Fetal surgery: a critical review.

Therapeutic fetal surgical procedures are predicated upon the ability to make an accurate fetal diagnosis. The earliest open fetal surgical procedures were introduced in the 1960s to treat Rh isoimmunisation. They were introduced when it became possible to predict impending fetal demise. Open procedures were abandoned when percutaneous approaches proved superior. The introduction of fetal ultrasound allowed the diagnosis of other congenital anomalies, some being amenable to fetal interventions. Open fetal surgical procedures were initially utilised, with significant maternal morbidity. For some anomalies, percutaneous approaches became favoured. In general, all of these procedures involved significant risks to the mother, to save a baby that was likely to die before or shortly after birth without fetal intervention. Fetal repair for myelomeningocele was a "sea change" in approach. The same maternal risks were taken to improve the quality of life of the affected fetus, not save its life. The completion of the "MOMs Trial" has occasioned a "tsunami" of centres in North America applying this approach. Others are attempting percutaneous repairs, with mixed results. This paper reviews the history of fetal surgery, focusing on the themes of the tension between accurate diagnosis and prognosis and open versus "minimally invasive" approaches.

Development of an animal model to study congenital urinary obstruction.

PURPOSE: We outline the development of a reliable model of obstructive uropathy in fetal lambs highlighting our understanding of the critical time points for interventions and the variability of any such model. We identify some discoveries that may have clinical implications. METHODS: The model requires 60-day-gestation fetal lambs. In lambs, glomerulogenesis is complete by 90 days gestation. (Term is 145 days.) The ability to develop a reliable method of creating bladder outlet obstruction in females, ligating both the urethra and urachus was critical. The lambs are bred to an accuracy of ±24 h. RESULTS: Creating the model at 50-60 days gestation, produces different expressions of renal dysplasia in groups of lambs undergoing identical interventions at the same stage of gestation. Early complete urethral obstruction can produce the Potter phenotype. An appropriately timed vesico-amniotic shunt preserves renal development, producing a shrunken, non-compliant bladder. Shunting the normal fetal bladder at 80 days gestation produces a similar bladder. Provision of a low-pressure valve in the shunt preserves bladder development and compliance. Using a high-pressure shunt produces results similar to non-shunted lambs. DISCUSSION: We developed a reliable animal model for obstructive uropathy. Being alert to peripheral results can lead to new findings.

Examination of the secondary palate on stored 3D ultrasound volumes of the fetal face.

OBJECTIVES: To examine the use of oblique planes from stored three-dimensional (3D) ultrasound volumes of the fetal face for viewing the secondary palate at various gestational ages. METHODS: 3D ultrasound volumes of the fetal face acquired with surface rendering at 15-35 weeks' gestation in 31 fetuses with confirmed normal secondary palates were reviewed. The secondary palate was viewed in three oblique planes targeted at the uvula: the oblique axial, the oblique sagittal and the reverse face view. The detection and appearance of the secondary palate, including the soft palate, with these views at various gestational ages were compared. RESULTS: The various surfaces of the secondary palate could be viewed in all 31 fetuses in the oblique axial and the reverse face views, and in all except two fetuses in the oblique sagittal view. Both of these were < 19 weeks' gestation, at which age the uvula could not be identified clearly in this plane. CONCLUSIONS: The oblique axial, the oblique sagittal and the reverse face view targeted at the uvula allow visualization of the various aspects of the fetal secondary palate on 3D ultrasound in the second and third trimesters of pregnancy. The uvula could be used as a landmark for viewing the soft palate, but was not always easily identifiable before 19 weeks' gestation.

A case of amyoplasia in a monochorionic twin pregnancy: a sequela from twin-twin transfusion syndrome?

OBJECTIVE: To present and discuss the sonographic and clinical findings in one twin of a monochorionic pair affected by amyoplasia. METHODS: On ultrasound examination at 21 weeks in a monochorionic twin pregnancy, twin I was smaller, hydropic, with multiple contractures consistent with amyoplasia and oligohydramnios. Twin II was anatomically normal with polyhydramnios. RESULTS: The twins were delivered at 28 weeks' gestation. The clinical findings were consistent with twin-twin transfusion syndrome (TTTS). CONCLUSION: It is postulated that TTTS may be a causative factor in the excessive incidence of amyoplasia in monozygotic twin pregnancy.

Activated extracellular signal-regulated kinase correlates with cyst formation and transforming growth factor-beta expression in fetal obstructive uropathy.

Human renal dysplasia is frequently associated with urinary tract obstruction and the abnormal expression of mitogen-activated protein kinase (MAPK). Here, we determined the renal responses and MAPK expression in developing kidneys that were obstructed in fetal lambs. Kidneys were harvested at various times after obstruction (gestation day 60) through normal term (day 145). Dilation of Bowman's capsule and proximal tubules was seen 2 days after obstruction and involved the whole cortex 18 days later, with numerous cysts present throughout the kidney at term. The proliferation marker Ki-67 and transforming growth factor-beta (TGF-beta) were detected 2 days after obstruction and progressively increased in tubules, cysts, and the interstitium. In control kidneys, p38 was expressed in tubules only during the fetal stage, whereas phosphorylated extracellular signal-regulated kinase (P-ERK) was limited to ureteric buds and collecting ducts at all stages examined. However, Jun-N-terminal kinase (JNK) was absent in the fetal kidney but present in tubules at term. In obstructed kidneys, cyst epithelia were positive for p38 and P-ERK but negative for JNK throughout all stages. These studies show that P-ERK correlated spatially and temporally with Ki-67 and TGF-beta expression, which suggests that ERK may contribute to cyst formation and fibrosis in the obstructed fetal kidney.

Antenatal diagnosis of anophthalmia by three-dimensional ultrasound: a novel application of the reverse face view.

The prenatal diagnosis of anophthalmia can be made on the demonstration of absent eye globe and lens on the affected side(s) on two-dimensional ultrasound examination, but when the fetal head position is unfavorable three-dimensional (3D) ultrasound may reveal additional diagnostic sonographic features, including sunken eyelids and small or hypoplastic orbit on the affected side(s). We present two cases of isolated anophthalmia diagnosed on prenatal ultrasound examination in which 3D ultrasound provided additional diagnostic information. The reverse face view provides valuable information about the orbits and the eyeballs for prenatal diagnosis and assessment of anophthalmia.

Viewing of the soft and the hard palate on routine 3-D ultrasound sweep of the fetal face--a feasibility study.

OBJECTIVES: To report a technique to view the fetal soft and hard palates, utilizing acquired routine 3-D volumes of the fetal face. METHOD: The axial, sagittal and coronal planes in acquired volumes of 3-D surface rendering of 5 normal fetal faces obtained at 19, 21, 23, 26 and 28 weeks, respectively, were reviewed by focusing on the uvula. RESULTS: The surfaces of the soft and the hard palate could be viewed in oblique axial, oblique sagittal and targeted coronal planes in all fetuses. CONCLUSION: Rotating or tilting of the axial, sagittal and coronal planes of the fetal head allows the visualization of the various aspects of the soft and hard palates, with the uvula as a useful landmark.

A case of thanatophoric dysplasia: the early prenatal 2D and 3D sonographic findings and molecular confirmation of diagnosis.

OBJECTIVE: To present the early 2D and 3D ultrasound findings and the molecular confirmation in a case of thanatophoric dysplasia. METHODS: On ultrasound examination, there was frontal bossing, increased nuchal translucency and short limbs at 12 weeks' gestation and a small thorax and short and bowed long bones on 3D at 16 weeks. Amniocentesis and DNA analysis confirmed the mutation of FGFR3 gene indicating thanatophoric dysplasia. RESULTS: After medical termination of pregnancy, the postmortem X-ray and pathology examination findings were consistent with the diagnosis. CONCLUSION: 3D anatomy scan and molecular confirmation may be helpful in early diagnosis and genetic counseling of thanatophoric dysplasia.

Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group.

Successful treatment of localized non-Hodgkin's lymphoma (NHL) in childhood with 18 months of cyclophosphamide, vincristine, methotrexate (MTX), and prednisone (COMP) prompted a randomized clinical trial to determine whether a 6-month course of the same therapy was as effective as an 18-month course when combined with local irradiation. Two successive Childrens Cancer Study Group (CCSG) protocols (CCG 551 and CCG 501) entered 232 eligible patients from October 1979 until April 1986. Initially, all children with localized disease were considered eligible, but by a subsequent amendment, those with lymphoblastic (LB) histology were excluded. Hence, the study population consisted of 211 patients with nonlymphoblastic (NLB) and 21 with LB disease. Early relapses (before 6 months) occurred in 13 patients with NLB histology. Late relapses were seen in seven patients, three with LB histology. Among the 104 randomized patients who followed the prescribed therapy, there were four recurrences and no differences between 6-month and 18-month therapy. The overall survival for NLB disease was 91% on CCG 551 and 98% on CCG 501. We conclude that 6 months of COMP is excellent therapy for children with localized NLB NHL.

Serum creatine kinase levels parallel the clinical course for rhabdomyomatous Wilms tumor.

A right-sided renal mass in an 11-month-old girl was diagnosed by percutaneous needle biopsy as Wilms tumor, which on histologic examination was found to be predominantly rhabdomyomatous. As part of the examination, serum creatine kinase (CK) and CK-MB levels were measured and were significantly elevated at 994 U/L (reference range, 42-180 U/L) and 40 U/L (reference range, 0-3 U/L), respectively. Subsequently, an 8-month-old girl was admitted to the hospital with septicemia and was found to have an abdominal mass. A diagnosis of bilateral Wilms tumor was made following percutaneous biopsy of both kidneys; histologic examination confirmed that the tumor was predominantly rhabdomyomatous. Serum CK and CK-MB levels also were measured and were significantly elevated at 685 U/L and 84.4 U/L, respectively. In both cases, the serum CK and CK-MB levels reflected the clinical course; elevation in serum levels was associated with tumor recurrence, infarction, or chemotherapy-related necrosis. We conclude that these enzymes have clinical usefulness as markers for Wilms tumor showing rhabdomyomatous morphologic features.

Aortic thrombosis after umbilical artery catheterization.

Neonatal arterial thrombosis has become more common with the use of umbilical artery catheters; however, catheter-induced aortic thrombosis is rare. A review of the literature disclosed a 100% mortality from medically managed neonatal aortic thrombosis. Two cases of umbilical artery catheterinduced acute neonatal thrombosis were managed successfully by surgical thrombectomy. Severe lower extremity ischemia and hypertension with aortic occlusion developed in two neonates, and intractable congestive heart failure developed in one of the neonates. This seems to be the first documented report of successful surgical treatment of umbilical artery catheter-induced aortic thrombosis. Acute neonatal aortic occlusion should be considered a surgical emergency.

Fetal diagnosis and fetal surgery.

Accurate fetal diagnosis became possible by the steadily increasingly complex techniques of amniocentesis, ultrasound, and ultrasound-guided fetal blood sampling and chorion villous sampling. A high degree of diagnostic accuracy for a wide variety of structural and metabolic anomalies is required. The field of fetal diagnosis has been extended to the point that a journal dedicated to this subject alone is a viable proposition. It is becoming apparent, however, that lesions that were well known and well understood when recognized in neonatal life appear in general to have a worse prognosis if the lesion is diagnosed in utero. Fetal surgery began with attempts to perform in utero transfusions for babies with erythroblastosis fetalis. For a while, there was competition between open surgical procedures and the percutaneous placement of blood through catheters introduced into the fetal peritoneal cavity from outside the mother's abdomen. For fetal transfusion, closed techniques proved far safer and just as efficacious. There has been a worldwide interest in shunting of hydrocephalus and obstructive uropathy. The results of shunting hydrocephalus have been disappointing, with most of the patients surviving, but most of the survivors being severely handicapped. The results of shunting obstructive uropathy were that only about 50 per cent of the babies survived, but it appeared that those that did survive did well. Other lesions that have been shunted have been hydrothoraces or fetal ascites. A limited number of open procedures have been carried out in the last few years in San Francisco, and it may well be that diaphragmatic hernia (in appropriately selected patients) will be a lesion that can be corrected by in utero surgery. The future of this field is exciting, but before this form of treatment becomes routine, the ethical implications of the possibility of fetal surgery must be defined much more clearly than is currently the case.

Magnetic resonance imaging as an adjunct to planning an anorectal pull-through.

Magnetic resonance imaging (MRI) is a relatively new diagnostic tool that generates images of sections of the body taken in any plane. We report the use of MRI as a tool to plan surgical procedures in patients with imperforate anus, imaging the pelvis and lumbosacral spine in the sagittal, transverse, and coronal planes. MRI clearly reveals the extent of the pelvic musculature even in patients with severe sacral agenesis. MRI is extremely useful in assessing patients under consideration for reoperation, clearly demonstrating the relationship between the pulled through colon and the "striated muscle complex." A very useful addition is the ability, on the same study, to detect previously unsuspected anomalies such as tethered cord, lipoma of the filum terminale, and renal dysplasia. We conclude that MRI is a very useful examination in selected patients with imperforate anus.

A case of zinc chloride ingestion.

Zinc chloride is a powerful corrosive agent. Reports of zinc chloride ingestion are uncommon, and there is little information about its toxicity and management. The authors report the clinical course of a 10-year-old girl who accidentally ingested an acid soldering flux solution (pH, 3.0; zinc chloride, 30% to < 60%). Systemic effects after the ingestion were unremarkable except for lethargy. Thus, chelation therapy was not considered. Severe gastric corrosion was caused by local caustic action. An antral stricture of the stomach approximately 3 weeks after the ingestion developed, and she underwent a modified Heineke-Mikulicz antropyloroplasty. Postoperatively, she made an uneventful recovery. On follow-up, although she was tolerating a normal diet, results of a barium meal showed her stomach to be totally aperistaltic. Results of a nuclear medicine study showed moderately delayed gastric emptying. Careful long-term follow-up is necessary, because there is potential risk for malignancy in the damaged stomach.

Immunologic response in splenectomized and partially splenectomized rats.

One of the following procedures was carried out in 112, 200-gr, Sprague-Dawley rats: (A) sham operation, (B) hemisplenectomy, (C) 90% splenectomy, (D) total splenectomy and autologous spleen transplants in either omental, muscle, or subcutaneous pouch after total splenectomy, and (E) homologous splenic transplants after splenectomy. The rats were challenged intravenously with sheep, cat and guinea pig erythrocytes 6 wk, 3 mo, and 6 mo postoperative. All totally splenectomized rats had significantly reduced primary responses, regardless of whether fragments of splenic tissue had been grafted or not. There was initial lowering of primary response in partially splenectomized animals but they responded significantly better than totally splenectomized rats. After 6 mo the primary response in the hemisplenectomy group was not significantly different from the nonoperated control group. The primary response in the 90% splenectomy group had improved significantly when compared to the total splenectomy group and normal controls. Total splenectomy and partial splenectomy did not appreciably reduce the ability to mount secondary and teritary responses.

Sodium deficit causing decreased weight gain and metabolic acidosis in infants with ileostomy.

The records of 11 infants, 25 to 38 weeks' gestation, with metabolic abnormalities induced by ileostomy fluid losses were reviewed. At operation for necrotizing enterocolitis (NEC) (9) or meconium ileus (MI) (2), they weighed between 1,100 and 3,100 g and were from one to 41 days old. All developed total body sodium depletion and metabolic acidosis from ileostomy bicarbonate loss. In seven, sodium depletion was severe enough to require supplementation; six initially lost or failed to gain weight despite being fed adequate diet and calories. However, after receiving sodium supplementation (three with NaCl and three with NaHCO3), these six patients gained weight and improved their metabolic acidosis. The other five subjects did not initially receive sodium supplementation. Four gained weight; one of these later received supplemental NaHCO3 for a metabolic acidosis. The fifth patient failed to thrive until his ileostomy was closed. All infants initially had urine Na less than 10 mEq/L and normal serum Na. All infants whose urine Na rose above 10 mEq/L and had serum HCO3- greater than or equal to 20 mEq/L grew adequately. A direct relationship existed between ileostomy output and sodium intake required for growth. This expressed mathematically (Na intake = 1.2 + [0.13 x ileostomy output] shows a basal sodium need (with no ileostomy output) of 1.2 mEq/kg/d and an additional requirement of 0.13 mEq/kg/d of sodium for each mL/kg/d of ileostomy output. We conclude that infants with ileostomies are at extreme risk of total body sodium depletion with resultant metabolic acidosis and inadequate weight gain. These infants require sodium supplementation with a combination of NaCl and NaHCO3.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of chick embryo hyperflexion on tracheoesophageal development.

Chick embryos were hyperflexed by placement of a ligature at two critical stages in the development of the foregut, in order to test the theory that esophageal atresia and tracheoesophageal fistula result from embryonic hyperflexion. Only one "H-type" tracheoesophageal fistula was found. There were no significant disturbances of either tracheal or esophageal growth.

Creation and repair of diaphragmatic hernia in the fetal lamb: techniques and survival.

Diaphragmatic hernias were created in 54 fetal lambs at 72 to 82 days gestation via a left thoracotomy. The diaphragmatic hernia was repaired in 30 lambs at 106 to 123 days gestation, and 14 of these lambs subsequently aborted. The majority of those surviving to term were delivered for survival. Four lambs with an unrepaired diaphragmatic hernia were intensively resuscitated at delivery and their diaphragmatic hernias repaired; survival in these lambs ranged from 20 minutes to 89 hours. Nine lambs with repaired diaphragmatic hernia were resuscitated following delivery; survival times ranged from one hour, 45 minutes to 123 days, with three lambs surviving to be sacrificed at 43, 62, and 123 days. Three of the lambs that died before sacrifice, died of causes unrelated to their lung function. These results show that in-utero repair of the diaphragmatic hernia in the fetal lamb results in improved survival. We feel, however, that direct application of these results in humans would be premature.

The creation and repair of diaphragmatic hernia in fetal lambs: morphology of the type II alveolar cell.

A model for creating and repairing diaphragmatic hernia in fetal lambs has been developed. Morphometric studies of the type II alveolar cells were carried out in three groups of term lambs. The upper lobes only were sampled. Morphometric analysis of the 30 type II cells from each lobe showed that while there were no differences between the left upper lobe (LUL) and right upper lobe (RUL) cells in normal lambs, there were significant differences between sides in the experimental groups. In lambs with a nonrepaired diaphragmatic hernia (DH) the type II cells were significantly smaller in the LUL compared with the RUL. In lambs with a repaired DH, the LUL type II cells were significantly larger than those in the RUL. There were some trends when the groups were compared, but in general they did not reach statistical significance. These findings suggest that local factors profoundly influence the development of these cells.

Early fetal obstructive uropathy produces Potter's syndrome in the lamb.

BACKGROUND: If creating an obstructive uropathy early in glomerulogenesis produces MCDK (Multicystic Dysplastic Kidney), then a very early obstruction may produce Potter's Syndrome (PS) with oligohydramnios. METHODS: Fetal lambs at 50 days' gestation underwent urethral and urachal ligation using fine SILASTIC (Dow Corning, Midland, MI) tubing and were delivered by cesarean section at 145 days' gestation. At the time of death, kidney weight, length, and lung volumes were measured. These samples were examined histologically. Urinary sodium, chloride, potassium, and osmolarity also were measured. These were compared with normal-term fetuses. RESULTS: One ewe miscarried. Two of 3 of 50-day obstructive uropathy lambs survived. The 2 survivors had dysplastic kidneys. One with large gastroschisis did not have PS but the other had renal, pulmonary, and chest wall hypoplasia. Both male lambs had undescended testes with a large bladder. Kidney weights were 2 g in the PS lamb and 16 g in controls. Lung volume was 84 mL in the PS lamb and 340 mL in controls. The lamb's face was compressed and the fetus was hydropic. Urine sodium, potassium, and osmolarity levels were higher than that of controls. CONCLUSIONS: This is the first successful model ligating the penile urethra and urachus in a 50-day lamb. The authors' previous 60-day model did not have PS, but an earlier obstructive uropathy caused MCDK with PS.