Bilateral Oophorectomy and All-Cause Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Importance: Preventive bilateral salpingo-oophorectomy is offered to women at high risk of ovarian cancer who carry a pathogenic variant in BRCA1 or BRCA2; however, the association of oophorectomy with all-cause mortality has not been clearly defined. Objective: To evaluate the association between bilateral oophorectomy and all-cause mortality among women with a BRCA1 or BRCA2 sequence variation. Design, Setting, and Participants: In this international, longitudinal cohort study of women with BRCA sequence variations, information on bilateral oophorectomy was obtained via biennial questionnaire. Participants were women with a BRCA1 or BRCA2 sequence variation, no prior history of cancer, and at least 1 follow-up questionnaire completed. Women were followed up from age 35 to 75 years for incident cancers and deaths. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) and 95% CIs for all-cause mortality associated with a bilateral oophorectomy (time dependent). Data analysis was performed from January 1 to June 1, 2023. Exposures: Self-reported bilateral oophorectomy (with or without salpingectomy). Main Outcomes and Measures: All-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality. Results: There were 4332 women (mean age, 42.6 years) enrolled in the cohort, of whom 2932 (67.8%) chose to undergo a preventive oophorectomy at a mean (range) age of 45.4 (23.0-77.0) years. After a mean follow-up of 9.0 years, 851 women had developed cancer and 228 had died; 57 died of ovarian or fallopian tube cancer, 58 died of breast cancer, 16 died of peritoneal cancer, and 97 died of other causes. The age-adjusted HR for all-cause mortality associated with oophorectomy was 0.32 (95% CI, 0.24-0.42; P < .001). The age-adjusted HR was 0.28 (95% CI, 0.20-0.38; P < .001) and 0.43 (95% CI, 0.22-0.90; P = .03) for women with BRCA1 and BRCA2 sequence variations, respectively. For women with BRCA1 sequence variations, the estimated cumulative all-cause mortality to age 75 years for women who had an oophorectomy at age 35 years was 25%, compared to 62% for women who did not have an oophorectomy. For women with BRCA2 sequence variations, the estimated cumulative all-cause mortality to age 75 years was 14% for women who had an oophorectomy at age 35 years compared to 28% for women who did not have an oophorectomy. Conclusions and Relevance: In this cohort study among women with a BRCA1 or BRCA2 sequence variation, oophorectomy was associated with a significant reduction in all-cause mortality.

Bilateral salpingo-oophorectomy at the time of benign hysterectomy among females with disabilities: a population-based cross-sectional study.

BACKGROUND: Up to 40% of patients aged ≤55 years undergo concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy, with practice variation in bilateral salpingo-oophorectomy occurring along the lines of patient health and social factors. Disability is common in premenopausal women and is an important determinant of reproductive health more broadly; however, studies on bilateral salpingo-oophorectomy rates among women with disabilities are lacking. OBJECTIVE: This study aimed to examine whether the use of concomitant bilateral salpingo-oophorectomy at the time of benign hysterectomy differs by preexisting disability status in adult females aged ≤55 years. STUDY DESIGN: This population-based cross-sectional study used data from the 2016-2019 US National Inpatient Sample. Females undergoing inpatient hysterectomy for a benign gynecologic indication (n=74,315) were classified as having physical (6.1%), sensory (0.1%), intellectual or developmental (0.2%), or multiple (0.2%) disabilities and compared with those without a disability. Logistic regression was used to estimate risk ratios for differences in bilateral salpingo-oophorectomy rates by disability status, adjusted for patient and clinical factors. Models were stratified by potentially avoidable or potentially appropriate bilateral salpingo-oophorectomy based on the presence of clinical indications for ovarian removal and by age group. RESULTS: Bilateral salpingo-oophorectomy at the time of benign hysterectomy occurred in 26.0% of females without a disability, with rates clearly elevated in those with a physical (33.2%; adjusted risk ratio, 1.10; 95% confidence interval, 1.05-1.14) or intellectual or developmental (31.1%; adjusted risk ratio, 1.32; 95% confidence interval, 1.02-1.64) disability, possibly elevated in those with multiple disabilities (38.2%; adjusted risk ratio, 1.20; 95% confidence interval, 0.94-1.45), and similar in those with a sensory disability (31.2%; adjusted risk ratio, 0.98; 95% confidence interval, 0.83-1.13). The results were similar but with lower statistical precision for potentially avoidable and potentially appropriate bilateral salpingo-oophorectomy, which occurred in 9.1% and 17.0% of females without a disability, respectively. The largest differences in bilateral salpingo-oophorectomy rates among women with any disability were observed in the perimenopausal 45- to 49-year age group. CONCLUSION: Females with disabilities experienced elevated concomitant bilateral salpingo-oophorectomy rates at the time of benign hysterectomy, particularly those with an intellectual or developmental disability and those of perimenopausal age, although some estimates were imprecise. Equity-focused physician training in surgical counseling and research into the epidemiology and experiences of gynecologic conditions among females with a disability may be beneficial.

Robenacoxib versus meloxicam following ovariohysterectomy in cats: A randomised, prospective clinical trial involving owner-based assessment of pain.

BACKGROUND: Injectable non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to queens undergoing ovariohysterectomy (OVH), but the requirement for postoperative administration is unclear and practices vary. Existing studies assessing efficacy rely on pain scoring by experienced clinicians. However, following OVH, most cats are discharged within hours of recovery. METHODS: Cats undergoing OVH were randomly assigned to two treatment groups: MEL and ROB. Cats in the MEL group (n = 76) received meloxicam (0.2 mg/kg) and those in the ROB group (n = 65) received robenacoxib (2 mg/kg). Owners were contacted by a blinded assessor 3 days postoperatively and asked to identify physical or behavioural changes and to assign pain scores using a numerical rating scale. RESULTS: More cats in the ROB group displayed abnormal behaviours than cats in the MEL group (p = 0.03). Most owners assigned a pain score of 0 (72%) (n = 101), but pain scores were significantly higher in the ROB group than in the MEL group (p = 0.005). LIMITATION: Methods of owner assessment of pain in cats have not been validated. CONCLUSIONS: Both meloxicam and robenacoxib are effective in controlling postoperative pain. Meloxicam may have improved efficacy in certain patient populations. Applying a blanket approach to prescribing NSAIDs to cats undergoing OVH postoperatively may not be necessary. This has safety, environmental and cost implications.

Ovarian preservation compared to oophorectomy in premenopausal women with early-stage, low-grade endometrial Cancer: A cost-effectiveness analysis.

OBJECTIVES: Standard treatment for endometrial cancer is a hysterectomy, bilateral salpingo-oophorectomy, and lymph node assessment. In premenopausal women, removal of the ovaries may not be necessary and could increase the risk of all-cause mortality. We sought to estimate the outcomes, costs, and cost-effectiveness of oophorectomy versus ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. METHODS: A decision-analytic model was designed using TreeAge software comparing oophorectomy to ovarian preservation in premenopausal women with early-stage, low-grade endometrial cancer. We used a theoretical cohort of 10,600 women to represent our population of interest in the United States in 2021. Outcomes included cancer recurrences, ovarian cancer diagnoses, deaths, rates of vaginal atrophy, costs, and quality-adjusted life years (QALYs). The cost-effectiveness threshold was set at $100,000/QALY. Model inputs were derived from the literature. Sensitivity analyses were conducted to evaluate the robustness of the results. RESULTS: Oophorectomy resulted in more deaths and higher rates of vaginal atrophy, while ovarian preservation resulted in 100 cases of ovarian cancer. Ovarian preservation resulted in lower costs and higher QALYs making it cost effective when compared to oophorectomy. Sensitivity analyses demonstrated the probability of cancer recurrence after ovarian preservation and probability of developing ovarian cancer were the most impactful variables in our model. CONCLUSION: Ovarian preservation is cost-effective in premenopausal women with early-stage, low-grade endometrial cancer when compared to oophorectomy. Ovarian preservation may prevent surgical menopause, which may improve quality of life and overall mortality without compromising oncologic outcomes, and should be strongly considered in premenopausal women with early stage disease.

The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

A Revised Markov Model Evaluating Oophorectomy at the Time of Hysterectomy for Benign Indication: Age 65 Years Revisited.

OBJECTIVE: To perform an updated Markov modeling to assess the optimal age for bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign indication. METHODS: We performed a literature review that assessed hazard ratios (HRs) for mortality by disease, age, hysterectomy with or without BSO, and estrogen therapy use. Base mortality rates were derived from national vital statistics data. A Markov model from reported HRs predicted the proportion of the population staying alive to age 80 years by 1-year and 5-year age groups at time of surgery, from age 45 to 55 years. Those younger than age 50 years were modeled as either taking postoperative estrogen or not; those 50 and older were modeled as not receiving estrogen. Computations were performed with R 3.5.1, using Bayesian integration for HR uncertainty. RESULTS: Performing salpingo-oophorectomy before age 50 years for those not taking estrogen yields a lower survival proportion to age 80 years than hysterectomy alone before age 50 years (52.8% [Bayesian CI 40.7-59.7] vs 63.5% [Bayesian CI 62.2-64.9]). At or after age 50 years, there were similar proportions of those living to age 80 years with hysterectomy alone (66.4%, Bayesian CI 65.0-67.6) compared with concurrent salpingo-oophorectomy (66.9%, Bayesian CI 64.4-69.0). Importantly, those taking estrogen when salpingo-oophorectomy was performed before age 50 years had similar proportions of cardiovascular disease, stroke, and people living to age 80 years as those undergoing hysterectomy alone or those undergoing hysterectomy and salpingo-oophorectomy at age 50 years and older. CONCLUSION: This updated Markov model argues for the consideration of concurrent salpingo-oophorectomy for patients who are undergoing hysterectomy at age 50 and older and suggests that initiating estrogen in those who need salpingo-oophorectomy before age 50 years mitigates increased mortality risk.

Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway.

Weight gain is a hallmark of decreased estradiol (E2) levels because of menopause or following surgical ovariectomy (OVX) at younger ages. Of note, this weight gain tends to be around the abdomen, which is frequently associated with impaired metabolic homeostasis and greater cardiovascular risk in both rodents and humans. However, the molecular underpinnings and the neuronal basis for these effects remain to be elucidated. The aim of this study is to elucidate whether the kappa-opioid receptor (k-OR) system is involved in mediating body weight changes associated with E2 withdrawal. Here, we document that body weight gain induced by OVX occurs, at least partially, in a k-OR dependent manner, by modulation of energy expenditure independently of food intake as assessed in Oprk1-/-global KO mice. These effects were also observed following central pharmacological blockade of the k-OR system using the k-OR-selective antagonist PF-04455242 in wild type mice, in which we also observed a decrease in OVX-induced weight gain associated with increased UCP1 positive immunostaining in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Remarkably, the hypothalamic mTOR pathway plays an important role in regulating weight gain and adiposity in OVX mice. These findings will help to define new therapies to manage metabolic disorders associated with low/null E2 levels based on the modulation of central k-OR signaling.

An evaluation of memory and attention in BRCA mutation carriers using an online cognitive assessment tool.

BACKGROUND: The objective of this study was to evaluate the impact of various surgical, hormonal, and lifestyle factors on memory and attention in women with a BRCA1 or BRCA2 mutation. METHODS: BRCA mutation carriers enrolled in a longitudinal study were invited to complete an online brain health assessment tool designed to screen for cognitive deficits. Four measures of memory and executive attention were assessed individually, and an overall score was compiled adjusting for age. Exposures, including preventive surgery, hormone use, and lifestyle factors, were captured by questionnaire. Performance on each of the 5 subtasks was analyzed according to various exposures. Analysis of covariance was used to compare overall scores. RESULTS: In total, 880 women completed the online cognitive assessment. The average age of the participants was 54 years (range, 23-86 years). The mean overall test score was 54.4 (range, 0-93). The individual subtask scores declined with age at test completion (P < .0001) and increased with level of education (P ≤ .01). Women who underwent a preventive oophorectomy had a significantly higher overall score compared with women who did not undergo this surgery (55.5 vs 50.5; P = .01). Reconstructive breast surgery was also associated with a higher overall score (56.5 vs 52.3; P = .005). Chemotherapy and hormone-replacement therapy were not predictive of the overall score. CONCLUSIONS: These findings are reassuring to high-risk women who undergo early surgical menopause for their cancer predisposition. Further studies are needed to evaluate cognitive function over time when memory deficits become more prevalent.

Changing trends in Black-White racial differences in surgical menopause: a population-based study.

BACKGROUND: Bilateral oophorectomy before menopause, or surgical menopause, is associated with negative health outcomes, including an increased risk for stroke and other cardiovascular outcomes; however, surgical menopause also dramatically reduces ovarian cancer incidence and mortality rates. Because there are competing positive and negative sequelae associated with surgical menopause, clinical guidelines have not been definitive. Previous research indicates that White women have higher rates of surgical menopause than other racial groups. However, previous studies may have underestimated the rates of surgical menopause among Black women. Furthermore, clinical practice has changed dramatically in the past 15 years, and there are no population-based studies in which more recent data were used. Tracking actual racial differences among women with surgical menopause is important for ensuring equity in gynecologic care. OBJECTIVE: This population-based surveillance study evaluated racial differences in the rates of surgical menopause in all inpatient and outpatient settings in a large, racially diverse US state with historically high rates of hysterectomy. STUDY DESIGN: We evaluated all inpatient and outpatient surgeries in North Carolina from 2011 to 2014 for patients aged between 20 and 44 years. Surgical menopause was defined as a bilateral oophorectomy, with or without an accompanying hysterectomy, among North Carolina residents. International Classification of Diseases, Ninth Revision, and Current Procedural Terminology codes were used to identify inpatient and outpatient procedures, respectively, and diagnostic indications. We estimated age-, race-, and ethnicity-specific rates of surgical menopause using county-specific population estimates based on the 2010 United States census. We used Poisson regression with deviance-adjusted residuals to estimate the incidence rate ratios in the entire state population. We tested changes in surgery rates over time (reference year, 2011), differences by setting (reference, inpatient), and differences by race and ethnicity (reference, non-Hispanic White). We then described the surgery rates between non-Hispanic White and non-Hispanic Black patients. RESULTS: Between 2011 and 2014, 11,502 surgical menopause procedures for benign indications were performed in North Carolina among reproductive-aged residents. Most (95%) of these surgeries occurred concomitant with a hysterectomy. Over the 4-year study period, there was a 39% reduction in inpatient surgeries (incidence rate ratio, 0.61) and a 100% increase in outpatient surgeries (incidence rate ratio, 2.0). Restricting the analysis to surgeries among non-Hispanic White and Black patients, the increase in outpatient surgeries was significantly higher among non-Hispanic Black women (P<.01) for year-race interaction (reference, 2011 and non-Hispanic White). The overall rates of bilateral oophorectomy for non-Hispanic Black women rose more quickly than for non-Hispanic White women (P<.01). In 2011, the rate of surgical menopause was greater among White women than among Black women (17.7 vs 13.2 per 10,000 women). By 2014, the racial trends were reversed (rate, 24.8 per 10,000 for non-Hispanic White women and 28.4 per 10,000 for non-Hispanic Black women). CONCLUSION: Our findings suggest that the rates of surgical menopause increased in North Carolina in the early 2010s, especially among non-Hispanic Black women. By 2014, the rates of surgical menopause among non-Hispanic Black women had surpassed that of non-Hispanic White women. Given the long-term health consequences associated with surgical menopause, we propose potential drivers for the racially-patterned increases in the application of bilateral oophorectomy before the age of 45 years.

Assessment of a vessel and tissue-sealing device for ovariectomy in chickens to evaluate the potential application of the procedure to other avian species.

OBJECTIVE: To assess the feasibility of a novel technique involving a vessel and tissue-sealing device (VTSD) for ovariectomy in chickens to evaluate the potential application of the procedure to other avian species. ANIMALS: 20 domestic laying hens (Gallus domesticus), of which 10 were immature (< 4 months old) and 10 were adults (> 18 months old). PROCEDURES: Ovariectomy was performed with a VTSD through a left lateral celiotomy. Birds were allowed to recover for 14 days after the procedure and then were euthanized for necropsy. A board-certified veterinary pathologist performed complete necropsies, with particular attention to identifying any remaining ovarian tissue. RESULTS: All birds survived the procedure. For the mature and juvenile birds, the mean ± SD durations of anesthesia (interval from intubation to extubation) were 67.2 ± 7.6 minutes and 50.5 ± 5.1 minutes, respectively, and mean durations of surgery were 45.3 ± 8.5 minutes and 31.6 ± 5.1 minutes, respectively. Three birds had severe hemorrhage during ovariectomy. At necropsy, ovarian tissue was present grossly in 2 mature birds and histologically in 6 additional birds (2 mature and 4 juvenile birds), indicating incomplete excision in 8 (40%) birds. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the evaluated VTSD can be used to successfully perform ovariectomies in both juvenile and mature chickens, although the procedure was associated with major hemorrhage and incomplete excision of ovarian tissue in some cases. Use of this VTSD for ovariectomy in birds of other species, particularly birds with reproductive tract disease, should be investigated.

Anxio-depressive symptoms in Moroccan women with gynecological cancer: Relief factors.

INTRODUCTION: Psychosocial determinants can affect the mental health of women who have been diagnosed with gynecological cancer. The aim of this study was to examine how social support and self-esteem are associated with anxiety and depression symptoms in women with gynecological cancer, and who are treated by radical surgery. METHODS: A cross-sectional study was performed, within the oncology department of Ibn Rochd University Hospital, Casablanca, on 100 Moroccan women. They all had undergone radical surgery for gynecological cancer, hysterectomy and/or oophorectomy. RESULTS: Our results showed that patients with gynecological cancer treated by radical surgery exhibited high prevalence rates of anxiety (66%) and depression symptoms (59%). Associations showed that age, having children, medical coverage system, area of residence, working status and socioeconomic status were significantly related to the prevalence of anxiety and depression symptoms (P<0.05). The general social support, family support and significant other support besides high self-esteem reduce significantly the risk of getting anxiety and depression symptoms (P-values<0.05). DISCUSSION: Among patients with gynecological cancer treated by radical surgery, high prevalence of anxiety and depression symptoms was found. Social support and high self-esteem could help improve mental health issues related to this type of cancer.

Cajanolactone A, a stilbenoid from Cajanus cajan, inhibits energy intake and lipid synthesis/storage, and promotes energy expenditure in ovariectomized mice.

BACKGROUND: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. METHODS: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. FINDINGS: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. INTERPRETATION: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.

Evaluation of a laparoscopic abdominal simulator assessment to test readiness for laparoscopic ovariectomy in live dogs.

OBJECTIVE: To predict readiness for laparoscopic ovariectomy of live dogs on the basis of performance on a high-fidelity laparoscopic abdominal simulator and to determine interrater reliability of the assessment. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Seventeen fourth-year veterinary students. METHODS: After a standardized laparoscopic training course, each participant performed a laparoscopic ovariectomy with a simulator. This performance was scored in real time by two evaluators using a rubric. Participants achieving a score of 112 of 160 performed a laparoscopic ovariectomy in a live dog, supervised by an instructor in the room. Two evaluators scored video recordings of each procedure using the rubric. Participants' opinions about the simulator were collected with a survey. RESULTS: All participants scored above the threshold (range, 126-151) and successfully completed laparoscopic ovariectomy in a live dog, with an average of 10 of 17 participants requiring verbal guidance and 5 of 17 participants requiring intervention from the instructor. Interrater concordance was excellent for the rubrics used to score performance on the simulator (R = 0.91) and in vivo (R = 0.81). All participants agreed that the simulator should be used to assess trainee readiness prior to surgery in a live dog. CONCLUSION: Participants achieving a score of at least 126 of 160 on the simulator were able to perform a laparoscopic ovariectomy in a live dog under supervision. The scoring system for the simulator had excellent interrater concordance. CLINICAL SIGNIFICANCE: This simulator and scoring system can be used in laparoscopic training programs to assess readiness for progression to the operative setting.

Rural disparities in surgical care from gynecologic oncologists among Midwestern ovarian cancer patients.

OBJECTIVE: Up to one-third of women with ovarian cancer in the United States do not receive surgical care from a gynecologic oncologist specialist despite guideline recommendations. We aim to investigate the impact of rurality on receiving surgical care from a specialist, referral to a specialist, and specialist surgery after referral, and the consequences of specialist care. METHODS: We utilized a retrospective cohort created through an extension of standard cancer surveillance in three Midwestern states. Multivariable adjusted logistic regression was utilized to assess gynecologic oncologist treatment of women 18-89 years old, who were diagnosed with primary, histologically confirmed, malignant ovarian cancer in 2010-2012 in Kansas, Missouri and Iowa by rurality. RESULTS: Rural women were significantly less likely to receive surgical care from a gynecologic oncologist specialist (adjusted odds ratio (OR) 0.37, 95% confidence interval (CI) 0.24-0.58) and referral to a specialist (OR 0.37, 95% CI 0.23-0.59) compared to urban women. There was no significant difference in specialist surgery after a referral (OR 0.56, 95% CI 0.26-1.20). Rural women treated surgically by a gynecologic oncologist versus non-specialist were more likely to receive cytoreduction and more complete tumor removal to ≤1 cm. CONCLUSION: There is a large rural-urban difference in receipt of ovarian cancer surgery from a gynecologic oncologist specialist (versus a non-specialist). Disparities in referral rates contribute to the rural-urban difference. Further research will help define the causes of referral disparities, as well as promising strategies to address them.

Concomitant Bilateral Salpingo-Oophorectomy at Hysterectomy: Differences by Race and Menopausal Status in the Veterans Affairs Health Care System, 2007-2014.

Background: Hysterectomy can be performed with concomitant bilateral salpingo-oophorectomy (BSO) to treat symptomatic pathology of the ovary (e.g., endometriosis) or to prevent ovarian cancer. Our objective was to examine the relationship between race and concomitant BSO by menopausal status in the Veterans Affairs (VA) health care system. Methods: This is a longitudinal study utilizing VA administrative data to identify hysterectomies provided or paid for by VA (i.e., source of care) between 2007 and 2014. We defined BSO as removal of both ovaries and fallopian tubes at the time of hysterectomy, identified by International Classification of Diseases-Ninth Revision codes. Covariates included demographic (e.g., ethnicity) and gynecological diagnoses (e.g., endometriosis). We used generalized linear models with a log-link and binomial distribution to estimate associations of race with BSO by menopausal status and source of care. Results: We identified 6,785 Veterans with hysterectomies, including 2,320 with concomitant BSO. Overall, Black Veterans were more likely to be single, obese, and undergo abdominal hysterectomy. After adjustment, premenopausal Black Veterans had a 41% lower odds of BSO than their White counterparts (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.51-0.68). Stratifying on source of care, these results remained unchanged (provided: OR: 0.61, 95% CI: 0.52-0.72; paid: OR: 0.58, 95% CI: 0.48-0.71). There was insufficient evidence of an association among postmenopausal Veterans. Conclusions: Premenopausal Black Veterans are less likely to undergo BSO even after adjustment for salient characteristics. Our findings may have implications for equitable gynecological care for Veterans. Additional research is needed to better understand the role of differential preferences or cancer risk in these racial differences.

Clinical assays for assessment of homologous recombination DNA repair deficiency.

Homologous recombination DNA repair deficiency (HRD) is a functional defect in homologous recombination DNA repair, arising from germline or somatic mutations in BRCA1/2 or other mechanisms. Cells with HRD are more sensitive to platinum and poly(ADP-ribose) polymerase inhibitors (PARPi). HRD generates permanent changes in the genome with specific, quantifiable patterns ("genomic scars"). Clinical tests for HRD, such as the Myriad genomic instability score and Foundation Medicine loss of heterozygosity test, aim to predict the presence of HRD based on genomic features. Clinical trials of PARPi in ovarian cancer have evaluated genetic mutations and HRD genomic assays as potential biomarkers of response. Patients with HRD due to BRCA1/2 mutations are more likely to respond to PARPi than those with wild-type (WT) BRCA1/2. In some clinical trials, patients with WT BRCA1/2 who were predicted to be HRD by a genomic test exhibited greater clinical benefit from PARPi than patients with WT BRCA1/2 and no evidence of HRD. HRD tests therefore hold promise as predictive biomarkers for PARPi and other DNA-damaging agents. However, HRD tests vary in terms of the specific genomic features they measure, and the methods used to determine thresholds defining patients with HRD. Also, HRD test results and PARPi responses can be discordant: for instance, tumors with reversion mutations that restore HR function still exhibit a "genomic scar" of HRD, and PARPi resistance mechanisms independent of HR can result in lack of PARPi response despite HRD. Emerging methods to predict HRD, including genomic and functional assays, may overcome some of these challenges. Evaluation of HRD in the clinical setting is an important tool that has potential to aid patient selection for PARPi and other DNA-damaging agents in ovarian cancer, but understanding the details of these tests and their limitations is critical to ensure their optimal clinical application.

Prophylactic Gynecologic Surgery at Time of Colectomy Benefits Women with Lynch Syndrome and Colon Cancer: A Markov Cost-Effectiveness Analysis.

BACKGROUND: Women with Lynch syndrome who have completed childbearing should be offered prophylactic hysterectomy and bilateral salpingo-oophorectomy for gynecologic cancer prevention. The benefit of prophylactic gynecologic surgery at the time of colon cancer resection is unclear. OBJECTIVE: This study aimed to compare the cost, quality of life, and likelihood of being alive and free from colon, endometrial, and ovarian cancer between operative choices for patients with Lynch syndrome undergoing surgery for colon cancer. DESIGN: A Markov decision tree spanning 40 years was constructed for a hypothetical cohort of 30-year-old women with Lynch syndrome who had been diagnosed with colon cancer. Outcomes of 6 surgical strategies were compared, including segmental or total abdominal colectomy with or without hysterectomy alone or combined with bilateral salpingo-oophorectomy. SETTINGS: A Markov cost-effectiveness analysis was performed at a single center. PATIENTS: A literature search was performed identifying studies of patients with genetically diagnosed Lynch syndrome that described cost, risk of mortality, and quality of life after colon cancer resection and prophylactic gynecologic surgery. MAIN OUTCOME MEASURES: The primary outcomes measured were quality-adjusted life-years and the likelihood of being alive and free from colon, endometrial, and ovarian cancer 40 years after surgery. RESULTS: Women with Lynch syndrome who underwent a total abdominal colectomy and hysterectomy with bilateral salpingo-oophorectomy had the highest likelihood of being alive and cancer free. Total abdominal colectomy with hysterectomy was a close second, but yielded the largest amount of quality-adjusted life-years and lowest cost. LIMITATIONS: This study is limited by the statistical method and quality of studies used. CONCLUSIONS: Total abdominal colectomy with prophylactic hysterectomy at 30 years of age was the most cost-effective surgical choice in women with Lynch syndrome and colon cancer. The addition of bilateral salpingo-oophorectomy offered the highest event-free survival and lowest mortality. However, the additional morbidity of premature menopause of prophylactic salpingo-oophorectomy for younger women outweighed the benefit of ovarian cancer prevention. See Video Abstract at http://links.lww.com/DCR/B287. LA CIRUGÍA GINECOLÓGICA PROFILÁCTICA EN EL MOMENTO DE LA COLECTOMÍA BENEFICIA A LAS MUJERES CON SÍNDROME DE LYNCH Y CÁNCER DE COLON: UN ANÁLISIS DE COSTO-EFECTIVIDAD DE MARKOV: Las mujeres con síndrome de Lynch que han completado la maternidad deberían recibir histerectomía profiláctica y salpingooforectomía bilateral para la prevención del cáncer ginecológico. El beneficio de la cirugía ginecológica profiláctica en el momento de la resección del cáncer de colon no está claro.Comparar el costo, la calidad de vida y la probabilidad de estar viva y libre de cáncer de colon, endometrio y ovario entre las opciones quirúrgicas para pacientes con síndrome de Lynch sometidos a cirugía por cáncer de colon.Se construyó un árbol de decisión de Markov que abarca cuarenta años para una cohorte hipotética de mujeres de 30 años con síndrome de Lynch diagnosticadas con cáncer de colon. Se compararon los resultados de seis estrategias quirúrgicas, incluida la colectomía abdominal segmentaria o total con o sin histerectomía sola o combinada con salpingooforectomía bilateral.Se realizó un análisis de costo-efectividad de Markov en un solo centro.se realizó una búsqueda bibliográfica para identificar estudios de pacientes con síndrome de Lynch con diagnóstico genético que describieron el costo, el riesgo de mortalidad y la calidad de vida después de la resección del cáncer de colon y la cirugía ginecológica profiláctica.años de vida ajustados por calidad y probabilidad de estar vivo y libre de cáncer de colon, endometrio y ovario 40 años después de la cirugía.Las mujeres con síndrome de Lynch que se sometieron a una colectomía e histerectomía abdominal total con salpingooforectomía bilateral tuvieron la mayor probabilidad de estar vivas y libres de cáncer. La colectomía abdominal total con histerectomía fue un segundo lugar cercano, pero produjo la mayor cantidad de años de vida ajustados por calidad y el costo más bajo.Este estudio está limitado por el método estadístico y la calidad de los estudios utilizados.La colectomía abdominal total con histerectomía profiláctica a los 30 años fue la opción quirúrgica más rentable en mujeres con síndrome de Lynch y cáncer de colon. La adición de salpingooforectomía bilateral ofreció la mayor supervivencia libre de eventos y la menor mortalidad. Sin embargo, la morbilidad adicional de la menopausia prematura de la salpingooforectomía profiláctica para las mujeres más jóvenes superó el beneficio de la prevención del cáncer de ovario. Consulte Video Resumen en http://links.lww.com/DCR/B287. (Traducción-Dr. Yesenia Rojas-Khalil).

Participation of Pediatric Surgery Training Programs in Fertility Preservation Initiatives.

Purpose: The significant reduction in childhood cancer mortality has allowed for greater emphasis on survivorship issues, including infertility. This study evaluated the participation of pediatric surgery training programs in fertility preservation (FP) and exposure of fellows to adnexal cases. Materials and Methods: A survey was distributed to pediatric surgery fellowship program directors in the United States and Canada through email. Questions focused on FP participation, operative cases, FP program limitations, and fellow completion of adnexal cases. Results: Survey participation was 49% (28/57). Overall, 43% (12/28) of training programs report participation in FP initiatives. Of those who participated, the most common procedures performed were testicular tissue biopsy (58%) and testicular sperm extraction (42%) in males, and surgical transposition of the ovaries (83%) and laparoscopic oophorectomy (67%) in females. The greatest cited limitations on participation were that FP was another department's responsibility (50%) and lack of multidisciplinary team (31%). Notably, lack of operative experience in benign ovarian and testicular procedures (0%) was not a limitation. All programs, regardless of participation in FP, noted that their fellows performed benign and malignant adnexal cases. Conclusion: Less than half of pediatric surgery training programs participate in FP initiatives, despite adequate advanced minimally invasive training of fellows to perform these procedures.