Replacement of intestinal mucosa with urothelium in rat augmented bladders using intravesical photodynamic therapy with 5-aminolaevulinic acid.

PURPOSE: We evaluated the efficacy of intravesical aminolevulinic acid (delta-aminolevulinic acid hydrochloride) (Frontier Scientific, Logan, Utah) and photodynamic therapy for the removal of small intestinal mucosa in augmented bladders in a rat model. MATERIALS AND METHODS: Enterocystoplasty was performed in 70 female rats using a patch of terminal ileum. A total of 28 were used to determine the pharmacokinetics (0.3, 0.6 and 0.9 M) and dwell time (30, 60 and 90 minutes) of intravesically administered aminolevulinic acid to optimize intestinal mucosal absorption and minimize bladder mucosal absorption. The remaining augmented rats were treated with intravesical photodynamic therapy at light doses of 75, 100 and 125 J. Ileal and bladder tissues were evaluated by light microscopy. Cystometric studies to evaluate bladder volume were measured before and after photodynamic therapy. RESULTS: The concentration of 0.3 M aminolevulinic acid with a dwell time of 30 minutes resulted in an average +/- SE bowel-to-bladder concentration of 2,156 +/- 269/749 +/- 62 ng/gm (ratio 2.9:1). After photodynamic therapy histology revealed uniform ablation and replacement of the intestinal mucosa with urothelium and minimal damage to the bladder wall at all light doses. Bladder cystometry revealed no significant change in bladder capacity after photodynamic therapy. CONCLUSIONS: In the rat model intravesical aminolevulinic acid and photodynamic therapy resulted in the replacement of intestinal mucosa with urothelium, leaving the underlying muscular layer intact. This could potentially be a viable option for patients with a preexisting bladder augment.

Primary lower urinary tract reconstruction for nonfunctioning renal moieties associated with obstructing ureteroceles.

PURPOSE: Upper pole heminephrectomy is the conventional treatment for severely compromised nonfunctioning renal units associated with ureteroceles due to the potential morbidity of leaving a nonfunctioning renal moiety in place. This approach often fails to address the pathological anatomical defect present at the bladder level, and during long-term followup the majority of patients require subsequent lower tract surgery due to persistent ureterocele, new or persistent vesicoureteral reflux, or recurrent infections. We determined the success of primary lower urinary tract reconstruction for nonfunctioning renal moieties and the morbidity associated with leaving nonfunctioning renal units in situ. MATERIALS AND METHODS: We present the collective experience of 2 institutions using definitive lower urinary tract reconstruction without upper tract ablative surgery in 16 patients with duplex collecting systems and an associated nonfunctioning renal moiety due to obstructing ureteroceles. RESULTS: At a mean followup of 62 months upper tract dilatation was decreased or completely resolved in all patients, no loss of renal function was present and 15 of 16 patients (94%) had no evidence of persistent reflux. Postoperative complications in the form of a urinary tract infection occurred in 2 of 16 patients (13%). No patient was febrile. No patient had development of hypertension, proteinuria or tumor during followup. CONCLUSIONS: We believe that primary, single stage, lower urinary tract reconstruction in children with severely compromised or nonfunctioning renal moieties damaged by ureteroceles is superior to upper urinary tract ablative surgery, successfully correcting the obstructive or refluxing pathology with minimal morbidity and risk during long-term followup.

Preservation of renal function in children with myelomeningocele managed with basic newborn evaluation and close followup.

PURPOSE: Children with myelomeningocele who leak with high intravesical pressures are at risk for upper urinary tract deterioration. Urodynamic study shortly after birth and routinely thereafter has been advocated to predict which newborns are at risk for upper tract deterioration. We hypothesize an approach that excludes routine application of urodynamic evaluation in neonates, reserving this study for use only when clinically indicated, is a safe and effective management option. MATERIALS AND METHODS: Of 188 patients seen in the myelomeningocele clinic 84 underwent initial evaluation at age 6 months or less and comprise the study group. Initial evaluation consisted of a history, physical examination, urine culture and renal ultrasound. Infants with hydronephrosis or evidence of retention were placed into a high risk group and all others were placed into a low risk group. High risk patients underwent prompt urodynamic evaluation. High and low risk patients were followed closely at 2 to 4-month intervals with serial physical examination, upper tract imaging and urine culture. Conversion from low to high risk occurred with new onset hydronephrosis, febrile urinary tract infection, urinary retention or incidental finding of vesicoureteral reflux at the time of evaluation for continence. These findings warranted urodynamic evaluation and appropriate intervention. Upper tract deterioration, defined as new onset hydronephrosis, was distinguished from renal deterioration, defined as cortical thinning or scarring, failure of renal growth or decreased renal function on renal scan. RESULTS: A total of 18 infants were placed into the high risk group at initial evaluation, including 12 for retention and 6 for hydronephrosis. The majority of patients were treated with clean intermittent catheterization or vesicostomy. Of the 65 infants placed into the low risk group 29 were converted to high risk at a mean age of 3.1 years, most commonly for febrile urinary tract infection (45%), and appropriate intervention was instituted. Mean followup is 10.4 years (range 0.25 to 26.5). Despite the occurrence of upper tract deterioration, renal deterioration occurred in only 2 of the 162 total renal units (1.2%). CONCLUSIONS: Basic evaluation of the newborn with myelomeningocele along with careful followup and intervention when indicated results in an excellent rate of renal preservation and represents a safe method of management.

Use of small intestinal submucosa for corporal body grafting in cases of severe penile curvature.

PURPOSE: Small intestinal submucosa is a unique biomaterial that has been found to promote tissue specific regeneration in the urinary tract. We present our experimental and clinical experience with small intestinal submucosa (SurgiSis, Cook Biotech, Spencer, Indiana) for pediatric corporal body reconstruction. MATERIAL AND METHODS: A total of 20 Fischer rats underwent implantation of a 7 x 3 mm. small intestinal submucosa graft following excision of an ellipse of tunica albuginea and 14 control animals underwent tunical excision with reimplantation of this autologous segment. The animals were euthanized, and the penis was sectioned and histologically studied at intervals of 1, 2, 4, 6, 16 and 24 weeks. In 15 pediatric patients small intestinal submucosa was used for corporal body grafting. The grafting procedure was performed along the ventral (hypospadias cases) or dorsal (epispadias cases) surface of the corporal bodies. The tunica albuginea was incised full thickness at the point of maximal curvature down to the cavernosal tissue and the defect was filled with a single layer of small intestinal submucosa. RESULTS: Measurements of the animal small intestinal submucosa grafts did not reveal significant graft contraction through 6 months. There was no graft expansion or ballooning after pharmacological induction of an artificial erection. Histologically, marked inflammation at 1 week precipitously decreased to a normal appearing tunica albuginea at 3 and 6 months. In all clinical cases small intestinal submucosa was found to be technically easy to handle. Mean followup is 14 months (range 5 to 26). All patients have a straight phallus as documented by observation of spontaneous erections or artificial erection at the time of stage 2 hypospadias repair. No complications occurred. CONCLUSIONS: Small intestinal submucosa demonstrates tissue specific regeneration properties in the rat and human tunica albuginea. It is an off-the-shelf material that is safe, technically easy to use and readily available.