title: Induction of systemic serum procalcitonin and cardiocirculatory reactions after isolated limb perfusion with recombinant human tumor necrosis factor-alpha and melphalan.
abstract: OBJECTIVE
  Isolated, hyperthermic limb perfusion (ILP) with recombinant human tumor necrosis factor-alpha (rhTNF-alpha) and melphalan is a highly effective treatment for locoregional metastases of malignant melanoma and for advanced soft tissue sarcoma of the limb. The major systemic side effects are characterized by the induction of a systemic inflammatory response syndrome (SIRS). Procalcitonin (PCT), a serum marker of bacterial sepsis, was investigated with respect to its role in SIRS after ILP.
  
  
  METHODS
  University surgical oncology division with an integrated eight-bed intensive care unit.
  
  
  METHODS
  Thirty-seven patients were treated by ILP with rhTNF-alpha and melphalan (n = 26) or with cytostatics alone (n = 11) for soft tissue sarcoma or malignant melanoma.
  
  
  METHODS
  The course of serum PCT, interleukin (IL)-6, and IL-8 was analyzed intra- and postoperatively. Hemodynamic variables including heart rate, mean arterial pressure, cardiac index, pulmonary arterial pressure, pulmonary capillary occlusion pressure, and pulmonary and systemic vascular resistance were recorded in parallel.
  
  
  RESULTS
  PCT was significantly elevated over baseline after ILP with a maximum between 8 hrs (peak level 16.0+/-18.8 (SD) ng/mL) and 36 hrs (13.8+/-15.7 ng/mL) (p < .001). The increase in serum PCT was significantly more pronounced after ILP with rhTNF-alpha/melphalan than after ILP with cytostatics alone (p < .001). IL-6 and IL-8 were also significantly increased after ILP (p = .001), reaching peak concentrations at 1 hr and 4 hrs postoperatively. Significant changes in heart rate, mean arterial pressure, cardiac index, and systemic vascular resistance were observed during and after ILP; however, PCT levels could not be correlated to these variables. 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 with rhTNF-alpha/melphalan. It may be induced directly by rhTNF-alpha or other 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 hemodynamic variables, this marker cannot be applied to assess the severity of SIRS reaction after ILP.
authors.affiliation: Division of Surgery and Surgical Oncology, Robert Rössle Hospital and Tumor Institute, Max Delbrück Center for Molecular Medicine, Charité, The Humboldt University at Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kettelhack
authors.forename: P
authors.initials: P
authors.lastname: Hohenberger
authors.forename: G
authors.initials: G
authors.lastname: Schulze
authors.forename: B
authors.initials: B
authors.lastname: Kilpert
authors.forename: P M
authors.initials: PM
authors.lastname: Schlag
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002116:Calcitonin / Q000097:blood* / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000379:methods* / Q000706:statistics & numerical data; D002945:Cisplatin / Q000008:administration & dosage; D005121:Extremities; D005260:Female; D006023:Glycoproteins / Q000097:blood* / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary; D008558:Melphalan / Q000008:administration & dosage*; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood* / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012509:Sarcoma / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000556:secondary; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
chemical_list: D018906:Antineoplastic Agents, Alkylating; C000606589:CALCA protein, human; D006023:Glycoproteins; D015850:Interleukin-6; D016209:Interleukin-8; D011498:Protein Precursors; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D002945:Cisplatin; D008558:Melphalan