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Gynecologic Oncology

Gynecologic Oncology 2022 #2

Content

FUNDAMENTAL ONCOLOGY
Tsarapaev P.V., Korotkova E.A., Alferov A.A., Gershteyn E.S., Baryshnikova M.A., Payanidi Yu.G., Zhordania K.I., Kushlinskiy N.E.
Soluble Form Of P-Selectin 1 Glycoprotein Ligand In Blood Plasma Of Patients With Ovarian Cancer
4
Objective of the study is to carry out a comparative analysis of the content of soluble form of P-selectin glycoprotein ligand 1 (sPSGL-1) in blood plasma of practically healthy donors and patients with ovarian cancer.
Materials and methods. The material for the research was blood plasma obtained from 64 patients with primary ovarian cancer at different stages of tumor process and blood plasma of 16 healthy donors (a control group).Quantitative assessment of the content of soluble form of P-selectin glycoprotein ligand 1 (sPSGL-1) in the blood plasma was carried out using RayBio® Human PSGL-1 (CD162) ELISA Kit for direct enzyme immunoassay test (USA).
Results. Statistically signifi cant decrease of soluble form of P-selectin glycoprotein ligand 1 (sPSGL-1) level in blood plasma of patients with ovarian serous adenocarcinoma compared to the control group, as well as statistically signifi cant increase in the concentration of marker associated rather with endometrioid adenocarcinoma, than with the serous one were revealed.
Conclusion. The increase in the concentration of soluble form of P-selectin glycoprotein ligand 1 (sPSGL-1) in blood plasma of patients with ovarian serous adenocarcinoma compared to the endometrioid one is likely due to varying degrees of migration of lymphocytes to an area of infl ammation in primary tumor.
Keywords: ovarian cancer, soluble form of P-selectin glycoprotein ligand 1 (sPSGL-1), blood plasma.
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BREAST CANCER
Kazubskaya T.P., Kurbanova M.B., Shidakova F.Kh., Kozlova V.M., Khvan O.T., Mikhailova S.N., Sorokina S.S., Mekheda L.V.
Preventive Mastectomy In A Carrier Of Gene PTEN and CHEK2 Mutations, Responsible For Various Neoplasia Syndromes
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The progress in the development of genomic technologies and the expansion of genetic testing have contributed to the identifi cation of germline mutations in one individual in two and more specifi c genes associated with the development of neoplasia. This phenomenon involving a combination of pathogenic mutations in different genes has been called: “Multilocus inherited neoplasia allele syndrome (MINAS)”. At present the signifi cance of the carriage of pathological variants of several genes, responsible for the development of various tumor syndromes still remains unknown. This article presents the clinical case of a patient with a combination of pathogenic mutations in PTEN and CHEK2 genes associated with rare inherited neoplasia syndromes (Cowden and Li-Fraumeni type 2) in order to assess the features of phenotypic manifestation of genotype identifi ed.
Keywords: Multilocus inherited neoplasia allele syndrome (MINAS), PTEN, CHEK2, multiple fi broadenomas, preventive mastectomy.
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OVARIAN CANCER
Rumyantsev A.A., Tyulyandina A.S., Pokataev I.A., Shevchyuk A.S., Nechyushkina V.M., Zhordania K.I., Israelyan E.R., Tyulyandin S.A.
Dose-Dense Chemotherapy For Disseminated Ovarian Cancer After Suboptimal Cytoreduction: The Final Results Of Phase Ii Of The Trial.
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Introduction: Patients with disseminated ovarian cancer (OC) who undergo suboptimal primary cytoreduction have poor prognosis. We conducted phase II of a single group study which addressed and examined effi ciency and safety of dose-dense chemotherapy for this category of patients. The present publication focuses on the fi nal analysis of the fi ndings.
Patients and methods: Nonrandomized study of phase II was carried out. The concise inclusion criteria were: FIGO stage III or IV of epithelial ovarian cancer; suboptimal primary debulking cytoreductive surgery (residual tumor size > 10 mm); ECOG performance status ≤ score of 2. All patients underwent up to 6 cycles of dose-dense chemotherapy consisting of paclitaxel 80 mg/m2 on day 1, 8, 15 + carboplatin AUC6 on day 1, cycles every 21 days. The primary endpoint of the trial was progression-free survival (PFS). Statistical design of the study was based on the historical data: 1-year progressionfree survival (PFS) in the aforementioned category of patients was 51 %. The expected 1-year survival after dose-dense chemotherapy could make up 70 %. 39 patients have to be enrolled in the study to obtain signifi cant differences with onetailed α = 0,05 and β = 0,20.
Results. A total of 39 patients were enrolled in the study, the median age was 56,9 years, 23% had stage IV of the disease. With a median follow-up of 47,6 months progression of the disease was observed in 25 patients, the rate of 1-year progression-free survival (PFS) was 78,3 %, median progression-free survival (PFS) — 18,4 months. The rate of overall 1-year survival made up 94,6 %, an estimated median of overall survival — 52,8 months. A substantial incidence of severe (grade ≥ 3) hematological toxicity was observed: neutropenia (82,1 %), anemia (53,8 %), thrombocytopenia (15,3 %).
Conclusion: Dose-dense chemotherapy is an effective fi rst-line treatment for disseminated ovarian cancer (OC) after suboptimal cytoreductive surgery, but a considerable incidence of severe toxicity limits the use of this type of treatment.
Keywords: ovarian cancer, dose-dense chemotherapy, nonoptimal cytoreduction, suboptimal cytoreduction.
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UTERINE CANCER
Kadushkin D.A., Payanidi Yu.G., Artamonova E.V., Shevchyuk A.S., Zhordania K.I.
Uterine Carcinosarcoma. Stratifi cation Of The Treatment Strategy
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Objective of the study is to carry out an analysis of the data of current Russian and foreign literature on the effectiveness of different strategies of treatment of patients with carcinosarcoma of the uterus.
Materials and мethods. The review comprises the scholarly articles of Russian and foreign authors on the subject, published in PubMed over the past 10 years.
Results. The evaluation of the effectiveness of surgical, chemotherapy, as well as radiation treatment of patients with different stages of the disease. The paper presents the evaluation of feasibility of performing lymphadenectomy of pelvic lymph nodes additionally to the extent of surgical intervention. The analysis of recurrence rate, progression-free survival (PFS), mean survival of patients with uterine carcinosarcoma depending on the strategy of management, as well as on a combination of different types of treatment was carried out.
Conclusion. It is necessary to continue the search for criteria which will allow to choose the optimal strategy of treatment of patients with uterine carcinosarcoma based on all prognostic factors and to have the possibility to affect the prognosis of the disease.
Keywords: uterine carcinosarcoma, diagnosis, treatment.
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СERVICAL CANCER
Chernyshova A.L., Kolomiets L.A., Trushchyuk Yu.M., Dil O.S., Chernov V.I., Marchenko E.S., Сhekalkin T.L., Antipov V.A., Krasilnikov S.E.
The Use Of Nickel Titanium Implants In Radical Trachelectomy In Patients Of Reproductive Age With Invasive Cervical Cancer.
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Objective of the study is to demonstrate the effectiveness of the novel technology developed at the Department of Gynecology of Scientifi c Research Institute of Oncology of Tomsk National Research Medical Center, used in radical organpreservation surgical intervention for invasive cervical cancer in patients of reproductive age.
Materials and мethods. The study comprised 101 patients of reproductive age (32,9±5,4 years) with morphologically verifi ed diagnosis of invasive cervical cancer (stages IA1-IB3). All patients underwent organ-preserving surgery — radical trachelectomy. A shape memory mesh implant woven in the form of a stocking of superelastic nickel-titanium wire with subsequent fi xation by individual sutures around the perimeter was used for uterine closure and the reinforcement of uterovaginal anastomosis. A mesh implant was made of superelastic thin nickel-titanium wires with a diameter of 60–40 μm on wire knitting machines.
Results. The paper describes the results of development and introduction of the technique based on the use of shape memory implant made of nickel-titanium in radical trachelectomy in order to perform uterine closure and to reinforce anastomosis site in patients of reproductive age. The advantage of the use of this type of implant lies in its unique physical and chemical properties — good integration with surrounding tissues and maximum functional effi ciency in these types of surgical procedures.
Conclusion. The use of this technique provided positive outcomes in the course of pregnancy and satisfactory reproductive results.
Keywords: radical trachelectomy, organ-preservation treatment, laparoscopy, laparotomy, cervical cancer, implant, nickel-titanium.
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Protasova A.E., Orlova R.V., Lyashchenko V.A.
Analysis Of Socio-Demographic, Clinical And Morphological Features Of Advanced Types Of Invasive Cervical Cancer
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Objective of the study is to carry out an analysis of sociodemographic, clinical and morphological features of patients with newly diagnosed advanced (IIB-IVB) types of invasive cervical cancer (CC).
Materials and methods. The retrospective study was conducted at Saint-Petersburg State Budgetary Healthcare Institution “City Clinical Oncologic Dispensary”. 564 patients with newly diagnosed IIB–IVB stage cervical cancer (FIGO, 2009) who had received different types of treatment for the period from 2018 to 2020 were enrolled. An in-depth analysis of randomly selected 152 medical records was undertaken for the evaluation of the features of sociodemographic, clinical and reproductive profi le of the patients. Methods of descriptive statistics as well as contingency tables based on χ2 Pearson’s Goodness-of-Fit test were used for the statistical analysis.
Results. An array of specifi c features of the profi les of the patients with advanced types (IIB-IVB) of cervical cancer was revealed: the majority of patients (88,82 %) related to an age group older than 40 years, had not worked (57,24 %), had given birth (90,79 %), had not seen an obstetrician-gynecologist for a long time (65,67 % — for 1–5 years, 26,28 % — for more than 5 years), sought medical help only once clinical symptoms of the disease appeared (88,15 %).
Conclusion. Long-delayed gynecological check ups, avoiding routine gynecological examination and irregular screenings are essential modifi able factors of the late diagnosis of cervical cancer.
Keywords: cervical cancer, IIB–IVB, sociodemographic features, clinical and morphological features, specific characteristics of reproductive system.
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INTERDISCIPLINARY QUESTIONS
Kaplieva I.V., Frantsiyants E.M., Verenikina E.V., Zakharchenko V.R., Pogorelova Yu.A., Trepitaki L.K., Sheiko E.A., Myagkova T.Yu., Ardzha A.Yu.
Kallikrein-Kinin System: Key To Understanding Mechanisms Of Development Of Thromboembolic Complications In Women With Gynecologic Cancer In Early Postoperative Period
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Objective of the study. Identifi cation of characteristics of the kallikrein-kinin system (KKS) in patients with endometrial cancer (EM) or ovarian cancer (OC) who developed secondary thromboembolic complications (VTEC) in the early postoperative period.
Material and methods. Women aged 60.5±2.29 years. Groups: 1) Main groups — OC (п = 8) or EM (п = 7) with VTEC; 2) Comparison groups — OC (п = 6) or EM (п = 7) without VTEC; 3) Donors (п = 8). Blood levels of prekallikrein, kallikrein 1 (KK1) and 14 (KK14), and kininogen (KG) were measured by ELISA.
Results. Levels of KK1 were elevated in all women by an average of 1.5 times. KK14 increased twice only in OC patients without VTEC. All women with VTEC showed elevated KK1/KK14: in EM by 2.3 times, in OC by 1.6 times, while in women without VTEC, levels of KG decreased: in EM by 3.9 times, in OC by 2.3 times.
Conclusions. ElevatedKK1/KK14 ratio (over 2 SU in EM and over 1.6 SU in OC) together with normal blood levels of KG are pathogenetically signifi cant factors underlying VTEC development, while KG defi cient in the blood with growing or normal levels of KK1 indicate no VTEC in the early postoperative period in women with OC or EM.
Keywords: thrombosis, ovarian cancer, endometrial cancer, prekallikrein, kallikrein 1, kallikrein 14, kininogen, blood.
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Eltsov I.V., Abdullaev A.G., Matveev N.L., Kononets P.V.
Resection And Anterior Abdominal Wall Reconstruction Surgery In The Recurrence Of Pseudomyxoma. A Clinical Observation
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Background and relevance of the subject. Pseudomyxoma peritonei (PMP) is a rare type of abdominal carcinomatosis, the development of mucinous ascites dominates its clinical picture. Based on the literature data, the incidence of pseudomyxoma peritonei (PMP) is 1-2 cases per 1 million of the population. Nevertheless, despite extensive intraperitoneal spread, surgical treatment in combination with HIPEC (Hyperthermic intraperitoneal chemotherapy) allows to achieve 90 % 5-year survival rate, and 10-year — at the level of 73 % [3].
Objective of the work is to present a clinical observation of successful treatment of recurrence of pseudomyxoma peritonei (PMP) in the anterior abdominal wall.
Materials and methods. A 67-year-old patient, diagnosed with mucinous tumor of the appendix of low grade of malignancy pT4aN1M1a, stage IV, condition after nonradical surgical treatment of 20.03.2017 that involved resection of a segment of the greater omentum and Mayo hernia repair with reconstruction using local tissues, performed for umbilical hernia. Condition after surgical intervention of 22.05.2017 which involved appendectomy, hysterectomy with bilateral alpingooophorectomy, removal of the greater omentum, optimal cytoreductive surgery — CC0 with HIPEC — cisplatin 100 mg/m2, perfusion 60 minutes at 43° C. Progression of the disease in October 2019 manifested in the formation of mucinous peritoneal carcinoma of low grade of malignancy. PCI -36. PSS (Prior surgical score) — 2. U1 (higher surgical complexity). Condition after perinectomy, right hemicolectomy (28.10.2019), optimal cytoreduction — CC0. Early postoperative intraperitoneal chemotherapy — cisplatin 100 mg/m2. Progression in May 2021. Formation of cystic solid intra-abdominal pseudomyxoma masses with invasion into the anterior abdominal wall.
Results. Elective cytoreductive surgery CC2 was performed in June 2021 and it involved: small bowel resection, removal of recurrent tumor with the resection of anterior abdominal wall, including subtotal resection of the right rectus abdominis muscle, TAR (Transversus Abdominis Muscle Release) reconstruction of the anterior abdominal wall using a combination of polypropylene meshes (inlay-bridge reconstruction). The course of an early postoperative period was complicated by post-surgical seroma which was aspirated by puncture.
Six months later (January 2022) at follow-up examination after surgical intervention of 30.06.2021, the condition of the patient was satisfactory, she was capable to perform moderate physical labour, ate properly, had no manifestations of dyspepsia, malabsorbtion, bowel and bladder functions were normal. Based on the fi ndings of abdominal contrast enhanced computer tomography scan (CT) of 18.01.2022, there were no symptoms of progressive tumor growth.
Conclusion. The optimal cytoreductive intervention combined with HIPEC allowed to reach recurrence-free period of survival of 29 months, overall survival of 5 years (at the time this article was written). However, there is a challenge of progressive growth of pseudomyxoma, that can develop not only in cases of lesions of the appendix, but also in mucinous ovarian tumors, in which the possibility to perform optimal cytoreduction is the key prognostic factor as well. This clinical observation presents the case of tumor recurrence in the anterior abdominal wall. Considering tissue deficiency, performing extensive resection of anterior abdominal wall is fraught with serious complications. The possibility of the use of anterior abdominal wall reconstruction technique, described above, permitted to perform a radical intervention, to restore anatomical integrity of the anterior abdominal wall and to preserve satisfactory quality of life of the patient.
Keywords: pseudomyxoma peritonei, recurrence, anterior abdominal wall reconstruction.
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COLLEAGUES WRITE TO US
Sushinskaya T.N., Kuznetsov A.I., Shchepkina E.V., Stuklov N.I., Epifanova S.V.
Detection of cervical cancer metastasis using machine learning algorithms
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Objective of the study is to develop a method of diagnosis of regional lymph node metastasis in patients with cervical cancer (CC) based on certain hematological parameters using machine learning algorithms. Machine learning algorithm is an effective technique of data classification, particularly in medical field where it is extensively used for diagnostic purposes.
Materials and methods. 495 patients of P. A. Gertsen Moscow Scientifi c Research Oncologic Institute — a Branch of Federal State Budgetary Institution “National Medical Research Center of Radiology” of the Ministry of Healthcare of the Russian Federation aged from 18 to 82 years (42 years) with verifi ed diagnosis of cervical cancer were divided into 2 groups according to the presence or absence of regional lymph node metastasis: with metastases and without metastases. An examination of 21 parameters of blood samples collected from each patient with cervical cancer determined that the patients were most appropriately visually separable based on 7 components: ESR (erythrocyte sedimentation rate), erythrocytes, hemoglobin, fi brinogen, D-dimer, platelet aggregation with ADP (adenosine diphosphate) and SFMC (soluble fi brin monomer complex).
The following algorithms were chosen to conduct machine learning: Decision Tree (DT), Random Forest (RF), K-nearest Neighbors (KNN), Support Vector Machine (SVM), Adaboost and XGBoost.
Results. Accuracy of the models constructed on training and testing samples (70% and 30% respectively) highlighted that Adaboost (100%, 98,8%) and XGBoost (100 %, 99,8 %) models are the most accurate (Fig.2). The assessment of the models based on ROC-AUC showed that XGBoost (100 %, 99,8 %) is slightly better than Adaboost (100 %, 98,8 %). However, R2 revealed that XGBoost (100%, 80,5%) provides more accurate proportion of explained variance than Adaboost (84,9%, 66,1%).
Conclusion. Experimental fi ndings indicate that “Support Vector Machine” technique (SVM) ensures the highest grade of accuracy (98%) with maximum proportion of explained variance (82,9% and 80,5%, respectively).
“Support Vector Machine” is the most precise technique (98 %) with maximum explanatory power (82,9%) for the diagnosis of the presence of cervical cancer metastases in regional lymph nodes based on hematological parameters.
Keywords: cervical cancer, CC, metastases, machine learning, algorithms, predictive modeling, diagnosis, accuracy, ROC-AUC, R2
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