Donor-derived duodenal adenocarcinoma of a bladder-drained pancreas allograft.

The subset of the population that received bladder-drained allograft pancreata during peak utilization of the technique in the 1990s is approaching 20-30 postoperative years. This time frame is salient, as it parallels the time in which patients in the urologic literature develop adenocarcinomas after bladder reconstruction using gastrointestinal segments. We present the case of a 57-year-old simultaneous pancreas/kidney recipient who presented with microhematuria twenty-four years after transplantation and was found to have an adenocarcinoma of the duodenum of his failed, bladder-drained pancreas. After allograft pancreatectomy/duodenectomy, he remains disease-free eleven months postoperatively. As this patient population ages, practitioners should consider pathology of the donor duodenum and pancreas in recipients who present with gross or microscopic hematuria.

Self-Reported Race/Ethnicity Is Not Associated with Abnormal Semen Parameters after Accounting for Body Mass Index and Socioeconomic Status.

PURPOSE: We evaluated whether consideration of body mass index (BMI) and socioeconomic status alters the reported association between race/ethnicity and abnormal semen parameters. MATERIALS AND METHODS: We conducted a retrospective review of all men who underwent semen analysis (SA) for fertility evaluation at an integrated academic health care system from 2002 to 2021. Men were excluded if they had a diagnosis of Klinefelter's syndrome, history of varicocele, prior testicular surgery, prior history of chemotherapy or radiation for cancer, or prior testosterone-modulating medication use. Chi-square and Kruskal-Wallis tests were used to analyze categorical and continuous variables across self-reported racial groups, respectively. Logistic regression was used to evaluate the association between race and abnormal semen parameters according to WHO 2010 criteria, controlling for potential confounders. RESULTS: Among 2,750 men meeting inclusion criteria, 2,037 (74.1%) identified as White Non-Hispanic, 207 (7.5%) as Black Non-Hispanic, 245 (8.9%) as Hispanic and 261 (9.5%) as Asian. Median age was 35 years (IQR 32-40). Black men had an older median age (37 years, IQR 33-42, p=0.002) than other groups at the time of index SA. While Black men had higher odds of abnormal sperm concentration (OR 1.46, 95% CI 1.06-2.02, p=0.02) and abnormal total motile sperm count (OR 1.65, 95% CI 1.21-2.25, p=0.001) compared to other men after adjusting for age alone, the association of race with abnormal semen parameters was rendered insignificant with the progressive inclusion of BMI, insurance status and neighborhood income as covariates. CONCLUSIONS: In men undergoing SA for fertility evaluation, we did not see evidence of an association between race/ethnicity and abnormal semen parameters after controlling for BMI, insurance status and neighborhood income.

The adverse association between stimulant use for attention deficit hyperactivity disorder (ADHD) and semen parameters.

This study examined the relationship between stimulant medications used for the treatment of attention deficit hyperactivity disorder and semen parameters. We performed a retrospective cohort study at a large, academic institution between 2002 and 2020. We included men with a semen analysis without prior spermatotoxic medication use, empiric medical therapy exposure or confounding medical diagnoses (varicocele, Klinefelter's syndrome, cryptorchidism, cystic fibrosis, diabetes, cancer or cancer-related treatment, and azoospermia). Men were stratified by stimulant exposure (methylphenidate or amphetamines). A multivariable linear regression was fit to assess the association between individual semen parameters, age, stimulant exposure and non-stimulant medication use. Of 8,861 men identified, 106 men had active prescriptions for stimulants within 90 days prior to semen testing. After controlling for age and exposure to non-stimulant medications, stimulant use was associated with decreased total motile sperm count (ß: -18.00 mil/ejaculate and standard error: 8.44, p = 0.033) in the setting of decreased semen volume (ß: -0.35 ml, and standard error: 0.16, p = 0.035), but not sperm concentration, motility and morphology. These findings suggest a role for reproductive physicians and mental health providers to consider counselling men on the potential negative impact of stimulants prescribed for attention deficit hyperactivity disorder on semen volume during fertility planning.

Becoming what you are seeking: Building Relational Self-Awareness in emerging adults.

Emerging adults are attempting to navigate a rapidly shifting and immensely complicated landscape of modern love, often without meaningful sex and relationship education. Although individually oriented relationship education programs for emerging adults make a difference in the knowledge, attitudes, and beliefs of the recipients (Simpson et al., Journal of Youth and Adolescence, 2018, 47, 477) and most emerging adults report they yearn for relationship education (Weissbourd et al., The talk: How adults can promote young people's healthy relationships and prevent misogyny and sexual harassment, 2017), these programs are not widely available. Educators who are working with emerging adults in a classroom or psychoeducational setting are well-positioned to help emerging adults identify and enact healthy and purposeful relational and sexual choices. The first part of the paper orients readers to the "topography" of the modern love landscape by describing four macro cultural themes that impact the intimate lives of emerging adults. The second part of the paper introduces relationship educators to Relational Self-Awareness (Solomon, Loving Bravely: 20 lessons of self-discovery to help you get the love you want, New Harbinger, 2017), an integrative approach to helping emerging adults understand the self-in-relationship. Each of the five pillars of Relational Self-Awareness is defined and operationalized, and specific recommendations are provided for how educators can integrate these pillars into their existing curricula. Clinical implications and future directions are offered.

Los adultos emergentes están intentando orientarse ante un panorama de amor moderno rápidamente cambiante e inmensamente complicado, generalmente sin sexo significativo ni educación sobre las relaciones. Aunque los programas de educación sobre las relaciones para adultos emergentes con orientación individual marcan una diferencia en el conocimiento, las actitudes y las creencias de los destinatarios (Simpson et al., 2018), y la mayoría de los adultos emergentes informan que desean recibir educación sobre las relaciones (Weissbourd et al., 2017), estos programas no son ampliamente accesibles. Los educadores que trabajan con adultos emergentes en un aula o en un entorno psicoeducativo están bien posicionados para ayudarlos a identificar y a adoptar elecciones sexuales y relacionales saludables y significativas. La primera parte del artículo guía a los lectores por la "topografía" del panorama del amor moderno mediante la descripción de cuatro temas macroculturales que repercuten en las vidas íntimas de los adultos emergentes. En la segunda parte del artículo se presenta la autoconciencia relacional (Solomon, 2017) a los educadores sobre relaciones, un enfoque integrador para ayudar a los adultos emergentes a comprender el yo en las relaciones. Se definen y se operacionalizan cada uno de los cinco pilares de la autoconciencia relacional, y se dan recomendaciones específicas sobre cómo los educadores pueden integrar estos pilares en sus planes de estudio existentes. Se comentan las consecuencias clínicas y las futuras direcciones del estudio.

Anti-TNF agents and potential effects on male fertility: are men being counseled?

BACKGROUND: Adult men with autoimmune conditions are commonly prescribed anti-tumor necrosis factor (anti-TNF) agents; however, there is a paucity of quality evidence as to their effect on male fertility (e.g. semen parameters and sperm quality). Our objective was to determine if men with autoimmune conditions are being counseled regarding the unknown reproductive effects of anti-TNF agents prior to initiation of therapy. METHODS: A retrospective analysis of 1010 male patients age 18-45 who were prescribed an anti-TNF agent were assessed for (1) receipt of counseling regarding potential reproductive effects; (2) screening for anatomic or laboratory abnormalities associated with infertility; (3) election for sperm cryopreservation. RESULTS: Only 10.3% of men received counseling, and this was not associated with age (p = 0.77). Those who received counseling were significantly more likely to have a genitourinary exam performed, be assessed for presence of a varicocele, be asked about or endorse low libido or erectile dysfunction, have a testosterone, LH, FSH, or prolactin level checked, and have a semen analysis performed (all, p < 0.0001). Rates of sperm cryopreservation were low, but statistically higher in men who received counseling (5.77% (+) counseling, 1.10% (-) counseling) (p = 0.002). CONCLUSIONS: The limited current literature lacks a consensus regarding the short- and long-term male reproductive effects of anti-TNF therapy. Despite this lack of clarity, rates of pre-initiation counseling were low. Rates of sperm cryopreservation, while improved in the counseled group remained low, suggesting prescribing physicians may be unaware of this option for patients.

Do partial AZFc deletions affect the sperm retrieval rate in non-mosaic Klinefelter patients undergoing microdissection testicular sperm extraction?

BACKGROUND: The purpose of this study is to evaluate the prognostic factors for sperm retrieval and determine if Y chromosome deletion is associated with deleterious effects on spermatogenesis in non-mosaic Klinefelter patients. Whether Y chromosome deletion determines the sperm retrieval rate in non-mosaic Klinefelter patients has not yet been addressed. METHODS: We retrospectively collected medical records of azoospermic patients from Sep 2009 to Dec 2018, and enrolled 66 non-mosaic 47, XXY patients who were receiving mTESE. The predictive values of patients age, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol and Y chromosome deletion were assessed for successful sperm recovery. RESULTS: Testicular sperm recovery was successful in 24 (36.4%) of 66 men. The mean age (36.0 vs. 36.6 years), and levels of FSH (30.0 vs 36.9 IU/L), LH (17.7 vs 21.9 IU/L), testosterone (2.4 vs. 2.1 ng/ml), prolactin (9.1 vs. 8.8 ng/ml), and estradiol (19.4 vs. 22.3 pg/ml) did not show any significant difference when comparing patients with and without successful sperm retrieval. Partial deletion of azoospermic factor c (AZFc) was noted in 5 (20.8%) of 24 patients with successful sperm retrieval, including three b2/b3 and two gr/gr deletion cases, whereas 4 (9.5%) of 42 patients with unsuccessful sperm retrieval were noted to have AZFc partial deletion (one b2/b3, one sY1206 and two gr/gr deletion), though the difference was not statistically significant (p = 0.27). CONCLUSION: According to present results, age and AZFc partial deletion status should not be a deterrent for azoospermic males with non-mosaic Klinefelter syndrome to undergo mTESE.

Outcomes of Acellular Dermal Matrix for Immediate Tissue Expander Reconstruction with Radiotherapy: A Retrospective Cohort Study.

BACKGROUND: Despite increasing literature support for the use of acellular dermal matrix (ADM) in expander-based breast reconstruction, the effect of ADM on clinical outcomes in the presence of post-mastectomy radiation therapy (PMRT) has not been well described. OBJECTIVES: To analyze the impact ADM plays on clinical outcomes on immediate tissue expander (ITE) reconstruction undergoing PMRT. METHODS: We retrospectively reviewed patients who underwent ITE breast reconstruction from 2004 to 2014 at MD Anderson Cancer Center. Patients were categorized into four cohorts: ADM, ADM with PMRT, non-ADM, and non-ADM with PMRT. Outcomes and complications were compared among cohorts. RESULTS: Over 10 years, 957 patients underwent ITE reconstruction (683 non-ADM, 113 non-ADM with PMRT, 486 ADM, and 88 ADM with PMRT) with 1370 reconstructions. Overall complication rates for the ADM and non-ADM cohorts were 39.0% and 16.7%, respectively (P < 0.001). Within both cohorts, mastectomy skin flap necrosis (MSFN) was the most common complication, followed by infection. ADM use was associated with a significantly higher rate of infections and seromas in both radiated and non-radiated groups; however, when comparing radiated cohorts, the incidence of explantation was significantly lower with the use of ADM. CONCLUSIONS: The decision to use ADM for expander-based breast reconstruction should be performed with caution, given higher overall rates of complications, including infections and seromas. There may, however, be a role for ADM in cases requiring PMRT, as the overall incidence of implant failure is lower than non-ADM cases.

The Prognostic Impact of a Positive Vascular Margin on pT3 Clear Cell Renal Cell Carcinoma.

PURPOSE: We examined the impact of positive vascular margins in patients with pT3 clear cell renal cell carcinoma. MATERIALS AND METHODS: After excluding patients with nonvascular positive margins, metastasis, lymph node involvement, neoadjuvant therapy or nonclear cell histology, we identified 224 patients with venous tumor invasion through our institutional database from 1999 to 2013. Kaplan-Meier analysis and log rank tests were used to evaluate whether positive vascular margins were associated with progression-free survival or cancer specific survival. RESULTS: There were 41 patients (18%) with a positive vascular margin. Margin status was directly related to the level of invasion (p <0.0001). Compared to the negative vascular margin group the positive group had a significantly worse progression-free survival (p=0.01) but not cancer specific survival (p=0.3). Similarly the level of vascular thrombus invasion was significantly associated with worse progression-free survival (p=0.02) but not cancer specific survival (p=0.4). The 3-year progression-free survival was worst with inferior vena cava invasion and best with segmental/muscular venous branch invasion (54%, 95% CI 34-70 vs 76%, 95% CI 64-85). Among patients with only main renal vein thrombus, vascular margin status was not associated with progression-free survival (p=0.5) or cancer specific survival (p=0.2). CONCLUSIONS: In patients with pT3N0/XM0 clear cell renal cell carcinoma positive vascular margins are associated with risk of disease progression. However, the risk of relapse associated with positive vascular margins is driven by the extent of vascular thrombus invasion. These findings suggest that the clinical significance of vascular margin status as currently defined in pT3 clear cell renal cell carcinoma is minimal.

Association of the minimal cyclophosphamide equivalent dose and outcome of microdissection testicular sperm extraction in patients with persistent azoospermia after chemotherapy.

Objective: To investigate whether the minimal cyclophosphamide equivalent dose (mCED), a novel approach for estimating alkylating agent exposure, is associated with the sperm retrieval rates by microdissection testicular sperm extraction (mTESE) in azoospermic postchemotherapy cancer survivors. Design: A retrospective cohort study conducted between 2002 and 2017. Setting: An academic medical center. Patients: A total of 28 azoospermic postchemotherapy cancer survivors who underwent mTESE. Interventions: Chemotherapy exposure and mCED calculation. Main Outcome Measures: The primary outcome was the association between the mCED and sperm retrieval rate using mTESE. The mCED value for each patient's regimen received was estimated using the lowest recommended dosing regimen from the range of recommended doses at the time of administration. Results: Spermatozoa were successfully retrieved in 11 (39.3%) of the patients. Age at the time of receiving chemotherapy and mCED were significant factors associated with sperm retrieval. An mCED of <4,000 mg/m2 had a higher sperm retrieval rate (10/14, 71.4%) than an mCED of >4,000 mg/m2 (0/8, 0). The hormone levels were not significantly different when comparing patients with and without successful sperm retrieval. Seminoma, nonseminomatous germ cell tumor, and acute lymphoblastic leukemia had favorable sperm retrieval rates-100% (2/2), 66.7% (2/3), and 66.7% (2/3), respectively-although the numbers of patients in each group were small. Conclusion: Among this cohort of patients with cancer who required chemotherapy regimens, successful sperm retrieval by mTESE was only noted among cancer survivors receiving an mCED of <4,000 mg/m2.

Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery.

PURPOSE: We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. MATERIALS AND METHODS: Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater. RESULTS: Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. CONCLUSIONS: Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

A Prior History of Cryptozoospermia Is Associated with a Significantly Higher Chance of a Successful Microdissection Testicular Sperm Extraction Compared to Non-Obstructive Azoospermia.

BACKGROUND: Our study sought to evaluate the rates of successful sperm retrieval following microdissection testicular sperm extraction (mTESE) in patients with a prior history of cryptozoospermia, compared to patients with non-obstructive azoospermia (NOA). METHODS: A retrospective chart analysis evaluating all mTESE procedures was performed from January 2004 to August 2018. Inclusion criteria involved all males >18 years of age with a diagnosis of cryptozoospermia and/or NOA that underwent a mTESE. The patient's genetic profile, hormonal profile, semen analysis, testicular volumes, pathology and comorbidities were analyzed. RESULTS: We identified 40 patients with cryptozoospermia and 221 patients with NOA. Successful mTESE occurred in 34/40 (85%) cryptozoospermic males compared to 104/221 (48%) NOA males (p < 0.001). In univariate and multivariate analyses, patients with cryptozoospermia were more likely to undergo a successful mTESE than patients with NOA (OR 5.56 [1.79-17.29], p = 0.003; OR 5.41 [1.94-15.08], p = 0.0013), respectively. Factors that were associated with a statistically significant lower chance of successful mTESE included Sertoli-cell only pathology, pre-operative testosterone < 300 ng/dL and FSH > 7.6 mIU/mL. CONCLUSION: Despite patients with a history of cryptozoospermia having a significantly higher chance of a successful sperm retrieval than patients with NOA, couples should be counselled on the possibility of an unsuccessful sperm extraction, in order to optimize the pre-operative IVF planning and to manage operative expectations.

Characteristics of men who use direct-to-consumer men's health telemedicine services.

The characteristics of men who use direct-to-consumer (DTC) men's health services are not well understood. We conducted an online survey of adult men via ResearchMatch, assessing sociodemographic data, health behaviors, and concern for low testosterone and infertility. Logistic regression estimated the association between participant characteristics and familiarity with and reported use of DTC services such as Hims® and Roman®. Among 1276 men surveyed, 62.2% were concerned about low testosterone. While almost half (48.5%) were familiar with men's DTC health services, only 37 (2.9%) reported using these services. On multivariable analysis, men who used DTC men's health services were more likely to be younger (age 18-39: odds ratio [OR] 2.94, 95% confidence interval [CI] 1.03-8.38, p = 0.04; age 40-59: OR 3.26, CI 1.17-9.10, p = 0.02; referent age ≥60), have annual income between $75k and $100k (OR 5.25, CI 1.39-19.87.45, p = 0.02), and be concerned about low testosterone (OR 3.81, CI 1.46-9.96, p = 0.01). In conclusion, younger men and those with mid-range incomes were more likely to use online DTC men's health services compared to older or wealthier men. Likewise, men with concerns about low testosterone were more likely to use DTC services, but other health-conscious behaviors and frequency of doctor visits did not predict use.

Prevalence of Hyperprolactinemia and Clinically Apparent Prolactinomas in Men Undergoing Fertility Evaluation.

OBJECTIVE: To determine prevalence of hyperprolactinemia and prolactinoma among men presenting for initial fertility evaluation. METHODS: We performed a retrospective review of men presenting for initial fertility evaluation at a tertiary care, academic health system between 1999 and 2018. Men with measured prolactin levels were analyzed to determine prevalence of hyperprolactinemia and prolactinoma. We compared clinical characteristics of men with and without hyperprolactinemia. Univariable and multivariable analysis were used to determine factors associated with hyperprolactinemia. We assessed effects of hyperprolactinemia and prolactinoma on testosterone levels, semen parameters and pregnancy outcomes after treatment. RESULTS: A total of 3101 men had serum prolactin level measured. 65 (2.1%) had hyperprolactinemia. Patients with hyperprolactinemia had lower testosterone (median 280 ng/dL vs 313 ng/dL, P = 0.038) and lower total motile sperm count (median 7.0 million vs 34.7 million, P = 0.001) compared to men without hyperprolactinemia. 43.1% of men with hyperprolactinemia had oligospermia vs 21.5% of men without hyperprolactinemia (P<0.001). Univariable analysis demonstrated that men with elevated luteinizing hormone (LH) (OR 1.077, P = 0.001) and follicle-stimulating hormone (FSH) (OR 1.032, P = 0.002) were more likely to have hyperprolactinemia. Men with oligospermia were more likely to have hyperprolactinemia (OR 2.334, P = 0.004). On multivariable analysis, neither hormone parameters nor oligospermia were associated with elevated prolactin (P>0.05). Of the 65 men with hyperprolactinemia, 11 (17%) were diagnosed with a prolactinoma, resulting in an overall prevalence of 11 in 3101 (0.35%). CONCLUSION: The overall prevalence of prolactinoma in our cohort of men undergoing fertility evaluation was 35-fold higher than the prevalence in the general male population.

Reproductive urologic consultation in subfertile men: predictors of establishing care and patient perceptions after abnormal semen testing.

OBJECTIVE: To evaluate the predictors of establishing care with a reproductive urologist (RU) among men with abnormal semen analyses (SAs) ordered by nonurologists and examine patient perceptions of abnormal SAs in the absence of RU consultation. DESIGN: Retrospective cohort study with cross-sectional survey. SETTING: Large, integrated academic healthcare system during 2002-2019. PATIENT(S): We identified adult men undergoing initial SAs with nonurologists who had abnormalities. Patients with index SAs during 2002-2018 were included for the analysis of RU consultation. Men tested in 2019 were recruited for cross-sectional survey. INTERVENTION(S): Cross-sectional survey. MAIN OUTCOME MEASURE(S): RU consultation and accurate perception of abnormal SAs. RESULT(S): A total of 2,283 men had abnormal SAs ordered by nonurologists, among whom 20.5% underwent RU consultation. Mixed-effect logistic regression modeling identified oligospermia as the strongest predictor of RU care (odds ratio, 3.08; 95% confidence interval, 2.43-3.90) with a significant provider-level random intercept. We observed substantial provider-level heterogeneity among nonurologists with provider-specific rates of RU evaluation ranging from 3.7% to 35.8%. We contacted 310 men who did not undergo RU consultation with a 27.2% survey response rate. Of respondents, 6.7% reported receiving an RU referral. Among men with abnormal SAs not evaluated by RU, 22.7% appropriately perceived an abnormal SA. CONCLUSION(S): In men with abnormal SAs diagnosed by nonurologists, the rate of RU consultation was low and associated with substantial provider-level variation among ordering providers. Patients without RU consultation reported inaccurate perceptions of their SA. Multidisciplinary efforts are needed to ensure that subfertile men receive appropriate RU evaluation.

Selective Serotonin Reuptake Inhibitor (SSRI) Use is Not Associated With Impaired Semen Parameters.

OBJECTIVE: To examine the association between selective serotonin reuptake inhibitor (SSRI) use and semen quality. METHODS: We performed a retrospective review of all men undergoing semen analysis (SA) for fertility evaluation from 2002-2020 at a single academic medical center. Men were excluded if they had prior exposure to spermatotoxic medications, clomiphene citrate, gonadotropins, selective estrogen receptor modulators, or medical conditions known to impact male fertility. SSRI exposure was defined by an outpatient prescription within 90 days prior to any semen test. Differences between men with and without SSRI exposure were assessed with Wilcoxon rank sum for continuous variables and chi-squared testing for proportions. Univariable and multivariable linear regression models were fit to evaluate the relationship between SSRI use and individual semen parameters, controlling for age at the time of the semen analysis and non-SSRI drug use. RESULTS: A total of 8861 men were identified, of whom 153 men (1.7%) were exposed to SSRIs prior to SA. Median age was 35 years (interquartile range: 32-39) and was similar between groups (P = .999). Non-SSRI medication use was significantly higher in men taking SSRIs (78.4% vs 23.3%, < .001). On univariable and multivariable analyses, SSRI exposure was not associated with differences in semen volume, sperm concentration, motility, total motile sperm count, or normal morphology. CONCLUSION: In adult men undergoing fertility evaluation, SSRI exposure was not associated with impaired semen parameters. These data may help inform reproductive counseling and medical decision-making regarding SSRI use in men seeking paternity.

Deep learning models for histologic grading of breast cancer and association with disease prognosis.

Histologic grading of breast cancer involves review and scoring of three well-established morphologic features: mitotic count, nuclear pleomorphism, and tubule formation. Taken together, these features form the basis of the Nottingham Grading System which is used to inform breast cancer characterization and prognosis. In this study, we develop deep learning models to perform histologic scoring of all three components using digitized hematoxylin and eosin-stained slides containing invasive breast carcinoma. We first evaluate model performance using pathologist-based reference standards for each component. To complement this typical approach to evaluation, we further evaluate the deep learning models via prognostic analyses. The individual component models perform at or above published benchmarks for algorithm-based grading approaches, achieving high concordance rates with pathologist grading. Further, prognostic performance using deep learning-based grading is on par with that of pathologists performing review of matched slides. By providing scores for each component feature, the deep-learning based approach also provides the potential to identify the grading components contributing most to prognostic value. This may enable optimized prognostic models, opportunities to improve access to consistent grading, and approaches to better understand the links between histologic features and clinical outcomes in breast cancer.

Perceptions of Infertility and Semen Analysis Testing Among American Men Without Children.

OBJECTIVE: To determine whether health-conscious men are more likely to be concerned about infertility and self-initiate semen analysis at a laboratory/clinic or through a direct-to-consumer at-home product without a health care provider recommendation. METHODS: Cross-sectional survey conducted online via ResearchMatch.org between November 2019 and January 2020. Men age 18 and older without children (n = 634) were included for analysis. Outcomes were likelihood of self-initiating a semen analysis, prevalence of infertility concern. RESULTS: Of the 634 participants, 186 expressed concern about infertility but only 29% were likely to discuss these concerns with a health care provider. More men would self-initiate a semen analysis using an at-home product than through a traditional laboratory/clinic (14.2% vs 10.4%, P = .04). Odds of self-initiating a traditional semen analysis were higher for men concerned about low testosterone (odds ratio [OR] 2.30, 95% confidence interval [CI] 1.12-4.74, P = .023) and infertility (OR 3.91, 95% CI 2.14-7.15, P <.001). Self-initiating an at-home semen analysis was associated with concern for low testosterone and infertility as well as middle age (age 40-59: OR 3.02, 95% CI 1.16-7.88, P = .024) and fitness tracker use (OR: 1.95, 95% CI 1.12-3.39, P = .018). CONCLUSION: Many men were unlikely to discuss infertility concerns with a health care provider. Middle aged men and those who used fitness trackers were more likely to self-initiate fertility evaluation through at-home semen analysis. Concern about low serum testosterone was pervasive and strongly associated with concern for being infertile and self-initiating a semen analysis of any kind.

Determining breast cancer biomarker status and associated morphological features using deep learning.

Background: Breast cancer management depends on biomarkers including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (ER/PR/HER2). Though existing scoring systems are widely used and well-validated, they can involve costly preparation and variable interpretation. Additionally, discordances between histology and expected biomarker findings can prompt repeat testing to address biological, interpretative, or technical reasons for unexpected results. Methods: We developed three independent deep learning systems (DLS) to directly predict ER/PR/HER2 status for both focal tissue regions (patches) and slides using hematoxylin-and-eosin-stained (H&E) images as input. Models were trained and evaluated using pathologist annotated slides from three data sources. Areas under the receiver operator characteristic curve (AUCs) were calculated for test sets at both a patch-level (>135 million patches, 181 slides) and slide-level (n = 3274 slides, 1249 cases, 37 sites). Interpretability analyses were performed using Testing with Concept Activation Vectors (TCAV), saliency analysis, and pathologist review of clustered patches. Results: The patch-level AUCs are 0.939 (95%CI 0.936-0.941), 0.938 (0.936-0.940), and 0.808 (0.802-0.813) for ER/PR/HER2, respectively. At the slide level, AUCs are 0.86 (95%CI 0.84-0.87), 0.75 (0.73-0.77), and 0.60 (0.56-0.64) for ER/PR/HER2, respectively. Interpretability analyses show known biomarker-histomorphology associations including associations of low-grade and lobular histology with ER/PR positivity, and increased inflammatory infiltrates with triple-negative staining. Conclusions: This study presents rapid breast cancer biomarker estimation from routine H&E slides and builds on prior advances by prioritizing interpretability of computationally learned features in the context of existing pathological knowledge.

Underutilization of primary medical care among men presenting for fertility evaluation.

OBJECTIVE: To determine the proportion of men presenting for fertility evaluation who reported having an established primary care physician (PCP). DESIGN: Retrospective, observational study. SETTING: Academic health center. PATIENTS: All men presenting for initial male factor infertility consultation with a single reproductive urologist between 2002 and 2018. INTERVENTIONS: Men were asked to provide the name of their PCP at the time of initial visit. MAIN OUTCOME MEASURES: Descriptive statistics characterized the proportion of men with a PCP at the time of evaluation and associations between PCP status and clinical characteristics. RESULTS: Among 4,127 men presenting for initial fertility consultation, 844 (20.5%) reported having an established PCP, 480 (11.6%) reported no PCP, and 2,803 (67.9%) did not have data available. Among 1,302 men who had a prior primary care visit within our healthcare system, 414 (31.8%) had been seen within 1 year before their fertility evaluation. Men with an established PCP were slightly older than those without a PCP, with higher body mass index, and lower systolic blood pressure. Hormonal profiles were similar across groups, but men with an established PCP had a significantly higher total motile sperm count than those without a PCP, median 53 (interquartile range, 11-109) versus 35 (interquartile range, 8-98). CONCLUSIONS: More than one third of men presenting for fertility evaluation did not have an established PCP. Reproductive urologists are uniquely positioned to facilitate the critical relationship between young men and PCPs, which should be a key component of the male fertility treatment paradigm.

Sperm retrieval success and testicular histopathology in idiopathic nonobstructive azoospermia.

Prior studies have investigated sperm retrieval rates in men with nonobstructive azoospermia (NOA) secondary to specific etiologies, yet most cases of NOA are idiopathic. We compared sperm retrieval rates and testicular histopathology in idiopathic NOA (iNOA) and nonidiopathic NOA (niNOA). We performed a retrospective review of men with NOA who underwent microdissection testicular sperm extraction (microTESE) between 2000 and 2016. Men with no history of malignancy or cryptorchidism and negative genetic evaluation were considered idiopathic. Multivariable regression determined the association between idiopathic etiology and primary outcomes of sperm retrieval and active spermatogenesis on histopathology. Among 224 men, 86 (38.4%) were idiopathic, 75 (33.5%) were nonidiopathic, and 63 (28.1%) did not undergo genetic testing. Median age and serum testosterone were higher among iNOA or no testing versus niNOA. Median follicle-stimulating hormone (FSH) was lower among iNOA or no testing versus niNOA. A higher proportion of iNOA or no testing versus niNOA had a clinical varicocele. Sperm retrieval rates were similar between iNOA, niNOA, and no testing (41.8% vs 48.0% vs 55.6%, respectively; P = 0.255). Active spermatogenesis was seen in a higher proportion of iNOA or no testing versus niNOA (31.4% and 27.0% vs 16.0%, P = 0.073). On multivariaile analysis, iNOA was not associated with sperm retrieval or spermatogenesis (P = 0.430 and P = 0.078, respectively). Rates of sperm retrieval and spermatogenesis on testis pathology were similar in men with iNOA and niNOA. These data will be useful to clinicians in preoperative counseling for men with NOA and negative genetic evaluation.