Michael C. Carr

Long-term outcomes in children treated by prenatal vesicoamniotic shunting for lower urinary tract obstruction.

Objective: Limited information is available about long-term outcomes in children treated prenatally for lower urinary tract obstruction. Our aim was to evaluate outcomes in children treated in utero with vesicoamniotic shunts. Methods: Clinical outcomes in 20 pregnancies with a singleton male fetus, oligo/anhydramnios, and lower urinary tract obstruction were studied using chart review and phone and written clinical questionnaire for parents, pediatricians, and urologists. Results: Overall 1-year survival was 91%. Two neonatal deaths occurred from pulmonary hypoplasia. Mean gestational age at delivery was 34.6 weeks, mean days from shunting to delivery were 84.4, and mean birth weight was 2,574 g. Prenatal urinary prognosis was good in 13, borderline in 2, and poor in 3 of the survivors. Mean age at follow-up was 5.83 years. Posterior urethral valves were confirmed in 7 males, urethral atresia in 4, and prune belly syndrome in 7. Eight children had acceptable renal function, 4 had mild insufficiency, and 6 required dialysis and eventual renal transplant. Eleven children had normal bladder function with spontaneous voiding, 6 required catheterization, and 1 child still had a vesicostomy. Height and weight were below the 25th percentile in 9 children. Persistent respiratory problems were present in 8, musculoskeletal problems in 9, and frequent urinary tract infections were reported in 9. Health-related quality of life results in our group with lower urinary tract obstruction were similar to those in a healthy child population. Conclusion: Male children who underwent prenatal bladder shunting were neurodevelopmentally normal. Although one third of the surviving babies required dialysis and transplantation, the majority have acceptable renal and bladder function and report satisfactory quality of life. Level of Evidence: III

The Response of the Fetal Kidney to Obstruction

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.

Abnormal Germ Cell Development in Cryptorchidism

Background: Previous studies suggest that two fundamental, probably androgen-dependent, steps in maturation of germ cells normally occur in the prepubertal testis: the disappearance of gonocytes (the fetal stem cell pool) and the appearance of adult dark spermatogonia (the adult stem cell pool) at 2–3 months of age and the appearance of primary spermatocytes (the onset of meiosis) at 4–5 years. Previous studies of small series of cryptorchid boys suggest that both steps are defective in undescended testes and to a lesser degree in descended testes contralateral to unilaterally undescended testes. The purpose of this study is to confirm the previous findings of defective germ cell maturation in a large series of boys with unilateral undescended testes. Patients: Seven hundred and sixty-seven boys with unilateral cryptorchidism who had orchidopexy and bilateral testicular biopsies between birth and 9 years of age were studied. Materials and Methods: Total and differential germ cell counts were performed on semithin histologic sections of the biopsies. The results from the undescended and contralateral descended testes were compared using the Wilcoxon signed-rank test and the Wilcoxon-Whitney-Mann U test. Results: Gonocytes failed to disappear and adult dark spermatogonia failed to appear in undescended testes under 1 year of age indicating a defect in the first step in maturation at 2–3 months resulting in failure to establish an adequate adult stem cell pool. Primary spermatocytes failed to appear in undescended testes and appeared in only 19% of contralateral descended testes at 4–5 years of age indicating a defect in the onset of meiosis. Conclusion: Unilaterally undescended testes fail to establish an adequate adult stem cell pool which normally occurs at 2–3 months of age and fail to establish adequate meiosis which normally occurs at 4–5 years of age. Similar but less severe changes are seen in the contralateral descended testes. Defects in the two pubertal steps in germ cell maturation are associated with reduced total germ cell counts.

The Effect of Obstruction on the Developing Bladder

Congenital bladder obstruction causes significant immediate and long-term consequences yet its pathophysiology remains poorly understood. A model of early fetal bladder obstruction in sheep has been developed to study the response of the developing bladder to high grade obstruction, with particular emphasis on the regulation of growth and development. Congenital bladder obstruction was produced in fetal sheep at 60 days of gestation and studied at 95 days of gestation (14 sheep) or term (12 sheep). A total of 24 age-matched normal sheep served as controls. Bladders were analyzed by total weight, stereological estimation of smooth muscle cell size, number and total mass, deoxyribonucleic acid concentration, muscarinic cholinergic receptor density, myosin isoform analysis and/or passive cystometrics. Congenital bladder obstruction caused a 4.6 times increase in bladder weight at term reflecting a 5.8 times increase in smooth muscle mass. This increase was predominantly that of cellular hypertrophy and less so of hyperplasia, based upon increased cell volume, increased protein-to-deoxyribonucleic acid ratio, and no significant increase in total cell number. Muscarinic cholinergic receptor number per smooth muscle cell increased 3.2 times but it did not change relative to myosin content. The ratio of myosin heavy chain isoforms SM1:SM2 is developmentally regulated and was seen to change from 1.6 at 100 days of gestation to 1.13 at term in normals. After 5 weeks of obstruction SM1:SM2 was 1.27 and it was 1.25 at term, indicating an effect on the developmental regulation of smooth muscle. Rapid fill cystometry in vivo measured the rate of stress relaxation to assess accommodative properties. The half-decay time was increased in all 3 obstructed bladders tested to greater than 15 seconds at 50% capacity (normal less than 5 seconds), suggesting reduced compliance. This study shows that an in utero model of bladder obstruction is feasible. Congenital bladder obstruction produces a variety of structural, biochemical and functional changes in the developing bladder indicative of alterations in the regulation of growth and differentiation.

Lower Urinary Tract Changes After Early Valve Ablation In Neonates and Infants: Is Early Diversion Warranted?

PURPOSE Severe hydronephrosis, high grade reflux and/or renal insufficiency often leads to proximal urinary tract diversion in male infants with posterior urethral valves. Even with this treatment progressive loss of renal function often occurs. Unfortunately with early diversion the bladder, already damaged by in utero obstruction, is also defunctionalized. Alternative treatment with valve ablation in the newborn period and without diversion may facilitate recovery of normal bladder function. MATERIALS AND METHODS We retrospectively reviewed the records of infants treated for posterior urethral valves before age 1 year at our institution in the last 8 years. Treatment comprised primary valve ablation in 23 patients and urinary diversion in 8. Preoperative and serial postoperative voiding cystourethrograms were scored for degree of trabeculation, bladder neck hypertrophy and prostatic urethral dilatation in all patients undergoing primary valve ablation. Recovery of bladder and renal function after primary valve ablation was compared to that of patients treated with urinary diversion. RESULTS All patients treated with primary valve ablation demonstrated marked improvement or resolution of bladder abnormalities on voiding cystourethrography by 1 year postoperatively. Bladder compliance and volume were statistically better than in patients treated with primary diversion. Upper tract diversion failed to halt progressive renal failure in 5 of the 6 patients who underwent diversion. Similarly primary valve ablation did not stop progressive renal failure in a matched group of patients. CONCLUSIONS Early ablation of posterior urethral valves results in the recovery of normal bladder appearance and function when performed in the first months of life. Severe renal insufficiency tends to progress even with upper tract diversion. Furthermore, this treatment prevents normal bladder cycling, which may inhibit bladder recovery in the patient with posterior urethral valves.

The Ascending Testis and the Testis Undescended Since Birth Share the Same Histopathology

PURPOSE The etiology of the ascending testis is controversial. We propose that ascending testis, defined as a testis previously thought to be descended and later noted to be out of the scrotum, is due to mild hypogonadotropic hypogonadism affecting both testes. The diagnosis of these low types of true undescended testes is difficult to make clinically in children since they are frequently confused with retractile testes. In this study we compared testicular biopsies in a group of boys with ascending testes with those in boys who had an undescended testis since birth (primary undescended testis). MATERIALS AND METHODS Between 1985 and 1995, 91 patients with ascending testes underwent orchiopexy and bilateral testis biopsy. The total germ cell count, processus vaginalis status, age at surgery and whether followup was done by a pediatrician or pediatric urologist were compared in patients with ascending and unilateral primary undescended testes. RESULTS The total germ cell count was similar in the undescended and the contralateral descended testis in patients with ascending and primary undescended testes. The processus vaginalis was more likely to be closed in ascending testes (57% versus 36%, p = 0.0001). Age at surgery and the total germ cell count were similar in patients followed by pediatricians and pediatric urologists. CONCLUSIONS The ascending testis has the same germ cell count as the primary undescended testis. Yearly followup by the primary care physician is recommended for patients with retractile testes.

Transient Asynchronous Testicular Growth in Adolescent Males With a Varicocele

PURPOSE We assessed the testicular growth of adolescent males followed nonsurgically for the presence of left varicocele. MATERIALS AND METHODS We retrospectively reviewed the charts of adolescent males with a diagnosis of unilateral left varicocele and ultrasound testis volume measurements seen during a 10-year period. A total of 161 boys underwent at least 2 testicular ultrasounds as part of the evaluation for left varicocele. Patients were excluded from study for a history of inguinal/scrotal pathology or endocrinopathy that could affect testicular size. Sonographic testicular volume was calculated using the Lambert volume (length x width x height x 0.71). The resulting volumes were compared to previously published criteria for surgical repair (15%, 20% and 2 cc size differentials). RESULTS Of the 71 boys with 3 followup ultrasounds 38 (54%) initially had a 15% or greater volume differential. After nonsurgical followup with ultrasounds for 2 years 60 boys (85%) had testicular volume differentials in the normal range (less than 15%). Of the patients 71% were spared potential surgery by size criteria and 50% were spared surgery by the same 15% volume differential criteria. CONCLUSIONS Adolescent males with unilateral left varicocele often demonstrate asynchronous testicular growth that usually equalizes in time. Therefore, sonographic testicular size measurement at a single point during adolescence is insufficient to determine the need for varicocelectomy. When contemplating varicocelectomy we recommend at least 2, and preferably 3, testicular volume measurements 1 year apart to establish accurately decreased left testicular volume compared to a normal right testis.

Demucosalized Augmentation Gastrocystoplasty with Bladder Autoaugmentation in Pediatric Patients

PURPOSE Potential metabolic complications in urinary reconstruction with bowel or stomach are due to the presence of the gastrointestinal mucosal layer. The advantage or disadvantage of each tissue has been debated. We report a procedure in which the mucosa of a gastric pedicle flap is removed and the remaining muscularis flap is transferred to an autoaugmented bladder. MATERIALS AND METHODS Seven female and 4 male patients underwent the procedure at our institutions from October 1992 to November 1994. A retrospective chart review was performed to compare preoperative to postoperative urodynamic findings, continence status and complications. RESULTS Mean followup was 23 months (range 8 to 33). Preoperative urodynamics showed an average bladder capacity of 109 cc (range 45 to 200) and compliance of 3 ml./cm. water (range 1 to 6). Urinary continence was achieved in 10 patients on clean intermittent catherization every 3 to 4 hours and 1 was wet due to low urethral resistance. All patients underwent postoperative urodynamics. Bladder capacity increased to 236 cc (range 150 to 300) with an average compliance of 9 ml./cm. water (range 5 to 14). No metabolic complications were noted. CONCLUSIONS The gastric muscularis appears to be preserved along with the native urothelium to provide a compliant tissue that can be an alternative to bowel and stomach for bladder augmentation. Because the procedure involves demucosalizing the gastric patch as well as performing bladder autoaugmentation, operative time is increased compared to normal gastrocystoplasty or enterocystoplasty. However, the lack of metabolic complications and mucus-free urine are important considerations and substantial advantages.

A Gender Assessment Team: experience with 250 patients over a period of 25 years.

Purpose: To describe a Gender Assessment Team that has provided a multidisciplinary approach to the diagnosis, medical and surgical treatment, genetic counseling, and psychosocial support of patients with ambiguous genitalia, intersex disorders, and other genital anomalies, collectively termed disorders of sex development; and to determine the major diagnostic categories and approach.Methods: A retrospective review of 250 patients evaluated by the Team at Childrens Hospital and Regional Medical Center in Seattle, WA, from January 1981 through December 2005. The Team included the following specialties: medical genetics, cytogenetics, gynecology, pediatric urology, endocrinology, and psychiatry.Results: Of the subjects, 177 were infants, 46 were children or adolescents, and 27 had a multisystem genetic condition. The most common diagnoses were congenital adrenal hyperplasia (14%), androgen insensitivity syndrome (10%), mixed gonadal dysgenesis (8%), clitoral/labial anomalies (7%), hypogonadotropic hypogonadism (6%), and 46,XY small-for-gestational-age males with hypospadias (6%).Conclusion: The six most common diagnoses comprised 50% of the cohort. The expertise of a multidisciplinary team allowed for integrated care for patients with disorders of sex development and identification of novel conditions. Geneticists play an important role in a team approach through knowledge of genetic testing options and diagnosis of patients with karyotypic abnormalities and syndromes with genital anomalies.

The physical characteristics of young males with varicocele.

To determine if there is an association with habitus in young males with varicocele, as adolescent boys with varicoceles appear to be mostly taller and leaner than age‐matched controls.