Abstract

BackgroundCytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis.MethodsA new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals.ResultsNo postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II.ConclusionThe combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality.

Highlights

  • Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin

  • Complete cytoreductive surgery plus HIPEC is effective in the prevention and treatment of peritoneal metastases and it should lead to long-term survival for serosa-invasive carcinoma patients [2]

  • Perfusion characteristics Intraoperatively the required tissue temperature was reached within 9–11 minutes in the HIPEC group

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Summary

Introduction

Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a new treatment modality. Complete cytoreductive surgery plus HIPEC is effective in the prevention and treatment of peritoneal metastases and it should lead to long-term survival for serosa-invasive carcinoma patients [2]. The technique of hyperthermic intraperitoneal chemoperfusion in humans has been employed in cancer therapy, controlled studies using this approach are rare. Intraperitoneal chemotherapy results in a high local drug concentration with less systemic exposure compared to conventional i.v. drug administration [3,4]. The additional toxic effect of MMC at temperatures higher than 39°C has been demonstrated both in animals and in in vitro models [7,8]

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