299 Intraperitoneal cytostatic-loaded supramolecular hydrogel and intestinal anastomotic healing INTRODUCTION Colorectal cancer (CRC) is the third most prevalent cancer type worldwide and a common cause of morbidity and mortality generally attributable to metastatic disease 1, 2. The prognosis of CRC patients with peritoneal metastases (PM) is very poor. For a selective group of patients, there are life-prolonging treatment options available. A common strategy for physically fit patients with limited disease burden is cytoreductive surgery (CRS) with or without adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) 1, 3. Patients who are not considered eligible may undergo a new palliative treatment option that is currently being investigated called pressurized intraperitoneal aerosol chemotherapy (PIPAC) 4-8. Despite the introduction of HIPEC and PIPAC, treatment failure is still a major issue in CRC patients with PM. As intraperitoneal delivery of cytostatic drugs is the preferred route for PM treatment, intraperitoneal drug delivery systems are being investigated 9. One such system is a supramolecular hydrogel, which has shown potential in the field of PM therapy. The development of targeted therapies using drug-loaded hydrogels can help deliver drugs directly to the affected area, improving therapeutic outcomes 10, 11. In recent years, our research team has conducted several experiments investigating the feasibility, safety, tissue compatibility and therapeutic efficacy of a supramolecular hydrogel loaded with mitomycin C (MMC) 12, 13. The main function of this injectable hydrogel is to form an intraperitoneal depot of slow-releasing MMC, aiming to establish prolonged exposure of the PM to the cytostatic agent. The therapeutic efficacy in a PM rat model was investigated before and demonstrated that there is a clinically relevant survival benefit for MMC-loaded hydrogel compared to injection of free MMC 13. Intraperitoneal chemotherapy is usually preceded by cytoreductive surgery, which frequently includes a colon resection to remove the primary tumor, often requiring a colonic or colorectal anastomosis. Anastomotic leakage (AL) is considered one of the most important complications after such a colon resection. It occurs in 1 to 19% of the cases and has a negative impact on survival 14, 15. Chemotherapeutics, including MMC, that are administered intraperitoneally are suspected to have an effect on anastomotic healing after surgery 16, 17. As the therapeutic benefit of MMC-loaded hydrogel in PM has been demonstrated by previous work, it is crucial to investigate its influence on anastomotic healing before considering this treatment option for in combination with CRS for PM of colorectal origin in humans. The aim of this study was to investigate whether intraperitoneal administration of hydrogel (both unloaded and MMC-loaded) affects colonic anastomotic healing; specifically, whether it results in a higher incidence of AL in a rodent animal model. For this purpose, the previously investigated supramolecular hydrogel was intraperitoneally applied in healthy rats after creating a sufficient end-to-end colon anastomosis. 13
RkJQdWJsaXNoZXIy MTk4NDMw