Performance of IOTA Simple Rules Risks, ADNEX Model, Subjective Assessment Compared to CA125 and HE4 with ROMA Algorithm in Discriminating between Benign, Borderline and Stage I Malignant Adnexal Lesions.

BACKGROUND: Borderline ovarian tumors (BOTs) and early clinical stage malignant adnexal masses can make sonographic diagnosis challenging, while the clinical utility of tumor markers, e.g., CA125 and HE4, or the ROMA algorithm, remains controversial in such cases. OBJECTIVE: To compare the IOTA group Simple Rules Risk (SRR), the ADNEX model and the subjective assessment (SA) with serum CA125, HE4 and the ROMA algorithm in the preoperative discrimination between benign tumors, BOTs and stage I malignant ovarian lesions (MOLs). METHODS: A multicenter retrospective study was conducted with lesions classified prospectively using subjective assessment and tumor markers with the ROMA. The SRR assessment and ADNEX risk estimation were applied retrospectively. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) were calculated for all tests. RESULTS: In total, 108 patients (the median age: 48 yrs, 44 postmenopausal) with 62 (79.6%) benign masses, 26 (24.1%) BOTs and 20 (18.5%) stage I MOLs were included. When comparing benign masses with combined BOTs and stage I MOLs, SA correctly identified 76% of benign masses, 69% of BOTs and 80% of stage I MOLs. Significant differences were found for the presence and size of the largest solid component (p = 0.0006), the number of papillary projections (p = 0.01), papillation contour (p = 0.008) and IOTA color score (p = 0.0009). The SRR and ADNEX models were characterized by the highest sensitivity (80% and 70%, respectively), whereas the highest specificity was found for SA (94%). The corresponding likelihood ratios were as follows: LR+ = 3.59 and LR- = 0.43 for the ADNEX; LR+ = 6.40 and LR- = 0.63 for SA and LR+ = 1.85 with LR- = 0.35 for the SRR. The sensitivity and specificity of the ROMA test were 50% and 85%, respectively, with LR+ = 3.44 and LR- = 0.58. Of all the tests, the ADNEX model had the highest diagnostic accuracy of 76%. CONCLUSIONS: This study demonstrates the limited value of diagnostics based on CA125 and HE4 serum tumor markers and the ROMA algorithm as independent modalities for the detection of BOTs and early stage adnexal malignant tumors in women. SA and IOTA methods based on ultrasound examination may present superior value over tumor marker assessment.

Risk Assessment of Endometrial Hyperplasia or Endometrial Cancer with Simplified Ultrasound-Based Scoring Systems.

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

Magnetic Resonance-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids-Efficiency Assessment with the Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging and the Potential Role of the Administration of Uterotonic Drugs.

OBJECTIVE: The assessment of the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) when qualifying patients with uterine fibroids (UFs) for magnetic resonance-guided high-intensity ultrasound (MR-HIFU). MATERIAL AND METHODS: This retrospective, single center study included 283 women who underwent DCE-MRI and were treated with MR-HIFU. The patients were divided according to non-perfused volume (NPV) as well as by the type of curve for patients with a washout curve in the DCE-MRI study and patients without a washout curve. The studied women were assessed in three groups according to the type of uterotonics administered. Group A (57 patients) received one dose of misoprostol/diclofenac transvaginally and group B (71 patients) received oxytocin intravenously prior to the MR-HIFU procedure. The remaining 155 women (group C) were treated with the traditional non-drug enhanced MR-HIFU procedure. RESULTS: The average NPV value was higher in no washout group, and depended on the uterotonics used. CONCLUSIONS: We demonstrated a correlation between dynamic contrast enhancement curve types and the therapeutic efficacy of MR-HIFU. Our results suggest that DCE-MRI has the potential to assess treatment outcomes among patients with UFs, and patients with UFs that present with a washout curve may benefit from the use of uterotonic drugs. More studies are required to draw final conclusions.

Sonographic Assessment of Complex Ultrasound Morphology Adnexal Tumors in Pregnant Women with the Use of IOTA Simple Rules Risk and ADNEX Scoring Systems

BACKGROUND: To evaluate the accuracy of subjective assessment (SA), the International Ovarian Tumor Analysis (IOTA) group Simple Rules Risk (SRR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the preoperative differentiation of adnexal masses in pregnant women. METHODS: The study population comprised 36 pregnant women (median age: 28.5 years old, range: 20-42 years old) with a mean gestation age of 13.5 (range: 8-31) weeks at diagnosis. Tumors were prospectively classified by local sonographers as probably benign or probably malignant using SA. Final tumor histological diagnosis was used as the reference standard in all cases. Logistic regression SRR and ADNEX models were used to obtain a risk score for every case. Serum CA125 and human epidydimis protein 4 (HE4) concentrations were also retrieved and the Risk of Ovarian Malignancy Algorithm (ROMA) value was calculated. The calculated predictive values included positive and negative likelihood ratios of ultrasound and biochemical tests. RESULTS: Final histology confirmed 27 benign and 9 malignant (including 2 borderline) masses. The highest sensitivity (89%) and specificity (70%) were found for the subjective tumor assessment. Although no malignancy was classified as benign using the SRR criteria (sensitivity = 100%), the specificity of this scoring system was only 37%. At the cut-off risk level of >20%, the ADNEX model had a sensitivity of 78% and a specificity of 70%. Serum levels of CA125, HE4 and the ROMA risk model correctly identified adnexal malignant tumors with a sensitivity of 67%, 25% and 25%, respectively. Corresponding specificities were 72%, 100% and 100%, respectively. The highest positive and negative likelihood ratios were found for SA (LR+ = 3.0 and LR- = 0.16, respectively). Overall diagnostic accuracy of all predictive methods used in this study were similar (range: 70-75%) except for SRR (53%). CONCLUSION: Subjective assessment remains the best predictive method in complex adnexal masses found at prenatal ultrasound in pregnant women. For less experienced sonographers, both the SRR and ADNEX scoring systems may be also used for the characterization of such tumors, while serum tumor markers CA125 and HE4, along with the ROMA algorithm appear to be less accurate.

Diabetic Mastopathy. Review of Diagnostic Methods and Therapeutic Options.

Diabetic mastopathy is a rare breast condition that may occur in insulin-treated men and women of any age. The etiology is still unclear; however, the autoimmunological background of the disease is highly suspected. The changes in diabetic mastopathy may mimic breast cancer; therefore, its diagnostic process is demanding, and treatment options are not clear and limited. Lesions in DM are usually multiple; therefore, surgical removal is not fully effective. A well-done anamnesis with core-needle biopsy is essential and definitive in most cases. In this review, we summarize up-to-date knowledge of diagnostic methods and therapeutic options for diabetic mastopathy treatment and present three cases of diabetic mastopathy-type lesions in ultrasound and radiological examinations.

Tumor budding index and microvessel density assessment in patients with endometrial cancer: A pilot study.

The present study aimed to analyze the association between tumor budding index (TBI) and microvessel density (MVD) and selected clinicopathological features in female patients with endometrial cancer (EC). The present study included 137 patients, of whom 117 had endometrial endometrioid cancer and 3 had non-endometrioid EC (NEEC). Additionally, 8 cases of simple endometrial hyperplasia and 9 cases of atypical endometrial hyperplasia were included in the present study. Patient age, menopausal status, tumor histological type, grade and International Federation of Gynecologists and Obstetricians (FIGO) clinical stage were investigated. Immunohistochemistry was utilized to detect MVD using a CD34 antibody, and a laminin-5γ2 antibody was used for TBI assessment. In nonmalignant endometrial lesions, the TBI was significantly lower than that in patients with EC and NEEC (P=0.002). Significant differences in median TBI (MD-TBI) were also observed between patients with low-grade EC (MD-TBI, 4.5) and high-grade EC (MD-TBI, 16.2; P=0.01). Age, body mass index and tumor FIGO stage were not indicated to be associated with the MD-TBI. Premenopausal patients with EC had lower MD-TBI values than postmenopausal patients (0.3 vs. 11.1; P<0.005). The median MVD-CD34 in the study group was 19 (range, 13-29). Significant differences in MVD-CD34 were observed between malignant and nonmalignant endometrial lesions (P=0.01). Histological grade was markedly associated with tumor MVD-CD34 (P=0.001). The MVD was higher in high-grade cancer (G3; MVD-CD34, 24.9) than in grade G1 and G2 lesions (MVD-CD34, 14 and 18.6, respectively; P=0.01). FIGO clinical stage was not associated with MVD-CD34 in low and high stage lesions (MD, 18.4 for FIGO stage I/II; MD, 17.6 for FIGO stage III/IV; P=0.2). High MVD was markedly associated with high MD-TBI (P=0.0002). In conclusion, TBI could be a valuable indicator of tumor aggressiveness in patients with EC. The presence of the tumor budding phenomenon with increased MVD may have the potential to further refine clinical management decisions when endometrial malignancy is detected.

Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively: multicentre cohort study.

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.

The Role of miRNA and Related Pathways in Pathophysiology of Uterine Fibroids-From Bench to Bedside.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. Their prevalence usually is estimated at 30-40%, but may reach up to 70-80% in predisposed groups of women. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. The mechanisms leading to UFs formation and growth still remain poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is thought to be a starting point of all pathways leading to UF formation. Micro-ribonucleic acids (miRNAs) are non-coding single-stranded RNAs about 22 nucleotides in length, that regulate gene expression. One of recent advances in this field is the comprehension of the role of miRNAs in tumorigenesis. Alterations in the levels of miRNAs are related to the formation and growth of several tumors which show a distinct miRNA signature. The aim of this review is to summarize the current data about the role of miRNAs in the pathophysiology of UFs. We also discuss future directions in the miRNA research area with an emphasis on novel diagnostic opportunities or patient-tailored therapies. In our opinion data concerning the regulation of miRNA and its gene targets in the UFs are still insufficient in comparison with gynecological malignancies. The potential translational use of miRNA and derived technologies in the clinical care is at the early phase and needs far more evidence. However, it is one of the main areas of interest for the future as the use of miRNAs in the diagnostics and treatment of UFs is a new and exciting opportunity.

Prognostic significance of TEM7 and nestin expression in women with advanced high grade serous ovarian cancer.

OBJECTIVES: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS: To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times. MATERIAL AND METHODS: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry. RESULTS: Patients median age was 54 yrs (range: 29-72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12-23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS. CONCLUSIONS: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents.

Analysis of Health Behaviors and Personal Values of Childless Women, Pregnant Women and Women Who Recently Delivered.

Preconception lifestyle modifications and reduction of several known risk factors may have an influence on future pregnancy outcomes. The aim of the study was to analyze health behaviors and personal values as well as to assess the relationship between these factors in women without children, in pregnant women and in women who had already delivered babies. The questionnaire survey included the Health Behavior Inventory (HBI), the Personal Value List (PVL) and sociodemographic data and was conducted in 538 women. These women were divided into three groups: women who had recently delivered (n = 235), pregnant women (n = 121) and childless women (n = 182). Pregnant women demonstrated a significantly higher level of declared health behaviors, and also, they rated higher on the subscales values "positive mental attitude" and "health practices", in comparison to women who had recently delivered and to childless women. In all tested groups, the highest rated personal value was "a successful family life", while the most appreciated symbol of happiness was "love and friendship". Our results suggest that the system of values and the perception of happiness symbols may influence women's health behaviors. Positioning "health" in the hierarchy of personal values as the most important one may facilitate the introduction of healthy behaviors. This, in turn, could reduce several adverse pregnancy outcomes that are potentially modifiable with changing preconception health attitudes. Our results also identify several unanswered questions and highlight areas where new research is needed.

Mig-7 expression and vasculogenic mimicry in malignant ovarian tumors.

OBJECTIVES: To investigate the possible association of vasculogenic mimicry (VM), VE-cadherin and MIG-7 expression with clinicopathological features of women with malignant ovarian masses. MATERIAL AND METHODS: VM was studied with the PAS reaction and VE-cadherin was assessed with immunohistochemistry in 108 women with malignant ovarian tumors. Additionally, quantitative expression of MIG-7 mRNA was performed in 52 ovarian cancers with qRT-PCR. RESULTS: VM was found in 48/108 cases (44%), more often in higher FIGO stage tumors (83% cases; 40 vs. 8; p = 0.01). High expression of VE-cadherin was present in 37% of all ovarian masses. Ovarian tumors without VM more often expressed low levels of VE-cadherin than tumors where VM was found (37.6% vs.14.6%). No expression or very low expression of MIG-7 mRNA was found in all normal ovarian tissues and in 32 cancer samples. Median RQ of MIG-7 mRNA in tumor samples was higher than in normal ovarian tissue (RQ = 0.29 vs. RQ = 0.05, respectively; p < 0.005) and higher than in non-malignant ovarian masses (0.98 vs. 0.05 respectively; p = 0.03). Expression of MIG-7 mRNA was significantly correlated with VM (p = 0.039). In tumors with PAS-positive structures median RQ MIG-7 mRNA was higher than in tumors with PAS-negative findings (1.89 vs. 0.13 respectively). VE-cadherin expression was more frequently found in tumors where MIG-7 mRNA was present (p = 0.004). CONCLUSIONS: Vasculogenic mimicry exists in malignant ovarian tumors and advanced clinical stages of malignancy are accompanied by a high incidence of VM formation. MIG-7 mRNA and VE-cadherin expression may serve as additional molecular markers of VM in ovarian malignancies.

Diagnostic hysteroscopy and the risk of malignant cells intraabdominal spread in women with endometrial cancer.

Although hysteroscopy is currently the undisputed gold standard for the examination of the uterine cavity in women with suspected endometrial cancer, it remains controversial as a procedure that can enhance metastasis spread. Endometrial cancer cells may shed during hysteroscopy and be passively transported with fluid flow into the peritoneal cavity. The paper presents the review of current knowledge regarding the risk of neoplasm metastases in women who had diagnostic hysteroscopy and the conditions that have to be met for the procedure to be safe. We searched PubMed, Ovid, Medline and Scopus databases for data published in the years 1985-2017. The following browsing criteria, the "MeSH headings": hysteroscopy, endometrial cancer, intraperitoneal or metastatic spread were used to find relevant papers. Based on the current data analysis we conclude that (1.) diagnostic hysteroscopy performed in women with endometrial cancer, especially in its early stages, is a very useful, efficient and safe diagnostic method and (2.) the distension media used for endoscopic procedures in the uterine cavity must be strictly controlled for relatively low pressures to prevent the increase in risk of endometrial cancer intraperitoneal spread.

Non-invasive therapeutic use of High-Intensity Focused Ultrasound (HIFU) with 3 Tesla Magnetic Resonance Imaging in women with symptomatic uterine fibroids.

Benign uterine fibroids are common female genital tract tumors and if symptomatic often require extensive surgery. When tumors are multiple and large or unusually located, the operative treatment may lead to significant morbidity and compromise quality of life. Recovery period after surgical treatment may be complicated by patient's medical condition and wound healing problems. Currently used other non-surgical treatment modalities usually provide only a temporal symptoms relief and may not be efficient in all affected women. In the last decade, minimally invasive treatment of uterine fibroids called Magnetic Resonance guided High-Intensity Focused Ultrasound (MRI HIFU) was introduced. This technique uses thermal ablation simultaneously with MRI imaging of the mass and tissue temperature measurements during the procedure where a focused ultrasound beam is applied externally to destroy tumors located in the human body. Successful application of MRI HIFU has been recently described in patients with various malignancies, such as breast, prostate and hepatocellular cancers as well as soft tissue and bone tumors. This technique is innovative and has been proven to be safe and effective but there are several limitations for treatment. The article highlights the relative advantages and disadvantages of MRI guided HIFU in women with uterine fibroids. The authors also describe high-resolution MRI technique on 3T MRI, along with the approach to interpretation of HIFU results applied to uterine fibroids that has been experienced at one institution.

Proliferation and maturation of intratumoral blood vessels in women with malignant ovarian tumors assessed with cancer stem cells marker nestin and platelet derived growth factor PDGF-B.

OBJECTIVES: Platelet-derived growth factor B (PDGF-B) and nestin have been suggested to be useful in the assessment of neoangiogenesis in malignant ovarian masses. We aimed to investigate a possible association of these markers with newly formed microcapillaries and perivascular cells in ovarian tumors. MATERIAL AND METHODS: Microvessel density (MVD) and pericytes were studied in 82 women with ovarian neoplasms, including 7 benign cysts, 7 borderline masses, 64 epithelial ovarian cancers and 4 other malignant ovarian tumors. Immunohistochemical staining included antibodies to CD34, PDGF-B and nestin. RESULTS: Median values of CD34-positive and nestin-positive MVD were: 24,5 (range:17-32) and 21 (range: 12-31), respectively. No significant correlation between intratumoral CD-34 positive MVD and nestin-positive MVD was found. Benign and borderline lesions more frequently than malignant tumors displayed low or medium values of nestin-positive MVD (p = 0.01). Histological grading of malignant tumors was associated with nestin-positive MVD (p = 0.01). Nestin expression in tumor cells was not correlated with tumor grade or histological subtype. PDGF-B expression was found in tumor microves-sels in 72% of cases (59/82). High expression of PDGF in pericapillary cells was strongly associated with high expression of this marker in cancer cells (p = 0.007). Significant correlations between PDGF-B and nestin expression in malignant tumor microvessels were also found (p = 0.04). Nestin and PDGF-B expressions were strongly associated with high grade tumors when compared to low grade or benign masses. CONCLUSIONS: We conclude that the assessment of PDGF-B and nestin-positive MVD could be used to identify only highly active, angiogenic malignant ovarian masses, where tumor vasculature is formed.

The use of sonographic subjective tumor assessment, IOTA logistic regression model 1, IOTA Simple Rules and GI-RADS system in the preoperative prediction of malignancy in women with adnexal masses.

BACKGROUND: Sonography based methods with various tumor markers are currently used to discriminate the type of adnexal masses. OBJECTIVE: To compare the predictive value of selected sonography-based models along with subjective assessment in ovarian cancer prediction. MATERIAL AND METHODS: We analyzed data of 271 women operated because of adnexal masses. All masses were verified by histological examination. Preoperative sonography was performed in all patients and various predictive models includ¬ing IOTA group logistic regression model LR1 (LR1), IOTA simple ultrasound-based rules by IOTA (SR), GI-RADS and risk of malignancy index (RMI3) were used. ROC curves were constructed and respective AUC's with 95% CI's were compared. RESULTS: Of 271 masses 78 proved to be malignant including 6 borderline tumors. LR1 had sensitivity of 91.0%, specificity of 91.2%, AUC = 0.95 (95% CI: 0.92-0.98). Sensitivity for GI-RADS for 271 patients was 88.5% with specificity of 85% and AUC = 0.91 (95% CI: 0.88-0.95). Subjective assessment yielded sensitivity and specificity of 85.9% and 96.9%, respectively with AUC = 0.97 (95% CI: 0.94-0.99). SR were applicable in 236 masses and had sensitivity of 90.6% with specificity of 95.3% and AUC = 0.93 (95% CI 0.89-0.97). RMI3 was calculated only in 104 women who had CA125 available and had sensitivity of 55.3%, specificity of 94% and AUC = 0.85 (95% CI: 0.77-0.93). CONCLUSIONS: Although subjective assessment by the ultrasound expert remains the best current method of adnexal tumors preoperative discrimination, the simplicity and high predictive value favor the IOTA SR method, and when not applicable, the IOTA LR1 or GI-RADS models to be primarily and effectively used.

Predicting the risk of malignancy in adnexal masses based on the Simple Rules from the International Ovarian Tumor Analysis group.

BACKGROUND: Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. OBJECTIVE: We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. STUDY DESIGN: This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. RESULTS: Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901-0.931) and other centers (0.916; 95% confidence interval, 0.873-0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR- 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR- 0.13, PPV 75.4%, and NPV 93.9%. CONCLUSION: Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally.

Evaluating the risk of ovarian cancer before surgery using the ADNEX model to differentiate between benign, borderline, early and advanced stage invasive, and secondary metastatic tumours: prospective multicentre diagnostic study.

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

External validation of diagnostic models to estimate the risk of malignancy in adnexal masses.

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