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Intrahepatic Bile Ducts (intrahepatic + bile_duct)
Selected AbstractsNotch2 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] 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] 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] Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ductJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006King-Teh Lee MD Abstract Background and Objectives Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC). Patients and Methods The immunohistochemical method and RT-PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone-containing IHD, and ICC. All the specimens were from hepatic resection. Results The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone-containing IHD and ICC, respectively. Among the specimens of stone-containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT-PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone-containing IHD and ICC, respectively. Conclusion Loss expression of DPC4/Smad4 gene was found both in stone-containing IHD and ICC. Dysplastic epithelium of stone-containing IHD had higher potential for malignant transformation. J. Surg. Oncol. 2006;94:338,343. © 2006 Wiley-Liss, Inc. [source] Onset of Apoptosis in the Cystic Duct During Metamorphosis of a Japanese Lamprey, Lethenteron reissneriTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 7 2010Mayako Morii Abstract A nonparasitic lamprey in Japan, Lethenteron reissneri, stops feeding prior to the commencement of metamorphosis. Resumption of feeding cannot take place due to major alterations in the digestive system, including loss of the gall bladder (GB) and biliary tree in the liver. This degeneration of bile ducts is considered to depend on programmed cell death or apoptosis, but molecular evidence of apoptosis remains lacking. Using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry with an antibody against active caspase-3, we showed that epithelial cells of the cystic duct (CD) and GB became TUNEL-positive by the early metamorphosing stage. Immunohistochemical staining of active caspase-3, a key mediator in the apoptotic cascade, showed that the apoptotic signal was initiated in the region around the CD in the late larval phase. In later stages, active caspase-3-positive epithelial cells were also observed in the large intrahepatic bile duct (IHBD) and peripheral small IHBDs. At the early metamorphosing stage, bile canaliculi between hepatocytes were dilated and displayed features resembling canaliculi in cholestasis. Onset of apoptosis around the CD, which is the pathway for the storage of bile juice, and progression of apoptosis towards the large IHBD, which is the pathway for the secretion of bile juice, may lead to temporary intrahepatic cholestasis. The present study represents the first precise spatial and temporal analysis of apoptosis in epithelial cells of the biliary tract system during metamorphosis of any lamprey species. Anat Rec 293:1155,1166, 2010. © 2010 Wiley-Liss, Inc. [source] Analysis of gene expression patterns in the developing chick liverDEVELOPMENTAL DYNAMICS, Issue 3 2005Masaaki Yanai Abstract The chick embryo has been used widely for studying liver development. However, in the past 30 years, the usage has decreased markedly due to lack of appropriate marker genes for differentiation in the developing chick liver. To use the chick embryo for analyzing the molecular mechanism of liver development, we surveyed marker genes in the developing chick liver by examining the expression pattern of genes that are well-characterized in the developing mammalian liver. By whole-mount in situ hybridization, Fibrinogen - gamma (FIB) expression was first detected at stage 12, specifically in the anterior intestinal portal, and its liver-specific expression persisted in the later stages. Albumin (ALB) expression was first detected at stage 30, when the liver starts maturing. Cytokeratin 19 (CK19) was first detected at stage 37 in the ductal plate of the liver, and its expression continued in the intrahepatic bile ducts derived from the ductal plate. Hex, a transcription factor, is an additional marker of bile duct differentiation. Hence, FIB, ALB, and CK19 expression can be used to trace hepatic induction, maturation, and bile duct differentiation, respectively. Developmental Dynamics 233:1116,1122, 2005. © 2005 Wiley-Liss, Inc. [source] The amazing universe of hepatic microstructure,HEPATOLOGY, Issue 2 2009Valeer J. Desmet An informal review is presented by the author of his 50 years of involvement in practice and research in hepatopathology. Some background for the author's attitude and meandering pathway into his professional career serves as introduction to a short discussion of the main topics of his interest and expertise. Histogenesis of liver cancer was the theme of early work for a Ph.D. thesis, the results of which were lost into oblivion due to local rules and circumstances, but were rescued three decades later. His conclusions about the cells of origin of liver cancer remain concordant with the newer concepts in the field after nearly half a century. Studies in the field of chronic hepatitis became a long saga, involving the first classification of this syndrome by "the Gnomes" in 1968, histochemical investigations of viral antigens, lymphocyte subsets and adhesion molecules, and a quarter century later, the creation of a new classification presently in use. Cholestasis was a broadening field in diagnostic entities and involved the study of liver lesions, comprising pathways of bile regurgitation (including reversed secretory polarity of hepatocytes) and so-called ductular reaction. The latter topic has a high importance for the various roles it plays in modulating liver tissue of chronic cholestasis into biliary cirrhosis, and as the territory of hepatic progenitor cells, crucial for liver regeneration in adverse conditions and in development of liver cancer. Study of the embryology of intrahepatic bile ducts helped to clarify the strange appearance of the ducts in "ductal plate configuration" in several conditions, including some forms of biliary atresia with poor prognosis and all varieties of fibrocystic bile duct diseases with "ductal plate malformation" as the basic morphologic lesion. (HEPATOLOGY 2009;50:333,344.) [source] A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),HEPATOLOGY, Issue 5 2005Markus Moser Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source] Peptide antibiotic human beta-defensin-1 and ,2 contribute to antimicrobial defense of the intrahepatic biliary treeHEPATOLOGY, Issue 4 2004Kenichi Harada Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD-1 and hBD-2 were assayed in specimens of bile. hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic biliary obstruction (EBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with normal hepatic histology. hBD-2 expression was evident in bile ducts exhibiting active inflammation. Serum C reactive protein levels correlated with biliary epithelial expression of hBD-2. Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis. Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined. Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1, or tumor necrosis factor-,. In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexisting component of the biliary antimicrobial defense system. Supplementary material for this article can be found on the Hepatology website (http:/interscience.wley.com/jpages/0270,9139/suppmat/index.html). (Hepatology 2004;40:925-932). [source] Murid herpesvirus-4 induces chronic inflammation of intrahepatic bile ducts in mice deficient in gamma-interferon signallingHEPATOLOGY RESEARCH, Issue 2 2009Babunilayam Gangadharan Aim:, Infection of gamma interferon receptor defective mice with murid herpesvirus-4 also known as murine gammaherpesvirus-68 results in multi-organ fibrosis. In this paper we characterise the pathological changes occurring in the liver in this model. Methods:, Standard immunohistochemistry and in situ hybridisation techniques were used to identify the cellular changes and the presence of virus at different times post infection. Results:, In liver sections from infected gamma interferon receptor defective mice sampled on day 16 to at least day 120, 79% showed proliferating intrahepatic bile ducts associated with a chronic mononuclear cell inflammation. Only 8% of wild type mice showed similar lesions. Coincident with the inflammatory response bile duct epithelial cells were positive for arginase 1. Around day 50 post infection onwards focal fibrotic lesions appeared in approximately 30% of gamma interferon receptor defective mice resulting in destruction of intrahepatic bile ducts. In contrast to the chronic persisting inflammatory response the presence of virus infected cells were only observed between day 12,20 post-infection. Conclusion:, Infection of gamma interferon receptor defective mice with a murine gammaherpesvirus initiates a chronic persisting inflammatory response with a pathological profile similar to the human fibrotic liver disorder Primary Sclerosing Cholangitis. [source] Role of X chromosome defects in primary biliary cirrhosisHEPATOLOGY RESEARCH, Issue 2007Pietro Invernizzi Similar to the majority of autoimmune conditions, primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by a striking female predominance; it is characterized by high titer serum autoantibodies to mitochondrial antigens, elevated serum immunoglobulin M, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. Familiarity and high concordance rates for the disease among monozygotic twins strongly support the role of genetics in the disease. Experimental efforts have been dedicated by our and other research groups to investigate the role of X chromosome abnormalities (i.e. monosomyrates and inactivation patterns) in autoimmunity. Our recent work has demonstrated enhanced X monosomy in women with PBC as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. We will review herein the most recent evidence on the role of the X chromosome in PBC onset and discuss the potential implications. Future developments of these findings will be discussed. [source] Preoperative biliary drainage before resection for cholangiocarcinoma (Pro)HPB, Issue 2 2008Y. NIMURA Abstract Three types of preoperative biliary drainage (BD): percutaneous transhepatic (PTBD), endoscopic (EBD), and endoscopic nasobiliary (ENBD) can be indicated before resection of cholangiocarcinoma. However, three randomized controlled trials (RCTs) have revealed that preoperative PTBD does not improve perioperative results. Other RCTs have revealed that preoperative EBD for malignant obstructive jaundice has no demonstrable benefit and after EBD for hilar cholangiocarcinoma there are highly developed infectious complications. Most patients with distal cholangiocarcinoma undergo pancreatoduodenectomy (PD) without preoperative BD. However, no RCTs have been performed to clarify the safety of major hepatectomy without preoperative BD for cholestatic patients with hilar cholangiocarcinoma. Furthermore, preoperative intrahepatic segmental cholangitis is a prognostic factor in the outcome of major hepatectomy for biliary cancer. Preoperative BD has another purpose in the preoperative management of patients with hilar cholangiocarcinoma. Selective cholangiography via ENBD and/or PTBD catheters provides precise information about the complicated segmental anatomy of the intrahepatic bile ducts and extent of cancer along the separated segmental bile ducts, which contributes toward designing a type of resective procedure. RCTs in biliary cancer patients undergoing major hepatectomy have revealed that bile replacement during external biliary drainage and perioperative synbiotic treatment can prevent postoperative infectious complications. Although preoperative EBD increases the risk of cholangitis, major hepatectomy combined with preoperative biliary drainage, preferably PTBD and/or ENBD, followed by portal vein embolization has been established as a safer management strategy for perihilar cholangiocarcinoma. [source] Primary biliary cirrhosis: an orchestrated immune response against epithelial cellsIMMUNOLOGICAL REVIEWS, Issue 1 2000M. Eric Gershwin Summary: Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis. The serologic hallmark of PBC is the presence of antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex. The mechanisms by which (and if) such antibodies produce liver tissue injury are unknown. However, the presence of these antibodies has allowed detailed immunological definition of the antigenic epitopes, the nature of reactive autoantibodies and the characterization of T-cell responses. Several mechanisms may now be proposed regarding the immune-mediated bile duct damage in PBC, including the possible role of T-cell-mediated cytotoxicity and intracellular interaction between the IgA class of antimitochondrial antibodies and mitochondrial autoantigens. There are major questions which remain unanswered, including, of course, etiology, but also the reasons for female predominance, the absence of PBC in children, the relative ineffectiveness of immunosuppressive drugs, and the specific role of mitochondrial antigens. The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection. [source] Sonographic findings of active Clonorchis sinensis infectionJOURNAL OF CLINICAL ULTRASOUND, Issue 1 2004Dongil Choi MD Abstract Purpose The aim of this study was to document the characteristic sonographic findings of clonorchiasis for the diagnosis of active infection in an endemic area. Methods In a village in northeastern China, residents underwent fecal examinations for detection of Clonorchis sinensis eggs. Shortly thereafter, residents were examined with abdominal sonography. An experienced radiologist performed the sonographic examinations and analyzed the findings. Subjects whose fecal examinations were positive for eggs were considered to have active clonorchiasis; those whose examinations were negative for eggs were used as control subjects. The distinguishing sonographic features of active clonorchiasis were identified by stepwise logistic regression analysis. Results The study population comprised 457 subjects; fecal examinations revealed C. sinensis eggs in 316 and no eggs in 141. Four sonographic findings distinguished subjects with active clonorchiasis from control subjects: increased periductal echogenicity (p < 0.001; R = 0.11; sensitivity, 35%; specificity, 91%), floating echogenic foci in the gallbladder (p < 0.001; R = 0.09; sensitivity, 28%; specificity, 94%), diffuse dilatation of the intrahepatic bile ducts (p < 0.01; R = 0.03; sensitivity, 67%; specificity, 48%), and gallbladder distention (p < 0.05; R = 0.02; sensitivity, 3%; specificity, 100%), in decreasing order of significance. Among these 4 sonographic findings, increased periductal echogenicity and floating echogenic foci in the gallbladder were more significantly associated with active infection than were the other 2. Conclusions Increased periductal echogenicity and floating echogenic foci in the gallbladder were identified as the 2 most significant findings for the sonographic diagnosis of active C. sinensis infection. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 32:17,23, 2004 [source] Pregnancy complicated by Caroli's disease with polycystic kidney disease: A case report and following observationsJOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH (ELECTRONIC), Issue 4pt2 2008Mika Tsunoda Abstract Caroli's disease and Caroli's syndrome are rare congenital disorders characterized by non-obstructive cystic dilatation of the intrahepatic bile ducts. These disorders are often associated with autosomal recessive polycystic kidney disease. A young woman at 11 weeks of gestation was referred to our hospital for proper management of Caroli's disease during pregnancy. Magnetic resonance imaging and laboratory tests revealed Caroli's disease with chronic renal failure caused by polycystic kidney disease. She received diet control, erythropoietin and prophylactic oral antibiotics. Her pregnancy course was uneventful, and she gave birth at 37 weeks of gestation. Thereafter, her renal function gradually worsened. Hemodialysis was begun 5 years after parturition. Though the courses of pregnancies complicated by Caroli's disease or Caroli's syndrome are variable and can include life-threatening conditions, uneventful outcomes can be expected if careful management prevents biliary and renal infection. [source] Expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ductJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006King-Teh Lee MD Abstract Background and Objectives Hepatolithiasis is etiologically related to cholangiocarcinoma. We underwent this study with an attempt to examine the expression of DPC4/Smad4 gene in stone-containing intrahepatic bile ducts (IHD) and intrahepatic cholangiocarcinoma (ICC). Patients and Methods The immunohistochemical method and RT-PCR analysis were used to study the expression of DPC4/Smad4 gene in normal IHD, stone-containing IHD, and ICC. All the specimens were from hepatic resection. Results The immunohistochemical study showed that all specimens from 24 normal IHD had marked expression of DPC4/Smad4 gene, while there was 4.4% (2/46) and 33.3% (3/9) loss of DPC4/Smad4 expression in stone-containing IHD and ICC, respectively. Among the specimens of stone-containing IHD, all the hyperplastic epithelial cells showed normal expression of DPC4/Smad4 gene while dysplastic epithelial cells showed 20% (2/10) loss expression of DPC4/Smad4. The RT-PCR analysis showed that the normal IHD had the highest content of DPC4/Smad4 mRNA, which was threefold and sixfold higher than that of stone-containing IHD and ICC, respectively. Conclusion Loss expression of DPC4/Smad4 gene was found both in stone-containing IHD and ICC. Dysplastic epithelium of stone-containing IHD had higher potential for malignant transformation. J. Surg. Oncol. 2006;94:338,343. © 2006 Wiley-Liss, Inc. [source] Genetic cholestasis, causes and consequences for hepatobiliary transportLIVER INTERNATIONAL, Issue 5 2003Peter L. M. Jansen Abstract: Bile salts take part in an efficient enterohepatic circulation in which most of the secreted bile salts are reclaimed by absorption in the terminal ileum. In the liver, the sodium-dependent taurocholate transporter at the basolateral (sinusoidal) membrane and the bile salt export pump at the canalicular membrane mediate hepatic uptake and hepatobiliary secretion of bile salts. Canalicular secretion is the driving force for the enterohepatic cycling of bile salts and most genetic diseases are caused by defects of canalicular secretion. Impairment of bile flow leads to adaptive changes in the expression of transporter proteins and enzymes of the cytochrome P-450 system involved in the metabolism of cholesterol and bile acids. Bile salts act as ligands for transcription factors. As such, they stimulate or inhibit the transcription of genes encoding transporters and enzymes involved in their own metabolism. Together these changes appear to serve mainly a hepatoprotective function. Progressive familial intrahepatic cholestasis (PFIC) results from mutations in various genes encoding hepatobiliary transport proteins. Mutations in the FIC1 gene cause relapsing or permanent cholestasis. The relapsing type of cholestasis is called benign recurrent intrahepatic cholestasis, the permanent type of cholestasis PFIC type 1. PFIC type 2 results from mutations in the bile salt export pump (BSEP) gene. This is associated with permanent cholestasis since birth. Serum gamma-glutamyltransferase (gamma-GT) activity is low to normal in PFIC types 1 and 2. Bile diversion procedures, causing a decreased bile salt pool, have a beneficial effect in a number of patients with these diseases. However, liver transplantation is often necessary. PFIC type 3 is caused by mutations in the MDR3 gene. MDR3 is a phospholipid translocator in the canalicular membrane. Because of the inability to secrete phospholipids, patients with PFIC type 3 produce bile acid-rich toxic bile that damages the intrahepatic bile ducts. Serum gamma-GT activity is elevated in these patients. Ursodeoxycholic acid therapy is useful for patients with a partial defect. Liver transplantation is a more definitive therapy for these patients. [source] Surgery for biliary atresiaLIVER INTERNATIONAL, Issue 3 2001Ryoji Ohi Abstract: Although the prognosis of biliary atresia has been improved in recent years, particularly in the era of liver transplantation, hepatic portoenterostomy, e.g., the Kasai operation, is still the first line of surgical treatment. Successful hepatic portoenterostomy depends on early diagnosis and operation, adequate operative technique, prevention of postoperative cholangitis, and precise postoperative management. The pathophysiology of the liver and of the intrahepatic bile ducts in this disease is still controversial. [source] Regulation of cholangiocyte proliferationLIVER INTERNATIONAL, Issue 2 2001Gene LeSage Abstract: Intrahepatic bile duct epithelial cells (i.e., cholangiocytes) are the target cells of chronic cholestatic liver diseases (i.e., cholangiopathies), which makes these cells of great interest to clinical hepatologists. This review will focus on "typical" cholangiocyte proliferation, whereas "atypical" (extension of cholangiocyte proliferation into parenchyma), and premalignant "oval" cell proliferation are reviewed elsewhere. The bile duct ligated (BDL) rat model, where most of the known mechanisms of cholangiocyte proliferation have been illustrated, was the first and remains the prototype animal model for "typical" cholangiocyte proliferation. Following a short overview of cholangiocyte functions, we briefly discuss the: (i) in vivo models [i.e., BDL (Fig. 1 and 4), chronic ,-naphthylisothiocyanate (ANIT) or bile acid feeding (Fig. 2), acute carbon tetrachloride (CCl4) feeding and partial hepatectomy; and (ii) in vitro experimental tools [e.g., purified cholangiocytes and isolated intrahepatic bile duct units (IBDU)] that are key to the understanding of the mechanisms of "typical" cholangiocyte growth. In the second part of the review, we discuss a number of potential factors or conditions [e.g., gastrointestinal hormones, nerves, estrogens, blood supply, and growth factors] as well as the intracellular mechanisms [e.g., adenosine 3,,5,-monophosphate (cAMP), and protein kinase C (PKC)] that may regulate "typical" cholangiocyte hyperplasia. Figure 1. Measurement of the number of intrahepatic bile ducts by histochemistry for ,-GT[a specific cholangiocyte marker (1, 3, 27)] in liver sections from normal rats [left] and rats that (immediately following bile duct ligation (BDL)) were infused by osmotic minipumps with 0.2% bovine serum albumin (BSA, control) [middle] or gastrin (2.5 nmol/kg/h) in 0.2% BSA [right] for 1 week. Following BDL [middle], there was a marked increase in the number of ducts as compared to normal rats [left]. Chronic gastrin infusion [right] markedly decreased the number of intrahepatic bile ducts as compared to BSA-treated BDL rats [middle]. Orig. magn., ×125. Reproduced with permission from reference (17). Figure 4. In situ immunohistochemistry for CK-19 [a cholangiocyte-specific marker (3)] in frozen liver sections n=6) from BDL [a] and BDL+vagotomy [b] rats. Note that vagotomy induced a marked decrease in the number of ducts as compared with BDL control rats. Orig. magn., ×125. Reproduced with permission from reference (11). Figure 2. In situ immunohistochemistry for cellular nuclear antigen (PCNA) in liver sections from normal rats [left] and normal rats fed 1% TC [middle] or 1% TLC [right] for 1 week. Chronic feeding of TC [middle] and TLC [right] induced a significant increase in the number of PCNA-positive cholangiocytes as compared with liver sections from normal rats [left]. Reproduced with permission from reference (7). [source] Marked diffuse dilations of the biliary tree associated with intrahepatic calculi, biliary sludges and a mucinous cyst of the pancreatic head in a 99-year-old womanPATHOLOGY INTERNATIONAL, Issue 8 2003Tadashi Terada A 99-year-old woman was admitted to Shizuoka Shimizu Municipal Hospital because of fever and anasarca. Imaging and laboratory tests showed pneumonia, urinary tract infection, and cardiac failure. The patient died 20 days after admission. An autopsy revealed marked diffuse dilations of the biliary tree ranging from the lower common bile duct to intrahepatic bile ducts. Intrahepatic calcium bilirubinate stones and biliary sludges were recognized within the dilated bile ducts. A unilocular cyst (2 cm in diameter) was present in the pancreatic head adjacent to the lower common bile duct, and it appeared to compress the common bile duct. Histologically, the walls of the dilated biliary tree showed proliferation of peribiliary glands, fibrosis, and infiltration of lymphocytes and neutrophils (cholangitis). The lumens of the dilated biliary ducts contained neutral and acidic mucins, fibrinous materials, bacteria, neutrophils, and Aspergillus fungi, in addition to the calculi and sludges. The background liver showed atrophy (400 g). The pancreatic unilocular cyst was composed of mucous columnar cells with a few infoldings, and the pancreas also showed foci of mucinous duct hyperplasia and ectasia; the pathological diagnosis of the cyst was cystic dilations of a pancreatic duct branch (mucinous ductal ectasia or mucinous cyst). Other lesions included aspiration pneumonia, emaciation, atrophy of systemic organs, gastric leiomyoma, serous cystadenoma of the right ovary, and arteriosclerotic nephrosclerosis. The present case suggests that a mucinous cyst of the pancreas may compress the biliary tree and lead to marked diffuse dilations of the biliary tree. Alternatively, the dilations of the bile ducts may be associated with aging or may be of congenital origin. The dilated bile ducts may, in turn, give rise to bacterial and fungal cholangitis and formation of biliary sludges and intrahepatic calcium bilirubinate stones. [source] Spontaneous occurrence of chronic non-suppurative destructive cholangitis and antimitochondrial autoantibodies in MRL/lpr mice: Possible animal model for primary biliary cirrhosisPATHOLOGY INTERNATIONAL, Issue 6 2001Koichi Tsuneyama MRL/MP mice bearing the lymphoproliferative gene lpr (known as MRL/MP- lpr/lpr or MRL/Ipr mice) are known to spontaneously develop severe autoimmune diseases such as glomerulonephritis, arteritis and arthritis at an early stage of their life. They have also been reported to develop severe sialadenitis, suggesting that this mouse could be a model for Sjögren's syndrome. Primary biliary cirrhosis, an autoimmune disease characterized by chronic non-suppurative destructive cholangitis and the occurrence of antimitochondrial antibodies, is frequently associated with Sjögren's syndrome. In this study, we examined whether cholangitis and/or antimitochondrial antibodies occur in this mouse model, using more than 100 young and old MRL/Ipr mice. We frequently found portal inflammation associated with cholangitis of small intrahepatic bile ducts, especially in older mice. There was also infiltration of inflammatory cells (monocytes) as well as CD4-positive T cells. Epithelioid granuloma and bile-duct loss were also occasionally found. These histological features resemble primary biliary cirrhosis. In addition, antimitochondrial antibodies were shown by immunocytochemistry to be present in the sera of MRL/Ipr mice. There is currently no established animal model for primary biliary cirrhosis. Therefore, further studies on MRL/Ipr mice, with respect to pathogenesis of primary biliary cirrhosis, are warranted. [source] Successful liver transplantation in a child with Caroli's diseasePEDIATRIC TRANSPLANTATION, Issue 4 2008Constance Meier Abstract:, CD is a rare autosomal recessive disease, characterized by multifocal cystic dilatation of intrahepatic bile ducts. The course of the disease is characterized by intrahepatic cholelithiasis, recurrent episodes of cholangitis, because of cholelithiasis, hepatic abscesses often ending in death caused by uncontrolled infection. Other conditions such as choledochal cyst and renal cystic disease are frequently associated, and patients have a higher risk for the development of cholangiocarcinoma. Endoscopic drainage of the bile duct is palliative and ineffective. OLT appears to be the treatment of choice. In monolobar cases partial liver resection has been shown to be a curative therapeutic option. We report on the course of disease in a Turkish girl who was diagnosed with CD in the neonatal period. At the age of 8.2 yr, she received OLT and is in good health 57 months post-transplantation. [source] | |||||||||||||