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Siberian journal of oncology

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Vol 19, No 4 (2020)
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https://doi.org/10.21294/1814-4861-2020-19-4

EPIDEMIOGICAL STUDIES

7-23 1645
Abstract

The aim of the study was to assess adherence to breast and cervical cancer screening ensuring compliance with ethical principles.

Material and methods. A total of 1,015 women of target age groups, living in Almaty, the Republic of Kazakhstan, participated in breast and cervical cancer screenings. A structured questionnaire was used to collect data from each participant (1,239 questionnaires: 674 for breast cancer screening and 565 for cervical cancer screening). Two hundred and twenty-four women participated in two screenings. The survey was conducted immediately after the respondents had had a mammography and / or Pap test. The questionnaire included the socio-demographic characteristics of women, questions on awareness of screening, level of knowledge before and after screening, sources of information, feelings before screening, after screening and and also after the receipt of test results. Binary logistic regression was used for data analysis.

Results. Sixty-one percent (95 % CI 57.7; 63.1) of women participated in screening for the first time, 39 % (95 % CI 36.4; 41.8) of respondents visited outpatient clinic for the second and the third time. Multivariable analysis revealed that the participation in screening was associated with the purpose of visit, awareness and confidentiality. Thus, women, who arrived at the outpatient clinic with purposes other than screening were 2.3 times less (OR=2 95 % CI 1.6; 3.1) likely to participate in next screening compared to those, who came to the clinic with the purpose of screening as well as those, who were referred by employers (OR=2 95 % CI 1.2; 3.2) or friend/family (OR=2 95 % CI 1.0; 4.3). Women, who had little information about screening as a whole and about screening test before it was taken, were 3 and 2 times less likely to come to screening again (OR=3 95 % CI 1.6; 5.9 and OR=2 95 % CI 0.8; 3.7, respectively). The confidentiality violation led to a decrease in chance (OR=3.5 95 % CI 2.2; 4.9) of being screened again for those women, who experienced nervousness and shame during the screening, and also indicated the presence of nonmedical people during the test.

Conclusion. Measures aimed to ensure compliance to ethics in screening for breast and cervical cancer will improve the quality of screening programs in accordance with international standards, as well as increase the personal responsibility for active participation in screening.

CLINICAL STUDIES

24-32 982
Abstract
Introduction. Advances in diagnostic imaging techniques have made it possible to measure a large number of blood flow parameters of pathological processes, and one of these techniques is perfusion computed tomography (PCT).
The aim of the study was to confirm the reliability of CT perfusion findings in determining the nature of focal pulmonary lesions using statistical analysis data.
Material and Methods. A 128-slice CT scanner was used to analyze PCT findings in60 patients with benign and malignant lung tumors. Conclusion. The average PS and TTP values are the main factors in determining the nature of pulmonary lesions.
Conclusion: multi-slice CT perfusion imaging is a valuable technique in determining the nature of focal pulmonary lesions. Practical recommendations are given for performing CT-perfusion imaging of the lungs.
33-40 1673
Abstract

Introduction. Mediastinal lymphadenopathy can be caused by a wide range of benign and malignant states. Determination of the genesis of lymphadenopathy is crucial for treatment planning and prognosis of the disease.
The purpose of the study was to evaluate the diagnostic accuracy of diffusion weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurements in differentiating malignant versus benign mediastinal lymphadenopathy.
Material and Methods. 48 consecutive patients with at least one enlarged mediastinal lymph node revealed on CT-scans were examined on 1,5 T MR-machine with conventional images and respiratory-triggered DWI. In all patients one of the biggest solid lymph nodes was selected for ADC measurements and mean ADCs of each node were recorded. ADCs were correlated with the results of complete diagnostic work-up (including histopathological diagnosis in 41 patients) and follow-up CT. Statistics included Student’s t-test, Mann-Whitney U-test and ROC-curve analysis.
Results. 27 lymph nodes were classified as malignant (metastases, lymphoma) and 21 lymph nodes were classified as benign (sarcoidosis, reactive hyperplasia, tuberculosis). Mean ADC of malignant lymph nodes (1,02 ± 0,29×10−3 mm2/s) was significantly lower than that of benign lymph nodes (1,57 ± 0,32×10−3 mm2/s), p<0,0001. The cut-off value of ≤1,3×10−3mm2/s for ADC indicated the malignancy with a sensitivity of 81,5 % and a specificity of 85,7%. The area under the ROC-curve was 0,89 (95 % confidence interval: 0,77, 0,96), p<0,0001.
Conclusion. DWI is a promising technique in chest pathology. DWI with ADC measurements could be used as a good complementary tool in the diagnostic work-up of patients with mediastinal lymphadenopathy.

41-48 1013
Abstract
The purpose of the study was to immediate results of neoadjuvant chemoradiotherapy in patients with locally advanced gastric cancer were analyzed in a multicenter randomized trial.
Material and Methods. The comparative analysis of neoadjuvant chemotherapy regimens, toxicity and postoperative complications was carried out. Patients of the study group received conformal radiation therapy (46 Gy in 2 Gy daily fractions) concurrently with chemotherapy with Capecitabine at a dose of 1850 mg/m2 divided in two equal doses during the course of radiation therapy, and Oxaliplatin at a dose of 85 mg/m2 on days 1 and 21. After an interval of 4–6 weeks and a control examination, in the absence of evident disease progression, patients were scheduled for surgery (gastrectomy or subtotal gastrectomy with D2 lymph node dissection) and 4 cycles of adjuvant chemotherapy according to the FOLFOX4 or CAPOX regimen. The treatment program for patients in the control group included surgery (gastrectomy or subtotal gastrectomy with D2 lymph node dissection) after randomization, and 6 cycles of adjuvant chemotherapy using the same regimens. The study included 70 patients with an equal distribution between groups.
Results. Among the patients of the study group, grade 1 and 2 toxicity was the most common; grade 3 toxicity occurred in 9 cases; grade 4 and 5 toxicity was not observed. Among the manifestations of hematological toxicity, thrombocytopenia and leukopenia were the most common (57–60 % of patients), and grade 3 hematological toxicity was observed in 6 (17.1 %) cases. Among the manifestations of gastrointestinal toxicity, nausea, vomiting and decreased appetite prevailed; grade 3 toxicity was observed only in 3 (8.6 %) cases. The radiation component of neoadjuvant therapy was completed in 32 (91 %) patients. Both protocol-prescribed oxaliplatin infusions were performed in 34 (97 %) patients. Changes in capecitabine administration were required in 8 patients. Immediately before surgery, some patients had grade 1–2 toxicity, which did not prevent performing surgery. There were no statistically significant differences in the frequency and severity of complications in the early postoperative period between the comparison groups. Grade 1–2 postoperative complications were the most common.
49-58 1586
Abstract
The aim of the study was to analyze the immediate and long-term outcomes of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in gastric cancer patients with peritoneal carcinomatosis (PC).
Material and methods. The treatment protocol included diagnostic laparoscopy with PCI score assessment and peritoneal biopsy and 4 courses of systemic chemotherapy with XELOX or FOLFOX followed by PIPAC with cisplatin and doxorubicin at 6–8 week intervals. Between the PIPAC cycles patients received systemic chemotherapy according to previous regimen. Each PIPAC procedure included laparoscopy, evaluation of Peritoneal Carcinomatosis Index (PCI) and peritoneal biopsies.
Results. 102 (80.3 %) patients had primary gastric cancer with PC and 25 (19.7 %) had peritoneal recurrence of gastric cancer. PCI<10 points was found in 60 (47.2%) patients, PCI 10–18 in 33 (26 %) patients and PCI>18 in 34 (26.7 %) patients. Diffuse type of cancer was diagnosed in 114 patients (89.7 %), intestinal type in 6 (4.7 %) patients and the mixed type in 7 (5.5 %) patients. 127 patients underwent 310 PIPAC procedures. No severe complications and were observed. Pathological response (PRGC score) was evaluated in 72 patients. Partial pathological response (PRGS 2) was achieved in 40 (55.6 %) cases and complete pathological response (PRGS 1) – in 10 (13.9 %). Survival was evaluated in 63 % (n=80) patients who received more than one PIPAC. The median survival was 16.0 months and one year survival rate was 77.9 %.
Conclusion. A new approach to the treatment of gastric cancer with PC combining systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy is a simple and save method allowing improvement of survival of patients with peritoneal dissemination of gastric cancer.
59-66 1511
Abstract
Introduction. Mutations in the isocytrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are considered driver genetic events in gliomas. Their frequency reaches 7080 % in low-grade gliomas and in secondary glioblastomas, and their oncogenic effect is realized by accumulation of the metabolite 2-hydroxyglutarate, which disrupts DNA and protein methylation processes.
The aim of the study was to analyze the associations between the presence of IDH1/2 mutations and clinical and morphological parameters of glial tumors.
Material and Methods. The study included 147 patients with glial brain tumors. Associations between IDH1/2 status and tumor histological type, age of disease onset, tumor localization, and clinical manifestations were investigated.
Results. Gliomas containing IDH1/2 mutations were characterized by a younger age at diagnosis (mean: 39.5 years) compared to IDH-negative cases (47.2 years) (p<0.01). IDH1/2-mutated tumors were more often localized in the frontal (53.4 %) and parietal lobes (61.3 %) than in the other areas of the brain (p<0.05). It was demonstrated that the incidence of epilepsy was significantly higher among patients with IDH1/2 genetic defects (69.2 % vs. 48.2 %, p<0.05). Patients with IDH1/2 mutations had more favorable course of the disease. Among individuals with a combination of these factors (localization of the tumor in the frontal or parietal lobe, presence of epilepsy, age younger than 39 years), the frequency of IDH1/2 mutations reached 21/27 (77.8 %), which was significantly higher than that in all other patients (44/119 (37.0 %), OR = 5.97, 95 % CI: 2.2415.91, p<0.001).
Conclusion. The presence of IDH1/2 genetic defects is associated with localization of glial tumors in the frontal and parietal lobes of the brain, earlier age at disease onset and the presence of epileptic syndrome.

LABORATORY AND EXPERIMENTAL STUDIES

67-78 1410
Abstract
The purpose of the study was to analyze the ability of five antitumor drugs from the pharmaceutical group of protein kinase inhibitors (gefitinib, imatinib, pazopanib, ponatinib and enzastaurin) to reactivate the expression of the epigenetically silenced GFP in HeLa TI cells, and to estimate the effect of epigenetically active drugs on: 1) acetylation and methylation of histones H3 and H4; 2) integral DNA methylation; 3) activity of HAT and HDAC1 enzymes; 4) expression levels of the genes encoding epigenetic regulation enzymes (DNMT1, DNMT3A, DNMT3B; SIRT1, HDAC1; SETD1A, SETD1B, SUV420H1, SUV420H2, SUV39H1, SUV39H2).
Material and Methods. The epigenetic activity of antitumor drugs was determined using the HeLa TI test system, a population of HeLa cells with the retroviral vector containing the epigenetically silenced GFP. The level of integral DNA methylation was analyzed using MspI/HpaII methyl-sensitive restriction analysis. Histone modifications were analyzed by Western blotting with antibodies to acetylated and methylated histones H3 and H4. The total activity of HAT enzymes was analyzed using Histone Acetyltransferase Activity Assay Kit. Expression of the epigenetic enzyme genes was analyzed using real-time quantitative RT-PCR.
Results. It was shown that only the enzyme inhibitor Cβ protein kinase enzastaurin had the ability to reactivate the expression of epigenetically silenced GFP in the HeLa TI cells. We showed that under the action of enzastaurin, the level of integral DNA methylation and expression of DNMT3A and DNMT3B DNA methyltransferase genes decreased. It was also found that enzastaurin reduced the expression levels of histone deacetylases HDAC1 and SIRT1, but did not affect the activity and expression levels of histone acetylases, the level of histone methylation (H3K4me3, H3K9me3, H3K27me3, H4K20me3), and the level of expression of the histone methyltransferases (SUV39H1, SUV39H2, SUV420H1, SUV420H2, SETD1A и SETD1B).
Conclusion. The data obtained are important for clarifying the mechanisms of action of 5 protein kinase inhibitors, in particular with respect to enzastaurin, the protein kinase Cβ inhibitor, for which the ability to reactivate epigenetically silent genes due to the effect on DNA methylation and histone acetylation was demonstrated.
79-87 1110
Abstract
The role of the expression of CD44 and CD24 in breast cancer (BC) has been explored in many laboratories around the world to identify predictive markers of tumor aggressiveness and patient’s response to anticancer therapy. These proteins participate in the process of tumor growth, metastasis and formation of cancer stem cells (CSCs). The study of CD44 and CD24 expression in triple negative (TN) BC, which is the most aggressive breast cancer subtype, is of particular interest.
The aim of this study was to determine the relationship between the expression of CD44 and CD24 markers in biopsy samples of TNBC patients before treatment and clinical/ morphological characteristics of the tumors.
Material and Methods. The study group included 67 patients with stage I–IV TNBC. Flow cytometry was used to determine the proportion of cells with CSC immunophenotype (CD44+/CD24-/low) in biopsy samples from the primary tumor of 65 patients and lymph nodes of 6 patients. In addition, the proportion of cells with all possible combinations of expression of these surface proteins was estimated.
Results. Cells with CSC immunophenotype were detected in all patients with a wide individual variability of CSC proportion from 0.4 % to 77.0 % (median – 10.9 %). There were no differences in the proportion of CSCs in the primary tumor and lymph nodes. No statistically significant correlation between the proportion of CSCs in the primary tumor and the clinical/morphological parameters, including tumor size and differentiation grade, evidence of regional or distant metastases, tumor, size of the fraction of proliferating cells estimated by Ki67 expression, was found in either single or multivariate analysis. There was also no association of the above parameters (except Ki67) with immunophenotypes. A high proportion of Ki67-positive cells in the primary tumor was associated with the CD44-CD24-phenotype. Conclusion. The expression of CD44 and CD24 in biopsy samples of TNBC before treatment did not correlate with the clinical and morphological characteristics of the tumors, excepting Ki67 expression.
88-93 907
Abstract
High aggressiveness of laryngeal and hypopharyngeal squamous cell carcinomas dictates the necessity of studying the molecular mechanisms of metastasis. Cancer metastasis is associated with remodeling of the cytoskeleton, which is carried out by actin-binding proteins (ABPs). Currently, there is insufficient data on the feasibility of determining the level of circulating ASBs in lymphogenous metastasis of laryngeal cancer (LC).
Material and Methods. Blood serum analysis was carried out in 42 LC patients and 15 healthy volunteers using ELISA kits on a microplate ELISA reader Multiskan FC 100 (ThermoFisher Scientific). Among ASBs, cofilin1 (CFL1), fascin1 (FSCN1), ezrin (EZR), profilin1 (PFN1), adenylyl cyclase associated protein 1 (CAP1) were studied. Statistical processing of the results was performed using the Statistica 6.0 software package.
Results. It was shown that the serum level of CAP1 was significantly higher in patients with LC compared with the group of healthy volunteers (p=0.00). As the size of the primary tumor increased, the levels of FSCN1, CAP1 and PFN1 significantly increased. The level of FSCN1 was 10 times higher and the level of CAP1 was 40% higher in LC patients with metastases than in LC patients without metastases. Thus, among the studied ASBs, FSCN1, CAP1, and PFN1 play an important role in the pathogenesis of LC.
Conclusion. The results of the serum level of ASB in LC were obtained for the first time, and they determine the fundamental basis for the development of new methods for predicting the development of metastases.
94-98 998
Abstract
Nowadays, circulating tumor cells (CTCs) are considered to be one of the most important mechanisms of tumor dissemination. Detection of CTCs in patients` blood is estimated as a prognostic factor for various tumors including colorectal cancer (CRC). However, CTCs may also be a source of tumor antigens capable of inducing both immune response and tolerance and participating in «immmunoediting».
The aim of the study was to assess the parameters of cell-mediated immunity in patients with stage IIIV CRC with respect to the presence or absence of CTCs.
Materials and Methods. We studied the parameters of cell-mediated immunity in 60 patients with stage IIIV CRC with respect to the presence or absence of CTCs. Before treatment, we evaluated the CTC levels in patients’ blood using CellSearch System™ and lymphocyte subsets: Т-В-NК-cells, T-reg, CD4+ and CD8+ expressing markers of activation (CD69+, СD38+, CD25+, HLA-DR+ СD95+); naïve and memory T-lymphocytes (CD45RA-/CD45RO+); NК-cells expressing CD335, perforin and granzyme B using flow cytometry (FACSCantoII, BD).
Results. A difference in the immunologic parameters between patients with CTCs and without CTCs depending on the stage of CRC was found. In СTС-positive patients with locally-advanced CRC, increase in the parameters of innate immunity (CD335+ NK-cells, neutrophils` respiratory burst) and activated Th (CD38+, CD25+, HLA-DR+) was found, while in СTС-positive patients with generalized CRC, suppression of cytotoxic lymphocytes of both innate (CD56/16+) and adaptive (CD8+CD25+) immunity was observed, which is, apparently, an unfavorable prognostic factor.
Conclusion. The presence of CTC in CRC patients is accompanied by some immunologic changes rather stimulating Thlink and innate immunity factors in II-III stages and doubtlessly suppressive in patients with IV stage.
99-104 935
Abstract
Aim: to evaluate the antitumor activity of the drug containing TNF-alpha and high-polymer double-stranded RNA (dsRNA) in the composition of virus-like particles (VLP-TNF-alpha) on B16-F10 melanoma cells.
Material and Methods. Analysis of the anti-proliferative effect of VLP-TNF-alpha as well as its components, TNFalpha and dsRNA, was carried out using the MTT -test. Apoptosis of melanoma cells was assessed by flow cytofluorimetry with FITC-annexin V.
Results. It was shown that the cytotoxic effect of the drug containing the combination of TNF-alpha and dsRNA on melanoma cells significantly exceeded the total cytotoxic effect of TNF-alpha or dsRNA alone (LD50 for combination drug was 0.05 μg/ml, TNF-alpha – 9.5 μg/ml, dsRNA>20 μg/ml).
Conclusion. The drug containing TNF-alpha and dsRNA molecules may be a promising drug for the treatment of malignant tumors, including melanoma.

ONCOLOGY PRACTICE

105-111 970
Abstract
Background. Adrenal glands are the site of solitary synchronous and metachronous metastases in non-small cell lung cancer (NSCLC). The presence of solitary adrenal metastasis from lung cancer provides survival benefit; however, currently, there are no exact treatment algorithms.
Objectives of the study: to assess shortand long-term treatment outcomes in patients with adrenal metastases from NSCLC.
Material and methods. Treatment outcomes of patients undergoing adrenalectomy for NSCLC were analyzed.
Results. From 1993 to 2014, 13 patients (11 males/2 females aged between 44 and 78, median age 58 years) with solitary adrenal metastases (adenocarcinoma (n=7), squamous cell carcinoma (n=4), large cell carcinoma (n=2); synchronous metastases – 5 cases (38.5%) and metachronous metastases – 8 cases (61.5 %), underwent adrenalectomy (one patient was given stereotactic radiation therapy for brain metastasis). Laparoscopic adrenalectomy was performed in 10 (76.9 %) cases, open adrenalectomy was performed in 3 (23.1 %) cases. The average adrenal tumor diameter was 74.6 ± 13.3 mm (25–170 mm). In the early postoperative period, two lethal outcomes were recorded. The median follow-up time after adrenalectomy was 20 months (3 to 267 months), the average follow-up time was 51.5 ± 23.5 months. The 3-year overall survival rates in patients with synchronous and metachronous metastases were 25.0 ± 2.2 % and 57.1 ± 1.9 %, respectively; however, the differences were not statistically significant (p=0.63; LogRank). The extent of surgery, morphological tumor type and status of regional lymph nodes produced no influence on the survival rate (p>0.05).
Conclusion. No factors influencing survival in patients with solitary adrenal metastases from NSCLC were identified.

REVIEWS

112-122 2727
Abstract

Objective: to generalize the world experience of lung cancer screening using modern diagnostic methods.
Material and Methods. Literature search was performed in Medline, Cochrane Library, Elibrary, PubMed systems, including publications describing the current capabilities of laboratory, instrumental and molecular genetic methods for early diagnosis of lung cancer, 58 of which were used to write this review.
Results. The review highlighted the results of international randomized trials of lung cancer screening using sputum Cytology and low-dose computed tomography. Special attention was paid to the description of modern molecular and genetic biomarkers of lung cancer, such as epigenetic markers, microRNAs, the use of proteomics technology, metabolomics, microbiome research, and biomarkers from liquid biopsy. The analysis of the world literature confirming the prospects of methods of non-invasive diagnostics of tumor processes based on the analysis of exhaled air was carried out.
Conclusion. The use of modern screening methods will significantly improve the effectiveness of early diagnosis and, as a result, cancer treatment. Starting treatment at an early stage can significantly increase the patient’s chances of recovery and faster social and labor adaptation. As a non – invasive method of cancer diagnosis, an electronic nose can act as a set of gas sensors and a certain method of information processing. An electronic nose based on relatively cheap gas sensors has comparable accuracy, ease of data collection, mobility, and other advantages compared to the above mentioned devices.

123-131 1670
Abstract
Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.
132-137 1015
Abstract
Introduction. Translocations of ALK receptor tyrosine kinase occur in approximately 5–9 % of lung adenocarcinomas. The use of ALK inhibitors usually results in the reduction of tumor size. Nevertheless, the extent and duration of response can vary significantly.
The aim of the study is to summarize the available information on the predictive role of various types of ALK translocations in response to ALK inhibitors.
Material and methods. The review presents the data from relevant laboratory and clinical studies published in PubMed database, as well as the authors’ own results.
Results. A number of experiments on cell cultures have demonstrated that the structure of ALK fusion affects the properties of the resulting chimeric protein, in particular its stability and sensitivity to crisotinib action. The few available clinical trials, evaluating the effect of ALK inhibitors depending on the type of translocation, showed heterogeneous results. While some of them detected associations between the so-called «short» variants of EML4-ALK rearrangements and worse survival when using crisotinib in comparison with the EML4-ALK type 1 variant, the others failed to confirm these observations. The study of 64 Russian patients receiving ALK inhibitors also did not support the effect of different ALK translocation variants on progression-free survival or objective response rate.
Conclusions. There is a diversity of reported associations, with none of them characterized by sufficient reproducibility. Current evidences do not support the predictive role of ALK variants.
138-145 2564
Abstract
Hormone-receptor positive breast cancer is the most common molecular subtype and represents 60–75 % of all breast cancers (BC). The presence of specific molecular targets such as the estrogen/progesterone receptor determines the use of hormone therapy for patients with this subtype. Tamoxifen, a selective estrogen receptor modulator, remains the first adjuvant treatment choice for the hormone-receptor positive BC patients. However, tamoxifen resistance is the major limitation of its efficacy. In this regard, the study of drug resistance mechanisms as well as search for biological prognostic markers of tamoxifen efficacy is very important. Cyclin D1 is a representative of the regulatory protein family, which plays a central role in the cell cycle regulation. The data on the association between cyclin D1 and estrogen-dependent signaling as well as the characteristics of CCND1 gene and its most studied polymorphic loci, were presented. The prognostic significance of cyclin D1 in hormone-receptor positive BC receptor-positive breast cancer was described. The experimental and clinical studies data on the association between the cyclin D1 expression level and tamoxifen efficacy are analyzed. Current approaches to overcoming hormone resistance based on cyclin D1 studies were considered.
146-151 1215
Abstract
The purpose of the study: to identify the significance of anaerobic bacteria and analyze their role in the development of infectious complications in cancer patients.
Material and Methods. The review includes data from clinical and in vitro studies published in Russian and international press for the period from 1989 to 2018.
Results. Data analysis has shown that many aspects related to anaerobic non-sporeforming bacteria are insufficiently studied, although they can cause severe hospital infections. This is especially true for patients with immune system defects, including cancer patients. In this category of patients, anaerobic bacteria can cause infections of the maxillofacial region, intra-abdominal infections, lower respiratory tract infections, urinary infections, and blood flow infections. In cancer patients, infectious complications are more severe, and may adversely affect treatment outcomes. A long process of anaerobic cultivation dictates the need for empirical treatment of infection for an average of 6 to 7 days. Since the middle of the last century, metronidazole was the «gold standard» of therapy. However, today the situation has changed dramatically. More than 80 % of anaerobic strains are resistant to metronidazole. The problem of resistance of anaerobic bacteria to other antibacterial drugs has not been sufficiently studied.
Conclusion. It is necessary to develop therapeutic approaches based on current data on the resistance mechanisms of non-sporeforming anaerobic bacteria.

CASE REPORTS

152-159 1074
Abstract
Retroperitoneal leiomyosarcomas (RpLMS) are highly aggressive tumors, which are characterized by poor prognosis and resistance to chemotherapy. Targeting tumor-specific molecular pathways have become a rapidly expanding field in drug development to increase efficacy of treatment of LMS. Here we present a case report of rapidly progressive RpLMS with gene mutations of key molecular pathways, which have not previously described in the literature. A 61-year-old man was admitted to our hospital with complaints of abdominal pain and fever. Radiological examination revealed retroperitoneal leiomyosarcoma, which was histologically confirmed by core-biopsy. The patient underwent radical (R0) en-bloc resection of tumor with left hemicolectomy, left total nephrectomy, left total adrenalectomy and distal subtotal pancreatectomy. Pathological assessment of the tumor revealed G3 leiomyosarcoma. The patient did not receive adjuvant therapy. Disease progression (local recurrence and pulmonary metastases) occurred 3 months after surgery, and the patient died 6 months after surgery. Immunohistochemical study revealed positive PD -L1 expression in tumor cells. The percentage of PD -L1- expressing cells was 30 %. Molecular-genetic testing allowed identification of somatic mutations in genes, such as PIK3CA, ALK, EGFR, ERBB, ESR1 and PD GFRA and confirmation of microsatellite stable status (MSS) of the tumor. Further studies to investigate spectrum of mutations in RpLMS are of great interest, since they can allow identification of potential targets for more effective antitumor therapy and to improve treatment results.


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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)