Objective of the study is to conduct a systematic analysis of the data available in current literature on the role of negative regulators of T-cell immunity (immune checkpoints), such as inhibitory receptors CTLA-4 (cytotoxic T-lymphocyte antigen- 4) and PD-1 (programmed cell death receptor-1) in the prevention of immune response to attack tumors.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles published in PubMed on the subject over the past 10 years.
Results. Intensive research on the mechanisms of tumor escape from immunological surveillance undertaken over the past two decades, have revealed that negative regulators of T-cell immunity — immune checkpoints, such as inhibitory receptors CTLA-4 (cytotoxic T-lymphocyte antigen-4) and PD-1 (programmed cell death receptor-1) play a decisive role in the prevention of immune response to attack tumors. In tumor growth the interaction between CTLA-4 and PD-1 with the corresponding ligands inhibits antitumor activity of effector lymphocytes and allows for progressive tumor growth.
Conclusion. Despite the provided data on successful immunotherapy of patients with ovarian cancer with immune checkpoints blockers, clinical effectiveness of these preparations for this type of tumor is lower than for other types of malignant neoplasms. It is believed that it is related to high heterogeneity of ovarian cancer cells. In this regard, it is reasonable to use an integrated approach to immunotherapy of ovarian cancer, as well as its combination with standard treatment methods, particularly with chemotherapy, which, as it turned out, in certain cases exhibits immunomodulatory effect.
Keywords: ovarian cancer, immunity checkpoints, CTLA-4, PD-1/PD-L1, immunity checkpoints blockers.
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Objective of the study is to conduct a systematic analysis of the data available in current literature on breast cancer metastasis to the caecum.
Materials and Methods. The review comprises the data from foreign and Russian scholarly articles and literature found in PubMed on the subject published over the past 10 years. The management and treatment strategy of patients with this pathology are examined based on a specifi c clinical case.
Results. Breast cancer is characterized by both lymphatic and hematogenous metastasis. In the process of hematogenous dissemination metastatic cells can penetrate practically all organs. Lobular cancer is more common to metastasize to the colon, however cases of ductal carcinoma with metastases to the colon are reported as well. Immunohistochemical examination is used for differential diagnosis of primary colon cancer and breast cancer metastases. The present clinical report highlights the advantages of immunohistochemical examination for the verifi cation of breast cancer metastasis to the caecum.
Conclusion. Breast cancer metastases in the colon are a rare pathology. However, the diagnosis of this pathology is a relevant issue. It should be noted that only large-scale morphologic and immunohistochemical examination provides a possibility to differentiate between a primary tumor and metastatic lesion of the colon.
Keywords: ductal carcinoma, cancer metastases, caecum.
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Objective of the research — is to study clinical and morphological prognostic factors for breast cancer patients with metastatic ovarian lesion.
Materials and Methods. The research comprised breast cancer patients with ovarian metastases and without ovarian metastases that made up the main experimental group and control group comparable to each other in major clinical and demographic factors. It is highlighted that metastatic ovarian lesion in breast cancer is diagnosed simultaneously with the detection of primary tumor which predetermines a different type of the course of disease.
Results. On the basis of immunohistochemical indicators metastatic ovarian tumors in breast cancer don’t have statistically signifi cant differences from primary tumor, which in turn requires consideration in the choice of treatment strategy for breast cancer progression with ovarian metastases. Analysis of the long-term indicators proved that the presence of ovarian metastases is a signifi cant unfavorable prognostic factor of overall 3-year survival of patients older than 50 years of age in menopause who received integrated treatment.
Conclusion. Despite high sensitivity of breast cancer to chemotherapy integrated treatment performed for patients with ovarian metastases doesn’t substantially affect overall survival and only surgical treatment reliably increases 3- and 5-year survival rate of patients (83,3%) which may be conditioned by including in the study of patients, who had initially had metastases into other organs (liver, lungs, bones) and received integrated treatment.
Keywords: breast cancer, metastatic ovarian tumors, video laparascopy, overall survival.
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Objective of the study is to carry out a systematic analysis of the data available in current literature on treatment strategy and management of pregnant patients with borderline ovarian tumors, as well as to highlight some controversial issues.
Materials and Methods. The review comprises the results of international studies, including in particular ESGO 2017 recommendations on this issue.
Results. Borderline ovarian tumors during pregnancy occur in 21-35%. The majority of them are diagnosed in the fi rst trimester of pregnancy at stage I (FIGO). Genetic research found that the development of borderline ovarian tumors is related to KRAS and BRAF gene mutations. BRCA1/2 gene mutations are identifi ed in 4,3% of patients with borderline ovarian tumors. The principal method of the diagnosis of ovarian tumors in pregnant patients is considered to be transvaginal ultrasonography, in cases, if diagnostics raise doubts, MRI scan should be performed. The evaluation of CA-125 marker level has limited use as its values vary with gestational age. Serous and mucinous histological types of borderline ovarian tumors occur most often. Torsion of the ovarian tumor, as well as tumor capsule rupture are not common and occur only if neoplasm is large in size, however, the presence of tumor can result in premature labor. If a borderline ovarian tumor is suspected in pregnant patient tumor removal or adnexectomy are indicated. The second trimester of pregnancy is considered to be the optimal time to perform the surgery.
Conclusion. There are no specifi c standard recommendations regarding the observation of patients with borderline ovarian cancer during pregnancy and after childbirth. Nevertheless, it would be reasonable to perform ultrasound check up as well as to determine CA-125 marker levels every 6 months for the period of 2 years and annually for 5 years after the delivery.
Keywords: borderline ovarian tumors, clinical recommendations, pregnancy, CA-125, ultrasound scan.
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Objective of the study is to enhance the effectiveness of the diagnosis of serous ovarian cancer using the method of immunocytochemical analysis of p53, p16, WT1 marker expression in the cells obtained in the aspiration material from uterine cavity.
Materials and Methods. Cell expression of p53, p16 and WT1 markers was determined in the aspiration material obtained from uterine cavity in 30 patients with serous ovarian cancer of stages III-IV. The group of patients with benign ovarian tumors (n = 20), patients with secondary (metastatic) lesions of the ovaries (n = 20) and healthy women (n = 20) served as the control groups. Cytospin multilayered preparations of Cytospin system were provided for cytologic examination of the endometrial aspiration material and for carrying out immunocytochemical reactions. Immunocytochemical study was performed with polyclonal antibodies (pAbs) to p53, p16, WT1.
Results. p53 marker manifested the greatest diagnostic signifi cance: its expression was observed in 19 of 30 cases of serous ovarian carcinoma, which accounted for 63,3%. WT1 marker positive reaction was seen in 14 of 30 observations, that made up 47% and p16 expression — in 15 of 30 cases, which corresponded to 50%. Dissemination of serous cancer cells was detected intraoperatively in the peritoneal cavity, in effusion fl uids in 96% of observations. Immunocytochemical examination of the aspirates collected from uterine cavity of patients with benign ovarian tumors revealed focal moderate expression of p53 protein in separate endometrial epithelial cells in 2 cases. Serous ovarian cystadenoma was identifi ed in these patients histologically, and there was no marker positive reaction observed in the rest of 28 samples of that group. No positive immunocytochemical reaction of p53, p16 and WT1 markers in the examined material was observed both in secondary ovarian lesions and in the control group.
Conclusions. The increased p53, p16, WT1 marker expression in the cells, obtained with aspiration from uterine cavity seen in immunocytochemical examination, can serve an additional diagnostic test for serous ovarian cancer.
Keywords: serous ovarian cancer, markers, aspirate from uterine cavity, predictors, imuunocytochemical method.
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Objective of the study is to evaluate the possibilities of dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) in the differential diagnosis of ovarian tumors.
Materials and Methods. 66 patients aged from 23 to 83 years diagnosed with ovarian tumors: 16 — with benign ovarian tumors (BOT), 34 — with malignant ovarian tumors (MOT), control group — 16 healthy women without ovarian disorders were examined. Before surgical intervention all patients underwent MRI with obtaining T1- and T2- weighted images (T1WI and T2WI), diffusion — weighted MR images (DWI with measured diffusion coeffi cient — DWI with MDC) and dynamic contrast — enhanced magnetic resonance imaging (DCE MRI).
Two regions were identifi ed on dynamic contrast — enhanced magnetic resonance images(DCE MRI): solid component of ovarian tumor (OT) and myometrium. Three types of MR — contrast agents (MRCA) accumulation were detected, for which the following pharmacokinetic parameters of dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) on the change of signal of the selected regions after the infusion of magnetic resonance contrast agent (MRCA) were calculated using a mathematical model: enhancement amplitude (EA), the time of half-rising (THR), maximal slope (MS) and the initial area under the curve for the fi rst 60 seconds after the beginning of the change of signal intensity of tissues. Also ratios of these parameters of ovarian tumor tissue or normal ovarian tissue to myometrium tissue were calculated: enhancement amplitude ratio (EAr), time of half rising ratio (THRr), maximal slope ratio (MSr) and initial area under the curve for 60 seconds after injection ratio (IAUC(60) ratio) correspondingly.
Results. Analysis of data of dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) revealed statistically signifi cant differences in enhancement amplitude ratio (EAr), time of half rising ratio (THRr), maximal slope ratio (MSr) and initial area under the curve for 60 seconds after injection ratio (IAUC(60) ratio) (p<0,05) in patient groups with benign ovarian tumors (BOT) + group without ovarian disorders and patient group with malignant ovarian tumors (MOT), as well as between patients with benign ovarian tumors (BOT) and malignant ovarian tumors (MOT). There were no statistically signifi cant differences in these parameters revealed between the groups with benign ovarian tumors (BOT) and malignant ovarian tumors (MOT). According to ROC (a receiver operating characteristic ) curve analysis, initial area under the curve for 60 seconds after injection ratio (IAUC(60) ratio) was the most reliable parameter of dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) of benign ovarian tumors (BOT) and malignant ovarian tumors (MOT) differentiation, its sensitivity being 82% and specifi city of 91%. Type III curve of MRI signal dependence on the time after the injection of MR — contrast agents (MRCA) was most characteristic of malignant ovarian tumors (MOT), and type I of dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) curve — of benign ovarian tumors (BOT).
Conclusion. Dynamic contrast — enhanced magnetic resonance imaging (DCE MRI) is an essential tool in the differential diagnosis of benign ovarian tumors (BOT) and malignant ovarian tumors (MOT).
Keywords: malignant adnexal tumors, ultrasound scan, dynamic contrast — enhanced magnetic resonance imaging (DCE MRI), morphological features of ovarian tumors based on MRI data.
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Objective of the study is to explore the possibilities of modern ultrasound technologies in the assessment of the effectiveness of radiation therapy in patients with cervical cancer.
Materials and Methods. The study comprised the materials of clinical observations of 96 patients with cervical cancer who had undergone radiation therapy in Federal State Budgetary Institution «NN. Blokhin National Medical Research Center of Oncology» of the Ministry of Healthcare of the Russian Federation for the period from 2015 to 2018.
Results. Elastic type V was established to be a statistically relevant (p < 0,05) sign of the progression of cervical cancer at a period of 6 months and more from the end of the treatment. In quantitative elastography a two-fold increase in the coeffi cient of stiffness as compared to the unchanged cervix is characteristic for the progression of the disease one year after the end of the treatment, and its average value made up 2,1 ± 0,14. Elastic type IV and coeffi cient of stiffness of 1,1 ± 0,07 identifi ed in elastography are characteristic for the full therapeutic effect one year after the treatment. Contrast-enhanced ultrasound allows to make a differential diagnosis of neoplasms identifi ed in liver and to assess the therapeutic effect in patients who underwent radiation therapy.
Conclusion. Elastography with the assessment of the coeffi cient of stiffness and contrast-enhanced ultrasound examination allow to determine the advance of tumor process with high accuracy which is substantial for the choice of an adequate strategy of management and treatment of such patients.
Keywords: cervical cancer, elastography, contrast-enhanced ultrasound examination, ultrasound diagnostics, gynecologic oncology, cervical cancer recurrence.
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Objective of the study is to show feasibility and effectiveness of the use of the concept of sentinel lymph nodes in diagnosing of micrometastases in surgical treatment of vulvar cancer.
Materials and Methods. The review comprises the data of foreign and Russian academic articles published in PubMed on the subject over the past 10 years.
Results. High effi ciency of the use of endoscopic access in performing of lymph node dissection in surgical treatment of patients with vulvar cancer, inter alia, with the goal of reducing postoperative complications and improving of the quality of life of this specifi c category of patients was proved.
Conclusion. Although the material obtained by biopsy of a lymph node enables to identify metastatic involvement of inguinal and femoral group of lymph nodes, possible false negative results are accounted for tumors that are located along the midline of vulva. It is regrettable that tumors of the midline appear to be the most challenging in terms of determining of treatment options. It is necessary to conduct further research on the development of the new possibilities of establishing principal corrective diagnosis of vulvar cancer.
Keywords: vulvar cancer, endoscopy, sentinel lymph nodes.
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Objective of the study is to conduct a systematic analysis of the data available in current literature on the clinical features and morphologic types of tumors in cases of hereditary solitary and multiple primary malignant neoplasms of female reproductive system.
Materials and Methods. The review includes the results of international and national studies on this issue.
Results. The detailed examination of clinical presentations of the diseases considering histological types of tumors of the organs involved in cancer in cases of hereditary breast cancer and ovarian cancer syndrome, BRCA1/2 gene mutations, as well as in Lynch syndrome and MMR gene mutations revealed that there are two molecular — genetic mechanisms of carcinogenesis of hereditary types of the diseases of female reproductive system.
Conclusion. Identifi cation of not only the organs that are susceptible to malignant transformation, but of predominant histological types of tumors, characteristic for known hereditary syndromes as well, is of great signifi cance for early diagnosis, clinical management, treatment and prevention of such diseases.
Keywords: hereditary breast — ovarian cancer syndrome (HBOC), Lynch syndrome, polyneoplasia, BRCA1/2 gene mutations, MMR gene mutations.
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