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In attempts to avoid the side-effects derived from a scald on the peritoneo-serosal surface during intraperitoneal hyperthermic perfusion (IPHP) for advanced gastric cancer, a randomized study using cimetidine, a histamine H2-receptor antagonist, was carried out on 18 patients with advanced gastric cancer. Cimetidine, 50 mg/kg, was administered intravenously and immediately before IPHP. The background characteristics of the patients and the types of surgical treatment used were almost the same between each group of patients, whether or not cimetidine was given. The perfusion time in the cimetidine and control groups was 123 +/- 9 and 117 +/- 9 min, respectively. The inflow and outflow temperatures of the perfusate were 46.3 +/- 0.4 and 44.2 +/- 0.1 degrees C in the cimetidine group, respectively, whereas in the control group the temperatures were 46.0 +/- 0.3 and 44.1 +/- 0.2 degrees C, respectively. In the nine patients who were given cimetidine, the histamine concentrations in the peripheral blood increased significantly, compared to those in the nine controls; this resulted from the release of histamine into the circulating blood. Higher concentrations of protein were observed in the post-hyperthermic intraperitoneal exudate of the control group for 3-24 h after IPHP and, consequently, post-hyperthermic hypoproteinaemia was remarkable in the control group. These data suggest that when pre-IPHP cimetidine was prescribed for patients with gastric cancer treated with IPHP, the peritoneo-serosal surface was protected from scald injury and the side-effects of IPHP were reduced.

Hyperthermia combined with recombinant human tumour necrosis factor (rH-TNF) was evaluated for antitumour efficacy in vivo. Use was made of human gastric cancer tissues xenografted into nude mice. When 100, 300, 600, and 1200 units of rH-TNF (2.4 x 10(6) units/mg protein) were given twice intraperitoneally, tumour regression did not occur in any animal. In contrast, a remarkable suppression of tumour growth was observed when 600 and 1200 units of rH-TNF was given in combination with hyperthermia at 43.5 +/- 0.1 degrees C. No effects were evident with the regimen of 100 and 300 units of rH-TNF plus hyperthermia at the same temperature, as compared with evidence obtained with hyperthermia alone. The tumoral blood flow, determined by the hydrogen diffusion method, decreased immediately after hyperthermia alone or hyperthermia plus 1200 units of rH-TNF, whereas a slight decrease was seen after rH-TNF alone. When hyperthermia plus 1200 units of rH-TNF were given, there was a remarkable delay in reversion to pretreatment values of tumoral blood flow, as compared to findings with rH-TNF only or heat only. These results are discussed in relation to the antitumour and side-effects of rH-TNF.