Correlation of Clinicopathologic Features of Resected Hepatocellular Carcinoma with Hepatitis C Virus Genotype

Clinicopathologic findings in patients with hepatocellular carcinoma complicating hepatitis C virus and outcomes after liver resection were compared between different viral genotypes. One hundred and forty-seven patients with both anti-hepatitis C virus antibody and hepatitis C virus RNA in their sera underwent curative resection for hepatocellular carcinoma in our department between 1991 and 1997. Of these patients, 115 were infected with hepatitis C virus genotype 1b (group 1), and 32 were infected with 2a or 2b (group 2). Clinicopathologic findings and outcomes after operation were compared between the two groups. Alanine aminotransferase activity was significantly higher in group 2 than in group 1. Genotypes did not differ concomitantly with histopathologic features of the carcinoma or adjacent hepatic tissue. Although the tumor-free survival rate did not differ significantly between the two groups, recurrence was not detected during the period beyond 3 years following operation in group 2, while recurrences arose during that period in 16 group 1 patients, most of whom continued to manifest active hepatitis. In 7 of these 16 patients, the recurrent tumors were histologically multicentric in origin. The cumulative survival rate was significantly lower in group 1 than 2. Multivariate analysis indicated that genotype 1b was an independent risk factor for short survival. Patients infected with genotype 1b may have a relatively high risk of ongoing hepatocarcinogenesis and more aggressive progression of associated liver dysfunction, resulting in a poorer outcome than with other genotypes.     

Lasting increase in D1 dopamine receptors in the lateral part of the substantia nigra pars reticulata after subchronic methamphetamine administration

To examine the possible involvement of D₁ dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D₁ receptors labeled with [³H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in K_d in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither K_d nor B_max changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [³H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D₁ receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization.     

Knee – spine syndrome: correlation between sacral inclination and patellofemoral joint pain

 Low back pain is an enormous clinical and public health problem. When we use spinal instrumentation, measurements of spinal and leg alignment in the standing position are thought to be important. Knee joint pain has also become an enormous clinical problem in the increasing elderly population. However, the correlation between spinal alignment, particularly sacral inclination, and knee joint pain is not clear. We examined the correlation between lumbar lordosis, sacral inclination, and patellofemoral joint pain in elderly subjects. Three hundred and ninety-nine people aged 50–85 years were examined. Clinical findings and physical status were determined. Measurements and determination of total lordosis from L1 to S1 and sacral inclination were made from standing radiographs. The knee joints were evaluated by using the standing knee flexion angle, radiographs, and the patellofemoral (PF) joint grinding test. Thirty-nine percent of subjects were excluded because they had definite osteo-arthritis at the femorotibial joints. Fifty-eight percent of the subjects had felt low back pain within the previous 3 months, and 16% of the subjects complained of PF joint grinding pain. Sixteen percent of the subjects showed knee flexion when standing. There was a significant difference in sacral inclination between the groups with and without PF joint grinding pain (P < 0.01). Sacral inclination was approximately 5° less in the knee flexion group. A correlation between sacral inclination and PF joint pain is defined, and its prevalence in the elderly is reported. We speculate that this phenomenon is caused by changing of lumbar alignment. In addition, we think this is a new pathological concept that we call the knee – spine syndrome. Received: July 23, 2001 / Accepted: May 2, 2002     

Elevated level of serum cystatin-C concentration is a useful predictor for myelosuppression induced by methotrexate for treatment of rheumatoid arthritis

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08–5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.     

Successful treatment of refractory enteropathy-associated T-cell lymphoma using high-dose chemotherapy and autologous stem cell transplantation

A 65-year-old woman presented with a 6-month history of abdominal pain and watery diarrhea. Type II enteropathy-associated T-cell lymphoma (EATL) was diagnosed based on the clinical presentation and pathological examination of the tumor. The patient received combination chemotherapy but did not achieve remission. Subsequently, high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) were performed. After these therapies, she achieved complete remission, which has been sustained for 18 months. Although the role of HDT-ASCT for EATL is still controversial, the clinical course of this patient suggests that ASCT can improve the prognosis in some patients with EATL.