Clinical Value of IOTA LR2 and IOTA LR2 Combined with CEUS in Assessing the Nature of Adnexal Masses

Clinical Value of IOTA LR2 and IOTA LR2 Combined with CEUS in Assessing the Nature of Adnexal Masses | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Value of IOTA LR2 and IOTA LR2 Combined with CEUS in Assessing the Nature of Adnexal Masses Xiaonan Yan, Yiwei Han, Jianmei Zhang, Cai Tian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3815785/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To investigate the preoperative assessment of adnexal tumor benignity and malignancy using the International Ovarian Tumour Analysis (IOTA) logistic regression model 2 (LR2) and LR2 combined with contrast-enhanced ultrasound (CEUS). Clinical application of LR2 and CEUS in the preoperative assessment of adnexal tumors was evaluated. Methods One hundred and ninety-eight adnexal tumors were selected, and their nature was evaluated preoperatively according to IOTA LR2 and LR2 combined with CEUS. Pathological and long-term follow-up results were used as the gold standard for comparison. Results For the diagnostic efficacy of LR2 for identifying the nature of ovarian masses, the AUC was 0.90 (0.85–0.94). For the diagnostic efficacy of LR2 combined with CEUS in identifying the benign and malignant nature of ovarian tumors, the AUC was 0.92 (0.88–0.97). Conclusion The IOTA LR2 model has high sensitivity but low specificity. Its diagnostic specificity can be significantly improved by combining it with CEUS. Therefore, LR2 combined with CEUS has high clinical value and can help ultrasonographers determine the benign or malignant nature of adnexal tumors. Biological sciences/Cancer/Cancer imaging Health sciences/Oncology/Cancer IOTA LR2 CEUS adnexal mass ultrasound diagnosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1.Introduction Ovarian cancer is the fifth leading cause of cancer-related death among women. Among the tumors of the female reproductive system, ovarian cancer is second in incidence only to uterine body and cervical cancers and has the highest mortality rate, posing a serious threat to women's lives and health 1 , 2 . Ovarian cancer lacks typical clinical manifestations in the early stages, so it is often detected at a late stage, and the prognosis of patients is poor, with a 5-year survival rate of only approximately 28%. Early detection of adnexal masses and early evaluation of their benign or malignant nature are of great clinical significance for improving the prognosis of patients with ovarian cancer. Currently, ultrasound is the imaging method of choice for evaluating the benignity or malignancy of adnexal masses 3 ; it is a low-cost and easily accessible examination method with rapid, safe, convenient, and reproducible imaging technology that is capable of dynamic, real-time, and non-invasive examination of the structure of the internal tissues of the human body and blood flow, among other characteristics. However, the ultrasound diagnosis of benign and malignant adnexal masses is mainly based on the subjective judgment of the examiner and is therefore highly dependent on the examiner's personal skills and experience 4 . In order to accurately predict the benign or malignant nature of adnexal masses to help clinicians choose more appropriate treatments, a number of ultrasound-related guidelines, grading systems, and prediction models have been developed 5 , 6 . International Ovarian Tumour Analysis (IOTA) is the largest multicenter, large-sample study of ultrasound for determining the nature of ovarian tumors, and the logistic regression model 2 (LR2) is the product of a large-sample, prospective study based on IOTA 7 . In recent years, contrast-enhanced ultrasonography (CEUS) has been developing and advancing, and is able to better observe the characteristics of blood vessels in adnexal masses 8 . Compared with color Doppler ultrasound, CEUS can show the blood flow of microvessels in adnexal masses in real time, dynamically, and clearly, and can help doctors more accurately assess adnexal masses that are difficult to identify as benign or malignant by traditional ultrasound 9 . The aim of this study was to investigate the ability of the IOTA LR2 and IOTA LR2 combined with CEUS to assess the benign or malignant nature of adnexal masses in patients and to validate it on the basis of postoperative pathological findings to explore the clinical value of the IOTA LR2 and IOTA LR2 combined with ultrasonography in predicting the nature of adnexal masses. 2. Materials and Methods 2.1 Materials Data were collected from 202 female patients who were admitted to the Department of Gynecology of the Second Hospital of Hebei Medical University and underwent surgery for adnexal masses from July 2019 to June 2022, including the patient's age, menstrual status (≥ 50 years of age and who underwent a hysterectomy and were categorized as postmenopausal), history of ovarian and breast cancers, the number of first-degree relatives with ovarian or breast cancers, the record of this surgery, and the complete postoperative clinical information including pathology results. The inclusion criteria were: 1. Adnexal mass detected by preoperative color Doppler ultrasonography; 2. surgical treatment at the Department of Gynecology, The Second Hospital of Hebei Medical University, within 120 days after the last ultrasonography; 3. Ultrasonography performed within 2 weeks before surgery; 4. Pathological results for the adnexal tumor; 5. Complete clinical data. The exclusion criteria were: 1. physiological cysts; 2. Adnexal masses combined with pregnancy; 3. History of adnexal malignant tumors; 4. Unclear pathological results; 5. Poor image quality or images without diagnostic signs. Based on the inclusion and exclusion criteria, 198 patients aged 9–79 years, 124 premenopausal women, and 74 postmenopausal women were included in this study. This study was approved by the Ethics Committee of the Second Hospital of Hebei Medical University, and written informed consent was obtained from all patients. Ultrasonography was performed by a sonographer with seven or more years of experience in gynecological ultrasonography who performed a thorough examination of the uterus, adnexa, and pelvis and analyzed and diagnosed according to the characteristics of the ultrasound image. Routine ultrasound imaging parameters included location, number, size, shape, echogenicity, borders, posterior echogenicity, blood flow, and concomitant ascites of the mass. Images were acquired using a 5–9 MHz intracavitary ultrasound probe. If the mass was too large to be visualized with transcavitary ultrasound, ultrasound images were acquired transabdominally using a 1–5 MHz curved probe. Patients’ ultrasound images were stored and acquired using the ultrasound working system of the Second Hospital of Hebei Medical University. SonoVue, an intravenous contrast agent manufactured by Bracco, Italy, was used as the contrast agent. Each SonoVue contrast agent contained 59 mg of phospholipid-coated sulfur hexafluoride (SF6) gas microbubbles, which were added to 5 mL of saline for injection and shaken vigorously to obtain a microbubble suspension with an average microbubble diameter of 2.5 µm. Methods for determining the nature of ovarian tumors: The ultrasound characteristics of adnexal masses were evaluated according to LR2 and LR2 combined with ultrasonography, during which the sonographer was blinded to the patient's histopathological findings. The LR2 model included: 1. Age (years); 2. Presence of peritoneal effusion; 3. Presence of a papillary protuberance with blood flow; 4. Maximum diameter of the solid portion (if the maximum diameter was ≥ 50 mm, it was recorded as 50 mm because a diameter > 50 mm does not increase the risk value with its growth); 5. Presence of irregularities in the inner wall of the cyst; and 6. Presence of acoustic shadows (Fig. 1 – 5 ). The benign and malignant risk values (%) were calculated by applying the LR2 software to the above six parameters. The risk value ranges from 1–95%, taking ≥ 10% as the malignant cutoff value, i.e., < 10% is considered benign and ≥ 10% is suspected malignant. Ultrasonography scoring criteria were used to assess the characteristics of peritoneal enhancement (0 points for intact, 1 point for inconspicuous or incomplete), the thickness of peritoneal enhancement (0 points for homogeneous, 1 point for uneven thickness), the characteristics of enhancement at peak enhancement compared with that of the peritoneum (0 points for no enhancement of the enhancement within the lesion, 1 point for low enhancement, and 2 points for equivocal or high enhancement), the internal area of lesion enhancement (homogeneous enhancement = 0 points, non-homogeneous enhancement = 1 point), and segregation within the lesion (no segregation-like enhancement = 0 points, segregation-like enhancement = 1 point), with a total score of 0–6 points, and a total score of ≥ 4 points was classified as malignant, and ≤ 3 points was classified as benign. Finally, histopathological results were compared with those of the patients. 2.2 Methods SPSS 20.0 statistical software were applied for statistical analysis. The chi-square test was used for categorical variable comparisons and the independent sample t-test or rank-sum test was used for continuous variable comparisons. Kappa coefficient was used to assess intergroup consistency, with κ ≥ 0.75 indicating high consistency, 0.40 ≤ κ < 0.75 indicating medium consistency, and κ < 0.40 indicating low consistency. The diagnostic performance of the ultrasound classification system was tested by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Statistical significance was set at p < 0.05. 3. Results Surgical excision was performed for 198 ovarian tumor tissue specimens. Among them, 132 (66.7%) were benign and 66 (33.3%) were nonbenign. LR2 assessed 118 patients (59.6%) as benign and 80 (40.4%) as nonbenign (Table 1 ). LR2 combined with CEUS assessed 125 (63.1%) patients as benign and 73 (36.9%) as nonbenign (Table 2 ). Of 124 premenopausal women, 105 (84.7%) were benign, and 19 (15.3%) were non-benign. LR2 assessed 96 patients (77.4%) as benign and 28 (22.6%) as nonbenign (Table 3 ). LR2 combined with CEUS assessed 100 patients (80.6%) as benign and 24 (19.4%) as non-benign(Table 4 ). Of 74 postmenopausal women, 27 (36.5%) were benign and 47 (63.5%) were nonbenign. LR2 classified 22 patients (29.7%) as benign and 52 (70.3%) as nonbenign (Table 5 ). LR2 combined with CEUS evaluated 25 patients (33.8%) as benign and 49 (66.2%) as nonbenign(Table 6 ). The sensitivity of LR2 diagnosis was 93.94%, the specificity was 86.36%, the positive predictive value was 77.5%, the negative predictive value was 96.61%, the positive likelihood ratio was 6.89%, the negative likelihood ratio was 0.07%, and the diagnostic accuracy was 88.89%. The diagnostic concordance with pathology was good, with a κ-value of 0.763; >0.75 indicates good concordance between LR2 and pathology, and P < 0.01 indicates a statistically significant difference between the results of LR2 and pathology. The diagnostic sensitivity of LR2 in combination with CEUS was 92.42%, the specificity was 90.91%, the positive predictive value was 83.56%, the negative predictive value was 96%, the positive likelihood ratio was 10.17, negative likelihood ratio 0.08, diagnostic accuracy 91.41%. The diagnostic concordance with pathology was good, with a κ-value of 0.81 > 0.75, indicating good concordance between the two methods of LR2 combined with CEUS and pathology (P = 0.143, indicating that LR2 combined with CEUS did not significantly from pathology). In non-menopausal women, LR2 diagnosis had a sensitivity of 89.47%, a specificity of 89.52%, a positive predictive value of 60.71%, a negative predictive value of 97.92%, a positive likelihood ratio of 8.54% and, negative likelihood ratio of 0.12%, and a diagnostic accuracy of 89.52%. Concordance with the pathological diagnosis was moderate, with a κ-value of 0.662 (P = 0.022). The sensitivity of LR2 combined with CEUS diagnosis was 89.47%, the specificity was 93.33%, the positive predictive value was 70.83%, the negative predictive value was 98%, the positive likelihood ratio was 13.41, the negative likelihood ratio was 0.07, and the diagnostic accuracy was 92.74%. Concordance with the pathological diagnosis was good, with a κ-value of 0.748 (P = 0.18). In postmenopausal women, the sensitivity of LR2 diagnosis was 95.74%, the specificity was 74.07%, the positive predictive value was 86.54%, the negative predictive value was 90.91%, the positive likelihood ratio was 3.69%, the negative likelihood ratio was 0.06%, and the diagnostic accuracy was 87.84%. Concordance with the pathological diagnosis was moderate, with a κ-value of 0.662 (P < 0.01). The sensitivity of LR2 combined with CEUS diagnosis was 93.62%, the specificity was 81.48%, the positive predictive value was 89.8%, the negative predictive value was 88%, the positive likelihood ratio was 5.06%, and the negative likelihood ratio was 0.23%, with a diagnostic accuracy of 89.19%. Concordance with the pathological diagnosis was good, with a κ-value of 0.763 (P = 0.727) (Table 7 ). The diagnostic efficacy of LR2 for identifying benign and malignant ovarian tumors showed an AUC of 0.90 (0.85–0.94). The diagnostic efficacy of LR2 combined with CEUS in identifying benign and malignant ovarian tumors showed an AUC of 0.92 (0.88–0.97) (Fig. 6 ). Table 1 Comparision of results of IOTA LR2 with histopathological findings Nature of the Mass as per IOTA LR2 Histopathological Result No. Benign Malignant Benign 114 4 118 Malignant 18 62 80 No. 132 66 198 Table 2 Comparision of results of Premenopausal IOTA LR2 with histopathological findings Nature of the Mass as per IOTA LR2 Histopathological Result No. Benign Malignant Benign 94 2 96 Malignant 11 17 28 No. 105 19 114 Table 3 Comparision of results of Postmenopausal IOTA LR2 with histopathological findings Nature of the Mass as per IOTA LR2 Histopathological Result No. Benign Malignant Benign 20 2 22 Malignant 7 45 52 No. 27 47 74 Table 4 Comparison of IOTA LR2 combined with CEUS results and histopathologic findings Nature of the Mass as per IOTA LR2 combined with CEUS Histopathological Result No. Benign Malignant Benign 120 5 125 Malignant 12 61 73 No. 132 66 198 Table 5 Comparison of Premenopausal IOTA LR2 combined with CEUS results and histopathologic findings Nature of the Mass as per IOTA LR2 combined with CEUS Histopathological Result No. Benign Malignant Benign 98 2 100 Malignant 7 17 24 No. 105 19 124 Table 6 Comparison of Postmenopausal IOTA LR2 combined with CEUS results and histopathologic findings Nature of the Mass as per IOTA LR2 combined with CEUS Histopathological Result No. Benign Malignant Benign 22 3 25 Malignant 5 44 49 No. 27 47 74 Table 7 Efficacy of IOTA LR2 and IOTA LR2 Combined With CEUS Scoring System in Diagnosing Benign and Malignant Ovarian Tumors (%) Method Sensitivity Specificity PPV NPV Accuracy LR2 93.94 86.36 77.5 96.61 88.89 LR2 combined with CEUS 92.42 90.91 83.56 96 91.41 4. Discussion Ovarian malignant tumors are the seventh most common cancer in women 10 , the third most common in the incidence of malignant tumors of the female reproductive system, and have the highest mortality rate among malignant tumors of the female reproductive system 11 , which is a serious threat to women's life and health and a major burden to global public health 12 , 13 . The stage of malignant ovarian tumors directly affects patient prognosis. Research shows that the five-year survival rate of patients with stage I ovarian cancer is 90% 14 , while that of patients with stage III and IV ovarian cancer is only 25%-30% 15 . However, because of the insidious onset of ovarian cancer, strong invasiveness, and atypical clinical symptoms in the early stage, more than 70% of patients are diagnosed when already in the late stage 16 ; hence, it is especially important to accurately predict the benignity or malignancy of adnexal tumors in the early stage. Ultrasound imaging technology is fast, safe, convenient, and repeatable, and is currently the main imaging method for detecting adnexal masses 17 , 18 . The intracavitary ultrasound probe can be placed in the vagina close to the vaginal fornix and cervix, so that the acoustic images of the pelvic organs can be displayed more clearly. In recent years, with the widespread use of intracavitary ultrasound, the accuracy and sensitivity of ultrasound in the diagnosis and treatment of adnexal masses have improved remarkably 19 . The ability of ultrasound to distinguish the nature of adnexal masses has important significance for the prognosis of patients with ovarian cancer. Adnexal masses are complex in origin, especially ovarian lesions. The ovary is the organ of female germ cells and sex hormone production, and the epithelial cells on its surface differentiate in multiple directions; therefore, physiologic and pathologic alterations are complex, the histologic types are numerous, and masses of different histologic origins have different morphologic characteristics, often exhibiting homogeneous and homogeneous heterogeneity. The subjective judgment of the sonographer is considered the most effective method for identifying the nature of adnexal masses before surgery; therefore, the seniority and experience of the sonographer significantly affects the accuracy of identification of benign and malignant pelvic masses, and sonographers with lower seniority due to less experience often have a low judgment accuracy rate 20 . It is difficult to preoperatively differentiate between benign and malignant adnexal masses. Correct identification of the characteristics of adnexal masses by the sonographer is very important in the selection of treatment for the patient, which helps the clinician to help the patient to choose the most appropriate treatment, such as whether or not to opt for surgical treatment and to choose the extent of the surgery, so as to improve the survival rate and quality of life 21 . Accurate assessment of the nature of the mass can also reduce unnecessary treatment and save medical resources 22 . The ultrasound team has recently developed a large number of scoring systems and diagnostic models to facilitate more accurate identification of the nature of adnexal masses during ultrasound examinations 23 . IOTA Working Group, a multicenter, large-sample, and ongoing team of researchers on adnexal lesions, is the largest study to date analyzing the ultrasonographic characteristics of benign and malignant adnexal masses 24 . IOTA LR2 is a product of IOTA's prospective study based on a large sample, which focuses more on ultrasound characteristics, including six parameters such as the patient's age, the presence of peritoneal effusion, the presence of papillae with blood flow, the maximal diameter of the solid portion, the regularity of the cyst's inner wall, and the presence of an acoustic shadow, and therefore has a high degree of sensitivity to detect as many true positive patients as possible 25 . Angiogenesis is closely related to tumor growth and metastasis, and is an independent prognostic indicator for the survival of patients with malignant tumors 26 . CEUS is a blood flow perfusion imaging method in which a contrast agent is pushed into the body by intravenous injection, and can reach the lesion with the blood flow to enhance the scattered signal intensity of the blood flow in the lesion. CEUS can clearly display the microvascular blood flow within the adnexal mass, and accurately evaluate the order and intensity of blood flow perfusion in the tumor, which is considered a better technique for identifying the nature of the adnexal mass 27 . This study included 198 eligible patients with adnexal masses to investigate the ability of the IOTA LR2 and IOTA LR2 combined with ultrasonography to preoperatively assess the benignity and malignancy of adnexal masses. The study procedure was double-blind, meaning that the sonographer was unaware of the patient's histopathological findings. Sensitivity is a measure of the ability of the diagnostic method to detect the presence of a disease, also known as the true positive rate; and specificity is a measure of the ability of the diagnostic method to correctly determine the absence of disease, also known as the true negative rate. The results of the present study showed that the sensitivity of the IOTA LR2 was 93.94% with a specificity of 86.36%, and that LR2 in combination with CEUS had a sensitivity of 92.42% with a specificity of 90.91%; this indicates that the diagnostic rate of LR2 is high, but the misdiagnosis rate is also high, whereas LR2 combined with CEUS can significantly improve the specificity and reduce the chance of misdiagnosis. Positive predictive value refers to the proportion of true positives to all positive results detected, and the negative predictive value is the opposite, i.e., the proportion of true negatives to all negative cases detected. Positive and negative predictive values are the diagnostic indexes of most concern to clinicians. The positive predictive value of LR2 in this study was 77.5%, and the negative predictive value was 96.61%; the positive predictive value of LR2 combined with CEUS was 83.56%, and the negative predictive value was 96%. The positive predictive value of LR2 combined with CEUS was significantly higher than that of LR2, but the positive and the negative predictive values were affected by the prevalence rate, while the likelihood ratio could exclude this interference, and the results would be more stable; the positive likelihood ratio for LR2 in the present study was 6.89%, and the negative likelihood ratio was 0.07%. The positive likelihood ratio of LR2 combined with CEUS was 10.17%, and the negative likelihood ratio was 0.08%. When the positive likelihood ratio is > 10 and the negative likelihood ratio is < 0.1, the test being evaluated is regarded as an ideal test. This further indicates that LR2 has a low leakage rate but a relatively high misdiagnosis rate, and that the misdiagnosis rate can be significantly reduced affecting the leakage rate by combining LR2 with CEUS. The area under the ROC curve (AUC) is currently considered a good indicator for evaluating the diagnostic efficacy of diagnostic tests, with AUC values closer to 1 indicating higher diagnostic efficacy, and those closer to 0.5 indicating poorer diagnostic efficacy. In this study, the AUC of IOTA LR2 was 0.90 (0.85–0.94), and the AUC of LR2 combined with CEUS was 0.92 (0.88–0.97), indicating that both had high diagnostic efficacies. We analyzed subgroups of pre- and postmenopausal women and found that LR2 combined with CEUS significantly improved the specificity of the test compared with LR2 alone in both subgroups. The limitations of this study include its single-center design and the relatively small number of patients. We performed case studies covering more regions and centers to further investigate the clinical value of LR2 alone and LR2 combined with CEUS in the evaluation of adnexal masses. In summary, ovarian malignant tumors are common malignant tumors of the female reproductive system with insidious onset, high morbidity and mortality, and poor prognosis, which require early detection and evaluation. Currently, ultrasonography is considered the main imaging tool for detecting adnexal masses, and LR2 can help junior doctors more accurately assess the nature of the mass based on ultrasonographic information, such as tumor size, blood flow, and cystic solid areas. CEUS, on the other hand, owing to its high sensitivity to blood flow, can play a significant role in the differential diagnosis of benign and malignant tumors and can significantly improve the accuracy of conventional ultrasound diagnosis. 5. Conclusion Our results show that the IOTA LR2 model has high sensitivity but low specificity, and can help sonographers initially determine the benign or malignant nature of adnexal masses. The combination of LR2 with CEUS can significantly reduce the misdiagnosis rate of LR2 alone; therefore, the combination of LR2 with CEUS has a higher value for clinical application, and can help sonographers more accurately assess the nature of adnexal masses in their clinical work. Declarations Acknowledgements: No funding or sponsorship was received for the current study or publication of this article. Authors’ contributions: (I) Conception and design: Tian C and Han YW. (II) Administrative support: Yan XN. (III) Provision of study materials or patients: Tian C. (IV) Collection and assembly of data: Han YW. (V) Data analysis and interpretation: Zhang JM. (VI) Manuscript writing: All authors. (VII) Final approval of manuscript: All authors. Funding: Hebei Provincial Health and Health Commission Scientific Research Fund Project: IOTA standard combined with ultrasound and contrast techniques to determine benign and malignant ovarian tumors. Data availability: All data generated or analyzed during the current study are included in this published article. Ethics approval and consent to participate: The current study was conducted in accordance with the declaration of Helsinki. The current study was conducted with approval from the Ethics Committee of The second Hospital of Hebei Medical University. Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. References Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer statistics, 2022. CA: a cancer journal for clinicians 72, 7–33, doi: 10.3322/caac.21708 (2022). Fei, H., Chen, S. & Xu, C. Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways. Journal of ovarian research 13, 82, doi: 10.1186/s13048-020-00680-1 (2020). Deslandes, A. et al. 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University","correspondingAuthor":false,"prefix":"","firstName":"Yiwei","middleName":"","lastName":"Han","suffix":""},{"id":265346720,"identity":"4e65dd24-0f9c-4676-815a-83a6cedd1f58","order_by":2,"name":"Jianmei Zhang","email":"","orcid":"","institution":"Xinhe county People’s Hospital of Hebei Province","correspondingAuthor":false,"prefix":"","firstName":"Jianmei","middleName":"","lastName":"Zhang","suffix":""},{"id":265346721,"identity":"74dd20de-15c9-4d68-9263-b5bbae5d04dc","order_by":3,"name":"Cai Tian","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIiWNgGAWjYBADHgYG5gMHPvwgXocBUAtb4sGZPSRoAVlkfJiDjQi18hG5Bx/z/Pkjwz+758NhoPvk+cUO4NdieCMv2Zi3zYBH4s7ZDYcLLBgMZ85OIKBlRo6ZNG8D0C83cjccnsHDkGBwm7AW8988fwx45G/kPDjMw0aEFnmJHDNmHjYDHoMbOQzEaTHgeWMsObfNmMfwRpoBMJAlCPtFvj3H8MObP3L2cjeSH3/48MNGnl+akC0XUBVI4FcOtqX/AGFFo2AUjIJRMMIBAGh4QzBJSbslAAAAAElFTkSuQmCC","orcid":"","institution":"Second Hospital of Hebei Medical University","correspondingAuthor":true,"prefix":"","firstName":"Cai","middleName":"","lastName":"Tian","suffix":""}],"badges":[],"createdAt":"2023-12-28 09:03:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3815785/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3815785/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49310195,"identity":"ccaab958-6d6e-4b39-bf39-efe13bbde288","added_by":"auto","created_at":"2024-01-08 13:02:48","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42813,"visible":true,"origin":"","legend":"\u003cp\u003eAdnexal masses with ascites\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/7411e4225152303d138174a8.jpeg"},{"id":49310381,"identity":"585fe86c-0024-4e51-89d9-fb5c0929d660","added_by":"auto","created_at":"2024-01-08 13:10:48","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50552,"visible":true,"origin":"","legend":"\u003cp\u003eBlood flow signal on the nipple of the inner wall of the cyst\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/0d5413f261fa1e6813c343ff.jpeg"},{"id":49310189,"identity":"70b39e5f-90a5-44be-ade6-e8d971cb165a","added_by":"auto","created_at":"2024-01-08 13:02:48","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":67124,"visible":true,"origin":"","legend":"\u003cp\u003eSolid tumor\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/49cff8fab2a549f7e34bf32a.jpeg"},{"id":49310382,"identity":"a48a0415-6fa8-43a8-ac8a-45d693dc9526","added_by":"auto","created_at":"2024-01-08 13:10:48","extension":"jpeg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":56495,"visible":true,"origin":"","legend":"\u003cp\u003eIrregular masses\u003c/p\u003e","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/f0c3b921c8d8461a02f948d2.jpeg"},{"id":49310380,"identity":"942fba96-b246-4b69-96b4-abf09385af3d","added_by":"auto","created_at":"2024-01-08 13:10:48","extension":"jpeg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":53854,"visible":true,"origin":"","legend":"\u003cp\u003eThe rear of the tumor is accompanied by sound shadow\u003c/p\u003e","description":"","filename":"floatimage5.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/75218e066486cded81f94df9.jpeg"},{"id":49310190,"identity":"d7c5d3f2-fe67-4bd9-8ef9-49d581438826","added_by":"auto","created_at":"2024-01-08 13:02:48","extension":"jpeg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":96352,"visible":true,"origin":"","legend":"\u003cp\u003eROC curves for determining the benign and malignant nature of ovarian tumors using IOTA LR2 and IOTA LR2 combined with CEUS\u003c/p\u003e","description":"","filename":"floatimage6.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/a1cee9c459722d6476692bbf.jpeg"},{"id":51112054,"identity":"cdc36370-daf2-4207-a5ec-e3d69eb71262","added_by":"auto","created_at":"2024-02-14 10:07:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":638184,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3815785/v1/a8227fe6-dbae-4708-b0cc-957161f77d7d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Value of IOTA LR2 and IOTA LR2 Combined with CEUS in Assessing the Nature of Adnexal Masses","fulltext":[{"header":"1.Introduction","content":"\u003cp\u003eOvarian cancer is the fifth leading cause of cancer-related death among women. Among the tumors of the female reproductive system, ovarian cancer is second in incidence only to uterine body and cervical cancers and has the highest mortality rate, posing a serious threat to women's lives and health\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Ovarian cancer lacks typical clinical manifestations in the early stages, so it is often detected at a late stage, and the prognosis of patients is poor, with a 5-year survival rate of only approximately 28%. Early detection of adnexal masses and early evaluation of their benign or malignant nature are of great clinical significance for improving the prognosis of patients with ovarian cancer.\u003c/p\u003e \u003cp\u003eCurrently, ultrasound is the imaging method of choice for evaluating the benignity or malignancy of adnexal masses\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e; it is a low-cost and easily accessible examination method with rapid, safe, convenient, and reproducible imaging technology that is capable of dynamic, real-time, and non-invasive examination of the structure of the internal tissues of the human body and blood flow, among other characteristics. However, the ultrasound diagnosis of benign and malignant adnexal masses is mainly based on the subjective judgment of the examiner and is therefore highly dependent on the examiner's personal skills and experience\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn order to accurately predict the benign or malignant nature of adnexal masses to help clinicians choose more appropriate treatments, a number of ultrasound-related guidelines, grading systems, and prediction models have been developed\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. International Ovarian Tumour Analysis (IOTA) is the largest multicenter, large-sample study of ultrasound for determining the nature of ovarian tumors, and the logistic regression model 2 (LR2) is the product of a large-sample, prospective study based on IOTA\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn recent years, contrast-enhanced ultrasonography (CEUS) has been developing and advancing, and is able to better observe the characteristics of blood vessels in adnexal masses\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Compared with color Doppler ultrasound, CEUS can show the blood flow of microvessels in adnexal masses in real time, dynamically, and clearly, and can help doctors more accurately assess adnexal masses that are difficult to identify as benign or malignant by traditional ultrasound\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. The aim of this study was to investigate the ability of the IOTA LR2 and IOTA LR2 combined with CEUS to assess the benign or malignant nature of adnexal masses in patients and to validate it on the basis of postoperative pathological findings to explore the clinical value of the IOTA LR2 and IOTA LR2 combined with ultrasonography in predicting the nature of adnexal masses.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Materials\u003c/h2\u003e \u003cp\u003e Data were collected from 202 female patients who were admitted to the Department of Gynecology of the Second Hospital of Hebei Medical University and underwent surgery for adnexal masses from July 2019 to June 2022, including the patient's age, menstrual status (\u0026ge;\u0026thinsp;50 years of age and who underwent a hysterectomy and were categorized as postmenopausal), history of ovarian and breast cancers, the number of first-degree relatives with ovarian or breast cancers, the record of this surgery, and the complete postoperative clinical information including pathology results. The inclusion criteria were: 1. Adnexal mass detected by preoperative color Doppler ultrasonography; 2. surgical treatment at the Department of Gynecology, The Second Hospital of Hebei Medical University, within 120 days after the last ultrasonography; 3. Ultrasonography performed within 2 weeks before surgery; 4. Pathological results for the adnexal tumor; 5. Complete clinical data. The exclusion criteria were: 1. physiological cysts; 2. Adnexal masses combined with pregnancy; 3. History of adnexal malignant tumors; 4. Unclear pathological results; 5. Poor image quality or images without diagnostic signs. Based on the inclusion and exclusion criteria, 198 patients aged 9\u0026ndash;79 years, 124 premenopausal women, and 74 postmenopausal women were included in this study. This study was approved by the Ethics Committee of the Second Hospital of Hebei Medical University, and written informed consent was obtained from all patients.\u003c/p\u003e \u003cp\u003eUltrasonography was performed by a sonographer with seven or more years of experience in gynecological ultrasonography who performed a thorough examination of the uterus, adnexa, and pelvis and analyzed and diagnosed according to the characteristics of the ultrasound image. Routine ultrasound imaging parameters included location, number, size, shape, echogenicity, borders, posterior echogenicity, blood flow, and concomitant ascites of the mass. Images were acquired using a 5\u0026ndash;9 MHz intracavitary ultrasound probe. If the mass was too large to be visualized with transcavitary ultrasound, ultrasound images were acquired transabdominally using a 1\u0026ndash;5 MHz curved probe. Patients\u0026rsquo; ultrasound images were stored and acquired using the ultrasound working system of the Second Hospital of Hebei Medical University.\u003c/p\u003e \u003cp\u003eSonoVue, an intravenous contrast agent manufactured by Bracco, Italy, was used as the contrast agent. Each SonoVue contrast agent contained 59 mg of phospholipid-coated sulfur hexafluoride (SF6) gas microbubbles, which were added to 5 mL of saline for injection and shaken vigorously to obtain a microbubble suspension with an average microbubble diameter of 2.5 \u0026micro;m.\u003c/p\u003e \u003cp\u003eMethods for determining the nature of ovarian tumors: The ultrasound characteristics of adnexal masses were evaluated according to LR2 and LR2 combined with ultrasonography, during which the sonographer was blinded to the patient's histopathological findings. The LR2 model included: 1. Age (years); 2. Presence of peritoneal effusion; 3. Presence of a papillary protuberance with blood flow; 4. Maximum diameter of the solid portion (if the maximum diameter was \u0026ge;\u0026thinsp;50 mm, it was recorded as 50 mm because a diameter\u0026thinsp;\u0026gt;\u0026thinsp;50 mm does not increase the risk value with its growth); 5. Presence of irregularities in the inner wall of the cyst; and 6. Presence of acoustic shadows (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). The benign and malignant risk values (%) were calculated by applying the LR2 software to the above six parameters. The risk value ranges from 1\u0026ndash;95%, taking\u0026thinsp;\u0026ge;\u0026thinsp;10% as the malignant cutoff value, i.e., \u0026lt;\u0026thinsp;10% is considered benign and \u0026ge;\u0026thinsp;10% is suspected malignant. Ultrasonography scoring criteria were used to assess the characteristics of peritoneal enhancement (0 points for intact, 1 point for inconspicuous or incomplete), the thickness of peritoneal enhancement (0 points for homogeneous, 1 point for uneven thickness), the characteristics of enhancement at peak enhancement compared with that of the peritoneum (0 points for no enhancement of the enhancement within the lesion, 1 point for low enhancement, and 2 points for equivocal or high enhancement), the internal area of lesion enhancement (homogeneous enhancement\u0026thinsp;=\u0026thinsp;0 points, non-homogeneous enhancement\u0026thinsp;=\u0026thinsp;1 point), and segregation within the lesion (no segregation-like enhancement\u0026thinsp;=\u0026thinsp;0 points, segregation-like enhancement\u0026thinsp;=\u0026thinsp;1 point), with a total score of 0\u0026ndash;6 points, and a total score of \u0026ge;\u0026thinsp;4 points was classified as malignant, and \u0026le;\u0026thinsp;3 points was classified as benign. Finally, histopathological results were compared with those of the patients.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Methods\u003c/h2\u003e \u003cp\u003eSPSS 20.0 statistical software were applied for statistical analysis. The chi-square test was used for categorical variable comparisons and the independent sample t-test or rank-sum test was used for continuous variable comparisons. Kappa coefficient was used to assess intergroup consistency, with κ\u0026thinsp;\u0026ge;\u0026thinsp;0.75 indicating high consistency, 0.40\u0026thinsp;\u0026le;\u0026thinsp;κ\u0026thinsp;\u0026lt;\u0026thinsp;0.75 indicating medium consistency, and κ\u0026thinsp;\u0026lt;\u0026thinsp;0.40 indicating low consistency. The diagnostic performance of the ultrasound classification system was tested by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eSurgical excision was performed for 198 ovarian tumor tissue specimens. Among them, 132 (66.7%) were benign and 66 (33.3%) were nonbenign. LR2 assessed 118 patients (59.6%) as benign and 80 (40.4%) as nonbenign (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). LR2 combined with CEUS assessed 125 (63.1%) patients as benign and 73 (36.9%) as nonbenign (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOf 124 premenopausal women, 105 (84.7%) were benign, and 19 (15.3%) were non-benign. LR2 assessed 96 patients (77.4%) as benign and 28 (22.6%) as nonbenign (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). LR2 combined with CEUS assessed 100 patients (80.6%) as benign and 24 (19.4%) as non-benign(Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOf 74 postmenopausal women, 27 (36.5%) were benign and 47 (63.5%) were nonbenign. LR2 classified 22 patients (29.7%) as benign and 52 (70.3%) as nonbenign (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). LR2 combined with CEUS evaluated 25 patients (33.8%) as benign and 49 (66.2%) as nonbenign(Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe sensitivity of LR2 diagnosis was 93.94%, the specificity was 86.36%, the positive predictive value was 77.5%, the negative predictive value was 96.61%, the positive likelihood ratio was 6.89%, the negative likelihood ratio was 0.07%, and the diagnostic accuracy was 88.89%. The diagnostic concordance with pathology was good, with a κ-value of 0.763; \u0026gt;0.75 indicates good concordance between LR2 and pathology, and P\u0026thinsp;\u0026lt;\u0026thinsp;0.01 indicates a statistically significant difference between the results of LR2 and pathology. The diagnostic sensitivity of LR2 in combination with CEUS was 92.42%, the specificity was 90.91%, the positive predictive value was 83.56%, the negative predictive value was 96%, the positive likelihood ratio was 10.17, negative likelihood ratio 0.08, diagnostic accuracy 91.41%. The diagnostic concordance with pathology was good, with a κ-value of 0.81\u0026thinsp;\u0026gt;\u0026thinsp;0.75, indicating good concordance between the two methods of LR2 combined with CEUS and pathology (P\u0026thinsp;=\u0026thinsp;0.143, indicating that LR2 combined with CEUS did not significantly from pathology).\u003c/p\u003e \u003cp\u003eIn non-menopausal women, LR2 diagnosis had a sensitivity of 89.47%, a specificity of 89.52%, a positive predictive value of 60.71%, a negative predictive value of 97.92%, a positive likelihood ratio of 8.54% and, negative likelihood ratio of 0.12%, and a diagnostic accuracy of 89.52%. Concordance with the pathological diagnosis was moderate, with a κ-value of 0.662 (P\u0026thinsp;=\u0026thinsp;0.022). The sensitivity of LR2 combined with CEUS diagnosis was 89.47%, the specificity was 93.33%, the positive predictive value was 70.83%, the negative predictive value was 98%, the positive likelihood ratio was 13.41, the negative likelihood ratio was 0.07, and the diagnostic accuracy was 92.74%. Concordance with the pathological diagnosis was good, with a κ-value of 0.748 (P\u0026thinsp;=\u0026thinsp;0.18).\u003c/p\u003e \u003cp\u003eIn postmenopausal women, the sensitivity of LR2 diagnosis was 95.74%, the specificity was 74.07%, the positive predictive value was 86.54%, the negative predictive value was 90.91%, the positive likelihood ratio was 3.69%, the negative likelihood ratio was 0.06%, and the diagnostic accuracy was 87.84%. Concordance with the pathological diagnosis was moderate, with a κ-value of 0.662 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). The sensitivity of LR2 combined with CEUS diagnosis was 93.62%, the specificity was 81.48%, the positive predictive value was 89.8%, the negative predictive value was 88%, the positive likelihood ratio was 5.06%, and the negative likelihood ratio was 0.23%, with a diagnostic accuracy of 89.19%. Concordance with the pathological diagnosis was good, with a κ-value of 0.763 (P\u0026thinsp;=\u0026thinsp;0.727) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe diagnostic efficacy of LR2 for identifying benign and malignant ovarian tumors showed an AUC of 0.90 (0.85\u0026ndash;0.94). The diagnostic efficacy of LR2 combined with CEUS in identifying benign and malignant ovarian tumors showed an AUC of 0.92 (0.88\u0026ndash;0.97) (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparision of results of IOTA LR2 with histopathological findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparision of results of Premenopausal IOTA LR2 with histopathological findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e114\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparision of results of Postmenopausal IOTA LR2 with histopathological findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of IOTA LR2 combined with CEUS results and histopathologic findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2 combined with CEUS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e120\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e198\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Premenopausal IOTA LR2 combined with CEUS results and histopathologic findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2 combined with CEUS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Postmenopausal IOTA LR2 combined with CEUS results and histopathologic findings\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNature of the Mass as per IOTA LR2 combined with CEUS\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eHistopathological Result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBenign\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEfficacy of IOTA LR2 and IOTA LR2 Combined With CEUS Scoring System in Diagnosing Benign and Malignant Ovarian Tumors (%)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSpecificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNPV\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAccuracy\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLR2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e93.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e77.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e88.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLR2 combined with CEUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e92.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e90.91\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e83.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e91.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eOvarian malignant tumors are the seventh most common cancer in women\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, the third most common in the incidence of malignant tumors of the female reproductive system, and have the highest mortality rate among malignant tumors of the female reproductive system\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, which is a serious threat to women's life and health and a major burden to global public health\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e. The stage of malignant ovarian tumors directly affects patient prognosis. Research shows that the five-year survival rate of patients with stage I ovarian cancer is 90%\u003csup\u003e14\u003c/sup\u003e, while that of patients with stage III and IV ovarian cancer is only 25%-30%\u003csup\u003e15\u003c/sup\u003e. However, because of the insidious onset of ovarian cancer, strong invasiveness, and atypical clinical symptoms in the early stage, more than 70% of patients are diagnosed when already in the late stage\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e; hence, it is especially important to accurately predict the benignity or malignancy of adnexal tumors in the early stage.\u003c/p\u003e \u003cp\u003eUltrasound imaging technology is fast, safe, convenient, and repeatable, and is currently the main imaging method for detecting adnexal masses\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e. The intracavitary ultrasound probe can be placed in the vagina close to the vaginal fornix and cervix, so that the acoustic images of the pelvic organs can be displayed more clearly. In recent years, with the widespread use of intracavitary ultrasound, the accuracy and sensitivity of ultrasound in the diagnosis and treatment of adnexal masses have improved remarkably\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The ability of ultrasound to distinguish the nature of adnexal masses has important significance for the prognosis of patients with ovarian cancer.\u003c/p\u003e \u003cp\u003eAdnexal masses are complex in origin, especially ovarian lesions. The ovary is the organ of female germ cells and sex hormone production, and the epithelial cells on its surface differentiate in multiple directions; therefore, physiologic and pathologic alterations are complex, the histologic types are numerous, and masses of different histologic origins have different morphologic characteristics, often exhibiting homogeneous and homogeneous heterogeneity. The subjective judgment of the sonographer is considered the most effective method for identifying the nature of adnexal masses before surgery; therefore, the seniority and experience of the sonographer significantly affects the accuracy of identification of benign and malignant pelvic masses, and sonographers with lower seniority due to less experience often have a low judgment accuracy rate\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIt is difficult to preoperatively differentiate between benign and malignant adnexal masses. Correct identification of the characteristics of adnexal masses by the sonographer is very important in the selection of treatment for the patient, which helps the clinician to help the patient to choose the most appropriate treatment, such as whether or not to opt for surgical treatment and to choose the extent of the surgery, so as to improve the survival rate and quality of life\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Accurate assessment of the nature of the mass can also reduce unnecessary treatment and save medical resources\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. The ultrasound team has recently developed a large number of scoring systems and diagnostic models to facilitate more accurate identification of the nature of adnexal masses during ultrasound examinations\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e. IOTA Working Group, a multicenter, large-sample, and ongoing team of researchers on adnexal lesions, is the largest study to date analyzing the ultrasonographic characteristics of benign and malignant adnexal masses\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. IOTA LR2 is a product of IOTA's prospective study based on a large sample, which focuses more on ultrasound characteristics, including six parameters such as the patient's age, the presence of peritoneal effusion, the presence of papillae with blood flow, the maximal diameter of the solid portion, the regularity of the cyst's inner wall, and the presence of an acoustic shadow, and therefore has a high degree of sensitivity to detect as many true positive patients as possible\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAngiogenesis is closely related to tumor growth and metastasis, and is an independent prognostic indicator for the survival of patients with malignant tumors\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. CEUS is a blood flow perfusion imaging method in which a contrast agent is pushed into the body by intravenous injection, and can reach the lesion with the blood flow to enhance the scattered signal intensity of the blood flow in the lesion. CEUS can clearly display the microvascular blood flow within the adnexal mass, and accurately evaluate the order and intensity of blood flow perfusion in the tumor, which is considered a better technique for identifying the nature of the adnexal mass\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study included 198 eligible patients with adnexal masses to investigate the ability of the IOTA LR2 and IOTA LR2 combined with ultrasonography to preoperatively assess the benignity and malignancy of adnexal masses. The study procedure was double-blind, meaning that the sonographer was unaware of the patient's histopathological findings.\u003c/p\u003e \u003cp\u003eSensitivity is a measure of the ability of the diagnostic method to detect the presence of a disease, also known as the true positive rate; and specificity is a measure of the ability of the diagnostic method to correctly determine the absence of disease, also known as the true negative rate. The results of the present study showed that the sensitivity of the IOTA LR2 was 93.94% with a specificity of 86.36%, and that LR2 in combination with CEUS had a sensitivity of 92.42% with a specificity of 90.91%; this indicates that the diagnostic rate of LR2 is high, but the misdiagnosis rate is also high, whereas LR2 combined with CEUS can significantly improve the specificity and reduce the chance of misdiagnosis. Positive predictive value refers to the proportion of true positives to all positive results detected, and the negative predictive value is the opposite, i.e., the proportion of true negatives to all negative cases detected. Positive and negative predictive values are the diagnostic indexes of most concern to clinicians. The positive predictive value of LR2 in this study was 77.5%, and the negative predictive value was 96.61%; the positive predictive value of LR2 combined with CEUS was 83.56%, and the negative predictive value was 96%. The positive predictive value of LR2 combined with CEUS was significantly higher than that of LR2, but the positive and the negative predictive values were affected by the prevalence rate, while the likelihood ratio could exclude this interference, and the results would be more stable; the positive likelihood ratio for LR2 in the present study was 6.89%, and the negative likelihood ratio was 0.07%. The positive likelihood ratio of LR2 combined with CEUS was 10.17%, and the negative likelihood ratio was 0.08%. When the positive likelihood ratio is \u0026gt;\u0026thinsp;10 and the negative likelihood ratio is \u0026lt;\u0026thinsp;0.1, the test being evaluated is regarded as an ideal test. This further indicates that LR2 has a low leakage rate but a relatively high misdiagnosis rate, and that the misdiagnosis rate can be significantly reduced affecting the leakage rate by combining LR2 with CEUS. The area under the ROC curve (AUC) is currently considered a good indicator for evaluating the diagnostic efficacy of diagnostic tests, with AUC values closer to 1 indicating higher diagnostic efficacy, and those closer to 0.5 indicating poorer diagnostic efficacy. In this study, the AUC of IOTA LR2 was 0.90 (0.85\u0026ndash;0.94), and the AUC of LR2 combined with CEUS was 0.92 (0.88\u0026ndash;0.97), indicating that both had high diagnostic efficacies. We analyzed subgroups of pre- and postmenopausal women and found that LR2 combined with CEUS significantly improved the specificity of the test compared with LR2 alone in both subgroups.\u003c/p\u003e \u003cp\u003eThe limitations of this study include its single-center design and the relatively small number of patients. We performed case studies covering more regions and centers to further investigate the clinical value of LR2 alone and LR2 combined with CEUS in the evaluation of adnexal masses.\u003c/p\u003e \u003cp\u003eIn summary, ovarian malignant tumors are common malignant tumors of the female reproductive system with insidious onset, high morbidity and mortality, and poor prognosis, which require early detection and evaluation. Currently, ultrasonography is considered the main imaging tool for detecting adnexal masses, and LR2 can help junior doctors more accurately assess the nature of the mass based on ultrasonographic information, such as tumor size, blood flow, and cystic solid areas. CEUS, on the other hand, owing to its high sensitivity to blood flow, can play a significant role in the differential diagnosis of benign and malignant tumors and can significantly improve the accuracy of conventional ultrasound diagnosis.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eOur results show that the IOTA LR2 model has high sensitivity but low specificity, and can help sonographers initially determine the benign or malignant nature of adnexal masses. The combination of LR2 with CEUS can significantly reduce the misdiagnosis rate of LR2 alone; therefore, the combination of LR2 with CEUS has a higher value for clinical application, and can help sonographers more accurately assess the nature of adnexal masses in their clinical work.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAcknowledgements: No funding or sponsorship was received for the current study or publication of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions: (I) Conception and design: Tian C and Han YW. (II) Administrative support: Yan XN. (III) Provision of study materials or patients: Tian C. (IV) Collection and assembly of data: Han YW. (V) Data analysis and interpretation: Zhang JM. (VI) Manuscript writing: All authors. (VII) Final approval of manuscript: All authors.\u003c/p\u003e\n\u003cp\u003eFunding: Hebei Provincial Health and Health Commission Scientific Research Fund Project: IOTA standard combined with ultrasound and contrast techniques to determine benign and malignant ovarian tumors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData availability: All data generated or analyzed during the current study are included in this published article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate:\u0026nbsp;The current study was conducted in accordance with the declaration of Helsinki. The current study was conducted with approval from the Ethics Committee of The second Hospital of Hebei Medical University. Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003eConsent for publication: Not applicable.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel, R. L., Miller, K. D., Fuchs, H. E. \u0026amp; Jemal, A. Cancer statistics, 2022. CA: a cancer journal for clinicians 72, 7\u0026ndash;33, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21708\u003c/span\u003e\u003cspan address=\"10.3322/caac.21708\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFei, H., Chen, S. \u0026amp; Xu, C. Bioinformatics analysis of gene expression profile of serous ovarian carcinomas to screen key genes and pathways. 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Journal of ultrasound 13, 9\u0026ndash;15, doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jus.2009.09.007\u003c/span\u003e\u003cspan address=\"10.1016/j.jus.2009.09.007\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2010).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"IOTA LR2, CEUS, adnexal mass, ultrasound diagnosis","lastPublishedDoi":"10.21203/rs.3.rs-3815785/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3815785/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eTo investigate the preoperative assessment of adnexal tumor benignity and malignancy using the International Ovarian Tumour Analysis (IOTA) logistic regression model 2 (LR2) and LR2 combined with contrast-enhanced ultrasound (CEUS). Clinical application of LR2 and CEUS in the preoperative assessment of adnexal tumors was evaluated.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eOne hundred and ninety-eight adnexal tumors were selected, and their nature was evaluated preoperatively according to IOTA LR2 and LR2 combined with CEUS. Pathological and long-term follow-up results were used as the gold standard for comparison.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eFor the diagnostic efficacy of LR2 for identifying the nature of ovarian masses, the AUC was 0.90 (0.85\u0026ndash;0.94). For the diagnostic efficacy of LR2 combined with CEUS in identifying the benign and malignant nature of ovarian tumors, the AUC was 0.92 (0.88\u0026ndash;0.97).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe IOTA LR2 model has high sensitivity but low specificity. Its diagnostic specificity can be significantly improved by combining it with CEUS. Therefore, LR2 combined with CEUS has high clinical value and can help ultrasonographers determine the benign or malignant nature of adnexal tumors.\u003c/p\u003e","manuscriptTitle":"Clinical Value of IOTA LR2 and IOTA LR2 Combined with CEUS in Assessing the Nature of Adnexal Masses","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-08 13:02:43","doi":"10.21203/rs.3.rs-3815785/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"116dff53-40f9-4583-a867-9d825f8466de","owner":[],"postedDate":"January 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":27967179,"name":"Biological sciences/Cancer/Cancer imaging"},{"id":27967180,"name":"Health sciences/Oncology/Cancer"}],"tags":[],"updatedAt":"2024-02-14T09:59:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-08 13:02:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3815785","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-3815785","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}