Postoperative serum Vascular Endothelial Growth Factor is an independent prognostic factor of disease free survival and overall survival in patients with non metastatic colon cancer.

BACKGROUND: Angiogenesis is essential for tumor growth and formation of metastasis. VEGF is the most potent agiogenic citokine. The aim was to investigate the predictive value of postoperative VEGF serum concentration in patients undergoing surgery for colon cancer. METHODS: Consecutive patients with colon cancer undergoing surgery with curative intent were included. VEGF was measured in serum at 48 h and postoperative day 4. Cox proportional hazards model was used to estimate its contribution with prognosis. RESULTS: A total of 94 patients were included. On multivariate analysis VEGF on postoperative day 4 (HR: 1.05; p = 0.011) was independent prognostic factor of decreased DFS and OS. Five-year DFS (57.7% vs. 85%; p = 0.001) and OS (93% vs. 72%; p = 0.005) were significantly lower in patients with postoperative serum VEGF greater than 370 pg/dl. CONCLUSION: Postoperative VEGF serum concentration was an independent predictor of recurrence. These results must be verified in a prospective independent testing cohort.

Peripheral blood leucocytes show differential expression of tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection: a prospective matched cohort study.

AIM: Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may induce overexpression of tumour progression-related genes in immune cells. The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leucocytes (PBL) after surgery for colorectal cancer. METHOD: Prospective matched cohort study. Patients undergoing surgery for colorectal cancer were included. Patients who had anastomotic leak or intra-abdominal abscess were included in the infection group (n = 23) and matched with patients without complications for the control group (n = 23). PBL were isolated from postoperative blood samples. Total RNA was extracted and hybridized to the Affymetrix Human Gene 1.0 ST microarray. RESULTS: Patients in the infection group displayed 162 upregulated genes and 146 downregulated genes with respect to the control group. Upregulated genes included examples coding for secreted cytokines involved in tumour growth and invasion (S100P, HGF, MMP8, MMP9, PDGFC, IL1R2). Infection also upregulated some proangiogenic genes (CEP55, TRPS1) and downregulated some inhibitors of angiogenesis (MME, ALOX15, CXCL10). Finally, some inhibitors (HP, ORM1, OLFM4, IRAK3) and activators (GNLY, PRF1, FGFBP2) of antitumour immunity were upregulated and downregulated, respectively, suggesting that the inflammatory environment caused by a postoperative infection favours immune evasion mechanisms of the tumour. CONCLUSION: Analysis of PBL shows differential expression of certain tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection, which in turn may promote the growth of residual cancer cells to become recurrent tumours.

Postoperative intra-abdominal infection and colorectal cancer recurrence: a prospective matched cohort study of inflammatory and angiogenic responses as mechanisms involved in this association.

BACKGROUND: Anastomotic leakage is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. The aim was to investigate the inflammatory and angiogenic responses in patients undergoing surgery for colorectal cancer who had postoperative intra-abdominal infection, and to compare the results with patients without complications. METHODS: Consecutive patients undergoing surgery for colorectal cancer with curative intent were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group and matched with patients who had an uncomplicated postoperative course. IL-6 and VEGF were measured in serum and peritoneal fluid. RESULTS: Serum concentration of IL-6 was higher in the infection group (n = 30) compared with the control group (n = 30) on day 4 (infection: 42.3 [27.6-1473.2] versus control: 0.6 [0.6-17.1] pg/ml; p = 0.008). IL-6 in peritoneal fluid was higher in the infection group at 48 h and day 4 (infection: 1000.2 [995.4-1574.0] versus control: 90.3 [35.2.6-106.1] pg/ml; p = 0.001). Serum VEGF was higher in the infection group on day 4 (infection: 1128.6 [427.3-10000.0] versus control: 438.3 [214.1-677.6] pg/ml; p = 0.001). Peritoneal VEGF concentration was higher in the infection group at 48 h and day 4 (infection: 10000.0 [2563.0-10000.0] versus control: 477.8 [313.5-814.4] pg/ml; p = 0.001). Two-year recurrence rate was higher in patients with infection (infection: 30% versus control: 4%; p = 0.001). CONCLUSIONS: Intra-abdominal infection increases IL-6 and VEGF after surgery for colorectal cancer. Amplification of inflammation and angiogenesis might be one of the mechanisms responsible for the higher recurrence rate observed in patients with anastomotic leakage or intra-abdominal abscess.