Postoperative Peritoneal Infection Enhances Migration and Invasion Capacities of Tumor Cells In Vitro An Insight Into the Association Between Anastomotic Leak and Recurrence After Surgery for Colorectal Cancer

Objective: The aim of this study was to investigate the effect of postoperative peritoneal infection on proliferation, migration, and invasion capacities of cancer cells lines in vitro after surgery for colorectal cancer. Background: Anastomotic leakage 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 enhance tumor progression features of residual cancer cells. Methods: Prospective matched cohort study. Patients undergoing surgery for colorectal cancer with curative intent (January 2008-March 2012) were included. Patients who had an anastomotic leak or intra-abdominal abscess were included in the infection group (n = 47). For each case patient, another patient with an uncomplicated postoperative course was selected for the control group (n = 47). In vitro treatments on cancer cell lines (MDA-MB-231 and SW620) were performed using baseline and postoperative serum and peritoneal fluid samples to determine cell proliferation and cell migration/invasion activities. Results: Postoperative peritoneal fluid from infected patients enhanced both cell migration (infection: 140 +/- 85 vs control: 94 +/- 30; P = 0.016) and cell invasion (infection: 117 +/- 31 vs control: 103 +/- 16; P = 0.024) capacities of cancer cell lines. With serum samples, these effects were only observed in cell migration assays (infection: 98 +/- 28 vs control: 87 +/- 17; P = 0.005). Some minor activation of cell proliferation was observed by treatment with serum from infection group. Two-year cumulative disease-free survival was significantly lower in patients with postoperative peritoneal infection (infection: 77.6% vs control: 90.6%; P = 0.032). Conclusions: Our results suggest that postoperative peritoneal infection enhances the invasive capacity of residual tumor cells after surgery, thus facilitating their growth to recurrent tumors.