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.

Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism.

The optimal management of prolonged priapism for patients with sickle cell anemia (SCA) has not been established. We prospectively studied in an outpatient setting the efficacy and safety of a procedure that employs aspiration of blood from the corpora cavernosa and irrigation with a dilute epinephrine solution under local anesthesia to relieve priapism in young patients with SCA. If hydration and analgesics failed to produce detumescence or if priapism had lasted >4 hours, the protocol was activated in the emergency room or clinic. Fifteen patients with homozygous SCA (Hb SS) were treated on 39 occasions; 10 patients were treated once, 1 patient twice, 2 patients 3 times, 1 patient 6 times, and 1 patient 15 times. Median age of patients at first treatment was 14.3 years (range, 3.9-18.3 years). The procedure was successful in producing immediate detumescence on 37 of 39 occasions (95% efficacy, 95% confidence intervals (CI): 81%-99%). No serious immediate or long-term side effects were observed. None of the patients who demonstrated detumescence required hospitalization. The 2 patients whose priapism persisted after aspiration and irrigation presented with episodes lasting >24 hours. All evaluable patients whose priapism resolved after aspiration and irrigation self-reported normal erectile function at a median of 40 months (range, 3-58 months) after the last procedure. Thus, aspiration of the corpora cavernosa followed by irrigation with dilute epinephrine is effective in producing immediate and sustained detumescence and should be the initial therapy employed for patients with SCA and prolonged priapism. (Blood, 2000; 95:78-82)

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.

Molecular analysis of collagens in bladder fibrosis.

PURPOSE: Fibrosis of bladder tissue is characterized by an abnormal deposition of connective tissue within different layers of the bladder wall, resulting in a low volume, high pressure vesical which may ultimately contribute to renal scarring and failure. These bladders are functionally referred to as "non-compliant" and may result from different etiologies: neurogenic, which encompasses myelodysplasia and spinal cord injury, or non-neurogenic, owing to obstruction or radiation therapy. To examine the molecular mechanisms responsible for this fibrosis, we have analyzed a well-characterized pediatric patient population for alteration(s) in collagen types I and III regulation at the protein and nucleic acid levels. MATERIALS AND METHODS: Immunohistochemical localization of collagen subtypes (I, III, and IV) was carried out using type specific monoclonal antibodies. Total collagen was determined by hydroxyproline analysis, and subtype specific expression of collagenous proteins, following cyanogen bromide extraction procedures, was quantified by competitive ELISA. Total RNA was extracted by guanidinium/phenol/chloroform, and slot blot hybridization analyses with radiolabeled human cDNA probes were quantified by densitometry of resulting autoradiograms. RESULTS: Connective tissue infiltration of detrusor smooth muscle bundles was specific for type III collagen. Protein analyses demonstrated: 1) an increase in total collagen, 2) a statistically significant increase in the type III: type I collagen ratio, and 3), an absolute increase in type III collagen protein in non-compliant bladder tissue. At the mRNA level, there was a coordinate increase in both collagen I and III steady-state mRNAs in non-neurogenic bladder tissue, whereas neurogenic bladder tissue was characterized by an increase in the type III: type I mRNA transcript ratio. CONCLUSIONS: These data suggest that regulation of collagen synthesis in bladder fibrosis is complex and is characterized by both transcriptional and post-transcriptional mechanisms, depending upon the etiology of the fibrosis.

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.

Type III collagen messenger RNA is modulated in non-compliant human bladder tissue.

PURPOSE: Previous studies have demonstrated that the non-compliant bladder is characterized histologically by an increased deposition of extracellular matrix protein, especially type III collagen, in the muscle wall. We sought to determine if an increased tissue level of type III collagen messenger RNA (mRNA) parallels the observed increase in protein expression. MATERIALS AND METHODS: Using a reverse transcription-polymerase chain reaction (RT-PCR) quantitative technique we measured and compared the bladder tissue concentration of type III collagen mRNA between an experimental group of patients (n = 7) with urodynamically proven non-compliant bladders (< 12 cc/cm. H2O) and a control group (n = 8) with normal bladder compliance (> 20 cc/cm. H2O). RESULTS: The mean (+/-S.E.M.) of type III collagen mRNA level in the non-compliant group was 11.72 +/- 2.56 attomole/milligram (amol/mg.) which was almost threefold higher than the level 4.26 +/- 0.74 amol/mg measured in the control group. This difference was statistically significant (p = 0.027). CONCLUSIONS: Type III collagen mRNA levels are increased in the human non-compliant bladder. Therefore the accumulation of type III collagen protein is, in part, transcriptionally regulated.

Pediatric Vesicoureteral Reflux Guidelines Panel summary report on the management of primary vesicoureteral reflux in children.

PURPOSE: The American Urological Association convened the Pediatric Vesicoureteral Reflux Guidelines Panel to analyze the literature regarding available methods for treating vesicoureteral reflux diagnosed following a urinary tract infection in children and to make practice policy recommendations based on the treatment outcomes data insofar as the data permit. MATERIALS AND METHODS: The panel searched the MEDLINE data base for all articles from 1965 to 1994 on vesicoureteral reflux and systematically analyzed outcomes data for 7 treatment alternatives: 1) intermittent antibiotic therapy, 2) bladder training, 3) continuous antibiotic prophylaxis, 4) antibiotic prophylaxis and bladder training, 5) antibiotic prophylaxis, anticholinergics and bladder training, 6) open surgical repair and 7) endoscopic repair. Key outcomes identified were probability of reflux resolution, likelihood of developing pyelonephritis and scarring, and possibility of complications of medical and surgical treatment. RESULTS: Available outcomes data on the various treatment alternatives were summarized in tabular form and graphically, and the relative probabilities of possible outcomes were compared for each alternative. Treatment recommendations were based on scientific evidence and expert opinion. The panel concluded that only a few recommendations can be derived purely from scientific evidence of a beneficial effect on health outcomes. CONCLUSIONS: For most children the panel recommended continuous antibiotic prophylaxis as initial treatment. Surgery was recommended for children with persistent reflux and other indications, as specified in the document.

Pediatric neurourology.

Children with voiding disturbances or neurologic dysfunction of the lower urinary tract present challenges to the practicing clinician. With careful clinical and radiologic evaluation, many of these disturbances can be managed. Complex situations, however, generally require expert urodynamic evaluation to delineate the cause of the bladder dysfunction and to guide management. These investigations combined with long-term follow up should provide new insights for further improvement in the management of neurogenic bladders in children. Urodynamic studies also have given us insights into the pathophysiology of abnormal voiding states secondary to dysfunctional bladders in children with posterior urethral valves, the prune belly syndrome, and the Hinman syndrome.

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.

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 absent cryptorchid testis: surgical findings and their implications for diagnosis and etiology.

On surgical exploration for impalpable testes, there is often found nothing or a nubbin of tissue at the end of the spermatic vessels. This situation is commonly referred to as an absent testis. Controversy exists on how to establish correctly this diagnosis and the degree of investigation required. In addition, there is disagreement concerning whether an absent testis results from early torsion or endocrinopathic event. What is accepted is that the spermatic vessels are singularly important in establishing testis location. In this study, the pathological findings of 117 cases of absent testis diagnosed by surgical exploration at our hospital were reviewed. This diagnosis represented 10% of 1,225 patients explored for cryptorchidism from 1985 to 1991. Average patient age at operation was 26.8 months (range 5 months to 14 years). Of these children 78 (67%) presented with an impalpable left testis. At operation 3 patients (3%) underwent laparoscopy only, while all others had groin exploration with or without transperitoneal exposure to ensure identification of spermatic vessels. In 110 cases surgical specimens or nubbins were excised. Pathological study of these remnants revealed vas deferens in 89 cases (81%), epididymal tissue in 40 (36%) and small amounts of seminiferous tubules with germinal elements in 7 (6.4%). Only 26 specimens (24%) had sufficient vascular tissue present to be suggestive of spermatic vessels. A significant number showed the presence of calcification (35.5%) and hemosiderin (30%) deposits within the remnant. A subset of patients with absent testis possesses testicular tissue of presumed increased malignant potential. Therefore, surgical exploration with spermatic vessel identification and remnant removal is the gold standard for the diagnosis and treatment of the absent testis. The surgeon continues to be responsible for spermatic vessel identification, since the vessels may be recognized at pathological examination in less than 25% of the cases. Also, the common finding of calcification and hemosiderin lends weight to the torsion etiology over endocrinopathy for an absent testis.

Normal epididymal anatomy in boys.

It is accepted that a range of epididymal anomalies exists in boys with cryptorchidism, varying from ductal patency aberrations to abnormal attachments of the epididymis to the testes or even complete absence. Despite several series characterizing these variations, there are few studies of normal controls for comparison. We document normal epididymal anatomy in boys. During an 18-month period ending in 1991, 94 boys (mean age 4.8 years, range 1 month to 18 years) underwent inguinal or scrotal exploration unrelated to cryptorchidism. Epididymal anatomy was recorded for all exposed testes. Indications for surgery included hydrocele or hernia in 85 boys, torsion in 8 and varicocele in 1. A total of 112 epididymides was examined and the configurations were recorded as type 1-head and tail attachment with a "looped" body in 94 of 112 cases (83.9%), type 2-complete attachment to the testis in 14 (12.5%), type 3-head attachment only in 3 (2.7%), type 4-tail attachment only in 0 (0%), type 5-nonfusion in 1 (0.9%) and type 6-anomalies of ductal patency in 0 (0%). These data reveal that the most common epididymal configuration in normal boys is a looped epididymis with the head and tail attached (84%) followed by complete fusion with the testes (12.5%). Other variations are rare. Absence of the epididymis was not observed.

Nonoperative management of blunt pediatric major renal trauma.

Although algorithms exist for the management of renal trauma in adults, guidelines have not been established in children. Of 1,175 patients entered into our Trauma Registry between 1987 and 1991, 61 (5.2%) presented with gross or microscopic hematuria. Eight of the 58 patients (13.8%) who had blunt abdominal trauma had major renal injuries. Gross hematuria (n = 10) was a significant predictor of major renal injury (n = 5) (p < 0.001). All 3 patients with microscopic hematuria and a major renal injury also had evidence of multisystem trauma. Admission blood pressure, hemoglobin, and trauma score were not predictors of major renal trauma. All cases were managed nonoperatively except for 1 patient who required a partial nephrectomy for continued hemorrhage. These data suggest that hematuria of any degree should be evaluated in the pediatric population, since major injuries can occur with even microscopic hematuria or in the absence of shock. Nonoperative management in this series resulted in no morbidity or delayed complications and suggests that surgical exploration be reserved for ongoing bleeding.

Biochemical characterization and quantitation of the collagenous components of urethral stricture tissue.

The collagenous composition of normal and strictured human urethral tissue was analyzed qualitatively by immunohistochemistry and quantitatively by 2-dimensional gel electrophoresis of cyanogen bromide digested tissue. Histological comparison of the normal and strictured urethral tissue showed that the normal urethral spongiosum was replaced by densely packed connective tissue fibers interspersed with fibroblasts in the strictured tissue. The immunohistochemical analysis of urethral tissue identified the presence of types I and III collagen fibers in normal spongiosum and in the connective tissue scar of strictured tissue. Estimation of the collagen type III:I ratio using scanning densitometry revealed a CB5:CB8 peptide ratio of 0.357 +/- 0.058 in the normal tissue, while the urethral stricture tissue had a CB5:CB8 ratio of 0.203 +/- 0.079 (p = 0.010). Total collagen content, as determined by hydroxyproline analysis, revealed no statistically significant differences between control and strictured tissue. Therefore, the normal urethral spongiosum was comprised of 75.1% type I collagen and 24.9% type III collagen. In contrast, the type I collagen in urethral stricture tissue was increased (83.9%), with a corresponding decrease in type III collagen (16.1%). This alteration in the ratio of collagen type III:I may explain the fibrotic noncompliant nature of urethral stricture scar tissue.

Is lamina propria matrix responsible for normal bladder compliance?

Immunohistochemistry using monoclonal and polyclonal antibodies to extracellular matrix proteins is a highly sensitive tool for the characterization of matrix components. For the first time in the normal and noncompliant human bladder we have used antibodies to collagen types I, III and IV, and elastin to provide morphological correlation with mechanical properties noted clinically. In the normal bladder elastin and collagen types I and III showed intense localization in the lamina propria with modest localization in the detrusor layer. In contrast, lamina propria staining in the noncompliant bladder was essentially unchanged, while there was intense localization within the detrusor layer. Significantly, this intense localization consisted of collagen type III and elastin with little increase in type I. Type IV collagen is associated with basement membranes and individual smooth muscle cells, and shows commensurate increase in specimens with muscle hypertrophy and/or hyperplasia. These observations suggest that in the normal bladder the lamina propria may be a major structural capacitance layer with the smooth muscle covering it. The collagen fibers of the lamina propria may gradually unfold during filling, thus, accounting for normal compliance while in the noncompliant bladder the capacitance layer shifts outward to the infiltrated smooth muscle, thus, preventing the normal expansion of the lamina propria. The smooth muscle infiltration consists of a deposition of collagen type III and elastin with little increase of collagen type I, and it results in a loss of compliance. The pattern of localization would suggest that the smooth muscle is responsible for this accumulation.

Lithogenic properties of enterocystoplasty.

Calculi formed in 26 of 87 patients (30%) following augmentation enterocystoplasty, of which 23 formed within the reservoir, at a mean interval of 25 months postoperatively. The calculi were composed principally of triple phosphates suggesting an important etiological role of bacteriuria and the urease reaction. Open cystolithotomy was the most successful means of removing the calculi.

Effects of pregnancy on muscarinic receptor density and function in the rabbit urinary bladder.

The contractile response of the rabbit urinary bladder to field stimulation consists of both cholinergic and purinergic components. In general, approximately 60% of the contractile response to field stimulation is cholinergic and 40% is purinergic. Although the purinergic response represents a significant proportion of the initial (phasic) pressure response to field stimulation of the isolated whole bladder, it contributes only 10-15% of the ability of field stimulation to empty the bladder. The current study investigates the effects of pregnancy on the contractile responses of the isolated urinary bladder to cholinergic and purinergic stimulation. The results of these studies indicate that pregnancy induces substantial changes in the physiology and pharmacology of the urinary bladder. The following data are consistent with the theory that pregnancy substantially increases the relative purinergic component of the response to field stimulation (and presumably neuronal stimulation): (1) there was a significantly greater response of the bladders isolated from pregnant rabbits to low-frequency field stimulation; (2) atropine was more effective at inhibiting the pressure generation of bladders isolated from virgin female rabbits; (3) field stimulation was more effective at emptying bladders isolated from virgin female rabbits; (4) the response of the bladders from pregnant rabbits to bethanechol was significantly reduced, whereas the response to ATP was significantly increased. In addition to these effects of pregnancy on bladder physiology, pregnancy induced a 50% decrease in the muscarinic receptor density of the urinary bladder body, which correlated very well with the 50% decrease in the contractile response to bethanechol.

Predictors of residual mass histology after 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.