JOURNAL OF ENDOUROLOGY Volume 7, Number 3, 1993 Mary Ann Liebert, Inc., Publishers Inhibition of Peritoneal Tumor-Cell Implantation: Model for Laparoscopie Cancer Surgery DAVID S. GOLDSTEIN, MD,* MICHAEL L. LU, PhD,* TOMOTAKA HATTORI, MD,* TIMOTHY L. RATLIFF, PHD.t KEVIN R. LOUGHLIN, MD,* and LOUIS R. KAVOUSSI, MD* ABSTRACT A serious concern in applying laparoscopie 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-GIy-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 = hep¬ arin + 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 signifi¬ cantly 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 2.77 mm3 in Group 4; < 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. INTRODUCTION LAPAROSCOPIC SURGERY is now being applied to diag¬ nose and treat a variety of urologie diseases traditionally approached by open surgical techniques.'·2 Its application to remove malignancies is of concern to many oncologie surgeons because of the possibility of tumor spillage. Meticulous adher¬ ence to basic surgical principles during open radical extirpative surgery has been the most accepted method to avoid this com¬ plication. Accidental spillage of tumor during open or laparoscopie surgery can result in recurrence and spread of the malignancy. The likelihood that cells will survive and flourish depends on the availability of adequate nutrition. Although some tumor cells can proliferate in suspension, most require adherence and implantation on an appropriate tissue surface to survive.3 Sev¬ eral mechanisms for cell attachment have been elucidated over the past decade.3-6 Damaged tissues, such as those injured by cautery or scalpel, appear to provide a friendlier environment for tumor-cell attachment, perhaps by exposure of the extracel¬ lular matrix. Extracellular matrix proteins interact with cell- surface proteins and affect various biologic functions.3'4'7 One extracellular matrix protein that has been implicated in tumor- cell attachment is fibronectin.3·5'6'8'9 The tripeptide responsi¬ ble for cell binding to fibronectin at its cell-attachment domain is L-arginyl-glycyl-L-aspartic acid (RGD),5 and soluble syn¬ thetic peptides containing this sequence inhibit the attachment of cells to fibronectin.3'5·6·9'10 * Department of Surgery, Division of Urology, Harvard Medical School, Boston, MA tDivision of Urological Surgery, Washington University School of Medicine, St Louis, MO 237