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Effect of hypertermic chemoimmunotherapy on peritoneal carcinomatosis in mice

Background/aims: Peritoneal carcinomatosis is prognostically a very bad sign and common cause of death in patients with intestinal and stomac carcinoma as well as other gastrointestinal and gynecologic tumors. During a tumor surgery risk of peritoneal carcinomatosis is high because tumor cells are "dropping off" from the tumor surface which infiltrate serosa of abdomenal cavity in which it has been developed, so iatrogen peritoneal carcinomatosis develops. Considering the fact that mean surviving of patients with peritoneal carcinomatosis is between 2.2 and 8.8 months and five years survival period has been found less than 2%, therapeutic and prophylactic modalities which would eventually stop or slow down occurance and development of peritoneal carcinomatosis are investigated. The aim of this study was research and compare different models of locoregional immunochemotherapy, hyperthermial intraperitonal chemotherapy (HIPEC) in unique animal model of induced peritoneal carcinomatosis in mice. Material and mathods:CBA mice were injected with mammary carcinoma (MCa) cells into abdomenal cavity and consequtive peritoneal carcinomatosis was induced. In so called prevention model biological response modifiers (BRM), combination of IL-2 and plant extract from Caucalis platicarpos (CDL) was injected into abdominal cavity seven and three days before injection of tumor cells, respectively. Immediately after the injection of tumor cells we rinsed abdomenal cavity with saline that was heated to 37°C or 43°C (hyperthermial treatment) and injected cytostatics (doxorubicyn, cisplatin, mitomicyn, 5-FU) either separately or in combination. In therapeutic model BRMs were injected on day 5th after injection of tumor cells ; hyperthermia treatment was performed immediately before injection of cytostatic drugs. Results: Combination of doxorubicyn and plant extract CDL was very effective in prevention consindering survival and pathological signs of peritoneal carcinomatosis. Doxorubicyn as a drug of choice alone or in combination with either CDL or 5-FU or cisplatin with reinforced influence caused by hyperthermia poped up among therapy models. Conclusion: Excellent results can be obtained by combing hyperthermia, doxorubicyn and plant extract CDL in prevention and treatment of peritoneal carcinomatosis. When hyperthermia and combination of cytostatics are used drug dosage should be reduced to at least to avoid or to decrease side effects but still keep antineoplastic effect. Naturally, to check these results huge controled clinical studies in more cooperative groups should be conducted.

hyperthermia; chemoimmunotherapy; peritoneal carcinomatosis; mouse

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