The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Breast density measured volumetrically in a clinical environment: cross-sectional study with photon counting technology.

OBJECTIVE: Mammographic breast density (BDen), the ratio of glandular volume (GVol) to breast volume (BVol), is the second most prevalent risk factor for breast cancer (BC). Newly developed photon counting technology allows precise and systematic measurements in clinical practice. Our objective is to see how these parameters change with age in women with and without cancer. MATERIALS AND METHODS: This retrospective study analyzed results of BDen, GVol, and BVol in 64,182 mammograms performed with photon counting technology on 32,448 consecutive women from April 2014 to December 2015. Only their first study was included. We excluded women with incomplete data or with breast implants. RESULTS: Mean age of women without BC diagnosed during the study period was 52.1 ± 9.9. BC and was found in 263 women (0.81%). Mean age was 53.0 ± 10.4. BDen, GVol, and BVol were 14%, 24%, and 2% greater in women with BC (P < 0.001 for BDen and GVol and P = 0.02 for BVol). BDen and GVol diminished following similar patterns across age in both groups, with soft slopes before and after a steep drop from 50 to 60, probably due to menopause. CONCLUSION: BDen diminishes with age in women with or without BC, but it is generally higher in women with BC. GVol could be a more robust indicator associated with BC risk than BDen. This technology can ease the way to studies of interventions to diminish BDen (or GVol) in the hope of diminishing BC incidence or predict if longitudinal changes are indicative of impending cancer.

"Are changes in breast density during the menstrual cycle relevant? To what?"

PURPOSE: Cancers can be hidden by high breast density (BDen)- the masking effect (ME). BDen is also a modifiable and highly prevalent breast cancer risk (BCR) factor. The purposes of this study were to determine how much glandular volume (GVol), breast volume (BVol) and their ratio: BDen change during the menstrual cycle, and if these changes could affect ME or be relevant to results of interventional studies aiming to diminish BCR using these parameters as surrogates. METHODS: We retrieved GVol, BVol and BDen data values obtained from 39,997 right mammograms performed with photon counting technique of 19,904 premenopausal women who reported their first day of last menses (FDLM). Many women had more than one study included over the years (with a different FDLM) but were not studied longitudinally. We segregated women by age (yearly), divided the menstrual cycle in 4 weeks, and assigned results with respect to the FDLM. RESULTS: All parameters vary cyclically, with higher values in week 4 (GVol and BDen) or week 1 (BVol). Mean inter-week differences were very small for the three parameters, and diminished with age. However, especially in the youngest women, inter-week differences could be more than 10% for BDen, 15% for GVol, and 50% for BVol. CONCLUSION: Small inter-week mean differences almost certainly rule out relevant changes to ME directly attributable to BDen. However, the possibility of large differences during the menstrual cycle in younger women, who are the ideal targets of interventional studies to diminish BCR, might distort results and should be accounted for.

Do ovarian endometriomas affect ovarian response to ovarian stimulation for IVF/ICSI?

RESEARCH QUESTION: Does the presence of ovarian endometriomas affect ovarian response to ovarian stimulation after adjusting for age and ovarian reserve markers? DESIGN: This retrospective cross-sectional study compared the ovarian response between patients with ovarian endometriomas and women with other infertility factors undergoing their first ovarian stimulation for IVF/intracytoplasmic sperm injection (ICSI). An age-specific nomogram model for the number of oocytes retrieved was built for both groups, and ovarian response was compared after adjusting for age, gonadotrophin dose, anti-Mullerian hormone (AMH) concentration and antral follicle count (AFC). RESULTS: A total of 923 patients were included: 101 women with at least one ovarian endometrioma, and 822 patients with other infertility factors. Comparisons of the nomograms for the number of oocytes retrieved demonstrated that response was significantly lower for women with endometrioma when the results were adjusted for age the z-score for the number of oocytes retrieved (-0.49 ± 0.71 versus -0.20 ± 0.86; 95% confidence interval [CI] -0.47 to -0.12) and also after adjustment for the total dose of gonadotrophins and AMH values (z-score mean difference -0.338; 95% CI -0.54, -0.14). When the z-score was adjusted for gonadotrophin dose and AFC, the number of oocytes retrieved was comparable between the two groups (z-score mean difference -0.038; 95% CI -0.34 to 0.27). CONCLUSIONS: Ovarian response after ovarian stimulation for IVF/ICSI in women with endometriomas is significantly lower than in controls after adjusting for age, gonadotrophin dose and AMH. Dose and protocol selection for ovarian stimulation in patients with endometrioma should be based on AFC rather than AMH, as the latter may be overestimated.

Clinical and Ultrasound Characteristics of the Microcystic Elongated and Fragmented (MELF) Pattern in Endometrial Cancer According to the International Endometrial Tumor Analysis (IETA) criteria.

OBJECTIVES: To describe sonographic features of the microcystic elongated and fragmented (MELF) pattern of myometrial invasion (MI) using the International Endometrial Tumor Analysis (IETA) criteria; to assess the effect of the MELF pattern on preoperative ultrasound evaluation of MI; and to determine the relationship of the MELF pattern to more advanced stage (≥ IB) and lymph node metastases in women with endometrioid endometrial cancer. METHODS/MATERIALS: We included 850 women with endometrioid endometrial cancer from the prospective IETA 4 study. Ultrasound experts performed all ultrasound examinations, according to the IETA protocol. Reference pathologists assessed the presence or absence of the MELF pattern. Sonographic features and accuracy of ultrasound assessment of MI were compared in cases with the presence and the absence of the MELF pattern. The MELF pattern was correlated to more advanced stage (≥IB) and lymph node metastases. RESULTS: The MELF pattern was present in 197 (23.2%) women. On preoperative ultrasound imaging the endometrium was thicker (p = 0.031), more richly vascularized (p = 0.003) with the multiple multifocal vessel pattern (p < 0.001) and the assessment of adenomyosis was more often uncertain (p < 0.001). The presence or the absence of the MELF pattern did not affect the accuracy of the assessment of MI. The MELF pattern was associated with deep myometrial invasion (≥ 50%) (p < 0.001), cervical stromal invasion (p = 0.037), more advanced stage (≥ IB) (p < 0.001) and lymph node metastases (p = 0.011). CONCLUSIONS: Tumors with the MELF pattern were slightly larger, more richly vascularized with multiple multifocal vessels and assessment of adenomyosis was more uncertain on ultrasound imaging. The MELF pattern did not increase the risk of underestimating MI in preoperative ultrasound staging. Tumors with the MELF pattern were more than twice as likely to have more advanced stage (≥ IB) and lymph node metastases.

Endometrial cancer off-line staging using two-dimensional transvaginal ultrasound and three-dimensional volume contrast imaging: Intermethod agreement, interrater reliability and diagnostic accuracy.

OBJECTIVES: The aim is to estimate agreement between two-dimensional transvaginal ultrasound (2D-TVS) and three-dimensional volume contrast imaging (3D-VCI) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer and to compare the two methods regarding inter-rater reliability and diagnostic accuracy. METHODS: Fifteen ultrasound experts assessed off-line de-identified 3D-VCI volumes and 2D-TVU video clips from 58 patients with biopsy-confirmed endometrial cancer regarding the presence of deep (≥50%) MI and CSI. Video clips and 3D volumes were assessed independently. Interrater reliability was measured using kappa statistics. Histological diagnosis after hysterectomy served as gold standard. Accuracy measurements were correlated to rater experience using Spearman's rank correlation coefficient (ρ). RESULTS: Agreement between 2D-TVU and 3D-VCI for diagnosing MI was median 76% (range 64-93%) and for CSI median 88% (range 79-97%). Interrater reliability was better for 2D-TVU than for 3D-VCI (Fleiss' kappa 0.41 vs. 0.31 for MI and 0.55 vs. 0.45 for CSI). Median accuracy for diagnosing deep MI was 76% (range 59-84%) with 2D-TVU and 69% (range 52-83%) for 3D-VCI; the corresponding figures for CSI were 88% (range 81-93%) and 86% (range 72-95%). Accuracy was significantly correlated to how many cases the raters assessed annually. CONCLUSIONS: Off-line assessment of MI and CSI in women with endometrial cancer using 3D-VCI has lower interrater reliability and lower accuracy than 2D-TVU video clip assessment. Since accuracy was correlated to the number of cases assessed annually it is advised to centralize these examinations to high-volume centres.

Training Performance in Diagnosis of Congenital Uterine Anomalies With 3-Dimensional Sonography: A Learning Curve Cumulative Summation Analysis.

OBJECTIVES: We evaluated learning curve cumulative summation (CUSUM) of 3-dimensional (3D) sonography for diagnosis of congenital uterine anomalies and the deviations of the level of trainees' performance at the control-stage CUSUM. METHODS: First-year (R1), second-year (R2), and third-year (R3) residents in obstetrics and gynecology received a training program to learn how to analyze 3D sonographic volumes and to classify congenital uterine anomalies. Each trainee worked on 155 3D sonographic volumes from preselected patients. Their results were evaluated by learning curve CUSUM and standard CUSUM. The time for each volume analysis was calculated for the expert examiner and the trainees. RESULTS: Trainees R1, R2, and R3 reached competence at the 85th, 58th, and 40th evaluations, respectively, with success rates of 80%, 81%, and 85%, and kept the process under control with error levels of less than 4.5% until the end of the test. The trainees significantly reduced the average time of the evaluation per volume (P < .001). CONCLUSIONS: Learning curve CUSUM provided quantitative indicators of the learning evolution of 3D sonography for diagnosis of congenital uterine anomalies by obstetrics and gynecology residents. The training received by the residents was adequate for diagnosis of congenital uterine anomalies using 3D sonography.

Normal and abnormal images of intrauterine devices: Role of three-dimensional sonography.

The purpose of this pictorial essay is to describe the diagnostic value of two-dimensional ultrasound (2DUS) and the additional information that three-dimensional ultrasound (3DUS) provides in the assessment of location, type and complications of IUDs.

Long-term Results for Expectant Management of Ultrasonographically Diagnosed Benign Ovarian Teratomas.

OBJECTIVE: To assess the natural history of ultrasonographically diagnosed benign ovarian teratomas in asymptomatic women. METHODS: We conducted a retrospective observational cohort study of 408 women (mean age 36.6 years, range 14-81 years) diagnosed as having an ovarian teratoma by transvaginal ultrasonography (except eight who only had a transabdominal study done) between January 2003 and December 2013 at a single tertiary care institution. Six hundred thirteen women were diagnosed with ovarian teratoma of whom 205 were promptly treated surgically, leaving 408 patients followed conservatively with follow-up scans at 3 and 6 months from diagnosis and then yearly. The ultrasonographic diagnosis of a benign ovarian teratoma required at least one of the following features: a cystic mass with mixed echogenicity, thick band-like echoes, a fat-fluid level, or echogenic tubercle with posterior shadowing. Clinical, ultrasonographic, and histologic data (in case of surgery) were retrieved for analysis. RESULTS: During follow-up, 130 of 408 (31.8%) women underwent surgery. The main reason for surgery was the physician's recommendation according to our protocol (n=115). One patient had adnexal torsion. Most surgeries (112/130 [86.2%]) were performed within the first 5 years after diagnosis. The remainder (278/408) is still being followed (median time 45.6 months, range 6-147 months). The vast majority of these lesions had no change and women remain asymptomatic. Histologic diagnosis of tumors removed surgically revealed a benign ovarian teratoma in 103 of 130 (79.2%) of the women. There were two borderline tumors, four endometriomas, three fibromas, seven serous cysts, two mucinous cysts, two stroma ovarii, seven other benign, and no case of malignant tumor. CONCLUSION: Our results demonstrate that expectant management might be a reasonable option for managing asymptomatic women who receive a ultrasonographic diagnosis of a benign ovarian teratoma. The risk of undergoing surgery for this lesion decreases significantly after 5 years to follow-up. With careful observation, the risk of missing a diagnosis of malignancy is low.

Borderline cystic tumors of the ovary: gray-scale and color Doppler sonographic findings.

PURPOSE: The aim of the study was to determine the value of gray-scale and color Doppler sonography in distinguishing borderline cystic tumors (BCTs) from benign cysts and malignant tumors of the ovary. METHODS: The gray-scale and color Doppler sonographic features of 383 ovarian lesions in 374 nonpregnant women were retrospectively studied. Sonography was performed transvaginally for all but 7 lesions, which were imaged suprapubically. All of the lesions were surgically resected via laparoscopy or laparotomy. RESULTS: The histopathologic diagnoses were 27 BCTs, 35 ovarian carcinomas, and 321 benign cysts. Sonography diagnosed 24 (89%) of 27 BCTs as malignant lesions. Patients with BCTs, were younger than those with ovarian cancer (p < 0.001). BCTs showed intracystic papillae in 17 cases (63%), diffuse internal echoes in 11 (41%), intracystic septa in 8 (30%), a heterogeneous echo pattern in 7 (26%), and a solid pattern in 4 (15%). BCTs showed blood flow in 24 cases (89%) and lower pulsatility and resistance indices (RI) compared with benign lesions (p < 0.001 for both). Multivariate analysis revealed intracystic papillae as the only independent predictor of BCTs (p < 0.001). CONCLUSIONS: When a cystic mass has papillae, this is the only abnormal finding detected by gray-scale transvaginal sonography, and color Doppler imaging shows low RI values within the mass, a BCT should be suspected.