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Summary: Background: Female Lynch syndrome carriers have an increased risk of developing endometrial cancer. Regardless, research on endometrial carcinoma tumorigenesis is scarce and no uniform, evidence-based gynaecological management guidelines exist. We therefore described gynaecological surveillance and surgery outcomes in a nation-wide Lynch syndrome cohort. Methods: For this retrospective cohort study, female Lynch syndrome carriers, prospectively registered in the Dutch Lynch syndrome database (StOET), were included up to February 28th 2022. Carriers were linked to the Dutch national pathology (PALGA) database. The number of carriers with/without gynaecological surveillance, number of index carriers with endometrial carcinoma before Lynch syndrome diagnosis were assessed, as well as uptake of risk-reducing surgery and characteristics of endometrial carcinomas including the requisite for adjuvant therapy according to current guidelines. Overall survival after endometrial carcinoma diagnosis was analyzed using Kaplan Meier time to event analyses, cumulative incidence was calculated after adjusting for competing risks (death and prophylactic hysterectomy). Findings: In total, 1046 registered female Lynch syndrome carriers were eligible for surveillance, of whom 313 (30.0%) did not have surveillance and 21.4% (n = 224 of 1046) opted for prophylactic hysterectomy. In carriers with surveillance, more cases of endometrial carcinoma and hyperplasia were found than in those without (37 endometrial carcinomas (7.3%) and 28 hyperplasias (5.5%) in 506 carriers with surveillance versus 14 (2.6%) and 4 (0.7%) in 540 carriers without surveillance, respectively); carriers with surveillance were generally younger than those without (median 56 years [IQR 48–65] versus median 65 years [IQR 49–75] at database assembly, respectively; p

Background: Laparoscopic hysterectomy is accepted worldwide as the standard treatment option for early-stage endometrial cancer. However, there are limited data on long-term survival, particularly when no lymphadenectomy is performed. We compared the survival outcomes of total laparoscopic hysterectomy (TLH) and total abdominal hysterectomy (TAH), both without lymphadenectomy, for early-stage endometrial cancer up to 5 years postoperatively., Methods: Follow-up of a multi-centre, randomised controlled trial comparing TLH and TAH, without routine lymphadenectomy, for women with stage I endometrial cancer. Enrolment was between 2007 and 2009 by 2:1 randomisation to TLH or TAH. Outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and primary site of recurrence. Multivariable Cox regression analyses were adjusted for age, stage, grade, and radiotherapy with adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI) reported. To test for significance, non-inferiority margins were defined., Results: In total, 279 women underwent a surgical procedure, of whom 263 (94%) had follow-up data. For the TLH (n = 175) and TAH (n = 88) groups, DFS (90.3% vs 84.1%; aHR[recurrence], 0.69; 95%CI, 0.31-1.52), OS (89.2% vs 82.8%; aHR[death], 0.60; 95%CI, 0.30-1.19), and DSS (95.0% vs 89.8%; aHR[death], 0.62; 95%CI, 0.23-1.70) were reported at 5 years. At a 10% significance level, and with a non-inferiority margin of 0.20, the null hypothesis of inferiority was rejected for all three outcomes. There were no port-site or wound metastases, and local recurrence rates were comparable., Conclusion: Disease recurrence and 5-year survival rates were comparable between the TLH and TAH groups and comparable to studies with lymphadenectomy, supporting the widespread use of TLH without lymphadenectomy as the primary treatment for early-stage, low-grade endometrial cancer., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives:  To analyze how well untrained examiners - without experience in the use of International Ovarian Tumor Analysis (IOTA) terminology or simple ultrasound-based rules (simple rules) - are able to apply IOTA terminology and simple rules and to assess the level of agreement between non-experts and an expert., Methods:  This prospective multicenter cohort study enrolled women with ovarian masses. Ultrasound was performed by non-expert examiners and an expert. Ultrasound features were recorded using IOTA nomenclature, and used for classifying the mass by simple rules. Interobserver agreement was evaluated with Fleiss' kappa and percentage agreement between observers., Results:  50 consecutive women were included. We observed 46 discrepancies in the description of ovarian masses when non-experts utilized IOTA terminology. Tumor type was misclassified often (n = 22), resulting in poor interobserver agreement between the non-experts and the expert (kappa = 0.39, 95 %-CI 0.244 - 0.529, percentage of agreement = 52.0 %). Misinterpretation of simple rules by non-experts was observed 57 times, resulting in an erroneous diagnosis in 15 patients (30 %). The agreement for classifying the mass as benign, malignant or inconclusive by simple rules was only moderate between the non-experts and the expert (kappa = 0.50, 95 %-CI 0.300 - 0.704, percentage of agreement = 70.0 %). The level of agreement for all 10 simple rules features varied greatly (kappa index range: -0.08 - 0.74, percentage of agreement 66 - 94 %)., Conclusion:  Although simple rules are useful to distinguish benign from malignant adnexal masses, they are not that simple for untrained examiners. Training with both IOTA terminology and simple rules is necessary before simple rules can be introduced into guidelines and daily clinical practice., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Imiquimod has been studied as a noninvasive pharmacological treatment alternative to large loop excision of the transformation zone (LLETZ) for high-grade cervical intraepithelial neoplasia (CIN), to prevent long-term obstetric complications from surgical treatment. This study aims to investigate womens' preferences for treatment of high-grade CIN with imiquimod or LLETZ. A labeled discrete choice experiment was conducted among 100 women with abnormal cervical cytology in 5 hospitals in the Netherlands between March 2014 and December 2015. Participants were asked to choose between imiquimod treatment or standard surgical treatment in 9 separate scenarios, based on the following treatment characteristics: treatment success rate, rate of side effects, risk of premature birth in subsequent pregnancies, and risk of subfertility after treatment. The levels of these characteristics differed for the imiquimod alternatives. Women assigned a positive utility to LLETZ compared with imiquimod. When making a choice for imiquimod, women preferred a higher treatment success rate and a lower risk of premature birth, infertility and side effects. The choice for imiquimod treatment was also influenced by the intention of a future pregnancy. Subgroup analyses revealed that a lower efficacy regarding imiquimod might be more acceptable for women who desired a future pregnancy compared with women who did not desire a future pregnancy. Women with a future pregnancy wish may prefer treatment of high-grade CIN with imiquimod cream over LLETZ, if the risk of subfertility and premature birth is low.

Background: Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which improves outcome and overall survival. The Risk of Malignancy Index is currently the most commonly used method in clinical practice, but has a relatively low diagnostic accuracy (sensitivity 75-80% and specificity 85-90%). Recent reports show that other methods, such as simple ultrasound-based rules, subjective assessment and (Diffusion Weighted) Magnetic Resonance Imaging might be superior to the RMI in the pre-operative differentiation of adnexal masses., Methods/design: A prospective multicenter cohort study will be performed in the south of The Netherlands. A total of 270 women diagnosed with at least one pelvic mass that is suspected to be of ovarian origin who will undergo surgery, will be enrolled. We will apply the Risk of Malignancy Index with a cut-off value of 200 and a two-step triage test consisting of simple ultrasound-based rules supplemented -if necessary- with either subjective assessment by an expert sonographer or Magnetic Resonance Imaging with diffusion weighted sequences, to characterize the adnexal masses. The histological diagnosis will be the reference standard. Diagnostic performances will be expressed as sensitivity, specificity, positive and negative predictive values and likelihood ratios., Discussion: We hypothesize that this two-step triage test, including the simple ultrasound-based rules, will have better diagnostic accuracy than the Risk of Malignancy Index and therefore will improve the management of women with adnexal masses. Furthermore, we expect this two-step test to be more cost-effective. If the hypothesis is confirmed, the results of this study could have major effects on current guidelines and implementation of the triage test in daily clinical practice could be a possibility., Trial Registration: ClinicalTrials.gov: registration number NCT02218502.