External validation of an artificial intelligence model for Gleason grading of prostate cancer on prostatectomy specimens.

OBJECTIVES: To externally validate the performance of the DeepDx Prostate artificial intelligence (AI) algorithm (Deep Bio Inc., Seoul, South Korea) for Gleason grading on whole-mount prostate histopathology, considering potential variations observed when applying AI models trained on biopsy samples to radical prostatectomy (RP) specimens due to inherent differences in tissue representation and sample size. MATERIALS AND METHODS: The commercially available DeepDx Prostate AI algorithm is an automated Gleason grading system that was previously trained using 1133 prostate core biopsy images and validated on 700 biopsy images from two institutions. We assessed the AI algorithm's performance, which outputs Gleason patterns (3, 4, or 5), on 500 1-mm2 tiles created from 150 whole-mount RP specimens from a third institution. These patterns were then grouped into grade groups (GGs) for comparison with expert pathologist assessments. The reference standard was the International Society of Urological Pathology GG as established by two experienced uropathologists with a third expert to adjudicate discordant cases. We defined the main metric as the agreement with the reference standard, using Cohen's kappa. RESULTS: The agreement between the two experienced pathologists in determining GGs at the tile level had a quadratically weighted Cohen's kappa of 0.94. The agreement between the AI algorithm and the reference standard in differentiating cancerous vs non-cancerous tissue had an unweighted Cohen's kappa of 0.91. Additionally, the AI algorithm's agreement with the reference standard in classifying tiles into GGs had a quadratically weighted Cohen's kappa of 0.89. In distinguishing cancerous vs non-cancerous tissue, the AI algorithm achieved a sensitivity of 0.997 and specificity of 0.88; in classifying GG ≥2 vs GG 1 and non-cancerous tissue, it demonstrated a sensitivity of 0.98 and specificity of 0.85. CONCLUSION: The DeepDx Prostate AI algorithm had excellent agreement with expert uropathologists and performance in cancer identification and grading on RP specimens, despite being trained on biopsy specimens from an entirely different patient population.

Hypogonadism, frailty, and postoperative outcomes among men undergoing radical nephrectomy.

BACKGROUND AND OBJECTIVE: Hypogonadism and frailty may impact postoperative outcomes for men undergoing radical nephrectomy (RN). We aimed to determine the prevalence of hypogonadism in men undergoing RN and whether hypogonadism and frailty are associated with adverse postoperative outcomes. METHODS: We identified men undergoing RN between 2012 and 2021 using the IBM Marketscan database. Frailty was determined using the Hospital Frailty Risk Score (HFRS). Patients were considered to have hypogonadism if diagnosed <5 years before RN. Length of stay (LOS), complications, emergency department (ED) visits, and readmissions were evaluated between men with and without hypogonadism at the time of surgery. Subgroup analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 13 598 men who underwent RN, 972 (7.1%) had hypogonadism. Men with hypogonadism were more frail compared to men without hypogonadism (HFRS: median: 8.2, interquartile range [IQR]: 5.2-11.7 vs. median: 7.0, IQR: 4.3-10.7, p < 0.001) and had increased incidence of postoperative ileus (13.0% vs. 10.8%, p = 0.045), acute kidney injury (25.5% vs. 21.6% p = 0.005), and cardiac arrest (1.2% vs. 0.6%, p = 0.034). Hypogonadism was not associated with LOS, 90-day ED visit or readmission. However, high-risk frailty was associated with increased risk of 90-day ED visit (hazard ratio [HR]: 2.1, 95% confidence interval [95% CI]: 1.9-2.4, p < 0.001) and 90-day inpatient readmission (HR: 2.6, 95% CI: 2.2-3.1, p < 0.001), compared to low-risk frailty patients. Among men with hypogonadism, TRT was not associated with any postoperative outcomes. CONCLUSIONS: Hypogonadism and frailty should be considered in the preoperative evaluation for men undergoing RN as risk factors for adverse postoperative outcomes.

ALDH2 Expression, Alcohol Intake and Semen Parameters among East Asian Men.

PURPOSE: Inactivating mutations in mitochondrial aldehyde dehydrogenase 2 (ALDH2) are highly prevalent. The most common variant allele, ALDH2*2, is present in 40%-50% of East Asians, and causes acetaldehyde accumulation, flushing and tachycardia after alcohol intake. The relationship between alcohol intake and ALDH2 genotype on semen parameters remains unknown. MATERIALS AND METHODS: We conducted a cross-sectional study to determine the association between ALDH2 genotype, alcohol consumption and semen parameters among East Asian men. Volunteers completed a survey and submitted a semen sample for analysis. Participants were genotyped to determine ALDH2 status (ALDH2*1/*1, ALDH2*1/*2, ALDH2*2/*2), and immunohistochemical staining was used to determine protein expression of ALDH2 in spermatozoa. RESULTS: Of 112 men 45 (40.2%) were ALDH2*2 carriers. Among ALDH2*2 carriers, alcohol consumption was associated with significantly lower total sperm motility (median 20% [interquartile range 11%-42%] vs 43% [IQR 31%-57%], p=0.005) and progressive sperm motility (19% [IQR 11%-37%] vs 36% [IQR 25%-53%], p=0.008). Among alcohol consumers, ALDH2*2 carriers had significantly lower total sperm motility (20% [IQR 11%--42%] vs 41% [IQR 19%-57%], p=0.02), progressive sperm motility (19% [IQR 11%-37%] vs 37% [IQR 17%-50%], p=0.02) and total motile sperm count (28 million [M; IQR 9-79M] vs 71M [IQR 23-150M], p=0.05) compared to ALDH2*1/*1 individuals. Secondly, ALDH2 expression in human spermatozoa was significantly lower in ALDH2*2 carriers (ALDH2*1/*1 vs ALDH2*1/*2, p=0.01; ALDH2*1/*1 vs ALDH2*2/*2, p <0.001). CONCLUSIONS: Our findings suggest genotyping ALDH2, coupled with alcohol cessation counseling, may improve semen parameters among men.

Primary malignancies of the epididymis: clinical characteristics and prognostic factors.

INTRODUCTION We sought to describe clinical characteristics and identify prognostic factors among patients with primary malignancies of the epididymis (PMEs). MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2015) was queried to identify patients with PME. Descriptive statistics and multivariable Cox proportional hazards models were used. RESULTS: Eighty-nine patients with PME were identified. Median age was 57 years (5-85), and median overall survival (OS) was 16.8 years. The most commonly represented histologies were rhabdomyosarcoma (19.1%), B-cell lymphoma (16.9%), leiomyosarcoma (16.9%), and liposarcoma (12.4%). In multivariable analysis, tumor size ≥ 4 cm was associated with worse OS (HR = 4.46, p = 0.01) compared to tumors < 4 cm. Patients with nonsarcomatoid histology had OS similar to patients with sarcomatoid histology (HR = 0.95, p = 0.92). Disease with regional invasion (HR = 5.19, p = 0.007) and distant metastasis (HR = 29.80, p = 0.0002) had worse OS compared to localized disease. Receipt of radiotherapy was associated with enhanced OS (HR = 0.10, p = 0.006), whereas receipt of chemotherapy was not associated with OS. CONCLUSIONS: We describe the largest cohort of PMEs to date. Larger lesions and tumor stage were independently associated with poor overall survival, while receipt of radiotherapy was associated with enhanced overall survival.

Male and Female Sexual Dysfunction in Pediatric Cancer Survivors.

BACKGROUND: Pediatric cancer survivors suffer indirect long-term effects of their disease; however, there is a paucity of data regarding the effect of pediatric cancer survivorship on sexual function. AIM: To assess the prevalence and risk factors associated with sexual dysfunction among pediatric cancer survivors. METHODS: Pediatric cancer survivors were recruited to complete an online survey using the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF-5), both validated questionnaires to assess female sexual dysfunction (FSD) and erectile dysfunction (ED). Patient demographics, oncologic history, prior treatment, and sexual habits were also queried. Logistic regression was used to evaluate risk factors for sexual dysfunction, and Mann-Whitney U test was used to identify factors associated with individual domains of the FSFI. OUTCOMES: The main outcome measures were FSFI and IIEF-5 score, which are used to diagnose FSD (FSFI<26.55) and ED (IIEF-5<22). RESULTS: A total of 21 (72.4%) female respondents and 20 (71.4%) male respondents were sexually active and completed the survey and FSFI or IIEF-5 questionnaire, respectively. Mean (±SD) age was 23.7 (4.1) years, and average age at diagnosis was 9.1 (5.0), with no difference between genders. Overall, 25.0% (5/20) of male and 52.4% (11/21) of female pediatric cancer survivors reported sexual dysfunction (P = .11). Oncologic history and prior treatment were not associated with sexual function. Females who reported difficulty relaxing during intercourse in the last 6 months had higher odds of reporting sexual dysfunction (odds ratio: 13.6, 95% confidence interval: 1.2-151.2, P = .03). Subgroup analysis of FSFI domains found that previous radiation therapy was correlated with decreased lubrication and satisfaction during intercourse, whereas previous treatment to the pelvic region significantly reduced satisfaction and increased pain during intercourse. CLINICAL IMPLICATIONS: Female pediatric cancer survivors have higher odds of reporting sexual dysfunction after treatment and should be screened appropriately to provide early intervention and to mitigate risk. STRENGTH & LIMITATIONS: Our study includes validated questionnaires to assess FSD and ED and queries specific characteristics to assess their association with sexual dysfunction. However, the study is limited by sample size and its cross-sectional survey design. CONCLUSIONS: The prevalence of female sexual dysfunction in this cohort is higher than that in the general population of equivalent-aged individuals, and clinicians should be aware of these potential long-term sequelae. Greenberg DR, Khandwala YS, Bhambhvani HP, et-al. Male and Female Sexual Dysfunction in Pediatric Cancer Survivors. J Sex Med 2020;17:1715-1722.

Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study.

BACKGROUND: Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively. RESULTS: 71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients. CONCLUSIONS: This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

Emergent neuroimaging for seizures in epilepsy: A population study.

We determined how often patients with epilepsy presented to the emergency department (ED) for seizure and the frequency and predictors for undergoing emergent neuroimaging during those visits. We conducted a retrospective population-based cohort study using administrative claims' data from 2007 to 2015. Adults with epilepsy were identified based on a diagnosis of epilepsy and an outpatient prescription for an antiepileptic medication. The Bonferroni corrected significance level was 0.0018. We identified 381,362 patients with a mean follow-up period of 1.99 years, of whom 35,015 (9.2%) patients presented to the ED for seizure at least once. Patients with at least one ED visit were younger, more likely to be male, had fewer comorbidities, and had longer follow-up as compared with those with no ED visit (all p < 0.001). Among the 35,015 patients presenting to the ED, 13.6% had neuroimaging, mostly commonly head computed tomography (CT; 95.5%). Patients undergoing neuroimaging were younger (46 versus 48 years) and with higher rates of psychosis (17.4% versus 13.8%) and depression (16.1% versus 12.2%; p < 0.001). This helps to quantify the burden of ED and emergent neuroimaging utilization for patients with epilepsy and can help inform efforts to curtail unnecessary neuroimaging.

Intracranial Hemorrhage in Deep Vein Thrombosis/Pulmonary Embolus Patients Without Atrial Fibrillation.

Background and Purpose- Deep vein thrombosis (DVTs) is a common disease with high morbidity if it progresses to pulmonary embolus (PE). Anticoagulation is the treatment of choice; warfarin has long been the standard of care. Early experience with direct oral anticoagulants (DOACs) suggests that these agents may be may be a safer and equally effective alternative in the treatment of DVT/PE. Nontraumatic intracranial hemorrhage (ICH) is one of the most devastating potential complications of anticoagulation therapy. We sought to compare the rates of ICH in patients treated with DOACs versus those treated with warfarin for DVT/PE. Methods- The MarketScan Commercial Claims and Medicare Supplemental databases were used. Adult DVT/PE patients without known atrial fibrillation and with prescriptions for either a DOAC or warfarin were followed for the occurrence of inpatient admission for ICH. Coarsened exact matching was used to balance the treatment cohorts. Cox proportional-hazards regressions and Kaplan-Meier survival curves were used to estimate the association between DOACs and the risk of ICH compared with warfarin. Results- The combined cohort of 218 620 patients had a median follow-up of 3.0 months, mean age of 55.4 years, and was 52.1% women. The DOAC cohort had 26 980 patients and 8 ICH events (1.0 cases per 1000 person-years), and the warfarin cohort had 191 640 patients and 324 ICH events (3.3 cases per 1000 person-years; P<0.0001). The DOAC cohort had a lower hazard ratio for ICH compared with warfarin in both the unmatched (hazard ratio=0.26; P=0.0002) and matched (hazard ratio=0.20; P=0.0001) Cox proportional-hazards regressions. Conclusions- DOACs show superior safety to warfarin in terms of risk of ICH in patients with DVT/PE.

The association between frailty, hypogonadism, and postoperative outcomes among men undergoing radical cystectomy.

INTRODUCTION: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes. MATERIALS AND METHODS: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes. RESULTS: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT. CONCLUSIONS: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC.

Prosteria - National Trends and Outcomes of More Frequent Than Guideline Recommended Prostate Specific Antigen Screening.

OBJECTIVE: To characterize national trends in and associated outcomes of more often than annual prostate-specific antigen (PSA) screening, which we term "prosteria." METHODS: Men in the Optum Clinformatics Data Mart with ≥2 years from first PSA test to censoring at the end of insurance or available data (January 2003 to June 2019) or following exclusionary diagnoses or procedures, such as PCa treatment, were included. PSAs within 90 days were treated as one PSA. Prosteria was defined as having ≥3 PSA testing intervals of ≤270 days. RESULTS: A total of 9,734,077 PSAs on 2,958,923 men were included. The average inter-PSA testing interval was 1.5 years, and 4.5% of men had prosteria, which increased by 0.53% per year. Educated, wealthy, non-White patients were more likely to have prosteria. Men within the recommended screening age (ie 55-69) had lower rates of prosteria. Prosteria patients had higher average PSA values (2.5 vs 1.4 ng/mL), but lower values at PCa diagnosis. Prosteria was associated with biopsy and PCa diagnosis; however, there were comparable rates of treatment within 2 years of diagnosis. CONCLUSION: In this large cohort study, prosteria was common, increased over time, and was associated with demographic characteristics. Importantly, there were no clinically meaningful differences in PSA values at diagnosis or rates of early treatment, suggesting prosteria leads to both overdiagnosis and overtreatment. These results support current AUA and USPTF guidelines and can be used to counsel men seeking more frequent PSA screening.

Sociodemographic factors associated with Wilms tumor treatment and survival: a population-based study.

INTRODUCTION: Though Wilms tumor (WT) is one of the most common malignancies in children, there is a paucity of epidemiologic studies exploring sociodemographic disparities in treatment and survival. Here, we leveraged a national cancer registry to examine sociodemographic factors associated with receipt of adjuvant therapy, either chemotherapy or radiation, as well as overall survival among pediatric patients with WT. MATERIALS AND METHODS: Within the Surveillance Epidemiology and End Results database (2000-2016), we identified 2043 patients (≤ 20 years of age) with unilateral WT. Multivariable logistic regression and Cox proportional hazard models were constructed to examine the association of sociodemographic factors with, respectively, adjuvant chemotherapy/radiotherapy and overall survival (OS). RESULTS: Patients in the lowest SES quintile (OR 0.56, 95% CI 0.33-0.93, p = 0.03) were less likely to receive chemotherapy as compared to those in the highest SES quintile, though this association did not persist in sensitivity analyses including only patients at least 2 years of age and patients with regional/distant disease. In addition, female patients were more likely to receive chemotherapy (OR 1.46, 95% CI 1.08-1.97, p = 0.02) than male patients. Age, race, year of diagnosis, insurance status, and tumor laterality were not associated with receipt of chemotherapy. No sociodemographic variables were associated with receipt of radiotherapy. Lastly, as compared to Non-Hispanic-White patients, Hispanic patients had worse OS (HR 1.59, 95% CI 1.08-2.35, p = 0.02); no other sociodemographic variables were associated with OS. CONCLUSIONS: This study suggests multilevel sociodemographic disparities involving ethnicity and SES in WT treatment and survival.

Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine. METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE. RESULTS: We identified 117 918 men who underwent 162 646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE. CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

Biliary cancer brain metastases: a multi-institution case series with case reports.

Background: Biliary cancers are rare, and few reported cases of brain metastases from primary biliary cancers exist, especially describing patients in the United States. This report assesses the proportion and incidence of brain metastases arising from primary biliary cancers [cholangiocarcinoma (CCA) and gallbladder cancer] at Stanford University and the University of California, San Francisco, describes clinical characteristics, and provides a case series. Methods: We queried 3 clinical databases at Stanford and the University of California, San Francisco to retrospectively identify and review the charts of 15 patients with brain metastases from primary biliary cancers occurring between 1990 to 2020. Results: Among patients with brain metastases analyzed at Stanford (3,585), 6 had a primary biliary cancer, representing 0.17% of all brain metastases. Among biliary cancer patients at the University of California, San Francisco (1,055), 9 had brain metastases, representing an incidence in biliary cancer of 0.85%. A total of 15 biliary cancer patients with brain metastases were identified at the two institutions. Thirteen out of 15 patients (86.7%, 95% CI: 59.5-98.3) were female. The median overall survival from primary biliary cancer diagnosis was 214 days (95% CI: 71.69-336.82 days) and subsequent OS from the time of brain metastasis diagnosis was 57 days (95% CI: 13.43-120.64 days). Death within 90 days of brain metastasis diagnosis occurred in 66.67% of patients (95% CI: 38.38-88.17). Conclusions: Brain metastases from primary biliary cancers are rare, with limited survival once diagnosed. This report can aid health care providers in caring for patients with brain metastases from primary biliary cancers.

Deep learning enabled classification of Mayo endoscopic subscore in patients with ulcerative colitis.

OBJECTIVE: Previous reports of deep learning-assisted assessment of Mayo endoscopic subscore (MES) in ulcerative colitis have only explored the ability to distinguish disease remission (MES 0/1) from severe disease (MES 2/3) or inactive disease (MES 0) from active disease (MES 1-3). We sought to explore the utility of deep learning models in the automated grading of each individual MES in ulcerative colitis. METHODS: In this retrospective study, a total of 777 representative still images of endoscopies from 777 patients with clinically active ulcerative colitis were graded using the MES by two physicians. Each image was assigned an MES of 1, 2, or 3. A 101-layer convolutional neural network model was trained and validated on 90% of the data, while 10% was left for a holdout test set. Model discrimination was assessed by calculating the area under the curve (AUC) of a receiver operating characteristic as well as standard measures of accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: In the holdout test set, the final model classified MES 3 disease with an AUC of 0.96, MES 2 disease with an AUC of 0.86, and MES 1 disease with an AUC 0.89. Overall accuracy was 77.2%. Across MES 1, 2, and 3, average specificity was 85.7%, average sensitivity was 72.4%, average PPV was 77.7%, and the average NPV was 87.0%. CONCLUSION: We have demonstrated a deep learning model was able to robustly classify individual grades of endoscopic disease severity among patients with ulcerative colitis.

The Association of Medicaid Insurance and Affordable Care Act Expansions with Survival among Patients with Testicular Cancer.

INTRODUCTION: Following passage of the Affordable Care Act, Medicaid access was expanded in several states beginning in 2014. We sought to determine the oncologic implications by comparing outcomes between testicular germ cell tumor patients with Medicaid and those without insurance, and by assessing for changes in outcomes after 2014. METHODS: A total of 18,506 men with seminomatous or nonseminomatous germ cell tumors were identified within the Surveillance, Epidemiology, and End Results database (2007-2016). Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, cumulative incidence plots and segmented Poisson regression models were used. RESULTS: Compared to no insurance, Medicaid insurance was not associated with differences in all-cause mortality or cancer-specific mortality among seminoma patients (all-cause mortality: HR=1.24, p=0.87; cancer-specific mortality: HR=0.92, p=0.75) or nonseminoma patients (all-cause mortality: HR=1.13, p=0.33; cancer-specific mortality: HR=1.10, p=0.51). Among matched Medicaid and uninsured patients, there was again no difference in cancer-specific mortality for those with seminoma (p=0.81) or nonseminoma (p=0.23). There was a 99% increase in Medicaid enrollment in expansion states in the post-Affordable Care Act era. There was no difference in post-expansion all-cause mortality between expansion states and nonexpansion states for men with seminoma (p=0.42) or nonseminoma (p=0.53). CONCLUSIONS: Medicaid enrollment increased in expansion states following the Affordable Care Act. However, there was no difference in survival between Medicaid patients and uninsured patients, or between patients in expansion states versus nonexpansion states, highlighting the need for population-level policy interventions to improve access and quality of care among testicular cancer patients with Medicaid.

The quality of systematic reviews and meta-analyses assessing the treatment and management of male infertility.

BACKGROUND: Male factor infertility (MFI) is a common medical condition which requires high-quality research to guide clinical practice; however, systematic reviews (SRs) and meta-analyses (MAs) often vary in quality, raising concerns regarding the validity of their results. We sought to perform an objective analysis of SRs and MAs in MFI treatment and management and to report on the quality of published literature. METHODS: A comprehensive search in PubMed/MEDLINE and Embase was used to identify relevant publications. Primary search terms were male infertility, male sterility, and male subfertility. Two authors independently performed searches, screened citations for eligibility, extracted data for analysis, and graded methodological quality using the validated AMSTAR (A Measurement Tool to Assess Systematic Reviews) instrument, a validated tool used in the critical appraisal of SRs/MAs. RESULTS: Of 27 publications met inclusion criteria and were included in the analysis. Mean AMSTAR score (± SD) among all publications was 7.4 (1.9) out of 11, reflecting "fair to good" quality. Non-pharmacological medical treatment for MFI was the most commonly assessed intervention (n = 13, 48.1%). No publications met all AMSTAR criteria. While the number of SRs/MAs has increased over time (P = 0.037), the quality of publications has not significantly changed (P = 0.72). SRs/MAs of the Cochrane Library had higher AMSTAR score than non-Cochrane SRs/MAs (8.5 vs 6.3, P = 0.002). CONCLUSIONS: The methodological quality of SRs/MAs should be assessed to ensure high-quality evidence for clinical practice guidelines in MFI treatment and management. This review highlights a need for increased effort to publish high-quality studies in MFI treatment and management.

The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users.

INTRODUCTION: International studies have suggested that social disruptions caused by the COVID-19 pandemic have led to sexual dysfunction, but the impact on males in the United States is less defined. AIM: To examine changes in male sexual function during the COVID-19 pandemic and to evaluate associated demographic variables. METHODS: Prepandemic survey data was collected between October 20, 2019 and March 1, 2020 on adult males in the United States. Follow-up survey data collected for comparison during the COVID-19 pandemic between August 1, 2020 and October 10, 2020 included International Index of Erectile Function (IIEF) scores, Patient Health Questionnaire for Depression and Anxiety with 4 items (PHQ-4) scores, and questions regarding sexual frequency. Questions were also asked about mask-wearing habits, job loss, relationship changes, and proximity to individuals who tested positive for COVID-19. MAIN OUTCOME MEASURES: Differences in prepandemic and pandemic male sexual function assessed by self-reported IIEF domain scores and sexual frequency RESULTS: Seventy six men completed both prepandemic and pandemic surveys with a mean age of 48.3 years. Overall, there were no differences in either overall IIEF score or any subdomain score when comparing men's pre-pandemic and pandemic survey data. There was an increase in sexual frequency during the pandemic with 45% of men reporting sex ten or more times per month during the pandemic compared to only 25% of men prior to the pandemic (P = .03). Among the subgroup of 36 men who reported a decrease in IIEF, the decrease was an average of 3.97, and significantly associated with higher PHQ-4 depression subscale scores (1.78 vs 1.03, P = .02). CONCLUSION: The COVID-19 pandemic is associated with increased sexual frequency and no change in overall sexual function in males in the United States. Interventions intended to promote male sexual health during the COVID-19 pandemic should include a focus on mental health. Chen T, Bhambhvani HP, Kasman AM, et al. The Association of the COVID-19 Pandemic on Male Sexual Function in the United States: A Survey Study of Male Cannabis Users. J Sex Med 2021;9:100340.

Brain Metastases from Endometrial Cancer: Clinical Characteristics, Outcomes, and Review of the Literature.

BACKGROUND: Brain metastases from endometrial cancer are rare and poorly described. We aimed to estimate the proportion of brain metastases at our institution that arose from endometrial cancer, and to detail clinicopathologic features and survival outcomes. METHODS: We retrospectively identified and reviewed the charts of 30 patients with brain metastases from endometrial cancer seen at Stanford Hospital from 2008 to 2018. RESULTS: Among all patients with brain metastases, the proportion arising from endometrial cancer was 0.84%. The median age at diagnosis was 62 years (range, 39-79 years), and the median overall survival from brain metastasis diagnosis was 6.8 months (range, 1.0-58.2 months). Most patients harbored endometrioid histology (53.3%), and some had concurrent metastases to lung (50.0%), bone (36.7%), and liver (20.0%). The median time from endometrial cancer diagnosis to brain metastasis development was 20.8 months (range, 1.4 months to 11.2 years), and the median number of brain metastases was 2 (range, 1-20). Patients with non-endometrioid histologies had more brain metastases than those with endometrioid histology (6.21 vs. 2.44, P = 0.029). There was no difference in overall survival by histology. CONCLUSIONS: We describe the largest cohort to date of patients with brain metastases originating from endometrial cancer. These patients represent a small fraction of all patients with brain metastases and have poor prognoses. These data enable providers caring for patients with brain metastases from endometrial cancer to appropriately counsel their patients.

A population-level analysis of nonsquamous penile cancer: The importance of histology.

BACKGROUND: Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used. RESULTS: 666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045). CONCLUSIONS: The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM.

Clinicopathologic features, outcomes, and prognostic factors of testicular sarcoma: a population-based study.

PURPOSE: To describe clinical characteristics and identify prognostic factors among men with testicular sarcoma, and to compare survival with other testicular cancers. METHODS: The surveillance, epidemiology, and end results (SEER) database (1975-2016) was queried to identify adults with testicular sarcoma. Multivariable Cox proportional hazards, Fine and Gray competing-risks regression, propensity score matching, and Kaplan-Meier analyses were used. RESULTS: 230 men were included in this study. Median age at diagnosis was 58 years (range 18-94), and median OS was 10.3 years. Patients with tumors larger than 8 cm in size had worse OS (HR 1.88, p = 0.016) compared to patients with tumors < 8 cm. Disease with distant metastasis was associated with worse OS (HR 4.70, p < 0.0001) and worse CSS (HR 11.41, p < 0.0001) as compared to disease localized to the testis. Men with rhabdomyosarcoma had worse CSS (HR 3.25, p = 0.03) as compared to men with liposarcoma. Testicular sarcoma patients had worse OS than matched patients with either seminomatous germ cell tumors (GCTs, p < 0.0001) or nonseminomatous GCTs (p = 0.0019), and similar survival to matched patients with sex cord stromal tumors, testicular lymphoma, or sarcomas of the lower limb-the most common anatomic site of origin of soft tissue sarcomas. CONCLUSIONS: In the largest cohort of men with testicular sarcoma to date, we identified tumor size, disease extent, and rhabdomyosarcoma histology as independent predictors of worse survival. Stage-adjusted survival was worse as compared to men with GCTs, and similar to men with sex cord stromal tumors, testicular lymphoma, and sarcomas of other primary sites.