Effect of risk-reducing salpingo-oophorectomy on sex steroid hormone serum levels among postmenopausal women: an NRG Oncology/Gynecologic Oncology Group study.

BACKGROUND: Risk-reducing salpingo-oophorectomy is an effective ovarian cancer risk reduction strategy. However, bilateral oophorectomy has also been associated with increased long-term nonneoplastic sequelae, effects suggested to be mediated through reductions in systemic sex steroid hormone levels. Currently, it is unclear whether the postmenopausal ovary contributes to the systemic hormonal milieu or whether postmenopausal ovarian volume or other factors, such as body mass index and age, affect systemic hormone levels. OBJECTIVE: We examined the impact of oophorectomy on sex steroid hormone levels in postmenopausal women. Furthermore, we explored how well ovarian volume measured by transvaginal ultrasound correlated with direct ovarian measures obtained during surgical pathology evaluation and investigated the association between hormone levels and ovarian volumes. STUDY DESIGN: Postmenopausal women who underwent risk-reducing salpingo-oophorectomy (180 cases) or ovarian cancer screening (38 controls) enrolled in an international, prospective study of risk-reducing salpingo-oophorectomy and risk of ovarian cancer algorithm-based screening among women at increased risk of ovarian cancer (Gynecologic Oncology Group-0199) were included in this analysis. Controls were frequency matched to the cases on age at menopause, age at study entry, and time interval between blood draws. Ovarian volume was calculated using measurements obtained from transvaginal ultrasound in both cases and controls and measurements recorded in surgical pathology reports from cases. Serum hormone levels of testosterone, androstenedione, androstenediol, dihydrotestosterone, androsterone, dehydroepiandrosterone, estrone, estradiol, and sex hormone-binding globulin were measured at baseline and follow-up. Spearman correlation coefficients were used to compare ovarian volumes as measured on transvaginal ultrasound and pathology examinations. Correlations between ovarian volumes by transvaginal ultrasound and measured hormone levels were examined using linear regression models. All models were adjusted for age. Paired t tests were performed to evaluate individual differences in hormone levels before and after risk-reducing salpingo-oophorectomy. RESULTS: Ovarian volumes measured by transvaginal ultrasound were only moderately correlated with those reported on pathology reports (Spearman rho [ρ]=0.42). The median time interval between risk-reducing salpingo-oophorectomy and follow-up for the cases was 13.3 months (range, 6.0-19.3), and the median time interval between baseline and follow-up for the controls was 12.7 months (range, 8.7-13.4). Sex steroid levels decreased with age but were not correlated with transvaginal ultrasound ovarian volume, body mass index, or time since menopause. Estradiol levels were significantly lower after risk-reducing salpingo-oophorectomy (percentage change, -61.9 post-risk-reducing salpingo-oophorectomy vs +15.2 in controls; P=.02), but no significant differences were seen for the other hormones. CONCLUSION: Ovarian volumes measured by transvaginal ultrasound were moderately correlated with volumes directly measured on pathology specimens and were not correlated with sex steroid hormone levels in postmenopausal women. Estradiol was the only hormone that declined significantly after risk-reducing salpingo-oophorectomy. Thus, it remains unclear whether the limited post-risk-reducing salpingo-oophorectomy changes in sex steroid hormones among postmenopausal women impact long-term adverse outcomes.

Beyond Sedlis-A novel histology-specific nomogram for predicting cervical cancer recurrence risk: An NRG/GOG ancillary analysis.

PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.

Prospective follow-up of quality of life for participants undergoing risk-reducing salpingo-oophorectomy or ovarian cancer screening in GOG-0199: An NRG Oncology/GOG study.

BACKGROUND: Risk-reducing salpingo-oophorectomy (RRSO) and ovarian cancer screening (OCS) are management options for women at increased risk of ovarian cancer. Long-term effects of these interventions on quality of life (QOL) are not well understood. METHODS: GOG-0199 is a prospective cohort study of women at increased ovarian cancer risk who chose either RRSO or OCS as their risk management intervention. At study entry, 6, 12, 24 and 60 months of follow-up, participants completed the QOL questionnaire, which included the Medical Outcome Study Short Form-36, the Impact of Events Scales, the Center for Epidemiological Studies Depression Scale, the State-Trait Anxiety Inventory, the Functional Assessment of Cancer Therapy - Endocrine Subscale, and the Sexual Activity Questionnaire. QOL measures were compared between the RRSO and OCS cohort at baseline and over time. RESULTS: Five-hundred-sixty-two participants in the RRSO cohort and 1,010 in the OCS completed the baseline and at least one follow-up questionnaire. At baseline, participants selecting RRSO reported lower health-related QOL (HRQOL), greater ovarian cancer-related stress, greater anxiety, and more depressive symptomatology, which improved during follow-up, especially for ovarian cancer-related stress. Screening was not found to adversely impact HRQOL. Hormone-related menopausal symptoms worsened and sexual functioning declined during follow-up in both cohorts, but more so among participants who underwent RRSO. CONCLUSIONS: HRQOL improved after surgery among women who chose RRSO and remained stable among participants undergoing screening. The adverse effects of RRSO and screening on short-term and long-term sexual activity and sexual functioning warrant consideration in the decision-making process for high-risk women.

Lean mass explains the association between muscular fitness and bone outcomes in 13-year-old boys.

AIM: This study investigated the associations between fitness indices and bone outcomes in young males. METHODS: Data were collected between autumn and winter 2014-2015 on 121 males with a mean age of 13.1 ± 0.1 years: 41 swimmers, 37 footballers, 29 cyclists and 14 nonathletes. Participants were recruited from athletic clubs and schools across South West England. Lean mass, areal bone mineral density and hip structural estimates were measured using dual-energy X-ray absorptiometry. The relationships between bone outcomes and the vertical jump, standing long jump and the 20-m shuttle run test were analysed using three regression models: model 1 was adjusted by age and stature, model 2 added vigorous physical activity and model 3 then added lean mass. RESULTS: The boys' performance in the vertical jump and standing long jump was positively associated with the majority of bone outcomes in models 1 and 2, but most of these disappeared in model 3. The 20-m shuttle run test was positively associated with most bone outcomes in all three models. Lean mass played a key role in the association between muscular fitness and bone outcomes. CONCLUSION: Vigorous physical activity did not explain the associations between fitness and bone outcomes, but lean mass did.

Soft tissues, areal bone mineral density and hip geometry estimates in active young boys: the PRO-BONE study.

PURPOSE: Soft tissues, such as fat mass (FM) and lean mass (LM), play an important role in bone development but this is poorly understood in highly active youths. The objective of this study was to determine whether FM or LM is a stronger predictor of areal bone mineral density (aBMD) and hip geometry estimates in a group of physically active boys after adjusting for height, chronological age, moderate-to-vigorous physical activity (MVPA), FM, and LM. METHODS: Participants included 121 boys (13.1 ± 1.0 years) from the PRO-BONE study. Bone mineral content (BMC) and aBMD were measured at total body, femoral neck and lumbar spine using dual-energy X-ray absorptiometry (DXA), and hip structural analysis was used to estimate bone geometry at the femoral neck. Body composition was assessed using DXA. The relationships of FM and LM with bone outcomes were analysed using simple and multiple linear regression analyses. RESULTS: Pearson correlation coefficients showed that total body (less head) aBMD was significantly correlated with LM but not FM. Multiple linear regression analyses showed that FM, after accounting for height, age, MVPA and LM had no significant relationship with aBMD or hip geometry estimates, except for arms aBMD. By contrast, there were positive associations between LM and most aBMD and hip geometry estimates, after accounting height, age, MVPA and FM. CONCLUSIONS: The results of this study suggest that LM, and not FM, is the stronger predictor of aBMD and hip geometry estimates in physically active boys. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN17982776.

Is cardiac autonomic function associated with cardiorespiratory fitness and physical activity in children and adolescents? A systematic review of cross-sectional studies.

BACKGROUND: Heart rate variability (HRV) is considered to explain improvements in cardiovascular health accrued by physical activity (PA) and cardiorespiratory fitness (CRF) over and above traditional cardiovascular risk factors. OBJECTIVE: To systematically address associations between HRV, PA and CRF in children and adolescents. DATA SOURCES: Medline, EMBASE, SportDISCUS and CINAHL Plus were searched on 5th September 2015 and updated on 4th August 2016. ELIGIBILITY CRITERIA: Observational studies comparing HRV in different groups of PA and CRF, and/or studies investigating associations between PA, CRF and HRV. Sports practices and PA intensities were also included. The square root of the mean of the sum of the squares of differences between adjacent RR intervals (RMSSD), the spectral density in the high (HF) and low (LF) frequency, and the LF/HF ratio were included. Risk of bias was assessed using the adapted Newcastle-Ottawa Scale (NOS). RESULTS: Heterogeneity exists in the assessment of the exposures and outcomes, and sample characteristics. Risk of bias (NOS) was observed in most of the studies. Studies with low risk of bias showed positive associations between moderate-to-vigorous PA and RMSSD. The evidence for the associations between PA and frequency indices is weak. Similarly, the evidence for the association between CRF and HRV is weak. CONCLUSIONS: Despite the heterogeneity in the studies, moderate-to-vigorous PA is positively associated with RMSSD, but less clear are the associations between CRF and HRV, as well as other PA intensities. Further research is needed to clarify the role of PA and CRF on HRV in children and adolescents.

Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study.

OBJECTIVE:  To compare the predictive accuracy and clinical utility of five risk scoring systems in the assessment of patients with upper gastrointestinal bleeding. DESIGN:  International multicentre prospective study. SETTING:  Six large hospitals in Europe, North America, Asia, and Oceania. PARTICIPANTS:  3012 consecutive patients presenting over 12 months with upper gastrointestinal bleeding. MAIN OUTCOME MEASURES:  Comparison of pre-endoscopy scores (admission Rockall, AIMS65, and Glasgow Blatchford) and post-endoscopy scores (full Rockall and PNED) for their ability to predict predefined clinical endpoints: a composite endpoint (transfusion, endoscopic treatment, interventional radiology, surgery, or 30 day mortality), endoscopic treatment, 30 day mortality, rebleeding, and length of hospital stay. Optimum score thresholds to identify low risk and high risk patients were determined. RESULTS:  The Glasgow Blatchford score was best (area under the receiver operating characteristic curve (AUROC) 0.86) at predicting intervention or death compared with the full Rockall score (0.70), PNED score (0.69), admission Rockall score (0.66, and AIMS65 score (0.68) (all P<0.001). A Glasgow Blatchford score of ≤1 was the optimum threshold to predict survival without intervention (sensitivity 98.6%, specificity 34.6%). The Glasgow Blatchford score was better at predicting endoscopic treatment (AUROC 0.75) than the AIMS65 (0.62) and admission Rockall scores (0.61) (both P<0.001). A Glasgow Blatchford score of ≥7 was the optimum threshold to predict endoscopic treatment (sensitivity 80%, specificity 57%). The PNED (AUROC 0.77) and AIMS65 scores (0.77) were best at predicting mortality, with both superior to admission Rockall score (0.72) and Glasgow Blatchford score (0.64; P<0.001). Score thresholds of ≥4 for PNED, ≥2 for AIMS65, ≥4 for admission Rockall, and ≥5 for full Rockall were optimal at predicting death, with sensitivities of 65.8-78.6% and specificities of 65.0-65.3%. No score was helpful at predicting rebleeding or length of stay. CONCLUSIONS:  The Glasgow Blatchford score has high accuracy at predicting need for hospital based intervention or death. Scores of ≤1 appear the optimum threshold for directing patients to outpatient management. AUROCs of scores for the other endpoints are less than 0.80, therefore their clinical utility for these outcomes seems to be limited.Trial registration Current Controlled Trials ISRCTN16235737.