No 1S (2020): Supplement

Prevention and early diagnosis of reproductive tract malignancies are one of the most important socio-medical tasks, which depends mainly on physicians’ cancer awareness and is necessary to develop an effective patient management strategy. Of greatest importance are the development and implementation of effective screening programs focused on the detection of early-stage cancers, often at an asymptomatic stage, in a practically healthy target population. These measures are aimed at cancer risk reduction, detection of early disease, and improvement in treatment strategies. Oncological preventive activities should include strengthening physicians’ cancer awareness, availability of primary care and diagnostic tests, clear patient referral guidelines, coordinating care, and timely appropriate treatment. The cancer care system is effective only if all these stages are accessible and consistent.

Treatment of menopausal syndrome in patients with breast cancer is aimed not only at maintaining the quality of life, but also at increasing life expectancy, including by reducing refusal rates of anti-recurrence therapy. The most effective treatment option is menopausal hormone therapy, which, with some exceptions, is contraindicated in patients with breast cancer. Phytoestrogens and serotonin-norepinephrine reuptake inhibitors are an alternative to relieve vasomotor symptoms. If non-hormonal treatment of genitourinary menopausal syndrome has no effect, estrogens should be considered for vaginal treatment. Promising treatment modalities include a tissue-selective estrogen complex, estetrol, ospemifene and vaginal dehydroepiandrosterone. Loss of bone mineral density and fractures in breast cancer patients has many causes. Effective treatments include bisphosphonates and denosumab.

Aim. To compare long-term oncological outcomes of extended, combined, and standard surgical interventions. Materials and methods. The study included women with histologically verified T3-4N0-1M0-1ovarian cancer. Patients in group A underwent extended and combined surgical interventions, while patients in group B were subjected to standard surgery. In the preoperative period, all patients received 6 courses of PCT, a combination of platinum and taxanes. We compared the rates of achieving optimal and conditionally radical operations after extended and combined operations and standard surgical procedures at the stage of interval cytoreduction. The structure, rates and causes of intra- and postoperative complications were estimated. The endpoints analyzed were overall and recurrence-free survival. Results. From 2010 to 2018, we selected archived medical records of 150patients with advanced ovarian cancer (stages IIIC-IV). Long-term follow-up data were available for 143 (95.3%) patients. In groups A and B, complete cytoreduction was achieved in 56.7% and 40.8% of patients, respectively. In group A, 10 (33.3%) patients had intraoperative complications; 6 (19.9%) and 2 (6.7%) patients had grade I-II and grade III-IVpostoperative complications, respectively (p = 0.82). In group B, intraoperative complications were seen in 16 (13.3%) patients. Postoperative grade I-II and grade III-IVcomplications were observed in 22 (18.3%) and 7 (5.8%) patients, respectively. The median follow-up in the study and control group was 39 and 29 months, respectively. The median of RFS in the study group was not achieved; in the control group, it was 10.48 months (CI95% 8.233-12.66). In the study group, three-year recurrence-free survival was 59%. In the control group, three-year recurrence-free survival was 21%. Median OS in the study group was not achieved; in the control group, it was 37.3 months. (CI 95% 30.51-44.07). In the study group, three-year overall survival was 79 months. In the control group, three-year overall survival was 43%. Conclusion. Combined and extended surgical interventions for advanced ovarian cancer at the stage of interval cytoreduction are feasible and associated with better oncological outcomes of complete cytoreduction.

Aim. To review strategies for prophylactic surgery in carriers of BRCA1 or BRCA2 gene mutations and their short and long-term outcomes regarding overall health and health-related quality of life. Materials and methods. Between January 2007 and December 2018, 752 women with ovarian cancer were tested for the most common mutations of BRCA1 (5382insC, 4153delA, 185delAG, 061G, 2080delA, 3875del4, 3819del5) and BRCA2 (6174delT) genes using allele-specific PCR. Patients with suspected hereditary ovarian cancer (n = 327) or concurrent breast and ovarian cancer (n = 16) were identified. The entire coding sequences of BRCA1 and BRCA2 genes were analyzed in these patients using high-resolution analysis of melting PCR products followed by sequencing of fragments with abnormal denaturation curves. Results. The study identified 97 patients with ovarian cancer who had common mutations of BRCA1 genes [5382insC in BRCA1 gene, 4153delA in BRCA1 gene, 185delAG in BRCA1 gene, and C61G in BRCA1 gene in 74 (76.3%), 13 (13.4%), 7 (7.2%), and 1 (1%) of patients, respectively], and BRCA1 gene C61G in 1 (1%), BRCA1 gene 2080delA in 2 (2.1%)) and two patients with the 617delLTmutation in the BRCA2 gene, as well as 19patients with rare mutations: in the BRCA1 gene (n = 14) and the BRCA2gene (n = 5). The following recurrent alleles of BRCA1 were identified among rare mutations: R1751X in 5 (35.7%), R1699W in 3 (21.4%), G1706E in 2(14.3%), c.2643delA in 2(14.3%), c.5215 + 1G> Tin 2(14.3%) (n = 2) andBRCA2: Y1762Xin 2(40%), and c. 6999dupA in 3 (60%). Among relatives who carried mutations, 2/72 (2.7%) were diagnosed with ovarian cancer and fallopian tube cancer. In healthy carriers of BRCA1 gene mutations, hysterectomy with adnexa removal and bilateral adnexectomy were performed in 5 (62.5%) and 3 (37.8%) patients, respectively. In all 8 cases of prophylactic surgery, no adenocarcinoma cells were detected in removed ovaries and fallopian tubes. Conclusion. Thus, salpingectomy during various gynecological surgeries is safe and may offer protection against ovarian cancer without compromising endocrine function. Besides, a delayed salpingectomy strategy may also serve as an effective alternative preventive strategy for women with a genetic predisposition to ovarian cancer.

Aim. To examine the incidence of cervical cancer in the Tula region and conduct a retrospective analysis of its temporal changes between the years 2012 and 2018. Material and methods. This descriptive observational retrospective epidemiological study analyzed state medical statistics for the years 2012-2018. The incidence of cervical cancer was presented as both absolute annual incidence (i.e., number of cases per year) and as crude and standardized rates per 100,000 of the female population in the Tula region, one of the regions of Central Russia. Results. Over 7 years, the absolute incidence increased by 21.4% with a mean annual increase of 3.3%. The mean absolute annual incidence of cervical cancer cases over this period was 203.71 [95% CI 153.46; 197.4]. Over 7years, the standardized incidence rate increased by 20.3% with a mean annual increase of 3.1%. The mean incidence rate for the analyzed period was 16.6 per 100,000 of the female population [95% CI 3.94; 25.89]. The crude incidence rate also increased over 7 years by 26.3% with a mean annual increase of 4%. The mean incidence rate was 24.64per 100,000 of the female population [95% CI 17.9; 23.14]. Conclusion. The present study showed a steady increase in the incidence of cervical cancer in the region. This situation suggests the need for additional research to identify risk factors characteristic of the territory. Prophylactic human papillomavirus vaccines represent a revolutionary approach in preventing and potentially eliminating cervical cancer.

Aim. To compare Ki-67 proliferation marker expression in unspecified type of breast cancer determined by traditional visual assessment and digital microscopy using PatternQuant software (QuantCenter 3DHISTECH). Material and methods. A comparative study including 50 patients with unspecified type of breast cancer was conducted to compare the determination of the Ki-67 proliferation marker by a pathologist using the traditional visual quantitative assessment and by digital microscopy using PatternQuant software (QuantCenter 3DHISTECH). Results. Despite comparable mean Ki-67 expressions, their maximum and minimum values determined by a pathologist were slightly higher than by automated assessment. This is especially important in determining a threshold for Ki-67 expression (14%) in each individual case to distinguish molecular subtypes of breast cancer. Conclusion To objectify the quantitative assessment, a further standardized examination of breast cancer proliferation markers is recommended, especially in cases of significant tumor heterogeneity.

Aim. To investigate the effectiveness of conventional cervical cytology and HPV-SRS testing in the detection of HSIL. Materials and methods. The study included 84 patients, who underwent conventional cervical cytology, HPV testing by self-sampling and physician-sampling, and colposcopy. Patients with abnormal colposcopy findings underwent a cervical biopsy. Statistical analysis was performed using Statistica 10 software. The prognostic value of diagnostic tests was assessed according to generally accepted formulas. Results. The sensitivity of conventional cytology was 10%, specificity - 98.1%; physician-sampling for an HPV test - 50% and 74.1%; self-sampling for the HPV test - 70% and 57.4%, respectively. HPV-cytology co-testing with self-sampling of the vaginal sample had a sensitivity of 70%. A combination of colposcopy with the HPV test regardless of sampling technique resulted in a sensitivity of 80%; HPV-cytology co-testing with colposcopy demonstrated a specificity of 75.9%. Conclusion. HPV testing using the self-sampling technique, both in combination with cytology and as a single method, allows the diagnosis of a larger number of patients with HSIL.

Aim. To investigate the effectiveness of the ICG fluorescence technique in the detection of sentinel lymph nodes (SLN) in patients with endometrial cancer (EC). Materials and methods. The study comprised 100 patients with morphologically and clinically verified stage T1a-1bNxM0 EC, who were managed at the Petrov National Medical Research Center of Oncology of Minzdrav of Russia from September 2015 to September 2017. Results. The use of ICG resulted in the detection of220 SLNs in the whole study cohort (n = 100). Ninety (90%) patients were found to have bilateral SLNs. In 9/100 (9%), staining was detected only on one side. Only in one case, no SLNs were identified. The sensitivity, specificity, and accuracy of the method were 100%, 93%, and 93%, respectively. Numerous studies confirm the fact that in patients with EC, intraoperative detection, biopsy and morphological examination of SLNs contribute to a better assessment of regional lymphatic collectors, more accurate staging of the disease, and a patient-tailored surgery, which in turn can increase the overall survival of patients with EC. Conclusion. The use of the ICG fluorescence technique for the detection of SLNs in patients with EC allows effective and safe staging of the disease.

Aim. To assess sexual function in men who underwent radical prostatectomy and their female partners using the Index of Regulatory Adaptive Status (IRAS). Materials and methods. The study included healthy couples (n = 25) and couples (n = 50) in which male spouses underwent radical prostatectomy (RP) 6 months before. Men were surveyed using the IIEF-5, and QoL questionnaires and the FSFI was used to assess sexual function in women. IRAS was measured in all participants. Statistical analysis was performed using STATISTICA 10. Results. Erectile dysfunction, as measured by IIEF-5, was identified in men after nerve-sparing RP. They also had reduced QoL and IRAS scores. IRAS was more informative showing 49.0% lower scores than in healthy men, while ICEF-5 and QOL were lower by 32.6% and 46.2%, respectively. In men after non-nerve-sparing RP IRAS, IIEF-5, and QOL scores were 85.6%, 78.2%, and 75% lower than in healthy men. ED in men resulted in female sexual dysfunction (FSD) in their wives. Their IRAS scores were more informative in estimating FSD than FSFI. In women without FSD IRAS was 48.8% lower than in women with FSD, while FSFI was lower by 23.4%. Conclusion. The study findings suggest the feasibility of using IRAS to assess sexual dysfunction in men after radical prostatectomy and their female partners.

Endometrial cancer is the most prevalent gynecological cancer. About 2.9-14.4% of patients with endometrial cancer are aged below 40, and the incidence of cancer in this age group is on the rise. Most cases of endometrial cancer in women of this age are diagnosed at an early stage with no myometrial invasion and lymph node involvement. Therefore, such patients have a high cure rate, and for them, a quality of life is an extremely important outcome after treatment. Fertility preservation is one of the most important issues of long-term quality of life of cancer survivors of childbearing age. Presentation A 33-year-old woman T. first presented with complaints of heavy menstrual bleeding. Her diagnostic evaluation included hysteroscopy and fractional curettage with a sampling of both the endometrial and the endocervical mucosa. Histopathological study revealed highly differentiated endometrial adenocarcinoma. Taking into account the patient’s age, nulliparous status and her desire to preserve fertility, conservative treatment was initiated. Conclusion Conservative fertility-sparing treatment is highly effective in young patients with stage IA and G1 primary and recurrent endometrial adenocarcinoma. This treatment modality is safe and effective when applied to patients who met indications and most likely to comply with planned therapy.