Comparative analysis of regional chemotherapy methods on an experimental rat model with peritoneal carcinomatosis

Peritoneal carcinomatosis is a variant of implantation metastasis of tumors sprouting the serous membrane of an organ. At the moment, the most effective treatment for this disease is regional chemotherapy. Systemic chemotherapy is not effective enough. The standard for the treatment of peritoneal carcinomatosis was cytoreductive interventions followed by open or closed hypertermic intraperitoneal chemoperfusion (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC). Purpose of the study: in an animal experiment to compare the efficacy and safety of regional chemotherapy methods HIPEC and PIPAC Materials and methods: the study was conducted on 44 rats of Wistar females. To simulate carcinomatosis, a strain of ascites ovarian tumor (OA) from the Russian Oncology Cancer Research Center N.N. Petrova. was used. The safety of the technique was evaluated clinically and based on laboratory blood tests. Efficiency - based on mass spectrometry, pathomorphological data and in assessing the life expectancy of animals. Results: the conducted methods HIPEC (open, closed) and PIPAC have shown their safety in experiments on laboratory animals. The closed HIPEC technique is most effective. The analysis of the incidence of postoperative complications demonstrated a greater aggressiveness of open and closed techniques compared to the more “sparing” PIPAC method. Conclusions: the experiment showed comparable safety of all animals tested. Due to the peculiarities of the technique, the PIPAC method can be used as an option for multi-stage treatment in cases where CPC and HIPEC are not possible due to a high index of peritoneal carcinomatosis, and as a neoadjuvant treatment to prevent peritoneal carcinomatosis. In any case, the prospects for using this method require further research.

Cytoreductive surgery and hyperthermal intraperitoneal chemoperfusion in colorectal cancer and cancer of ovaries: our experience and perspectives of a new method

Objective. Studying of results of the cytoreductive operations and hyperthermal intraperitoneal chemoperfusion application for treatment of canceromatosis in colorectal cancer and ovarian cancer. Materials and methods. In 10 patients, suffering colorectal cancer (6 men and 4 women) were performed peritonectomy, diathermo-ablation of implants, made from visceral peritoneum. Average value of the peritoneal canceromatosis index have constituted 18 (14 - 21). In 11 patients, suffering ovarian cancer, panhisterectomy, peritonectomy, omentectomy, and ablation of the visceral peritoneum implants was conducted. Median value of the peritoneal canceromatosis index was 16 (12 - 20). For hyperthermal intraperitoneal chemoperfusion oxaliplatin was used. Results. Complete and optimal cytoreduction (degree CC0-CC1 in accordance to classification of P. H. Sugarbaker) was achieved in 5 patients, while suboptimal one (degree CC2) - in 10, and nonoptimal (degree CC3) cytoreduction - in 6 patients. Intraoperative complications were absent. Postoperative complications have occurred in 5 (23.8%) patients: the wound infection, persisting ileus, episode of partial ileus. Of 10 patients, suffering colorectal cancer, 5 died in 9-12 mo. One-year barrier have had survived 45.5% patients. Of 11 women-patients, suffering ovarian cancer, 7 died in 6-24 mo. One-year barrier have had survived 36.4% women-patients. Conclusion. In patients, suffering colorectal cancer, the survival median was 12 mo, while in the women-patients, suffering ovarian cancer - 18 mo. Cytoreductive operations and hyperthermal intraperitoneal chemoperfusion constitute perspective method for the survival enhancement in patients, suffering canceromatosis, but only if their selection was organized.

Modeling of Chemoperfusion vs. Intravenous Administration of Cisplatin in Wistar Rats: Adsorption and Tissue Distribution

Hyperthermic intraperitoneal chemoperfusion (HIPEC) is an established form of locoregional chemotherapy of peritoneum tumors. However, its efficacy and safety status remain a controversy, partially, due to scarce data on pharmacokinetics and toxicity profile of drugs under HIPEC. In the current study, 24 female Wistar rats were randomly assigned to receive cisplatin as HIPEC (n = 12, 20 mg/kg) or intravenously (i.v., n = 9, 4 mg/kg). The subgroups of three animals were used for the initial, intermediate, and late phases of the pharmacokinetic assessment. The animals were sacrificed on days 1 and 5. Blood, liver, kidney, and ovaries were evaluated for platinum content. Histological and immunohistochemical evaluation was undertaken in the liver and kidney. A trend for higher blood plasma platinum levels was observed for HIPEC compared to i.v. Significantly lower (p < 0.001) relative platinum binding to the proteins was observed in HIPEC animals compared to the i.v. administration. A five-fold higher concentration of cisplatin in HIPEC resulted in a ca. 2.5-fold increase in total blood platinum and ca. two-fold increase in blood ultrafitrable platinum (“free” Pt). Immunohistochemistry revealed higher kidney and liver damage after i.v. administration of cisplatin compared to HIPEC, although a five-fold higher dose of cisplatin was applied in HIPEC. Together with relatively lower absorption to the systemic circulation in HIPEC, higher protein binding is probably the primary reason for lower observed toxicity in HIPEC animals.

CHALLENGES IN CHOICE OF THE TREATMENT STRATEGY FOR PATIENTS WITH RECURRENT PSEUDOMYXOMA PERITONEI

Pseudomixoma peritonei is a rare type of peritoneal carcinomatosis accompanied by accumulation of mucus and high recurrence rate and in some cases complicated with intestinal obstruction. In the last 10–15 years, there has been observed a significant improvement in overall survival of patients with recurrent pseudomyxoma, who underwent cytoreductive surgery in combination with intraperitoneal chemotherapy. However, the frequency of recurrences of peritoneal pseudomyxoma after optimal cytoreduction can reach 80–90 % in the first 2 years.The purpose of the study was to analyze the results of combined therapy (cytoreductive surgery and hypothermic intraperitoneal chemoperfusion) in patients with recurrent pseudomyxoma peritonei, who previously underwent cytoreductive surgery.Material and Methods. The study included 43 patients previously undergoing cytoreductive surgery for pseudomyxoma peritonei in the Thoracic Oncology Department of the N.N. Blokhin National Medical Research Center of Oncology.Results. Re-operations were performed in 11 of the 43 patients with recurrent pseudomixoma peritonei after previously performed cytoreductive surgery. Repeated intraperitoneal chemoperfusion with hyperthermia was performed in 6 patients. Of the 11 reoperated patients, 7 had a complete cytoreduction (CC-0), recurrence was detected within 22 to 47 months; 2 patients had CC-1 and recurrence was observed within 12 and 15 months. Optimal cytoreduction (CC0-1) was achieved in 7 of the 11 patients. The maximum follow-up period was 44 months. Recurrence was noted in 9 patients, while the majority of patients had a satisfactory quality of life. Two patients showed signs of partial intestinal obstruction. None of the patients died during the follow-up period. In two patients with optimal (CC-0) cytoreduction, there were no signs of disease progression 9 and 15 months after re-surgery. One-year disease-free survival rate was 51 %.Conclusion. Repeated surgeries for recurrent pseudomyxoma present a great challenge for surgeons due to the difficulty in achieving optimal cytoreduction. Optimal cytoreduction in initial surgery should be considered as the main condition for repeated surgery. Moreover, additional criterion for a favorable prognosis is the time to progression of disease.