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Review Article

An overview of esophageal atresia and tracheoesophageal fistula

McGowan, Nathan A. PA-C; Grosel, John MD

Author Information
doi: 10.1097/01.JAA.0000830180.79745.b9
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Abstract

Congenital tracheoesophageal fistula (TEF) and associated esophageal atresia are rare, serious anomalies afflicting neonates. TEF is a fistula between the trachea and esophagus; esophageal atresia is a congenital anomaly in which a section of the esophagus fails to develop, creating an abnormal gap between the esophagus and stomach (Figure 1). These conditions often are present concomitantly, and may present prenatally or in the first days or weeks of life. Severe complications of esophageal atresia/TEF, including the inability to pass food into the stomach and aspiration or choking, can be fatal.

F1-7
FIGURE 1.:
In Type C esophageal atresia and TEF, the most common type, the esophagus ends in a blind pouch and a TEF joins the distal portion of the esophagus to the trachea.Image courtesy of the Centers for Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities.

Esophageal atresia and TEF have multiple different pathophysiologic manifestations, and patients with TEF often have additional congenital anomalies.1 Early detection is imperative to improve patient outcome, and clinicians should be aware of the clinical signs and symptoms as well as the appropriate steps in diagnosis and management.

PREVALENCE AND PATHOGENESIS

On a worldwide scale, the prevalence of esophageal atresia and TEF varies between one and four in 10,000 births.2 Males have a higher prevalence than females at a 3:2 ratio, although this may not necessarily be the case on a regional level, as genetic and environmental factors may influence sex disparity in a smaller population size.2

The esophagus and trachea develop in utero from the foregut. The foregut is derived from the primitive gut tube, a folding of the endodermal layer that occurs near the end of the third week of development.2 Growth factors, such as NODAL and FGF4, and transcription factors, such as HEX, SOX2, DOXA2, and CDX2, are involved in the timing and signaling that results in the differentiation of the primitive gut tube into individual structures (trachea and esophagus).2

FB1
Box 1

As the gut tube is regionalized, the foregut becomes positioned in the ventral respiratory field.2 Here, the foregut separates into the ventral foregut, a respiratory structure with two lung buds, and the dorsal foregut, a gastrointestinal structure.2 The separation of the foregut, which is reliant on appropriate rearrangement of the cytoskeleton and shape of the cell, is primarily regulated by the Fgf, Wnt, and Bmp signaling pathways from the surrounding mesenchyme to the epithelium.3 The homeobox gene Barx1, which is expressed in the mesenchyme at the separation site, inhibits the action of the Wnt signaling pathway, and its deletion may lead to defects in foregut separation, such as esophageal atresia and/or TEF.3

CLASSIFICATION

Esophageal atresia and associated TEF are historically categorized into one of five distinct morphologic types as defined by the Gross classification (Figure 2).4 In a 5-year retrospective study of 396 infants with esophageal atresia/TEF, Lal and colleagues found that type C was the most common type, with an incidence of 84.7%.4

F2-7
FIGURE 2.:
Gross classification of esophageal atresia and TEF. Type A is esophageal atresia without associated TEF; the trachea is unaffected. Type B is esophageal atresia with a proximal TEF. Type C is esophageal atresia with a distal TEF. Type D is esophageal atresia with proximal and distal TEFs. Type E, commonly referred to as an H-type fistula, is a TEF without an associated esophageal atresia.

A further descriptor of esophageal atresia/TEF is long gap, in which the blind ends of the esophageal atresia are separated by a distance greater than three or more vertebral bodies.4 Surgical intervention for long-gap esophageal atresia/TEF may necessitate esophageal replacement.4

ASSOCIATED ANOMALIES

Clinically, there is a high association between TEF and other congenital anomalies, the most common of which are collectively referred to as VATER, or more recently, VACTERL (Tables 1 and 2).5 The developmental anomalies of VACTERL are Vertebral, Anorectal, Cardiac, Tracheoesophageal, Renal, and Limb; three or more components are necessary for a diagnosis of VACTERL association.2 Interestingly, a recent review study has suggested that TEF (alone or with esophageal atresia) is more often not associated with other VACTERL anomalies, and may be better considered as either isolated anomalies or as part of different multiple malformation syndromes than VACTERL.1 The authors found that esophageal atresia alone and esophageal atresia/TEF together were associated with VACTERL in only 11.5% and 22.2% of patients, respectively.1 Esophageal atresia/TEF also may be present in patients with non-VACTERL syndromes including CHARGE (Coloboma, Heart anomaly, choanal Atresia, Retardation, Genital anomaly, and Ear anomaly) syndrome, Anophtalmia-Esophageal-Genital (AEG) syndrome, Feingold syndrome, and trisomy 18.2

TABLE 1. - Incidence rates of VACTERL associations17
VACTERL association Incidence rate
Vertebral anomaly 60%-80%
Anal atresia 55%-90%
Cardiac malformation 40%-80%
Tracheoesophageal 50%-80%
Renal malformation 50%-80%
Limb malformation 40%-50%

TABLE 2. - VACTERL anomalies18-20
  • Vertebral—hemivertebrae, vertebral fusions, extra or absent vertebrae, hypoplastic sacrum, scoliosis

  • Anorectal—imperforate anus, anal atresia, anorectal anomaly with fistula to the bladder, cloacal anomaly

  • Cardiac—ventricular septal defect, atrial septal defect, tetralogy of Fallot, truncus arteriosus, transposition of the great arteries

  • Tracheoesophageal—esophageal atresia, TEF

  • Renal—aplasia, renal dysplasia, horseshoe kidney, obstructive nephropathy

  • Limb—radial anomalies, thumb aplasia or hypoplasia, and polydactyly


DIAGNOSIS

Diagnosis of TEF may be complicated by the high variability of clinical manifestations and associations. TEF may be suspected on prenatal fetal anatomy ultrasound, which typically is performed at 16 to 20 weeks gestation, if polyhydramnios is seen concurrently with a small or absent fluid-filled fetal stomach.6 The sensitivity of prenatal ultrasound in identifying TEF is 26%, with 99% specificity and 35% positive predictive value.6 In patients with suspected esophageal atresia/TEF on prenatal ultrasound, fetal MRI may be helpful in confirming the diagnosis.4 Because there is only a 26% sensitivity on prenatal ultrasound, many TEFs are initially diagnosed postnatally.6 Postnatal diagnosis of esophageal atresia/TEF often begins with a clinical suspicion based on signs such as increased salivation, respiratory distress, or inability to swallow.2,7 Confirmation of esophageal atresia is made when an orogastric tube cannot be inserted, and is shown to be coiled in the thoracic inlet on radiography.7 Preoperative bronchoscopy can be used to both identify a TEF and provide operative ventilation.4

MANAGEMENT

Once esophageal atresia/TEF is diagnosed in a neonate, preoperative management must begin immediately with humidified oxygen, IV fluids, temperature maintenance, and, if indicated, acid suppression and IV antibiotics.8 More information may be gathered on the extent, length, and involvement of the fistula(e) by diagnostic bronchoscopy or, less commonly, esophageal pouch contrast studies.4 Additionally, a recent review of case reports suggested that MRI may be useful both in preoperative planning and in postoperative assessment of repair.9

Because the anatomy of esophageal atresia/TEF is quite variable, surgical management may vary; however, standard care is to ligate the TEF and open and connect the proximal and distal ends of the esophagus.4 To prevent aspiration pneumonia, surgical repair is preferred in the first days of life.10 Surgical repair may be either thorascopic or open thoracotomy.4 A retrospective study by Lal and colleagues reviewed treatment of esophageal atresia/TEF at 11 children's hospitals over 5 years.4 This study found that 82.8% of patients underwent primary repair with esophagoesophagostomy and ligation of the TEF.4 Often, a transanastomotic feeding tube for feeding and gastric decompression is placed while the patient is in the OR.4 Less commonly used methods of esophageal atresia/TEF repair are initial gastrostomy tube placement or initial fistula ligation, both followed by delayed primary esophageal repair; and a Foker procedure, defined as staged operative esophageal lengthening with delayed esophageal anastomosis.4 Thorascopic repair of esophageal atresia/TEF is possible, depending on patient weight and comorbidities.11 A study by Wu and colleagues found that thorascopic repair of esophageal atresia/TEF resulted in longer operative time, but shorter average length of stay and time to first oral feeding than open repair.11 The same study found no statistical difference in complication rates between the open and thorascopic approaches.11

Patients require close and attentive postoperative management. They typically are received from surgery with a pleural drain and on postoperative antibiotics to cover oral flora.4 Before patients start oral feedings, several methods of nutrition may be used, some concurrently, including total parenteral nutrition, gastric or jejunal feeds via transanastomotic tube, and gastric feeds via gastrostomy tube.4 Lal and colleagues found that due to gastroesophageal reflux, 90% of infants were on proton pump inhibitors and/or histamine2 blockers in the days immediately after surgery, with 83% being discharged on acid suppression, and 48% continuing on acid suppression 1 year postoperatively.4 A small number of patients (13.5%) were refractory to acid suppression and required surgical intervention, most commonly in the form of Nissen fundoplication.4

COMPLICATIONS

Postoperative complications of esophageal atresia/TEF repair include anastomotic stricture, anastomotic leak, vocal cord paralysis or paresis, recurrent fistula, surgical site infection, and postoperative shock or sepsis.4 Lal and colleagues found that overall postoperative morbidity was 61.9%, with anastomotic stricture accounting for 42.5% of all morbidity.4 Additionally, the study found that the median number of dilations required for patients with anastomotic strictures was three.4 The same study found that anastomotic leak was the second most common complication, occurring 22.9% of the time.4

TEF IN ADULTS

Although TEF is most commonly associated with neonates, it also may present in adults. TEF in adults is a rare occurrence, requiring special consideration. In adults, TEF is usually acquired, most often due to esophageal or pulmonary malignancies, and less often due to ingestion of caustic substances or surgical interventions.12 Much less commonly, TEF in adults presents as either a new diagnosis of congenital TEF or as a recurrence in adulthood after surgery in infancy.13 Downey and colleagues studied congenital adult presentations at one facility over 12 years and found that the clinical presentation in these patients corresponded to clinical presentation in neonates: cough and aspiration events, often manifesting as recurrent pneumonia.13 Surgical intervention in this population was determined by the location of the fistula and the degree of esophageal function and ranged from tracheal and esophageal defect repair via cervical incision to thoracotomy and total esophageal resection.13 The authors suggest that clinicians consider recurrent or new TEF in adults who present with chronic cough, aspiration, and recurrent pneumonia requiring hospitalization.13

PROGNOSIS

Because there are five types of esophageal atresia/TEF, differing degrees of severity of each type, and a variety of associations, prognosis is difficult to quantify. An overall survival rate has been reported at 80.8% to 92.5%, though prognosis is significantly influenced by associated anomalies.4,14 A retrospective study by Masuya and colleagues found that mortality was not significantly affected by the Gross classification.14 The Spitz classification (Table 3), initially published in 1994 and updated in 2007, was developed to predict survival in patients with esophageal atresia/TEF, and assigns patients to one of three groups based on birth weight (over or under 1,500 g [3.3 lb]) and presence or absence of major cardiac anomalies.15,16 This classification makes a distinction between major cardiac anomalies, which require surgery or medical management for heart failure, and minor cardiac anomalies, such as patent ductus arteriosus and atrial septal defect.15

TABLE 3. - Spitz classification of esophageal atresia/TEF15,16
Group Characteristics Survival %
1 Birth weight greater than 1,500 g without major cardiac disease 97
2 Birth weight less than 1,500 g or major cardiac disease 59
3 Birth weight less than 1,500 g with major cardiac disease 22

CONCLUSION

Esophageal atresia and TEF provide a diagnostic and clinical management challenge to clinicians, but the importance of early detection and appropriate intervention cannot be overstated. Clinicians versed in the clinical signs of esophageal atresia/TEF in neonates can help patients avoid a delay in operative management, improving the clinical outcome. Clinicians should be aware of the Gross classification system for esophageal atresia/TEF, the most common associated VACTERL anomalies, diagnostic procedures, and preoperative and postoperative management. An understanding of these components will ensure that patients are given the best opportunity for both survival and minimizing morbidity.

REFERENCES

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Keywords:

esophageal atresia; tracheoesophageal fistula; Gross classification; VACTERL; congenital; neonate

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