Risk Factors of Hepatocellular Carcinoma in Chronic Hepatitis C and Cirrhosis: Special Reference to Laparoscopic Findings

Abstract: It remains unclear whether the hepatitis C virus genotype is associated with the severity and outcome of HCV-related liver disease. The aim of this study was to determine whether hepatitis C virus genotype influenced the risk of developing hepatocelMar carcinoma. Two hundred and sixty nine patients who had chronic hepatitis C and cirrhosis without hepatocellular carcinoma were studied. The stage and activity of hepatitis were determined at laparoscopy and patients were followed up until the development of hepatocellular carcinoma or for a maximum of 16 years. Hepatitis C virus genotypes were determined by a genotyping enzyme-linked immunosorbent assay. A cross-sectional study revealed that the prevalence of hepatitis C virus genotype 1 increased and that of genotype 2 decreased with the progression of liver disease (pc 0.01). A follow-up study using the Kaplan-Meier method showed that hepatocellular carcinoma occurred more frequently in patients with hepatitis C virus genotype 1 (p<0.01), patients with a more advanced disease stage (p<0.01), and patients with reddish markings (p<0.05). Cox multivariate proportional hazards analysis confirmed that these three risk factors were independent. Hepatocellular carcinoma developed more frequently in patients with hepatitis C virus genotype 1 and pre-cirrhosis (stage 3 chronic hepatitis with nodules) or liver cirrhosis, in whom hepatitis showed continued activity and progression. (Dig Endosc 1999; 11: 24–31)     

Relationship between metabolic disorders and relative risk values of brain infarction estimated by protein-conjugated acrolein, IL-6 and CRP together with age

BackgroundWe have recently found that the median relative risk value (RRV) (0–1) of brain infarction estimated by protein-conjugated acrolein (PC-Acro), IL-6 and CRP together with age was in the order silent brain infarction (SBI) (0.80) > carotid atherosclerosis (CA) (0.76) > white matter hyperintensity (WMH) (0.46) > control (0.14). We clarified how metabolic disorders [hypertension (HT), hyperlipidemia (HL) and hyperglycemia (HG)] are correlated with RRV.MethodsThe levels of PC-Acro, IL-6 and CRP in plasma were measured by ELISA. SBI and WMH were evaluated by MRI, and CA was evaluated by duplex carotid ultrasonography.ResultsThe median RRV of metabolic disorders was in the order HT + HG (0.84) > HT + HL (0.73) > HT (0.65) ≈ HG (0.65) > HL (0.61) > HL + HG (0.48) > no metabolic disorder (0.24) > normal (0.11). Correlation with SBI was in the order HT + HG (52%) > HT + HL (42%) > HT (40%) > HG (34%) ≈ HL(33%) > HL + HG (14%) ≈ no metabolic disorder (14%).ConclusionThe results indicate that HT is the most strongly associated factor with SBI among metabolic disorders and that the seriousness of metabolic disorder estimated by RRV was well correlated with SBI.     

Anaplastic oligodendroglial tumors harboring 1p/19q deletion can be successfully treated without radiotherapy

Although anaplastic oligodendroglial tumors are known to be chemosensitive, patients under this diagnosis have been traditionally treated with radiotherapy. To avoid possible neurotoxicity, we prospectively treated patients with anaplastic oligodendroglial tumors harboring 1p/19q deletion, with exclusive procarbazine, ACNU, and vincristine chemotherapy without radiotherapy. Twenty-five patients were enrolled in the study (12 with 1p/19q co-deletion, 2 with 1p mono-deletion, 2 with 19q mono-deletion, and 9 without 1p/19q deletion). The median progression-free survival (PFS) was 50 months for all the patients, and those with tumors harboring 1p/19q deletion were progression free for a significantly longer period than those without the deletion (p=0.0391). The median overall survival (OS) time was not reached in both patient groups with and without 1p/19q deletion (p=0.230), and the 5-year OS rate was 62.2% for all patients. The excellent treatment results warrant a large-scale clinical study to confirm the efficacy of upfront chemotherapy omitting radiotherapy as initial therapy for anaplastic oligodendroglial tumors with 1p/19q deletion.     

Intracranial Metastasis in a Patient with Hepatocellular Carcinoma and Gastric Cancer

A 76-year-old man was referred to our hospital with visual disturbance, weakness of the left upper and lower limbs, and gait disturbance. He had previously received transarterial chemoembolization for hepatocellular carcinoma (HCC) 3 and 10 years ago. When he had received radiofrequency ablation for HCC recurrence 2 years ago, total gastrectomy was also performed for his gastric cancer. Subsequently, sorafenib had been administrated for concomitant lung metastatic tumors. On admission, MRI revealed an intra-axial tumor with perifocal edema. The level of carcinoembryonic antigen, but not alpha-fetoprotein, markedly increased. The tumor was successfully removed by craniotomy and pathological examination revealed that it was composed of adenocarcinoma, which was consistent with the primary gastric cancer. After surgery, his neurological disturbances rapidly resolved. Additional gamma-knife treatment was also performed for another small brain metastasis detected after craniotomy. Subsequently, sorafenib administration was discontinued and S-1 was administered postoperatively. Successful treatment of intracranial metastasis of gastric cancer is important and meaningful, even in patients with multiple primary malignancies.Key words: Multiple primary malignancy, Hepatocellular carcinoma, Gastric cancer, Double cancer, Intracranial metastasis, Surgical resection     

Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by doxorubicin on cerebellar granule neurons in mouse

Cell cycle regulators such as cyclin-dependent kinases (Cdks) and their inhibitors (Ckis) have been reported to be involved in neuronal cell death (NCD) induced by a variety of insults such as ischemia, UV-irradiation, nerve growth factor (NGF)-withdrawal, and anticancer therapeutics. But their precise interactive regulation has still to be unveiled. In the present study, we focused on cell cycle regulators such as Cdk4, p21(WAF1) and p53 to clarify their regulatory mechanisms, using NCD induced by doxorubicin (D-NCD) in mouse cerebellar granule neurons as a model. Doxorubicin induced NCD in a dose-dependent manner, a typical feature of apoptosis as determined by TUNEL assay. Doxorubicin increased the protein expression of p53 in time- and dose-dependent manners. The protein expression of p21(WAF1), a Cki of Cdk4, was stimulated by doxorubicin at low concentrations, but it disappeared at high concentrations. Doxorubicin activated the kinase activity of Cdk4 without the enhancement of Cdk4 protein. 3-Amino-9-thio(10H)-acridone (3-ATA), the specific inhibitor of Cdk4, prevented D-NCD in a dose-dependent manner. Wortmannin, an inhibitor of ATM (ataxia telangiectasia, mutated) that has high homology with the phosphatidyl-inositol-3-kinase (PI3K) family and has protein kinase activity for the induction of p53 with specificity for serine and threonine residues, inhibited the activation of Cdk4 without the induction of p53 in D-NCD. These data suggest that (1) Cdk4 is one of the essential components for inducing NCD, that (2) p53 may prevent D-NCD through the induction of p21(WAF1) at low concentrations of doxorubicin, and that (3) Cdk4 might be activated by the same signal-molecules, like ATM, that are necessary for the activation of p53 in D-NCD.     

Histologic characteristics of normal perivascular spaces along the optic tract: new pathogenetic mechanism for edema in tumors in the pituitary region

BACKGROUND AND PURPOSE: Perivascular (PV) spaces are known to distend and cause edema along the optic tract (OT) in pituitary-region tumors. Interstitial fluid may be retained in PV spaces when tumors block their drainage outlets to subarachnoid spaces. However, these spaces and their outlets have not been anatomically elucidated. Our purpose was to evaluate how often large PV spaces are present along the OT and demonstrate their superficial communication points to adjacent subarachnoid spaces. METHODS: We examined serial histologic sections of 10 hemispheric blocks obtained from cadavers without cerebral abnormality. RESULTS: Large PV spaces, 0.5-1.5 mm in maximum height, were always present along the middle portion of the OT. Perforation points of the largest spaces were noted at the medial sulcus of the OT in seven hemispheres and through the OT in three. CONCLUSION: Large PV spaces are present along the middle portion of the OT. Their communication point to adjacent subarachnoid spaces was histologically demonstrated. The locations and variations of the outlet of large PV spaces explain the clinical features of edemas; these findings anatomically support the hypothesis that blockage of the outlets to subarachnoid spaces may play a role in distending the PV spaces and in causing edema in pituitary-region tumors. Only MR imaging has revealed this change; further pathologic investigations are awaited.     

Pulmonary sequestration associated by Mycobacterium intracellulare infection

A case of a 29-year-old woman with intralobar pulmonary sequestration infected with Mycobacterium intracellulare is presented. A chest CT scan revealed a density in the posterior segment of the left lower lobe, and an acid-fast bacillus sputum culture yielded Mycobacterium intracellulare. After 3 months of treatment with clarithromycin, streptomycin, rifampicin and ethambutol, the patient underwent partial resection of the left lower lobe. At the 6-month follow-up the patient's clinical status is excellent. A review of the literature revealed only three case reports of pulmonary sequestration associated with Mycobacterium avium-intracellulare complex infection.     

Treatment and prognosis of patients with intracranial nongerminomatous malignant germ cell tumors: a multiinstitutional retrospective analysis of 41 patients

BACKGROUND: The relative roles of surgical resection, radiotherapy, and chemotherapy in the management of patients with intracranial nongerminomatous malignant germ cell tumors have been controversial. The authors retrospectively investigated the results of different treatment regimens in patients with these tumors. METHODS: The records of 41 patients who were treated between 1981 and 2001 were reviewed. They were grouped into patients with a good prognosis (n=3), an intermediate prognosis (n=24), and a poor prognosis (n=14) based on the histology of their tumors. Fifteen patients (37%) underwent surgical resection and received radiotherapy, and 26 patients (63%) also received chemotherapy. The median follow-up of 18 patients who remained alive was 61 months (range, 14-194 months). RESULTS: The 5-year actuarial overall survival rates for patients in the good prognosis, intermediate prognosis, and poor prognosis groups were 100%, 68%, and 8%, respectively. In the analysis, histology alone had a statistically significant impact on overall survival (P<0.0001). All 3 patients in the good prognosis group were treated successfully with surgical resection and radiotherapy. In the intermediate prognosis group, the 5-year actuarial overall survival rate was 44% for patients who underwent surgical resection and received radiotherapy (n=9) and 84% for patients who also received chemotherapy (n=15; P=0.01). Patients in the poor prognosis group who underwent surgical resection and received radiotherapy (n=3) or who underwent incomplete resection and received both radiotherapy and chemotherapy (n=8) all died of disease, whereas 2 of 3 patients who underwent macroscopic total resection and received both radiotherapy and chemotherapy survived free of disease. CONCLUSIONS: The treatment of patients with intracranial nongerminomatous malignant germ cell tumors should be based on tumor histology. For patients who had a good prognosis (mature teratoma with germinoma), surgical resection and radiotherapy were sufficient; however, for patients in the intermediate prognosis group, multimodal treatment, including surgical resection, radiotherapy, and chemotherapy, was effective. Conversely, for patients in the poor prognosis group, more intensive multimodal treatment, including macroscopic total resection, may improve the survival rate.