Effects of granulocyte-colony stimulating factor (G-CSF) prophylaxis in high risk patients (ASA III and IV) with colorectal cancer on perioperative cytokine levels, complications and global quality of life

The effects of a prophylaxis with G-CSF on postoperative outcome was examined in high risk patients with colorectal carcinoma. In a pilot study we examined whether changes in cytokine levels and leukocyte count correlate with the onset of complications and influence global quality of life.

Patients (ASA class III and IV) with colorectal cancer were randomized in a double-blinded pilot study to: prophylaxis with G-CSF (12 hours before surgery, 12 and 36 hours after surgery) versus placebo. Measurements of G-CSF, IL-6, IL-18, Procalcitonin (PCT) in plasma, leukocyte count, percentage of polynuclear granulocytes (PMNs) and their phagocytic activity were started before operation and continued till day 6 after surgery. TNF-a release was determined after LPS in vitro stimulation of whole blood. All complications were documented as well as quality of life (QL) at discharge, 2 and 6 months after surgery using the EORTC QLQ 30 questionnaire and for global QL the index-points of the area under the curve (AUC) were calculated.

In one patient of the placebo group surgery was cancelled after randomization (withdrawal). In all measurements IL-6 and IL-18 levels and the leukocyte count of the G-CSF group were above placebo and normal values. Only in the placebo group phagocytic activity of granulocytes fell below normal values. There was no difference between the groups regarding IL-8, PCT and TNF-a release. All values were within normal range besides PCT. PCT values were elevated on day 1 after operation on average up to 1.9 and at day 3 on 1.2 ng/ml (normal <0.5 ng/ml). Patient 2 developed fever on day 5 after surgery and leukocytosis on the basis of an anastomotic leakage. Patient 4 had the highest IL-6 levels of all patients on day 6 and on day 8 a duodenal ulcer perforation. Patient 5 developed a bowel atony on day 5 and showed the highest IL-18 levels of all patients on day 6.

The development of postoperative early phase complications is accompanied by changes of cytokine- and bloodcell patterns. Prophylactic treatment with G-CSF elevated IL-6 and IL-18 levels and improved phagocytic activity of granulocytes. The expected influence on global quality of life could not be demonstrated in the pilot study. The correlations found are being further examined in an ongoing randomized, double-blinded trial with 80 patients.

Affiliations

1. Clinic of Anesthesiology and Intensive Care Medicine, Philipps-University Marburg, Germany
   • A Torossian
   •  & H Wulf
2. Institute of Theoretical Surgery, Philipps-University Marburg, Germany
   • M Middeke
   • , I Celik
   • , W Lorenz
   •  & A Bauhofer
3. Clinic of Visceral-, Thorax- and Abdominal Surgery, Philipps-University Marburg, Germany
   • U Plaul

Reprints and Permissions