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Bile Duct (bile + duct)
Kinds of Bile Duct Terms modified by Bile Duct Selected AbstractsTEACHING DEEP CANNULATION OF THE BILE DUCT DURING ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHYDIGESTIVE ENDOSCOPY, Issue 4 2007Kiichi Tamada When performing endoscopic retrograde cholangiopancreatography (ERCP), the smooth introduction of the duodenoscope into the papilla of Vater, an appropriate view of the papilla of Vater, and deep cannulation of the bile duct are essential. The operator must know the difference between the side-viewing endoscope and the forward-viewing endoscope. The rotation of the body and the left arm of the operator, switching with the left wrist, and dialing of the endoscope are essential for appropriately viewing the papilla of Vater. When training operators to do ERCP, a model is useful for helping them understand basic handling. The approach to deep cannulation of the bile duct should be selected based on the type of papilla (slit type, onion type, tongue protrusion type, flat type, and tumor type). Cannulation is more difficult in patients with the tongue protrusion-type of papilla than with a slit type, onion type, or tumor type. According to previous reports, therapeutic ERCP requires the ability to cannulate the common bile duct deeply 80% of the time; 180 to 200 supervised ERCP are necessary to achieve this success rate. [source] The effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile duct ligated ratsHEPATOLOGY RESEARCH, Issue 12 2008Arezou Rezaei Aim:, N-acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2. Methods:, Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real-time reverse transcription polymerase chain reaction [RT,PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups. Results:, N-acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase-2 expression, it significantly decreased its level by 65%. N-acetylcysteine treatment also significantly decreased matrix metalloproteinase-2 activity and normalized tissue inhibitor of matrix metalloproteinase-2 expression. Conclusion:, Collectively, N-acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and activity. In addition, administration of N-acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase-2 and amelioration of oxidative stress in the liver of bile duct ligated rats. [source] Endothelial, but not the inducible, nitric oxide synthase is detectable in normal and portal hypertensive ratsLIVER INTERNATIONAL, Issue 6 2002Michael Martin Stumm Abstract:Background: Chronic portal hypertension is accompanied by a nitric oxide (NO) dependent vasodilation. Three isoforms of NO producing synthases (NOS) are characterized: neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Sources of increased NO levels in chronic hypertension is disputed. Methods: To determine eNOS and iNOS expression in different organs of portal hypertensive and control rats, we divided Sprague-Dawley rats in 6 groups: (1) Partial portal vein ligated rats, (2) Bile duct ligated rats, (3) Carbon tetrachloride treated rats, (4) Sham operated rats, (5) Untreated control rats, and (6) LPS treated rats. Immunohistochemistry (IHC) and immunoblotting (IB) using antibodies against eNOS or iNOS were carried out on samples from thymus, aorta, heart, lung, oesophagus, liver, spleen, kidney, pancreas, small and large intestine. Results: IHC revealed an even eNOS expression in all groups. Expression of iNOS was restricted to macrophages in organs of LPS treated and the thymus of rats. IB mirrored these results. Conclusion: In chronic portal hypertension, the main source for NO production depends on eNOS activity. [source] Bile ducts as a source of pancreatic , cellsBIOESSAYS, Issue 9 2004Zoë D. Burke In recent years, there have been a number of well-documented examples demonstrating that one cell type can be converted to another. Two such examples are the appearance of ectopic pancreas in the liver and formation of hepatic tissue in the pancreas. The conversion of liver to pancreas raises the intriguing possibility of generating insulin-producing , cells for therapeutic transplantation into diabetics. There is now a striking addition to the growing list of pancreatic conversions: the formation of pancreatic tissue in the developing biliary system.1 BioEssays 26:932,937, 2004. © 2004 Wiley Periodicals, Inc. [source] ENDOSCOPIC OCCLUSION OF CYSTIC DUCT USING N -BUTYL CYANOACRYLATE FOR POSTOPERATIVE BILE LEAKAGEDIGESTIVE ENDOSCOPY, Issue 4 2010Eric K. Ganguly Bile leak after cholecystectomy is well described, with the cystic duct remnant the site of the leak in the majority of cases. Endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement has a high success rate in such cases. When ERCP fails, options include surgery, and percutaneous and endoscopic transcatheter occlusion of the site of bile leak. Here, we describe a case of endoscopic transcatheter occlusion of a persistent cystic duct bile leak after cholecystectomy using N -butyl cyanoacrylate glue. A 51-year-old man had persistent pain and bilious drainage following a laparoscopic cholecystectomy. The bile leak persisted after endoscopic placement of a biliary stent for a confirmed cystic duct leak. A repeat ERCP was carried out and the cystic duct was occluded with a combination of angiographic coils and N -butyl cyanoacrylate glue. The patient's pain and bilious drainage resolved. A follow-up cholangiogram confirmed complete resolution of the cystic duct leak and a patent common bile duct. [source] ALTERNATIVE METHODS IN THE ENDOSCOPIC MANAGEMENT OF DIFFICULT COMMON BILE DUCT STONESDIGESTIVE ENDOSCOPY, Issue 2010Dong Ki Lee The endoscopic method is accepted as a first treatment modality in the management of extrahepatic bile duct. Most large stones can be removed with basket and mechanical lithotripsy after endoscopic sphincterotomy. Currently, in treating large extrahepatic bile duct stones, endoscopic papillary large balloon dilation with mid-incision endoscopic sphincterotomy is actively performed instead of applying mechanical lithotripsy after full endoscopic sphincterotomy. Herein, we describe the conceptions, proper indications, methods and complications of endoscopic papillary large balloon dilation with regards to currently published reports. In addition, intracorporeal lithotripsy by peroral cholangioscopy with an ultra-slim upper endoscope is introduced, which is more convenient than previous conventional intracorporeal lithotripsy methods using mother,baby endoscopy or percutaneous transhepatic cholangioscopy. Lastly, biliary stenting with the choleretic agent administration method is briefly reviewed as an alternative treatment option for frail and elderly patients with large impacted common bile duct stones. [source] ROLE OF ENDOSCOPY IN SCREENING OF EARLY PANCREATIC CANCER AND BILE DUCT CANCERDIGESTIVE ENDOSCOPY, Issue 2009Kiyohito Tanaka In the screening of early pancreatic cancer and bile duct cancer, the first issue was ,what are the types of abnormality in laboratory data and symptoms in case of early pancreatic cancer and bile duct cancer?' Early cancer in the pancreaticobiliary region has almost no symptoms, however epigastralgia without abnormality in the gastrointestinal (GI) tract is a sign of early stage pancreaticobiliary cancer. Sudden onset and aggravation of diabetes mellitus is an important change in the case of pancreatic cancer. Extracorporeal ultrasonography is a very useful procedure of checking up changes of pancreatic and biliary lesions. As the role of endoscopy in screening, endoscopic ultrasonography (EUS) is the most effective means of cancer detection of the pancreas, and endoscopic retrograde cholangiopancreatography (ERCP) is most useful of diagnosis tool for abnormalities of the common bile duct. Endoscopic retrograde cholangiopancreatography is an important modality as the procedure of sampling of diagnostic materials. Endoscopic ultrasonography-fine needle aspiration (EUS-FNA) has the role of histological diagnosis of pancreatic mass lesion also. Especially, in the case of pancreas cancer without evidence of cancer by pancreatic juice cytology and brushing cytology, EUS-FNA is essential. Intra ductal ultrasonography (IUDS) and perotral cholangioscopy (POCS) are useful for determination of mucosal extent in extrahepatic bile duct cancer. Further improvements of endoscopical technology, endoscopic procedures are expected to be more useful modalities in detection and diagnosis of early pancreatic and bile duct cancers. [source] RISK FACTORS FOR RECURRENT BILE DUCT STONES AFTER ENDOSCOPIC PAPILLARY BALLOON DILATION: LONG-TERM FOLLOW-UP STUDYDIGESTIVE ENDOSCOPY, Issue 2 2009Akira Ohashi Background:, Little is known about the long-term results of endoscopic papillary balloon dilation (EPBD) for bile duct stones. Methods:, Between 1995 and 2000, 204 patients with bile duct stones successfully underwent EPBD and stone removal. Complete stone clearance was confirmed using balloon cholangiography and intraductal ultrasonography (IDUS). Long-term outcomes of EPBD were investigated retrospectively in the year 2007, and risk factors for stone recurrence were multivariately analyzed. Results:, Long-term information was available in 182 cases (89.2%), with a mean overall follow-up duration of 9.3 years. Late biliary complications occurred in 22 patients (12.1%), stone recurrence in 13 (7.1%), cholangitis in 10 (5.5%), cholecystitis in four, and gallstone pancreatitis in one. In 11 of 13 patients (84.6%), stone recurrence developed within 3 years after EPBD. All recurrent stones were bilirubinate. Multivariate analysis identified three risk factors for stone recurrence: dilated bile duct (>15 mm), previous cholecystectomy, and no confirmation of clean duct using IDUS. Conclusion:, Approximately 7% of patients develop stone recurrence after EPBD; however, retreatment with endoscopic retrograde cholangiopancreatography is effective. Careful follow up is necessary in patients with dilated bile duct or previous cholecystectomy. IDUS is useful for reducing stone recurrence after EPBD. [source] CHARACTERISTIC INTRADUCTAL ULTRASONOGRAPHIC FEATURES OF PORTAL BILIOPATHYDIGESTIVE ENDOSCOPY, Issue 4 2008Tsukasa Ikeura The term ,portal biliopathy' is used to describe cholangiographic abnormalities seen in patients with extrahepatic portal vein obstruction. Portal biliopathy is mainly composed of extrinsic compression of the bile duct caused by enlarged venous collaterals. Herein we report a case of asymptomatic portal biliopathy caused by idiopathic extrahepatic portal vein obstruction. In the present case, intraductal ultrasonography showed normal anatomic layers of the distal common bile duct wall, surrounded by numerous tubular structures which were suspected to be collateral vessels. We suggest that intraductal ultrasonography may be a helpful imaging procedure for detection of this pathological condition. [source] TEACHING DEEP CANNULATION OF THE BILE DUCT DURING ENDOSCOPIC RETROGRADE CHOLANGIOGRAPHYDIGESTIVE ENDOSCOPY, Issue 4 2007Kiichi Tamada When performing endoscopic retrograde cholangiopancreatography (ERCP), the smooth introduction of the duodenoscope into the papilla of Vater, an appropriate view of the papilla of Vater, and deep cannulation of the bile duct are essential. The operator must know the difference between the side-viewing endoscope and the forward-viewing endoscope. The rotation of the body and the left arm of the operator, switching with the left wrist, and dialing of the endoscope are essential for appropriately viewing the papilla of Vater. When training operators to do ERCP, a model is useful for helping them understand basic handling. The approach to deep cannulation of the bile duct should be selected based on the type of papilla (slit type, onion type, tongue protrusion type, flat type, and tumor type). Cannulation is more difficult in patients with the tongue protrusion-type of papilla than with a slit type, onion type, or tumor type. According to previous reports, therapeutic ERCP requires the ability to cannulate the common bile duct deeply 80% of the time; 180 to 200 supervised ERCP are necessary to achieve this success rate. [source] NEW APPLICATION OF NARROW BAND IMAGING FOR CHOLANGIOPANCREATOSCOPYDIGESTIVE ENDOSCOPY, Issue 2007Mitsuhiro Kida The usefulness of narrow band imaging (NBI), which is based on the principle that the depth of light penetration depends on its wavelength, has been accepted for evaluating malignant or benign lesions in the pharynx, the upper, and lower gastrointestine. The purpose of the present paper was to investigate NBI for diagnosing biliopancreatic disease. Using NBI it has become easy to detect the surface microstructure of biliary mucosa and subjacent vascular network of the bile duct, and inflammatory scarring stenosis is visualized as a whitish scar and multiple inflammatory red spots. However, bile duct cancer was detected as a stenosis with abnormal subjacent vessels and irregular surface. Concerning pancreatic duct, NBI has clearly shown vascular network and spreading of branch-type intraductal papillary mucinous neoplasm to the main pancreatic duct. In contrast, bile juice has been detected as red fluid and bleeding as black red. Therefore, it is important to flush the biliary system before observing with NBI. [source] INTRADUCTAL ULTRASONOGRAPHY OF THE GALLBLADDER IN APPLICATION OF THE ENDOSCOPIC NASO-GALLBLADDER DRAINAGEDIGESTIVE ENDOSCOPY, Issue 1 2007Daisuke Masuda Background:, Although endoscopic naso-gallbladder drainage (ENGBD) for gallbladder disease is useful, the procedure is difficult and investigations involving many cases are lacking. Furthermore, reports on transpapillary intraductal ultrasonography (IDUS) of the gallbladder using a miniature probe are rare. Methods:, A total of 150 patients (119 suspected of having gallbladder carcinoma, 24 with acute cholecystitis (AC), and seven with Mirizzi's syndrome (MS)) were the subject. (i) ENGBD: We attempted to put ENGBD tube into the GB. (ii) IDUS of the gallbladder: Using the previous ENGBD tube, we attempted to insert the miniature probe into the gallbladder and perform transpapillary IDUS of the gallbladder. In five patients, we attempted three-dimensional intraductal ultrasonography (3D-IDUS). Results:, (i) ENGBD: Overall success rate was 74.7% (112/150); the rate for the patients suspected of having gallbladder carcinoma was 75.6% (90/119), and was 71.0% (22/31) for the AC and MS patients. Inflammation and jaundice improved in 20/22 successful patients with AC and MS. Success rate was higher when cystic duct branching was from the lower and middle parts of the common bile duct than from the upper part, and was higher when branching was upwards than downwards. (ii) IDUS of the gallbladder: Success rate for miniature probe insertion into the gallbladder was 96.4% (54/56). Lesions could be visualized in 50/54 patients (92.6%). Of these, detailed evaluation of the locus could be performed in 41. In five patients attempted 3D-IDUS, the relationship between the lesion and its location was readily grasped. Conclusion:, IDUS of the gallbladder is superior for diagnosing minute images. Improvement on the device will further increase its usefulness. [source] INTRADUCTAL ULTRASONOGRAPHY FOR THE STAGING OF BILE DUCT CARCINOMADIGESTIVE ENDOSCOPY, Issue 2005Kiichi Tamada Intraductal ultrasonography is useful in the staging of extrahepatic bile duct cancer including tumor depth infiltration, pancreatic parenchymal invasion, portal vein invasion, and right hepatic artery invasion. However, it has limitations in assessing lymph node metastases. The assessment of longitudinal cancer extension along the bile duct is a promising aspect of this area. However, a thickening of the bile duct wall may represent either inflammatory changes that may result from mechanical irritation by a biliary drainage catheter or other factors, or the longitudinal extension of the cancer. [source] Indication of Endoscopic Papillectomy for Tumors of the Papilla of Vater and Its ProblemsDIGESTIVE ENDOSCOPY, Issue 2003HIROYUKI MAGUCHI Discussions have just started in Japan as to the indication, technique and complication of endoscopic papillectomy for tumors of the papilla of Vater. We indicate endoscopic papillectomy for tumors satisfying the following: 1exposed tumor-type adenoma, or carcinoma in adenoma; 2without invasion of duodenal muscularis; and 3no infiltration into the pancreas or the bile duct. Endoscopic papillectomy was performed on 12 patients with tumors of the papilla of Vater that satisfied the above criteria. En bloc snare excision was achieved in 11 out of 12 cases without endoscopic sphincterotomy (EST) or epinephrine injection. Pancreatic stenting was done in 8 cases for prevention of pancreatitis, and bile duct stenting in nine cases for prevention of cholangitis. Postoperative early complications were observed in 5 cases; pancreatitis in 2; pancreatitis and bleeding in 1; bleeding in 1; and bleeding and perforation in 1. Neither recurrence nor metastasis of tumor has been detected during the average postoperative period of 620 days. The treatment can be acknowledged as less invasive therapy. However, management of complications is important, for which further study needs to be accumulated. [source] Sphincter of Oddi dysfunction: role of sphincterotomyDIGESTIVE ENDOSCOPY, Issue 4 2001Choichi Sugawa Sphincter of Oddi dysfunction (SOD) is one of the causes of post-cholecystectomy syndrome and biliary pain and is a challenge from both the diagnostic and therapeutic points of view. Sphincter of Oddi dysfunction is typically diagnosed months to years after cholecystectomy. Continued biliary type pain after cholecystectomy may occur in as many as 10,20% of patients. Ten percent or more of these patients may eventually be shown to have SOD. The syndrome is often associated with a variety of other gastrointestinal disorders thought to be caused by dysmotility. According to the Milwaukee classification, patients with biliary pain can be divided into three types. Type I patients show all the objective signs suggestive of a disturbed bile outflow (i.e. elevated liver function tests, dilated common bile duct and delayed contrast drainage during endoscopic retrograde cholangiopancreatography). Type II patients have biliary type pain along with one or two of the criteria from type I. Type III patients have biliary pain only, with no other abnormalities. The present paper will focus primarily on SOD syn-drome, papillary stenosis and the diagnostic and therapeutic approaches, in particular endoscopic sphincterotomy. [source] Newly Developed Ultrasonic Probe With Ropeway System for Transpapillary Intraductal Ultrasonography of the Bilio,Pancreatic Ductal SystemDIGESTIVE ENDOSCOPY, Issue 3 2000Naotaka Fujita Background: Intraductal ultrasonography of the bile/pancreatic duct using a thin-caliber ultrasonic probe (IDUS) provides excellent images of these ducts and the surrounding structures. Insertion of the device through the papilla of Vater is essential to carry out this examination. We developed a new probe with a ropeway system (XUM5RG-29R; Olympus, Tokyo) for transpapillary IDUS. Its usefulness such as ease of application and safety were prospectively evaluated. Patients and methods: During the period of October 1997 to April 1998, transpapillary IDUS using the probe was performed in 194 patients at seven medical institutions. The success rates of insertion of the probe into the bile/pancreatic duct, observation of the area of interest, and the incidence of complications were evaluated. Results: Passage of the probe through the papilla was successful without difficulty in all the patients. Successful introduction of the probe into the pancreatic duct, bile duct and both of the ducts was achieved in 98.4, 100 and 85% of the patients, respectively. Once the probe was introduced into the aimed duct, it was possible to obtain IDUS images of the area of interest in all but five patients. Mild acute pancreatitis developed in eight patients (4.1%), all of whom recovered with conservative therapy only. Conclusions: It is possible to introduce the new ultrasonic probe into the desired duct once a guide wire has been inserted. This type of ultrasonic probe is quite useful when performing transpapillary IDUS of the bile and/or pancreatic duct. [source] Carcinoma of the gall-bladder associated with primary sclerosing cholangitis and ulcerative colitisDIGESTIVE ENDOSCOPY, Issue 1 2000Mitsuru Seo A 64-year-old Japanese male was admitted to Fukuoka University Hospital to undergo further examination for an elevated ,-glutamyltransferase (,-GTP) level. Endoscopic retrograde cholangiography (ERC) showed dilatation of the intrahepatic bile duct and stenosis of the proximal portion of the common bile duct. No abnormality was found in the gall-bladder. Since the fecal occult blood test was positive, sigmoidoscopy and a barium enema were performed. Sigmoidoscopy showed a hyperemic and hemorrhagic mucosa in the rectum, but a barium enema study did not show any abnormal findings in the entire colon. We diagnosed the patient to have primary sclerosing cholangitis (PSC) and ulcerative proctitis based on these radiological and endoscopic findings. Bloody stool and fever occurred 4 months after the first admission. The patient's colitis extended to the entire colon. Because of the failure of corticosteroid therapy, a subtotal colectomy was performed. Given that a mass was intraoperatively palpable in the gall-bladder, a cholecystectomy was simultaneously performed. In the whole resected colon, diffuse ulcerations and mucosal islands were found. Grossly, a flat polypoid lesion, measuring 2 cm in diameter, was found in the fundus of the resected gall-bladder. Sections of this lesion in the gall-bladder revealed cystic atypical glands and some atypical cell clusters invading the subserosa. The present case suggests that careful observations are needed for patients with ulcerative colitis who have an elevated ,-GTP level even if the colitis is limited to the distal colon and the serum alkaline phosphatase level is normal. [source] Altered membrane glycoprotein targeting in cholestatic hepatocytesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2010Giuseppa Esterina Liquori Eur J Clin Invest 2010; 40 (5): 393,400 Abstract Background, Hepatocytes are polarized epithelial cells with three morphologically and functionally distinct membrane surfaces: the sinusoidal, lateral and canalicular surface domains. These domains differ from each other in the expression of integral proteins, which concur to their polarized functions. We hypothesize that the cholestasis-induced alterations led to partial loss of hepatocyte polarity. An altered expression of membrane proteins may be indicative of functional disorders. Alkaline liver phosphatase (ALP), one of the most representative plasma membrane glycoproteins in hepatocytes, is expressed at the apical (canalicular) pole of the cell. Because the release of ALP protein in the bloodstream is significantly increased in cholestasis, the enzymatic levels of plasma ALP have major relevance in the diagnosis of cholestatic diseases. Here we assess the cholestasis-induced redistribution of membrane glycoproteins to investigate the ALP release. Materials and methods, We performed enzymatic histochemistry, immunohistochemistry, lectin histochemistry, immunogold and lectin-and immunoblotting studies. Experimental cholestasis was induced in rats by ligation of common bile duct (BDL). Results, The BDL led to altered membrane sialoglycoprotein targeting as well as to ultrastructural and functional disorders. Disarrangement of the microtubular system, thickening of the microfilamentous pericanalicular ectoplasm and disturbance of the vectorial trafficking of membrane glycoprotein containing vesicles were found. Conclusions, Altogether, results indicate that the cholestasis-induced partial loss of hepatocyte cell polarity leads to mistranslocation of ALP to the sinusoidal plasma membrane from where the enzyme is then massively released into the bloodstream. [source] Notch2 signaling promotes biliary epithelial cell fate specification and tubulogenesis during bile duct development in mice,HEPATOLOGY, Issue 3 2009Jan S. Tchorz Intrahepatic bile duct (IHBD) development begins with the differentiation of hepatoblasts into a single continuous biliary epithelial cell (BEC) layer, called the ductal plate. During ductal plate remodeling, tubular structures arise at distinct sites of the ductal plate, forming bile ducts that dilate into the biliary tree. Alagille syndrome patients, who suffer from bile duct paucity, carry Jagged1 and Notch2 mutations, indicating that Notch2 signaling is important for IHBD development. To clarify the role of Notch2 in BEC differentiation, tubulogenesis, and BEC survival, we developed a mouse model for conditional expression of activated Notch2 in the liver. We show that expression of the intracellular domain of Notch2 (Notch2ICD) differentiates hepatoblasts into BECs, which form additional bile ducts in periportal regions and ectopic ducts in lobular regions. Additional ducts in periportal regions are maintained into adulthood and connect to the biliary tight junction network, resulting in an increased number of bile ducts per portal tract. Remarkably, Notch2ICD-expressing ductal plate remnants were not eliminated during postnatal development, implicating Notch2 signaling in BEC survival. Ectopic ducts in lobular regions did not persist into adulthood, indicating that local signals in the portal environment are important for maintaining bile ducts. Conclusion: Notch2 signaling regulates BEC differentiation, the induction of tubulogenesis during IHBD development, and BEC survival. (HEPATOLOGY 2009.) [source] Bile duct proliferation in Jag1/fringe heterozygous mice identifies candidate modifiers of the alagille syndrome hepatic phenotype,HEPATOLOGY, Issue 6 2008Matthew J. Ryan Alagille syndrome (AGS) is a heterogeneous developmental disorder associated with bile duct paucity and various organ anomalies. The syndrome is caused by mutations in JAG1, which encodes a ligand in the Notch signaling pathway, in the majority of cases and mutations in the NOTCH2 receptor gene in less than 1% of patients. Although a wide array of JAG1 mutations have been identified in the AGS population, these mutational variants have not accounted for the wide phenotypic variability observed in patients with this syndrome. The Fringe genes encode glycosyltransferases, which modify Notch and alter ligand-receptor affinity. In this study, we analyzed double heterozygous mouse models to examine the Fringe genes as potential modifiers of the Notch-mediated hepatic phenotype observed in AGS. We generated mice that were haploinsufficient for both Jag1 and one of three paralogous Fringe genes: Lunatic (Lfng), Radical (Rfng), and Manic (Mfng). Adult Jag1+/,Lfng+/, and Jag1+/,Rfng+/, mouse livers exhibited widespread bile duct proliferation beginning at 5 weeks of age and persisting up to 1 year. The Jag1+/,Mfng+/, livers showed a subtle, yet significant increase in bile duct numbers and bile duct to portal tract ratios. These abnormalities were not observed in the newborn period. Despite the portal tract expansion by bile ducts, fibrosis was not increased and epithelial to mesenchymal transition was not shown in the affected portal tracts. Conclusion: Mice heterozygous for mutations in Jag1 and the Fringe genes display striking bile duct proliferation, which is not apparent at birth. These findings suggest that the Fringe genes may regulate postnatal bile duct growth and remodeling, and serve as candidate modifiers of the hepatic phenotype in AGS. (HEPATOLOGY 2008;48:1989,1997.) [source] Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia,,HEPATOLOGY, Issue 5 2006Cara L. Mack Biliary atresia is an inflammatory fibrosclerosing lesion of the bile ducts that leads to biliary cirrhosis and is the most frequent indication for liver transplantation in children. The pathogenesis of biliary atresia is not known; one theory is that of a virus-induced, subsequent autoimmune-mediated injury of bile ducts. The aim of this study was to determine whether autoreactive T cells and autoantibodies specific to bile duct epithelia are present in the rotavirus (RRV)- induced murine model of biliary atresia and whether the T cells are sufficient to result in bile duct inflammation. In vitro analyses showed significant increases in IFN-,,producing T cells from RRV-diseased mice in response to bile duct epithelial autoantigen. Adoptive transfer of the T cells from RRV-diseased mice into naïve syngeneic SCID recipients resulted in bile duct,specific inflammation. This induction of bile duct pathology occurred in the absence of detectable virus, indicating a definite response to bile duct autoantigens. Furthermore, periductal immunoglobulin deposits and serum antibodies reactive to bile duct epithelial protein were detected in RRV-diseased mice. In conclusion, both cellular and humoral components of autoimmunity exist in murine biliary atresia, and the progressive bile duct injury is due in part to a bile duct epithelia,specific T cell,mediated immune response. The role of cellular and humoral autoimmunity in human biliary atresia and possible interventional strategies therefore should be the focus of future research. (HEPATOLOGY 2006;44:1231,1239.) [source] Roles of AKT and sphingosine kinase in the antiapoptotic effects of bile duct ligation in mouse liver,HEPATOLOGY, Issue 6 2005Yosuke Osawa Tumor necrosis factor (TNF) receptor, and Fas-mediated apoptosis are major death processes of hepatocytes in liver disease. Although antiapoptotic effects in the injured liver promote chronic hepatitis and carcinogenesis, scant information is known about these mechanisms. To explore this issue, we compared acute liver injury after TNF-, or anti-Fas antibody (Jo2) between livers from sham-operated mice and chronic injured liver via bile duct ligation (BDL). BDL inhibited hepatocyte apoptosis induced by TNF-, but not by Jo2. On the other hand, BDL inhibited the massive hemorrhage seen in livers treated with either TNF-, or Jo2. Inactivation of AKT blocked the antiapoptotic effect of BDL. Sphingosine kinase knockout mice also lost the antihemorrhagic effect of BDL and attenuated the antiapoptotic effects of BDL. In bile duct,ligated livers, hepatic stellate cells (HSCs) were activated and produced tissue inhibitor of metalloproteinase 1 in a sphingosine kinase (SphK)-1,dependent mechanism. In conclusion, BDL exerts antiapoptotic effects that appear to require activation of AKT in hepatocytes and SphK in HSCs.(HEPATOLOGY 2005;42:1320,1328.) [source] Secretin activation of the apical Na+ -dependent bile acid transporter is associated with cholehepatic shunting in rats,HEPATOLOGY, Issue 5 2005Gianfranco Alpini The role of the cholangiocyte apical Na+ -dependent bile acid transporter (ASBT) in bile formation is unknown. Bile acid absorption by bile ducts results in cholehepatic shunting, a pathway that amplifies the canalicular osmotic effects of bile acids. We tested in isolated cholangiocytes if secretin enhances ASBT translocation to the apical membrane from latent preexisting intracellular stores. In vivo, in bile duct,ligated rats, we tested if increased ASBT activity (induced by secretin pretreatment) results in cholehepatic shunting of bile acids. We determined the increment in taurocholate-dependent bile flow and biliary lipid secretion and taurocholate (TC) biliary transit time during high ASBT activity. Secretin stimulated colchicine-sensitive ASBT translocation to the cholangiocyte plasma membrane and 3H-TC uptake in purified cholangiocytes. Consistent with increased ASBT promoting cholehepatic shunting, with secretin pretreatment, we found TC induced greater-than-expected biliary lipid secretion and bile flow and there was a prolongation of the TC biliary transit time. Colchicine ablated secretin pretreatment-dependent bile acid,induced choleresis, increased biliary lipid secretion, and the prolongation of the TC biliary transit. In conclusion, secretin stimulates cholehepatic shunting of conjugated bile acids and is associated with increased cholangiocyte apical membrane ASBT. Bile acid transport by cholangiocyte ASBT can contribute to hepatobiliary secretion in vivo. (HEPATOLOGY 2005.) [source] Systemic infusion of angiotensin II exacerbates liver fibrosis in bile duct,ligated rats,HEPATOLOGY, Issue 5 2005Ramón Bataller Recent evidence indicates that the renin,angiotensin system (RAS) plays a major role in liver fibrosis. Here, we investigate whether the circulatory RAS, which is frequently activated in patients with chronic liver disease, contributes to fibrosis progression. To test this hypothesis, we increased circulatory angiotensin II (Ang II) levels in rats undergoing biliary fibrosis. Saline or Ang II (25 ng/kg/h) were infused into bile duct,ligated rats for 2 weeks through a subcutaneous pump. Ang II infusion increased serum levels of Ang II and augmented bile duct ligation,induced liver injury, as assessed by elevated liver serum enzymes. Moreover, it increased the hepatic concentration of inflammatory proteins (tumor necrosis factor , and interleukin 1,) and the infiltration of CD43-positive inflammatory cells. Ang II infusion also favored the development of vascular thrombosis and increased the procoagulant activity of tissue factor in the liver. Livers from bile duct,ligated rats infused with Ang II showed increased transforming growth factor ,1 content, collagen deposition, accumulation of smooth muscle ,-actin,positive cells, and lipid peroxidation products. Moreover, Ang II infusion stimulated phosphorylation of c-Jun and p42/44 mitogen-activated protein kinase and increased proliferation of bile duct cells. In cultured rat hepatic stellate cells (HSCs), Ang II (10,8 mol/L) increased intracellular calcium and stimulated reactive oxygen species formation, cellular proliferation and secretion of proinflammatory cytokines. Moreover, Ang II stimulated the procoagulant activity of HSCs, a newly described biological function for these cells. In conclusion, increased systemic Ang II augments hepatic fibrosis and promotes inflammation, oxidative stress, and thrombogenic events. (HEPATOLOGY 2005;41:1046,1055.) [source] Kupffer cell,derived interleukin 10 is responsible for impaired bacterial clearance in bile duct,ligated miceHEPATOLOGY, Issue 2 2004Tetsuya Abe Extrahepatic cholestasis often evokes liver injury with hepatocyte apoptosis, aberrant cytokine production, and,most importantly,postoperative septic complications. To clarify the involvement of aberrant cytokine production and hepatocyte apoptosis in impaired resistance to bacterial infection in obstructive cholestasis, C57BL/6 mice or Fas-mutated lpr mice were inoculated intraperitoneally with 107 colony-forming units of Escherichia coli 5 days after bile duct ligation (BDL) or sham celiotomy. Cytokine levels in sera, liver, and immune cells were assessed via enzyme-linked immunosorbent assay or real-time reverse-transcriptase polymerase chain reaction. BDL mice showed delayed clearance of E. coli in peritoneal cavity, liver, and spleen. Significantly higher levels of serum interleukin (IL) 10 with lower levels of IL-12p40 were observed in BDL mice following E. coli infection. Interferon , production from liver lymphocytes in BDL mice was not increased after E. coli infection either at the transcriptional or protein level. Kupffer cells from BDL mice produced low levels of IL-12p40 and high levels of IL-10 in vitro in response to lipopolysaccharide derived from E. coli. In vivo administration of anti,IL-10 monoclonal antibody ameliorated the course of E. coli infection in BDL mice. Furthermore, BDL- lpr mice did not exhibit impairment in E. coli killing in association with little hepatic injury and a small amount of IL-10 production. In conclusion, increased IL-10 and reciprocally suppressed IL-12 production by Kupffer cells are responsible for deteriorated resistance to bacterial infection in BDL mice. Fas-mediated hepatocyte apoptosis in cholestasis may be involved in the predominant IL-10 production by Kupffer cells. (HEPATOLOGY 2004;40:414,423.) [source] Derivation, characterization, and phenotypic variation of hepatic progenitor cell lines isolated from adult ratsHEPATOLOGY, Issue 2 2002Li Yin Liver progenitor cells (LPCs) cloned from adult rat livers following allyl alcohol injury express hematopoietic stem cell and early hepatic lineage markers when cultured on feeder layers; under these conditions, neither mature hepatocyte nor bile duct, Ito, stellate, Kupffer cell, or macrophage markers are detected. These phenotypes have remained stable without aneuploidy or morphological transformation after more than 100 population doublings. When cultured without feeder layers, the early lineage markers disappear, and mature hepatocyte markers are expressed; mature hepatocytic differentiation and cell size are also augmented by polypeptide and steroidal growth factors. In contrast to hepatocytic potential, duct-like structures and biliary epithelial markers are expressed on Matrigel. Because they were derived without carcinogens or mutagens, these bipotential LPC lines provide novel tools for models of cellular plasticity and hepatocarcinogenesis, as well as lines for use in cellular transplantation, gene therapy, and bioreactor construction. [source] The effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 in hepatic fibrosis in bile duct ligated ratsHEPATOLOGY RESEARCH, Issue 12 2008Arezou Rezaei Aim:, N-acetylcysteine can inhibit the formation of intracellular reactive oxygen intermediates. Cellular redox state plays a role in regulating the secretion of matrix metalloproteinase-2. We investigated the effects of N-acetylcysteine on the expression of matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2. Methods:, Bile duct ligated rats were used as a model of hepatic fibrosis. We compared the level of gene expression (using real-time reverse transcription polymerase chain reaction [RT,PCR]), liver function parameters, hepatic reactive oxygen production, lipid peroxidation and glutathione state in experimental groups. Results:, N-acetylcysteine treatment significantly improved liver function parameters including the plasma levels of aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase and bilirubin. In addition, significant improvement of glutathione state and reactive oxygen production were observed. Hepatic lipid peroxidation was reversed by N-acetylcysteine treatment. Although N-acetylcysteine treatment did not completely normalize the increased matrix metalloproteinase-2 expression, it significantly decreased its level by 65%. N-acetylcysteine treatment also significantly decreased matrix metalloproteinase-2 activity and normalized tissue inhibitor of matrix metalloproteinase-2 expression. Conclusion:, Collectively, N-acetylcysteine showed inhibition of matrix metalloproteinase-2 expression and activity. In addition, administration of N-acetylcysteine was associated with downregulation of the expression of tissue inhibitor of matrix metalloproteinase-2 and amelioration of oxidative stress in the liver of bile duct ligated rats. [source] In-hospital mortality after resection of biliary tract cancer in the United StatesHPB, Issue 1 2010James E. Carroll Jr Abstract Objective:, To assess perioperative mortality following resection of biliary tract cancer within the U.S. Background:, Resection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies. Methods:, Using the Nationwide Inpatient Sample 1998,2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection. Results:, 31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age ,50 (vs. <50; age 50,59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70,17.93; age 60,69 OR 7.25, 95% CI 2.29,22.96; age , 70 OR 9.03, 95% CI 2.86,28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61,5.16; renal failure, OR 4.72, 95% CI 2.97,7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39,2.37). Conclusion:, Increased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection. [source] Electrical activation of common bile duct nerves modulates sphincter of Oddi motility in the Australian possumHPB, Issue 4 2005Y. Sonoda Abstract Background: Sphincter of Oddi (SO) motility is regulated by extrinsic and intrinsic nerves. The existence of neural circuits between the SO and the proximal extrahepatic biliary tree has been reported, but they are poorly understood. Using electrical field stimulation (EFS), we determined if a neural circuit exists between the common bile duct (CBD) and the SO in anaesthetized Australian brush-tailed possums. Methods: The gallbladder, cystic duct or CBD were subjected to EFS with a stimulating electrode. Spontaneous SO phasic waves were measured by manometry. Results: EFS at sites on the distal CBD (12,20 mm proximal to the SO), but less commonly at more proximal CBD, evoked a variety of responses consisting of an excitatory and/or inhibitory phase. Bi-phasic responses consisting of an excitation followed by inhibition were the most common. Tri-phasic responses were also observed as well as excitation or inhibition only. These evoked responses were blocked by topical application of local anaesthetic to the distal CBD or transection of the CBD. EFS at sites on the gallbladder body, neck or cystic duct did not consistently evoke an SO response. Pretreatment with atropine or guanethidine reduced the magnitude of the evoked response by about 50% (p<0.05), pretreatment with hexamethonium had no consistent effect and pretreatment with a nitric oxide synthase inhibitor increased the response. Discussion: A neural circuit(s) between the SO and the distal CBD modulates SO motility. Damage to this area of the CBD during bile duct exploration surgery could adversely affect SO motility. [source] Handling of biliary complications following laparoscopic cholecystectomy in the setting of Tripoli Central HospitalHPB, Issue 3 2002A Elhamel Background Laparoscopic cholecystectomy (LC) has an increased incidence of bile duct injury and bile leak when compared with open cholecystectomy. This study reviews management of these complications in a general hospital setting. Data collected from patients diagnosed and treated in one surgical unit for biliary complications after LC between 1992 and 1996 were analysed. Method A total of 14 patients were examined. Diagnosis was defined mainly by Endoscopic retrograde cholangiopancreatography (ERCP) and undetected choledocholitiasis was discovered in association with two of these complications. 43% of patients presented after LC with early postoperative bile leak or jaundice due to partial or complete bile duct excision or slippage of clips from the cystic duct. 57% presented with late biliary strictures. Thirteen patients were treated surgically, with biliary reconstruction (11 patients), direct repair (one) and cystic duct ligation in combination with clearance of bile duct from large multiple stones (one). One patient, who had clip displacement from cystic duct in combination with misplaced clip on right hepatic duct, was treated elsewhere. Postoperatively, one patient developed anastomotic leak and another died from sequellaie of bile duct transection requiring staged operations. Conclusions It is concluded that, in an environment similar to that where the authors had to work, LC should be performed in hospitals with facility to perform ERCP or when access for this technique is available in a nearby institution. Early recognition and immediate management of biliary injuries is dependent on individual resources and circumstances but, if required, consultation with colleagues or referral of patients with suspected or established biliary complications should not be delayed. [source] | |||||||||||||||||||||||||||||||||||||