The role of sildenafil in the treatment of erectile dysfunction in patients with pelvic fracture urethral disruption.

PURPOSE: Erectile dysfunction (ED) is a common sequel of pelvic fracture urethral disruption (PFUD). After repair of the urethral injury ED may be the most devastating long-term effect for the patient. Some patients with ED may regain normal erectile function. We prospectively studied the response to sildenafil and the erectile function of patients with ED due to PFUD. MATERIALS AND METHODS: The erectile function of patients referred to us with PFUD for urethroplasty were prospectively evaluated before surgery. Patients underwent nocturnal penile tumescence testing and, if results were abnormal, penile duplex ultrasonography with intracavernous injection and arteriography were performed to diagnose the etiology of ED. Patients were questioned about erectile function every 3 months after surgery and if they complained of ED they were offered 100 mg sildenafil. Patients were followed for at least 18 months after surgery. RESULTS: A total of 29 consecutive patients were evaluated and 22 (76%) of them had ED before surgery. Sufficient followup was available for 15 of the patients. Overall 47% of these patients responded favorably to sildenafil. Of the patients 60% with neurogenic ED and 20% of those with arterial ED responded to this treatment. In 33% of the patients ED resolved within the followup period. All patients with spontaneous resolution of ED previously responded to sildenafil (71% of sildenafil responders). CONCLUSIONS: In patients with ED due to PFUD, those with neurogenic ED are more likely to respond to sildenafil than those with arterial damage. Favorable response to sildenafil may predict spontaneous resumption of normal erectile function over time.

Transurethral incision of ureteroneocystostomy strictures in kidney transplant recipients.

OBJECTIVES: To report the treatment of patients who presented with vesico-ureteric stricture after kidney transplantation, using a minimally invasive endourological approach. PATIENTS AND METHODS: Patients (10 men and four women, mean age 34 years, range 22-55) were assessed at presentation by serum creatinine level, ultrasonography and intravenous pyelography when the serum creatinine level was < 200 micromol/L. When there was hydronephrosis of the allograft a percutaneous antegrade pyelogram was taken, followed by inserting a nephrostomy. After decompression a stent nephrostomy was passed into the bladder and the strictures at the vesico-ureteric junction incised along the stent during cystoscopy. RESULTS: All 14 patients were treated endourologically by an endoscopic incision through the bladder; 13 fared well and one died from sepsis and transplantation problems. The mean follow-up was 8 months. CONCLUSIONS: Simple incision of the stricture via cystoscopy was safe and effective, and succeeded in most patients. The endourological management of ureteric lesions is feasible and is currently our first-line management of ureteric complications after kidney transplantation.

The incidence and causes of erectile dysfunction after pelvic fractures associated with posterior urethral disruption.

PURPOSE: Erectile dysfunction is a common sequel of pelvic fractures, particularly those associated with posterior urethral injury when it can be neurogenic or arteriogenic due to damage to the cavernous nerves or branches of the pudendal arteries. We studied erectile function of patients with posterior urethral injuries due to pelvic fractures. MATERIALS AND METHODS: Patients referred for posterior urethral reconstruction and strictures due to pelvic fractures were evaluated before reconstruction. All patients underwent nocturnal penile tumescence testing, and if those results were abnormal, penile duplex ultrasound with intracavernous injection was performed. Patients with normal vascular function on duplex ultrasound were diagnosed with neurogenic erectile dysfunction. Those patients with abnormal arterial function on duplex ultrasound underwent arteriography to further define the extent and location of arterial damage. RESULTS: The study included 25 consecutive patients with posterior urethral strictures and a mean age of 28.6 years. Of the patients 18 (72%) had erectile dysfunction as demonstrated by nocturnal penile tumescence and all underwent penile duplex ultrasound. Ultrasound confirmed normal vascular response in 13 of the 18 patients and they were diagnosed with probable neurogenic erectile dysfunction. The remaining 5 patients (28%) with erectile dysfunction had an abnormal arterial response, and significant arterial pathology was confirmed by arteriography. CONCLUSIONS: Erectile dysfunction is common in patients with pelvic fractures associated with urethral injury. We believe that erectile function should be assessed and documented in such patients before attempting urethroplasty. In the majority of these patients erectile dysfunction is caused by disruption of the cavernous nerves with sparing of arterial inflow.

Is the pediatric ureter as efficient as the adult ureter in transporting fragments following extracorporeal shock wave lithotripsy for renal calculi larger than 10 mm.?

PURPOSE: We determined whether the thin ureter of the young child transports stone fragments after extracorporeal shockwave lithotripsy (ESWL) as efficiently as the adult ureter does. This determination was done by comparing the outcome after lithotripsy of renal stones greater than 10 mm. between young children and adults. MATERIALS AND METHODS: Our study group consisted of 38 children 6 months to 6 years old (median 3 years) with renal stones greater than 10 mm. in diameter. This group was further divided into 3 subgroups according to the longest stone diameter on plain abdominal film. There were 21 children with a renal stone diameter of 10 to 15 mm. (subgroup 1), 8, 16 to 20 mm. (subgroup 2) and 9 greater than 20 mm. (subgroup 3). The control group consisted of 38 adults older than 20 years randomly selected from the local ESWL registry. Each adult was matched with a child regarding stone diameter and localization. The control group was similarly divided into subgroups 1a, 2a and 3a. ESWL was performed with the unmodified Dornier HM-3 lithotriptor (Dornier Medical Systems, Inc., Marietta, Georgia). The stone-free rate, complication rate, and need for tubes, including stent or nephrostomy, and greater than 1 ESWL session were compared. RESULTS: The stone-free rate was 95% in the study and 78.9% in the control group (p = 0.086). Stone-free rates were 95%, 100% and 89% in subgroups 1, 2 and 3, and 95%, 65% and 56% in subgroups 1a, 2a and 3a, respectively. There were 10 children and 4 adults who underwent greater than 1 ESWL session (p = 0.14). Then there were 10 children and 6 adults who required a tube before ESWL (p = 0.04), and almost all of them were included in subgroups 3 and 3a. Early complications were rare in both the study and control groups. Late complications had included 2 cases of Steinstrasse in the control and none in the study group. CONCLUSIONS: The stone-free rate after ESWL for large renal stones is higher in young children compared to adults with matching stone size. Renal stones greater than 20 mm. often require more than 1 ESWL session. The pediatric ureter is at least as efficient as the adult for transporting stone fragments after ESWL.

Renal cell carcinoma: evaluation of the 1997 TNM system and recommendations for follow-up after surgery.

OBJECTIVE: We evaluated the tumor recurrence pattern after radical or nephron-sparing surgery for localized renal cell carcinoma. Based on this pattern, we suggest a surveillance protocol after surgery. METHODS: The outcome of 200 consecutive patients with localized renal cell carcinoma (RCC) that were operated on between January 1982 and December 1997 was evaluated retrospectively. Radical nephrectomy was performed in 155 patients (77.5%), and nephron-sparing surgery in 45 patients (22.5%). The timing and site of disease recurrence were correlated with parameters of the primary tumor. RESULTS: One hundred and twenty-four patients (62%) had pathological stage T1, 26 (13%) had stage T2, and 50 (25%) had stage T3 (41 stage T3a, 8 stage T3b, and 1 stage T3c). The mean follow-up was 47 months (range 6--169 months). Four patients (3.2%) with stage T1, 6 patients (23%) with T2, and 13 patients (26%) with T3 developed recurrent disease. None of the patients with a stage T1 tumor, smaller than 4 cm, had tumor recurrence. There were no recurrences after nephron-sparing surgery compared to 23 recurrences (14.8%) among patients after radical nephrectomy (p = 0.01). Only 1 patient who underwent pulmonary lobectomy for asymptomatic metastases smaller than 2.5 cm, found by routine chest CT, attained long-term survival. CONCLUSIONS: The prognosis of patients after radical nephrectomy for renal cell carcinoma, smaller than 4 cm, is excellent and they do not need radiological follow-up. Patients with larger T1 tumors, 4--7 cm in diameter, or a higher stage should be followed with CT of the chest and abdomen done every 6 months for 5 years and then annually. Following partial nephrectomy of small renal tumors periodic renal ultrasonography should be done to rule out local recurrence in the operated kidney.

Extracorporeal shock wave lithotripsy is highly effective for ureteral calculi in children.

PURPOSE: Treatment of ureteral calculi in the pediatric population represents a unique challenge. Extracorporeal shock wave lithotripsy (ESWL*) and ureteroscopy have been advocated for the treatment of such stones. We present our experience with ESWL monotherapy for ureteral stones in children in the last decade. MATERIALS AND METHODS: Between 1989 and 1999 we treated 21 boys and 17 girls with a mean age of 8 years (range 8 months to 14 years) with ureteral stones at our institution. Records were reviewed and analyzed for presentation, metabolic and anatomical anomalies, stone size and location, outcome and complications. Average stone size was 9.5 x 6.5 mm. (range 3 to 32). Stones were in the upper ureter in 17 cases, mid ureter in 2 and lower ureter in 19. All patients underwent ESWL with a Dornier HM3 lithotriptor under general anesthesia. Nephrostomies were placed in an anuric infant with bilateral ureteral obstruction and in 2 patients with nonfunctioning kidneys (4 renal units). Ureteral catheters were used in 15 patients for better identification and localization of the stone during ESWL. The catheters were removed immediately postoperatively. RESULTS: Of the patients 31 (81.5%) were free of stones after 1 session of ESWL, 5 (13.1%) after 2 and 1 after 3. One patient underwent ureteroscopy for residual fragments after 2 ESWL sessions. The stone-free rate following 1 ESWL session was 100% for ureteral calculi 10 mm. or smaller regardless of location. Of the 12 patients with stones larger than 10 mm. 8 (67%) were free of stones following 1 ESWL session. The overall success rate of ESWL was 97.3%. No child had postoperative urinary infection or ureteral obstruction. CONCLUSIONS: ESWL is an efficient and safe modality for the treatment of pediatric ureteral stones.

[Penile prosthesis for erectile dysfunction--long-term follow-up].

Our armamentarium for the treatment of erectile dysfunction has recently been expanded by addition of Viagra and the MUSE. However, their long-term results are still unknown. The insertion of a penile prosthesis is invasive, expensive, and irreversible, but under optimal condition provides an acceptable, definitive solution for erectile dysfunction. We evaluated our long-term results with penile prosthesis insertion (PPI). From 1987-1998, 57 patients underwent PPI in our department. Mean age was 55 years and the common causes of erectile dysfunction were atherosclerotic disease (23), radical pelvic surgery (15), and diabetes mellitus (14). Semirigid prostheses were inserted in 12 and inflatable prostheses in 45, including 42 single-component and 3 multi-component prostheses. Recently we interviewed these patients by telephone, using a standard questionnaire. Those not satisfied with the surgical results (83% of the living patients) were examined in our clinic. Mean follow-up was 53 months. In 37 (84%) the prosthesis was mechanically functional (rates after 1, 5 and 10 years were 87.8%, 80%, and 75%, respectively). In only 2 (2.5%) had serious complications led to prosthesis removal. All mechanical failures had occurred in those with inflatable prostheses after a mean of 48.5 months (range 4-113). At the time of the survey 68% were sexually active and 64% were satisfied with the surgical result. We conclude that PPI is safe treatment for erectile dysfunction. Although the rate of mechanically functioning prostheses decreases with time, modern multi-component prostheses may lead to better mechanical results.

[Penile reconstruction after complete glans amputation during ritual circumcision].

Circumcision, so commonly performed, is considered a safe procedure rarely associated with significant complications. A case of complete amputation of the glans penis during neonatal circumcision is reported. The glans was successfully reimplanted, with good post-operative functional and esthetic results.

Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder.

Previous studies indicate that bladder instability in man may be associated with increased spontaneous rhythmic contractile activity. Ca(2+) influx plays a central role in smooth muscle contractions, and recent evidence suggests that steroid hormones rapidly affect Ca(2+) influx. Therefore we tested the hypothesis that estrogen and progesterone modulates spontaneous rhythmic detrusor contractions. Tissues were secured to isometric force (F) transducers in tissue baths and length-adjusted until K(+)-depolarization produced maximum contractions (F(o)). Spontaneous rhythmic contractions (SRC) were sampled before and immediately after addition of estradiol or progesterone (10(-5) M) to tissue baths. The average frequency and amplitude of SRC were, respectively, 0.156 Hz and 0.053 F/F(o) (n = 24). Estradiol caused an immediate reduction in SRC, such that by 10 min, tone, frequency and amplitude were each reduced by, respectively, 36%, 46% and 47% (n = 7, P < 0.05). However, progesterone caused an immediate weak contraction, and at steady state (10 min), progesterone increased frequency of SRC by 152% but decreased SRC amplitude by 50% (n = 10, P < 0.05). Novel therapies using unique steroids that do not interact with genomic receptors may potentially reduce bladder smooth muscle activity, thereby reducing detrusor instability.

Differential effects of sex hormones and phytoestrogens on peak and steady state contractions in isolated rabbit detrusor.

PURPOSE: Recent evidence suggests that sex steroids may produce rapid inhibition of voltage operated Ca2+ channels (VOCCs). Detrusor smooth muscle is highly dependent upon Ca2+ influx for receptor-activated contractions. Thus, we examined the relative effectiveness of a select group of sex steroids and dietary phytoestrogens to relax detrusor contracted with the muscarinic receptor agonist, bethanechol (BE) and the purinergic P2X receptor agonist, alpha,beta-methylene ATP (alpha,beta-MeATP). MATERIALS AND METHODS: Isolated strips of rabbit detrusor were secured to isometric force transducers in a tissue bath and length-adjusted until maximum contractions were achieved. Peak (P) contractile responses were recorded for alpha,beta-MeATP (P(ATP)) and BE (P(BE)) and steady-state (SS) responses were recorded for BE (SS(BE)) in the presence and absence of selected sex steroids and phytoestrogens (10 microM, unless indicated). RESULTS: The L-type VOCC inhibitor, nifedipine (1 to 10 microM), completely inhibited P(ATP) but reduced SS(BE) by approximately 50%, whereas the VOCC and non-VOCC inhibitor, SKF 96365, inhibited SS(BE) by approximately 95%, suggesting that P(ATP) was entirely dependent on L-type VOCCs, but (BE)-induced contractions depended also on activation of non-VOCCs. 17Beta-estradiol (estradiol) and progesterone inhibited P(ATP) by approximately 60% and 20%, respectively, and 32 microM estradiol and ethinyl estradiol inhibited SS(BE) by approximately 80 and 95%, respectively. Inhibition by estradiol was potentiated, rather than blocked, by the nuclear estrogen receptor antagonist, tamoxifen. Moreover, tamoxifen alone nearly completely relaxed SS(BE). The inactive metabolite of estradiol, 17alpha-estradiol, inhibited both P(ATP) and P(BE) by approximately 40%. Testosterone had no effect on P(ATP) and P(BE). The phytoestrogen and tyrosine kinase inhibitor, genistein, inhibited SS(BE) by 44%, whereas daidzein, a phytoestrogen without tyrosine kinase inhibitory activity, produced only a 7% inhibition. None of the phytoestrogens examined inhibited P(BE), whereas all inhibited P(ATP) by approximately 20 to 35%. A comparison of inhibition of (BE) and alpha,beta-MeATP-induced contractions by selected estrogen isomers showed some distinct differences. For example, estrone did not inhibit P(BE) or SS(BE), but inhibited P(ATP) by approximately 20%, whereas DES inhibited SS(BE) by nearly 90%, but P(ATP) by a lesser degree (approximately 70%). CONCLUSIONS: Our data support the hypothesis that 17beta-estradiol, ethinyl estradiol, DES, tamoxifen and genistein may relax detrusor contractions by inhibition of both VOCCs and non-VOCCs. Moreover, our data show that genistein, a dietary phytoestrogen with tyrosine kinase inhibitory activity, selectively reduced alpha,beta-MeATP-induced peak and BE-induced steady-state contractions, sparing the maximum response to BE. Lastly, the inactive isomer, 17alpha-estradiol, inhibited both BE- and alpha,beta-MeATP-induced contractions. These data suggest that certain dietary phytoestrogens (for example, genistein) or sex steroids, especially those with weak activity at the nuclear steroid site (for example, 17alpha-estradiol), or tamoxifen may prove therapeutically useful in treating overactive bladder caused by elevated muscarinic and purinergic receptor activation.

Bethanechol activates a post-receptor negative feedback mechanism in rabbit urinary bladder smooth muscle.

PURPOSE: Recent studies using vascular and gut smooth muscles indicate that contractile receptor agonists may activate post-receptor down-regulatory mechanisms causing a temporary reduction in the strength of subsequent contractions. Our data indicate a similar mechanism exists in detrusor smooth muscle of the urinary bladder. MATERIALS AND METHODS: Each isolated strip of female rabbit detrusor was placed in a tissue bath, secured to an isometric force transducer, and length-adjusted until depolarization with 110 mM KCl produced a maximum contraction (S0). Subsequent contractions were normalized to S0 (S/S0) or to a first stimulus with 30 mM KCl or caffeine (S/S1). Tissues were pretreated with the muscarinic receptor agonist, bethanechol (BE), then stimulated with KCl, caffeine, or Bay k 8644 to identify potential post-receptor down-regulation. RESULTS: Contractions induced by 30 mM KCl had three phases labeled fast peak (FP), slow peak (SP) and steady-state (SS). In tissues exposed for 30 min. to a maximum BE concentration then washed for 5 min., the KCl-induced FP and SP, but not SS, responses were reduced by approximately 40%. Smaller reductions in peak KCl-induced contractions occurred in tissues pretreated for a shorter duration or with a 100-fold lower BE concentration. This down-regulation induced by bethanechol pretreatment was reversible, lasting approximately 1-2 h. Not only were KCl-induced contractions reduced by BE pretreatment, but also those produced by the intracellular Ca(2+)-mobilizer, caffeine, and the L-type Ca2+ channel agonist, Bay k 8644. CONCLUSIONS: Pretreatment of isolated strips of rabbit detrusor with a muscarinic receptor agonist produced short-term down-regulation of KCl-induced peak contractions that may have involved inhibition of both influx of extracellular Ca2+ and release of intracellular Ca2+. Reductions in the degree of this novel modulatory response during disease conditions and aging could enhance contractile activity, possibly causing detrusor instability.