[Experimental study on TNF-alpha linked percutaneous isolated hepatic chemoperfusion (PIHP)].
Recently, isolated hepatic perfusion (IHP) with high-dose TNF-alpha for hepatic malignancies has again attracted attention as a locoregional chemotherapy. A novel system of hepatic venous isolation and charcoal hemoperfusion (HVI.CHP) is a minimal invasive surgery for high-dose chemotherapy of the liver. This study was undertaken to determine whether this novel system could limit systemic exposure to TNF-alpha following hepatic arterial infusion (HAI) when combined with anti TNF-alpha antibody. Beagles were allocated into two groups; group I (n = 4), TNF-alpha + anti TNF-alpha antibody and group II (n = 5), TNF-alpha only (control). All animals received HAI of 50 micrograms/kg of recombinant human TNF-alpha over 20 min with complete hepatic venous isolation. In group I, 250 micrograms/kg of antibody was administered into the hepatic venous outflow line over 30 min after the initiation of HAI. The Cmax (ng/ml) of systemic TNF level was significantly lower in group I (125 +/- 57) than in group II (825 +/- 283) (p < 0.05). The AUC (mg.min/ml) of the systemic TNF level was significantly lower in group I (2.0 +/- 1.0) than in group II (34.5 +/- 9.5) (p < 0.01). By use of anti TNF antibody, systemic exposure to TNF was reduced efficiently. These results indicated that HVI.CHP may be applicable to the TNF-alpha linked chemoperfusion to the liver in combination with anti TNF-alpha antibody.
First Dept. of Surgery, Kobe University School of Medicine.
N
N
Kusunoki
Y
Y
Ku
Y
Y
Kuroda
D000818:Animals; D001323:Autoantibodies / Q000008:administration & dosage; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods*; D004285:Dogs; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics
D001323:Autoantibodies; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha