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.

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.

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 (13): clinical and ultrasound characteristics of endometrioid ovarian cancer.

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. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.

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.

Imaging in gynecological disease (9): clinical and ultrasound characteristics of tubal cancer.

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.

Unilocular adnexal cysts with papillary projections but no other solid components: is there a diagnostic method that can classify them reliably as benign or malignant before surgery?

OBJECTIVES: To develop a logistic regression model for discrimination between benign and malignant unilocular solid cysts with papillary projections but no other solid components, and to compare its diagnostic performance with that of subjective evaluation of ultrasound findings (subjective assessment), CA 125 and the risk of malignancy index (RMI). METHODS: Among the 3511 adnexal masses in the International Ovarian Tumor Analysis (IOTA) database there were 252 (7%) unilocular solid cysts with papillary projections but no other solid components ('unilocular cysts with papillations'). All had been examined with transvaginal ultrasound using the IOTA standardized research protocol. The ultrasound examiner had also classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for all unilocular cysts with papillations (175 tumors in the training set and 77 in the test set) and for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy (113 tumors in the training set and 53 in the test set). The gold standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: A model containing six variables was developed for all unilocular cysts with papillations. The model had an area under the receiver-operating characteristics curve (AUC) on the test set of 0.83 (95% CI, 0.74-0.93). The optimal risk cut-off, as defined on the training set (0.35), resulted in sensitivity 69% (20/29), specificity 79% (38/48), positive likelihood ratio (LR +) 3.31 and negative likelihood ratio (LR-) 0.39 on the test set. The corresponding values for subjective assessment when using the ultrasound examiner's dichotomous classification of the mass as benign or malignant were 97% (28/29), 79% (38/48), 4.63 and 0.04. A model containing four variables was developed for unilocular cysts with papillations for which the ultrasound examiner was not certain about benignity/malignancy. The model had an AUC of 0.74 (95% CI, 0.60-0.88) on the test set. The optimal risk cut-off of the model, as defined on the training set (0.30), resulted in sensitivity 57% (12/21), specificity 78% (25/32), LR + 2.61 and LR- 0.55 on the test set. The corresponding values for subjective assessment were 95% (20/21), 78% (25/32), 4.35 and 0.06. CA 125 and RMI had virtually no diagnostic ability. CONCLUSIONS: Even though logistic regression models to predict malignancy in unilocular cysts with papillations can be developed, they have at most moderate performance and are not superior to subjective assessment for discrimination between benignity and malignancy.

Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses.

OBJECTIVES: To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). METHODS: We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 4-9.9 cm; n = 1457) and large tumors (diameter ≥ 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiver-operating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. RESULTS: The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (56-84% vs 67-93% in medium-sized tumors and 74-95% in large tumors) while specificity was lowest in large tumors (60-87%vs 83-95% in medium-sized tumors and 83-96% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 7-11 cm. CONCLUSION: Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size.

Adnexal masses difficult to classify as benign or malignant using subjective assessment of gray-scale and Doppler ultrasound findings: logistic regression models do not help.

OBJECTIVE: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray-scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI). METHODS: We used data from the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined using transvaginal gray-scale and Doppler ultrasound following a standardized research protocol carried out by an experienced ultrasound examiner using a high-end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver-operating characteristics curve (AUC), sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created. RESULTS: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (odds ratio (OR) = 1.04; 95% CI, 1.02-1.06). The model had an AUC of 0.68 (95% CI, 0.59-0.78) on the training set and an AUC of 0.65 (95% CI, 0.53-0.78) on the test set. On the test set, a cut-off of 25% probability of malignancy (corresponding to the largest diameter of the largest solid component of 23 mm) resulted in a sensitivity of 64% (18/28), a specificity of 55% (31/56), an LR+ of 1.44 and an LR- of 0.65. The corresponding values for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cut-off = 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment were 1.45 and 0.63, of CA 125 (cut-off = 35 U/mL) were 1.24 and 0.84 and of RMI (cut-off = 200) were 1.21 and 0.92. CONCLUSIONS: About 7% of adnexal masses that are considered appropriate for surgical removal cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses.

Effect of cancer prevalence on the use of risk-assessment cut-off levels and the performance of mathematical models to distinguish malignant from benign adnexal masses.

OBJECTIVE: Two logistic regression models have been developed for the characterization of adnexal masses. The goal of this prospective analysis was to see whether these models perform differently according to the prevalence of malignancy and whether the cut-off levels of risk assessment for malignancy by the models require modification in different centers. METHODS: Centers were categorized into those with a prevalence of malignancy below 15%, between 15 and 30% and above 30%. The areas under the receiver-operating characteristics curves (AUC) were compared using bootstrapping. The optimal cut-off level of risk assessment for malignancy was chosen per center, corresponding to the highest sensitivity level possible while still keeping a good specificity. RESULTS: Both models performed better in centers with a lower prevalence of malignant cases. The AUCs of the two models for centers with fewer than 15% malignant cases were 0.97 and 0.95, those of centers with 15-30% malignancy were 0.95 and 0.93 and those of centers with more than 30% malignant cases were 0.94 and 0.92. This decrease in performance was due mainly to the decrease in specificity from over 90 to around 76%. In the centers with a higher percentage of malignant cases, a sensitivity of at least 90% with a good specificity could not be obtained by choosing a different cut-off level. CONCLUSIONS: Overall the models performed well in all centers. The performance of the logistic regression models worsened with increasing prevalence of malignancy, due to a case mix with more borderline and complex benign masses seen in those centers. Because the cut-off of 0.10 is optimal for all three types of center, it seems reasonable to use this cut-off for both models in all centers.

Improving the preoperative classification of adnexal masses as benign or malignant by second-stage tests.

OBJECTIVE: The aim of this study was to establish when a second-stage diagnostic test may be of value in cases where a primary diagnostic test has given an uncertain diagnosis of the benign or malignant nature of an adnexal mass. METHODS: The diagnostic performance with regard to discrimination between benign and malignant adnexal masses for mathematical models including ultrasound variables and for subjective evaluation of ultrasound findings by an experienced ultrasound examiner was expressed as area under the receiver-operating characteristics curve (AUC), sensitivity and specificity. These were calculated for the total study population of 1938 patients with an adnexal mass as well as for subpopulations defined by the certainty with which the diagnosis of benignity or malignancy was made. The effect of applying a second-stage test to the tumors where risk estimation was uncertain was determined. RESULTS: The best mathematical model (LR1) had an AUC of 0.95, sensitivity of 92% and specificity of 84% when applied to all tumors. When model LR1 was applied to the 10% of tumors in which the calculated risk fell closest to the risk cut-off of the model, the AUC was 0.59, sensitivity 90% and specificity 21%. A strategy where subjective evaluation was used to classify these 10% of tumors for which LR1 performed poorly and where LR1 was used in the other 90% of tumors resulted in a sensitivity of 91% and specificity of 90%. Applying subjective evaluation to all tumors yielded an AUC of 0.95, sensitivity of 90% and specificity of 93%. Sensitivity was 81% and specificity 47% for those patients where the ultrasound examiner was uncertain about the diagnosis (n = 115; 5.9%). No mathematical model performed better than did subjective evaluation among the 115 tumors where the ultrasound examiner was uncertain. CONCLUSION: When model LR1 is used as a primary test for discriminating between benign and malignant adnexal masses, the use of subjective evaluation of ultrasound findings by an experienced examiner as a second-stage test in the 10% of cases for which the model yields a risk of malignancy closest to its risk cut-off will improve specificity without substantially decreasing sensitivity. However, none of the models tested proved suitable as a second-stage test in tumors where subjective evaluation yielded an uncertain result.

Endometriomas: their ultrasound characteristics.

OBJECTIVES: To describe the ultrasound characteristics of endometriomas in pre- and postmenopausal patients and to develop rules that characterize endometriomas. METHODS: All patients included in the International Ovarian Tumor Analysis (IOTA) studies were used in our analysis. Patients with an adnexal mass were scanned by experienced sonologists using a standardized research protocol. The gold standard was the histology of the surgically removed adnexal mass. The gray-scale and Doppler ultrasound characteristics of the endometriomas were compared with those of other benign and malignant masses. Based on decision-tree analysis, the existing literature and clinical experience, ultrasound rules for the detection of endometriomas were created and evaluated. RESULTS: Of all 3511 patients included in the IOTA studies, 713 (20%) had endometriomas. Fifty-one per cent of the endometriomas were unilocular cysts with ground glass echogenicity of the cyst fluid. These characteristics were found less often among other benign tumors or malignancies, or among the small set of endometriomas (4%) that were found in postmenopausal patients. Based on the decision-tree analysis, the optimal rule to detect endometriomas was 'an adnexal mass in a premenopausal patient with ground glass echogenicity of the cyst fluid, one to four locules and no papillations with detectable blood flow'. Based on clinical considerations, the following rule: 'premenopausal status, ground glass echogenicity of the cyst fluid, one to four locules and no solid parts' seems preferable. CONCLUSIONS: Several rules had a good ability to characterize endometriomas. The ultrasound characteristics of endometriomas differ between pre- and postmenopausal patients. Masses in postmenopausal women whose cystic contents have a ground glass appearance have a high risk of malignancy.

Ovarian cancer prediction in adnexal masses using ultrasound-based logistic regression models: a temporal and external validation study by the IOTA group.

OBJECTIVES: The aims of the study were to temporally and externally validate the diagnostic performance of two logistic regression models containing clinical and ultrasound variables in order to estimate the risk of malignancy in adnexal masses, and to compare the results with the subjective interpretation of ultrasound findings carried out by an experienced ultrasound examiner ('subjective assessment'). METHODS: Patients with adnexal masses, who were put forward by the 19 centers participating in the study, underwent a standardized transvaginal ultrasound examination by a gynecologist or a radiologist specialized in ultrasonography. The examiner prospectively collected information on clinical and ultrasound variables, and classified each mass as benign or malignant on the basis of subjective evaluation of ultrasound findings. The gold standard was the histology of the mass with local clinicians deciding whether to operate on the basis of ultrasound results and the clinical picture. The models' ability to discriminate between malignant and benign masses was assessed, together with the accuracy of the risk estimates. RESULTS: Of the 1938 patients included in the study, 1396 had benign, 373 had primary invasive, 111 had borderline malignant and 58 had metastatic tumors. On external validation (997 patients from 12 centers), the area under the receiver-operating characteristics curve (AUC) for a model containing 12 predictors (LR1) was 0.956, for a reduced model with six predictors (LR2) was 0.949 and for subjective assessment was 0.949. Subjective assessment gave a positive likelihood ratio of 11.0 and a negative likelihood ratio of 0.14. The corresponding likelihood ratios for a previously derived probability threshold (0.1) were 6.84 and 0.09 for LR1, and 6.36 and 0.10 for LR2. On temporal validation (941 patients from seven centers), the AUCs were 0.945 (LR1), 0.918 (LR2) and 0.959 (subjective assessment). CONCLUSIONS: Both models provide excellent discrimination between benign and malignant masses. Because the models provide an objective and reasonably accurate risk estimation, they may improve the management of women with suspected ovarian pathology.

Acoustic streaming cannot discriminate reliably between endometriomas and other types of adnexal lesion: a multicenter study of 633 adnexal masses.

OBJECTIVE: To determine the ability of acoustic streaming to discriminate between endometriomas and other adnexal masses. METHODS: We used data from 1938 patients with an adnexal mass included in Phase 2 of the International Ovarian Tumor Analysis (IOTA) study. All patients had been examined by transvaginal gray-scale and Doppler ultrasound following a standardized research protocol. Assessment of acoustic streaming was voluntary and was carried out only in lesions containing echogenic cyst fluid. Acoustic streaming was defined as movement of particles inside the cyst fluid during gray-scale and/or color Doppler examination provided that the probe had been held still for two seconds to ensure that the movement of the particles was not caused by movement of the probe or the patient. Only centers where acoustic streaming had been evaluated in > 90% of cases were included. Sensitivity, specificity, positive and negative likelihood ratios (LR+, LR-), and positive and negative predictive values (PPV and NPV) of acoustic streaming with regard to endometrioma were calculated. RESULTS: 460 (24%) masses were excluded because they were examined in centers where

Imaging in gynaecology: How good are we in identifying endometriomas?

AIM: To evaluate the performance of subjective evaluation of ultrasound findings (pattern recognition) to discriminate endometriomas from other types of adnexal masses and to compare the demographic and ultrasound characteristics of the true positive cases with those cases that were presumed to be an endometrioma but proved to have a different -histology (false positive cases) and the endometriomas missed by pattern recognition (false negative cases). METHODS: All patients in the International Ovarian Tumor Analysis (IOTA ) studies were included for analysis. In the IOTA studies, patients with an adnexal mass that were preoperatively examined by expert sonologists following the same standardized ultrasound protocol were prospectively included in 21 international centres. Sensitivity and specificity to discriminate endometriomas from other types of adnexal masses using pattern recognition were calculated. Ultrasound and some demographic variables of the masses presumed to be an endometrioma were analysed (true -positives and false positives) and compared with the variables of the endometriomas missed by pattern recognition (false negatives) as well as the true negatives. RESULTS: IOTA phase 1, 1b and 2 included 3511 patients of which 2560 were benign (73%) and 951 malignant (27%). The dataset included 713 endometriomas. Sensitivity and specificity for pattern recognition were 81% (577/713) and 97% (2723/2798). The true positives were more often unilocular with ground glass echogenicity than the masses in any other category. Among the 75 false positive cases, 66 were benign but 9 were malignant (5 borderline tumours, 1 rare primary invasive tumour and 3 endometrioid adenocarcinomas). The presumed diagnosis suggested by the sonologist in case of a missed endometrioma was mostly functional cyst or cystadenoma. CONCLUSION: Expert sonologists can quite accurately discriminate endometriomas from other types of adnexal masses, but in this dataset 1% of the masses that were classified as endometrioma by pattern recognition proved to be malignancies.

Microvessel density assessment in benign and malignant endometrial changes.

Tumor angiogenesis is believed to be a prognostic indicator associated with tumor growth and metastasis. Microvessel density (MVD) assessment with common endothelial markers such as CD34 has been found to influence prognosis among endometrial carcinoma patients. The CD105/endoglin antibody has been reported to preferentially bind to proliferated endothelial cells in tissues participating in angiogenesis. The aim of this study was to evaluate the quantification of angiogenesis by assessing MVD in endometrial lesions when comparing the performance of anti-CD34 and anti-CD105 in women with benign and malignant endometrial changes. The study included 58 women (37 postmenopausal) with normal, hyperplastic and malignant endometrium in which preoperative transvaginal sonography was performed. Histological results of the removed endometrium were correlated with MVD assessed in "hot areas" where high densities of microvessels were detected within tumoral tissue. Endometrial cancer was confirmed in 37 women (3 premenopausal). Benign hyperplasia (14 cases), secretory or proliferative endometrium (5 cases) or endometrial atrophy (2 cases) was found in the remaining women. Malignant changes were mostly noted as FIGO stage I and II (28 cases) and had a low (1 or 2) histological grade (29 cases). Median MVD's assessed with CD105 and CD34 were 10.4 and 32.3, respectively. Median MVD assessed with CD34 was almost twice higher in women with endometrial cancer than in women with benign endometrium (CD34 MVD = 41.8 vs. 27.6, p=0.004). In cases of CD105 MVD significant differences between women with benign and malignant endometrial changes were also found (CD105 MVD = 11.8, vs. 6.4; p=0.00007). The menopausal status, but not the clinical stage or histological grading was significantly correlated with both CD34 MVD (p=0.02) and CD105 MVD (p=0.0003). A significant correlation was also found between CD34 and CD105 measured MVD (p=0.000001). In conclusion, transition from endometrial hyperplasia to endometrial cancer appears to be accompanied by microvessel density changes. MVD assessed with both CD34 and CD105 antibodies could be used as a potential prognostic factor in women with endometrial cancer. Our study showed that endoglin, by staining the proliferating microvessels could be more specific and sensitive marker for tumor neoangiogenesis than the more commonly used marker, CD34.

Microvessel density and CpG island methylation of the THBS2 gene in malignant ovarian tumors.

We aimed to investigate the role of thrombospondin-2 (THBS2) related angiogenic activity in malignant ovarian tumors and to determine if aberrant methylation associated inactivation is involved in down-regulating THBS2 expression in ovarian cancer. The methylation status of the THBS2 promoter region and microvessel density (MVD) was studied in 70 malignant ovarian tumors and in 15 control ovarian samples. A methylation specific PCR (MSP) method was used to distinguish methylated from unmethylated DNA in the promoter regions of the THBS2 gene. MVD was assessed with anti-CD34 antibodies and the results were compared between tumors with average (AVD) and high (HVD) microvessel density. Alterations in the expression of trombospondin-2 were more often seen in early (FIGO stage I and II ) than in late stage tumors (66% vs. 30%, p=0.01). Age, menopausal status, the histological type and tumor grade did not correlate with thrombospondin-2 expression, however, silencing of THBS2 gene was more often seen in higher rather than in lower grade (50% vs. 28%) cancers and in nonserous rather than in serous (43% vs. 32%) tumors. In 81% of THBS2 mRNA-negative tumors, ahypermethylated promoter region of THBS2 was found (p=0.00003). An unmethylated product of the MSP reaction was more often detected in high grade tumors (93% vs. 76%, p=0.04). The incidence of THBS2 hypermethylation was not related to the tumor histological type, but unmethylated THBS2 was more often found in serous rather than in nonserous tumor (96% vs. 74%, p=0.01). The median MVD in malignant the tumor samples was 21,7 (range: 7.6-55.2). In the group with HVD, 54% were THBS2 mRNAnegative, conversely, in the group with AVD tumors only 26% of the cases had undetectable THSB2 mRNA. A significant correlation between microvessel density and the expression of trombospondin-2 (p=0.009) was found. In the samples with HVD, 51% had hypermethylated THBS2, however methylation pattern had no significant influence on microvessel density. In conclusion, hypermethylation might be responsible for altered expression of thrombospondin-2 in ovarian cancer. The THSB2 methylation pattern had no significant influence on microvessel density.

[Sonographic evaluation of cervical length and cervical canal width in 24th week of twin pregnancy in prediction of preterm delivery]. / Ultrasonograficzny pomiar szyjki macicy w ciazy blizniaczej i jego wartosc w przewidywaniu porodu przedwczesnego.

OBJECTIVE: Sonographic evaluation of the cervical length and cervical canal width in 24th week of twin pregnancy in prediction of preterm delivery. MATERIALS AND METHODS: 43 primiparous patients with twin pregnancy. Group I (n = 16, 37.2%) with spontaneous delivery before 36 of gestation; group II (n = 27, 62.8%) delivering in term. Sonographic measurements of the cervical length and cervical canal width were done in 24th week of gestation. RESULTS: Mean values of cervical length in group I were: 25.6 mm (+/- 3.7 mm); and in group II--32.5 mm (+/- 6.0 mm). Corresponding values of canal width were: 14.6 mm (+/- 11.8 mm) and 6.2 mm (+/- 3.0 mm). CONCLUSIONS: We suggest, that cervical length is more valuable parameter in predicting risk of preterm delivery in twin pregnancy.

[Ultrasound fetal biometry and birth weight prognosis with the use of Aoki method and classical regression analysis]. / Zastosowanie modelu predykcyjnego Aoki i klasycznego modelu regresji w ultrasonograficznym i analitycznym przewidywaniu masy urodzeniowej noworodka.

We have attempted to estimate prognostic value of neonatal birth weight prediction with the use of fetal sonographic data: biparietal diameter, femur length, transverse and longitudinal abdominal diameter. Clinical and ultrasound data from 265 pregnant women with singleton gestation who delivered within 7 days from the last ultrasound scan were analyzed. For the fetal weight estimation we have calculated fetal abdominal area in the equation proposed by Aoki in 1990. Predicted and observed neonatal birth weight centiles and coefficients of determination were calculated with the use of regression analysis. Prediction method of neonatal weight with Aoki method explained 70% of variability in our population. In contrast, regression analysis on ultrasound data explained 99% of observer variability in neonatal birth weight. We conclude that own method of birth weight prediction could be of value, however it should be tested in a new prospectively examined population.