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.

Performance of the WID-qEC test versus sonography to detect uterine cancers in women with abnormal uterine bleeding (EPI-SURE): a prospective, consecutive observational cohort study in the UK.

BACKGROUND: To detect uterine cancer, simpler and more specific index tests are needed to triage women with abnormal uterine bleeding to a reference histology test. We aimed to compare the performance of conventional index imaging tests with the novel WID-qEC DNA methylation test in terms of detecting the presence or absence of uterine cancers in women with abnormal uterine bleeding. METHODS: EPI-SURE was a prospective, observational study that invited all women aged 45 years and older with abnormal uterine bleeding attending a tertiary gynaecological diagnostic referral centre at University College London Hospital (London, UK) to participate. Women meeting these inclusion criteria who consented to participate were included. Pregnant women and those with previous hysterectomy were excluded. A cervicovaginal sample for the WID-qEC test was obtained before standard assessment using index imaging tests (ie, ultrasound) and, where applicable, reference histology (ie, biopsy, hysteroscopy, or both) was performed. Technicians performing the WID-qEC test were masked to the final clinical outcome. The result of the WID-qEC test is defined as the sum of the percentage of fully methylated reference (ΣPMR) of the ZSCAN12 and GYPC regions. Patients were followed until diagnostic resolution or until June 12, 2023. The primary outcome was to assess the real-world performance of the WID-qEC test in comparison with ultrasound with regard to the area under the receiver-operating-characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values. EPI-SURE is registered with ISRCTN (16815568). FINDINGS: From June 1, 2022, to Nov 24, 2022, 474 women were deemed eligible to participate. 74 did not accept the invitation to participate, and one woman withdrew after providing consent. 399 women were included in the primary analysis cohort. Based on 603 index imaging tests, 186 (47%) women were recommended for a reference histology test (ie, biopsy, hysteroscopy, or both). 12 women were diagnosed with cancer, 375 were not diagnosed with cancer, and 12 had inconclusive clinical outcomes and were considered study dropouts. 198 reference histology test procedures detected nine cases of cancer and missed two; one further cancer was directly diagnosed at hysterectomy without a previous reference test. The AUC for detection of uterine cancer based on endometrial thickness in mm was 87·2% (95% CI 71·1-100·0) versus 94·3% (84·7-100·0) based on WID-qEC (p=0·48). Endometrial thickness assessment on ultrasound scan was possible in 379 (95%) of the 399 women and a prespecified cut-off of 4·5 mm or more showed a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 79·1% (74·5-82·9), a positive predictive value of 11·8% (6·5-20·3), and a negative predictive value of 99·6% (98·0-99·9). The WID-qEC test was possible in 390 (98%) of the 399 patients with a sensitivity of 90·9% (95% CI 62·3-98·4), a specificity of 92·1% (88·9-94·4), a positive predictive value of 25·6% (14·6-41·1), and a negative predictive value of 99·7% (98·3-99·9), when the prespecified threshold of 0·03 ΣPMR or more was applied. When a higher threshold (≥0·3 ΣPMR) was applied the specificity increased to 97·3% (95% CI 95·1-98·5) without a change in sensitivity. INTERPRETATION: The WID-qEC test delivers fast results and shows improved performance compared with a combination of imaging index tests. Triage of women with abnormal uterine bleeding using the WID-qEC test could reduce the number of women requiring histological assessments for identification of potential malignancy and specifically reduce the false positive rate. FUNDING: The Eve Appeal, Land Tirol, and the European Research Council under the European Union's Horizon 2020 Research and Innovation Programme.

Ultrasonographic evaluation of endometrial stripe thickness is insufficient to rule out uterine serous carcinoma.

PURPOSE: Uterine serous carcinoma (USC) is a rare endometrial cancer representing less than 10% of uterine cancers but contributing to up to 50% of the mortality. Delay in diagnosis with this high-grade histology can have significant clinical impact. USC is known to arise in a background of endometrial atrophy. We investigated endometrial stripe (EMS) thickness in USC to evaluate current guidelines for postmenopausal bleeding in the context of this histology. METHODS: Retrospective chart review was conducted using ICD-9 and ICD-10 codes over an 18-year period. We included 139 patients with USC and compared characteristics of patients with EMS ≤ 4 mm and EMS > 4 mm. Chi-square or Fisher's exact tests were used to compare proportions and two-tailed t-tests to compare means. A p-value of < 0.05 was considered statistically significant. RESULTS: Most patients were white, obese, and multiparous. Thirty-two (23%) had an EMS ≤ 4 mm; 107 (77%) had an EMS > 4 mm. There were no statistically significant differences in age at diagnosis or presenting symptoms between groups, and postmenopausal bleeding was the most common symptom in each group. CONCLUSION: Nearly 25% of patients with USC initially evaluated with transvaginal ultrasound were found to have an EMS ≤ 4 mm. If transvaginal ultrasound is used to triage these patients, one in four women will potentially experience a delay in diagnosis that may impact their prognosis.

Development and Validation of a Nomogram Prediction Model for Endometrial Malignancy in Patients with Abnormal Uterine Bleeding.

PURPOSE: This study aimed to identify the risk factors and sonographic variables that could be integrated into a predictive model for endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) in women with abnormal uterine bleeding (AUB). MATERIALS AND METHODS: This retrospective study included 1837 patients who presented with AUB and underwent endometrial sampling. Multivariable logistic regression was developed based on clinical and sonographic covariates [endometrial thickness (ET), resistance index (RI) of the endometrial vasculature] assessed for their association with EC/AEH in the development group (n=1369), and a predictive nomogram was proposed. The model was validated in 468 patients. RESULTS: Histological examination revealed 167 patients (12.2%) with EC or AEH in the development group. Using multivariable logistic regression, the following variables were incorporated in the prediction of endometrial malignancy: metabolic diseases [odds ratio (OR)=7.764, 95% confidence intervals (CI) 5.042-11.955], family history (OR=3.555, 95% CI 1.055-11.971), age ≥40 years (OR=3.195, 95% CI 1.878-5.435), RI ≤0.5 (OR=8.733, 95% CI 4.311-17.692), and ET ≥10 mm (OR=8.479, 95% CI 5.440-13.216). A nomogram was created using these five variables with an area under the curve of 0.837 (95% CI 0.800-0.874). The calibration curve showed good agreement between the observed and predicted occurrences. For the validation group, the model provided acceptable discrimination and calibration. CONCLUSION: The proposed nomogram model showed moderate prediction accuracy in the differentiation between benign and malignant endometrial lesions among women with AUB.

A Case Series on Endometrial Cancer, Despite Endometrial Thickness Being Less than Four Millimetres and A Brief Review of Recent Literature on Endometrial Cancer.

The most common presentation of the most common gynaecological malignancy (Endometrial Cancer) is abnormal PV bleeding. Transvaginal sonography (TVS) is the first line investigation to assess the endometrial nature. Four to five (4-5) millimetre endometrial thicknesses is considered as the normal cut off in post menopausal women. But endometrial cancer can be present while endometrial thickness is less than 4mm. The author describes three cases of isolated endometrial cancer in Glangwili General Hospital in Wales, UK that was diagnosed despite endometrial thickness being less than 4mm and a brief review of the literature on its prevalence, risk factors, clinical presentation, diagnosis and therapeutic approach.

Additional value of Doppler ultrasound to B-mode ultrasound in assessing for uterine intracavitary pathologies among perimenopausal and postmenopausal bleeding women: a multicentre prospective observational study in Vietnam.

PURPOSE: To determine the role of Doppler ultrasonography when combined with B-mode ultrasonography in diagnosing uterine intracavitary pathologies (UIPs) in perimenopausal and postmenopausal bleeding women. METHODS: This multicentre prospective observational study included 150 women aged > 40 years with abnormal uterine bleeding (AUB), who were hospitalised at Hospital X and Hospital Y between June 2016 and June 2019. All participants underwent transvaginal B-mode ultrasound and transvaginal Doppler ultrasound, and the results of sonography were compared to histopathological endpoint. RESULTS: The morphological features, structure, margin, border line of the endometrial-mass lesion, intracavitary uterine fluid, and Doppler signal clearly differed between benign and malignant intracavitary pathologies (p < 0.0001). However, echogenicity had a limited value in differentiating among UIPs (p = 0.1). The sensitivity and specificity of the pedicle sign in diagnosing endometrial polyps were 50.0% and 97.6%; for the circular pattern in endometrial fibroids were 46.2% and 100.0%; for the multiple vessel pattern in endometrial cancer were 64.0% and 96.0%; and for the scattered vessel pattern in endometrial hyperplasia were 43.96% and 56.43%, respectively. The additional value of Doppler ultrasound was greater than that of separate B-mode ultrasound in assessing UIPs in our study. CONCLUSIONS: B-mode ultrasound used in combination with Doppler as a noninvasive tool was significantly valuable in the diagnostic procedures for UIPs in perimenopausal and postmenopausal bleeding women. Doppler ultrasound and B-mode transvaginal ultrasound should be used together routinely for discrimination between malignant diseases and benign endometrial changes. Further studies are needed to better understand the benefits of combining Doppler ultrasound and B-mode ultrasound in routine sonographic practice.

Asymptomatic endometrial thickening in postmenopausal women: predictor of malignant pathology?

It is not standardised what is the endometrial thickness that discriminates between normal and potentially malignant. The objective of this study was to determine the endometrial thickness cut-off point from which the risk of endometrial cancer (EC) increases in asymptomatic postmenopausal women; and to evaluate the risk factors linked to malignant endometrial pathology as well as other associated ultrasound findings.This was a retrospective observational study that included hysteroscopies performed at the Hospital Materno-Infantil on 267 asymptomatic menopausal women with an increase in endometrial thickness (AET) >5 mm, from 2015 to 2019. The results shows that the prevalence of malignant pathology in asymptomatic postmenopausal women with a casual finding of endometrial thickening was 3.7%. This percentage was 16.3% when the cut-off point of AET was established at 10 mm. There was a significant association for the diagnosis of malignant pathology with this cut-off point.There is a significant association between the 10 mm endometrial thickness cut-off point from which the risk of EC increases in asymptomatic postmenopausal women.Impact statementWhat is already known on this subject? Several studies have established the cut-off point for asymptomatic endometrial thickening (AET) for atypical endometrial hyperplasia and endometrial cancer at 10 mm. Although no cut-off point has optimal accuracy for the diagnosis of malignant endometrial pathology, it has been found that with a cut-off value of AET >10 mm no cases are missed. Likewise, a cut-off point of AET > 11 mm may provide a balance between cancer detection and histopathological workup extension.What do the results of this study add? A significant association was found at the cut-off point of AET > 10 mm, which suggests that screening postmenopausal women at this thickness is acceptable and unlikely to miss cases of endometrial hyperplasia and endometrial cancer.What are the implications of these findings for clinical practice and/or further research? After analysing our results we can conclude, like other published studies, that by establishing a cut-off point of 10 mm we obtain a good discrimination between benign and malignant pathology, which would allow us to diagnose 100% of malignant pathology. Above this cut-off point, the risk of endometrial cancer increases, and it would therefore be advisable to extend the study. A multicentre study is needed to confirm the cut-off point at which the risk of endometrial cancer increases in postmenopausal women with asymptomatic endometrial thickening.

The WID-qEC test: Performance in a hospital-based cohort and feasibility to detect endometrial and cervical cancers.

The majority of endometrial and cervical cancers present with abnormal vaginal bleeding but only a small proportion of women suffering from vaginal bleeding actually have such a cancer. A simple, operator-independent and accurate test to correctly identify women presenting with abnormal bleeding as a consequence of endometrial or cervical cancer is urgently required. We have recently developed and validated the WID-qEC test, which assesses DNA methylation of ZSCAN12 and GYPC via real-time PCR, to triage women with symptoms suggestive of endometrial cancer using ThinPrep-based liquid cytology samples. Here, we investigated whether the WID-qEC test can additionally identify women with cervical cancer. Moreover, we evaluate the test's applicability in a SurePath-based hospital-cohort by comparing its ability to detect endometrial and cervical cancer to cytology. In a set of 23 cervical cancer cases and 28 matched controls the receiver operating characteristic (ROC) area under the curve (AUC) is 0.99 (95% confidence interval [CI]: 0.97-1.00) with a sensitivity and specificity of 100% and 92.9%, respectively. Amongst the hospital-cohort (n = 330), the ROC AUC is 0.99 (95% CI: 0.98-1) with a sensitivity and specificity of 100% and 82.5% for the WID-qEC test, respectively, and 33.3% and 96.9% for cytology (considering PAP IV/V as positive). Our data suggest that the WID-qEC test detects both endometrial and cervical cancer with high accuracy.

[Diagnostic strategy for intrauterine lesions]. / Stratégie diagnostique des lésions intra-utérines.

DIAGNOSTIC STRATEGY FOR INTRAUTERINE LESIONS The diagnostic strategy for intrauterine lesions is a question that arises very frequently in gynecological consultations. Endometrial cancer is more frequent in postmenopausal women and bleeding is the first clinical sign in more than 90% of cases. Pelvic ultrasound and endometrial biopsy have a very important place in the diagnostic strategy. After a single episode of abnormal uterine bleeding and when the ultrasound estimates the thickness of the endometrium to be less than or equal to 4 mm, it is possible to postpone further uterine exploration. In the event of recurrent abnormal uterine bleeding or when the thickness of the endometrium is greater than 4 mm in a postmenopausal woman, additional uterine explorations (hysteroscopy and histology) are recommended. If endometrial cancer is discovered, the key examination is lumbopelvic MRI.

STRATÉGIE DIAGNOSTIQUE DES LÉSIONS INTRA-UTÉRINES La stratégie diagnostique des lésions intra-utérines est une question qui se pose très fréquemment en consultation de gynécologie. Le cancer de l'endomètre survient le plus souvent chez des femmes ménopausées, et les saignements sont le premier signe clinique dans plus de 90 % des cas. L'échographie pelvienne et la biopsie d'endomètre ont une place très importante dans la stratégie diagnostique. Lors d'un épisode unique de saignement utérin anormal et lorsque l'échographie estime l'épaisseur de l'endomètre inférieure ou égale à 4 mm, il est possible de surseoir à une exploration utérine complémentaire. En cas de saignements utérins anormaux récidivants ou lorsque l'épaisseur de l'endomètre est supérieure à 4 mm chez une femme ménopausée, des explorations utérines complémentaires (hystéroscopie et histologie) sont en revanche recommandées. En cas de découverte d'un cancer de l'endomètre, l'examen clé est l'IRM lombopelvienne.

Retrospective analysis of endometrial cancer among Afro-Caribbean women in Barbados 2008-2017.

Endometrial cancer data amongst Barbadian women was collected, to inform screening and management in this under-studied population. We analysed all recorded primary cases between January 1st 2008, and December 31st, 2017. Age-specific incidence, and crude mortality rates were calculated. Descriptive statistics characterized demographics, risk factors, prescription data and histopathology. Log-rank tests assessed simple group differences by EC type. Survival analysis based on tumour type was plotted using Kaplein-Meir curves. There were 270 recorded cases of EC, averaging 66 (8.8) years old (SD 8.75), with parity of 3.60 (2.3). Cases were postmenopausal with 257 (95%) experiencing postmenopausal bleeding. Of the 270 cases, 113 (42%) had type 1 tumours and 157(58%) had type 2 tumours. Weak evidence suggests the latter imparted worse survival (log rank test = 0.02). Estimated crude incidence rate was 18.64 per 100,000 women. Crude mortality rate from EC between January 1st, 2008 and December 31st, 2019 was 27%.

The relationship between endometrial thickening and endometrial lesions in postmenopausal women.

PURPOSE: The study aims to investigate the relationship between endometrial thickening and endometrial lesions in postmenopausal women. METHODS: Totally 390 postmenopausal patients with endometrial thickening ≥ 5 mm were enrolled from June 2016 to April 2020, among whom 188 patients were asymptomatic and 202 patients were symptomatic. RESULTS: There were 50 cases with endometrial cancer and precancerous lesions and 150 cases with benign lesions in the symptomatic group, significantly higher than that in the asymptomatic group. The most common pathological type in the asymptomatic group was endometrial polyp. In the asymptomatic group, statistically significant differences were found in endometrial thickness between patients with endometrial cancer and precancerous lesion (group B) and those with benign lesions and non-organic lesions (group A). Statistically significant differences were also found in age, endometrial thickness, hypertension, full-term delivery time and miscarriage times between group A and group B. Regression analysis indicated that hypertension and endometrial thickness were independent risk factors for endometrial cancer and precancerous lesions in the symptomatic group. ROC analysis showed that 10.5 mm was the optimal threshold for predicting endometrial cancer and precancerous lesions in the asymptomatic group, with sensitivity of 100% and specificity of 78.3%. CONCLUSION: The incidence of endometrial cancer and precancerous lesions in postmenopausal women with endometrial thickening and vaginal bleeding is higher than that of asymptomatic women. The endometrial thickening in postmenopausal asymptomatic women is mainly benign, and the threshold for predicting endometrial cancer and precancerous lesions is 10.5 mm.

Comparison of 3D ultrasound, 2D ultrasound and 3D Doppler in the diagnosis of endometrial carcinoma in patients with uterine bleeding: A systematic review and meta-analysis.

Endometrial cancer is a common malignancy affecting women worldwide. Usually, it clinically manifests with uterine bleeding, although identical clinical manifestations occur in benign conditions as well, with several endometrial biopsies being conducted unnecessarily. Therefore, an accurate, non-invasive diagnostic test is needed for first-line assessment, so as unnecessary biopsies are limited as much as possible. This systematic review aims to assess the diagnostic accuracy of three-dimensional ultrasound, a relatively novel method in gynecologic assessment, compared to two-dimensional ultrasound and three-dimensional Doppler in the prediction of uterine malignancy in women with abnormal uterine bleeding. The accuracy of endometrial volume, as a diagnostic parameter assessed by three-dimensional ultrasound is compared to diagnostic parameters from the other two methods, namely endometrial thickness and 3D Doppler indices (vascularization index, flow index and vascularization flow index). Articles relevant to our research question were systematically sought in the Web of Science, Scopus and MEDLINE/PubMed databases and underwent rigorous evaluation for inclusion according to the PRISMA 2020 guidelines. Eligible studies were thoroughly assessed for risk of bias and relevant data was extracted and analyzed. Studies were heterogenous and extracted data varied from study to study. Data on endometrial volume was compared to other diagnostic parameters. Forest plots with pooled percentages and hierarchical summary receiver operating characteristic curves were constructed for each comparison. Relative sensitivity and specificity ratios were calculated for each comparison to test for statistical significance. Endometrial volume and thickness comparison showed sensitivity 83% for both parameters and specificity 75% and 69% respectively, with volume being more specific than thickness (p < 0.05). Endometrial volume and Doppler indices comparison showed that sensitivity was 73%, 82%, 81% and 82%, while specificity was 72%, 76%, 75% and 76% for endometrial volume, vascularization index, flow index and vascularization-flow index respectively. All three Doppler indices were significantly more sensitive in the diagnosis of malignancy compared to endometrial volume (p < 0.05) While endometrial thickness remains a reliable predictor of uterine malignancy, endometrial volume appears promising as a method with higher specificity and more reliable measurements. Similarly, vascular indices seem as competent and even more sensitive than endometrial volume as predictors, with the added advantage of semi-automated and reproducible measurements that reflect the whole organ. More comparative studies with standardized protocols should be established, so as reliable cut-off values can be determined and thus standardize and streamline the diagnostic algorithm via the implementation of the three-dimensional modalities in the settings that they are available.

Periprocedural imaging compared to endometrial biopsy: is biopsy required prior to uterine artery embolisation?

AIM: To compare the detection rate of magnetic resonance imaging (MRI) and ultrasound relative to endometrial biopsy for endometrial abnormalities in both pre- and post-menopausal women. MATERIALS AND METHODS: The present study was an institutional review board-approved, single-institution retrospective analysis of patients who underwent pelvic MRI within 1 year of diagnostic-quality biopsies from 2008-2018 (n=668). There were 303 patients who received uterine artery embolisation (UAE) and 478 patients who received pelvic ultrasound within the study period. Medical records were evaluated for radiological-histopathological correlation, demographics, laboratory studies, and clinical follow-up. RESULTS: In this cohort of 668 patients, there were 37 biopsies positive for malignancy; women with malignancy were older (58 versus 47 years, p<0.0001) and more likely to be post-menopausal (66% versus 12%, p<0.0001). There were 303 patients who underwent UAE and underwent a diagnostic-quality endometrial biopsy during the pre-procedural evaluation, none of whom were post-menopausal and had a mean age of 45 years. In women with abnormal uterine bleeding (AUB) or post-menopausal bleeding (PMB), the sensitivity of MRI for detecting endometrial cancer was 96.2%, with a negative predictive value (NPV) of 99.8%, compared to 68% and 97% for ultrasound, respectively. The receiver operating characteristic (ROC) curve of pre-biopsy MRI in identifying pre-malignant and malignant endometrial pathology demonstrated an AUC of 0.8920 (p<0.0001). CONCLUSION: In women with AUB or PMB, MRI has a 99.8% NPV in ruling out endometrial cancer. Further consideration should be made towards optimising pre-procedural evaluation for UAE.

[Anti-inflammatory and hemostatic effects of total extract, saponins, and flavonoids of Clinopodium chinense in female rats with abnormal uterine bleeding and mechanism].

This study aims to explore the anti-inflammatory and hemostatic effects of the total extract of Clinopodium chinense(TEC), total saponins of C. chinense(TSC), and total flavonoids of C. chinense(TFC) in female rats with abnormal uterine bleeding(AUB), and the possible mechanism. Mifepristone(i.g., 12.4 mg·kg~(-1)) and misoprostol(i.g., 130 µg·kg~(-1)) were used to induce AUB in SD female rats conceiving on the same day. Then the AUB rats were randomized into model group, TEC group, TSC group, TFC group, Yimucao Granules(LG) group, and estradiol valerate(EV) group, with 8 rats in each group. Another 8 non-pregnant female rats were selected as normal group. During the experiment, each group was given the corresponding drug by gavage once a day for 7 days. After the administration, blood and uterine tissue were collected. The uterine bleeding volume was measured by ultraviolet spectrophotometry and the pathological changes of endometrium were observed based on hematoxylin-eosin(HE) staining. In addition, the microvessel density of endometrium was determined by immunohistochemistry, and the content of thromboxane B2(TXB2), 6-keto-PGF_(1α), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in plasma and levels of lutenizing hormone(LH), follicle stimulating hormone(FSH), estradiol(E_2), and progesterone in serum were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA and protein expression of estrogenreceptor α(ERα), progesterone receptor(PR), matrix metalloproteinase(MMP)-2, MMP-9, and vascular endothelial growth factor(VEGF) in uterine tissue was determined by Western blot. Compared with the model group, TEC, TSC, and TFC can reduce uterine bleeding volume, alleviate the pathological damage of endometrium, and increase the microvessel density in endometrium. Moreover, TEC and TSC can significantly raise plasma TXB2 level and ratio of TXB2 to 6-keto-PGF_(1α), and TEC and TFC can significantly reduce the levels of IL-6 and TNF-α. In addition, TEC significantly elevated serum progesterone level and TFC significantly increased serum levels of E_2, FSH, and LH. TSC can significantly raise serum progesterone and FSH levels. In addition, TEC can significantly down-regulate the protein expression of PR, MMP-2, and VEGF and TSC significantly reduced the expression of MMP-9. TFC significantly decreased the expression of PR, MMP-9, and VEGF, and up-regulated the expression of ERα. In conclusion, TEC, TSC, and TFC all show therapeutic effects on AUB, particularly TEC. TSC exerts the effects by enhancing the coagulation function and promoting endometrial repair, and TFC by regulating estrogen levels and reducing inflammatory response. This study reveals the mechanism of C. chinense against AUB and also explains the holistic characteristics of Chinese medicine.

A three-portal laparoscopic hysterectomy in a chimpanzee (Pan troglodytes) with a uterine manipulator and vessel sealing device.

OBJECTIVE: To report the treatment and outcome of a a captive chimpanzee (Pan troglodytes) undergoing 3-portal laparoscopic hysterectomy. Additionally, the technique used for successful urinary catheterization is described. ANIMALS: A 29-year-old female intact chimpanzee with uterine bleeding. STUDY DESIGN: Clinical case report. METHODS: Uterine changes consistent with adenomyosis and/or endometriosis were noted on abdominal ultrasonographic and computed tomographic examinations. A urinary catheter was placed before a 3-portal laparoscopic hysterectomy with a uterine manipulator (VCare) and a vessel sealer (Ligasure). The uterus was submitted for histopathology. RESULTS: Preoperative urinary catheterization was achieved with several modifications and prevented bladder protrusion into the surgical field. Laparoscopy provided excellent visualization of the pelvic structures and VCare effectively maneuvered the uterus for a safe and efficient dissection. The use of the vessel sealer was effective, and bleeding was minimal. Anesthesia and surgery lasted 240 and 150 minutes, respectively. No complications were encountered. Histopathological changes of the uterus were consistent with adenomyosis and myometrial hyperplasia. The chimpanzee recovered uneventfully and returned to normal behavior with no recurrence of uterine bleeding 5 months after surgery. CONCLUSION: The 3-portal laparoscopic technique reported here allowed hysterectomy without complication in this chimpanzee. Urinary catheterization was technically challenging but successful.

Pilot study of women's perspectives when abnormal uterine bleeding occurs during perimenopause.

OBJECTIVE: We gained insights into women's experiences and knowledge about the occurrence of vaginal bleeding during perimenopause requiring evaluation. METHODS: Qualitative inquiry was chosen to explore topics in greater depth to understand individuals' experiences. Interviews with individuals were chosen due to the sensitive nature of gynecologic symptoms and management. Interviews were completed following gynecologic care to explore individuals' experiences with the evaluation and management of vaginal bleeding during perimenopause. RESULTS: Twelve individuals were interviewed between December 2019 and March 2020. Patient uncertainty about the medical significance of developing vaginal bleeding during perimenopause was associated with self-appraisal and gathering information from multiple sources. This experience of seeking evaluation and treatment resulted in varying degrees of trust concerning information received within or outside the clinic. Regarding new technologies that could replace the current invasive tests performed for diagnosis (i.e. ultrasound, hysteroscopy and biopsy), most women preferred the smartphone app and tampon home collection option. CONCLUSIONS: The experience of irregular or heavy vaginal bleeding during perimenopause is fraught with ambiguity, feelings of uncertainty about how to make sense of symptoms and inevitably begins with a period of self-appraisal.

Outpatient hysteroscopy is effective for uterine cavity evaluation following failed office-based endometrial biopsy.

BACKGROUND: Failure to obtain an office-based endometrial biopsy for abnormal uterine bleeding is not uncommon. Although operating room-based procedures are traditionally considered the gold standard assessment tool in these circumstances, outpatient hysteroscopy is a less invasive, more cost-effective, and safer alternative. However, there is no contemporary Canadian literature on the effectiveness of an outpatient approach for this specific population. OBJECTIVE: We aim to evaluate the effectiveness and outcomes of outpatient hysteroscopy for uterine cavity evaluation for patients who have failed an in-office endometrial biopsy attempt. METHODS: We conducted a retrospective cohort study of all patients referred to an academic outpatient hysteroscopy unit between January 2015 and January 2018, who underwent an outpatient hysteroscopy following failed endometrial biopsy. Data were collected from electronic medical records. RESULTS: Of the 407 consecutive patients who underwent an outpatient hysteroscopic procedure, 68 met inclusion criteria. Postmenopausal bleeding was the most common indication for initial biopsy, and most failures were attributed to cervical stenosis. Outpatient hysteroscopies were successfully completed in 96% of cases (n = 65/68). Failure resulted from either anxiety and discomfort (n = 2), or severe intrauterine adhesions (n = 1). Overall, 10% of patients subsequently required an operating room-based hysteroscopy, either to complete a myomectomy or polypectomy, or to allow general anesthesia. Outpatient hysteroscopy identified endometrial hyperplasia and cancer in 4.5% and 3% of patients, respectively. CONCLUSION: Outpatient hysteroscopy following unsuccessful office endometrial biopsy attempts appears to be a feasible, safe, and cost-effective investigation strategy that may prevent the need for an operating room-based procedure in 90% of cases.

[Clinical analysis of 23 cases with simultaneous double primary gynecological malignant tumors].

Objective: To investigate the clinicopathological features, diagnosis, treatment and prognosis of simultaneous double primary gynecological malignant tumors. Methods: A total of 23 patients with simultaneous double primary malignant tumors of female reproductive system primarily treated in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 1, 2010 to December 31, 2020 were retrospectively collected. The age, symptoms, tumor stage, tumor type, treatment and prognosis of patients were collected and followed up. Results: (1) The number of patients with gynecological tumors in our hospital increased year by year in the past 11 years. A total of 8 987 patients with gynecological malignant tumors were firstly diagnosed and cured in our hospital, including 3 474 cases of cervical cancer, 3 484 cases of endometrial cancer, 1 329 cases of ovarian malignancies, 171 cases of fallopian tube cancer, 182 cases of uterine sarcoma, 42 cases of vaginal cancer, 192 cases of vulvar cancer, 110 cases of trophoblastic tumor and 3 cases of other gynecological malignancies. The top three cancers were endometrial cancer, cervical cancer and ovarian malignancies. (2) There were 23 patients identified with simultaneous double primary gynecological tumors in the past 11 years, accounting for 0.26% (23/8 987) of female malignant tumors. There were 3 cases of cervical cancer complicated with endometrial cancer, 3 cases of cervical cancer complicated with ovarian cancer, 16 cases of endometrial cancer combined with ovarian cancer, and 1 patient with endometrial cancer combined with fallopian tube cancer. (3) All 23 patients underwent surgical treatment. According to the first diagnosis of the tumor, the surgical methods included cervical cancer radical surgery, endometrial cancer staging surgery and ovarian cancer cytoreductive surgery. After operation, radiotherapy and chemotherapy were supplemented according to the results of pathological examination and tumor staging. (4) The age of 23 patients ranged from 28 to 66 years, with an average age of (49.4±9.7) years. All patients had vaginal bleeding or conscious pelvic mass as their main clinical manifestation. The clinical stage was found in 7 patients (30%, 7/23) with advanced gynecological cancer (stage Ⅲ-Ⅳ), and 16 patients (70%, 16/23) with early stage gynecological cancer (stage Ⅰ-Ⅱ). According to the nonspecific tumor markers, 13 patients (57%, 13/23) had elevated CA125 and CA199. (5) Among the 23 patients, 1 case was uncontrolled and 3 cases recurred during the follow-up period, and the sites of uncontrolled or recurred were all located in the abdominopelvic cavity. Three cases died. Among the 3 patients who died, 1 patient was an uncontrolled patient, whose tumor type was cervical adenosquamous cell carcinoma combined with ovarian clear cell adenocarcinoma. The overall survival time was 19 months with postoperative supplementary radiotherapy and chemotherapy. There were 2 recurrent patients, and the tumor types were endometrioid carcinoma complicated with high-grade serous ovarian carcinoma and ovarian endometrioid carcinoma, respectively. After surgery, all patients received supplementary chemotherapy and recurred 60 and 21 months after surgery, respectively, and the overall survival time was 78 and 28 months, respectively. Another patient recurred 43 months after surgery, and survived with tumor for 14 months after recurrence. The remaining 19 patients were tumor-free and were still being followed up. Conclusions: There are no specific markers for simultaneous double primary gynecological malignant tumors. The most common clinical symptoms are vaginal bleeding or pelvic mass. The treatment principle of simultaneous double primary gynecological malignant tumor is the same as that of single gynecological malignant tumor, but need to be taken into account the characteristics of two tumors. Surgery is the main treatment method, and radiotherapy and chemotherapy play an important auxiliary role. The prognosis of simultaneous double primary gynecological malignancies is related to the late stage of the two malignancies.

Histopathological pattern of endometrial biopsies in patients with abnormal uterine bleeding in a tertiary referral hospital in Jordan.

BACKGROUND: Abnormal uterine bleeding (AUB) is a symptom that deviates from the normal menstrual cycle. AUB is characterized by changes in the frequency, volume, and duration of the menstrual flow. The etiology of AUB, which varies with age, may be attributed to both structural and non-structural causes. OBJECTIVES: Determine the histopathological pattern of endometrial biopsies in patients with AUB across different age and parity groups who have undergone dilation and curettage (D&C), along with the discrepancy between D&C and histopathological findings after hysterectomy. DESIGN: Retrospective chart review SETTING: Tertiary referral hospital PATIENTS AND METHODS: We collected data on all patients diagnosed with AUB between January 2015 and December 2020. Histopathological findings of all D&C endometrial biopsy samples were examined after being categorized by age and parity groups. Sensitivity, specificity, positive predictive value, and NPV were calculated to evaluate the diagnostic accuracy of D&C. MAIN OUTCOME MEASURES: Histopathological pattern of D&C endometrial biopsies by age and parity groups. SAMPLE SIZE: 3233 patients. RESULTS: Most patients were in the 18-39 year age group, with normal cyclical findings being the most common histopathological finding. Malignant lesions were observed in 42 patients with a majority being older than 50 years. In 13.3% (42/316) of patients, D&C failed to detect intrauterine disorder that was found on hysterectomy. The overall accuracy of D&C in determining the existence of normal versus pathological findings was 75.60%, the sensitivity was 72.90%, the specificity was 77.90%, the positive predictive value was 73.86% and the NPV was 77.05% in our patients. CONCLUSION: Normal cyclic changes account for the highest proportion of histopathological findings. However, hyperplasia and malignancies are important causes of perimenopausal and postmenopausal bleeding. While the use of D&C as a sampling tool for AUB cases remains questionable, the use of D&C in diagnosing premalignant and malignant cases is highly effective. LIMITATIONS: Single-center, retrospective design, incomplete medical records, and inter-rater reliability could not be determined. CONFLICT OF INTEREST: None.

Clinical Features, Management and Maternal-Infant Prognosis in Patients with Complete Uterine Rupture in the Second and Third Trimester of Pregnancy.

Objectives: Our study aimed to investigate the clinical features, management, and maternal-infant prognosis in patients with complete uterine rupture in the second and third trimester of pregnancy. Methods: A total of 15 patients with complete uterine rupture in their second and third trimester of pregnancy who were admitted to our hospital between January 2012 and December 2020 were included in our study. The patients enrolled were divided into the scar group (11 patients) and the non-scar group (4 patients) according to the existence or absence of a uterine scar. The general data, clinical characteristics and follow-up results in the 2 groups were compared. Results: There was no significant difference in age, pregnancy duration or delivery cycle between the 2 groups (P > .05). The incidence of original scar rupture in the scar group was significantly higher than in the non-scar group (P > .05). No significant difference was found in clinical characteristics between the scar and the non-scar groups (P > .05). The most common clinical features included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. A total of 3 patients were misdiagnosed as having surgical disease. After completing relevant examinations, the uterine rupture was repaired surgically; the patients were discharged after blood transfusion, and their condition resolved. In all, 3 patients in the non-scar group and 1 patient in the scar group were transferred to the intensive care unit (ICU). All 15 patients were discharged after treatment. Follow-up was completed by all patients for 12 to 36 months, with an average follow-up time of 23.09 ± 2.19 months. Of the 15 patients, 2 underwent induced abortion after 24 months due to unplanned pregnancy. A 5-minute Apgar score of ≤7 in the scar group was higher than that in the non-scar group, but the difference was not statistically significant (P > .05). Perinatal mortality in the 15 patients was 40.00% (6/15). Conclusion: The most common clinical features in patients with complete uterine rupture in the second and third trimester of pregnancy included abdominal pain, inability to lie flat, hemorrhagic shock, prenatal vaginal bleeding and uterine rupture, mostly occurring in the lower segments of the uterus and cervix. In addition, a remarkably worse maternal-infant prognosis was seen in patients with complete uterine rupture in the second and third trimester of scarless pregnancy compared with patients with complete uterine rupture in the second and third trimester of scarred pregnancy.