Pressure-limited vesico-amniotic shunt tube for fetal obstructive uropathy.

INTRODUCTION: In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development. MATERIALS AND METHODS: We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology. RESULTS: Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 +/- 41 mL with a valve shunt and 8.8 +/- 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 +/- 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt. CONCLUSION: A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.

Early bladder wall changes after creation of obstructive uropathy in the fetal lamb.

Vesico-amniotic shunting of obstructive uropathy in fetal lambs produced a thick-walled, poorly compliant bladder. We report the early histological changes in the obstructed bladder wall. We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. Vesicostomy or vesico-amniotic shunt tube insertion and biopsy of the bladder wall were performed 21 days later. The fetuses were delivered at term (145 days) and the kidneys and bladder sampled for histology. Colloidal iron (Col Fe), and alpha-smooth muscle actin (alpha-SMA) immunohistochemical stains were used for these samples. Seventeen fetuses were shunted with 15 biopsies taken at that time. Six (shunt failure or missed urachal ligation) were excluded. All biopsies taken at shunting had positive Col Fe and alpha-SMA. Term lambs had mild multicystic dysplastic kidney (MCDK) in five, severe MCDK in two, and hydronephrosis in four. All bladders had small volume and were severely fibrotic. Fetal shunt operations 3 weeks after the creation of obstructive uropathy provided partial preservation of renal histology but did not preserve normal bladder histology. We suggest that the high hyaluronic acid synthesis activity or hyperplasia of the myofibroblasts in the dilated fetal bladder wall at the time of shunting results in irreversible damage to the developing bladder muscle and fibrosis.

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective.

PURPOSE: The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention. METHODS: We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination. RESULTS: Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 +/- 5 mL) compared with controls (71 +/- 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis. CONCLUSIONS: In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.

Fetal hydrops in experimental obstructive uropathy resolves after vesicostomy formation: is this cause and effect?

The association of obstructive uropathy and hydrops is rare but often fatal. Hydrops has been observed in our fetal lamb model with obstructive uropathy. We created a vesicoamniotic shunt 21 days after creating the obstruction to explore the effect of relieving the obstruction on the hydrops. Fetal lambs underwent urethral and urachal ligation at 60 days gestation. We created a vesicostomy (female) or urethrostomy (male) in 12 lambs to release the pressure 21 days after creating the obstruction. The fetuses were delivered at term (145 days), and the urinary tract was removed for histological examination. Six fetuses had severe hydrops at the time of the vesicostomy (group A), and six had no hydrops (group B). Only two lambs from group A survived (33%), and four lambs survived from group B (66%). Three lambs miscarried, and one was stillborn from group A. Two lambs from group B miscarried. In our fetal lamb model, hydrops appears to be associated with massive urinary ascites. We hypothesize that a connection exists between urinary ascites and hydrops. Vesicostomy, by bypassing the obstruction, may allow the lambs to recover from their hydrops. However, it is possible that by 21 days after creation of the obstruction, the damage created by the hydrops is irreversible.

The early effects of urinary tract obstruction on glomerulogenesis.

PURPOSE: Our obstructive uropathy model in fetal lambs showed that renal cystic changes appeared 3 weeks after obstruction. In this study, the authors investigated the changes resulting from complete urinary tract obstruction in the first 7 days after obstruction. METHODS: An obstructive uropathy was created in fetal lambs at 60 days' gestation by ligating the urethra and urachus. They were delivered 48 hours, 3 days, 5 days, and 7 days later by cesarian section. The kidneys were removed and processed for histologic examination. RESULTS: Eighteen fetuses were operated on and 15 (4 at 48 hours, 4 at 3 days, 2 at 5 days, and 5 at 7 days; 83%) survived. Macroscopically, bladder dilatation and slightly dilated ureters were identified from 48 hours. Microscopically, dilatation of proximal tubules started from 48 hours after obstruction and increased by 7 days. Glomerular cysts in the nephrogenic zone also were identified from 48 hours. Dysplastic changes were not found. CONCLUSIONS: The first areas in the developing kidney that suffer damage after obstructive uropathy are the proximal tubule and the nephrogenic zone. This change started 48 hours after obstruction. Shunting procedures need to be performed considerably earlier than previously thought.

Effects of early vesicostomy in obstructive uropathy on bladder development.

PURPOSE: Creation of a vesico-amniotic shunt for obstructive uropathy removes the normal fetal urination cycle. It is unclear how this affects bladder function at term. The authors measured the bladder volume and reviewed the bladder histology after fetal vesicostomy. METHODS: The authors created an obstructive uropathy in fetal lambs at 60 days' gestation by ligating the urethra and urachus. Vesicostomy (female) or urethrostomy (male) were performed 21 days after obstruction to release the obstruction. The fetuses were killed at term (145 days). RESULTS: Thirteen fetuses were shunted. Seven fetuses miscarried after shunting. Six survived, and 3 had a successful shunt with a very small bladder (5 to 7 mL). Two had incomplete shunts that failed some time after shunting. These both had huge bladders (399 mL). In one, the obstruction was unsuccessful. Histologic examination showed that the obstruction caused bladder muscle hypertrophy. Shunted lambs had severe fibrosis of the bladder wall and very poor bladder compliance. CONCLUSIONS: Shunt operations after obstructive uropathy may salvage the kidney but fail to preserve bladder function. The fetus needs a normal urination cycle for normal bladder development. This requirement exists even when the obstruction is successfully bypassed.

Six cases of children with a benign cervical tumor who required tracheostomy.

Cervical tumors sometimes cause airway obstruction. We have treated six children with benign cervical tumors who required tracheostomy. Two cervical and one glossal lymphangiomata treated with local injection of OK432 after creating a tracheostomy were successfully decannulated after the treatment. One patient with a giant cervical lymphangioma needed an EXIT (ex utero intrapartum treatment) procedure. He underwent tracheostomy at 10 months of age after long-term endotracheal intubation, but he died of sepsis and hypoxic brain damage at 18 months. One patient with a subglottic hemangioma treated with steroids finally achieved closure of the tracheostomy at 2 years of age. A 7-year-old girl with a tracheal schwannoma underwent tracheostomy performed a week after admission, but she already had hypoxic brain damage resulting from problems with intubation. Most patients with a lymphangioma or hemangioma in the cervical region have required early tracheostomy before commencing treatment with OK-432 or steroids. If there is any sign of possible airway compromise, then it is vital to perform an early tracheostomy, even for benign tumors.

Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb.

PURPOSE: It was still unclear how urinary tract obstruction alters normal nephrogenesis and leads to renal dysplasia. The authors created an obstructive uropathy model in fetal lambs and reviewed the pathology of the obstructed kidney to determine the optimal timing for decompression of the obstruction. METHODS: Obstructive uropathy was created in fetal lambs at 60 days' gestation by ligating the urethra and urachus. They were delivered 20 to 31 days later by cesarian section. The kidneys were processed for histologic examination. RESULTS: Thirty-four 60-day lambs were operated on. Dysplastic changes were noted in 25 fetuses, and 24 fetuses had cysts in the nephrogenic zone. The cystic components in multicystic dysplastic kidneys (MCDK) are mainly in the proximal tubules. CONCLUSIONS: In utero urinary tract obstruction causes reduction of numbers of functioning nephrons and produces cysts in the nephrogenic zone and in the deeper cortex. These cysts and dilated proximal tubules suppress new nephron formation. Twenty days after obstruction, there were early features of dysplasia, but the nephrogenic zones still were present. Early shunting may salvage renal function.

Successful resection of prostatic rhabdomyosarcoma by the posterior sagittal approach combined with preoperative chemotherapy.

The authors used a posterior sagittal approach to successfully remove a huge prostatic rhabdomyosarcoma from a 3-year-old boy after he had received intensive chemotherapy. This procedure enables safe removal of the prostatic rhabdomyosarcoma under direct vision and with minimal damage to other pelvic organs.