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The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5γ2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P

Background: Abnormal uterine bleeding (AUB) represents a common diagnostic challenge, as it might be related to both benign and malignant conditions. Endometrial cancer may not be detected with blind uterine cavity sampling by dilatation and curettage or suction devices. Several scoring systems using different ultrasound image characteristics were recently proposed to estimate the risk of endometrial cancer (EC) in women with AUB. Aim: The aim of the present study was to externally validate the predictive value of the recently proposed scoring systems including the Risk of Endometrial Cancer scoring model (REC) for EC risk stratification. Material and methods: It was a retrospective cohort study of women with postmenopausal bleeding. From June 2012 to June 2020 we studied a group of 394 women who underwent standard transvaginal ultrasound examination followed by power Doppler intrauterine vascularity assessment. Selected ultrasound features of endometrial lesions were assessed in each patient. Results: The median age was 60.3 years (range ± 10.7). The median body mass index (BMI) was 30.4 (range ± 6.0). Histological examination revealed 158 cases of endometrial hyperplasia (EH) and 236 cases of EC. Of the studied ultrasound endometrial features, the highest areas under the curve (AUCs) were found for endometrial thickness (ET) (AUC = 0.76; 95% CI: 0.71–0.81) and for interrupted endomyometrial junction (AUC = 0.70, 95% CI: 0.65–0.75). Selected scoring systems presented moderate to good predictive performance in differentiating EC and EH. The highest AUC was found for REC model (AUC = 0.75, 95% CI: 0.70–0.79) and for the basic model that included ET, Doppler score and interrupted endometrial junction (AUC = 0.77, 95% CI: 0.73–0.82). REC model was more accurate than other scoring systems and selected single features for differentiating benign hyperplasia from EC at early stages, regardless of menopausal status. Conclusions: New scoring systems, including the REC model may be used in women with AUB for more efficient differentiation between benign and malignant conditions.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinomas.METHODS: This was a retrospective multicenter study of patients with a histological diagnosis of pure endometrioid carcinoma. We identified 161 patients from the International Ovarian Tumor Analysis (IOTA) database who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016, and another 78 patients from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition.RESULTS: Median age of the 239 patients was 55 years (range, 19-88 years). On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. Median largest tumor diameter was 102.5 mm (range, 20-300 mm) and median largest diameter of the largest solid component was 63 mm (range, 9-300 mm). Papillary projections were present in 70 (29.3%) masses. Most cancers (188 (78.7%)) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to develop from endometriosis. These cancers, compared with those without evidence of tumor developing from endometriosis, more often manifested papillary projections on ultrasound (46.9% (23/49) vs 24.7% (47/190)), were less often bilateral (8.2% (4/49) vs 24.7% (47/190)) and less often associated with ascites (6.1% (3/49) vs 28.4% (54/190)) and fluid in the pouch of Douglas (24.5% (12/49) vs 48.9% (93/190)). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor developing from endometriosis (36.3% (41/113)) had a large central solid component entrapped within locules, giving the tumor a cockade-like appearance.CONCLUSIONS: Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas developing from endometriosis differ from those without evidence of tumor developing from endometriosis, the former being more often unilateral cysts with papillary projections and no ascites. (Less)

BACKGROUND: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. OBJECTIVE: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. STUDY DESIGN: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. RESULTS: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (

Purpose: To externally validate and compare the performance of previously published diagnostic models developed to predict malignancy in adnexal masses. Experimental Design: We externally validated the diagnostic performance of 11 models developed by the International Ovarian Tumor Analysis (IOTA) group and 12 other (non-IOTA) models on 997 prospectively collected patients. The non-IOTA models included the original risk of malignancy index (RMI), three modified versions of the RMI, six logistic regression models, and two artificial neural networks. The ability of the models to discriminate between benign and malignant adnexal masses was expressed as the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and likelihood ratios (LR+, LR−). Results: Seven hundred and forty-two (74%) benign and 255 (26%) malignant masses were included. The IOTA models did better than the non-IOTA models (AUCs between 0.941 and 0.956 vs. 0.839 and 0.928). The difference in AUC between the best IOTA and the best non-IOTA model was 0.028 [95% confidence interval (CI), 0.011–0.044]. The AUC of the RMI was 0.911 (difference with the best IOTA model, 0.044; 95% CI, 0.024–0.064). The superior performance of the IOTA models was most pronounced in premenopausal patients but was also observed in postmenopausal patients. IOTA models were better able to detect stage I ovarian cancer. Conclusion: External validation shows that the IOTA models outperform other models, including the current reference test RMI, for discriminating between benign and malignant adnexal masses. Clin Cancer Res; 18(3); 815–25. ©2011 AACR.

Background: The CA-125 tumor marker has limitations when used to distinguish between benign and malignant ovarian masses. We therefore establish likelihood curves of six subgroups of ovarian pathology based on CA-125 and menopausal status. Methods: This cross-sectional study conducted by the International Ovarian Tumor Analysis group involved 3,511 patients presenting with a persistent adnexal mass that underwent surgical intervention. CA-125 distributions for six tumor subgroups (endometriomas and abscesses, other benign tumors, borderline tumors, stage I invasive cancers, stage II–IV invasive cancers, and metastatic tumors) were estimated using kernel density estimation with stratification for menopausal status. Likelihood curves for the tumor subgroups were derived from the distributions. Results: Endometriomas and abscesses were the only benign pathologies with median CA-125 levels above 20 U/mL (43 and 45, respectively). Borderline and invasive stage I tumors had relatively low median CA-125 levels (29 and 81 U/mL, respectively). The CA-125 distributions of stage II–IV invasive cancers and benign tumors other than endometriomas or abscesses were well separated; the distributions of the other subgroups overlapped substantially. This held for premenopausal and postmenopausal patients. Likelihood curves and reference tables comprehensibly show how subgroup likelihoods change with CA-125 and menopausal status. Conclusions and Impact: Our results confirm the limited clinical value of CA-125 for preoperative discrimination between benign and malignant ovarian pathology. We have shown that CA-125 may be used in a different way. By using likelihood reference tables, we believe clinicians will be better able to interpret preoperative serum CA-125 results in patients with adnexal masses. Cancer Epidemiol Biomarkers Prev; 20(11); 2420–8. ©2011 AACR.

Objectives To describe clinical history and ultrasound findings in patients with tubal carcinoma. Methods Patients with a histological diagnosis of tubal cancer who had undergone preoperative ultrasound examination were identified from the databases of 13 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed together all available digital ultrasound images and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings. Results We identified 79 women with a histological diagnosis of primary tubal cancer, 70 of whom (89%) had serous carcinomas and 46 (58%) of whom presented at FIGO stage III. Forty-nine (62%) women were asymptomatic (incidental finding), whilst the remaining 30 complained of abdominal bloating or pain. Fifty-three (67%) tumors were described as solid at ultrasound examination, 14 (18%) as multilocular solid, 10 (13%) as unilocular solid and two (3%) as unilocular. No tumor was described as a multilocular mass. Most tumors (70/79, 89%) were moderately or very well vascularized on color or power Doppler ultrasound. Normal ovarian tissue was identified adjacent to the tumor in 51% (39/77) of cases. Three types of ultrasound appearance were identified as being typical of tubal carcinoma using pattern recognition: a sausage-shaped cystic structure with solid tissue protruding into it like a papillary projection (11/62, 18%); a sausage-shaped cystic structure with a large solid component filling part of the cyst cavity (13/62, 21%); an ovoid or oblong completely solid mass (36/62, 58%). Conclusions A well vascularized ovoid or sausage-shaped structure, either completely solid or with large solid component(s) in the pelvis, should raise the suspicion of tubal cancer, especially if normal ovarian tissue is seen adjacent to it. Copyright (C) 2013 ISUOG. Published by John Wiley & Sons Ltd. (Less)

OBJECTIVES: To develop a risk prediction model to preoperatively discriminate between benign, borderline, stage I invasive, stage II-IV invasive, and secondary metastatic ovarian tumours. DESIGN: Observational diagnostic study using prospectively collected clinical and ultrasound data. SETTING: 24 ultrasound centres in 10 countries. PARTICIPANTS: Women with an ovarian (including para-ovarian and tubal) mass and who underwent a standardised ultrasound examination before surgery. The model was developed on 3506 patients recruited between 1999 and 2007, temporally validated on 2403 patients recruited between 2009 and 2012, and then updated on all 5909 patients. MAIN OUTCOME MEASURES: Histological classification and surgical staging of the mass. RESULTS: The Assessment of Different NEoplasias in the adneXa (ADNEX) model contains three clinical and six ultrasound predictors: age, serum CA-125 level, type of centre (oncology centres v other hospitals), maximum diameter of lesion, proportion of solid tissue, more than 10 cyst locules, number of papillary projections, acoustic shadows, and ascites. The area under the receiver operating characteristic curve (AUC) for the classic discrimination between benign and malignant tumours was 0.94 (0.93 to 0.95) on temporal validation. The AUC was 0.85 for benign versus borderline, 0.92 for benign versus stage I cancer, 0.99 for benign versus stage II-IV cancer, and 0.95 for benign versus secondary metastatic. AUCs between malignant subtypes varied between 0.71 and 0.95, with an AUC of 0.75 for borderline versus stage I cancer and 0.82 for stage II-IV versus secondary metastatic. Calibration curves showed that the estimated risks were accurate. CONCLUSIONS: The ADNEX model discriminates well between benign and malignant tumours and offers fair to excellent discrimination between four types of ovarian malignancy. The use of ADNEX has the potential to improve triage and management decisions and so reduce morbidity and mortality associated with adnexal pathology. ispartof: BMJ - British Medical Journal vol:349 issue:oct07 3 ispartof: location:England status: published

Background:To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3.Methods:This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery.Results:The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5.Conclusions:This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.British Journal of Cancer advance online publication 17 June 2014; doi:10.1038/bjc.2014.333 www.bjcancer.com.

Objective: To compare the diagnostic value of the simultaneous evaluation of osteopontin (OPN), insulin-growth factor II (IGF II), leptin, prolactin with the use of transvaginal ultrasonography and CA 125 determination for detection of ovarian cancer. Material and methods: Eighty-three patients with an adnexal mass were included in this study and underwent sonography and ELISA assays of the four serum protein markers before surgery, associated also with the determination of CA125. For the evaluation of diagnostic performance of bio-markers we also used split-point analysis to produce a score-based classification method in which a score of 1 or below is required for benign mass, whereas a score of 2 or above indicates cancer. Results: Ten patients with ovarian cancer and 73 patients with benign ovarian neoplasm were included in the study. The median concentrations of OPN, IGF II, leptin and prolactin were not significantly different in the two groups of patients. With receiver operating characteristic curve analysis, the area under the curve was respectively 0.384 for OPN, 0.395 for IGF II, 0.570 for leptin, 0.453 for prolactin and 0.838 for CA125. Using split-point scoring methods, the simultaneous evaluation of the four new serum markers had sensitivity of 80% and specificity of 10%. With the use of only CA125 a sensitivity of 68% and specificity of 40% were obtained. The ultrasonography showed a sensitivity of 80% but a specificity of 92%. Conclusions: Although previously proposed with encouraging results in the screening of ovarian cancer, the simultaneous evaluation of these new biomarkers not seems to be useful in the preoperative evaluation of patients with an adnexal mass when compared with CA125 and transvaginal ultrasonography. This study was supported by Assessorato Igiene e Sanita, Regione Autonoma della Sardegna.