Postoperative septic complications and neoplastic progression in colorectal cancer

Abstract

Abstract Background Proinflammatory cytokines, mainly interleukin (IL) 6, may induce suppressive effects on antitumour immunity. IL-6 inhibits T lymphocyte proliferation and maturation of dendritic cells. In the postoperative period, an increase in IL-6 serum level due to surgical trauma is a normal finding. Very high levels of IL-6 are detected only in patients with septic complications. In consideration of the suppressive effects of IL-6 on antitumour immunity, septic complications may promote a worsening of the late prognosis of patients undergoing radical treatment for cancer. To detect a possible negative effect on cancer progression due to sepsis after colorectal surgery, this study was carried out in patients who underwent radical surgery (Dukes' B and C stages). Cancer-related late recurrence and mortality rates were compared in patients with and without postoperative septic complications. Methods Patients who underwent operation for colorectal cancer between January 1987 and December 1998 were studied. Patients treated by emergency surgery, patients aged over 80 years, those with a previous or second neoplasm and patients treated with steroid therapy or other immunomodulatory drugs were excluded. Major surgical postoperative septic complications were considered: wall and intra-abdominal abscess and anastomotic leakage. Five-year survival (Kaplan–Meier curve) and recurrence rates were recorded. Results Some 210 patients were studied; 137 patients with a mean age of 65 (range 22–80) years and median follow-up of more than 5 years (range 12–144 months) had Dukes' B disease (77 men and 60 women). Of these 137 patients, 28 (20 per cent) had septic complications. Thirteen of 28 patients with sepsis had progression of cancer disease compared with 26 of 109 without sepsis (P < 0·03). In patients with sepsis the 5-year mortality rate was 32 per cent (nine of 28), worse than that in patients without sepsis (19 per cent; 21 of 109). Seventy-three patients (41 men and 32 women), of mean age 64 (range 38–80) years, with median follow-up greater than 5 years (range 13–120 months), had Dukes' C lesions. Of these 73 patients, 16 (22 per cent) had septic complications. Thirteen of 16 patients with sepsis had progression of cancer disease compared with 33 of 57 without sepsis. In those with sepsis the 5-year mortality rate was 75 per cent (12 of 16), significantly worse than that in patients without sepsis (40 per cent; 23 of 57) (P < 0·02). Conclusion The immunological response against cancer is generally impaired after major surgery owing to lymphocytopenia and lack of dendritic cells. It is known that IL-6 promotes suppression of antitumour-specific (dendritic cells and CD8 cytotoxic cells) and aspecific (IL-2 activation of lymphokine-activated killer cells) systems. The increase in IL-6 levels after surgery is relevant in patients with septic complications and this phenomenon may negatively influence the immunological control of malignant spread. As hypothesized, septic complications after radical surgery for colorectal cancer were followed by an increased recurrence rate in patients with both Dukes' B and C tumours. This finding supports a significant role for the immune system in the control of malignant progression of disease. The postoperative course represents a vulnerable period since septic complications and secondary immunosuppression negatively influence a cancer-related prognosis.