BACKGROUND/AIMS: Maximal duration of intravenous (IV) corticosteroid (CS) treatment and efficacy of cyclosporin A (CsA) have not been clarified for patients with severe ulcerative colitis. We aimed to evaluate and compare the effectiveness of CS and CsA combination therapy with prolonged CS therapy alone in patients with severe UC refractory to initial CS therapy. METHODS: We retrospectively reviewed the medical records of 84 episodes of severe UC in 59 patients between April 1999 and May 2005. RESULTS: Among 84 episodes with IV CS therapy, 45 (53.6%) experienced an early response, while 39 (46.4%) did not respond within 2 weeks. The remaining 36 episodes excluding 3 which underwent colectomy were assigned to either combination therapy of IV CS and CsA or prolonged IV CS treatment alone for additional 2 weeks. Twelve of 16 episodes (75.0%) responded to therapy with combinations of IV CsA and CS, and 16 of 20 episodes (80.0%) to prolonged IV CS treatment alone. There was no statistical difference in response and colectomy rate after 4 weeks between CsA-use group and CsA-non-use group (p=1.00). CONCLUSIONS: These results suggest that CS and CsA combination has no additional benefit over prolonged CS therapy alone in terms of short-term response and that CS can be safely prolonged even after the first 14 days of treatment for severe UC.
Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; Carcinoma, Squamous Cell/*metabolism/pathology ; Cyclin D1/immunology/*metabolism ; Cyclin-Dependent Kinase Inhibitor p16/immunology/*metabolism ; Esophageal Neoplasms/*metabolism/pathology ; Esophagus/*abnormalities/metabolism/pathology ; Female ; G1 Phase ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Tumor Markers, Biological/metabolism ; Tumor Suppressor Protein p53/immunology/*metabolism

Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal ; metabolism ; Antigens, Neoplasm ; immunology ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; diagnosis ; metabolism ; pathology ; Cell Cycle Proteins ; immunology ; metabolism ; Cervical Intraepithelial Neoplasia ; diagnosis ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; DNA Topoisomerases, Type II ; immunology ; metabolism ; DNA-Binding Proteins ; immunology ; metabolism ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; immunology ; metabolism ; Uterine Cervical Neoplasms ; diagnosis ; metabolism ; pathology ; Young Adult

OBJECTIVETo explore the relationship among HBV-associated histopathological indexes, x gene mutations and the methylation status of p16INK4A promoter in liver with chronic hepatitis B virus infection, in order to illustrate their role in p16INK4A hypermethylation and HCC progression.

METHODSTwenty-three cases of surgically resected HBV-associated hepatocellular carcinoma and twenty-five fine needle aspiration biopsy cases of chronic hepatitis B were chosen for this study. The methylation status of the p16INK4A promoter in tumors, their corresponding peritumoral samples and chronic hepatitis B cases was determined by methylation-specific polymerase chain reaction (MSP). EnVision two-step immunohistochemical staining showed the expression of viral antigens in situ. Tissue HBV DNA levels were determined by real-time fluorescence quantitative PCR. Polymerase chain reaction and the direct sequencing method was used for mutation analysis of HBV x gene.

RESULTSIn peritumoral samples (P = 0. 025) and chronic hepatitis B cases (P = 0.029), the expression of HBx protein in methylated groups was all significantly higher than that in unmethylated groups of p16INK4A gene. But in tumors, there was no such significant difference. Other HBV antigens including HBsAg and HBcAg, tissue HBV DNA levels and point mutations of HBV x gene did not show a relationship with the methylation status of p16INK4A gene.

CONCLUSIONThe data suggest that p16INK4A hypermethylation correlated closely with higher HBx expression in precancerous lesions. HBx may play an important role in the early stage of HBV-associated hepatocarcinogenesis via induction of hepermethylation of p16INK4A promoter.

Adult ; Carcinoma, Hepatocellular ; genetics ; metabolism ; virology ; Cyclin-Dependent Kinase Inhibitor p16 ; genetics ; DNA Methylation ; DNA, Viral ; genetics ; metabolism ; Female ; Hepatitis B Core Antigens ; metabolism ; Hepatitis B Surface Antigens ; metabolism ; Hepatitis B virus ; genetics ; immunology ; metabolism ; Hepatitis B, Chronic ; genetics ; metabolism ; virology ; Humans ; Liver ; metabolism ; pathology ; virology ; Liver Cirrhosis ; genetics ; metabolism ; virology ; Liver Neoplasms ; genetics ; metabolism ; virology ; Male ; Middle Aged ; Point Mutation ; Polymerase Chain Reaction ; methods ; Promoter Regions, Genetic ; genetics ; Trans-Activators ; genetics ; metabolism