Objective of the study is to identify common proinfl ammatory markers in COVID-19 and ovarian cancer (OC) with paraneoplastic syndrome (PNS) for the assessment of the possibility of timely diagnosis of malignant process.
Materials and Methods. The literature review was carried out based on subject — specifi c sources from 2000-2021 in NCBI, PubMed, MEDLINE, ScienceDirect and other databases. Markers in COVID-19 and ovarian cancer (OC) with paraneoplastic syndrome (PNS) are the focus of the assessments. The analysis comprises publications from different countries of the world, including Russia, that provide description of various research on the detection of markers of acute and chronic infl ammation in these diseases and their relationship with the tumor process and paraneoplastic syndrome (PNS) associated with it. The analysis is based on works that introduce reliable clinical and laboratory data on the subject.
Results. Analysis of the coincident informative markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6, tumor necrosis factor-α (TNF-α) and TLRs in COVID-19 and ovarian cancer (OC) with paraneoplastic syndrome (PNS) allows to identify or reliably predict severe course or the presence of these diseases even before the visual detection and imaging of the disease. The risks associated with co-occurring ovarian cancer (OC) with paraneoplastic syndrome (PNS) and COVID-19 are related to the similarity of the pathogenetic pathways of the development of these diseases and their severe complications or even lethal outcome.
Conclusion. Analysis of the coincident informative markers C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IL-6, tumor necrosis factor-α (TNF- α) and TLRs allows to identify or reliably predict the development or the presence of these diseases even before the diagnosis has been made. Data on the presence of common proinfl ammatory markers in somatic (COVID-19) and oncological (ovarian cancer with paraneoplastic syndrome) diseases and their effect on tumor progression provided ground for recommending laboratory diagnostics of the disease and for the prognosis of complications, that is of particular relevance for patients with ovarian cancer who contract COVID-19. A great many of the phenomena outlined in the review and conclusions and assumptions, made on their basis, may be premature and illconsidered due to the short period of the existence of COVID-19 and the small population sample size. Therefore, it is exceptionally valuable to further study this subject in order to assess the relevance and credibility of these fi ndings based on suffi cient number of observations and evidence.
Keywords: proinfl ammatory markers, COVID-19, ovarian cancer, paraneoplastic syndrome.
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Introduction. Spontaneous T-cell reactions to tumor became a major determinant in understanding prognosis of the disease. Pronounced infi ltration of effector T-cells and memory cells in many tumors, including breast cancer, correlate with improved clinical results and sensitivity to the treatment, particularly in tumors, in which clonal T-cell expansion has occurred. Bone marrow serves as an important site for activation and accumulation of tumor-specifi c T-cells.
Objective of the work is to study T- and NK-cell subpopulations of bone marrow lymphocytes of patients with breast cancer and to evaluate their prognostic value.
Materials and Methods. The detailed examinations of bone marrow of 107 patients, who underwent treatment in the Breast Medical Oncology Department in the period 2013-2016 , were performed. Thus, the duration of follow-up after the surgical treatment was mostly from 5 to 8 years. At diagnosis patients underwent standard receptor status testing, examination of Her2/neu, Ki-67 expression etc. All patients underwent morphologic examination of the bone marrow (myelogram). Information on the patients’ length of life was collected through individual interviews and requests to civil registration offi ces. Wherever possible, specifi c inquiries were made regarding the patients’ length of life, as well as periods of progression-free survival and metastasis-free survival etc.
Results. The role of T- and NK-bone marrow lymphocytes in the prognosis of breast cancer was investigated in 107 patients based on survival indicators at the follow-up period from 5 to 8 years. T-lymphocytes (CD3), T-helper cells (CD4), T-cytotoxic lymphocytes (CD8), CD4/CD8 ratio, activated T-cells and their subpopulations (HLA-DR-positive), as well as NK-cells (CD3-negative CD56+ or CD16+) were examined. The prognostic signifi cance of CD4-lymphocytes, their relationship with overall survival was reliable and was observed predominantly within a follow-up period for up to 105 months after surgery. Mature T-cells negatively affected the prognosis (progression-free survival) during a shorter follow-up period (up to 70 months after surgery). Activated CD8-lymphocytes (HLA-DR+) were associated with a favorable prognosis (progression-free survival) that was observed most consistently in the follow-up period for up to 9 years after surgery.
Keywords: breast cancer, prognosis, bone marrow, T-cells, NK-cells.
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Objective of the study is to research the specifi c features of tumor lymphoid microenvironment in primary operable patients with ovarian cancer.
Materials and Methods. Samples of tumor tissue of 53 patients with primary operable ovarian cancer were included in the research. A degree of lymphocyte infi ltration of the tumor (TIL) and their subpopulations were evaluated using fl ow cytometry technique, spatial localization of immune cells — on histological sections (hematoxylin — eosin).
Results. A median of tumor-infi ltrating lymphocyte (TIL) content in the samples of tumor tissue was 1,35%. The results of the assessment of tumor-infi ltrating lymphocyte count obtained by different techniques proved to be consistent. Herewith, fl ow cytometry provides highly accurate result of the automated cell counting based on immunological phenotype, while morphological analysis complements the features and peculiarities of spatial localization of tumor-infi ltrating lymphocytes (TIL) in tumor tissue. Cell subpopulation structure in patients with tumor-infi ltrating lymphocyte (TIL) level lower (group 1) and higher (group 2) than median values are the key aspect of tumor-infi ltrating lymphocyte (TIL) analysis. It was revealed, that among “linear” TIL populations in patients of group 2 the level of T-cells CD3CD19- is statistically signifi cantly higher compared to patients of group 1. Conversely, a percentage content of NK-cells with CD3-CD16+CD56+ and CD3- CD8+ phenotypes in the group of patients with TIL level lower than a median value, exceeded the respective indicators of patients from group 2. Correlation analysis determined a signifi cant inverse relationship between NK-cell count and a degree of lymphocyte infi ltration of the tumor (TIL) (r = — 0,5117). T-cell structure reveals that a proportion of CD3+CD4+ lymphocytes is higher in patients with tumor-infi ltrating lymphocyte (TIL) content greater than 1,35%. The examination of tumor tissue of 3 populations, that mediate regulatory functions — CD4, CD8, NKT lymphocytes found that only NKT-cell population with CD3+CD16+CD56+ phenotypes is statistically signifi cantly higher in a group of patients with a median of tumor-infi ltrating lymphocytes (TIL) < 1,35%. A signifi cant direct correlation between the tumor-infi ltrating lymphocytes (TIL) density in tumor samples and the level of T-regulatory cells with CD4+CD279(PD1)+ phenotype (r = 0,5975) has been identified.
Conclusion. Lymphoid microenvironment in breast cancer is characterized by the following parameters:
1) low degree of tumor infi ltration by lymphocytes (TIL);
2) a spatial localization of lymphocytes doesn’t depend on a degree of tumor infi ltration by lymphocytes (TIL);
3) a signifi cant direct correlation of a degree of tumor infi ltration by lymphocytes (TIL) with T-regulatory cells with CD4+CD279(PD1)+ phenotype (r = 0,5975) and an inverse correlation with NK-cell level (r = -0,5117) have been demonstrated for tumor-infiltrating lymphocyte (TIL) structure.
Keywords: flow cytometry, tumor-infiltrating lymphocytes (TIL), immunophenotype, ovarian cancer
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Objective of the study is research and analysis of the clinical and diagnostic features of endometrioid ovarian cancer (EOC) depending on genetic changes identified.
Materials and Methods. The study includes retrospective data on 124 patients with endometrioid ovarian cancer (EOC) — solitary or being a part of multiple primary tumors both in combination with similar histotype of endometrial cancer and with neoplasms of other localizations, who underwent treatment at Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation for the period from 2000 to 2019, and then were under follow-up. The median of observation made up 85,5 months (in the range from 1 to 214 months). Statistical analysis was performed using the programs of statistical software SPSS (IBM®SPSS® Statistics ν.26) and Microsoft®Excel®2010 program.
Results. Endometrioid ovarian cancer (EOC) of different stages alone was identifi ed in 76 patients (61,3%). A combination of endometrioid ovarian cancer (EOC) and endometrial cancer of similar histotype that had developed synchronously was observed in 43 cases (34,7%), whereby one of these patients had had a history of metachronous renal cancer. All patients underwent molecular genetic testing, that provided specifi c clinical cases of the genetic heterogeneity of endometrioid ovarian cancer (EOC). For instance, microsatellite instability-high cancer (MSI-H), and then germline mutation in gene MSH2 were initially detected in ovarian tumors of one patient, that confi rmed the presence of Lynch syndrome in this patient. Germline mutation in gene MLH1 was identifi ed in another case. Germline mutation 5382insC in gene BRCA1 was diagnosed in the third patient with poorly-differentiated endometrioid adenocarcinoma of both ovaries stage IIIC.
Conclusion. Endometrioid ovarian cancer is a genetically heterogeneous disease. Defi ciency in the unpaired DNA bases (MSI-H/dMMR) repair system, including that associated with Lynch syndrome, mutations in genes BRCA1/2 and other molecular genetic changes can be revealed. The need to study these issues is accounted for by potential applicability and practical value, as it can optimize the treatment of this category of patients by expanding the possibilities of targeted therapy. Keywords: endometrioid ovarian cancer, polyneoplasia, genetic heterogeneity.
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Objective of the study is to conduct a systematic review of the data available in current literature on the possibilities of conservative treatment of metastasis in central nervous system of ovarian cancer.
Materials and Methods. The review comprises the data from foreign and Russian academic articles found in PubMed on the subject published over the past 10 years. The paper addresses the strategy of management of patients with such disease based on a specifi c clinical case.
Results. Standard treatment for central nervous system metastases spread from different tumors, as a rule, is surgery in combination with various methods of radiation and antitumor drug therapy. Since metastatic involvement of central nervous system in ovarian cancer is rare, it is diffi cult to determine treatment strategy. The clinical case reviewed in the paper outlines the advantages of the conservative method of treatment for this disorder.
Conclusion. Since the matter of choosing treatment tactics for ovarian cancer metastasis in central nervous system has not been suffi ciently studied and covered in the world literature, the optimal treatment strategy for this disorder is a combination of radiation therapy and anti tumor drug therapy.
Keywords: ovarian cancer, metastases in central nervous system (CNS), radiation therapy, antitumor drug therapy.
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Objective of the study is to conduct systematic review of the data available in current literature on the new possibilities of diagnostics, prevention and treatment of venous thrombotic complications in cancer patients.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles (49 papers) found in PubMed on the subject published over the past 10 years, the fi ndings of the authors’ own research are provided as well.
Results. Cancer patients are at high risk of thrombotic complications, which worsen antitumor treatment outcomes and are one of the leading causes of death. Disorders of the hemostatic system, caused both directly by the tumor and by treatment methods play a primary role in the pathogenesis of thrombotic complications. Direct oral anticoagulants (DOACs) along with low-molecular-weight-heparins (LMWH) are the main medicines for the treatment of patients with cancer-associated venous thromboembolic complications when the risk of bleeding is low and there are no drug interactions with the current systemic therapy.
Conclusion. Low-molecular-weight-heparins (LMWH) are the basis of specifi c prophylaxis of thromboembolic complications in cancer patients. The use of low-molecular-weight-heparins (LMWH) after surgery and during chemotherapy effectively reduces the intensity of intravascular blood coagulation and the incidence of venous thrombosis. D-Dimer should be considered an indicator of exclusion of venous thromboembolic complications or of thrombosis recurrence, as well as an indicator of the assessment of the effectiveness of anticoagulant prophylaxis. Hemostasis biomarkers can play a substantial role in the prognosis of cancer.
Keywords: cancer patients, thrombotic complications, D-Dimer, anticoagulants.
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Pseudomyxoma, associated with low grade tumor of the appendix, multicystic, papillary or epithelioid mesothelioma et al. — are diseases, characterized by predominantly peritoneal lesions and involvement, and, often, by borderline malignancy. The introduction of cytoreductive surgeries without- or in combination with intraperitoneal and/or systemic chemotherapy permitted to improve their prognosis. However, the possibilities to preserve reproductive function in such patients — is a debatable question, and we made an effort to consider it based on a specifi c clinical case.
Conclusion. Peritoneal carcinomatosis in patients of reproductive age requires treatment that often leaves no chance to preserve fertility. However, in some cases the modern therapy allows to consider the possibility of future pregnancy in such patients.
Keywords: cytoreductive surgery, HIPEC, mesothelioma, pregnancy.
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Objective of the study is conduct a systematic review of the data available in current literature on the clinically significant gynecologic cancer syndromes, and to testify how their early detection and effective treatment (supportive care) improve quality of life and social adaptation of patients.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in PubMed on the subject published over the past 10 years.
Results. In oncology supportive care refers to a range of practices for the prevention and treatment of the complications of cancer and side effects of antitumor treatment. This defi nes the scope of supportive care during the period of active treatment and rehabilitation. A variety of clinical scenarios of a complicated course of the underlying disease or adverse events of antitumor treatment require collective efforts of multidisciplinary team of professionals. Effectiveness of supportive care often depends on the timely involvement of a relevant specialist, while an attending physician supervises the processes of antitumor treatment and supportive care. In this regard, the need for an early identifi cation of pathological condition falling within the remit of supportive care and other medical specialties should not be underestimated.
Conclusion. Adverse events that occur in patients with gynecologic cancers extend far beyond the actual antitumor treatment. Regretfully, there is no meaningful universal algorithm for prescribing a specifi c option of supportive therapy that allows to prevent, not to mention resolve any of these issues, therefore, further research in this area is required.
Keywords: gynecologic oncology, supportive care, quality of life.
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The history of the establishment of the Department of Gynecologic Oncology is inherently linked to the history of Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center of Oncology” of the Ministry of Healthcare of the Russian Federation and is its integral part. In light of the activities and events held in October 2021, dedicated to the 70th anniversary of the Oncologic Center, it is appropriate and important to examine and refer to the archive records of Professor V.P.Kozachenko and to highlight the milestones of the emergence and development of the Department.
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