scholarly journals Coordinated development of the mouse extrahepatic bile duct: implications for neonatal susceptibility to biliary injury

2019 ◽  
Author(s):  
Gauri Khandekar ◽  
Jessica Llewellyn ◽  
Alyssa Kriegermeier ◽  
Orith Waisbourd-Zinman ◽  
Nicolette Johnson ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Duct ◽  
Biliary Atresia ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Collagen I ◽  
Cell Junctions ◽  
Reporter Mouse ◽  
Extrahepatic Bile Ducts

AbstractBackground & AimsThe extrahepatic bile duct is the primary tissue initially affected by the cholangiopathy biliary atresia. Biliary atresia affects neonates exclusively and current animal models suggest that the developing bile duct is uniquely susceptible to damage. In this study, we aimed to define the anatomical and functional differences between the neonatal and adult mouse extrahepatic bile ducts.MethodsWe studied mouse passaged cholangiocytes, mouse BALB/c neonatal and adult primary cholangiocytes and isolated extrahepatic bile ducts, and a collagen reporter mouse. Methods included transmission electron microscopy, lectin staining, immunostaining, rhodamine uptake assays, bile acid toxicity assays, and in vitro modeling of the matrix.ResultsThe cholangiocyte monolayer of the neonatal extrahepatic bile duct was immature, lacking the uniform apical glycocalyx and mature cell-cell junctions typical of adult cholangiocytes. Functional studies showed that the glycocalyx protected against bile acid injury and that neonatal cholangiocyte monolayers were more permeable than adult monolayers. In adult ducts, the submucosal space was filled with collagen I, elastin, hyaluronic acid, and proteoglycans. In contrast, the neonatal submucosa had little collagen I and elastin, although both increased rapidly after birth. In vitro modeling suggested that the composition of the neonatal submucosa relative to the adult submucosa led to increased diffusion of bile. A Col-GFP reporter mouse showed that cells in the neonatal but not adult submucosa were actively producing collagen.ConclusionWe identified four key differences between the neonatal and adult extrahepatic bile duct. We showed that these features may have functional implications, suggesting the neonatal extrahepatic bile ducts are particularly susceptible to injury and fibrosis.Lay SummaryBiliary atresia is a disease that affects newborns and is characterized by extrahepatic bile duct injury and obstruction with resulting liver injury. We identify four key differences between the epithelial and submucosal layers of the neonatal and adult extrahepatic bile duct and show that these may render the neonatal duct particularly susceptible to injury.HighlightsThe apical glycocalyx is thin and patchy in neonatal compared to adult cholangiocytesNeonatal cholangiocytes have immature cell-cell junctions and increased permeabilityThe neonatal submucosal space has minimal collagen I or elastinThe neonatal submucosal space contains many actively collagen-secreting cellsGraphical abstract

scholarly journals Efemp1 modulates elastic fiber formation and mechanics of the extrahepatic bile duct

2021 ◽  
Author(s):  
Jessica Llewellyn ◽  
Emilia Roberts ◽  
Chengyang Liu ◽  
Ali Naji ◽  
Richard K. Assoian ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Bile Duct ◽  
Biliary Atresia ◽  
Bile Ducts ◽  
Matrix Protein ◽  
Extrahepatic Bile Duct ◽  
Fiber Formation ◽  
Extracellular Matrix Protein ◽  
Elastic Fibers ◽  
Extrahepatic Bile Ducts

AbstractEGF-Containing Fibulin Extracellular Matrix Protein 1 (EFEMP1, also called fibulin 3) is an extracellular matrix protein linked in a genome-wide association study to biliary atresia, a fibro-inflammatory disease of the neonatal extrahepatic bile duct. EFEMP1 is expressed in most tissues and Efemp1 null mice have decreased elastic fibers in visceral fascia; however, in contrast to other short fibulins (fibulins 4 and 5), EFEMP1 does not have a role in the development of large elastic fibers, and its overall function remains unclear. We demonstrated that EFEMP1 is expressed in the submucosa of both neonatal and adult mouse and human extrahepatic bile ducts and that, in adult Efemp1+/- mice, elastin organization into fibers is decreased. We used pressure myography, a technique developed to study the mechanics of the vasculature, to show that Efemp1+/- extrahepatic bile ducts are more compliant to luminal pressure, leading to increased circumferential stretch. We conclude that EFEMP1 has an important role in the formation of elastic fibers and mechanical properties of the extrahepatic bile duct. These data suggest that altered expression of EFEMP1 in the extrahepatic bile duct leads to an abnormal response to mechanical stress such as obstruction, potentially explaining the role of EFEMP1 in biliary atresia.

scholarly journals Proximal Extrahepatic Bile Ducts: Comprehensive Review

2021 ◽  
Vol 4 (1) ◽  
pp. 74-93
Author(s):  
M. A. Shorikov ◽  
O. N. Sergeeva ◽  
M. G. Lapteva ◽  
N. A. Peregudov ◽  
B. I. Dolgushin
Keyword(s):  
Bile Duct ◽  
Bile Flow ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Hepatic Duct ◽  
Biliary Tree ◽  
Comprehensive Review ◽  
Extrahepatic Bile Ducts ◽  
And Function ◽  
Variant Anatomy

Proximal extrahepatic bile ducts are the biliary tree segment within formal boundaries from cystic ductcommon hepatic duct junction to sectoral hepatic ducts. Despite being a focus of attention of diagnostic and interventional radiologists, endoscopists, hepatobiliary surgeons and transplantologists they weren’t comprehensively described in available papers. The majority of the authors regard bile duct confluence as a group of merging primitively arranged tubes providing bile flow. The information on the proximal extrahepatic bile duct embryonal development, variant anatomy, innervation, arterial, venous and lymphatic supply is too general and not detailed. The present review brought together and systemized exiting to the date data on anatomy and function of this biliary tract portion. Unique, different from the majority of hollow organs organization of the proximal extrahepatic bile duct adapts them to the flow of the bile, i.e. viscous aggressive due to pH about 8.0 and detergents fluid, under higher wall pressure than in other parts of biliary tree. 

Cholangioscopy in diagnosis of diseases of extrahepatic bile ducts

2019 ◽  
Vol 1 (6) ◽  
pp. 30-36
Author(s):  
A. G. Shuleshov ◽  
N. V. Fomicheva ◽  
D. N. Ulyanov ◽  
A. S. Balalykin ◽  
D. V. Danilov ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Bile Duct ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Diagnostic Purpose ◽  
Vascular Pattern ◽  
Direct Visualization ◽  
Bile Duct Diseases ◽  
Extrahepatic Bile Ducts ◽  
Diagnosis Of Diseases

An analysis of the diagnosis of extrahepatic bile duct diseases in 115 patients is presented. With the diagnostic purpose they performed ERCP, EPT, cholangioscopy. The method of direct visualization of the mucous membrane of the bile ducts allows you to identify endoscopic signs of strictures. Differential diagnosis of benign and malignant strictures of the bile ducts using cholangioscopy is difficult. Nevertheless, we were able to identify some typical signs for malignant strictures, including ulceration and mucosal infiltration, vascular pattern irregularity, stricture asymmetry.

Adenocarcinoma with pyloric gland phenotype of the extrahepatic bile ducts: a previously unrecognized and distinctive morphologic variant of extrahepatic bile duct carcinoma

2012 ◽  
Vol 43 (12) ◽  
pp. 2292-2298 ◽  
Author(s):  
Jorge Albores-Saavedra ◽  
Fredy Chablé-Montero ◽  
Nahum Méndez-Sánchez ◽  
Miguel Ángel Mercado ◽  
Mario Vilatoba-Chapa ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Bile Duct Carcinoma ◽  
Pyloric Gland ◽  
Duct Carcinoma ◽  
Extrahepatic Bile Duct Carcinoma ◽  
Extrahepatic Bile Ducts

Implantation of a Tissue-Engineered Neo-Bile Duct in Domestic Pigs

2015 ◽  
Vol 56 (1-2) ◽  
pp. 61-75 ◽  
Author(s):  
Benjamin Struecker ◽  
Karl-Herbert Hillebrandt ◽  
Nathanael Raschzok ◽  
Korinna Jöhrens ◽  
Antje Butter ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Ducts ◽  
Ex Vivo ◽  
Extrahepatic Bile Duct ◽  
Biliary Cirrhosis ◽  
Biliary Leakage ◽  
Domestic Pigs ◽  
Bilioenteric Anastomosis

Background: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric anastomosis (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring ascending cholangitis, secondary biliary cirrhosis). In the case of inherent extrahepatic biliary atresia or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy. Methods: We present data on the implantation of in vitro-generated neo-bile ducts in 5 domestic pigs. The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, creatinine, and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 pig. Fourteen days after implantation, the pigs were sacrificed and the bile ducts were explanted. Results: All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue. Conclusion: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long-term replacement of native bile ducts must be further evaluated.

scholarly journals Mixed adenoneuroendocrine carcinoma of the extrahepatic bile duct: a case report

2019 ◽  
Vol 47 (7) ◽  
pp. 3421-3426 ◽  
Author(s):  
Hai-Wen Zhang ◽  
Kai Kou ◽  
Jun Qi ◽  
En-Bo Xie ◽  
Meng Wang ◽  
...  
Keyword(s):  
Bile Duct ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Large Cell ◽  
Treatment Method ◽  
World Health ◽  
Neuroendocrine Neoplasms ◽  
Histopathological Diagnosis ◽  
Mixed Adenoneuroendocrine Carcinoma ◽  
Extrahepatic Bile Ducts

Background The concept of mixed adenoneuroendocrine carcinoma (MANEC) was introduced in the 2010 World Health Organization classification of digestive neuroendocrine neoplasms. Bile duct invasion by MANEC is exceptionally rare. We herein report a case of MANEC with invasion of multiple bile ducts. Case presentation: A 60-year-old man presented with a 7-day history of upper abdominal pain, and a mass in the cystic duct was suspected based on computed tomography findings. The patient underwent resection of the extrahepatic bile ducts with concomitant radical lymphadenectomy and Roux-en-Y cholangiojejunostomy. Large cell neuroendocrine carcinoma was detected in a component of the resected tumor. According to the pathological and immunohistochemical features of the tumor, the final histopathological diagnosis was a biliary MANEC, tumor stage T2N0M1 (Stage IIIC). The patient recovered uneventfully and was discharged from the hospital 10 days after surgery. Conclusions We have described a rare case of extrahepatic MANEC invading multiple bile ducts, with particular emphasis on the physician’s awareness of MANEC and its optimal treatment. MANEC arising from extrahepatic bile ducts is rare, and surgical resection is the most effective treatment method.

scholarly journals Magnetic Resonance Imaging in Primary Sclerosing Cholangitis

2021 ◽  
Vol 3 (2) ◽  
pp. 20-24
Author(s):  
Aldona Wybraniec-Zaręba ◽  
Julia Tuchalska-Czuroń ◽  
Gabriela Półtorak-Szymczak ◽  
Mariusz Furmanek ◽  
Jerzy Walecki ◽  
...  
Keyword(s):  
Bile Duct ◽  
Magnetic Resonance ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Bile Ducts ◽  
Extrahepatic Bile Duct ◽  
Magnetic Resonance Cholangiopancreatography ◽  
Left Liver Lobe ◽  
Bile Duct Stenosis ◽  
Mri Features

Primary sclerosing cholangitis (PSC) is a chronic liver disease in which there are inflammation and scarring of the bile ducts leading to fibrosis, destruction and narrowing of the bile ducts, resulting in cholestasis. In the long run, PSC can cause liver cirrhosis and failure. In clinical practice, the diagnosis of PSC is generally based on blood tests and imaging studies (currently preferably magnetic resonance cholangiopancreatography). To make a diagnosis of PSC it is necessary to exclude secondary causes of sclerosing cholangitis. The most common MRI features of PSC concerning bile ducts are: bile duct dilatation, beading, extrahepatic bile duct stenosis, wall enhancement and thickening. The most common MRI features of PSC concerning hepatic parenchyma are: rounded shape of the liver caused by hypertrophy of caudate lobe and left liver lobe, atrophy of the right lobe, enlargement of portal and/or portacaval lymph nodes, peripheral parenchymal inflammation, wedge-shaped confluent fibrosis, heterogeneity of the liver parenchyma, periportal oedema, cirrhosis with indirect signs of portal hypertension such as splenomegaly, ascites and collateral vasculature.

scholarly journals Cystic form of biliary atresia. Treatment experience

2020 ◽  
Vol 10 (1) ◽  
pp. 17-24
Author(s):  
Irina I. Borisova ◽  
Anatoliy V. Kagan ◽  
Svetlana A. Karavaeva ◽  
Aleksey N. Kotin
Keyword(s):  
Surgical Treatment ◽  
Bile Duct ◽  
Common Bile Duct ◽  
Biliary Atresia ◽  
Bile Ducts ◽  
Surgical Intervention ◽  
Ultrasound Examination ◽  
Duct Cyst ◽  
Cystic Form ◽  
The Common

Background. The cystic form of biliary atresia is a rare form of atresia of the biliary tract, which is a relatively favorable variant of the defect and can be diagnosed antenatally. In practice, it is important not only to suspect this diagnosis, but also to differentiate this variant of impaired development of the external bile duct from the cyst of the common bile duct. This is due to the difference in approaches and methods of surgical treatment of choledochal cysts and biliary atresia. Obliteration (atresia) of the bile ducts in the absence of timely surgical intervention quickly leads to the progression of cirrhosis and the development of liver failure. The method of choice in the treatment of AD is Kasai surgery, often palliative in nature, but allowing to delay the time until liver transplantation. The cyst of the common bile duct rarely requires early surgical treatment, and the risk of cirrhosis is significantly lower. Surgical intervention is aimed at removing the cyst and restoring the flow of bile by anastomosing the external bile ducts with the intestines, which is a radical method of treatment and leads to the recovery of the child. External similarity in ultrasound examination of the fetus and newborn baby of the cystic form of biliary atresia of the bile ducts with a cyst of the common bile duct does not always allow differentiation of one defect from another, which can lead to untimely correction of the defect and an unfavorable outcome. Aim. Demonstrate a rare type of biliary atresia. Materials and methods. Between 2001 and 2019, 33 patients with biliary atresia were treated in the Childrens City Multidisciplinary Clinical Specialized Center for High Medical Technologies in St. Petersburg, only two patients had a cystic form. Both children were initially treated as patients with bile duct cyst. Children were operated on at the age of 2 and 3.5 months. The first patient underwent surgery Kasai, the second hepaticoyunoanastomosis. Results. During the observation period (9 years and 4 years), the synthetic function of the liver is normal, and there are currently no indications for transplantation. Conclusion. If a fetus or a newborn with neonatal jaundice is detected during ultrasound examination of a cystic formation in the gates of the liver, it is very important to correctly and quickly make a differential diagnosis between the cystic form of biliary atresia of the biliary tract and the common bile duct cyst.

Biliary Atresia

1989 ◽  
Vol 11 (2) ◽  
pp. 57-62
Author(s):  
Elizabeth A. Wanek ◽  
Frederick M. Karrer ◽  
Carlos T. Brandt ◽  
John R. Lilly
Keyword(s):  
Biliary Atresia ◽  
Biliary Obstruction ◽  
Bile Flow ◽  
Bile Ducts ◽  
Current Treatment ◽  
Histopathologic Examination ◽  
The Past ◽  
The World ◽  
Hepatic Portoenterostomy ◽  
Extrahepatic Bile Ducts

Biliary atresia is a pathologic entity in which there is obliteration of some portion of the extrahepatic bile ducts. In the past, occlusion of the proximal ducts (at the liver hilus) was referred to as "noncorrectable" (Fig 1). If only the distal duct is occluded (and the proximal duct is patent), the lesion was referred to as "correctable." The distinction is academic because current treatment and prognosis are identical. The disease is panductular, ie, both extrahepatic and intrahepatic ducts are involved. Early in the disease, however, occlusion is complete only in the extrahepatic system. Without intervention, intrahepatic biliary obstruction and, subsequently, cirrhosis supervene. In the past, except for a few cases of the correctable variant, surgical procedures were unsuccessful until Morio Kasai performed a hepatic portoenterostomy, which was first reported in English in 1968. Bile flow was effectively reestablished in both correctable and noncorrectable forms of biliary atresia. The operation was only successful when done before the patient was 4 months of age. Subsequent confirmation of Kasai's results were reported throughout the world. ETIOLOGY/PATHOLOGY Biliary atresia was originally thought to be a congenital malformation. Careful histopathologic examination of excised surgical specimens indicate that this is not the case; instead, the disease is a dynamic, progressive panductular sclerotic process that may continue in the intrahepatic ducts even after surgical relief of biliary obstruction.

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