To study the mechanisms underlying the effects of intraperitoneal chemoperfusion and to develop the optimal chemoperfusion regimen, an animal model of peritoneal carcinomatosis closely resembles a human model of peritoneal carcinomatosis is required. In our study, the model of peritoneal carcinomatosis in rats with ascitic ovarian cancer was used. material and methods. There were three groups of rats with ascitic ovarian cancer: 1 – the control group (n=15) having no treatment; 2 – rats receiving normothermic intraperitoneal chemoperfusion with cisplatin, 40 mg/kg (n=12); 3 – rats receiving hyperthermic intraperitoneal chemoperfusion with cisplatin, 20 mg/kg (n=14). All animals were euthanized with subsequent autopsy. results. Ascitic ovarian cancer developed in 100 % of the animals injected with the tumor cells. The median overall survival of rats in the control group was 9.5 days. At autopsy, all rats had ascites, and rats surviving 15‒17 days after the tumor cell injection had white tumor nodes measuring 1–3 mm in the greater omentum, intestinal mesentery, parietal and visceral peritoneum. The nodes were histologically verified as metastases of low-differentiated ovarian tumor. In 2 and 5 rats from groups 2 and 3 respectively, metastases in paratracheal lymph nodes and tumor hydrothorax were detected with no evidence of peritoneal carcinomatosis. The median survival of rats in groups 2 and 3 was significantly higher than that in the control group, being 37.5 and 25.5 months, respectively (р=0,256). conclusion. This in vivo study proved that localization of ascitic ovarian tumor, development of the tumor in all animals injected with tumor cells, fast ascites progression and peritoneal carcinomatosis make this ascitic ovarian cancer an adequate preclinical model of peritoneal carcinomatosis to study intraperitoneal chemoperfusion. Further studies are needed to understand the reasons and mechanisms of the tumor hydrothorax development in rats after intraperitoneal chemoperfusion.
Introduction. Therapy of malignant tumors is one of the most important problems of modern pediatric oncology. The presence of distant metastases is considered as the main sign of generalization of the tumor process. In order to improve the results of treatment of these patients, we proposed to supplement cytoreductive surgery with intraoperative isolated chemoperfusion of the lung and/or pleura with cytostatic. The purpose of the study is to determine the effectiveness of metastasectomy combined with isolated lung/pleura chemoperfusion (ILCP/PCP) under conditions of hyperoxia in children. Materials and methods. For 10 years of research (2008–2018) on the basis of the N.N. Petrov National Medical Research Center of Oncology produced 45 ILCP and PCP in 30 patients with intrapulmonary and intrapleural metastases of various malignant bone tumors. The ILCP method is a surgical procedure, during which the lung is temporarily switched off from the circulation and perfused with modified saline containing high concentrations of an antitumor drug (melphalan or cisplatin), which allows delivery of high doses of cytostatics while avoiding systemic exposure to the drug. In cases of detection of metastatic lesions of the parietal pleura after metastasectomy, PCP was performed, consisting in drainage of the pleural cavity and intraoperatively conducting, after suturing the surgical wound, hyperthermic (42 o С) chemoperfusion of the pleural cavity with a cisplatin solution for 2 hours. Results. In children with malignant bone tumors, 37 isolated chemoperfusions with cisplatin and 8 with melphalan were performed. In 27 patients, 36 ILCP were performed, in 7 patients – 9 PCP. Nine (20 %) patients underwent bilateral perfusion with an interval from 1.5 to 31 months. There were no lethal outcomes during operations and in the postoperative period. The average duration of surgical interventions was 270 ± 90 (120–520) minutes. The number of remote foci – from 1 to 56 (average value – 9). The average blood loss was 300 ± 200 (150–1000) ml. The mean follow-up was 45 months; median overall survival – 38 months; 3-year overall survival – 65.5 ± 9.4 %. Survival without progression – 40.5 ± 10.5 % (n = 30). Conclusions. ILCP/PCP with cytostatics is a method of complex therapy that can improve the quality and increase the life expectancy of patients, especially with the exhausted possibility of other treatment options.
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