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Objective: To evaluate the effectiveness of hysteroscopy for the detection and treatment of endometrial polyps versus expectant management in women with postmenopausal bleeding (PMB), a thickened endometrium and benign endometrial sampling., Design: Multicentre, randomised controlled trial., Setting: Three academic hospitals and nine non-academic teaching hospitals in the Netherlands., Population: Women with PMB, an endometrial thickness >4 mm and benign result from endometrial sampling., Methods: Women were randomised to either further diagnostic workup by hysteroscopy (preceded by saline infusion sonography) or expectant management., Main Outcomes: The primary outcome measure was recurrence of PMB within a year after randomisation. Secondary outcome measures were time to recurrent bleeding and recurrent bleeding after more than 1 year. In the hysteroscopy group, the presence of polyps and the results of their histology were registered., Results: Between January 2010 and October 2013, 200 women were randomised; 98 to hysteroscopy and 102 to expectant management. Within 1 year a total of 15 women (15.3%) in the hysteroscopy group experienced recurrent bleeding, versus 18 (18.0%) in the expectant management group (relative risk 0.85 (95% CI 0.46-1.59). In the hysteroscopy group, 50/98 (51%) polyps were diagnosed of which 6/98 (6%) showed evidence of endometrial (pre)malignancy; final pathology results after hysterectomy showed three women with hyperplasia with atypia and three women with endometrial cancer., Conclusion: In women with PMB, a thickened endometrium and benign endometrial sampling, operative hysteroscopy does not reduce recurrent bleeding. Hysteroscopy detected focal endometrial (pre)malignancy in 6% of women who had benign endometrial sampling. This finding indicates that in these women, further diagnostic workup is warranted to detect focal (pre)malignancies, missed by blind endometrial sampling., Tweetable Abstract: In women with PMB, hysteroscopy does not reduce recurrent bleeding but is warranted to detect focal malignancy., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Postmenopausal bleeding (PMB) can be the first sign of endometrial cancer. In case of thickened endometrium, endometrial sampling is often used in these women. In this systematic review, we studied the accuracy of endometrial sampling for the diagnoses of endometrial cancer, atypical hyperplasia and endometrial disease (endometrial pathology, including benign polyps). We systematically searched the literature for studies comparing the results of endometrial sampling in women with postmenopausal bleeding with two different reference standards: blind dilatation and curettage (D&C) and hysteroscopy with histology. We assessed the quality of the detected studies by the QUADAS-2 tool. For each included study, we calculated the fraction of women in whom endometrial sampling failed. Furthermore, we extracted numbers of cases of endometrial cancer, atypical hyperplasia and endometrial disease that were identified or missed by endometrial sampling. We detected 12 studies reporting on 1029 women with postmenopausal bleeding: five studies with dilatation and curettage (D&C) and seven studies with hysteroscopy as a reference test. The weighted sensitivity of endometrial sampling with D&C as a reference for the diagnosis of endometrial cancer was 100% (range 100-100%) and 92% (71-100) for the diagnosis of atypical hyperplasia. Only one study reported sensitivity for endometrial disease, which was 76%. When hysteroscopy was used as a reference, weighted sensitivities of endometrial sampling were 90% (range 50-100), 82% (range 56-94) and 39% (21-69) for the diagnosis of endometrial cancer, atypical hyperplasia and endometrial disease, respectively. For all diagnosis studied and the reference test used, specificity was 98-100%. The weighted failure rate of endometrial sampling was 11% (range 1-53%), while insufficient samples were found in 31% (range 7-76%). In these women with insufficient or failed samples, an endometrial (pre) cancer was found in 7% (range 0-18%). In women with postmenopausal bleeding, the sensitivity of endometrial sampling to detect endometrial cancer and especially atypical hyperplasia and endometrial disease, including endometrial polyps, is lower than previously thought. Therefore, further diagnostic work-up for focal pathology is warranted, after a benign result of endometrial sampling., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Objective: To determine whether structured assessment of outpatient endometrial biopsies decreases the number of inconclusive samples., Design: Retrospective cohort study., Setting: Single hospital pathology laboratory., Population: Endometrial biopsy samples of 66 women with postmenopausal bleeding, collected during the usual diagnostic work-up and assessed as insufficient for a reliable histological diagnosis., Methods: Endometrial biopsy samples were requested from the pathology laboratories. The retrieved samples were systematically reassessed by a single pathologist specialized in gynecology., Main Outcome Measure: Disagreement between initial assessment and conclusion after structured reassessment., Results: We retrieved 36 of 66 endometrial biopsy samples from six different pathology laboratories. Structured reassessment of the retrieved samples by a single pathologist specialized in gynecology did not change the conclusion in 35 of the 36 samples. The remaining sample contained a large amount of endometrial tissue and the diagnosis at reassessment was endometrial hyperplasia without atypia. All other samples contained insufficient material for a reliable diagnosis., Conclusion: A structured reassessment of endometrial biopsies samples, which were classified as inconclusive due to insufficient material, did not change the conclusion. Although it might be helpful for pathologists to have diagnostic criteria for adequacy and/or inadequacy of an endometrial biopsy sample, the gain in efficiency is likely to be small.

Objective: To determine which doctor- and patient-related factors affect failure of outpatient endometrial sampling in women with postmenopausal bleeding, and to develop a multivariable prediction model to select women with a high probability of failed sampling., Design: Prospective multicenter cohort study., Setting: Three teaching hospitals in the Netherlands., Population: Women presenting with postmenopausal bleeding with an indication for endometrial sampling., Methods: Multivariable logistic regression was performed to evaluate the impact of doctor's training level and patient's characteristics on failure of sampling., Main Outcome Measures: Failure of endometrial sampling, classified as technical failure or insufficient tissue for diagnosis., Results: In 74 (20.8%) of the 356 included women, sampling technically failed, and in 84 (29.8%) the amount of tissue was insufficient for diagnosis. Nulliparity [odds ratio (OR) 3.8, 95% confidence interval (CI) 1.8-7.9] and advanced age (OR 1.03 per year, 95% CI 1.00-1.06) were associated with technical failure. Advanced age was associated with insufficient sampling (OR 1.04 per year, 95% CI 1.01-1.07), and endometrial thickness >12 mm decreased the chance of insufficient sampling (OR 0.3, 95%CI 0.1-0.8). The prediction model for total failure had an area under the ROC curve of 0.64 (95% CI 0.58-0.70)., Conclusions: In women with postmenopausal bleeding, the failure rate of endometrial sampling is relatively high and is associated with nulliparity and advanced age. Endometrial thickness >12 mm decreased the chance of failure. A multivariable prediction model for total failure based on patient characteristics has a moderate capacity to discriminate between women at high or low risk of failure., (© 2013 Nordic Federation of Societies of Obstetrics and Gynecology.)

Postmenopausal bleeding is associated with an elevated risk of having endometrial cancer. The aim of this review is to give an overview of existing prediction models on endometrial cancer in women with postmenopausal bleeding. In a systematic search of the literature, we identified nine prognostic studies, of which we assessed the quality, the different phases of development and their performance. From these data, we identified the most important predictor variables. None of the detected models completed external validation or impact analysis. Models including power Doppler showed best performance in internal validation, but Doppler in general gynecological practice is not easily accessible. We can conclude that we have indications that the first step in the approach of women with postmenopausal bleeding should be to distinguish between women with low risk versus high risk of having endometrial carcinoma and the next step would be to refer patients for further (invasive) testing.

We describe the design of a randomised controlled trial to evaluate the efficacy of endometrial polyp removal in women with postmenopausal bleeding. We designed a trial in which patients with postmenopausal bleeding and endometrial thickness >4 mm undergo hysteroscopy. If during hysteroscopy an endometrial polyp was diagnosed, patients were asked to participate in this trial and after informed consent allocated to immediate removal of the polyp or expectant management. This trial suffered from lack of recruitment related both to doctors seeking for informed consent as well as to patients' unwillingness to participate in this trial. However, a randomised controlled trial on this subject is still necessary to evaluate the efficacy of uterine cavity evaluation in the diagnostic work-up of women with postmenopausal bleeding, focussing on benign pathology. Therefore, we propose an alternative design, which might be more feasible.

Objective: To assess the accuracy of the cervical smear in the diagnosis of endometrial cancer in women with postmenopausal bleeding, with an emphasis on the diagnostic relevance of normal endometrial cells., Study Design: Women presenting with abnormal postmenopausal bleeding, not using hormone replacement therapy, were included prospectively. Cervical cytology was coded according to both the Papanicolaou (Pap) classification and the Dutch coding system (CISOE-A), which classifies endometrial and other cell types separately. For both classification systems, likelihood ratios (LR) for the presence of (pre) malignancy of the endometrium were calculated., Results: We included 543 women with postmenopausal bleeding. A (pre) cancerous endometrial lesion was present in 64 women (11.7%). A Pap III increased the probability of (pre) malignancy (LR 3.5), whereas Pap IV and Pap V virtually proved the presence of carcinoma. The CISOE-A classification showed similar results. The presence of normal endometrial cells did not increase the probability of endometrial (pre) malignancy., Conclusion: Adding the results of the cervical smear to endometrial thickness could detect incidental endometrial cancers that are missed by transvaginal sonography (< 5 mm). In women with postmenopausal bleeding the presence of normal endometrial cells is not predictive of endometrial cancer.

Purpose: To determine the accuracy of endometrial thickness measurement with transvaginal ultrasonography (TVUS) to diagnose endometrial polyps in women with postmenopausal bleeding in whom a carcinoma has been ruled out., Methods: In women with postmenopausal bleeding, endometrial thickness was measured with TVUS. If endometrial thickness was >4 mm, office hysteroscopy was performed. At hysteroscopy, the uterine cavity was assessed for the presence of polyps. Patients with malignancy were excluded. We used receiver operating characteristics (ROC) analysis to assess the capacity of TVUS endometrial thickness measurement to diagnose endometrial polyps. Findings at hysteroscopy were considered to be the reference standard., Results: We included 178 patients with postmenopausal bleeding and endometrial thickness >4 mm. Hysteroscopy showed an endometrial polyp in 90 patients (50%). The ROC analysis revealed that endometrial thickness had an area under the curve of 0.64 in the diagnosis of endometrial polyps., Conclusion: In women with postmenopausal bleeding in whom carcinoma has been ruled out, measurement of endometrial thickness with TVUS is not useful in the diagnosis of endometrial polyps.

Objective: To estimate the incidence of recurrent postmenopausal bleeding among women who were diagnosed with an endometrial thickness greater than 4 mm., Methods: We designed a prospective cohort study and included consecutive women not using hormone replacement therapy, presenting with a first episode of postmenopausal bleeding. We evaluated patients who had an endometrial thickness greater than 4 mm at transvaginal ultrasonography and benign endometrial sampling; presence of carcinoma was ruled out by office endometrial sampling, hysteroscopy, and/or dilation and curettage. Time until recurrent bleeding was measured, and diagnosis at recurrent bleeding was recorded., Results: Among 318 patients who had an endometrial thickness greater than 4 mm, 222 patients had benign histology results and were available for follow-up. During follow-up, 47 (21%, 95% confidence interval 16-27%) patients had recurrent bleeding, with a median time to recurrent bleeding of 49 weeks (interquartile range 18 to 86 weeks). There was no difference with respect to recurrence rate between patients with polyp removal, patients with a normal hysteroscopy, and patients with office endometrial sampling alone at the initial workup. Two patients were diagnosed with atypical endometrial hyperplasia upon recurrent bleeding., Conclusion: The recurrence rate of postmenopausal bleeding in women with endometrial thickness greater than 4 mm is 20%. This recurrence rate is not related to incorporation of hysteroscopy or polyp removal at the initial workup., Level of Evidence: II.

The objective is to assess among women with postmenopausal bleeding the relationship of age and time since menopause on one hand and the presence of endometrial cancer and atypical hyperplasia on the other hand. In a multicenter prospective cohort study, 614 women presenting with postmenopausal bleeding were included. Women underwent transvaginal sonography and, in cases where the endometrial thickness was >4 mm, endometrial sampling. Splines were used to assess the association between each of the continuous variables and (pre)malignancy of the endometrium. Subsequently, univariate and multivariate analysis were performed. The average age for women without (pre)malignancy was 61.7 years (SD 9.8). As malignant and premalignant cases were found to have similar age, these subgroups were merged in the analyses. Age was an independent predictor of (pre)malignancy. In women younger than 55 years, the odds ratio was 1.9 (95% CI: 1.1-3.3) for each year under 55 years of age and 1.03 (95% CI: 1.00-1.06) for each year over 55 years of age. The risk of (pre)malignancy of the endometrium was 4.9% in women less than 3 years postmenopausal versus 19.7% in women more than 20 years postmenopausal. However, in a multivariate analysis only age contributed to the prediction of risk. This study demonstrates that, in postmenopausal women with vaginal bleeding, the risk of (pre)malignancy of the endometrium is low in women under 50 years of age, increases considerably until 55 years of age, and rises only modestly with further advancing age. Future studies should explore whether these findings can be incorporated in the diagnostic work-up of women with postmenopausal bleeding.

Objective: To assess patients' preferences for diagnostic management of postmenopausal bleeding (PMB)., Design: A structured interview., Setting: A teaching hospital with office hysteroscopy facilities., Population: Thirty-nine women with PMB and with a completed work-up including an office hysteroscopy., Methods: A structured interview was taken from 39 women who had had an office hysteroscopy in the diagnostic work-up for PMB. Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e. expectant management after ultrasound or complete diagnostic work-up, including invasive procedures., Main Outcome Measures: Women were informed about the probability of endometrial carcinoma versus benign disease and about advantages and disadvantages of different diagnostic strategies, i.e., expectant management after ultrasound or complete diagnostic work-up including invasive procedures. Women were asked to make a trade-off between different options., Results: Most women wanted to be 100% certain that carcinoma could be ruled out. Only 5% of the women were willing to accept more than 5% risk of false reassurance. If the risk of recurrent bleeding due to benign disease exceeded 25%, the majority of women would prefer immediate diagnosis and treatment of benign lesions., Conclusion: Women with PMB are prepared to undergo hysteroscopy to rule out any risk on cancer. This finding implicates that the measurement of endometrial thickness with transvaginal ultrasound as a first-line test in the assessment of PMB should be reconsidered.

Objectives: The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment., Design: Multicenter, prospective cohort study., Setting: A university hospital and seven teaching hospitals in the Netherlands., Sample: Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding., Methods: Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months., Main Outcome Measures: Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures., Results: A strategy with transvaginal sonography alone with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy integrating characteristics of the women with transvaginal sonography could result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal decrease in diagnostic procedures, or a minor increase in false reassurances (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the procedures. AUCs associated with these strategies could improve from 0.76 (0.73-0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated strategy., Conclusion: Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.

Objective: To evaluate the effectiveness of hysteroscopy for the detection and treatment of endometrial polyps versus expectant management in women with postmenopausal bleeding (PMB), a thickened endometrium and benign endometrial sampling.Design: Multicentre, randomised controlled trial.Setting: Three academic hospitals and nine non-academic teaching hospitals in the Netherlands.Population: Women with PMB, an endometrial thickness >4 mm and benign result from endometrial sampling.Methods: Women were randomised to either further diagnostic workup by hysteroscopy (preceded by saline infusion sonography) or expectant management.Main Outcomes: The primary outcome measure was recurrence of PMB within a year after randomisation. Secondary outcome measures were time to recurrent bleeding and recurrent bleeding after more than 1 year. In the hysteroscopy group, the presence of polyps and the results of their histology were registered.Results: Between January 2010 and October 2013, 200 women were randomised; 98 to hysteroscopy and 102 to expectant management. Within 1 year a total of 15 women (15.3%) in the hysteroscopy group experienced recurrent bleeding, versus 18 (18.0%) in the expectant management group (relative risk 0.85 (95% CI 0.46-1.59). In the hysteroscopy group, 50/98 (51%) polyps were diagnosed of which 6/98 (6%) showed evidence of endometrial (pre)malignancy; final pathology results after hysterectomy showed three women with hyperplasia with atypia and three women with endometrial cancer.Conclusion: In women with PMB, a thickened endometrium and benign endometrial sampling, operative hysteroscopy does not reduce recurrent bleeding. Hysteroscopy detected focal endometrial (pre)malignancy in 6% of women who had benign endometrial sampling. This finding indicates that in these women, further diagnostic workup is warranted to detect focal (pre)malignancies, missed by blind endometrial sampling.Tweetable Abstract: In women with PMB, hysteroscopy does not reduce recurrent bleeding but is warranted to detect focal malignancy. [ABSTRACT FROM AUTHOR]