Molecular and Immunophenotypic Correlates of Metastatic Epithelioid Angiomyolipoma Include Alterations of TP53, RB1, and ATRX.

CONTEXT.­: Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. OBJECTIVE.­: To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. DESIGN.­: Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. RESULTS.­: Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. CONCLUSIONS.­: Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs.

Progression of Chronic Kidney Disease Following Radical and Partial Nephrectomy.

OBJECTIVE: To compare renal functional outcomes, as determined by percent decline in estimated glomerular filtration rate (eGFR) and CKD stage progression following radical (RN) and partial nephrectomy (PN) stratified by preoperative CKD stage. MATERIALS AND METHODS: We retrospectively evaluated adults treated with RN or PN between 1980 and 2018 for unilateral, sporadic, solid renal masses. Multivariable linear models for percent change in eGFR (n = 3046) and competing-risk Cox proportional hazards models for increase in CKD staging (n = 5805) were used to determine if there was a significant interaction between type of surgery (RN vs PN) and preoperative CKD stage. RESULTS: Percent change in eGFR at 1 year was significantly worse for RN (n = 1724; 57%) compared with PN (n = 1322; 43%) for all preoperative CKD stages. RN (n = 3227; 56%) was more likely to result in CKD stage progression compared with PN (n = 2578; 44%) for preoperative CKD stages I-IIIb (P <.001) but not for CKD stage IV (P = .8). CONCLUSION: RN was more likely to result in decline in eGFR and CKD stage progression compared to PN for patients with preoperative CKD stage IIIb or less. Additionally, RN was associated with a significantly greater decline in eGFR at 1 year relative to PN in the CKD stage IV subset. Our data support performing PN for renal preservation when feasible.

Assessing the Impact of Hospital Dismissal Summary Readability on Patient Outcomes Following Prostatectomy.

PURPOSE: To assess the impact of decreasing the reading level of hospital dismissal summary information on the number of unplanned patient contacts with providers following robot-assisted radical prostatectomy. METHODS: A multidisciplinary team revised the hospital dismissal summary given to patients following prostatectomy to decrease the reading level from a 13th grade to seventh grade level. We conducted a retrospective cohort study comparing 30-day outcome measures including: patient-initiated telephone calls and online messages, unplanned clinic visits, readmission rates, and emergency department visits pre- and post-intervention. Other perioperative practices remained unchanged between the cohorts. RESULTS: A total of 110 patients were included in the study (pre-intervention n=60, post-intervention n=50). Patient age (P =.72), race (P =.59), marital status (P =.39), and education level (P = 1.0) were similar between the groups. Pre-intervention, 11.7% of patients had a self-reported education lever lower than the 13th grade, compared to 2% of patients post-intervention with an education level at or below the seventh grade. Following revision of the dismissal information, the number of patient-initiated messages (per patient) significantly decreased (mean 2.3 vs 1.4; P =.02). Patients who received the new dismissal information were significantly less likely to have an emergency department visit (20% vs 4%;P = .02). There were no differences in 30-day unplanned office visits (P =.75) or readmissions (P = 1.0). CONCLUSION: Reducing grade level readability of hospital dismissal information was associated with significantly lower rates of patient-initiated messages and emergency department visits. This intervention represents a valuable opportunity for improving the quality of patient care and decreasing postoperative care burden on the healthcare system.

Varicocele Repair Prior to Assisted Reproductive Technology: Patient Selection and Special Considerations.

Clinical varicoceles are one of the most commonly identified physical exam abnormalities in men presenting with infertility. Clinical varicoceles can cause impaired spermatogenesis and surgical correction can improve semen parameters in select men. Increasingly, andrologists are performing varicocele repairs prior to intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) to boost male fertility potential. In this review, we evaluated the available literature 1) to determine if varicocelectomy prior to IUI or assisted reproductive technologies proved to improve sperm production or pregnancy outcomes; and 2) to identify who may be the ideal candidate for pre-IUI/ART varicocelectomy. Overall, few studies have explored this topic and little can be concluded about the impact of varicocelectomy prior to IUI. The evidence, however, does support that correcting a clinical varicocele can increase pregnancy outcomes in couples who plan to pursue IVF or ICSI. When selecting patients for varicocelectomy prior to IUI or ART, clinicians should evaluate female age as improvement in semen parameters can take 6 months after varicocelectomy and this duration of time may be deleterious in cases of advanced maternal age when each cycle becomes increasingly important. Overall, the currently limited literature regarding clinical varicoceles correction demonstrates that pregnancy rates can be increased when comparing patients who have undergone varicocelectomy prior to ART with those who had clinical varicocele but did not undergo surgery.

Renal Mass Biopsy is Associated with Reduction in Surgery for Early-Stage Kidney Cancer.

OBJECTIVE: To determine whether use of renal mass biopsy may be associated with a reduction in surgery for patients with small, localized renal cell carcinoma (cT1aN0M0), especially among older patients and patients with greater comorbidity burden. METHODS: A total of 106,258 patients with cT1aN0M0 renal cell carcinoma from 2004 to 2015 were analyzed in the National Cancer Data Base. Multivariable logistic regression identified independent associations with nonsurgical management, receipt of biopsy, and pathologic upstaging. Marginal effects were derived by age and comorbidity. A sensitivity analysis was conducted in years identifying patients undergoing active surveillance (2010-2015). RESULTS: There was increased use of biopsy (8.0%-15.3%) and nonsurgical management (11.7%-15.6%) over time. Biopsy was significantly associated with use of nonsurgical management (OR 4.80 [95%CI 4.58-5.02], P <.001) as well as active surveillance (OR 1.87 [1.69-2.07], P <.001) in the sensitivity analysis. Individual predicted probability of undergoing nonsurgical management ranged from 3% to 92% (median 31.4% with use of biopsy) and increased with age and comorbidity. Pathologic tumor upstaging (≥pT3a) occurred more frequently for patients receiving biopsy compared to no biopsy (5.8% vs 3.3%, P <.001). After adjustment, biopsy remained a statistically significant predictor of upstaging (OR 1.31 [95%CI 1.24-1.38], P <.001). CONCLUSION: Overall, biopsy demonstrated a strong, independent association with reduced use of surgery for cT1aN0M0 kidney cancer, especially with increasing age and comorbidity. The potential association of renal mass biopsy with upstaging warrants caution, but it is uncertain whether it impacts prognosis relative to true perinephric fat invasion.

Access to Urological Care and Internet Connectivity in the United States: A Geospatial Analysis.

INTRODUCTION: Telemedicine video visits have been suggested as a mechanism to improve access to urological care in geographically isolated communities. However, Internet availability is not consistent across the United States. This study aims to better understand the interplay of broadband Internet, urologist density and county demographics to inform the strategic deployment of urological telemedicine. METHODS: A geospatial analysis was conducted to assess associations between broadband Internet and urologist density. Adequate broadband Internet availability was determined to be greater than 50% county coverage. Data were obtained from 2015 Federal Communications Commission filings. Physician density in 2015 was obtained from 2016-2017 Area Health Resources Files. A univariate regression was performed to estimate the associations of county demographics with broadband availability and urologist density. RESULTS: More than 10.9 million Americans lack access to local urology care and broadband Internet. Overall 31.7 million Americans lack access to a urologist but have reliable broadband Internet coverage. Counties with no urologists were associated with having less accessibility to broadband Internet and greater distance to the nearest county with a urologist. Counties without Internet availability or urologists were more likely to be rural (OR 9.93) and be designated as a whole county health professional shortage area (OR 10.05). CONCLUSIONS: A quarter of communities that lack access to local urologists also lack access to broadband Internet. Telemedicine cannot address poor access to urology care in communities without high-speed Internet. Future studies are needed to establish whether, pending expanded access to broadband Internet coverage, telemedicine will improve patient outcomes in geographically isolated communities.

Patient Decision-making and Predictors of Genital Satisfaction Associated With Testicular Prostheses After Radical Orchiectomy: A Questionnaire-based Study of Men With Germ Cell Tumors of the Testicle.

OBJECTIVE: To better understand patient decision-making and genital satisfaction associated with postorchiectomy testicular prosthesis (TP) implantation in patients with germ cell tumors of the testicle. MATERIALS AND METHODS: An electronic survey to assess TP decision-making and genital satisfaction was distributed to patients via an institutional database (n = 70) and social media outlets (n = 167). Statistical analyses were performed using chi-square tests for categorical variables, Wilcoxon-Mann-Whitney tests for continuous variables, and multivariate regression analyses to identify independent predictors of receiving a prosthesis, genital satisfaction, and prosthesis satisfaction. RESULTS: 24.9% of respondents elected to receive a TP, but 42% of men without a prosthesis reported never being offered one. Identifying as a heterosexual man (2.86) and receiving a TP (odds ratio = 3.29) were both positive predictors of overall genital satisfaction. Having the orchiectomy performed at an academic institution (odds ratio = 2.87) was a positive predictor of testicular prosthesis TP placement. 89.8% of TP recipients were satisfied with the look of their prosthetic, but only 59.3% of respondents were satisfied with prosthetic feel. CONCLUSION: There are high levels of genital satisfaction in those who elect to receive a TP postorchiectomy. Associations between TP placement, genital satisfaction, and sexuality merit further investigation. Our results also indicate that patients who pursue an orchiectomy at an academic institution are more likely to receive a TP. The use of social media to recruit study participants in urology should be explored further.

The Effect of Adjunct Mechanical Traction on Penile Length in Men Undergoing Primary Treatment for Peyronie's Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: To accurately characterize the effect of penile traction therapy (PTT) on stretched penile length (SPL) after primary treatment for men with PD. MATERIALS AND METHODS: A systematic search was performed for studies that evaluated the correction of PD using penile traction as secondary treatment published through January 2018. Studies were included if (1) a singular primary treatment of PD (injection or surgical treatment) was performed for all included men, (2) if there was a control group with no adjunct traction, and (3) if patients were required to wear the traction device for greater than 2 h/d. Estimates were pooled using random-effects meta-analysis. RESULTS: Data were obtained from 4 studies involving 348 men with an average age of 55.7 ± 2.0 years. Men who used PTT after primary intervention had SPLs 1.02 cm greater [95% CI: 0.64 to 1.40; I2=0%] when compared with men who did not use traction after primary intervention (p = 0.009). When performing subgroup analysis by primary therapy, no difference was seen in men undergoing penile traction after surgical correction when compared with men undergoing penile traction after injection therapy (1.01 vs 1.29 cm, p = 0.84). CONCLUSION: PTT may be a promising technique to reduce length loss in men undergoing PD treatment. Future work should be done to determine the ideal timing and subpopulations who would benefit from PTT.

Emerging immunotherapies in ovarian cancer.

Despite a global effort to significantly reduce mortality, ovarian cancer remains the fifth leading cause of cancer death among American women, and five-year survival rates remain discouragingly low at 45%. Novel therapies are urgently needed. Notably, higher infiltration of activated immune cells into the tumor microenvironment correlates with improved ovarian cancer survival, suggesting that promoting their activity could favorably impact clinical outcomes. Immunotherapy has recently demonstrated impressive clinical benefit in a variety of solid tumors. Immunotherapy strategies tested in ovarian cancer include vaccines, adoptive T cell therapy, and immune checkpoint blockade. Ultimately, a combination immunotherapy approach that integrates immunotherapy with other cancer treatment modalities in additive or synergistic ways will most effectively improve survival.

Depressed mood and suicidality in individuals exposed to tetrabenazine in a large Huntington disease observational study.

BACKGROUND: Tetrabenazine, a treatment for chorea in Huntington disease, carries a boxed warning due to safety, especially related to suicidality. OBJECTIVE: To compare the frequency of depressed mood and suicidality among a closely monitored cohort of individuals with Huntington disease who were exposed and not exposed to tetrabenazine. METHODS: A longitudinal prospective study involving 1360 individuals with HD evaluated at 48 research centers in Australia, Canada, and the United States was examined for frequency of depressed mood that triggered a risk assessment, suicidal thoughts, suicide attempts, and completed suicide among individuals with prior, new, and no exposure to tetrabenazine.. Seventy-seven individuals were on tetrabenazine at study enrollment (prior exposure), 64 individuals were exposed to tetrabenazine during the study's course (new exposure), and 1219 individuals had no exposure to tetrabenazine. RESULTS: The hazard ratio for depressed mood among those with prior exposure to tetrabenazine compared to no exposure was 0.9 (95% CI, 0.5-1.6) and for those with new exposure compared to no exposure was 1.2 (95% CI, 0.8-1.9). One individual (1.3%) with prior exposure, one individual (1.6%) with new exposure, and 35 individuals (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard ratio for suicidal ideation among those with prior exposure to tetrabenazine compared to no exposure was 0.5 (95% CI, 0.1-3.8) and for those with new exposure to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1-4.4). Among individuals with prior or new exposure to tetrabenazine, no suicide attempts or suicides occurred. Among those with no exposure to tetrabenazine 17 suicide attempts (1.4%) and four suicides (0.3%) occurred. CONCLUSIONS: In a large observational study with close clinical supervision, tetrabenazine treatment was not associated with an increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide.