[Pulmonary metastasis from hepatic epithelioid hemangioendothelioma; report of a case].

A 30-year-old female complaint of epigastralgia was diagnosed hepatic epitheloid hemangio endothelioma (EHE) by liver biopsy. The multiple nodules in bilateral lungs and liver were revealed on computed tomography (CT). The tumors of the left lung were resected under video-assisted thoracoscopic surgery. Pathologically these lesions were diagnosed as metastasis from EHE of the liver, and the patient was treated with interleukin-2 from hepatic artery for 12 months.

Role and mutational heterogeneity of the p53 gene in hepatocellular carcinoma.

The mutational spectrum of the p53 gene was analyzed in 53 hepatocellular carcinomas. Somatic mutations of the p53 gene were detected in 17 cases (32%). Among these 17 mutations, 9 were missense mutations; the mutations in the other 8 cases were nonsense mutations, deletions, or mutations at the intron-exon junctions. These mutations were found in a wide region stretching from exon 4 to exon 10 without any single mutational hot spot. G:C to T:A transversions were predominant, suggesting the involvement of environmental mutagens in the mutagenesis of the p53 gene in a subset of the hepatocellular carcinoma cases. Mutations of the p53 gene occurred frequently in advanced tumors, although several tumors in the early stages also showed mutations. A deletion map of chromosome 17 was constructed by using 10 polymorphic probes and was compared with the p53 gene mutation in each case. Loss of heterozygosity (LOH) on chromosome 17p was observed in 49% of the cases (24 of 49), and two commonly deleted regions were detected (around the p53 locus and at 17p13.3 to the telomere). Sixteen of the 17 cases with p53 gene mutations showed LOH around the p53 locus, and mutations were rare in hepatocellular carcinomas without LOH. However, no mutations were detected in 8 cases with LOH on 17p, suggesting the possibility that an unidentified tumor suppressor gene(s) located on 17p may have also been involved in hepatocarcinogenesis.

Age-dependent and tissue-specific changes of DNA methylation within and around the c-fos gene in mice.

The degree of DNA methylation in the c-fos gene and its vicinity in liver, brain and spleen of mice of different ages was examined using methylation-sensitive restriction endonucleases. The gene had an invariable unmethylated domain from 1.8kb upstream of the cap site to the first intron. The domain was flanked on both sides with partially methylated areas, where tissue-specificity and age-dependent changes were observed. The tissue-specificity was found on the 14th day of gestation. Increases of methylation were observed during the late fetal and one month postnatal developmental periods in the three tissues. After that, the methylation states remained unchanged. One exception was seen in the exon 2 area in liver, where methylation continued to increase throughout life. This revealed the importance of the late fetal- and post-natal developmental periods in the establishment of tissue-specificity in DNA methylation profiles and further showed that some of the developmental changes could extend into the senescent phase.

A case of malignant fibrous histiocytoma of the ilium, evaluation by blood-pool scintigraphy.

A rare case of malignant fibrous histiocytoma (MFH) of the ilium was presented and blood-pool scintigraphic images and angiographic images were correlated. Hypervascular tumor and lacking of contrast material with arteriovenous shunts were shown by angiography. Intensive tracer accumulation was shown by blood-pool scintigraphy. After radiation therapy and transcatheter arterial embolization of the tumor, tracer accumulation was noticeable reduced. These findings suggested a vascular tumor such as angiosarcoma, but surgery revealed MFH of the bone. Blood-pool scintigraphy was useful in the evaluation of the vascular characteristics of the tumor.

[Diagnosis of type B hepatitis].

Since 1965, when Blumberg discovered the Australia antigen, the hepatitis B surface antigen (HBsAg), the research on viral hepatitis has rapidly progressed. The identification of specific hepatitis B associated antigens and antibodies in blood, and liver tissue, together with the improvement of detection systems, have enhanced our knowledge about the mechanism of liver injury and the natural history of hepatitis B virus (HBV) infection. Now it has been recognized that HBV has no direct cytopathic effect on hepatocytes and that hepatocyte necrosis is associated with the virus induced immunological reaction of the host. From the reaction, there are two types of HBV infection, i.e., transient (acute) and persistent (chronic) infection. In addition to the conventional measurements, such as HBsAg, anti-HBs, anti-HBc, HBeAg, anti-HBe and anti-IgM HBc, recently pre S1, pre S2 antigen/antibody systems and polymerized human albumin receptor and antibody have been developed. The significance of the detection of these antigen/antibody systems was discussed. On the other hand, to determine the presence of HBV, the state of HBV replication or the infectivity directly, HBV associated DNA polymerase and HBVDNA should have been detected. (Very recently, the polymerase chain reaction method has been introduced to detect very small amounts of HBVDNA). In this presentation, the change of these viral markers in various cases was shown, and especially emphasized was anti-IgM HBc in acute hepatitis and HBeAg/Ab status in chronic liver disease. Lastly, the present state of Interferon therapy for type B chronic hepatitis was mentioned.

[Percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma].

Percutaneous local treatment for hepatocellular carcinoma is minimally invasive. Moreover, since local radical cure may be possible, the procedure has become widely performed. Percutaneous radiofrequency ablation (PRFA) was recently introduced in Japan. Excellent results are expected. PRFA was conducted on 244 tumor nodules found in 177 cases of hepatocellular carcinoma (a total of 349 procedures), and the usefulness was examined. 1. Tumor markers significantly decreased after PRFA and a favorable necrotic effect was obtained on CT images. 2. Mild post-operative inflammatory reaction and exacerbation of liver dysfunction was noted, but recovery was achieved in one week. There were no major complications. 3. The cumulative local recurrence in 1 year was 5.4%, which is lower than that with percutaneous microwave coagulation therapy. 4. PRFA is a safe and handy procedure for hepatocellular carcinoma, which promises the favorable effect of coagulation necrosis. PRFA will likely become a key method among local ablation therapies.

Accumulation of allelic loss on arms of chromosomes 13q, 16q and 17p in the advanced stages of human hepatocellular carcinoma.

We examined loss of heterozygosity at 13 loci on 5 chromosomes in hepatocellular carcinomas (HCCs) from 56 patients. In 42 of these cases, regenerative nodules of liver cirrhosis were also analyzed. High frequencies of allelic losses were detected on chromosomes 13q (47%), 16q (40%) and 17p (64%), whereas losses on chromosome 4p and 11p were observed in less than 22% of cases in HCCs. In contrast, LOH was not detected on any loci in cirrhotic nodules. On chromosome 13q, the common region of allelic loss was mapped to the region including the retinoblastoma (RB) locus, by using 8 polymorphic probes. Furthermore, one case with 13q loss had an interstitial deletion of the RB gene, indicating the involvement of inactivation of the RB gene in hepatotumorigenesis. Losses were associated with portal-vein thrombosis or intrahepatic metastasis, increased tumor size, a poorly differentiated phenotype and clinical stage. Losses occurring together on 13q, 16q and 17p were significantly higher in patients in clinical stage IV or histologically poorly differentiated tumors, suggesting that the accumulation of allelic loss occurs in advanced tumors and that patients with multiple allelic losses may have a worse prognosis than those with a single loss.