Functional outcomes after prostate cancer treatment: A comparison between single and multiple modalities.

Prostate cancer is a widely common and treatable disease, and functional outcomes can greatly affect survivor quality of life. A retrospective review of the SEER-Medicare database was performed to identify patients who underwent prostate cancer treatment between January 1, 2004 and December 31, 2013 and review the rates of diagnosis and treatment of common functional side effects of surgery, radiation, or a combination of the 2 and perform a comparison of the outcomes. A total of 67,527 patients were included in the analysis. Radiation therapy (RT)-only compared to radical prostatectomy (RP)-only had lower rates of diagnosis of erectile dysfunction (30.4%, 95% CI 29.9%-30.9% vs. 56.1%, 95% CI 55.1%-57.04%, P < 0.0001), UI (29.7%, 95% CI 29.0%-30.3% vs. 44.5%, 95% CI 43.3%-45.6%, P < 0.0001), but higher rates of urethral stricture disease (8.44%, 95% CI 8.1%-8.8% vs. 5.35%, 95% CI 4.9%-5.9%, P < 0.0001), cystitis (33.1% 95% CI 32.4%-33.7% vs. 20.3%, 95% CI 19.2%-21.4%, P < 0.0001), and proctitis (14.7%, 95% CI 14.3%-15.1& vs. 2.75%, 95% CI 2.3%-3.3%, P < 0.0001). Compared to either single modality, the RP-then-RT group had higher incontinence medication use (12.0% 95% CI 10.8%-13.2% vs. 9.8%, 95% CI 9.5%-10.1% for RT-only and 8.3%, 95% CI 7.8%-8.8% for RP-only, P < 0.0001), overall incontinence therapy (18.5%, 95%CI 17.1%-20.0% vs. 10.2%, 95%CI 9.9%-10.5% for RT-only and 14.9%, 95% CI 14.3%-15.5% for RP-only, P < 0.0001), and stricture therapy (12.7%, 95% CI 11.5%-13.9% vs. 8.2%, 95% CI 8.0%-8.5% for RT-only and 9.1% 95% CI 8.6%-9.6% for RP-only, P < 0.0001). The RT-then-RP group had higher rates of stricture (25.4% compared to 8.2% for RT-only, 9.1% for RP-only, and 12.7% for RP-then-RT) and fistula (1.0% compared to 0.07% for RT-only, 0.18% for RP-only, and 0.092% for RP-then-RT) treatment than all the other groups. Multimodality therapy is generally associated with higher treatments rates for conditions such as erectile dysfunction , incontinence, urethral stricture disease , irritative cystitis and proctitis in patients older than 65. Radiation therapy followed by prostatectomy is associated with significantly worse functional outcomes. Patients undergoing or anticipating undergoing multimodality therapy for prostate cancer should be counseled regarding the possibility of increased risk of declining functional outcomes.

Does significantly elevated lung shunt fraction (LSF >20%) promote extrahepatic progression in patients with hepatocellular carcinoma treated with radioembolization?

PURPOSE: Radioembolization with yttrium-90 (Y-90) is an effective locoregional therapy for primary and metastatic liver tumors, but its use is restricted or contraindicated for patients with elevated lung shunt fraction (LSF) because of an increased risk of developing pulmonary adverse events, including but not limited to radiation pneumonitis. Elevated LSF is also thought to be correlated with liver tumor progression and metastases. METHODS: In this retrospective cohort study, we examine rates of metastasis development, rates of adverse events and overall survival (OS) in 23 patients with hepatocellular carcinoma (HCC) and elevated LSF >20% on Tc-99 m macroaggregated albumin scan treated with Y-90 radioembolization at our institution from 2005 to 2016. To minimize confounding variables, patients with baseline extrahepatic metastases or portal vein tumor thrombosis were excluded. Kaplan-Meier estimates were performed for OS and time to development of metastases. RESULTS: No patient developed clinical and imaging signs of radiation pneumonitis. Median intention to treat OS from day of radioembolization was 21.3 months; median censored OS was 14.7 months. Five out of 23 patients (22%) developed at least one metastasis during follow-up, for an incidence of 20 per 1000 patient-years (compared to the historical rate of 6 per 1000 patient-years for HCC patients in general). CONCLUSION: HCC patients with LSF >20% treated with Y-90 radioembolization have acceptable toxicities and appear to have a rate of extrahepatic tumor development (22%) higher than expected for patients with HCC.

Male Infertility Diagnosis and Treatment in the Era of In Vitro Fertilization and Intracytoplasmic Sperm Injection.

As assisted reproductive technologies use increases, the evaluation of male factor infertility has often become overlooked. However, male evaluation remains critically important, with benefits seen in overall health, as well as in natural and assisted pregnancy and birth rates. A comprehensive assessment of the male partner should be offered to all couples seeking infertility care.

Fast two-photon imaging of subcellular voltage dynamics in neuronal tissue with genetically encoded indicators.

Monitoring voltage dynamics in defined neurons deep in the brain is critical for unraveling the function of neuronal circuits but is challenging due to the limited performance of existing tools. In particular, while genetically encoded voltage indicators have shown promise for optical detection of voltage transients, many indicators exhibit low sensitivity when imaged under two-photon illumination. Previous studies thus fell short of visualizing voltage dynamics in individual neurons in single trials. Here, we report ASAP2s, a novel voltage indicator with improved sensitivity. By imaging ASAP2s using random-access multi-photon microscopy, we demonstrate robust single-trial detection of action potentials in organotypic slice cultures. We also show that ASAP2s enables two-photon imaging of graded potentials in organotypic slice cultures and in Drosophila. These results demonstrate that the combination of ASAP2s and fast two-photon imaging methods enables detection of neural electrical activity with subcellular spatial resolution and millisecond-timescale precision.

Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness.

Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required.

Performance of robotic simulated skills tasks is positively associated with clinical robotic surgical performance.

OBJECTIVE: To compare user performance of four fundamental inanimate robotic skills tasks (FIRST) as well as eight da Vinci Skills Simulator (dVSS) virtual reality tasks with intra-operative performance (concurrent validity) during robot-assisted radical prostatectomy (RARP) and to show that a positive correlation exists between simulation and intra-operative performance. MATERIALS AND METHODS: A total of 21 urological surgeons with varying robotic experience were enrolled. Demographics were captured using a standardized questionnaire. User performance was assessed concurrently in simulated (FIRST exercises and dVSS tasks) and clinical environments (endopelvic dissection during RARP). Intra-operative robotic clinical performance was scored using the previously validated six-metric Global Evaluative Assessment of Robotic Skills (GEARS) tool. The relationship between simulator and clinical performance was evaluated using Spearman's rank correlation. RESULTS: Performance was assessed in 17 trainees and four expert robotic surgeons with a median (range) number of previous robotic cases (as primary surgeon) of 0 (0-55) and 117 (58-600), respectively (P = 0.001). Collectively, the overall FIRST (ρ = 0.833, P < 0.001) and dVSS (ρ = 0.805, P < 0.001) simulation scores correlated highly with GEARS performance score. Each individual FIRST and dVSS task score also demonstrated a significant correlation with intra-operative performance, with the exception of Energy Switcher 1 exercise (P = 0.063). CONCLUSIONS: This is the first study to show a significant relationship between simulated robotic performance and robotic clinical performance. Findings support implementation of these robotic training tools in a standardized robotic training curriculum.

Low-Intensity Extracorporeal Shock Wave as a Novel Treatment for Erectile Dysfunction.

The paradigm of erectile dysfunction (ED) treatment was fundamentally altered following the introduction of oral phosphodiesterase type 5 inhibitors. Unfortunately, a significant number of men exhibit a suboptimal response and require additional management strategies. One of the novel, minimally invasive strategies being developed is low-intensity extracorporeal shock wave therapy. Used in the hope of delaying placement of an inflatable penile prosthesis, the final phase of ED treatment, low-intensity extracorporeal shock wave therapy is a unique application of an established technology that may hopefully one day expand the medical options for patients with ED. This commentary will highlight the physiology underlying this technique and summarize the most recent studies.

Multi-Institutional Validation of Fundamental Inanimate Robotic Skills Tasks.

PURPOSE: Our group has previously reported the development and validation of FIRST (Fundamental Inanimate Robotic Skills Tasks), a series of 4 inanimate robotic skills tasks. Expanding on the initial validation, we now report face, content and construct validity of FIRST in a large multi-institutional cohort of experts and trainees. MATERIALS AND METHODS: A total of 96 residents, fellows and attending surgeons completed the FIRST exercises at participating institutions. Participants were classified based on previous robotic experience and task performance was compared across groups to establish construct validity. Face and content validity was assessed from participant ratings of the tasks on a 5-point Likert scale. RESULTS: A total of 51 novice, 22 intermediate and 23 expert participants with a median previous robotic experience of 0 (range 0 to 3), 10 (range 5 to 30) and 200 cases (range 55 to 2,000), respectively (p<0.001), were assessed across all 4 inanimate robotic skills tasks. Expert and intermediate groups reliably outperformed novices (p<0.01). Experts also performed better than intermediates on all exercises (p<0.01). A survey of participants on their perceptions of the tasks yielded excellent face and content validity. CONCLUSIONS: We confirm robust face, content and construct validity of 4 inanimate robotic training tasks in a large multi-institutional cohort. FIRST tasks are reliably able to discern among expert, intermediate and novice robotic surgeons. Validation data from this large multi-institutional cohort is useful as we incorporate these tasks into a comprehensive robotic training curriculum.

External validation of Global Evaluative Assessment of Robotic Skills (GEARS).

BACKGROUND: We demonstrate the construct validity, reliability, and utility of Global Evaluative Assessment of Robotic Skills (GEARS), a clinical assessment tool designed to measure robotic technical skills, in an independent cohort using an in vivo animal training model. METHODS: Using a cross-sectional observational study design, 47 voluntary participants were categorized as experts (>30 robotic cases completed as primary surgeon) or trainees. The trainee group was further divided into intermediates (≥5 but ≤30 cases) or novices (<5 cases). All participants completed a standardized in vivo robotic task in a porcine model. Task performance was evaluated by two expert robotic surgeons and self-assessed by the participants using the GEARS assessment tool. Kruskal-Wallis test was used to compare the GEARS performance scores to determine construct validity; Spearman's rank correlation measured interobserver reliability; and Cronbach's alpha was used to assess internal consistency. RESULTS: Performance evaluations were completed on nine experts and 38 trainees (14 intermediate, 24 novice). Experts demonstrated superior performance compared to intermediates and novices overall and in all individual domains (p < 0.0001). In comparing intermediates and novices, the overall performance difference trended toward significance (p = 0.0505), while the individual domains of efficiency and autonomy were significantly different between groups (p = 0.0280 and 0.0425, respectively). Interobserver reliability between expert ratings was confirmed with a strong correlation observed (r = 0.857, 95 % CI [0.691, 0.941]). Experts and participant scoring showed less agreement (r = 0.435, 95 % CI [0.121, 0.689] and r = 0.422, 95 % CI [0.081, 0.0672]). Internal consistency was excellent for experts and participants (α = 0.96, 0.98, 0.93). CONCLUSIONS: In an independent cohort, GEARS was able to differentiate between different robotic skill levels, demonstrating excellent construct validity. As a standardized assessment tool, GEARS maintained consistency and reliability for an in vivo robotic surgical task and may be applied for skills evaluation in a broad range of robotic procedures.

Current state of practice regarding testosterone supplementation therapy in men with prostate cancer.

Hypogonadal men are characterized by low serum testosterone and symptoms of low energy, decreased libido, and muscle mass as well as impaired concentration and sexual functioning. Men with prostate cancer (PCa) currently on active surveillance or post-therapy, have traditionally been excluded from management paradigms given the decade-old concern that testosterone caused PCa growth. However, there appears to be little or no relationship between serum testosterone concentration and PCa. Androgen action in the prostate has long been known to be affected by the kinetics of receptor saturation and, as such, testosterone beyond a certain baseline is unable to stimulate prostatic growth due to complete intra-prostatic androgen receptor binding. Given this physiologic concept, many clinical investigators have begun to promote testosterone supplementation therapy (TST) as safe in men with PCa. This review examines the basics of testosterone physiology and summarizes the most recent findings on the use of TST in men with PCa on active surveillance and following treatment with external beam radiotherapy, brachytherapy and radical prostatectomy.