Characteristics of patients with chronic hepatitis C who develop hepatocellular carcinoma after a sustained response to interferon therapy

BACKGROUND: The objective of the current study was to determine the characteristic features of sustained responders who develop hepatocellular carcinoma after treatment with interferon for chronic hepatitis C. METHODS: This study included 3626 patients with chronic hepatitis C who had received interferon monotherapy. Cox proportional hazards analysis was used to compare sustained responders who did and did not develop hepatocellular carcinoma, and nonsustained responders who developed hepatocellular carcinoma in a multicenter, retrospective cohort study. RESULTS: Among 1197 sustained responders, 27 patients developed hepatocellular carcinoma (2.3%). Compared with sustained responders who did not develop hepatocellular carcinoma, patients who developed disease more often were male (P = 0.0212), were older (P = 0.0068), and had advanced-stage histologic disease before interferon therapy (P = 0.0345). Conversely, compared with patients with hepatocellular carcinoma who were not sustained responders, patients who were sustained responders tended to be older at the time of the initiation of interferon therapy (P = 0.0552) and at the time hepatocellular carcinoma was detected (P = 0.0593), and they also were predominantly male (P = 0.0507). The histologic staging and serum aminotransferase levels at the initiation of interferon therapy, the interval to the detection of tumor, and the tumor size showed no significant differences between the two groups. CONCLUSIONS: Sustained responders in the group at high risk for developing hepatocellular carcinoma after interferon therapy were older, more often were male, and had more advanced histologic disease stage. Such patients should be followed carefully periodically for > 10 years after they complete interferon therapy.     

Multicentric Castleman's disease associated with inherited epidermolysis bullosa

Multicentric Castleman's disease (MCD) is a rare disorder characterized by fever, polyclonal hypergammaglobulinemia, and generalized lymphadenopathy. It has three histological characteristics: a recognizable architecture, germinal center abnormalities, and plasmacytosis. Inherited epidermolysis bullosa (EB) is also a rare disorder caused by a genetic defect. We report a 43-year-old patient with dystrophic EB, non-Hallopeau-Siemens recessive type or dominant type, displaying clinicopathologic features of MCD. In addition, his serum interleukin-6, which is thought to be responsible for the clinical symptoms in MCD, was elevated.     

Age-associated prevalence and risk factors of Lewy body pathology in a general population: the Hisayama study

In dementia with Lewy bodies (DLB), the Lewy bodies (LBs) are an essential substrate. Although LB pathology has gained increasing attention as one of the major causes of dementia, little is known about the exact prevalence of LB pathology in the general population. In addition, the pathology of Alzheimer-type dementia (ATD) is frequently associated with DLB. To investigate the prevalence of LB pathology in a community-based population and to evaluate the relationship between LB and ATD pathology, we performed an analysis of 102 consecutive autopsy cases. The survey extended over 2.5 years and autopsy rate was 70.5%. LB pathology was detected using -synuclein immunohistochemistry and was assessed based on consensus guidelines for DLB. ATD pathology was evaluated by both CERAD and NIA-RI criteria. Twenty-nine subjects were clinically demented. LB pathology was present in 23 (22.5%) of 102 cases, and in 12 (41.4%) of the demented subjects. The LB score was not significantly different between DLB cases and non-demented subjects with LB pathology (nd-LB), while the Braak stages were significantly different between the two groups. Prevalence of LB pathology constantly increased with age. DLB cases accompanying severe ATD pathology showed more rapid increase of LB scores than did DLB cases without severe ATD pathology. Moreover, DLB cases with severe ATD pathology had poorer prognoses than those without severe ATD pathology. Our results suggested that aging and severe ATD pathology have a strong effect on the evolution of LB pathology.     

Predictive factors for remission and death in 73 patients with autoimmune hepatitis in Japan

The prognosis of patients with autoimmune hepatitis (AIH) has not been clearly defined. The aim of this study was to define the prognostic factors of AIH in a population with long-term follow-up in Japan. Seventy-three patients who were diagnosed as having type 1 AIH between January, 1972 - August, 1999 were enrolled in this study. Initial treatment included prednisolone (PSL) (n=62), other drug regimens (n=7), and none (n=4). We examined the relation between several factors obtained at diagnosis in relation to disease activity found at the final observation point (January, 2000 - April, 2000). Multivariate logistic regression and Cox regression were used for statistical analysis. During the observation period, 8 patients died of the following: hepatic failure (n=4), hepatocellular carcinoma (n=1), severe infection (n=1), and unknown causes (n=2). At the end point, the number of patients in complete remission was 13, those with a normal alanine aminotransferase (ALT) level requiring some treatment was 35, and those with an abnormal ALT level despite medication was 17. Factors related to remission were total bilirubin (TB) (Odds ratio, 0.87), and immunoglobulin G (IgG) (Odds ratio, 1.00). Factors related to death were the aspartate aminotransaminase (AST)/ALT ratio (Odds ratio, 11.67) and response to initial PSL regimen (Odds ratio, 0.03). The results of this study show an importance of achieving a good PSL response at onset, and that initial TB, the AST/ALT ratio, and IgG levels are useful for therapeutic strategy.     

Combination chemotherapy with irinotecan and ifosfamide as second-line treatment of refractory or sensitive relapsed small cell lung cancer: a phase II study

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m(2)) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m(2)) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42-77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0-2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8-64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3-4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0-1 and sensitive cases with only one metastatic site.     

A digital method of sperm immobilization test: comparison to the conventional method

Antisperm antibodies have been found in infertile patients and those causing immobilization of sperm are considered to be closely related to unexplained infertility. These antibodies are usually identified by a sperm immobilization test which involves counting motile sperm under microscope. This test is subjective as it relies on the judgement of the examiner with respect to sperm motility. In this study, we analyzed motile sperm by a digital method using Sperm Quality Analyzer. The results were compared with those obtained by the conventional method. We found that the two methods yielded identical results, with 14 of 66 samples tested being positive and 52 negative for sperm immobilizing antibodies. These results show that the digital method is objective and of value in the measurement of motile sperm in determination of sperm immobilizing antibodies.     

Microglial ecto-Ca(2+)-ATPase activity in a rat model of focal homologous blood clot embolic cerebral ischemia: an enzyme histochemical study

Post-ischemic changes in ecto-Ca(2+)-ATPase activity in microglia and the infarcted tissue were studied in a rat model of focal embolic cerebral ischemia using an enzyme histochemical method. Ecto-Ca(2+)-ATPase activity was observed in whole brains in non-operated and sham-operated control animals. In addition, this enzyme activity was determined to be localized in ramified microglia. At 30 min after ischemia, non-microglial ecto-Ca(2+)-ATPase activity in the infarcted tissue slightly decreased and continued to decrease thereafter. The ecto-Ca(2+)-ATPase activity in microglia did not appear changed at this time. The decrease of enzyme activity in the infarcted tissue made it much easier to clearly observe ecto-Ca(2+)-ATPase-positive microglia. The enzyme activity of microglia in the ischemic area began to decrease 2 or 4h after embolization and remarkably decreased, except in the perinuclear cytoplasm, apical parts of the processes, and several parts along the processes, 8h after ischemia. By 12h after onset of embolization, the enzyme activity of microglia and infarcted tissue had almost completely disappeared. Ecto-Ca(2+)-ATPase of microglia is likely to play an important role in the metabolism of extracellular nucleotides in the ischemic area immediately after the onset of embolization by means of ecto-enzymes. Thus, the findings of the present study suggest that microglia might serve to protect the infarcted tissue in the ischemic brain.