A new animal model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing mice in the treatment of peritoneal carcinomatosis of ovarian origin

Abstract

We set out to develop and evaluate the morbidity of a non-invasive hyperthermic intraperitoneal chemotherapy (HIPEC) procedure in mice. HIPEC has been shown to improve overall survival in treating ovarian cancer with peritoneal carcinomatosis. However, related complications, toxicity and the lack of randomized trials limits its widespread use. To improve the surgical technique, there is a need for animal models that allow teams to work on large groups without burdensome logistics. To develop the model, we first determined optimal HIPEC conditions in 20 Black Six mice without carcinomatosis. To evaluate HIPEC morbidity, peritoneal carcinomatosis cells of ovarian origin were injected into the peritoneum of 10 pathogen-free Nude mice. The mice underwent HIPEC 21 days later under general anesthesia. An inflow catheter was introduced into the left hypochondria and an outflow catheter was introduced into the left iliac fossa. Bath infusion was oxaliplatin (920mg/m2) at 43°C for 12minutes. The mice were monitored and sacrificed two weeks after the procedure. No deaths were observed during the procedure and infusion was well tolerated throughout the HIPEC. One mouse died the day after the procedure. No major dehydration, hemoperitoneum or evisceration was observed. This mouse model of closed abdomen HIPEC has limited morbidity and could be a useful model to study HIPEC regimens and its effects on peritoneal carcinomatosis.