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.

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.

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.

Different phenotypes of dysplastic kidney in obstructive uropathy in fetal lambs.

PURPOSE: The cause of cyst production in renal dysplasia is uncertain. The authors hypothesized that different patterns of renal dysplasia result from variations in the timing and site of the urinary tract obstruction. METHODS: The authors operated on fetal lambs at 50 and 60 days' gestation. Male lambs underwent urethral and urachal ligation and female lambs unilateral ureteric ligation. They were delivered by cesarean section at 145 days' gestation and killed. RESULTS: Of 12 lambs operated on at 50 days' gestation, 4 survived. Of 26 lambs operated on at 60 days, 21 survived. The authors identified 3 types of dysplastic kidneys. Type A, fibrotic kidneys (2.2 g) with no cysts and interstitial fibrosis. There were reduced numbers of proximal tubules, but distal tubules and collecting ducts persisted. (50-day obstruction, n = 5 kidneys); type B, Sponge-like kidneys (37g): these had large cysts with minimal interstitial fibrosis. (87% of 60-day uretheral and urachal ligation model n = 12 kidneys); Type C, Small kidneys (4.8 g) with no large cysts (60-day Ureteric ligation model n = 7 kidneys). CONCLUSION: The authors produced 3 different types of renal dysplasia by creating urinary tract obstruction at different sites and gestational ages.

Testicular proximity can induce gubernaculum formation after delivery.

PURPOSE: This paper presents the hypothesis that after delivery as late as 38 weeks' gestation, a testis placed near the internal ring can induce the formation of a gubernaculum and undergo a belated but otherwise normal descent. METHODS: Two boys with a gastroschisis were each born with one of their testes prolapsed through the defect. The testis was sutured just lateral to the deep inferior epigastric vessels at the time of the primary closure of the gastroschisis. RESULTS: One boy born at 34 weeks had his left testis prolapsed through a left-sided gastroschisis defect. At 3 months, he was admitted to the hospital with a large left inguinal hernia. The repair was complicated by the presence of a large mass of jellylike tissue extending through the internal ring to the upper scrotum. A second boy was born at 38 weeks' gestation. The testis made its way uneventfully into the right hemiscrotum by 10 months of age. CONCLUSION: These cases suggest that testicular proximity is a critical factor in the formation of the gubernaculum and that the testis can induce the formation of the gubernaculum as late as 38 weeks gestation.

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.

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.

Glomerular size in renal dysplasia secondary to obstructive uropathy: a further exploration of the fetal lamb model.

BACKGROUND/PURPOSE: Creating an obstructive uropathy early in glomerulogenesis would produce multicystic dysplastic kidneys (MCDK). Measuring the mean planar area of the glomeruli (GMPA) may clarify the pathogenesis of MCDK. METHODS: Fetal lambs at 60 days' gestation had their left ureter ligated and were delivered by cesarian section at 145 days' gestation. Kidney weight and length were recorded. GMPA in 3 zones (outer, middle, inner) of the sectioned kidney was measured using a computerized planimeter. The obstructed kidneys were compared with contralateral unobstructed kidneys. The unpaired Student's t test was used to determine significance. RESULTS: One ewe miscarried. Four of 5 (80%) 60-day lambs survived. All had dysplastic kidneys. Mean kidney weights were 4.3 +/- 0.84 g in MCDK and 16.8 +/- 3.6 g in controls (P< .05). The GMPA of the outer, middle, and inner zones of the MCDK were 2.7 x 10(-3) mm2, 3.2 x 10(-3) mm2, and 4.0 x 10(-3) mm2, respectively. Controls were 2.8 x 10(-3) mm2, 4.4 x 10(-3) mm2, and 6.0 x 10(-3) mm2. The glomeruli of 60-day fetal kidneys were 3.0 x 10(-3) mm2, 6.1 x 10(-3) mm2, and 11.0 x 10(-3) mm2. MCDK had smaller glomeruli in the inner and middle zones than controls. CONCLUSION: Fetal glomeruli appear to grow from the inner zone of the kidney. Early urinary tract obstruction stops this growth.

The pathogenesis of dysplastic kidney in a urinary tract obstruction in the female fetal lamb.

BACKGROUND/PURPOSE: The type of renal dysplasia resulting from obstructive uropathy depends on the completeness of the obstruction and its timing with respect to the stage of glomerulogenesis at the time of the obstruction. The authors created a successful obstructive uropathy model in the female fetal lamb to demonstrate the differing pathogenesis of renal dysplasia. METHODS: Female fetal lambs at 60 and 90 days' gestation had their urethra and urachus ligated transabdominally and were delivered by cesarean section at 145 days (full term). Kidney length and cortical thickness were measured, and samples were examined histologically. In the lambs operated on at 90 days, the urine was collected at delivery and Na and CI were measured and compared with the results obtained from normal full-term lambs. RESULTS: Seven of 10 female lambs had hydronephrosis or dysplastic kidneys. The cortext to kidney length ratio was 10+/-3% in the 90-days hydronephrotic group versus 29+/-6% in the controls (P<.001). Morphologically, the 90-day model had dilatation of the collecting tubules with normal glomerular numbers. The 60-day model had tubular cysts with fibromuscular cuffing and reduced glomerular numbers. The fetal urine Na was 47+/-3.3 mmol/L in controls versus 78+/-24 mmol/L in the hydropnephrotic lambs (P<.05). The urine CI in these lambs was 38+/-8.6 mmol/L in controls versus 55+/-14.5 mmol/L in the hydronephrotic lambs (P<.05). CONCLUSIONS: An obstructive uropathy model was created in female fetal lambs. There were no dysplastic changes in the kidneys in lambs operated on at 90 days' gestation, but there were definite dysplastic changes in those operated on at 60 days. Concentrations of Na and CI in the fetal urine are higher than normal in the 90-day model.

'Stab and Split': a 'bloodless' and 'scarless' skin incision technique for minor surgery.

The 'stab and split' skin incision technique was applied to children requiring minor surgery. A small stab incision was made on a skin crease and split open with mosquito forceps. After the surgical procedure was completed, the wound was closed in layers with a subcuticular suture to the skin. In all cases, splitting caused virtually no blood loss because subcutaneous veins were left intact, and the wounds healed well, especially in infants. 'Stab and split' is an effective alternative incision technique for minor surgery in younger children.

A case with duodenal duplication cyst: prenatal diagnosis and surgical management.

OBJECTIVE: We report the first case of a subhepatic cystic mass diagnosed in utero that subsequently proved to be a duodenal duplication cyst. METHOD: Conventional prenatal abdominal ultrasound. RESULTS: On prenatal ultrasonography, the differential diagnosis was choledochal cyst, bowel duplication cyst, or omental cyst. CONCLUSION: The prenatal detection of a cystic mass allowed close neonatal surveillance and timely surgical intervention prior to the onset of potentially serious complications.

Postnatal follow-up of hydronephrosis detected by prenatal ultrasound: the natural history.

Babies with hydronephrosis detected antenatally who were born at or referred to our hospital from 1990 to 1995 were followed up with ultrasound (U/S), micturating cystourethrogram (MCU) or nuclear medicine studies after birth. One hundred and three patients were diagnosed antenatally at 17-42 weeks gestation. Twelve cases were excluded from the analysis of the results because of incomplete data. Fifty-one (56%) patients had hydronephrosis without organic obstruction, and 80% of these became normal in 3 years. Fifteen patients (17%) had a normal scan 4 days after birth. This suggests the possibility of antenatal spontaneous regression. Seven (8%) had a ureterocele and 4 (5%) had pelviureteric junction (PUJ) obstruction. Four (5%) had vesicoureteric reflux, and 4 (5%) had primary megaureter. Two (2%) had posterior urethral valves (PUV), 3 (3%) had refluxing primary megaureter, and 1 (1%) had urethral atresia. Fifteen patients (17%) underwent surgical intervention. Six had a nephrectomy, 1 a vesicostomy, 3 an Anderson-Hynes pyeloplasty, 3 had the ureterocele unroofed, 1 had a ureteric reimplant, and 1 ablation of valves. In 42 infants with 60 abnormal kidneys, the renal anteroposterior diameter of the pelvis was measured. Retrospectively, 48 kidneys diagnosed as having hydronephrosis, antenatally had a renal pelvis diameter > or = 4 mm before 33 weeks gestation or > or = 7 mm after 33 weeks gestation. One patient with PUJ obstruction lost kidney function, but there is no good marker to detect these patients. Early unroofing of ureteroceles may rescue kidney function. Our follow-up protocol for antenatal hydronephrosis is U/S at 4 days, 1 month and 1 year of age. An MCU is not required unless the ureter is seen on antenatal U/S. If dilatation persists past 1 month, a radionucleotide (MAG3) scan and repeat U/S are performed at 3 months. The methods for assessing obstruction and the indications for surgical intervention in these patients require reexamination.

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.

Management and outcome of inoperable Wilms tumor. A report of National Wilms Tumor Study-3.

METHODS: The authors reviewed 131 children enrolled in National Wilms Tumor Study-3 (NWTS-3) who received preoperative treatment for tumors unable to be resected at surgery or judged inoperable by imaging evaluation. Preoperative biopsies were performed on 103 patients. Patients were assigned a pretreatment stage: stage II (11 patients), stage III (39 patients), stage IV (66 patients), and unknown (15 patients). The chemotherapy regimen included dactinomycin and vincristine (81 patients), dactinomycin, vincristine, and doxorubicin (30 patients), dactinomycin, vincristine, doxorubicin, and cyclophosphamide (10 patients), and other (8 patients). Preoperative radiation therapy was started concurrently with chemotherapy (27 patients) or because of lack of response (14 patients). Two patients were given preoperative irradiation without chemotherapy. RESULTS: Response to therapy was assessed after the first trial of chemotherapy. Partial responses were noted in 110 patients (85%), 3 had complete responses, 13 had no response or progression of disease, and 5 patients were not able to be evaluated. There were no significant differences in preoperative response to the different chemotherapy regimens. Median time interval from diagnosis to nephrectomy was 58.5 days. When compared with NWTS-3 patients not receiving preoperative treatment, survival was reduced for patients treated preoperatively (88% vs. 74%, respectively, 4-year survival), which was only partially explained by differences in stage distribution. Median duration of follow-up was 5.9 years. Lack of response to the preoperative treatment was associated with a poor prognosis. Eight children died before removal of the primary tumor. All eight had either progressive disease or no response to the preoperative treatment. CONCLUSIONS: The use of preoperative treatment can facilitate subsequent surgical resection in selected patients with inoperable Wilms tumors. Although these very large tumors--judged unable to be resected--have a somewhat worse prognosis, nephrectomy was completed in 93% of patients after preoperative treatment. However, preoperative treatment will lead to less accurate surgical and pathologic staging, and undertreatment should be avoided in these high-risk patients.

An evaluation of abdominal staging procedures performed in pediatric patients with advanced Hodgkin's disease: a report from the Childrens Cancer Study Group.

Forty-nine children and adolescents underwent staging laparotomy in the course of a cooperative group (CCG) study of advanced Hodgkin's disease (HD). The purpose of the study was to evaluate the toxicity of a regimen of 12 cycles of doxorubicin, bleomycin, vinblastine, and imidazole carboxamide (ABVD) plus 2,100 cGy regional irradiation in patients with stage III-IV disease. Review of the biopsies and specimens from these 49 laparotomies identified distinct patterns of abdominal involvement and permitted an evaluation of the importance of different aspects of the staging procedure and an assessment of the value of non-invasive techniques in determining the extent of abdominal disease. The major observations from these studies were: (1) computed tomography (CT) and gallium 67 scans (GA) were specific (few false positives), but not sensitive, indicators of abdominal disease; (2) negative findings at laparotomy in 29 patients permitted a contraction of the abdominal radiation fields with no subsequent abdominal recurrence in these patients; (3) in five patients, stage IV status was established only by laparotomy and open hepatic biopsy; (4) all patients with lower abdominal or pelvic involvement also had upper abdominal node or splenic involvement; (5) involvement of splenic hilar nodes was a sensitive predictor of splenic involvement; (6) disease in the inferior paraaortic nodes accurately predicted the presence of more distal disease, ie, in the iliac or pelvic node groups; and (7) in a limited experience, transposition of the ovaries protected ovarian function from the effects of pelvic irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of preoperative therapy on the histologic features of Wilms' tumor. An analysis of cases from the Third National Wilms' Tumor Study.

Preoperative chemotherapy is being used with increasing frequency in the US for the management of selected children with Wilms' tumor, despite relatively limited knowledge as to the effects of such therapy on tumor histologic features. The authors reviewed pathologic material from all preoperatively treated unilateral Wilms' tumors registered on the third National Wilms' Tumor Study. Preoperative therapy was associated with increased ambiguity of tumor stage. The prevalence of anaplasia in the 83 evaluable specimens was similar to, although slightly increased over, that in comparable high-stage untreated Wilms' tumors (11% versus 5% to 8%), and it appeared to retain its adverse connotations. These data also suggest that alterations of tumor character and distribution by therapy provide useful prognostic information. All 17 children whose residual viable tumor was limited to intrarenal sites at the time of resection were alive and disease-free at last follow-up. Extensive (greater than 90%) tumor necrosis, low mitotic activity, and high degrees of differentiation of residual tumor were also associated with favorable outcomes. Although careful utilization of preoperative chemotherapy can be of value in children with otherwise difficult-to-manage Wilms' tumors, the potential benefits of preoperative tumor bulk reduction must be weighed against the risk of overtreatment or undertreatment as a result of increased ambiguity of tumor stage.

Solitary intrahepatic biliary cyst: diagnostic and therapeutic strategy.

This paper describes a newborn infant in whom an intrahepatic biliary cyst was successfully demonstrated by antenatal ultrasound. Postnatally, percutaneous cyst aspiration and computed tomography enhanced with intravenous cholangiographic contrast proved extremely helpful in the selection of surgical procedure. The lesion was completely removed at 12 weeks of age without complications.

Wilms' tumour: a 30 year experience at Wellington Hospital.

Over the 30 year period from 1958-88, 20 cases of Wilms' tumour have been treated at Wellington Hospital. All eight patients presenting prior to 1976 have died. The 12 patients presenting after 1976 were treated according to the guidelines of the National Wilms' Tumour Study Group and ten of these are alive (mean follow up seven years). Four of the patients received preoperative chemotherapy and this was found to facilitate surgical removal of the tumour. The concept of partial nephrectomy in the management of Wilms' tumour is discussed. Retrospective analysis of this series has shown that this would have been a feasible management option in four of the cases reviewed.

Fetal gastroschisis complicated by bowel dilation: an indication for imminent delivery?

Antenatal diagnosis of fetal gastroschisis permits study of bowel appearance throughout gestation. Fetal bowel dilation has been regarded as a 'high-risk' condition requiring imminent cesarean delivery. We report 2 cases of gastroschisis with onset of bowel dilation in the third trimester. At surgery, the bowel was patent. Neither fetus had evidence of acute bowel damage following expectant management and vaginal delivery. Both underwent a one-stage repair. We conclude that antenatal bowel dilation does not necessarily reflect bowel injury or a poorer neonatal prognosis. In our experience, bowel dilation in fetal gastroschisis does not represent a separate indication for cesarean delivery and can be associated with a good outcome following vaginal delivery.