A. Bannowsky

Recovery of erectile function after nerve-sparing radical prostatectomy: improvement with nightly low-dose sildenafil.

To evaluate the effect of low‐dose sildenafil for rehabilitating erectile function after nerve‐sparing radical prostatectomy (NSRP), as the delay to recovery of erectile function after NSRP remains under debate.

Nocturnal tumescence: a parameter for postoperative erectile integrity after nerve sparing radical prostatectomy.

PURPOSE The exact process and time required for rehabilitation of erectile function after nerve sparing prostatectomy remain unclear to date. Different theories of the pathophysiology of postoperative erectile dysfunction are currently being discussed. In a prospective study we performed recordings of nocturnal penile tumescence and rigidity during the acute phase after nerve sparing radical prostatectomy, ie in the first night after removal of the catheter, to assess the organic penile integrity. MATERIALS AND METHODS In 27 patients with local prostate carcinoma who had been sexually active before the intervention, we performed unilateral or bilateral nerve sparing radical prostatectomy. Preoperative sexual function of all patients was evaluated by the International Index of Erectile Function-5 questionnaire. On the day of catheter removal (postoperative day 7 to 14) an NPTR recording was performed on the following night with an erectometer (RigiScan). RESULTS All patients had a preoperative IIEF score greater than 18. After removal of the catheter 25 of 27 patients (93%) showed 1 to 5 nocturnal rigidity increases by greater than 70% for at least 10 minutes. In a control group of 4 patients who underwent radical prostatectomy without nerve sparing, no nocturnal erections were recorded. CONCLUSIONS NPTR recording during the acute phase after nerve sparing radical prostatectomy showed residual erectile function as early as the first night after catheter removal. These results are significant for selecting adequate pharmacological treatment for optimal therapy and rehabilitation of satisfactory erections and sexual function. In cases of early nocturnal tumescence, application of a PDE5 inhibitor can support successive organ rehabilitation. However, if tumescence does not occur, penile injection therapy is recommended.

Penile fractures: controversy over surgical or conservative treatment.

Patients typically present with complaints of a classic ‘cracking’ sound, sharp penile pain, rapid detumescence and swelling with or without ecchymosis of the penile shaft. The penis may be bent as well as having ecchymosis confined to Buck’s fascia, resulting in massive oedema. Additionally, injured fascial compartments will lead to an extension of the ecchymosis into the scrotum, perineum, the suprapubic area and the inguinal regions [7]. The massive swelling will involve lateral penile deviation in the direction of the unaffected penile side [1,2,10], except for the rare case of a bilateral rupture, which will lead to dorsal or ventral deviation [15]. Sometimes there is a palpable defect in the tunica.

Melanocortin receptor agonists in the treatment of male and female sexual dysfunctions: results from basic research and clinical studies

Introduction: Over the last 20 years, basic and clinical research activities studying the male and female sexual responses have led to several pharmacological options to treat male erectile dysfunction (ED) and female arousal and orgasmic disorders. While some strategies exclusively focus on peripheral mechanisms – such as nitric oxide/cyclic GMP signaling, which is known to play a role in the control of genital vascular and nonvascular smooth muscle – others have considered the central pathways involved in mediating arousal and orgasmic functions in females as well as the induction of penile erection in males. Aside from dopaminergic agonists, drugs known to target the central melanocortin system have also been assumed to have a promising potential in the treatment of female and male sexual dysfunctions. Areas covered: The present review summarizes the achievements that have been made in the clinical development of melanocortin receptor (MCR) agonists (melanotan I, melanotan II, bremelanotide) for the treatment of symptoms of sexual arousal and orgasmic disorders in adult females and ED in males. Expert opinion: The data available at present have facilitated our understanding of how the melanocortin pathway regulates both the male and female sexual functions. Indeed the data warrant further investigation to demonstrate the impact of the activation of MCRs by specific agonists on penile erection and female arousal and orgasm function.

Increasing the dose of vardenafil on a daily basis does not improve erectile function after unilateral nerve-sparing radical prostatectomy.

INTRODUCTION Several treatment regimens for rehabilitation of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) are currently discussed. The optimal and most cost-effective therapy is still not found yet. AIM To evaluate the effect of vardenafil, a PDE5 inhibitor, dose escalation on recovery of EF after unilateral nsRP. METHODS Thirty-six sexually active patients received a unilateral nsRP. All patients completed an International Index of Erectile Function-5 items (IIEF-5) questionnaire concerning EF preoperatively. Group 1 (N = 12 patients) received vardenafil 5 mg/day vs. group 2 (N = 12) who received vardenafil 10 mg/day at night beginning the day of catheter removal. A control of 12 patients underwent follow-up without PDE5 inhibitors. MAIN OUTCOME MEASURE The IIEF-5 was the primary end point. IIEF-5 questionnaires were completed at baseline, 3, 6, and 12 months after nsRP. RESULTS In group 1 (5 mg/day vardenafil) the IIEF-5 score decreased from a preoperative 22.4 mean score to 4.2 at 3 months, 8.9 at 6 months, and 13.4 mean score at 12 months after nsRP vs. preoperative 22.8, 4.1 at 3 months, 7.9 at 6 months, and 12.8 mean score at 12 months in group 2 (10 mg/day vardenafil). In the control group the preoperative IIEF-5 mean score of 21.9 decreased to 3.8 at 3 months, 6.1 at 6 months, and 8.9 at 12 months. Statistical evaluation showed significant difference in IIEF-5 score and time to recovery of EF between groups 1 and 3 and between groups 2 and 3 (P < 0.01). No statistical differences were found between groups 1 and 2. CONCLUSIONS Daily low-dose vardenafil lead to significant improvement of recovery of EF. In this study doubling the dosage did not improve the recovery of EF further.

Innervation and Function of the Female Urinary Bladder and Urethra

Abstract Only few, but nonetheless specific anatomical differences exist between the female and the male urinary bladder. In men, the prostate gland, as a potentially obstructive organ, and in women the pelvic floor due to possible insufficiency after childbirth or through fluctuation of estrogen, may give rise to specific problems. The detailed knowledge of the anatomical, morphological and physiological fundamentals is of essential importance for understanding the mechanisms and innervation of the female urinary bladder.

Randomized phase III study of adjuvant versus progression-triggered treatment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemotherapy (CBC) (AUO-trial AB22/00).

250 Background: Cisplatin-based chemotherapy (CBC) has been widely used in trials of adjuvant therapy for LABC after RC. A high proportion of patients are unfit for CBC after RC for LABC. We therefore performed a prospective randomized phase III trial on G-monotherapy administered as adjuvant therapy (G-adj) vs in case of progression (G-prog) in pts not suitable for CBC. METHODS Between 7/2000 and 12/2008 120 of 178 planned pts with LABC unfit for CBC were randomized between 6 adjuvant cycles of G (q3w) starting within 12 wks after RC and G in case of disease progression. The primary endpoint of the trial was progression-free survival (PFS). Secondary endpoints included cancer-specific (CSS) and overall survival (OS) as well as treatment related toxicity. RESULTS The trial of 178 planned pts was closed early due to slow accrual. Of 120 randomized pts from 29 centers 114 were eligible for analysis. Median age of 81 male and 33 female pts was 72 (45-82) years. Lymph-node positive disease was found in 52/114 (47%) of pts at the time of surgery. The intention-to-treat analysis demonstrated a 10% difference in PFS after 3 years 50% (G-adj) vs 40% (G-prog) with a median PFS of 23 mo (G-adj) vs 17 mo (G-prog). The difference in PFS was not statistically significant (nss) (p= 0.335; HR 1.375, 95%CI 0.719 - 2.627). CSS at 3ys: 56% (G-adj) vs 50% (G-prog) with a median CSS of 49 mo (G-adj) vs 38 mo (G-prog). The difference in CSS was nss (p= 0.622; HR 1.166, 95%CI 0.632 - 2.149). OS at 3ys: 49% (G-adj) vs 48% (G-prog) with a median OS of 32 mo (G-adj) vs 31 mo (G-prog). The difference in OS was nss (p= 0.426; HR 1.225, 95%CI 0.743 - 2.018). Treatment with G was usually well tolerated, with less than 15% grade 3/4 toxicities..There was one treatment related death in the G-adj arm. CONCLUSIONS The study-hypothesis of a 15% difference in PFS after 3 years in favor of G-adj vs G-prog could not be confirmed. Nevertheless a marked difference in survival in favor of G-adj was shown by Kaplan-Meier plots regarding PFS, CSS and OS within the first 24 months after RC. CLINICAL TRIAL INFORMATION NCT00146276.

Rare and Challenging Tumor Entity: Phyllodes Tumor of the Prostate

Cystic epithelial-stromal tumors of the prostate are rare, with 82 cases reported in literature. These cases have been published under a variety of diagnoses, including phyllodes tumor and prostatic stromal proliferation of uncertain malignant potential as well as a malignant tumor called “prostatic stromal sarcoma”. We report a case of a 60-year-old man with the histological diagnosis of phyllodes tumor of the prostate in transurethral resection specimen.

Rehabilitation der erektilen Funktion nach nervenschonender radikaler Prostatektomie

OBJECTIVE Despite objective published data regarding rehabilitation of erectile function (EF) after nerve-sparing radical prostatectomy (nsRP) the gold-standard treatment is still under debate. The aim of this study was to evaluate the distribution of the different treatment options in Germany. PATIENTS AND METHODS Between October 2010 and May 2012 a questionnaire was sent to urologists in outpatient, general and university hospitals and rehabilitation hospitals in Germany. The survey consisted of various questions concerning, e.g. if and what kind of therapy urologists choose to support rehabilitation of EF after nsRP. Further questions dealt with the frequency, duration and optimal start of the chosen therapy. RESULTS Currently 188 urologists have completed and returned the questionnaire. The distribution was urologists in hospitals n=79 and outpatient/ambulatory n=106, with 24 % performing surgical treatment and urologists in rehabilitation hospitals n=3. The question about the rehabilitation concept showed 39 different forms of treatment within this group. To increase EF after nsRP PDE5 inhibitors were mostly administered (88 %) with 45 % on request compared to 55 %on a daily or regular basis ≥ 3 times/week. The use of penile injection therapy, medicated urethral system for erection (MUSE) and vacuum constriction devices (VCD) was prescribed by 32 %, 6 % and 30 % of urologists, respectively. Only 14 % of the urologists did not choose any active kind of rehabilitation treatment for EF recovery after nsRP. CONCLUSION Many different therapeutic concepts are currently performed in Germany to increase EF recovery after nsRP. The use of PDE5 inhibitors is the most commonly chosen treatment option. Despite published data regarding effectiveness, the optimal treatment seems to be still unknown.

Phosphodiesterase isoenzymes in the human urethra: A molecular biology and functional study

Experimental and clinical studies have suggested a role for phosphodiesterase (PDE) isoenzymes in the control of the human lower urinary tract. This study aimed to investigate the expression of PDE isoenzymes and the effects of PDE inhibitors (PDE-Is) in isolated human urethral smooth muscle (USM). The expression of messenger ribonucleic acid (mRNA) specifically encoding for PDE isoenzymes and isoforms (1A, 1B, 1C, 2A, 4A, 4B, 4C, 4D, 5A and 11A) was analyzed by means of reverse transcriptase polymerase chain reaction (RT-PCR). Using a tissue bath technique, the effects of vinpocetine (PDE1-I), erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA-HCl=MEP1) (PDE2-I), rolipram (PDE4-I), sildenafil, vardenafil and tadalafil (PDE5-Is) (0.01-10µM) on the tension of USM induced by norepinephrine were investigated. The production of cyclic guanosine monophosphate (cyclic GMP) and cyclic adenosine monophosphate (cyclic AMP) was measured by means of radioimmunoassays. RT-PCR analysis revealed the expression of PDE1B, PDE1C, PDE4A, PDE4C, PDE4D, PDE5A and PDE11A. The tension induced by norepinephrine (NE) was reversed by the PDE inhibitors with the following rank order of efficacy: rolipram (mean: -39%)≥sildenafil (-35%)>vardenafil (-26%)>tadalafil (-20%)>vinpocetine (-16%)>MEP1 (-2%). The relaxing effects of the drugs were paralleled by an elevation in tissue levels of cyclic AMP and cyclic GMP. Selective inhibitors of PDE4 and PDE5 can antagonize the tension induced by alpha-adrenergic stimulation of USM. PDE inhibition might represent an interesting option to facilitate the relaxation of the human outflow region.