Tumor Marker Levels Before and After Curative Treatment of Hepatocellular Carcinoma as Predictors of Patient Survival.

BACKGROUND: α-fetoprotein (AFP) is used as a marker for hepatocellular carcinoma (HCC), which is influenced by hepatitis. Protein-induced vitamin K absence or antagonist II (PIVKA-II) is a sensitive diagnostic marker. Changes in these markers after treatment may reflect curability and predict outcome. METHODS: We conducted an analysis of prognosis in 470 HCC patients who received curative treatments, and examined the relationship between changes in AFP and PIVKA-II levels after 1 month of treatment in 156 patients. Subjects were divided into three groups according to changes in both levels: (1) normal (L) group before treatment, (2) normalization (N) or (3) decreased but still above normal level or unchanged (ANU) group after treatment. RESULTS: High AFP and PIVKA-II levels were significantly associated with poor tumor-free and overall survival. The presence of large size and advanced stage were significantly associated with prevalence of DU group. Overall survival in the AFP-L group was significantly better than that of other groups and overall survival in PIVKA-II-L and N groups were significantly better than that of the PIVKA-II-ANU groups. The combination of changes in the AFP- ANU and PIVKA-II- ANU groups showed the worst tumor-free and overall survivals. Multivariate analysis identified high pre-treatment levels of AFP and PIVKA-II and combination of AFP- ANU and PIVKA-II- ANU as significant determinants of poor tumor-free and overall survival, particularly in patients who underwent hepatectomy. CONCLUSION: We conclude that high levels of AFP or PIVKA-II after treatment for HCC did not sufficiently reflect curative efficacy of treatment and reflected a poor predictor of prognosis in HCC patients

Three-dimensional echocardiographic assessments of exercise-induced changes in left ventricular shape and dyssynchrony in patients with dynamic functional mitral regurgitation.

Aims: Left ventricular (LV) shape and LV dyssynchrony are two cofactors associated with functional mitral regurgitation (MR) in patients with heart failure. Both can be accurately examined by real-time three-dimensional echocardiography (3DE). We examined the relationship between dynamic MR and exercise-induced changes in LV shape and synchronicity using 3DE. Methods and results: Fifty patients with systolic LV dysfunction underwent 2D and 3D quantitative assessment of LV function, shape, and synchronicity at rest and during symptom-limited exercise test. According to the magnitude of change in MR, patients were divided into EMR group (15 patients, 30%), if the degree of MR increased during test, and NEMR group. During exercise, the changes in LV volumes and ejection fraction were similar in both groups, whereas changes in mitral valvular deformation parameters, in LV sphericity index, and in the extent of LV dyssynchrony were more pronounced in the EMR group. At rest, only the 3D sphericity index could distinguish the two groups. By stepwise multiple regression model, dynamic changes in the systolic dyssynchrony index, sphericity index, and coaptation distance were associated with dynamic MR (r2 = 0.45, P = 0.012). Conclusion: Dynamic MR during exercise is related to the 3D changes in LV shape and in LV synchronicity

Autoantibodies against the specific epitope of human tropomyosin(s) detected by a peptide based enzyme immunoassay in sera of patients with ulcerative colitis show antibody dependent cell mediated cytotoxicity against HLA-DPw9 transfected L cells

BACKGROUND AND AIMS—Recent studies suggest that tropomyosin (TM) may act as a putative autoantigen in ulcerative colitis (UC). Recently, we identified, by computer homology analysis, a specific peptide (HIAEDADRK) in human TM that can bind to HLA-DPw9. The aim of this study was to investigate the presence of autoantibodies against this peptide in UC.
METHODS—Antibodies were measured by ELISA with a synthetic peptide in 20 healthy volunteers, 48 patients with UC, 26 with Crohn's disease (CD), eight with primary sclerosing cholangitis (PSC), and six with primary biliary cirrhosis (PBC). The functional significance of antibodies was investigated by antibody dependent cell mediated cytotoxicity (ADCC) against DPw9 transfected L cells using a standard( 51)Cr release assay.
RESULTS—Optical density values (mean (SD)) of sera from patients with UC (1.40 (0.52)) and PSC (1.65 (0.12)) were significantly higher than those from healthy volunteers (0.32 (0.28)) (p<0.05), CD (0.50 (0.34)) (p<0.05) and PBC (0.14 (0.09)) (p<0.05). Values in UC decreased with clinical improvement. The ADCC activity of UC sera correlated well with antibody titre against this synthetic peptide.
CONCLUSIONS—Anti-TM antibody was detected in UC sera by a specific peptide based ELISA with high reproducibility. This peptide may be an antigenic epitope of TM involved in the immunopathogenesis of UC and, perhaps, PSC.


Keywords: tropomyosin; antibody dependent cell mediated cytotoxicity; HLA-DPw9; ulcerative coliti

Aberrant crypt foci: endoscopic assessment and cell kinetics characterization

Abstract Background and aims Aberrant crypt foci (ACF) are preneoplastic lesions in animal models of colorectal cancer. The aim of the study is to investigate if ACF are involved in human colorectal carcinogenic process and if they can be helpful in predicting the presence of a colorectal neoplasia. Methods The study included, between 2003 and 2005, 182 patients, 62 with adenoma, 55 with colorectal carcinoma, 53 without colorectal lesions, and 12 with nonneoplastic mucosal polyps. The number of rectal ACF was determined by colonoscopy. Proliferation and apoptosis indexes were evaluated by immunohistochemistry in rectal ACF, in normal rectal mucosa, and in carcinomatous tissue. Results The mean number of rectal ACF in patients with rectal neoplasia was 12.64, significantly higher than in patients with neoplastic lesions elsewhere in the colon (p?=?0.01). The apoptosis index in ACF of patients with colorectal carcinoma or adenoma aged 50 years or older was significantly lower than in younger patients (1.3% vs 2.7%, p?=?0.01) and, in patients with carcinoma, lower than in normal mucosa (1.1% vs 2.1%, p?=?0.002). The proliferation index was significantly higher in ACF of patients with colorectal neoplasia aged less than 50 years than in normal mucosa (10.9% vs 7.7%, p?=?0.02). The apoptosis index in ACF foci of patients with carcinoma (1.1%) was significantly lower than in patients without lesions (2.2%) and than in normal mucosa (2%). The mean number of ACF is significantly higher in patients with polyps larger than 1 cm (11.28 vs 6.27, p?=?0.02). Conclusion Aberrant crypt foci probably precede the appearance of neoplasia and may be helpful in predicting the presence of a colorectal neoplastic lesion