In-vivo investigation of the cytotoxic effect of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) on human colonic cancer cells in a rodent peritoneal carcinomatosis model

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Peritoneal Carcinomatosis describes the advanced stage of gastrointestinal and gynecological malignancies. A large number of patients is diagnosed in the presence of secondary symptoms such as ascites, bowel obstruction and icterus, which marks an advanced stage of their condition. These patients have a reported average survival of only a few months.When the local tumor mass is limited with regular bowl function present and good general state, cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) may be considered. However, CRS with HIPEC is an extensive surgical procedure with a wide range of possible complications. Thus, this only curative option is not applicable to the grand majority of patients as their body state or tumor progress may not allow such extensive surgery. In the last few years, a new experimental treatment alternative called Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has been introduced at the Marienhospital Herne which is gaining rapid acceptance as a valuable palliative treatment option in peritoneal carcinomatosis. Its primary goals are ascites control and local tumor regressionTo improve patients’ outcome and safety, the aim of this study is to establish a novel in-vivo PIPAC model for peritoneal carcinomatosis in the rat. Moreover, this study will closely examine the penetration depth of the applied chemotherapeutic drug and measure its cytotoxic effect by histopathological analysis and detection of objective tumor regression. For this purpose, commercially available human colonic cancer cells will be cultivated to develop a highly concentrated tumor cell suspension. This suspension will then be applied to rats by means of a subperitoneal injection, which, 3 weeks after implantation, will develop into peritoneal carcinomatosis. There will be 3 study groups in this experiment. The first group develops peritoneal carcinomatosis and receives three applications of PIPAC with Oxaliplatin, at treatment intervals of 6 weeks. The second group develops peritoneal carcinomatosis and does not receive any treatment, and hence serves as a control group. Then there is a third group of rats which has not received any tumor cell application and does not receive any surgical treatment, and thus serves as another control.Following the third application of PIPAC in week 15, the rats will not receive any further treatment until week 22. The purpose of this study design is to evoke similar criteria as applied in humans. In the clinical setting, patients receive 3 cycles of PIPAC therapy with intervals of 6 weeks. Following the third PIPAC cycle, patients will have a three month PIPAC break and receive staging exams in between. Thus, the aim of this study design is to mimic our patients’ conditions to see whether there is any benefit to this therapy as compared to the control rats. Moreover, this study aims to establish an in-vivo PIPAC model.