Exogenous Hormones and Breast Cancer Risk: Contraception, Menopausal Hormone Therapy, and Breast Cancer Survivors.

The use of exogenous estrogen and progesterone/progestin medications spans the reproductive and postreproductive lives of millions of women providing control over pregnancy timing, management of premenopausal and postmenopausal symptoms, and prevention of disease, including endometrial and ovarian cancer. These same hormones can also increase the risk of breast cancer in some settings and their use in breast cancer survivors may increase the risk of breast cancer recurrence. Given both the benefits and risks of these exogenous hormones, a detailed understanding of the available scientific evidence is imperative to help counsel individuals in their use across various settings.

When Should Prophylactic Oophorectomy Be Recommended at the Time of Elective Hysterectomy?

Gynecologists are frequently confronted with the decision of when to recommend oophorectomy at the time of an elective hysterectomy. When deciding if oophorectomy should be recommended, first a careful history and risk assessment must be performed to determine if a patient is a candidate for a risk-reducing oophorectomy. If the patient does not have a hereditary ovarian cancer risk, then it is recommended the surgeon carefully consider the implications of ovarian removal on the health of their patient. This review covers the potential benefits and risks of prophylactic oophorectomy and offers a decision aid for when to recommend this procedure.

Better late than never: why obstetricians must implement enhanced recovery after cesarean.

Despite persistent concerns about high cesarean delivery rates internationally, there has been less attention on improving perioperative outcomes for the millions of women who will experience a cesarean delivery each year. Enhanced recovery after surgery, a standardized, evidence-based, interdisciplinary protocol, has been successfully used in other surgical specialties including gynecology to improve quality of care and patient satisfaction while reducing overall health care costs through reduced length of stay. Enhanced recovery after surgery society guidelines for cesarean delivery were just released in August 2018. Obstetric patients, who face the dual challenge of being postpartum and postoperative, could benefit greatly from protocols that optimize their return to physiological function and reduce surgical morbidity. Although enhanced recovery after surgery has been widespread in other surgical specialties, uptake of this protocol in obstetrics has lagged behind. We believe enhanced recovery after surgery for cesarean delivery can effectively address 3 challenges faced by obstetrician/gynecologists. These are: (1) improving care for the high number of women undergoing cesarean deliveries; (2) using evidence-based care bundles to prevent maternal morbidity and mortality, address disparities, and reduce costs; and (3) limiting postoperative opioid prescribing in response to the opioid crisis. Enhanced recovery after surgery for cesarean delivery and other standardized care protocols have the potential to reduce the disproportionately high rates of maternal morbidity and mortality in the United States, and ensure all patients, regardless of demographics or location, receive the same level of high-quality peripartum care.

Reducing surgical site infections after hysterectomy: metronidazole plus cefazolin compared with cephalosporin alone.

BACKGROUND: Organisms that are isolated from vaginal cuff infections and pelvic abscesses after hysterectomy frequently include anaerobic vaginal flora. Metronidazole has outstanding coverage against nearly all anaerobic species, which is superior to both cefazolin and second-generation cephalosporins. Cefazolin plus metronidazole has been demonstrated to reduce infectious morbidity compared with either cefazolin or second-generation cephalosporins in other clean-contaminated procedures, which include both as colorectal surgery and cesarean delivery. OBJECTIVE: The purpose of this study was to evaluate whether the combination of cefazolin plus metronidazole before hysterectomy was more effective in the prevention of surgical site infection than existing recommendations of cefazolin or second-generation cephalosporin. STUDY DESIGN: This was a retrospective cohort study of patients in the Michigan Surgical Quality Collaborative from July 2012 through February 2015. The primary outcome was surgical site infection. Patients who were >18 years old and who underwent abdominal, vaginal, laparoscopic, or robotic hysterectomy for benign or malignant indications were included if they received 1 of the following prophylactic antibiotic regimens: cefazolin, second-generation cephalosporin, or cefazolin plus metronidazole. Multivariate logistic regression modeling was performed to evaluate the independent effect of an antibiotic regimen, and propensity score matching was used to validate the findings. RESULTS: The study included 18,255 hysterectomies. The overall rate of surgical site infection was 1.8% (n=329). The unadjusted rate of surgical site infection was 1.8% (n=267) for cefazolin, 2.1% (n=49) for second-generation cephalosporin, and 1.4% (n=13) for cefazolin plus metronidazole. After adjustment for differences in patient and operative factors among the antibiotic cohorts, compared with cefazolin plus metronidazole, we found the risk of surgical site infection was significantly higher for patients who received cefazolin (odds ratio, 2.30; 95% confidence interval, 1.06-4.99) or second-generation cephalosporin (odds ratio, 2.31; 95% confidence interval, 1.21-4.41). CONCLUSION: In this large cohort, the use of prophylactic cefazolin plus metronidazole resulted in lower surgical site infection rates after hysterectomy compared with cefazolin or second-generation cephalosporin.

Surgical site infection following hysterectomy: adjusted rankings in a regional collaborative.

BACKROUND: Surgical site infection after abdominal hysterectomy (defined as open and laparoscopic) will be a metric used to rank and penalize hospitals in the Hospital Acquired Condition Reduction program. Hospitals whose Hospital Acquired Condition Reduction score places them in the bottom quartile will lose 1% of reimbursement from the Centers of Medicaid and Medicare Services. OBJECTIVES: The objectives of this analysis were to develop a risk adjustment model for surgical site infection after hysterectomy, to calculate adjusted surgical site infection rates, to rank hospitals by the predicted to expected (P/E) ratio, and to compare the number of outlier hospitals with the number in the bottom quartile. STUDY DESIGN: This was a retrospective analysis of hysterectomies from the Michigan Surgical Quality Collaborative performed between July 1, 2012, and July 1, 2014. Superficial, deep, and organ space surgical site infections were categorized according to Centers for Disease Control and Prevention criteria. Deep and organ space surgical site infections were considered 1 group for this analysis because these spaces are contiguous after hysterectomy. Hospital rankings focused on deep/organ space events because the Hospital Acquired Condition Reduction program will rank and penalize based on them, not superficial surgical site infection. Hierarchical multivariable logistic regression, which takes into account hospital effects, was used to identify risk factors for all surgical site infections and deep/organ space surgical site infections. Predicted to expected ratios for deep surgical site infection were calculated for each hospital and used to determine hospital rankings. Outliers were defined as those hospitals who predicted to expected confidence intervals crossed the reference line of 1. The number of outlier hospitals was compared with the number in the bottom quartile. RESULTS: The overall surgical site infection rate following hysterectomy was 2.1% (351 of 16,548). Deep/organ space surgical site infection accounted for 1.0% (n = 167 of 16,548). Deep surgical site infection was associated independently with younger age, longer surgical times, gynecological cancer, and open hysterectomy. There was a marginal association with blood transfusion. After risk adjustment of rates and ranking by the predicted to expected ratio, there was a change in quartile rank for 42.8% of hospitals (21 of 49). Two hospitals were identified as outliers. However, if the bottom quartile was identified, as called for by the Hospital Acquired Condition Reduction program, 10 additional hospitals would be targeted for a penalty. Hospitals with < 300 beds were most likely to see their quartile rank worsen, whereas those > 500 beds were most likely to see their quartile rank improve (P = .01). CONCLUSION: After adjusting for patient-related factors and site variation, more than 40% of hospitals will change quartile rank with respect to deep surgical site infection. Identifying a quartile of hospitals that are statistically different from others was not feasible in our collaborative because only 2 of 12 hospitals were outliers. These findings suggest that under the Hospital Acquired Condition Reduction program, many hospitals will be unjustly penalized.

Controversies in Screening Mammography.

The utility and effectiveness of screening mammography in diagnosing breast cancer at earlier stages and reducing disease-specific mortality remain controversial especially as to when to start and stop routine mammographic screening, and whether mammograms should be performed annually or biennially in average-risk women. This manuscript will analyze the available moderate and high-quality data to analyze both the benefits (lives saved and life-years saved) and inconveniences/harms (additional views, extra biopsies/overdiagnosis, and overtreatment of ductal carcinoma in situ) of different mammography screening guidelines to assist the practitioner in counseling their patients in clinical practice.

Use of other treatments before hysterectomy for benign conditions in a statewide hospital collaborative.

OBJECTIVE: We sought to analyze use of alternative treatments and pathology among women who underwent hysterectomy in the Michigan Surgical Quality Collaborative. STUDY DESIGN: Perioperative hysterectomy data including demographics, preoperative alternative treatments, and pathology results were analyzed from 52 hospitals participating in the Michigan Surgical Quality Collaborative from Jan. 1 through Nov. 8, 2013. Women who underwent hysterectomy for benign indications including uterine fibroids, abnormal uterine bleeding (AUB), endometriosis, or pelvic pain were eligible. Pathology was classified as "supportive" when fibroids, endometriosis, endometrial hyperplasia, adenomyosis, adnexal pathology, or unexpected cancer were reported and "unsupportive" if these conditions were not reported. Multivariable analysis was done to determine independent associations with use of alternative treatment and unsupportive pathology. RESULTS: Inclusion criteria were met by 56.2% (n = 3397) of those women who underwent hysterectomy (n = 6042). There was no documentation of alternative treatment prior to hysterectomy in 37.7% (n = 1281). Alternative treatment was more likely to be considered among women aged <40 years vs those aged 40-50 and >50 years (68% vs 62% vs 56%, P < .001) and among women with larger uteri. Unsupportive pathology was identified in 18.3% (n = 621). The rate of unsupportive pathology was higher among women age <40 years vs those aged 40-50 and >50 years (37.8% vs 12.0% vs 7.5%, P < .001), among women with an indication of endometriosis/pain vs uterine fibroids and/or AUB, and among women with smaller uteri. CONCLUSION: This study provides evidence that alternatives to hysterectomy are underutilized in women undergoing hysterectomy for AUB, uterine fibroids, endometriosis, or pelvic pain. The rate of unsupportive pathology when hysterectomies were done for these indications was 18%.

Outcome of unexpected adnexal neoplasia discovered during risk reduction salpingo-oophorectomy in women with germ-line BRCA1 or BRCA2 mutations.

OBJECTIVE: This study computed the risk of clinically silent adnexal neoplasia in women with germ-line BRCA1 or BRCA2 mutations (BRCA(m+)) and determined recurrence risk. METHODS: We analyzed risk reduction salpingo-oophorectomies (RRSOs) from 349 BRCA(m+) women processed by the SEE-FIM protocol and addressed recurrence rates for 29 neoplasms from three institutions. RESULTS: Nineteen neoplasms (5.4%) were identified at one institution, 9.2% of BRCA1 and 3.4% of BRCA2 mutation-positive women. Fourteen had a high-grade tubal intraepithelial neoplasm (HGTIN, 74%). Mean age (54.4) was higher than the BRCA(m+) cohort without neoplasia (47.8) and frequency increased with age (p < 0.001). Twenty-nine BRCA(m+) patients with neoplasia from three institutions were followed for a median of 5 years (1-8 years.). One of 11 with HGTIN alone (9%) recurred at 4 years, in contrast to 3 of 18 with invasion or involvement of other sites (16.7%). All but two are currently alive. Among the 29 patients in the three institution cohort, mean ages for HGTIN and advanced disease were 49.2 and 57.7 (p = 0.027). CONCLUSIONS: Adnexal neoplasia is present in 5-6% of RRSOs, is more common in women with BRCA1 mutations, and recurs in 9% of women with HGTIN alone. The lag in time from diagnosis of the HGTIN to pelvic recurrence (4 years) and differences in mean age between HGTIN and advanced disease (8.5 years) suggest an interval of several years from the onset of HGTIN until pelvic cancer develops. However, some neoplasms occur in the absence of HGTIN.

Injury during pregnancy and nervous system birth defects: Texas, 1999 to 2003.

BACKGROUND: Case reports and series have suggested an association between injury during pregnancy and several nervous system and nervous system-related adverse fetal/neonatal outcomes. This study's purpose is to further determine if there is an association between injury during pregnancy and nervous system birth defects in infancy. METHODS: Through a case-control study, the association between injury during pregnancy and nervous system birth defects was tested using the Texas Birth Defects Registry (1999-2003). Semiautomated probabilistic bias analysis was used to correct for systematic error from misclassification of injury during pregnancy. RESULTS: Of the 59,750 infants eligible for this study, 4144 (6.94%) were diagnosed with a nervous system birth defect and 315 (0.53%) of the infants' mothers were injured during pregnancy. Among these 315 women, 25 (7.94%) delivered an infant with a subsequent nervous system birth defect. The adjusted odds ratio for the association between injury during pregnancy and nervous system birth defects among all study infants was 1.00; 95% confidence interval, 0.63-1.56 and 2.44; 95% confidence interval, 1.08-5.53 among breech presentation infants. Probabilistic bias analysis supported these findings. CONCLUSION: No association between injury during pregnancy and nervous system birth defects was identified. Further exploration into the association among breech presentation infants is warranted.

Does tamoxifen use increase the risk of endometrial cancer in premenopausal patients?

In a large, nationwide retrospective longitudinal cohort study that examined the occurrence of endometrial cancer and other uterine pathology in patients using tamoxifen for treatment of invasive breast cancer compared with breast cancer patients not receiving tamoxifen, the authors found a 3.77-fold increased risk of endometrial cancer in premenopausal patients using tamoxifen. These data conflict with multiple previously published randomized controlled trials that demonstrated an increased risk of endometrial cancer in the postmenopausal population (but not in premenopausal patients). The experts suggest that a study design issue in the recent study may explain these disparate findings.

Effect of frozen storage on dynamic tensile properties of human placenta.

Dynamic mechanical properties of placenta tissue are needed to develop computational models of pregnant occupants for use in designing restraint systems that protect the fetus and mother. Tests were performed on 21 samples obtained from five human placentas at a rate of 1200 %/s using a set of custom designed thermoelectrically cooled clamps. Approximately half of the samples from all five subjects were tested within 48 h of delivery. The remaining samples were frozen for 5-7 days and then thawed before testing. True failure stresses and strains were not significantly different between fresh and frozen samples (p-value = 0.858 and 0.551, respectively), suggesting that soft tissue may be stored frozen up to a week without adversely affecting dynamic material response.

Descriptive epidemiology of birth trauma in the United States in 2003.

The rate of birth trauma in the US has been reported to range between 0.2 and 37 birth traumas per 1000 births. Because of the minimal number of population-based studies and the inconsistencies among the published birth trauma rates, the rate of birth trauma in the US remains unclear. This is a cross-sectional study that was conducted using 890 582 in-hospital birth discharges from the 2003 Healthcare Cost and Utilization Project Kids' Inpatient Database. A neonate was defined as having birth trauma if their hospital discharge record contained an International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code from 767.0 to 767.9. Weighted data were used to calculate rates for all birth traumas and specific types of birth traumas, and rates and odds ratios by demographic, hospital and clinical variables. Weighted data represented a national estimate of 3 920 787 in-hospital births. Birth trauma was estimated to occur in 29 per 1000 births. The three most frequently diagnosed birth traumas were injuries to the scalp, other injuries to the skeleton and fracture of the clavicle. Significant univariable predictors for birth trauma included male gender, Asian or Pacific Islander race, living in urban or wealthy areas, being born in Western, urban and/or teaching hospital, a co-diagnosis of high birthweight, instrument delivery, malpresentation and other complications during labour and delivery. Birth trauma risk factors including those identified in this study may be useful to consider during labour and delivery. In conclusion, additional research is necessary to identify ways to reduce birth trauma and subsequent infant morbidity and mortality.

Radiologic-Histopathologic Correlation of Transvaginal US and Risk-reducing Salpingo-oophorectomy for Women at High Risk for Tubo-ovarian Carcinoma.

Purpose: To examine radiologic-histopathologic correlation and the diagnostic performance of transvaginal US prior to risk-reducing salpingo-oophorectomy (RRSO) in women at high risk for tubo-ovarian carcinoma (TOC). Materials and Methods: This retrospective study included 147 women (mean age, 49 years; age range, 28-75 years) at high risk for TOC who underwent transvaginal US within 6 months of planned RRSO between May 1, 2007, and March 14, 2018. Histopathologic results were reviewed. Fellowship-trained abdominal radiologists reinterpreted transvaginal US findings by using standardized descriptors. Descriptive statistical analysis and multiple logistic regression were performed. Results: Of the 147 women, 136 had mutations in BRCA1, BRCA2, Lynch syndrome, BRIP1, and RAD51D genes, and 11 had a family history of TOC. Histopathologic reports showed 130 (88.4%) benign nonneoplastic results, 10 (6.8%) benign neoplasms, five (3.4%) malignant neoplasms, and two (1.4%) isolated p53 signature lesions. Transvaginal US results showed benign findings in 95 (64.6%) women and abnormal findings in 11 (7.5%) women; one or both ovaries were not visualized in 41 (27.9%) women. Hydrosalpinx was absent in all TOC and p53 signature lesions at transvaginal US. Transvaginal US had 20% sensitivity (one of five), 93% specificity (132 of 142), 9% positive predictive value (one of 11), and 97% negative predictive value (132 of 136) for TOC. Cancer was detected in one of five women at transvaginal US, and three of five false-negative lesions were microscopic or very small. Conclusion: Preoperative transvaginal US had low sensitivity for detecting TOC in women at high risk for TOC. Clinically relevant precursors and early cancers were too small to be detected.Keywords: Genital/Reproductive, UltrasoundSupplemental material is available for this article.© RSNA, 2020.

Prospective Imaging Trial Assessing Gadoteridol Retention in the Deep Brain Nuclei of Women Undergoing Breast MRI.

RATIONALE AND OBJECTIVES: To assess for indirect evidence of gadoteridol retention in the deep brain nuclei of women undergoing serial screening breast MRI. METHODS: This HIPAA-compliant prospective observational noninferiority imaging trial was approved by the IRB. From December 2016 to March 2018, 12 consented subjects previously exposed to 0-1 doses of gadoteridol (group 1) and 7 consented subjects previously exposed to ≥4 doses of gadoteridol (group 2) prospectively underwent research-specific unenhanced brain MRI including T1w spin echo imaging and T1 mapping. Inclusion criteria were: (1) planned breast MRI with gadoteridol, (2) no gadolinium exposure other than gadoteridol, (3) able to undergo MRI, (4) no neurological illness, (5) no metastatic disease, (6) no chemotherapy. Regions of interest were manually drawn in the globus pallidus, thalamus, dentate nucleus, and pons. Globus pallidus/thalamus and dentate nucleus/pons signal intensities and T1-time ratios were calculated using established methods and correlated with cumulative gadoteridol dose (mL). RESULTS: All subjects were female (mean age: 50 ± 12 years) and previously had received an average of 0.5 ± 0.5 (group 1) and 5.9 ± 2.1 (group 2) doses of gadoteridol (cumulative dose: 8 ± 8 and 82 ± 31 mL, respectively), with the last dose an average of 492 ± 299 days prior to scanning. There was no significant correlation between cumulative gadoteridol dose (mL) and deep brain nuclei signal intensity at T1w spin echo imaging (p = 0.365-0.512) or T1 mapping (p = 0.197-0.965). CONCLUSION: We observed no indirect evidence of gadolinium retention in the deep brain nuclei of women undergoing screening breast MRI with gadoteridol.

Executive Summary of the Early-Onset Breast Cancer Evidence Review Conference.

The Centers for Disease Control and Prevention launched the Bring Your Brave campaign to increase knowledge about early-onset breast cancer, defined as breast cancer in women aged 18-45 years. The American College of Obstetricians and Gynecologists convened a panel of experts in breast disease from the Society for Academic Specialists in General Obstetrics and Gynecology to review relevant literature, validated tools, best practices, and practice guidelines as a first step toward developing educational materials for women's health care providers about early-onset breast cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at an in-person meeting of stakeholder professional and patient advocacy organizations in April 2019. This article summarizes the relevant literature, existing guidance, and validated tools to guide health care providers in the prevention, early detection, and special considerations of early-onset breast cancer. Substantive knowledge gaps were noted and summarized to provide guidance for future research.

Guidance for Evaluation and Management of Blunt Abdominal Trauma in Pregnancy.

Blunt abdominal trauma is the leading type of traumatic injury in pregnancy, with motor vehicle crashes, falls, and assault being the most common etiologies. Several adverse outcomes can occur in pregnancy, including placental abruption, preterm labor and preterm delivery, uterine rupture, and pelvic fracture. Understanding and integration of key anatomic and physiologic changes in pregnancy are key when evaluating a pregnant trauma patient. Pregnant women should be managed in a medical center with the ability to provide adequate care to both trauma patients-the pregnant woman and fetus. Multiple clinical providers are usually involved in the care of pregnant trauma patients, but obstetric providers should play a central role in the evaluation and management of a pregnant trauma patient given their unique training, knowledge, and clinical skills. An algorithm for management of trauma in pregnancy should be used at all sites caring for pregnant women. An alignment of policies within each system optimizes appropriate triage, integration of care, management, and monitoring of pregnant trauma patients and their fetuses. Ensuring effective protocols for prehospital and hospital treatment, as well as thorough training of involved health care providers, is essential in ensuring that optimal care is provided.

Fetal outcome in motor-vehicle crashes: effects of crash characteristics and maternal restraint.

OBJECTIVE: This project was undertaken to improve understanding of factors associated with adverse fetal outcomes of pregnant occupants involved in motor-vehicle crashes. STUDY DESIGN: In-depth investigations of crashes involving 57 pregnant occupants were performed. Maternal and fetal injuries, restraint information, measures of external and internal vehicle damage, and details about the crash circumstances were collected. Crash severity was calculated using vehicle crush measurements. Chi-square analysis and logistic regression models were used to determine factors with a significant association with fetal outcome. RESULTS: Fetal outcome is most strongly associated with crash severity (P < .001) and maternal injury (P = .002). Proper maternal belt-restraint use (with or without airbag deployment) is associated with acceptable fetal outcome (odds ratio = 4.5, P = .033). Approximately half of fetal losses in motor-vehicle crashes could be prevented if all pregnant women properly wore seat belts. CONCLUSION: Higher crash severity, more severe maternal injury, and lack of proper seat belt use are associated with a higher risk of adverse fetal outcome. These results strongly support recommendations that pregnant women use properly positioned seatbelts.

Trauma during pregnancy: outcomes and clinical management.

Trauma affects up to 6% to 7% of all pregnancies, and accounts for up to 46% of maternal death. Adverse consequences such as preterm labor and delivery, abruptio, fetomaternal hemorrhage, and fetal demise may be seen with even apparently minor degrees of injury. Maternal physiologic considerations are reviewed and a protocol for evaluation and management of the injured gravida is presented.

Transplacental passage of vancomycin in noninfected term pregnant women.

OBJECTIVE: To evaluate the transplacental passage of vancomycin in term, uninfected pregnant women. METHODS: A single vancomycin 1-g dose was administered intravenously at four separate time intervals to 13 uncomplicated nonlaboring women undergoing scheduled cesarean delivery. Samples of maternal blood and fetal cord blood were collected at time of delivery and vancomycin concentrations assayed. RESULTS: Vancomycin concentrations in maternal serum ranged from 2.6 to 19.8 mcg/mL. In cord blood samples, vancomycin concentrations ranged from 2.8 to 9.4 mcg/mL and persisted above the group B streptococci vancomycin breakpoint of 1 mcg/mL. Only 6 of 13 women received the full 1-g vancomycin dose because 53.8% (7 of 13) had some manifestation of red man syndrome during the infusion. No other short term sequelae were identified in any patients or their fetuses. A strong correlation (r(2)=0.93, P<.001) between cord and maternal serum concentrations versus time was noted. Cord vancomycin concentrations approached maternal serum concentrations 4 hours after the infusion ended. CONCLUSION: Vancomycin crosses the placenta in a predictable manner in concentrations that exceed the usual group B streptococci breakpoint. Adverse events were common, suggesting that longer infusion times and weight adjusted doses should be used.