J. Kettenbach, C. Schmuckenschlager, M. Ploder, B. Wessner, F. Laengle, E. Roth, J. Lammer, A. Spittler; Vienna/AT

Purpose
The only potential curative therapies for primary and secondary liver tumors are operative strategies such as liver resection or orthotopic liver transplantation. However, the majority of patients with primary or secondary malignancies are not candidates for surgical resection because of tumor size, progression, location, multifocality, inadequate functional hepatic reserve to coexistent cirrhosis or a bad general condition of patients. Minimally invasive treatments such as percutaneous radio frequency ablation (RFA) and ethanol instillation (PEI) are alternative therapies with the objective of generating tumor necrosis. 80% of the macrophages of the body are situated in the liver. Interventional therapies in the liver are possibly accompanied by an activation of Kupffer cells which then produce a variety of inflammatory cytokines and cause an imbalance of the redox status. The aim of the present work was to determine the patients peripheral immunological and oxidative status before and after percutaneous tumor ablation.

Material and methods
In this prospective study 25 patients (mean age 67.010.6 years) were included. Patients recieved either radiofrequency ablation (n=13) or ethanol injection (n=12). The control group consisted of 7 healthy volunteers (mean age 29.97.4 years). Four blood samples were taken from each patient: 0.5h before, 0.5h, 24h and 5 days (d)after intervention. Human leucocyte antigen-DR ( HLA-DR ) expression on monocytes was detected by flow cytometry (Beckman Coulter). Ex-vivo lipopolysaccharide (LPS) induced tumor necrosis factor- ( TNF- ) production and constitutive plasma interleukin-6 ( IL-6 ) were measured by a chemoluminescence immuno assay (Immulite). Procalcitonin ( PCT ) was determined by a semiquantitatve test system (Brahms). Peroxide levels and antioxidative capacity were measured spectrophotometrically using commercially available test kits (Immundiagnostik). Statistical analysis was performed using the statistical software package SPSS. Differences between points of time andgroups were calculated by Mann-Whitney test.

Results
Taken all patients together,HLA-DR expression (0.5h postop p<0.05; 24h postop p<0.01; 5 d postop p<0.001) and TNF- production (0.5h postop p<0.01) were significantly diminished. Plasma IL-6 (24h postop p<0.001; 5d postop p<0.001) and PCT levels (24h postop p<0.05) were significantly enhanced compared with pretreatment values. 5d after intervention the peroxide levels were significantly higher, whereas antioxidative capacity did not change. Significant differences between the two treatment-groups were found in IL-6 (24h postop p<0.001), PCT (24h postop p<0.01) and peroxide levels (1h postop p<0.05). Figures 1-4: Data are presented as boxplots with median values and interquartile ranges. The green box represents the control group (healthy volunteers), purple boxes stand for the 4 points of time of treatment groups (RFA and PEI together). * p<0.05, ** p<0.01, *** p<0.001 versus preoperative value of the treatment groups. ++ p<0.01 versus healthy control group.

Conclusion
Although in all patients interventions were minimal invasive treatments, we assume that during percutaneous ablation Kupffer cells were activated triggering a transient immunosuppression. In addition altered peroxide levels indicate the occurrence of oxidative stress