GynecologyGynecology2079-56962079-5831Consilium Medicum8414410.26442/20795696.2022.2.201387Research ArticleThe differential diagnosis algorithm of ovarian tumors in reproductive patients: a prospective studyPodzolkovaNatalia M.<p>D. Sci. (Med.), Prof.</p>rediska2406@yandex.ruhttps://orcid.org/0000-0001-9183-7030OsadchevVasilii В.<p>Cand. Sci. (Med.)</p>vosadchev@mail.ruhttps://orcid.org/0000-0001-5351-0854BabkovKirill V.<p>Cand. Sci. (Med.)</p>kirill.babkov@mail.ruhttps://orcid.org/0000-0001-6260-2734SafonovaNatalia E.<p>Graduate Student</p>rediska2406@yandex.ruhttps://orcid.org/0000-0002-9949-9192Russian Medical Academy of Continuous Professional EducationPletnev City Clinical Hospital1504202224280873010202124032022Copyright © 2022, Consilium Medicum2022<p><strong>Aim.</strong> The aim of the study was to evaluate the efficiency of different methods of preoperative diagnostics and to develop an algorithm for examining patients of reproductive age with ovarian tumors.</p>
<p><strong>Materials and methods. </strong>The study included 100 patients operated in the gynecological and oncogynecological departments of Pletnev State Clinical Hospital (Moscow) in the period from Sep 2019 to Dec 2020. The inclusion criteria were reproductive age (1840 years); unilateral/bilateral nature of ovarian lesion; ovarian tumor existing for at least 3 months and confirmed by the data of instrumental research methods; the size of the pathological formation of the ovary according to instrumental examination 30 mm; normal/elevated level of biochemical markers and diagnostic calculation indices: Carbohydrate Antigen 125 (СА 125), Carbohydrate Antigen 19-9, Carcinoembryonic Antigen, Human Epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), Risk of Malignancy Index (RMI). All patients underwent determination of the level of cancer markers CA 125 and HE4, followed by calculation of the RMI and ROMA indices for premenopause, gray scale ultrasound examination with Doppler blood flow assessment was performed. Next, a contrast-enhanced ultrasound examination (CEUS) was performed.</p>
<p><strong>Results. </strong>Sensitivity (Se) of the Ovarian-Adnexal Imaging-Reporting-Data System (O-RADS) in predicting tumor malignancy was 84.8% (95% confidence interval 95% CI 8088), specificity (Sp) 88.1% (95% CI 8591), accuracy (Acc) 0.86 (95% CI 0.820.90), odds ratio (OR) 41.18 (95% CI 21.080.7), area under the curve (AUC) 0.744. Se of CEUS in predicting malignancy was 90.9% (95% CI 8595), Sp 92.5% (95% CI 8997), Acc 0.92 (95% CI 0.880.96), OR 150.0 (95% CI 76.5294.0), AUC 0.895.</p>
<p><strong>Conclusion. </strong>Patients with O-RADS 2 are shown to be monitored by a gynecologist for 6 months with a control ultrasound examination once every 3 months. When O-RADS 3 criteria are identified, it is recommended to include the determination of cancer markers and surgical treatment in a gynecological hospital with subsequent morphological examination of the obtained material as a preoperative diagnosis. The identification of O-RADS 4 and O-RADS 5 criteria requires additional examination methods, such as the study of cancer markers (CA 125, HE4, ROMA, RMI), contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging. CEUS showed high diagnostic efficiency in the presence of O-RADS 4 criteria, which made it possible to determine the necessary management tactics for patients with complex tumors. If the characteristics of the tumor are unclear, it is necessary to consider the possibility of surgical treatment in an oncological hospital.</p>diagnosticscancer markerscontrast-enhanced ultrasound examinationovarian tumorultrasoundO-RADSдиагностикаонкомаркерыультразвуковое исследование с внутривенным контрастированиемопухоль яичникаультразвуковое исследованиеO-RADS[Ovarian Cancer Statistics. Toronto, ON: Canadian Cancer Society; 2019. Available at: www.cancer.ca/en/cancer-information/cancer-type/ovarian/statistics/?region=on. Accessed: 18.02.2022.][Борисова ЕА. Комплексная дифференциальная диагностика опухолей придатков матки: автореф. дис. … канд. мед. наук. Иркутск; 2018. Режим доступа: https://www.dissercat.com/content/kompleksnaya-differentsialnaya-diagnostika-opukholei-pridatkov-matki/read. Ссылка активна на 18.02.2022 [Borisova EA. Kompleksnaia differentsial'naia diagnostika opukholei pridatkov matki: avtoref. dis. … kand. med. nauk. Irkutsk; 2018. Available at: https://www.dissercat.com/content/kompleksnaya-differentsialnaya-diagnostika-opukholei-pridatkov-matki/read. Accessed: 18.02.2022 (in Russian)].][Gupta KK, Gupta VK, Naumann RW. Ovarian cancer: screening and future directions. Int J Gynecol Cancer. 2019;29(1):195-200. DOI:10.1136/ijgc-2018-000016][Приказ Министерства здравоохранения РФ от 20 октября 2020 г. N1130н «Об утверждении Порядка оказания медицинской помощи по профилю "акушерство и гинекология"». Режим доступа: https://mz19.ru/bnsi/detail.php?id=10199. Ссылка активна на 18.02.2022 [Order of the Ministry of Health of the Russian Federation dated October 20, 2020 number 1130n «On approval of the Procedure for providing medical care in the profile "obstetrics and gynecology"». Available at: https://mz19.ru/bnsi/detail.php?id=10199. Accessed: 18.02.2022 (in Russian)].][Orr B, Edwards RP. Diagnosis and Treatment of Ovarian Cancer. Hematol Oncol Clin North Am. 2018;32(6):943-64. DOI:10.1016/j.hoc.2018.07.010][Министерство здравоохранения Российской Федерации. Письмо от 04.12.2018 г. №15-4/10/2-7838 «Диагностика и лечение доброкачественных новообразований яичников с позиции профилактики рака. Клинические рекомендации (протокол лечения)». Режим доступа: https://zdrav36.ru/files/1544538622_novoobrazovaniya-yaichnikov.pdf. Ссылка активна на 18.02.2022 [Ministry of Health of the Russian Federation. Letter dated 04.12.2018 No.15-4/10/2-7838 «Diagnosis and treatment of benign ovarian neoplasms from the perspective of cancer prevention. Clinical recommendations (treatment protocol)». Available at: https://zdrav36.ru/files/1544538622_novoobrazovaniya-yaichnikov.pdf. Accessed: 18.02.2022 (in Russian)].][Goff BA, Matthews BJ, Larson EH, et al. Predictors of comprehensive surgical treatment in patients with ovarian cancer. Cancer. 2007;109(10):2031-42. DOI:10.1002/cncr.22604][Committee Opinion No.716: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk. Obstet Gynecol. 2017;130(3):e146-9. DOI:10.1097/AOG.0000000000002299][Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66:7-30. DOI:10.3322/caac.21332][Состояние онкологической помощи населению России в 2019 году. Под ред. А.Д. Каприна, В.В. Старинского, Г.В. Петровой. М.: МНИОИ им. П.А. Герцена, 2020 [Sostoianie onkologicheskoi pomoshchi naseleniiu Rossii v 2019 godu. Pod red. AD Kaprina, VV Starinskogo, GV Petrovoi. Moscow: P.A. Herzen Moscow State Medical Research Institute, 2020 (in Russian)].][Хамзин И.З., Соломатина А.А., Тюменцева М.Ю., и др. Современные методы гемостаза и овариальный резерв при органосохраняющих операциях на яичниках. Международный медицинский журнал. 2017;3(14):39-43 [Khamzin IZ, Solomatina AA, Tyumentseva MU, et al. Modern methods of hemostasis and ovarian reserve during organ-preserving operations on the ovaries. International Medical Journal. 2017;3(14):39-43 (in Russian)].][Andreotti RF, Timmerman D, Strachowski LM, et al. O-RADS US Risk Stratification and Management System: A Consensus Guideline from the ACR Ovarian-Adnexal Reporting and Data System Committee. Radiology. 2020;294(1):168-85. DOI:10.1148/radiol.2019191150][Волченко Н.Н., Борисова О.В., Ермолаева А.Г., и др. Срочная интраоперационная морфологическая диагностика в онкологии. Онкология. Журнал им. П.А. Герцена. 2015;4(4):5-11 [Volchenko NN, Borisova OV, Ermolaeva AG, et al. Rapid intraoperative morphological diagnosis in oncology. Oncology. P.A. Herzen Journal of Oncology/Onkologiya. Zhurnal imeni P.A. Gertsena. 2015;4(4):5-11 (in Russian)]. DOI:10.17116/onkolog2015445-11][Salvador S, Scott S, Glanc P, et al. Guideline No.403: Initial Investigation and Management of Adnexal Masses. J Obstet Gynaecol Can. 2020;42(8): 1021–9.e3. DOI:10.1016/j.jogc.2019.08.044][Ionescu CA, Matei A, Navolan D, et al. Correlation of ultrasound features and the Risk of Ovarian Malignancy Algorithm score for different histopathological subtypes of benign adnexal masses. Medicine (Baltimore). 2018;97(31):e11762. DOI:10.1097/MD.0000000000011762][Sevinc A, Adli M, Kalender ME, Camci C. Benign causes of increased serum CA-125 concentration. Lancet Oncol. 2007;8:1054-5. DOI:10.1016/S1470-2045(07)70357-1][Moro F, Pasciuto T, Djokovic D, et al. Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses. Ultrasound Obstet Gynecol. 2019;53(1):116-23. DOI:10.1002/uog.19174][Dochez V, Caillon H, Vaucel E, et al. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res. 2019;12(1):28. DOI:10.1186/s13048-019-0503-7][Lycke M, Kristjansdottir B, Sundfeldt K. A multicenter clinical trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index. Gynecol Oncol. 2018;151(1):159-65. DOI:10.1016/j.ygyno.2018.08.025][Солопова А.Е., Дудина А.Н. O-RADS и ADNEX MR scoring system: стандартизация оценки и современные подходы к стратификации рисков злокачественности образований яичников. Акушерство, Гинекология и Репродукция. 2019;13(4):345-53. [Solopova AE, Dudina AN. О-RADS and ADNEX MR scoring system: standardization of assessment and modern approaches to stratification of ovarian malignancy risks. Obstetrics, Gynecology and Reproduction. 2019;13(4):345-53 (in Russian)]. DOI:10.17749/2313-7347.2019.13.4.345-353][Подзолкова Н.М., Осадчев В.Б., Бабков К.В., Сафонова Н.Е. Возможности применения стратификационной системы O-RADS и ультразвукового исследования с контрастным усилением в дифференциальной диагностике опухолей яичников. Вопросы гинекологии, акушерства и перинатологии. 2021;20(6):101-9 [Podzolkova NM, Osadchev VB, Babkov KV, Safonova NE. Vozmozhnosti primeneniia stratifikatsionnoi sistemy O-RADS i ul'trazvukovogo issledovaniia s kontrastnym usileniem v differentsial'noi diagnostike opukholei iaichnikov. Voprosy ginekologii, akusherstva i perinatologii. 2021;20(6):101-9 (in Russian)]. DOI:10.20953/1726-1678-2021-6-101-109][American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins – Gynecology. Practice Bulletin No.174: Evaluation and Management of Adnexal Masses. ACOG. Obstet Gynecol. 2016;128(5):e210–26. DOI:10.1097/aog.0000000000001768][Alcazar JL, Diaz L, Florez P, et al. Intensive training program for ultrasound diagnosis of adnexal masses: protocol and preliminary results. Ultrasound Obstet Gynecol. 2013;42:218-23. DOI:10.1002/uog.12440][Suh-Burgmann E, Hung YY, Kinney W. Outcomes from ultrasound follow-up of small complex adnexal masses in women over 50. Am J Obstet Gynecol. 2014;211:623.e1-7. DOI:10.1016/j.ajog.2014.07.044][Suh-Burgmann E, Kinney W. Potential harms outweigh benefits of indefinite monitoring of stable adnexal masses. Am J Obstet Gynecol. 2015;213:816.e1-4. DOI:10.1016/j.ajog.2015.09.005]