ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

Imaging in gynecological disease (26): clinical and ultrasound characteristics of benign retroperitoneal pelvic peripheral-nerve-sheath tumors.

OBJECTIVE: To describe the clinical and sonographic characteristics of benign, retroperitoneal, pelvic peripheral-nerve-sheath tumors (PNSTs). METHODS: This was a retrospective study of patients with a benign, retroperitoneal, pelvic PNST who had undergone preoperative ultrasound examination at a single gynecologic oncology center between 1 January 2018 and 31 August 2022. All ultrasound images, videoclips and final histological specimens of benign PNSTs were reviewed side-by-side in order to: describe the ultrasound appearance of the tumors, using the terminology of the International Ovarian Tumor Analysis (IOTA), Morphological Uterus Sonographic Assessment (MUSA) and Vulvar International Tumor Analysis (VITA) groups, following a predefined ultrasound assessment form; describe their origin in relation to nerves and pelvic anatomy; and assess the association between their ultrasound features and histotopography. A review of the literature reporting benign, retroperitoneal, pelvic PNSTs with preoperative ultrasound examination was performed. RESULTS: Five women (mean age, 53 years) with a benign, retroperitoneal, pelvic PNST were identified, four with a schwannoma and one with a neurofibroma, of which all were sporadic and solitary. All patients had good-quality ultrasound images and videoclips and final biopsy of surgically excised tumors, except one patient managed conservatively who had only a core needle biopsy. In all cases, the findings were incidental. The five PNSTs ranged in maximum diameter from 31 to 50 mm. All five PNSTs were solid, moderately vascular tumors, with non-uniform echogenicity, well-circumscribed by hyperechogenic epineurium and with no acoustic shadowing. Most of the masses were round (n = 4 (80%)), and contained small, irregular, anechoic, cystic areas (n = 3 (60%)) and hyperechogenic foci (n = 5 (100%)). In the woman with a schwannoma in whom surgery was not performed, follow-up over a 3-year period showed minimal growth (1.5 mm/year) of the mass. We also summarize the findings of 47 cases of benign retroperitoneal schwannoma and neurofibroma identified in a literature search. CONCLUSIONS: On ultrasound examination, no imaging characteristics differentiate reliably between benign schwannomas and neurofibromas. Moreover, benign PNSTs show some similar features to malignant retroperitoneal tumors. They are solid lesions with intralesional blood vessels and show degenerative changes such as cystic areas and hyperechogenic foci. Therefore, ultrasound-guided biopsy may play a pivotal role in their diagnosis. If confirmed to be benign PNSTs, these tumors can be managed conservatively, with ultrasound surveillance. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Addendum to the consensus opinion from the International Deep Endometriosis Analysis (IDEA) group: sonographic evaluation of the parametrium.

Preoperative sonographic staging in patients with suspected parametrial endometriosis is essential to plan the surgical intervention and to anticipate the need for a multidisciplinary approach, and hence optimize surgical outcome. The results of a recent metanalysis suggest that defining more accurately the ultrasonographic criteria of parametrial involvement in endometriosis is needed. The aim of this addendum to the IDEA-consensus is to highlight the sonographic characteristics of the parametrium and identify ultrasound techniques to diagnose deep endometriosis in this area. This article is protected by copyright. All rights reserved.

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.

Quality of life after extended pelvic exenterations.

BACKGROUND: The aim of the study was to compare health-related quality of life (QoL) and oncological outcome between gynaecological cancer patients undergoing pelvic exenteration (PE) and extended pelvic exenteration (EPE). EPEs were defined as extensive procedures including, in addition to standard PE extent, the resection of internal, external, or common iliac vessels; pelvic side-wall muscles; large pelvic nerves (sciatic or femoral); and/or pelvic bones. METHODS: Data from 74 patients who underwent PE (42) or EPE (32) between 2004 and 2019 at a single tertiary gynae-oncology centre in Prague were analysed. QoL assessment was performed using EORTC QLQ-C30, EORTC CX-24, and QOLPEX questionnaires specifically developed for patients after (E)PE. RESULTS: No significant differences in survival were observed between the groups (P > 0.999), with median overall and disease-specific survival in the whole cohort of 45 and 49 months, respectively. Thirty-one survivors participated in the QoL surveys (20 PE, 11 EPE). No significant differences were observed in global health status (P = 0.951) or in any of the functional scales. The groups were not differing in therapy satisfaction (P = 0.502), and both expressed similar, high willingness to undergo treatment again if they were to decide again (P = 0.317). CONCLUSIONS: EPEs had post-treatment QoL and oncological outcome comparable to traditional PE. These procedures offer a potentially curative treatment option for patients with persistent or recurrent pelvic tumour invading into pelvic wall structures without further compromise of patients´ QoL.

Preoperative staging of ovarian cancer: comparison between ultrasound, CT and whole-body diffusion-weighted MRI (ISAAC study).

OBJECTIVES: To compare the performance of transvaginal and transabdominal ultrasound with that of the first-line staging method (contrast-enhanced computed tomography (CT)) and a novel technique, whole-body magnetic resonance imaging with diffusion-weighted sequence (WB-DWI/MRI), in the assessment of peritoneal involvement (carcinomatosis), lymph-node staging and prediction of non-resectability in patients with suspected ovarian cancer. METHODS: Between March 2016 and October 2017, all consecutive patients with suspicion of ovarian cancer and surgery planned at a gynecological oncology center underwent preoperative staging and prediction of non-resectability with ultrasound, CT and WB-DWI/MRI. The evaluation followed a single, predefined protocol, assessing peritoneal spread at 19 sites and lymph-node metastasis at eight sites. The prediction of non-resectability was based on abdominal markers. Findings were compared to the reference standard (surgical findings and outcome and histopathological evaluation). RESULTS: Sixty-seven patients with confirmed ovarian cancer were analyzed. Among them, 51 (76%) had advanced-stage and 16 (24%) had early-stage ovarian cancer. Diagnostic laparoscopy only was performed in 16% (11/67) of the cases and laparotomy in 84% (56/67), with no residual disease at the end of surgery in 68% (38/56), residual disease ≤ 1 cm in 16% (9/56) and residual disease > 1 cm in 16% (9/56). Ultrasound and WB-DWI/MRI performed better than did CT in the assessment of overall peritoneal carcinomatosis (area under the receiver-operating-characteristics curve (AUC), 0.87, 0.86 and 0.77, respectively). Ultrasound was not inferior to CT (P = 0.002). For assessment of retroperitoneal lymph-node staging (AUC, 0.72-0.76) and prediction of non-resectability in the abdomen (AUC, 0.74-0.80), all three methods performed similarly. In general, ultrasound had higher or identical specificity to WB-DWI/MRI and CT at each of the 19 peritoneal sites evaluated, but lower or equal sensitivity in the abdomen. Compared with WB-DWI/MRI and CT, transvaginal ultrasound had higher accuracy (94% vs 91% and 85%, respectively) and sensitivity (94% vs 91% and 89%, respectively) in the detection of carcinomatosis in the pelvis. Better accuracy and sensitivity of ultrasound (93% and 100%) than WB-DWI/MRI (83% and 75%) and CT (84% and 88%) in the evaluation of deep rectosigmoid wall infiltration, in particular, supports the potential role of ultrasound in planning rectosigmoid resection. In contrast, for the bowel serosal and mesenterial assessment, abdominal ultrasound had the lowest accuracy (70%, 78% and 79%, respectively) and sensitivity (42%, 65% and 65%, respectively). CONCLUSIONS: This is the first prospective study to document that, in experienced hands, ultrasound may be an alternative to WB-DWI/MRI and CT in ovarian cancer staging, including peritoneal and lymph-node evaluation and prediction of non-resectability based on abdominal markers of non-resectability. © 2021 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.

Terms, definitions and measurements to describe sonographic features of lymph nodes: consensus opinion from the Vulvar International Tumor Analysis (VITA) group.

In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Interobserver agreement of transvaginal ultrasound and magnetic resonance imaging in local staging of cervical cancer.

OBJECTIVE: To evaluate interobserver agreement for the assessment of local tumor extension in women with cervical cancer, among experienced and less experienced observers, using transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI). METHODS: The TVS observers were all gynecologists and consultant ultrasound specialists, six with and seven without previous experience in cervical cancer imaging. The MRI observers were five radiologists experienced in pelvic MRI and four less experienced radiology residents without previous experience in MRI of the pelvis. The less experienced TVS observers and all MRI observers underwent a short basic training session in the assessment of cervical tumor extension, while the experienced TVS observers received only a written directive. All observers were assigned the same images from cervical cancer patients at all stages (n = 60) and performed offline evaluation to answer the following three questions: (1) Is there a visible primary tumor? (2) Does the tumor infiltrate > ⅓ of the cervical stroma? and (3) Is there parametrial invasion? Interobserver agreement within the four groups of observers was assessed using Fleiss kappa (κ) with 95% CI. RESULTS: Experienced and less experienced TVS observers, respectively, had moderate interobserver agreement with respect to tumor detection (κ (95% CI), 0.46 (0.40-0.53) and 0.46 (0.41-0.52)), stromal invasion > ⅓ (κ (95% CI), 0.45 (0.38-0.51) and 0.53 (0.40-0.58)) and parametrial invasion (κ (95% CI), 0.57 (0.51-0.64) and 0.44 (0.39-0.50)). Experienced MRI observers had good interobserver agreement with respect to tumor detection (κ (95% CI), 0.70 (0.62-0.78)), while less experienced MRI observers had moderate agreement (κ (95% CI), 0.51 (0.41-0.62)), and both experienced and less experienced MRI observers, respectively, had good interobserver agreement regarding stromal invasion (κ (95% CI), 0.80 (0.72-0.88) and 0.71 (0.61-0.81)) and parametrial invasion (κ (95% CI), 0.69 (0.61-0.77) and 0.71 (0.61-0.81)). CONCLUSIONS: We found interobserver agreement for the assessment of local tumor extension in patients with cervical cancer to be moderate for TVS and moderate-to-good for MRI. The level of interobserver agreement was associated with experience among TVS observers only for parametrial invasion. © 2021 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 (22): clinical and ultrasound characteristics of ovarian embryonal carcinomas, non-gestational choriocarcinomas and malignant mixed germ cell tumors.

OBJECTIVE: To describe the clinical and ultrasound characteristics of three types of rare malignant ovarian germ cell tumor: embryonal carcinoma, non-gestational choriocarcinoma and malignant mixed germ cell tumor. METHODS: This was a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database, we identified patients with a histological diagnosis of ovarian embryonal carcinoma, non-gestational choriocarcinoma or malignant mixed germ cell tumor, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 2000 and 2020. Additional patients with the same histology were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. Three examiners reviewed all available ultrasound images and described them using pattern recognition. RESULTS: One patient with embryonal carcinoma, five patients with non-gestational ovarian choriocarcinoma and seven patients with ovarian malignant mixed germ cell tumor (six primary tumors and one recurrence) were identified. Seven patients were included in the IOTA studies and six patients were examined outside of the IOTA studies. The median age at diagnosis was 26 (range, 14-77) years. Beta-human chorionic gonadotropin levels were highest in non-gestational choriocarcinomas and alpha-fetoprotein levels were highest in malignant mixed germ cell tumors. Most tumors were International Federation of Gynecology and Obstetrics (FIGO) Stage I (9/12 (75.0%)). All tumors were unilateral, and the median largest diameter was 129 (range, 38-216) mm. Of the tumors, 11/13 (84.6%) were solid and 2/13 (15.4%) were multilocular-solid; 9/13 (69.2%) manifested abundant vascularization on color Doppler examination. Using pattern recognition, the typical ultrasound appearance was a large solid tumor with inhomogeneous echogenicity of the solid tissue and often dispersed cysts which, in most cases, were small and irregular. Some tumors had smooth contours while others had irregular contours. CONCLUSIONS: A unilateral, large solid tumor with inhomogeneous echogenicity of the solid tissue and with dispersed small cystic areas in a young woman should raise the suspicion of a rare malignant germ cell tumor. This suspicion can guide the clinician to test tumor markers specific for malignant germ cell tumors. © 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.

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.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors.

The European Society of Gynaecological Oncology (ESGO), the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG), the International Ovarian Tumour Analysis (IOTA) group and the European Society for Gynaecological Endoscopy (ESGE) jointly developed clinically relevant and evidence-based statements on the preoperative diagnosis of ovarian tumors, including imaging techniques, biomarkers and prediction models. ESGO/ISUOG/IOTA/ESGE nominated a multidisciplinary international group, including expert practising clinicians and researchers who have demonstrated leadership and expertise in the preoperative diagnosis of ovarian tumors and management of patients with ovarian cancer (19 experts across Europe). A patient representative was also included in the group. To ensure that the statements were evidence-based, the current literature was reviewed and critically appraised. Preliminary statements were drafted based on the review of the relevant literature. During a conference call, the whole group discussed each preliminary statement and a first round of voting was carried out. Statements were removed when consensus among group members was not obtained. The voters had the opportunity to provide comments/suggestions with their votes. The statements were then revised accordingly. Another round of voting was carried out according to the same rules to allow the whole group to evaluate the revised version of the statements. The group achieved consensus on 18 statements. This Consensus Statement presents these ESGO/ISUOG/IOTA/ESGE statements on the preoperative diagnosis of ovarian tumors and the assessment of carcinomatosis, together with a summary of the evidence supporting each statement.

Declaración de consenso de ESGO/ISUOG/IOTA/ESGE sobre el diagnóstico preoperatorio de los tumores de ovario La Sociedad Europea de Oncología Ginecológica (ESGO), la Sociedad Internacional de Ecografía en Obstetricia y Ginecología (ISUOG), el Grupo Internacional de Análisis de Tumores de Ovario (IOTA) y la Sociedad Europea de Endoscopia Ginecológica (ESGE) elaboraron conjuntamente declaraciones de importancia para la práctica clínica y con base empírica sobre el diagnóstico preoperatorio de los tumores de ovario, a partir de imágenes, biomarcadores y modelos de predicción, entre otras técnicas. La ESGO/ISUOG/IOTA/ESGE designó a un grupo internacional multidisciplinar, que incluye a personas expertas de la práctica clínica y la investigación que han demostrado liderazgo y experiencia en el diagnóstico preoperatorio de los tumores de ovario y en el tratamiento de las pacientes con cáncer de ovario (19 personas expertas de toda Europa). También se incluyó en el grupo a una representante de las pacientes. Para garantizar que las declaraciones tenían una base empírica, se revisó la literatura actual y se valoró de forma crítica. Se redactaron declaraciones preliminares basadas en la revisión de la literatura pertinente. La totalidad del grupo debatió durante una teleconferencia cada declaración preliminar y se llevó a cabo una primera ronda de votaciones. Las declaraciones se eliminaron cuando no se obtuvo el consenso entre los miembros del grupo. Los votantes tuvieron la oportunidad de aportar comentarios/sugerencias a la par que sus votos. Las declaraciones se revisaron en consecuencia. Se llevó a cabo otra ronda de votaciones según las mismas reglas para que todo el grupo pudiera evaluar la versión revisada de las declaraciones. El grupo logró un consenso sobre 18 declaraciones. Esta Declaración de Consenso presenta estas declaraciones de la ESGO/ISUOG/IOTA/ESGE sobre el diagnóstico preoperatorio de los tumores de ovario y la evaluación de la carcinomatosis, junto con un resumen de la evidencia que apoya cada declaración.

Imaging in gynecological disease (19): clinical and ultrasound features of extragastrointestinal stromal tumors (eGIST).

OBJECTIVE: To describe the clinical and sonographic characteristics of extragastrointestinal stromal tumors (eGISTs). METHODS: This was a retrospective multicenter study. The data of patients with a histological diagnosis of eGIST who had undergone preoperative ultrasound examination were retrieved from the databases of nine large European gynecologic oncology centers. One investigator from each center reviewed stored images and ultrasound reports, and described the lesions using the terminology of the International Ovarian Tumor Analysis and Morphological Uterus Sonographic Assessment groups, following a predefined ultrasound evaluation form. Clinical, surgical and pathological information was also recorded. RESULTS: Thirty-five women with an eGIST were identified; in 17 cases, the findings were incidental, and 18 cases were symptomatic. Median age was 57 years (range, 21-85 years). Tumor marker CA 125 was available in 23 (65.7%) patients, with a median level of 23 U/mL (range, 7-403 U/mL). The vast majority of eGISTs were intraperitoneal lesions (n = 32 (91.4%)); the remaining lesions were retroperitoneal (n = 2 (5.7%)) or preperitoneal (n = 1 (2.9%)). The most common site of the tumor was the abdomen (n = 23 (65.7%)), and less frequently the pelvis (n = 12 (34.3%)). eGISTs were typically large (median largest diameter, 79 mm) solid (n = 31 (88.6%)) tumors, and were less frequently multilocular-solid tumors (n = 4 (11.4%)). The echogenicity of solid tumors was uniform in 8/31 (25.8%) cases, which were all hypoechogenic. Twenty-three solid eGISTs were non-uniform, either with mixed echogenicity (9/23 (39.1%)) or with cystic areas (14/23 (60.9%)). The tumor shape was mainly lobular (n = 19 (54.3%)) or irregular (n = 10 (28.6%)). Tumors were typically richly vascularized (color score of 3 or 4, n = 31 (88.6%)) with no shadowing (n = 31 (88.6%)). Based on pattern recognition, eGISTs were usually correctly classified as a malignant lesion in the ultrasound reports (n = 32 (91.4%)), and the specific diagnosis of eGIST was the most frequent differential diagnosis (n = 16 (45.7%)), followed by primary ovarian cancer (n = 5 (14.3%)), lymphoma (n = 2 (5.7%)) and pedunculated uterine fibroid (n = 2 (5.7%)). CONCLUSIONS: On ultrasound, eGISTs were usually solid, non-uniform pelvic or abdominal lobular tumors of mixed echogenicity, with or without cystic areas, with rich vascularization and no shadowing. The presence of a tumor with these features, without connection to the bowel wall, and not originating from the uterus or adnexa, is highly suspicious for eGIST. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

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.

Role of CA125/CEA ratio and ultrasound parameters in identifying metastases to the ovaries in patients with multilocular and multilocular-solid ovarian masses.

OBJECTIVES: To investigate ultrasound features and the best cut-off value of the cancer antigen 125/carcinoembryonic antigen (CA125/CEA) ratio to discriminate ovarian metastases from benign and primary malignant ovarian neoplasms in two selected groups of morphological ovarian masses, namely multilocular masses with five or more locules and multilocular-solid masses. METHODS: Patients with multilocular (five or more locules) or multilocular-solid ovarian masses, operated on within 3 months of ultrasound examination, and with tumor markers (CEA and CA125) available at diagnosis, were identified retrospectively from three ultrasound centers. The masses were described using the International Ovarian Tumor Analysis (IOTA) terminology. Ultrasound and clinical characteristics were compared between those with an ovarian neoplasm (including benign and primary malignant neoplasms) and those with an ovarian metastasis. Receiver-operating characteristics curve (ROC) analysis was used to evaluate the ability of CA125, CEA and CA125/CEA to differentiate between ovarian neoplasms and ovarian metastases, and their predictive performance was assessed. RESULTS: In total, 350 (88.4%) patients with an ovarian neoplasm (including 99 benign, 43 borderline and 197 primary epithelial ovarian carcinomas, seven malignant rare tumors and four other types of invasive ovarian tumor) and 46 (11.6%) patients with an ovarian metastasis were analyzed. On ultrasound examination, ovarian neoplasms were smaller than ovarian metastases (median largest diameter, 97 (range, 20-387) mm vs 146 (range, 43-259) mm, respectively; P < 0.0001) and presented with a lower number of cysts with > 10 locules (18.9% vs 54.3%; P < 0.0001). ROC curve analysis showed that the best cut-off value of CEA for distinguishing between ovarian neoplasms and ovarian metastases was 2.33 ng/mL. The predictive performance of this CEA cut-off value was: area under the curve (AUC), 0.791 (95% CI, 0.711-0.870); accuracy, 73.7%; sensitivity, 73.1%; specificity, 78.3%; positive predictive value (PPV), 96.2%; and negative predictive value (NPV), 27.7%. The best cut-off value of CA125/CEA for distinguishing between ovarian neoplasms and ovarian metastases was 11.92. The predictive performance of this CA125/CEA cut-off value was: AUC, 0.758 (95% CI, 0.683-0.833); accuracy, 79.8%; sensitivity, 82.3%; specificity, 60.9%; PPV, 94.1%; and NPV, 31.1%. CONCLUSIONS: CA125/CEA ratio and CEA alone did not show any significant difference in their ability to distinguish between ovarian neoplasms (including benign and malignant) and ovarian metastases in masses with multilocular and those with multilocular-solid morphology. Therefore, in this morphological subgroup of ovarian masses, CEA alone is sufficient to differentiate between ovarian neoplasms and ovarian metastases. Copyright © 2018 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.

Diagnostic pitfalls in ovarian androgen-secreting (Leydig cell) tumours: case series.

Leydig cell tumours of the ovary are rare and represent a diagnostic challenge not only due to their sporadic incidence but also due to the seemingly normal imaging. We present three cases of pre- and postmenopausal women who were presented with severe clinical signs of hyperandogenism where modern imaging modalities (including computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography combined with computed tomography (PET-CT)) failed to identify the tumour. Two patients underwent non-expert ultrasound, CT and MRI examination with uniform conclusion that ovaries are of normal appearance. One of the two patients even had a PET-CT performed, which was inconclusive. Our case reports show the importance of examination by specialists with established skills in gynaecologic ultrasonography in the diagnosis of the Leydig cell tumours. The most useful diagnostic tool seems to be the combination of age (postmenopause), symptoms (onset of hirsutism and virilisation), high total testosterone plasma values and expert sonography. On ultrasound, these tumours are unilateral, usually small, solid intraovarian nodules of a slightly increased echogenicity in contrast to the surrounding ovarian tissue, delineated by abundant perfusion with an enhanced vascularity. The appropriate setting of the sensitive colour Doppler is crucial for the detection of intraovarian Leydig cell tumour. Impact statement What is already known on this subject? A diagnosis of Leydig cell tumours is based on ultrasound performed by a trained examiner or by MRI. CT or PET/CT are not among the primary methods of choice. According to the results of imaging investigations surgical treatment is planned. Because these tumours are usually benign and have a good prognosis the unilateral salpingo-oophorectomy is a standard procedure. What do the results of this study add? Our case series show how difficult it can be to establish the diagnosis of Leydig cell tumours by imaging, including transvaginal ultrasound, the most frequently recommended diagnostic tool. We demonstrate in three cases how easily a small hyperechogenic tumour can be overseen or interchanged for a different gynaecological pathology if transvaginal scan is not performed by an experienced examiner trained in sonographic features of gynaecologic neoplasms. What are the implications of these findings for clinical practice and/or further research? This case series demonstrate how important it is to see the patient in the whole complexity with their medical history, proper clinical symptoms evaluation, laboratory test and not to rely solely just on sophisticated high-end investigations, such as the PET-CT, a CT and an MRI. It also emphasises the importance of specialists with established skills in gynaecologic ultrasonography. Further effort should be made to define the resources for the appropriate training of such sonographers.

The role of ultrasound in primary workup of cervical cancer staging (ESGO, ESTRO, ESP cervical cancer guidelines).

OBJECTIVE: In 2018 three European societies have joined to create clinically relevant guidelines on the diagnosis and management of cervical cancer. The European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) agreed on diagnostic approaches in cervical cancer staging. DESIGN: Review article. SETTING: Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague. METHODS: A literature review of published data on cervical cancer staging. RESULTS: Physical examination with biopsy still has its place in histological confirmation of malignancy but doesnt offer much information on the extent of the disease. It is historically the first time when transvaginal/transrectal ultrasound (TVS/TRS) is recommended as an alternative to the magnetic resonance (MRI) in a primary workup. Both imaging modalities offer excellent soft tissue contrast resolution, which is crucial in tumour detection and evaluation of local extent of tumour, including the depth of tumour infiltration in the bladder and rectal wall. These new advances in imaging rendered the use of cystoscopy and rectoscopy redundant. Similarly, with the implementation of modern imaging in pretreatment staging, intravenous urography has lost its role in the staging. Apart from the local extent of the disease, it is necessary to accurately evaluate the lymph node status in order to plan optimal treatment. The detection rate of imaging reflects the prevalence of lymph node metastases depending on tumor stage and size of metastasis. In the early stage disease (T1a, T1b1, T2a1) with negative lymph nodes on TVS/TRS or MRI, surgicopathological staging of pelvic lymph nodes is a method of choice for detection of small volume metastases. Both imaging modalities might not detect small metastatic lesions within non-enlarged lymph nodes, but by identifying the characteristic changes of the infiltrated lymph nodes they have very low rate of false positives. In locally advanced cervical cancer (T1b2 and higher, except T2a1) or early stages with positive lymph nodes detected on ultrasound or MRI, computed tomography (CT) or CT in combination with positron emission tomography (PET-CT) are recommended to assess distant spread including paraaortic lymph nodes and chest. PET-CT is the preferred option in cases indicated for primary chemoradiation. Unfortunatelly no imaging method is accurate enough to exclude small volume metastasis in paraaortic nodes. In the cases with negative paraaortic lymph nodes on CT or PET-CT, surgicopathological staging with dissection of the paraaortic lymph nodes may be considered. In order to reduce false positive findings by imaging methods, it is recomended to obtain an ultrasound or CT-guided tru-cut biopsy from any equivocal extrauterine lesion to avoid inappropriate treatment. CONCLUSION: This review offers scientific evidence that led to the recent changes in the cervical cancer staging.

Diagnosis of endometriosis 1st part - Overview of diagnostic approaches.

Cíl studie: Shrnutí současných poznatků a trendů v oblasti diagnostiky endometriózy. Typ studie: Literární přehled. Název a sídlo pracoviště: Centrum pro komplexní léčbu endometriózy a Onkogynekologické centrum, Gynekologicko-porodnická klinika, 1. lékařská fakulta, Univerzita Karlova a Všeobecná fakultní nemocnice Praha; Department of Gynaecology and Obstetrics, Burton Hospitals NHS, UK. Metodika: Systematický přehledový článek. Výsledky: Diagnóza endometriózy v primární péči je stanovena na podkladě anamnézy, fyzikálního vyšetření a základního ultrazvukového vyšetření, které zobrazí přítomnost endometroidních cyst, adenomyózy a nepřímé známky srůstů. Použití krevních či močových biomarkerů se nedoporučuje. Pacientky s podezřením na přítomnost endometriózy by měly být odeslány do specializovaného centra léčby endometriózy, kde jsou k dispozici zkušení sonografisté anebo radiologové v rámci expertního ultrazvuku anebo magnetické rezonance a specializovaný chirurgický tým. Vysoká diagnostická přesnost obou zobrazovacích metod nepodporuje rutinní využití laparoskopie v diagnostice endometriózy, může však být zvažována k vyloučení povrchové anebo extrapelvické endometriózy u symptomatických pacientek s negativním nálezem při zobrazovacích metodách. Závěr: Během základního ultrazvukového vyšetření by ošetřující gynekolog měl být schopen zobrazit přítomnost endometroidních cyst, adenomyózy a nepřímé známky adhezí a na základě ultrazvukového nálezu anebo typických symptomů odeslat pacientku do centra pro léčbu endometriózy. Expertní ultrazvukové vyšetření pánevní endometriózy je obvykle dostupné ve specia-lizovaných centrech léčby endometriózy. Vzhledem k vysoké diagnostické přesnosti ultrazvuku, jeho běžné dostupnosti v gynekologii, nižší ceně a absenci kontraindikací ve srovnání s magnetickou rezonancí je ultrazvuk metodou volby v zobrazení rozsáhlé pánevní endometriózy, zatímco magnetická rezonance je využívána jako metoda druhé volby v obtížných případech.