A Round-up of the Latest Issues in Pediatric Urology

by Mark P. Cain, MD

Introduction
The Pediatric Urology Section at the American Urological Association 98th Annual Meeting in Chicago, Illinois, provided new insights into some of the older problems in the field of pediatric urology. In addition, some excellent reviews were provided for some of the more common clinical issues in this field.

Urethrorrhagia Idiopathica

Urethrorrhagia is a benign condition that usually presents with painless blood spotting in a preadolescent or adolescent male's underwear. This creates significant anxiety for both the patient and parents, despite the fact that this self-limited condition rarely causes long-term clinical sequelae. The presumptive etiology is localized irritation in the bulbar urethra distal to the external sphincter, consistent with the bulbar urethritis commonly described when the patient is evaluated endoscopically. The condition usually presents in peripuberty, and it has been speculated that this may be due to increasing estrogens effecting the development of the mucosa in the posterior urethra. The recommended evaluation has usually included urinalysis and urine culture, as well as an ultrasound of the kidneys and bladder. Invasive testing, such as voiding cystourethrogram, retrograde urethrogram, and cystourethroscopy have been discouraged because they have been ineffective in locating sources of the bleeding.

A new hypothesis regarding the etiology of urethrorrhagia was proposed by Herz and colleagues.[1] The authors hypothesized that urethrorrhagia may be a manifestation of voiding dysfunction with external sphincter dyssynergia, and that management of this underlying voiding dysfunction would result in faster and more durable response to the distressing blood spotting and dysuria. This study evaluated 68 males and 4 females who presented with blood spotting in their underwear, of whom a large percentage also complained of dysuria, constipation, and prior history of urinary tract infection. It should be noted that most patients with simple urethrorrhagia do not have a recent or remote history of urinary tract infection as part of the symptom complex.

The study authors evaluated the patients in a systematic fashion with renal and bladder ultrasound, urinalysis, urine culture, uroflow with electromyogram, and, occasionally, voiding cystourethrogram. The patients were divided into 2 different groups. Group 1 comprised 37 patients (average age, 9.8 years), managed with antibiotics, urinary analgesics, and anticholinergic medication. Group 2 included 35 patients (average age, 8.4 years), managed with an aggressive bladder regimen, including treatment of dysfunctional elimination syndrome with biofeedback and a bowel regimen. In Group 1, a full response was seen in 13 patients and a partial response was seen in 6; no response was seen in 18. The average time to resolution was 12.1 months. In Group 2, a full response was seen in 29 patients and a partial response was seen in 2; no response was seen in 4. Group 2's time to resolution was much quicker, with 5.2 months the mean time to symptom relief.

This was a select group of patients with a combination of both voiding dysfunction and urethral symptoms, including blood spotting and dysuria. This study suggests that a history of underlying dysfunctional elimination syndrome may be an important factor in some of these patients and that management of this particular underlying problem would likely hasten the resolution. Since this is primarily a benign condition that creates a great deal of alarm in the child and parents, the prompt relief of symptoms as demonstrated in this study would suggest that urethrorrhagia be considered in patients presenting with blood spotting with dysuria.

An interesting abstract provided a retrospective analysis over 14 years of 66 males with urethrorrhagia who presented at an average age of 9 years.[2] The vast majority of patients had blood spotting on their underpants as the presenting symptom, and one third also complained of dysuria. A smaller percentage also complained of a slow urinary stream. An analysis of the radiographic evaluation concluded that upper tract studies do not add any significant information to assist in making the diagnosis. Of the 66 patients, 55 were evaluated with ultrasound and 11 with intravenous pyelogram, and these were all considered essentially normal studies. In contrast, 52 of the 66 patients had a voiding cystourethrogram (VCUG) performed and 11 also had a retrograde urethrogram performed. Fifty-six percent of the voiding studies were normal, but 17% showed bulbar irregularity, 17% showed meatal stenosis, and 4% demonstrated a urethral stricture. Bulbar irregularity was also seen in 36% of the patients on retrograde urethrogram and 27% demonstrated a urethral stricture.

Meatal stenosis was treated with meatotomy, with usual resolution of the symptoms. In 35 of the 66 patients, cystourethroscopy had been performed, usually by the referring urologist. Abnormal findings were identified in all of the patients who had cystoscopy, usually consisting of bulbar inflammation and narrowing. Four patients had a stricture at the time of initial cystoscopy. More important, 4 additional patients developed urethral strictures after the initial cystoscopy was performed, which was described as normal. Based on the findings of their retrospective study, the authors recommended that upper tract studies are unnecessary in the evaluation of young boys with urethrorrhagia.

The voiding study was abnormal in 44% of the patients; the authors suggest that VCUG is beneficial in the diagnosis of idiopathic urethrorrhagia. However, the findings in this study of bulbar irregularity and meatal stenosis would not generally change the management of these patients, as meatal stenosis would usually be evident on physical exam, and the bulbar irregularity did not really change the medical management of these patients. The authors did hypothesize that meatal stenosis may be an etiologic factor in some patients, and this is consistent with distal obstructions suggested in Herz and colleagues' study.[1] As has been recommended by others, these authors advocate avoiding cystourethroscopy, as it could result in iatrogenic strictures, which was demonstrated in 6% of the patient population in this study. If symptoms persist or suggest an obstructive lesion, voiding cystogram or retrograde urethrogram can be performed.

Vesicoureteral Reflux
The management of vesicoureteral reflux has traditionally been medical management with antibiotic prophylaxis, with open surgical correction reserved for those patients with either breakthrough infections, persistence of reflux, or parental preference to proceed with definitive therapy. With the recent US Food and Drug Administration (FDA) approval of another injectable agent, Deflux (dextranomer/hyaluronic acid copolymer; Q-Med; Uppsala, Sweden), that has been widely marketed in the United States, there has been a slow shift in the indications for intervention in some centers. With this potential shift in the treatment recommendations for reflux, it becomes even more necessary to identify patients with a high likelihood of early spontaneous resolution of vesicoureteral reflux.

Gutow and colleagues[3] presented their analysis of timing of reflux during the voiding cystourethrogram as a predictive factor for spontaneous resolution. In total, 168 patients were evaluated, with 245 refluxing ureters. All findings were based on the initial voiding cystourethrogram. The majority of the ureters refluxed during the filling phase, with only 40 ureters refluxing during voiding or high-pressure phase of the study. Of interest, there was no difference in the eventual resolution, the need for eventual surgery, or change in the grade of reflux. The time to resolution was more rapid in the patients with reflux during the filling phase. This is an interesting finding, because the intuitive thought would be that patients with reflux during voiding would have a longer submucosal tunnel and would be more likely to have more rapid resolution of the reflux with observation. The authors hypothesize that the patients who refluxed during the voiding phase were more likely to have underlying voiding dysfunction and be more prone to urinary tract infection with a higher likelihood of intervention. Although their evaluation did not identify statistically significant difference with regard to need for surgery, there was a trend towards greater intervention in those with reflux during voiding. Hypothetically, these patients would also be good candidates for injectable therapy, as with a presumed longer submucosal tunnel they would be expected to have a good result with the subtrigonal implant therapy.

Elmore and colleagues[4] presented their results of the recently FDA-approved agent Deflux. Thirty-five patients completed follow-up evaluation, with voiding cystourethrogram at 3 months, including 54 infected ureters. Results were analyzed following a single Deflux injection. Preoperatively, there was a wide range of grade of reflux, the majority being Society for Fetal Urology (SFU) Grade 2 or 3. Overall, the authors reported that 63% (22 out of 35 ureters) of the patients had a successful outcome. With respect to number of ureters successfully managed, there was a 70% success rate (38 out of 54), which seems to be the recurring number in most of the literature following a single injection of Deflux. The interesting finding in this study was that de novo contralateral reflux was identified in 2 of 35 patients. This is a commonly described finding with unilateral open ureteral reimplantation. The cited risk of contralateral reflux typically ranges between 7% and 20%, depending on how many previous voiding cystourethrograms had been performed that demonstrated unilateral vesicoureteral reflux only. In addition, 1 patient of the 35 developed asymptomatic ureteral obstruction. This is the first patient described in any United States series and stresses the importance of follow-up radiograph evaluation of the upper tracts following ureteral surgery.

Ureteroceles
A review of the current management options for ureteroceles was presented during the Society of Pediatric Urology meeting on April 26, 2003. A panel of video presentations demonstrated the options for surgical intervention for ureteroceles, including open upper tract surgery, laparoscopic upper pole surgery, endoscopic ureterocele puncture, and lower urinary tract reconstruction. The videos demonstrated how each of these approaches could be applied to any patient; with multiple treatment options, however, the procedure should be selected based on patient age, presence of function in the ureterocele unit, and presence of reflux in either the lower pole or other renal units. One alternative approach that has been described previously in highly selected patients is watchful waiting.

Outcomes of watchful waiting for ureteroceles were presented from a group in Ottawa, Canada.[5] In a carefully selected group of 11 patients enrolled from 1990-2001, they demonstrated that watchful waiting was a reasonable option in some patients who present with ureteroceles. All 11 patients in the series presented with an antenatal diagnosis. No patient had high-grade lower pole vesicoureteral reflux, significant obstruction, severe hydronephrosis in the upper pole, or history of urinary tract infection. Patients were all managed with antibiotic prophylaxis for a mean of 1.5 years. They were evaluated with voiding cystourethrogram, ultrasound, and upper tract functional studies at diagnosis, followed by ultrasound every 3-6 months for 2 years and then 6 months thereafter. The majority of patients had low-grade hydronephrosis of SFU Grade 2 or less. This resolved in over half of the patients during follow-up. In addition, associated reflux to the lower pole was only Grade 2 or 3 in 6 patients, and in 5 patients it resolved with watchful waiting. Only 1 patient required surgery for breakthrough urinary tract infection. The difference between this study and the previous series presented in the literature[4] was that watchful waiting had previously been recommended only in patients with reasonable upper pole function. In this series, the function of the upper pole segment did not affect the outcome of watchful waiting. It should be mentioned that this was a very carefully selected group of patients who were followed carefully over time. In analyzing the patients, 4 presented with a single-system ureterocele with no evidence of obstruction, and in most centers, surgical intervention would not be considered in this patient. The 7 remaining patients all had ectopic ureteroceles, but again only had mild hydronephrosis in the upper pole and lower-grade reflux. In selecting patients for observational therapy, these criteria should be kept in mind.

Bladder Augmentation
Enterocystoplasty continues to be the most commonly used method for bladder augmentation. Despite its widespread use, there are short-term and long term risks associated with this procedure, including mucus production, electrolyte disturbances, increased risk of bladder stones, long-term risk of perforation, and also a small risk of malignancy. Ureterocystoplasty has been advocated in patients with dilated and poorly functioning upper tracts or with very dilated distal ureters. Most reports have shown favorable response in using the ureter as an alternative to augmentation cystoplasty.


Husmann and coworkers[6] presented their long-term results using ureterocystoplasty as an alternative to bladder augmentation with a bowel source. The study included 22 patients accumulated over the last 15 years. All patients presented with incontinence, and 18 out of 22 had a neuropathic bladder as the etiology of their urinary incontinence. Four had a history of posterior urethral valves. Two patients underwent ureterocystoplasty using segments from both ureters. Fourteen of the patients presented with a refluxing megaureter and 8 had nonrefluxing megaureters. The patients were evaluated based on strict urodynamic criteria of end-fill capacity with pressures < 40 cm of water. When augmented with a single-system ureter, they found a 2.5-fold increase in bladder capacity; when both ureters were used, a 3- to 4.5-fold increase in pressure-specific bladder capacity was seen. Despite the improvement in overall bladder capacity in the majority of the patients, the outcomes based on continence were less satisfactory. Only 9% of the patients were continent and voiding after the ureterocystoplasty. Nine percent were also continent and voiding with the addition of anticholinergic medications. Twenty-three percent were continent, but required intermittent catheterization to empty. An additional 13% were continent with intermittent catheterization and anticholinergics. This left 45% or almost half of the patients with persistent incontinence after ureterocystoplasty, and all of these patients eventually required repeat augmentation with an intestinal segment. Also of note, 1 patient developed perforation of the ureterocystoplasty following renal transplantation and died of overwhelming sepsis. The authors point out that although the risk of mucus, cancer, and stone are decreased with ureterocystoplasty, this procedure is associated with a reoperation rate of almost 50% and does not avoid the long-term risk of perforation seen in intestinal bladder augmentation.

References
1. Herz DB, Weiser A, Franco I, Reda E, Levitt S. Voiding dysfunction as an etiology for bulbar urethritis (urethrorrhagia) in children. Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 410.
2. Palagira AV, Steinhardt GF, Dector RM. A retrospective analysis on the diagnosis and management of idiopathic urethrorrhagia. Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 412.
3. Gutow SG, Karellas M, Murphy JP, Gatti JM. Prognostic value of reflux during the filling versus voiding phase of the VCUG. Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 416.
4. Elmore JM, Ewalt DH, Snodgrass WT. Initial results of Deflux injection for vesicoureteral reflux: the Dallas experience. Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 487.
5. Leonard MP, DiRenna T. Watchful waiting for antenatally detected ureteroceles. Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 420.
6. Husmann DA, Snodgrass W, Kramer SA. Ureterocystoplasty: How good is it? Program and abstracts of the American Urological Association 98th Annual Meeting; April 26-May 1, 2003; Chicago, Illinois. Abstract 485.

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