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Gynecologic Oncology

Gynecologic Oncology 2019 #3

Content

FUNDAMENTAL ONCOLOGY
Mkrtchyan V.A., Vorotnikov I.K., Chernysheva O.A., Palladina A.D., Tupitsyn N.N.
Bone Marrow NK-Cells In Breast Cancer Patients Are Interdependent With Biological Peculiarities Of Tumor And Patient’s Erythropoiesis
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Objective of the study. The aim of the work was to study bone marrow NK cells of patients with breast cancer and the features of erythropoiesis in these patients.
Materials and methods. In the article, we provide data of natural immunity cell content in bone marrow of 64 breast cancer patients and 10 women with non-malignant processes in breast.
Results. There were no signifi cant differences in natural immunity cells between groups of patients with malignant and non-malignant processes in breast. NK-cell levels (CD56+CD3- and CD16+CD3-) in bone marrow were much higher in patients with low level of proliferative activity (Ki-67) of cancer cells than in a group of patients with high proliferative activity cancer cells. That NK-cell populations (CD56+CD3- and CD16+CD3-) were interdependent with the erythropoiesis disturbances in breast cancer patients and were signifi cantly higher in cases with reduced content of basophilic and polychromatophylic normoblasts.
Conclusion. In general, our data indicate the existence of relations between bone marrow NK-cells and biological peculiarities of tumor as well as erythropoiesis in breast cancer patients.
Keywords: breast cancer, NK-cells, erythropoiesis.
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Mikhailova I.N., Treschalina E.M., Markina I.G., Kiselevskiy M.I.
Some Similarities Between Placental Development And Progression Of Malignant Tumors
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Objective of the study is the analysis of information on peculiar biological properties of the progression of malignant growth that have common roots or signaling pathways with placental reactions mediated by trophoblast for the purpose of identifying new markers.
Materials and methods. Analysis of the literature is carried out based on literary sources on the subject published for the period of 1972–2019. The article emphasizes on the processes similar in pathogenesis and pathophysiology, related to the development of trophoblast and carcinogenesis, metastasis, invasion or other type of tumor dissemination. Clinical observations made in the research of the processes stated above in breast cancer, non-small cell lung cancer, metastatic cutaneous melanoma, tumors of hematopoietic and lymphoid tissues et al. were used for the collection of materials. The article quotes prospective clinical studies of placental miRNA, metastatic cutaneous melanoma, non-small cell lung cancer and experiments made in vitro, in vivo or ex vivo on various models of human tumors: estrogen receptor-positive (ER-positive) breast cancer (MCF7, T47D, MDAMB-231), chorioncarcinoma JEG3, colorectal adenocarcinoma HT-29.
Results. Analysis of the works demonstrates signifi cant evidence basis of the results of research implemented in identifying of the new prognostic and therapeutic tumor markers of the malignant process progression. Identifi ed were the following markers: for ERα+ breast cancer — markers of invasion and metastasis placenta-specifi c protein I and signaling pathway Furin/NICD/PTEN and a marker of distant metastases integrin α5, which can predict the control of autophagy, the activity of placenta-mediated extracellular matrix ECM and drug sensitivity; for metastatic cutaneous melanoma — a marker of positive prognosis of survival is characterized by a high level of ERα+ and preventive role of estrogen therapy; for non-small cell lung cancer — a marker of negative prognosis of survival hypoxanthine phosphoribosyl — transferase I; for tumors of hematopoietic and lymphoid tissues — fetomaternal microchimerism as a marker of the beginning of peripheral blood allogeneic stem cell transplantation therapy; for colorectal cancer, choriocarcinoma et al. — the profi le of placental microRNA miR-451 and miR-720, the markers of negative prognosis for liver cancer, lung cancer, lymphoma, metastatic cutaneous melanoma, mesothelioma, T-cell lymphoma and mycosis fungoides MRX 34, MesomiR-1 and Cobomarsen/MRG-106 (phases 1–2 of clinical trials). The work introduces the possibility of tissue regeneration based on targeted mesenchymal stem cell delivery to the damaged area in terms of restoration of innate immunity in malignant disease.
Conclusion. Publications on the subject especially those over the past two years describing the search for new tumor markers of malignant progression based on the similarity with placental reactions, including those related to trophoblasts, make evident the effectiveness of the research summarized in the «Results» section.
Keywords: placenta, trophoblast, malignant progression, targeted cancer therapy.
Information about the confl ict of interests. The authors declare that there is no confl ict of interest regarding the publication of this article.
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OVARIAN CANCER
Sevyan N.V., Naskhletashvili D.R., Karakhan V.B., Bekyashev A.Kh., Prozorenko E.V., Pogosova A.A., Belov D.M., Mitrofanov A.A., Mamedova L.T., Polyakov B.I.
Combination Treatment For Cerebral Metastases From Ovarian Cancer: Clinical Cases
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Brain metastatic lesions in patients with ovarian cancer occurs rarely. Incidence of intracranial metastases is a factor of poor prognosis. This work presents two cases of brain metastatic lesions in ovarian cancer in which comprehensive and combination treatment resulted in long-term relapse-free survival of the patients.
Keywords: ovarian cancer, cerebral metastases, combination treatment.
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СERVICAL CANCER
Fedorov A.A., Popov A.A., Vrotskaya V.S., Petrukhin V.A., Krasnopolskaya K.V., Chechneva M.A., Magilevskaya E.V., Novikova E.G., Shevchyuk A.S., Novikova O.V.
Preconception Surgery Preparation After Organ Preservation Operations In Cervical Cancer
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Objective of the study is to determine surgical treatment indications and to investigate reproductive and pregnancy outcomes in patients who underwent cerclage in previously operated cervix.
Materials and methods. Cervical cerclage has been performed in Moscow Regional Scientifi c Research Institute of Obstetrics and Gynecology as preconception surgery preparation since 2011. The necessity to create conditions for carrying pregnancy to full term in patients who are at high risk for the development of anatomic and functional insuffi ciency of the cervix, cervical stump or utero-vaginal anastomosis became an indication for surgery. To implant a prosthetic mesh to patients who underwent cervical amputation or radical abdominal vaginal trachelectomy (RAT) we used transabdominal (laparotomy, laparoscopy, robot-assisted laparoscopy) access. Patients included in the study were divided into three groups: group I comprised 22 patients who underwent radical abdominal (20) or vaginal (2) trachelectomy, group II — 62 patients who underwent high amputation and/or repeat cervical conization with the length of the fl attened part of cervical canal of less than 25 mm. Moreover, this type of surgery was performed on patients with a history of recurrent miscarriage and perinatal losses. This group included 54 patients.
Results. The following reproductive outcomes were obtained: 4 patients who had undergone abdominal trachelectomy had surgical delivery on 27th–35th week of gestation. In group II consisting of patients who had undergone amputation and/or cervical conization 25 patients had assisted delivery, one of them twice, with an average gestation period being 37,4 weeks. Also 3 patients are currently pregnant. Among patients of group III 28 patients with an average gestational age of 37,2 weeks had assisted birth, and, what is more, 2 patients are currently pregnant.
Conclusion. Based on the results obtained, cervical cerclage helps to prevent perinatal losses in patients who had a history of surgery for cervical cancer and recurrent miscarriage. To date, 57 patients have had assisted birth.
Keywords: cervical cerclage, cervical cancer, trachelectomy, isthmic cervical insuffi ciency, perinatal losses.
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Payanidi Yu.G., Korolenkova L.I., Dobrokhotova Yu.E., Shevchyuk A.S., Zhordania K.I.
Cervical Dysplasia And Pregnancy (ESGO Recommendations, 2017). Pro Et Contra
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Objective of the study is to conduct a systemic analysis of the data available in current literature on the management strategy of pregnant patients with preinvasive cervical lesions.
Materials and methods. The overview comprises the results of international research including ESGO 2017 recommendations on the subject.
Results. The risk of progression of severe cervical intraepithelial neoplasia, including preinvasive cancer before invasion during pregnancy is minimal, therefore the treatment should be delayed until after postpartum period. Priority diagnostic efforts of clinicians should focus on identifying or ruling out invasive process. Visible tumor is absent, preinvasive cervical lesions are detected by cytological examination at the fi rst visit or at registration of a pregnant woman with intended/ desired pregnancy for prenatal care and check-ups. It is particularly necessary to carry out cytological examination of pregnant women especially in the areas where cervical cancer preventive measures are not introduced at the state level. Pregnant women with cytologically verifi ed cases of low grade squamous intraepithelial lesions (LSIL or CIN1) or with histological high grade squamous intraepithelial lesions (HSIL/CIN2 or CIN3) need to undergo colposcopy to confi rm the diagnosis. If CIN2 or CIN3 are suspected, all the more invasion, biopsy must be performed. In such cases an excisional biopsy allows to establish the depth of invasion. If cytological features of the lesion of glandular epithelium are present (AGC, adenocarcinoma in situ) it requires extensive diagnostics: colposcopy and mandatory loop biopsy and even loop excision in cases when there is no proper biopsy target for colposcopic examination. Endocervical curettage and endometrial biopsy are contraindicated for pregnant women. Diagnostics of preinvasive lesions of the cervix in pregnant women must be performed by a skilled expert-level colposcopist.
Conclusion. Preinvasive cervical lesions are not an indication for a cesarean section. The examination is carried out 8 weeks after delivery when treatment decision is made — excisional in most cases.
Keywords: cervical intraepithelial neoplasia, HSIL, CIN2–3, preinvasive cancer, clinical recommendations, pregnancy, colposcopy, cytological examination.
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Kaprin A.D., Novikova E.G., Rerberg A.G., Chulkova O.V., Maltsagova Ch.R.
Regional Chemotherapy: A Current Approach In The Treatment Of Locally Advanced Cervical Cancer
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Objective of the study. New possibilities in the treatment of cervical cancer, including neoadjuvant intra-arterial chemotherapy, are currently being actively explored. A key component of the effectiveness of this chemotherapeutic agent administration method is the drug delivery directly to tumors. The objective is to evaluate the effectiveness of combined administration of chemotherapeutic agents in the form of intra-arterial superselective chemoinfusion of platinum preparations with systemic administration of taxane-based preparations, and consequently to increase resectability of tumor process.
Materials and Methods. 86 patients diagnosed with cervical cancer (cT1bN0M0 — cT3bN1M0) aged from 29 to 56 years (average age — 38 years) underwent treatment in the Department of Radiosurgery and Gynecology of P.A. Gertsen Institute — a branch of Federal State Budgetary Institution «National Medical Research Center of Radiology» of the Ministry of Healthcare of the Russian Federation for the period from December 2015 to December 2018. According to morphological examination all women (100%) had squamous cell carcinoma G1–3. All patients received 2 sessions of regional chemotherapy using cisplatin (75 mg/m2) intraarterially, paclitaxel (175 mg/m2) — given systemically the day after. The interval between treatment sessions was 21 days.
Results. All patients underwent examination ( contrast material — enhanced pelvis MRI scan, SCC marker) before the beginning of the treatment and after receiving two sessions of chemotherapy (regional chemotherapy — cisplatin 75 mg/ m2, systemic administration of paclitaxel at a dose of 175 mg/m2). Clinical response manifested as the reduction of pain syndrome, absence of previously existing bloody discharge from genital tract was observed in all patients. Tumor response was evaluated based on RECIST 1.1 criteria. Complete tumor regression occurred in 23 (27%) patients, partial regression — in 40 (41%) patients, stabilization of tumor process — in 21 (24%) women. The progression of tumor process was identifi ed in 1 (1%) patient. The objective response made it possible to perform surgical treatment in 64 (75%) women, to carry out radiation therapy in 21 (24%) patients, systemic chemotherapy was given to 1 (1%) patient due to the progression of tumor process manifested by lung metastasis.
Conclusion. Based on the results, it has been concluded that intra-arterial chemotherapy given to patients with locallyadvanced cervical cancer permits to achieve objective response in 95% of patients. As a result, it was possible to proceed to the surgical phase of treatment and the majority of patients (75%) underwent surgical procedure.
Keywords: primary inoperable cervical cancer, intra-arterial administration of platinum preparations, neoadjuvant chemotherapy, systemic administration of taxanes, combined treatment.
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INTERDISCIPLINARY QUESTIONS
Oleynikova I.N., Gens G.P., Sirota N.A., Shikina V.E., Kirkin V.V.
Distress, Quality Of Life And Neoangiogenesis In Patients With Ovarian Cancer
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Objective of the study is to evaluate the impact of distress on the quality of life and neoangiogenesis in patients with ovarian cancer.
Materials and methods. The study comprised 121 patients with morphologically verified diagnosis of ovarian cancer, the median of age was 55,5 ± 9,05 years. The VEGF A level in blood serum of the patients was determined using the method of enzyme-linked immunosorbent assay (ELISA). Distress screening form was used to reveal distress and EORTC QLQ C-30 — for the assessment of quality of life.
Results. Clinically signifi cant distress was diagnosed in 58% of patients. Using the method of regression analysis it was established that distress is an independent factor that reduces the quality of life of patients with ovarian cancer. The correlation between serum VEGF A indicator and severity of distress experienced by the patients was statistically significant, — with Spearman’s rank correlation coeffi cient rho = 0,36; 95% confi dence interval = 0,16–0,46; p<0,05. Regression analysis determined that distress is an independent factor that increases VEGF A in blood serum of patients with ovarian cancer.
Conclusion. The results of research that we have carried out indicate clinical relevance of distress for ovarian cancer patients as this condition reduces the quality of life and through the stimulation of neoangiogenesis process can exert an influence on tumor process progression.
Keywords: ovarian cancer, distress, vascular endothelial growth factor A (VEGF A), quality of life.
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TO US WRITE COLLEGUAES
Ashrafi an L.A., Kurtser M.A., Gerasimova A.A., Klimenko P.A.
Borderline And Malignant Ovarian Tumors Occurred During Pregnancy
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Objective of the study is an early pre-operative diagnosis and optimization of the treatment with radical and organ-preservation operations followed by chemotherapy.
Materials and methods. 40 pregnant women with borderline and malignant tumors underwent examination. Ultrasound scans, determination of CA-125, sFas, VEGF, IL-6 in blood serum, fi ne needle biopsy of the ovaries were carried out preoperatively. The results were compared with morphological assessment.
Results. The research that had been conducted provided the possibility to advance treatment strategy that can reduce obstetric complications, improve birth outcomes while simultaneously treating ovarian tumors in a mother.
Conclusion. To devise treatment strategy it is necessary to consider the results of pre-operative tumor diagnosis.
Keywords: malignant ovarian tumors, ultrasound scan.
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 Letter from IGCS 78