Taurolidine improves survival by abrogating the accelerated development and proliferation of solid tumors and development of organ metastases from circulating tumor cells released following surgery.
BACKGROUND
Surgical trauma is partly responsible for enhancing tumor growth through a variety of mechanisms that are still not fully elucidated. The use of perioperative immunostimulants may modulate these effects. This study examined the effect of administration of taurolidine after laparotomy or laparoscopy on the growth of solid tumor, the establishment of hepatic and lung metastases, and effects on natural killer (NK) and lymphokine-activated killer (LAK) cell function.


METHODS
B16 melanoma right flank tumors were established in mice (n = 180). These animals underwent anesthesia only (control) or laparotomy or laparoscopy (n = 60 per group) and were randomized to receive either saline or taurolidine (n = 30 per group) at specific time points. Survival was determined in each group, and in a further 90 mice tumor growth was followed over 10 days postoperatively. The experiment was repeated in 540 mice, which underwent one of the three procedures and were treated with either saline or taurolidine. NK and LAK cell cytotoxicity (NKCC, LAKCC) was determined at several time points postoperatively. In a further experiment, B16 melanoma tumor cells were delivered via tail vein injection (n = 180) and intrasplenic injection (n = 180). The effect of saline or taurolidine administration on survival after the establishment of metastases was determined, and again in a further 180 mice the establishment of metastatic deposits in the liver or lungs was determined after 8 days.


RESULTS
Survival appeared to be significantly decreased in both the solid-tumor model and the metastatic models undergoing laparotomy compared to laparoscopy and controls (P < 0.0001) and to a lesser extent in the laparoscopy group compared to controls (P < 0.001). Flank tumor growth and metastatic tumor formation were more significant in laparotomy groups compared to laparoscopy groups and controls, but also to a lesser extent in laparoscopy groups compared to controls (P </= 0.05). NKCC and LAKCC were significantly decreased in the same patterns (P < or = 0.03). However, treatment with taurolidine abolished these effects, restoring NKCC and LAKCC (P < or = 0.04) and laparoscopy groups (P < or = 0.001).


CONCLUSIONS
It appears that changes that occur after the trauma of laparotomy, and to a lesser extent, after laparoscopy, significantly enhance the growth of primary tumors as well as the development of metastases from circulating tumor cells and are associated with a suppression of host antitumor surveillance mechanisms. This not only affected tumor progression in the immediate postoperative period, but also ultimately affected survival. Taurolidine, a known immunostimulant, appears to abrogate the effects of surgical trauma on primary and metastatic tumor growth and also enhances survival. This may have significant value in the management of tumor-bearing patients undergoing resection.
Da Costa
M L
ML
Department of Surgery, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Redmond
H P
HP
Bouchier-Hayes
D J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D010535:Laparoscopy; D007813:Laparotomy; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009360:Neoplastic Cells, Circulating; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013829:Thiadiazines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D013829:Thiadiazines; D013654:Taurine; C012566:taurolidine