EPIDEMIOGICAL STUDIES
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
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.
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.
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.
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.
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
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.
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.
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.
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.
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
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
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.
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.
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
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