Universal tumor DNA testing in epithelial ovarian cancer patients can function not only as an efficient prescreen for hereditary cancer testing, but may also guide treatment choices. This innovation, ...introduced as Tumor-First workflow, offers great opportunities, but ensuring optimal multidisciplinary collaboration is a challenge. We investigated factors that were relevant and important for large-scale implementation. In three multidisciplinary online focus groups, healthcare professionals (gynecologic oncologists, pathologists, clinical geneticists, and clinical laboratory specialists) were interviewed on factors critical for the implementation of the Tumor-First workflow. Recordings were transcribed for analysis in Atlas.ti according to the framework of Flottorp that categorizes seven implementation domains. Healthcare professionals from all disciplines endorse implementation of the Tumor-First workflow, but more detailed standardization and advice regarding the logistics of the workflow were needed. Healthcare professionals explored ways to stay informed about the different phases of the workflow and the results. They emphasized the importance of including all epithelial ovarian cancer patients in the workflow and monitoring this inclusion. Overall, healthcare professionals would appreciate supporting material for the implementation of the Tumor-First workflow in the daily work routine. Focus group discussions have revealed factors for developing a tailored implementation strategy for the Tumor-First workflow in order to optimize care for epithelial ovarian cancer patients. Future innovations affecting multidisciplinary oncology teams including clinical geneticists can benefit from the lessons learned.
Risk-reducing salpingo-oophorectomy (RRSO) is advised for female
germline pathogenic variant (GPV) carriers to reduce tubal/ovarian cancer risk. RRSO may also affect breast cancer (BC) incidence. The ...aim was to investigate the effect of RRSO on BC incidence and histopathological features in female
GPV carriers.
Prospectively collected clinical data from
GPV carriers in our hospital-based data/biobank were linked to the Dutch Nationwide Pathology Databank (PALGA) in January 2022. Multivariable Cox-proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (95% CIs), where the pre-RRSO group was considered the reference group and the primary endpoint was the first primary BC. Histopathological features of BCs pre- and post-RRSO were compared using descriptive statistics.
In 1312 women, 164 incident primary BCs were observed. RRSO did not decrease BC risk for
GPV (HR: 1.48, 95% CI: 0.91-2.39) or
GPV (HR: 0.95, 95% CI: 0.43-2.07) carriers. BCs tended to be smaller post-RRSO (median: 12 mm) than pre-RRSO (15 mm,
: 0.08). There were no statistically significant differences in histopathological features.
RRSO did not decrease BC risk or affect BC features in
GPV in this study, although BCs diagnosed post-RRSO tended to be smaller.
Besides experiencing vasomotor symptoms, after surgical menopause and bilateral salpingo-oophorectomy (BSO), women experience moderate to severe psychological and sexual symptoms.
To systematically ...review and meta-analyze the effect of systemic hormone replacement therapy (sHRT) on psychological well-being and sexual functioning in women after surgical menopause and BSO.
Medline/Pubmed, EMBASE and PsychInfo were systematically searched until November 2021. Randomized controlled trials investigating the effect of sHRT on psychological well-being and/or sexual functioning in surgically menopausal women and women after BSO were eligible for inclusion. Two independent authors performed study selection, risk of bias assessment and data extraction. Standardized mean differences (SMDs) were calculated.
Primary outcomes for psychological well-being were defined as overall psychological well-being, depression, and anxiety. Primary outcomes for sexual functioning were defined as overall sexual functioning, sexual desire, and sexual satisfaction. All outcomes were assessed on short (≤12 weeks) or medium term (13–26 weeks).
Twelve studies were included. Estradiol had a beneficial effect on depressed mood on short term 3–6 years after surgery or 2 years (median) after surgery with high heterogeneity (SMD: −1.37, 95%CI: −2.38 to −0.37, P = .007, I2 79%). Testosterone had a beneficial effect on overall sexual functioning on short to medium term 4.6 years (mean) after surgery (SMD 0.38, 95%CI 0.11–0.65, I2 0%) and on sexual desire on medium term at least 3–12 months after surgery (SMD 0.38, 95%CI 0.19–0.56, I2 54%). For most studies, risk of bias was uncertain.
Estradiol may beneficially affect psychological symptoms after surgical menopause or BSO and testosterone might improve sexual desire and overall sexual functioning.
This review only included patient-reported outcomes, thereby reflected perceived and not simply objective symptoms in surgically menopausal women and women after BSO. The small number of studies highly varied in nature and bias could not be excluded, therefore our results should be interpreted with great caution.
Independent randomized controlled clinical trials investigating the effects of estrogen-progesterone and testosterone on psychological and sexual symptoms after surgical menopause are needed.
CRD42019136698.
Stuursma A, Lanjouw L, Idema DL, et al. Surgical Menopause and Bilateral Oophorectomy: Effect of Estrogen-Progesterone and Testosterone Replacement Therapy on Psychological Well-being and Sexual Functioning: A Systematic Literature Review. J Sex Med 2022;19:1778–1789.
Analyzing
tumor pathogenic variants (TPVs) in epithelial tubal/ovarian cancers (EOCs) has become an essential part of the diagnostic workflow in many centers to guide treatment options and genetic ...cascade testing. However, there is no standardization of testing procedures, including techniques, gene assays, or sequencers used, and data on the execution of tumor tests remains scarce. Therefore, we evaluated characteristics of
tumor testing in advanced-stage EOC with real-world national data. Pathology reports of patients diagnosed with EOC in 2019 in the Netherlands were obtained from the Dutch Pathology Registry (PALGA), and data regarding histological subtype and
tumor tests were extracted. A total of 999 patients with advanced-stage EOC were included. Tumor tests were performed for 502 patients (50.2%) and
TPVs were detected in 14.7%. Of all tests, 48.6% used hybrid capture techniques and 26.5% used PCR-based techniques. More than half of the tests (55.0%) analyzed other genes in addition to
. Overall, this study highlights the heterogeneity in the execution of
tumor tests. Despite a lack of evidence of quality differences, we emphasize that adequate reporting and internal and external quality monitors are essential for the high-quality implementation and execution of reliable
tumor testing, which is crucial for identifying all patients with
TPVs.
Histology restricted genetic predisposition testing of ovarian carcinoma patients is a topic of debate as the prevalence of BRCA1/2 pathogenic variants (PVs) in various histological subtypes is ...ambiguous. Our primary aim was to investigate the proportion of germline BRCA1/2 PVs per histological subtype. Additionally, we evaluated (i) proportion of somatic BRCA1/2 PVs and (ii) proportion of germline PVs in other ovarian carcinoma risk genes.
PubMed, EMBASE and Web of Science were systematically searched and we included all studies reporting germline BRCA1/2 PVs per histological subtype. Pooled proportions were calculated using a random-effects meta-analysis model. Subsets of studies were used for secondary analyses.
Twenty-eight studies were identified. The overall estimated proportion of germline BRCA1/2 PVs was 16.8% (95% CI 14.6 to 19.2). Presence differed substantially among patients with varying histological subtypes of OC; proportions being highest in high-grade serous (22.2%, 95% CI 19.6 to 25.0) and lowest in clear cell (3.0%, 95% CI 1.6 to 5.6) and mucinous (2.5%, 95% CI 0.6 to 9.6) carcinomas. Somatic BRCA1/2 PVs were present with total estimated proportion of 6.0% (95% CI 5.0 to 7.3), based on a smaller subset of studies. Germline PVs in BRIP1, RAD51C, RAD51D, PALB2, and ATM were present in approximately 3%, based on a subset of nine studies.
Germline BRCA1/2 PVs are most frequently identified in high-grade serous ovarian carcinoma patients, but are also detected in patients having ovarian carcinomas of other histological subtypes. Limiting genetic predisposition testing to high-grade serous ovarian carcinoma patients will likely be insufficient to identify all patients with a germline PV.
•Probability of finding germline BRCA1/2 PVs varies widely among histological subtypes of ovarian carcinoma (OC).•Germline BRCA1/2 PVs are most frequently detected in high-grade serous OC patients.•Limiting testing to high-grade serous histology will be insufficient to identify all OC patients with germline BRCA1/2 PVs.
Abstract
Objective
The aim was to study clinical, histopathological and immunological changes in the vagina and cervix of women with primary SS, which might explain vaginal dryness.
Methods
We ...included 10 pre-menopausal female primary SS patients with vaginal dryness and 10 pre-menopausal controls undergoing a laparoscopic procedure. The vaginal health index was recorded. Multiplex immunoassays and flow cytometry were performed on endocervical swab and cervicovaginal lavage samples to evaluate cellular and soluble immune markers. Mid-vaginal and endocervical biopsies were taken and stained for various leucocyte markers, caldesmon (smooth muscle cells), avian V-ets erythroblastosis virus E26 oncogene homologue (ERG; endothelial cells) and anti-podoplanin (lymphatic endothelium). The number of positive pixels per square micrometre was calculated.
Results
One patient was excluded because of Clamydia trachomatis, and two controls were excluded because of endometriosis observed during their laparoscopy. Vaginal health was impaired in primary SS. CD45+ cells were increased in vaginal biopsies of women with primary SS compared with controls. Infiltrates were predominantly located in the peri-epithelial region, and mostly consisted of CD3+ lymphocytes. In the endocervix, CD45+ infiltrates were present in patients and in controls, but a higher number of B lymphocytes was seen in primary SS. Vascular smooth muscle cells were decreased in the vagina of primary SS patients. No differences were found in leucocyte subsets in the vaginal and endocervical lumen. CXCL10 was increased in endocervical swab samples of primary SS patients.
Conclusion
Women with primary SS show impaired vaginal health and increased lymphocytic infiltration in the vagina compared with controls. Vaginal dryness in primary SS might be caused by vascular dysfunction, possibly induced by IFN-mediated pathways.
Objective
The aim of this study was to evaluate and compare reliability, costs, and radiation dose of dual-energy X-ray absorptiometry (DXA) to MRI and CT in measuring muscle mass for the diagnosis ...of sarcopenia.
Methods
Thirty-four consecutive DXA scans performed in surgically menopausal women from November 2019 until March 2020 were analyzed by two observers. Observers analyzed muscle mass of the lower limbs in every scan twice. Reliability was assessed by calculating inter- and intra-observer variability. Reliability from CT and MRI as well as radiation dose from CT and DXA were collected from literature. Costs for each type of scan were calculated according to the guidelines for economic evaluation of the Dutch National Health Care Institute.
Results
The 34 participants had a median age of 58 years (IQR 53–65) and a median body mass index of 24.6 (IQR 21.7–29.7). Inter-observer variability had an intraclass correlation coefficient (ICC) of 0.997 (95% CI 0.994–0.998) with a relative variability of 0.037 ± 0.022%. Regarding intra-observer variability, observer 1 had an ICC of 0.998 (95% CI 0.996–0.999) with a relative variability of 0.019 ± 0.016% and observer 2 had an ICC of 0.997 (95% CI 0.993–0.998) with a relative variability of 0.016 ± 0.011%. DXA costs were €62, CT €77, and MRI €195. The estimated radiation dose of CT was 2.5–3.0 mSv, for DXA this was 2–4 µSv.
Conclusions
DXA has lower costs and a lower radiation dose, with low inter- and intra-observer variability, compared to CT and MRI for assessing lower limb muscle mass.
Trial registration
Netherlands Trial Register; NL8068.
Critical relevance statement
DXA is a good alternative for CT and MRI in assessing lower limb muscle mass, with lower costs and lower radiation dose, while inter-observer and intra-observer variability are low.
Key points
• Screening for sarcopenia should be optimized as the population ages.
• DXA outperformed CT and MRI in the measured metrics.
• DXA validity should be further evaluated as an alternative to CT and MRI for sarcopenia evaluation.
Graphical Abstract
Preventive health strategies for women at increased hereditary risk of ovarian cancer include gynecologic screening (GS) and/or prophylactic oophorectomy (PBSO). Hormone replacement therapy (HRT) is ...often prescribed to compensate for postsurgical endocrine deficiencies. This study examined the impact of HRT use on levels of endocrine symptoms and sexual functioning among premenopausal women who have undergone PBSO. Comparisons were made with similar women undergoing GS.
Questionnaire data on endocrine symptoms and sexual functioning were obtained from 450 premenopausal, high-risk women who had participated in this nationwide, cross-sectional, observational study.
Thirty-six percent of women had undergone PBSO and 64% had opted for GS. In the PBSO group, 47% of the women were current HRT users. They reported significantly fewer vasomotor symptoms than nonusers (P < .05). However, compared with premenopausal women undergoing GS, oophorectomized HRT users were more likely to report vasomotor symptoms (P < .01). HRT users and nonusers reported comparable levels of sexual functioning. Compared with women in the GS group, oophorectomized HRT users reported significantly more sexual discomfort due to vaginal dryness and dyspareunia (P < .01).
Although HRT has a positive impact on surgically induced vasomotor symptoms, it may be less effective than is often assumed. Symptom levels remain well above those of premenopausal women undergoing screening, and sexual discomfort is not alleviated by HRT. Physicians need to provide younger high-risk women considering PBSO with realistic information about both benefits and drawbacks of this preventive strategy, including information about premature menopause and HRT.
Purpose
Frailty is associated with a higher risk for negative postoperative outcomes. This study aimed to determine the association between the screening tool of the Dutch safety management system, ...Veiligheidsmanagementsysteem (VMS) ‘frail elderly’ and postoperative complications in a gynecological population.
Methods
This cohort study included women aged 70 years or older, who were scheduled for any kind of gynecological surgery. VMS screening data (including risk for delirium, falling, malnutrition, and functional impairment) were extracted from the electronic patient records. VMS score could range between 0 and 4 patients with a VMS score of one or more were considered frail. Data on possible confounding factors and complications within 30 days after surgery, classified with the Clavien–Dindo classification, were collected. Regression analysis was performed.
Results
157 women were included with a median age of 74 years (inter quartile range 71–79). Most patients underwent prolapse surgery (52%) or hysterectomy (31%). Forty-one patients (26%) experienced any postoperative complication. Sixty-two patients (39%) were considered frail preoperatively by the VMS screening tool. Frailty measured with the VMS screening tool was not independently associated with postoperative complications in multivariable analysis (Odds ratio 1.18; 95% CI 0.49–2.82). However, a recent fall in the last 6 months (
n
= 208) was associated with postoperative complications (Odds ratio 3.90; 95% CI 1.57–9.66).
Conclusion
An independent association between frailty, determined by the VMS screening tool ‘Frail elderly’, and postoperative complications in gynecological surgery patients could not be confirmed. A recent fall in the last 6 months seems associated with postoperative complications.
To investigate the impact of frailty and dependence on health-related quality of life (HRQOL) in elderly women diagnosed with epithelial ovarian cancer (EOC).
Data was gathered from a prospectively ...collected data biobank, OncoLifeS (Oncological Life Study) at the University Medical Center of Groningen. Women with a diagnosis of EOC, ≥65 years of age, with baseline assessment available from January 2016 to May 2018 were included. HRQOL was determined using the EORTC QLQ-C30 yielding scores on Global Health Status, five functional scales, three symptom scales, and six single items. The summary score was also calculated. Frailty was measured using the Groningen Frailty Indicator (GFI), and dependence using the Instrumental Activities of Daily Living (IADL). To evaluate the impact of frailty and dependence on HRQOL, linear regression was performed. Analyses were adjusted for age and tumor stage.
84 patients were included. Median age was 71 years (IQR: 68–75), 78% had advanced stage and 81% serous histology. Overall, the median global health status was 67 (IQR: 50–83). HRQOL scales with lowest scores were: role functioning (median: 66.7; IQR: 33–100), fatigue (median: 33.3; IQR: 22–56) and insomnia (median: 33.3; IQR: 0–67). Being frail was associated with worse functioning on all HRQOL scales and higher symptom scores (p = .001). Conversely, being independent was associated with better functioning on all HRQOL scales and lower symptom scores. These associations remained significant after adjusting for age and tumor stage.
In women ≥65 years, diagnosed with EOC, frailty and dependence are associated to reduced HRQOL. These associations remain significant adjusting for age and stage.
•Frailty and dependence are main determinants of deterioration of HRQOL in elderly ovarian cancer patients.•Age is not a significant determinant of HRQOL in our population.•Functionality is a better determinant of HRQOL in our patients than age or clinical and sociodemographic factors.
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