Elizabeth B. Yerkes

Role of the Angiotensin Type 2 Receptor Gene in Congenital Anomalies of the Kidney and Urinary Tract, CAKUT, of Mice and Men

Angiotensin type 2 receptor gene null mutant mice display congenital anomalies of the kidney and urinary tract (CAKUT). Various features of mouse CAKUT impressively mimic human CAKUT. Studies of the human type 2 receptor (AGTR2) gene in two independent cohorts found that a significant association exists between CAKUT and a nucleotide transition within the lariat branchpoint motif of intron 1, which perturbs AGTR2 mRNA splicing efficiency. AGTR2, therefore, has a significant ontogenic role for the kidney and urinary tract system. Studies revealed that the establishment of CAKUT is preceded by delayed apoptosis of undifferentiated mesenchymal cells surrounding the urinary tract during key ontogenic events, from the ureteral budding to the expansive growth of the kidney and ureter.

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.

DOES EVERY PATIENT WITH PRENATAL HYDRONEPHROSIS NEED VOIDING CYSTOURETHROGRAPHY

PURPOSE Prenatal ultrasound has allowed early identification of urinary tract abnormalities that may require urological followup or early intervention. While all children with prenatal hydronephrosis should undergo ultrasound within the first few weeks of life, we believe that there is a subset of postnatal hydronephrosis for which voiding cystourethrography can be avoided if careful observation is continued. MATERIALS AND METHODS For 5 years 175 infants with a history of prenatal hydronephrosis were evaluated by ultrasound. Of 60 infants with less than Society for Fetal Urology grade II unilateral or bilateral hydronephrosis 44 underwent voiding cystourethrography as part of the early evaluation and 16 were observed without voiding cystourethrography. Four infants for whom we would routinely obtain voiding cystourethrography were excluded from study due to severe prenatal hydronephrosis, renal duplication, hydroureter, ipsilateral small or echogenic kidney and grade II or higher hydronephrosis. RESULTS Voiding cystourethrography was positive in 6 of the 40 infants (15%) with less than grade II hydronephrosis. Of these cases 3 had grade III or higher vesicoureteral reflux and 1 with high grade reflux required reimplantation. None of the 16 patients followed without voiding cystourethrography has required further evaluation or intervention. In all patients with negative or no voiding cystourethrography parenchyma was preserved and hydronephrosis stabilized or resolved. CONCLUSIONS Prenatal and postnatal ultrasound in infants should be used to guide further urological evaluation. Among infants with less than grade II hydronephrosis postnatally 15% had reflux on voiding cystourethrography, which is significantly higher than that reported among normal children (approximately 1%). However, none of the 16 infants observed without voiding cystourethrography on short-term antibiotic prophylaxis had deleterious renal events with 6 months to 4.5 years of followup. Therefore, we question the actual significance of the reflux detected in the first cohort of infants. Voiding cystourethrography can provide a definitive answer. However, we also believe that it is not absolutely mandatory based on the outcome in the observed group. With careful counseling and followup most patients with less than grade II hydronephrosis can be observed without urological sequela.

Laparoscopic evaluation for a contralateral patent processus vaginalis: part III

OBJECTIVES Between May 1, 1992 and August 1, 1996, 759 consecutive children younger than 10 years of age were evaluated and treated for known inguinal hernia. These children were participating in a prospective investigation of the potential role of diagnostic laparoscopy in the evaluation of the contralateral inguinal anatomy. The initial two series of data (parts I and II of this three-part series) were previously presented at the 1993 and 1995 American Academy of Pediatrics meetings. METHODS Of 759 patients, 100 children were diagnosed with bilateral inguinal hernias and therefore did not undergo laparoscopy. Thirty-two patients did not undergo laparoscopic evaluation due to technical difficulties or complicated clinical situations. The patients contralateral inguinal region was carefully examined under anesthesia, and predictions were made regarding the likelihood of contralateral patent processus vaginalis (CPPV). Six hundred twenty-seven children underwent diagnostic laparoscopy to confirm the presence or absence of CPPV. Laparoscopy was initially exclusively performed through the umbilicus prior to repair of the known hernia, but over the last 26 months, 250 children successfully underwent laparoscopy through the ipsilateral hernia sac. RESULTS Of patients younger than 1 year of age, 114 were diagnosed with both a known unilateral hernia and CPPV, whereas 132 had a unilateral hernia only (46% versus 54%). Among children older than 1 year of age, 148 (39%) were diagnosed with unilateral hernia and CPPV, and 233 (61%) were diagnosed with a unilateral hernia alone. After examination under anesthesia, 233 of the 627 patients were suspected of having a CPPV, and 107 were confirmed at laparoscopy (46%). The remaining 394 patients were not believed to have a CPPV. Normal inguinal anatomy was confirmed in 234 patients (59%), but 160 patients were found at laparoscopy to have a CPPV (41%). CONCLUSIONS A contralateral patent processus vaginalis may be present in a surprising number of young patients being evaluated for a known inguinal hernia. Laparoscopy can be performed without a separate incision when the ipsilateral hernia sac is of sufficient width to allow passage of the scope. Laparoscopy is the best method for evaluating the contralateral inguinal region, particularly in younger children, as it prevents unnecessary inguinal exploration and it decreases the risk that the child will later present with a clinical contralateral hernia.

Y-TO-I WRAP: USE OF THE DISTAL SPONGIOSUM FOR HYPOSPADIAS REPAIR

PURPOSE Rather than resecting the distal spongiosum lateral to the open urethra for hypospadias, we mobilized this tissue with the urethral plate away from the corpora cavernosa, subsequently wrapping it around various types of urethroplasty to prevent fistula formation. MATERIALS AND METHODS The distal spongiosum was preserved and used for coverage in 25 hypospadias repairs in 1 year. We initially applied it in this manner when the distal spongiosum persisted as a pillar of healthy erectile tissue but later when the distal tissue appeared more fibrous in nature. The wrap was used to cover various types of urethroplasty, including advancement in 6 cases, tubularization in 10, flip-flap repair in 6 and an island onlay pedicle graft in 3. RESULTS All patients have at least 1 year of followup. There has been no fistula formation or residual chordee. In 1 patient minor meatal retraction did not require a secondary procedure. Cosmetic results have been good. CONCLUSIONS A distal wrap of corpus spongiosum may be used to avoid fistula formation without causing residual or recurrent curvature. It re-creates a nearly normal urethra in some cases.

Long-Term Followup and Outcome of Continent Catheterizable Vesicostomy Using the Rink Modification

PURPOSE Multiple techniques have been described to create a Mitrofanoff channel in the pediatric population. A small subset of patients only requires creation of a catheterizable channel without bladder augmentation. These patients are ideal candidates for a procedure that avoids the use of intestine, especially in the absence of a suitable appendix. We used a modification of the Casale vesicostomy, as described by Rink, to create a continent vesicostomy in these children. We report our long-term experience with this technique. MATERIALS AND METHODS We retrospectively reviewed the medical records of all patients who underwent continent vesicostomy at our institution between 1992 and 2000. Patient diagnosis, stomal site, associated bladder procedures, stomal continence, followup and complications associated with continent vesicostomy were documented. RESULTS Of the 31 patients who underwent continent vesicostomy, as described by Rink, 14 were female and 17 were male. Average age was 9 years (range 2.5 to 22). Primary diagnosis included neuropathic bladder in 15 cases, the prune-belly syndrome in 6, cloacal exstrophy/anomaly in 5 and other in 5. The stoma was placed in the lower abdomen in 17 patients, in the umbilicus in 7 and in a neoumbilicus in 7. Simultaneous procedures included ureteral reimplantation in 8 cases, bladder augmentation in 5, bladder neck surgery in 4 and reduction cystoplasty in 2. Mean followup was 41 months. All patients achieved excellent stomal continence. Complications included stomal stenosis requiring revision in 14 cases (45%). Stenosis developed in 60% of the patients with neuropathic bladder and in 86% with an umbilical stoma. Eventually 6 patients underwent conversion to an alternative catheterizable channel. CONCLUSIONS Continent vesicostomy can be performed successfully when there is any underlying bladder pathology with 100% stomal continence. Despite the higher rate of stomal problems with this type of Mitrofanoff channel we think that continent vesicostomy is a reasonable alternative in patients with a large bladder requiring only catheterizable channel creation. Because of the excellent results reported with the Monti-Yang technique, we would currently recommend this procedure over continent vesicostomy when bowel is used for bladder reconstruction.

Angiotensin type 2 receptor is important in the normal development of the ureter

Abstract In humans, the actions of angiotensin II are transduced through the AT1 and AT2 receptors which have recently been implicated in renal organogenesis. Polymorphisms in the human angiotensin II receptor genes have been linked to cardiovascular and nephrological disorders. In this study we evaluated 35 patients with either primary obstructive megaureter or posterior urethral valves. Each was genotyped for the A1166 AT1 polymorphism and the recently described A-1332G AT2 transition. The incidence of these genetic variants was also evaluated in normal controls without any ultrasonographic urological abnormalities. Similar to our previous findings in congenital urological abnormalities, the AT1 receptor genotype distribution did not differ between patients with either primary obstructive megaureter or posterior urethral valves versus controls. In contrast, compared with normal controls, there was a dramatic increase in the occurrence of the AT2 A-1332G transition in patients with primary obstructive megaureter (75.0% vs. 41.9% in controls, P<0.025). In patients with posterior urethral valves, there was no difference in the occurrence of the transition versus controls (36.9%, P=NS). Thus, there is no correlation between the AT1 receptor gene polymorphism and urological abnormalities. However there is an increased incidence in the AT2 genetic variant in patients with primary obstructive megaureter.

Percutaneous Cystolithotomy in the Pediatric Augmented Bladder

PURPOSE Bladder stones are a common problem following augmentation cystoplasty. With the addition of Mitrofanoff channels for intermittent catheterization and more aggressive bladder neck tightening procedures, the incidence of stones has increased and endoscopic access to the bladder has become more complicated. We present our results of percutaneous endoscopic cystolithotomy in children with bladder augmentation. MATERIALS AND METHODS We performed percutaneous extraction of bladder calculi in 13 children with bladder augmentation. All patients performed catheterization either via a Mitrofanoff channel, artificial urinary sphincter or plicated ileal limb of an ileocecal reservoir. The prior suprapubic tube site was dilated with an Amplatz set for access, and stones were removed intact or fragmented by laser or electrohydraulic lithotripsy. RESULTS Percutaneous extraction was successful in 12 of the 13 patients (92%). The remaining patient had a small posterior bladder perforation and open cystolithotomy was performed. All patients were discharged home in 24 to 36 hours, and there have been no stone recurrences with a mean followup of 24 months. CONCLUSIONS Percutaneous stone removal using the previous suprapubic tract is a simple, effective and minimally invasive option for removing stones in an augmented bladder. This technique avoids potential injury to the continence mechanism of the reconstructed bladder neck or Mitrofanoff channel. Percutaneous stone removal has become our procedure of choice for managing calculi in the augmented bladder.

SHUNT INFECTION AND MALFUNCTION AFTER AUGMENTATION CYSTOPLASTY

PURPOSE Maintenance of a sterile intraperitoneal environment is critical in patients with ventriculoperitoneal shunts. Recent series have reported a broad discrepancy in the rate of shunt infection (0% to 20%) following augmentation cystoplasty. The need for distal shunt revision has not been well defined. We report the incidence of shunt infection and revision at our institution after bladder augmentation. MATERIALS AND METHODS We retrospectively reviewed the records of all patients with myelodysplasia and a ventriculoperitoneal shunt who underwent augmentation cystoplasty since August 1990. All patients included in the study had a minimum of 12 months of followup. RESULTS A total of 55 patients with a ventriculoperitoneal shunt secondary to myelodysplasia required augmentation cystoplasty for management of a neuropathic bladder. Standard perioperative intravenous and oral antibiotic preparation, mechanical bowel preparation and intraoperative shunt isolation were used. Mean postoperative followup was 60.4 months (range 12 to 111). One patient presented with an extruded peritoneal shunt tip and positive cultures from cerebrospinal fluid and urine. Bladder perforation occurred in 2 patients and the shunt was empirically externalized. Revision was required for 5 (9%) distal shunt obstructions, including 1 cerebrospinal fluid pseudocyst. CONCLUSIONS The incidence of shunt infection after augmentation cystoplasty is low (less than 2% in this large series), and presence of a ventriculoperitoneal shunt should not preclude bladder augmentation. Meticulous perioperative and intraoperative preparation contributes to the low rate of adverse events. Although the rate of distal revision after augmentation is significant, it does not exceed the reported distal failure rate for ventriculoperitoneal shunts in children without a history of urological surgery.

Coronal cuff: A problem site for buccal mucosal grafts

PURPOSE Urethral reconstruction of complex hypospadias or epispadias continues to present a significant challenge. Buccal mucosa as an onlay or tube graft is an excellent option when faced with paucity of penile skin. We identified the factors that lead to success or failure in these repairs. MATERIALS AND METHODS During 6 years we placed 34 buccal mucosal grafts in 31 patients to repair complex hypospadias and epispadias. Penile skin was preferentially used for urethroplasty but a free buccal mucosal graft was used for reconstruction due to lack of adequate penile skin. The cases were complicated with an average of 5 previous unsuccessful repairs each in 16. Grafts ranged from 1.5 to 10 cm. and 10 patients required pieced grafts. We created 1 combination, 16 onlay and 17 full tube grafts. Buccal mucosa was used with a Thiersch-Duplay urethroplasty in 8 patients. RESULTS Anastomotic stricture in 5 patients was proximal in 4. Fistula was a complication in 13 grafts that generally developed on the distal shaft, particularly at the coronal cuff. Of the 7 patients who underwent proximal Thiersch-Duplay urethroplasty with a distal buccal graft 6 had a coronal fistula. Fistula was more common with tube and pieced than with onlay grafts. CONCLUSIONS Fistula is overwhelmingly the most common complication after buccal mucosal graft urethroplasty. Most fistulas develop at the coronal cuff, and we suspect that skin coverage and potential blood supply have not been good in that region. Anticipation of this problem during stage 1 of hypospadias repair would allow more advantageous distribution of the existing penile skin. Good distal skin coverage cannot be compromised in these complex cases.