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

Abstract

Background: Therapeutic strategies to prevent port site recurrences in laparoscopy surgery of malignancies have not been investigated until now. Methods: 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. Results: 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. Conclusion: 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.

Divergent effects of taurolidine as potential anti-neoplastic agent: Inhibition of bladder carcinoma cells in vitro and promotion of bladder tumor in vivo

“…Additionally, TRD has been reported to reduce tumor necrosis factor · (TNF-·) and interleukin-1 ß (IL-1ß) synthesis and activity (20)(21)(22). The reduction of tumor angiogenesis, supposedly by preventing the activation of VEGF production in tumor cells (23,24) and the induction of cell apoptosis (10,25,26), might be an explanation for the antineoplastic properties of TRD.…”

Tumor Cell Dissemination during Laparoscopy: Prevention and Therapeutic Opportunities

“…Topical treatment of port sites can decrease the incidence of recurrences at the incision. In the animal model, trocar recurrences were suppressed by taurolidine, the combination taurolidine + heparin [66], 5-FU [67], povidone-iodine [56, 68, 69, 70, 71], methotrexate [56], but not chlorhexidine [71]. A number of animal studies suggest that it is possible to reduce the incidence of wound tumors via peritoneal and wound irrigation with a variety of agents.…”

Trokarkanalmetastasen: Was ist gesichert?

“…Diese durch Kohlendioxid hervorgerufene Vera È nderungen der Immunfunktion wurden auch durch Puttick et al [59] besta È tigt, die u È ber eine signifikant verminderte spontane und stimulierte Produktion von TNF-alpha in Peritonealmakrophagen nach Helium-und Kohlendioxidinsufflation berichteten. In einer anderen Studie konnte gezeigt werden, dass es nach Kohlendioxidinsufflation im Vergleich zur Helium-und der Kontrollgruppe zu einem signifikanten Anstieg der Freisetzung des wachstumsstimulierenden IL-1û in Peritonealmakrophagen kommt [64]. Es scheint, dass die Insufflation von Kohlendioxid und die zusa È tzliche intrazellula Ère Azidose sowohl einen hemmenden als auch einen stimulierenden Effekt auf die Produktion und Freisetzung unterschiedlicher intrazellula È rer Zytokine haben kann.…”

“…Durch die lokale intraperitoneale Applikation des zytotoxischen PVP-Jods in einer Konzentration von 1,0 bzw. 0,25% konnte in mehreren unabha Èngigen Studien eine Reduktion des intraperitonealen Tumorwachstums und der Entwicklung von Trokarkanalmetastasen nach laparoskopischen Eingriffen erreicht werden [1, 64,71]. Hierbei fu È hrte die Zytotoxizita Èt der Substanz auch zu einer Scha Èdigung der Peritonealmakrophagen, wodurch die lokale Immunabwehr negativ beeinflusst werden ko È nnte [64].…”

“…0,25% konnte in mehreren unabha Èngigen Studien eine Reduktion des intraperitonealen Tumorwachstums und der Entwicklung von Trokarkanalmetastasen nach laparoskopischen Eingriffen erreicht werden [1, 64,71]. Hierbei fu È hrte die Zytotoxizita Èt der Substanz auch zu einer Scha Èdigung der Peritonealmakrophagen, wodurch die lokale Immunabwehr negativ beeinflusst werden ko È nnte [64]. Nach einer intraperitonealen Instillation von PVP-Jod im Rattenmodell wurde zudem eine signifikante Erho È -hung intrazellula Èrer Zytokine, welche das Tumorzellwachstum direkt stimulieren ko È nnen, im Peritonealsekret nachgewiesen [64].…”