Postoperative intra-abdominal infection increases angiogenesis and tumor recurrence after surgical excision of colon cancer in mice
Accepted 30 June 2009. published online 23 September 2009.
Background
Recent reports have suggested that anastomotic leakage is associated with greater rates of tumor recurrence and cancer-specific mortality after surgery for colorectal cancer. The impact of postoperative intra-abdominal infection on long-term oncologic results, however, is still controversial, and no direct causal relationship has been found between both processes. Our aim was to investigate the influence of postoperative intraabdominal infection on angiogenesis and tumor growth in an animal model of colon cancer.
Methods
Balb/c mice were randomized immediately after injection of 5×106 B51LiM cells into the cecal wall into 2 groups: cecal resection without postoperative infection (group 1), and cecal resection with postoperative intra-abdominal infection (group 2). A total of 18 days after cell injection, cecectomy was performed, and infection was induced in group 2 by intraperitoneal injection of 3×108 colony-forming units of Bacteroides fragilis. On postoperative day 12, the mice were killed.
Results
Comparing group 1 with group 2, tumor recurrence was more frequent in animals with intraabdominal infection (65% vs 100%, respectively; P =.02). VEGF serum levels were greater at the time of sacrifice in the group with infection (11±10 vs 30±23pg/mL; P < .05). Tumor angiogenesis was also increased in the postoperative infection group. The mean (± standard deviation) microvessel density was 16 ±7 versus 28 ±11 vessels per high-power field (P < .05).
Conclusion
We concluded that postoperative intra-abdominal infection increases angiogenesis and tumor recurrence after operative excision of a colon cancer in mice.
aColorectal Surgery Unit, Department of Surgery, Hospital del Mar, Barcelona, Spain
bColorectal Cancer Research Group, Cancer Research Program, Municipal Institute for Medical Research (IMIM-Hospital del Mar), Barcelona, Spain
cDepartment of Microbiology, Laboratori de Referència de Catalunya, Barcelona, Spain
dDepartment of General Surgery, University of Heidelberg, Heidelberg, Germany
Reprint requests: Miguel Pera, MD, Colorectal Surgery Unit, Department of Surgery, Hospital del Mar, Passeig Marítim 25-29, 08003 Barcelona, Spain.
Supported by a research grant from the Asociación Española Contra el Cáncer (No. 449).