Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (24): clinical and ultrasound characteristics of ovarian mature cystic teratomas.

OBJECTIVE: To describe the clinical and ultrasound features of ovarian mature cystic teratomas (MCTs). METHODS: This was a retrospective study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histologically confirmed diagnosis of MCT who had undergone transvaginal ultrasound examination between 1999 and 2016 (IOTA phases 1, 2, 3 and 5) in one of five centers. Ultrasound was performed by an experienced examiner who used the standardized IOTA examination technique and terminology. In addition to extracting data from the IOTA database, available two-dimensional grayscale and color or power Doppler images were reviewed retrospectively to identify typical ultrasound features of MCT described previously and detect possible new features using pattern recognition. All images were reviewed by two independent examiners and further discussed with two ultrasound experts to reach consensus. RESULTS: Included in the study were 454 patients with histologically confirmed MCT. Median age was 33 (range, 8-90) years and 66 (14.5%) patients were postmenopausal. Most MCTs were described by the original ultrasound examiner as unilocular (262/454 (57.7%)) or multilocular (70/454 (15.4%)) cysts with mixed echogenicity of cystic fluid (368/454 (81.1%)), acoustic shadowing (328/454 (72.2%)) and no or little vascularization on color Doppler (color score 1, 240/454 (52.9%); color score 2, 123/454 (27.1%)). The median largest lesion diameter was 66 (range, 15-310) mm. A correct preoperative diagnosis of MCT was suggested by the original ultrasound examiner in 372/454 (81.9%) cases. On retrospective review of ultrasound images of 334 MCTs that had quality sufficient for assessment, 'dots and/or lines' and/or 'echogenic white ball' (typical features according to the literature) were present in 271/334 (81.1%) masses. We identified four new ultrasound features characteristic of MCT: 'cotton wool tufts', 'mushroom cap sign', 'completely hyperechogenic lesion' and 'starry sky sign'. At least one classical or novel ultrasound feature was present in 315/334 (94.3%) MCTs. Twenty-nine (8.7%) MCTs manifested vascularized solid tissue, of which seven exhibited no typical features. CONCLUSION: We provide a comprehensive overview of conventional and newly described ultrasound features of MCTs. Only a small proportion of MCTs did not manifest any of the typical features. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Imaging in gynecological disease (23): clinical and ultrasound characteristics of ovarian carcinosarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of ovarian carcinosarcoma. METHODS: This was a retrospective multicenter study. Patients with a histological diagnosis of ovarian carcinosarcoma, who had undergone preoperative ultrasound examination between 2010 and 2019, were identified from the International Ovarian Tumor Analysis (IOTA) database. Additional patients who were examined outside of the IOTA study were identified from the databases of the participating centers. The masses were described using the terms and definitions of the IOTA group. Additionally, two experienced ultrasound examiners reviewed all available images to identify typical ultrasound features using pattern recognition. RESULTS: Ninety-one patients with ovarian carcinosarcoma who had undergone ultrasound examination were identified, of whom 24 were examined within the IOTA studies and 67 were examined outside of the IOTA studies. Median age at diagnosis was 66 (range, 33-91) years and 84/91 (92.3%) patients were postmenopausal. Most patients (67/91, 73.6%) were symptomatic, with the most common complaint being pain (51/91, 56.0%). Most tumors (67/91, 73.6%) were International Federation of Gynecology and Obstetrics (FIGO) Stage III or IV. Bilateral lesions were observed on ultrasound in 46/91 (50.5%) patients. Ascites was present in 38/91 (41.8%) patients. The median largest tumor diameter was 100 (range, 18-260) mm. All ovarian carcinosarcomas contained solid components, and most were described as solid (66/91, 72.5%) or multilocular-solid (22/91, 24.2%). The median diameter of the largest solid component was 77.5 (range, 11-238) mm. Moderate or rich vascularization was found in 78/91 (85.7%) cases. Retrospective analysis of ultrasound images and videoclips using pattern recognition in 73 cases revealed that all tumors had irregular margins and inhomogeneous echogenicity of the solid components. Forty-seven of 73 (64.4%) masses appeared as a solid tumor with cystic areas. Cooked appearance of the solid tissue was identified in 28/73 (38.4%) tumors. No pathognomonic ultrasound sign of ovarian carcinosarcoma was found. CONCLUSIONS: Ovarian carcinosarcomas are usually diagnosed in postmenopausal women and at an advanced stage. The most common ultrasound appearance is a large solid tumor with irregular margins, inhomogeneous echogenicity of the solid tissue and cystic areas. The second most common pattern is a large multilocular-solid mass with inhomogeneous echogenicity of the solid tissue. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Reproductive outcome after early miscarriage: comparing vaginal misoprostol treatment with expectant management in a planned secondary analysis of a randomized controlled trial.

OBJECTIVE: To compare the reproductive outcome after early miscarriage between women managed expectantly and those treated with vaginal misoprostol. METHODS: This study was a planned secondary analysis of data collected prospectively in a randomized controlled trial comparing expectant management with vaginal misoprostol treatment (single dose of 800 µg) in women with early embryonic or anembryonic miscarriage and vaginal bleeding. The outcome measures were the number of women with a clinical pregnancy conceived within 14 months after complete miscarriage and the outcome of these pregnancies in terms of live birth, miscarriage, ectopic pregnancy and legal termination of pregnancy. The participants replied to a questionnaire sent by post covering their reproductive history ≤ 14 months after the index miscarriage was complete. Supplementary information and data for women who did not return their questionnaire were retrieved from medical records. RESULTS: Of 94 women randomized to misoprostol treatment and 95 allocated to expectant management, 94 and 90 women, respectively, were included for analysis. Information on reproductive outcome was available for 89/94 (95%) and 83/90 (92%) women, respectively. Complete miscarriage without surgical evacuation was achieved within 31 days in 85% (76/89) of the women in the misoprostol group and in 65% (54/83) of those managed expectantly. The proportion of women treated with surgical evacuation was 33% (27/83) in the expectant-management group vs 12% (11/89) in the misoprostol group. At 14 months after the index miscarriage was complete, 75% (67/89) of women treated with misoprostol and 75% (62/83) of those managed expectantly had achieved at least one clinical pregnancy, while 40% (36/89) and 35% (29/83), respectively, had had at least one live birth (mean difference, 5.5% (95% CI, -9.7 to 20.3%)). When considering the outcome of all pregnancies conceived within 14 months after the index miscarriage was complete, 63% (56/89) of women in the misoprostol group and 55% (46/83) of those in the expectant-management group delivered a live baby after a pregnancy (mean difference, 7.5% (95% CI, -7.9 to 22.4%)). CONCLUSION: Women with early miscarriage can be reassured that fertility is similar after misoprostol treatment and expectant management. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Psychological impact of early miscarriage and client satisfaction with treatment: comparison between expectant management and misoprostol treatment in a randomized controlled trial.

OBJECTIVES: To compare the short- and long-term emotional distress (grief, anxiety and depressive symptoms) after early miscarriage and satisfaction with treatment between women randomized to expectant management vs vaginal misoprostol treatment. METHODS: This was a preplanned analysis of data collected during a randomized controlled trial comparing expectant management with misoprostol treatment in women with early anembryonic or embryonic miscarriage and vaginal bleeding. If the miscarriage was not complete on day 31 after inclusion, surgical evacuation was recommended. The main outcomes were levels of anxiety and grief, depressive symptoms and client satisfaction with the treatment, which were assessed using the following validated psychometric self-assessment instruments: Spielberger State-Trait Anxiety Inventory (STAI, Form Y), Perinatal Grief Scale (PGS), Montgomery-Åsberg Depression Rating Scale (MADRS-S; self-reported version) and Client Satisfaction Questionnaire (CSQ-8). All women were assessed at four timepoints: on the day of randomization, on the day when the miscarriage was judged to be complete, and at 3 months and 14 months after complete miscarriage. The psychometric and client satisfaction scores were compared between the misoprostol group and the expectant-management group at each assessment. Analysis was performed by the intention-to-treat principle. RESULTS: Ninety women were randomized to expectant management and 94 to misoprostol treatment. The psychometric and client satisfaction scores were similar in the two treatment groups at all assessment timepoints. At inclusion, 41% (35/86) of the women managed expectantly and 37% (34/92) of those treated with misoprostol had a STAI-state score of > 46 ('high level of anxiety'), and 9% (8/86) and 10% (9/91), respectively, had symptoms of moderate or severe depression (MADRS-S score ≥ 20). In both treatment groups, symptom scores for anxiety and depression were significantly higher at inclusion than after treatment and remained low until 14 months after complete miscarriage. Grief reactions were mild in both groups, with a median PGS score of 40.0 at 3 months and 37.0 at 14 months after complete miscarriage in both treatment groups. Four women treated with misoprostol and two women managed expectantly had a PGS score of > 90 (indicating deep grief) 3 months after complete miscarriage, while one woman managed expectantly had a PGS score of > 90 14 months after complete miscarriage. Women in both treatment groups were satisfied with their management, as indicated by a median CSQ-8 score of > 25 at each assessment. More than 85% of participants in each of the two groups reported that they would recommend the treatment they received to a friend. CONCLUSIONS: The psychological response to and recovery after early miscarriage did not differ between women treated with misoprostol and those managed expectantly. Satisfaction with treatment was high in both treatment groups. Our findings support patient involvement when deciding on the management of early miscarriage. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding.

OBJECTIVE: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. RESULTS: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. CONCLUSIONS: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Vessel morphology depicted by three-dimensional power Doppler ultrasound as second-stage test in adnexal tumors that are difficult to classify: prospective diagnostic accuracy study.

OBJECTIVES: To assess whether vessel morphology depicted by three-dimensional (3D) power Doppler ultrasound improves discrimination between benignity and malignancy if used as a second-stage test in adnexal masses that are difficult to classify. METHODS: This was a prospective observational international multicenter diagnostic accuracy study. Consecutive patients with an adnexal mass underwent standardized transvaginal two-dimensional (2D) grayscale and color or power Doppler and 3D power Doppler ultrasound examination by an experienced examiner, and those with a 'difficult' tumor were included in the current analysis. A difficult tumor was defined as one in which the International Ovarian Tumor Analysis (IOTA) logistic regression model-1 (LR-1) yielded an ambiguous result (risk of malignancy, 8.3% to 25.5%), or as one in which the ultrasound examiner was uncertain regarding classification as benign or malignant when using subjective assessment. Even when the ultrasound examiner was uncertain, he/she was obliged to classify the tumor as most probably benign or most probably malignant. For each difficult tumor, one researcher created a 360° rotating 3D power Doppler image of the vessel tree in the whole tumor and another of the vessel tree in a 5-cm3 spherical volume selected from the most vascularized part of the tumor. Two other researchers, blinded to the patient's history, 2D ultrasound findings and histological diagnosis, independently described the vessel tree using predetermined vessel features. Their agreed classification was used. The reference standard was the histological diagnosis of the mass. The sensitivity of each test for discriminating between benign and malignant difficult tumors was plotted against 1 - specificity on a receiver-operating-characteristics diagram, and the test with the point furthest from the reference line was considered to have the best diagnostic ability. RESULTS: Of 2403 women with an adnexal mass, 376 (16%) had a difficult mass. Ultrasound volumes were available for 138 of these cases. In 79/138 masses, the ultrasound examiner was uncertain about the diagnosis based on subjective assessment, in 87/138, IOTA LR-1 yielded an ambiguous result and, in 28/138, both methods gave an uncertain result. Of the masses, 38/138 (28%) were malignant. Among tumors that were difficult to classify as benign or malignant by subjective assessment, the vessel feature 'densely packed vessels' had the best discriminative ability (sensitivity 67% (18/27), specificity 83% (43/52)) and was slightly superior to subjective assessment (sensitivity 74% (20/27), specificity 60% (31/52)). In tumors in which IOTA LR-1 yielded an ambiguous result, subjective assessment (sensitivity 82% (14/17), specificity 79% (55/70)) was superior to the best vascular feature, i.e. changes in the diameter of vessels in the whole tumor volume (sensitivity 71% (12/17), specificity 69% (48/70)). CONCLUSION: Vessel morphology depicted by 3D power Doppler ultrasound may slightly improve discrimination between benign and malignant adnexal tumors that are difficult to classify by subjective ultrasound assessment. For tumors in which the IOTA LR-1 model yields an ambiguous result, subjective assessment is superior to vessel morphology as a second-stage test. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort.

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound-based risk model for preoperative prediction of lymph-node metastases in women with endometrial cancer: model-development study.

OBJECTIVE: To develop a preoperative risk model, using endometrial biopsy results and clinical and ultrasound variables, to predict the individual risk of lymph-node metastases in women with endometrial cancer. METHODS: A mixed-effects logistic regression model for prediction of lymph-node metastases was developed in 1501 prospectively included women with endometrial cancer undergoing transvaginal ultrasound examination before surgery, from 16 European centers. Missing data, including missing lymph-node status, were imputed. Discrimination, calibration and clinical utility of the model were evaluated using leave-center-out cross validation. The predictive performance of the model was compared with that of risk classification from endometrial biopsy alone (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk defined as endometrioid cancer Grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). RESULTS: Lymphadenectomy was performed in 691 women, of whom 127 had lymph-node metastases. The model for prediction of lymph-node metastases included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and undefined tumor with an unmeasurable endometrium. The model's area under the curve was 0.73 (95% CI, 0.68-0.78), the calibration slope was 1.06 (95% CI, 0.79-1.34) and the calibration intercept was 0.06 (95% CI, -0.15 to 0.27). Using a risk threshold for lymph-node metastases of 5% compared with 20%, the model had, respectively, a sensitivity of 98% vs 48% and specificity of 11% vs 80%. The model had higher sensitivity and specificity than did classification as high-risk, according to endometrial biopsy alone (50% vs 35% and 80% vs 77%, respectively) or combined endometrial biopsy and ultrasound (80% vs 75% and 53% vs 52%, respectively). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. CONCLUSIONS: Based on endometrial biopsy results and clinical and ultrasound characteristics, the individual risk of lymph-node metastases in women with endometrial cancer can be estimated reliably before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (18): clinical and ultrasound characteristics of urinary bladder malignancies.

OBJECTIVE: To describe the clinical and ultrasound characteristics of urinary bladder malignancies diagnosed on transvaginal ultrasound in women presenting with suspected gynecological problems. METHODS: This was a multicenter retrospective study of women with a histological diagnosis of urinary bladder malignancy that was suspected on transvaginal ultrasound examination. The cases were collected from three centers that specialize in the use of pelvic ultrasound and had been examined between January 2007 and October 2018. Clinical data were obtained from the computer databases and all tumor images were assessed by two of the authors (D.J. and J.K.) to identify characteristic sonographic patterns. We compared the characteristics of tumors between women presenting with symptoms suspicious of urinary bladder malignancy and those without such symptoms. RESULTS: Thirty women with a confirmed diagnosis of urinary bladder malignancy on histological examination were included. Median age at diagnosis was 70.5 (range 36-88) years. The most common presenting symptom was postmenopausal bleeding, which was recorded in 18 (60%) women. Ten (33%) women had symptoms suspicious of bladder malignancy, of whom six had unexplained visible hematuria, three had unexplained recurrent urinary tract infections and one had dysuria and microhematuria. On histological examination, 23 (77%) women were diagnosed with primary bladder malignancy whilst seven (23%) had metastases in the bladder from other primary tumors. Out of 23 primary tumors, 21 (91%) were of urothelial origin (12 low grade and nine high grade). Most low-grade urothelial carcinomas appeared on ultrasound as irregular papillary growth (11/12, 92%) and were moderately to highly vascular on color Doppler examination (8/12, 67%). The ultrasound appearances of primary non-urothelial and metastatic tumors varied, without a clear common morphological tumor pattern. The tumors found in women with symptoms suggestive of bladder malignancy did not differ unequivocally from those detected in other women in terms of size, ultrasound morphology, vascularity or histological type. CONCLUSION: Urinary bladder malignancies can be detected in patients undergoing transvaginal ultrasound examination for suspected gynecological problems. Primary urothelial cancers have a relatively uniform morphological pattern, whilst the appearances of other bladder malignancies are more variable. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (16): clinical and ultrasound characteristics of serous cystadenofibromas in adnexa.

OBJECTIVE: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. METHODS: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999 and 2012. In the IOTA database, which contains data collected prospectively, the tumors were described using the terms and definitions of the IOTA group. In addition, three authors reviewed, first independently and then together, ultrasound images of serous cystadenofibromas and described them using pattern recognition. RESULTS: We identified 233 women with a histological diagnosis of serous cystadenofibroma. In the IOTA database, most cystadenofibromas (67.4%; 157/233) were described as containing solid components but 19.3% (45/233) were described as multilocular cysts and 13.3% (31/233) as unilocular cysts. Papillary projections were described in 52.4% (122/233) of the cystadenofibromas. In 79.5% (97/122) of the cysts with papillary projections, color Doppler signals were absent in the papillary projections. Most cystadenofibromas (83.7%; 195/233) manifested no or minimal color Doppler signals. On retrospective analysis of 201 ultrasound images of serous cystadenofibromas, using pattern recognition, 10 major types of ultrasound appearance were identified. The most common pattern was a unilocular solid cyst with one or more papillary projections, but no other solid components (25.9%; 52/201). The second most common pattern was a multilocular solid mass with small solid component(s), but no papillary projections (19.4%; 39/201). The third and fourth most common patterns were multi- or bilocular cyst (16.9%; 34/201) and unilocular cyst (11.9%; 24/201). Using pattern recognition, shadowing was identified in 39.8% (80/201) of the tumors, and microcystic appearance of the papillary projections was observed in 34 (38.6%) of the 88 tumors containing papillary projections. CONCLUSIONS: The ultrasound features of serous cystadenofibromas vary. The most common pattern is a unilocular solid cyst with one or more papillary projections but no other solid components, with absent color Doppler signals. Most serous cystadenofibromas were poorly vascularized on color Doppler examination and many manifested acoustic shadowing. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Imaging in gynecological disease (15): clinical and ultrasound characteristics of uterine sarcoma.

OBJECTIVE: To describe the clinical and ultrasound characteristics of uterine sarcomas. METHODS: This was a retrospective multicenter study. From the databases of 13 ultrasound centers, we identified patients with a histological diagnosis of uterine sarcoma with available ultrasound reports and ultrasound images who had undergone preoperative ultrasound examination between 1996 and 2016. As the first step, each author collected information from the original ultrasound reports from his/her own center on predefined ultrasound features of the tumors and by reviewing the ultrasound images to identify information on variables not described in the original report. As the second step, 16 ultrasound examiners reviewed the images electronically in a consensus meeting and described them using predetermined terminology. RESULTS: We identified 116 patients with leiomyosarcoma, 48 with endometrial stromal sarcoma and 31 with undifferentiated endometrial sarcoma. Median age of the patients was 56 years (range, 26-86 years). Most patients were symptomatic at diagnosis (164/183 (89.6%)), the most frequent presenting symptom being abnormal vaginal bleeding (91/183 (49.7%)). Patients with endometrial stromal sarcoma were younger than those with leiomyosarcoma and undifferentiated endometrial sarcoma (median age, 46 years vs 57 and 60 years, respectively). According to the assessment by the original ultrasound examiners, the median diameter of the largest tumor was 91 mm (range, 7-321 mm). Visible normal myometrium was reported in 149/195 (76.4%) cases, and 80.0% (156/195) of lesions were solitary. Most sarcomas (155/195 (79.5%)) were solid masses (> 80% solid tissue), and most manifested inhomogeneous echogenicity of the solid tissue (151/195 (77.4%)); one sarcoma was multilocular without solid components. Cystic areas were described in 87/195 (44.6%) tumors and most cyst cavities had irregular walls (67/87 (77.0%)). Internal shadowing was observed in 42/192 (21.9%) sarcomas and fan-shaped shadowing in 4/192 (2.1%). Moderate or rich vascularization was found on color-Doppler examination in 127/187 (67.9%) cases. In 153/195 (78.5%) sarcomas, the original ultrasound examiner suspected malignancy. Though there were some differences, the results of the first and second steps of the analysis were broadly similar. CONCLUSIONS: Uterine sarcomas typically appear as solid masses with inhomogeneous echogenicity, sometimes with irregular cystic areas but only very occasionally with fan-shaped shadowing. Most are moderately or very well vascularized. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study.

OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Misoprostol treatment vs expectant management in women with early non-viable pregnancy and vaginal bleeding: a pragmatic randomized controlled trial.

OBJECTIVE: To compare vaginal misoprostol treatment with expectant management in early non-viable pregnancy with vaginal bleeding with regard to complete evacuation of the uterine cavity within 10 days after randomization. METHODS: This was a parallel randomized controlled, open-label trial conducted in Skåne University Hospital, Sweden. Patients with anembryonic pregnancy or early fetal demise (crown-rump length ≤ 33 mm) and vaginal bleeding were randomly allocated to either expectant management or treatment with a single dose of 800 µg misoprostol administered vaginally. Patients were evaluated clinically and by ultrasound until complete evacuation of the uterus was achieved (no gestational sac in the uterine cavity and maximum anteroposterior diameter of the intracavitary contents < 15 mm as measured by transvaginal ultrasound on midsagittal view). Follow-up visits were planned at 10, 17, 24 and 31 days. Dilatation and evacuation (D&E) was recommended if miscarriage was not complete within 31 days, but was performed earlier at patient's request, or if there was excessive bleeding as judged clinically. Analysis was by intention to treat. The main outcome measure was number of patients with complete miscarriage without D&E ≤ 10 days. RESULTS: Ninety-four patients were randomized to misoprostol treatment and 95 to expectant management. After exclusion of three patients and withdrawal of consent by two patients in the expectant management group, 90 women were included in this group. Miscarriage was complete ≤ 10 days in 62/94 (66%) of the patients in the misoprostol group and in 39/90 (43%) of those in the group managed expectantly (risk difference (RD) = 23%; 95% CI, 8-37%). At 31 days, the corresponding figures were 81/94 (86%) and 55/90 (61%) (RD = 25%; 95% CI, 12-38%). Two patients from each group underwent emergency D&E because of excessive bleeding and one of these in each group received blood transfusion. The number of patients undergoing D&E at their own request was higher in the expectantly managed group, 15/90 (17%) vs 3/94 (3%) in the misoprostol group (RD = 14%; 95% CI, 4-23%), as was the number of patients making out-of-protocol visits, 50/90 (56%) vs 27/94 (29%) (RD = 27%; 95% CI, 12-40%). Compared with the expectant management group, more patients in the misoprostol group experienced pain (71/77 (92%) vs 91/91 (100%); RD = 8%; 95% CI, 1-17%) and used painkillers (59/77 (77%) vs 85/91 (93%); RD = 17%; 95% CI, 5-29%). No major side effect was reported in any group. CONCLUSIONS: In women with early non-viable pregnancy and vaginal bleeding, misoprostol treatment is more effective than is expectant management for complete evacuation of the uterus. Both methods are safe but misoprostol treatment is associated with more pain than is expectant management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

International Endometrial Tumor Analysis (IETA) terminology in women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm: agreement and reliability study.

OBJECTIVE: To estimate intra- and interrater agreement and reliability with regard to describing ultrasound images of the endometrium using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: Four expert and four non-expert raters assessed videoclips of transvaginal ultrasound examinations of the endometrium obtained from 99 women with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm but without fluid in the uterine cavity. The following features were rated: endometrial echogenicity, endometrial midline, bright edge, endometrial-myometrial junction, color score, vascular pattern, irregularly branching vessels and color splashes. The color content of the endometrial scan was estimated using a visual analog scale graded from 0 to 100. To estimate intrarater agreement and reliability, the same videoclips were assessed twice with a minimum of 2 months' interval. The raters were blinded to their own results and to those of the other raters. RESULTS: Interrater differences in the described prevalence of most IETA variables were substantial, and some variable categories were observed rarely. Specific agreement was poor for variables with many categories. For binary variables, specific agreement was better for absence than for presence of a category. For variables with more than two outcome categories, specific agreement for expert and non-expert raters was best for not-defined endometrial midline (93% and 96%), regular endometrial-myometrial junction (72% and 70%) and three-layer endometrial pattern (67% and 56%). The grayscale ultrasound variable with the best reliability was uniform vs non-uniform echogenicity (multirater kappa (κ), 0.55 for expert and 0.52 for non-expert raters), and the variables with the lowest reliability were appearance of the endometrial-myometrial junction (κ, 0.25 and 0.16) and the nine-category endometrial echogenicity variable (κ, 0.29 and 0.28). The most reliable color Doppler variable was color score (mean weighted κ, 0.77 and 0.69). Intra- and interrater agreement and reliability were similar for experts and non-experts. CONCLUSIONS: Inter- and intrarater agreement and reliability when using IETA terminology were limited. This may have implications when assessing the association between a particular ultrasound feature and a specific histological diagnosis, because lack of reproducibility reduces the reliability of the association between a feature and the outcome. Future studies should investigate whether using fewer categories of variable or offering practical training could improve agreement and reliability. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Differences in ultrasound features of papillations in unilocular-solid adnexal cysts: a retrospective international multicenter study.

OBJECTIVES: To identify ultrasound features of papillations or of the cyst wall that can discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. METHODS: From the International Ovarian Tumor Analysis (IOTA) database derived from seven ultrasound centers, we identified patients with an adnexal lesion described at ultrasonography as unilocular-solid with papillations but no other solid components. All patients had undergone transvaginal ultrasound between 1999 and 2007 or 2009 and 2012, by an experienced examiner following the IOTA research protocol. Information on four ultrasound features of papillations had been collected prospectively. Information on a further seven ultrasound features was collected retrospectively from electronic or paper ultrasound images of good quality. The histological diagnosis of the surgically removed adnexal lesion was considered the gold standard. RESULTS: Of 204 masses included, 131 (64.2%) were benign, 42 (20.6%) were borderline tumors, 30 (14.7%) were primary invasive tumors and one (0.5%) was a metastasis. Multivariate logistic regression analysis showed the following ultrasound features to be associated independently with malignancy: height of the largest papillation, presence of blood flow in papillations, papillation confluence or dissemination, and shadows behind papillations. Shadows decreased the odds of malignancy, while the other features increased them. CONCLUSION: We have identified ultrasound features that can help to discriminate between benign and malignant unilocular-solid cysts with papillations but no other solid components. Our results need to be confirmed in prospective studies. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prospective temporal validation of mathematical models to calculate risk of endometrial malignancy in patients with postmenopausal bleeding.

OBJECTIVES: To validate prospectively five mathematical models published in 2007 for calculating the risk of endometrial malignancy in a defined high-risk group of patients with postmenopausal bleeding and sonographic endometrial thickness ≥ 4.5 mm. METHODS: Of 1012 consecutive patients, 379 fulfilled our inclusion criteria, which were the same as those of the original study in which the models were created (endometrial thickness ≥ 4.5 mm, no fluid in the uterine cavity, detectable Doppler signals in the endometrium). A standardized history was taken, and clinical and transvaginal grayscale and power Doppler ultrasound examinations were performed following the study protocol. All data were collected prospectively and the five models were applied prospectively to the study patients' data to assess their risk of endometrial malignancy. Using the histological diagnosis of the endometrium as gold standard, we calculated the area under the receiver-operating characteristics curve (AUC), and sensitivity, specificity and likelihood ratios when using the same cut-offs as in the original study, for each of the five models. RESULTS: Ninety-three (25%) patients had malignant endometrium. The performance of the models was similar to that in the original study, with AUCs ranging from 0.86 to 0.90. The model with the best diagnostic performance included endometrial thickness, heterogeneous endometrial echogenicity and areas of densely packed vessels on power Doppler (AUC, 0.90; sensitivity, 81%; specificity, 84% at preselected cut-off). The models were well calibrated. CONCLUSIONS: On temporal validation, the five models for calculating the risk of endometrial malignancy in a defined high-risk group of patients retained their good diagnostic performance and were well calibrated. The models make it possible to reclassify high-risk patients as having a low or relatively low risk, moderately high risk or very high risk of endometrial cancer, and so can be used for individualized patient management. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.