Between December and September 2018 123 patients with head and neck tumors underwent ultrasound examination. The median age of the patients was 57 years (range 19–76 years). Metastatic lymph nodes were suspected in all patients. A fine needle aspiration biopsy was performed prior to treatment. Aplio 500 (Тoshiba, Japan) ultrasound device was used. According to findings of cytological examination, all patients were divided into 2 groups. Group I consisted of 58 patients with cytologically confirmed metastatic lymph nodes. Group II comprised 65 patients with lymphoid reticular hyperplasia. The values of Young’s modulus for metastatic lymph nodes were: median – 134.2 kPa, 2.5–97.5 percentiles – 7.3–181.7 kPa. The corresponding values for hyperplastic lymph nodes were: 20.1 kPa, 6.9–138.3 kPa. Thus, significant differences in the values of Young’s modulus between metastatic and hyperplastic lymph nodes were detected in patients with head and neck cancer (p<0.001). The best diagnostic values for detecting metastatic lymph nodes in patients with head and neck cancer were achieved with a threshold value of the Young’s modulus of 33.2 kPa (sensitivity – 89.7 %, specificity – 84.6 %), AU C – 0.899. The values of the Young’s modulus in the metastatic lymph nodes did not depend on the primary tumor and on the localization of the lymph nodes studied (submandibular, paratracheal, cervical, supraclavicular groups).

The purpose of the study was to analyze long-term outcomes of intraoperative radiation therapy (IORT) in patients with stage III non-small cell lung cancer (NS CLC).

Material and Methods. The study included 103 patients with stage III NS CLC treated at the Cancer Research Institute (Tomsk, Russia). All patients were divided into two groups. Group I consisted of 51 patients, who underwent radical surgery and IORT at a single dose of 15 Gy. Group II (control group) comprised 52 patients, who underwent radical surgery alone. There were 34 (33 %) pneumonectomies, 39 (37.9 %) lob-, bilobectomies, 9 (8.7 %) reconstructive surgeries and 21 (20.4 %) combined surgeries. A compact pulsed betatron MIB-6E with the average electron energy of 6 MeV, located directly in the operating unit, was used for performing IORT. The Kaplan-Meier method was used for survival analysis. The significance of differences in survival between groups was assessed using the log rank test.

Results. Excluding the cases lost to follow-up and deaths from concomitant non-malignant diseases, treatment outcomes were followed up in 97 of 103 patients with NS CLC for 3, 5, and 10 years. The 3-year and disease-free survival rates were significantly higher in the IORT group than in the control group (p<0.05). The IORT reduced the frequency of locoregional recurrence from 28.6 % to 20.8 % and increased recurrence-free survival from 12 to 17.1 months. In patients with stage III NS CLC, who received combined modality treatment including IORT, the 5and 10-year disease-free survival rates were 18.7 % and 12.5 %, respectively. In the control group patients, the corresponding values were 14.3 % and 6.1 %, respectively (р<0.05). The 5and 10-year overall survival rates were 29.2 % and 18.7 % versus 20.4 % and 8.2 %, respectively (р<0.05).

Aim: to study complications of preoperative chemoembolization of the gastroduodenal artery and external beam radiation therapy in patients with pancreatic head cancer.

Material and Methods. Sixty patients underwent chemoembolization of the gastroduodenal artery and external beam radiation therapy. Femoral artery angiography was performed using the Seldinger’s technique. Lipiodol 5–7 ml and gemcitabine 400 mg/m2 were used for transarterial chemoembolization. Radiation therapy was given at a total dose of 50 Gy (2 Gy/fraction, 5 times a week, over 5 weeks) using AGAT -R apparatus.

Results. Complications after chemoembolization of the gastroduodenal artery were observed in 18.3 % of patients: abdominal pain in 3.3 % of patients; pain and nausea in 3.3 %; pain, nausea and fever in 6.7 %; pain, nausea and increased blood amylase in 1.7 %; pain, nausea and fever, blood amylase in 1.7 %; nausea, fever and blood amylase in 1.7 %. Radiation-induced injuries were observed in 23.3 % of patients: erythema in 18.3 %, grade 1 leukopenia in 1.7% and grade 2 leukopenia in 3.3 %.

Conclusion. Complications of neoadjuvant therapy in terms of frequency and severity were consistent with literature data, were manageable with conservative treatment, and did not increase the duration of the preoperative period.

The purpose of the study was to evaluate the frequency of isolation of multi-resistant Acinetobacter baumannii in cancer patients and identify the mechanisms of resistance to carbapenems.

Material and Methods. We analyzed 942 strains of A. baumannii isolated from clinical samples of cancer patients in the period 2014–16. The level of resistance to ampicillin-sulbactam, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin, and to other antibiotics was determined. Carbapenem-resistant (Car-R) strains were examined for the presence of carbapenemases.

Results. Between 2014 and 2016, the number of strains resistant to: ampicillin-sulbactam was 95.5–74.6 % (p≤0.0001), piperacillin – tazobactam 64.3–98.1 % (p<0.01), ceftazidime – 66.1–44.3 % (p≤0.0001), cefepime – 94.7–98.3 % (p≤0.01), ciprofloxacin – 95.8–91.8 % (p<0.05), amikacin – 77.7–91.0 % (p≤0.0001). An increase in the number of Car-R strains from 77.2 % in 2014 to 84.1 % in 2015 (p<0.05) and up to 90.0 % in 2016 (p<0.05) was observed. The resistance to imipenem was 100 %. The analysis of 6 strains in relation to acquired carbapenemases revealed the production of serine carbapenemases of the OXA-23 group in 100 % of cases.

Conclusion. A. baumannii remains to be highly resistant to almost all classes of antibiotics, and the resistance to carbapenems is caused by the production of carbapenemases OXA-23.

Primary glioblastoma (GB) is a rapidly progressing central nervous system tumor with aggressive biological behavior. Long-term glioblastoma survival, defined as survival beyond 3 years, is a rare phenomenon. Various factors contributing to such prolonged lifespan have been proposed.

Aim. This study aimed to compare demographic, clinical, morphologic, immunohistochemical and molecular features of primary GB in patients with different survival.

Material andMethods. This prospective study included 69 patients, who were treated at A.L. Polenov Neurosurgery institute. The analysis considered clinical, morphologic, immunohistochemical (Ki67, P53, INA , EGFR) and genetic (MGMT, VEGF and PDGFRA gene expression; ID H1/2 mutational status, 1p/19q co-deletion) characteristics of the disease.

Results. 11 (15.9 %) patients survived beyond 3 years. Prolonged survival was associated with younger patient age (p=0.002), use of more than 6 cycles of temozolomide in the 1st line therapy (p=0.016), use of the 2nd line therapy (p=0.017) and low level of MGMT expression in the tumor tissue (p=0.038). Other factors including patients’ gender, VEGF and PDGFRA mRNA expression levels, ID H1 mutation, 1p/19q deletion, and the immunohistochemical markers Ki67, p53, INA , EGFR, were not associated with prolonged survival (p>0.05).

Conclusion. Prolonged survival in GB patients is a non-random event and can be explained by several clinical and biological factors. A high percentage of 3-year survival of GB patients in our study may be explained by an individual approach to treatment and intensive chemotherapeutic tactics (from 6 to 15 cycles of temozolomide in the 1st line therapy and use of the 2nd line therapy), as opposed to standard short treatment protocols.

Various types of tissues was analyzed, and the algorithm for summing neutron and photon doses in neutronMiRNA s are involved in the regulation of numerous critical biological processes, including cell proliferation, differentiation, migration and invasion. They function as oncogenes or tumor suppressors according to the nature of the target. It has been previously determined that miR-204-5p miRNA is characterized by the increased level in melanoma. The aim of this study was to determine the effects of changes in the level of microRNA expression when dacarbazine was exposed to melanoma cells in vitro and synthetic miR-204-5p in vivo. The expression levels of miR-204-5p and miR-211 in melanoma cells were determined by real-time PCR. Antitumor effects in vivo were verified in assessing the growth dynamics of the tumor node. Toxic effects were assessed by animal behavior, fluid intake, feed, and ALT , AST , creatinine, urea levels. In the model of melanoma C57BL6, it was revealed that the introduction of the synthetic miR-204-5p did not cause significant changes in the investigated microRNA in tumor cells. At the same time, the antitumor effects of dacarbazine in melanoma cells in vitro led to an increase in the level of the investigated microRNA by more than 20 times. The results of the study indicated the possibility of compensating the level of miR-204-5p under the influence of cytostatic therapy. Taking into account the previously revealed miR-204-5p inhibitory effect on the proliferation of melanoma cells, we can assume that this miRNA can play a role in maintaining the dermal state of tumor cells. Further studies are required to understand the metastasis development and predict the response to antitumor therapy for melanoma.

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by downregulatoin of the EMT.

Objective: to study the effect of MEK and mTOR co-inhibition on cell viability, ability to form 3D-spheroids and migratory capacity of melanoma cell lines, and correlation of these changes with EMTand autophagy-related markers.

Material and Methods. Melanoma cell lines Mel Z and Mel MTP were derived from patients, who were treated at the N.N. Blokhin National Medical Research Center of Oncology. The antiproliferative effect of binimetinib and/or rapamycin was studied by the MTT -test. 3D spheroids were formed using RGD peptides. Cell migration and invasion were assessed by a Boyden chamber migration assay. The expression levels of autophagy and EMT markers were investigated by immunocytochemistry or immunoblotting.

Results. Rapamycin increased cytotoxicity of binimetinib in both 2D and 3D melanoma cell line cultures. At the same time, binimetinib and rapamycin reduced invasion, but not migration capacity of melanoma cells in vitro. The effectiveness of the combination was associated with a decrease in the EMT markers (N-cadherin and β-catenin) and autophagy markers (Beclin 1, p62/SQST M1 and LC3BII ) in melanoma cells.

Conclusion. Inactivation of autophagy and EMT leads to overcoming the resistance to current anti-melanoma therapy and can be considered as a promising target for the treatment of melanoma.

Introduction. Cutaneous melanoma is a challenge to treat due to rapid progression of disease and acquired resistance to therapy. Autophagy and the epithelial-to-mesenchymal transition (EMT) are closely interrelated and play a key role in tumor progression. Targeted co-inhibition of MEK and mTOR kinases is a potential target for melanoma therapy by downregulatoin of the EMT.

Objective: to study the effect of MEK and mTOR co-inhibition on cell viability, ability to form 3D-spheroids and migratory capacity of melanoma cell lines, and correlation of these changes with EMTand autophagy-related markers.

Material and Methods. Melanoma cell lines Mel Z and Mel MTP were derived from patients, who were treated at the N.N. Blokhin National Medical Research Center of Oncology. The antiproliferative effect of binimetinib and/or rapamycin was studied by the MTT -test. 3D spheroids were formed using RGD peptides. Cell migration and invasion were assessed by a Boyden chamber migration assay. The expression levels of autophagy and EMT markers were investigated by immunocytochemistry or immunoblotting.

Results. Rapamycin increased cytotoxicity of binimetinib in both 2D and 3D melanoma cell line cultures. At the same time, binimetinib and rapamycin reduced invasion, but not migration capacity of melanoma cells in vitro. The effectiveness of the combination was associated with a decrease in the EMT markers (N-cadherin and β-catenin) and autophagy markers (Beclin 1, p62/SQST M1 and LC3BII ) in melanoma cells.

Conclusion. Inactivation of autophagy and EMT leads to overcoming the resistance to current anti-melanoma therapy and can be considered as a promising target for the treatment of melanoma.

The purpose of the study was ex vivo examination of lymph node perfusion in patients with metastatic breast cancer.

Material and Methods. Lymph nodes affected with metastatic breast cancer were examined. These nodes were subsequently subjected to microsurgical dissection with the isolation of the capsule, lymphatic vessels, parenchyma and stroma. All manipulations were performed after preliminary lymph node dissection using an axillary node sample, and the dissection of an isolated lymph node from this region was then performed. A total of 100 breast cancer patients underwent lymph node dissection and microsurgical lymph node dissection. The control group comprised samples taken from women who died in accidents and had no a history of cancer. Lymph nodes and vessels were isolated from the adipose tissue of the axillary region by the sonolipodestruction technique using LySonix 3000® ultrasonic device with PulseSelect™. A detailed examination of lymph nodes was carried out using OPTON microscope – OPMI 6 CFC and a set of microsurgical instruments. Color lymphography of isolated afferent lymphatic vessels with 0.5 % methylene blue solution was performed. Along with color lymphography, digital morphometry of the components of the lymphatic system (Image-Pro Plus 6.0) and microsurgical dissection of the lymph node capsule and lymphangion valves were performed.

Results. Data on non-metastatic and metastatic lymph nodes were obtained and digitally recorded. When studying the metastatic blockade of the lymphoid lobule and afferent lymphatic vessels by the method of antegrade color lymphography, we revealed the compensatory development of lymphatic bypass – intracapsular neo-lymphatic microangiogenesis that was confirmed by histological studies.

Conclusion. Color lymphography reliably determines the areas and the extent of functional perfusion. Post-radiation changes in tissues markedly change the logistics of lymph flow and regional metastasis. The lymph node capsule with metastases undergoes a pathological transformation characterized by the development of a network of lymphatic capillaries, the severity of which depends on the extent of metastatic block. Lymph node metastasis changes the lymphatic hydrodynamics by changing the number of lymphatic vessels and their diameter.

Pseudomixoma peritonei is a rare type of peritoneal carcinomatosis accompanied by accumulation of mucus and high recurrence rate and in some cases complicated with intestinal obstruction. In the last 10–15 years, there has been observed a significant improvement in overall survival of patients with recurrent pseudomyxoma, who underwent cytoreductive surgery in combination with intraperitoneal chemotherapy. However, the frequency of recurrences of peritoneal pseudomyxoma after optimal cytoreduction can reach 80–90 % in the first 2 years.

The purpose of the study was to analyze the results of combined therapy (cytoreductive surgery and hypothermic intraperitoneal chemoperfusion) in patients with recurrent pseudomyxoma peritonei, who previously underwent cytoreductive surgery.

Material and Methods. The study included 43 patients previously undergoing cytoreductive surgery for pseudomyxoma peritonei in the Thoracic Oncology Department of the N.N. Blokhin National Medical Research Center of Oncology.

Results. Re-operations were performed in 11 of the 43 patients with recurrent pseudomixoma peritonei after previously performed cytoreductive surgery. Repeated intraperitoneal chemoperfusion with hyperthermia was performed in 6 patients. Of the 11 reoperated patients, 7 had a complete cytoreduction (CC-0), recurrence was detected within 22 to 47 months; 2 patients had CC-1 and recurrence was observed within 12 and 15 months. Optimal cytoreduction (CC0-1) was achieved in 7 of the 11 patients. The maximum follow-up period was 44 months. Recurrence was noted in 9 patients, while the majority of patients had a satisfactory quality of life. Two patients showed signs of partial intestinal obstruction. None of the patients died during the follow-up period. In two patients with optimal (CC-0) cytoreduction, there were no signs of disease progression 9 and 15 months after re-surgery. One-year disease-free survival rate was 51 %.

Conclusion. Repeated surgeries for recurrent pseudomyxoma present a great challenge for surgeons due to the difficulty in achieving optimal cytoreduction. Optimal cytoreduction in initial surgery should be considered as the main condition for repeated surgery. Moreover, additional criterion for a favorable prognosis is the time to progression of disease.

The extent of surgery for anal rectal cancer (ARC) is determined by the clinical efficacy of neoadjuvant chemoradiotherapy (CRT). An approach using medium intensity ultrasound combined with chemotherapy was developed. Advantages of sonodynamic chemotherapy (SD CT) were evaluated to improve the CRT efficacy and the quality of life of patients with ARC affecting the skin.

Material and methods. 34 patients with morphologically verified сТ2–3N0–1M0 ARC received 2 cycles of polychemotherapy (PCT): intravenous bolus of mitomycin C 10 mg/m2 on days 1 and 29 + continuous infusion of 5-fluorouracil 1000 mg/m2 daily on days 1–4 and 29–32. Patients received CRT 3 weeks after the second PCT cycle. Prior to each session of standard external and intracavitary irradiation, 18 patients of the main group received a 2-hour extemporaneous mixture to the primary tumor site: 5 mg of the Coletex SP-1 hydrogel material with propolis based on sodium alginate plus 100 mg of gemcitabine-medac together with mid-frequency ultrasound (0.88 MHz, I =1.0 Вm/cm2, Patent No. 2638616). 16 controls received capecitabine 825 mg/m2 orally twice a day with 12-hour intervals during the radiation course.

Results. Controlled general clinical effect after external irradiation + SD CT in the main group was 25.7 % (p<0.05) higher than in controls, and complete regression was 1.4 times more frequent (77.8 % vs. 56.2 %). Radical surgery after CRT was necessary only in 11.1 % cases in the main group vs. 43.8 % in controls (p<0.05). No local recurrences were observed during 612 months in 16 patients of the main group without surgery, while 22.2 % (p<0.05) of controls showed local recurrence. The rates of pelvic relapses and distant metastases were similar in both groups.

Conclusion. The positive effect of the proposed method for ARC treatment is determined by the combination of therapeutic factors including the action of a radiosensitizing agent introduced into tumor tissues.

Hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer and is the final stage of chronic liver disease, usually occurring in patients with cirrhosis (CP). Chronic infection with hepatitis C virus (HCV) leads to progressive liver inflammation and cirrhosis because this virus specifically affects liver tissue. Previously used interferon therapy had a relatively low efficiency and very high risks of side effects. During the period of administration of interferon (IFN) schemes it was proved that elimination of the virus significantly reduced risk of liver cancer development. Discovery of direct-acting antiviral (DAA ) drugs have revolutionized HCV therapy with virus elimination rate of more than 95 % and an excellent safety profile. However, the risk of transformation of liver cirrhosis into hepatocellular carcinoma is still high even after complete eradication of the virus. Numerous studies have shown conflicting results on the possible relationship between the use of new antiviral drugs and the increase in the frequency of newly diagnosed or recurrent hepatocellular carcinoma. Thus, the long-term prognosis in terms of risk for HCC development among patients with sustained virological response (SVR) remains unclear.

The purpose of the study was to analyze the literature on the effect of antiviral therapy of chronic hepatitis C with interferon-containing regimens and drugs of direct antiviral action on the risk of developing or recurring hepatocellular carcinoma.

Material and Methods. We analyzed publications available from PubMed, S copus, E-library, Web of S cience using the key words “hepatocellular carcinoma”, “chronic hepatitis C”, “direct-acting antiviral drugs”, “liver cirrhosis”, “interferons”, and “sustained virological response”. Of the 99 studies found, 21 were used to write a systematic review.

Results. Eradication of the virus reduces the risks of HCC. Despite reports on high risk of occurrence or recurrence of hepatocellular carcinoma in patients with cirrhosis after treatment with DAA s compared with interferon-containing regimens, there is not enough data confirming the direct link between the use of DAA s and the development of hepatocellular carcinoma. No statistically significant difference in the frequency of HCC between patients treated with interferon or DAA s was detected.

Conclusion. Eradication of the virus is the most significant factor in the prevention of HCC; therefore, treatment of CHC should not be delayed due to the risk of HCC. Patients with liver cirrhosis require a long period of follow-up, even after successful treatment of chronic hepatitis C with DAA drugs. Stratification of HCC risk requires further research.

Purpose: to assess current data on the effect of different approaches to preoperative bowel preparation before elective colorectal surgery on short-term treatment outcomes.

Material and Methods. Online system PubMed of U.S. National Library of Medicine was used to find articles with key words “mechanical bowel preparation”, “surgical site infection”, “oral antibiotics”. A total of 226 articles were reviewed. 31 articles were selected for final review. Furthermore, ClinicalTrials.gov site was used to find actual and recruiting trials.

Results. Mechanical bowel preparation (MBP) used to be a standard procedure for a long time. Nowadays, routine use of MBP seems to be debatable. Alternative approaches, e.g. absolutely no preparation or the use of MBP in combination with oral antibiotics, are considered. Data on performing different kinds of bowel preparation is reviewed in this article.

Conclusion. Optimal approach of preoperative bowel preparation is still questionable. Combination of mechanical bowel preparation and oral antibiotics seems to be a preferable method. However, there is not enough evidence to exclude anothertechniques. It’s required to conduct additional randomized controlled trials.

Currently, the presence of the germinal mutation BRCA1 5382insC in breast cancer patients is one of the determining factors for prescribing platinum-based drugs. However, this type of mutation is found in no more than 10 % of patients, thus limiting the feasibility of administering platinum-based drugs. Various somatic changes in the BRCA1 gene in breast tumors, in particular the deletions of this gene, can play an important role in the tumor sensitivity to platinum drugs.

Case description. We present the case of a 42-year-old woman diagnosed with breast cancer. The deletion of the BRCA1 gene was detected in the tumor. The patient had a complete response to preoperative chemotherapy according to the CP regimen.

Conclusion. The frequency of the germline mutation of the BRCA1 gene does not exceed 10 %, and the deletion frequency of this gene can vary from 30 to 45 %, thus greatly increasing the feasibility of using platinum-based drugs in mutationnegative patients to achieve complete pathologic response and high survival rates.

We report a case of disseminated gastrointestinal stromal tumor effectively treated with imatinib, a selective tyrosine kinase inhibitor.

Background. Treatment of gastrointestinal stromal tumors (GIST ) still remains a clinical challenge. Since 2001 a breakthrough has occurred in the treatment of patients with GIST due to a successful use of imatinib, the targeted drug from the group of tyrosine kinase inhibitors, which is effective in the first line of inoperable and/or metastatic GIST , and is also used for neoadjuvant and adjuvant therapy for localized GIST . Genetic mutational analysis used for the correct prescription of targeted therapy suggests that it is inappropriate to administer imatinib in patients with a mutation in the succinate dehydrogenase gene and D842V mutation in the platelet-derived growth factor gene. However, in different regions of the Russian Federation, such diagnostic procedure may not always be available for a number of technical reasons. The lack of response to therapy and, consequently, the progression of the disease, may be associated with a decrease in the therapeutic concentration of imatinib in the blood plasma. Determination of the concentration of active metabolites of imatinib in the serum allows timely identification of potential causes of insufficient response to therapy and individual correction of the dose of the drug.

Material and Methods. To assess a significance of the correlation between increasing/decreasing the dose of imatinib and achieving a therapeutic response, we used a laboratory high-performance liquid chromatography method to determine the concentration of imatinib in serum.

Conclusion. Determination of a decreased concentration of active metabolites of imatinib in plasma by high-performance liquid chromatography with detection of tandem mass spectrometry method in a patient with disseminated GIST allowed us to correct the dose of the drug and achieve a positive effect with a duration of 51 months (since the dose was increased). The method of high-performance liquid chromatography with the detection of the method of tandem mass spectrometry is not an absolute alternative to gene mutation analysis, however, it can be effectively used for correction of the dose of imatinib in patients with GIST.