icodextrin and Colonic-Neoplasms

There is no standard treatment in patients with high risk metachronous peritoneal carcinomatosis (PC) in colonic cancer, as perforated tumour or synchronous ovarian metastasis. Icodextrin 4% (ICDX), presently used to prevent postoperative abdominal adhesions, could inhibit the coactivation of the tumour cells and the microenvironment cells, associated with the development of PC. The aim of this study was to inhibit the formation of the PC in a murine model mimicking surgical situation using ICDX and intraperitoneal (IP) prophylactic chemotherapy. We created a model of growing PC in mice using cells of murine colonic cancer CT26. Cells and treatments were injected simultaneously. Five groups were created: CT26 (control group), CT26 + ICDX (ICDX group), CT26 + chemotherapy (oxaliplatin and 5FU) (chemo group), CT26 + chemotherapy + ICDX (ICDX chemo group), ICDX (toxicity group). At day 15, PC was evaluated with rodents PCI. In the chemo group, PCI was significantly lower than in the control group (3.2 versus 8.4, p = 0.02). ICDX had a synergetic effect on PC with chemotherapy; indeed PCI in ICDX chemo group was lower than in chemo group (1.4 versus 3.2, p = 0.04). There was no morbidity linked to ICDX in toxicity group. Safety of ICDX needs to be verified, particularly on colonic anastomosis before ICDX associated to IP chemotherapy could be used as a preventive treatment of PC in high risk patients. This prophylactic treatment is easy to use and would be administrated at the end of a curative surgery for a colonic cancer.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Survival; Colonic Neoplasms; Dialysis Solutions; Disease Models, Animal; Fluorouracil; Glucans; Glucose; Icodextrin; Infusions, Parenteral; Mice; Organoplatinum Compounds; Oxaliplatin; Peritoneal Neoplasms

Peroperative peritoneal trauma activates a cascade of peritoneal defense mechanisms responsible for postoperative adhesion formation. The same cascade seems to play a role in the process of intra-abdominal tumor recurrence. Icodextrin is a glucose polymer solution that is absorbed slowly from the peritoneal cavity, allowing prolonged "hydroflotation" of the viscera, thereby decreasing adhesion formation. This study evaluated the adhesion-preventing properties of icodextrin and its effect on peritoneal metastasis.. Reproducible rat models of peritoneal trauma were used, allowing semiquantitative scoring of adhesion formation or tumor load. In one experiment, peritoneal trauma was inflicted; one group was treated by peroperative intra-abdominal instillation of 7.5% icodextrin, one by instillation of RPMI (placebo), and one had no instillate (controls). In another experiment involving a different model of peritoneal trauma, the coloncarcinoma cell line CC531 was injected intraperitoneally to induce tumor load, again using these three groups.. Treatment of peritoneally traumatized rats with icodextrin caused a 51% reduction in postoperative adhesion formation ( P < .001). However, peroperative intra-abdominal treatment with icodextrin did not affect intraperitoneal tumor cell adhesion and growth of free intra-abdominal tumor cells in rats with this model of severe peritoneal trauma.. A 7.5% icodextrin solution is effective in reducing postoperative adhesions without promoting tumor recurrence and therefore may prove useful and safe in oncologic surgery.

Topics: Adenocarcinoma; Animals; Cell Adhesion; Cell Division; Colonic Neoplasms; Female; Glucans; Glucose; Icodextrin; Neoplasm Transplantation; Peritoneum; Postoperative Complications; Rats; Rats, Inbred Strains; Specific Pathogen-Free Organisms; Tissue Adhesions