David H. Ewalt

RENAL LESION GROWTH IN CHILDREN WITH TUBEROUS SCLEROSIS COMPLEX

PURPOSE Renal lesions, including angiomyolipoma, renal cysts (simple and polycystic kidney disease) and renal cell carcinoma, develop in patients with tuberous sclerosis complex. While there is limited information that these lesions may grow in adults with tuberous sclerosis complex, the incidence, characterization and growth rate in children have not been reported. Also, the age at which these lesions first appear, thus providing insight into their natural history, is unknown. We present our data from a longitudinal renal surveillance study of children with tuberous sclerosis complex. MATERIALS AND METHODS Since 1985 children with tuberous sclerosis complex at our hospital have undergone periodic renal imaging by ultrasonography or computerized tomography to monitor renal lesions. A total of 35 girls and 25 boys 1 to 18 years old have undergone at least 2 or more annual renal ultrasounds. RESULTS On initial evaluation 33 of 60 children (55%) (mean age 6.9 years) had an identifiable renal lesion, which increased to 48 of 60 (80%) at followup (mean age 10.5 years). Angiomyolipoma was the most frequent lesion (75%) followed by simple renal cysts (17%). Angiomyolipomas increased in size and/or number in 10 of 18 boys (56%) and 18 of 27 girls (66%). The largest growth rate in 1 year was from 0 to 4 cm. and from 5 to 9 cm. in diameter. The youngest patient demonstrated lesions at age 2 years. The average age at which a normal ultrasound became abnormal was 7.2 years. While a total of 27 patients had a normal ultrasound on entering the study, lesions had developed in 15 at followup (11 with angiomyolipomas, 4 with cysts). Five patients had cysts that had disappeared at followup. A 7-year-old boy had a 9 cm. renal cell carcinoma removed. One patient has renal lesions characteristic of autosomal dominant polycystic kidney disease. CONCLUSIONS Renal involvement in patients with tuberous sclerosis complex begins in infancy, and angiomyolipoma is the most common lesion (75%). Angiomyolipomas are more likely to grow than remain stable, although the rate of growth varies. Simple renal cysts may appear or disappear with time but angiomyolipomas do not disappear. An initially normal renal ultrasound does not rule out future development of lesions. Periodic surveillance is indicated in children with tuberous sclerosis complex.

Prevalence of priapism in children and adolescents with sickle cell anemia

A questionnaire survey was conducted of patients with homozygous sickle cell anemia (Hb SS) and sickle cell beta(0)-thalassemia (Hb S-beta(0)) between 5 and 20 years of age to determine the prevalence and characteristics (number of episodes, timing, duration, cause, or precipitating event) of priapism. Ninety-eight male patients or their parents were surveyed by the same male investigator using a structured verbal interview, which was modified according to the age of the patient. Ninety-four patients had Hb SS and four Hb S-beta(0) thalassemia. Eleven (11%) patients were known to have experienced priapism previously. In response to the questionnaire, 16 of the remaining 87 (18%) patients reported having had priapism on one or more occasions. The actuarial probability of experiencing priapism by 20 years of age was 89% (+/- 9%). The mean age at the initial episode was 12 years, the mean number of episodes per patient was 15.7 (median, 1; range, 1-100), and the mean duration of an episode was 125 minutes. Episodes typically occurred around 4:00 am, and 75% of the patients surveyed had at least one episode starting during sleep or upon awakening from sleep. The prevalence of priapism in children and adolescents with SCA is much higher than previously described. Since early intervention and treatment may prevent irreversible penile fibrosis and impotence, patients and parents should be educated about this complication in advance of its occurrence.

Management of ectopic ureterocele associated with renal duplication: a comparison of partial nephrectomy and endoscopic decompression.

PURPOSE We compared the efficacy of primary endoscopic decompression versus partial nephrectomy for treating ectopic duplex ureteroceles. MATERIALS AND METHODS We retrospectively reviewed the records of patients with renal duplication and upper pole ectopic ureterocele. Patients were classified according to the initial radiological evaluation. The operation performed was arbitrarily chosen by the surgeon. RESULTS A total of 54 patients had unilateral upper or bilateral upper pole ureterocele with no associated vesicoureteral reflux. Partial nephrectomy was performed in 26 patients, of whom 4 (15%) required additional surgery for new onset ipsilateral lower pole reflux. Endoscopic decompression was performed in 28 patients, of whom 18 (64%) required additional treatment due to reflux into the ipsilateral lower pole ureter and ureterocele in 9, reflux into the ureterocele only in 4, ipsilateral lower pole reflux only in 3 and persistent ureterocele obstruction in 2 (p<0.01). An ectopic ureterocele with vesicoureteral reflux into 1 or more moieties was identified in 111 patients, including 56 of 67 (84%) treated with partial nephrectomy and 37 of 44 (84%) treated with endoscopy who have persistent reflux or required further surgery for reflux resolution. CONCLUSIONS In patients with an ectopic ureterocele and no vesicoureteral reflux partial nephrectomy should be considered the treatment of choice. However, when the initial cystogram reveals vesicoureteral reflux, partial nephrectomy and endoscopic ureterocele decompression have identical definitive cure rates of only 16%. The majority of the latter patients require continued observation and/or additional surgery for managing persistent reflux.

Ureterocele Associated with Ureteral Duplication and a Nonfunctioning Upper Pole Segment: Management by Partial Nephroureterectomy Alone

We reviewed the records of 87 patients with a ureterocele associated with duplication and a nonfunctioning upper pole segment. All patients involved in this study were treated by partial nephroureterectomy and observation. Additional surgery to correct vesicoureteral reflux became necessary in 54 cases (62%). A careful retrospective chart and radiographic review identified that the need for additional surgery was directly related to the number of renal moieties that had a ureterocele or vesicoureteral reflux present. In particular, when a ureterocele alone was present 21 of 21 patients (100%) did not require additional surgery. When low grade (less than 3/5) reflux was present into 1 ureter 8 of 15 patients (60%) did not require surgery. The presence of high grade reflux into 1 moiety or vesicoureteral reflux into more than 1 moiety, regardless of the grade of reflux, almost inevitably resulted in the need for further surgery with only 2 of 50 patients (4%) with these abnormalities cured by partial nephroureterectomy alone. Our data suggest that this latter group of patients may be treated more efficaciously by complete genitourinary reconstruction rather than partial nephroureterectomy alone.

The tuberous sclerosis complex: a comprehensive review

Tuberous sclerosis was first reported by von Recklinghausen in 1862 and named by Bourneville in 1880. Transmission is autosomal dominant, but roughly 65% to 85% of the patients arise via spontaneous mutation. The incidence of tuberous sclerosis is estimated between 1:6,000 and 1:10,000 individuals. The notion of the “classic triad” of epilepsy, mental retardation, and facial angiofibromata (adenoma sebaceum) has been frequently cited in literature. However, few affected individuals develop all of the aforementioned signs, and emphasis of these limited features is misleading. It seems more appropriate to recognize that tuberous sclerosis complex may present as a wide spectrum of disease. The diagnostic criteria for Tuberous Sclerosis Complex were revised by a subcommittee at the recent Tuberous Sclerosis Consensus Conference. These clinical diagnostic criteria are outlined in Table 1. Pathologically, tuberous sclerosis is a disorder of cellular migration, proliferation, and differentiation. Manifestations may be systemic and variable. A variety of associated lesions have been reported in the literature including subependymal brain nodules and calcifications, astrocytomas, retinal phacomas, sclerotic bone lesions, dental enamel pitting, and hamartomatous or cystic lesions of the brain, heart, lungs, kidneys, spleen, liver, uterus, and soft tissues. Although many of the clinical manifestations of tuberous sclerosis are secondary to hamartomatous growths, true neoplasms do occur, particularly in the kidneys and brain. Depending on the degree of clinical expression and organ involvement specifically, select patients may experience significant morbidity and mortality. Advances in genetics, imaging modalities, medical therapies, and surgical techniques have unmasked some of the mysteries surrounding this fascinating disorder and, undoubtedly, will continue to affect the associated complications.

Prenatal diagnosis of a prolapsed ureterocele with magnetic resonance imaging

Ectopic ureterocele with ureteral duplication is the most common type of ureterocele found in children. Early accurate diagnosis is desirable to decrease the risk of urosepsis and renal damage. Prenatal imaging with ultrasonography detects the vast majority of ureteroceles; however, in some cases, the diagnosis may remain in doubt. We report on the use of magnetic resonance imaging to clarify the prenatal diagnosis of a prolapsed ureterocele.

IS ENDOSCOPIC DECOMPRESSION OF THE NEONATAL EXTRAVESICAL UPPER POLE URETEROCELE NECESSARY FOR PREVENTION OF URINARY TRACT INFECTIONS OR BLADDER NECK OBSTRUCTION

PURPOSE It has been hypothesized that endoscopic decompression of the duplex extravesical ureterocele is necessary to prevent the complications of urinary tract infections and progressive hydronephrosis. This study was performed to test this premise. MATERIALS AND METHODS Infants younger than 2 weeks with an extravesical ureterocele associated with a duplex upper pole moiety were assigned to immediate endoscopic puncture of the ureterocele followed by antibiotic prophylaxis or antibiotic prophylaxis with plans for delayed surgical intervention. Radiographic studies and catheterized urine cultures were obtained at ages 3 and 6 months and for fever greater than 38.5C. All patients included in this study were followed through 6 months of life. RESULTS Of the patients 32 underwent endoscopic puncture of the ureterocele. Median patient age at endoscopy was 5 days (range 3 to 13). During the first 6 months of life complications developed in 4 (12%), including febrile urinary tract infections in 3 (9%) and with progressive hydronephrosis due to incomplete puncture of the ureterocele in 1 (3%). The remaining 40 patients were treated with antibiotic prophylaxis and delayed open surgery. Median time to open surgery was 3 months (range 2 to 6). During the first 6 months of life complications developed in 5 (13%), including 3 (8%) febrile urinary tract infections and progressive hydronephrosis in 2 (5%). No statistical difference was noted between the 2 treatment groups. CONCLUSIONS In patients with extravesical duplex ureteroceles neonatal complications of urinary tract infection and progressive hydronephrosis are not significantly different between those treated with immediate endoscopic decompression versus delayed open surgical intervention.

Renal Metanephric Adenoma With Previously Unreported Cytogenetic Abnormalities: Case Report and Review of the Literature

We report a case of a renal metanephric adenoma in a 10-year-old boy, in which cytogenetic analysis showed a balanced translocation, t(9;15)(p24;q24) and a balanced paracentric inversion of chromosome 12, inv(12)(q13q15). Immunohistochemically, the tumor showed diffuse reactivity for cytokeratin AE1/AE3, CAM5.2, CD57, and WT1; patchy reactivity for CD56; and focal reactivity for cytokeratin 7, epithelial membrane antigen, and CD10. Tumor cells were entirely nonreactive for α-methyl acyl coenzyme A racemase. Published cytogenetic data for metanephric adenomas are limited, and this is the first report of these cytogenetic abnormalities. The involvement of the chromosome region 9p24 is particularly interesting because of the recent identification of a tumor suppressor gene, KANK (kidney ankyrin repeat-containing protein), at this locus.

Predictors of residual mass histologyafter chemotherapy for advanced testis cancer

The records of 15 patients with Stage B3 or B2/C germ cell testis tumors who underwent full surgical debulking of a residual mass after completion of chemotherapy were reviewed retrospectively to look for predictors of residual mass histology. The density, character, and change in volume of the retroperitoneal mass on computerized tomography before and after chemotherapy were compared with the histology in the primary tumor and in the residual mass. One of 6 patients without teratoma in the primary tumor had a 97 percent reduction in the mass which contained residual teratoma. Two patients with residual seminoma had a 50 percent decrease in tumor volume, and both patients died of tumor progression despite salvage chemotherapy. Two patients with pure seminomas had only residual fibrosis in masses that decreased in volume by 77 and 75 percent, respectively. One of these masses was discrete and the other was diffuse. Seven of 9 patients (78%) with teratoma in the primary tumor had either teratoma (4 of 9, 44%) or carcinoma (3 of 9, 33%) in the residual mass, and the change in mass volume ranged from a 93 percent decrease to a 540 percent increase in size. All 7 patients with residual teratoma and/or carcinoma remain free of disease after observation or further chemotherapy. For the entire series, the mass density and character did not correlate consistently with the primary tumor or residual mass histology. Residual fibrosis alone or teratoma and/or carcinoma were seen with least (0 to 50%) and greatest (more than 90%) decreases in mass volume.

Urinary Tract Reconstruction in Children Undergoing Renal Transplantation

In children, congenital urinary tract anomalies contribute to end-stage renal disease in 20% to 30% of cases. As more and more children with myelomeningocele, posterior urethral valves, prune belly syndrome, and other serious congenital anomalies of the urinary tract survive early infancy, more of these patients will be in need of renal transplantation. Of these, a significant proportion will have persisting abnormal anatomic and physiological characteristics of the urinary tract requiring reconstructive surgery before transplantation. Before undertaking these procedures, urologic evaluation should be performed in all such children. Comprehensive evaluation includes a careful history and physical examination with radiological imaging of the urinary tract (renal ultrasonography and voiding cystourethrography). In selected instances, further evaluation of bladder function and urethral anatomy may require urodynamic evaluation or cystourethroscopy. The goal of these investigations is to ensure that the bladder will hold urine at a low intravesical pressure during the storage phase and that it can be evacuated with certainty. This presentation focuses on the pretransplantation evaluation and the various possible urinary tract reconstructions that may be performed in children destined for renal transplantation.