Anne Timmermans

Endometrial thickness measurement for detecting endometrial cancer in women with postmenopausal bleeding: a systematic review and meta-analysis

OBJECTIVE: To estimate the accuracy of endometrial thickness measurement in the detection of endometrial cancer among women with postmenopausal bleeding with individual patient data using different meta-analytic strategies. DATA SOURCES: Original data sets of studies detected after reviewing the included studies of three previous reviews on this subject. An additional literature search of published articles using MEDLINE databases was preformed from January 2000 to December 2006 to identify articles reporting on endometrial carcinoma and sonographic endometrial thickness measurement in women with postmenopausal bleeding. METHODS OF STUDY SELECTION: We identified 90 studies reporting on endometrial thickness measurements and endometrial carcinoma in women with postmenopausal bleeding. TABULATION, INTEGRATION, AND RESULTS: We contacted 79 primary investigators to obtain the individual patient data of their reported studies, of which 13 could provide data. Data on 2,896 patients, of which 259 had carcinoma, were included. Several approaches were used in the analyses of the acquired data. First, we performed receiver operator characteristics (ROC) analysis per study, resulting in a summary area under the ROC curve (AUC) calculated as a weighted mean of AUCs from original studies. Second, individual patient data were pooled and analyzed with ROC analyses irrespective of study with standardization of distributional differences across studies using multiples of the median and by random effects logistic regression. Finally, we also used a two-stage procedure, calculating sensitivities and specificities for each study and using the bivariate random effects model to estimate summary estimates for diagnostic accuracy. This resulted in rather comparable ROC curves with AUCs varying between 0.82 and 0.84 and summary estimates for sensitivity and specificity located along these curves. These curves indicated a lower AUC than previously reported meta-analyses using conventional techniques. CONCLUSION: Previous meta-analyses on endometrial thickness measurement probably have overestimated its diagnostic accuracy in the detection of endometrial carcinoma. We advise the use of cutoff level of 3 mm for exclusion of endometrial carcinoma in women with postmenopausal bleeding.

Regional and temporal variation in hysterectomy rates and surgical routes for benign diseases in the Netherlands

Abstract  Objective. To provide descriptive statistics on hysterectomy for benign gynecological conditions in the Netherlands and to analyze regional and temporal variations in hysterectomy rates and surgical routes. Design. Retrospective cohort study. Setting. Dutch hospitals. Population. All women with a hysterectomy for benign gynecological conditions in the Netherlands in 1995–2005. Methods. This study is based on an analysis of the Dutch registry of hospital admissions for 1995–2005. Main outcome measures. The age‐adjusted hysterectomy rate and age‐ and diagnosis‐adjusted proportion of vaginal hysterectomies for each Dutch healthcare region and time period. Results. The average annual crude hysterectomy rate for benign disease only, was 17.2 per 10 000 women of all ages. The vaginal route was chosen for 50.8% of the patients. During the study period, the number of hysterectomies for bleeding disorders declined almost 25%. Among 27 Dutch healthcare regions, the age‐adjusted hysterectomy rates for bleeding disorders and pelvic organ prolapse varied 2.2‐ and 2.3‐fold, respectively. The average annual age‐ and diagnosis‐adjusted proportion of vaginal hysterectomies varied from 43.4 to 63.8%. The regional differences with regard to rate and proportion declined slightly over time. Conclusions. The Netherlands is among the countries with the lowest hysterectomy rates and the highest proportion of vaginal hysterectomies. The regional differences indicate that a further decrease in the hysterectomy rates and an increase in the proportion of vaginal hysterectomies are possible.

Patients’ preferences in the evaluation of postmenopausal bleeding

Objective  To assess patients’ preferences for diagnostic management of postmenopausal bleeding (PMB).

The accuracy of endometrial sampling in women with postmenopausal bleeding: a systematic review and meta-analysis

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.

Factors attributing to the failure of endometrial sampling in women with postmenopausal bleeding

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.

Diagnostic strategies for endometrial cancer in women with postmenopausal bleeding: cost-effectiveness of individualized strategies

OBJECTIVE To evaluate the cost-effectiveness of diagnostic strategies incorporating the diagnostic value of patient characteristics for endometrial carcinoma using prediction models. STUDY DESIGN A decision analytic model was created to compare four diagnostic strategies for women with postmenopausal bleeding: the main outcome measures were 5 year survival, costs, and cost-effectiveness of three model based strategies compared to the strategy reflecting current practice. RESULTS A strategy selecting women for endometrial biopsy based on their history only, dominated all other strategies (more effective, less cost). In a clinical scenario where transvaginal sonography (TVS) was assumed to be an integral part of the consultation without additional costs, a strategy selecting high-risk women for TVS became the most cost-effective strategy. CONCLUSIONS Strategies taking into account the individual probability based on a prognostic model are less costly than the currently applied strategy for a similar effectiveness. The most cost-effective strategy depends on the clinical setting: in areas where TVS is performed by the consulting gynecologist without extra costs, selective TVS based on history is the most cost-effective strategy. When TVS is not readily available and therefore incurs extra costs, a risk selection based on patient characteristics is most cost-effective.

What is the recurrence rate of postmenopausal bleeding in women who have a thin endometrium during a first episode of postmenopausal bleeding

Objective. To determine the incidence and significance of recurrent postmenopausal bleeding among women diagnosed with an endometrial thickness ≤4 mm after a first episode of postmenopausal bleeding. Methods. Consecutive patients not using hormone replacement therapy (HRT) presenting with a first episode of postmenopausal bleeding and an endometrial thickness ≤4 mm at transvaginal ultrasonography (TVU) were managed expectantly. In case of recurrent bleeding, the patient was evaluated according to the hospitals local policy with TVU, office endometrial sampling, hysteroscopy or dilatation and curettage (D&C) or a combination of these tests. We evaluated the incidence of recurrent bleeding, potential risk factors for recurrent bleeding, and the diagnosis made after recurrent bleeding. Results. A total of 607 patients were registered with a first episode of postmenopausal bleeding, of whom 249 had an endometrial thickness ≤4 mm. Follow‐up took place with a median of 174 weeks (range: 4–250 weeks). During follow‐up, 25 of the 249 patients (10%; 95% CI: 6.6–14%) had recurrent bleeding. Median time until recurrence of bleeding was 49 weeks (range: 9–186 weeks). Two patients with recurrent bleeding turned out to have an endometrial carcinoma (8%; 95% CI: 2.2–25%), and 1 patient had a malignant melanoma. Time since menopause, age, body mass index, hypertension, diabetes and anticoagulants were not predictive for recurrent bleeding. Conclusion. The recurrence rate after a first episode of postmenopausal bleeding managed expectantly is low and cannot be predicted by patient characteristics. Patients with recurrent bleeding should be re‐evaluated, as they bear a considerable risk of carcinoma.

Laparoscopic entry techniques: a protocol for daily gynaecological practice in The Netherlands

This Dutch model protocol aims to formulate recommendations on insertion of laparoscopic instruments in order to reduce entry-related complications. It was written on behalf of the Dutch Society of Gynaecological Endoscopy and Minimal Invasive Surgery and serves as guidance to safe entry in laparoscopy for the Dutch gynaecologist in daily practice. It was translated and made suitable for publication in English. Despite the variety of methods described for creating pneumoperitoneum, no one single method can claim to be fundamentally superior to another. The practising laparoscopist should be familiar with at least more than one entry technique.

Management of women with postmenopausal bleeding: evidence‐based review

Patients with postmenopausal bleeding (PMB) have a 10–15% chance of having endometrial carcinoma; they should therefore be seen within 2 weeks of referral. Cervical and vulval cancers remain important components of the differential diagnosis and can only be assessed by clinical examination. There are well‐developed and evidence‐based strategies on how best to investigate women with PMB. These strategies are formulated in several guidelines.