Intraoperative versus Early Postoperative Intraperitoneal Chemotherapy after Cytoreduction for Colorectal Peritoneal Carcinomatosis: an Experimental Study

Abstract

Background. Perioperative intraperitoneal chemotherapy is used as an adjunct to cytoreductive surgery (CS) for peritoneal carcinomatosis (PC) in order to prolong survival. Worldwide, hyperthermic intraperitoneal chemotherapy (HIPEC), early postoperative intraperitoneal chemotherapy (EPIC), and combinations of the two are used. It remains unclear which regimen is most beneficial. Methods. The rat colon carcinoma cell line CC-531 was injected into the peritoneal cavity of 80 WAG/Rij rats to induce PC. Animals were randomized into four treatment groups (n = 20): CS only, CS followed by HIPEC (mitomycin 35 mg/m 2 at 41.5°C), CS followed by EPIC during 5 days (i.p. injection of mitomycin on day 1 and 5-fluorouracil on days 2-5), and CS followed by HIPEC plus EPIC. Primary outcome was survival. Results. In rats treated with CS only, median survival was 53 days (95% confidence interval (CI) 49-57 days). In rats treated with CS followed by HIPEC, survival was significantly (P = 0.001) increased (median survival 94 days, 95% CI 51-137 days). In the group treated with EPIC after CS, 12 out of 20 rats were still alive at the end of the experiment (P \ 0.001 as compared with CS only). In the group receiving both treatments, 11 rats died of toxicity, and therefore this group was not included in the survival analysis.Conclusions. Both EPIC and HIPEC were effective in prolonging survival. The beneficial effect of EPIC on survival seemed to be more pronounced than that of HIPEC.Further research is indicated to evaluate and compare the possible benefits and adverse effects associated with both treatments.

Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

“…It is hypothesized that HIPEC is more efficacious compared to conventional intraperitoneal therapy since it not only takes advantage of the hyperthermic effect, but also enables distribution of the drug in all parts of the peritoneal cavity [16]. Nevertheless, the efficacy of HIPEC is still controversial as several studies claim that no synergistic effect exists between the anti-cancer agent and the hyperthermia [15,17].…”

Safe temperature range for intraoperative and early postoperative continuous hyperthermic intraperitoneal perfusion in a swine model of experimental distal gastrectomy with Billroth II reconstruction

“…Intraoperative hyperthermic intraperitoneal chemotherapy (IHIC) alone and IHIC combined with early postoperative intraperitoneal chemotherapy have been performed in previous studies [10,26-28]. Improved survival has been reported in these studies, albeit with certain levels of mortality and severe complications [11,29].…”

“…In recent years, the improved survival associated with hyperthermic intraperitoneal perfusion chemotherapy for peritoneal carcinomatosis of gastric cancer [5,6] has been verified by both experimental [7] and clinical research [5,8]. Moreover, cytoreductive surgery plus hyperthermic intraperitoneal perfusion chemotherapy has become the priority treatment for gastric cancers with peritoneal carcinomatosis [9], and survival can be prolonged by intraoperative and early postoperative intraperitoneal chemotherapy [10,11]. This treatment may result in the timely elimination of free cancer cells resulting from operative factors or spontaneous dissemination.…”

Regimens of Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer

“…The overall survival with EPIC therapy was superior to that with HIPEC in a murine model (64). However, a clinical study found that the 5-year survival of patients treated using EPIC, as compared to HIPEC, was worse and was associated with a higher rate of digestive fistulas (55).…”