Correlations between increased erection hardness and improvements in emotional well-being and satisfaction outcomes in men treated with sildenafil citrate for erectile dysfunction.

To explore relationships between erection hardness and other outcomes in men with erectile dysfunction (ED). Pooled analyses were conducted on 27 randomized, double-blind, placebo-controlled trials and six open-label trials from the worldwide sildenafil database. Outcomes included erection hardness graded subjectively, hardness and sexual satisfaction questions from the International Index of Erectile Function, general and sexually-specific emotional well-being from the self-esteem and relationship questionnaire, and the erectile dysfunction inventory of treatment satisfaction. Hardness outcomes improved (with a possible dose-response relationship for the achievement of fully hard and rigid erections) and correlated positively with the other outcomes. Sildenafil 100 mg produced optimal erection hardness (fully hard and rigid erections) in a substantial proportion of men with ED. Because optimal erection hardness correlated positively with some emotional well-being and satisfaction outcomes, sildenafil 100 mg may be the most appropriate dosage for treatment of ED for most men.

[Stone management in children]. / Steintherapie im Kindesalter.

The extracorporeal shock-wave lithotripsy (ESWL) is still the treatment of choice for almost all stones in children. But with advances in instrumentation, endourological procedures are being performed more frequently in younger patients. Especially in the treatment of distal ureteral stones retrograde ureteroscopy now competes with ESWL. Finally, the recent literature supports percutaneous nephrolithotomy as a safe and effective treatment option for large renal calculi and staghorn calculi. This gives the clinician the opportunity to choose from a wide range of treatment alternatives. Proper treatment planning, technique and availability of appropriate instrumentation are important to achieve an optimal outcome.

[Value of perineal HistoScanning™ template-guided prostate biopsy]. / Stellenwert der perinealen HistoScanning™-gestützten Templateprostatabiopsie.

BACKGROUND: Modern imaging modalities improve prostate diagnostics. OBJECTIVES: This study was performed to determine the outcome characteristics of biopsy procedures using the results of HistoScanning(TM) analysis (HS) for identifying prostate cancer (PCa) in patients with perineal template-guided prostate biopsy. PATIENTS AND METHODS: A total of 104 consecutive men (mean age 69 years, mean PSA 9.9 ng/ml) underwent HS prior to the extended prostate biopsy procedure. Patients received a targeted transperineal (template-assisted) as well as a targeted transrectal prostate biopsy using HS projection reports supplemented by a standardized 14-core systematic transrectal prostate biopsy (Bx). The cancer detection rate was analyzed on the sector level and HS targeted results were correlated to biopsy outcome, sensitivity, specificity, predictive accuracy, negative predictive value (NPV) and positive predictive value (PPV). RESULTS: Of 104 patients, 44 patients (42%) were found to have PCa. Histology detected atypical small acinar proliferation in 3 patients (2.9%), high-grade prostatic intraepithelial neoplasia in 16 (15.4%), and chronic active inflammation in 74 (71.1%), respectively. The detection rate for each region was significantly higher in HS-targeted biopsies compared to Bx. The detection rate per patient was not significantly different, although a smaller number of regions were biopsied with the targeted approach. The overall sensitivity, specificity, predictive accuracy, NPV, and PPV on the sector level were 37.2, 85.6, 78.6, 88.7 and 30.8%, respectively. CONCLUSION: The use of HS analysis results in a higher detection rate of prostate cancer compared to common transrectal ultrasonography (TRUS)-guided Bx. This technique increases the informative value of TRUS imaging and improves the diagnostic impact at least in the targeted biopsy setting.

The renoprotective potential of endothelin receptor antagonists.

The endothelin system has been identified as having a substantial role in renal failure, both acute and chronic. Beside its well characterised haemodynamic effects, its mitogenic and pro-fibrotic properties have gained increased interest in the pathophysiology of chronic renal failure. This review outlines the role of endothelin in the pathogenesis of various renal diseases with a special focus on the potential of blocking this system with endothelin receptor antagonists. So far, most data were derived from animal models, but they provide strong evidence that endothelin receptor antagonists may represent a powerful therapeutic strategy in ameliorating the course of acute and chronic renal failure.

[Secondary malignancies in urinary diversions]. / Sekundärmalignome in Harnableitungen.

In contrast to ureterosigmoidostomy no reliable clinical data exist for tumor risk in different forms of urinary diversion using isolated intestinal segments.In 44 German urological departments, operation frequencies, indications, patient age, and operation dates of the different forms of urinary diversion, operated between 1970 and 2007, could be registered. The secondary tumors up to 2009 were registered as well and related to the numbers of the different forms of urinary diversions resulting in tumor prevalences.In 17,758 urinary diversions 32 secondary tumors occurred. The tumor risk in ureterosigmoidostomy (22-fold) and cystoplasty (13-fold) is significantly higher than in other continent forms of urinary diversion such as neobladders or pouches (p<0.0001). The difference between ureterosigmoidostomy and cystoplasty is not significant, nor is the difference between ileocecal pouches (0.14%) and ileal neobladders (0.05%) (p=0.46). The tumor risk in ileocecal (1.26%) and colonic neobladders (1.43%) is significantly higher (p=0.0001) than in ileal neobladders (0.5%). Of the 16 tumors that occurred following ureterosigmoidostomy, 16 (94%) developed directly at the ureterocolonic borderline in contrast to only 50% following urinary diversions via isolated intestinal segments.From postoperative year 5 regular endoscopic controls of ureterosigmoidostomies, cystoplasties, and orthotopic (ileo-)colonic neobladders are necessary. In ileocecal pouches, regular endoscopy is necessary at least in the presence of symptoms or should be performed routinely at greater intervals. Following neobladders or conduits, only urethroscopies for urethral recurrence are necessary.

[Urine-based diagnostics: an update on the Kiel Tumor Bank]. / Uringebundene Diagnostik: Ein Update der Kieler Tumorbank.

The heterogeneity of bladder tumors in their ability to invade and metastasize and their frequent recurrence pose a challenge for physicians who treat bladder cancer patients and for the researchers who work on bladder cancer diagnosis, recurrence, and treatment-related areas. For most new bladder cancer cases, investigation begins when patients are symptomatic (i.e., hematuria or irritative voiding). This mode of detection is often inadequate for nearly 15-30% of these new cases with high-grade bladder cancer, since the tumor is already in the invasive stage at the time of diagnosis. Bladder cancer patients are on a mandatory 3-month to 6-month surveillance schedule because bladder tumors frequently recur. The current mode of detecting bladder cancer involves cystoscopy, which is an invasive and relatively expensive procedure. Voided urine cytology, the standard noninvasive marker, is highly tumor specific and has good sensitivity for detecting high-grade tumors. However, its sensitivity for detecting low-grade tumors is low; its accuracy depends on the examiner's expertise; and it is not available everywhere. Marker systems are readily available for use in practice. Their utility remains under discussion.

Refluxing chimney versus nonrefluxing LeDuc ureteroileal anastomosis for orthotopic ileal neobladder: a comparative analysis for patients with bladder cancer.

PURPOSE: Radical cystectomy and various techniques of urinary diversion are gold standard treatments for invasive bladder cancer. However, postoperative hydronephrosis is a common complication in these patients. A special focus was placed on the type of ureteroileal anastomosis used with 2 different techniques performed at 1 institution. MATERIALS AND METHODS: Between 1995 and 2003 a total of 106 consecutive patients with bladder cancer underwent cystectomy followed by construction of an ileal neobladder. The nonrefluxing technique of ureter tunneling described by LeDuc and the refluxing chimney technique used for ureter implantation into the ileum-neobladder were compared. Hydronephrosis due to ureteral strictures was studied immediately following surgery and up to 5 years after surgery. RESULTS: A total of 204 RU were included in the study. The LeDuc technique was used in 132 RU (64%) and the chimney technique was used in 72 RU (36%). Hydronephrosis rate of 2% were found in each of the 2 groups after 5 years of followup. CONCLUSIONS: Postoperative hydronephrosis due to ureteral strictures is observed at the same rate during long-term followup with the LeDuc and chimney techniques. We favor the chimney technique compared to the LeDuc tunnel due to easier technical preparation and a better chance to identify the ureters endoscopically at a later time. The chimney does give extra length to reach the ureteral stump, especially in cases of distal ureteral carcinoma in situ.

Impact of electrostimulation of neurovascular bundles and pudendal nerves on the membranous urethra in male rabbits.

PURPOSE: The pathophysiology of post-prostatectomy incontinence is supposed to be multifactorial. The impact of the neurovascular bundles on sphincter function is still under debate. We clarified the impact of cavernous nerves function on the MU. We compared MU pressure responses in male rabbits following electrophysiological stimulation trials on the neurovascular bundles vs pudendal nerve stimulation. MATERIALS AND METHODS: Six male Chinchilla Bastard rabbits were included in this study. Pudendal and cavernous nerve branches were exposed bilaterally in all animals. Randomized electrostimulation of pudendal nerve fibers and the cavernous nerves, as confirmed by erection,) were done using a biphasic signal form of 0.3 mA for 200 microseconds. Stimulation frequency was changed in a randomized pattern from 10 to 40 Hz. Changes in MU pressure were measured urodynamically via a transurethral microtip catheter placed in the MU. Stimulation responses of the 2 nerve structures were compared. RESULTS: Mean baseline pressure in the MU without stimulation was 23 cm H(2)O (range 20 to 25) in all animals. During unilateral pudendal stimulation the mean pressure response increased highly significantly to 33, 43, 59 and 60 cm H(2)O at 10, 20, 30 and 40 Hz, respectively (p <0.005). In contrast, compared to baseline pressure cavernous nerve stimulation did not result in any significant changes in proximal urethral pressure (mean 23 cm H(2)O, range 20 to 25, p >0.05). CONCLUSIONS: Our results confirm the primacy of the pudendal nerve in the external urethral sphincter innervation. In contrast, stimulation of the cavernous nerves did not produce any pressure changes in the MU. These results confirm that the neurovascular bundles have no functional impact on the MU.

Fertility in cryptorchidism: an experimental model.

Because the long-term efficacy of treatment for cryptorchidism is difficult to evaluate in humans, we developed an animal model to study the effects of cryptorchidism on fertility. Sprague-Dawley rats were treated within the first few days of life to create either mechanical or endocrinological cryptorchidism. The ability to father offspring was used as a measure of fertility. Significant differences in fertility between rats with bilateral cryptorchidism and controls were observed, regardless of whether the cause was mechanical or endocrinological. Rats with unilateral cryptorchidism were significantly less fertile than those that underwent unilateral orchiectomy. Further development of this model will permit prospective evaluation of different treatment modalities in cryptorchidism.

Fertility in cryptorchidism: further development of an experimental model.

Further development of an experimental model for evaluating fertility in cryptorchidism led to studies of unilateral cryptorchidism, endocrinological cryptorchidism, and the effects of treatment. The results demonstrate that rats with unilateral mechanical cryptorchidism have a significant diminution in the ability to impregnate females (impregnation rate, 45%) when compared with sham-operated controls (84%) and rats undergoing unilateral orchiectomy (88%). In addition, we demonstrated that lower doses of estradiol caused cryptorchidism and resulted in infertility of approximately the same degree as higher doses (impregnation rates, 18% and 0%, respectively), but avoided obvious side effects. Treatment of estradiol-induced cryptorchidism with human chorionic gonadotropin resulted in testicular descent, but did not significantly improve the ability to bear offspring (10% with hCG vs. 0% without). Surgical orchiopexy after surgically induce mechanical cryptorchidism resulted in improved fertility (30% vs. 0%); however, the improvement was still significantly less than the control rate. In summary, this experimental model demonstrates the effects of various aspects of cryptorchidism and its treatment on fertility and can easily be adapted to evaluate important clinical problems.

Fertility in cryptorchidism: improved timing of fixation and treatment in an experimental model.

Modifications were made in an experimental model in the rat to make it more analogous to human cryptorchidism and more useful in evaluating treatment. The age of experimental bilateral cryptorchidism was changed from 3 days to 11 days. Neither group was able to father offspring. The age at orchiopexy also was modified from the range of 21 to 28 days to exactly 21 days. The ability to father offspring improved significantly (72 versus 30 per cent) and it was not significantly different from previously reported sham operated rats (84 per cent). The current experimental model demonstrates that early surgical treatment can restore fertility to mechanically cryptorchid animals. The model can be used to evaluate the effects of varying types and timing of treatment.

Mechanisms of venous occlusion during canine penile erection: an anatomic demonstration.

Hemodynamic studies have clearly demonstrated that intracorporeal injection of papaverine causes an increase of venous outflow resistance, and we therefore undertook a study of the venous drainage of the canine penis to delineate the anatomic changes in the venular structure during papaverine-induced erection. In 11 dogs, the corpora cavernosa were examined by corrosion casting in six and serial trichrome staining and histologic sectioning in five. Low-power scanning electron microscopy of the corrosion casts demonstrated the existence of a venular plexus interposed between the tunica albuginea and the sinusoidal spaces. After papaverine injection, this subalbugineal venular plexus is compressed between the dilated sinusoids from below and the tunica albuginea from above, such that venous drainage is effectively impeded. Examination of two cadaveric human penile corrosion casts by low-power scanning electron microscopy revealed evidence of a similar subalbugineal venular plexus draining into the emissary veins along the shaft of the penis. Based on the above, a model for the anatomic basis of venous occlusion during penile erection is outlined. Along with arteriolar and sinusoidal smooth-muscle relaxation, this can account for the three basic hemodynamic changes necessary for erection: increased arterial inflow, increased intracorporeal pressure, and increased venous outflow resistance.

The continent ileal bladder for urinary tract reconstruction after cystectomy: a survey of 44 patients.

The continent ileal bladder is an ileal pouch that is anastomosed to the urethral stump for urinary diversion after radical cystectomy. The ureters are implanted by an antireflux nipple ureteroileostomy. We report our results in 44 patients who underwent this type of diversion. The perioperative morbidity and mortality were comparable to those of an ileal conduit diversion. Urodynamic evaluation showed the ileal bladder to be a low pressure reservoir with a capacity that increased to more than 300 ml. The ileal bladder was emptied by straining without significant residual urine in all patients. After a training period of a few months all patients were continent in the daytime. However, some patients required pads at night because of occasional loss of urine.

Clinical significance of sacral and pudendal nerve anatomy.

The neuroanatomy and neurophysiology of the external urethral closure mechanisms still are under debate because the motor fibers that emanate from the sacral plexus and pudendal nerve to supply this segment have not been traced, nor has their functional interrelationship been established. Therefore, we dissected 3 male human cadavers (aged 31 to 69 years) by tracing the entire sacral plexus, particularly the pudendal nerve, from the cauda equina throughout the branching of the nerves to their final destination. The dissection demonstrated that the extrinsic urethral sphincter, formed by the rhabdosphincter around the membranous urethra as well as the levator ani muscle and pelvic floor (especially the transversus perinei muscle), is innervated by somatic nerve fibers that emanate primarily from sacral roots S2 and S3. In 5 patients with neurogenic lower urinary tract dysfunction electrostimulation of the sacral root and pudendal nerve markedly increased intraurethral closure pressures. Stimulation of the pudendal nerve or its transversus perinei branch alone resulted in an increase in intraurethral closure pressure to 60 to 70 cm. water--an increase similar to that produced by stimulation of the sacral root without neurotomy. By means of neurotomy and/or neural blockade with lidocaine we were able to differentiate between the contributions of each muscular element to the external sphincteric mechanism. Almost 70 per cent of the closure pressure of the external urethral sphincter is induced by stimulation of the S3 ventral root, while the other 30 per cent derives from S2 and S4 neuronal impulses.

Hemodynamics of papaverine- and phentolamine-induced penile erection.

We investigated the hemodynamic changes induced in the canine corpora cavernosa by intracorporeal injection of papaverine or phentolamine. In six dogs studied, papaverine profoundly increased the resistance to venous outflow, whereas phentolamine (an alpha-adrenergic blocker) had little or no effect. In four other dogs, flow within the internal pudendal artery was measured with an ultrasonic flow probe placed directly on the artery. Papaverine increased arterial flow by 300 to 700 per cent over baseline levels, whereas the increase with phentolamine was only 50 to 100 per cent. We conclude that papaverine, by virtue of its direct smooth-muscle-relaxing properties, has a dual hemodynamic effect: it decreases the resistance to arterial inflow, thereby allowing large increases in the flow of blood into the penis during tumescence; and increases the resistance to venous outflow. Phentolamine only decreases the resistance to arterial inflow, more modestly than papaverine, and does not increase the resistance to venous outflow.

Bladder wall tension during physiological voiding and in patients with an unstable detrusor or bladder outlet obstruction.

OBJECTIVE: To develop and evaluate a new clinical method for measuring bladder wall tension (BWT) on detrusor contraction during physiological voiding and under pathological conditions, as in experimental trials during subvesical obstruction the ability to generate pressure increases, whereas the contractile force per cross-sectional area of detrusor muscle decreases. PATIENTS AND METHODS: In all, 24 patients were divided into three equal groups: group 1 (mean age 58, sd 8.6 years) comprised men with bladder outlet obstruction in accordance with the Abrams-Griffiths nomogram; group 2 (four men and four women, 56, sd 7.2 years) had detrusor instability; and group 3 (54, sd 9.6 years) had normal bladder emptying. BWT, as the detrusor force per cross-sectional area of bladder tissue (in N/cm2), was calculated after a urodynamic evaluation and ultrasonographic estimate of bladder wall thickness. RESULTS: In all patients it was possible to measure BWT; the mean (sd) maximum BWT in group 1 was 9.8 (3.9) N/cm2, in group 2 during bladder instability was 11.7 (2.6) N/cm2 and in group 3 was 2.8 (0.5) N/cm2. CONCLUSIONS: Estimating BWT in humans is possible by combining a urodynamic evaluation with an ultrasonographic estimate of bladder wall thickness. Further clinical research should elucidate the clinical relevance of BWT under comparable conditions.

Blood gas analysis in drug-induced penile erection.

To elucidate the hemodynamic changes during erection, we measured corporeal blood gases in 6 monkeys before, during, and after erection induced by either papaverine or phentolamine or a combination of the two. Papaverine alone caused a strong erection (maximal tumescence and rigidity) by means of a rapid, large increase in pO2 and pCO2 with a pH drop to the acidic range. Phentolamine alone caused 'delayed' tumescence with less rigidity; the intracorporeal pO2 level increased, but pCO2 and pH values did not change significantly. The combination of both drugs offered no advantage over papaverine alone. We conclude that papaverine is a potent erection-inducing drug that acts in a bimodal manner, namely, it increases the arterial inflow and, at the same time, decreases the venous outflow. Phentolamine affects the arterial component of erectile function only.

Further evidence of venous outflow restriction during erection.

To elucidate the effect of venous outflow restriction during erection, we studied eight dogs during artificial saline perfusion of the penis with and without neurostimulation to induce erection. With the infrarenal aorta clamped temporarily, saline infusion rates of 0.9 and 1.9 ml/min raised the mean intracorporeal pressure to 34 and 42 cm H2O, respectively, before stabilisation or return to baseline. When cavernous nerve stimulation was initiated, the mean intracorporeal pressure rose to 124 and 184 cm H2O (with infusion rates of 0.9 and 1.9 ml/min respectively) to induce full erection. Our results show that venous outflow restriction takes place during erection and that it is necessary not only to induce full erection but also to maintain it. Evaluation of venous competence is therefore essential during the investigation of impotence.

The effect of cigarette smoking on penile erection.

Clinical observations suggest that cigarette smoking impairs erectile function in patients with moderate arterial insufficiency. To evaluate the effects of smoking on the physiology of erection, we studied six healthy adult mongrel dogs in which bipolar cuff electrodes were implanted around the cavernous nerves. After threshold stimulation parameters for penile erection were established, cigarette smoke collected in a 60-ml. syringe was released slowly near the dog's mouth, to be inhaled by natural breathing. Stimulation of the cavernous nerve was repeated and blood samples for nicotine, cotinine and blood gases were obtained before and after each cigarette. The systolic and intracorporeal pressure, flow through the internal pudendal artery, and venous flow from the corpora cavernosa were recorded at baseline and with each electrostimulation after smoke inhalation. Five of the six dogs were unable to achieve full erection after inhalation of smoke from two to three cigarettes. Some decrease of flow through the internal pudendal artery occurred and the venous restriction ability was almost completely abolished by smoking. Further, when nicotine was injected intravenously into two additional dogs, the same phenomenon was observed. These findings support the idea that cigarette smoking may contribute to impotence in some patients.

Priapism induced by chlorpromazine and trazodone: mechanism of action.

To investigate the mechanism of drug-induced priapism, we gave the antipsychotic agent chlorpromazine and the antidepressant trazodone to 14 dogs by intravenous and intracorporeal injection. Bilateral intracorporeal pressure, blood flow within the internal pudendal artery, and systemic blood pressure were monitored. Venous outflow restriction was evaluated by continuous saline infusion of the corpus cavernosum with the infrarenal aorta clamped. When delivered by intracorporeal injection, both drugs induced erection in a manner similar to that of intracorporeal injection of papaverine. Internal pudendal arterial flow increased slightly at the beginning of tumescence, and excellent venous restriction occurred. Intravenous injection, however, could neither induce an erection nor facilitate an erection after sub-threshold neurostimulation. We believe that the alpha-adrenergic antagonist properties of chlorpromazine and trazodone probably cause priapism by local action.