Project description:ObjectivesThe vaginal surgical approach has not become the standard of care, despite its advantages. The Hominis™ Surgical System is a humanoid shaped robot-assisted system that was designed specifically for robotic vaginal natural orifice transluminal endoscopic surgery (RvNOTES). We aimed to present our experience with the first RvNOTES bilateral salpingo-oophorectomy (BSO) performed by the Hominis system.Study designA two-center prospective study of BSO by RvNOTES in women with nonmalignant indications conducted between August and December 2018. Women older than 18 years were offered to participate. Exclusion criteria included a history of abdominal malignancy, pelvic or abdominal irradiation, Crohn's disease, pelvic inflammatory disease, severe infections in the lower abdomen, active diverticulitis, deep infiltrating recto-vaginal endometriosis, and an active vaginal infection. The primary outcome of the study was the rate of conversion to open or laparoscopic approaches. Secondary outcomes included intra- and postoperative adverse events, operative time, estimated blood loss, length of hospital stay, and 6-week follow-up assessment.ResultsEight women aged 50-70 years with BMI of 19-30 kg/m2 were recruited. All the procedures were completed successfully without conversions to open surgery. No intraoperative complications were observed. Median blood loss was 10 mL (range: 10-50). The median duration of the procedure was 45 min (range: 38-91), and decreased over the study period. Surgeons' usability assessment was very favorable, with a median of 5 on a 1-5 scale. The median visual analog scale (VAS) score was 1 (range: 1-3).ConclusionsThis is the first documentation of a surgery performed via the vagina using robotic instrumentation developed for this purpose. The disruptive technology of RvNOTES, with its fast learning curve, will make gynecological surgeries accessible to more women.
Project description:ObjectivesTo investigate the association between bilateral salpingo-oophorectomy (BSO) and long-term health outcomes in women with a personal history of breast cancer.Methods and analysisWe used data on women diagnosed with invasive breast cancer between 1995 and 2019 from the National Cancer Registration Dataset (NCRD) in England. The data were linked to the Hospital Episode Statistics-Admitted Patient Care dataset to identify BSO delivery. Long-term health outcomes were selected from both datasets. Multivariable Cox regression was used to examine the associations, with BSO modelled as a time-dependent covariate. The associations were investigated separately by age at BSO.ResultsWe identified 568 883 women, 23 401 of whom had BSO after the breast cancer diagnosis. There was an increased risk of total cardiovascular diseases with an HR of 1.10 (95% CI 1.04 to 1.16) in women who had BSO<55 years and 1.07 (95% CI 1.01 to 1.13) for women who had BSO≥55 years. There was an increased risk of ischaemic heart diseases, but there was no association with cerebrovascular diseases. BSO at any age was associated with an increased risk of depression (HR 1.20, 95% CI 1.12 to 1.28) and increased risk of second non-breast cancer in older women (HR 1.21, 95%CI 1.08 to 1.35). BSO in older women was associated with reduced risk of all-cause mortality (HR 0.92, 95% CI 0.87 to 096), but not in women who had BSO<55 years.ConclusionIn women with a personal history of breast cancer, BSO before and after the age of 55 years is associated with an increased risk of long-term outcomes. BSO after 55 years is associated with reduced all-cause mortality. Family history or genetic predisposition may confound these associations.
Project description:IntroductionWomen at high inherited risk of ovarian cancer are advised to undergo risk-reducing bilateral salpingo-oophorectomy (RRBSO) at age 40-45 years or when their families are complete. Most women are premenopausal at this age, so RRBSO will induce surgical menopause. Despite the clear benefits of RRBSO for cancer risk reduction, much less is known about the impact on non-cancer outcomes that contribute to health and well-being and inform surveillance and management strategies.Methods and analysisThis will be a multicentre, prospective cohort study of 105 premenopausal high-risk women undergoing RRBSO and an age-matched comparison group of 105 premenopausal women not planning oophorectomy or pregnancy in the next 2 years. The aim of this study is to measure the impact of RRBSO on sexual function (primary outcome) at 24 months in high-risk premenopausal women compared with the comparison group. Secondary outcomes include menopausal symptoms and menopause-related quality of life, mood, sleep quality, markers of cardiovascular disease and pre-diabetes, bone density and markers of bone turnover, and the impact of hormone replacement therapy use on these outcomes. Data analysis methods will include logistic and linear regression using general estimating equations accounting for the repeated outcome measurements within each participant.Ethics and disseminationThe study has been approved by institutional ethics committees at each participating centre. Findings will be disseminated through peer-reviewed publications and conference presentations, and national and international networks of centres managing high-risk women, and will inform national and international clinical guidelines.Trial registration numberThe pre-results protocol for this trial is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; registration no: ACTRN12615000082505).
Project description:BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for BRCA1 and BRCA2 mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for BRCA2 mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers was followed for a mean of 5.4 and 4.9?years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer for BRCA1 (HR?=?1.23; 95% CI 0.94-1.61) or BRCA2 (HR?=?0.88; 95% CI 0.62-1.24) mutation carriers. For BRCA2 mutation carriers, HRs were 0.68 (95% CI 0.40-1.15) and 1.07 (95% CI 0.69-1.64) for RRSO carried out before or after age 45?years, respectively. The HR for BRCA2 mutation carriers decreased with increasing time since RRSO (HR?=?0.51; 95% CI 0.26-0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk for BRCA1 mutation carriers. A potentially beneficial effect for BRCA2 mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
Project description:IntroductionLittle is known about hysterectomy and bilateral salpingo-oophorectomy (BSO), which are associated with both health risks and benefits, among women Veterans.Purpose of the studyTo compare the prevalence of hysterectomy with or without BSO, and early hysterectomy, between postmenopausal Veterans and non-Veterans.Design and methodsWe used baseline data from the Women's Health Initiative Clinical Trial and Observational Study. Multinomial logistic regression models examined differences in the prevalence of hysterectomy (neither hysterectomy nor BSO, hysterectomy without BSO, and hysterectomy with BSO) between Veterans and non-Veterans. Generalized linear models were used to determine whether early hysterectomy (before age 40) differed between Veterans and non-Veterans. Analyses were stratified by birth cohort (<65, ≥65 years at enrollment).ResultsThe unadjusted prevalence of hysterectomy without BSO was similar among Veterans and non-Veterans in both birth cohorts (<65: 22% vs 21%; ≥65: 22% vs 21%). The unadjusted prevalence of hysterectomy with BSO was equivalent among Veterans and non-Veterans in the >65 cohort (21%), but higher among Veterans in the <65 cohort (22% vs 19%). In adjusted analyses, although no differences were observed in the >65 cohort, Veterans in the <65 cohort had higher odds of hysterectomy without BSO (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03, 1.36) and with BSO (OR 1.26, 95% CI 1.10, 1.45), as well as elevated risk of early hysterectomy (relative risk 1.32, 95% CI 1.19, 1.47), compared with non-Veterans.ImplicationsAging women Veterans may have higher prevalence of hysterectomy and BSO than non-Veterans. This information contributes to understanding the health needs and risks of women Veterans and can inform clinical practice and policy for this population.
Project description:ObjectivesTo determine if bilateral salpingo-oophorectomy, compared with ovarian conservation, is associated with all cause or cause specific death in women undergoing hysterectomy for non-malignant disease, and to determine how this association varies with age at surgery.DesignPopulation based cohort study.SettingOntario, Canada from 1 January 1996 to 31 December 2015, and follow-up to 31 December 2017.Participants200 549 women (aged 30-70 years) undergoing non-malignant hysterectomy, stratified into premenopausal (<45 years), menopausal transition (45-49 years), early menopausal (50-54 years), and late menopausal (≥55 years) groups according to age at surgery; median follow-up was 12 years (interquartile range 7-17).ExposuresBilateral salpingo-oophorectomy versus ovarian conservation.Main outcomes measuresThe primary outcome was all cause death. Secondary outcomes were non-cancer and cancer death. Within each age group, overlap propensity score weighted survival models were used to examine the association between bilateral salpingo-oophorectomy and mortality outcomes, while adjusting for demographic characteristics, gynaecological conditions, and comorbidities. To account for comparisons in four age groups, P<0.0125 was considered statistically significant.ResultsBilateral salpingo-oophorectomy was performed in 19%, 41%, 69%, and 81% of women aged <45, 45-49, 50-54, and ≥55 years, respectively. The procedure was associated with increased rates of all cause death in women aged <45 years (hazard ratio 1.31, 95% confidence interval 1.18 to 1.45, P<0.001; number needed to harm 71 at 20 years) and 45-49 years (1.16, 1.04 to 1.30, P=0.007; 152 at 20 years), but not in women aged 50-54 years (0.83, 0.72 to 0.97, P=0.018) or ≥55 years (0.92, 0.82 to 1.03, P=0.16). Findings in women aged <50 years were driven largely by increased non-cancer death. In secondary analyses identifying a possible change in the association between bilateral salpingo-oophorectomy and all cause death with advancing age at surgery, the hazard ratio gradually decreased during the menopausal transition and remained around 1 at all ages thereafter.ConclusionIn this observational study, bilateral salpingo-oophorectomy at non-malignant hysterectomy appeared to be associated with increased all cause mortality in women aged <50 years, but not in those aged ≥50 years. While caution is warranted when considering bilateral salpingo-oophorectomy in premenopausal women without indication, this strategy for ovarian cancer risk reduction does not appear to be detrimental to survival in postmenopausal women.
Project description:Congenital nephrogenic diabetes insipidus (NDI) primarily arises from an X-linked recessive inheritance caused by mutations in the AVPR2 gene, which is responsible for approximately 90% of cases. This condition has an incidence rate of 4-8 per million male live births, with females being much less frequently affected. Symptoms typically manifest shortly after birth, predominantly in males. The key clinical features of NDI include excessive urination (polyuria), compensatory excessive thirst (polydipsia), cognitive impairment, consistently low urine specific gravity, dehydration, and imbalances in electrolyte levels. This case study highlights an unusual occurrence of NDI in a 50-year-old Chinese woman attributed to a mutation in the AVPR2 gene. For more than a year, she had been suffering from excessive urination and severe thirst. The patient, who had undergone surgery for cervical cancer, developed polyuria and hypernatremia postoperatively. Initial laboratory analyses revealed normal blood sodium and chloride levels but reduced urine osmolality and specific gravity. Imaging assessments revealed no irregularities. To validate the diagnosis of NDI, she participated in a water deprivation and vasopressin test. Subsequent genetic tests revealed a thymine (T) to adenine (A) mutation, leading to a missense mutation in the AVPR2 gene. As part of her treatment, she was placed on a low-sodium diet and prescribed oral hydrochlorothiazide and indomethacin for 1 month, resulting in a marked improvement in her symptoms. To the best of our knowledge, this is the first documented case of NDI diagnosed postoperatively in an older female patient with AVPR2 heterozygosity. This case highlights an unusual instance of an X-linked recessive clinical presentation of NDI in an elderly female patient. This study also underscores the importance of conducting water deprivation, vasopressin tests, and genetic testing in establishing the underlying cause for individuals diagnosed with NDI.
Project description:ImportancePreventive surgery is strongly recommended for individuals with a BRCA mutation at a young age to prevent ovarian cancer and improve overall survival. The overall effect of early surgical menopause on various health outcomes, including bone health, has not been clearly elucidated.ObjectiveTo evaluate the association of prophylactic bilateral salpingo-oophorectomy with bone mineral density (BMD) loss among individuals with a BRCA mutation.Design, setting, and participantsThis retrospective cohort study of participants with a BRCA mutation who underwent oophorectomy through the University Health Network, Toronto, Ontario, Canada, recruited participants from January 2000 to May 2013. Eligibility criteria included having a BRCA mutation, at least 1 ovary intact prior to surgery, and no history of any cancer other than breast cancer. Bone mineral density was measured using dual-energy x-ray absorptiometry before and after surgery. Data analysis began in December 2018 and finished in January 2019.Main outcomes and measuresThe annual change in BMD from baseline to follow-up was calculated for the following 3 anatomical locations: (1) lumbar spine, (2) femoral neck, and (3) total hip.ResultsA total of 95 women had both a baseline and postsurgery BMD measurement with a mean (SD) follow-up period of 22.0 (12.7) months. The mean (SD) age at oophorectomy was 48.0 (7.4) years. Among women who were premenopausal at time of surgery (50 [53%]), there was a decrease in BMD from baseline to follow-up across the lumbar spine (annual change, -3.45%; 95% CI, -4.61% to -2.29%), femoral neck (annual change, -2.85%; 95% CI, -3.79% to -1.91%), and total hip (annual change, -2.24%; 95% CI, -3.11% to -1.38%). Self-reported hormone therapy use was associated with significantly less bone loss at the lumbar spine (-2.00% vs -4.69%; P = .02) and total hip (-1.38% vs -3.21; P = .04) compared with no hormone therapy use. Among postmenopausal women at time of surgery (45 [47%]), there was also a significant decrease in BMD across the lumbar spine (annual change, -0.82%; 95% CI, -1.42% to -0.23%) and femoral neck (annual change, -0.68%; 95% CI, -1.33% to -0.04%) but not total hip (annual change, -0.18%; 95% CI, -0.82% to 0.46%).Conclusions and relevanceThis study found that oophorectomy was associated with postoperative bone loss, especially among women who were premenopausal at the time of surgery. Targeted management strategies should include routine BMD assessment and hormone therapy use to improve management of bone health in this population.
Project description:Pathogenic germline variants underlie up to 20% of ovarian cancer (OC) and are associated with varying degrees of risk for OC. For mutations in high-penetrance genes such as BRCA1/2, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in cancer prevention is well-established and improves mortality. However, in moderate-penetrance genes where the degree of risk for OC is less precisely defined, the role of RRSO is more controversial. Although national guidelines have evolved to incorporate gene-specific recommendations, studies demonstrate significant variations in practice. Given this, our multidisciplinary group has reviewed the available literature on risk estimates for genes associated with OC, incorporated levels of evidence, and set thresholds for consideration of RRSO. We found that the benefit of RRSO is well-established for pathogenic variants in BRCA1/2 as well as BRIP1 and RAD51C/D where the risk of OC is elevated beyond our threshold for RRSO. In PALB2, RRSO is particularly controversial as newer studies consistently demonstrate an increased risk of OC that is dependent on family history, making uniform recommendations challenging. Additionally, new guidelines for Lynch syndrome provide gene-specific risks, questioning the role of RRSO, and even hysterectomy, for MSH6 and PMS2 mutation carriers. Given these uncertainties, shared decision making should be used around RRSO with discussion of individual risk factors, family history, and adverse effects of surgery and premature menopause. Herein, we provide a clinical guide and counseling points.
Project description:ImportanceThe link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.ObjectiveTo determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.Design, setting, and participantsThis multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy. Of these, 627 participants were BRCA1+; 453, BRCA2+; and 3, both. Participants were prospectively followed up for a median 5.1 (interquartile range [IQR], 3.0-8.4) years after ascertainment, BRCA testing, or RRSO (whichever occurred last). Follow up data available through October 14, 2014, were included in the analyses. Censoring occurred at uterine cancer diagnosis, hysterectomy, last follow-up, or death. New cancers were categorized by histologic subtype, and available tumors were analyzed for loss of the wild-type BRCA gene and/or protein expression.Main outcomes and measuresIncidence of uterine corpus cancer in BRCA+ women who underwent RRSO without hysterectomy compared with rates expected from the Surveillance, Epidemiology, and End Results database.ResultsAmong the 1083 women women who underwent RRSO without hysterectomy at a median age 45.6 (IQR: 40.9 - 52.5), 8 incident uterine cancers were observed (4.3 expected; observed to expected [O:E] ratio, 1.9; 95% CI, 0.8-3.7; P = .09). No increased risk for endometrioid endometrial carcinoma or sarcoma was found after stratifying by subtype. Five serous and/or serous-like (serous/serous-like) endometrial carcinomas were observed (4 BRCA1+ and 1 BRCA2+) 7.2 to 12.9 years after RRSO (BRCA1: 0.18 expected [O:E ratio, 22.2; 95% CI, 6.1-56.9; P < .001]; BRCA2: 0.16 expected [O:E ratio, 6.4; 95% CI, 0.2-35.5; P = .15]). Tumor analyses confirmed loss of the wild-type BRCA1 gene and/or protein expression in all 3 available serous/serous-like BRCA1+ tumors.Conclusions and relevanceAlthough the overall risk for uterine cancer after RRSO was not increased, the risk for serous/serous-like endometrial carcinoma was increased in BRCA1+ women. This risk should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women.