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Biochimica Et Biophysica Acta.... Apr 2018The larger ducts of the biliary tree contain numerous tubulo-alveolar adnexal glands that are lined with biliary epithelial cells and connected to the bile duct lumen... (Review)
Review
The larger ducts of the biliary tree contain numerous tubulo-alveolar adnexal glands that are lined with biliary epithelial cells and connected to the bile duct lumen via small glandular canals. Although these peribiliary glands (PBG) were already described in the 19th century, their exact function and role in the pathophysiology and development of cholangiopathies have not become evident until recently. While secretion of serous and mucinous components into the bile was long considered as the main function of PBG, recent studies have identified PBG as an important source for biliary epithelial cell proliferation and renewal. Activation, dilatation, and proliferation of PBG (or the lack thereof) have been associated with various cholangiopathies. Moreover, PBG have been identified as niches of multipotent stem/progenitor cells with endodermal lineage traits. This has sparked research interest in the role of PBG in the pathogenesis of various cholangiopathies as well as bile duct malignancies. Deeper understanding of the regenerative capacity of the PBG may contribute to the development of novel regenerative therapeutics for previously untreatable hepatobiliary 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.
Topics: Bile Duct Diseases; Bile Ducts; Cell Differentiation; Cell Proliferation; Cilia; Epithelial Cells; Humans; Multipotent Stem Cells; Regeneration; Stromal Cells
PubMed: 28778591
DOI: 10.1016/j.bbadis.2017.07.037 -
The International Journal of... Feb 2011The mammalian biliary system, consisting of the intrahepatic and extrahepatic bile ducts, is responsible for transporting bile from the liver to the intestine. Bile duct... (Review)
Review
The mammalian biliary system, consisting of the intrahepatic and extrahepatic bile ducts, is responsible for transporting bile from the liver to the intestine. Bile duct dysfunction, as is seen in some congenital biliary diseases such as Alagille syndrome and biliary atresia, can lead to the accumulation of bile in the liver, preventing the excretion of detoxification products and ultimately leading to liver damage. Bile duct formation requires coordinated cell-cell interactions, resulting in the regulation of cell differentiation and morphogenesis. Multiple signaling molecules and transcription factors have been identified as important regulators of bile duct development. This review summarizes recent progress in the field. Insights gained from studies of the molecular mechanisms of bile duct development have the potential to reveal novel mechanisms of differentiation and morphogenesis in addition to potential targets for therapy of bile duct disorders.
Topics: Animals; Bile Ducts, Extrahepatic; Bile Ducts, Intrahepatic; Biliary Tract Diseases; Cell Differentiation; Gene Expression Regulation, Developmental; Hepatocytes; Humans; MicroRNAs; Morphogenesis; Receptors, Notch; Signal Transduction; Transforming Growth Factor beta; Wnt Proteins; beta Catenin
PubMed: 20601079
DOI: 10.1016/j.biocel.2010.06.020 -
International Journal of Surgery... Oct 2020For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and... (Review)
Review
For a technically successful liver transplant (LT), secure bile duct anastomosis to prevent biliary complications (BC's) like biliary anastomotic stricture (BAS) and bile leak (BL) is mandatory. BC's after living donor liver transplantation (LDLT) are relatively more common compared to deceased donor LT (DDLT), particularly owing to surgical factors (small diameter, and/or multiple bile duct openings on the graft), and non-surgical factors (immunologic reactions). Adequate blood supply to the bile duct both in donor and recipient, meticulous anastomotic technique, mucosal eversion for better approximation thus avoiding lesser fibrosis, proper use of internal or external stent drainage, and tension-free anastomosis, may contribute to the decrease of BC's after LDLT. Further, if BC's are not dealt with in a timely manner, these could progressively lead to severe morbidities and even mortality. While the endoscopic approach is preferred initially to deal with biliary leaks or strictures, the more invasive percutaneous approach may be required in case of endoscopic failure. Dedicated and experienced endoscopists, and interventional radiologists are key members of the multidisciplinary team in a successful LDLT program. In this review, we have tried to summarize current concepts in surgical techniques of biliary reconstruction in LDLT, incidence and risk factors for BC's, and principles followed to try and reduce the incidence of the same.
Topics: Bile Ducts; Biliary Tract Diseases; Biliary Tract Surgical Procedures; Humans; Liver Transplantation; Living Donors; Plastic Surgery Procedures; Risk Factors
PubMed: 32387205
DOI: 10.1016/j.ijsu.2020.04.069 -
Biochimica Et Biophysica Acta.... Apr 2018Cholangiopathies encompass a heterogeneous group of disorders affecting biliary epithelial cells (i.e. cholangiocytes). Early diagnosis, prognosis and treatment still... (Review)
Review
UNLABELLED
Cholangiopathies encompass a heterogeneous group of disorders affecting biliary epithelial cells (i.e. cholangiocytes). Early diagnosis, prognosis and treatment still remain clinically challenging for most of these diseases and are critical for adequate patient care. In the past decade, extensive research has emphasized microRNAs (miRs) as potential non-invasive biomarkers and tools to accurately identify, predict and treat cholangiopathies. MiRs can be released extracellularly conjugated with lipoproteins or encapsulated in extracellular vesicles (EVs). Research on EVs is also gaining attention since they are present in multiple biological fluids and may represent a relevant source of novel non-invasive biomarkers and be vehicles for new therapeutic approaches. This review highlights the most promising candidate miRs and EV-related biomarkers in cholangiopathies, as well as their relevant roles in biliary pathophysiology. 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.
RESEARCH STRATEGY
PubMed search (April 2017) was done with the following terms: "microRNA", "miRNA", "miR", "extracellular vesicles", "EV", "exosomes", "primary biliary cholangitis", "primary biliary cholangitis", "PBC", "primary sclerosing cholangitis", "PSC", "cholangiocarcinoma", "CCA", "biliary atresia", "BA", "polycystic liver diseases", "PLD", "cholangiopathies", "cholestatic liver disease". Most significant articles in full-text English were selected. The reference lists of selected papers were also considered.
Topics: Animals; Bile Duct Diseases; Bile Ducts; Biomarkers; Disease Models, Animal; Epithelial Cells; Extracellular Vesicles; Gene Expression Profiling; Humans; MicroRNAs
PubMed: 28711597
DOI: 10.1016/j.bbadis.2017.06.026 -
Transplantation Jun 2023End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support...
BACKGROUND
End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.
METHODS
Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration.
RESULTS
Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP.
CONCLUSIONS
Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.
Topics: Humans; Liver Transplantation; Living Donors; Liver; Bile Ducts; Perfusion; Bile Duct Diseases; Organ Preservation
PubMed: 36721302
DOI: 10.1097/TP.0000000000004531 -
World Journal of Gastroenterology Oct 2023Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since... (Review)
Review
Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.
Topics: Humans; Bile Ducts; Cholangiocarcinoma; Bile Duct Neoplasms; Biliary Tract Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37900587
DOI: 10.3748/wjg.v29.i38.5361 -
The Surgical Clinics of North America Dec 1990Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to... (Review)
Review
Bile duct strictures are an uncommon but serious complication of primary operations on the gallbladder or biliary tree. Most strictures occur as a result of injury to the bile duct during cholecystectomy. In addition, strictures can occur at the site of previous biliary anastomoses for reconstruction of the biliary tree. Most patients with benign bile duct strictures present soon after their initial operation; however, in some cases, presentation is delayed for years. Cholangiography is essential for defining the anatomy of the biliary tree prior to management. In many cases, nonoperative biliary drainage is useful to treat sepsis and biliary fistulas. A number of alternatives exist for elective repair of bile duct strictures. Experience would suggest, however, that a choledochojejunostomy or hepaticojejunostomy performed through a Roux-en-Y limb of jejunum is the preferable management in most cases. Postoperative biliary stenting may be valuable in optimizing the results. Nonoperative management by percutaneous transhepatic or endoscopic balloon dilatation has been reported to be successful in a number of small series. Long-term results are limited, however. Comparative data suggest that surgical repair for benign postoperative strictures is associated with fewer long-term problems and with similar overall morbidity and costs.
Topics: Bile Ducts; Cholangiography; Cholecystectomy; Constriction, Pathologic; Humans; Intraoperative Complications; Postoperative Complications; Stents
PubMed: 2247820
DOI: 10.1016/s0039-6109(16)45289-8 -
Biochimica Et Biophysica Acta.... Apr 2018The generation of bioengineered biliary tissue could contribute to the management of some of the most impactful cholangiopathies associated with liver transplantation,... (Review)
Review
The generation of bioengineered biliary tissue could contribute to the management of some of the most impactful cholangiopathies associated with liver transplantation, such as biliary atresia or ischemic cholangiopathy. Recent advances in tissue engineering and in vitro cholangiocyte culture have made the achievement of this goal possible. Here we provide an overview of these developments and review the progress towards the generation and transplantation of bioengineered bile ducts. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni and Peter Jansen.
Topics: Animals; Bile Duct Diseases; Bile Ducts; Bioartificial Organs; Biomedical Engineering; Cell Culture Techniques; Coculture Techniques; Disease Models, Animal; Epithelial Cells; Humans; Liver Transplantation; Organ Culture Techniques; Tissue Engineering
PubMed: 29097260
DOI: 10.1016/j.bbadis.2017.10.034 -
World Journal of Gastroenterology Jun 2006The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed... (Review)
Review
The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts (SEMvcc) technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra- and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a more complex vascular network. After common duct ligation (BDL), progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor (VEGF) is evaluated. VEGF-A, VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand, the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.
Topics: Animals; Bile Ducts; Capillaries; Cell Proliferation; Cholestasis; Hepatic Artery; Liver Diseases; Microcirculation; Microscopy, Electron, Scanning; Rats; Vascular Endothelial Growth Factor A
PubMed: 16773711
DOI: 10.3748/wjg.v12.i22.3546 -
International Journal of Surgery... Jun 2021liver lateral section graft is the most common graft type used for transplantation in children worldwide. Compared to whole liver grafts, a higher rate of biliary...
BACKGROUND
liver lateral section graft is the most common graft type used for transplantation in children worldwide. Compared to whole liver grafts, a higher rate of biliary complications has been described. Historically, 2 techniques have been described for transection of liver - trans-hilar or trans-umbilical parenchymal transection. Though these techniques allow dividing the biliary system at two distinct positions, the usual surgical strategies do not take advantage of this advantage.
MATERIAL AND METHODS
A retrospective study was conducted on 40 candidates who volunteered for donation of their left lateral liver section for transplantation, between October 2017 and April 2019. Preoperative imaging was analyzed to depict the arterial and biliary anatomy of the liver and their variations, with a dedicated attention to the left liver (segments 2, 3 and 4). Anatomy of the biliary system was taken into account for defining the optimal surgical strategy - either through a trans-hilar or a trans-umbilical parenchymal transection.
RESULTS
In 26/40 patients, arterial or biliary variations were much relevant for decision-making on the optimal plane of liver division (trans-umbilical (N = 14) and trans-hilar (N = 26)). This resulted in 23 grafts with a single artery and bile duct, 6 grafts with double arteries and a single bile duct, and 9 grafts with double bile ducts and a single artery; only two grafts had complex anatomy. There was no arterial complication and the overall incidence of biliary problems was 14.7%. All grafts are functioning well at a mean follow-up of 19.6 ± 8.5 months.
CONCLUSIONS
Anatomical variations are frequent and their knowledge is relevant for procurement of lateral section liver graft. Knowledge of these variation, or -better- preoperative biliary imaging is helpful in guiding parenchymal transection at procurement and preparing optimal liver grafts.
Topics: Adolescent; Adult; Anatomic Variation; Arteries; Bile Ducts; Child; Humans; Liver; Liver Transplantation; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Tissue and Organ Procurement; Umbilicus
PubMed: 34077810
DOI: 10.1016/j.ijsu.2021.105979