Nelson Bennett

Bladder Overactivity and Hyperexcitability of Bladder Afferent Neurons after Intrathecal Delivery of Nerve Growth Factor in Rats

Nerve growth factor (NGF) has been proposed as an important mediator inducing bladder overactivity under pathological conditions such as spinal cord injury, bladder outlet obstruction, or cystitis. We therefore examined the effects of chronic NGF treatment on bladder activity and the properties of bladder afferent neurons. In adult female rats, NGF (2.5 μg/μl) was infused continuously into the intrathecal space at the L6–S1 level of spinal cord for 1 or 2 weeks using osmotic pumps (0.5 μl/h). Bladder afferent neurons were labeled with axonal transport of Fast Blue injected into the bladder wall. After intrathecal injection of NGF, cystometrograms under an awake condition showed bladder overactivity revealed by time-dependent reductions in intercontraction intervals and voided volume. ELISA analyses showed significant increases in NGF levels in L6–S1 dorsal root ganglia of NGF-treated rats. In patch-clamp recordings, dissociated bladder afferent neurons exhibiting tetrodotoxin (TTX)-resistant action potentials from NGF-treated animals were larger in diameter and had significantly lower thresholds for spike activation compared with sham rats. In addition, the number of TTX-resistant action potentials during 600 ms depolarizing pulses was significantly increased time dependently after 1 or 2 weeks of NGF application. The density of slowly inactivating A-type K+ currents was decreased by 52% in bladder afferent neurons with TTX-resistant spikes after 2 week NGF treatment. These results indicate that increased NGF levels in bladder afferent pathways and NGF-induced reduction in A-type K+ current density could contribute to the emergence of bladder overactivity as well as somal hypertrophy and hyperexcitability of bladder afferent neurons.

Sickle Cell Disease Status and Outcomes of African-American Men Presenting with Priapism

INTRODUCTION Priapism is associated with sickle cell disease (SSD); however, few men receive education about this condition, which contributes to attenuated return of functional erections. AIM To define the demographics, SSD status, and treatment outcomes of African-American men presenting with priapism. MAIN OUTCOME MEASURES Demographics, medical history, self-report of sickle cell status, and outcome assessment using International Inventory of Erectile Function (IIEF) of men with priapism were retrospectively reviewed. METHODS A review of 39 cases of venocclusive priapism in African-American men was conducted. Charts were reviewed for demographics, medical history including SSD status by patient self-report, serum hemoglobin electrophoresis results, and priapism treatment and outcome. RESULTS Mean duration of presenting priapism episode was 22 +/- 12 hours (6-70 hours). Eight percent of men had priapism for <12 hours, 59% 12-24 hours, 22% 24-36 hours, and 11% >36 hours. All patients with priapism events of >12 hours complained of reduction in erectile rigidity. No patients with priapism >36 hours duration had return of spontaneous functional erections, but 44% (24-36 hours), 78% (12-24 hours) and 100% (<12 hours) were able to generate functional erections with or without the use of sildenafil. Follow-up IIEF erectile function domain scores paralleled incidence of functional erections. Penile shunt surgery was required in 28%. Only 5% of men recalled learning that priapism was a complication of SSD. Six men denied a history of SSD; however, hemoglobin electrophoresis revealed abnormal hemoglobin S and elevated hemoglobin F levels in four of these men. CONCLUSIONS The association of SSD and venocclusive priapism is well known in the medical community, yet few patients ever receive education regarding the emergency nature of the condition. The majority of men presents in a delayed fashion, and a significant proportion requires shunt surgery leading to long-term erectile dysfunction. Of those who denied having SSD, two-thirds had SSD by hemoglobin electrophoresis.

Chronology of erectile function in patients with early functional erections following radical prostatectomy

INTRODUCTION The association between erectile dysfunction (ED) and radical prostatectomy (RP) is well established. It is our clinical experience that some men who have functional erections in the days to weeks after RP go on to lose erectile function (EF) after the first 3 months postsurgery. AIM To assess EF over a 12-month period in patients with functional erections at 3 months following RP. METHODS As part of a large prospective quality-of-life (QOL) study of men undergoing RP at our institution, EF is measured postoperatively at regular time intervals using serial administration of the International Index of Erectile Function (IIEF) questionnaire. For study inclusion, patients had to have functional erections (a score 4 or 5 on IIEF question 3) at the third postoperative month, and have at least 12 months of follow-up. MAIN OUTCOME MEASURES Assessment of EF and phosphodiesterase type 5 inhibitor (PDE5i) use at 3, 6, and 12 months after RP. RESULTS At 3 months, 76 of 482 patients (16%) had functional erections. Between 3 to 6 months postoperatively, 20% of men deteriorated in their functional status. Of these men, 91% had functional erections at 1 year. Comparing patients who did not require PDE5i to obtain a functional erection at 3 months with those who did, the EF outcomes were superior at 6 months (80% vs. 72%, P = 0.74) and 12 months (100% vs. 88%, P = 0.33). CONCLUSION The recovery of functional erections in the early postoperative phase, especially without the need for PDE5i, is a good prognostic indicator for EF at 12 months. However, a distinct cohort of men lose functional erections within 6 months after surgery. It is important to inform patients of this possibility, as it has an impact on their QOL and, potentially, on their compliance with post-RP therapy for ED.

FK506 and Erectile Function Preservation in the Cavernous Nerve Injury Model: Optimal Dosing and Timing

INTRODUCTION The immunophilin-ligand FK506 has been shown to ameliorate erectile function and preserve cavernous nerve (CN) architecture in short-term-studies using rat models of CN injury. AIM The aim of this series was to ascertain the optimal dose and timing of FK506 administration in this animal model. METHODS Rats underwent bilateral CN crush and were treated with FK506 at different time points. There were control (C) and sham groups for each time point. Based on preliminary experiments, the CN-crush rats had no treatment (C) or either FK506 1 mg/kg (BL) or 3.2 mg/kg (BH) for 3 days prior to and the day of CN crush (PRE), on the day of and for 3 days following CN crush (POST) and for 3 days pre-, on the day of, and 3 days post-CN crush (PP). MAIN OUTCOME MEASUREMENTS All animals had measurement of intracavernosal pressure/mean arterial blood pressure (ICP/MAP) ratios at 28 days post-CN crush. Structural analysis was conducted in the POST groups. Penile tissue was assessed for apoptosis with terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay and immunohistochemically for neural factors (growth associated protein 43 [GAP43], nerve growth factor [NGF], and neural nitric oxide synthase [nNOS]). The CN architecture was examined by transmission electron microscopy (TEM). RESULTS Sham animals had an ICP/MAP ratio of 70%. Only the BH-POST group revealed an improved ICP/MAP ratio compared with C (50 +/- 9% vs. 32 +/- 8%, P < 0.01). nNOS staining was significantly restored reaching sham levels in BL-POST and BH-POST groups vs. C (P < 0.05). NGF and GAP43 staining displayed no significant differences between C and treatment groups (P < 0.05). Apoptosis was significantly reduced in BL-POST and BH-POST groups compared with C (16 +/- 4%, 21 +/- 9%, and 63 +/- 7%, P < 0.001). TEM exhibited preservation of CN architecture for BH-POST compared with C. CONCLUSION These results suggest that short-term treatment with doses of FK506 higher than previously utilized preserves erectile function in the rat CN-injury model. Pretreatment appears to offer no advantage. However, FK506 administration just prior to CN injury and for a short-time post-injury achieves the best functional and structural preservation outcomes.

Colorectal Surgery and Its Impact on Male Sexual Function

The quality of functional outcome has become increasingly important in view of improvement in prognosis with colorectal cancer patients. Sexual dysfunction remains a common problem after colorectal cancer treatment, despite the good oncologic outcomes achieved by expert surgeons. Although radiotherapy and chemotherapy contribute, surgical nerve damage is the main cause of sexual dysfunction. The autonomic nerves are in close contact with the visceral pelvic fascia that surrounds the mesorectum. The concept of total mesorectal excision (TME) in rectal cancer treatment has led to a substantial improvement of autonomic nerve preservation. In addition, use of laparoscopy has allowed favorable results with regards to sexual function. The present paper describes the anatomy and pathophysiology of autonomic pelvic nerves, prevalence of sexual dysfunction, and the surgical technique of nerve preservation in order to maintain sexual function.

Coronary Heart Disease, Diabetes, and Sexuality in Men

Erectile dysfunction (ED) has been well recognized as a marker of increased cardiovascular risk for more than 15 years, especially in younger men. Early detection of ED represents an opportunity to intervene to decrease the risk of future cardiovascular events and limit the progression of ED severity. Evidence suggests there is a window of opportunity of 3 to 5 years from the onset of ED to subsequent cardiovascular events. This opportunity is usually missed if the onus is placed on the patient to seek care for his sexual problems. Unfortunately, these clear messages have not been incorporated into routine cardiovascular care. The reasons for these disparities within specialties are discussed in this article, in addition to management algorithms. Lifestyle modification is usually recommended as the first-line treatment to correct ED and lessen cardiovascular risk, but evidence suggests that this might be effective only in men without established cardiovascular comorbidities. In men with type 2 diabetes mellitus and established cardiovascular disease, lifestyle modification alone is unlikely to be effective. Cardiovascular medications are often associated with sexual dysfunction but changes in medication are more likely to be beneficial in men with milder recent-onset ED. A balanced view must be taken related to medication adverse events, taking into account optimal management of established cardiovascular disease. Testosterone deficiency has been associated with different metabolic disorders, especially metabolic syndrome and type 2 diabetes mellitus. Testosterone deficiency syndrome has been associated with an independent burden on sexual function globally and increased cardiovascular and all-cause mortality. Testosterone replacement therapy has been shown to improve multiple aspects of sexual function and, in some studies, has been associated with a decrease in mortality, especially in men with type 2 diabetes mellitus. Recent studies have suggested that phosphodiesterase type 5 inhibitors, the first-line medications to treat ED, could decrease cardiovascular and all-cause mortality, through multiple mechanisms, predominantly related to improved endothelial function.

Breast cancer in men: Emasculation by association?

The occurrence of breast cancer in men is rare in comparison to women. Public knowledge that men can get breast cancer and of male breast self-examination are lacking. Research in the course and treatment of breast cancer in men is needed. Men generally present in more advanced stages of breast cancer than women, and have a poorer prognosis. In this article, the epidemiology, common symptoms, diagnostic methods, and current treatment of breast cancer in men are described. Gender differences in presentation and course of illness are discussed. Additionally, the psychological implications of breast cancer for male gender roles and masculine identity are explored. Directions for further investigation are given. Treatment providers are encouraged to educate themselves and their male patients on breast cancer in men and male breast examination techniques so that this disease may be identified earlier in its course and survival rates improved.

Peyronie's Disease and Injectable Collagenase Clostridium histolyticum: Safety, Efficacy, and Improvements in Subjective Symptoms

OBJECTIVE To report on an early adopter series of collagenase Clostridium histolyticum (CCh) for Peyronies disease (PD). Postapproval studies of CCh have been anticipated after recent Food and Drug Administration authorization of its use for men with PD as definitive and durable nonsurgical interventions have been long desired. MATERIALS AND METHODS From May 2014 to October 2015, a database consisting of PD patients with >30° of penile curvature received CCh from a single provider at a single institution. Objective penile curvature measurements and deformity directions were assessed pre- and posttreatment. Using the validated Peyronies Disease Questionnaire (PDQ), changes in subjective symptoms of intercourse ability, penile pain, and bother were also noted. RESULTS We followed 49 unique PD patients treated with CCh. Mean follow-up was 183 days with a median of 6 injections over 3 cycles performed per patient. The mean pretreatment penile curvature was 49.3 degrees. Curvature was reduced by 15.4 degrees (32.4%, P < .01) after therapy. There were 10 out of 22 patients who regained ability to perform vaginal intercourse. Subjectively, there was an improvement in the ability to perform intercourse (29.1% improvement, P < .01) and bother symptoms (mean decrease 43.2%, P < .01), but no significant changes in penile pain (P = .89). Five notable bleeding events (10.2%) were noted, including 1 penile fracture requiring operative exploration. CONCLUSION CCh use for PD yielded improvements in penile curvature, subjective intercourse, and bother symptoms. Further postanalysis studies of greater follow-up are needed to assess long-term durability, efficacy, and safety.

The Who, How and What of Real-World Penile Implantation in 2015: The PROPPER Registry Baseline Data

PURPOSE To date, the published data on patients treated with penile implantation generally consist of small series of single surgeon, retrospective experiences rather than prospective or large, multicenter evaluations. This study establishes a baseline of data collection from the PROPPER (Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration). The PROPPER is the first large, prospective, multicenter, multinational, monitored, and internal review board approved study of real-world outcomes for patients with penile implants. MATERIALS AND METHODS Data from the PROPPER study were examined to determine patient baseline characteristics and primary and secondary etiologies before treatment of erectile dysfunction. Data include type and size of implant received, surgical steps/techniques used during implantation, and duration of hospital stay. RESULTS Through April 2, 2015 a total of 1,019 patients were enrolled in the study at 11 sites, with radical prostatectomy being the predominant etiology in 285 (28%). Of those 285 patients treated with radical prostatectomy 280 (98.2%) received an AMS 700™. Of these patients 65.0% (182 of 280) had placement of the reservoir in the traditional retropubic space vs 31.8% (89 of 280) in a submuscular location. Of those patients not treated with radical prostatectomy receiving an AMS 700, fewer underwent reservoir placement in the submuscular location (17.7%, 124 of 702, vs 80.9%, 568 of 702; p <0.001). Of those patients receiving an AMS 700, those treated with radical prostatectomy and those with diabetes had more outpatient admissions (less than 24 hours, 56.8% and 52.1%, respectively) compared to those with cardiovascular disease and Peyronies disease (42.0% and 35.6%, respectively, p <0.001). CONCLUSIONS This first-of-its-kind, large, prospective, multicenter study reveals most penile implant cases in North America receive an inflatable penile prosthesis and that radical prostatectomy is the most common primary etiology of penile implant surgery. Moreover, patients treated with radical prostatectomy were more likely to have the reservoir placed in a submuscular location, have a longer operating room time and be admitted to the hospital overnight compared with other patient groups.

Priapism in Sickle Cell Anemia: Emerging Mechanistic Understanding and Better Preventative Strategies

Sickle cell anemia is a common and disabling disorder profoundly affecting mortality as well as quality of life. Up to 35% of men with sickle cell disease are affected by painful, prolonged erections termed ischemic priapism. A priapic episode may result in fibrosis and permanent erectile dysfunction. The severity of sickle cell disease manifestations is variable dependent on a number of contributing genetic factors; however, priapism tends to cluster with other severe vascular complications including pulmonary hypertension, leg ulceration, and overall risk of death. The mechanisms underlying priapism in sickle cell disease have begun to be elucidated including hemolysis-mediated dysregulation of the nitric oxide signaling pathway and dysregulation of adenosine-mediated vasodilation. A better understanding of these mechanisms is leading toward novel preventative strategies. This paper will focus on the mechanisms underlying development of ischemic priapism in sickle cell disease, current acute and preventative treatment strategies, and future directions for improved management of this disorder.