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1.
Reprod Fertil ; 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38583465

Currently, the optimal treatment to increase the chance of pregnancy and live birth in patients with colorectal endometriosis and subfertility is unknown. Evidence suggests that that both surgery and in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) are effective in improving live birth rate (LBR) among these women. However, the available evidence is of low quality, reports highly heterogeneous results, lacks direct comparison between both treatment options and does not assess whether a combination strategy results in a higher LBR compared to IVF/ICSI-only treatment. Additionally, the optimal timing of surgery within the treatment trajectory remains unclear. The primary objective of the TOSCA study is to assess the effectiveness of surgical treatment (potentially combined with IVF/ICSI) compared to IVF/ICSI-only treatment to increase the chance of an ongoing pregnancy resulting in a live birth in patients with colorectal endometriosis and subfertility, measured by cumulative LBR. Secondary objectives are to assess and compare quality of life and cost-effectiveness in both groups. Patients will be followed for 40 months after inclusion or until live birth. The TOSCA study is expected to be completed in 6 years.

2.
J Assist Reprod Genet ; 41(4): 1067-1076, 2024 Apr.
Article En | MEDLINE | ID: mdl-38438769

PURPOSE: When resecting endometriomas with the stripping technique, in the majority of cases, a thin line of adjacent ovarian cortex is attached to the endometrioma. In this study, we performed histological analysis to determine (antral) follicle density in the ovarian cortex tissue attached to stripped endometriomas and assessed patient- and surgical characteristics that could affect this. METHODS: Histological slides of previously removed endometriomas were assessed. Follicles in the attached ovarian tissue were classified according to maturation, and follicular density was determined. Immunofluorescent staining of antral follicles in a subset of endometriomas was also performed. RESULTS: In 90 out of 96 included endometriomas (93.7%), ovarian tissue attached to the cyst wall was observed. One thousand nine hundred forty-four follicles at different maturation stages were identified (3 follicles/mm3). Follicle density was negatively associated with age (p < 0.001). Antral follicles (< 7-mm diameter) were present in the ovarian tissue attached to 35 endometriomas (36.5%) derived from younger patients compared to endometriomas where none were detected (30 versus 35 years, p = 0.003). Antral follicle density was 1 follicle/mm3. Based on immunofluorescence, healthy antral follicles were identified in two out of four examined endometriomas. CONCLUSIONS: Ovarian tissue attached to stripped endometriomas holds potential as a non-invasive source for antral follicles. In theory, application of IVM could be an interesting alternative FP option in young patients with endometriomas who undergo cystectomy in order to transform the surgical collateral damage to a potential oocyte source. Our results encourage future research with fresh tissue to further assess the quality and potential of these follicles. TRIAL REGISTRATION: Clinical Trials.gov Identifier: B21.055 (METC LDD), date of registration 12-08-2021, retrospectively registered.


Endometriosis , Ovarian Follicle , Humans , Female , Endometriosis/pathology , Ovarian Follicle/pathology , Ovarian Follicle/growth & development , Adult , Ovary/pathology
3.
BJOG ; 131(5): 716-724, 2024 Apr.
Article En | MEDLINE | ID: mdl-37973607

OBJECTIVE: To assess the various factors that influence environmentally sustainable behaviour in gynaecological surgery and examine the differences between gynaecologists and residents. DESIGN: An interview study. SETTING: Academic and non-academic hospitals in the Netherlands. POPULATION: Gynaecologists (n = 10) and residents (n = 6). METHODS: Thematic analysis of semi-structured interviews to determine the various factors that influence environmentally sustainable behaviour in gynaecological surgery and to examine the differences between gynaecologists and residents. By using the Desmond framework and the COM-B BCW, both organisational and individual factors related to behaviour were considered. MAIN OUTCOME MEASURES: Factors that influence environmentally sustainable behaviour. RESULTS: Awareness is increasing but practical knowledge is insufficient. It is crucial to integrate education on the environmental impact of everyday decisions for residents and gynaecologists. Gynaecologists make their own choices but residents' autonomy is limited. There is the necessity to provide environmentally sustainable surgical equipment without compromising other standards. There is a need for a societal change that encourages safe and open communication about environmental sustainability. To transition to environmentally sustainable practices, leadership, time, collaboration with the industry and supportive regulatory changes are essential. CONCLUSION: This study lays the groundwork for promoting more environmentally sustainable behaviour in gynaecological surgery. The key recommendations, addressing hospital regulations, leadership, policy revisions, collaboration with the industry, guideline development and education, offer practical steps towards a more sustainable healthcare system. Encouraging environmentally sustainable practices should be embraced to enhance the well-being of both our planet and our population, driving us closer to a more environmentally sustainable future in healthcare.


Communication , Delivery of Health Care , Humans , Female , Gynecologic Surgical Procedures , Qualitative Research , Netherlands
4.
BJOG ; 131(5): 709-715, 2024 Apr.
Article En | MEDLINE | ID: mdl-37806784

OBJECTIVE: To determine the user experience of wearing comfort of reusable sterile surgical gowns and compare these gowns with conventional disposable surgical gowns. DESIGN: Cross-sectional survey. SETTING: An academic hospital in the Netherlands. POPULATION: Gynaecologists, surgeons, residents and operating room assistants (n=80). METHODS: Quantitative and qualitative data were obtained via a written questionnaire. Participants provided subjective comments and scored the reusable gown on each individual topic with a score from 1 to 5 (1 = unsatisfactory, 2 = moderate, 3 = good, 4 = very good, 5 = excellent) and compared the reusable gown with the conventional disposable alternative (better, equal or worse). MAIN OUTCOME MEASURES: Wearing comfort: ventilation and temperature regulation, fit and length, functionality, barrier function and ease of use. RESULTS: The results of the overall scores of the reusable gown are scored as 'very good' (mean 4.3, SD ± 0.5) by its users. Regarding comparison of the gowns, more than 79% (lowest score 79%, highest score 95%) of the participants scored the reusable gown equal or higher on six of seven topics. The topic 'ease of use' was scored equal or higher by 59% of the participants. Subjective comments provided information on possible improvements. CONCLUSIONS: The findings of this study demonstrate that there is professional acceptance regarding the utilisation of reusable surgical gowns. To facilitate broader adoption, it is imperative to foster collaboration among suppliers and healthcare institutions. The reusable surgical gown is an environmentally sustainable, safe and comfortable alternative in the operating room.


Surgical Attire , Humans , Cross-Sectional Studies , Operating Rooms , Protective Clothing , Health Facilities , Disposable Equipment
5.
Arch Gynecol Obstet ; 308(5): 1531-1541, 2023 11.
Article En | MEDLINE | ID: mdl-37639036

PURPOSE: Patients often undergo repeat surgery for endometriosis, due to recurrent or residual disease. Previous surgery is often considered a risk factor for worse surgical outcome. However, data are scarce concerning the influence of subsequent endometriosis surgery. METHODS: A retrospective study in a centre of expertise for endometriosis was conducted. All endometriosis subtypes and intra-operative steps were included. Detailed information regarding surgical history of patients was collected. Surgical time, intra-operative steps and major post-operative complications were obtained as outcome measures. RESULTS: 595 patients were included, of which 45.9% had previous endometriosis surgery. 7.9% had major post-operative complications and 4.4% intra-operative complications. The patient journey showed a median of 3 years between previous endometriosis surgeries. Each previous therapeutic laparotomic surgery resulted on average in 13 additional minutes (p = 0.013) of surgical time. Additionally, it resulted in more frequent performance of adhesiolysis (OR 2.96, p < 0.001) and in a higher risk for intra-operative complications (OR 1.81, p = 0.045), however no higher risk for major post-operative complications (OR 1.29, p = 0.418). Previous therapeutic laparoscopic endometriosis surgery, laparotomic and laparoscopic non-endometriosis surgery showed no association with surgical outcomes. Regardless of previous surgery, disc and segmental bowel resection showed a higher risk for major post-operative complications (OR 3.64, p = 0.017 respectively OR 3.50, p < 0.001). CONCLUSION: Previous therapeutic laparotomic endometriosis surgery shows an association with longer surgical time, the need to perform adhesiolysis, and more intra-operative complications in the subsequent surgery for endometriosis. However, in a centre of expertise with experienced surgeons, no increased risk of major post-operative complications was observed.


Endometriosis , Female , Humans , Endometriosis/surgery , Retrospective Studies , Dissection , Intraoperative Complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Treatment Outcome
6.
Eur J Obstet Gynecol Reprod Biol ; 288: 114-123, 2023 Sep.
Article En | MEDLINE | ID: mdl-37506597

Intra-operative fluorescent imaging of endometriosis could help to optimize surgical treatment. Potential biomarkers to use as target for endometriosis-binding fluorescent probes were identified using a new five-phase transcriptomics-based approach to broaden the search for biomarkers. Using publicly available datasets, a differentially expressed gene (DEG) analysis was performed for endometriosis versus surgically relevant surrounding tissue (peritoneum, bladder, sigmoid, rectum, transverse colon, small intestine, vagina, and fallopian tubes) for which data was available. The remaining relevant surrounding tissues were analyzed for low expression levels. DEGs with a predicted membranous or extracellular location and with low expression levels in surrounding tissue were identified as candidate targets. Modified Target Selection Criteria were used to rank candidate targets based on the highest potential for use in fluorescent imaging. 29 potential biomarkers were ranked, resulting in Folate receptor 1 as the most potential biomarker. This is a first step towards finding a fluorescent tracer for intra-operative visualization of endometriosis. Additionally, this approach, using transcriptomics analysis to identifying candidate targets for a specific type of tissue for use in fluorescence-guided surgery could be translated to other surgical fields. TWEETABLE ABSTRACT: A new approach using transcriptomics analysis is shown to identify candidate targets for intra-operative fluorescent imaging for endometriosis, resulting in 29 potential candidates.


Endometriosis , Female , Humans , Endometriosis/diagnostic imaging , Endometriosis/genetics , Endometriosis/surgery , Transcriptome , Biomarkers , Gene Expression Profiling , Rectum
7.
Ann Med Surg (Lond) ; 85(5): 1371-1378, 2023 May.
Article En | MEDLINE | ID: mdl-37229054

Veress needles (VN) are commonly used in establishing pneumoperitoneum in laparoscopic surgery. Previously, a VN with a new safety mechanism 'VeressPLUS' needle (VN+) was developed to reduce the amount of overshoot. Methods: Eighteen participants (novices, intermediates, and experts) performed in total of 248 insertions in a systematic way on Thiel-embalmed bodies with wide and small bore versions of the conventional VN (VNc) and the VN+. Insertion depth was measured by recording the graduations on the needle under direct laparoscopic vision. Results: Participants graded the bodies and the procedures as lifelike. Overall, a significant reduction (P<0.001) in average insertion depth was found for the VN+ compared to the VNc of 26.0 SD16 mm versus 46.2 SD15 mm. The insertion depth difference in the novice group was higher compared to the intermediates and experts (P<0.001). The average insertion depth for both needle types was less (P<0.001) for female participants compared to male. Conclusion: This study indicated that the VN+ significantly reduced the insertion depth in all tested conditions. Whether the difference between female and male performance can be linked to differences in muscle control or arm mass should be further investigated. Useful technical information was gathered from this study to further improve the VN+.

8.
Hum Reprod Open ; 2023(2): hoad019, 2023.
Article En | MEDLINE | ID: mdl-37250430

STUDY QUESTION: What is the additional value of the comprehensive complication index (CCI) and ClassIntra system (classification for intraoperative adverse events (ioAEs)) in adverse event (AE) reporting in (deep) endometriosis (DE) surgery compared to only using the Clavien-Dindo (CD) system? SUMMARY ANSWER: The CCI and ClassIntra are useful additional tools alongside the CD system for a complete and uniform overview of the total AE burden in patients with extensive surgery (such as DE), and with this uniform data registration, it is possible to provide greater insight into the quality of care. WHAT IS KNOWN ALREADY: Uniform comparison of AEs reported in the literature is hampered by scattered registration. In endometriosis surgery, the usage of the CD complication system and the CCI is internationally recommended; however, the CCI is not routinely adapted in endometriosis care and research. Furthermore, a recommendation for ioAEs registration in endometriosis surgery is lacking, although this is vital information in surgical quality assessments. STUDY DESIGN SIZE DURATION: A prospective mono-center study was conducted with 870 surgical DE cases from a non-university DE expertise center between February 2019 and December 2021. PARTICIPANTS/MATERIALS SETTING METHODS: Endometriosis cases were collected with the EQUSUM system, a publicly available web-based application for registration of surgical procedures for endometriosis. Postoperative adverse events (poAEs) were classified with the CD complication system and CCI. Differences in reporting and classifying AEs between the CCI and the CD were assessed. ioAEs were assessed with the ClassIntra. The primary outcome measure was to assess the additional value toward the CD classification with the introduction of the CCI and ClassIntra. In addition, we report a benchmark for the CCI in DE surgery. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 870 DE procedures were registered, of which 145 procedures with one or more poAEs, resulting in a poAE rate of 16.7% (145/870), of which in 36 cases (4.1%), the poAE was classified as severe (≥Grade 3b). The median CCI (interquartile range) of patients with poAEs was 20.9 (20.9-31.7) and 33.7 (33.7-39.7) in the group of patients with severe poAEs. In 20 patients (13.8%), the CCI was higher than the CD because of multiple poAEs. There were 11 ioAEs reported (11/870, 1.3%) in all procedures, mostly minor and directly repaired serosa injuries. LIMITATIONS REASONS FOR CAUTION: This study was conducted at a single center; thus, trends in AE rates and type of AEs could differ from other centers. Furthermore, no conclusion could be drawn on ioAEs in relation to the postoperative course because the power of this database is not robust enough for that purpose. WIDER IMPLICATIONS OF THE FINDINGS: From our data, we would advise to use the Clavien-Dindo classification system together with the CCI and ClassIntra for a complete overview of AE registration. The CCI appeared to provide a more complete overview of the total burden of poAEs compared to only reporting the most severe poAEs (as with CD). If the use of the CD, CCI, and ClassIntra is widely adapted, uniform data comparison will be possible at (inter)national level, providing better insight into the quality of care. Our data could be used as a first benchmark for other DE centers to optimize information provision in the shared decision-making process. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

9.
J Med Syst ; 47(1): 19, 2023 Feb 04.
Article En | MEDLINE | ID: mdl-36738376

Literature proposes numerous initiatives for optimization of the Operating Room (OR). Despite multiple suggested strategies for the optimization of workflow on the OR, its patients and (medical) staff, no uniform description of 'optimization' has been adopted. This makes it difficult to evaluate the proposed optimization strategies. In particular, the metrics used to quantify OR performance are diverse so that assessing the impact of suggested approaches is complex or even impossible. To secure a higher implementation success rate of optimisation strategies in practice we believe OR optimisation and its quantification should be further investigated. We aim to provide an inventory of the metrics and methods used to optimise the OR by the means of a structured literature study. We observe that several aspects of OR performance are unaddressed in literature, and no studies account for possible interactions between metrics of quality and efficiency. We conclude that a systems approach is needed to align metrics across different elements of OR performance, and that the wellbeing of healthcare professionals is underrepresented in current optimisation approaches.


Benchmarking , Operating Rooms , Humans , Efficiency, Organizational , Workflow
10.
J Med Chem ; 65(19): 12956-12969, 2022 10 13.
Article En | MEDLINE | ID: mdl-36167503

In this work, cysteine staples were used as a late-stage functionalization strategy to diversify peptides and build conjugates targeting the melanocortin G-protein-coupled receptors [melanocortin receptor-1 (MC1R) and MC3R-MC5R]. Monocyclic and bicyclic agonists based on sunflower trypsin inhibitor-1 were used to generate a selection of stapled peptides that were evaluated for binding (pKi) and functional activation (pEC50) of the melanocortin receptor subtypes. Stapled peptides generally had improved activity, with aromatic stapled peptides yielding selective MC1R agonists, including a xylene-stapled peptide (2) with an EC50 of 1.9 nM for MC1R and >150-fold selectivity for MC3R and MC4R. Selected stapled peptides were further functionalized with linkers and payloads, generating a series of conjugated peptides with potent MC1R activity, including one pyridazine-functionalized peptide (21) with picomolar activity at MC1R (Ki 58 pM; EC50 < 9 pM). This work demonstrates that staples can be used as modular synthetic tools to tune potency and selectivity in peptide-based drug design.


Pyridazines , Receptor, Melanocortin, Type 1 , Cysteine , Melanocortins , Peptides/pharmacology , Receptor, Melanocortin, Type 1/agonists , Receptor, Melanocortin, Type 3 , Receptor, Melanocortin, Type 4 , Receptors, Melanocortin/metabolism , Structure-Activity Relationship , Xylenes
11.
Surg Innov ; 29(1): 73-79, 2022 Feb.
Article En | MEDLINE | ID: mdl-33788655

Background. During the COVID-19 pandemic the question arises if laparoscopy, as an aerosol forming procedure, poses a potential risk for viral transmission of SARS-CoV-2 to healthcare workers. Methods. A literature search was conducted using PubMed, Embase and MEDLINE. Articles reporting information regarding COVID-19 or other relevant viruses and laparoscopy, surgical smoke, aerosols and viral transmission were included. Results. Although aerosols produced during laparoscopy do not originate from the respiratory tract, the main transmission route of SARS-CoV-2, research did show SARS-CoV-2 to be present in other body fluids. The transmission risk via this route is however considered very low. As previous research showed potential viral transmission during laparoscopy for viruses that spread through contaminated body fluids, there might be a potential risk of SARS-CoV-2 transmission during laparoscopy, albeit considered very small. Conclusion. Due to the small risk compared to widely known benefits of laparoscopy, there is no reason to replace laparoscopy by laparotomy due to COVID-19 infection. To avoid the potential small risk of viral transmission, additional safety measures are advised.


COVID-19 , Laparoscopy , COVID-19/prevention & control , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Laparoscopy/adverse effects , Pandemics/prevention & control , SARS-CoV-2
12.
BJOG ; 129(8): 1376-1385, 2022 07.
Article En | MEDLINE | ID: mdl-34889037

OBJECTIVE: To study the preferences of women with deep endometriosis (DE) with bowel involvement when they have to choose between conservative (medication) or surgical treatment. DESIGN: Labelled discrete choice experiment (DCE). SETTING: Dutch academic and non-academic hospitals and online recruitment. POPULATION OR SAMPLE: A total of 169 women diagnosed with DE of the bowel. METHODS: Baseline characteristics and the fear of surgery were collected. Women were asked to rank attributes and choose between hypothetical conservative or surgical treatment in different choice sets (scenarios). Each choice set offered different levels of all treatment attributes. Data were analysed by using multinomial logistic regression. MAIN OUTCOME MEASURES: The following attributes - effect on/risk of pain, fatigue, pregnancy, endometriosis lesions, mood swings, osteoporosis, temporary stoma and permanent intestinal symptoms - were used in this DCE. RESULTS: In the ranking, osteoporosis was ranked with low importance, whereas in the DCE, a lower chance of osteoporosis was one of the most important drivers when choosing a conservative treatment. Women with previous surgery showed less fear of surgery compared with women without surgery. Low anterior resection syndrome was almost equally important for patients as the chance of pain reduction. Pain reduction had higher importance than improving fertility chances, even in women with desire for a future child. CONCLUSIONS: The risk of developing low anterior resection syndrome as a result of treatment is almost equally important as the reduction of pain symptoms. Women with previous surgery experience less fear of surgery compared with women without a surgical history. TWEETABLE ABSTRACT: First discrete choice experiment in patients with deep endometriosis.


Endometriosis , Osteoporosis , Rectal Diseases , Rectal Neoplasms , Endometriosis/pathology , Endometriosis/surgery , Female , Humans , Pain , Postoperative Complications , Pregnancy , Rectal Diseases/surgery , Syndrome
13.
Acta Obstet Gynecol Scand ; 100(11): 2082-2090, 2021 Nov.
Article En | MEDLINE | ID: mdl-34490608

INTRODUCTION: The implementation of advanced minimally invasive surgical (MIS) techniques has broadened. An extensive body of literature shows that high hospital and surgeon volumes lead to better patient outcomes. However, no information is available regarding volume trends in the post-implementation phase of MIS. This study investigated these trends and poses suggestions to adjust these developments. This knowledge can provide guidance to optimize patient safe performance of new surgical techniques. MATERIAL AND METHODS: A national retrospective cohort study in the Netherlands. The number of advanced laparoscopic (level 3 and 4) and robotic procedures and the number of gynecologists performing them were collected through a web-based questionnaire to determine hospital and gynecological surgeon volume. These volumes were compared with our previously collected data from 2012. RESULTS: The response rate was 85%. Hospitals produced larger volumes for advanced laparoscopic and robotic procedures. However, still 63% of the hospitals perform low-volume level 4 laparoscopic procedures. Additionally, gynecological surgeon volumes appeared to decrease for level 3 procedures, as the group of gynecologists performing fewer than 20 procedures expanded (64% vs. 44% in 2012), with 15% of the gynecologists performing fewer than ten procedures. Despite an increase in surgeon volumes for level 4 laparoscopy and robotic surgery, volumes continued to be low, as still 49% of gynecologists performed fewer than 10 level 4 procedures per year and 41% performed fewer than 20 robotic procedures per year. CONCLUSIONS: The broad implementation of advanced MIS procedures resulted in an increasing number of these procedures with increasing hospital volumes. However, as a side-effect, a disproportionate rise in number of gynecologists performing these procedures was observed. Therefore, surgeon volumes remain low and even decreased for some procedures. Centralization of complex procedures and training of specialized MIS gynecologists could improve surgeon volumes and therefore consequently enhance patient safety.


Gynecology , Laparoscopy/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Surgeons/statistics & numerical data , Female , Hospitals, High-Volume , Hospitals, Low-Volume , Humans , Netherlands , Retrospective Studies , Robotic Surgical Procedures/statistics & numerical data , Surveys and Questionnaires
14.
Acta Obstet Gynecol Scand ; 100(7): 1165-1175, 2021 07.
Article En | MEDLINE | ID: mdl-33483970

Advances in preoperative diagnostics as well as in surgical techniques for the treatment of endometriosis, especially for deep endometriosis, call for a classification system, that includes all aspects of the disease such as peritoneal endometriosis, ovarian endometriosis, deep endometriosis, and secondary adhesions. The widely accepted revised American Society for Reproductive Medicine classification (rASRM) has certain limitations because of its incomplete description of deep endometriosis. In contrast, the Enzian classification, which has been implemented in the last decade, has proved to be the most suitable tool for staging deep endometriosis, but does not include peritoneal or ovarian disease or adhesions. To overcome these limitations, a comprehensive classification system for complete mapping of endometriosis, including anatomical location, size of the lesions, adhesions and degree of involvement of the adjacent organs, that can be used with both diagnostic and surgical methods, has been created through a consensus process and will be described in detail-the #Enzian classification.


Consensus , Endometriosis/classification , Severity of Illness Index , Symptom Assessment/standards , Databases, Factual , Endometriosis/diagnosis , Endometriosis/pathology , Female , Humans , Societies, Medical
15.
Fertil Steril ; 115(3): 702-714, 2021 03.
Article En | MEDLINE | ID: mdl-33070963

OBJECTIVE: To study the experiences, considerations, and motivations of patients with endometriosis in the decision-making process for deep endometriosis (DE) treatment options. DESIGN: Qualitative study using semi-structured in-depth focus group methodology. SETTING: University medical center. PATIENT(S): A total of 19 Dutch women diagnosed with DE between 27 and 47 years of age. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Focus group topics were disease impact and motives for treatment, expectations of the treatment process, and important factors in the decision process. RESULT(S): Women reported that pain, fertility, and strong fear of complications are important decisive factors in the treatment process. The goal of conceiving a child is considered important, however, sometimes doctors emphasize this topic too much. It emerged that complication counseling is frequently about surgical complications, whereas side effects of hormonal treatments are neglected. Shared decision making and information about treatment options, complications, and side effects are not always optimal, making it difficult to make a well-considered choice. Despite negative experiences encountered after surgery, the positive effect of surgery ensures that most women do not regret their choice. CONCLUSION(S): In the treatment decision process for patients with DE, pain is almost always the most important decisive factor. The wish to conceive and strong fear of complications can change this choice. Doctors should understand the importance of fertility for the majority of women, but, also, if this is not considered paramount, respect that view. To improve shared decision making, exploration of treatment goals, training of healthcare providers, and better patient information provision are desirable.


Decision Making/physiology , Endometriosis/psychology , Fertility Preservation/psychology , Infertility, Female/psychology , Pain/psychology , Qualitative Research , Adult , Endometriosis/epidemiology , Endometriosis/therapy , Female , Fertility Preservation/methods , Focus Groups , Humans , Infertility, Female/epidemiology , Infertility, Female/therapy , Middle Aged , Motivation/physiology , Pain/epidemiology , Pain Management/methods , Pain Management/psychology , Physician-Patient Relations
16.
Bioorg Med Chem Lett ; 30(4): 126953, 2020 02 15.
Article En | MEDLINE | ID: mdl-31932225

GPR81 is a novel drug target that is implicated in the control of glucose and lipid metabolism. The lack of potent GPR81 modulators suitable for in vivo studies has limited the pharmacological characterization of this lactate sensing receptor. We performed a high throughput screen (HTS) and identified a GPR81 agonist chemical series containing a central acyl urea scaffold linker. During SAR exploration two additional new series were evolved, one containing cyclic acyl urea bioisosteres and another a central amide bond. These three series provide different selectivity and physicochemical properties suitable for in-vivo studies.


Receptors, G-Protein-Coupled/agonists , Urea/analogs & derivatives , Amides/chemistry , Amides/metabolism , High-Throughput Screening Assays , Humans , Molecular Conformation , Protein Binding , Receptors, G-Protein-Coupled/metabolism , Receptors, Ghrelin/agonists , Receptors, Ghrelin/metabolism , Structure-Activity Relationship , Urea/metabolism
17.
Ned Tijdschr Geneeskd ; 1632019 10 14.
Article Nl | MEDLINE | ID: mdl-31647618

The healthcare sector contributes significantly to global warming due to carbon emissions; this sector is, therefore, partially responsible for the negative effects of climate change on public health. Carbon emissions by the healthcare sector amount to 7% of the total carbon footprint of the Netherlands. It is anticipated that measures to reduce carbon emissions in the operating room (OR) can make an important contribution to reducing carbonemissions in the hospital as a whole. The most important elements contributing to the carbon footprint of the OR are: energy consumption for heating, ventilation and air conditioning (HVAC); the emission of inhalation anaesthetics; the purchase of materials and equipment; and waste production. Direct carbon emissions by the OR can be reduced through the use of sustainable energy and setback of the HVAC outside office hours. Anaesthetists can dramatically reduce the carbon footprint of the OR by choosing for intravenous anaesthetics instead of inhalation anaesthetics. Indirect carbon emissions and waste production by the OR can be reduced through circular procurement, choosing reusable over disposable products and recycling.


Carbon Footprint , Operating Rooms , Anesthetics, Inhalation , Humans , Netherlands , Waste Management
18.
Eur J Surg Oncol ; 45(8): 1328-1340, 2019 Aug.
Article En | MEDLINE | ID: mdl-30857878

OBJECTIVE: To investigate the ovarian survival (OS) after ovarian transposition (OT) and pelvic radiation. DESIGN: Systematic review. Electronic databases were searched to identify studies on OT prior to external beam radiation therapy (EBRT, to the pelvic). Primary outcome was the ovarian function after radiotherapy and ovarian transposition. Secondary outcomes were complication-rate. Only studies in English, German or French were included. SETTING: Not applicable. PATIENTS: Fertile women undergoing ovarian transposition prior to pelvic radiation therapy. INTERVENTIONS: We included all studies, containing >5 patients, treated with OT prior to radiation therapy. MAIN OUTCOME MEASURE: Ovarian function. RESULTS: Our search yielded a total of 1130 studies of which 38 were eligible with a total of 765 patients. All studies were cohort studies or case-series. Heterogeneity among studies could not be rejected hence meta-analysis could not be performed. OS after OT and EBRT ranged from 20% to 100%. The median follow-up ranged from 7 to 102 months. OS was higher after OT and brachytherapy (OS 63.6-100%) when compared to OT and EBRT (20-100%) and OT concomitant chemoradiotherapy (0-69.2%). Only 22 studies (with 112 patients) reported on complications: among these studies the complication-rate was 0%-28.6%. CONCLUSION: From our systematic review of literature we conclude that the preservation of ovarian function after OT prior to EBRT is successful in 20-100% of patients. Most favorable outcome with regard to preservation of ovarian function is seen in patients after OT and BT, followed by OT and EBRT and OT and RT combined with chemotherapy.


Brachytherapy/adverse effects , Ovary/radiation effects , Pelvic Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Aged , Brachytherapy/methods , Female , Humans , Middle Aged , Ovarian Function Tests/methods , Ovary/pathology , Ovary/surgery , Pelvic Neoplasms/pathology , Radiotherapy Dosage , Recovery of Function , Risk Assessment
19.
Arch Gynecol Obstet ; 299(1): 159-165, 2019 01.
Article En | MEDLINE | ID: mdl-30498966

OBJECTIVE: To estimate the risk of uterine leiomyosarcoma in patients undergoing gynecological surgery and also to identify groups at risk for unrecognized uterine leiomyosarcoma. METHODS: A national cohort study was performed evaluating all uterine leiomyosarcoma (ULMS) diagnosed in The Netherlands between January 2000 and September 2015. Cases were identified and supplied by the nationwide network and registry of histo- and cytopathology in The Netherlands (PALGA). Unexpected and expected ULMS were compared. Approval for this study was granted by the Medical Ethics Committee of all participating hospitals and by the review board of PALGA. RESULTS: 262 original cases were included. The overall incidence of ULMS in our study was 0.25% or 1:400 patients. The incidence of unexpected ULMS was 0.12% or 1:865 patients. Preoperatively, a malignancy was unexpected in 46% of the cases and expected in 54%. Abnormal uterine bleeding constituted most of the symptoms. 90% of women underwent abdominal hysterectomy and/or bilateral salpingo-oophorectomy. CONCLUSIONS: Leiomyosarcoma are rare. Women aged 40-50 years with abnormal uterine bleeding are most at risk for unexpected ULMS. In contrast, this risk is low in postmenopausal women. ULMS were highly uncommon in women aged under 40 years.


Leiomyosarcoma/epidemiology , Uterine Neoplasms/epidemiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Gynecologic Surgical Procedures , Humans , Hysterectomy , Incidence , Laparoscopy , Leiomyosarcoma/surgery , Middle Aged , Netherlands/epidemiology , Pelvic Neoplasms/surgery , Uterine Neoplasms/surgery
20.
J Ultrasound Med ; 38(4): 989-996, 2019 Apr.
Article En | MEDLINE | ID: mdl-30244483

OBJECTIVES: To assess the added value of magnetic resonance imaging (MRI) after dynamic transvaginal ultrasound (TVUS) in the diagnostic pathway for preoperative staging of pelvic endometriosis. METHODS: A prospective observational study was conducted between April 22, 2014, and May 1, 2015. During that period, 363 patients with a clinical suspicion of endometriosis were included. All patients underwent a history, clinical examination, and dynamic TVUS examination. Most of the patients (n = 274) underwent conservative treatment according to the European Society of Human Reproduction and Embryology guidelines. Eighty-nine patients were selected for surgery, of whom 72 patients underwent the complete diagnostic pathway: ie, history, clinical examination, dynamic TVUS, and MRI. All data were analyzed by the nonparametric McNemar test for comparing each step in the diagnostic algorithm. RESULTS: The sensitivity and specificity for the history, pelvic examination, and dynamic TVUS were 93.7% and 55.6% (P < .001), respectively; when MRI findings were included, the sensitivity and specificity were 85.9% and 62.5%. Adding MRI routinely to the diagnostic procedure of endometriosis did not significantly improve the sensitivity or specificity. CONCLUSIONS: There is no significant added value of routine MRI after dynamic TVUS for the preoperative staging of endometriosis.


Endometriosis/diagnostic imaging , Magnetic Resonance Imaging/methods , Pelvis/diagnostic imaging , Preoperative Care/methods , Ultrasonography , Adult , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Severity of Illness Index , Vagina , Young Adult
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