TNF-alpha and endotoxin serum levels in cancer patients undergoing intraperitoneal hyperthermic perfusion

Intraperitoneal hyperthermic perfusion (IPHP) is performed as one treatment for patients with advanced gastrointestinal cancer complicated by peritoneal dissemination or carcinomatous peritonitis. However, the anticancer mechanism of IPHP and its safety have not yet been fully elucidated. It has been experimentally known that endotoxinemia occurs by high body temperature, and that endotoxin stimulates the macrophage, monocyte and endothelial cell to induce the production of TNF-alpha. TNF-alpha is one of cytokines to be induced at the initial phase as a host immune response and play an important role to initiate the systemic inflammatory response syndrome (SIRS). We have tested whether the serum concentrations of TNF-alpha and endotoxin are elevated following IPHP. Eleven patients with gastro-intestinal cancer underwent surgery combined with IPHP. Mixed venous blood obtained from pulmonary artery (PA-blood) was collected at four sampling points. TNF-alpha and endotoxin levels in the PA-blood were measured by ELISA and a limulus amoebocyte lysate assay respectively. In all patients the serum TNF-alpha levels in PA-blood were temporarily elevated following IPHP from less than 10 pg/ml before IPHP to 42.8 +/- 26.6 pg/ml; endotoxin levels were not altered. This study shows that IPHP has the ability to induce endogenous TNF-alpha not mediated by endotoxin.