Mechanisms and prevention of port-site tumor recurrence after laparoscopy in a murine model

Abstract

Background/Purpose: Although minimally invasive surgery (MIS) has been broadly applied in patients with cancer of the gastrointestinal tract, the etiology of port-site tumor recurrence (PSR) after laparoscopic cancer surgery remains unclear. The authors report here an analysis of PSR in a model of murine neuroblastoma after laparoscopic tumor biopsy and propose a mechanism for this complication as well as a potential treatment. Methods: Immature 5- to 7-week old male A J mice (18–23 g) were subcutaneously inoculated with the minimally immunogenic TBJ-neuroblastoma (TBJ-NB) in the left flank and divided into three treatment groups. The following operations were performed 14 days after tumor inoculation: group 1, additional intraperitoneal or intravenous injection of TBJ-NB during CO 2 pneumoperitoneum; group 2, simulated transperitoneal tumor biopsy using MIS techniques during either CO 2 pneumoperitoneum or gasless suspension; Group 3, intraperitoneal (IP) or intravenous (IV) administration of cyclophosphamide on postoperative days 0 and 3 to prevent PSR after simulated tumor biopsy during CO 2 pneumoperitoneum. Results: In group 1, the incidence of PSR was 0% in the intravenously injected mice versus 63% in mice injected intraperitoneally with TBJ-NB. In group 2, no significant difference in the incidence of PSR was seen between simulated tumor biopsy (89%) animals with CO 2 pneumoperitoneum versus animals with gasless suspension (81%). In group 3, mice that did not receive any chemotherapy had an 89% incidence of PSR. Administration of cyclophosphamide via either the IP or IV route effectively prevented PSR, although there was no difference in the incidence of PSR between the two routes (IP 12% versus IV 13%). Conclusions: The data suggest that PSR in tumor-bearing hosts may be caused by direct seeding of exfoliated tumor cell, and not by hematogenous metastases. Contrary to the other reports, CO 2 pneumoperitoneum was not found to be essential for the development of PSR. Furthermore, the authors conclude that postoperative chemotherapy may be useful in preventing PSR after MIS in patients bearing chemotherapy-sensitive tumors such as neuroblastoma.