Alberto Lais

The Response of the Fetal Kidney to Obstruction

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.

Influence of Voiding Dysfunction on the Outcome of Endoscopic Treatment for Vesicoureteral Reflux

PURPOSEnSome patients with vesicoureteral reflux also experience voiding dysfunction. Dextranomer/hyaluronic acid copolymer (Deflux, Q-MED AB, Uppsala, Sweden) is an effective endoscopic treatment for vesicoureteral reflux. In an open label study we investigated the effect of voiding dysfunction on the efficacy of endoscopic treatment with dextranomer/hyaluronic acid copolymer in patients with vesicoureteral reflux.nnnMATERIALS AND METHODSnA total of 320 children 3 to 11 years old with grade II to IV vesicoureteral reflux confirmed by voiding cystourethrography underwent endoscopic treatment with dextranomer/hyaluronic acid copolymer. Of the patients 50 were re-treated with dextranomer/hyaluronic acid copolymer because of persistent reflux (grade II or greater). The first implantation technique was recorded on videotape. Voiding cystourethrography and micturition details were recorded at the 3 to 6-month followup visit and compared with baseline measurements.nnnRESULTSnAt baseline 13 patients had known voiding dysfunction and 18 were misdiagnosed as not having voiding dysfunction. Of the 50 patients who required re-treatment, the initial implant was correctly positioned in 45 according to the videotape. Endoscopic observation at the time of re-treatment revealed no evidence of the implant in 15 patients. The implant was displaced in 27 patients and remained correctly positioned in 3. A total of 27 patients had voiding dysfunction, the majority of whom had urgency and frequency incontinence, had not received any anticholinergic therapy and had a displaced implant.nnnCONCLUSIONSnUncontrolled voiding dysfunction contributed to endoscopic treatment failure with dextranomer/hyaluronic acid copolymer in our series. Therefore, we suggest that patients with voiding dysfunction be treated at least 6 months before endoscopic therapy with anticholinergics and/or micturition rehabilitation.

The use of intravesical oxybutynin chloride in patients with detrusor hypertonicity and detrusor hyperreflexia

Intravesical oxybutynin chloride was administered to 11 children and 7 adults with upper motor neuron bladder dysfunction who were refractory to oral use or who had intolerable side effects from the medication. This therapy was combined with clean intermittent catheterization to ensure complete emptying of the bladder. Five children and 5 adults discontinued therapy due to side effects or the inconvenience of the procedure. The remaining 6 children and 2 adults continue the medication successfully and have shown on followup urodynamic studies that bladder volumes are greater and intravesical pressures are lower than before medication. Intravesical oxybutynin chloride seems to be an effective modality to treat some of these patients but it is not without significant side effects.

The Neurosurgical Implications of Continuous Neurourological Surveillance of Children with Myelodysplasia

Between 1979 and 1990, 148 newborns with myelodysplasia were followed with serial urodynamic studies and neurological assessment. Of the patients 59 (40%) exhibited changes in neurological status by age 5 years, of whom 28 (19%) showed signs of deterioration. Most changes occurred before age 2 years. A total of 22 children underwent repeat neurosurgical exploration because of a change in urethral sphincter innervation (17), deterioration of function of the lower extremities (3), or changes on computerized tomography or magnetic resonance imaging (2). Postoperative urodynamic evaluation demonstrated improvement in 11 children, stabilization in 9 and further deterioration in 2. The earlier that a change was detected and secondary surgery was performed, the better the outcome. These findings indicate that the neurological lesion in myelodysplasia is a dynamic disease process requiring continuous neurological, orthopedic and urodynamic surveillance. Early identification and prompt neurosurgical reexploration seem to arrest and even reverse the neurological deterioration that takes place in a substantial number of these children.

Robot-Assisted Laparoscopic Ileal Bladder Augmentation: Defining Techniques and Potential Pitfalls

PURPOSEnLaparoscopic bladder augmentation has been limited because of the extensive suturing required. The use of robot-assisted laparoscopic (RAL) procedures may circumvent this limitation and allow more efficient suturing. The purpose of the study is to define the techniques and the potential pitfalls in performing RAL bladder augmentation in an animal model.nnnMATERIALS AND METHODSnTen swine underwent RAL bladder augmentation using 20 cm of ileum. In five animals, the bowel anastomosis was performed intracorporeally. In the others, the bowel ends were externalized through one of the ports, and a free-hand bowel anastomosis was performed. The operative time was recorded. The anastomoses were evaluated for patency and leakage.nnnRESULTSnThe mean procedure time was 6 hours 44 minutes (range 5 hours 50 min-8 hours 5 min) with a rapid learning curve. We identified minor technical modifications that were helpful, such as placement of hitch stitches, irrigation of the isolated bowel loop extracorporeally, and leaving the bladder wall attachment intact to maintain bladder suspension. Leakage at the bowel-bowel anastomosis occurred in one animal with use of a stapling technique. Because this could be a potentially fatal complication, we altered our technique to perform the bowel-bowel anastomosis outside the peritoneal cavity. Subsequently, there was no further incidences of bowel leakage, and all anastomoses were patent. The mean bowel-bowel anastomosis time was equivalent to using the two techniques. Leakage at the bowel-bladder anastomosis was seen in two animals, both occurring early in the series.nnnCONCLUSIONnRAL bladder augmentation can be safely and efficiently performed. There is a rapid learning curve. We identified minor technical modifications in techniques to help reduce operative time and potential complications. We recommend performing the bowel-bowel anastomosis outside the peritoneum to avoid the risk of leakage. Leakage at the bowel-bladder anastomosis may occur but can be managed with simple catheter drainage.

Retroperitoneal laparoscopy for renal biopsy in children

PURPOSEnWe report our experience with the retroperitoneal laparoscopic approach for treating pediatric patients and when the percutaneous needle approach is not possible due to uncontrolled hypertension, bleeding disorders, anti-clotting medications and anatomical abnormalities.nnnMATERIALS AND METHODSnRetroperitoneal laparoscopic renal biopsy was performed in 20 patients 2 to 18 years old (mean age 9.7) during a 16-month period. At the same time 53 percutaneous needle biopsies and 1 open biopsy were performed. The child is in a flank position, and 2 trocars are used via a direct vision approach. The first trocar is 12 mm. in diameter and positioned on the posterior axillary line, and the second trocar is 5 mm. in diameter and is entered 4 cm. anteriorly. Gentle dissection is done to free the lower pole of the selected kidney, biopsy forceps are used to grasp the specimen under direct vision and the biopsy site is fulgurated using bipolar electrocautery.nnnRESULTSnBiopsy was performed successfully in all cases except 1, which was converted to an open procedure. Mean operative time was 40 minutes, blood loss was minimal and mean hospital stay was 1.2 days postoperatively. No pain medication was required postoperatively, and all patients returned to their usual activities within 3 to 5 days. A minor intraoperative complication, which was a peritoneal tear with no postoperative sequelae, occurred in 1 case.nnnCONCLUSIONSnThe retroperitoneal laparoscopic technique is simple and safe, and does not require extensive laparoscopic experience. We believe that this approach is reliable, and has less morbidity and several advantages compared to open surgery. It should be selected as the first choice for treating pediatric patients when percutaneous needle renal biopsy is contraindicated.

Contralateral Ureteral Meatal Advancement in Unilateral Antireflux Surgery

PURPOSEnContralateral vesicoureteral reflux is a well-known development after successful unilateral ureteral reimplantation that is not apparently influenced by the reimplantation technique. We sought to determine whether bilateral reimplantation should be performed routinely in unilateral cases.nnnMATERIALS AND METHODSnFrom 1984 to 1995 we performed contralateral ureteral meatal advancement in 53 children 1 to 9.5 years old (mean age 2.5) undergoing surgery for unilateral grades II to V vesicoureteral reflux, including 12 with reflux in duplex systems. Ureteral meatal advancement involves a transverse Y shaped mucosal incision from the nonrefluxing orifice to the opposite hemitrigone. The inferior half of the ureteral orifice is then advanced toward the midline using 3 or 4 long-term resorbable sutures. The control group included 98 children who underwent unilateral surgery for grades II to V reflux from 1990 to 1995.nnnRESULTSnNo evidence of vesicoureteral reflux was observed in the 53 children who underwent contralateral meatal advancement. There was no obstruction or other complications. At followup contralateral reflux was found in 11 controls after unilateral reimplantation.nnnCONCLUSIONSnContralateral reflux has been reported in up to 27% of previously reported cases and in 11% of our control group after successful unilateral antireflux surgery. Contralateral ureteral meatal advancement has proved effective for preventing reflux in 100% of cases. It requires minimal invasion of the nonrefluxing ureter, and little additional operative time and cost.

Bladder bioengineering: our experience

Background Tissue engineering techniques aim to substitute or restore the structure and function of organs and systems. The bladder has been recently considered as a promising organ for tissue engineering regeneration for augmentation or substitution. We present our experience on an experimental model and a pilot clinical study. Methods The experimental model: 10 minipigs underwent 50% volume cystectomy and bladder wall substitution using a 5 × 4 cm acellular intestinal submucosa membrane as graft, covered by omentum. In 4 pigs, autologous stem cells, bone marrow-derived, were injected into the scaffold. The animals were sacrificed at 5 weeks, and 3 months from grafting. The clinical study: 5 exstrophic patients, 8–17 years old (mean 10.4 years), presenting poor bladder capacity and compliance after bladder closure and urethra-genitalia reconstruction, who refused enterocystoplasty received intestinal submucosa membrane (cm 5 × 4) bladder grafting. Follow-up lasted 3 years. Results All animals but 1 survived. The regenerated bladders had normal capacity. The newly developed wall was lined by normal looking mucosa. At histology, 3 layers were well defined: urothelium (inner), fibrocells and muscular cells within rich connective tissue (intermediate) and a well vascularized adventitial coat. No residual scaffold was observed at 3 months. The muscular component was 28% in the engineered bladder wall, versus 44% in the native wall (p<0.05). In the clinical study at 6 months follow-up, bladder capacity increased from 102 mls to 136 mls (mean). The difference was significant (p<0.05). At biopsy, the newly generated bladder wall appeared similar to the animal model histology. No complications occurred, but 2 patients required enterocystoplasty at 3 years follow-up. Conclusions Bladder regeneration is feasible by tissue engineering techniques in animal models and in humans. Functional and histological results are not as with normal bladder wall. Further improvements are necessary before any extensive clinical application.