Sclerosing cholangitis is a spectrum of chronic progressive cholestatic liver disease characterized by inflammation, fibrosis, and stricture of the bile ducts, which can be classified as primary and secondary sclerosing cholangitis. Primary sclerosing cholangitis is a chronic progressive liver disease of unknown cause. On the other hand, secondary sclerosing cholangitis has identifiable causes that include immunoglobulin G4-related sclerosing disease, recurrent pyogenic cholangitis, ischemic cholangitis, acquired immunodeficiency syndrome-related cholangitis, and eosinophilic cholangitis. In this review, we suggest a systemic approach to the differential diagnosis of sclerosing cholangitis based on the clinical and laboratory findings, as well as the typical imaging features on computed tomography and magnetic resonance (MR) imaging with MR cholangiography. Familiarity with various etiologies of sclerosing cholangitis and awareness of their typical clinical and imaging findings are essential for an accurate diagnosis and appropriate management.
Adult ; Aged ; Aged, 80 and over ; Bile Ducts/*pathology ; Cholangiography/*methods ; Cholangitis/diagnosis/*pathology ; Cholangitis, Sclerosing/*diagnosis/pathology ; Cholestasis/diagnosis/*pathology ; Chronic Disease ; Constriction, Pathologic/diagnosis ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin G/immunology ; Liver/pathology ; Magnetic Resonance Imaging/methods ; Male ; Middle Aged ; Tomography, X-Ray Computed/methods

The main causes of biliary obstruction are stones and cancers. Fascioliasis is a very rare case which causes biliary obstruction. Fascioliasis is a zoonosis caused by Fasciola hepatica which infects herbivores like sheep and cattle. F. hepatica lives in the biliary system or the liver parenchyma of a host. In Korea, the occurrence of this infection in human is very rare and only few cases have been reported. A 32-year-old male presented with upper abdominal pain and jaundice. His laboratory finding revealed elevated liver transaminases. Abdomen CT scan showed mild left intrahepatic bile duct dilatation. On ERCP, adult F. hepatica worms were found and were thus removed. Concurrently, clonorchiasis was diagnosed by stool exam and serologic enzyme-linked immunosorbent assay test. Clonorchiasis was treated with praziquantel. Herein, we report a case of intrahepatic bile duct dilatation due to F. hepatica infection with concurrent Clonorchis sinensis infestation.
Adult ; Animals ; Anthelmintics/therapeutic use ; Benzimidazoles/therapeutic use ; Bile Ducts, Intrahepatic ; Cholangiopancreatography, Endoscopic Retrograde ; Clonorchiasis/complications/*diagnosis/drug therapy ; Clonorchis sinensis/immunology/isolation & purification ; Enzyme-Linked Immunosorbent Assay ; Fasciola/isolation & purification ; Fascioliasis/complications/*diagnosis/parasitology ; Humans ; Liver/enzymology ; Male ; Praziquantel/therapeutic use ; Tomography, X-Ray Computed ; Transaminases/metabolism

Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (K D) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody-dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.
Animals ; Antibodies, Monoclonal/genetics/*immunology ; Antibody-Dependent Cell Cytotoxicity ; Bile Ducts, Intrahepatic/drug effects/immunology/pathology ; CHO Cells ; Cell Adhesion/drug effects ; Cell Proliferation/drug effects ; Cholangiocarcinoma/*drug therapy/immunology/pathology ; Cricetinae ; Disease Models, Animal ; Endocytosis/drug effects ; Humans ; Immunoglobulin G/genetics/*immunology ; Liver Neoplasms/*drug therapy/immunology/pathology ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Neural Cell Adhesion Molecule L1/genetics/*immunology/metabolism ; Protein Binding ; Protein Structure, Tertiary ; Recombinant Fusion Proteins/immunology/metabolism/*therapeutic use

No abstract available.
Autoimmune Diseases/*diagnosis/drug therapy/immunology ; Azathioprine/therapeutic use ; Common Bile Duct/pathology ; Emphysema ; Fibrosis ; Humans ; Immunoglobulin G/blood ; Immunosuppressive Agents/therapeutic use ; Lung/*radiography ; Male ; Middle Aged ; Pancreatitis/*diagnosis/drug therapy/immunology ; Stents ; Tomography, X-Ray Computed

BACKGROUNDThe prevalence of chronic pancreatitis has increased during recent years in Asia-Pacific areas as well as in China. The etiologies vary in different regions and periods. This study aimed to investigate the changing etiologies of chronic pancreatitis within 20 years at Peking Union Medical College Hospital in China.

METHODSRetrospective analysis of the etiologies of 636 cases of chronic pancreatitis at Peking Union Medical College Hospital from 1990 to 2010 was performed. Patients were divided into two groups according to two time periods (1990 - 2000 and 2001 - 2010). Statistical analysis was performed using the chi-square test.

RESULTSThe morbidity rate of chronic pancreatitis in China has recently increased. The main etiology changed from biliary diseases in the 1990s (decreased from 36.8% to 28.1%) to alcohol abuse after the year 2000 (increased from 26.5% to 36.8%). The main etiology of biliary diseases is stones in the cholecyst or bile duct, and the percentage of cholecystitis cases has increased. Autoimmune disease, including autoimmune pancreatitis, has increased quickly and currently accounts for 7.3% of cases because a greater number of autoimmune pancreatitis cases are being diagnosed. Approximately 9.5% of chronic pancreatitis cases are caused by multiple factors such as alcohol abuse and bile duct stones. Other factors include cholecystectomy and acute pancreatitis.

CONCLUSIONSThe main etiology of chronic pancreatitis has changed from biliary disease to alcohol abuse in recent years. Autoimmune factors have also obviously increased.

Adult ; Alcoholism ; complications ; Bile Duct Diseases ; complications ; China ; epidemiology ; Female ; Humans ; Male ; Middle Aged ; Pancreatitis, Chronic ; epidemiology ; etiology ; immunology ; Retrospective Studies ; Risk Factors

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 investigate whether lipopolysaccharide (LPS) stimulates cholangiocyte proliferation via the IL-6/STAT3 pathway in vivo.

METHODSRats were randomized into three groups: LPS group (injected intravenously with LPS 2.5 mg/kg), anti-IL-6 group (injected intravenously with anti-IL-6 0.5 mg/kg 1hr after LPS injection), and control group. At 6, 12, 24, 48 and 72 h after LPS injection, LPS concentration in plasma was detected by kinetic turbidimetric limulus test. IL-6 concentrations in liver homogenate was determinded by ELISA, cholangiocyte proliferation was checked by immunohistochemistry, expression of IL-6 mRNA was quantified by real-time RT-PCR, the level of phophorylated-STAT3 (P-STAT3) protein was analyzed by western blotting.

RESULTSCholangiocytes responded to LPS by a marked increase in cell proliferation, IL-6 secretion and P-STAT3 expression. Anti-IL-6 neutralizing antibody inhibited LPS-induced cholangiocytes proliferation, and decreased levels of IL-6 and p-STAT3.

CONCLUSIONSLPS promotes cholangiocyte proliferation through the IL-6/STAT3 pathway.

Animals ; Antibodies, Monoclonal ; administration & dosage ; Bile Ducts, Intrahepatic ; cytology ; Cell Proliferation ; Epithelial Cells ; cytology ; physiology ; Immunohistochemistry ; Interleukin-6 ; genetics ; immunology ; metabolism ; Lipopolysaccharides ; blood ; pharmacology ; Liver ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; STAT3 Transcription Factor ; metabolism ; Signal Transduction

Amputation neuroma or traumatic neuroma is a tumor-like secondary hyperplasia that may develop after an accidental or surgical trauma. Amputation neuroma of the bile duct has occasionally been reported which occurred in the cystic duct stump late after the cholecystectomy. However, even if the amputation neuroma is suspected in a patient with late-onset jaundice after cholecystectomy, the differential diagnosis from a malignancy is difficult preoperatively. We experienced a case of the amputation neuroma of common bile duct (CBD) developed in a 70-year-old man who presented with a polypoid mass in CBD. He had undergone cholecystectomy 25 years ago and choledochojejunostomy 12 years ago, respectively. We have performed pylorus-preserving pancreatico-duodenectomy (PPPD) under the impression of CBD cancer. He had not been diagnosed of amputation neuroma until having undergone PPPD. We report a case of CBD neuroma mimicking CBD cancer, which was confirmed after PPPD.
Aged ; Common Bile Duct Neoplasms/*diagnosis/radiography ; Diagnosis, Differential ; Humans ; Male ; Neuroma/*diagnosis/pathology/radiography ; Pancreaticoduodenectomy ; S100 Proteins/immunology ; Tomography, X-Ray Computed

Adult ; Aged ; Bile Duct Neoplasms ; blood ; virology ; Biomarkers ; blood ; DNA, Viral ; blood ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; metabolism ; Hepatitis B virus ; genetics ; immunology ; Hepatitis, Viral, Human ; blood ; virology ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Liver ; metabolism ; pathology ; virology ; Male ; Middle Aged

Rats develop strong resistance to re-infection and super-infection by Clonorchis sinensis. The present study investigated the antibodies present in the sera and bile juice of rats that were primary infected and re-infected with C. sinensis. The serum level of specific IgG antibodies, which were elevated 2 wk of the primary infection, peaked at 4 wk and subsequently remained unchanged even during re-infection. The total IgE level in serum increased slowly from 388 ng / ml to 3,426 ng / ml beginning 2 wk after the primary infection, and remained high up to 8 wk but dropped to a normal level (259 ng / ml) after treatment. In resistant re-infected rats, the serum IgE level increased rapidly and peaked within 1 wk, whereas no increase was observed in immunosuppressed rats. The serum level of specific IgA antibodies was elevated beginning 1 wk after infection, and decreased 4 wk after treatment. The total bile IgA level unchanged during the primary infection but increased in treated and re-infected rats. The elevated levels of serum IgE and bile IgA indicate that these immunoglobulins may be correlated with the development of resistance to re-infection by C. sinensis in rats.
Animals ; Antibodies, Helminth/analysis/*blood/*immunology/metabolism ; Bile/*immunology ; Clonorchiasis/blood/*immunology ; Clonorchis sinensis/*immunology/*physiology ; Immunoglobulin A/analysis/blood ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors