Inhibition of Peritoneal Tumor-Cell Implantation: Model for Laparoscopic Cancer Surgery

Abstract

A serious concern in applying laparoscopic surgery to malignancies is the possibility of tumor spillage and seeding. We developed a model of peritoneal tumor implantation using a murine bladder tumor cell line, MBT-2. Anesthetized C3H male mice underwent mock laparoscopy with or without peritoneal disruption and instillation of tumor cells via a 16-gauge angiocatheter, and the effect of heparin and the pentapeptide Gly-Arg-Gly-Asp-Ser (GRGDS) on tumor cell adherence and growth was evaluated. Animals were divided into six groups: Group 1 = tumor cells only; Group 2 = peritoneal disruption + tumor cells; Group 3 = heparin + tumor cells; Group 4 = peritoneal disruption + heparin + tumor cells; Group 5 = GRGDS + tumor cells; and Group 6 = peritoneal disruption + GRGDS + tumor cells. In all animals, a greater tumor burden was noted at the sites of peritoneal disruption. Moreover, 50% and 63% of animals in Groups 1 and 2 developed tumors compared with 17% and 31% of those in Groups 3 and 4, respectively. There was significantly more tumor at the sites of peritoneal disruption in the "tumor only" groups than in those that received heparin (mean tumor volume 32.32 mm3 in Group 2 v 2.77 mm3 in Group 4; p < 0.05). The GRGDS-treated groups showed a trend toward decreased number and size of tumors compared with the tumor only groups, although the differences were not statistically significant. These findings imply that prophylactic irrigation with substances that decrease cell adherence may prevent tumor implantation after accidental intraoperative tumor spillage.