Avinash Nehra

Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: urologic and cardiovascular implications.

Abstract Erectile dysfunction (ED) occurs in varying degrees in an estimated 20 to 30 million American men and is associated with adverse effects on quality of life; particularly personal well-being, family and social interrelationships. Research into ED has focused primarily on the physiologic mechanisms of corpus cavernosum smooth muscle relaxation, and penile erection as the end result of smooth muscle relaxation. These processes are mediated by cholinergic, nonadrenergic, noncholinergic (NANC, e.g., nitric oxide), vasoactive intestinal peptide (VIP), and potentially calcitonin gene-related peptide (CGRP) containing nerves. Release of nitric oxide following sexual stimulation from non-adrenergic, non cholinergic nerves and vascular endothelium activates guanylyl cyclase and induces intracellular cGMP synthesis. In turn, cGMP results in lowering intracellular concentrations, inhibits contractility of the penile smooth muscle, and induces an erectile response. Phosphodiesterase type 5 (PDE 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, and subsequent penile flaccidity. Sildenafil citrate is a potent PDE type 5 reversible and selective inhibitor which blocks cGMP hydrolysis effectively. FDA approval of sildenafil citrate as the first oral agent for ED in males has resulted in significant interest. We discuss the clinical and pharmacologic properties of sildenafil citrate as well as the urologic and cardiac implications.

Proton Pump Inhibitors: Review of Emerging Concerns

&NA; First introduced in 1989, proton pump inhibitors (PPIs) are among the most widely utilized medications worldwide, both in the ambulatory and inpatient clinical settings. The PPIs are currently approved by the US Food and Drug Administration for the management of a variety of gastrointestinal disorders including symptomatic peptic ulcer disease, gastroesophageal reflux disease, and nonulcer dyspepsia as well as for prevention of gastrointestinal bleeding in patients receiving antiplatelet therapy. PPIs inhibit gastric acid secretion, and the most commonly associated adverse effects include abdominal pain, diarrhea, and headache. Although PPIs have had an encouraging safety profile, recent studies regarding the long‐term use of PPI medications have noted potential adverse effects, including risk of fractures, pneumonia, Clostridium difficile diarrhea, hypomagnesemia, vitamin B12 deficiency, chronic kidney disease, and dementia. These emerging data have led to subsequent investigations to assess these potential risks in patients receiving long‐term PPI therapy. However, most of the published evidence is inadequate to establish a definite association between PPI use and the risk for development of serious adverse effects. Hence, when clinically indicated, PPIs can be prescribed at the lowest effective dose for symptom control.

Mid-term Outcomes Following Salvage Lymph Node Dissection for Prostate Cancer Nodal Recurrence Status Post–radical Prostatectomy

BACKGROUND Patients with oligometastatic prostate cancer lymph node recurrence can be treated with many options including salvage lymph node dissection (sLND). OBJECTIVE Evaluation of outcomes of sLND and identification of clinicopathologic features in predicting further biochemical and radiological relapse after sLND for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS Between November 1, 2009 and March 31, 2015, 117 patients with biochemical recurrence (BCR) after radical prostatectomy (RP) underwent sLND by a single surgeon after a standardized 11C-choline positron emission tomography/computed tomography. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Biochemical response (BR) was defined as a prostate-specific antigen (PSA) < 0.2ng/ml after sLND, BCR was defined as a PSA greater than 0.2 ng/ml with an increased trend after sLND, and radiological recurrence (RAR) was defined as a positive 11C-choline positron emission tomography/computed tomography imaging study or biopsy proven metastasis after sLND. Kaplan-Meier method was used to assess time to BCR, RAR, and cancer-specific mortality. Preoperative and postoperative predictors of BCR and RAR were assessed with Cox regression analyses. RESULTS AND LIMITATIONS All patients had confirmed lymph node metastasis on final sLND pathology. Median follow-up after sLND was 20.2 mo (interquartile range: 11.8-33.6). All but one patient had a decrease in PSA while 93/117 (79.5%) patients achieved BR after sLND. In those who achieved BR, a subsequent BCR occurred in 40% of cases (n=37/93). The 5-yr BCR, RAR, and cancer-specific mortality-free survival rates were 31%, 51%, and 97% respectively. At multivariate analyses, predictors of both BCR and RAR were pathological stage of the tumor at original RP and whether the nodes were castrate resistant prostate cancer. Given the nonrandomized nature, it is not known how these men would have fared according to survival or quality of life by observation, and/or other systemic therapy. CONCLUSIONS An optimal candidate for sLND tends to have pT2 at the original RP and a castration sensitive disease state. sLND could be considered part of a multimodal treatment approach in select patients with castrate-resistant prostate cancer in which delayed/reduced cancer progression could be achieved with a cytoreductive surgery. PATIENT SUMMARY We found that by performing a salvage lymph node dissection there are many men that can experience a biochemical response and eliminate further 11C-choline positron emission tomography/computed tomography radiographic recurrences.

Detection of recurrent prostate cancer after primary radiation therapy: An evaluation of the role of multiparametric 3T magnetic resonance imaging with endorectal coil.

OBJECTIVES The value of multiparametric magnetic resonance imaging (mpMRI) in staging prostate cancer (PCa) before salvage prostatectomy is currently unclear because of the minimal data comparing mpMRI results to final pathologic stage at surgery. The aim of the study is to determine the diagnostic performance of mpMRI in characterizing viable recurrent tumor and lymph node metastasis following radiation therapy (RT) failure. METHODS AND MATERIALS Between January 2007 and July 2014, 19 patients with biopsy-proven recurrent PCa after primary RT underwent 3T mpMRI and subsequent salvage prostatectomy with extended pelvic lymphadenectomy. mpMRI images were independently reviewed by 2 genitourinary MRI radiologists (R1 and R2), blinded to the pathology results, to evaluate extraprostatic extension (EPE), seminal vesicle invasion (SVI), and pelvic lymph node metastasis (PLNM). Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic curves, and interobserver agreement (R1 and R2) were evaluated for each outcome on a per-patient basis. Final pathologic results were used as a gold standard for comparison in all patients. A multivariate analysis was conducted to assess the relationship between the index lesions apparent diffusion coefficient value and its enhancement characteristics with the Gleason score. RESULTS EPE was found in 14 (73.7%) patients, SVI in 13 (68.4%), and PLNM in 5 (26.3%). mpMRI sensitivity for PLNM was 60.0% (R1 and R2) with specificity of 85.7% (R1) and 92.8% (R2). With regards to SVI, the sensitivity was 61.5% (R1) and 76.9% (R2), with a specificity of 66.6% (R1 and R2). Sensitivity for EPE was 50.0% (R1) and 71.43% (R2), with a specificity of 80.0% (R1) and 100.00% (R2). No significant associations were found at multivariate analysis. The evaluation of PLNM, SVI, and PCa recurrence within the prostate demonstrated moderate interobserver agreement (κ, 0.51-0.57). CONCLUSIONS mpMRI has good accuracy for detecting PLNM, SVI, and EPE after RT. mpMRI provides useful information in locally recurrent PCa following primary radiation therapy.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging

Purpose We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. Materials and Methods After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. Results A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92–17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90–21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. Conclusions The combination of 11C‐choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.

A Survey of Perceptions and Acceptance of Wearable Technology for Health Monitoring in a Urological Patient Population

Introduction: Through real‐time monitoring of biophysical parameters, physical activity monitors may represent a medium by which urologists can actively engage patients and improve treatment outcomes. We examined patient reported acceptance of physical activity monitor technology in an ambulatory urology setting. Methods: Patients treated at a single urology department during a 6‐month period were identified. A web based survey was conducted evaluating patient characteristics and acceptance of physical activity monitors. Results: A total of 1,043 (19%) patients completed the survey, of whom 210 (20%) reported using physical activity monitors for health and wellness. Overall 854 (82%) respondents were willing to use these devices for urological care. Compared to patients who disagreed, those willing to use physical activity monitors for medical care reported greater perceived medical benefit (86% vs 14%), improved communication (85% vs 26%), confidentiality (89% vs 45%), less interference with daily activity (4% vs 55%) and improved health (81% vs 13%, all p <0.0001). Benefits and usefulness among accepting patients included health monitoring convenience (82%), goal related feedback (82%), ease of communication (57%) and monitoring of post‐procedure recovery (56%). After controlling for associated patient characteristics, the degree of perceived burden, medical benefit, health improvement and enhancement in communication were modifiable, and independently associated with physical activity monitor acceptance. Conclusions: There is a high level of acceptance for wearable technology among urology patients. This may have significant implications for improving patient engagement, perioperative care pathways and surgical outcomes. Finally, these findings may assist urologists in directing future efforts to clinically integrate physical activity monitors to enhance patient acceptance and potential outcomes.