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Noninvasive visualization of the biliary tree is of paramount importance in any patient who may require a biliary surgical intervention. Most hospitals and imaging centers offer ultrasound, computed tomography (CT), cholescintigraphy (commonly known as hepatobiliary iminodiacetic acid scan), and MRI whenever acute biliary pathology is suspected. PET combined with CT is sometimes utilized to evaluate biliary malignancy and metastatic disease. Unfortunately, these imaging modalities are often ordered incorrectly and have numerous limitations. This article discusses the strengths and weaknesses or each imaging modality and focuses on appropriateness of their utilization in clinical practice., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Anatomy has remained an interest of physicians throughout the ages. The biliary tract spans from the liver to the hepatoduodenal mesentery, pancreas, and into the duodenum. Therefore, it is important for not only hepatobiliary surgeons but also general gastrointestinal surgeons, gastroenterologists, radiologists, and pathologists to be familiar with biliary anatomy and its variants. While surgery for hilar cholangiocarcinoma is one of the most challenging procedures, cholecystectomy is one of the most common procedures done from the beginning of surgical training. We hope that by answering the following questions, you will gain a comprehensive understanding of biliary anatomy and a greater appreciation for it., (© 2023. The Society for Surgery of the Alimentary Tract.)

Patch grafting, a novel strategy for transplantation of stem/progenitor organoids into porcine livers, has been found successful also for organoid transplantation into other normal or diseased solid organs in pigs and mice. Each organoid contained ∼100 cells comprised of biliary tree stem cells (BTSCs), co-hepato/pancreatic stem/progenitors, and partnered with early lineage stage mesenchymal cells (ELSMCs), angioblasts and precursors to endothelia and stellate cells. Patch grafting enabled transplantation into livers or pancreases of ≥10 8th (pigs) or ≥10 6th-7th (mice) organoids/patch. Graft conditions fostered expression of multiple matrix-metalloproteinases (MMPs), especially secretory isoforms, resulting in transient loss of the organ's matrix-dictated histological features, including organ capsules, and correlated with rapid integration within a week of organoids throughout the organs and without emboli or ectopic cell distribution. Secondarily, within another week, there was clearance of graft biomaterials, followed by muted expression of MMPs, restoration of matrix-dictated histology, and maturation of donor cells to functional adult fates. The ability of patch grafts of organoids to rescue hosts from genetic-based disease states was demonstrated with grafts of BTSC/ELSMC organoids on livers, able to rescue NRG/FAH-KO mice from type I tyrosinemia, a disease caused by absence of fumaryl acetoacetate hydrolase. With the same grafts, if on pancreas, they were able to rescue NRG/Akita mice from type I diabetes, caused by a mutation in the insulin 2 gene. The potential of patch grafting for cell therapies for solid organs now requires translational studies to enable its adaptation and uses for clinical programs., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cholangiocytes, biliary epithelial cells, are known to spontaneously self-organize into spherical cysts with a central lumen. In this work, we explore a promising biocompatible stereolithographic approach to encapsulate cholangiocytes into geometrically controlled 3D hydrogel structures to guide them towards the formation of branched tubular networks. We demonstrate that within the appropriate mix of hydrogels, normal rat cholangiocytes can proliferate, migrate, and organize into branched tubular structures with walls consisting of a cell monolayer, transport fluorescent dyes into the luminal space, and show markers of epithelial maturation such as primary cilia and continuous tight junctions. The resulting structures have dimensions typically found in the intralobular and intrahepatic biliary tree and are stable for weeks, without any requirement of bulk supporting material, thereby offering total access to the external side of these biliary epithelial constructs., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflict of interest The authors of this study have no conflicts of interest to declare. Please refer to the accompanying ICMJE disclosure forms for further details.

The study of the fractal architecture of various organs and structures expanded the possibilities for determining the ranges of their functioning and structural arrangement, which, as a result, was reflected in the development of new approaches to diagnostics and therapeutic impacts. The architecture of the excretory duct systems, similar to the hemo- and lymph- circulatory beds and the bronchial tree, is considered fractal. At the same time, information about hitherto unknown structures of the biliary tree continues to appear in the literature. We aimed to study the features of the spatial geometry of the biliary tree and assess the significance of both its fractal and Euclidean characteristics for the development of approaches that facilitate comprehensive description of intrahepatic biliary tract architecture. We investigated the architecture of the biliary trees of six men, seven male canines, and seven male Wistar rats using the corrosion casting method. Corrosion casts were prepared by injecting solidifying latexes into the bile ducts. The preparations were studied using a light stereomicroscope and a scanning electron microscope. Biliary tree branching is of various types. In addition, the correlation between variations in the caliber and length of the bile ducts and their order is not significant. Therefore, the biliary tree should not be considered as a classical fractal and it consists of the main modules, represented by the network of the bile canaliculi (first nonfractal module) and a biliary tree with a fractal branching (second module) that drains the bile canaliculi mesh and the additional modules represented by the mucosal biliary glands (in mammals with the gallbladder) or the periportal biliary plexus (in mammals without a gallbladder) and the aberrant biliary ducts. Such a configuration of the biliary bed should optimally ensure the smooth implementation of the physiological function of the liver, as well as its adaptation to different pathologies accompanied by biliary hypertension. It also might be considered in the diagnosis and assessment of ductular reaction, biliary regeneration, and/or carcinogenesis., (© 2021 Anatomical Society.)

"The anatomy of the biliary tree is notoriously variable. This variation is the bane of the hepatobiliary surgeon, to whom an understanding of biliary anatomic variation is key to the planning and safe conduct of liver surgery, from oncological resections to split-liver transplantation. The hepatic diverticulum, also termed "the liver bud," is the first semblance of the biliary system in the human embryo. A variety of techniques used in the mid twentieth century for imaging the biliary tree have since been abandoned in favor of more practical, safer, less invasive, and more sensitive and specific contemporary methods.", (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

It has been demonstrated that the liver remarkably alter its tissue structures during regeneration, and various types of liver stem or progenitor cells locating in specific areas in the liver tissue contribute to regeneration. Therefore, it is important to analyze the dynamic rearrangement of the liver tissue structures in 3D for better understanding the process and mechanism of liver regeneration. Here we describe a macroscopic analysis method to visualize the whole 3D structure of the vasculatures and the biliary tree, which are dynamically remodeled during regeneration, and a microscopic analysis method to visualize detailed structures at the cellular level, which can compensate what cannot be detected in the macroscopic analysis.

Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, toward pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) toward insulin-producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N = 12) or 120 mg/kg (N = 12) of streptozotocin. Liver, pancreas, and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepatopancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with upregulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepatopancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures toward pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the pathophysiology and complications of this disease. Stem Cells 2016;34:1332-1342., (© 2016 AlphaMed Press.)

Working knowledge of extrahepatic biliary anatomy is of paramount importance to the general surgeon. The embryologic development of the extrahepatic biliary tract is discussed in this article as is the highly variable anatomy of the biliary tract and its associated vasculature. The salient conditions related to the embryology and anatomy of the extrahepatic biliary tract, including biliary atresia, choledochal cysts, gallbladder agenesis, sphincter of Oddi dysfunction, and ducts of Luschka, are addressed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives Adenocarcinomas of the biliary tract frequently present diagnostic challenges because of their histologic overlap with benign and preinvasive lesions. The molecular profiles of biliary adenocarcinomas vary by anatomical location. Variations in IDH1/2, common in intrahepatic cholangiocarcinoma, can lead to defective production of 5-hydroxymethylcytosine (5-hmC). Limited ancillary studies are available for biliary adenocarcinomas, and loss of 5-hmC staining could serve as a helpful ancillary diagnostic tool for biliary tract malignancies. Methods We evaluated 93 cases—20 benign biliary lesions, 15 preinvasive biliary neoplasms, 46 invasive biliary carcinomas, and 12 pancreatic adenocarcinomas—for 5-hmC staining. Preoperative biopsies from 16 cases of biliary carcinoma were also stained. Sixteen nonneoplastic/reactive bile duct biopsies served as controls. Results Loss of 5-hmC was seen in 41 of 46 (89.1%) biliary malignancies vs 0 of 20 benign tumors (P  < .001), for a sensitivity and specificity of 89.1% and 100%, respectively. Intrahepatic cholangiocarcinoma showed loss of 5-hmC in 11 of 13 (84.6%) cases, similar to the 30 of 33 (90.9%) cases in other biliary adenocarcinomas (P  = .61). Similarly, 5-hmC loss was more frequent in distal bile duct adenocarcinomas than in pancreatic ductal adenocarcinomas, at 15 of 17 (88.2%) vs 4 of 12 (33.3%), respectively (P  = .0045). There was no difference in the frequency of 5-hmC loss in patients that received neoadjuvant therapy vs those who did not (90.9% vs 88.6%, P   >.99). 5-hmC immunohistochemistry in preoperative biopsies was concordant with the resection specimen in 81.3% (13/16) of cases. Conclusions Loss of 5-hmC is not unique to intrahepatic cholangiocarcinoma among biliary carcinomas, but is a useful diagnostic marker differentiating malignancies of the biliary tree from benign mimics. [ABSTRACT FROM AUTHOR]

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

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

Abstract Background Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. Methods PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta‐Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random‐effects model. Results Eight observational studies (3 cohort and 5 case–control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0–71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51–0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38–0.94) and GBC was 0.78 (95% CI: 0.68–0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66–1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69–0.88) and 0.70 (95% CI: 0.61–0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non‐steroidal anti‐inflammatory drugs (aRR: 0.80, 95% CI: 0.72–0.89) and metformin (aRR: 0.80, 95% CI: 0.72–0.90). Conclusions Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC.

Background: Biliary tract cancers (BTCs), encompassing cholangiocarcinoma (CCA), gallbladder (GBC), and ampulla of Vater cancers (AVC), are common hepatobiliary cancer after hepatocellular carcinoma with a high mortality rate. As there is no effective chemopreventive agent to prevent BTCs, this study aimed to explore the role of statins on the risk of BTCs. Methods: PubMed, Embase, and Cochrane Library from inception until 24 April 2020 were searched according to the Meta‐Analyses of Observational Studies in Epidemiology (MOOSE) guidelines. The adjusted risk ratios (aRRs) of BTCs and individual cancer were pooled using a random‐effects model. Results: Eight observational studies (3 cohort and 5 case–control studies) were included with 10,485,231 patients. The median age was 68.0 years (IQR: 67.0–71.5) and 48.3% were male. Statins were associated with a lower risk of all BTCs (aRR: 0.67; 95% CI: 0.51–0.87). The pooled aRR for CCA was 0.60 (95% CI: 0.38–0.94) and GBC was 0.78 (95% CI: 0.68–0.90). There was only one study on AVC with aRR of 0.96 (95% CI: 0.66–1.41). The pooled aRR for lipophilic and hydrophilic statins was 0.78 (95% CI: 0.69–0.88) and 0.70 (95% CI: 0.61–0.80), respectively. The effects were attenuated in studies that adjusted for aspirin and/or non‐steroidal anti‐inflammatory drugs (aRR: 0.80, 95% CI: 0.72–0.89) and metformin (aRR: 0.80, 95% CI: 0.72–0.90). Conclusions: Statins, both lipophilic and hydrophobic, were associated with a lower risk of BTCs, particularly CCA and GBC. [ABSTRACT FROM AUTHOR]

Obstructive cholestasis can lead to significant alterations of the biliary tree depending on the extent and duration of the biliary occlusion. Current experimental studies reported about advanced techniques for corrosion cast and 3D reconstruction (3D-reco) visualizing delicate microvascular structures in animals. We compared these two different techniques for visualization and quantitative assessment of the obstructed murine biliary tree with classical 2D histology. Male mice (n = 36) were allocated to 3 different experiments. In experiments 1 and 2, we injected two different media (Microfil© for 3D-reco, MV; Batson's No.17 for corrosion cast, CC) into the extrahepatic bile duct. In experiment 3 we sampled liver tissue for 2D histology (HE, BrdU). Time points of interest were days 1, 3, 5, 7, 14, and 28 after biliary occlusion. We used different types of software for quantification of the different samples: IMALYTICS Preclinical for 3D scans (MV); NDP.view2 for the digital photography of CC; HistoKat software for 2D histology. We achieved samples in 75% of the animals suitable for evaluation (MV and CC, each with 9/12). Contrasting of terminal bile ducts (4th order of branches) was achieved with either technique. MV permitted a fast 3D-reco of the hierarchy of the biliary tree, including the 3rd and 4th order of branches in almost all samples (8/9 and 6/9). CC enabled focused evaluation of the hierarchy of the biliary tree, including the 4th to 5th order of branches in almost all samples (9/9 and 8/9). In addition, we detected dense meshes of the smallest bile ducts in almost all CC samples (8/9). MV and CC allowed a quantitative assessment of anatomical details of the 3rd and 4th order branches of almost every sample. The 2D histology identified different kinetics and areas of proliferation of hepatocytes and cholangiocytes. Complementary usage of 3D-reco, corrosion casting and 2D histology matched dense meshes of small bile ducts with areas of intensive proliferative activity of cholangiocytes as periportal proliferative areas of 4th and 5th order branches (∼terminal bile ducts and bile ductules) matched with its morphological information the matching assessment of areas with increased proliferative activity (BrdU) and a partial quantification of the characteristics of the 4th order branches of the biliary tree. The 3D-reco and corrosion casting of the murine biliary tree are feasible and provide a straightforward, robust, and reliable (and more economical) procedure for the visualization and quantitative assessment of architectural alterations, in comparative usage with the 2D histology. [ABSTRACT FROM AUTHOR]

Purpose: To compare quantitative biliary measurements obtained with three different magnetic resonance cholangiopancreatography (MRCP) acquisition methods. Methods: This retrospective study was IRB-approved. Patients with combinations of clinically indicated 3D FSE MRCP with sensitivity encoding (SENSE), 3D FSE SENSE MRCP with compressed sensing (CS-FSE; acceleration factor 8), and 3D gradient and spin-echo (GRASE) MRCP, acquired between October 2018 and March 2020, were included. The MRCP + Tuning Threshold algorithm (Perspectum Ltd., Oxford, UK) was used to segment 3D biliary models from MRCP data, with multiple metrics quantified from the models. Single measure, two-way, mixed-effects intra-class correlations, Bland–Altman analyses, and Wilcoxon signed-rank tests were used to compare quantitative measurements. Results: From 160 MRCP datasets (25 3D FSE, 67 3D CS-FSE, 68 3D GRASE) in 69 patients, 48 datasets (7 [28%] 3D FSE, 14 [21%] 3D CS-FSE, 27 [40%] 3D GRASE) failed post-processing due to motion artifacts. The remaining 112 MRCP datasets (18 3D FSE, 53 3D CS-FSE, 41 3D GRASE) from 60 patients were included in the analysis. There was good to excellent agreement between 3D FSE and 3D CS-FSE MRCP for diameter of the left and right hepatic ducts, biliary volume, number and length of ducts, and total length of dilations (ICC: 0.83–0.93). The only metrics that exhibited good agreement between 3D FSE and 3D GRASE MRCP were biliary volume (ICC: 0.75) and total number of dilations (ICC: 0.77). Conclusion: 3D CS-FSE MRCP produces comparable biliary diameter metrics and global duct quantification to 3D FSE MRCP at a significantly reduced acquisition time. [ABSTRACT FROM AUTHOR]

Background Many factors have been incriminated in occurrence of bile duct injuries during laparoscopic cholecystectomy (LC). Misidentification of the anatomy and lack of surgeon's experience seems to be preliminary; however, many techniques were used to avoid such injuries. Aim of the work To asses feasibility of delineation of biliary tree by intracholecystic injection of methylene blue (MB) during LC. Patients and methods A prospective study had been conducted in Ain Shams University Hospitals between January 2019 and January 2020. The study included 60 patients who presented to outpatient department (OPD) with abdominal ultrasound showing chronic calcular cholecystitis and all underwent intracholecystic injection of MB during LC. Results As regards MB delineation of different parts of gall bladder and biliary tract component, gall bladder delineation occurred in all patients (100%), whereas cystic duct delineated in 80% of patients (48/60) and common bile duct (CBD) delineated in 41.7% of patients (25/60) as general and separate assessment of each element alone with no detected cases of bile duct injury. There was significant increase in CBD delineation in patients with single stone and thin-walled gall bladder. Extravasation of dye from the gall bladder into the abdominal cavity occurred and this led to anatomical misidentification and significant prolongation of operative time (extra time was needed for irrigation and suction). Conclusion The technique by which the MB is injected into the lumen of gall bladder to delineate the cystic duct and CBD is feasible, cheap, and performed without any radiation exposure and without using special equipment. By this technique, no cases of biliary injury were detected; however, critical view of safety remains the gold standard surgical technique to prevent bile duct injury. [ABSTRACT FROM AUTHOR]

The biliary tree is a network of tubes that connects the liver to the gallbladder, an organ right beneath it. The bile duct is the major tube in the biliary tree. The dilatation of a bile duct is a key indicator for more major problems in the human body, such as stones and tumors, which are frequently caused by the pancreas or the papilla of vater. The detection of bile duct dilatation can be challenging for beginner or untrained medical personnel in many circumstances. Even professionals are unable to detect bile duct dilatation with the naked eye. This research presents a unique vision-based model for biliary tree initial diagnosis. To segment the biliary tree from the Magnetic Resonance Image, the framework used different image processing approaches (MRI). After the image's region of interest was segmented, numerous calculations were performed on it to extract 10 features, including major and minor axes, bile duct area, biliary tree area, compactness, and some textural features (contrast, mean, variance and correlation). This study used a database of images from King Hussein Medical Center in Amman, Jordan, which included 200 MRI images, 100 normal cases, and 100 patients with dilated bile ducts. After the characteristics are extracted, various classifiers are used to determine the patients' condition in terms of their health (normal or dilated). The findings demonstrate that the extracted features perform well with all classifiers in terms of accuracy and area under the curve. This study is unique in that it uses an automated approach to segment the biliary tree from MRI images, as well as scientifically correlating retrieved features with biliary tree status that has never been done before in the literature. [ABSTRACT FROM AUTHOR]

Background/Aim: Biliary tree and pancreatic duct can appear in different variations whose proper understanding is obligatory for surgeons. Magnetic resonance cholangiopancreatography (MRCP) is considered a safe and accurate tool for evaluating biliary tree and pancreatic duct. Typical anatomy for right hepatic duct (RHD) and left hepatic duct (LHD) is reported as 57% and 63%, respectively. The most common (4-10%) pancreatic anomaly is divisum. In the present study, we evaluated and determined the prevalence of biliary tree and pancreatic duct variations among patients at a university hospital. Materials and Methods: The MRCP records of 370 patients from 2015 to 2017 were obtained for cross-sectional study. Images were retrospectively reviewed for variations by two independent senior radiologists. Demographic data were obtained for all the patients. Huang et al. classification was used for RHD and LHD variations. The cystic duct was reported based on its course and insertion pattern. The pancreatic duct was observed for the presence of divisum, its course, and configuration. Results: Three hundred and twenty-five patients were included in the final study. Most commonly observed variant for RHD were A1 (34.2%) and A2 (32.2%). For LHD, B1 (71.4%) was the most common variant. Cystic duct insertion was commonly seen as right lateral insertion (27.7%). Pancreatic divisum was observed in 0.6% of cases. Nationality, origin, and gender-specific variations were obtained. Conclusion: Variations in biliary anatomy and pancreatic duct are very diverse and extend from the intrahepatic biliary system down to the pancreas. Performing a similar study on a larger population is mandatory to illustrate the range of variations present within the community. [ABSTRACT FROM AUTHOR]

Contrast enhanced MRI of the liver provides valuable information in the evaluation of both chronic liver disease and focal liver lesions. Currently, two classes of MRI contrast agents are available for clinical use, namely the extracellular contrast agent (ECA) and the hepatobiliary agent (HBA). The use of appropriate contrast agents for liver MRI requires knowledge of the clinical situation and question to be answered. ECAs have been used for decades since their introduction into clinical practice and provide excellent dynamic phase information that is useful in characterizing focal liver lesions. In the last decade, HBAs, particularly Gadoxetate, have been found useful for characterizing lesions with functioning hepatocytes and more importantly in evaluating the biliary tree. Gadoxetate, however, provides less satisfactory dynamic phase images compared to ECAs, particularly during the arterial phase. In this perspective article, we will discuss the various intravenous contrast agents used for liver MRI and their ideal utilization. [ABSTRACT FROM AUTHOR]

Purpose: Autoimmune liver diseases (AILD), including primary sclerosing cholangitis (PSC), autoimmune sclerosing cholangitis (ASC), and autoimmune hepatitis (AIH), have overlapping clinical features but distinct management strategies and outcomes. The purpose of this study was to assess the diagnostic performance of quantitative magnetic resonance cholangiopancreatography (MRCP) parameters for distinguishing PSC/ASC from AIH in children and young adults. Materials and methods: This IRB-approved, cross-sectional study included participants from an institutional AILD registry that underwent baseline serum liver biochemistry testing and 3D fast spin-echo MRCP. The biliary tree was extracted and modeled from MRCP images using novel proprietary software (MRCP+ ™; Perspectum Diagnostics; Oxford, United Kingdom), and quantitative parameters were generated (e.g., biliary tree volume; number and length of bile ducts, strictures, and dilations; bile duct median/maximum diameters). Mann–Whitney U tests were performed to compare laboratory values and MRCP metrics between patient cohorts (clinical diagnosis of PSC/ASC versus AIH). Receiver operating characteristic (ROC) curves and multivariable logistic regression were used to assess diagnostic performance of serum biochemistry values and MRCP parameters for discriminating PSC/ASC from AIH. Results: Thirty percent (14/47) of MRCP exams failed post-processing due to motion artifact. The remaining 33 patients included 20 males and 13 females, with a mean age of 15.1 ± 3.9 years. Eighteen patients were assigned the clinical diagnosis of PSC or ASC and 15 of AIH. All but one quantitative MRCP parameter were significantly different between cohorts (p < 0.05) and predictive of diagnosis (ROC p < 0.05), including numbers of bile duct strictures (area under curve [AUC] = 0.86, p < 0.0001) and dilations (AUC = 0.87, p < 0.0001) and total length of dilated ducts (AUC = 0.89, p < 0.0001). Laboratory values were not significantly different between cohorts (p > 0.05). The best multivariable model for distinguishing PSC/ASC from AIH included total length of dilated ducts (odds ratio [OR], 1.08; 95% CI 1.02–1.14) and maximum left hepatic duct diameter (OR, 1.21; 95% CI 0.57–2.56) [AUC = 0.92]. Conclusion: Quantitative MRCP parameters provide good discrimination of PSC/ASC from AIH. [ABSTRACT FROM AUTHOR]

Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The most common sites are the head and neck, followed by the genitourinary tract and the extremities. Gallbladder RMS in pediatric patient has rarely been reported in literature. A 5-year-old boy presented to our clinic with right upper quadrant abdominal pain for about 2 weeks. Abdominal ultrasound (US) and contrast-enhanced computed tomography (CT) revealed a 2.7 × 1.8 cm mass located in the neck of gallbladder. Magnetic resonance cholangiopancreatography (MRCP) confirmed the heterogeneous mass within the gallbladder without invasion of the surrounding structures, without gallbladder wall thickening, and without dilation of the biliary tree. Liver function tests, alpha-fetoprotein (AFP), carcinoembryonic agent (CEA), and cancer antigen 19-9 (CA19-9) were within normal values. The patient underwent an uneventful laparoscopic cholecystectomy. The pathology analysis confirmed a botryoid rhabdomyosarcoma (RMS) of the gallbladder with clear margins. No metastases were detected by postoperative positron emission tomography (PET) scan. The patient received 11 postoperative cycles of chemotherapy with vincristine, cyclophosphamide, and actinomycin-D. At one year of follow up he is well and free of disease. Due to its rare occurrence, the preoperative diagnosis of gallbladder RMS is challenging. Gallbladder RMS should be considered in the differential diagnosis of pediatric patients who present a gallbladder mass. [ABSTRACT FROM AUTHOR]

Choledochal cyst is a congenital disease of the biliary tract with extrahepatic and/or intrahepatic biliary tree dilatation. There is a female majority (4:1). Controlling biliary sepsis and curing pancreatitis are prerequisites of surgery. Here, a 35-year-old female patient, came with complaints of epigastric and right upper abdominal pain for three days. On examination per abdomen was soft, non distended, right hypochondriac tenderness was present, no guarding, bowel sounds were audible. Magnetic Resonance Cholangiopancreatography (MRCP) was done which showed fusiform dilatation of Common Bile Duct (CBD), Common Hepatic Duct (CHD), right and left hepatic duct, along with mild dilatation of central intrahepatic biliary radicals (4.8-5 mm)- suggestive of choledochal cyst type IVA. Hepatico-duodenostomy was done. The entire extrahepatic biliary tree should be removed when the choledochal cyst is diagnosed whether or not symptoms are present. Despite being congenital, the condition is typically discovered in adulthood as well. The treatment of choledochal cysts has evolved. The current standard of care is cyst excision and hepaticojejunostomy. [ABSTRACT FROM AUTHOR]

The liver is a vital organ with distinctive anatomy, histology and heterogeneous cell populations. These characteristics are of particular importance in maintaining immune homeostasis within the liver microenvironments, notably the biliary tree. Cholangiocytes are the first line of defense of the biliary tree against foreign substances, and are equipped to participate through various immunological pathways. Indeed, cholangiocytes protect against pathogens by TLRs-related signaling; maintain tolerance by expression of IRAK-M and PPARγ; limit immune response by inducing apoptosis of leukocytes; present antigen by expressing human leukocyte antigen molecules and costimulatory molecules; recruit leukocytes to the target site by expressing cytokines and chemokines. However, breach of tolerance in the biliary tree results in various cholangiopathies, exemplified by primary biliary cholangitis, primary sclerosing cholangitis and biliary atresia. Lessons learned from immune tolerance of the biliary tree will provide the basis for the development of effective therapeutic approaches against autoimmune biliary tract diseases. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. [ABSTRACT FROM AUTHOR]

Cholangiocarcinomas (CCAs) are anatomically classified into intrahepatic, perihilar, and distal types. The gross pathological classification of intrahepatic CCAs divides them into mass-forming, periductal-infiltrating, and intraductal-growth types; and perihilar/distal CCAs into flat- and nodular-infiltrating and papillary types. Unique preinvasive lesions appear to precede individual gross types of CCA. Biliary intraepithelial neoplasia, a flat lesion, precedes periductal-, flat-, and nodular-infiltrating CCAs, whereas intraductal papillary neoplasm of the bile duct (IPNB) precedes the intraductal-growth and papillary type of CCAs. IPNBs are heterogeneous in their histological and pathological profiles along the biliary tree. Hepatobiliary cystadenomas/adenocarcinomas are reclassified as cystic IPNBs and hepatic mucinous cystic neoplasms. Peribiliary glands may participate in the development of CCAs. These latest findings present a new challenge for understanding the pathology of CCAs. [ABSTRACT FROM PUBLISHER]

Background & Aims: Biliary tree, liver, and pancreas share a common embryological origin. We previously demonstrated the presence of stem/progenitor cells of endodermal origin in the adult human extrahepatic biliary tree. This study evaluated the human foetal biliary trees as sources of stem/progenitor cells of multiple endodermal-derived mature fates. Methods: Human foetal intrahepatic and extrahepatic biliary tree tissues and isolated cells were tested for cytoplasmic and surface markers of stem cells and committed progenitors, as well as endodermal transcription factors requisite for a liver versus pancreatic fate. In vitro and in vivo experiments were conducted to evaluate the potential mature fates of differentiation. Results: Foetal biliary tree cells proliferated clonogenically for more than 1month on plastic in a serum-free Kubota medium. After culture expansion, cells exhibited multipotency and could be restricted to certain lineages under defined microenvironments, including hepatocytes, cholangiocytes, and pancreatic islet cells. Transplantation of foetal biliary tree cells into the livers of immunodeficient mice resulted in effective engraftment and differentiation into mature hepatocytes and cholangiocytes. Conclusions: Foetal biliary trees contain multipotent stem/progenitor cells comparable with those in adults. These cells can be easily expanded and induced in vitro to differentiate into liver and pancreatic mature fates, and engrafted and differentiated into mature cells when transplanted in vivo. These findings further characterise the development of these stem/progenitor cell populations from foetuses to adults, which are thought to contribute to liver and pancreas organogenesis throughout life. [ABSTRACT FROM AUTHOR]

The anterior gradient protein-2 (AGR2) is overexpressed in numerous tumours such as breast, prostate or pancreas carcinomas and recently reported in fibrolamellar hepatocellular carcinoma (HCC). In the present study, we further describe AGR2 expression patterns all along the adult and fetal biliary tree and in cholangiocarcinomas. Immunohistochemistry using anti-AGR2 antibodies was performed in adult and fetal livers, gallbladders as well as cholangiocarcinomas and HCCs. In adult and fetal liver, the tall epithelial cells covering the large bile ducts as well as gallbladder epithelial cells showed strong AGR2 staining. Hilar and extrahepatic cholangiocarcinomas, and a subset of intrahepatic cholangiocarcinomas, which displayed a morphological mucus-excreting feature, also displayed AGR2 expression. In contrast, AGR2 expression was not detected in typical HCCs. Our study shows that the differential expression of AGR2 is a phenotypic feature of the cholangiocytes covering different segments of the biliary tree. This pattern of expression is conserved during fetal and adult life, as well as during biliary carcinogenesis. [ABSTRACT FROM AUTHOR]

The development of multidetector row computed tomography (MDCT) has led to the acquisition of true isotropic voxels that can be postprocessed to yield images in any plane of the same resolution as the original axially acquired images. This, coupled with rapid MDCT imaging during peak target organ enhancement has led to a variety of means to review imaging information beyond that of the axial perspective. Postprocessing can be utilized to identify variant biliary anatomy to guide preoperative planning of biliary-related surgery, determine the level and cause of biliary obstruction and assist in staging of biliary cancer. Postprocessing can also be used to identify pancreatic ductal variants, visualize diagnostic features of pancreatic cystic lesions, diagnose and stage pancreatic cancer, and differentiate pancreatic from peripancreatic disease. [ABSTRACT FROM AUTHOR]

Abstract: Multiple bile duct hamartomas [von Meyenburg complex (VMC)] are benign liver malformations that include biliary cystic lesions, with congenital hepatic fibrosis being the cause of ductal plate malformations. This rare entity is usually isolated and detected incidentally in 0.6–5.6% of reported autopsy series. Its clinical significance is that it may be misdiagnosed as malignant liver disease. Imaging findings of VMC are nonspecific. We present a rare case of VMC in a patient who presented with epigastric and upper right abdominal pain, and jaundice of 2 months'' duration. Ultrasonography, computed tomography, and magnetic resonance imaging showed a periportal multicystic mass simulating biliary cystadenoma/cystadenocarcinoma. The patient underwent laparotomy. A diagnosis of VMC was made after histopathologic examination of the wedge biopsy of the liver. [Copyright &y& Elsevier]

Rhabdomyosarcoma (RMS) is the most common tumour of the biliary tree in childhood. In children, it is a rare lesion, accounting for about 1% of all RMS. Hepatobiliary botryoid RMS is a disease affecting young children at a median age of about 3 years. In literature, the radiological findings of hepatobiliary RMS have been described in small series and some case reports. In this case report, we present a rare case of RMS of the extrahepatic biliary tree initially diagnosed as a choledochal cyst. [ABSTRACT FROM AUTHOR]

Background/Aims: The finer branches of the biliary tree play an important role in biliary regeneration. They are consistently escorted by microvessels. Defects in the vascularization of these structures could impair bile duct regeneration. Therefore, we investigated the pattern of the escorting microvessels during the development of bile duct loss in the human liver, using chronic rejection as a model. Methods: The number of interlobular bile ducts, bile ductules and extraportal biliary cells with and without escorting microvessels and the expression of VEGF-A were studied in follow-up biopsies of 12 patients with chronic rejection and 16 control patients with acute rejection without progression to chronic rejection. Results: The controls showed a proliferation of bile ductules at 1-week and 1-month. Proliferation of bile ductules without microvessels preceded proliferation of bile ductules with microvessels. Proliferation of the microvascular compartment followed biliary proliferation. This sequence of events was not observed in the chronic rejection group, in which all biliary structures decreased in time. VEGF-A expression was increased at 1-week and 1-month in both groups. Conclusions: An immediate proliferative response of the finer branches of the biliary tree followed by proliferation of the microvascular compartment after biliary injury seems to be a prerequisite for bile duct regeneration. [Copyright &y& Elsevier]

Objective: Endoscopic retrograde cholangiopancreaticography (ERCP)-guided brushing has been the standard of practice for surveillance and detection of carcinoma in the biliary tree. Few studies have evaluated the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in diagnosing clinically suspected cholangiocarcinoma. The role of this method in diagnosing clinically suspected gallbladder malignancies has not been extensively evaluated in the USA. This study investigates the role of EUS-FNA in the diagnosis of clinically suspected biliary tree and gallbladder malignancies in a large patient series. Methods: EUS-FNAs were obtained from 46 bile duct and seven gallbladder lesions. On-site rapid interpretation was provided using air-dried Diff Quik stained smears. In addition, alcohol fixed Papanicoloau stained smears and Thin Prep preparations ( Cytye Corp., Marlborough, MA, USA) were evaluated before providing a final cytological diagnosis. Tissue biopsies and/or clinical follow-up were used as the standards to determine operating characteristics for EUS-FNA. Results: The mean ages for bile duct and gallbladder lesions were 66 years (range: 37–84 years), and 69 years (range 49–86 years), respectively. All cases diagnosed as suspicious/malignant on preliminary evaluation were confirmed on final cytological interpretation (27/27). The operating characteristics show that EUS-FNA is highly specific (100%) with sensitivity rates of 87% and 80% from clinically suspected malignancies of biliary tract and gallbladder, respectively. Sampling error in three cases and associated acute inflammation in two cases resulted in false-negative diagnoses. Conclusions: EUS-FNA of biliary tree and gallbladder carcinoma is highly specific and should be considered for evaluation of clinically suspicious lesions. Marked inflammation may result in false-negative diagnoses. [ABSTRACT FROM AUTHOR]

Hydatid disease oldie liver is a parasitic infection. Surgery still remains as the primary choice of treatment. Caustic sclerosing cholangitis is reported following surgical treatment. Hypertonic saline (20%), povidone iodine (1%), and silver nitrate (0.5%) are extensively used as scolicidal solutions. The effects of these scolicidal agents on liver and biliary tree are investigated by direct injection into the common bile duct of rats. At the end of 15 wk, liver function tests, cholangiography, and histopathological examination of the liver and biliary tree were performed. Liver function tests were within normal limits, except elevation of alkaline phosphatase in 2 and 1 rats of the silver nitrate and povidone iodine groups, respectively. Differences were not statistically significant (p > .05). Cholangiograms of the rats in all groups were normal. Histopathologic changes comprising low-grade inflammatory changes were induced in all study groups. The intensity of the lesions were more remarkable with silver nitrate and minimal with hypertonic saline. We suggest that direct injection of scolicidal agents into the cyst should be avoided particularly in case of biliary communication. If this is to be practiced, hypertonic saline should be preferred as a scolicidal agent. [ABSTRACT FROM AUTHOR]

Background: Biliary or pancreatic fistulae occur frequently after operative repair of liver or pancreatic injuries. The existing literature is based on a few retrospective series. The objective of this prospective study is to evaluate the clinical course and efficacy of non-operative treatment of biliary fistuli (BF) and pancreatic fistuli (PF) post-traumatic fistulae. Study design: Patients who following a trauma laparotomy, developed BF or PF were prospectively followed during a 38-month period (June 1999–August 2001). Demographics, injury type and severity, fistula characteristics and daily output, complications, interventions and cost were recorded. Optimal nutrition, wound management, and control of infection were priorities in fistula management. A fistula was considered completely healed if the patient was on regular diet and the output was zero for at least 48 h. Results: Of 160 patients (injury severity score: 21+10) with trauma laparotomy for a liver or pancreatic injury, nineteen patients (12%) developed a fistula (11 BF, 8 PF). No patient died. Infections occurred in 45% (5/11) of BF patients and 50% (4/8) of PF patients. Only two patients required an operation, one for bilio-pericardium and one more for a pancreatic pseudo-cyst. Fistula management was responsible for more than half of the hospital stay and cost. Patients with PF had longer hospital stays (44+28 days) and charges (US$ 345,000+218,000) than patients with BF (22+12 days and US$ 103,000+61,000, respectively). Conclusions: Most post-traumatic BF and PF can be managed non-operatively. BF resolves earlier than PF. Both entities are responsible for substantial increases in hospital length of stay and charges. [Copyright &y& Elsevier]

The purpose of this study was to examine the feasibility of contrast-enhanced virtual MR cholangioscopy (CE VMRC). Intraluminal views of the extrahepatic biliary tree were generated in ten patients undergoing abdominal MRI post mangafodipir trisodium administration employing coronal 2.5-mm 3D fast low-angle shot (FLASH) images (TR 6.8 ms, TE 2.3 ms, matrix 195 x 512) with fat saturation and a commercially available software. Contrast-enhanced VMRC was compared with single-shot turbo spin-echo T2-weighted MR cholangiography (T2 MRC) in terms of ductal visualization and artifact presence, utilizing a five-point grading scale. Four anatomic segments were evaluated: the intra- and extra-pancreatic segment of the common bile duct (CBD), and the cystic duct and the area of hepatic duct bifurcation. Both CE VMRC and T2 MRC depicted 38 of 40 segments. There were no significant differences between CE VMRC and T2 MRC in ranking ductal segments visualization ( p=0.27). The high contrast between intraluminal fluid and extraluminal tissues facilitated the generation of endoscopic views. Contrast-enhanced virtual MR cholangioscopy is a feasible technique providing endoscopic views of the CBD. Initial results show correlation of CE VMRC with projectional MR cholangiography. [ABSTRACT FROM AUTHOR]

Epithelial cell therapies have been at an impasse because of inefficient methods of transplantation to solid organs. Patch grafting strategies were established enabling transplantation of ≥107th organoids/patch of porcine GFP+ biliary tree stem/progenitors into livers of wild type hosts. Grafts consisted of organoids embedded in soft (~100 Pa) hyaluronan hydrogels, both prepared in serum-free Kubota's Medium; placed against target sites; covered with a silk backing impregnated with more rigid hyaluronan hydrogels (~700 Pa); and use of the backing to tether grafts with sutures or glue to target sites. Hyaluronan coatings (~200–300 Pa) onto the serosal surface of the graft served to minimize adhesions with neighboring organs. The organ's clearance of hyaluronans enabled restoration of tissue-specific paracrine and systemic signaling, resulting in return of normal hepatic histology, with donor parenchymal cells uniformly integrated amidst host cells and that had differentiated to mature hepatocytes and cholangiocytes. Grafts containing donor mature hepatocytes, partnered with endothelia, and in the same graft biomaterials as for stem/progenitor organoids, did not engraft. Engraftment occurred if porcine liver-derived mesenchymal stem cells (MSCs) were co-transplanted with donor mature cells. RNA-seq analyses revealed that engraftment correlated with expression of matrix-metalloproteinases (MMPs), especially secreted isoforms that were found expressed strongly by organoids, less so by MSCs, and minimally, if at all, by adult cells. Engraftment with patch grafting strategies occurred without evidence of emboli or ectopic cell distribution. It was successful with stem/progenitor organoids or with cells with a source(s) of secreted MMP isoforms and offers significant potential for enabling cell therapies for solid organs. [ABSTRACT FROM AUTHOR]

Intraductal papillary neoplasm of the bile duct (IPNB), a pre-invasive neoplasm of the bile duct, is being established pathologically as a precursor lesion of invasive cholangiocarcinoma (CCA), and at the time of surgical resection, approximately half of IPNBs show stromal invasion (IPNB associated with invasive carcinoma). IPNB can involve any part of the biliary tree. IPNB shows grossly visible, exophytic growth in a dilated bile duct lumen, with histologically villous/papillary neoplastic epithelia with tubular components covering fine fibrovascular stalks. Interestingly, IPNB can be classified into four subtypes (intestinal, gastric, pancreatobiliary and oncocytic), similar to intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNBs are classified into low-grade and high-grade based on lining epithelial features. The new subclassification of IPNB into types 1 (low-grade dysplasia and high-grade dysplasia with regular architecture) and 2 (high-grade dysplasia with irregular architecture) proposed by the Japan–Korea pathologist group may be useful in the clinical field. The outcome of post-operative IPNBs is more favorable in type 1 than type 2. Recent genetic studies using next-generation sequencing have demonstrated the existence of several groups of mutations of genes: (i) IPNB showing mutations in KRAS, GNAS and RNF43 belonged to type 1, particularly the intestinal subtype, similar to the mutation patterns of IPMN; (ii) IPNB showing mutations in CTNNB1 and lacking mutations in KRAS, GNAS and RNF43 belonged to the pancreatobiliary subtype but differed from IPMN. IPNB showing mutation of TP53, SMAD4 and PIK3CA might reflect complicated and other features characterizing type 2. The recent recognition of IPNBs may facilitate further clinical and basic studies of CCA with respect to the pre-invasive and early invasive stages. [ABSTRACT FROM AUTHOR]

Background: An aberrant biliary duct of segment 5 (B5) is a rare anomaly of the biliary tract. All anatomical anomalies of the biliary tract are risk factors for bile duct injury during surgery. We report a case of cholelithiasis with an aberrant B5 that was detected during a detailed preoperative imaging examination and treated with laparoscopic cholecystectomy. Case presentation: A 69-year-old woman was admitted to the emergency room of our hospital with abdominal pain. She was diagnosed with cholelithiasis, and an aberrant B5 branching off the hepatic duct was suggested during preoperative imaging. Laparoscopic cholecystectomy was performed at our surgical department. There were no intra- or postoperative complications, and the patient was discharged on the fourth day after surgery. Conclusions: Laparoscopic cholecystectomy can be safely performed without intra- or postoperative complications in patients with cholelithiasis and an aberrant B5 if it is accurately diagnosed preoperatively. [ABSTRACT FROM AUTHOR]