IMPORTANCE:This study aimed to evaluate if there is a difference between outcomes when retropubic or transobturator midurethral sling surgery is performed at the time of colpocleisis. OBJECTIVES:The purpose of this study was to compare the surgical outcomes of the retropubic midurethral sling (RP-MUS) versus the transobturator midurethral sling (TO-MUS) in women who underwent concomitant colpocleisis, specifically 2-year MUS failure and 1-year lower urinary tract symptoms (LUTSs). A secondary aim was to identify factors associated with these surgical outcomes. STUDY DESIGN:All cases of concomitant MUS and colpocleisis within a closed, integrated health care delivery system were reviewed between April 1, 2010, and March 31, 2020. Postoperative MUS failure was defined as (1) postoperative stress urinary incontinence symptoms and/or (2) additional anti-incontinence surgery. Postoperative LUTSs were defined as (1) MUS lysis and/or (2) overactive bladder requiring management with a new treatment. RESULTS:Of the 558 women included, 454 (81%) received RP-MUS and 104 (19%) received TO-MUS. Cohort demographics were similar. Neither MUS failure (7% RP-MUS and 9% TO-MUS, P = 0.450) nor LUTSs (7% RP-MUS and 12% TO-MUS, P = 0.171) were significantly different between RP-MUS and TO-MUS. In multivariable analysis, age was found to be significantly associated with LUTSs (odds ratio 0.29, 95% confidence interval 0.09-0.93, P = 0.038 among 70-74-year-olds; odds ratio 0.28, 95% confidence interval 0.09-0.83, P = 0.022 among 75-79-year-olds). CONCLUSIONS:At the time of colpocleisis, both RP-MUS and TO-MUS were highly successful and associated with a low incidence of LUTSs, including MUS lysis. The findings of this large study support RP-MUS and TO-MUS as similarly effective anti-incontinence options at time of colpocleisis.

Supplemental Methods: to be published with the manuscript.

Background:There are over 150,000 transgender adolescents in the United States, yet research on outcomes following gender-affirming mastectomy in this age group is limited. We evaluated gender-affirming mastectomy incidence, as well as postoperative complications, including regret, in adolescents within our integrated health care system. Methods:Gender-affirming mastectomies performed from January 1, 2013 - July 31, 2020 in adolescents 12-17 years of age at the time of referral were identified. The incidence of gender-affirming mastectomy was calculated by dividing the number of patients undergoing these procedures by the number of adolescents assigned female at birth ages 12-17 within our system at the beginning of each year and amount of follow-up time within that year. Demographic information, clinical characteristics (comorbidities, mental health history, testosterone use), surgical technique, and complications, including mention of regret, of patients who underwent surgery were summarized. Patients with and without complications were compared to evaluate for differences in demographic or clinical characteristics using chi-squared tests. Results:The incidence of gender-affirming mastectomy increased 13-fold (3.7 to 47.7 per 100,000 person-years) during the study period. Of the 209 patients who underwent surgery, the median age at referral was 16 years (range 12-17) and the most common technique was double-incision (85%). For patients with greater than 1-year follow-up (n=137, 65.6%), at least one complication was found in 7.3% (n=10), which included hematoma (3.6%), infection (2.9%), hypertrophic scars requiring steroid injection (2.9%), seroma (0.7%), and suture granuloma (0.7%); 10.9 % underwent revision (n=15). There were no statistically significant differences in patient demographics and clinical characteristics between those with and without complications (p>0.05). Two patients (0.95%) had documented postoperative regret but neither underwent reversal surgery at follow-up of 3 and 7 years postoperatively. Conclusion:Between 2013-2020, we observed a marked increase in gender-affirming mastectomies in adolescents. The prevalence of surgical complications was low and of over 200 adolescents who underwent surgery, only two expressed regret, neither of which underwent a reversal operation. Our study provides useful and positive guidance for adolescent patients, their families, and providers regarding favorable outcomes with gender-affirming mastectomy.

Objective: Evaluate the incidence and characteristics of breast cancers (BC) diagnosed following an epithelial ovarian cancer (EOC) diagnosis in women with pathogenic BRCA mutations. Methods: Retrospective cohort study of all women in an integrated healthcare system with BRCA mutations diagnosed with EOC from 1/1/1997-12/31/2018. Primary outcome was rate of subsequent BC diagnosis. Sec-ondary outcomes included risk factors associated with development of BC, median time to detection following EOC, and method of detection. Results: There were 284 women with BRCA-associated EOC identified. Fifty-two women had risk-reducing mastectomy and were excluded. Of the 232 eligible women with a median follow-up of 5.6 years, 33 (14%) women were diagnosed with BC following EOC: 27 (11%) new cases and 6 (3%) recurrences. Twelve (36%) cases of BC were detected on screening mammogram, 4 (12%) on screening MRI, and 9 (27%) on work-up after presenting with a palpable lump. Twenty-nine (87%) were early stage (0-II) disease. Median interval from EOC to BC diagnosis was 80 months (IQR 32, 134) for new and 63 months (IQR 21, 94) for recurrent BCs. There was one death from breast cancer while 12 women died of ovarian cancer. Conclusions: Most BC following BRCA-associated EOC is early stage and not associated with mortality. Given BC rate similar to general population and median diagnosis at 6.6 years following ovarian cancer, increased BC screening may not be warranted in the early years after EOC diagnosis.

Objective To assess CA 125 and transvaginal ultrasound surveillance in women with BRCA1 or BRCA2 pathogenic variants in a pragmatic clinical setting with>1 year follow up. Methods Retrospective cohort study in a large integrated health care system of women identified from 1/1/2003 to 12/31/2017 with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Demographic and clinical data were collected from date of genetic testing until oophorectomy, an ovarian cancer diagnosis, or 7/1/2019. Primary outcome was frequency and findings of CA 125 tests and ultrasounds performed; secondary outcome was epithelial ovarian cancers diagnosed. Results There were 1418 women, age ≥ 30 years with a BRCA1 or BRCA2 pathogenic variant with at least one intact ovary. Of the total of 1683 ultrasounds and 2437 CA 125 tests done, 1022 ultrasounds and 1709 CA 125 tests were performed for surveillance in 771 women followed >1 year. Of these women 241 (31%) women had no surveillance, and 530 (69%) women underwent any surveillance. Only 108 (20%) underwent regular surveillance. The number who underwent regular surveillance declined each year. Twenty-one women underwent surveillance indicated surgery with only 2 ovarian cancers found by surveillance. Conclusions Many women with BRCA1 or BRCA2 pathogenic variants undergo ultrasound and CA 125 surveillance testing but abnormal surveillance testing led to diagnosis of ovarian cancer in only two cases. These findings question the use of CA 125 and ultrasound surveillance in the clinical setting for ovarian cancer detection in women with BRCA1 or BRCA2 pathogenic variants.

Objective: To identify factors associated with prevalent diabetic retinopathy (DR) among Chinese American adults with type 2 diabetes mellitus (T2DM), and to compare these factors to ones previously described for a population-based sample of Latinos with a higher DR prevalence. Design: Population-based cross-sectional study. Participants: Total of 4582 Chinese Americans aged 50 or older residing in Monterey Park, California. Methods: Participants completed an in-home questionnaire on sociodemographic status and medical history, and a comprehensive clinical eye examination, using the same protocol implemented in the Los Angeles Latino Eye Study. Fundus photographs from 7 Early Treatment Diabetic Retinopathy Study fields were graded in a masked manner using a modified Airlie House grading system to assess presence and severity of DR. Logistic regression analyses based on a conceptual model of DR risk identified factors associated with prevalent DR. Main Outcome Measures: Odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with DR and vision-threatening DR (VTDR). Results: In total, 238 participants were diagnosed with any DR; 27 of these were classified as having VTDR. Both any DR and VTDR showed statistically significant positive associations with T2DM duration (OR5-9 years = 1.24; OR10-14 years = 2.07; OR15+years = 3.99), glycosylated hemoglobin (HbA(1c)) (OR6.5%-6.9% = 1.33; OR7%-7.9% = 1.86; OR8%+ = 3.22), systolic blood pressure (SBP) (ORper 10 mmHg+ = 1.19), and insulin treatment (ORinsulin+ = 2.44). For VTDR, we also found novel associations with antihypertensive drugs (OR = 0.18; 95% CI = 0.06-0.61) and statins (OR: 4.96; 95% CI: 1.60-16.41). Chinese Americans and Latinos had a nearly identical DR probability based on HbA(1c) and SBP. However, Latinos had a higher DR probability at every year of duration of T2DM (>= 5 years). Conclusions: Although we observed an overall lower DR prevalence in Chinese Americans than in Latinos (35.8% of individuals with TD2M among Chinese Americans vs. 42.0% among Latinos), our data indicate that the impact of increasing HbA(1c) and SBP on DR probability is incrementally the same in both populations. However, increasing T2DM duration is associated with higher DR probability in Latinos than in Chinese Americans, even after controlling for other known predictors. Novel factors associated with VTDR include antihypertensive drugs and statins. However, to determine whether these drugs impact VTDR susceptibility, we need longitudinal data and more cases. (C) 2017 by the American Academy of Ophthalmology

Objective: To evaluate whether endometriosis-associated genetic variation affects risk of ovarian cancer.Design: Pooled genetic analysis.Setting: University hospital.Patient(s): Genetic data from 46,176 participants (15,361 ovarian cancer cases and 30,815 controls) from 41 ovarian cancer studies.Intervention(s): None.Main Outcome Measure(s): Endometriosis-associated genetic variation and ovarian cancer.Result(s): There was significant evidence of an association between endometriosis-related genetic variation and ovarian cancer risk, especially for the high-grade serous and clear cell histotypes. Overall we observed 15 significant burden statistics, which was three times more than expected.Conclusion(s): By focusing on candidate regions from a phenotype associated with ovarian cancer, we have shown a clear genetic link between endometriosis and ovarian cancer that warrants further follow-up. The functional significance of the identified regions and SNPs is presently uncertain, though future fine mapping and histotype-specific functional analyses may shed light on the etiologies of both gynecologic conditions. (C) 2016 by American Society for Reproductive Medicine.

Abstract Background: In U.S. women, lifetime risk of ovarian cancer is 1.37%, but some women are at a substantially lower or higher risk than this average. Methods: We have characterized the distribution of lifetime risk in the general population. Published data on the relative risks and their variances for five well-accepted risk and protective factors for ovarian cancer, oral contraceptive use, parity, tubal ligation, endometriosis, and first-degree family history of ovarian cancer in conjunction with a genetic risk score using genome-wide significant common, low penetrance variants were used. The joint distribution of these factors (i.e., risk/protective factor profiles) was derived using control data from four U.S. population–based studies, providing a broad representation of women in the United States. Results: A total of 214 combinations of risk/protective factors were observed, and the lifetime risk estimates ranged from 0.35% [95% confidence interval (CI), 0.29–0.42] to 8.78% (95% CI, 7.10–10.9). Among women with lifetime risk ranging from 4% to 9%, 73% had no family history of ovarian cancer; most of these women had a self-reported history of endometriosis. Conclusions: Profiles including the known modifiable protective factors of oral contraceptive use and tubal ligation were associated with a lower lifetime risk of ovarian cancer. Oral contraceptive use and tubal ligation were essentially absent among the women at 4% to 9% lifetime risk. Impact: This work demonstrates that there are women in the general population who have a much higher than average lifetime risk of ovarian cancer. Preventive strategies are available. Should effective screening become available, higher than average risk women can be identified. Cancer Epidemiol Biomarkers Prev; 24(4); 671–6. ©2015 AACR.

Objective Ovarian cancer is a hormone-related disease with a strong genetic basis. However, none of its high-penetrance susceptibility genes and GWAS-identified variants to date are known to be involved in hormonal pathways. Given the hypothesized etiologic role of gonadotropins, an assessment of how variability in genes involved in the gonadotropin signaling pathway impacts disease risk is warranted. Methods Genetic data from 41 ovarian cancer study sites were pooled and unconditional logistic regression was used to evaluate whether any of the 2185 SNPs from 11 gonadotropin signaling pathway genes was associated with ovarian cancer risk. A burden test using the admixture likelihood (AML) method was also used to evaluate gene-level associations. Results We did not find any genome-wide significant associations between individual SNPs and ovarian cancer risk. However, there was some suggestion of gene-level associations for four gonadotropin signaling pathway genes: INHBB (p=0.045, mucinous), LHCGR (p=0.046, high-grade serous), GNRH (p=0.041, high-grade serous), and FSHB (p=0.036, overall invasive). There was also suggestive evidence for INHA (p=0.060, overall invasive). Conclusions Ovarian cancer studies have limited sample numbers, thus fewer genome-wide susceptibility alleles, with only modest associations, have been identified relative to breast and prostate cancers. We have evaluated the majority of ovarian cancer studies with biological samples, to our knowledge, leaving no opportunity for replication. Using both our understanding of biology and powerful gene-level tests, we have identified four putative ovarian cancer loci near INHBB, LHCGR, GNRH, and FSHB that warrant a second look if larger sample sizes and denser genotype chips become available.

BACKGROUND:There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.METHODS:Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic "risk score" was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk.RESULTS:Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48-1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041).CONCLUSIONS:The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted.

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'. We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n = 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n = 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.