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

Abstract

Background In this study, we have evaluated hepatotoxicity, secondary cytokine production and hepatic acute‐phase response (APR) in patients who underwent isolated hepatic perfusion (IHP) with tumour necrosis factor (TNF) α and melphalan for irresectable colorectal liver metastases. Design An extracorporeal veno‐venous bypass was used to shunt blood from the lower body and intestines to the heart. Inflow catheters were placed in the 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‐α plus 1 mg kg⁻¹ melphalan (IHP_TM group, n = 6) or 1 mg kg⁻¹ melphalan (IHP_M group, n = 3). The liver was washed with macrodex before restoring vascular continuity. Results After the washout procedure, a TNF‐α peak (169 ± 38 pg mL⁻¹) was demonstrated in the IHP_TM group only. Both groups demonstrated peak levels of interleukin 6 (IL‐6) in the perfusate as well as systemically. These were significantly higher in the IHP_TM group. Acute‐phase protein (APP) levels followed a similar pattern as has been demonstrated after major surgery, with no significant differences between both groups. The addition of TNF‐α to the perfusate did not lead to a significant difference in APP levels 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 when TNF was added. This phenomenon cannot be extrapolated to APP induction, which appeared unaffected by the addition of TNF, presumably because the surgical procedure itself already causes maximal stimulation of APP production.