This review aims to provide up-to-date information on the factors associated with an increased risk of vaginal fistula in women with cervical cancer, as well as on methods of their prevention and treatment. It includes data on various types of vaginal fistulas in cervical cancer patients and risk factors for their development, according to foreign and Russian research articles published over the last 20 years. Cervical cancer is one of the most challenging oncological diseases in the Russian Federation, because it is detected at stage III–IV in more than 30 % of women. Such a high incidence of cervical cancer and the need for radiotherapy determine high risk of fistulas, which significantly impairs the quality of life. Thus, identification of factors associated with vaginal fistulas, as well as methods of their prevention and treatment remains a highly relevant task for the Russian healthcare system.

The 92 patients in the aged group of 25 to 84 (mean 56 years) diagnosed with an ovarian tumor (OT) have been prospectively examined. All patients were undergone a routine MRI and have been obtained DWI (b value = 50, 800 and 1000 mm2/s) with the construction of the map of the apparent diffusion coefficient (ADC). A statistically reliable significant difference of the intensity signal of solid tissue of OT on DWI at value b = 1000 and T2-WI between patients with benign ovarian tumors (BOT) and malignant ovarian tumor (MOT) (p < 0,001) as well as by ADC (p = 0,009) was revealed. Statistically significant difference of intensity signal on T2WI and on DWI with ADC of solid and cystic components of OT between the primary MOT and metastatic ovarian were not detected. The average value of ADC of the solid tissue of MOT was 0,6 × 10-3 mm2/s, whereas of BOT consisted of 0,3 × 10-3 mm2/s. According to the ROC analysis the average value of ADC 0,35 × 10-3 mm2/s can serve as a threshold for the differential diagnosis of BOT and MOT with the sensitivity 95 %, specificity 60 %, with the positive predictive value 90 % and negative predictive value 75 %: with ADC below this value is more likely BOT, at exceeding of the trigger value is MOT. Thus, the analysis of the solid component of OT with using conventional MRI with DWI/ADC maps is most informative in the differential diagnosis of the BOT and MOT. MOT was characterized the higher signal intensity on DWI, T2WI and also higher ADC values than for BOT. Additionally, MOT had bilateral lesion, irregular shape, larger size, cystic-solid structure, irregular septs and ascites.

The paper analyzes the data available in the foreign and Russian literature over the past 10 years on main radiodiagnostic techniques and approaches in case of ovarian space-occupying lesions, by using both ultrasonic color Doppler mapping and complex MRI approaches in combination with routine MRI, diffusion-weighted MRI studies, and follow-up contrast-enhanced MRI. It shows that only the comprehensive introduction of the above radiodiagnostic techniques can achieve the necessary sensitivity and specificity of diagnosis of ovarian tumors. The system for assessing the risk index for ovarian tumor malignancy is discussed, by taking into account the menopausal status, the tumor marker CA-125, and ultrasonographic findings. The paper presents the Adnexa MR scoring system based on the breast imaging-reporting and data system (BI-RADS) that gives schemes for calculating and analyzing the risk of ovarian tumor malignancy in terms of certain MR criteria.

Background. Clinical studies have shown that the most oncological patients have impaired immunological reactivity. Monitoring of the immune system status of patients with solid tumors includes a subpopulation analysis of immunocompetent cells. It is based on the study of expression of surface antigens and intracellular structures, and an analysis of the functional activity of immunocompetent cells. Today two, three, and even four-color reagents are used for subpopulation analysis of lymphocytes. Fluorescent conjugate with monoclonal antibodies (MAB) of the ICO series and fluorescent dyes Imd-306, Imd-506 (cyanine) and phycoerythrin (a group of phycobiliproteins) was received and characterized in N.N. Blokhin National Medical Research Center of Oncology. These conjugates have proved themselves in one and two-color analysis of subpopulations of peripheral blood lymphocytes by flow cytometry. The purpose of this study is to assess the possibility of sharing several immunofluorescent probes (IFP) on the basis of different Mab series of ICO and dyes FITC, Imd306, Imd506 and PE for three-color analysis of lymphocyte subpopulations of donors and patients with oncological diseases by flow cytometry method. Materials and methods. A panel of immunofluorescent probes (IFP) CD3FITC, CD4PE, CD8-Imd506, CD4-Imd306 was used in the work. Probes are obtained with MAB (ICO series) and fluorophores FITC, PE, Imd-306, Imd-506. The specific activity of the probes was evaluated in the immunofluorescence reaction by flow cytometry. Donor’s peripheral blood was used to optimize the conditions of the immunofluorescence reaction. Clinical approbation of the obtained sets was carried out on 2 groups of patients with oncological diseases before and after surgical treatment. The first group included 64 patients with cancer of the oral mucosa. The second group consists of 35 patients with ovarian cancer. Results . We have shown that for the three-color analysis of human lymphocytes by flow cytometry, it is recommended to use sets of labeled MAB: CD3-FITC (10 μg/ml) + CD4-Imd306 at a concentration of 5–10 μg/ml; CD3-FITC + CD4-PE at a concentration of 20 μg/ml and CD3-FITC + CD8 Imd506 at a concentration of 10 μg/ml. The final concentration of immunoglobulin in the solution of IPS is indicated. It was shown that even before the beginning of treatment in patients with cancer of the oral mucosa the subpopulation CD3+ CD4+ content was significantly lowered in the structure of T cells, and the total level of CD8+ lymphocytes significantly exceeds the parameters of the donor group. Analysis of linear CD markers of lymphoid cells in patients with ovarian cancer revealed a significant decrease in the total number of CD3+ T-lymphocytes in comparison with donors. There was no evidence of the effect of surgical treatment on the subpopulation structure of lymphoid cells. Conclusion. Combinations of fluorescent probes CD3-FITC/CD4-Imd306/CD8-Imd506 and CD3-FITC/CD4-PE/CD8-Imd506 can be used for trichromatic analysis by flow cytometry of the lymphocyte subpopulations of both healthy donors and cancer patients. Comparative studies of the specific activity of combinations of IFP based on Mab ICO series and reference commercial test systems (BD Biosciences) on lymphocytes of healthy donors and oncological patients (ovarian cancer, oral mucosa cancer) showed comparable results. The application of the obtained probes made it possible to reveal violations of the subpopulation structure of peripheral blood lymphocytes in patients with ovarian cancer and cancer of the oral mucosa, in particular, CD3 – /CD8+, CD3+/CD4+, CD3+.

Background.Clinical studies have shown that the most oncological patients have impaired immunological reactivity. Monitoring of the immune system status of patients with solid tumors includes a subpopulation analysis of immunocompetent cells. It is based on the study of expression of surface antigens and intracellular structures, and an analysis of the functional activity of immunocompetent cells. Today two, three, and even four-color reagents are used for subpopulation analysis of lymphocytes. Fluorescent conjugate with monoclonal antibodies (MAB) of the ICO series and fluorescent dyes Imd-306, Imd-506 (cyanine) and phycoerythrin (a group of phycobiliproteins) was received and characterized in N.N. Blokhin National Medical Research Center of Oncology. These conjugates have proved themselves in one and two-color analysis of subpopulations of peripheral blood lymphocytes by flow cytometry.The purposeof this study is to assess the possibility of sharing several immunofluorescent probes (IFP) on the basis of different Mab series of ICO and dyes FITC, Imd306, Imd506 and PE for three-color analysis of lymphocyte subpopulations of donors and patients with oncological diseases by flow cytometry method.Materials and methods.A panel of immunofluorescent probes (IFP) CD3FITC, CD4PE, CD8-Imd506, CD4-Imd306 was used in the work. Probes are obtained with MAB (ICO series) and fluorophores FITC, PE, Imd-306, Imd-506. The specific activity of the probes was evaluated in the immunofluorescence reaction by flow cytometry. Donor’s peripheral blood was used to optimize the conditions of the immunofluorescence reaction. Clinical approbation of the obtained sets was carried out on 2 groups of patients with oncological diseases before and after surgical treatment. The first group included 64 patients with cancer of the oral mucosa. The second group consists of 35 patients with ovarian cancer.Results. We have shown that for the three-color analysis of human lymphocytes by flow cytometry, it is recommended to use sets of labeled MAB: CD3-FITC (10 μg/ml) + CD4-Imd306 at a concentration of 5–10 μg/ml; CD3-FITC + CD4-PE at a concentration of 20 μg/ml and CD3-FITC + CD8 Imd506 at a concentration of 10 μg/ml. The final concentration of immunoglobulin in the solution of IPS is indicated. It was shown that even before the beginning of treatment in patients with cancer of the oral mucosa the subpopulation CD3+ CD4+ content was significantly lowered in the structure of T cells, and the total level of CD8+ lymphocytes significantly exceeds the parameters of the donor group. Analysis of linear CD markers of lymphoid cells in patients with ovarian cancer revealed a significant decrease in the total number of CD3+ T-lymphocytes in comparison with donors. There was no evidence of the effect of surgical treatment on the subpopulation structure of lymphoid cells.Conclusion.Combinations of fluorescent probes CD3-FITC/CD4-Imd306/CD8-Imd506 and CD3-FITC/CD4-PE/CD8-Imd506 can be used for trichromatic analysis by flow cytometry of the lymphocyte subpopulations of both healthy donors and cancer patients. Comparative studies of the specific activity of combinations of IFP based on Mab ICO series and reference commercial test systems (BD Biosciences) on lymphocytes of healthy donors and oncological patients (ovarian cancer, oral mucosa cancer) showed comparable results. The application of the obtained probes made it possible to reveal violations of the subpopulation structure of peripheral blood lymphocytes in patients with ovarian cancer and cancer of the oral mucosa, in particular, CD3 – /CD8+, CD3+/CD4+, CD3+.

For the first time in Russia the immunophenotype of tumor infiltrated lymphocytes (TIL) was investigated with the use of a method of quantitative flow cytometry. Samples from 104 patients, suffering from solid tumors (such as breast cancer, ovarian cancer, melanoma and oral cavity squamous carcinoma), were analyzed in this investigation. In the difference of cytomorphological analysis, the method of flow cytometry identified TIL in 100% of cases. In the structure of CDS+Т- lymphocytes the ratio CD4/CD8 was equal to 1,1±0,1. Serial gating strategy allowed to assess minor subpopulations of regulatory T-lymphocytes CD45+CD4+CD127+low/neg and CD45+CD8+CD28-CD11b-. Regulatory mechanisms with involvement of CD8 T-cells played the main role in the generation of immune responses at the tissue level ofpatients, suffering from solid tumors, independent of nosological form of disease.

Ovarian cancer (OC) is characterized by its late diagnosis, mainly local tumor dissemination within the abdomen and small pelvis, and a relatively high susceptibility to drug therapy . Intraabdominal chemotherapy (CT) allows the higher intraabdominal drug concentrations to be produced as compared to systemic CT and, according to the data of some investigations, improves the results of treatment in a few patients with minimal tumor foci. In this connection, it is urgent to master the procedure of intraperitoneal CT, including to pl ace an intraabdominal port, to elaborate a regimen, and to determine the spectrum of its toxicity and safety.Subjects and methods. The paper gives the preliminary results of a pilot trial using intraabdominal CT in 8 patients with disseminated OC and fallopian tubes who have undergone optimal-volume surgical interventions in stage 1. All the patients received CT by the scheme: intravenous paclitaxel (135 mg/m 2) on day 1, intraabdominal cisplatin (75 mg/m 2) on day 2, and intraabdominal paclitaxel (60 mg/m 2) on day 8. A total of 6 courses were scheduled.Results. At the analysis of the results, 5 out the 8 patients received all the scheduled courses of CT, 3 patients continued treatment, including 1 patient in whom the intraabdominal port w as removed after the first course of CT because of significant fibrosis along the in traabdominal catheter, thereafter she continued to be treated by the standard intravenous scheme. Among local toxicity signs, there was a preponderance of grades 1–2 abdominal pains occurring after the intraabdominal administrations of chemotherapy preparations. Systemic toxicity, including hematological one, was moderate; in any cases it did not cause life-threatening complications or lead to the increase of course intervals or to the refusal of intraabdominal CT. At a median follow-up of 10.2 months (range 1.9–24.7 months or more), one patient w as found to have disease progression 12 months of therapy termination.

The research has enrolled 96 patients with rare ovarian clear cell cancer treated at N.N. Blokhin Russian Cancer Research Center from 1978 to 2000. A necessity to divide patients into two groups has emerged after histopathological slide review. The first group included 71 patients with ovarian clear cell carcinoma (OCCC). Twenty five patients with mixed malignant epithelial ovarian tumor (MMEOT) with mandatory presence of clear cell component were included into the second group. Clinical par- ticularities of clear cell ovarian cancer were studied. We performed a comparative study of clinical course of OCCC and MMEOT. Our data suggest that clear cell ovarian cancer has a number of typical clinical and biological particularities both in OCCC and MMEOT.

Ovarian cancer (OC) is characterized by its late diagnosis, mainly local tumor dissemination within the abdomen and small pelvis, and a relatively high susceptibility to drug therapy . Intraabdominal chemotherapy (CT) allows the higher intraabdominal drug concentrations to be produced as compared to systemic CT and, according to the data of some investigations, improves the results of treatment in a few patients with minimal tumor foci. In this connection, it is urgent to master the procedure of intraperitoneal CT, including to pl ace an intraabdominal port, to elaborate a regimen, and to determine the spectrum of its toxicity and safety. Subjects and methods. The paper gives the preliminary results of a pilot trial using intraabdominal CT in 8 patients with disseminated OC and fallopian tubes who have undergone optimal-volume surgical interventions in stage 1. All the patients received CT by the scheme: intravenous paclitaxel (135 mg/m 2) on day 1, intraabdominal cisplatin (75 mg/m 2) on day 2, and intraabdominal paclitaxel (60 mg/m 2) on day 8. A total of 6 courses were scheduled. Results . At the analysis of the results, 5 out the 8 patients received all the scheduled courses of CT, 3 patients continued treatment, including 1 patient in whom the intraabdominal port w as removed after the first course of CT because of significant fibrosis along the in traabdominal catheter, thereafter she continued to be treated by the standard intravenous scheme. Among local toxicity signs, there was a preponderance of grades 1–2 abdominal pains occurring after the intraabdominal administrations of chemotherapy preparations. Systemic toxicity, including hematological one, was moderate; in any cases it did not cause life-threatening complications or lead to the increase of course intervals or to the refusal of intraabdominal CT. At a median follow-up of 10.2 months (range 1.9–24.7 months or more), one patient w as found to have disease progression 12 months of therapy termination.

Objective: to specify the prognostic value of DNA levels, their distribution by the phase of a cell cycle, as well as the proliferative activity index in borderline ovarian tumors (BOT). Subjects and methods. The study included 88 patients with BOT whose age was 16 to 80 years (mean age 42.4±1.4 years), 51 (57.9%) patients being under 45 years of age. A control group consisted of 18 patients with benign ovarian masses (BOM). An EPICS-XL (Coulter, USA) laser flow cytofluometer was used to study cellular DNA. The findings were analyzed, by applying the MultiCycle program (Phoenix Flow Systems, USA) employed to analyze ploidy and the count of tumor cells in each phase of a cell cycle. Results. Diploid and aneuploid tumors were found in 55 (62.5%) and 33 (27.5%) patients with BOT, respectively. Comparative analysis of DNAflow cytometric parameters in the BOT and BOM groups revealed statistically significant differences in DNA index (DNAi). Analysis of the distribution of tumors by age indicated that DNAi and the distribution of their cell cycle were age-unassociated. As the disease progressed, the patients with diploid tumors increased in number and those with aneuploid tumors decreased. At the same time these differences were statistically insignificant. The analysis of the distribution of a tumor cell cycle by the stage of the disease in patients with BOT did not reveal any significant differences in the compared groups either. Examining the distribution of tumor cells by the phases of a cell cycle showed that the rate of cell fission in serous BOTs was higher than that in mucinous BOTs. Conclusion. BOTs are a heterogeneous group more than half (61.9%) of them are aneuploid, in 42.4% of the patients, their number was in the range of 20-40%. No regularities were found in the distribution of the number of diploid BOTs in relation to the age of patients and to the stage of the disease.

The specific clinical course and difficulty in prognosis of ovarian cancer necessitate search for new objective biological markers to individualize treatment policy. Cell cycle parameters as determined by laser DNA flow cytofluorometry may be used as such markers.

Эпидемиологические исследования показывают, что в последнее время отмечается тенденция роста заболеваемости злокачественными опухолями яичников. Целью нашего исследования являлось изучение влияния клинико-морфологических факторов на возникновение рецидивов РЯ I-IIА стадии и на отдаленные результаты лечения. В основу исследования положен анализ клинико-морфологических данных обследования и лечения 282 больных, страдающих РЯ I-IIА стадии, оперированных в гинекологических стационарах общего профиля, а также проходивших лечение в РОНЦ им. Н.Н.Блохина РАМН с 1971 по 2001 г. Средний возраст больных составил 50,5 года (от 16 до 76 лет). Из 282 пациенток у 94 (33,3%) развился рецидив заболевания в сроки от 3 мес до 16,5 года. По предварительным данным нашего исследования, достоверно значимыми благоприятными прогностическими факторами являются: молодой возраст больных (до 40 лет), минимальная степень распространенности опухолевого процесса (IA стадия), муцинозный гистологический тип опухоли, высокая и умеренная степени дифференцировки. Ухудшают прогноз заболевания светлоклеточный гистологический тип опухоли, низкая степень дифференцировки опухолевых клеток и такие неблагоприятные клинические факторы, как острое начало заболевания, разрыв капсулы опухоли и наличие сращений ее с окружающими органами и тканями.