Effect of repeated transcatheter arterial embolization on the survival time in patients with hepatocellular carcinoma. An analysis by the Cox proportional hazard model.

One hundred fifty-eight patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) as repeatedly as possible. Survival rates at the end of the first, second, and third year were 76.5%, 54.5%, and 41.1%, respectively. In 142 patients with repeated TAE, a significantly increased number of patients with complete necrosis of tumor was observed after repetition of the therapy. Adjusting the imbalance in prognostic factors among patients by using Cox proportional hazard model, it proved that the best response during the repeated therapy, rather than the first response, was significantly associated with survival period of the patients. Aside from the factor of response to the treatment, tumor size was the worst prognostic factor at the time when diagnosis was made. Other significant factors were portal vein invasion by HCC and bilirubin. The survival period of patients with HCC treated by repeated TAE was, therefore, affected by cancer factors, liver cirrhosis factors, and therapy-responsiveness factors. It is concluded that even if complete necrosis of tumor is not obtained after the first trial, repetition of TAE is an effective measure for prolonging of survival time in patients with HCC.     

Theophylline disrupts diurnal rhythms of humoral factors with loss of meal cyclicity

To test the possibility that theophylline induced circadian disappearance of food intake might depend upon rhythmic disruption of blood glucose, insulin and free fatty acids (FFA), theophylline was administered chronically. This markedly lengthened postprandial intermeal intervals during the dark, and induced approximately identical intermeal intervals and identical meal sizes in the light and dark periods. In contrast to the clear light-dark dependent oscillations of serum glucose, insulin and FFA in the controls, the theophyllinized rats lost circadian fluctuation of each of these three chemical substances. Further, theophyllinized rats, unlike controls, had no time-dependent fluctuation in the levels of these substances at ? 120, ?60 or ?15 min preceding the onset of the first meal before the dark. These findings, together with previous reports, explain the disappearance of nocturnal feeding rhythm in theophyllinized rats in terms of functional destruction of circadian regulation in the hypothalamus which modulate the production of chemical determinants of food intake.     

Hepatoblastoma in an 82-year-old man. An autopsy case report

An autopsy case of adult hepatoblastoma is presented. The patient was an 82-year-old male with chronic hepatitis of 7 years' duration. The liver tumor was detected 6 months before death. Autopsy revealed a large hepatic tumor occupying about 80% of the entire liver. Histologically, the tumor showed typical features of mixed epithelial- and mesenchymal-type hepatoblastoma. The epithelial component consisted of fetal and embryonal cell types. The mesenchymal component showed primitive spindle-shaped cells with various degrees of cellularity. Chondroid areas and a few foci of osteoid formation were also present.     

Differential contribution of the FcRγ chain to the surface expression of the T cell receptor among T cells localized in epithelia: analysis of FcRγ-deficient mice

The function of the Fc receptors γ chain (FcR_γ) for the expression of the T cell receptor (TCR) complex and for T cell development, especially for T cells localized in epithelia, was investigated by analyzing FcR_γ-deficient mice. In wildtype mice, CD8αα⁺β^?TCRαβ⁺ T cells of intestinal intraepithelial lymphocytes (i-IEL) utilized CD3ζ homodimers and ζ-FcR_γ heterodimers, whereas CD8α α⁺β^?TCR_γδ⁺ i-IEL used ζ-FcR_γ and FcR_γ homodimers in the TCR complex. On the other hand, these T cells in FcR_γ-deficient mice contained only ζ homodimers. The surface expression of the TCR complex was reduced in CD8αα⁺β^?i-IEL and dendritic epidermal T cells (DETC) in these mice, whereas the development of these T cells was normal. The degree of reduction appeared to depend on the expression level of FcR_γ. In contrast to these populations, TCR_γδ⁺ intraepithelial T cells in reproductive organs (r-IEL) were dramatically decreased, suggesting that the development of r-IEL is FcR_γ-dependent, probably due to the predominant usage of FcR_γ homodimers in the TCR complex. These results indicate that the FcR_γ chain contributes differently to the TCR expression and to the development of T cells localized in epithelia.     

Favorable efficacy of long-term lamivudine therapy in patients with chronic hepatitis B: an 8-year follow-up study

The long-term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7-8.7 years). The rates of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow-up. Our results suggest that long-term lamivudine therapy improves long-term prognosis, especially when additional treatment for breakthrough hepatitis is used.     

Feeding suppression induced by intra-ventricle III infusion of 1,5-anhydroglucitol

1,5-Anhydroglucitol (1-DG) has been known as an antimetabolic glucose analogue. Using gas chromatography, 1-DG was found to be physiologically present in rat serum. In order to investigate its direct and long-term effects on feeding, 1-DG was infused during the light period into the rat third ventricle in doses of 3.0, 6.0 and 12.0 mumol/rat. Its effects were then compared to those of similarly applied 2-deoxy-D-glucose (2-DG). Following initial hyperphagia, both of these glucose-analogues produced suppressive effects on feeding during the subsequent day throughout the light and dark periods. On the third day after 2-DG injection reduction of feeding did not recover completely to the pretreatment baseline levels, but it did recover after 1-DG. Both 1-DG and 2-DG caused linear dose-related hypophagia, with the slope for 1-DG being about half of that for 2-DG. It is suggested that the delayed hypophagia which followed the initial hyperphagia produced by deoxyglucose was a result of sustained inactivation of the Na-pump due to intracellular ATP deficiency caused by accumulation of deoxy-glucose-6-phosphate.     

Factors contributing to ribavirin dose reduction due to anemia during interferon alfa2b and ribavirin combination therapy for chronic hepatitis C

Background Recent studies indicate that combination therapy with ribavirin and interferon alfa2b (IFN2b) is effective for chronic hepatitis C virus (HCV) infection. However, reversible hemolytic anemia is a common side effect of this therapy.Methods We determined those factors that contribute to ribavirin dose reduction due to anemia during this treatment by using multiple logistic regression analysis in Japanese patients. The study included 123 patients with chronic hepatitis C (85 male, 38 female; mean age, 50 years; range, 20–70 years), who received 24-week combination therapy. All patients were treated with IFN2b daily for 2 weeks, followed by three times weekly dosing for 22 weeks, with oral ribavirin twice daily, at a total daily dose of 600 or 800mg.Results Of the 123 patients, 34 patients required dose reduction of ribavirin, and 78 patients required no dose reduction. Overall, 20 patients discontinued. On univariate analysis, reduction of the ribavirin dose correlated significantly with pretreatment hemoglobin (Hb) levels of less than 14g/dl, female sex, and patient age 55 years or older. On multivariate analysis, pretreatment Hb of less than 14g/dl level and age 55 years or older were significantly associated with ribavirin dose reduction. The hazard ratios were 3.56 (95% confidence interval [CI], 1.48–8.53) for pretreatment Hb levels of less than 14g/dl, and 2.50 (95% CI, 1.05–5.94) for age 55 years or more.Conclusions Because patient age of 55 years or more, and Hb levels of less than 14g/dl are significant factors that influence ribavirin-induced hemolytic anemia, more careful monitoring is necessary during combination therapy for patients with these risk factors.     

Efficacy and anticarcinogenic activity of interferon for hepatitis C virus-related compensated cirrhosis in patients with genotype 1b low viral load or genotype 2

Background: We assessed the efficacy and anticarcinogenic effects of interferon (IFN) therapy in patients with hepatitis C virus (HCV)-related cirrhosis. Methods: The study subjects were 123 Japanese patients with HCV-related cirrhosis with genotype 1b low viral load or genotype 2 who received IFN from 1989 to 2005 (18 patients continue to receive IFN therapy). They included 81 men and 42 women aged 29-74 years (median, 56 years). Results: Univariate analysis identified four parameters that significantly influenced SVR; viral load (low HCV concentration, P < 0.001), duration of IFN therapy (>/= 52 weeks, P = 0.029), daily dose of IFN (>/= 6 million units, P = 0.018), induction therapy (presence, P = 0.010) and choline esterase (> 1.0 DeltapH, P = 0.037). Multivariate analysis identified viral load (risk ratio = 6.329, P < 0.001) and daily dose of IFN (risk ratio = 2.62, P = 0.042) as two independent parameters thatinfluenced SVR. During the observation period, newly developed hepatocellular carcinoma (HCC) was detected in 22 patients. The rates of development of HCC in patients with SVR were 5.8% at the fifth year and 10.3% at the 10th year, compared with 25.8% at the fifth year and 42.5% at the 10th year in non-SVR patients. Multivariate analysis showed that IFN efficacy (SVR) was the only independent factor of hepatocarcinogenesis (hazard ratio: 0.185, 95% confidence interval: 0.042-0.810, P = 0.025) Conclusion: Among patients with HCV-related cirrhosis, the rate of development of HCC is significantly less in patients with SVR.