Renal biomarkers, clinical parameters, and renal Doppler velocimetry in bitches with cystic endometrial hyperplasia-pyometra complex.

Cystic endometrial hyperplasia (CEH)-pyometra complex is the most common uterine infection in adult and elderly bitches and can cause renal dysfunction. The aim of this study was to measure and compare urinary creatinine, urea, symmetric dimethylarginine (SDMA), urinary protein-creatinine ratio (UPC), measurement of systolic blood pressure (SBP), and Doppler velocimetry of renal arteries in patients with CEH-pyometra complex before and after an average of 6 months of treatment, evaluating the possibility of the changes persisting. The evaluation was conducted at two moments: M1 (at the diagnosis of CEH-pyometra, n = 36) and M2 (after an average of six months of treatment, n = 16). For the control group, eight bitches with no changes in blood tests or history of conditions underwent Doppler ultrasound evaluation of the renal arteries. At both M1 and M2, we measured creatinine, urea, and serum SDMA, UPC, SBP, and Doppler ultrasound of the renal arteries. Patients were evaluated according to the following groups: azotemic (AZO) and non-azotemic (NAZO), and open and closed cervix pyometra. The parameters were compared between animals present in both moments presented as M1R (bitches that were in M1 and M2) and M2. Statistical significance was considered when p < .05. The medians found for creatinine in M1 were as follows: 1.15 mg/dL, being 1.8 mg/dL for AZO (12/36) and 0.95 mg/dL for NAZO (24/36); and in M2: 0.85 mg/dL (16/16), being 1.15 mg/dL for AZO (4/16) and 0.8 mg/dL for NAZO (12/36). For urea, in M1 it was 36 mg/dL (32/36), with AZO being 103 mg/dL (11/32) and 33 mg/dL in NAZO (21/32); and in M2 32 mg/dL (16/ 16), being 29 mg/dL for AZO (4/36), and 31 mg/dL for NAZO (3/15). The median SDMA measured in M1R was 17 µg/dL (15/16), with AZO being 31 µg/dL (3/15), and NAZO being 16.5 µg/dL (12/15); and in M2, SDMA was 12 µg/dL (16/16), with AZO being 12.5 µg/dL (4/16), and NAZO being 12 µg/dL (12/16). The median UPC measured in M1 was 1.15 (10/36), with AZO being 0.25 (1/10), and NAZO being 1.38 (9/10); and in M2, it was 0.2 (13/16), being 0.1 in AZO (4/13), and 0.2 (9/16) in NAZO. For SBP, in M1, it was 118 mmHg (30/36), with AZO being 102 mmHg (10/30) and 133 mmHg in NAZO (20/30); and in M2 142.5 mmHg (12/16), being 155 mmHg for AZO (4/12), and 140 mg/dL for NAZO (8/12). When comparing animals with open and closed cervixes, a difference was found between SDMA measurements (p = .001). There was a distinction between PI and RI of the left and right kidneys consecutively (p = .007; p = .033; p = .019; p = .041). Correlations found in M1: SDMA × PI RIM DIR (r = 0.873; p = .002), SDMA × PSV RIM ESQ (r = 0.840; p = .004), SDMA × EDV RIM ESQ (r = 0.675; p = .046). With this study, we conclude a return to normality of renal biomarkers and clinical parameters after six months. Yet, there is a persistence of Doppler velocimetric measurements between the two moments. Thus, this parameter is not suitable for identifying and classifying chronic kidney injury in bitches with pyometra.

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

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

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: systematic review and diagnostic test accuracy meta-analysis.

OBJECTIVE: This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. DATA SOURCES: MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. STUDY ELIGIBILITY CRITERIA: Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. METHODS: This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. RESULTS: A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26-6.32; I2=74%). Similar degrees of risk were reported for thresholds between 3.0 and 5.9 mm (relative risk, 5.08; 95% confidence interval, 2.26-11.41; I2=0%), 6.0 and 9.9 mm (relative risk, 4.34; 95% confidence interval, 1.68-11.23; I2=0%), 10.0 and 13.9 mm (relative risk, 4.11; 95% confidence interval, 1.55-10.87; I2=86%), and ≥14.0 mm (relative risk, 2.53; 95% confidence interval, 1.04-6.16; I2=78%) with no significant difference among subgroups (P=.885). Regarding diagnostic accuracy, the pooled sensitivity decreased from thresholds below 5.9 mm (relative risk, 0.81; 95% confidence interval, 0.49-0.85) to above 14.0 mm (relative risk, 0.28; 95% confidence interval, 0.18-0.40). Furthermore, the specificity increased from 0.70 (95% confidence interval, 0.61-0.78) for endometrial thickness between 3.0 and 5.9 mm to 0.86 (95% confidence interval, 0.71-0.94) when the endometrial thickness is ≥14.0 mm. For 3.0 to 5.9 mm and 10.0 to 13.9 mm thresholds, the highest diagnostic odds ratios of 10 (95% confidence interval, 3-41) and 11 (95% confidence interval, 2-49), with areas under the curve of 0.81 (95% confidence interval, 0.77-0.84) and 0.82 (95% confidence interval, 0.79-0.86), respectively, were retrieved. The summary point analysis revealed that the 3.0 to 5.9 mm cutoff point was placed higher in the summary receiver operator curve space than the other subgroups, indicating increased endometrial carcinoma or atypical endometrial hyperplasia diagnosis using these cutoffs. CONCLUSION: Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Determining a threshold measurement of endometrial thickness for asymptomatic postmenopausal women: A tertiary centre case series.

BACKGROUND: An incidental finding of a thickened endometrium on ultrasound in the postmenopausal patient without bleeding is a common presentation to gynaecological services; however there is limited evidence to guide clinical practice as to when hysteroscopic evaluation and endometrial sampling is required. AIMS: To determine the endometrial thickness at which endometrial sampling is indicated in asymptomatic postmenopausal women referred with thickened endometrium on ultrasound. MATERIALS AND METHODS: A single-centre retrospective case series of postmenopausal women without bleeding undergoing hysteroscopy was conducted. Logistic regression was used to examine the association between a range of variables and pre-malignant or malignant pathology and endometrial thickness. The optimal endometrial thickness threshold was identified to maximise model sensitivity. RESULTS: A total of 404 postmenopausal women were included in this study, having undergone a hysteroscopy at the study site between 1 July 2008 and 30 June 2018. The mean (SD) age of patients at presentation was 65 (9.09) years and the mean body mass index was 29.86 kg/m2 (6.52). Of these women, nine (2.2%) were diagnosed with endometrial carcinoma and seven (1.7%) had endometrial hyperplasia with atypia. The most common histopathological finding was of a benign endometrial polyp (153: 37.9%). When including hyperplasia with or without atypia in histopathology of interest, a cut-off of ≥9 mm provides the greatest sensitivity (83.3%) and specificity (63.8%) for a diagnosis of pre-malignant or malignant pathology (classification accuracy of 64.8%; area under the receiver operating characteristic: 0.7358, 95% CI: 0.6439, 0.8278) in this cohort. CONCLUSIONS: Using an endometrial thickness of ≥9 mm can be used as a cut-off for endometrial sampling in postmenopausal women without bleeding.

Diagnosis of endometrium hyperplasia and screening of endometrial intraepithelial neoplasia in histopathological images using a global-to-local multi-scale convolutional neural network.

BACKGROUND AND OBJECTIVE: Endometrial hyperplasia (EH), a uterine pathology characterized by an increased gland-to-stroma ratio compared to normal endometrium (NE), may precede the development of endometrial cancer (EC). Particularly, atypical EH also known as endometrial intraepithelial neoplasia (EIN), has been proven to be a precursor of EC. Thus, diagnosing different EH (EIN, hyperplasia without atypia (HwA) and NE) and screening EIN from non-EIN are crucial for the health of female reproductive system. Computer-aided-diagnosis (CAD) was used to diagnose endometrial histological images based on machine learning and deep learning. However, these studies perform single-scale image analysis and thus can only characterize partial endometrial features. Empirically, both global (cytological changes relative to background) and local features (gland-to-stromal ratio and lesion dimension) are helpful in identifying endometrial lesions. METHODS: We proposed a global-to-local multi-scale convolutional neural network (G2LNet) to diagnose different EH and to screen EIN in endometrial histological images stained by hematoxylin and eosin (H&E). The G2LNet first used a supervised model in the global part to extract contextual features of endometrial lesions, and simultaneously deployed multi-instance learning in the local part to obtain textural features from multiple image patches. The contextual and textural features were used together to diagnose different endometrial lesions after fusion by a convolutional block attention module. In addition, we visualized the salient regions on both the global image and local images to investigate the interpretability of the model in endometrial diagnosis. RESULTS: In the five-fold cross validation on 7812 H&E images from 467 endometrial specimens, G2LNet achieved an accuracy of 97.01% for EH diagnosis and an area-under-the-curve (AUC) of 0.9902 for EIN screening, significantly higher than state-of-the-arts. In external validation on 1631 H&E images from 135 specimens, G2LNet achieved an accuracy of 95.34% for EH diagnosis, which was comparable to that of a mid-level pathologist (95.71%). Specifically, G2LNet had advantages in diagnosing EIN, while humans performed better in identifying NE and HwA. CONCLUSIONS: The developed G2LNet that integrated both the global (contextual) and local (textural) features may help pathologists diagnose endometrial lesions in clinical practices, especially to improve the accuracy and efficiency of screening for precancerous lesions.

Risk of atypical hyperplasia and endometrial carcinoma after initial diagnosis of non-atypical endometrial hyperplasia: A long-term follow-up study.

OBJECTIVES: The strong association between atypical endometrial hyperplasia and endometrial carcinoma is well established, but data on the risk of atypical hyperplasia and carcinoma in Danish women with non-atypical endometrial hyperplasia are almost non-existent. This study aimed to investigate the prevalence of atypical hyperplasia and endometrial carcinoma diagnosed within 3 months of initial diagnosis (defined as concurrent disease) and the risk of atypical hyperplasia and carcinoma more than 3 months after initial diagnosis (classified as progressive disease) in Danish women initially diagnosed with non-atypical endometrial hyperplasia. DESIGN: This cohort study recruited 102 women diagnosed with non-atypical endometrial hyperplasia at Randers Regional Hospital in Randers, Denmark, between 2000 and 2015. METHODS: The endometrium was evaluated by transvaginal ultrasound examination and office mini-hysteroscopy with biopsies in all non-hysterectomized women. Data regarding subsequent hysterectomy or endometrial sampling were obtained from medical records and the Danish Pathology Registry (Patobank). RESULTS: A total of 15 women were diagnosed with atypical hyperplasia or carcinoma during follow-up. Concurrent atypical hyperplasia or carcinoma was seen in 2.9% (3/102), and among women who remained at risk for more than 3 months after initial diagnosis of non-atypical endometrial hyperplasia (n = 94), progression to atypical hyperplasia or carcinoma was seen in 13% (median follow-up 5.2 years, range 3.6 months to 15.1 years). Sixty-six percent of the women with progressive disease were diagnosed with atypical hyperplasia or carcinoma more than 1 year after initial diagnosis, but only two were diagnosed later than 5 years (5.2 and 9 years). CONCLUSIONS: The risk of being diagnosed with atypical endometrial hyperplasia or endometrial carcinoma more than 5 years after an initial diagnosis of non-atypical endometrial hyperplasia seems to be low in Danish women. Specialized follow-up more than 5 years after diagnosis of non-atypical endometrial hyperplasia may not be warranted.

Sonoelastography evaluation in the diagnosis of endometrial pathology combined with chronic endometritis in infertile women.

Endometrial pathology, including hyperplastic processes in the structure of reproductive disorders, occupies one of the leading places along with inflammatory diseases of the pelvic organs, contributing to infertility in 80% of cases and irregular menstrual cycle in 40-43%. This study aims to optimize the diagnostic algorithm in patients with endometrial hyperplasia combined with chronic endometritis and determine qualitative indicators of compression sonoelastography in patients with endometrial pathology and infertility. A comprehensive clinical and laboratory examination of 90 infertile patients aged 25 to 45 years with endometrial hyperplasia combined with chronic inflammation, retention cysts, and benign ovarian tumors was carried out. The results of clinical-laboratory and complex ultrasound examination with compression sonoelastography were compared with the data of pathomorphological and immunohistochemical studies. A high percentage of pelvic inflammatory disease (55.0%), benign lesions of the cervix (67.5%), hyperplastic processes of the myometrium (37.5%), an increasing number of polyps by 2.9 times, leiomyomas and adenomyosis - by 2.3 times (p<0.05) was established. In the case of a combination of endometrial hyperplasia and ovarian cysts, a high percentage of comorbidity of gynecological pathology is verified (37.8%), and the use of compression sonoelastography allows to establish class II and class III elastograms in 91.1% of cases which characterize benign endometrial lesions, reduce the number of false-positive results in 95.6% of cases, correctly interpret the nature of pathological changes and increase the sensitivity of ultrasound techniques.

Doppler ultrasonographic evaluation of medically treated female dogs with cystic endometrial hyperplasia-pyometra complex.

Monitoring the treatment outcome of canine cystic endometrial hyperplasia-pyometra complex (CEH-P) is essential to identify nonresponding patients who might require a rapid intervention to avoid life-threatening conditions. Uterine artery Doppler characterization may contribute to monitoring medically treated CEH-P, but published studies are currently lacking. Therefore, the aim of this longitudinal prospective observational study was to evaluate uterine artery resistance changes in the medical treatment of female dogs with CEH-P. Twelve diestrous female dogs suffering from CEH-P were treated with a combined protocol of cabergoline, cloprostenol, and antibiotics. The animals were clinically and ultrasonographically evaluated before the beginning of treatment (day 0) and on days 3, 7, 14, 21, and 28. The widest transverse diameter and luminal diameter of uterine horns were measured, as well as the peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine arteries. The resistance index (RI), pulsatility index (PI), and notch deep index (NDI) were calculated. On day 3, nine of 12 animals showed clinical improvement. In all these female dogs, the widest transverse sectional diameter (P < 0.01), luminal diameter (P < 0.01), PSV (P < 0.01), and EDV (P < 0.01) progressively decreased, while RI (P < 0.01), PI (P < 0.01), and NDI (P < 0.01) increased up to day 21. In nonresponding dogs (3/12), Doppler parameters remained unchanged. Although comparisons of PSV, EDV, and NDI were significantly different, these results should be cautiously interpreted due to the low statistical power. female dogs that responded to this treatment showed an increase in uterine artery resistance, along with clinical and ultrasonographic improvement.

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.

Can a higher endometrial thickness threshold exclude endometrial cancer and atypical hyperplasia in asymptomatic postmenopausal women? A systematic review.

BACKGROUND: Asymptomatic postmenopausal women incidentally found to have thickened endometrium (>4 mm) on transvaginal ultrasound (TVUS) often undergo hysteroscopy and dilatation and curettage despite having a low absolute risk of endometrial cancer. A low threshold for investigation may be unnecessary in these women. AIM: This systematic literature review examines whether an increased TVUS endometrial thickness threshold has superior diagnostic accuracy for endometrial malignancies and premalignancies in asymptomatic postmenopausal women than the current threshold of ≥4 mm. METHODS: Pubmed, EMBASE and Cochrane Database of Systematic Reviews were systematically searched using keywords for publications between 2011 and 2021. Studies were included if they reported TVUS endometrial thickness analysis in asymptomatic postmenopausal women and excluded if they were written in a non-English language. Quality of evidence in the included articles was evaluated according to recommendations by the Grading of Recommendations Assessment Development and Evaluation Working Group and reported results were tabulated. RESULTS: Of seven studies (N = 2986), better evidence identified 12 mm as the optimal diagnostic threshold (area under the curve receiver operating characteristic (AUC ROC) 0.716, 95% CI 0.534-0.897, P = 0.019) for endometrial cancer in asymptomatic postmenopausal women. Two higher quality studies (n = 488 and n = 4751) identified 11 mm as optimal for diagnosing both endometrial carcinoma and atypical hyperplasia (AUC ROC 0.587, 95% CI 0.465-0.708, P = 0.144 and 2.59 relative risk, 95% CI 1.66-4.05, P < 0.001). CONCLUSION: Evidence for improved detection of endometrial premalignancies and malignancies using alternative endometrial thickness thresholds is not rigorous. Evidence for improved outcomes using alternative thresholds is inadequate. Observation of asymptomatic postmenopausal women without risk factors and with an endometrial thickness of less than 10 mm may be reasonable.

Cystic endometrium on ultrasound scan: Sonographic-hysteroscopic-pathologic correlation.

OBJECTIVE: To assess the correlation between ultrasound findings of cystic endometrium and hysteroscopic and histopathologic findings. METHODS: A retrospective study was performed across two London hospital sites between January and December 2020. RESULTS: The percentage chance of having either endometrial hyperplasia or cancer was lower in our cohort of women with postmenopausal bleeding and ultrasound findings of cystic endometrium, compared with population estimates for women with postmenopausal bleeding alone (4.1% vs 10%-15% for endometrial cancer and 1.4% vs 5%-10% for endometrial hyperplasia). Conversely, a higher proportion of women in our cohort were diagnosed with endometrial polyps compared with population estimates for postmenopausal bleeding (68% vs 2%-12%). The rate of endometrial hyperplasia was significantly higher in our cohort of premenopausal women with abnormal uterine bleeding and cystic endometrium compared with population estimates for premenopausal patients with abnormal uterine bleeding (15.4% vs 1.4%). CONCLUSION: Cystic endometrium appears to be a powerful predictor of endometrial pathology. The high rate of endometrial hyperplasia in premenopausal women with cystic endometrium would advocate the need to obtain histologic diagnoses. Further studies are required to confirm whether cystic endometrium in women with postmenopausal bleeding confers a lower risk of endometrial hyperplasia and cancer.

Evaluation of frozen section biopsy for fast track diagnosis of endometrial pathology in high-risk women with abnormal uterine bleeding.

OBJECTIVE: To study the accuracy of frozen section biopsy for endometrial pathology in high-risk women with abnormal uterine bleeding (AUB). STUDY DESIGN: A case-control study was conducted between November 2017 to April 2019, a total of 150 women with postmenopausal bleeding, perimenopausal AUB, and high-risk women of age < 40 years with AUB were recruited. All women underwent transvaginal sonography and Doppler, based on age-appropriate endometrial thickness cut-offs 80 women then underwent hysteroscopy. Based on hysteroscopy, women suspicious of malignancy were taken as cases (n = 40) and those with benign findings as controls (n = 40). All cases and controls underwent dilatation and curettage (D & C) with frozen section (FS) and routine histopathology. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR), negative LR, and overall test accuracy of FS were 90.9%, 93.19%, 83.33%, 96.19%, 13.8, 0.1 and 86.25% respectively for diagnosing endometrial hyperplasia and cancer taking histopathology as the gold standard. Correlation between frozen section biopsy and histopathology was highly significant (p < 0.001) on D & C specimens and the level of agreement was good (K = 0.778). CONCLUSION: In women suspicious of malignancy on hysteroscopy, frozen section has high accuracy on D&C specimen and can be used to diagnose endometrial hyperplasia and cancer in an effort to fast-track investigations and work-up for definitive treatment while awaiting final histopathology.

Clinicopathological and ultrasound features of endometrial cancer in postmenopausal women: a retrospective study in a single institute in South Korea.

INTRODUCTION: endometrial cancer is the most common type of cancer in the female genital tract. Most patients are diagnosed during postmenopausal periods. This study aimed to investigate the demographic characteristics as well as cutoff value of endometrial thickness and ultrasound characteristics of endometrial cancer in postmenopausal patients. METHODS: we retrospectively analyzed 244 postmenopausal women who underwent endometrial sampling from February 2016 to December 2019. Information of patients was obtained through medical records. The patients were divided into two groups according to histopathological results. Group A included patients with endometrial cancer and group B included patients with non-malignant lesions. Data were summarized based on demographic and ultrasound characteristics. RESULTS: hypertension and history of endometrial hyperplasia were associated with the incidence of endometrial cancer in this study. Endometrial cancer was diagnosed in all ranges when the endometrial thickness was ≥5 mm. Endometrial fluid collection, with increased endometrial thickness, was a risk factor associated with endometrial cancer. CONCLUSION: regardless of symptoms and risk factors, endometrial histological confirmation in postmenopausal women should be conducted immediately if endometrial abnormalities such as an endometrial thickness ≥5 mm or endometrial fluid collection are detected by transvaginal ultrasound.

The Value of Shear Wave Elastography in Predicting the Risk of Endometrial Cancer and Atypical Endometrial Hyperplasia.

OBJECTIVES: To evaluate shear wave elastography (SWE) technology diagnosis value of endometrial cancer (EC) and atypical endometrial hyperplasia (AEH), and to establish predictive logistic regression models for the diagnosis of EC and AEH. METHODS: Clinical information collection, transvaginal conventional ultrasonography, and SWE check were performed on 122 patients, who were perimenopausal or postmenopausal vaginal bleeding with ≥4.5 mm thick endometrium. The maximal (Emax) and mean (Emean) of Young's modulus for the endometrium were obtained. Using pathology as the gold standard, ROC curves were plotted to evaluate Young's modulus on the diagnostic effectiveness of EC and AEH. Single-factor analysis and bivariate logistic regression methods were applied to assess the clinical variables, transuaginal conventional ultrasonography variables, and Young's modulus on the identification of EC and AEH. RESULTS: Out of 122 cases of endometrial lesions, 85 cases were benign lesions, and the remaining 37 cases were EC and AEH. The Emax and Emean for the benign group were 29.80 ± 11.40 and 17.96 ± 8.05 kPa, respectively. The Emax and Emean values for EC and AEH group were 59.49 ± 16.95 and 38.46 ± 17.10 kPa, respectively. Emax and Emean for both groups were statistically significant, with p <.001. In the logistical regression analysis, endometrial thickness, Color score, and Young's modulus were identified as independent risk factors for EC and AEH. CONCLUSIONS: SWE technology plays an important role in the diagnosis of EC and AEH, and the diagnostic effectiveness would be higher when combined with conventional ultrasonography.

Endometrial sampling before or after saline contrast sonohysterography in women with postmenopausal bleeding (ESPRESSO trial): A multicenter randomized controlled trial.

INTRODUCTION: The aim of this study is to evaluate the quality of the endometrial sample obtained by office endometrial aspiration when performed before or after saline contrast sonohysterography (SCSH) in women with postmenopausal bleeding and a thickened endometrium. To conduct a complete, minimally invasive and cost-effective diagnostic workup in women with postmenopausal bleeding and a thickened endometrium, ideally both the office endometrial sampling and SCSH are performed. However, it is not known whether both tests affect each other when performed one after another. MATERIAL AND METHODS: Women with postmenopausal bleeding and an endometrial thickness >4 mm were eligible. Women were randomized into two groups: one group received endometrial aspiration before SCSH, the other group received SCSH before endometrial aspiration. The primary outcome was the proportion of sufficient endometrial samples. Reliability of the SCSH images and pain during procedures were secondary outcomes. RESULTS: During the inclusion period, 513 eligible women with postmenopausal bleeding visited the participating hospitals, 293 of whom received information about the study. Of these women, 232 (79%) agreed to participate. In the SCSH-aspiration group, 65 women (59%) had a sufficient endometrial sample compared with 70 (67%) in the aspiration-SCSH group (odds ratio 1.46, 95% CI 0.83-2.54, P = .19). The proportion of reliable sonographic images was significantly higher in the SCSH-aspiration group (n = 88, 87%) compared with the aspiration-SCSH group (n = 71, 74%) (OR 2.38, 95% CI 1.38-4.99, P = .02) in the per protocol analysis. CONCLUSIONS: This study shows that the quality of an endometrial sample in women with postmenopausal bleeding is not affected by SCSH. Both procedures can be performed in one outpatient visit to perform an optimal diagnostic workup.

A descriptive angiographic study of the uterine arteries during pregnancy, the postpartum period and CEH/pyometra in bitches.

The aim of this descriptive study was to monitor the changes in uterine arteries during pregnancy, postpartum period and pyometra in bitches using angiography. Fifteen uteri of mixed breed bitches on days 24, 30, 33, 40, 43, 47, 50 and 56 of pregnancy and weeks 1, 2, 3, 4 and 7-8 of postpartum and two CEH/pyometra bitches were examined after ovariohysterectomy. The results showed that with the onset of normal pregnancy and in about 30 ± 1 days of gestation, anastomoses begin to form between the left and right middle uterine arteries, developing during the next days and continuing until 4 weeks postpartum. On 4th week after parturition, when physiologic changes occur and the uterus returns to non-pregnant conditions, these anastomoses begin to degenerate, and they completely disappear approximately on the 7th-8th week after parturition. Similarly, in CEH/pyometra bitches, anastomoses were formed between left and right median uterine arteries. These findings can be considered as a part of the physiological changes of the uterus and its vessels during pregnancy and postpartum periods and could affect the results and interpretation of relevant findings.

Ultrasound diagnosis of endometrial cancer by subjective pattern recognition in women with postmenopausal bleeding: prospective inter-rater agreement and reliability study.

OBJECTIVES: To assess the inter-rater agreement and reliability of using subjective pattern recognition for diagnosing endometrial cancer (EC) on ultrasound in women with postmenopausal bleeding (PMB). METHODS: This was a prospective cross-sectional study conducted at a gynecological rapid-access clinic, between October 2016 and December 2017, in which consecutive women with PMB and endometrial thickness of ≥ 4.5 mm on transvaginal ultrasound examination were included. Women on hormone replacement therapy or tamoxifen and those with a history of primary gynecological malignancy were excluded. Two raters independently performed ultrasound examinations, blinded to each other's findings, and classified women as having uniformly thickened endometrium, benign endometrial polyp or EC, using subjective pattern recognition. Inter-rater reliability of ultrasound diagnosis was assessed using Cohen's kappa (κ) statistic. All women subsequently underwent either outpatient endometrial biopsy, hysteroscopy or hysterectomy. RESULTS: Forty women were included in the study, with a median age of 61 (interquartile range (IQR), 57-69) years and a median endometrial thickness of 11.0 (IQR, 6.2-20.3) mm. Final histological analysis confirmed 16 (40%) women with EC, 16 (40%) with benign endometrial polyp, four (10%) with atrophic endometrium, three (8%) with proliferative endometrium and one (3%) with endometrial hyperplasia. Inter-rater agreement for the ultrasound diagnoses of uniformly thickened endometrium, benign endometrial polyp and EC was 14/16 (87.5%), 22/30 (73.3%) and 28/34 (82.4%), respectively; inter-rater reliability was good (κ = 0.69; 95% CI, 0.49-0.88). When the ultrasound diagnoses were grouped as either cancer or no cancer, inter-rater agreement was 85% and inter-rater reliability was good (κ = 0.78; 95% CI, 0.61-0.95). Rater A correctly identified 14/16 cases of EC and Rater B identified 15/16. EC was misdiagnosed as benign polyps on ultrasound in two women by Rater A and in one woman by Rater B. The overall accuracies of Rater A and Rater B in differentiating between benign endometrial pathologies and malignancy were 90% and 90%, respectively. CONCLUSIONS: Our results show good inter-rater reliability of subjective pattern recognition in diagnosing uniformly thickened endometrium, benign endometrial polyp and EC on ultrasound in women with PMB. Our findings should facilitate wider use of subjective pattern recognition in routine clinical practice. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasonographic appearance of pseudo-placentational endometrial hyperplasia in a dog.

A 5-year-old, clinically normal intact female Miniature Schnauzer was presented for demonstrative ultrasonography in a seminar. She had two pregnancies in the past and had a natural mating 2 months previously. Ultrasonography revealed a segmental and circumferential mural thickening of the right uterine horn. The endometrium was markedly thickened with multiple organized hyperechoic linear striations, perpendicular to the mucosal surface. Histology revealed focal endometrial hyperplasia resembling the maternal tissue of the normal canine placenta. A diagnosis of spontaneous pseudo-placentational endometrial hyperplasia (PEH) was made. This study described a unique ultrasonographic appearance of PEH, which may facilitate the diagnosis of PEH.

Computational augmentation of neoplastic endometrial glands in digital pathology displays.

The pathologic diagnosis of neoplasia requires localization and classification of lesional tissue, a process that depends on the recognition of an abnormal spatial distribution of neoplastic elements relative to admixed normal background tissue. In endometrial intraepithelial neoplasia (EIN), a pre-cancer usually managed by hysterectomy, a clonally mutated proliferation of cytologically altered glands ('neoplastic-EIN') aggregates in clusters that also contain background non-neoplastic glands ('background-NL'). Here, we used image analysis to classify individual glands within endometrial tissue fragments as neoplastic-EIN or background-NL, and we used the distribution of predictions to localize foci diagnostic of EIN. Nuclear coordinates were automatically assigned and were used as vertices to generate Delaunay triangulations for each gland. Graph statistical variables were used to develop random forest algorithms to classify glands as neoplastic-EIN or background-NL. Individual glands in an independent validation set were scored by a 'ground truth' biomarker (PAX2 immunohistochemistry). We found that exclusion of small glands led to improvement in classification accuracy. Using an inclusion threshold of 200 nuclei per gland, our final model classification accuracy was 77.5% in the validation set, with a positive predictive value of 0.81. We leveraged this high positive predictive value in a point cloud overlay display to assist end-user identification of EIN foci. This study demonstrates that graph theory approaches applied to small-scale anatomic elements in the endometrium allow biologic classification by machine learning, and that spatial superimposition over large-scale tissue expanses can have practical diagnostic utility. We expect this augmented diagnostic approach to be generalizable to commonly encountered problems in other organ systems. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Assessment of Tamoxifen-Related Endometrial Changes in Premenopausal Female Patients With Diffusion-Weighted Magnetic Resonance Imaging.

PURPOSE: To evaluate tamoxifen-related endometrial changes in premenopausal female patients with diffusion-weighted magnetic resonance imaging (DWI). METHODS: This prospective study was performed on 71 premenopausal female patients (mean age, 41 years) who were receiving tamoxifen therapy. All patients underwent magnetic resonance imaging with DWI of the pelvis and hysteroscopic-guided endometrial biopsy. The apparent diffusion coefficient (ADC) values of the endometrial plate were calculated and correlated with pathological results. RESULTS: The mean ADCs of tamoxifen-related benign endometrial lesions (1.35 ± 0.19 and 1.32 ± 0.13 × 10 mm/s) were significantly higher (P = 0.001) than those of normal endometrial plate (0.95 ± 0.11 and 0.93 ± 0.11 × 10 mm/s) by both reviewers, respectively. The cutoff ADC values used to differentiate tamoxifen-related benign endometrial lesions from normal endometrium were 1.07 and 1.02 × 10 mm/s with areas under the curve of 0.94 and 0.93 and accuracy of 94.4 and 95.8 by both reviewers, respectively. The mean ADC values of endometrial polyp (EP) (1.44 ± 0.19 and 1.42 ± 0.22 × 10 mm/s) were significantly higher (P = 0.001) than those of endometrial hyperplasia (EH) (1.25 ± 0.19 and 1.23 ± 0.19 × 10 mm/s) by both reviewers, respectively. The cutoff ADC values used to differentiate EP from EH were 1.38 × 10 and 1.36 × 10 mm/s with areas under the curve of 0.81 and 0.77 and accuracy of 80% and 70% by both reviewers, respectively. There was an insignificant difference in ADC value between typical and atypical EH. The ADC values of endometrial cancer (0.80 and 0.78 × 10 mm/s) were lower than those of tamoxifen-related benign endometrial lesions. The final diagnosis was normal endometrium (n = 36), benign endometrial lesions either EH (n = 17), or EP (n = 16), and endometrial cancer in only 2 patients. CONCLUSIONS: We concluded that DWI helps in detection and characterization of different tamoxifen-related endometrial changes in the premenopausal female patients.