidental microscopic neuroendocrine cell proliferations with biliary lithiasis, indicating a potential neuroendocrine metaplastic pathogenesis that merits further exploration. [ABSTRACT FROM AUTHOR]