Pediatric Problems - From Hydronephrosis to Enuresis - Discussed at AAP Meeting

American Academy of Pediatrics

MEETING REVIEW Pediatric Problems— From Hydronephrosis to Enuresis— Discussed at AAP Meeting Highlights from the American Academy of Pediatrics Section on Urology, October 17-19, 1998, San Francisco, Calif. [Rev Urol. 1999;1(3):148-152] Over the past decade, there has been an exponential increase in clinical research in pediatric urology. Most of this work is presented at the American Academy’s Section on Urology Scientific Sessions each year. Below are some of the highlights of the 1998 meeting. Many of these presentations will impact the practice of pediatric urology. Hydronephrosis/Kidney There is a paucity of literature that evaluates the fate of kidneys with less than 20% function in children. ElGalley and associates evaluated longterm follow-up in 23 children with reflux (n = 8), myelomeningocele (n = 3), megaureter (n = 3), ureteropelvic junction obstruction (n = 3), posterior urethral valves (n = 2), cloacal exstrophy (n = 2), atrophic kidney (n = 1), and prune belly syndrome (n = 1) who had a kidney that provided less than 25% of the total renal function.1 The age of presentation was less than 1 year in 14 patients, and between 1 and 4 years in 5 patients. Follow-up ranged from 2.5 Meeting reviewed by Ellen Shapiro, MD, FACS, FAAP, New York University School of Medicine, New York, N.Y. 148 REVIEWS IN UROLOGY SUMMER 1999 years to 21 years, with a mean follow-up of 10 years. Surgery was performed in 20 patients, and 13 of these patients underwent more than 1 procedure. Nuclear imaging demonstrated that the poorly functioning kidney deteriorated >10% in 5 patients and <10% in 7 patients. The function remained stable in 3 patients and improved <5% in 5 patients and >5% in 3 patients. In 3 patients who showed >5% improvement, the surgery on the kidney had been performed for obstruction. In the absence of a control group, the impact of treatment on preservation of renal function is unknown. Complications occurred in 83% of the patients, including recurrent urinary tract infections in 9, renal pain requiring hospitalization in 5, hypertension in 2, and gross hematuria in 3. Although the complication rate in this group was high, 10 patients (43%) did not have hypertension or pyelonephritis. Therefore, preservation of poorly functioning kidneys can be considered as long as close follow-up is provided long term. Ureteroceles Shekarriz and colleagues examined the long-term results of partial nephrectomy and primary ureterocele incision in children with ectopic ureteroceles.2 Group 1 underwent transurethral incision or puncture. Group 2 underwent upper tract partial or total nephrectomy with partial ureterectomy or ureteroureterostomy. Group 3 underwent a lower tract approach with excision and reimplantation with or without upper tract surgery. Almost all of the patients in groups 1 and 2 were age 1 year or less, while half were 1 year or less in group 3. The incidence of preoperative vesicoureteral reflux was 54%, 56%, and 83% in groups 1, 2, and 3, respectively. None of the patients in group 3 required additional procedures, whereas in groups 1 and 2, 100% and 41%, respectively, required secondary surgery. The mean number of additional procedures required was 2.1 and 1.5, respectively. Five patients in group 2 had persistent reflux and are currently being followed. In group 2, the reoperation rate in patients with and without preoperative reflux was 57% and 20%, respectively. Of the 25 prenatally diagnosed patients, 3 patients (12%) developed urinary tract infections (UTIs) prior to initial surgery at 2, 3, and 6 months of age. AAP The antenatally diagnosed patients underwent surgery at approximately 3 months of age. These investigators concluded that partial nephrectomy is a safe and effective means of managing ectopic ureteroceles in patients who have no preoperative reflux, since additional surgery is needed in only 20%. Transurethral decompression was never definitive, suggesting that ureterocele puncture should have a limited role in the initial management of ectopic ureteroceles. Husmann and associates examined the effectiveness of endoscopic incision versus partial nephrectomy in patients with ectopic ureteroceles associated with duplex systems.3 The ectopic ureteroceles were graded based on the initial radiographic evaluation. •Grade I: 1 upper pole ureterocele; no reflux •Grade II: bilateral upper pole ureteroceles; no reflux •Grade II-A: 1 ureterocele and ≤ grade II/V reflux into 1 renal moiety •Grade II-B: 1 ureterocele and ≥ grade III/V reflux into 1 renal moiety •Grade III: 1 ureterocele and reflux into 2 or more moieties or bilateral upper pole ureteroceles and reflux into 1 moiety •Grade IV: 1 ureterocele and reflux into 3 systems or bilateral ureteroceles and reflux into 2 systems Seventy-two patients were managed by endoscopy, and 88 patients underwent partial nephrectomy. Twenty-two patients with grade I abnormalities were treated with partial nephrectomy, and 4 required additional treatment for delayed onset of ipsilateral lower pole reflux. In contrast, of the 26 patients treated endoscopically, 18 (69%) required additional treatment—for persistent ureterocele obstruction in 3, reflux into the ureterocele in 4, ipsilateral lower pole reflux in 4, and reflux into the ureterocele and ureter in 7. Six patients had a grade II abnormality; 4 were treated by partial nephrecto- my, and 2 by endoscopy. None of these patients required additional surgery. A more significant difference in the need for additional surgery was found between patients with grades II-A, II-B, III, or IV who were treated with partial nephrectomy and endoscopy. Sixty-five percent of patients treated by partial nephrectomy and 76% of patients treated by endoscopy required additional surgery. Therefore, in ectopic ureteroceles with grade I or II abnormalities (no associated reflux), partial nephrectomy was definitive in 85%. Endoscopic management was definitive in only 36%. The authors suggest that grade I or II should be managed by partial nephrectomy, while grades II-A, II-B, III, and IV can be temporized by endoscopic management with plans for definitive surgical reconstruction. Jayanthi and Koff reported on the long-term outcome of transurethral puncture of ectopic ureteroceles.4 Twenty-one children were identified; 11 presented with antenatal hydronephrosis and 10 with UTI. The voiding cystourethrogram showed low grade reflux in 7, ipsilateral lower pole reflux in 8, and bilateral/contralateral reflux in 6. The postoperative voiding study demonstrated no reflux in 8, but 5 of these patients had recurrence of reflux up to 4 years following the puncture. Fifty percent developed reflux into the ureterocele and upper pole segment. Four patients (19%) required repuncture between 1 to 13 months after the initial procedure for persistent or recurrent upper pole hydroureteronephrosis. Open surgery was performed in 67%. Thirteen have undergone ureterocele excision with ureteral reimplantation, 9 for recurrent UTI and 4 for progressive reflux. One patient underwent a ureteroureterostomy for worsening upper pole reflux. In this series, no patient underwent a partial nephrectomy. The authors concluded that transurethral puncture of ectopic ureteroceles is effective short-term therapy. Since it is not definitive in the majority of children, long-term follow-up is needed. Strand and colleagues reviewed their experience with single stage complete urinary tract reconstruction for duplex ectopic ureteroceles.5 In their series, complete upper and lower urinary tract reconstruction was safe, even in infants less than 6 months of age. Although postoperative complications requiring further surgery were minimal, common sheath ureteral reimplantation was less successful with a high rate of postoperative reflux (80%). Cryptorchidism/Testis Lee and colleagues compared inhibin-B and follicle-stimulating hormone (FSH) levels with paternity and sperm parameters in fertile and infertile men with a history of cryptorchidism.6 These levels indicate the integrity of the seminiferous tubule, since inhibin-B, which is produced by the Sertoli’s cell, is the principal form of inhibin in men and regulates FSH secretion by a closed-loop negative feedback mechanism. FSH is a major stimulator of inhibin production. It was found that among fertile men, 84% had inhibin levels in the normal range, while only 22% of the infertile men had normal inhibin levels. Thirty-three percent of the infertile men had an elevated FSH level, low inhibin-B levels, and azoospermia. Only 27% of the fertile group had subnormal sperm counts, while 78% of the infertile group had subnormal sperm counts. This study suggests that decreased inhibin-B levels and sperm densities indicate a seminiferous tubule defect with elevated FSH levels, pointing to a lack of adequate feedback to regulate the hypothalamic-pituitary-FSH axis normally. Coughlin and associates examined the correlation of age of orchidopexy, paternity, sperm counts, and hormone levels in 348 fertile and 53 infertile men.7 There was no correlation SUMMER 1999 REVIEWS IN UROLOGY 149 AAP continued between fertility or infertility versus age at orchidopexy. Also, there was no correlation between sperm density, serum FSH, or luteinizing hormone levels and the age at surgery. A negative correlation was found between the age of orchidopexy and inhibin-B and testosterone levels. They concluded that a negative correlation of age with inhibin-B and testosterone levels in adult men may suggest that early surgery preserves potential for spermatogenesis and androgen production. Higher levels of inhibin-B and testosterone at younger ages of surgery may, in turn, result in more normal spermatogenesis long term. Kaefer and colleagues revisited the incidence of intersex in patients who have an undescended testis and hypospadias.8 Rajfer and Walsh reported that when there was an undescended testis and hypospadias, and the genitalia were unambiguous, the incidence of intersex was 27%.9 Kaefer’s group stratified this group of individuals on the basis of meatal position and whether the gonad was palpable. Thirty-five patients presented with undescended testis, hypospadias, and nonambiguous genitalia. An intersex condition was found with nearly equal frequency in males with unilateral (n = 32) and bilateral (n = 43) cryptorchidism (27% and 32%, respectively). Intersex was more prevalent when the gonad was impalpable. Those patients with impalpable testes were 5 times more likely to have an intersex condition than patients with a palpable undescended testis (47% versus 10%). Meatal position was evenly distributed between perineal, proximal shaft, and distal locations. If there was a perineal hypospadias, there was a significantly greater likelihood of an abnormal karyotype or abnormal gonadal sex differentiation. Therefore, this study shows that ability to palpate an undescended testis is an important predictor of an intersex state in all cases of 150 REVIEWS IN UROLOGY SUMMER 1999 cryptorchidism with hypospadias. When the testis is impalpable, this increases the likelihood of an intersex state. Also, the more severe the hypospadias, the greater the likelihood will be that the patient has an abnormal karyotype. Color Doppler ultrasonography of the scrotum has become part of our armamentarium for diagnosing acute scrotal pain. In some reports, at least 35% of boys are diagnosed with “epididymitis” without a specific etiology based on the findings of physical examination and imaging. Javidan and colleagues compared ultrasound diagnoses with the findings at surgery to further understand the etiology of epididymitis in boys with acute scrotal pain.10 The study identified 124 males who were at least 2 years of age. All patients underwent either surgery and/or an ultrasound that revealed definitive enlargement of the appendix testis. Of these patients, 79 had Doppler ultrasound studies, 45 had surgery without imaging, and 50 had both imaging and surgery. Of the patients who had imaging and surgery, 16 had a testicular torsion, 24 had intermittent torsion, and 11 were found to have an appendix torsion. Seventeen of 24 patients with presumed intermittent torsion were found to have the bell clapper deformity. Thirteen patients did not undergo surgery and were felt to have appendix torsion, since the urinalysis was negative and a “blue dot” sign was seen in 1. In the other 12 patients, an enlarged appendix was seen on ultrasound, and epididymal and testicular flow were increased in 9 and 5 cases, respectively. This study suggests that epididymal enlargement and increased blood flow in the epididymis and testis are common findings in patients with intermittent testis torsion or appendix torsion. Testicular blood flow may appear normal or decreased rather than absent in patients with ongoing testicular tor- sion. Therefore, the finding of epididymitis should not automatically be attributed to voiding dysfunction, and the diagnosis of intermittent testicular torsion as well as appendix torsion should be entertained. Herz and colleagues reviewed a 10year experience with intermittent testicular torsion at the Children’s Hospital of Pittsburgh.11 The study examined 2 groups of boys with intermittent torsion of the spermatic cord: 1 group was treated electively by orchidopexy, and the other group required emergent surgery for acute torsion. Thirty-four boys were evaluated who had a history of recurrent testicular pain. Eighteen (53%) were treated by elective orchidopexy, since they were thought to have intermittent testicular torsion. The other 16 boys were operated on emergently for acute testicular torsion. The mean number of recurrent painful episodes was 2 in the elective group and 3 in the emergent group. The elective group had a significantly better salvage rate of 94% versus 50% in the emergent group. An ipsilateral bell clapper deformity was found in 94% of boys in the elective group and 100% in the emergent group. A contralateral bell clapper deformity was found in 83% and 78% in the elective and emergent groups, respectively. This report underscores the need to be highly suspicious of intermittent testicular torsion in young boys with recurrent testicular pain, and to proceed electively with bilateral transscrotal orchidopexy. Hypospadias/Penis The exact etiology of hypospadias remains unknown. In a small group of children with severe hypospadias, defects can be identified in the testosterone biosynthetic pathway. This study examines 115 patients with coronal midshaft and penoscrotal hypospadias.12 An early morning fasting blood was drawn to measure pregnenolone, progesterone, 17- AAP hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone, androstenedione, and testosterone concentrations to identify defects in enzymes on the testosterone biosynthetic pathway. Sixtyfive age-matched controls were also evaluated. Of 85 patients with coronal and midshaft hypospadias, 56 (66%) were found to have enzyme defects diagnosed by an elevation of their precursor to product ratios that range from 1.5-fold to over 9-fold when compared with controls. Of 30 patients with penoscrotal hypospadias, enzyme defects were found in 12 (40%). The most common defects were 3 ß-hydroxysteroid dehydrogenase and 17 α-hydroxylase, as well as 17 to 20 lyase defects. Androstenedione levels were normal, suggesting that 17-ketosteroid reductase was functional. Therefore, a deficiency or delayed maturation of enzymes necessary for testosterone biosynthesis in Leydig’s cells of the developing embryo may result in hypospadias. Silver and Russell further examined other etiologies for hypospadias. The enzyme 5 α-reductase type 2 (SRD5A2) converts testosterone to dihydrotestosterone and is required for virilization of the male external genitalia.13 The 5 α-reductase deficiency syndrome is due to a variety of mutations in the autosomal gene for this enzyme and is associated with ambiguous genitalia. Although the clinical 5 α-reductase deficiency is rare, isolated hypospadias is common, and the etiology is unknown. Gestational or subclinical deficiencies of SRD5A2 may result in hypospadias. These investigators examined SRD5A2 mutations in males with isolated hypospadias. Prepuce and penile skin removed at the time of hypospadias repair was evaluated for 5 α-reductase 2 mutations using single strand confirmation polymorphism and DNA sequence analysis. Of the 73 specimens examined, 6 (8.2%) had a mutation of 1 or both alleles of Key words Hydronephrosis • Ureterocele • Cryptorchidism • Hypospadias • Enuresis Main Points • Preservation of poorly functioning kidneys is an option provided there is close long-term follow-up. • In patients with no preoperative reflux, partial nephrectomy can be used to manage ectopic ureteroceles. • Patients with elevated FSH levels, decreased inhibin-B levels, and decreased sperm densities may have a seminiferous tubule defect. • In patients who have cryptorchidism with hypospadias, an impalpable testis and a severe hypospadias increase the likelihood of an intersex condition. • Consider intermittent testicular torsion or appendix torsion in cases of acute scrotal pain; epididymitis from voiding dysfunction should not be an automatic diagnosis. • Laser soldering for hypospadias repair has been shown to decrease operating time and have a low complication rate. • Bladder dysfunction and detrusor hypercontractility are common in children who fail conventional therapies for enuresis. the SRD5A2 gene. There was no correlation between the severity of hypospadias and the number of alleles or the specific mutation. Therefore, approximately 10% of males with isolated hypospadias have at least 1 mutation in the SRD5A2 gene. Mutations have been shown to decrease the efficiency of the enzyme, which may lead to a local deficiency of DHT during urethral development. It is postulated that those males with hypospadias who have normal 5 αreductase type 2 alleles and no other endocrine abnormality may have abnormal temporal expression of the SRD5A2 protein. Kirsch and colleagues reviewed the experience of laser soldering using an 808 nm diode laser and wavelength matched human albumin solder for urethral surgery in children.14 Fiftyseven males were entered into this study; 37 received standard suturing, and 20 underwent sutureless laser hypospadias repair. Hypospadias repairs were either parameatal skin flaps in 34 or onlay island tube or flap in 23. In the laser group, sutures were used only for tissue alignment. The results of this study show that operating times were 5 times faster with laser soldering in both the simple and complex repairs. Fistula rate was 5% in the laser group and 11% in the controls. These preliminary results demonstrate that the laser technique is easy to perform and has a low complication rate. Monsour and colleagues reported the American experience using topical steroids for the management of persistent phimosis in boys.15 Studies performed in Europe and Australia have shown this approach to be efficacious. Twenty boys with phimosis were placed on a month’s course of twice-daily topical 0.05% betamethasone cream. Nineteen patients completed the treatment. In 13 patients (68%), foreskins were easily retractable. In the other 6 patients, outcomes were unsuccessful, and they were advised to undergo circumcision. A short course of topical steroid provides conservative management for phimosis in some children. Enuresis Yeung and colleagues examined bladder function in children with primary nocturnal enuresis who had failed treatment with DDAVP and/or SUMMER 1999 REVIEWS IN UROLOGY 151 AAP continued enuretic alarms.16 Five different voiding patterns were recognized that were related to sleep and arousal states. A. Normal daytime urodynamic studies with: 1. Significant bladder instability at night; normal volume voiding precipitated by large unstable detrusor contractions (9 boys, 36%) 2. Frequent small volume voiding at night, probably representing latent bladder instability with small functional capacity (2 boys, 8%) B. Abnormal daytime urodynamic studies with: 1. Small bladder capacity and dyssynergia with marked bladder instability associated with poor sleep at night (2 boys, 8%) 2. Obstructive pattern with marked detrusor hypercontractility during daytime and high pressure voiding at night (6 boys, 24%) 3. Dysfunctional voiding during the daytime with frequent small volume voiding at night (4 girls, 1 boy, 20%). Cystoscopy was performed, and 4 of 6 boys with a type B-2 voiding pattern were found to have trabeculation and congenital obstructive urethral lesions. The authors concluded that bladder dysfunction, including instability during sleep, and detrusor hypercontractility due to outflow obstruction are common in children who fail conventional enuretic therapies. This underscores the importance of a careful history to uncover bladder dysfunction, which could result in persistent nocturnal enuresis and treatment failures. ■ References 1. El-Galley RES, El-Leithy TR, Wiley B, et al. Long-term follow-up for the poorly functioning kidney in children. Pediatrics. 1998;102(3, 152 REVIEWS IN UROLOGY SUMMER 1999 suppl, pt2):842. Abstract 37. 2. Shekarriz B, Upadhyay J, Fleming P, et al. Longterm outcome based on the initial surgical approach for extravesical ureteroceles. Pediatrics. 1998;102(3, suppl, pt 2):838. Abstract 30. 3. Husmann D, Strand WR, Ewalt D, et al. Management of ectopic ureteroceles associated with renal duplication: a comparison between partial nephrectomy and endoscopic management. Pediatrics. 1998;102(3, suppl, pt 2):839. Abstract 31. 4. Javanthi VR, Koff SA. Long-term outcome of transurethral puncture of ectopic ureteroceles–initial success, late problems. Pediatrics. 1998;102(3, suppl, pt 2):840. Abstract 32. 5. Strand WR, Ewalt DH, Clement MR, Allen TD. Single stage complete urinary tract reconstruction for duplex ectopic ureteroceles. Pediatrics. 1998;102(3, suppl, pt 2):840. Abstract 33. 6. Lee PA, Coughlin MT, Bellinger MF. Comparison of inhibin-B and FSH levels among fertile and infertile formerly cryptorchid men. Pediatrics. 1998;102(3, suppl, pt 2):828. Abstract 1. 7. Coughlin MT, Lee PA, O’Leary LA, Bellinger MF. Correlation of age of orchidopexy in paternity, sperm counts and hormone levels: significant negative correlations with inhibin-B and testosterone. Pediatrics. 1998;102(3, suppl, pt 2):829. Abstract 4. 8. Kaefer M, Diamond D, Hendren WH, et al. The incidence of intersex in children with cryptorchidism and hypospadias: stratification based on gonadal palpability and meatal position. Pediatrics. 1998;102(3, suppl, pt 2):830. Abstract 7. 9. RajferJ, Walsh PC. The incidence of intersexuality in patients with hypospadias and cryptorchidism. J Urol. 1976;116:769-770. 10. Javidan J, Gonzalez R, Barthold JS. Comparison of doppler ultrasonography and surgical findings in children with acute scrotal pain. Pediatrics. 1998;102(3, suppl, pt 2):858. Abstract 81. 11. Herz DB, Bellinger MF, Schneck FX. Intermittent torsion of the spermatic cord: the 10-year experience of the Children’s Hospital of Pittsburgh. Pediatrics. 1998;102(3, suppl, pt 2):858. Abstract 82. 12. Aaronson IA, L-Sherbiny M. Testicular enzyme deficiency as a cause of hypospadias. Pediatrics. 1998;102(3, suppl, pt 2):852. Abstract 64. 13. Silver RI, Russell DW. 5 α-reductase type 2 mutations are present in some boys with isolated hypospadias. Pediatrics. 1998;102(3, suppl, pt 2):852. Abstract 65. 14. Kirsch AJ, Copper CS, Canning DA, et al. Preliminary results of a prospective clinical trial of laser soldering for hypospadias repair. Pediatrics. 1998;102(3, suppl, pt 2):853. Abstract 68. 15. Monsour MA, Rabinovitch HH, Dean GE. The use of topical steroids in the treatment of phimosis in children. Pediatrics. 1998;102(3, suppl, pt 2:857. Abstract 79. 16. Yeung CK, Chiu HN, Sit FKY. Bladder dysfunction in children with primary refractory monosymptomatic primary nocturnal enuresis. Pediatrics. 1998;102(3, suppl, pt 2):837. Abstract 25. Other Contributors In addition to the Medical and Contributing Editors, the following authors contributed to this issue: James Choi, MD Senior Resident Columbia College of Physicians & Surgeons New York, N.Y. Ed Ikeguchi, MD Neurourology Fellow Columbia College of Physicians & Surgeons New York, N.Y. Steven A. Kaplan, MD Given Foundation Professor Vice Chairman and Administrator Department of Urology Columbia College of Physicians & Surgeons New York, N.Y. Steven R. Potter, MD Resident The Brady Urological Institute The Johns Hopkins Hospital Baltimore Alexis E. Te, MD Assistant Professor Columbia College of Physicians & Surgeons New York, N.Y.