Cholangiocytes (epithelial cells lining the intra- and extrahepatic bile ducts) and hepatocytes are two major components of liver epithelia. Although cholangiocytes are less numerous than hepatocytes, they are involved in both bile secretion and diverse cellular processes such as cell-cycle phenomena, cell signaling, and interactions with other cells, matrix components, foreign organisms, and xenobiotics. Cholangiocytes are also targets in several human diseases including cholangiocarcinoma, primary sclerosing cholangitis, autoimmune cholangitis, and vanishing bile-duct syndrome. The rapid advances in experimental biology technologies are greatly expanding interest in and knowledge of the physiology and pathophysiology of cholangiocytes. This review focuses on the progress of in vivo and in vitro experimental models in elucidating the physiologic functions of cholangiocytes and the pathophysiology of various cholangiopathies. The following aspects are reviewed: isolation of cholangiocytes from the liver and their heterogeneity, various culture systems, establishment of cholangiocyte cell lines, isolation and usage of intrahepatic bile-duct units, three-dimensional modeling of the bile duct, experimental models for inducing cholangiocyte proliferation, and various cholangiopathies such as cholangiocarcinoma, primary sclerosing cholangitis, and autoimmune cholangitis.
Animals ; Bile Duct Diseases/etiology ; Bile Ducts/*cytology/physiology/*physiopathology ; Disease Models, Animal ; Epithelial Cells/metabolism/physiology ; Humans ; Imaging, Three-Dimensional ; Mice ; Models, Animal

The most commonly associated anomalies in patients with extrahepatic biliary atresia are cardiovascular, digestive and splenic defects. Of the cardiovascular anomalies, there are very few reports of biliary atresia with cardiomyopathy. We report the first case of a child with extrahepatic biliary atresia and restrictive cardiomyopathy. The patient was a 13-month-old boy diagnosed with extrahepatic biliary atresia at the age of 2 months, when he underwent laparotomy for definite diagnosis.Hepatic portoenterostomy was performed after confirmative cholangiogram. Recently, he developed severe cough and dyspnea, and his respiratory symptoms worsened. Chest radiograph showed cardiomegaly. Two- dimensional echocardiography showed marked biatrial enlargement. On M- mode echocardiogram, a slight increase in left ventricular dimension was seen in early diastole with a relatively good left ventricular function. Mitral inflow Doppler tracing showed an increased E-velocity (1.1 m/sec) with decreased deceleration time (75 m/sec), and increased E/A ratio (0.33). He was diagnosed as having restrictive cardiomyopathy with characteristic echocardiographic features.
Bile Ducts, Extrahepatic/*abnormalities ; Biliary Atresia/*complications/physiopathology/radiography/ultrasonography ; Cardiomyopathy, Restrictive/*complications/physiopathology/radiography/ultrasonography ; Human ; Infant ; Lung/radiography ; Male ; Radiography, Thoracic

OBJECTIVETo observe the occurrence and progression of liver fibrosis induced by pig serum exposure and bile duct ligation, and analyze the relationship between hepatic inflammation and liver fibrosis.

METHODSChronically immune-mediated liver fibrosis was induced in rats by weekly injection of pig serum (IPS) into the peritoneal cavity at 3 ml/kg for 12 weeks. Cholestatic fibrosis was induced by common bile duct ligation (BDL). The Knodell score was used to evaluate the histological changes in the liver, and immunohistochemistry was performed using anti-SMA, anti-ED1, anti-CK7, and anti-CD45 antibodies. Quantitative real time PCR (qPCR) analysis was employed to quantify the mRNA expression of the genes related to inflammation, including interleukin-1beta (IL-1beta), IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, regulated upon activation normal T cell expressed and secreted (RANTES), transforming growth factor-beta, platelet-derived growth factor A, as well as the genes associated with fibrogenesis, namely collagen 1, alphaSMA, MMP-9 and TIMP-1.

RESULTSKnodell scores for periportal necrosis, intralobular degeneration and focal necrosis, and portal inflammation were all significantly higher in the BDL group than in the IPS group (P<0.01), whereas the scores for fibrosis was higher in the IPS group (P<0.05). Immunohistochemistry showed obvious inflammation with numerous alphaSMA-positive cells in the liver of the rats in BDL group; the liver of the rats in IPS group showed numerous alphaSMA-positive myofibroblasts with limited inflammatory cell infiltration. qPCR demonstrated a significant up-regulation of the genes related to extracellular matrix remodeling such as collagen 1 (P<0.01), alphaSMA (P<0.01), MMP-9 (P<0.01) and TIMP-1 (P<0.01) in the rat liver in IPS group compared with those in the normal control group, and the mRNA expressions of the inflammation-related cytokines, except for RANTES, were comparable with those in the control. In contrast, the BDL group showed a significant up-regulation of all the pro-inflammatory genes examined with also increased expression of the fibrogenesis-related genes (P<0.05).

CONCLUSIONLiver fibrosis induced by IPS is characterized by active ECM remodeling in the absence of obvious inflammation, indicating that chronic development of liver fibrosis can be independent of active hepatic inflammation. BDL-induced liver fibrosis highlights obvious inflammation and fibrous proliferation in the liver.

Animals ; Bile Ducts ; surgery ; Cholestasis ; complications ; physiopathology ; Ligation ; Liver Cirrhosis, Experimental ; etiology ; immunology ; pathology ; Male ; Rats ; Rats, Inbred F344 ; Serum ; immunology ; Swine

OBJECTIVETo explore the clinical and histopathological features of primary biliary cirrhosis (PBC).

METHODSThe clinical, laboratory, as well as histological features of 27 cases of PBC were retrospectively analyzed.

RESULTSThe male to female ratio was 1:8 (3:24), aged from 22 to 69 years. The main clinical manifestations included: fatigue (62.9%, 17/27), jaundice (59.2%, 16/27) and pruritus (29.6%, 8/27), with all of patients having markedly elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase and 95.8% (23/27) of the patients being positive for anti-mitochondrial antibody (AMA). The main histopathological changes were: necroinflammation of interlobular bile ducts (100%, 27/27), lymphocyte aggregation or lymphocyte follicles (15%, 4/27), granuloma (26%, 7/27), decreased number of interlobular bile ducts and smaller bile duct proliferation (55%, 15/27), feathery degeneration of hepatocytes (59%, 16/27); bilirubinostasis in hepatocytes and/or canaliculi (52%, 14/27); fibrosis and distortion of lobules (26%, 7/27), pseudolobular formation (11%, 3/27).

CONCLUSIONSThe main clinical features of PBS are fatigue and pruritus, markedly elevated phosphatase and gamma-glutamyl transpeptidase, and positive AMA with or without jaundice. Its histopathological hallmarks are (1)necroinflammmation and ductopenia involved mainly in interlobular bile ducts; (2)lymphocyte aggregation, granuloma formation and bile ductular proliferation in the portal area; and (3)feathery degeneration of hepatocytes.

Adult ; Aged ; Bile Ducts, Intrahepatic ; Fatigue ; Female ; Hepatocytes ; Humans ; Liver Cirrhosis, Biliary ; physiopathology ; Male ; Middle Aged ; Mitochondria ; Pruritus ; Young Adult ; gamma-Glutamyltransferase

We describe here a patient who obtained a good analgesic effect with high-dose fentanyl patches for controlling cancer pain. A 52-year-old man was referred to our hospital because of severe cancer pain that was 7/10 on a numeric rating scale (NRS). He had been diagnosed with locally advanced cholangiocarcinoma 3 months previously. We prescribed weak opioids and an antidepressant, but his pain was not relieved. We introduced strong opioids (transdermal fentanyl patches for the background pain and a short-acting opioid for the breakthrough pain) and his pain was tolerable on 250 microg/hr of fentanyl patches for 3 months. With time, however, his pain intensity became worse and this reached up to 8/10 to 9/10 on the NRS. Percutaneous transhepatic biliary drainage was performed, which did not relieve his pain. We increased gradually the dose of transdermal fentanyl to 1,050 microg/hr (20 patches). At this dose, the patient was mentally alert, with good pain control (NRS 2/10 to 3/10) and no exacerbation of side effects. To the best of our knowledge, we report here on the highest dose of transdermal fentanyl that has been successfully used for treating a patient suffering from visceral cancer pain.
Administration, Cutaneous ; Analgesics, Opioid/administration & dosage ; Bile Duct Neoplasms/*drug therapy ; *Bile Ducts, Intrahepatic ; Cholangiocarcinoma/*drug therapy ; Fentanyl/*administration & dosage ; Humans ; Male ; Middle Aged ; Pain/*drug therapy/physiopathology ; Pain Measurement

No abstract available.
Bile Ducts/physiopathology ; Biliary Tract Diseases/*diagnosis/radiography/therapy ; Cholangiopancreatography, Endoscopic Retrograde ; Constriction, Pathologic/therapy ; Hepatitis B, Chronic/diagnosis ; Humans ; Liver Neoplasms/diagnosis/therapy ; Liver Transplantation ; Male ; Middle Aged ; *Stents

Betacoronavirus ; isolation & purification ; pathogenicity ; Bile Acids and Salts ; metabolism ; Bile Ducts, Intrahepatic ; pathology ; virology ; Cell Culture Techniques ; Coronavirus Infections ; complications ; pathology ; Cytokine Release Syndrome ; etiology ; physiopathology ; Cytopathogenic Effect, Viral ; Epithelial Cells ; enzymology ; pathology ; virology ; Humans ; Hyperbilirubinemia ; etiology ; Liver ; pathology ; Organoids ; pathology ; virology ; Pandemics ; Peptidyl-Dipeptidase A ; analysis ; Pneumonia, Viral ; complications ; pathology ; Receptors, Virus ; analysis ; Serine Endopeptidases ; analysis ; Viral Load

OBJECTIVETo study the effect of heme oxygenase-1 (HO-1) on peribiliary vascular plexus (PVP) in rat bile duct ischemia/reperfusion injury.

METHODSTotal 128 male SD rats were randomly divided into saline group (Saline), empty virus group (Adv), induced group (Adv-HO-1) and suppressed group (HO-1 siRNA), and there were 32 rats in each group. Rats were injected using 0.5 ml of saline, empty adenovirus, HO-1 adenovirus and siRNA adenovirus (2×10(9) TU/rat) via the dorsal penile vein 24 hours before surgery. Liver function was analyzed at 1 hour and 1, 7, 14 days after reperfusion. HO-1, hypoxiainducible factor-1α (HIF-1α), stromal cell derived factor-1α (SDF-1α) and vascular endothelial growth factor (VEGF) protein content was analyzed by Western blot. The endothelial progenitor cells (EPCs) ratio in the liver and peripheral blood was detected by flow cytometry. Small vascular around the bile duct was observed by α-smooth muscle actin and von Willebrand factor double immunofluorescence staining.

RESULTSReduced liver injury and higher expression of HIF-1α, SDF-1α and VEGF in the induced group after surgery (q = 5.68-7.52, P < 0.01). EPCs ratio in the liver and peripheral blood was significantly higher in the induced group than saline group (q = 12.14 and 15.26, P < 0.01), and the suppressed group at 7 days after surgery were less than saline group significantly (q = 4.83 and 5.07, P < 0.01). In comparison to the suppressed group, higher density of small vascular around the bile duct was seen in the liver tissue of induced group.

CONCLUSIONSHO-1 can induce the expression of HIF-1α, SDF-1α and VEGF, and mobilize the release of EPCs to the peripheral from the bone marrow. EPCs migrate to the liver and promote damaged PVP repair and regeneration.

Animals ; Bile Ducts ; blood supply ; Chemokine CXCL12 ; metabolism ; Endothelial Cells ; cytology ; Heme Oxygenase (Decyclizing) ; physiology ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Male ; Neovascularization, Physiologic ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Stem Cells ; cytology ; Vascular Endothelial Growth Factor A ; metabolism

Endoscopy plays an important role in the diagnosis and treatment of postoperative complications of gastric cancer. Endoscopic intervention can avoid the second operation and has attracted wide attention. Early gastric anastomotic bleeding after gastrectomy is the most common. With the development of technology, emergency endoscopy and endoscopic hemostasis provide a new treatment approach. According to the specific circumstances, endoscopists can choose metal clamp to stop bleeding, electrocoagulation hemostasis, local injection of epinephrine or sclerotherapy agents, and spraying specific hemostatic agents. Anastomotic fistula is a serious postoperative complication. In addition to endoscopically placing the small intestine nutrition tube for early enteral nutrition support treatment, endoscopic treatment, including stent, metal clip, OTSC, and Over-stitch suture system, can be chosen to close fistula. For anastomotic obstruction or stricture, endoscopic balloon or probe expansion and stent placement can be chosen. For esophageal anastomotic intractable obstruction after gastroesophageal surgery, radial incision of obstruction by the hook knife or IT knife, a new method named ERI, is a good choice. Bile leakage caused by bile duct injury can be treated by placing the stent or nasal bile duct. In addition, endoscopic methods are widely used as follows: abdominal abscess can be treated by the direct intervention under endoscopy; adhesive ileus can be treated by placing the catheter under the guidance of endoscopy to attract pressure; alkaline reflux gastritis can be rapidly diagnosed by endoscopy; gastric outlet obstruction mainly caused by cancer recurrence can be relieved by metal stent placement and the combination of endoscopy and X-ray can increase success rate; pyloric dysfunction and spasm caused by the vagus nerve injury during proximal gastrectomy can be treated by endoscopic pyloromyotomy, a new method named G-POEM, and the short-term outcomes are significant. Endoscopic submucosal dissection (ESD) allows complete resection of residual gastric precancerous lesions, however it should be performed by the experienced endoscopists.
Anastomosis, Surgical ; adverse effects ; Bile Ducts ; injuries ; Constriction, Pathologic ; etiology ; therapy ; Digestive System Fistula ; etiology ; therapy ; Duodenogastric Reflux ; diagnostic imaging ; etiology ; Endoscopy, Gastrointestinal ; methods ; Enteral Nutrition ; instrumentation ; methods ; Female ; Gastrectomy ; adverse effects ; Gastric Outlet Obstruction ; surgery ; Gastritis ; diagnosis ; Gastrointestinal Hemorrhage ; etiology ; therapy ; Hemostasis, Endoscopic ; methods ; Hemostatics ; administration & dosage ; therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local ; surgery ; Postoperative Complications ; diagnosis ; therapy ; Precancerous Conditions ; surgery ; Pylorus ; innervation ; physiopathology ; surgery ; Stents ; Stomach Neoplasms ; complications ; surgery ; Treatment Outcome ; Vagus Nerve Injuries ; etiology ; surgery