Focal p53 protein expression and lymphovascular invasion in primary prostate tumors predict metastatic progression.

TP53 is one of the most frequently altered genes in prostate cancer. The precise assessment of its focal alterations in primary tumors by immunohistochemistry (IHC) has significantly enhanced its prognosis. p53 protein expression and lymphovascular invasion (LVI) were evaluated for predicting metastatic progression by IHC staining of representative whole-mounted prostate sections from a cohort of 189 radical prostatectomy patients with up to 20 years of clinical follow-up. Kaplan-Meier survival curves were used to examine time to distant metastasis (DM) as a function of p53 expression and LVI status. TP53 targeted sequencing was performed in ten tumors with the highest expression of p53 staining. Nearly half (49.8%) of prostate tumors examined showed focal p53 expression while 26.6% showed evidence of LVI. p53(+) tumors had higher pathologic T stage, Grade Group, Nuclear Grade, and more frequent LVI. p53 expression of > 5% and LVI, individually and jointly, are associated with poorer DM-free survival. TP53 mutations were detected in seven of ten tumors sequenced. Four tumors with the highest p53 expression harbored likely pathogenic or pathogenic mutations. High levels of p53 expression suggest the likelihood of pathogenic TP53 alterations and, together with LVI status, could enhance early prognostication of prostate cancer progression.

Patient Perpetrated Sexual Harassment of Urologists: A Survey Based Study.

INTRODUCTION: Patient perpetrated sexual harassment has been studied with family physicians, surgical residents and dermatologists with the prevalence ranging from 27% to 77%. To our knowledge this phenomenon has not yet been studied in urology. METHODS: We surveyed urologists in the United States about their age, employment/training status and their experiences of patient perpetrated sexual harassment. Surveys were anonymous and hosted on a web based platform. Pearson chi-square analysis was used to assess risk factors and descriptive statistics were used to describe prevalence. RESULTS: A total of 190 urologists completed the survey. Patient perpetrated sexual harassment was reported by 49.5% of respondents. Women were more likely to report patient perpetrated sexual harassment when compared with men, at 69% and 23%, respectively (p <0.0001). Being a resident/fellow portended higher rates of patient perpetrated sexual harassment compared to staff/attendings, at 69% and 44%, respectively (p=0.004). Respondents 40 years or younger were more likely to have reported patient perpetrated sexual harassment when compared to those 41 years old or older, at 65% and 39%, respectively (p=0.001). CONCLUSIONS: The results of this survey study suggest that the prevalence of patient perpetrated sexual harassment in the field of urology may be high. Professional societies should perform further investigation into this matter. We suggest proactive development of guidelines and protocols to address patient perpetrated sexual harassment in urology.

Relationship between chronic testicular pain and mental health diagnoses.

BACKGROUND: Chronic testicular pain (orchialgia) has been defined as intermittent or constant unilateral or bilateral testicular pain that lasts 3 months or longer, significantly interfering with daily activities, and prompting the patient to seek medical attention. In many instances, the etiology of the pain is not identified. The contribution of psychological factors is unclear. The purpose of this study was to identify the categories of mental health (MH) diagnoses that are most frequently associated with orchialgia and determine if a correlation exists between MH diagnoses and orchialgia. METHODS: A retrospective review was performed to identify all adult patients within the San Antonio Military Health System with a new diagnosis of orchialgia from January 2005 to April 2015. Patients with acute pathology or recent inguinal/scrotal surgery were excluded. A comparative cohort of all men presenting with hydroceles within the same timeframe was obtained. The presence of coexisting MH diagnoses in both cohorts was then determined. RESULTS: Four hundred and forty-four men met the inclusion criteria for orchialgia, with 133 men presenting with hydroceles. The incidence of orchialgia increased significantly over the study period (P=0.001). MH diagnoses in the study population did trend upward over the years, but not significantly (P=0.063). MH diagnoses were not significantly higher in the cases compared to the controls (21.6% vs. 18.8%, P=0.479). The prevalence of anxiety was twice as high in the cases (9% vs. 4.5%), though not significantly (P=0.075). The prevalence of all MH diagnoses was significantly higher than in the general US population based on National Institute of Mental Health statistics. CONCLUSIONS: The incidence of orchialgia rose significantly over time, but it was not significantly associated with MH diagnoses. These results may also be skewed by the overall higher percentage of MH diagnoses in the study population than in the general population.

Evaluation and treatment of erectile dysfunction.

Erectile dysfunction (ED) is a prevalent and important disease that has been associated with various comorbidities. The evaluation of patients with ED should include a general health assessment followed by a discussion of reversible factors and lifestyle changes that might help preserve erectile capacity. Numerous effective treatment options are currently available. A frank discussion about use and side effects of these therapies is required to optimize success. Although oral pharmacologic treatments can be initiated and monitored by the primary care physician, patients who do not experience response to these treatments may be best served by referral to a sexual medicine specialist for further assessment and consideration of other treatment options. This article discusses the physiology and pathophysiology of erectile function in men, how the primary care physician may address the clinical problem of ED in practice, and when specialty referral is indicated.

Androgen blockade for the treatment of high-flow priapism.

INTRODUCTION: High-flow priapism (HFP) may occur secondary to perineal trauma, congenital arterial malformations, and iatrogenic insults. In cases that do not resolve spontaneously, standard management is by selective embolization, resulting in resolution rates as high as 78%; however, erectile dysfunction (ED) is a frequent complication, occurring in up to 39% of cases. AIM: We report our use of androgen blockade (AB) to suppress nocturnal erections as an alternative treatment for HFP. METHODS: A retrospective review of all patients treated at our institution for HFP was undertaken. Included in this study were any patients treated with single- or combination-agent AB for HFP. Operative reports and medical records were examined to determine patient characteristics and outcomes. Treatment efficacy, side effects, and residual ED were assessed using a questionnaire. MAIN OUTCOME MEASURES: The primary clinical outcomes assessed were resolution of HFP, tolerability, and side effects of treatment. RESULTS: Seven patients with HFP were treated with AB. Priapism was a result of trauma in three patients and a persistent high-flow state after shunt procedures in four. Mean follow-up was 2 years (range 4 to 64 months). Therapy consisted primarily of 7.5 mg intramuscular monthly leuprolide injections, although bicalutamide and ketoconazole were also utilized as adjunct treatments. Therapy duration ranged from 2 months to 6 months and was discontinued after symptom resolution. One patient discontinued daily ketoconazole after 1 week because of severe hot flashes. The remaining six patients reported complete resolution of HFP. The primary complaints during therapy were decreased libido and fatigue. All patients reported some degree of ED during therapy. There was no reported residual ED or other hypogonadal symptoms on withdrawal of therapy. CONCLUSION: AB is a successful option for treating HFP with acceptable side effects and return to baseline potency on treatment withdrawal.

The future is today: emerging drugs for the treatment of erectile dysfunction.

IMPORTANCE OF THE FIELD: Erectile dysfunction (ED) is the most common male sexual dysfunction presented for treatment affecting between 10 and 20% of men. PDE type 5 inhibitors (PDE5I) now account for the largest segment of the ED market. While these drugs are highly efficacious for many men, a relatively large subset of ED patients who do not respond to PDE5I is increasingly recognized. AREAS COVERED IN THIS REVIEW: In this review, we discuss clinical and preclinical evidence supporting various emerging compounds that regulate penile erection both centrally (clavulanic acid, dopamine and melanocortin receptor agonists) and peripherally (novel PDE5I, soluble and particulate guanylil cyclase activators, rho-kinase inhibitors and maxi-K channel openers). WHAT THE READER WILL GAIN: The reader will gain a broad understanding of erectile (patho-)physiology and gain insights in the mechanisms of action, efficacy and adverse events of various compounds under development for the treatment of ED. TAKE HOME MESSAGE: We expect emerging drugs to allow treatment protocols tailored to the specific needs of each individual patient, taking into consideration the efficacy of erectile performance enhancement and the potential for adverse events. This tailored approach may include combination of various emerging drugs to enhance efficacy in difficult-to-treat patients.