Objective: To estimate the incidence of malignant neoplasms of lymphoid tissue (MNLT) among employees of the siberian chemical combine (SCC) occupationally exposed to prolonged ionizing radiation.

Material and methods. The study included 44,041 employees of the SCC, of whom 16,938 were occupationally exposed to prolonged low-intensity ionizing radiation (IR). Of 295 cases with hemoblastoses, there were 89 with occupational exposure to IR. The structure and incidence of hemoblastoses (based on the number of person-years of observation, (PYO), as well as the standardized relative risk (SRR) of their development and excess relative risk (err) per unit dose of radiation (GR) were evaluated. Calculation of SRR was carried out for the following intervals of the total dose of external exposure: 0; >0–0.05; >0.05–0.10; >0.10-0.15; >0.15–0.20; >0.20-0.30; >0.30-0.50; >0.5–1.0; ≥ 1.0 Gy. The control group consisted of occupationally non-exposed employees of the SCC. The calculation of SRR and err was performed using the poisson regression using the amfit module of the EPICURE package.

Results. The incidence of MNLT among males of SCC was 17.1 per 100,000 PYO, with the highest incidence rates for Non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL) and chronic leukemia (CL) excluding CLL. Among females of the SCC, the incidence of MNLT was 21.3 per 100,000 PYO. It was found that in none of the intervals of the external exposure there was no statistically significant excess of the SRR compared with the control group. The results of ERR/GY calculation also did not demonstrate the increased risk of hemoblastosis among people occupationally exposed to IR.

Conclusion. Occupational exposure in the studied dose range does not increase the risk of developing MNLT.

Background. Cancer is a leading cause of death in children and adolescents worldwide. The cancer incidence rate in children and adolescents has been on the rise for decades. Climatic, geographic and social factors of the region play an important role for cancer incidence.

Objective: to analyze the cancer incidence and mortality rates in children and adolescents of Prymorsky krai.

Methods. Cancer incidence rates in Russia for 2008–2018 as well as cancer incidence among children treated at the regional pediatric hematology/oncology center (Vladivostok, Russia) for 2014–2019 were analyzed.

Results. No statistically significant differences in the cancer incidence rates for the 2008–2018 period between children and adolescents of Primorsky krai and the russian federation in the whole and the far-eastern federal district were found. In in Primorsky krai, there was a variability in the incidence rate during the analyzed period, a negative average annual growth rate in the group of children under 14 years of age (-0.86 %). For the 2008–2018 period, the cancer mortality rate in children and adolescents of Primorsky krai significantly decreased (from 5.65 ‰ in 2008 to 2.6 ‰ in 2018), with the average annual increase rate in children aged 017 years of -9.17 %. In 2014–2019, the quality of cancer detection improved significantly, and the number of children and adolescents with stage iiiiv cancer reduced.

Conclusion. Cancer prevention and early detection can potentially reduce the cancer incidence and mortality rates in children and adolescents in Primorsky krai. Population-based cancer registries are needed for quantifying the burden of cancer in children and adolescents and assessing prevention and control programs.

Background. Prostate-specific antigen (PSA ) is predominantly produced by prostate epithelium, however, other tissues can serve as its minor sources in both men and women, including breast tissue. In women, elevated serum PSA levels have been described in different physiological and pathological conditions, including benign breast diseases and breast cancer (BC). PSA is considered as a potential serum tumor marker for BC, but evidences of its possible clinical significance are insufficiently convincing.

Aim of the study: investigation of PSA levels in female BC patients and assessment of perspectives of its study as a diagnostic tool for early detection of BC.

Material and methods. Serum PSA levels were measured by chemiluminescence immunoassay (ARCHITECT , Abbott) in 99 female patients with histologically confirmed BC (carcinoma in situ – 11, stage I – 56, stage IIA – 32) and 25 conditionally healthy female donors.

Results. In the donor group, serum PSA was revealed in 22/25 (88,0 %) cases, and its mean level was 4.0 ± 0.9 ng/l. In the group of BC patients, detectable PSA level was revealed in 68/99 (68.7 %) cases, and its mean level was 2.8 ± 0.9 ng/l. Differences between groups of BC patients and donors in mean marker values were not statistically significant (p>0,05). Serum PSA levels were higher in young women: in the group of BC patients under 40 years old, percentage of PSA -positive cases was 89 %, in the group of patients over 50 years old – 60 %; in groups of donors under 40 and over 50 years old – 100 % and 80 %, respectively. In cases of in situ carcinoma, the mean serum PSA was higher than in cases with stages I and II (3.0 ± 1.2 ng/l vs 1.9 ± 0.3 ng/l and 1.6 ± 0.3 ng/l, respectively; p>0,05). In the group of BC patients, no PSA levels were found to be dependent on the histological type, grade and molecular subtype of the tumor.

Conclusion. The PSA level has no clinical significance in early stages of BC, since the proportion of cases with elevated PSA levels and it’s mean value in patients with early stages of BC don’t differ from those in the group of healthy women. 

Introduction. Esophageal adenocarcinoma develops from areas of intestinal metaplasia in Barrett’s esophagus, similar to how intestinal metaplasia transforms into gastric adenocarcinomas in the stomach. Atypia with intraepithelial neoplasia is difficult to distinguish from reactive and regenerative changes, especially in erosive mucosa of the esophagus. Observation of patients with Barrett’s esophagus allows the identification of adenocarcinoma in the earlier, more curable stages in many patients.

The aim of our study was to study the prospects of using a classifier based on miRNA profiling in histological samples of Barrett’s esophagus to determine the risk of malignancy and treatment tactics.

Material and Methods. In this study, 119 samples of archival histological material in the form of paraffin blocks were used: 89 samples of gastric mucosa with dysplasia and 30 samples of Barrett’s esophagus. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p,-31-5p,-34a-5p,-375 was determined using real-time RT-PC R. Samples were stratified into different groups using the C-RT decision tree algorithm.

Results. 26.7 % of Barrett’s esophagus samples were classified by expression of the proposed miRNAs as cancer, which may indicate a potential development of a malignant tumor in the mucosa of the esophagus when morphological changes have not yet been found.

Background. Over the past 20 years, there has been a change in approaches to the treatment of breast cancer, in particular, a significant increase in the role of drug therapy. Breast cancer response to neoadjuvant chemotherapy is currently considered as a surrogate biomarker, which allows evaluation of the clinical course and prognosis of the disease. To solve this problem, it is necessary to assess the functional and metabolic changes in tumor tissue during treatment. Doppler ultrasound is a non-invasive, affordable, and low-cost imaging technique that can be safely used for repeated measurements.

The purpose of the study was to study vascular changes in the tumor by power Doppler ultrasound for the evaluation of the early breast cancer response to neoadjuvant chemotherapy.

Material and Methods. From May 2017 to August 2019, 63 patients with breast cancer received neoadjuvant chemotherapy. Changes in the tumor blood flow were assessed before starting the treatment and prior to the second course of neoadjuvant chemotherapy using Doppler scanning. Changes in tumor blood floor after chemotherapy were compared with the pathological tumor response after surgical treatment.

Results. In the vast majority of cases (78 %), there was a decrease in the number of tumor vessels after the first cycle of neoadjuvant chemotherapy independent of the grade of pathological response. In 8 cases with increased vascularization after the first cycle of neoadjuvant chemotherapy, histological examination of the removed tumor showed no response / weak response to treatment in the absence of peritumoral inflammation. In 5 cases, a sharp increase in the number of vessels around large areas of intranodular necrosis and peritumoral inflammation was observed. In general, a comparison of changes in tumor vascularization and pathological response revealed a weak, although statistically significant, negative correlation between changes in the tumor blood flow after neoadjuvant chemotherapy and pathological response.

Conclusion. It was not possible to establish an unambiguous relationship between the reaction of the vascular bed and the tumor response to the cytostatic effect. An increase in the number of tumor vessels in the absence of peritumoral inflammation was the only situation when changes in tumor blood flow during chemotherapy can be unambiguously interpreted as a predictive criterion for the absence / weak response of the tumor to treatment.

Localized and metastatic tumors are known to lead to the formation of circulating tumor cell (CTC ) clusters in the blood. Currently, there is a heightened interest in the study of molecular and biological characteristics of CTC s. Recent studies have shown the presence of different populations of CTC s in the blood of cancer patients. Some cells are cancer stem cells, some tumor cells undergo epithelial-mesenchymal transition (EMT), and most CTC s do not have features of either stem cells or EMT.

The aim of the study was to evaluate the five-year metastasis-free survival rate in patients with invasive breast carcinoma, depending on the presence of various populations of circulating tumor cells in the blood before treatment.

Material and Methods. A prospective study included 47 patients with newly diagnosed invasive breast cancer (T1–4N0–3M0), who were treated at Cancer Research Institute, Tomsk National Research Medical Center. The patients aged 31 to 69 years. The presence of different populations of CTC s in the blood of patients before treatment was determined by multicolor flow cytometry on the BD FACS Canto system, using different fluorochrome-labeled monoclonal antibodies to EpCam, CD 45, CD 44, CD 24, and N-cadherin. Five-year metastasis-free survival was evaluated by the Kaplan–Meier method. The differences were considered significant at p<0.05.

Results. The results obtained demonstrated that the presence of both stem-like and non-stem CTC s showing signs of EMT with Epcam+CD 45-CD 44-CD 24-Ncadherin+, Epcam+CD 45-CD 44+CD 24-Ncadherin+, and Epcam(m)- CD 45-CD 44+CD 24-Ncadherin+ phenotypes in the blood of breast cancer patients before  treatment reduced the five-year metastasis-free survival rate (p=0.0016, p=0.017 and p=0.011, respectively).

Conclusion. Thus, CTC s in the EMT state are informative for liquid biopsy to assess the risk of hematogenous metastasis and can be considered as targets for selection of personalized chemotherapy. 

Background. We previously found that a decrease in the number of NKT cells and activated CD 25+ peripheral blood lymphocytes (PBLs) before neoadjuvant chemotherapy was associated with an increased likelihood of disease progression in patients with locally advanced triple-negative breast cancer (TN BC).

The purpose of this study was to determine the relationship between the initial number of NKT-and CD 25+ PBLs and relapsefree survival (RFS)/overall survival (OS ) in patients with TN BC who received neoadjuvant chemotherapy with cisplatin and paclitaxel followed by surgery.

Material and Methods. The study included patients with stage II and III TN BC. The follow-up time was 36 and 66.9 months. Immediately before chemotherapy, the percentage of CD 3+CD 16+CD 56+ (NKT) -, CD 25+- and CD 8+ PBLs was determined by flow cytometry. Statistical analysis of the data was carried out using the Statistics 7 software package. The Kaplan-Meier method was used to determine the relationship between immunological parameters and RFS/ OS .

Results. The decreased level of NKT cells before treatment was associated with a decrease in the 3-year RFS [Me: 20.1 (0.533 and 39.7) months] compared to that observed in patients with higher percentage of these cells than in the control (Me was not achieved). There were no statistically significant differences in the 3-year OS between the groups. The initially reduced number of CD 25+ lymphocytes in comparison with the control was associated with decreased rates of both RFS and OS . The difference in DFS and OS was more significant between the groups of patients who simultaneously had an increased initial number of both NKT and CD 25+ cells and patients in whom both cell populations were below normal levels.

Conclusion. The initial (prior to chemotherapy) number of NKT and activated CD 25+ PBLs can apparently be a predictive factor in TN BC patients, who received neoadjuvant chemotherapy with cisplatin and paclitaxel. 

Glucocorticoids (GC ) have been an integral component of the treatment of leukemias and lymphomas for several decades. Specific cytotoxic effect of GC on transformed lymphoblasts mediates their use at the stage of the remission induction as well as consolidation of treatment. However, the main problem of the long-term GC use is the development of atrophic and metabolic side effects as well as GC resistance. The biological effects of GC are realized via activation of the glucocorticoid receptor (GR) by two mechanisms: transrepression (TR) associated with the therapeutic effects of GC , and transactivation (TA ), which mediates the development of metabolic and atrophic complications. It was demonstrated that an increase in the expression of the GC - dependent gene REDD1 associated with GC -induced skin, muscle and bone atrophy of the skin, muscle and bone tissue was realized via the induction of transactivation. Therefore, identification of potential inhibitors of REDD1 expression and study of their biological effects in combination with GC in models of leukemia and lymphoma is of particular interest. In our recent study we have selected a number of drugs from the class of PI 3K/Akt/mTO R modulators using bioinformatic screening. These drugs effectively inhibited REDD1 expression, modulated GR activity and shifted it towards transrepression, and prevented the development of GC -induced side effects in mice. Here we aimed to study the effects of potential inhibitors of REDD1 expression from different pharmacological groups, the compounds Emetine and CGP -60474, on leukemia and lymphoma cells in combination with GC . We demonstrated antitumor effect of the compounds in vitro, a decrease in the expression of TA -associated genes and an increase in TR induction. Further studies of the antitumor effects of REDD1 expression inhibitors (Emetine and CGP -60474 is a promising area of research.

Background. Photodynamic Therapy is one of the treatment methods used in modern oncology. Evaluation of the efficacy in vivo of photosensitizers on tumor models is generally accepted, but the photodynamic  therapy technique in mice is not without drawbacks.

The purpose of the study was evaluation of the efficacy of photodynamic therapy in mice with Ehrlich tumor model after subcutaneous and intracutaneous injection of tumor cells.

Material and Methods. The study was conducted on BAL B/C mice of both sexes. Fotoditazin® and Radachlorin® were used as photosensitizers. For photoactivation, the Alod laser apparatus with a wavelength of 662 nm was used.

Results. A comparison of photodynamic therapy with subcutaneous and intracutaneous localization of Ehrlich tumor was performed. It was shown that depending on the location and depth of inoculation of Ehrlich tumor, the pharmacokinetics (both the fluorescence intensity over time and the contrast ratio of the tumor/surrounding tissue) and pharmacodynamics (tumor growth inhibition, survival) of photosensitizers are significantly different. Higher contrast of the tumor/surrounding tissue is observed with intracutaneous localization of the tumor.

Conclusion. A model with intracutaneous localization of Ehrlich tumor can be recommended for a primary assessment of efficacy; it allows the use of fewer animals in the experiment. When planning experiments to study photosensitizers and evaluating their results, the advantages and disadvantages of different methods for modeling tumors in mice should be taken into account.

The purpose of the study was to analyze the antitumor effects of the extract of mycelium from Duddingtonia flagrans (strain F-882) on xenografts of human C33a cervical cancer cells.

Material and Methods. To evaluate the antitumor effect, we used the absolute values of xenograft volumes and calculated the tumor growth inhibition and the index of tumor growth.

Results. At the first stage of the experiment, a 4-week subcutaneous injection of the water extract of F-882 resulted in an almost twofold slowdown in xenograft growth, with the tumor growth inhibition value of 50.6 %. In the second stage of the experiment, a 2.5-week subcutaneous injection followed by a 1.5-week intratumoral injection of F-882 also caused the tumor growth inhibition. After completing F-882 injections, the effect of tumor growth inhibition continued for 2.5 weeks and the tumor growth inhibition value was 58.7 %.

Conclusion. The mycelium extract F-882 was shown to have an antitumor effect on subcutaneous xenografts of human C33a cervical carcinoma cells.

Background. The incidence of skin cancer has been steadily increasing worldwide. Squamous cell skin carcinoma (SCSC ) is the second most common form of epithelial cancer. Treatment of SCSC remains a challenge, and the 10-year survival rate does not exceed 20 % in patients with regional lymph node  metastases and 10 % in patients with distant metastases.

The aim of the study was to evaluate the treatment outcomes in SCSC patients using modern cryogenic technologies.

Material and Methods. Between 2013 and 2019, 64 patients with SCSC were treated at N.N. Petrov Research Center for Oncology (St. Petersburg, Russia). All patients were divided into two groups. Group I consisted of 32 patients who underwent cryosurgery. Group II comprised 32 patients who underwent conventional surgery.

Results. No significant differences in the treatment outcomes between Group I and Group II patients were found. Cryosurgery has several advantages over other surgical modalities. The duration of surgery was shortened by an average of 54 %. Cryosurgery is less invasive than surgery; therefore, pain and bleeding are minimized. The procedure was well tolerated by all patients. According to the «VAS » scale, the intensity of the pain syndrome in the first day after surgery was 70 % lower in Group I than in Group II . In Group I patients, the length of hospital stay was shortened by 7–9 days (57 %), and postoperative complications were not observed. In Group II , local complications were noted in 3 (9.4 %) patients. Cryosurgery was proven effective in 40.6% of elderly patients with the Charlson Comorbidity Index of more than 7 points, to whom palliative therapy is usually recommended.

Conclusion. Cryosurgery for patients with SCSC was safe and did not cause any negative impact on the immediate and long-term treatment outcomes. Cryosurgery is a method of choice in the treatment of patients with a comorbidity.

Purpose of the study: to systematize published data on the effectiveness of drugs used to treat patients
with chronic lymphocytic leukemia.

Material and Methods. A literature search was conducted using Medline, Pubmed databases. 93 publications were selected to write this review.

Results. General information about chronic lymphocytic leukemia (biological features, criteria for establishing diagnosis, staging, criteria for evaluating antitumor therapy response) was presented. The focus was made on antitumor drugs used as monotherapy and in combination with other anti-cancer agents. The use of drugs belonging to the classes of cytostatics, monoclonal antibodies, as well as drugs that affect the signaling pathways of the B-cell receptor, BCL -2 inhibitors, immunomodulators was discussed. The gold standard for first-line therapy remains the RFC scheme. With a positive Coombs test, bendamustine is an equivalent alternative to the FC regimen. The use of chlorambucil is limited in situations in which the goal of therapy is the palliative treatment of older people with serious comorbidity. In subsequent lines of therapy, molecular action drugs are beginning to take an increasingly important place.

Conclusion. During the past twenty years, significant advances have been made in understanding biological features of chronic lymphocytic leukemia, the synthesis of several dozen new therapeutic drugs of targeted action, some of which are already undergoing clinical testing. These drugs may lead to serious complications. The review is devoted to new drugs, the efficacy and safety of which has already been tested in a clinical setting.

Background. Successful treatment of patients with EG FR-positive non-small cell lung cancer (NSCLC ) is directly related to epidermal growth factor receptor (EG FR) tyrosine kinase inhibitors (TKIs). Currently, three generations of EG FR TKIs are used for treatment of EG FR-positive NSCLC . The issue of what drug or what sequence of its administration will be the optimal treatment option for a particular patient seems relevant.

Purpose: To analyze available data on the use of TKIs for the treatment of advanced EG FR-positive NSCLC patients, as well as to assess the possible mechanisms of resistance to them and determine the optimal sequence of EG FR TKI therapy.

Material and Methods. The review includes data from randomized controlled trials, as well as data from real-world studies on the efficacy of EG FR TKIs and subsequent therapy options in cases of drug resistance.

Results. The choice of the optimal first-line treatment option for patients with EG FR-positive NSCLC depends on many factors. To our opinion, afatinib therapy with subsequent osimertinib therapy allows maximal prolongation of low-toxic targeted therapy and delayed administration of cytostatic drugs in patients with T790M mutation.

Conclusion. Considering the dominant mechanism of resistance development (presence of EG FR -T790M mutation), the use of the second- and third-generation EG FR inhibitors seems to be an optimal treatment option for patients with activating EG FR mutations.

The purpose of the study was to analyze various methods of stopping bleeding from the presacral venous plexus.

Material and Methods. Literature search was carried out using Elibrary, Medline, Embase databases from January 1960 to November 2018.

Results. Bleeding from the presacral venous plexus is a rare but potentially life-threatening complication in pelvic surgery. The inferior vena cava, the veins of the presacral and internal spinal plexuses are dilated under general anesthesia, and act as a large venous “blood pool” in the pelvis because of the lack of functional valves. Hydrostatic pressure in this venous pool can reach two to three times the pressure of the inferior vena cava. Thus, rupture of even a small presacral vein may result in heavy bleeding. Among the many reported methods of stopping this bleeding, the most effective are as follows: mechanical tamponade; technique of pressing the bleeding site; ectrocoagulation; the use of hemostatic materials.

Сonclusion. The variety of methods used for stopping bleeding from the presacral venous plexus indicate a need of searching for more effective methods.

Glial tumors comprise about 60 % of primary malignant brain tumors, and 70 % of them show morphological signs of high-grade cancer (High Grade Gliomas III , IV WHO 2016) [1, 2]. Despite a significant technical pre- and intraoperative progress as well as advances in radiotherapy and chemotherapy, the overall median survival is very low, being less than 20 months [3] and less than 12 months in patients with relapse [4]. Recent studies have shown that chemo- and radioresistance is due to the existence of cancer stem cells [5, 6]. Poor treatment outcomes require the development and implementation of new approaches to the treatment of highgrade gliomas. In recent years, increasing attention has been paid to the development of immunotherapeutic treatment approaches, including the development of oncolytic virotherapy. Tropism to target cancer cells, as well as various viral vectors, has been developed using methods of genetic engineering; synergism of viruses and adjuvant therapy has been studied. Despite extensive experimental studies of the mechanism of oncolysis [1], there are only a few reports on Phase I–II clinical trials. This review considers the most successful applications of oncolytic viruses in relation to glioblastoma in animal models and their translation into clinical practice in patients.

The purpose of the study was to systematize and summarize modern ideas about the role of hypoxia in the development of tumor radioresistance.

Material and Methods. PubMed, eLibrary and Springer databases were used to identify reviews published from 1953 to 2020, of which 57 were selected to write our review.

Results. Radiation therapy is one of the most important components in cancer treatment. The major drawback of radiation therapy is the development radiation resistance in cancerous cells and secondary malignancies. The mechanisms of cancer radioresistance are very complicated and affected by many factors, of which hypoxia is the most important. Hypoxia is able to activate the mechanisms of angiogenesis, epithelial-mesenchymal transformation and contribute to the formation of the pool of cancer stem cell, which are characterized by chemo- and radioresistance. In turn, the severity of hypoxia largely dependent on tumor blood flow. Moreover, not only the quantitative but also the qualitative characteristics of blood vessels can affect the development of tissue hypoxia in the tumor.

Conclusion. A comprehensive assessment of the severity of hypoxia, as well as characteristics of angiogenesis and EMT can contribute to a better understanding of the mechanisms of development of cancer radioresistance.

Background. Gastrointestinal stromal tumor (GIST ) is a rare neoplasm with an incidence of only 10–20 cases per million population. All gastrointestinal neoplasms may have malignant potential and most of them are sporadic tumors. GIST occurring during pregnancy is extremely rare, therefore, surgeons face challenging ethical, surgical and oncological issues. Case. We describe a clinical cause of GIST found at the 16–17-th week of pregnancy in a 31-year-old woman. The patient was under the supervision of obstetricians-gynecologists, radiologists and oncologists, and a weekly ultrasound examination was performed. Caesarean delivery was performed at the 26th week of pregnancy due to disease progression and in order to start anticancer therapy as soon as possible. Conclusion. We described the first reported case of a successful treatment in a 31-yearold pregnant patient with GIST of the small intestine complicated by peritoneal carcinomatosis and ascites. We compared our case with other reported cases of GIST during pregnancy and discussed the problems faced by both patients and surgeons. There are no recommendations on the optimal timing of tumor resection during pregnancy, and therefore key decisions must be made in a multidisciplinary team (MDT ), taking into account the wishes of the patient. Our clinical case demonstrates the feasibility of changing the approaches to the management and treatment of patients with intraperitoneal dissemination, as well as emphasizes the importance of interdisciplinary team including oncologists, obstetricians, gynecologists, neonatologists and other specialists.

Primary gastrointestinal melanoma is a rare tumor with a frequency of 1 new case per 5–7 years. Over the past 100 years, there have been no more than 25 reported cases of primary melanoma of the stomach and colon. The rarity of the disease and nonspecific clinical features pose diagnostic challenges. The tumor is characterized by an aggressive growth and early metastasis. Case description. We present a rare clinical case of primary gastrointestinal melanoma with metastatic involvement of the adrenal glands, liver and retroperitoneal lymph nodes. Conclusion. To date, treatment standards for primary gastrointestinal melanoma have not been developed and are the subject of debate. However, palliative chemotherapy used for the treatment of primary skin melanoma may lead to disease stabilization in patients with gastrointestinal melanoma.