Elsevier

Surgery

Volume 147, Issue 1, January 2010, Pages 120-126
Surgery

Original Communication
Postoperative intra-abdominal infection increases angiogenesis and tumor recurrence after surgical excision of colon cancer in mice

https://doi.org/10.1016/j.surg.2009.06.035Get rights and content

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 ± 23 pg/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.

Section snippets

Animals

A total of 70 Balb/c mice (Harlan Interfauna Iberica, Barcelona, Spain), 6–8 weeks of age, weighing 19–21 g, were used for the experiments. The animals were allowed free access to a standard laboratory diet and water. All procedures were reviewed and approved by the IMIM-Hospital del Mar Animal Care and Use Committee in accordance with European guidelines.

Tumor cell line

A colonic adenocarcinoma cell line (B51LiM), obtained from Robert S. Bresalier, MD, at the Henry Ford Health Sciences Center, Detroit, MI, was

Operative findings and postoperative mortality

After randomization of the 70 mice, 28 were assigned to group 1 and 42 to group 2. Of the 70 mice, 11 died within 48 hours after the cecal injection (3 in group 1 and 8 in group 2); in most animals, the cause of death was cecal ischemia. Another 10 animals (14%) were excluded from the study at the time of cecal resection: in 5 of these 10 animals, there was no tumor in the cecum; in the other 5 animals, there were peritoneal implants, probably because of the spillage of cells during the cecal

Discussion

Several cohort and case-control studies have shown that postoperative intra-abdominal infection is associated with greater rates of tumor recurrence and cancer-specific mortality after potentially curative resection for colorectal cancer.5, 6, 7, 8, 9, 10, 11, 12, 13, 14 In this report, we provide direct evidence pointing to a causative role of intra-abdominal infection in the recurrence of resected cecal tumors by using the in vivo B51LiM colon cancer mouse model and postoperative infection

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    Supported by a research grant from the Asociación Española Contra el Cáncer (No. 449).

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