[Two cases of unresectable advanced gastric cancer treated with S-1, CDDP and trastuzumab].

We report two cases of unresectable advanced gastric cancer treated with S-1, CDDP and trastuzumab. A significant reduction of tumors was observed in these cases. A 77-year-old man was diagnosed as unresectable gastric cancer. The pathological diagnosis was tub2 and human epidermal growth factor receptor 2(HER2)positive(3+IHC method). We started chemotherapy(S-1+CDDP+trastuzumab). After 2 courses of S-1+CDDP, the findings of upper gastrointestinal endoscopy and CT were much improved to PR. But after 6 courses of S-1+CDDP, they worsened to PD. The regimen of chemotherapy was changed to weekly paclitaxel. The other patient, a 68-year-old woman, was diagnosed as far advanced gastric cancer. The pathological diagnosis was tub2=por2 and HER2 positive(3+IHC method). We started chemotherapy(S- 1+CDDP+trastuzumab). After 3 courses of S-1+CDDP, the tumor reduced significantly to PR. We continued this regimen. From the result of the ToGA trial, addition of trastuzumab to chemotherapy(capecitabine+CDDP or fluorouracil+CDDP) has been recommended as a new standard first-line regimen for HER2-positive advanced gastric cancer. But there is no evidence that trastuzumab added to the other regimen improved survival in patients with advanced gastric cancer. It is necessary to conduct a clinical trial to evaluate the treatment effect of this chemotherapy.

Analysis by comparative genomic hybridization of gastric cancer with peritoneal dissemination and/or positive peritoneal cytology.

Peritoneal metastasis is an important prognostic factor in cases of gastric cancer. Although studies on comparative genomic hybridization (CGH) in gastric cancer have been reported, there are few reports on the peritoneal metastasis (P) and peritoneal cytology (CY) factors in this cancer. In this study, we analyzed the chromosomal changes in the primary tumor with a combination of laser microdissection analysis and CGH in an attempt to detect the unknown abnormal chromosomal regions. We analyzed 34 primary tumors, including 13 primary tumors with peritoneal metastasis (P1) and/or positive peritoneal cytology (CY1) using a combination of laser microdissection and CGH. The minimal overlapping regions in gains were assigned to 5p14 (46.2%), 7q21.3 (61.5%), 7q31 (46.2%), 7q36 (46.2%), 8q23 (53.8%), 15q26 (46.2%), 20q12 (61.5%), 20q13.1 (53.8%), and 20q13.2 (53.8%) in primary tumors with P1 and/or CY1. The minimal regions of losses that occurred most frequently were 4q34-q35 (23.1%) and 22q11.2 (23.1%). There were significant differences in the minimal regions of 5p14 (P=0.033), 7q21.3 (P < 0.0001), 7q31 (P=0.013), 7q36 (P=0.033), and 22q11.2 (P=0.048) between primary tumors with and without P1 and/or CY1. In this study, gain/amplification of 5p14, 7q21.3, 7q31, and 7q36, and loss of 22q11.2 were significant in gastric cancer cases with peritoneal dissemination and/or positive peritoneal cytology.

Association of gastric and intestinal phenotypic marker expression of gastric carcinomas with tumor thymidylate synthase expression and response to postoperative chemotherapy with 5-fluorouracil.

PURPOSE: It is well known that both gastric and intestinal phenotypic markers are expressed in gastric carcinomas, irrespective of their histological type. In the present study, the associations among phenotypic marker expression of gastric carcinomas, tumor thymidylate synthase (TS) expression, and the chemotherapeutic response to 5-fluorouracil (5-FU) were examined. METHODS: The gastric and intestinal phenotypic marker expression of the tumor was determined by the combination of the expression of human gastric mucin (HGM), MUC6, MUC2, and CD10, and was evaluated in comparison with tumor TS expression in 137 advanced gastric carcinomas in 137 patients (75 with postoperative chemotherapy with 5-FU and 62 without postoperative chemotherapy). Tumors were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of HGM, MUC6, MUC2, and CD10 stainings. The associations among the gastric and intestinal phenotypic marker expression of the tumor, tumor TS expression, effect of postoperative chemotherapy with 5-FU, and the patient's prognosis were examined. RESULTS: Of the 137 gastric carcinomas, 48 (35.0%), 58 (42.3%), 23 (16.8%), and 8 (5.8%)were classified as the G-, GI-, I- and UC-phenotype, respectively. The high TS expression of more than 25% tumor cell positivity was found in 25 (52.1%) of the 48 G-phenotype tumors, 39 (67.2%) of the 58 GI-phenotype tumors, 18 (78.3%) of the 23 I-phenotype tumors, and 4 (50.0%) of the 8 UC-phenotype tumors. The I-phenotype tumors were significantly correlated with the higher rate of the high TS expression as compared with the G-phenotype tumors (P<0.05). Among 48 patients with the G-phenotype tumor, the 5-year survival rate in patients with and without postoperative chemotherapy was 39.7 and 27.8%, respectively. The patients with postoperative chemotherapy had a significantly better prognosis than those without postoperative chemotherapy (P<0.05). Conversely, there were no significant correlations between the presence of postoperative chemotherapy and the patient's prognosis among patients with GI-, I-, and UC-phenotype tumors. CONCLUSIONS: These results indicate that postoperative chemotherapy with 5-FU could be effective for patients with the G-phenotype tumor, since the incidence of intratumoral expression of TS, the target enzyme of 5-FU, is significantly low in G-phenotype tumors.

Successful curative resection of gastric cancer with AIDS infection.

This report describes the case of a 47-year-old Japanese man with human immunodeficiency virus (HIV) infection with AIDS, who was successfully treated for gastric cancer. A review of gastric cancer associated with HIV is also presented. Prior to surgical treatment, azidothymidine (AZT), nerfinavir (NFV), and lamivudine (3TC) were administered to the patient in order to improve his blood CD4 count and reduce the viral burden. Consequently, distal gastrectomy was performed as a curative resection without any complications. The gastric cancer included a signet-ring cell carcinoma, as was noted in eight of the nine reported cases associated with HIV. This suggests that the HIV virus may play a role in causing signet-ring cell carcinoma, especially in the stomach.