Mustafa F. Usta

The Management of Peyronie's Disease: Evidence‐based 2010 Guidelines

INTRODUCTION The field of Peyronies disease is evolving and there is need for a state-of-the-art information in this area. AIM To develop an evidence-based state-of-the-art consensus report on the management of Peyronies disease. METHODS To provide state-of-the-art knowledge regarding the prevalence, etiology, medical and surgical management of Peyronies Disease, representing the opinion of leading experts developed in a consensus process over a 2-year period. MAIN OUTCOME MEASURES Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. CONCLUSIONS The real etiology of Peyronies disease and the mechanisms of formation of the plaque still remain obscure. Although conservative management is obtaining a progressively larger consensus among the experts, surgical correction still remains the mainstay treatment for this condition.

Treatment of Peyronie's disease with oral colchicine : long-term results and predictive parameters of successful outcome

As recent clinical and animal studies have indicated, colchicine, with its anti‐fibrotic, anti‐mitotic and anti‐inflammatory activities, has suppressive effects in the pathogenesis of Peyronies disease.Oral colchicine treatment was initiated in 60 Peyronies patients during their acute phase (mean duration of disease: 5.7±4.3 months). Long‐term results, based on changes of subjective and objective criteria, were assessed and predictive factors of successful outcome were investigated. After a mean follow‐up of 10.7±4.7 months, the penile deformity improved in 30%, remained unchanged in 48.3% and deteriorated in 21.7%. Pain resolved in 95%. Best results were obtained in those with no risk factor for vascular disease, presenting during the initial 6 months of disease, degree of curvature <30°, no erectile dysfunction by history and positive response to combined injection and stimulation test.In conclusion since tunica albuginea is affected as a whole in Peyronies disease, systemic oral agents, such as colchicine, may be preferred in the early phase of the disease.

The role of reactive oxygen species in testicular dysfunction associated with varicocele

Objective To determine the level of malondialdehyde (MDA), an indirect indicator of lipid peroxidation‐induced injury by reactive oxygen species, in testicular biopsy specimens from infertile patients with and without varicocele.

Prevalence of the Complaint of Ejaculating Prematurely and the Four Premature Ejaculation Syndromes: Results from the Turkish Society of Andrology Sexual Health Survey

INTRODUCTION In addition to the previously known lifelong and acquired premature ejaculation (PE) syndromes, the existence of two more PE syndromes has been suggested: natural variable PE and premature-like ejaculatory dysfunction. However, epidemiological studies investigating the prevalence of these four PE syndromes have yet to be conducted. AIM To determine the prevalence of the complaint of ejaculating prematurely across the four PE syndromes. METHODS This study, conducted between June 2009 and December 2009, was designed as a non-interventional, observational cross-sectional field survey. Participating couples were randomly selected from 17 provinces of Turkey. All participants were asked to complete a questionnaire including data regarding demographics, socioeconomic status, social and cultural factors, medical and sexual history, current medications, and ejaculation time. Subjects with a complaint of ejaculating prematurely were classified as lifelong, acquired, and natural variable PE, or premature-like ejaculatory dysfunction. MAIN OUTCOME MEASURES The main outcome measures were prevalence of complaint of ejaculating prematurely in the general population and across the four PE syndromes. RESULTS A total of 2,593 couples (mean age, 41.9±12.7 years for males and 38.2±12.1 years for females) were enrolled. Five-hundred twelve subjects (20.0%) complained of ejaculating prematurely. Fifty-eight (2.3%), 100 (3.9%), 215 (8.5%), and 131 (5.1%) subjects were classified as lifelong, acquired, and natural variable PE, and premature-like ejaculatory dysfunction, respectively. CONCLUSIONS The prevalence of the complaint of ejaculating prematurely among Turkish men was 20.0%, with the highest PE syndrome being natural variable PE (8.5%) and premature-like ejaculatory dysfunction (5.1%).

Patient and partner satisfaction and long-term results after surgical treatment for Peyronie’s disease

OBJECTIVES To assess the long-term functional outcome, patient and partner satisfaction, and predictive factors for unfavorable results in men treated with a surgical approach for severe Peyronies disease. METHODS Sixty-one patients underwent surgical treatment for Peyronies disease between 1997 and 2001 and were retrospectively evaluated. All patients were assessed preoperatively with a detailed sexual and medical history, focused physical examination, and penile duplex ultrasonography. Nineteen patients underwent penile plaque excision/incision and grafting with Tutoplast cadaveric pericardial grafting material (group 1). Penile prosthesis implantation and manual modeling was performed in 31 patients (group 2a), and 11 men were treated with penile prosthesis implantation and pericardial grafting (group 2b). RESULTS The mean follow-up of the patients was 21.9 +/- 13.6 months (range 12 to 48). Complete penile straightening was achieved in 15 patients (78.9%) in the excision/incision and grafting group. In the 42 men who underwent reconstruction using penile prosthesis implantation (group 2a,b), penile curvature resolved completely in 37 patients (88%). Long-term postoperative residual curvatures greater than 30 degrees occurred in 3 patients (15.7%) and 2 patients (4.8%) in groups 1 and 2a,b, respectively. One penile prosthesis (2.3%) was explanted in the second group for erosion. Patient responses to our questionnaire showed that overall 83.6% of the patients and 76.9% of the partners were satisfied with the surgical result. CONCLUSIONS According to the results of this long-term, retrospective study, pericardial grafting can be used successfully after plaque excision/incision procedures in men undergoing surgical treatment for severe Peyronies disease. In patients with Peyronies disease and erectile dysfunction, implantation of a penile prosthesis and correction of the curvature with a graft can provide an acceptable, functionally straight penis without any increased risk of complications compared with penile prosthesis implantation alone.

Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats.

Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVβgal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1–2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3′,5′-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVβgal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.

Adeno-associated viral gene transfer of dominant negative RhoA enhances erectile function in rats.

We previously reported the inhibition of Rho-kinase to result in increased intracavernosal pressure (ICP) in an in vivo rat model of erection. Expression of an upstream activator of Rho-kinase, RhoA, has been demonstrated in the penile vasculature; however, the functional role of RhoA in the regulation of erection remains unknown. We used adeno-associated viral gene transfer of a dominant negative RhoA mutant (T19NRhoA) into rat cavernosum to test the hypothesis that RhoA activation is physiologically important for maintenance of the non-erect state and inhibition of this pathway leads to erection. Anesthetized, male, Sprague-Dawley rats transfected with the T19NRhoA mutant exhibited an elevated baseline ICP/mean arterial pressure (MAP) and nerve stimulation-induced ICP/MAP as compared with beta-galactosidase-transfected controls. The novel findings of this study demonstrate a functional role of RhoA in maintaining the flaccid penis and provide support for the inhibition of RhoA as a potential therapy for the enhancement of erectile function.

Trauma, Gender Reassignment, and Penile Augmentation

INTRODUCTION Penile trauma is common with standard management options. Gender reassignment techniques are rapidly changing and penile augmentation remains a controversial topic. Consequently, there is need for a state-of-the-art information in this area. AIM This study aims to develop an evidence-based state-of-the-art consensus report on the management of penile trauma, gender, reassignment and penile augmentation. METHODS The study provides state-of-the-art knowledge regarding the prevalence, etiology, medical and surgical management of penile trauma, gender reassignment and penile augmentation, representing the opinion of leading experts developed in a consensus process over a 2-year period. MAIN OUTCOME MEASURES Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. CONCLUSIONS Penile fracture should be managed surgically. Information should be readily available to patients to help them decide the surgical technique desired for gender reassignment and to justify any form of penile augmentation.

Testicular-sparing surgery: a reasonable option in selected patients with testicular lesions

To describe our experience of inguinal exploration in patients who had a reasonable chance of having a benign testicular lesion.

Varicocele-Induced Testicular Dysfunction May Be Associated with Disruption of Blood-Testis Barrier

The objective of this study was to examine E-cadherin and α-catenin expression at the junctions between adjacent Sertoli cells in testicular specimens from patients with varicocele in order to determine the presence of a possible link between blood-testis barrier and pathophysiology of varicocele. A total of 51 testicular biopsies were obtained from 28 infertile men with unilateral or bilateral varicocele. Twenty-three patients had bilateral and 5 had unilateral varicocele, Grade I varicocele was detected in 30 (59%), grade II in 15 (29%) and grade III in 6 (12%) patients. Abnormal expression of E-cadherin and α-catenin at the junctions between adjacent Sertoli cells was demonstrated in 100% and 90% of the patients with varicocele, respectively. In those with grade I-III varicocele, the mean E-cadherin and α-catenin expression were 7.6 ± 11.4 and 39 ± 36; 7.6 ± 0.0 and 49 ± 30; 8.3 ± 9.3 and 58 ± 33, respectively, but the difference was not significant. Reduced E-cadherin and α-catenin expression at the junctions between adjacent Sertoli cells may be associated with disruption of blood-testis barrier in varicocele.