Search

Simple Summary: Patients with high-grade uterine cancer (UC) have a risk of around 20% of the cancer spreading to the lymph nodes, while this is only around 10% in patients with low-grade uterine cancer. CA125 is a marker that can be detected in blood and is associated with increased tumor spread. Studies on CA125 and its association with tumor spread within low-grade UC exist but are limited for high-grade UC. The primary aim of this retrospective study was to assess whether elevated CA125 is predictive for UC spread and survival. Secondarily, we studied the additional value of preoperative imaging by CT scan in relation to CA125 specifically in high-grade UC. We observed that elevated CA125 was related to advanced stage and LNM in high-grade UC and a worse prognosis. If CA125 was normal, the additional value of CT to predict lymph node spread was limited. Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific—(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC. [ABSTRACT FROM AUTHOR]

Objective Design Setting Population Methods Main Outcome Measures Results Conclusion To evaluate whether physical function and quality of life was influenced by discharge on the same‐day after a total laparoscopic hysterectomy.Multicentre non‐inferiority randomised controlled trial.Five teaching hospitals and two university hospitals in the Netherlands.Patients undergoing laparoscopic hysterectomy for benign or premalignant disease.Following informed consent, participants were allocated 1:1 either to same‐day discharge (SDD) or next‐day discharge (NDD).The primary outcome was physical function at 7 days after surgery measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function short Form 10A. Secondary outcomes were physical function and quality of life at 1 and 3 days and 6 weeks after surgery measured with PROMIS short Form 10A and the EuroQol questionnaire (EQ‐5D‐5L).Two hundred and five patients were included of whom 105 were allocated to SDD and 100 to NDD. Physical function 7 days after surgery was 35.95 in the SDD group and 35.63 in the control group (mean difference 0.32; 95% CI [0.07–0.57]). As the upper limit of the 95% CI does not exceed the non‐inferiority margin of 4 points, non‐inferiority of SDD could be demonstrated. No difference in physical function nor quality of life on Days 1 and 3 and 6 weeks could be found.This research demonstrates same‐day discharge after laparoscopic hysterectomy is non‐inferior to next day discharge in physical function 7 days after surgery. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT.Study Design: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands. Women suffering from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future fertility desire, were eligible for this trial. Women who declined randomisation were asked to participate in the observational cohort. The outcome measure was reintervention rate at 24 months of follow-up.Results: 276 women were followed in the observational cohort of which 87 women preferred an initial treatment with LNG-IUS and 189 women preferred an initial treatment with endometrial ablation. At 24 months of follow-up women in the LNG-IUS-group were more likely to receive a reintervention compared to the women in the ablation group, 28/81 (35 %) versus 25/178 (14 %) (aRR 2.42, CI 1.47-3.98, p-value 0.001). No differences in reintervention rates were found between women in the observational cohort and women in the RCT.Conclusions: Women who receive an LNG-IUS are more likely to undergo an additional intervention compared to women who receive endometrial ablation. Reintervention rates of women in the cohort and RCT population were comparable. The results of this study endorse the findings of the RCT and will contribute to shared decision making in women with heavy menstrual bleeding. [ABSTRACT FROM AUTHOR]

Background: The symptom of heavy menstrual bleeding has a substantial impact on professional, physical, and social functioning. In 2021, results from a randomized controlled trial comparing a 52-mg levonorgestrel-releasing intrauterine system and radiofrequency nonresectoscopic endometrial ablation as treatments for women with heavy menstrual bleeding were published. Both treatment strategies were equally effective in treating heavy menstrual bleeding during 2-year follow-up. However, long-term results are also relevant for both patients and healthcare providers., Objective: This study aimed to assess long-term differences in reintervention risk and menstrual blood loss in women with the symptom of heavy menstrual bleeding treated according to a strategy starting with a 52-mg levonorgestrel-releasing intrauterine system or radiofrequency nonresectoscopic endometrial ablation., Study Design: This study was a long-term follow-up study of a multicenter randomized controlled trial (MIRA trial), in which women were allocated to either a 52-mg levonorgestrel-releasing intrauterine device (n=132) or radiofrequency nonresectoscopic endometrial ablation (n=138). Women from the original trial were contacted to fill out 6 questionnaires. The primary outcome was the reintervention rate after allocated treatment. Secondary outcomes included surgical reintervention rate, menstrual bleeding measured by the Pictorial Blood Loss Assessment Chart, (disease-specific) quality of life, sexual function, and patient satisfaction., Results: From the 270 women who were randomized in the original trial, 196 (52-mg levonorgestrel-releasing intrauterine system group: n=94; radiofrequency nonresectoscopic endometrial ablation group: n=102) participated in this long-term follow-up study. Mean follow-up duration was 7.4 years (range, 6-9 years). The cumulative reintervention rate (including both medical and surgical reinterventions) was 40.0% (34/85) in the 52-mg levonorgestrel-releasing intrauterine system group and 28.7% (27/94) in the radiofrequency nonresectoscopic endometrial ablation group (relative risk, 1.39; 95% confidence interval, 0.92-2.10). The cumulative rate of surgical reinterventions only was significantly higher among patients with a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system compared with radiofrequency nonresectoscopic endometrial ablation (35.3% [30/85] vs 19.1% [18/94]; relative risk, 1.84; 95% confidence interval, 1.11-3.10). However, the hysterectomy rate was similar (11.8% [10/94] in the 52-mg levonorgestrel-releasing intrauterine system group and 18.1% [17/102] in the radiofrequency nonresectoscopic endometrial ablation group; relative risk, 0.65; 95% confidence interval, 0.32-1.34). Most reinterventions occurred during the first 24 months of follow-up. A total of 171 Pictorial Blood Loss Assessment Chart scores showed a median bleeding score of 0.0. No clinically relevant differences were found regarding quality of life, sexual function, and patient satisfaction., Conclusion: The overall risk of reintervention after long-term follow-up was not different between women treated according to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system and those treated using a strategy starting with radiofrequency nonresectoscopic endometrial ablation. However, women allocated to a treatment strategy starting with a 52-mg levonorgestrel-releasing intrauterine system had a higher risk of surgical reintervention, which was driven by an increase in subsequent endometrial ablation. Both treatment strategies were effective in lowering menstrual blood loss over the long term. The results of this long-term follow-up study can support physicians in optimizing the counseling of women with heavy menstrual bleeding, thus promoting informed decision-making regarding choice of treatment., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive., Objective: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up., Study Design: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished)., Results: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%-32%), dysmenorrhea (47%-49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups., Conclusion: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In Dutch practice, gynecologists are used to assessing the position of the LNG-IUD by performing a two-dimensional transvaginal ultrasonography (TVUS) directly after insertion and do not routinely invite patients for another consultation 4-12 weeks after insertion. There is no consensus whether a TVUS six weeks after insertion is routinely needed., Objective: This study aimed to assess the incidence of malposition using 2-dimensional transvaginal ultrasonography during routine investigation 6 weeks after insertion. In addition, we investigated the relationship between malposition of the levonorgestrel 52-mg intrauterine device and unfavorable bleeding patterns and pelvic pain., Study Design: We performed a large prospective cohort study. Patients seeking a levonorgestrel 52-mg intrauterine device were eligible for inclusion. Transvaginal ultrasonography was performed to check position of the levonorgestrel 52-mg intrauterine device immediately after insertion and 6 weeks later. Patients filled in questionnaires about bleeding pattern and pelvic pain 6 weeks after insertion., Results: From March 2015 to December 2016, we enrolled 500 patients. Data from the transvaginal ultrasonography assessment 6 weeks after insertion were available for 448 patients, and complete data (transvaginal ultrasonography and questionnaire data) were available for 363 patients (72.6%). Malposition rate was 6.3% (28/448 patients). Malposition was seen in 15 of 198 patients (7.6%) with unfavorable bleeding and/or pelvic pain and in 3 of 165 patients (1.8%) with favorable bleeding patterns and no pelvic pain ( P =.03).Malposition was seen in 14 of 186 patients (7.5%) with an unfavorable bleeding pattern and in 4 of 177 patients (2.3%) with favorable bleeding patterns ( P =.008). Malposition was seen in 5 of 50 patients (10%) with pelvic pain and in 13 of 313 patients (4.2%) without pelvic pain ( P =.08)., Conclusion: The malposition rate of the levonorgestrel 52-mg intrauterine device observed using transvaginal ultrasonography 6 weeks after insertion was 6.3%. If patients have no complaints of unfavorable bleeding and/or pelvic pain, the risk for malposition is low (1.8%) and a routine transvaginal ultrasonography is not necessary. However, if patients experience unfavorable bleeding, a transvaginal ultrasonography should be considered to exclude malposition, because the effect of malposition on contraceptive effectiveness is unsure. Future research should focus on cost-benefit analysis., (© 2022 The Authors.)

Objective: To evaluate the effect of an informative 360-degree virtual reality (VR) video on preoperative anxiety before visiting a one-stop clinic for abnormal uterine bleeding., Study Design: A randomized controlled trial was performed in a teaching hospital in the Netherlands. A total of 83 women scheduled for a first consultation at the one-stop clinic between April 2017 and September 2017 were included in the analysis. All women received a standard information leaflet about the clinic. 40 women were randomized to receive a 360-degree VR-video of the clinic in addition. The primary outcome was change in the Visual Analogue Scale for Anxiety (VAS-A), measured at baseline (before randomization) and in the waiting room (before visit, after randomization). Anxiety assessed with the State-Trait Anxiety Inventory (STAI-S) was a secondary outcome. Other secondary outcomes included anxiety during the visit and the opinion of the women about the provided information., Results: Only 27 out of the 40 women actually watched the VR-video. Women in the VR-group who actually watched the video reported lower levels of anxiety at baseline compared to women in the VR-group who did not watch the video. In the intention-to-treat analysis, there was no difference in change in anxiety between the VR-group and the control group (mean difference VAS-A = 0.07, 95% CI -0.96 to 1.10; mean difference STAI-S = 1.97, 95% CI -1.82 to 5.77). In the per-protocol analysis, women in the VR-group reported lower anxiety scores in the waiting room. However, the change in anxiety scores between baseline and waiting room was comparable in both groups. 31% of the women who watched the VR-video reported that the video resulted in a reduction of anxiety, 69% reported that the video is of added value and 65% would use a VR-video again in future., Conclusions: Adding the informative 360-degree VR-video to conventional information did not result in a reduction of anxiety prior to visiting the one-stop clinic. However, the majority of women who watched the video felt that it was of added value. Remarkable was that women who reported higher anxiety at baseline seemed less willing to watch the video., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Preoperative histopathological classification determines the primary surgical approach in endometrial carcinoma (EC) patients but has only moderate agreement between preoperative and postoperative diagnosis. The aim of the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study is to determine whether histopathological assessment and a small panel of diagnostic biomarkers decreases discrepancies between preoperative and postoperative diagnosis in EC. Preoperative endometrial tissue of 378 included patients with EC was stained with 15 different antibodies. Clinically relevant discrepancies in grade or histological subtype between original preoperative and reviewed postoperative diagnosis were observed in 75 (20%) patients. Highest clinically relevant discrepancy was found in grade 2 ECs (20%), compared to 5% and 14% in respectively grade 1 and 3 endometrioid endometrial carcinomas (EECs). A practical two-biomarker panel with PR and p53 improved diagnostic accuracy (AUC = 0.92; 95%CI = 0.88-0.95) compared to solely morphological evaluation (AUC = 0.86). In preoperative high-grade EC, the diagnostic accuracy of histological subtype was improved by a three-immunohistochemical biomarker panel (PR, IMP3, and L1CAM) (AUC = 0.93; 95%CI = 0.88-0.98) compared to solely morphological evaluation (AUC = 0.81). In conclusion to improve correct preoperative diagnosis in EC, we recommend use of a panel of at least two easily accessible immunohistochemical biomarkers (PR and p53), only in grade 2 ECs. Overall, this will reduce clinically relevant discrepancies in tumor grade and subtype with postoperative diagnosis with 6% (from 20% to 14%). Addition of PR, IMP3, and L1CAM for histological subtyping in high-grade EECs resulted in a further decrease in discrepancies with 8% (from 20% to 12%)., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Despite endometrial ablation/resection being a very successful treatment for women with heavy menstrual bleeding, re-intervention with additional surgery is needed in 12%-25% of cases. Introducing a levonorgestrel-intrauterine system (LNG-IUS) immediately after ablation could preserve the integrity of the uterine cavity and suppress the regenerated or non-ablated endometrial tissue. Therefore, this combined treatment can perhaps lower the re-intervention rate. The aim of this systematic review was to assess the impact of the combined treatment., Material and Methods: The MEDLINE, EMBASE, and Cochrane library were systematically searched. No language restrictions were applied. All types of studies were included reporting on the results of endometrial ablation or resection combined with immediate insertion of LNG-IUS for treatment of heavy menstrual bleeding. The primary outcome was the number of hysterectomies after the ablation procedure. Secondary outcomes included re-intervention rates, removals of LNG-IUS, bleeding pattern, patient satisfaction, adverse effects, and complications. Our protocol was registered in PROSPERO, an international prospective register of systematic reviews under registration number CRD42020151384., Results: Six studies with a retrospective design and one case series with a follow-up duration varying from 6 to 55 months were included. In total, 427 women were treated with the combined treatment. The studies described a lower hysterectomy and re-intervention rate after combined treatment compared with treatment with endometrial ablation/resection alone. Hysterectomy rate varied from 0% to 11% after combined treatment compared with 9.4% to 24% after endometrial ablation/resection alone. Bleeding patterns and patient satisfaction appeared to be in favor of the combined treatment group. No intra- or post-operative complications or complications in the removal of LNG-IUS were described. The most reported adverse effects after combined treatment were weight gain, mood changes, and headaches. An additional 11 studies with only an abstract available substantiated these findings. All the included studies had poor methodological quality., Conclusions: Based on the available literature, inserting an LNG-IUS immediately after endometrial ablation/resection seems to lower the hysterectomy and re-intervention rates compared with ablation/resection alone. However, as only limited observational studies of low methodological quality are available, high-quality research is necessary to confirm the findings of this systematic review., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding., Objective: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding., Study Design: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function., Results: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups., Conclusion: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)