Laser Ablation in the Management of Obstructive Uropathy in Neonates

Introduction

Posterior urethral valves (PUV) are a congenital source of obstruction of the male urethra that can have severe long-term effects on both the upper and lower urinary tract. Congenital ureteroceles likewise are a significant source of upper tract obstruction and can sometimes cause urethral and lower tract obstruction as well. Although a fraction of patients with minor urinary tract obstruction may present as older children, the vast majority today in developed countries are diagnosed on prenatal ultrasound, making early treatment in the neonatal period the new standard. ^{1 –3} In addition to changes in patterns of diagnosis, improvements in pediatric anesthesia and endoscopic technology and technique have resulted in an increasing shift of the timing of intervention toward younger ages. ^{4 –7} In the treatment of PUV, traditional practice involved cutaneous vesicostomy followed by delayed intervention, often at 2 years of age or even older, although today primary valve ablation is the new standard of care. ⁸ Although long-term outcomes appear to be similar with early versus delayed intervention, early definitive intervention appears to be a durable trend with the ultimate endpoint being immediate neonatal treatment. ⁹

While the most commonly used technique for treatment of obstructive uropathy involves cystoscopic incision of the valve or ureterocele with cold knife or electrosurgery (such as bugbee electrode or Whitaker hook), an alternative approach is to ablate the obstructive tissue with laser energy. ¹⁰ Laser ablation of PUV was first described in 1987 using neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, with an effective outcome in a small cohort of six boys (age 7–20 months) and performed in an antegrade manner through cutaneous vesicostomy. ¹¹ Since that time, it has been utilized only sporadically with infrequent case series. In 2000, Bhatnagar et al. reported on a cohort of 23 older boys (age 3 months–9 years) using the Nd:YAG laser. ¹² The largest pediatric series to date and the first to report the use of holmium: yttrium aluminum-garnet (Ho:YAG) laser was recently published in 2013 by Mandal et al. with a cohort of 40 boys (mean age 24 months) in the treatment of PUV. ¹³ This study compared these patients in a nonrandomized retrospective manner to 40 boys who underwent electrofulguration. They noted significantly shorter operative times and higher rates of spontaneous voiding after catheter removal, as well as nonsignificant trends toward lower rates of refulguration, urethral stricture, and incontinence in the children treated with laser ablation. Despite this encouraging evidence, the mean age for this study was 24 months (range 3–60 months) with no neonates. The literature contains only two reports of laser ablation in neonates (defined as <28 days old) for either PUV (n=13; Biewald and Schier, 1992) or ureterocele (n=4; Jankowski and Palmer 2006). ^14,15 In this study, we sought to present our data on the feasibility and immediate results of Ho:YAG laser ablation for obstructive uropathy in neonates.

Materials and Methods

A retrospective case series was performed by reviewing our prospectively maintained surgical database for all consecutive infants <28 days old (i.e., neonates) treated for urethral valves or ureterocele by a single pediatric urologist between July 2012 and December 2013. Congenital obstructions were identified in utero and confirmed by postnatal renal/bladder ultrasound (RBUS) and voiding cystourethrogram (VCUG) consistent with diagnoses of either urethral valves (anterior or posterior) or ureterocele. During the study period, endoscopic Ho:YAG laser ablation was used exclusively and no alternative endoscopic modalities were used; in addition, no patients required vesicostomy as all eligible patients proceeded with primary retrograde endoscopic ablation. Patients with progressive renal deterioration after birth despite urethral catheterization due to bilateral upper tract obstruction may have required nephrostomy placement and, thus, were excluded because no immediate neonatal ablation procedure was performed. Patients who were not clinically stable to proceed with cystoscopic surgery by 28 days of life were excluded. All patients in the study were full-term at birth (≥37 weeks gestational age), although premature infants were not expressly excluded. No absolute size or weight criteria were used as long as a neonatal cystoscope was able to be effectively inserted into the urethral meatus, and no eligible patient had a procedure aborted for this reason.

The procedures were carried out using an 8F pediatric cystoscope (KARL STORZ GmbH & Co. KG, Tuttlingen, Germany) with a zero degree lens. After cystoscope insertion, the anterior wall of the bladder was transilluminated and a 16F angiocatheter was inserted suprapubically through the abdominal wall under direct visualization into the bladder lumen and left in place to maintain continuous flow of irrigation during the case. A 200-μm laser fiber was utilized and laser energy was set at 0.6 J/pulse at a rate of 6 Hz. Ureterocele puncture was conducted by making a transverse incision along the distal/medial aspect of the ureterocele; this location was selected to avoid windsock effect and the incision was continued until visual decompression was noted. For urethral valve cases, ablation was performed at 5 o'clock and 7 o'clock through the full thickness of the valve until the urothelium was incised. Care was taken to visualize and avoid the verumonantum, and the laser allowed for precise delineation of the incisional margins. At the conclusion of the case, the suprapubic angiocatheter was withdrawn. Neonatal circumcision was performed when indicated clinically. Indwelling urinary catheters were placed at the conclusion of the case and generally removed on postoperative day number one.

Intraoperative and postoperative data were reviewed to determine any complications of the procedure, including bleeding/hemorrhage, urinary tract infections, failed trial of void, or recurrent stricture or obstruction. Patients were maintained on amoxicillin prophylaxis at the time of diagnosis and given a single dose of perioperative antibiotics in the operating room. All urethral valve patients had VCUG or video urodynamics performed at 4–6 weeks postoperatively. All ureterocele patients had VCUG and RBUS at 3 months postoperatively to assess for vesicoureteral reflux (VUR), ureterocele decompression, or change in hydroureteronephrosis. All patients had additional RBUS performed every 3 months for the first year, then every 6 months thereafter.

Results

Seventeen neonates underwent retrograde transurethral laser ablation procedures at a median age of 7 days (range 3–27). There were nine cases of urethral valve ablation (seven posterior, two anterior) and eight ureterocele ablations. Median operative time was 23 minutes (range 18–33). All patients voided after postoperative catheter removal. There were no intraoperative complications, and no reoperative procedures were required for any case at mean follow-up of 10.1 months (range 4–18).

For patients with urethral valves, data are summarized in Table 1. No patients had change in VUR on postoperative VCUG: all children (n=7) with preoperative VUR continued to have reflux, and all children (n=2) with no VUR preoperatively continued to have no reflux. No patient presented to the office or emergency room with complaint of postoperative hematuria. Median nadir serum creatinine was 0.9 (range 0.4–1.8). No patient had evidence of residual valve tissue or urethral stricture on follow-up imaging.

Among patients with ureteroceles, all patients demonstrated partial or complete decompression of the ureterocele and improvement in hydroureteronephrosis at 3 months, as summarized in Table 2. No patient had change in VUR (either new-onset, worsening, or resolution) postoperatively; however, three patients had persistent VUR that ultimately required ureteral reimplantation, all of which were into lower pole moieties of duplicated systems. One patient with a history of persistent reflux had a urinary tract infection subsequent to ureterocele ablation but before ureteral reimplantation.

Discussion

In this study, seventeen neonates underwent laser ablation procedures for the treatment of conditions related to obstructive uropathy. Patients had clinical outcomes on follow-up that matched expected benchmarks for their disease courses. There were no intraoperative, anesthetic, or postoperative complications nor any reoperations required at mean 10.1 months of follow-up. Standard postoperative imaging demonstrated resolution of the abnormal obstructive tissues and stable or improved disease.

The study was limited by its retrospective design as a case series, although somewhat ameliorated by the exclusive use of the described technique during the study period, thus reducing potential selection bias. Follow-up was limited by the time period the technique was adopted and used. The population was also heterogeneous, combining different disease entities including ureteroceles, PUV, and anterior urethral valves; this limits the specific conclusions of the study, but from a technical standpoint is illustrative of the broader uses of laser technology that can be applied within the neonatal population. The relatively small sample size limits drawing wider conclusions for general adoption in the pediatric urologic community, yet to our knowledge this is the largest series to date on the use of Ho:YAG laser in the neonatal population. Prior studies with larger cohort sizes, such as that conducted by Mandal et al. in 40 boys with PUV, were conducted in an area where routine antenatal imaging is much less pervasive, and with a mean patient age of 2 years, the local treatment practices likely differ significantly from contemporary practice settings elsewhere. ¹³ The largest previously published neonatal cohort by Biewald and Schier in 1992 discussed outcomes in 13 patients. ¹⁴ However, this population also has significant differences from our present cohort, with major practice changes in the intervening decades. For example, the Biewald cohort includes only four patients who were diagnosed antenatally. In addition the neodymium laser was used in this older study, in contrast to the holmium laser, which has the advantages of greater precision, shallower penetration, less variability between different tissues, and less potential for thermal tissue injury. ¹⁶

In addition to the reassuring clinical endpoints, the use of the laser also appeared to be a technically efficient tool for these procedures with short operative times (range 18–33 minutes). From a technological standpoint, improvements in cystoscopic and optic technology have allowed for the construction of smaller cystoscopes over time while maintaining excellent visualization. The laser fiber lends itself well to these small cystoscopes as the small caliber fibers can fit well through the working channels of the instruments and still allow for some irrigation flow. Our use of temporary intraoperative suprapubic angiocatheters also contributes to good irrigation and visualization during the case. This obviates the need to delay the procedure until an older age when a larger sized continuous-flow pediatric resectoscope could be used, which would be necessary if one were using a cold knife or Whitaker hook. Although small bugbee electrodes can still be used with small neonatal cystoscopes, in our experience, the laser fiber offers greater precision and control. Laser energy not only maintains the advantages of good hemostasis comparable to coagulation electrosurgery but also has the theoretical advantage of less thermal tissue damage and earlier re-epithelialization of tissue. ¹⁷ These advantages have lent themselves to the adoption of the laser elsewhere in urologic practice, including as a common modality for treatment of urethral and ureteral strictures.

Conclusions

Ho:YAG laser ablation appears to be a safe, effective, and efficient method for the management of urethral valves and ureteroceles in the neonatal period based upon our case series. With a continuing trend toward early prenatal detection of these conditions, a corresponding trend toward early definitive intervention has followed naturally in recent years. It remains to be seen if earlier interventions translate into better clinical outcomes and further study is necessary in this area. While early intervention was previously considered age less than 1 year, this is now relatively late according to current practice and neonatal intervention may well become the true early standard. For the foreseeable future, it is likely that surgical intervention in neonates will continue, and advancements in cystoscopic technology and safer pediatric anesthesia will continue to enable this development. Laser ablation thus remains an important alternative to electrosurgery in this population.