New Therapeutic Strategies to Avoid Intra- and Extraperitoneal Metastases during Laparoscopy: Results of a Tumor Model in the Rat

<i>Background:</i> Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. <i>Methods:</i> The effects of taurolidine, heparin, and povidone iodine on the growth of rat and human colon adenocarcinoma as well as gallbladder carcinoma were investigated in vitro. Furthermore, cytokine release of growth-stimulating IL-1β by peritoneal macrophages was measured after incubation with carbon dioxide and additional incubation with the different agents. In the third experiment, prevention of intra- and extraperitoneal metastases by intraperitoneal instillation of the different agents during laparoscopy was investigated in a colon carcinoma model in the rat. Tumor cells were administered intraperitoneally in 100 rats, and pneumoperitoneum (8 mm Hg) was established over 30 min with carbon dioxide. Rats received either tumor cells, cells + heparin, cells + povidone iodine, cells + taurolidine, or cells + taurolidine + heparin. <i>Results:</i> In vitro, tumor cell growth decreased after incubation with taurolidine, taurolidine/heparin, and povidone iodine. Cytokine release was stimulated by incubation with carbon dioxide and could only be suppressed by incubation with taurolidine in vitro. In vivo, intraperitoneal tumor weight was lower in rats receiving heparin (251 ± 153 mg) and povidone iodine (134 ± 117 mg) compared to the control group (541 ± 291 mg), but even less when taurolidine (79 ± 82 mg) or taurolidine/heparin (18.3 ± 30 mg) were instilled. <i>Conclusion:</i> Heparin slightly inhibits intraperitoneal tumor growth in vivo, while povidone iodine and taurolidine cause a significant decrease in tumor cell growth in vitro as well as intraperitoneal tumor growth in vivo. Cytokine release of peritoneal macrophages is only suppressed by taurolidine. Total tumor take and trocar metastases are only suppressed by taurolidine and taurolidine/heparin.