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Annals of Surgical Oncology 10:562-568 (2003)
© 2003 Society of Surgical Oncology

NEW APPROACHES TO THE TREATMENT OF HEPATIC MALIGNANCIES

Pentoxifyllin Attenuates the Systemic Inflammatory Response Induced During Isolated Limb Perfusion With Recombinant Human Tumor Necrosis Factor-{alpha} and Melphalan

Peter Hohenberger, MD, PhD, Eicke Latz, MD, Christoph Kettelhack, MD, PhD, Amir-Hossein Rezaei, MD, Ralf Schumann, MD, PhD and Peter M. Schlag, MD, PhD

From the Division of Surgery and Surgical Oncology, Robert Rössle Hospital and Tumor Institute, Max Delbrück Center for Molecular Medicine (PH, EL, CK, PMS); and Institute of Microbiology, Charité (A-HR, RS), The Humboldt University at Berlin, Germany.

Correspondence: Address correspondence and reprint requests to: Peter Hohenberger, MD, Division of Surgery and Surgical Oncology, Robert Rössle Hospital, Charité, Campus Berlin-Buch, Lindenberger Weg 80, D-13125 Berlin, Germany; Fax: 49-30-9417-1439; E-mail: hohenberger{at}rrk-berlin.de

ABSTRACT

Background: Isolated limb perfusion (ILP) with recombinant human tumor necrosis factor-{alpha} (rhTNF-{alpha}) and melphalan harbors the risk of septic shock–like syndrome. Pentoxifyllin (PTX) produced a beneficial effect on cytokine response and survival in animal experiments of septic shock, and we were interested to explore its effect during TNF-ILP in humans.

Methods: Eighteen consecutive patients underwent TNF-ILP and received PTX (30 mg/kg/day), whereas another 13 consecutive patients did not. PTX was given systemically after the limb extracorporeal circulation was started. Cardiac index, systemic vascular resistance (SVR), and pulmonary vascular resistance were recorded via a Swan-Ganz catheter. Blood levels of TNF-{alpha}, interleukin-6, procalcitonin, and lipopolysaccharide-binding protein were determined before, during, and after ILP.

Results: After reperfusion, systemic levels of TNF-{alpha} were significantly less increased in the PTX group (peak, 2.8 vs. 1.3 ng/mL; P < .05), as were interleukin-6 values (peak, 68 vs. 22 pg/mL; P < .02) and lipopolysaccharide-binding protein plasma levels (peak, 215 vs. 105 µg/mL; P < .03). Differences in cardiac index, SVR, and mean arterial blood pressure were not significantly different. Norepinephrine or dobutamine to maintain SVR was less required in the PTX group.

Conclusions: PTX attenuates systemic cytokine production and influences components of the systemic inflammatory response after TNF-ILP. PTX may play a beneficial role in the management of septic shock–like syndrome, particularly in patients with leakage from the ILP circuit.

Key Words: Isolated limb perfusion • TNF-{alpha} • Septic shock • Pentoxifyllin • SIRS • Cytokine




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[Abstract] [Full Text] [PDF]


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