Premsant Sangkum

The Effect of Duration of Penile Traction Therapy in Patients Undergoing Intralesional Injection Therapy for Peyronie's Disease

PURPOSE The concomitant use of penile traction therapy with interferon α-2b has been previously described. We present an update on our clinical experience to assess the benefit and duration of daily traction. MATERIALS AND METHODS A retrospective review of patients who underwent interferon α-2b therapy between 2001 and 2012 was performed. Charts were reviewed and data collected regarding various patient demographics, vascular parameters, objective length and curvature measurements, and use of penile traction therapy. Penile traction therapy was further stratified according to duration of daily use. RESULTS A total of 112 patients underwent a median of 12 interferon α-2b injections (range 6 to 24). Daily use of penile traction therapy was reported by 31% of patients. There were no differences in patient demographics, initial vascular status, pretreatment stretched penile length, erect circumference and curvature between patients who followed a penile traction therapy regimen and those who did not. Overall, the use of penile traction therapy did not effect change in penile circumference (with therapy +3.2 mm [SD 6.5] vs no therapy +2.1 mm [SD 7.4], p=0.45), change in curvature (with therapy -8.1 degrees [SD 16.0] vs no therapy -9.9 degrees [SD 11.8], p=0.49) or change in stretched penile length (with therapy +2.4 mm [SD 0.9] vs no therapy +1.3 mm [SD 0.8], p=0.56). Men who used penile traction therapy 3 or more hours per day gained significantly greater stretched penile length compared to those who did not use penile traction therapy (4.4 mm [SD 0.5] vs 1.3 mm [SD 0.8], p=0.04). CONCLUSIONS Routine penile traction therapy during intralesional injection with interferon α-2b for Peyronies disease may result in a small but subjectively meaningful improvement in stretched penile length, without affecting curvature, if used for at least 3 hours a day.

Erythrocytosis and Polycythemia Secondary to Testosterone Replacement Therapy in the Aging Male

INTRODUCTION Testosterone replacement therapy (TRT) is a common treatment for hypogonadism in aging males. Men with low to low-normal levels of testosterone have documented benefit from hormone replacement. Recent meta-analyses have revealed that increases in hemoglobin (Hb) and hematocrit (Hct) are the variants most commonly encountered. Clinically, this response is described as erythrocytosis or polycythemia secondary to TRT. However, the recent Food and Drug Administration warning regarding the risk for venothromboembolism (VTE) has made the increases in Hb and Hct of more pertinent concern. The risks associated with androgen replacement need further examination. AIM To review the available literature on erythrocytosis and polycythemia secondary to TRT. To discuss potential etiologies for this response, the role it plays in risk for VTE, and recommendations for considering treatment in at-risk populations. METHODS A literature review was performed through PubMed regarding TRT and erythrocytosis and polycythemia. MAIN OUTCOME MEASURES To assess the mechanisms of TRT-induced erythrocytosis and polycythemia with regard to basic science, pharmacologic preparation, and route of delivery. To review Hct and risk for thrombotic events. To offer clinical suggestions for therapy in patients at risk for veno-thrombotic events. RESULTS Men undergoing TRT have a 315% greater risk for developing erythrocytosis (defined as Hct > 0.52) when compared with control. Mechanisms involving iron bioavailability, erythropoietin production, and bone marrow stimulation have been postulated to explain the erythrogenic effect of TRT. The association between TRT-induced erythrocytosis and subsequent risk for VTE remains inconclusive. CONCLUSIONS All TRT formulations cause increases in Hb and Hct, but injectables tend to produce the greatest effect. The evidence regarding the risk for VTE with increased Hct is inconclusive. For patients with risk factors for veno-thrombotic events, formulations that provide the smallest effect on blood parameters hypothetically provide the safest option. Further trials are needed to fully evaluate the hematological side effects associated with TRT. Jones SD Jr, Dukovac T, Sangkum P, Yafi FA, and Hellstrom WJG. Erythrocytosis and polycythemia secondary to testosterone replacement therapy in the aging male. Sex Med Rev 2015;3:101-112.

Device Survival after Primary Implantation of an Artificial Urinary Sphincter for Male Stress Urinary Incontinence

Purpose: The AMS 800™ artificial urinary sphincter remains the gold standard for the surgical management of male stress urinary incontinence. We reviewed artificial urinary sphincter device survival after primary implantation. Materials and Methods: Retrospective data were collected from the AMS 800 patient information form database. Since 1972, 77,512 patient information forms for primary artificial urinary sphincter implantation have been completed in the United States. Following exclusion of procedures performed in children and females, and those labeled with an unknown surgical technique, 27,096 artificial urinary sphincter cases were included in the analysis. Collected variables included patient age, surgical approach, number of cuffs and surgeon volume. Measured outcomes included device explantation, device revision, component revision and time to each event. Results: Artificial urinary sphincter insertion was performed by low volume implanters in 22,165 (82.6%) cases. The approach was perineal in 18,373 cases (67.8%) and a tandem cuff was used in 2,224 cases (8.2%). Overall 5,723 cases required revision or explantation (21.1%). Younger age and penoscrotal approach were associated with higher device explantation and revision rates, while the use of a tandem cuff was associated with higher explantation rates. On multivariate analysis younger age, penoscrotal approach and use of a tandem cuff but not surgeon volume were significant factors associated with device explantation and component revision. Conclusions: These data provide a general overview of artificial urinary sphincter device survival and may serve urologists when counseling patients. Younger age, penoscrotal approach and use of a tandem cuff may be associated with inferior outcomes.

Therapeutic advances in the treatment of Peyronie's disease

Peyronies disease (PD) is an under‐diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration‐approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon‐alpha‐2B, however, their use is considered off‐label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD‐associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non‐responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

Transforming Growth Factor-β1 Induced Urethral Fibrosis in a Rat Model

PURPOSE We sought to develop a reproducible TGF-β1 injection technique to induce urethral fibrosis in the rat urethra. MATERIALS AND METHODS A total of 32 male Sprague Dawley® rats weighing 300 to 350 gm were anesthetized with ketamine/xylazine intraperitoneally. Using a 5 mm penoscrotal incision the rat urethra was exposed. In the experimental group varying doses of TGF-β1 (5, 10 and 25 μg) were injected in each side of the urethral wall. Normal saline infiltration was used in the sham treated group. Rats were sacrificed 2 and 4 weeks following TGF-β1 injection. Urethral specimens were stained with hematoxylin and eosin, and Masson trichrome, and Western blot evaluations were performed. Normal and strictured urethral tissues from patients were collected and evaluated in the same fashion. RESULTS There was no evidence of urethral wall thickening or fibrosis in the sham treated group. Varied histological evidence of fibrosis was noted in all experimental groups. There was a significant increase in collagen type I expression 2 weeks after injection of 5, 10 and 25 μg TGF-β1. Collagen type III expression was significantly increased 2 weeks after injecting 10 and 25 μg of TGF-β1, which persisted to 28 days after injection. CONCLUSIONS TGF-β1 injection can successfully generate a reproducible rat model of urethral spongiofibrosis. This technique is simple, inexpensive and reproducible. Our series is a proof of concept study. Additional studies in larger animals are needed to further confirm our findings.

Erectile dysfunction in urethral stricture and pelvic fracture urethral injury patients: diagnosis, treatment, and outcomes

Urethral stricture disease, pelvic fracture urethral injury (PFUI), and their various treatment options are associated with erectile dysfunction (ED). The etiology of urethral stricture disease is multifactorial and includes trauma, inflammatory, and iatrogenic causes. Posterior urethral injuries are commonly associated with pelvic fractures. There is a spectrum in the severity of both conditions and this directly impacts the treatment options offered by the surgeon. Many published studies focus on the treatment outcomes and the relatively high recurrence rates after surgical repair. This communication reviews the current knowledge of the association between ED and urethral stricture disease, as well as PFUI. The incidence, pathophysiology, and clinical ramifications of both conditions on sexual function are discussed. The treatment options for ED in those patients are reviewed and summarized.

Update on Medical Management of Peyronie’s Disease

The treatment of Peyronie’s disease (PD) is a challenge for the clinician. In the quest to straighten the penis, alleviate pain, prevent further shortening, and restore erectile function, many non-surgical treatments have been offered in lieu of an operative approach, which is still considered the gold standard for definitive treatment. This communication is an update on the different approaches used in the minimally invasive management of this frustrating and yet intriguing condition.

Collagenase Clostridium histolyticum (Xiaflex) for the Treatment of Urethral Stricture Disease in a Rat Model of Urethral Fibrosis

OBJECTIVE To evaluate the treatment effect of collagenase Clostridium histolyticum (CCH) in a rat model of urethral fibrosis. MATERIALS AND METHODS Thirty male Sprague-Dawley rats (300-350 g) were divided into 5 groups. The rat urethra was injected with normal saline in the sham group and, in the other 4 groups, the rat urethra was injected with 10 μg of transforming growth factor beta 1 to create fibrosis of the urethra. Two weeks following transforming growth factor beta 1 injection, the rats were injected with varying doses of CCH or vehicles, depending on their group. The rats were then euthanized at 4 weeks after CCH or vehicle injection. Urethral tissue was harvested for histologic and molecular analyses. Type I and III collagen levels were evaluated by Western blot analysis. RESULTS There was urethral fibrosis and to significant increase in collagen type I and III expressions in the urethral fibrosis group compared with the sham group (P <.05). Urethral injection of CCH appeared to be safe and significantly reduce urethral fibrosis as well as collagen type I and III expressions in the high-dose CCH treatment groups when compared with the treatment control group (P <.01). CONCLUSION This study demonstrated a beneficial effect of CCH injections in a rat model of urethral fibrosis. These findings suggest a potential role for CCH as a therapeutic option in urethral stricture patients and warrant further investigation.

The Non-Surgical Treatment of Peyronie Disease: 2013 Update

Peyronie disease is a common cause of penile deformity and sexual dysfunction. Although surgery is regarded as the definitive management for this condition, there are many medical and minimally invasive therapies available, with widely varying efficacy reported in the literature. The purpose of this review is to describe the current state-of-the-art for each of the most commonly used as well as several developing non-surgical treatments. Further, we hope to offer perspectives that will aid practitioners in deciding among these treatments that are either already in use or have the potential to be used as alternatives to surgery in the management of this frustrating disease.

Failure to attain stretched penile length after intracavernosal injection of a vasodilator agent is predictive of veno-occlusive dysfunction on penile duplex Doppler ultrasonography.

Penile duplex Doppler ultrasound (PDDU) assesses the etiology of erectile dysfunction. Peak systolic velocity (PSV), end‐diastolic velocity (EDV), and resistive index (RI) are common PDDU parameters. We assessed whether stretched penile length (SPL) in the flaccid state and measured penile length at peak erection after intracavernosal injection (ICI) of a vasodilator during PDDU correlated with the etiology of erectile dysfunction. We performed a retrospective review of 93 patients who underwent PDDU for erectile dysfunction. Normal and stretched penile length were measured, both at a flaccid state prior to ICI and at peak erection during PDDU. Collected data included patient demographics, vascular, and anatomic parameters. The mean age was 52 years. SPL was equivalent to peak penile length after ICI in 60 patients (65%, group 1) and did not match in 33 (35%, group 2). There were no significant differences between the two groups in terms of flaccid, stretched, and post‐ICI erect penile lengths, IIEF score, PSV, percent rigidity or tumescence, and vasodilator dose used. Patients in group 2 had less of a change in penile length from flaccid to erect state (36% vs. 44%, p = 0.02), higher EDV (12.0 vs. 8.5, p = 0.041), lower RI (0.6 vs. 1.0, p = 0.046), and more veno‐occlusive dysfunction (82% vs. 53%, p = 0.001). On multivariate analysis, failure to reach maximum SPL at peak ICI erection (OR 2.255, CI 1.191–4.271, p = 0.0126), EDV (OR 1.281, CI 1.115–1.471, p < 0.001) and RI (OR 0.694, CI 0.573–0.723, p = 0.009) predicted veno‐occlusive dysfunction. Failure to reach maximal SPL during PDDU using ICI with a vasodilator agent predicted veno‐occlusive dysfunction, which is independent of both penile rigidity and tumescence. This measurement could serve as another diagnostic tool for predicting veno‐occlusive dysfunction when PDDU is not readily available. Limitations include the subjective nature of penile measurements and different PGE1 doses used.