Gynecologic Oncology

Gynecologic Oncology 2022 #4


Tsandekova M.R., Porkhanova N.V., Kutilin D.S.
Serous Ovarian Adenocarcinoma Molecular Subtypes And Patient Survival
Objective of the research is to study the gene copy number in the tissues of patients with serous ovarian adenocarcinoma and its effect on patient survival.
Materials and Methods of the research. The study comprised 200 women diagnosed with serous ovarian adenocarcinoma. At the fi rst stage, bioinformatic analysis of open databases was carried out. GISTIC, MutSig and RAE algorithms were used to identify genomic regions whose size varied signifi cantly in a number of tumor samples. At stage 2, for high-quality isolation of tumor and normal cells, an approach based on laser microdissection with non-contact capture was used. The determination of the relative gene copy number was carried out using Real-Time qCR method.
Results. Using bioinformatic algorithms, 34 genes were selected as markers of serous ovarian adenocarcinoma (CYP1-A1, -A2, -B1, CYP19A, ESR1/2, GPER, STS, SULT1-A, -E1, BAX, BCL-2, TP-53, MDM2, CASP-9, CASP-3, CASP-7, CASP-8, PRKCI, SOX2, OCT4, PIK3, PTEN, CMYC, SOX18, AKT1, NOTCH1, BRCA1/2, EXO1, SCNN1A, KRAS, EGFR and BRAF). A statistically signifi cant (p<0,05) increase in the copy number of PIK3CA and BCL2 genes and a decrease in the copy number of BAX, CASP3 and CASP8 were found in a sample of 200 patients. Based on differences in gene copy number, 2 molecular subtypes of serous ovarian adenocarcinoma, corresponding to 2 histologic subtypes – high (MDM2, SOX2, ESR1, CYP1-B1, SULT1-E1, TP-53, BRCA2) and low (PIK3CA, PTEN, BCL2, BAX, CASP-3, CASP-8) grade of malignancy, were identifi ed. These subtypes possessed also molecular heterogeneity, that made it possible to divide each of them into subgroups — 3 subgroups for high-grade serous adenocarcinoma, and 4 subgroups – for low-grade serous adenocarcinoma. The overall survival of patients was infl uenced by the copy number of 4 genes – SOX2, SULT1E1, BCL2 and PTEN.
Conclusion. The study gave an opportunity to identify subtypes of serous ovarian adenocarcinoma of low and high grade of malignancy at the molecular genetic level, as well as the intricacies of their clinical course.
Keywords: serous ovarian adenocarcinoma, gene copy number, molecular subtypes, survival rate
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Mustafina E.A., Shevchuk A.S., Payanidi Yu.G., Zanozina E.A., Komarov I.G., Zhordania K.I.
Surgical Treatment Of Endometrial Cancer Recurrences.
Objective of the study is to carry out an analysis of the data of academic medical literature on the treatment of endometrial cancer recurrences.
Materials and Methods. The review includes an analysis of the data obtained from scholarly articles found in PubMed, eLIBRARY on the subject, published over the past 20 years.
Results. Endometrial cancer is the most common gynecologic cancer in the developed countries of the world. Mortality from this pathology hasn’t declined over the past decades, despite breakthroughs and advances in the methods of diagnosis and treatment. Recurrence of the disease still remains one of the leading causes of mortality. Moreover, currently there is no unifi ed classifi cation of recurrent endometrial cancer, and the results of treatment of unrelated groups of patients were obtained mostly from retrospective material with a small number of observations, that was provided by select large oncologic institutions. As a result, there is insuffi cient coverage of the issues related to the treatment of recurrent endometrial cancer and, in particular, to its surgical aspect in international and domestic clinical guidelines. The strategy of treatment of patients with recurrent endometrial cancer depends on tumor localization, its size, presence or absence of peritoneal carcinomatosis and distant metastases, on the duration of recurrence-free period, general state of health of a patient and on whether a patient underwent previous adjuvant treatment (radiation therapy, chemotherapy or their combination).
The analysis of outcomes of treatment of patients with recurrent endometrial cancer, presented in current literature, revealed that overall survival of such patients is signifi cantly higher after combination treatments, that include surgical intervention, than only after chemo- or radiation therapy. Factors affecting surgical success include good functional status of a patient, long interval after the primary treatment of endometrial cancer , potential resectability of the tumor without distant metastases and microscopic features of tumor growth in resection margins. Therefore, a surgeon must be reasonably confi dent about attaining complete cytoreduction. Possible post-operative complications and their effect on the quality of life of patients need to be considered as well. Conclusion. A major factor infl uencing on an overall improvement of long-term outcomes of the treatment of endometrial cancer, are adequacy and effi ciency of the therapy for relapse of the disease. Further research are needed to objectively assess the role of surgical treatment of endometrial cancer recurrence and to develop evidence-based clinical recommendations.
Keywords: recurrence, metastases, endometrial cancer, surgical treatment, cytoreductive operation
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Shevchuk A.S., Afanasieva K.V.
Robot-Assisted Surgeries In Gynecologic Oncology: The First Experience Of Federal State Budgetary Institution “N.N. Blokhin National Medical Research Center Of Oncology” Of The Ministry Of Healthcare Of The Russian Federation
Objective of the work is to analyze the fi rst experience of surgical interventions using Da Vinci robotic-assisted surgical system in the Department of Gynecologic Oncology of N. N. Blokhin National Medical Research Center of Oncology.
Materials and Methods. 30 robot-assisted surgeries for gynecologic cancer were performed at the Department of Gynecologic Oncology of N. N. Blokhin National Medical Research Center of Oncology for the period from June 2021 to September 2022. The mean age of patients was 57 years (range 34–71), mean body mass index was 33,55 kg/m3 (range 23,8 — 48). Indications for surgery were IA stage endometrial cancer in 20 (66,8%) patients, IB stage — in 7 (23,3%) patients, IB1 stage cervical cancer — in 1 (3,3%) patient, atypical endometrial hyperplasia — in 1 (3,3%) patient, IA stage uterine sarcoma — in 1 (3,3%) patient.
Results. Hysterectomy with or without bilateral salpingo-oophorectomy was performed in 15 (50%) patients, hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy — in 14 (46,7%) patients. Radical trachelectomy with pelvic lymphadenectomy was attempted in 1 (3,3%) patient with invasive cervical cancer. Median time of surgery for hysterectomy made up 141 minutes, varying from 90 to 180 minutes. Hysterectomy with pelvic lymphadenectomy proved to be more time-consuming — from 120 to 240 minutes ( median was — 172 minutes.). Median docking time was 18 minutes (range — 15–40 minutes). The median estimated blood loss during all surgical procedures made up 65 ml (range 50–300 ml). Conversion was required in 1 (3,3%) patient due to the bleeding from parametrial vessels. No post-operative complications were observed in any patient.
Conclusion. Robot-assisted surgery is a promising trend in gynecologic oncology, it signifi cantly enhances the capabilities of surgeons and upholds excellent ergonomics. To obtain objective indisputable results further accumulation of knowledge and carrying out a comparative analysis are required.
Keywords: robot-assisted surgeries, gynecologic oncology, robot-assisted radical hysterectomy with bilateral salpingoophorectomy, sentinel lymph node biopsy, pelvic lymphadenectomy
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Zharkova E.Yu., Mavrichev S.A.
The Effectiveness Of The Use Of Treosulfan In Combination With Irinotecan In The Treatment Of Patients With Platinum-Resistant And Platinum-Refractory Ovarian Cancer
The median of overall survival of patients with platinum-resistant ovarian cancer doesn’t exceed 10–12 months. Effective treatment regimens haven’t yet been developed. A prospective study on the effectiveness of the use of treosulfan in combination with irinotecan in the treatment of platinum-resistant ovarian cancer was carried out at Republican Applied Research Center of Oncology and Medical Radiology named after N. N.Aleksandrov. The study included 152 patients. All patients received second-line chemotherapy regimens, based on treosulfan at a dose of 6mg/m2 in a combination with irinotecan at a dose of 180 mg/m2 on the 1-st day, interval between cycles was 21 days. A total of 791 cycles of chemotherapy were administered. The median time to progression was 6,63 months, median overall survival — 16,9 months. Thus, the combined use of treosulfan and irinotecan revealed suffi ciently high effi ciency and can be recommended as a therapy for platinumresistant ovarian cancer.
Keywords: platinum-resistant ovarian cancer, chemotherapy, treosulfan, irinotecan
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Korolenkova L.I., Leshkina G.V.
The Impact Of HPV Testing And Endocervical Sampling For Cytologic Examination On Enhancing The Effi ciency Of Early Diagnosis And Screening Of Precancerous Lesion (CIN2–3) And Early Cervical Cancer.
Objective of the study is to improve the early diagnosis of obligate precancer and latent types of cervical cancer by identifying the rate of association and signifi cance of HPV-testing for the viruses of high oncogenic risk for these lesions, as well as to determine relevance of obtaining endocervical specimen for reducing underdiagnosis of CIN2–3+.
Materials and Methods. The study comprised 718 patients with CIN2–3, microinvasive cervical cancer and invisible types of cervical cancer who had abnormal smears and histological verifi cation of the diagnosis in the biopsy specimens obtained by loop excision of the transformation zone and/or zone of conization of the cervix. Prior to excisional intervention in the process of examination and diagnosis, testing for HPV of high carcinogenic risk (HCR) was performed using double hybrid capture technique, and specimens for cytology examination were also collected separately as scarifi ed segments, obtained with a fan-shaped cytology brush from ectocervix and with an endocervical cytology brush from the canal.
Results. The study revealed 100% — association between CIN2–3 and latent types of cervical cancer with HPV of high oncogenic risk and an increase in the rate of association with types 16 and 18 with increasing severity of cervical neoplasia. It was shown that endocervical cytological sampling contributed to the improvement of the identifi cation of CIN2–3 and invisible cervical cancer by 14,2% and to the accuracy of the diagnosis of severe lesions — by 22,4%.
Conclusion. High oncogenic risk HPV tests have 100% sensitivity and negative predictive value for CIN2+ and should be included in Federal Compulsory Medical Insurance — funded algorithms of screening and routine examinations for women over 30 years of age, which is in line with the clinical guidelines, as well as for younger women who have abnormal smears of unclear grade (ASCUS, ASC-H, LSIL). Obtaining an endocervical component in cervical samples for cytological examination signifi cantly increases the effectiveness of screening and diagnostic measures for the detection of precancerous lesions and latent types of cervical cancer and should be mandatory and performed using appropriate devices (either a device with an endocervical component, or using two devices separately).
Keywords: cervical dysplasia, CIN2–3, cervical cancer, HPV-testing, cytological screening, early diagnosis, endocervical sample
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Ivanova A.S., Obukhova O.A., Kurmukov I.A.
Pre-Rehabilitation As A Possible Component Of ERAS Protocol In Modern Operative Gynecologic Oncology.
Objective of the study is to discuss the impact of surgical stress on functional status, and the influence of pre-rehabilitation program — on the severity of post-traumatic response and to identify a group of patients for whom pre-operative preparation, based on pre-rehabilitation program in gynecologic oncology, is indicated.
Materials and Methods. The review comprises the data of foreign and Russian scholarly articles found in PubMed, ScienceDirect and E-library on the subject, published over the past 10 years.
Results. Pre-rehabilitation of patients undergoing major surgical interventions in gynecologic oncology can contribute to increased functionality by the time of surgery and accelerate recovery of functional status and quality of life after surgery. These programs are being actively introduced in abdominal, thoracic, colorectal surgery; relevant studies, albeit on a smaller scale, are also being carried out in gynecologic oncology. Identifi cation of health disorders associated with cancer, including those signifi cantly affecting the course of post-operative period and patient recovery after an elective surgical intervention should begin at the moment when cancer is diagnosed and include the assessment of patient’s physical and psychological state.
Conclusion. Carrying out a pre-rehabilitation program at the preoperative stage will allow to reduce the severity and duration of the systemic impact of surgical trauma, which, in turn, will speed up recovery and improve the quality of life of patients.
Keywords: pre-rehabilitation, gynecology, oncology, functionality, quality of life, chemoradiation therapy
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Dudinskaya E.N., Ilyushchenko A.K.
Osteoporosis In Women: Current Possibilities Of Diagnosis And Treatment.
Objective of the study is to carry out a systematic analysis of the data available in current literature on the prevalence, diagnosis and the possibilities of treatment of postmenopausal osteoporosis in women of different age groups.
Materials and Methods. The review comprises the data of Russian and foreign scholarly articles found in PubMed on the subject, published over the past 10 years.
Results. The work evaluates general and expert knowledge of osteoporosis in women. The articles outlines how to defi ne osteoporosis risk factors, both modifi able and non-modifi able. The major mechanisms of the occurrence of postmenopausal osteoporosis, the role of drug therapy and lifestyle in the correction of risk factors are presented. Considering high incidence of gynecologic cancers and early menopause, associated with their treatment, the paper addresses the issues of osteoporosis incidence in women of younger age.
Conclusion. Postmenopausal osteoporosis is a fairly common problem in women, including those with gynecologic cancers. In this regard, intensifi ed identifi cation of osteoporosis in women with early menopause, prescribing measures for the prevention of osteoporosis and its complications in this category of patients are required.
Keywords: osteoporosis, gynecologic cancers, rehabilitation
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