Continuous hyperthermic peritoneal perfusion (CHPP) with anticancer agents (mitomycin C and cisplatin) in warm saline was performed in patients with peritoneal dissemination of gastric cancer following resection of the primary lesion. The effect of CHPP was examined by a second-look operation. This study includes 41 cases of gastric cancer with peritoneal dissemination but without liver metastasis treated during the past 6 years. The overall median survival was 14.6 months to 64.2 months from CHPP to death and the 3-year survival rate was 28.5%. Second look surgery revealed a remarkable diminution in the degree of peritoneal dissemination in 7 (50%) of 14 patients with disappearance of ascites after only one course of CHPP in 7 (77.8%) of 9 patients. Long-term 3 year-survival was noted in 4 (9.8%) patients on CHPP. Side effects were renal insufficiency in 2 (5%) patients, leukopenia in 2 (5%) patients, and perforation of the small intestine in 1 (2%) patient. These results suggest the effectiveness of CHPP in the treatment of gastric cancer with peritoneal dissemination.

Continuous hyperthermic peritoneal perfusion (CHPP) with a solution which contains 30 mg mitomycin C and 300 mg cisplatin has been introduced as a prophylactic treatment for peritoneal recurrence after curative resection of 79 advanced gastric cancers. The control group consisted of 81 patients with advanced gastric cancer who underwent curative surgery during the same period. CHPP was performed for 60 minutes by perfusing MMC- and CDDP-containing saline solutions warmed at 43.5 degrees C by a special CHPP device. In patients with pathologically confirmed serosal invasion-positive tumors, the survival rate of the CHPP group was significantly higher than that of the control group. A survival advantage for stage IV patients was also obtained by CHPP. However, there was no survival advantage between the CHPP group and the control group with serosal invasion-negative tumors. Adverse effects were observed in four patients who underwent CHPP: One developed severe bone marrow suppression, and transient hyperazotemia was observed in the other three. There was no difference in the incidence of mortality and morbidity between the two groups. These results indicate that CHPP is a safe, readily available prophylactic therapy for peritoneal recurrence after gastric cancer surgery.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis,

The growth fractions of 101 gastric carcinomas were determined in situ by immunostaining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings, bromodeoxyuridine (BrdU) labeling index, and DNA ploidy pattern. DNA ploidy patterns were determined by flow cytometric analysis. The Ki-67 labeling rates are rated from 4.6% to 82% (mean, 22%). A significant correlation was found between Ki-67 labeling rates and BrdU labeling indices. Sixty-seven percent of tumors with lymph node metastases showed Ki-67 labeling rates of less than 22%, whereas 33% of tumors without lymph node metastases showed Ki-67 labeling rates of less than 22%. There was a significant correlation between these two groups. Tumors with vessel invasion more often have higher Ki-67 labeling rates than those without vessel invasion. By the DNA ploidy classification, the mean Ki-67 labeling rates of aneuploid tumors was significantly higher than that of diploid tumors. This method yielded similar results to those obtained by BrdU labeling and flow cytometric study. The measurement of Ki-67 labeling rates may be useful to decide the therapeutic modalities.

The correlation between the clinical features in 103 patients with primary gastric carcinoma and amplification of epidermal growth factor receptor (EGFR) gene was analyzed retrospectively. EGFR gene amplification was examined by slot-blot hybridization using DNA extracted from formalin-fixed, paraffin-embedded tissues. EGFR expression was also examined immunohistochemi-cally using the same tissues with a monoclonal antibody that is monospecific for EGFR. In 5 of 103 cases (4.9%), a 2- to 11-fold amplification of EGFR gene was detected. Four of these 5 cases were poorly differentiated adenocarcinomas. All of them had overexpressions of EGFR. The cumulative survival rate of patients with EGFR gene amplification was significantly lower than that of the patients without amplification (p < 0.05) and all of them died within 3 years. Except for tumor size (p < 0.03), there were no significant clinicopa-thologic differences between the two groups. On the other hand, 41 of 103 cases (39.8%) exhibited expression of EGFR. However, there was no significant correlation between EGFR expression and clinicopathologic factors or prognosis. These results indicate that EGFR gene amplification may occur in advanced stages during the progression and be an important indicator of poor short-term prognosis in gastric carcinoma.