Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan

Objectives: Isolated, hyperthermic limb perfusion (ILP) with recombinant hu man tumor necrosis factor-alpha (rhTNF-alpha) and melphalan is a highly eff ective treatment for locoregional metastases of malignant melanoma and for advanced soft tissue sarcoma of the limb. The major systemic side effects a re characterized by the induction of a systemic inflammatory response syndr ome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was in vestigated with respect to its role in SIRS after (LP. Setting: University surgical oncology division with an integrated eight-bed intensive care unit. Patients: Thirty-seven patients were treated by ILP with rhTNF-alpha and me lphalan (n = 26) or with cytostatics alone (n = 11) for soft tissue sarcoma or malignant melanoma. Interventions: The course of serum PCT, interleukin (IL)-6, and IL-8 was an alyzed intra- and postoperatively. Hemodynamic variables including heart ra te, mean arterial pressure, cardiac index, pulmonary arterial pressure, pul monary capillary occlusion pressure, and pulmonary and systemic vascular re sistance were recorded in parallel. Measurements and Main Results: PCT was significantly elevated over baseline after ILP with a maximum between 8 hrs (peak level 16.0 +/- 18.8 (SD) ng/m l) and 36 hrs (13.8 +/- 15.7 ng/mL) (p <.001). The increase in serum PCT wa s significantly more pronounced after ILP with rhTNF-alpha/melphalan than a fter ILP with cytostatics alone (p <.o01). IL-6 and IL-8 were also signific antly increased after ILP (p =.001), reaching peak concentrations at 1 hr a nd 4 hrs postoperatively. Significant changes in heart rate, mean arterial pressure, cardiac index, and systemic vascular resistance were observed dur ing and after ILP; however, PCT levels could not be correlated to these var iables. Pulmonary arterial pressure, pulmonary capillary occlusion pressure , and pulmonary vascular resistance showed no significant changes. Conclusions: Serum procalcitonin is induced as part of the SIRS after ILP w ith rhTNF-alpha/melphatan. It may be induced directly by rhTNF-alpha or oth er cytokines, because serum peaks of IL-6 and IL-8 precede the peak of PCT. Because there is no correlation between serum levels of PCT and hemodynami c variables, this marker cannot be applied to assess the severity of SIRS r eaction after ILP.