gms | German Medical Science

Objective: In selected patients with peritoneal carcinomatosis from colorectal cancer prognosis can be improved by hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery. Animal models are important to evaluate new treatment modalities. The purpose of this study was to devise a system which can be used routinely for HIPEC of peritoneal carcinomatosis in tumour bearing rats and to evaluate the tumor response of peritoneal carcinomatosis in tumor-bearing rats after HIPEC.

Methods: We used a new peritoneal perfusion system in rats. For this purpose the CC531 colon carcinoma, implanted intraperitoneal in Wag/Rija rats (2,5x106 cells), was treated by hyperthermic intraperitoneal chemotherapy with mitomycin c (MMC). After 10 days of tumour growth the animals were randomized into five groups of six animals each: group 1: control (n=6), group 2 (shame operated) (n=6), group 3: HIP (only hypertherm perfusion without MMC (n=6), group 4: HIPEC with mitomycin in a concentration of 30 mg/m2 (n=6), group 5: mitomycin i.p. in a concentration of 15 mg/m2 (n=6). HIPEC was performed over 90 minutes. The perfusion fluid was maintained at 40,5°C. After 10 days, total tumour weight and the extend of tumour spread, as assessed by the modified Peritoneal cancer index (PCI) were compared to autopsy.The relative number of apoptotic cells and bodies in the entire cancer cell population was detremined by counting their numbers in 10 high-power fields. The index represents the percentage of visible cancer cells.

Results: 10 days after inoculation of tumour cells, 100 % of rats develop small tumour nodules on peritoneal surfaces. No postoperative deaths were reported. The postoperative morbidity rate was 23,5 %. All control animals developed massive intraperitoneal tumor growth. Tumor load was significantly reduced in group III and group V and lowest in group IV . In group II tumor load was significantly higher than in group I. Port site metastases were significantly decreased in group IV compared with group I and group II.Most apoptosis were seen in group IV.

Conclusion: The model offers the possibility to study the mechanism of hyperthermic intraperitoneal chemotherapy and new drugs in this therapy. These findings indicate that HIPEC is an effective treatment for peritoneal carcinomatosis in this animal model. HIPEC reduced macroscopic and microscopic intraperitoneal tumor spread. Keywords: HIPEC, mitomycin, animal model, peritoneal carcinomatosis