The etiologies of erectile dysfunction (ED) after nerve-sparing radical prostatectomy have not been clearly elucidated. The aim of this study was to evaluate the effects of cavernous nerve injury on cavernous fibrosis, and to consider measures to prevent irreversible damage to the cavernous tissues. Twenty male Sprague-Dawley rats constituted the study population. The animals were divided into 2 groups; group 1 consisted of sham-operated rats (n = 10), and group 2 consisted of rats that underwent incision of both cavernous nerves (n = 10). Three months later, all rats underwent intracavernous papaverine injection (300 and 600 mg), and intracorporal pressures were recorded. Transforming growth factor-beta(1) (TGF-beta(1)) messenger RNA (mRNA) expression from rat penile tissue was measured using reverse transcriptase-polymerase chain reaction. Hypoxia-inducible factor-1alpha (HIF-1alpha), TGF-beta(1), and collagen I and III protein expressions were determined by Western blot analysis and immunohistochemical staining. Erectile function as studied with intracavernosal papaverine injection and histological analysis of penile cross-sections at 3 months was similar in both groups. TGF-beta(1) mRNA expression, HIF-1alpha, TGF-beta(1), and collagen I and III protein expressions were significantly greater in the neurotomy group. Immunohistochemical staining for TGF-beta(1), HIF-1alpha, and collagen III were qualitatively more positive in the neurotomy group, whereas collagen I staining was similar. This study demonstrates an increase in TGF-beta(1), HIF-1alpha, and collagen III synthesis in rat cavernosal smooth musculature after cavernous neurotomies. In theory, cavernous fibrosis may be reduced by employing various vasoactive agents or interventions that increase oxygenation to the corporal tissues during the postoperative period.

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 þ sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbgal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS þ 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 0 ,5 0 -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 þ 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 AdCMVbgal. 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.

OBJECTIVE To examine the characteristics, management practices and outcomes of patients presenting with symptoms of benign prostatic hyperplasia (BPH) in Asia, with a focus on comorbidities and sexuality. PATIENTS AND METHODS In this multinational prospective observational registry, eligible patients with BPH attending a urology clinic for the first time were enrolled. Details of comorbidities, sexuality and symptoms of BPH were collected through the International Prostate Symptom Score (IPSS), International Index of Erectile Dysfunction‐5 (IIEF‐5) and the Danish Prostate Symptom Score (DAN‐PSS‐1) questionnaires. The follow‐up was scheduled at 1–3 or 3–6 months, depending on the treatment. RESULTS In 994 men aged 40–88 years the most common comorbidities were hypertension (38%) and obesity (36%). Nocturia was the most common symptom for consultation. A previous episode of acute urinary retention (AUR) was recorded in 12%. About 90% of the men had moderate‐to‐severe lower urinary tract symptoms (LUTS), and the severity increased with age. Sexual dysfunction was reported by 82%, and it correlated with the severity of LUTS. Of 918 sexually active men, only 20% had normal erectile function; 36%, 19% and 25% reported severe, moderate and mild erectile dysfunction (ED), respectively. BPH medication was started in 78%, 9% had surgery, and in 13% an approach of watchful waiting was adopted. In all, 89% of patients completed the follow‐up. The symptoms of BPH resolved in 93% after surgery, in 83% on BPH medication and in 34% of those on ‘watchful waiting’. Surgery, which led to a mean reduction of 17.0 IPSS points, was the most effective in improving LUTS. Improvement on the DAN‐PSS‐1 items of reduced erection and reduced ejaculation was higher with medication, while surgery led to better outcomes on the DAN‐PSS‐1 item of pain/discomfort on ejaculation. For ED, from baseline to after treatment, the mean IIEF‐5 scores changed from 19.1 to 18, from 14.2 to 14.8, and from 4.5 to 5.5 for those with mild, moderate and severe ED at baseline, respectively. Only 2.3% of patients had an episode of AUR while on treatment. About 5.5% of patients on BPH medication and 6% of surgical patients reported adverse events. CONCLUSION Asian patients with BPH usually present with LUTS; sexual dysfunction is also very common. BPH medication is the most frequent treatment approach, followed by watchful waiting and surgery. Medication and surgery resulted in a greater reduction of LUTS and improvement in sexual dysfunction than watchful waiting. As Asian men remain sexually active even at advanced ages, sexual function should be assessed and discussed with the patient before deciding the management strategy for LUTS associated with BPH.

We have previously reported on the use of Tutoplast 1 cadaveric pericardium as an alternative material for grafting the tunica albugineal defect after Peyronie's plaque excision with satisfactory results in 11 patients. We now review long-term outcomes in this cohort of men. Eleven patients with signi®cant penile curvature interfering with sexual intercourse were evaluated after at least 12 months of conservative therapy. All patients underwent pre-operative evaluation, including penile duplex Doppler ultrasound studies. Chemically processed and gamma-irradiated pericardium (Biodynamics International, Parsippany, NJ) was used to graft the cavernosal defect after surgical excision of the penile plaque. Three patients simultaneously underwent placement of penile prostheses secondary to documented erection problems identi®ed at duplex Doppler ultrasound evaluation. The long-term postoperative complications and erectile function were evaluated with a mean follow-up of 30 months (range 25 ± 35 months). All patients reported resolution of penile curvature allowing for normal sexual function after a mean follow-up of the ®rst 14 months. Thirty months after placement of cadaveric pericardium, the three prosthetic patients still reported excellent sexual function. For the eight patients who did not undergo placement of a prosthesis, three with small to medium plaque size (`265 cm) continued to do well. The remaining ®ve patients with a large plaque size (b265 cm) did well initially, but later reported dif®culty maintaining erection due to venous leakage, thus they are currently using either a vacuum constriction device or an Actis ring. Three out of these ®ve venous leakage patients had ventral plaques; two had dorsal plaques, one of signi®cant size (465 cm). We conclude that for those patients who do not undergo placement of a prosthesis, a better long-term outcome is observed when the plaque is small to medium in size (`265 cm) and dorsally located. Patients with ventral plaque, extreme curvature, or plaque size b465 cm were more likely to have venoocclusive dysfunction, necessitating further intervention.

OBJECTIVE To evaluate in an animal model the intermediate and long‐term efficacy of cadaveric pericardium, dermis, vein and Gore‐Tex‰ as grafting materials for tunica albuginea substitution after plaque excision for Peyronie's disease. MATERIALS AND METHODS The study comprised 100 male Sprague‐Dawley rats (300–325 g) divided into five equal groups: group 1, sham‐operated controls; and groups 2–5 which underwent wedge excision of the tunica albuginea and replacement with either cadaveric pericardium, dermis, vein or Gore‐Tex grafts. Ten rats in each group had the cavernosal nerve stimulated electrically to assess erectile function at 4 months, and the remaining 10 rats at 6 months. After death the sampled tissues were fixed in 10% formalin, paraffin‐embedded, and stained with Masson's trichrome and Verhoff's van Giesen for collagen and elastic fibres. RESULTS Erectile function, assessed by cavernosal nerve stimulation, did not differ significantly in any of the groups (P > 0.05). The histological assessment of penile cross‐sections showed minimal fibrosis surrounding the patch in the dermal and vein grafts, and moderate to severe fibrosis in the Gore‐Tex graft at 4 and 6 months. In the pericardial graft there was a moderate degree of fibrosis at 4 months with only minimal fibrosis at 6 months. CONCLUSIONS These results show that cadaveric pericardium allows complete penile expansion and is strong enough to withstand normal intracorporal pressures. There was minimal fibrosis in the pericardial, dermal and vein grafts, and moderate fibrosis in the Gore‐Tex graft at 6 months. The pericardial graft is a satisfactory grafting material when used for tunica albuginea substitution, including the surgical management of Peyronie's disease.