[A case of advanced gastric cancer with peritoneal dissemination responding remarkably to TS-1/CDDP combination chemotherapy].

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.

Hepatitis B virus infection in lymphatic tissues in inactive hepatitis B carriers.

BACKGROUND/AIMS: Hepatitis B virus (HBV) infection in extrahepatic tissues is controversial. To clarify whether episomal HBV can infect nonhepatic tissues, we investigated the molecular forms of HBV in the lymphatic cells of inactive HBV carriers who lacked viremia, thus avoiding contamination with HBV genomes originating from the viral particles present in the serum. METHODS: We assessed HBV genome, replicative forms, and viral integrants in the liver, serum, peripheral blood mononuclear cells (PBMC), and lymph nodes of 21 inactive HBV carriers who tested positive for antibodies against the HBV core antigen (anti-HBc). RESULTS: Of the 21 anti-HBc positive individuals, HBV-DNA was detected in liver samples of 15 (71.4%), in the lymph nodes of 11 (52.4%), and in PBMC of three (14.3%). However, none of the detected HBV genomes from lymphatic tissues included the replicative forms of HBV. In one case, integrated HBV was present in the lymphatic tissues and the host-viral junction was present in the intronic sequences of chromosome 17. CONCLUSIONS: These data suggest that human lymphatic tissues cannot support viral replication in anti-HBc positive inactive HBV carriers, while retaining the viral genome as an integrated form.

Diverse p53 gene aberration in hepatocellular carcinoma detected by dual-color fluorescence in situ hybridization.

BACKGROUND AND AIM: In order to evaluate loss of the p53 gene more precisely, we performed dual-color fluorescence in situ hybridization (dual-color FISH) for chromosome 17 and p53 gene together with DNA polymorphism analysis of the p53 gene in hepatocellular carcinoma (HCC). METHODS: Dual-color FISH using probes specific for the centromere of chromosome 17 and the p53 gene was performed for 41 HCC and DNA polymorphism analysis was also performed for them. RESULTS: Of the 34 HCC tested by dual-color FISH, 20 had loss of at least one p53 gene (58.8%). In contrast, of the 32 HCC tested by DNA polymorphism analysis, 23 gave informative results, among which only eight had loss of heterozygosity (LOH) of the p53 gene (34.8%). Notably, among 14 cases positive for loss of the p53 gene by dual-color FISH, seven cases were negative for LOH of the p53 gene. Moreover, dual-color FISH revealed that the percentage of cells that lost at least one p53 gene increased as the HCC became less differentiated (P < 0.01), whereas LOH did not reveal any such correlation. CONCLUSIONS: These data suggest that loss of the p53 gene was present in a considerable number of HCC, and diversity of the p53 gene aberration increases with progression of HCC. Dual-color FISH is an effective method for detection of p53 gene aberration, and it can provide new insight into oncogenesis in HCC.

Circulating antibody to hepatitis B core antigen does NOT always reflect the latent hepatitis B virus infection in the liver tissue.

Accumulating evidence suggests the presence of latent hepatitis B virus (HBV) infection in the liver of individuals negative for HBV surface antigen (HBsAg) but positive for antibodies to HBV core antigen (anti-HBc) at low titer. It remains unclear, however, whether positive anti-HBc in the serum invariably reflects latent HBV infection. In this study, we examined the presence of HBV genomes in the liver tissue of 33 donors and 30 recipients of living-related liver transplantation with positive for anti-HBc together with time course changes in their anti-HBc titer. None of these anti-HBc-positive healthy donors or recipients was positive for HBV-DNA nor anti-HBc at high titer (200 dilution) in their sera. However, HBV-DNA was detected in the liver tissue of 24 of 33 healthy anti-HBc-positive donors (72.7%) and five of 30 anti-HBc-positive recipients (16.7%). Interestingly, anti-HBc was continuously positive in all healthy donors tested. In contrast, anti-HBc titers in 75% of recipients, who were positive for anti-HBc at the time of liver transplantation, gradually decreased after the operation, and finally became negative after the mean follow up period of 9.0 months (range 1.2-45.1). Notably, HBV-DNA was never detected in the liver of those recipients who were transiently positive for anti-HBc. In conclusion, our findings suggested the possibility that presence of circulating anti-HBc does not always reflect the presence of HBV genomes in the liver tissue of anti-HBc-positive patients.