Martin Kaefer

ESTIMATING NORMAL BLADDER CAPACITY IN CHILDREN

PURPOSE An accurate estimation of normal bladder capacity can be helpful in evaluating the patient with genitourinary disease and in interpreting urodynamic data. Prior studies have provided initial estimates. We propose 2 new equations that are practical, easy to use and more accurate than those previously published. MATERIALS AND METHODS We retrospectively reviewed the records of more than 5,000 children undergoing radionuclide cystography at our institution. Radionuclide cystography was conducted by instilling (99m)technetium pertechnetate via gravity drip in awake children. Bladder capacity was believed to be achieved when rate of inflow diminished to a minimal rate, initiation of voiding occurred or significant discomfort was indicated. Patients with vesicoureteral reflux, infravesical obstruction, urinary tract infection, dysfunctional voiding or other lower urinary tract pathology were excluded from the study. Linear and nonlinear regression modeling established the relationship between age and bladder capacity. RESULTS A total of 2,066 children (598 boys and 1,468 girls) had normal radionuclide cystography and were included in the analysis. Analysis of variance demonstrated that increasing age was strongly predictive of bladder capacity (p <0.0001). Because a nonlinear model was the most accurate formula for all ages (4.5 x age(0.40) = capacity [ounces]), 2 practical linear equations were determined: 2 x age (years) + 2 = capacity (ounces) for children less than 2 years old, and age (years) divided by 2 + 6 = capacity (ounces) for those 2 years old or older. Although girls had larger capacities than boys, the rate of increase was not significantly different between them. CONCLUSIONS The relationship between normal bladder capacity and age in children follows a nonlinear curve. This nonlinear relationship can be approximated by 2 practical linear formulas that are easy to remember and are derived from a larger population than any prior study. These formulas provided accurate estimations of bladder capacity when prospectively applied to normal patients.

IMPROVED BLADDER FUNCTION AFTER PROPHYLACTIC TREATMENT OF THE HIGH RISK NEUROGENIC BLADDER IN NEWBORNS WITH MYELOMENINGOCELE

PURPOSE High pressure dyssynergic voiding may result in irreversible damage to the urinary tract. Prophylactic therapy in the form of clean intermittent catheterization and anticholinergic medication may significantly decrease the incidence of upper urinary tract deterioration. Whether prophylactic therapy in the high risk bladder may also lead to improved long-term bladder dynamics prompted us to study the effect of early versus late treatment of bladder hypertonicity and detrusor-sphincter dyssynergia on the ultimate need for bladder augmentation. MATERIALS AND METHODS We retrospectively reviewed urological outcomes in patients with myelodysplasia who were at risk for urological deterioration within year 1 of life based on bladder sphincter dyssynergia and/or high filling or voiding pressure. We recorded the dates when high risk voiding dynamics were initially observed, and when intermittent catheterization and anticholinergic therapy were initiated. Patients in whom treatment began at the time a high risk profile was noted (prophylactic group seen between 1985 and 1990) were compared to controls with the same high risk voiding parameters who did not receive early therapy (observation group seen between 1978 and 1984 with therapy instituted 1 year or longer after high risk was noted). The number of augmentations performed in each group was indexed to the total number of years of followup in the 2 populations, respectively. Patients with less than 2 years of followup were excluded from further analysis. RESULTS Of the 45 patients at risk clean intermittent catheterization and anticholinergic medication were immediately initiated in 18, while 27 were treated expectantly. Patients in the observation group were followed an average of 4.1 years (range 1.1 to 14) before clean intermittent catheterization and anticholinergic medication were started. Of the 27 children treated expectantly 11 (41%) required augmentation, whereas only 3 of the 18 (17%) treated prophylactically required enterocystoplasty. When the number of augmentations was indexed to total years of followup in each of the 2 groups (296 versus 156 years) patients in the expectant group were nearly twice as likely to require augmentation. CONCLUSIONS Identification and early proactive treatment of the high pressure, dyssynergic lower urinary tract significantly decreases the need for bladder augmentation as children with neurogenic bladder secondary to myelomeningocele mature.

Continent Urinary Diversion: The Children's Hospital Experience

PURPOSE Continent urinary diversion has become increasingly important for treating childhood urinary tract pathology that cannot be managed by direct reconstructive techniques. We review our 9-year experience with continent diversion. MATERIALS AND METHODS Since 1986 continent diversions were created in 74 patients 3 to 38 years old (mean age 13.7). The underlying pathological condition was the exstrophy/epispadias complex in 34 patients, neurological disorders in 23, malignancy in 13 and other congenital anomalies in 4. Followup averaged 5.2 years after the last procedure. Nonbladder reservoirs in 39 patients (53%) were fashioned from ileocolic (17), colic (7), gastrocolic (6), sigmoid (3), gastrosigmoid (2), ileosigmoid (2), ileal (1) and gastroileac (1) segments. When possible, the native bladder was incorporated into the reconstructive strategy. A total of 26 patients underwent bladder augmentation with intestine or stomach, including ileal (11), gastric (8), sigmoid (3), gastroileac (2) and ileocolic (2) segments. Nine other patients did not require bladder augmentation. Continence mechanisms were a flap valve (Mitrofanoff principle) in 50 patients, nipple valve in 15 and ileal plication (Indiana pouch) in 9. When the Mitrofanoff principle was used with a native bladder reservoir in 30 cases, outlet resistance was altered by bladder neck division (15), fascial sling placement (6) or Young-Dees-Leadbetter bladder neck reconstruction (2). In the remaining 7 patients the bladder neck remained intact. RESULTS Excellent continence was obtained. The Mitrofanoff principle initially provided continence in 41 patients (82%). Six of the 9 incontinent patients were dry after a single revision. A total of 13 patients (87%) with nipple valves and 7 (78%) with Indiana pouches were dry, and the remaining 5 were cured after a single revision. Ultimately continence was achieved in 71 of the 74 patients (96%) after a maximum of 2 operations. Of the 48 complications in 29 patients the most common were difficulty in catheterizing (11), stones (11), infection (8) and upper tract deterioration (4). CONCLUSIONS Many options exist for reconstructing complex anomalies. Choices must be individualized based on patient anatomy. The dry state may be achieved in most cases without resorting to a bag on the abdomen.

RESERVOIR CALCULI: A COMPARISON OF RESERVOIRS CONSTRUCTED FROM STOMACH AND OTHER ENTERIC SEGMENTS

PURPOSE The intestinal augmented bladder has an increased propensity to form urinary calculi. Predisposing risk factors include chronic bacteriuria, urinary stasis and mucus production. Gastric reservoirs have negligible mucus production and the ability to acidify the urine. We determined whether they also have a decreased incidence of stones. MATERIALS AND METHODS We retrospectively reviewed the records of all patients undergoing augmentation cyptoplasty (215) or creation of a freestanding reservoir (44) between May 1976 and March 1996. Of these cases 83 were augmented with stomach and 179 were constructed from other intestinal segments, (that is ileal, ileocecal, sigmoid and/or a combination of these). Presenting diagnosis, patient age, gender, additional surgical procedures, interval to stone formation and calculous composition were recorded. Patients were excluded from study when there was less than 1 year of followup, as were those with renal or pre-augmentation bladder calculi. RESULTS Stones formed in 32 of 207 patients (15%) after an average interval of 3.6 years (range 0.5 to 8.6). The majority of stones were composed of struvite (magnesium ammonium phosphate). Reservoirs containing gastric segments were significantly less likely to form calculi than those augmented with other intestinal segments (2 of 70 versus 30 of 137, p <0.0001 Fishers exact test). Seven additional patients with pre-augmentation bladder stones who subsequently underwent gastrocystoplasty remain stone-free at an average followup of 3.0 years. CONCLUSIONS Calculous formation is rare in reservoirs that incorporate a gastric segment. In patients with gastric augmentation stones appear only to develop when the patient is on histamine blockade or has a propensity to form stones that only favor an acidic environment, such as uric acid.

Vascular Endothelial Growth Factor-Mediated Autocrine Stimulation of Prostate Tumor Cells Coincides with Progression to a Malignant Phenotype

Vascular endothelial growth factor (VEGF), which is often produced at high levels by tumor cells, is a well-known mediator of tumor angiogenesis. VEGF receptor tyrosine kinases, KDR/Flk-1 and Flt-1, have been thought to be expressed exclusively by endothelial cells. In this study, we have used a prostate tumor progression series comprised of a differentiated rat prostate epithelial cell line, NbE-1, and its highly motile clonal derivative, FB2. Injection of NbE-1 cells into the inferior vena cava of syngeneic rats indicated that these cells are nontumorigenic. Using the same model, FB2 cells generated rapidly growing and well-vascularized tumors in the lungs. NbE-1 expressed marginal levels of VEGF, whereas high levels of VEGF protein were detected in FB2-conditioned medium and in FB2 tumors in vivo. Analysis of (125)I-VEGF(165) binding to NbE-1 and FB2 cells indicated that only motile FB2 cells expressed the VEGF receptor Flt-1. Consistent with this finding, physiological concentrations of VEGF induced chemotactic migration in FB2 but not in NbE-1 cells. This is the first documentation of a functional Flt-1 receptor in prostate tumor cells. Our results suggest two roles for VEGF in tumor progression: a paracrine role as an angiogenic factor and a previously undescribed role as an autocrine mediator of tumor cell motility.

The Malone antegrade continence enema procedure: quality of life and family perspective.

PURPOSE Since introducing the Malone antegrade continence enema (MACE) procedure into our practice, it has been our bias that social confidence and independence are significantly improved and satisfaction is overwhelmingly high. We objectively determine outcomes after the MACE to refine patient selection, and maximize the quality of perioperative counseling and teaching. MATERIALS AND METHODS An anonymous questionnaire was mailed to all patients who had undergone the MACE procedure within the last 4 years. Patient/parent satisfaction, impact on quality of life and clinical outcome were assessed with Likert scales. Demographic information, MACE specifics, preoperative expectations, and unanticipated benefits and problems were also recorded. RESULTS A total of 65 questionnaires were returned from our first 92 patients (71%). Myelodysplasia was the primary diagnosis in 88% of patients. Complete or near complete fecal continence was achieved in 77% of patients and all others had improved incontinence. The highest level of satisfaction was reported by 89% of patients. Social confidence and hygiene were significantly improved. Daily time commitment, pain/cramping, intermittent constipation and time for fine-tuning the regimen were cited as unanticipated issues. CONCLUSIONS The MACE procedure has received high praise from patients and families after years of battling constipation and fecal incontinence. Significant improvement rather than perfection is the realistic expectation. Objective feedback from patients and families will continue to improve patient selection and education.

Spontaneous bladder perforations: a report of 500 augmentations in children and analysis of risk.

PURPOSE The spontaneous perforation of an augmented bladder is an uncommon but serious complication. To our knowledge our institution has the largest reported series of bladder augmentations. We examined our data to determine the incidence of spontaneous bladder perforation and to delineate associated risk factors. MATERIALS AND METHODS We performed a retrospective chart review of 500 bladder augmentation procedures performed during the preceding 25 years with a minimum followup of 2 years. RESULTS Spontaneous perforations occurred in 43 patients (8.6%), for a total of 54 events. The calculated risk was 0.0066 perforations per augmentation-year at risk. Approximately a third of the cases had perforated within 2 years of surgery, a third between 2 and 6 years postoperatively, and a third at more than 6 years after augmentation. Patients who underwent augmentation between 1997 and 2003 had a higher rate of perforation within 2 years of surgery than those operated on between 1978 and 1987. Increased risk of perforation was observed with the use of sigmoid colon and bladder neck surgery. A decreased risk was associated with the presence of a continent catheterizable channel. CONCLUSIONS We believe that this large and comprehensive series gives valuable insight into this serious complication. The delineation of these potential risk factors serves as a guide for further discussion and investigation.

Sibling vesicoureteral reflux in multiple gestation births.

Background. Vesicoureteral reflux (VUR) is the most commonly inherited disease of the genitourinary tract. Although the majority of evidence supports a genetic cause, the tendency for this condition to spontaneously improve over time has made it difficult to determine the actual mode of transmission. We report the incidence of VUR in siblings of multiple gestation births and for the first time compare the relative incidence of reflux between identical and fraternal twins. Methods. A database consisting of all radionuclide cystograms and voiding cystourethrograms performed between the years 1986 and 1996 was searched for multiple gestation births. The medical records of each patient were evaluated for age at presentation, zygosity, reflux grade, and time to resolution. Children with secondary causes of VUR (eg, posterior urethral valves) were excluded. Triplets were treated as 2 pairs of twins for statistical analysis. Results. Forty-six pairs met the inclusion criteria (31 dizygotic and 15 monozygotic). Overall, 23 (50%) of 46 siblings of index cases had demonstrable VUR. Comparison of VUR prevalence between identical and nonidentical twins was revealing with 80% (12/15) of identical twins and 35% (11/31) of fraternal twins having VUR. When only the youngest individuals in each group were considered, 100% (7/7) of the monozygotics and 50% (5/10) of the dizygotics demonstrated this trait. Conclusions. High concordance for VUR in identical twin siblings supports a genetic basis for the transmission of this disease. Results obtained from fraternal twin siblings provides convincing evidence that this trait is transmitted in an autosomal dominant fashion.

Increased Renal Echogenicity: A Sonographic Sign for Differentiating Between Obstructive and Nonobstructive Etiologies of in Utero Bladder Distension

PURPOSE The combination of in utero bladder distension and bilateral hydroureteronephrosis in male fetuses may result from a number of pathological processes. The prenatal and postnatal treatment of patients with an enlarged bladder is dictated by the specific etiology leading to these changes. We propose specific ultrasonographic criteria for differentiating between obstructive and nonobstructive etiologies in these fetuses. MATERIALS AND METHODS We reviewed the medical records and prenatal imaging studies of 18 cases of marked in utero bladder distension in which a diagnosis of posterior urethral valves, the megacystis-megaureter association or the prune-belly syndrome was confirmed postnatally. Amniotic fluid volume and renal echogenicity were assessed before knowledge of the specific diagnosis. Oligohydramnios was graded as mild, moderate or severe. Increased renal echogenicity was defined as greater echogenicity of the renal cortex and/or medulla than of adjacent liver tissue. Postnatal imaging, clinical course and outcome were also reviewed. RESULTS The study included 15 cases with adequate followup, including 8 in which a diagnosis of posterior urethral valves was confirmed postnatally. Nonobstructive etiologies included the megacystis-megaureter association in 6 cases and the prune-belly syndrome in 1. Seven of the 8 patients with posterior urethral valves had moderate to severe oligohydramnios, whereas all but 1 with a nonobstructive etiology had normal amniotic fluid. Seven of the 8 cases with posterior urethral valves had a marked bilateral increase in renal echogenicity, while none of the nonobstructive cases had this finding. CONCLUSIONS Increased renal echogenicity and oligohydramnios in the setting of bladder distension are highly predictive (87%) of an obstructive etiology. This finding is important in the prenatal counseling and treatment of boys with bilateral hydronephrosis and marked bladder dilatation.

THE INCIDENCE OF INTERSEXUALITY IN CHILDREN WITH CRYPTORCHIDISM AND HYPOSPADIAS: STRATIFICATION BASED ON GONADAL PALPABILITY AND MEATAL POSITION

PURPOSE The combined findings of cryptorchidism and hypospadias often indicate the existence of an intersex state. Testicular maldescent and incomplete tubularization of the urethral plate occur in a spectrum with the severity of the 2 processes likely dependent on the degree of pathophysiology in the androgenic hormonal axis. The incidence of intersexuality in children with undescended testes, hypospadias and otherwise nonambiguous male genitalia has been reported to be 27%. Although the likelihood of genotypic or gonadal ambiguity has previously been associated with meatal position in this population, to our knowledge our study is the first to evaluate the incidence of intersexuality relative to whether the undescended testis is palpable or nonpalpable. MATERIALS AND METHODS The database at our hospital was searched for all cases of undescended testes (2,105) and hypospadias (1,057) between 1982 and 1996. Radiographic, histological and karyotypic data were compiled for all patients presenting with both diagnoses. Gonadal palpability (palpable versus nonpalpable) and meatal position (anterior versus mid versus posterior) were recorded and correlated with the likelihood of identifying an intersex condition. Ten boys with a diagnosis of undescended testes subsequent to inguinal hernial repair were excluded from study. Patients with congenital adrenal hyperplasia or complete testicular feminization were also excluded from study due to the clearly female appearance of the external genitalia. Statistical significance was assessed using Fishers exact test. RESULTS We identified 79 patients presenting with undescended testes, hypospadias and a phallus that was believed to be a possible penis. Intersex conditions were identified with nearly equal frequency in the 44 cases of unilateral (30%) and 35 of bilateral (32%) cryptorchidism. In the unilateral undescended testes group patients with a nonpalpable testis were at least 3-fold more likely to have an intersex condition than those with a palpable undescended testis (50 versus 15%, p = 0.02). In the bilateral group patients with 1 or more nonpalpable testes were also nearly 3-fold as likely to have an intersex condition than those with bilateral palpable undescended gonads (47 versus 16%, p = 0.07). Meatal position was graded as anterior in 33% of cases, mid in 25% and posterior in 41% with the more posterior location conferring a significantly greater likelihood of an intersex condition (anterior 2 of 26, mid 1 of 20 and posterior 21 of 33). CONCLUSIONS Gonadal palpability is an important predictor of an intersex state in unilateral and bilateral cases of cryptorchidism with hypospadias. Patients with an undescended testis that cannot be palpated are significantly more likely to have an intersex condition than those in whom the undescended testis may be palpated on physical examination. The severity of hypospadias likewise has a strong positive correlation with an intersex state.