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Background. Applied standard methods of cervical cancer (CC) treatment have several disadvantages in terms of local and systemic toxicity and the risks of local recurrence. Our study proposed the use of neoadjuvant chemotherapy (NACT) in a dose-dense mode, followed by radical hysterectomy, in order to improve the results of treatment of locally advanced CC (IB2-IIB stages) (FIGO)/T1b2-2bN0M0 (TNM).Aim. Improvement of immediate and long-term results in treatment of locally advanced CC IB2-IIB stages (FIGO), determining the immediate effectiveness of dose-dense NACT, based on magnetic resonance imaging (MRI) data, and the identification of prognostic factors for tumor response to chemotherapy.Materials and methods. Between April 2016 to November 2019 120 women with IB2-IIB stages (FIGO) were included in this study. Of these, 58 patients underwent 3 cycles of intensified NACT according to the AP scheme (cisplatin 75 mg/m2, doxorubicin 35 mg/m2) and 62 patients underwent NACT according to the TR scheme (cisplatin 60 mg/m2, paclitaxel 60 mg/m2). The assessment of the effect of intensified NACT was performed according to the RECIST 1.1 criteria according to MRI data. Also 2 retrospective groups of patients were recruited: group I - surgical treatment without preoperative chemotherapy (25 patients with IB2-IB3 stages (FIGO) from November 2009 to August 2019), group II - concurrent chemoradiotherapy (44 patients with stage IIB cervical cancer (FIGO) from January 2013 to June 2018).Results. Complete clinical response was detected in 12 (10.0 %) patients, partial response - in 69 (57.5 %) patients, stable disease - in 35 (29.2 %) patients, progression was observed in 4 cases (3.3 %). After NACT in a dose dense mode, due to an objective clinical response (complete response, partial response and stable disease for stage IIA according to RECIST 1.1 criteria), 99 (82.5 %) patients underwent surgical treatment. For 21 (17.5 %) patients due to the absence achievement of objective clinical response (stable disease for stage IIB according to RECIST 1.1 criteria or progression), performed concurrent chemoradiotherapy. During the observation period, 113 (94.2 %) patients remained alive. Mortality for the first year was 1.7 % (2 cases). There was a coincidence of the results of a complete response according to MRI in 11 (91.7 %) cases out of 12 cases with the pathology data. According to multivariate analysis, it was revealed that parametrial invasion, according to the histological examination of the surgical material, is an independent prognostic factor for recurrence. According to comparative evaluation of disease-free survival curves between groups of IB2-IIB stages (FIGO) patients who received and did not receive dose-dense chemotherapy, it was found that disease- free survival in the group with NACT was higher compared to the group without NACT (p = 0.03, the log-rank criterion).Conclusions. The use of dose-dense NACT is an effective treatment mode for patients with IB2-IIB CC (FIGO), which in most cases allows achieving a tumor response with subsequent improvement in immediate and long-term results and can be considered as an alternative to standard treatment for locally advanced CC.

In our study we carried out an exploratory assessment of the antitumor activity of hyperthermic intraperitoneal perfusion (Hipep) with 0.9 % sodium chloride solution and compared it with the effect of a single normothermic intraperitoneal (i.p.) Administration of cisplatin in the maximum tolerated dose (mtd). Thirty-six mature female Wistar rats with transplanted i.p. Syngeneic ovarian carcinoma were randomized into three groups: control group (2 ml of 0.9 % sodium chloride i.p. At room temperature, n=12); cisplatin group (cisplatin 4 mg/kg i.p. At room temperature, n=12); Hipep group (open i.p. Perfusion with 0.9 % sodium chloride solution at a temperature of 40,5–41,5 °c for 45 minutes, n=12). The primary endpoint was the overall survival (os) of the animals in each of the three groups. The total peritoneal cancer index (pci), weight and degree of ascites haemorrhagia were assessed at autopsy. The median os in the control group, Hipep, and cisplatin was 19, 39, and 40 days, respectively (log-rank test р

Aim: to evaluate the endometrial expression of e-cadherin in relation to the estrogen-progesterone-receptor status of the endometrium.Materials and methods. In total 137 women were examined including 81 patients with infertility and 40 with a history of early pregnancy loss (main group); for comparison, 16 healthy fertile women (control group) were also examined. Endometrial aspiration biopsy was performed on 6–8 days after ovulation; in parallel, a peripheral blood sample was taken to determine the levels of estradiol and progesterone. A histological and immunohistochemical study of the endometrium with determination of estrogen (ER) and progesterone (PR) receptors and e-cadherin expression was carried out.Results. All fertile women (n = 16) and only 44 % (n = 53) of patients in the main group had the normal pattern of hormonereceptor endometrial interactions, i. e., low expression of ER and PR in the endometrial glands as well as reduced expression of ER and high expression of PR in the endometrial stroma. The endometrial e-cadherin expression was assessed in the following cohorts: a) women with normal hormone-receptor interactions (16 women in the control group and 53 women in the main group); b) with abnormal variants of hormone-receptor interactions in the endometrium (68 patients in the main group). The frequency of reduced e-cadherin expression was significantly lower in the cohort of women with normal estrogenprogesterone-receptor endometrial status (a) than in the cohort of women with abnormal variants of the endometrial “response” (b): in the luminal epithelium – in 5 % (3 out of 63) (а) vs. 17 % (8 out of 47) (b) (p < 0.05); in the glands – in 13 % (9 out of 69) (a) vs. 37 % (25 out of 68) (b) (p < 0.05).Conclusion. The estrogen-progesterone-receptor status of the endometrium is significant for the e-cadherin expression in the luminal epithelium and glands of the endometrium.

The article covers different aspects of clinical manifestations, diagnosis, and treatment of vulvar, vaginal, and cervical sarcomas.

Aim: to analyze the endometrial expression of leukemia inhibitory factor (LIF) related to the estrogen/progesterone receptor endometrial status in women with the history of reproductive dysfunctions.Materials and methods. The main group consisted of patients with the history of infertility (n = 81) or early pregnancy loss (n = 40). The control group included 16 women with normal fertility. At days 6–8 after ovulation, endometrial biopsy was performed and peripheral blood samples were taken to assess the estradiol and progesterone levels. Histological and immunohistochemical (to quantify the estrogen (ER)/progesterone (PR) receptors and LIF expression) examinations of the endometrium biopsy materials were carried out.Results. In the middle phase of the secretion, women of the control group showed higher levels of LIF expression in the endometrial glands (94%; n = 15) and stroma (88 %; n = 14) significantly more often than patients with reproductive dysfunctions – 69 % (n = 84) and 44 % (n = 53) respectively (p < 0.05). There was no difference in the endometrial LIF expression between women with infertility and those with early pregnancy loss. In women with a sizable hormone-receptor 'response', a pronounced expression of LIF in the luminal epithelium (87 %; n = 52 out of 60) and stroma (68 %; n = 47 out of 69) was detected more often (p < 0.01) than that in patients with impaired hormone-receptor interactions (61 %, n = 27 of 44; 29 %, n = 20 of 68). High PR expression in the endometrial glands (H-score > 105) indicates the risk of impaired LIF expression in the luminal epithelium (OR =2.6) and stroma (OR = 2.5). Overexpression of ER (H-score > 155) in the endometrial stroma is associated with the risk of sub-normal LIF expression in the endometrial glands (OR = 2.5) and stroma (OR = 2.8).Conclusion. A meaningful connection has been found between the endometrial estrogen/progesterone receptor status and the expression of LIF. Women with well-pronounced endometrial hormone-receptor interactions show high levels of endometrial LIF expression more often. The stromal ER and glandular PR expression levels are considered to be prognostic factors of reduced endometrial LIF expression in the uterine body mucosa.

Aim. To evaluate the expression of FOX proteins (FOXA1 and FOXA2) in the endometrium during the implantation window in women with a history of reproductive dysfunctions with different thickness of the endometrium. Materials and methods. The prospective cohort comparative study was conducted. The main group included patients with "thin" endometrium (7 mm according to ultrasound on preovulatory days; n=52), the comparison group consisted of women with normal endometrial thickness (7 mm according to ultrasound; n=62; women of both groups with reproductive dysfunctions of unknown reason), the control group included 16 healthy fertile women. Aspiration biopsy of the endometrium was performed on the 68 days after ovulation, as well as venipuncture to obtain a sample of peripheral blood to determine the levels of sex steroids (estradiol E2 and progesterone P). A combined histological and immunohistochemical study of endometrial biopsies was performed. Results. All women had ovulatory values of progesterone P16.1 nmol/l (68 days after ovulation) and normoestrogenemia (E2, pmol/l) in the blood. E2/P was similar in all groups (p0, 05). A pronounced expression of FOXA1 was noted in women with thin endometrium significantly more often (p0.05) with various hormone-receptor characteristics of the endometrium (42% n=22 out of 52) compared with healthy participants (0%; n=0). Reduced FOXA2 expression in the uterine mucosa was significantly more often detected on 68 days after ovulation in women with "thin" endometrium (56% n=29 of 52) than in women with normal endometrial thickness, both in women from the comparison group and in healthy women from the control group (p0.05). In a generalized analysis of the expression of FOX proteins in the endometrium on days 68 after ovulation, it was generally found that every second (50%; n=57 out of 114) women with a history of reproductive disorders (with a reduced and normal M-echo value) expression of proteomic markers differed from healthy women. In the case of "thin" endometrium, more than two thirds of patients (71%; n=37 out of 52) showed differences in endometrial expression of FOX proteins compared with women without a burdened reproductive history. Conclusion. In the majority of women (71%) with a thin endometrium and a history of reproductive dysfunctions, the expression of FOX proteins in the endometrium differed from the control group. Overall, endometrial expression of FOX proteins, which is likely to be different from healthy women, in patients with reproductive dysfunctions of unknown origin is a significant predictor of reproductive failure. At the same time, such an isolated indicator as M-echo value 7 mm according to ultrasound data is not an absolute prognostic marker of endometrial receptivity disorders.