Stefano Guerriero

Preoperative Assessment of Cervical Involvement in Endometrial Cancer by Transvaginal Ultrasound and Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis

Abstract Objective To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting cervical infiltration by endometrial carcinoma using meta-analysis assessment. Methods An extensive search of papers comparing TVS and MRI for assessing cervical infiltration in endometrial cancer in the same set of patients was performed in Medline (Pubmed), Web of Science, and the Cochrane Database. Quality was assessed using QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies-2). Quantitative meta-analysis was performed. Results Our extended search identified 12 articles that used both techniques in the same set of patients and were included in the meta-analysis. The risk of bias for most studies was high for patient selection and index tests in QUADAS-2. Overall, the pooled estimated sensitivity and specificity for diagnosing cervical infiltration in women with endometrial cancer were identical for both techniques [69 % (95 % CI, 51 %–82 %) and 93 % (95 % CI, 90 %–95 %) for TVS, and 69 % (95 % CI, 57 %–79 %) and 91 % (95 % CI, 90 %–95 %) for MRI, respectively]. No statistical differences were found when comparing both methods. Heterogeneity was high for sensitivity and moderate for specificity when analyzing TVS and moderate for both sensitivity and specificity in the case of MRI. Conclusion TVS and MRI showed very similar diagnostic performance for diagnosing cervical involvement in women with endometrial cancer.

Two‐dimensional transvaginal sonography vs saline contrast sonohysterography for diagnosing endometrial polyps: systematic review and meta‐analysis

ABSTRACTObjectiveTo compare the diagnostic performance of two‐dimensional transvaginal sonography (TVS) and saline contrast sonohysterography (SCSH) for the diagnosis of endometrial polyps in studies that used both tests in the same group of patients.MethodsThis was a systematic review and meta‐analysis. An extensive search was conducted of Medline (PubMed), Cochrane Library and Web of Science, for studies comparing the diagnostic performance of TVS and SCSH for identifying endometrial polyps, published between January 1990 and December 2019, that reported a definition of endometrial polyp on TVS and SCSH and used pathologic analysis as the reference standard. Quality of the included studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool. A random‐effects model was used to determine pooled sensitivity, specificity and positive and negative likelihood ratios of TVS and SCSH in the detection of endometrial polyps. Subanalysis according to menopausal status was performed.ResultsIn total, 1278 citations were identified; after exclusions, 25 studies were included in the meta‐analysis. In the included studies, the risk of bias evaluated using QUADAS‐2 was low for most of the four domains, except for flow and timing, which had an unclear risk of bias in 13 studies. Pooled sensitivity, specificity and positive and negative likelihood ratios for TVS in the detection of endometrial polyps were 55.0% (95% CI, 46.0–64.0%), 91.0% (95% CI, 86.0–94.0%), 5.8 (95% CI, 3.9–8.7) and 0.5 (95% CI, 0.41–0.61), respectively. The corresponding values for SCSH were 92.0% (95% CI, 87.0–95.0%), 93.0% (95% CI, 91.0–95.0%), 13.9 (95% CI, 9.9–19.5) and 0.08 (95% CI, 0.05–0.14), respectively. Significant differences were found when comparing the methods in terms of sensitivity (P < 0.001), but not for specificity (P = 0.0918). Heterogeneity was high for TVS and moderate for SCSH. On subanalysis according to menopausal status, SCSH was found to have higher diagnostic accuracy in both pre‐ and postmenopausal women; sensitivity and specificity did not differ significantly between the groups for either TVS or SCSH.ConclusionGiven that SCSH has better diagnostic positive and negative likelihood ratios than does TVS in both pre‐ and postmenopausal women, those with clinical suspicion of endometrial polyps should undergo SCSH if TVS findings are inconclusive. © 2020 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

ABSTRACTObjectivesTo 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.MethodsThis 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.ResultsOf 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)).ConclusionVessel 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 (17): ultrasound features of malignant ovarian yolk sac tumors (endodermal sinus tumors)

ABSTRACTObjectiveTo describe the clinical and sonographic characteristics of malignant ovarian yolk sac tumors (YSTs).MethodsIn this retrospective multicenter study, we included 21 patients with a histological diagnosis of ovarian YST and available transvaginal ultrasound images and/or videoclips and/or a detailed ultrasound report. Ten patients identified from the International Ovarian Tumor Analysis (IOTA) studies had undergone a standardized preoperative ultrasound examination, by an experienced ultrasound examiner, between 1999 and 2016. A further 11 patients were identified through medical files, for whom ultrasound images were retrieved from local image workstations and picture archiving and communication systems. All tumors were described using IOTA terminology. The collected ultrasound images and videoclips were used by two observers for additional characterization of the tumors.ResultsAll cases were pure YSTs, except for one that was a mixed tumor (80% YST and 20% embryonal carcinoma). Median age at diagnosis was 25 (interquartile range (IQR), 19.5–30.5) years. Seventy‐six percent (16/21) of women had an International Federation of Gynecology and Obstetrics (FIGO) Stage I–II tumor at diagnosis. Fifty‐eight percent (11/19) of women felt pain during the ultrasound examination and one presented with ovarian torsion. Median serum α‐fetoprotein (S‐AFP) level was 4755 (IQR, 1071–25 303) µg/L and median serum CA 125 level was 126 (IQR, 35–227) kU/L. On ultrasound assessment, 95% (20/21) of tumors were unilateral. The median maximum tumor diameter was 157 (IQR, 107–181) mm and the largest solid component was 110 (IQR, 66–159) mm. Tumors were classified as either multilocular‐solid (10/21; 48%) or solid (11/21; 52%). Papillary projections were found in 10% (2/21) of cases. Most (20/21; 95%) tumors were well vascularized (color score, 3–4) and none had acoustic shadowing. Malignancy was suspected in all cases, except in the patient with ovarian torsion, who presented a tumor with a color score of 1, which was classified as probably benign. Image and videoclip quality was considered as adequate in 18/21 cases. On review of the images and videoclips, we found that all tumors contained both solid components and cystic spaces, and that 89% (16/18) had irregular, still fine‐textured and slightly hyperechoic solid tissue, giving them a characteristic appearance.ConclusionMalignant ovarian YSTs are often detected at an early stage, in young women usually in the second or third decade of life, presenting with pain and markedly elevated S‐AFP. On ultrasound, malignant ovarian YSTs are mostly unilateral, large and multilocular‐solid or solid, with fine‐textured slightly hyperechoic solid tissue and rich vascularization. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology..

Imaging in gynecological disease (28): clinical and ultrasound characteristics of serous and mucinous cystadenomas in the adnexa

ABSTRACTObjectiveTo describe the clinical and ultrasound characteristics of serous and mucinous cystadenomas in the adnexa.MethodsThis was a retrospective international multicenter study. Using the International Ovarian Tumor Analysis (IOTA) database, patients with a histological diagnosis of serous or mucinous cystadenoma who had undergone preoperative ultrasound examination between 1999 and 2016 (IOTA studies phase 1, 1b, 2, 3 and 5) were identified. All masses were described using the standardized IOTA terminology. The diagnosis assigned by the original ultrasound examiner based on subjective assessment was recorded. Two reviewers assessed the available digital ultrasound images using pattern recognition to identify typical sonographic features of cystadenomas.ResultsA total of 1318 patients were included: 687 (52.1%) with serous cystadenomas and 631 (47.9%) with mucinous cystadenomas. Based on the data recorded prospectively in the IOTA database, for serous cystadenomas the median diameter of the largest tumor was 68 (range, 14–320) mm. Most serous cystadenomas were described as unilateral (588/687 (85.6%)), with unilocular (274/687 (39.9%)) or multilocular (221/687 (32.2%)) morphology, and most had anechoic cyst content (508/687 (73.9%)). Most serous cystadenomas were not vascularized (color score of 1; 327/687 (47.6%)) or were poorly vascularized (color score of  2; 253/687 (36.8%)) on color Doppler examination. The original ultrasound examiner correctly classified 91.1% (626/687) of serous cystadenomas as benign and suggested the correct specific diagnosis in 51.5% (354/687) of tumors. For mucinous cystadenomas, the median diameter of the largest tumor was 93 (range, 12–550) mm. Most mucinous cystadenomas were described as unilateral (594/631 (94.1%)) with multilocular morphology (357/631 (56.6%)), and most manifested low‐level echogenicity (334/631 (52.9%)). Most mucinous cystadenomas were poorly (color score of 2; 248/631 (39.3%)) or moderately (color score of 3; 194/631 (30.7%)) vascularized on color Doppler examination. The original ultrasound examiner correctly classified 87.5% (552/631) of mucinous cystadenomas as benign and suggested the correct specific diagnosis in 42.9% (271/631) of tumors. Based on pattern recognition (review of ultrasound images available for 433 tumors), the most typical sonographic features of serous cystadenomas were unilocular cyst (100/211 (47.4%)) or multilocular cyst with < 10 cyst locules (71/211 (33.6%)), whereas the typical features of mucinous cystadenomas were multilocular cyst with < 10 cyst locules (99/222 (44.6%)), unilocular cyst (78/222 (35.1%)) or multilocular cyst with > 10 cyst locules (31/222 (14.0%)). A honeycomb nodule was found in some mucinous cystadenomas (31/222 (14.0%)) but was not found in serous cystadenomas.ConclusionsSerous and mucinous cystadenomas exhibit typical sonographic features, allowing ultrasound examiners to assign a correct specific diagnosis to most tumors. Recognizing the ultrasound features of cystadenomas and avoiding misdiagnosing them as malignant can help prevent surgery for these benign tumors in asymptomatic patients. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA‐1 multinomial regression model: validation study

ABSTRACTObjectivesTo assess the ability of the International Endometrial Tumor Analysis (IETA)‐1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding.MethodsThis was a retrospective study, in which we validated the IETA‐1 model on the IETA‐3 study cohort (n = 1745). The IETA‐3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow‐up of non‐endometrial pathology, in the work‐up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow‐up of at least 1 year if endometrial sampling was not performed. The IETA‐1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non‐uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver‐operating‐characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio).ResultsThe median age of the women in the IETA‐3 cohort was 51 (range, 20–85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA‐1 model had an AUC of 0.81 (95% CI, 0.73–0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32–0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62–0.73) (n = 1532). The IETA‐1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95–0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75–0.91), compared with 0.62 (95% CI, 0.52–0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08–0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA‐1 model gave an AUC of 0.81 (95% CI, 0.71–0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60–0.81) (difference in AUC, 0.11; 95% CI, 0.01–0.20).ConclusionThe IETA‐1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.