Single-stage dorsal inlay for reconstruction of recurrent peno-glandular stenosis.

OBJECTIVE: To evaluate the validity of a single-stage dorsal inlay for recurrent peno-glandular stenosis following previous endourological or open urethroplastic surgery. Urethral glanular reconstruction included a deep dorsal incision followed by complete scar excision to create a deep groove presenting well-vascularized recipient bed ensuring appropriate graft healing. MATERIALS AND METHODS: Between April 2002 and January 2008, a total of 34 patients (mean age 51.5 years, 14-85 years) were enrolled in the study. Congenital anomalies included hypospadia (n = 19, 53%) and epispadia (n = 2, 6%). Condition of strictures was either iatrogenic (n = 7), due to infection (n = 5), or traumatic (n = 1). Foreskin grafts were used in 13 cases, foreskin and buccal mucosa in one case, penile skin in 6 cases, and inguinal skin/thigh (harvested by electrodermatom) in 14 cases. The combination of meticulous scar excision with a deep incision of the glans was used to provide a well-vascularized grafting bed, thus ensuring excellent graft healing. The outcome analysis included urinary flow, urethral calibration >18 ch, voiding cystometry, and patient's satisfaction in a follow-up regime every 3 months. RESULTS: The average graft length was 4.7 cm (median 8, range 1.5-14). Mean follow-up was 70 months. In 31 patients (91%), no recurrent glanular stenosis was observed resulting in a post-operative flow of average 26.2 ml/s (11-53). Three post-operative wound infections occurred resulting in stricture recurrence, which was treated with internal urethrotomy, buccal mucosa, or penile skin inlay, respectively. Cosmetic results were satisfactory in all patients. Post-operative voiding parameters were significantly improved (P < 0.001). CONCLUSION: The single-stage dorsal inlay for reconstruction of peno-glandular stenosis represents a reliable method even if the urethral plate is severely scarred or has been excised during previous surgery. The good results imply that a well-vascularized graft and the technical approach seem to be more important than the substitute material.

Patient-reported side effects of intradetrusor botulinum toxin type a for idiopathic overactive bladder syndrome.

OBJECTIVE: The aim of the study was a prospective assessment of patient-reported side effects in an open-label study after intradetrusor botulinum toxin injections for idiopathic overactive bladder (OAB). PATIENTS AND METHODS: Botulinum toxin A injection was performed in 56 patients with idiopathic OAB. Patients were followed up for 6 months concerning side effects and patients' satisfaction. RESULTS: Different types of side effects were assessed such as dry mouth (19.6%), arm weakness (8.9%), eyelid weakness (8.9%), leg weakness (7.1%), torso weakness (5.4%), impaired vision (5.4%) and dysphagia (5.4%). In all cases, symptoms were mild and transient. Urological complications such as gross hematuria (17.9%), acute urinary retention (8.9%) and acute urinary tract infection (7.1%) were noticed. In all cases, acute urinary retention was transient and treated with temporary intermittent self-catheterization. There was no statistically significant correlation between dosage and observed side effects. Patients' satisfaction rate was high (71.4%). CONCLUSION: Intradetrusor injection of botulinum toxin was associated with a high rate of neurourological side effects. In general, side effects were transient, mild and did not require special treatment.

Complications of the AdVance transobturator male sling in the treatment of male stress urinary incontinence.

OBJECTIVE: To evaluate prospectively the complication rate of the retrourethral transobturator sling (AdVance sling) for the functional treatment of male stress urinary incontinence (SUI). METHODS: In 230 patients with SUI due to nonintrinsic sphincter deficiency (without direct sphincter lesion) after radical prostatectomy (n=213), radical cystoprostatectomy with ileal neobladder (n=2) and transurethral resection of the prostate (n=15) a retrourethral transobturator sling was implanted. Patients were followed up for a median of 17 months (range, 4-42 months) with regard to intraoperative, early postoperative, and midterm postoperative complications. RESULTS: Overall complication rate of the AdVance sling was 23.9%. Despite one accidental sling misplacement, no intraoperative complication occurred. Forty-nine patients (21.3%) experienced urinary retention postsurgery. Two slings were explanted (0.9%), 1 due to initial wrong placement and the other due to a symphysitis, attributed to a Guillain-Barré syndrome and not to a sling infection. One sling was transected (0.4%) due to slippage of the sling with obstruction of the urethra. Further complications were local wound infection (0.4%), urinary infection with fever (0.4%), and persistent moderate perineal pain (0.4%). There was no correlation between postoperative acute urinary retention and age at sling implantation, time of incontinence before sling implantation, preoperative daily pad use, or prior invasive incontinence treatment, respectively. CONCLUSIONS: The retrourethral transobturator AdVance sling is a safe treatment option for male nonintrinsic sphincter deficiency SUI, with the main postoperative complication being transient acute urinary retention. Severe intra- and postoperative complications are rare and sling explantation rate is very low.

Prospective evaluation of the functional sling suspension for male postprostatectomy stress urinary incontinence: results after 1 year.

BACKGROUND: Although surgical techniques for radical prostatectomy (RP) have been refined significantly, a significant number of patients still suffer from persisting postprostatectomy stress urinary incontinence (SUI). In recent years, various minimally invasive sling systems have been investigated as treatment options for such incontinence. OBJECTIVE: The aim of the study was the prospective evaluation of the efficacy of the retrourethral transobturator sling for the functional treatment of male SUI after RP. DESIGN, SETTING, AND PARTICIPANTS: The study documents a single-centre prospective evaluation of the outcome of 124 patients with mild to severe SUI following RP in whom an AdVance sling was implanted between February 2006 and September 2008. MEASUREMENTS: All patients were comprehensively evaluated preoperatively and after 6 mo and 1 yr regarding daily pad use, 1-h and 24-h pad tests, residual urine, uroflowmetry, Incontinence Quality of Life Scale (I-QOL) score, and Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) score. Data were collected prospectively. RESULTS AND LIMITATIONS: After 6 mo, a cure rate (no pads or one dry security pad) of 55.8%, an improved rate (one to two pads or pad reduction≥50%) of 27.4%, and a failure rate of 16.8% were observed. After 1 yr, the cure rate was 51.4%, the improved rate was 25.7%, and the failure rate was 22.9%. Daily pad use and pad weight decreased significantly postoperatively. No significant changes were seen in residual urine and flow rate. Quality-of-life scores improved significantly. Postoperative acute urinary retention was seen in 12.9% of patients. One patient had a local wound infection that was cured with antibiotics. One patient had the sling removed due to misplacement. CONCLUSIONS: The retrourethral transobturator sling is an effective and attractive treatment option for male SUI resulting from RP after 1 yr of implantation.

Female sexual dysfunction: what's new?

PURPOSE OF REVIEW: The aim of this article is to summarize the most important and interesting achievements which have recently been made in the field of female sexual dysfunction. RECENT FINDINGS: During the last years, the characterization of the female sexual response has been re-examined, resulting in new approaches to the description of female sexual dysfunction, diagnostic criteria and (pharmacological and nonpharmacological) treatment options. The focus of this review is to summarize in brief the latest achievements in the classification, diagnosis, and therapy of symptoms of sexual arousal and orgasmic disorders in adult females. SUMMARY: Future research efforts may provide new diagnostic and (pharmacological and nonpharmacological) treatment algorithms suitable for use in daily clinical practice to approach the different categories of female sexual dysfunction symptoms.

The future of the oral pharmacotherapy of male erectile dysfunction: things to come.

The convincing clinical data on the use of the orally active phosphodiesterase inhibitors sildenafil, vardenafil and tadalafil for the treatment of male erectile dysfunction have boosted research activities on the physiology of the male erectile mechanism. This included both peripheral intracellular signal transduction in the corpus cavernosum as well as central brain and spinal cord pathways controlling penile erection. This work provided the basis for the development and introduction of several new therapeutic modalities into the management of erectile dysfunction, some of which are already offered to the patients. As the concept of 'taking a pill' as a cure for an illness or the relief of symptoms of a disease has become widely accepted by the consumers, the pharmacologic treatment of erectile dysfunction has primarily focussed on selective, orally available drugs acting by influencing intracellular or central regulatory mechanisms, combining a high response rate and the advantage of an on-demand intake. These agents are regarded as more efficacious, and have a faster onset of drug action in the target tissue and an improved effect to side-effect ratio. The purpose of this review is to describe the major novel and evolving pharmacologic advances in the field of oral pharmacotherapy for the treatment of male erectile dysfunction.

Functional responses of isolated human seminal vesicle tissue to selective phosphodiesterase inhibitors.

OBJECTIVES: To further elucidate the significance of the cyclic nucleotide-mediated signal transduction, we examined the in vitro functional responses of isolated seminal vesicle (SV) smooth muscle tissue to selective phosphodiesterase (PDE) inhibitors. METHODS: Using the organ bath technique, the effects of increasing concentrations (1 nM to 10 microM) of the PDE inhibitors vinpocetine (PDE1 inhibitor), rolipram (PDE4 inhibitor), and sildenafil and vardenafil (PDE5 inhibitors) on the tension induced by 10 microM of norepinephrine on SV tissue strips were investigated. To examine the drug effects on the tissue levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), the SV strips were exposed to different concentrations of the compounds (0.1, 1, and 10 microM). After freezing, homogenization, and extraction of cyclic nucleotides, cAMP and cGMP were measured using radioimmunoassays. In the experiments, sodium nitroprusside and forskolin were used as reference compounds. RESULTS: The norepinephrine-induced tension was reversed by the drugs in a dose-dependent manner. The rank order of efficacy was rolipram greater than sildenafil greater than vardenafil greater than or equal to vinpocetine greater than sodium nitroprusside greater than forskolin. The reversion of the norepinephrine-induced tension at maximum drug concentration ranged from 79% (rolipram) to 32% (forskolin). Only rolipram and sildenafil reached a median effective concentration. The effects of the PDE inhibitors were paralleled by a 1.7-fold to 173-fold increase in tissue cGMP or cAMP. CONCLUSIONS: Our results have demonstrated that PDE inhibitors can reverse the adrenergic tension of human SV tissue and increase levels of cyclic nucleotides. This outlines the potential significance of cAMP and cGMP in the control of SV smooth muscle function. These findings might be of importance with regard to the pharmacologic treatment of premature ejaculation.

Potential future options in the pharmacotherapy of female sexual dysfunction.

Female sexual dysfunction (FSD) is considered a common medical problem estimated to affect millions of women in the westernized countries. FSD has been classified into four different categories including sexual arousal disorder (FSAD), sexual desire disorder (HSDD), orgasmic disorder and sexual pain disorder. The focus of this article is the potential role of pharmacological compounds currently under development, in the treatment of sexual arousal and orgasmic disorders in order to enhance the sexual response in adult females. While a number of potential therapeutic options are available to date, not one of the pharmacological treatment regimens has been yet considered the Gold standard in the management of symptoms of FSD. This article reviews the rationale and potential benefits of using distinct drug formulations in the treatment of FSD.

Distribution and functional significance of phosphodiesterase isoenzymes in the human lower urinary tract.

To date, it is widely accepted that several disorders of the male and female urogenital tract, such as erectile dysfunction, bladder overactivity, urinary stone disease and the benign prostatic syndrome, can be therapeutically approached by influencing the function of the smooth musculature of the respective organs. In order to achieve a pronounced drug effect without significant adverse events, especially on the cardiovascular system, a certain degree of tissue selectivity is mandatory. Selective intervention in intracellular pathways regulating smooth muscle tone has become a promising strategy to modulate tissue function. Since the concept of taking a pill as a cure for an illness or the relief of symptoms has become widely accepted by the consumers, the pharmacological treatment of urological diseases has focused on selective, orally available drugs, acting via influencing intracellular regulatory mechanisms, thus combining a high response rate and the advantage of an on-demand intake. PDEs play a central role in controlling the levels of cyclic nucleotides (i.e. cAMP and/or cGMP), which are important second messengers in many transmitter pathways involved in the regulation of biological processes of urogenital tissues. Specifically, the use of isoenzyme selective phosphodiesterase (PDE) inhibitors offers great hope in the medical treatment of various genitourinary diseases. These agents are regarded efficacious, having a fast onset of drug action in the target tissue and an improved effect-to-side-effect ratio. The growing experience with the use of this class of compounds in urology is mainly based on basic research efforts and this field will remain the most exciting and innovative subject in genitourinary physiology and pharmacology for the next few years. These tremendous research efforts may lead to a vast pharmacological armamentarium of possible new treatment options. The purpose of this review is to summarize the current knowledge on the distribution and potential functional significance of PDE isoenzymes in the human lower urinary tract.

Phosphodiesterase inhibitors in female sexual dysfunction.

Based on the increasing knowledge on both the physiology of penile erection and the pathophysiology of erectile dysfunction, selective phosphodiesterase (PDE) inhibitors have been successfully introduced in the oral treatment of male erectile dysfunction. Because of their central role in smooth muscle tone regulation, PDEs remain an attractive target for drug development in urology. Since the distribution and functional significance of PDE isoenzymes vary in different tissues, selective inhibitors of the isoenzymes have the potential to exert at least partially specific effects on the target tissue. Currently, PDE inhibitors are under investigation with potential uses in urinary stone disease, overactive bladder and the so-called benign prostatic syndrome. The convincing clinical data on the use of the orally active PDE5 inhibitors sildenafil (VIAGRA), vardenafil (LEVITRA) and tadalafil (CIALIS) in the treatment of erectile dysfunction are accompanied by boosting research activities on intracellular signal transduction and PDE characterisation in female genital tissues with the aid of immunohistochemistry and immunocytochemistry and molecular biology. The expression of various PDE isoforms in the human clitoris, vagina and labia minora was shown by means of immunohistochemistry and RT-PCR analyses and it was concluded from functional studies that an increase in cGMP or cAMP might be involved in the regulation of female genital blood flow and the control of genital non-vascular smooth muscle. As a consequence, the efficacy and safety of the PDE5 inhibitor sildenafil in the treatment of symptoms of female sexual dysfunction (FSD), including female sexual arousal disorders (FSAD), have been evaluated. Although the experiences from these early clinical studies have so far not been conclusive, they suggest that, after appropriate evaluation of patients, inhibition of PDE5 might be of benefit for selected individuals with FSAD. Such research efforts will possibly allow the identification of efficacious and diagnostic tools for erectile dysfunction and of even more selective drugs in its therapy.