Immunohistologic study on the expressions of alpha-fetoprotein and protein induced by vitamin K absence or antagonist II in surgically resected small hepatocellular carcinoma.

Sixty-eight cases of single hepatocellular carcinoma (HCC) with less than 3 cm of diameter were immunohistochemically examined for the expressions of alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist II (PIVKA-II). In cancerous tissues, the expression rate was significantly higher for PIVKA-II (34 cases [50%]) than AFP (21 cases [31%]) (P <.05), suggesting a higher specificity of PIVKA-II to small HCC. Sixteen of the 68 cases (24%) were positive to both AFP and PIVKA-II, and in 8 of the 16 cases, AFP and PIVKA-II expressing areas within a nodule were clearly divided by a fibrous septum. According to histologic grades, PIVKA-II expression was confirmed in 2 of the 15 well-differentiated HCCs, and in the well-differentiated component of 6 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. AFP expression was not found in well-differentiated HCCs, but found in 16 of the 40 moderately differentiated HCCs (40%) and in the moderately differentiated component of 3 of the 12 "nodule-in-nodule"-type well-differentiated HCCs. The positive rate in the tissues was correlated to the serum levels for both AFP and PIVKA-II. In addition, frequency of tissue-PIVKA-II expression was higher than tissue-AFP expression in the cases whose serum protein level was within the normal range. This indicates that AFP and PIVKA-II have different patterns of tissue expression and of secretion to the blood. In comparison with tissue-AFP-negative cases, tissue-AFP-positive HCCs had a larger tumor size, higher frequencies of portal vein invasion and intrahepatic metastasis, a high Ki-67 labeling index, and a lower rate of recurrence-free survival. Thus, tissue-AFP-positive HCCs are suggested to be biologically more malignant than those HCCs that are AFP-negative and PIVKA-II-positive.     

Genotype,serum level of hepatitis C virus RNA and liver histology as predictors of response to interferon-α 2α therapy in Japanese patients with chronic hepatitis C

Abstract: To determine whether pretreatment HCV-RNA level, hepatitis C virus genotypes, alanine aminotransferase and histology correlate with subsequent response to interferon-α therapy or not, serum HCV-RNA levels and genotype were determined by branched DNA signal amplification assay and genotype-specific polymerase chain reaction in 43 patients with chronic active hepatitis C. Response to recombinant interferon-α 2α (504 million units in total) was defined as complete and sustained CR→SR, n=12), complete response followed by relapse (CR→Rel, n=17), and no response (NR, n=10), excluding dropouts (n=4). Patients who showed CR→SR had a lower HCV-RNA level (0.438 × 10⁶ eq/ml) compared to CR→Rel (2.452 × 10⁶ eq/ml, p=0.008) and NR (4.882 × 10⁶ eq/ml, p=0.009). A higher proportion of patients with CR→SR had type 2a HCV (67%) compared to the CR→Rel (28%) and the NR (0%). There was a trend for type 1b hepatitis C virus infection to have higher serum HCV-RNA levels. There was no correlation between pretreatment HCV-RNA level and alanine aminotransferase. However, no relation between pretreatment HCV-RNA level and liver histology was observed; a high proportion of patients with CAH2a showed CR→SR, compared to those with CAH2b (p=0.001). Moreover, the patients with CAH2b who had low level hepatitis C virus viremia did not show CR→SR. These data indicate that pre-treatment serum HCV-RNA levels, genotype and liver histology are good predictors of subsequent response to interferon-α therapy in Japanese patients with chronic hepatitis C virus infection.     

The physical activity patterns of cardiac rehabilitation program participants

PURPOSE: This investigation aimed to examine the physical activity patterns of cardiac rehabilitation program (CRP) participants. METHODS: The investigation enrolled 53 male and 24 female CRP participants between 46 and 88 years of age. By means of a uniaxial accelerometer (Life-Corder), the amount of physical activity (in kilocalories) and the time spent in physical activity at light (<3 metabolic equivalents [METs]), moderate (3 to 6 METs), and vigorous (>6 METs) intensity were evaluated. In addition to these variables, the MET levels for the CRP and non-CRP periods were calculated. RESULTS: The weekly amount of physical activity energy expenditure averaged 1597 +/- 846 kcal/week, and the time spent in light, moderate, and vigorous physical activity averaged, respectively, 375.5 +/- 124.5 minutes, 125.2 +/- 109.4 minutes, and 5.7 +/- 12.8 minutes per week. These levels were significantly lower on non-CRP days than on CRP days: 177 +/- 113 versus 299 +/- 161 kcal/day and, respectively, 49.3 +/- 19.3 versus 59.7 +/- 19.8 minutes, 10.5 +/- 14.6 versus 26.4 +/- 20.4 minutes, and 0.4 +/- 1.7 versus 1.4 +/- 3.0 minutes per day. CONCLUSIONS: These results indicate that the amount of physical activity was generally adequate on CRP days, but failed to reach target levels on non-CRP days. Thus CRP participants, when it is medically appropriate, should be encouraged to incorporate lifestyle physical activity, additional exercise, or both on non-CRP days to supplement their caloric expenditure from CRP exercise sessions.     

Expression of insulin-like growth factor receptors in primary human thyroid neoplasms

The presence of IGF-I receptors was demonstrated in normal and neoplastic tissues of human thyroid. Binding of (125I)IGF-I to thyroid membranes was dependent on time and temperature of incubation, and maximal binding was achieved at 4 degree C and 18 h of incubation. (125I)IGI-I binding was dose-dependently displaced by unlabelled IGF-I; half-maximal inhibition occurred at concentrations of 10-20 milligrams. IGF-II and insulin had relative potencies of 5 and 1% compared with IGF-I. Scatchard analysis of binding data revealed a single class of IGF-I receptors with high affinity (Ka: 1.2-8.6 x 10(9) 1/mol) in normal thyroid tissues. Affinity cross-linking and autoradiography demonstrated the type IIGF receptors. Specific binding of (125I)IGF-1 in thyroid cancer tissues (9.69 +/- 2.07% per 200 micrograms protein; mean +/- SEM, N = 8) was significantly (p less than 0.05) higher than that in the surrounding normal tissues (3.03 +/- 0.35%, N = 8). In contrast there was no difference in the binding between adenoma tissues (4.19 +/- 0.53%, N = 5) and the adjacent normal tissues (2.94 +/- 0.24%, N = 5). The higher IGF-I binding in cancer tissues was due to an increase in the binding capacity without any change in the affinity. The presence of IGF-I receptors suggests a possible role of IGF-I and its receptors in the growth of thyroid cancer cells.     

IgA class antibodies to 2-oxo-acid dehydrogenase complex are not predictive markers of histopathological progression in primary biliary cirrhosis

Although antimitochondrial antibody (AMA) is the characteristic serological feature of primary biliary cirrhosis (PBC), its pathogenic role remains unclear. In our previous study, we reported a positive correlation between immunoglobulin (Ig) A class anti-2-oxo-acid dehydrogenase complex (2-OADC) and histopathological stage. To determine whether the appearance of IgA class anti-2-OADC by immunoblotting represents an early marker of more aggressive disease or whether it is late finding during the disease course of PBC, we tested not only the entire IgA class but also IgA1, IgA2 and secretory IgA class anti-2-OADC in serial serum samples from 15 patients with PBC. During the median observation period of 51 months, four cases showed histopathological progression (from stage 1 to 2, stage 1 to 3, stage 1 to 4 and stage 2 to 4). There was no statistically significant correlation between the above IgA class anti-2-OADCs and histopathological progression. There was no significant correlation between histopathological stages and IgA2 class anti-2-OADC or secretory IgA class anti-2-OADC by immunoblotting. IgA class anti-2-OADC was more frequent in stages 3–4 than in stages 1–2 (p = 0.0049), but IgA1 class anti-2-OADC was more frequent in stages 1–2 than in stages 3–4 (p = 0.0232). Our present study demonstrated that serum IgA class 2-OADC was not a predictive marker of histopathological progression but was associated with the histopathological stage of PBC. Although the IgA class AMA may have a specific pathogenic role for PBC, the discrepant results between IgA and IgA1 class anti-2-OADC should be further assessed to investigate different functional activities depending on their molecular form.     

Recent clinical features of Wilson’s disease with hepatic presentation

Background We carried out this study to evaluate recent clinical features of Wilsons disease (WD) with hepatic presentation, especially in terms of age, degree of liver injury, and association with hepatocellular carcinoma (HCC).Methods Sixteen patients with hepatic manifestations were diagnosed with WD in the period 1976–2003. We divided this period into two periods, past and recent. The diagnosis was based on the presence of Kayser-Fleisher rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after D-penicillamine challenge, and increased hepatic copper concentrations. This retrospective study was done at Ehime University Hospital.Results Four patients, including a pair of siblings, had a family history of WD. Four patients had parental consanguinity. There were 6 patients aged over 40 years in the recent period, whereas no patients in the past period were over 40. Four patients had neurological manifestations. Ten patients had liver cirrhosis and 5 had chronic hepatitis. Two had fatty liver without obesity. All patients in the past period had liver cirrhosis. Three patients with liver cirrhosis were found to have HCC during the follow up. All patients were treated with either D-penicillamine or trientine chloride, or both. However, four patients had to discontinue these agents due to the side effects.Conclusions Recently, the number of patients diagnosed with WD has been increasing, not only in terms of those with classical-type WD but also in terms of elderly patients or patients with non-cirrhotic liver injury such as fatty liver and chronic hepatitis. The various clinical features of WD should be recognized and particular attention should focus on HCC as a complication.