Acute-phase response patterns in isolated hepatic perfusion with tumour necrosis factor alpha (TNF-alpha) and melphalan in patients with colorectal liver metastases

Background In this study, we have evaluated hepatotoxicity, secondary cytok ine production and hepatic acute-phase response (APR) in patients who under went isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) alp ha and melphalan for irresectable colorectal liver metastases. Design An extracorporeal veno-venous bypass was used to shunt blood from th e lower body and intestines to the heart. Inflow catheters were placed in t he hepatic artery and portal vein, and an outflow catheter in the inferior caval vein. The liver was perfused for 60 min with 0.4 mg of TNF-alpha plus 1 mg kg(-1) melphalan (IHPTM group, n = 6) or 1 mg kg(-1) melphalan (IHPM group, n = 3). The liver was washed with macrodex before restoring vascular continuity. Results After the washout procedure, a TNF-alpha peak (169 +/- 38 pg mL(-1) ) was demonstrated in the IHPTM group only. Both groups demonstrated peak l evels of interleukin 6 (IL-6) in the perfusate as well as systemically. The se were significantly higher in the IHPTM group. Acute-phase protein (APP) levels followed a similar pattern as has been demonstrated after major surg ery, with no significant differences between both groups. The addition of T NF-alpha to the perfusate did not lead to a significant difference in APP l evels and the time course between groups. Conclusions IHP with TNF and melphalan is followed by a transient systemic peak of TNF directly after liver washout. Secondary IL-6 induction was seen in the present study after IHP with and without TNF, which was highest whe n TNF was added. This phenomenon cannot be extrapolated to APP induction, w hich appeared unaffected by the addition of TNF, presumably because the sur gical procedure itself already causes maximal stimulation of APP production .