Hazem Orabi

Evaluation and treatment of erectile dysfunction in the aging male: a mini-review.

Before the 20th century, individuals often did not live beyond the reproductive years, and sexuality of the elderly was not an issue. However, in the current era it is known that as life expectancy improves, both men and women are seeking to preserve their sexuality into old age. While the appreciation of sexuality persists with aging, a decline in sexual activity is typically seen with, and can be attributed to both general health problems as well as specific sexual dysfunctions. Erectile dysfunction is the most frequently diagnosed sexual dysfunction in the older male population. This mini-review provides an overview of contemporary literature concerning epidemiology, pathophysiology, assessment and treatment of erectile dysfunction in the aging male.

Scaffoldless Tissue Engineering of Stem Cell Derived Cavernous Tissue for Treatment of Erectile Function

INTRODUCTION As one-third of erectile dysfunction (ED) patients do not respond to phosphodiesterase-5 inhibitors, there is great demand for new therapeutic options. Adipose tissue-derived stem cells (ADSCs) represent an ideal source for new ED treatment. AIM To test if ADSCs can be differentiated into smooth muscle cells (SMCs) and endothelial cells (ECs), if these differentiated cells can be used to engineer cavernous tissue, and if this engineered tissue will remain for long time after implantation and integrate into corporal tissue. METHOD Rat ADSCs were isolated and differentiated into SMC and ECs. The differentiated cells were labeled with 5-ethynyl-2-deoxyuridine (EdU) and used to construct cavernous tissue. This engineered tissue was implanted in penises of normal rats. The rats were sacrificed after 1 and 2 months; penis and bone marrow were collected to assess cell survival and inclusion in the penile tissues. MAIN OUTCOME MEASURES The phenotype conversion was checked using morphology, immunocytochemistry (immunohistochemistry [IHC]), and Western blot for SMC and EC markers. The cavernous tissue formation was assessed using rat EC antibody (RECA), calponin, and collagen. The implanted cell survival and incorporation into penis were evaluated with hematoxylin and eosin, Massons trichrome, and IHC (RECA, calponin, and EdU). RESULTS The phenotype conversion was confirmed with positive staining for SMC and EC markers and Western blot. The formed tissue exhibited architecture comparable to penile cavernous tissue with SMC and ECs and extracellular matrix formation. The implanted cells survived in significant numbers in the penis after 1 and 2 months. They showed proof of SMC and EC differentiation and incorporation into penile tissue. CONCLUSIONS The results showed the ability of ADSCs to differentiate into SMC and ECs and form cavernous tissue. The implanted tissue can survive and integrate into the penile tissues. The cavernous tissue made of ADSCs forms new technology for improvement of in vivo stem cell survival and ED treatment.

Tunica albuginea allograft: a new model of LaPeyronie's disease with penile curvature and subtunical ossification

The pathophysiology of LaPeyronies disease (PD) is considered to be multifactorial, involving genetic predisposition, trauma, inflammation and altered wound healing. However, these factors have not yet been validated using animal models. In this study, we have presented a new model obtained by tunica albuginea allograft. A total of 40, 16-week-old male rats were used. Of these, 8 rats served as controls and underwent a 10 × 2-mm-wide tunical excision with subsequent autografting, whereas the remaining 32 underwent the same excision with grafting of the defect with another rats tunica. Morphological and functional testing was performed at 1, 3, 7 and 12 weeks after grafting. Intracavernous pressure, the degree of penile curvature and elastic fiber length were evaluated for comparison between the allograft and control groups. The tissues were obtained for histological examination. The penile curvature was significantly greater in the allografted rats as compared with the control rats. The erectile function was maintained in all rats, except in those assessed at 12 weeks. The elastin fiber length was decreased in the allografted tunica as compared to control. SMAD2 expression was detected in the inner part of the allograft, and both collagen-II- and osteocalcin-positive cells were also noted. Tunica albuginea (TA) allograft in rats is an excellent model of PD. The persistence of curvature beyond 12 weeks and the presence of ossification in the inner layer of the TA were similar to those observed in men with PD. Validation studies using this animal model would aid understanding of the PD pathophysiology for effective therapeutic interventions.

Management of complex and redo cases of pelvic fracture urethral injuries

Objectives Pelvic fracture urethral injuries (PFUI) result from traumatic disruption of the urethra. A significant proportion of cases are complex rendering their management challenging. We described management strategies for eight different complex PFUI scenarios. Methods Our centre is a tertiary referral centre for complex PFUI cases. We maintain a prospective database (1995–2016), which we retrospectively analysed. All patients with PFUI managed at our institute were included. Results Over two decades 1062 cases of PFUI were managed at our institute (521 primary and 541 redo cases). Most redo cases were referred to us from other centres. Redo cases had up to five prior attempts at urethroplasty. We managed complex cases, which included bulbar ischemia, young boys and girls with PFUI, PFUI with double block, concomitant PFUI and iatrogenic anterior urethral strictures. Bulbar ischemia merits substitution urethroplasty, most commonly, using pedicled preputial tube. PFUI in young girls is usually associated with urethrovaginal fistula. Young boys with PFUI commonly have a long gap necessitating trans-abdominal approach. Our success rate with individualised management is 85.60% in primary cases, 79.13% in redo cases and 82.40% in cases of bulbar ischemia. Conclusion The definition of complex PFUI is ever expanding. The best chance of success is at the first attempt. Anastomotic urethroplasty for PFUI should be performed in experienced hands at high volume centres.

A novel method in decision making for the diagnosis of anterior urethral stricture: using methylene blue dye

Objective The use of methylene blue dye (MB) to highlight anatomical structures in urology has been well-established. Urethral stricture may extend about a centimeter beyond the abnormal area seen on urethrogram. Although the current literature suggests a tension-free and end- to- end anastomosis after excision of the strictured urethral segment with spongiofibrosis and surrounding corpus spongiosum in short bulbar strictures, some centers dealing with urethroplasty prefer anastomosis for short bulbar strictures while others prefer augmentation. With this study, use of MB for delineating stricture line and assessing spongiofibrosis in the diagnosis of urethral stricture was evaluated. Material and methods Five cc MB including 10 mg/mL is diluted with 10 cc saline. In the first scenario, MB is gently injected into urethra via the meatus before the urethroplasty procedure. Meanwhile, the extent of urethral segment stained by MB is noted. In the second scenario (MB spongiosography) in short bulbar stricture, insulin needles are inserted in spongiosa of the stricture site distally and proximally. MB is gently injected with distal needle. The two remaining needles are then observed. Presence of MB efflux in proximal needle implies deficiency of significant spongiofibrosis, so buccal augmentation is performed. Absence of efflux of MB implies significant spongiofibrosis and anastomotik site excised. Results Four hundred and ninety-two consecutive cases prospectively evaluated between 2010 and 2014. Precise staining of stricture was successfully observed in 464 (94%) patients. Grossly normal appearing urothelium remained pink. Histopathology confirmed that the stained urethra had a stricture. Of the 22 short bulbar idiopathic strictures, in 18 (82%) MB was seen across the stricture and urethral transection was avoided. Anastomosis was performed in 4 (18%) cases where no MB went across the primary excision. There were no known allergic complications. Conclusion MB aids in delineating the urethral lumen and exact site of stricture that needs augmentation. MB Spongiography in short bulbar strictures could be used as a beneficial guide in relation to the type of urethral repair to be performed in terms of augmentation versus excision and anastomosis.

PD29-11 MAGNETIC RESONANCE IMAGING (MRI) IN PELVIC FRACTURE URETHRAL INJURIES TO EVALUATE URETHRAL GAP: A NEW POINT OF TECHNIQUE

procedure, notably, if corporeal splitting and/or inferior pubectomy (CS/ IP) are required. Consequently, a long learning curve is surely needed. Herein, we used retrograde urethrogram (RGU) to envisage the intraoperative difficulty during AU for PFUI. We hypothesized that as deep as the urethra goes into the pelvis, the more complexity is anticipated. METHODS: A retrospective review for patients underwent AU for PFUI at a tertiary referral center was conducted between January 2010 and March 2016. The standard position for RGU is semi-lateral with only one obturator foramen is visualized. To address how deep the urethra goes into the pelvis, an imaginary line is drawn from the pubis symphysis down to a point midway between the tips of pubic rami, representing theoretically the midsagittal plane of the perineal membrane. Zones where the proximal end of the anterior urethra is present, are (A) anterior to the line, (B) on the line, and (C) across the line posteriorly (Fig.). The complexity of the procedure was defined as the need of any auxiliary maneuver beyond distal urethral mobilization (CS/ IP) to achieve adequate anastomosis. Predictors were tested only in patients with successful AU. Further analysis was performed to detect the association between this hypothesis and the outcome defined by the need for instrumentation after AU. RESULTS: 129 patients were analyzed. 39 (30%) patients required auxiliary procedures beyond mobilization of the distal urethra and 36 (27.9%) reported failure. Among patients with successful AU, zone C was the only factor significantly associated with complex AU [13 (44.8%) vs 12 (18.8%)]. Furthermore, zone C [Odds ratio (OR): 4.9, p1⁄40.006], as well as combined pelvic fracture (OR: 4.6, p1⁄40.009), were the only independent predictors of treatment failure. CONCLUSIONS: We defined a simple method to predict intraoperative complexity and treatment failure after AU for PFUI. This is might be of help for preoperative counseling and intraoperative planning by selecting cases for training and reserving particular ones for high volumesurgeons.

V1-10 IS CONTINENCE POSSIBLE IN PATIENTS WITH DOUBLE BLOCK AT BLADDER NECK -PROSTATE AND MEMBRANO -BULBAR URETHRA AFTER PELVIC FRACTURE URETHRAL INJURY?

hypospadias repair, urethral reconstruction, and correction of penile curvature. We set out to develop a retractor that would improve surgeon and assistant ergonomics and provide compression at the base of the penis to reduce blood loss. We describe this novel self-retaining penile retractor and our initial experience in its use. METHODS: This retractor is made of medical grade stainless steel. It has three components e a fixed hemostatic clamp attached to a scale, with also houses an artery forceps. This forceps moves along the scale to adjust the traction on the penis. The clamp is flat and compressive. The arms are non-traumatic and do not cause circumferential constriction. A stay suture taken through the glans is engaged by the artery forceps, and the height adjusted according to the penile length. The retractor has been used by reconstructive urologists in India, Turkey, Australia, Kuwait, Indonesia, and the United States of America. RESULTS: A total of 37 reconstructive cases were performed using this penile retractor (23 redo hypospadias repairs, 7 complex penile urethroplasties, 4 penile urethrocutaneous fistula repairs, and 3 surgeries for correction of Peyronie’s disease). For each case, surgeons were asked to score the retractor on a 4 point scale: 1. Extremely Non satisfactory, 2. Not Satisfactory, 3. Satisfactory, 4. Extremely Satisfactory. The average score was 3.65. Advantages noted were ease of application, reduction of assistant fatigue, stable operative exposure and non-traumatic tissue compression conferring a bloodless field. There were no complications attributable to the device. The main limitation is that it cannot be used for hypospadias proximal to the penoscrotal junction. This retractor is inexpensive, durable and easy to sterilize and can be used on adult and pediatric patients alike. CONCLUSIONS: In our experience this retractor has high utility in reconstruction of the penis and penile urethra. It affords improved ergonomics for the surgeon and assistant, which results in shorter operative times and reduced blood loss while avoiding tissue damage.

MP41-09 ADIPOSE-DERIVED STROMAL VASCULAR FACTOR (SVF) INJECTION IN SHORT RECURRENT BULBAR STRICTURE POST DVIU – AN INITIAL EXPERIENCE

INTRODUCTION AND OBJECTIVES: A recent study showed that adipose-derived stem cells are able to counteract urethral stricture formation in rats. The aim of this study was to evaluate the feasibility of autologous adipose derived stromal vascular fraction (SVF) transplantation into male urethra stricture walls after direct vision incision of urethra (DVIU). METHODS: A prospective clinical study was undertaken after ethics approval and appropriate patient consent. The inclusion criteria were: male patients older than 18 years, with single short recurrent not-obliterating urethral stricture (<2 cm). The exclusion criteria were: patients not willing to consent, multiple strictures and those not deemed suitable for endoscopic management. Failure was defined as need for further interventions. Preoperative workup included history, examination, retrograde urethrogram (RGU), voiding cystourethrogram (VCUG), urine culture, renal function tests, AUA score, IIEF, PROM. Plastic surgery team performs liposuction to extract 50 mls of fat from the patient’s abdominal wall. 50ml fat-SVF was obtained using a Goog Manufacturing Practice collagenase (Celase , Cytori Therapeutics, San Diego, USA) according to a standard protocol. SVF was diluted in 5 ml saline solution for the injection. A cystoscopy was performed and the stricture evaluated, a glide wire was placed and an urethrotomy performed at 6 o’clock position in bulbar urethra. Gide wire was left in situ. The SVF solution was injected at the site of the stricture and on either side of the stricture. A 12 Fr urinary catheter was placed. The urinary catheter was removed after 24 hrs. Follow up was of 3.5 months. RESULTS: Two patients were included in the study. The main characteristics are reported in table 1. No local or systemic side effects or complications were recorded. No recurrence of urethral stricture was detected in both patients after 3.5 months. Table 1 CONCLUSIONS: This is the first study to demonstrate a successful autologous SVF transplantation in male urethral stricture after DVIU. Further studies are necessary to confirm the efficacy of SVF in preventing urethral stricture recurrence.

Corrigendum to “Both Immediate and Delayed Intracavernous Injection of Autologous Adipose-derived Stromal Vascular Fraction Enhances Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury” [Eur Urol 2012;62:720–7]

Xuefeng Qiu , Thomas M. Fandel , Ludovic Ferretti , Maarten Albersen , Hazem Orabi , Haiyang Zhang , Guiting Lin , Ching-Shwun Lin , Tania Schroeder , Tom F. Lue * Knuppe Molecular Urology Laboratory, Department of Urology, University of California, San Francisco, CA, USA; Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, China; Department of Urology, University Hospital Leuven, Leuven, Belgium; Department of Urology, Assiut University, Egypt; American Medical Systems, Minnetonka, MN, USA