Update on Fetal Surgery

Society for Pediatric Urology 49th Annual Meeting

MEETING REVIEW Update on Fetal Surgery Highlights From the Society for Pediatric Urology 49th Annual Meeting April 29, 2000, Atlanta [Rev Urol. 2000;2(4):206-210] Key words: Fetal diseases • Myelomeningocele • Surgery, fetal • Valves, urethral A variety of innovative techniques in fetal surgery were presented at the Society for Pediatric Urology’s 49th Annual Meeting. Here, we focus on the current experience in surgery for myelomeningocele and posterior urethral valves. Fetal Surgery for Myelomeningocele As part of a panel discussion on the care of the patient with spina bifida in the 21st century, Michael Carr, MD, of the Children’s Hospital of Philadelphia presented the initial experience with surgery for a select group of patients with a prenatal diagnosis of myelomeningocele. Myelomeningocele is commonly associated with a Chiari II hindbrain malformation that consists of a small posterior fossa and downward displacement of the cerebellar vermis over the foramen magnum into the cervical spinal canal, with elongation of the brainstem and obliteration of the fourth ventricle.1 This leads to symptoms of hindbrain cranial nerve and spinal cord compression before 3 months of age in about 20% of infants with myelomeningocele.1 The etiology of the hydrocephalus in the majority of these children has been thought to be obstruction of cereReviewed by Ellen Shapiro, MD, FACS, FAAP, New York University School of Medicine, New York. brospinal fluid outflow from the fourth ventricle.2 It had been thought that herniation of the hindbrain seen with myelomeningocele was part of a cerebrospinal dysgenesis, but there is recent laboratory and clinical research to show that hindbrain herniation and hydrocephalus are acquired early in fetal life and progress during gestation.3-6 Spinal closure leads to worsening hydrocephalus, and ventriculoperitoneal (VP) shunts are placed to ameliorate this. Another area of experimental interest has focused on the 2-hit hypothesis, which attributes the neurologic problems to the initial error in embryologic development and to a secondary injury that occurs throughout gestation with continuous damage to the exposed neural tissue.7 If this is the case, intrauterine repair of the myelomeningocele may theoretically improve the neurologic outcome by decreasing the morbidity from trauma to the neural tissues.1,8 The first in utero myelomeningocele surgery was performed at Vanderbilt University in 1998 by Tulipan and Bruner.9 With their technique, the fetus is delivered through a small hysterotomy. The defect is repaired with the same standard neurosurgical closure used in control patients who undergo back closure after delivery. The fetus is then returned to the uterus, and the previously drained amniotic fluid is returned to the uterine cavity.8 Recently, the fetal surgical teams at Vanderbilt University and the Children’s Hospital of Philadelphia reported their findings in their first 29 patients and 10 patients, respectively, undergoing early fetal closure of the myelomeningocele.8 The Vanderbilt series showed that VP shunt placement at 6 months postnatally was required in 17 (59%) of 29 patients, compared with 21 (91%) of 23 control patients who had undergone closure of the myelomeningocele following delivery. All of the intrauterine repairs were performed between 24 and 30 gestational weeks. The investigators hypothesized that in utero myelomeningocele closure may promote the restoration of a more normal circulation of cerebrospinal fluid by relieving herniation of the hindbrain and cerebellum, a process that the mature newborn cannot undergo. This group has termed the phenomenon “hindbrain restoration,” which is possibly caused by the flexibility of the fetal cranium and plasticity of the poorly myelinated fetal brain. The functional neurologic levels of these patients cannot be accurately assessed, since most of them are not old enough to walk or toilet train. Nonetheless, the incidence of talipes is significantly reduced, but motor function has not been greater than that expected, based on the anatomic level continued on page 209 206 REVIEWS IN UROLOGY FALL 2000 Fetal Surgery continued from page 206 of the lesions. The Vanderbilt group did experience obstetric complications, including oligohydramnios, preterm uterine contractions, and preterm delivery. There was no significant neonatal morbidity associated with earlier gestational age delivery and lower birth weights.8 The Children’s Hospital of Philadelphia reported their experience in 10 patients.1 They performed myelomeningocele closure at 22 to 25 weeks’ gestation, and each fetus underwent serial fetal MRI. These studies showed significant cerebellar herniation and absence of spinal fluid spaces around the cerebellum at 19 to 24 weeks’ gestation. Six of 10 fetuses were subsequently delivered, and 4 were delivered prematurely. One of these neonates, delivered at 25 weeks, died. The 9 surviving neonates showed improvement in hindbrain herniation on the 3-week postoperative fetal scan. A postnatal scan showed only the mildest degree of hindbrain herniation in all 9 patients. One patient had a VP shunt placed for overt hydrocephalus. These MRI results supported the finding that after fetal closure, positive back pressure reduces the cerebellar herniation and expands the posterior fossa.1 The findings from these institutions are very promising. The pediatric urology group at Vanderbilt University has reported on the urologic aspects of 25 fetuses who have undergone in utero surgery.10 Sixteen patients, mean age 6.5 months, were evaluated urologically and were compared with myelodysplastic infants who had not undergone fetal intervention. Two patients had upper tract dilation on a sonogram, and 2 had reflux seen on a voiding cystourethrogram. Almost half of the patients (43%) had an areflexic bladder, while 6% and 19% showed uninhibited detrusor contractions and decreased compliance, respectively. Most of the patients had a normal bladder capacity for age, but 31% had a diminished bladder capacity. Two patients required long-term intermittent catheterization, and 1 was given anticholinergic medication. One patient experienced a significant urinary tract infection. These preliminary observations do not suggest improved lower urinary tract function following fetal surgery.10 It will be important to follow this group of patients closely to know how fetal surgery may impact on the GI and genitourinary (GU) tract dysfunction. In light of this, our laboratory has shown that in patients with myelomeningocele, there is a global defect in the development of smooth muscle in the lower GU and GI tracts by 20 weeks’ gestation.11 The peripheral nerve density is decreased in the smooth muscle, suggesting that an intact nervous system is important for the development of normal smooth muscle. Although fetal surgery may prevent progressive environmental injury to the somatic nervous system during the second half of gestation, it is unknown whether this will affect the development of smooth muscle during that period to achieve normal autonomic function.11 Fetal Surgery for Posterior Urethral Valves: Long-Term Postnatal Outcomes The Frank Hinman, Jr, Award was presented to 2 investigators at the Society for Pediatric Urology’s annual meeting. This year’s recipients were Nicholas M. Holmes, MD, and Laurence S. Baskin, MD, from the Univer- sity of California, San Francisco (UCSF). The UCSF’s fetal intervention team is world-renowned for its innovative approach to obstructive uropathy. They have recommended fetal intervention when there has been severe bilateral hydronephrosis with oligohydramnios. In addition, they study fetal urinary electrolytes, ß-microglobulin levels, karyotype, and renal sonography to evaluate the parenchyma for cortical cysts. These investigators reviewed the UCSF experience with fetal intervention for obstructive uropathy since 1981.12 Of the 40 fetuses evaluated, 36 underwent surgery. Only 39% (14/36) of the fetuses had a postnatal diagnosis of posterior urethral valves. The remaining patients had prune-belly syndrome or were females with urethral atresia or urogenital sinus anomalies. All of the fetuses with the diagnosis of posterior urethral valve had favorable electrolyte levels (hypotonic urine). Intervention was performed at a mean gestational age of 22.5 weeks. Only 2 patients were noted to have renal cortical cysts, 1 of whom also had increased parenchymal echogenicity. The fetuses underwent various in utero surgeries, including cutaneous ureterostomies (1), fetal bladder marsupialization (2), in utero valve ablation (2), and placement of a vesicoamniotic catheter (9). One patient who underwent valve ablation subsequently required a vesicoamniotic shunt for significant ascites. Another patient re- Main Points • Hindbrain herniation and hydrocephalus begin early in fetal life and progress during gestation. • Fetal closure of myelomeningocele can produce improvement in hindbrain herniation. • In theory, intrauterine repair of myelomeningocele may improve neurologic outcome by decreasing trauma to exposed neural tissue. • The rate of fetal demise following intervention for posterior urethral valves is 43%. • Fetal intervention for posterior urethral valves does not seem to alter the eventuality of renal failure. FALL 2000 REVIEWS IN UROLOGY 209 Fetal Surgery continued quired multiple shunt placements because of malfunction or migration of the shunt. Before delivery, there was a fetal demise of 43% (6/14). One pregnancy was electively terminated because of significant pulmonary hypoplasia, and the remaining deaths were caused by prematurity with postnatal respiratory failure. Long-term follow-up has shown that 5 (63%) of the 8 living patients have chronic renal insufficiency (mean serum creatinine level was 2.5 mg/dL in infants 6 months of age). Two patients have required renal transplantation. Five of the 8 living patients underwent urinary diversion (vesicostomy or cutaneous ureterostomy) and/or augmentation cystoplasty. Although some institutions are enthusiastic about fetal intervention, there is a fetal demise rate of 43% following fetal intervention for posterior urethral valves. It appears that inter- vention does not alter the outcome of renal failure, despite “favorable” fetal renal function. The investigators suggest that when counseling families, one must emphasize that intervention may assist in keeping the fetus viable to term, but will most likely not prevent the long-term sequelae of severe renal dysplasia associated with posterior urethral valves. ■ References 1. Sutton LN, Adzick NS, Bilaniuk LT, et al. Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA. 1999;282:1826-1831. 2. Dias MS, McLone DG. Hydrocephalus in the child with dysraphism. Neurosurg Clin North Am. 1993; 4:715-726. 3. McLone DG, Naidich TP. Developmental morphology of the subarachnoid space, brain vasculature, and contiguous structures, and the cause of the Chairi II malformation. Am J Neuroradiol. 1992; 13:463-482. 4. Bannister CM, Russell SA, Rimmer S. Prenatal brain development of fetuses with a myelomeningocele. Eur J Pediatr Surg. 1998;8(suppl 1): 15-17. 5. Osaka K, Tanimura T, Hirayama A, Matsumoto S. Myelomeningocele before birth. J Neurosurg. 1978;49:711-724. 6. Babcook CJ, Goldstein RB, Barth RA, et al. Prevalence of ventriculomegaly in association with myelomeningocele: correlation with gestational age and severity of posterior fossa deformity. Radiology. 1994;190:703-707. 7. Heffez DS, Aryanpur J, Hutchins GM, Freeman JM. The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury. Neurosurgery. 1990;26:987-992. 8. Bruner JP, Tulipan N, Paschall RL, et al. Fetal surgery for myelomeningocele and the incidence of shunt-dependent hydrocephalus. JAMA. 1999;282:1819-1825. 9. Tulipan N, Bruner JP. Myelomeningocele repair in utero: a report of three cases. Pediatr Neurosurg. 1998;28:177-180. 10. Holzbeierlein J, Pope JC, Adams MC, et al. Urodynamic profile of myelodysplastic children with spinal closure in utero [abstract]. Pediatrics. 1999;104:811. Abstract 17. 11. Shapiro E, Seller MJ, Lepor H, et al. Altered smooth muscle development and innervation in the lower genitourinary and gastrointestinal tract of the male human fetus with myelomeningocele. J Urol. 1998;160:1047-1053. 12. Holmes NM, Baskin LS. Fetal intervention for posterior urethral valves: long term postnatal outcomes. Paper presented at: 49th Annual Meeting of the Society for Pediatric Urology; April 29, 2000; Atlanta. Genitourinary Surgery continued continued from page 205 study of 99 women with transitional cell carcinoma of the bladder who underwent orthotopic urinary diversion with an ileal neobladder. Women were not candidates for the orthotopic neobladder if the tumor was located at the 210 REVIEWS IN UROLOGY FALL 2000 bladder neck or trigone. No recurrences have been noted in the urethra. The proportion of women in whom recurrences developed seems to be greater than in the male cohort. The increased recurrence rates are thought to be caused by the disease rather than the surgical approach. Discussion: The discussants validated the role of a neobladder in women with bladder cancer. ■