Successful Use of Fecal Microbiota Transplantation in Management of Nonobstructive Recurrent Cholangitis Following Total Pancreatectomy and Islet Autotransplant.

Alterations in the gut microbiome have been implicated in various pathologies. Fecal microbiota transplantation (FMT) has been offered as a novel treatment for conditions implicated in the disruption of the gut-microbiota axis. This case report details the successful treatment of recurrent nonobstructive cholangitis following a single FMT application in a patient who had previously undergone a hepatobiliary tract surgical diversion. Cholangitis was suspected secondary to reflux of an altered microbiome into the surgically reanastomosed biliary tract, and FMT was justified based on the history of recurrent Clostridioides difficile infections. This case supports the further evaluation of the utility of FMT as one potential treatment of post hepatobiliary surgical diversion cholangitis.

Predictive Factors of Canine Malignant Hepatic Diseases with Multifocal Hepatic Lesions Using Clinicopathology, Ultrasonography, and Hepatobiliary Ultrasound Scores.

Multifocal hepatic lesions in dogs arise from various benign and malignant liver diseases. Diagnosing these lesions is challenging because clinical signs, hematological data, and serum biochemistry are not definitive indicators. Ultrasound is utilized as a diagnostic imaging tool to evaluate liver parenchyma and detect hepatic lesions. This study aims to investigate the predictive factors that differentiate between benign and malignant multifocal hepatic lesions by examining ultrasound characteristics, blood tests, and serum biochemistry. In total, 43 dogs with multifocal hepatic lesions were included in this study. All dogs were classified into benign hepatic diseases (n = 32) and malignant haptic diseases (n = 11). For all dogs, their liver characteristics, lesion characteristics, and hepatobiliary ultrasound score by ultrasound were evaluated and we collected individual clinicopathological data for analysis. The findings of the univariate analysis revealed significant differences in four hematological and blood chemical parameters (hematocrit, white blood cell count, aspartate transaminase (AST), and alkaline phosphatase (ALP)) and six ultrasonographic parameters (liver parenchymal echogenicity, lesion homogeneity, lesion echogenicity, maximum lesion dimension, average lesion dimension, and hepatobiliary ultrasound score). Using multivariate analysis, only two parameters, hepatobiliary ultrasound score and lesion homogeneity, showed significant differences (p-value < 0.001 and p-value = 0.011, respectively). Additionally, these parameters demonstrated high accuracy in predicting malignant multifocal liver lesions, with accuracy rates of 97.67% and 93.02%, respectively. Therefore, the hepatobiliary ultrasound score and lesion homogeneity are considered effective parameters for screening malignant multifocal liver lesions in dogs.

Endoscopic management of postcholecystectomy complications at a Nigerian tertiary health facility.

BACKGROUND: Cholecystectomy and common bile duct exploration for biliary stone disease are common hepatobiliary surgeries performed by general surgeons in Nigeria. These procedures can be complicated by injury to the biliary tree or retained stones, requiring repeat surgical intervention. This study presents the experience of using endoscopic retrograde cholangiopancreatography (ERCP) in the management of hepatobiliary surgery complications at the academic referral center of Obafemi Awolowo University Teaching Hospital (OAUTHC) Ile-Ife, Nigeria. METHODS: All patients with postcholecystectomy complications referred to the endoscopy unit at OAUTHC from March 2018 to April 2023 were enrolled. Preoperative imaging included a combination of abdominal ultrasound, CT, MRI, magnetic resonance cholangiopancreatography (MRCP), and T-tube cholangiogram. All ERCP procedures were performed under general anesthesia. RESULTS: Seventy-two ERCP procedures were performed on 45 patients referred for postcholecystectomy complications. The most common mode of presentation was ascending cholangitis [16 (35.6%)], followed by persistent biliary fistula [12 (26.7%)]. The overall median duration of symptoms after cholecystectomy was 20 weeks, with a range of 1-162 weeks. The most common postcholecystectomy complication observed was retained stone [16 (35.6%)]. Other postcholecystectomy complications included bile leakage, bile stricture, bile leakage with stricture, and persistent bile leakage from the T-tube in 12 (26.7%), 11 (24.4%), 4 (8.9%), and 2 (4.4%) patients, respectively. Ampullary cannulation during ERCP was successful in all patients (45, 100%). Patients with complete biliary stricture (10/12) required hepaticojejunostomy. CONCLUSION: Endoscopic management of postcholecystectomy complications was found to be safe and reduce the number of needless surgeries to which such patients are exposed. We recommended prompt referral of such patients for ERCP.

Altered fatty acid metabolism rewires cholangiocarcinoma stemness features.

Background & Aims: Among the reprogrammed metabolic pathways described in cancer stem cells, aberrant lipid metabolism has recently drawn increasing attention. Our study explored the contribution of fatty acids (FA) in the regulation of stem-like features in intrahepatic cholangiocarcinoma (iCCA). Methods: We previously identified a functional stem-like subset in human iCCA by using a three-dimensional sphere (SPH) model in comparison to parental cells grown as monolayers (MON). In this study, quantification of intracellular free FA and lipidomic analysis (triacylglycerol [TAG] composition, de novo synthesis products) was performed by Liquid chromatography-mass spectrometry (LC-MS); quadrupole time-of-flight liquid chromatography/mass spectrometry (Q-TOF LC/MS), respectively, in both SPH and MON cultures. Results: Stem-like SPH showed a superior content of free FA (citric, palmitic, stearic, and oleic acids) and unsaturated TAG. Molecularly, SPH showed upregulation of key metabolic enzymes involved in de novo FA biosynthesis (AceCS1, ACLY, ACAC, FASN, ACSL1) and the mTOR signalling pathway. In patients with iCCA (n = 68), tissue expression of FASN, a key gene involved in FA synthesis, correlated with 5-year overall survival. Interference with FASN activity in SPH cells through both specific gene silencing (siRNA) or pharmacological inhibition (orlistat) decreased sphere-forming ability and expression of stem-like markers. In a murine xenograft model obtained by injection of iCCA-SPH cells, FASN inhibition by orlistat or injection of FASN-silenced cells significantly reduced tumour growth and expression of stem-like genes. Conclusion: Altered FA metabolism contributes to the maintenance of a stem-like phenotype in iCCA. FASN inhibition may represent a new approach to interfere with the progression of this deadly disease. Impact and implications: Recent evidence indicates that metabolic disorders correlate with an increased susceptibility to intrahepatic cholangiocarcinoma (iCCA). Our investigation emphasises the pivotal involvement of lipid metabolism in the tumour stem cell biology of iCCA, facilitated by the upregulation of crucial enzymes and the mTOR signalling pathway. From a clinical perspective, this underscores the dual role of FASN as both a prognostic indicator and a therapeutic target, suggesting that FASN inhibitors could enhance patient outcomes by diminishing stemness and tumour aggressiveness. These findings pave the way for novel therapeutic strategies for iCCA and shed light on its relationship with metabolic disorders such as diabetes, obesity, metabolic syndrome, and metabolic dysfunction-associated steatotic liver disease.

Real-time ultrasound AR 3D visualization toward better topological structure perception for hepatobiliary surgery.

PURPOSE: Ultrasound serves as a crucial intraoperative imaging tool for hepatobiliary surgeons, enabling the identification of complex anatomical structures like blood vessels, bile ducts, and lesions. However, the reliance on manual mental reconstruction of 3D topologies from 2D ultrasound images presents significant challenges, leading to a pressing need for tools to assist surgeons with real-time identification of 3D topological anatomy. METHODS: We propose a real-time ultrasound AR 3D visualization method for intraoperative 2D ultrasound imaging. Our system leverages backward alpha blending to integrate multi-planar ultrasound data effectively. To ensure continuity between 2D ultrasound planes, we employ spatial smoothing techniques to interpolate the widely spaced ultrasound planes. A dynamic 3D transfer function is also developed to enhance spatial representation through color differentiation. RESULTS: Comparative experiments involving our AR visualization of 3D ultrasound, alongside AR visualization of 2D ultrasound and 2D visualization of 3D ultrasound, demonstrated that the proposed method significantly reduced operational time(110.25 ± 27.83 s compared to 292 ± 146.63 s and 365.25 ± 131.62 s), improved depth perception and comprehension of complex topologies, contributing to reduced pressure and increased personal satisfaction among users. CONCLUSION: Quantitative experimental results and feedback from both novice and experienced physicians highlight our system's exceptional ability to enhance the understanding of complex topological anatomy. This improvement is crucial for accurate ultrasound diagnosis and informed surgical decision-making, underscoring the system's clinical applicability.

Clinicopathological features and surgical treatments of intraductal papillary neoplasm of the bile duct: a case report and literature review.

Intraductal papillary neoplasm of bile duct (IPNB), as a precancerous lesion of cholangiocarcinoma, is a rare biliary tract tumor. A 66-year-old female patient was found to have a bile duct mass by routine examination. The liver function tests and tumor markers were normal. Imaging findings revealed a 2.6 cm mass in the common hepatic duct, accompanied by dilatation of both intrahepatic and extrahepatic bile ducts. The patient underwent open extrahepatic bile duct resection, cholecystectomy and Roux-en-Y hepaticojejunostomy. We also conducted a literature review to summarize the clinicopathological features and surgical treatments of IPNB.

To compress or to breath-hold? A systematic review of the impact of motion mitigation techniques on motion, interfraction set-up errors, and intrafraction errors in patients with hepatobiliary and pancreatic malignancies.

BACKGROUND AND PURPOSE: Reducing motion is vital in treating hepatobiliary (HPB) and pancreatic malignancies. Abdominal compression (AC) and breath-hold (BH) techniques aim to minimise respiratory motion, yet their adoption remains limited, and practices vary. This review examines the impact of AC and BH on motion, set-up errors, and patient tolerability in HPB and pancreatic patients. MATERIALS AND METHODS: This systematic review, conducted using PRISMA and PICOS criteria, includes publications from January 2015 to February 2023. Eligible studies focused on AC and BH interventions in adults with HPB and pancreatic malignancies. Endpoints examined motion, set-up errors, intra-fraction errors, and patient tolerability. Due to study heterogeneity, Synthesis Without Meta-Analysis was used, and a 5 mm threshold assessed the impact of motion mitigation. RESULTS: In forty studies, 14 explored AC and 26 BH, with 20 on HPB, 13 on pancreatic, and 7 on mixed cohorts. Six studied pre-treatment, 22 inter/intra-fraction errors, and 12 both. Six AC pre-treatment studies showed > 5 mm motion, and 4 BH and 2 AC studies reported > 5 mm inter-fraction errors. Compression studies commonly investigated the arch and belt, and DIBH was the predominant BH technique. No studies compared AC and BH. There was variation in the techniques, and several studies did not follow standardised error reporting. Patient experience and tolerability were under-reported. CONCLUSION: The results indicate that AC effectively reduces motion, but its effectiveness may vary. BH can immobilise motion; however, it can be inconsistent between fractions. The review underscores the need for larger, standardised studies and emphasizes the importance of considering the patient's perspective for tailored treatments.

Endoscopic sphincterotomy to prevent post-ERCP pancreatitis after self-expandable metal stent placement for distal malignant biliary obstruction (SPHINX): a multicentre, randomised controlled trial.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) with fully covered self-expandable metal stent (FCSEMS) placement is the preferred approach for biliary drainage in patients with suspected distal malignant biliary obstruction (MBO). However, FCSEMS placement is associated with a high risk of post-ERCP pancreatitis (PEP). Endoscopic sphincterotomy prior to FCSEMS placement may reduce PEP risk. OBJECTIVE: To compare endoscopic sphincterotomy to no sphincterotomy prior to FCSEMS placement. DESIGN: This multicentre, randomised, superiority trial was conducted in 17 hospitals and included patients with suspected distal MBO. Patients were randomised during ERCP to receive either endoscopic sphincterotomy (sphincterotomy group) or no sphincterotomy (control group) prior to FCSEMS placement. The primary outcome was PEP within 30 days. Secondary outcomes included procedure-related complications and 30-day mortality. An interim analysis was performed after 50% of patients (n=259) had completed follow-up. RESULTS: Between May 2016 and June 2023, 297 patients were included in the intention-to-treat analysis, with 156 in the sphincterotomy group and 141 in the control group. After the interim analysis, the study was terminated prematurely due to futility. PEP did not differ between groups, occurring in 26 patients (17%) in the sphincterotomy group compared with 30 patients (21%) in the control group (relative risk 0.78, 95% CI 0.49 to 1.26, p=0.37). There were no significant differences in bleeding, perforation, cholangitis, cholecystitis or 30-day mortality. CONCLUSION: This trial found that endoscopic sphincterotomy was not superior to no sphincterotomy in reducing PEP in patients with distal MBO. Therefore, there was insufficient evidence to recommend routine endoscopic sphincterotomy prior to FCEMS placement. TRIAL REGISTRATION NUMBER: NL5130.

Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.

OBJECTIVE: Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors. DESIGN: We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic PBGD gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue. RESULTS: Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP. CONCLUSION: This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment.

Prospective cohort for early detection of liver cancer (Pearl): a study protocol.

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fastest-rising and fourth most common cause of cancer death worldwide. Liver cirrhosis is the largest underlying risk factor for HCC. Therefore, patients with cirrhosis should have regular ultrasound and biochemical screening to pick up early HCC. Early HCC can be cured; more advanced HCCs have limited treatment options and poor prognosis. Current screening methods are suboptimal with poor sensitivity in picking up early disease. In this study, the investigators aim to recruit people with liver cirrhosis into a Prospective cohort for early detection of liver cancer-the Pearl cohort. The investigators believe that by using state-of-the-art tests we can improve the detection of early HCC. METHODS AND ANALYSIS: This is a UK-based prospective, longitudinal, diagnostic, prognostic, multicentre, non-CTIMP study. Aiming to recruit 3000 patients with liver cirrhosis without a HCC diagnosis, the Pearl cohort will be followed actively for 3 years from recruitment and then passively via registry data for ten years thereafter. Blood and urine samples will be taken and information from routine care will be gathered. These will be used to assess novel diagnostic approaches for the detection early HCC and to develop models to identify those most at risk for developing HCC.Participants will be linked to national UK health registries to ensure long-term capture of HCC incidence and other relevant endpoints. Approximately 75 patients are predicted to develop de novo HCC within the 3-year follow up period. After this period, the study teams will obtain data on participants for at least 10 years after the last contact. This cohort will help develop an understanding of the incidence of HCC in a UK population stratified by underlying cirrhosis aetiology. ETHICS AND DISSEMINATION: Ethical approval has been granted by REC and the trial is registered on ClinicalTrials.gov. The results will be published in peer-reviewed journals and presented at relevant meetings. TRIAL REGISTRATION NUMBER: NCT05541601.

ctDNA in the reading room: A guide for radiologists.

Liquid biopsy with sequencing of circulating tumor DNA (ctDNA) is a minimally invasive method for sampling body fluids and offers a promising alternative to tissue biopsies that involve greater risks, costs, and time. ctDNA not only identifies actionable targets by revealing unique molecular signatures in cancer, but also may assess treatment response, treatment resistance and progression, and recurrence. Imaging correlates of these applications are already being identified and utilized for various solid tumors. Radiologists have new challenges in interpreting oncologic imaging. Given their integral role in cancer surveillance, they must become familiar with the importance of ctDNA in detecting recurrence and minimal residual disease, measuring treatment response, predicting survival and metastatic patterns, and identifying new molecular therapeutic targets. In this review, we provide an overview of ctDNA testing, and a snapshot of current clinical guidelines from the National Comprehensive Cancer Network and the European Society of Molecular Oncology on the use of ctDNA in lung, breast, colorectal, pancreatic, and hepatobiliary cancers. For each cancer type, we also highlight current research applications of ctDNA that are relevant to the field of diagnostic radiology.

Transduodenal resection of a large papillary tumor by means of intraoperative cholangioscopy.

INTRODUCTION: Papillary adenomas are very rare benign tumors of the gastrointestinal tract. If manageable, purely endoscopic resection is favored. As an alternative, surgical resection via ampullectomy or pancreaticoduodenectomy can be performed. Often, the depth of infiltration cannot be assessed with sufficient precision, leading to pancreaticoduodenectomy for safety reasons. CASE PRESENTATION: We present the case of a 77-year-old patient in whom a transduodenal papillary resection of a large papillary adenoma was performed, after two unsuccessful endoscopic attempts. Intraoperatively, a 3 cm large papillary adenoma was identified in the duodenum. The infiltration depth into the Vater's papilla was evaluated through intraoperative cholangioscopy. Due to the shallow depth of invasion, we strived for a papillary resection under endoscopic guidance, allowing complete tumor removal. The postoperative course was uneventful, and the patient was discharged on postoperative day 14. CLINICAL DISCUSSION: The decision between ampullectomy and pancreaticoduodenectomy is an intraoperative challenge. Intraoperative cholangioscopy demonstrated its potential to aid this decision-making process in this case. Larger-scale studies are needed to establish its clinical value. CONCLUSION: Intraoperative cholangiography can help surgeons assess the depth of infiltration of large papillary adenomas, leading to more precise surgical decisions about the necessary extent of resection.

Whether the Liver-to-Portal Vein Ratio is Applicable for Evaluating the European Society of Gastrointestinal and Abdominal Radiology Hepatobiliary Phase in Gd-EOB-DTPA-Enhanced MRI?

PURPOSE: This study aimed to verify whether the Liver-to-portal Ratio (LPR) can assess the adequacy of the Hepatobiliary Phase (HBP) for patients with different liver functions. METHODS: A total of 125 patients were prospectively enrolled in the study and graded into the non-cirrhosis group (45), Child-Pugh A group (40), and Child- Pugh B/C group (40). The LPR on HBP was calculated after eight HBPs were obtained within 5-40 minutes. The adequate HBP was determined according to the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus statement. The differences in LPR and lesions' conspicuity between 10-min HBP and adequate HBP were analyzed by paired t-test and Wilcoxon signed-rank test, respectively. The chisquare test was used to test the difference in proportion with LPR larger than 1.462 between 10-min HBP and adequate HBP. RESULTS: The differences in LPR and lesions' conspicuity between 10-min HBP and adequate HBP were significant in Child-Pugh A and Child-Pugh B/C groups (P < 0.05), except for the non-cirrhosis group (P > 0.05). The differences in proportion with LPR larger than 1.462 between 10-min HBP and adequate HBP were not statistically significant in all groups (all P > 0.05). CONCLUSION: The adequate HBP obtained according to the 2016 ESGAR consensus statement could provide larger LPR and better lesions' conspicuity than 10- min HBP, especially for cirrhotic patients; however, the efficacy of using an LPR cutoff of 1.462 as the standard of the adequate HBP may be compromised in patients with cirrhosis.

[Anastomotic leakage in hepato-pancreato-biliary surgery]. / Anastomoseninsuffizienzen in der hepatopankreatobiliären Chirurgie.

Severe complications following hepato-pancreato-biliary surgery are frequently due to leakage of anastomoses. Local intraoperative and systematic measures can reduce the incidence of leaks and leak-related sequelae. The early identification of leak-related sequelae, such as hemorrhage is pivotal to reduce the mortality risk. Therefore, perioperative risk stratification incorporating surgical and patient risk factors is crucial. The management of anastomotic leaks is complex and an interdisciplinary treatment is therefore recommended. The treatment depends on the institutional expertise, localization, characteristic features of the anastomosis and the onset of insufficiency. This article describes the different concepts of the diagnostics, prevention, consequences and management of anastomotic leakage in hepato-pancreato-biliary surgery in more detail.

Not just a BLiP: early experience with a novel multidisciplinary case conference for benign hepatopancreatobiliary disease at a tertiary Canadian healthcare center.

BACKGROUND: Benign Liver and Pancreas (BLiPs) rounds, implemented in 2022 at our Canadian tertiary care center, are a novel concept of a multidisciplinary case conference (MCC) for discussion of benign hepatopancreatobiliary (HPB) disease. BLiPs Rounds are a monthly virtual meeting of surgeons, gastroenterologists, and interventional radiologists experienced in biliary and pancreatic disease. METHODS: This case series was completed to review the patient cases discussed over the first year of BLiPs rounds, and to evaluate the effect of the multidisciplinary discussion on patient management plans. Meeting minutes were reviewed for BLiPs rounds between May 2022 and July 2023. Data were collected retrospectively on all discussed patients by review of the electronic medical record, and analyzed using frequencies and means with standard deviations. RESULTS: Between May 2022 and July 2023, 56 cases were discussed at 12 case conferences. 68% of cases concerned pancreatic pathology, 25% concerned biliary pathology, the remainder liver or duodenal pathology. 49 cases (88%) were presented to discuss therapeutic options, and 7 presented as diagnostic challenges. Cases were usually presented once, but 7 patients were discussed at multiple conferences due to complex issues or ongoing symptomatology. 40 patients (71%) had undergone previous endoscopic, percutaneous, or surgical interventions prior to discussion. Endoscopic intervention was recommended in 32% of cases, percutaneous interventional approach in 13%, a combined endoscopic and percutaneous approach in 9%, and surgery in 18%. Repeat imaging or observation was recommended in 29% of cases. Discussion at rounds led to a change or adjustment in the proposed management in 46 cases (82%). The plan recommended by the MCC was carried out in 71% of cases. CONCLUSION: BLiPs case conference provides a valuable venue to discuss cases, encourage interdisciplinary collaboration, and refine treatment approaches, leading to a change in proposed management plan in over three-quarters of cases presented.

Psychotropic medication and hepatobiliary health: Ultrasound observations on patients with schizophrenia.

OBJECTIVE: This study sought to examine the association between antipsychotic drug use and hepatobiliary health based on serum markers and ultrasound observations on a sample of patients with schizophrenia compared to age and gender matched healthy controls. METHODS: The 120 patients with schizophrenia and 60 control subjects had their blood drawn to measure liver function tests and underwent hepatobiliary ultrasonography to determine hepatobiliary lesions. Liver function tests included total cholesterol (TC), triglycerides (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Standardized cross-sectional images of the liver and kidneys were obtained from patients and controls, and analyses were stratified by length of taking psychotropic medication among those with schizophrenia. Liver echo attenuation coefficients, liver-kidney ratios, and liver fat content were determined. RESULTS: Psychotropic drug use was associated with greater liver burden and liver lesions in patients with schizophrenia compared to controls. The levels of TC, TG, ALT and AST in patients with schizophrenia were also all significantly higher among patients with schizophrenia. Long-term psychotropic medication was associated with increased levels of fatty liver in patients compared with controls. Levels of TC, TG, ALT and AST were all significantly higher in the long-term psychotropic medication use group than in the short-term group. Liver echo attenuation coefficient, liver-kidney ratio, and liver fat content were also higher in the long-term medication use group compared to the short-term group. CONCLUSION: Antipsychotic drug use, particularly long-term use, is associated with increased liver burden in patients with schizophrenia, impaired lipid metabolism, increased liver lesions and fat content.

Establishment and long-term expansion of adult hepatobiliary organoids co-cultured with liver endothelial cells.

The liver has a unique ability to regenerate in response to injury or disease with hepatocytes and biliary epithelial cells (BECs) driving the regenerative response. Liver progenitor cells (LPCs) also play role in regeneration with the ability to differentiate into either hepatocytes or BECs. However, during chronic liver disease, the regenerative capacity of the liver is impaired. The use of LPCs is a promising therapeutic strategy for patients with chronic liver diseases. LPCs can be expanded in vitro as self-renewing organoids, however, most approaches to LPC organoids do not include critical cells from the LPC niche in 3D organoid cultures. In this study, we highlight the role of liver endothelial cells (LiECs), as a part of LPC niche, in supporting the hepatobiliary organoids in long-term culture even in the absence of defined growth supplements, such as Wnt agonists. Furthermore, LiECs alter the gene expression profile of hepatobiliary organoids involved in inflammation, migration, extracellular matrix organization, and receptor signaling pathway through paracrine manner. Our findings expand the role of LiECs for regulating stemness of LPCs and elucidate a role for niche cells in a LPC organoid co-culture model with a reduction in growth supplements.

Biliary Anomalies in VACTERL Syndrome: A Case Report.

The VACTERL/VATER association is a rare congenital disorder characterized by the presence of at least three of its main components: vertebral defects, anal atresia, cardiovascular anomalies, tracheoesophageal fistulas, esophageal atresia, renal anomalies, and limb defects. The exact cause of the VACTERL association is not fully understood. Most cases occur randomly. However, some research suggests that genetics and environmental factors may play a role. In addition to the core components of the VACTERL association, affected individuals may also have anomalies beyond the typical features. Biliary anomalies, although not classically included in the definition, have been documented in individuals with VACTERL syndrome, adding more complexity to this condition. Patients with biliary anomalies may present with jaundice, abdominal pain, or poor growth. The presence of biliary anomalies in individuals with VACTERL syndrome can have an impact on their care and outcomes. Detecting and treating these anomalies usually involves a multidisciplinary team. Timely identification and proper management of these bile-related issues are essential to prevent complications such as cholangitis.

Gallstones in a Looking-Glass: A Case Report on the Successful Laparoscopic Management of Cholelithiasis in Situs Inversus Totalis.

Situs inversus is an uncommon congenital condition where the internal organs are arranged in a mirrored or reversed orientation within the body. In this unique anatomical variation, the placement of visceral organs is flipped, presenting a mirror-image configuration relative to their standard positions. While situs inversus itself does not predispose an individual to gallbladder disorders, the anatomical variation poses unique challenges for healthcare professionals in managing abdominal pathologies. This case report describes the successful management of a 52-year-old male patient with situs inversus totalis who presented with gallstone-induced obstructive jaundice and underwent endoscopic retrograde cholangiopancreatography (ERCP) with stenting, followed by a laparoscopic cholecystectomy. The surgical procedure required exceptional visual-motor skills and extensive reorientation to accurately identify and navigate the left upper quadrant anatomy, which is the mirror image of the typical surgical approach. The case highlights the importance of thorough preoperative planning, comprehensive anatomical knowledge, and a multidisciplinary team approach to ensure favorable outcomes for patients with this rare condition.