Dennis S. Peppas

Immunohistochemical description of nitric oxide synthase isoforms in human clitoris

PURPOSE Our aim was to identify and localize nitric oxide synthase isoforms in the human clitoris in support of the hypothesis that nitric oxide mediates erectile function in this organ. MATERIALS AND METHODS Nitric oxide synthase immunohistochemistry studies specific for neuronal, inducible and endothelial isoforms of the enzyme were performed on human clitoral tissue obtained from 4 patients (3 with female pseudohermaphroditism and 1 with true hermaphroditism) at feminizing genitoplasty and from 1 phenotypically normal woman at autopsy. RESULTS Neuronal nitric oxide synthase immunoreactivity was detected in nerve bundles and fibers coursing within the glans clitoris and corpora cavernosa of the clitoris, predominating in the latter tissue. Specific inducible nitric oxide synthase immunoreactivity was not identified. Endothelial nitric oxide synthase immunoreactivity was detected in vascular and sinusoidal endothelium of these tissues with a predominance in the glans clitoris. CONCLUSIONS The presence and anatomical localizations of nitric oxide synthase isoforms in the human clitoris indicate that nitric oxide is generated in this organ. These data suggest that nitric oxide may be involved in the erectile physiology of the clitoris as a modulator of clitoral smooth muscle activity. Functional studies are required to support this hypothesis.

Use of glycosylated hemoglobin to identify diabetics at high risk for penile periprosthetic infections

We report an 18-month prospective study of 90 patients undergoing penile prosthesis implantation to evaluate a possible cause-and-effect relationship between degree of diabetic control and the risk of infection complicating the operation. Long-term diabetic control was objectively evaluated by measurement of the glycosylated hemoglobin of the patient, which is known to provide an objective value for degree of control for the preceding 60 to 90 days. Of 90 patients 5 (5.5%) had a periprosthetic infection requiring explantation and all infections occurred in the 32 diabetics (36%) in the population (p less than 0.009). Of the 32 diabetics 13 (41.1%) were poorly controlled with time as demonstrated by a glycosylated hemoglobin level of greater than 11.5% and 4 of the infections occurred in this group. Of the 19 remaining controlled diabetics (glycosylated hemoglobin level less than 11.5%) only 1 infection occurred. Therefore, infection occurred in 31% of the poorly controlled versus 5% of the adequately controlled patients (p less than 0.0003). Measurement of glycosylated hemoglobin values appears to be a useful tool to evaluate diabetic patients before implantation of a penile prosthesis. Patients with a glycosylated hemoglobin level of 11.5% or greater should be more optimally controlled before undergoing implantation in an effort to avoid infectious complications.

The Cantwell-ransley epispadias repair in exstrophy and epispadias: Lessons learned

OBJECTIVES We evaluated our experience with the Cantwell-Ransley epispadias repair to determine the lessons that have been learned with the increased experience and follow-up. METHODS A total of 75 boys (60 with bladder exstrophy and 15 with complete epispadias) underwent a Cantwell-Ransley epispadias repair at our institute in the last 6 years. Primary repair was performed in 58 boys (45 with exstrophy and 13 with epispadias), and secondary repair was performed after prior failed closure in 17 boys (12 at the secondary exstrophy closure, 3 with exstrophy, and 2 with complete epispadias). RESULTS At a mean follow-up of 28 months, all patients had a horizontal or downward angled penis while standing. The incidence of urethrocutaneous fistulas in the immediate postoperative state was 21% and at 3 months was 15%. The incidence of urethrocutaneous fistulas was no more in those patients in whom paraexstrophy skin flaps were used at anterior closure than in those in whom the urethral plate was left intact. Two patients developed a urethral stricture at the proximal anastomotic area, and 4 patients had minor skin separation of the dorsal penile skin closure. Catheterization or cystoscopy, or both, has been performed in 60 patients and revealed an easily negotiable urethral channel in all. CONCLUSIONS The Cantwell-Ransley epispadias repair offers a straighter urethra, better correction of chordee and cosmesis, and a lower fistula rate in the exstrophy or epispadias patient.

Submucosal bladder neck injections of glutaraldehyde cross-linked bovine collagen for the treatment of urinary incontinence in patients with the exstrophy/epispadias complex.

During the last 7 years 19 patients underwent 33 transurethral injections of glutaraldehyde cross-linked bovine collagen into the bladder neck for stress incontinence. Of the 15 patients 14 have classic bladder exstrophy, 3 have complete male epispadias and 2 have cloacal exstrophy. The procedure was performed after a Young-Dees-Leadbetter bladder neck reconstruction in 15 patients and before it in 4. Injections were repeated in 10 patients after a mean of 12 months. After a mean followup of 26 months (range 9 to 84) improvement of continence was noted in 10 of 19 patients (53%) of whom 4 have significant improvement. Of the 8 patients whose condition failed to improve after collagen injections 6 underwent additional successful surgery to achieve urinary continence. Of the 10 patients who underwent repeated collagen injections 9 (90%) had additional improvement. Although there were no complications related to the injected collagen itself, postoperative complications developed in 2 patients. Submucosal injection of collagen to the bladder neck is simple and safe, and has a reasonable success rate. Thus, it may be used to improve continence in patients with the exstrophy/epispadias complex who lack full control after appropriate reconstructive surgery.

PREVALENCE AND REPAIR OF INGUINAL HERNIAS IN CHILDREN WITH BLADDER EXSTROPHY

PURPOSE We delineated the prevalence, recurrence rates and optimal treatment of inguinal hernia in the exstrophy population. MATERIALS AND METHODS Of 181 children with exstrophy followed at our hospital inguinal hernias developed in 121 (66.8%). RESULTS In a 12-year period inguinal hernias developed in 81.8% of the boys and 10.5% of the girls. In 18.2% of the cases the hernia was repaired via a preperitoneal approach at the same time as exstrophy closure. The remaining patients underwent an inguinal operation. Most patients had a wide defect at the internal ring in addition to a patent processus vaginalis. The overall recurrence rate was 8.3%. The incidence of synchronous or asynchronous bilaterality was 81.8%. CONCLUSIONS Children with bladder exstrophy should be carefully examined for inguinal hernias before bladder closure. If a unilateral hernia is present, the contralateral side should be explored. Careful preperitoneal repair should emphasize repair of the internal ring.

Applications of Osteotomy in the Cloacal Exstrophy Patient

During the last 18 years we treated 22 patients with cloacal exstrophy of whom 13 were referred for further treatment after initial treatment elsewhere. One patient underwent cystectomy with ileal conduit urinary diversion soon after birth and 9 of the remaining 21 underwent initial closure without osteotomy. Of these 9 patients significant complications developed in 8 (89%) after bladder closure, including dehiscence in 6 (1 underwent 2 unsuccessful closures), a vesicocutaneous fistula and postoperative ventral hernia in 1, and bladder prolapse in 1. In contrast, complications developed in only 2 of the 12 patients (17%) who underwent osteotomy at the time of initial closure, including bladder dehiscence in 1 and significant prolapse in 1. Patients who underwent osteotomy and those who did not were similar in terms of the size of omphalocele, presence of myelomeningocele and time of primary closure. We also found that osteotomy or failed closure has no effect on the eventual continence of cloacal exstrophy patients. While osteotomy is not the only variable involved in successful cloacal exstrophy closure, our results indicate the need for osteotomy in these patients to increase the success rate at the time of initial bladder closure.

Complete genitourinary reconstruction in female epispadias

While female epispadias is a rare congenital anomaly, the treatment of complete epispadias in the female patient does not significantly differ from that of their male counterparts, although the female defect can be overlooked as a cause of incontinence. Attention must be given to the creation of an adequate urethral channel so that an adequate bladder capacity can be achieved and eventual bladder neck plasty can be performed. Finally, attention must be given to the reconstruction of the external genital defect. During the last 7 years 11 female patients with complete epispadias were treated. Of these patients 4 were referred from elsewhere and 3 had failed a previous procedure (2 had recently undergone external genital and urethral reconstruction, 1 underwent urinary diversion after multiple failed bladder neck procedures). Nine patients underwent bladder neck plasty: 5 are completely continent day and night, 3 are dry for greater than 3 hours during the day, and 1 is dry for only 1 to 3 hours during the day and wet at night, for an overall continence rate of 87.5%. Our experience with these patients has taught us that the bladder in this condition is much like that found in complete male epispadias. Therefore, creating a urethral outlet with sufficient length and resistance along with simultaneous reconstruction of the external genitalia allows for bladder regrowth, thus, facilitating achievement of greater volumes and bladder neck reconstruction with an excellent chance of success.

Nonsurgical Management of Primary Vesicoureteral Reflux in Complete Ureteral Duplication: Is it Justified?

We reviewed the treatment of 56 children with vesicoureteral reflux and complete duplication of the collecting system, including 14 who had complete bilateral duplication. A total of 70 refluxing duplicated systems was analyzed. Of the patients 18% demonstrated spontaneous resolution of reflux within 42 months, 23% are currently stable on prophylactic antibiotics and 57.1% underwent surgical correction. Spontaneous resolution of reflux occurred in 58% of the children with grades I to III/V reflux. In comparing the group with reflux and duplication to a group with reflux into single systems, we conclude that the patients with duplication and lower grades of reflux can be managed nonoperatively, while infection is prevented with antibiotic prophylaxis.

The Cephalotrigonal Reimplant in Bladder Neck Reconstruction for Patients with Exstrophy or Epispadias

A modified technique of ureteroneocystostomy with bladder neck plasty was used in 36 of 75 patients undergoing staged repair of bladder exstrophy or epispadias between 1986 and 1992. This procedure entails mobilizing the ureter while preserving the trigonal hiatus as with the cross-trigonal technique. The distal ureteral segments are directed superiorly toward the bladder dome rather than across the mid line. Of 75 patients 36 underwent cephalotrigonal reimplantation and 39 had a conventional cross-trigonal reimplant. Continence rate was 77% in the patients who underwent cephalotrigonal reimplantation and 72% in those who had a cross-trigonal reimplant. No patient had ureteral obstruction or vesicoureteral reflux. The ureter in exstrophy patients enters the bladder from an inferior position within the true pelvis. Directing the ureter superiorly rather than across the mid line provides a more gradual course through the hiatus and submucosal tunnel. The cranial course of the distal ureter frees more of the trigone for use in the rolled segment of the bladder neck and provides more muscle area for the tube. This is especially important in the patient in whom the distance between the mid prostate and trigone is particularly short.

Complications of Paraexstrophy Skin Flaps in the Reconstruction of Classical Bladder Exstrophy

We reviewed the cases of the exstrophy/epispadias complex treated at our institution between July 1976 and April 1992. A total of 78 patients was identified who had paraexstrophy skin flaps used in the bladder closure, of whom 31 (40%) had a complication as a result of the flaps. The main complication encountered was a urethral stricture where the paraexstrophy skin flaps joined the urethral plate area. Multiple maneuvers were undertaken to correct these problems, including direct vision internal urethrotomy (12 cases), multiple urethral dilations (4), open revision (3) and full thickness skin grafts (5). Seven patients had such a complex stricture situation that they required either continent urinary diversion (5), colon conduit diversion (1) or cutaneous ureterostomy (1), the latter 2 patients having undergone vesicostomy elsewhere before referral. Of the remaining 24 patients who did not undergo a diversionary procedure 12 have undergone an epispadias repair and bladder neck reconstruction, 7 underwent an epispadias repair and 5 await further treatment. Freedom from complications in the initial closure of exstrophy significantly improves the chances of successful reconstruction. The avoidance of problems leading to obstruction, infection, hydronephrosis and reflux nephropathy will provide better kidneys regardless of bladder suitability for function or augmentation. Our use of paraexstrophy flaps has decreased but when they are required, special care in design, placement and followup is advised to avoid complicating strictures and their sequelae.