[Activity of the Russian antitumor compound chlonisol in models of eyelid tumors (experimental study)]. / Aktivnost' otechestvennogo protivoopukholevogo soedineniya khlonizol na modelyakh opukholei vek (eksperimental'noe issledovanie).

Eyelid tumors are the most common neoplasms in everyday ophthalmic practice and cover a wide range of benign and malignant lesions. Surgical methods, cryodestruction, laser therapy and radiation therapy are used in the treatment of malignant eyelid tumors. Chemotherapy does not occupy a prominent place in the treatment of malignant eyelid tumors, its use is limited to sensitive tumors. OBJECTIVE: To assess the antitumor activity of the Russian-developed chemical compound 2-[3-(2-chloroethyl)-3-nitrosoureido]-1.3-propandiol (chlonisol) on the models of transplantable tumors of various histogenesis implanted into the lower eyelid. MATERIAL AND METHODS: The study was carried out on 67 mice of lines 129/SN, BALB/c and C57BL/6 that had Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid. Tumor transplantation was done by injecting 0.05 ml of sterile sodium chloride solution containing 106 cells of Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1, or 10% suspension of tumor tissue of B16 melanoma. The injection was performed into the right lower eyelid in the direction from the outer towards the inner corner of the eye using a thin needle (29G). Chlonisol was administered at the maximum tolerated dose of 20 mg/kg or at the lower dose of 15 mg/kg intraperitoneally 24 hours after tumor transplantation. RESULTS: In mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and melanoma B16 transplanted under the skin of the lower eyelid, a single intraperitoneal injection of chlonisol at the dose of 20 or 15 mg/kg caused significant inhibition of tumor growth reaching 100%. Chlonisol significantly increased overall survival in animals with Ehrlich carcinoma (log rank test, p=0.0464), sarcoma 37 (log rank test, p<0.0001), lymphosarcoma LIO-1 (log rank test, p=0.0122) and B16 melanoma (log rank test, p<0.0001); the proportion of animals that were fully healed was 25, 78, 67 and 25%, respectively. CONCLUSION: Chlonisol has a pronounced antitumor effect in mice with Ehrlich carcinoma, sarcoma 37, lymphosarcoma LIO-1 and B16 melanoma transplanted into the eyelid.

Photo-oxygenation of water media using photoactive plasmonic nanocomposites.

Plasmonic nanocomposites ZnO-Ag and ZnO-SnO2-Ag(AgCl) were prepared by the polymer-salt method, and their structure and morphology were studied using XRD and SEM analyses. It was found that the addition of photoactive inorganic nanocomposites ZnO-Ag and ZnO-SnO2-Ag(AgCl) in pure water significantly enhances the effectiveness of its disinfection and purification during UV treatment and provides the effective water oxygenation. Oxygen photogeneration under blue light (λex. = 405 nm) can be related to the plasmon-excitation processes in ZnO-SnO2-Ag(AgCl) composites. Prepared composites demonstrate antibacterial activity against both Gram-positive and Gram-negative bacteria. The increase of Ag content in ZnO-Ag and ZnO-SnO2-Ag(AgCl) composites significantly enhances their antibacterial activity.

[Hyperthermic intraperitoneal chemotherapy combined with cytoreductive procedure in patients with peritoneal pseudomyxoma].

AIM: To study the results of intraperitoneal chemoperfusion combined with cytoreductive procedure in patients with peritoneal pseudomyxoma. MATERIAL AND METHODS: For the period 2006--2015 seven patients with peritoneal pseudomyxoma underwent aggressive treatment using hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure at the Department of General Oncology of N.N. Petrov Research Institute of Oncology. RESULTS: Two patients had postoperative complications. One of them died after 12 days postoperatively. Features of postoperative complications were predominantly determined by volume of cytoreduction. Advanced tumoral process caused death in 2 patients additionally. Other patients are still alive during 4--28 months after surgery. CONCLUSION: Hyperthermic intraperitoneal chemoperfusion combined with cytoreductive procedure is advisable for peritoneal pseudomyxoma to improve survival. Optimal cytoreduction should be developed in researches with large number of patients to decrease incidence of complications.

[New approaches to treatment for malignant tumors using perfusion technologies].

The paper summarizes and analyzes the results of complex treatment of patients with malignant tumors performed in the N.N.Petrov Research Institute of Oncology using perfusion technologies. Safety and efficacy data on various chemoperfusion is presented: intraperitoneal chemoperfusion combined with cytoreductive surgery in patients with locally advanced and disseminated gastric cancer, recurrent ovarian cancer and pseudomyxoma peritonei; isolated lung perfusion combined with metastasectomy in patients with lung metastases; isolated limb perfusion with/without cytoreduction in patients with locally advanced skin melanoma and locally advanced soft-tissue sarcoma. The conclusion is made that both intraperitoneal and isolated chemoperfusions are not associated with higher incidence of intra- and postoperative morbidity. However safety of the procedures could be increased through optimizing tactics of surgical procedures prior to chemoperfusions. The use of perfusion technologies provides significant survival advantage in patients who can't benefit from conservative treatment.

[Long-term results of isolated chemoperfusion of the lung with melphalan and cisplatin in combination with metastasectomy in treatment for resectable metastatic lung lesion].

For treatment of metastatic lung lesions there was used the method isolated chemoperfusion of the lung in combination with metastasectomy. The study includes 74 patients with metastases in the lungs who underwent 101 normothermal isolated chemoperfusion of the lung: of these 38 (37,6%) with melphalan and 63 (62,4%) with cisplatin without lethality. In the early postoperative period 1 (1,4%) patient died due to postperfusion lung edema. The period of observation of patients ranged from 2 to 99 months (median 29.3 months). Of 74 patients 53 (71,6%) patients are alive, 2 (2,7%) patients died from causes unrelated to the underlying disease. 43 (58,1%) patients showed progression of disease, what in 18 (41,9%) of them was the cause of death. Repeated appearance of metastases in perfused lung was detected in 30 (40,5%) patients. A 5-year disease-free (in the lungs) and observed survival of patients after isolated chemoperfusion of the lung with metastasectomy was 45% (median 46 months) and 59% (median not reached) respectively. There were established predictors of effectiveness of isolated chemoperfusion of the lung with metastasectomy: DFI> 13 months, ≤5 metastatic nodes in the lungs, the size of the largest metastasis in the lungs ≤20 mm, intralobular location of metastases in the lungs as well as the time of doubling the volume of metastases >64 days for chest computed tomography.

[Rationale for development of new domestic appliances theranostic apparatus for photodynamic therapy and fluorescent diagnostics in oncology].

The review discusses the relevance of creating original theranostic apparatus for photodynamic therapy (PDT) and fluorescent diagnostics (FD) to fulfill the needs and meet the objectives of oncology field specialists. Increased accuracy of diagnosis and improvement of treatment outcomes is possible only in case of the right combination of photosensitizer (PS) with the light source with a wavelength at which the maximum absorption of the PS is observed. The absence of medical devices combining functions of PDT and FD makes the development of the domestic theranostic apparatus for oncology an extremely important task.

[Intraoperative intraperitoneal chemoperfusion treatment with cisplatin and dioxadet on a model of peritoneal carcinomatosis in ovarian cancer: safety and efficacy evaluation].

A comparative study of safety and efficacy of normothermic and hyperthermic intraperitoneal chemoperfusion (IPEC and HIPEC) with cisplatin and dioxadet was carried out in 143 female Wistar rats. Ovarian cancer was inoculated intraperitoneally (i.p.). In 48 hours after ovarian cancer inoculation the drugs were administered i.p. or IPEC and HIPEC with the drugs were performed using maximum tolerated doses (MTD). Content of cisplatin was determined in the perfusate and blood plasma during HIPEC with the drug. The leukocyte count was measured using veterinary hematologic analyzer in peripheral blood of rats at different time points after HIPEC with dioxadet. Efficacy of the treatment was estimated in increase in median survival time (MST). During HIPEC cisplatin was accumulated in the abdominal cavity in a considerable amount with minimal systemic absorption. HIPEC with dioxadet didn't significantly affect the leukocyte count in peripheral blood while i.p. administration of dioxadet suppressed leukopoiesis. MST of rats after IPEC with cisplatin was 37.5 days which was significantly higher compared to MST after i.p. administration of cisplatin (19.5 days, p = 0.037). HIPEC with dioxadet was the most effective regimen of treatment with MST of rats reaching 49 days which was significantly higher compared to MST after HIPEC with cisplatin (25.5 days, p = 0.002).

[MULTIMODAL APPROACH IN THE TREATMENT OF PATIENTS WITH MALIGNANT PLEURAL LESIONS].

The study includes data on 54 patients with pleural malignant lesions (39 with metastatic pleural malignant tumors and 15 with pleural malignant mesothelioma) received treatment using a multimodal approach: maximum cytoreduction, intraoperative photodynamic therapy and hyperthermic chemoperfusion of pleural cavity. A control group of patients with malignant pleural mesothelioma consisted of 21 patients who had undergone only conservative treatment. It was found out that the use two-thoracotomy surgical approach had advantages over standard thoracotomy across IV intercostal space. The use of multimodal treatment was accompanied by relatively low (1.85%) postoperative mortality on the background of a relatively high number (79.6%) of postoperative complications, easily cured in the early postoperative period. The use of multimodal therapy in treatment for metastatic pleural malignant lesions was accompanied by a median of disease-free survival of 11 months and a median of overall survival of 23 months. The proposed multimodal treatment compared with conservative methods of therapy improved disease-free (12 months vs. 7.5 months) and overall (18.8 months vs. 10.2 months) survival. Thus the use of a multimodal approach in treatment for pleural malignant lesions is relatively safe but requires further study.

[CHEMOPERFUSION TECHNOLOGIES IN TREATMENT FOR MALIGNANT TUMORS].

The data of literature on possibility of the use of perfusion technologies in combined treatment for malignant tumors of different sites are presented. Possible complications during hyperthermic chemoperfusion are discussed and the effectiveness of this method is analyzed.

[PERFUSION TECHNOLOGIES IN TREATMENT OF PATIENTS WITH SKIN MELANOMA AND SOFT TISSUE SARCOMAS OF EXTREMITIES].

A steady increase of incidence of skin melanoma and soft tissue sarcomas of the extremities currently continues to be observed. Taking into account the high probability of developing of locally disseminated forms of skin melanoma and soft tissue sarcomas of extremities, the need to use combined methods in their treatment is quite high. In the 21st century the possibility of a use of isolated regional chemoperfusion provides a high objective response of tumor to chemotherapy without their systemic impact and improves the quality of life through preservation of the limb. This review describes the currently used drugs, and the results of ongoing clinical research in the world, as well as the results of our own study.

Simulation of Chemoperfusion Treatment for Abdominal Carcinomatosis.

Experimental perfusion system and technology for normothermic and hyperthermic intraperitoneal chemoperfusion are developed for the treatment of abdominal carcinomatosis in rats with transplanted ovarian cancer. MTD of cisplatin in normothermic intraperitoneal chemoperfusion and hyperthermic perfusion are 40 and 20 mg/kg, i.e. by 10- and 5-fold higher than the dose of this cytostatic for routine intraperitoneal injection. Normothermic intraperitoneal chemoperfusion with cisplatin increases median survival time by 200% (p=0.039) in comparison with intraperitoneal injection.

[Melphalan pharmacokinetics during isolated limb regional perfusion in patients with skin melanoma and soft tissue sarcoma].

The study of pharmacokinetics of melphalan in the perfusate and blood plasma during isolated limb regional perfusion (ILRP) was carried out in patients with melanoma (n=21) and soft tissue sarcoma (n = 24). Melphalan was administered as 10 mg/l for a lower extremity and 13 mg/l for a upper extremity. Quantification of melphalan in perfusate and blood samples was performed by means of liquid chromatography/tandem mass spectrometry. 30 samples of the perfusate and 27 venous blood samples were analyzed. During the first 5 minutes of ILRP concentration of melphalan in the perfusate decreased to 13.2% of the initial value, and by the end of perfusion (60 minutes) it was 3.3%. The amount of melphalan in the blood plasma of the patients by the end of ILRP wasn't higher than 1.6% from the administered dose. That demonstrates minor systemic absorption of the drug during ILRP. Moreover melphalan concentration in the blood plasma during the perfusion was in average 0.015-0.223 mg/l which is significantly lower compared to the blood plasma concentrations after intravenous administration of melphalan. Thus ILRP procedure provided 97% of the melphalan dose accumulation in the soft tissues of a limb and in tumor tissues. Also pharmacokinetic advantage of melphalan over systemic administration of the drug was shown.

[Immediate results of isolated chemoperfusion of the lung with melphalan and cisplatin in combination with metastasectomy in treatment for resectable metastatic lung lesions].

For treatment of metastatic lung lesions there was used the method of isolated chemoperfusion in combination with metastasectomy. The study included 74 patients (mean age 43 ± 13.4 years). There were performed 99 normothermic isolated chemoperfusions of the lung: with melphalan (39) and cisplatin (60). During surgery there were no lethality outcomes. In the immediate postoperative period it was recorded 1 (1.4%) death developed in 3 days after surgery. The cause of this death was postperfusion lung edema accompanied by increase of signs of respiratory insufficiency. There were following complications after isolated chemoperfusions of the lung: anemia--23 (23.1%), nausea--13 (13.1%), vomiting--5 (5.1%), atrial fibrillation--10 (10.1%), pneumonia-2 (2.0%), pulmonary infarction--2 (2.0%), chylothorax--1 (1.0%), pneumothorax--29 (29.3%), emphysema of soft tissues of the chest wall 73 (73.7% ). Thus isolated chemoperfusion of the lung with melphalan or cisplatin is a procedure reproducible and relatively safe.

[Use of flexible needles and ways to control their placement in robot-assisted prostate brachytherapy].

The article provides an overview of developments in the field of flexible needles and methods of control over their behavior in the human body as a part of modern robotic systems for prostate cancer brachytherapy. The authors describe the advantages of flexible needles over standard ones, features of their design, and results of their tests in phantom models.