BAB II

SCIENCE

Background
Esophageal atresia refers to a congenitally interrupted esophagus. One or more fistulae may be
present between the malformed esophagus and the trachea.
History of the Procedure
The condition was first described anecdotally in the 17th century.

In 1670, Durston described the
first case of esophageal atresia in one conjoined twin. In 1696, Gibson provided the first
description of esophageal atresia with a distal tracheoesophageal fistula (TEF). In 1862,
Hirschsprung (a famous pediatrician from Copenhagen) described 14 cases of esophageal atresia.
In 1898, Hoffman attempted primary repair of the defect but was not successful and resorted to
the placement of a gastrostomy.
At the start of the 20th century, surgeons were theorizing about how the lesion could be repaired.
In 1939 and 1940, Ladd of Boston and Lever of Minnesota first achieved surgical success in
stages; success meant that the affected children survived and skin-lined pharyngogastric conduits
were eventually constructed. In 1941, Haight of Michigan successfully repaired esophageal
atresia in a 12-day-old baby using a primary single-stage left-sided extrapleural approach.
Subsequent to that child's survival and with advances in surgical and anesthetic techniques,
esophageal atresia is now regarded as an eminently correctable congenital lesion.
Problem
The lack of esophageal patency prevents swallowing. In addition to preventing normal feeding,
this problem may cause infants to aspirate and literally drown in their own saliva, which quickly
overflows the upper pouch of the obstructed esophagus. If a TEF is present, fluid (either saliva
from above or gastric secretions from below) may flow directly into the tracheobronchial tree.
Epidemiology
Frequency
The incidence of esophageal atresia is 1 case in 3000-4500 births. This frequency may be
decreasing for unknown reasons.
Internationally, the highest incidence of this disorder is in Finland, where it is 1 case in 2500
births.
Etiology
No human teratogens that cause esophageal atresia are known. Esophageal atresia that occurs in
families has been reported. A 2% risk of recurrence is present when a sibling is affected. The
occasional association of esophageal atresia with trisomies 21, 13, and 18 further suggests
genetic causation. Also, twinning occurs about 6 times more frequently in patients with
esophageal atresia than in those without the condition.
Currently, most authorities believe that the development of esophageal atresia has a nongenetic
basis.
[3]
Debate about the embryopathologic process of this condition continues, and little about it
is known. The old His theory that lateral infoldings divide the foregut into the esophagus and
trachea is attractively simple, but findings from human embryology studies do not support this
theory.
In 1984, O'Rahilly proposed that a fixed cephalad point of tracheoesophageal separation is
present, with the tracheobronchial and esophageal elements elongating in a caudal direction from
this point.
[4]
This theory does not easily account for esophageal atresia but explains TEF as a
deficiency or breakdown of esophageal mucosa, which occurs as the linear growth of the organ
exceeds the cellular division of the esophageal epithelium.
In a 1987 report, Kluth eschews the concept that tracheoesophageal septation has a key role in
the development of esophageal atresia.

Instead, he bases the embryopathologic process on the
faulty development of the early, but already differentiated, trachea and esophagus, in which a
dorsal fold comes to lie too far ventrally; thus, the early tracheoesophagus remains undivided. He
also suggests that esophageal vascular events, ischemic events, or both may be causes in cases of
esophageal atresia without fistula.
In 2003, Spilde et al reported esophageal atresia-TEF formations in the embryos of rat models of
Adriamycin-induced teratogenesis.

Specific absences of certain fibroblast growth factor (FGF)
elements have been reported, specifically FGF1 and the IIIb splice variant of the FGF2R
receptor.

These specific FGF-signaling absences are postulated to allow the nonbranching
development of the fistulous tract from the foregut, which then establishes continuity with the
developing stomach.
In 2001, Orford et al postulated that the ectopic, ventrally displaced location of the notochord in
an embryo at 21 days' gestation can lead to a disruption of the gene locus, sonic hedgehog-
signaled apoptosis in the developing foregut, and variants of esophageal atresia.

This situation
may be due to various early gestation teratogenic influences such as twinning, toxin exposure, or
possible abortion. More studies are required.
Pathophysiology
The variants of esophageal atresia have been described using many anatomic classification
systems. To avoid ambiguity, the clinician should use a narrative description. Nevertheless,
Gross of Boston described the classification system that is most often cited (see the image
below)

Esophageal atresia classification according to Gross.

According to this system, the types of esophageal atresia and the approximate incidence in all
infants born with esophageal anomalies is as follows:
Type A - Esophageal atresia without fistula or so-called pure esophageal atresia (10%)
Type B - Esophageal atresia with proximal TEF (< 1%)
Type C - Esophageal atresia with distal TEF (85%)
Type D - Esophageal atresia with proximal and distal TEFs (< 1%)
Type E - TEF without esophageal atresia or so-called H-type fistula (4%)
Type F - Congenital esophageal stenosis (< 1%) (This is not discussed in this article.)
A fetus with esophageal atresia cannot effectively swallow amniotic fluid, especially when TEF
is absent.

In a fetus with esophageal atresia and a distal TEF, some amniotic fluid presumably
flows through the trachea and down the fistula to the gut. Polyhydramnios may be the result of
this change in the recycling of amniotic fluid through the fetus. Polyhydramnios, in turn, may
lead to premature labor. The fetus also appears to derive some nutritional benefit from the
ingestion of amniotic fluid; thus, fetuses with esophageal atresia may be small for their
gestational age.
The neonate with esophageal atresia cannot swallow and drools copious amounts of saliva.
Aspiration of saliva or milk, if the baby is allowed to suckle, can lead to an aspiration
pneumonitis. In a baby with esophageal atresia and a distal TEF, the lungs may be exposed to
gastric secretions. Also, air from the trachea can pass down the distal fistula when the baby cries,
strains, or receives ventilation.

This condition can lead to an acute gastric perforation, which is
often lethal. Prerepair esophageal manometric studies have revealed that the distal esophagus in
esophageal atresia is essentially dysmotile, with poor or absent propagating peristaltic waves.
This condition results in variable degrees of dysphagia after the repair and contributes to
gastroesophageal reflux.
The trachea is also affected by the disordered embryogenesis in esophageal atresia. The
membranous part of the trachea, the pars membranacea, is often wide and imparts a cross-
sectional D shape to the trachea, as opposed to the usual C shape. These changes cause
secondary anteroposterior structural weakening of the trachea, or tracheomalacia. This
weakening can result in a sonorous cough as the intrathoracic trachea resonates and partially
collapses with forceful expiration. Secretions can be difficult to clear and may lead to frequent
pneumonias. Also, the trachea can partially collapse during feeding, after repair, or with episodes
of gastroesophageal reflux; this partial collapse can lead to ineffective respiration; hypoxia; and,
somewhat inexplicably, apnea.
Presentation
A mother who is carrying a fetus with esophageal atresia may have polyhydramnios, which
occurs with approximately 33% of mothers with fetuses with esophageal atresia and distal TEF
and with virtually 100% of mothers with fetuses with esophageal atresia without fistula.
Characteristically, the neonate born with esophageal atresia drools and has substantial mucus,
with excessive oral secretions. If suckling at the breast or bottle is allowed, the baby appears to
choke and may have difficulty maintaining an airway. Significant respiratory distress may result.
In the delivery room, the affected infant may have the sonorous seal-bark cough that indicates
concomitant tracheomalacia. If an oral tube is placed to suction the stomach, as it is in some
delivery rooms, it characteristically becomes blocked 10-11 cm from the lips.
Vertebral defects, anorectal malformations, cardiovascular defects, tracheoesophageal defects,
renal anomalies, and limb deformities (VACTERL) are associated anomalies that should be
readily apparent upon physical examination.

If any of these anomalies are present, the presence
of the others must be assessed. The VACTERL syndrome occurs when 3 or more of the
associated anomalies are present. This syndrome occurs in approximately 25% of all patients
with esophageal atresia. Anomalies in this syndrome include the following:
Vertebral defects - Multiple or single hemivertebrae, scoliosis, rib deformities
Anorectal malformations -Imperforate anus of all varieties, cloacal deformities
Cardiovascular defects -Ventricular septal defect (most common),tetralogy of Fallot, patent
ductus arteriosus, atrial septal defects, atrioventricular canal defects, aortic coarctation, right-
sided aortic arch, single umbilical artery
Tracheoesophageal defects - Esophageal atresia
Renal anomalies - Renal agenesis including Potter syndrome, bilateral renal agenesis or
dysplasia, horseshoe kidney, polycystic kidneys, urethral atresia, ureteral malformations
Limb deformities - Radial dysplasia, absent radius, radial-ray deformities, syndactyly,
polydactyly, lower-limb tibial deformities
Other associated conditions include coloboma, heart defects, atresia choanae, developmental
retardation, genital hypoplasia, and ear deformities (CHARGE).
The following anomalies also occur with increased frequency in esophageal atresia
Neurologic defects -Neural tube defects, hydrocephalus, tethered cord, holoprosencephaly
GI defects -Duodenal atresia, ileal atresia, hypertrophic pyloric stenosis,omphalocele,
malrotation, Meckel diverticulum
Pulmonary defects - Unilateral pulmonary agenesis, diaphragmatic hernia
Genitalia defects - Undescended testicles, ambiguous genitalia,hypospadias
Also, trisomies 13, 21, or 18 and Fanconi syndrome may be present. The overall incidence of
associated anomalies is approximately 50%. Cardiovascular anomalies occur in 35% of cases,
genitourinary anomalies occur in 20% of cases, and associated gastrointestinal anomalies occur
in approximately 20% of cases. A tethered cord is usually detectable with ultrasonography in the
newborn period or later in life with MRI (or less desirably with CT scanning) if findings are
equivocal.
Indications
The indication and timing of surgical repair may be determined by using the Waterston, Spitz, or
Poenaru prognostic classification system.
In 1962, Waterston developed a prognostic classification system for esophageal atresia that is
still used today.
[14]
Category A includes patients who weigh more than 5.5 lb (2.5 kg) at birth and
who are otherwise well; category B includes patients who weigh 4-5.5 lb (1.8-2.5 kg) and are
well or who have higher birth weights, moderate pneumonia, and congenital anomalies; and
category C includes patients who weigh less than 4 lb (1.8 kg) or have higher birth weights,
severe pneumonia, and severe congenital anomalies. Management strategies are as follows:
Category A - Immediate primary repair
Category B - Delayed repair
Category C - Staged repair
In 1994, after analyzing findings in 387 patients, Spitz et al recognized that the presence or
absence of cardiac disease is a proven major prognostic factor.

Spitz et al suggested the
following groups, which are analogous to those in the Waterston classification system:
Group I - Birth weight more than 1.5 kg and no major cardiac disease
Group II - Birth weight less than 1.5 kg or major cardiac disease
Group III - Birth weight less than 1.5 kg and major cardiac disease
In 1993, Poenaru proposed a simpler, 2-group classification system based on logistic regression
analysis findings in 95 patients.

Note that birth weight is not a factor. Class I includes patients
who are low risk and do not meet criteria in class II, and class II includes patients who are high
risk and ventilator-dependent or who have life-threatening anomalies, regardless of pulmonary
status.
In 1989, Randolph et al refined the Waterston classification and reported a clinically helpful
system that used a patient's physiologic status to determine the surgical management (ie,
immediate repair, delayed primary repair, or staged repair).
[17]
Weight, gestational age, and
pulmonary condition were not considered. If the patient's physiologic parameters were good,
they were managed with immediate repair. Staged repairs were used for infants who were severe
compromised infants, especially those with severe cardiac anomalies. In this group, the survival
rate was 77%, and the overall survival was 90%.
The above prognostic groupings can allow for the stratification of high-risk patients with
esophageal atresia in planning for delayed repair, staged repair, or both; low-risk babies can
usually undergo early (first 24-48 h) primary single-stage repair. For instance, a 2-kg baby with
esophageal atresia and distal tracheoesophageal fistula (TEF) who also has tetralogy of Fallot is
in Waterston category C, Spitz group II, and Poenaru class II; in this patient, delayed or staged
repair may be best.
These classification systems help physicians to compare results in an organized and meaningful
way. When comparing the 3 prognostic classification systems, the Spitz classification appears to
have the most applicability in current practice.

Ductal-dependent cardiac lesions still seem to
significantly affect the survival of children born with esophageal atresia.

Relevant Anatomy
The treatment plan for each baby must be individualized. The prognostic classifications can
provide guidance in patients with multiple problems, but decisions in identifying the most life-
threatening anomaly must be made early.
Management plans for a delayed repair of the esophageal atresia may include placing a 10F
Replogle double-lumen tube through the mouth or nose well into the upper pouch to provide
continuous suction of pooled secretions from the proximal portion of the atretic esophagus. The
baby may be positioned in the 45 sitting position. Prophylactic broad-spectrum antibiotics such
as ampicillin and gentamicin may be used. General supportive care and total parenteral nutrition
are needed.
With careful bedside attendance, these measures may permit a delay of days to perhaps weeks.
Some have described cases in which the baby was discharged home with a Replogle tube in situ
while waiting for staged repair of an esophageal atresia. However, deaths have been reported in
infants in whom the tube did not maintain an empty upper pouch. A gastrostomy, distal
tracheoesophageal fistula (TEF) ligation, or cervical esophagostomy may permit longer delays in
the esophageal atresia repair. However, each intrusion carries a price.
A gastrostomy may be created if no distal TEF is present. In such cases, the stomach is small,
and laparotomy is required. In all cases of esophageal atresia in which a gastrostomy is created,
care should be taken to place it near the lesser curve to avoid damaging the greater curve, which
can be used in the formation of an esophageal substitute. When a baby is ventilated with high
pressures, the gastrostomy may offer a route of decreased resistance, causing the ventilation
gases to flow through the distal fistula and out the gastrostomy site. This condition may
complicate the use of ventilation.
In cases such as those above or in cases in which a distal fistula continues to cause lung soiling,
consider distal TEF ligation. This ligation is performed by means of a right-sided thoracotomy,
ideally performed via an extrapleural approach. The fistula may be clipped or simply ligated. If it
is ligated and divided, subsequent staged repair of the esophageal atresia may be difficult
because the distal esophageal segment tends to retract inferiorly to a substantial degree when it is
detached from its tracheal mooring. However, simple fistula ligation may allow subsequent
reopening of the fistula. Division of the fistula and attempts to anchor it at the mid chest with
sutures are usually unsuccessful.
A cervical esophagostomy or spit fistula may be constructed in the right or left side of the neck,
depending on the choice for subsequent esophageal substitution. It allows drainage of the upper
pouch and precludes aspiration from the upper pouch. Sham feeding may be commenced in cases
in which a long delay to repair is anticipated. This feeding may prevent subsequent oral aversion,
which is a real problem in babies who have not been fed by mouth in their early weeks to months
of life. However, cervical esophagostomy usually dooms the child to some form of esophageal
substitution.
Please see Preoperative details for a discussion of aortic arch position and surgery.

Contraindications
Potter syndrome is bilateral renal agenesis and has a 100% mortality rate; therefore, repair of
esophageal atresia is contraindicated.

Laboratory Studies
In babies with esophageal atresia, samples should be obtained to determine baseline values of the
following:
CBC count
Electrolyte levels
Venous gas concentrations
BUN and serum creatinine levels
Blood glucose level
Serum calcium level
ABG concentrations, as necessary
Imaging Studies
Prenatal ultrasonography may reveal the size of the gastric bubble, polyhydramnios, and
VACTERL anomalies, all of which may indicate esophageal atresia in the fetus.
The sensitivity of prenatal ultrasonography is approximately 40%.
A prenatal diagnosis of esophageal atresia may be associated with a worse prognosis.
Chest radiography (see the images below) is mandatory and should be performed as soon as
possible if esophageal atresia is suspected.
This chest radiograph reveals esophageal atresia and distal tracheoesophageal fistula. Note the
Replogle tube in the upper pouch and the GI air below the diaphragm.
This chest radiograph reveals esophageal atresia without tracheoesophageal fistula. Note the
absence of gas below the diaphragm.
The value of the chest radiography is enhanced if a Replogle tube is in place and if 5-10 mL of
air is injected to distend the upper pouch.
Great caution should be exercised if liquid contrast material is injected into the proximal pouch.
First, only about 1 mL of isotonic water-soluble contrast should be used to prevent spillage into
the airway. A catheter with an end-hole should be used. Second, if an upper pouch fistula is
present, the contrast material flows directly into the airway. Usually, a contrast-enhanced study
is unnecessary.
The heart shadow and size should be assessed.
Vertebral and rib anomalies should be assessed.
The lung fields should be assessed for possible aspiration pneumonitis and for the rarely
associated diaphragmatic hernia or congenital lung lesion.
The presence or absence of GI air below the diaphragm is an important finding. Complete
absence of gas in the GI tract denotes the absence of a distal tracheoesophageal fistula (TEF);
however, distal fistulae simply occluded by mucous plugs have been rarely reported. In cases
of esophageal atresia without fistula, assume that the distance between the ends of the atretic
esophagus is too long for early single-stage primary repair. These infants require a delayed
repair (see discussion about gastrostomy in Relevant Anatomy and about gap-o-gram below).
Early renal ultrasonography is mandatory and is used to evaluate associated kidney anomalies,
ureteral anomalies, or both.
Echocardiography is indicated early in the care of infants with esophageal atresia who have
clinical signs of cardiovascular disease.
[19]
However, a 1-day-old neonate with significant
congenital heart disease may have normal findings upon physical examination. Therefore, some
argue that echocardiography should be performed in all infants with esophageal atresia. This
examination also provides the surgeon with information regarding the side of the aortic arch. A
right-sided aortic arch is not uncommon in cases of esophageal atresia, and the surgeon should be
aware of this finding.
Limb radiography (see the image below) is indicated if the limbs appear abnormal. The
possibility of associated radial-ray deformities should be investigated.
This radiograph reveals a radius without a radial ray deformity.
Spinal ultrasonography is a simple test that takes advantage of the neonate's relatively
transparent lumber lamina in the assessment of an associated tethered cord. This examination
may be performed when the baby is younger than 1 month, although it is not critically important
in the early care of the infant.
In cases in which the distance between the 2 atretic ends of the esophagus is suspected to be too
long for a primary repair, a gap-o-gram (see the image below) is useful in assessing that distance.
Contrast material has been administered, and a probe has been placed
through the gastrostomy in this child with pure esophageal atresia. The air-filled upper pouch can
be observed superiorly, with a Replogle tube within it. This gap-o-gram reveals a very wide gap
(>5 vertebral bodies), which requires esophageal replacement. This study is a dynamic
investigation, one in which the surgeon and radiologist should be present to view the real-time
fluoroscopic images.
A gastrostomy is created, and the upper pouch is intubated with a 10F Replogle tube with
radiopaque markings. A small-diameter Bakes dilator is introduced into the gastrostomy and
directed superiorly under fluoroscopic guidance into the distal esophageal segment. With gentle
but definite force on both the Bakes dilator and the Replogle tube, the 2 ends are pushed toward
each other under fluoroscopic control.
At the point of least separation, an image is obtained, and the distance between the 2 ends is
determined in terms of vertebral bodies, which provide an inherent reference for measurement.
Generally, a separation distance of 2 (some say 3) vertebral bodies or fewer is usually small
enough for an anastomosis. If greater distances separate the ends, a delay of weeks to months
may be required for the ends to grow closer together, for reassessment with gap-o-grams every
4-6 weeks, or for esophageal replacement or lengthening surgery.

Medical Therapy
The preparation of a 1-day-old neonate for surgery includes the following measures:
Intravenous fluid containing an adequate glucose concentration (ie, 10% glucose) is
administered at a rate appropriate for the neonate's gestational age and weight.
Prophylactic broad-spectrum antibiotics (eg, ampicillin, gentamicin) are intravenously
administered.
The neonate is kept warm by using an incubator or overhead warmer and is positioned supine
in the Fowler position, with the head elevated by approximately 45.
A 10F Replogle tube is placed nasally or orally well into the upper pouch and is connected to a
continuous suction device. Every 30 minutes, the tube is checked for patency first by
suctioning with an empty syringe and then by gently injecting 5 mL of air. (Never use water.)
In small infants, an 8F double-lumen tube may be used instead.
The parents should be fully briefed about the nature of the congenital anomaly. A diagram is
invaluable for explaining not only the pathologic anatomy and intended repair but also the
possible complications. Their consent for treatment should be obtained, and the discussion with
them should be documented in appropriate detail on the baby's medical record.
Surgical Therapy
This section provides some details about surgical approaches for the repair of the most common
type of esophageal atresia (ie, esophageal atresia with distal tracheoesophageal fistula [TEF]) in
low-risk patients. Surgical techniques vary according to surgeons' preferences and variations in
pathologic anatomy.
[20]
Modifications for special anatomic challenges are briefly discussed. In
particular, infants born with esophageal atresia without fistula represent a specific and
challenging subgroup. These babies should undergo an early gastrostomy procedure in the
newborn period. (see discussion about delays in esophageal atresia repair in Relevant Anatomy).
A gap-o-gram should be performed to assess the prospects for anastomotic repair.
In infants with atresia without fistula, surgical decisions must be made regarding the length of
time to wait for the ends to grow closer; whether to perform one of numerous esophageal
lengthening procedures such as the Kimura, Livaditis, Scharli, or Foker procedures; whether to
perform an esophageal substitution procedure, with or without the formation of a cervical
esophagostomy; and whether to use a gastric tube (reversed and proximally based or antegrade
and distally based).
[21]
See the image below.
Contrast material has been administered, and a probe has been placed
through the gastrostomy in this child with pure esophageal atresia. The air-filled upper pouch can
be observed superiorly, with a Replogle tube within it. This gap-o-gram reveals a very wide gap
(>5 vertebral bodies), which requires esophageal replacement. This study is a dynamic
investigation, one in which the surgeon and radiologist should be present to view the real-time
fluoroscopic images.
The use of colonic (left chest or substernal), gastric pull-up, or jejunal vascularized graft
segments is difficult and should be based on the condition of the infant, the pathologic anatomy,
associated defects (eg, gastric pull-up is usually contraindicated in significant cardiac disease,
colonic esophageal replacement is usually contraindicated with concomitant imperforate anus),
and the surgeon's experience.
As a rule, a child's own esophagus is better than any substitution. Recent favorable reports of the
Foker technique used for serial dynamic lengthening in cases of long gap suggest that
advantage.
[22, 23, 24]
The Foker technique involves 2 thoracotomies. First, anchoring sutures are
placed securely at the 2 ends of the atretic esophagus and are brought out diagonally to the chest
wall. Over a period of days to weeks, the 2 ends are brought closer together by a series of daily
lengthenings by traction on the exposed sutures. The closure of the gap is monitored
radiologically with radio-opaque markers at the atretic ends. A second thoracotomy is then
performed to effect a tension-free anastomosis.
Preoperative Details
Bronchoscopy performed just prior to repair of the esophageal atresia may enable the following:
Detection of a upper pouch fistula
Localization of the distal fistula, which usually lies at a level just above that of the carina
Detection of an aberrant right upper lobe bronchus emanating from the trachea, which is not
uncommon in cases of esophageal atresia
Early assessment of the cross-sectional shape of the trachea, which may help in determining the
risk of significant postoperative tracheomalacia
Assessment of specific vascular anomalies (eg, right-sided aortic arch, aberrant right subclavian
artery [for which one looks for the pattern of pulsation on the tracheal wall])
Identification of a laryngotracheoesophageal cleft
The infant is endotracheally intubated without paralysis. The anesthesiologist must be mindful of
the distal fistula. With skill, the long end of the distal endotracheal tube bevel may be positioned
over the fistula to decrease the passage of gases into the stomach. This maneuver helps prevent
gastric distension, maximizes ventilation, and minimizes the chances of a gastric perforation. As
much as possible, the baby should be allowed to spontaneously breathe until the fistula is
occluded. In reality, and especially because the chest is open and the lung is retracted, the
anesthesiologist manually assists with the baby's ventilation. However, mechanical ventilation
should be avoided until the fistula is controlled. This procedure requires great skill, experience,
and focus on the part of an anesthesiologist in caring for these babies in the operating room.
Managing an infant with premature lungs
In positioning the baby in full right thoracotomy position, the surgeon must ensure that the
anesthesiologist has full and easy access to the infant's nose and to the Replogle tube, which is
not taped so that it can move in or out. If a right-sided aortic arch is detected preoperatively,
controversy exists about whether a left thoracotomy provides easier access. A left-sided
approach has its merits, but in this instance, the esophagus is still a right-sided structure, and
access from the right is best.
Lastly, the baby is covered with antiseptic solution, and drapes are placed with the areas from the
nipple to mid back and from the axilla to the 10th rib exposed.
Intraoperative Details
The surgeon should wear magnification loupes. The assistants and nurses should be briefed about
their duties and about special points of care regarding the delicate nature of the procedure and the
baby's tissues.
The procedure is performed as follows: A transverse right thoracotomy incision is made from the
anterior axillary line to approximately one finger's breadth posterior to the posterior axillary line
at a level 1 cm inferior to the palpable tip of the scapula. The latissimus dorsi is divided with the
coagulating current of the electrocautery device. The fascia lying just posterior to the posterior
margin of the serratus is divided with electrocautery, and the serratus is retracted anteriorly.
Usually, an incision in the serratus is not needed. The scapula is then lifted away from the chest
wall, and the ribs are counted from the first to the fourth. Ideally, the chest is entered through the
fourth interspace. With careful use of forceps and the electrocautery device, the outer and
innermost intercostal muscles are divided in this interspace down to the parietal pleura.
By using either moist sponges or peanut gauze on the forceps, the parietal pleura is dissected
away from the chest wall, proceeding posteriorly but also dissecting somewhat superiorly and
inferiorly as well. A small mechanical Finochietto-type rib retractor is placed in the open
thoracotomy site, and the pleural dissection proceeds to a point medial to the azygos vein. The
azygos vein is ligated and divided with fine silk. This extrapleural dissection then allows
retropleural repair of the esophagus. If an anastomotic leak occurs, it tends to be more contained
compared with the empyema that results if the repair is performed transpleurally.
At this point in the dissection, the anatomy is defined first by having the anesthesiologist push on
the indwelling Replogle tube; this action usually reveals the upper pouch that rhythmically
bulges out in the apex of the right chest cavity. The distal fistula is at the level of the carina and
usually lies just beneath the divided azygos vein. It expands slightly with each inspiration. One
must take great care not to mistake the aorta for the fistula. Mistaken ligation of the aorta is
possible; in case of doubt, a 25-gauge needle can be passed into the structure to check.
Gaining control of the fistula now relieves the anesthesiologist. A silicone rubber vessel loop can
be passed around the fistula at a convenient level near the trachea. Gentle retraction on this
occludes the fistula. Most advise dividing the fistula with suturing of its tracheal aspect. This
division can be accomplished by cutting into the fistula as it enters the back wall of the trachea in
short snips and by oversewing the tracheal aspect as it opens in stages. Usually, about 4
interrupted sutures suffice. Most advocate the use of an absorbable synthetic suture material such
as polyglactin. This sutured fistula site may be covered with an azygos or pleural patch for extra
security.
The fistula closure should be checked by covering the closure in saline and manually ventilating
the patient for a Valsalva test. If bubbles appear, the closure is leaking and must be resutured.
Turning his or her attention to the upper pouch, the anesthesiologist can again push on the
Replogle tube to facilitate placement of a traction suture into the distal end of the upper pouch.
The upper pouch is then dissected superiorly to increase its length. Blood supply to the upper
portion is linearly arrayed from the cervical and subclavian vessels; ischemia is not a concern.
This dissection must be carefully performed between the pouch and the trachea while the
presence of an upper pouch fistula that emanates from the side, not the end, of the pouch is
determined. Also, the back wall of the trachea may be inadvertently entered. This condition is
repairable with absorbable sutures.
Avoid extensive dissection of the distal end because its blood supply is segmental from the aorta,
and it can easily become ischemic. A gap between the ends may seem to be present. If it is very
lengthy, the muscular covering of the upper pouch may be cut without entry into the lumen to
achieve an extra 1 cm or so. Distal dissection may be performed; the risk of ischemia should be
recognized. If absolutely necessary, the 2 ends may be simply bridged using 2 stout silk sutures
in the hopes that they form a fistula and that they can be dilated to form a functional esophagus.
More commonly, the 2 ends are reasonably close, and an anastomosis is possible.
The distal portion of the upper pouch is cut off, and the proximal portion of the distal segment is
trimmed. Both the mucosal and muscularis layers of the esophagus should be carefully sutured in
a single layer to form an anastomosis with simple interrupted stitches. Once again, most advocate
the use of an absorbable synthetic suture with a caliber of approximately 5-0 (eg, braided
polyglactin). The back wall is sutured, and the upper pouch tube is passed through the half-
completed anastomosis into the stomach to help rule out a distal stricture and to empty the
stomach of accumulated gas.
This tube is left in place as the anterior wall of the anastomosis is completed. The tube is then
gently withdrawn from the body. Some advocate leaving the transanastomotic tube to act as a
stent, although this tube may be partially moved, potentially injuring the anastomosis. A small-
caliber 10F chest tube may be left in place as an extrapleural chest drain. The ribs are closed by
encircling them with two 3-0 absorbable sutures and by restoring their normal anatomic position.
The muscles and skin are closed in layers with absorbable sutures.
In some pediatric surgical centers, surgeons are gaining experience in repairing esophageal
atresia using a minimally invasive thoracoscopic approach.
[25, 26, 27, 28]
This approach should be
undertaken only by those who have extensive experience in pediatric thoracoscopic surgery.
Postoperative Details
The intubated patient is transported to the neonatal intensive care unit. Antibiotics are continued
until the chest drain is removed, and the endotracheal tube is suctioned as necessary. Oral
suctioning to a depth of no more than 7 cm from the lips is performed every half hour for the first
day, then every hour or more frequently as necessary on the second day. Thereafter, it is
performed as needed. Suctioning is required to handle the sometimes copious oral secretions that
can build up in the first day or so after surgery. As the swelling of the esophagus settles, the
secretions taper.
The chest draining tube is placed in 2 cm of water only to seal it; it is not connected to a suction
device, which could encourage an anastomotic leak. Morphine is infused as necessary for the
patient's comfort, and peripheral parenteral nutrition should be commenced. The endotracheal
tube should remain until weaning from ventilation is ensured, usually after 1-2 days. Premature
extubation and subsequent intubation in the setting of a freshly closed tracheal fistula invites
reopening of the fistula.
Watch for saliva exiting out the chest drain; this is a signal of anastomotic leakage. Often, it is
accompanied by visible distress. Signs of sepsis may or may not be present. A chest radiograph
should be obtained. Provided that the baby is stable, a contrast-enhanced study of the esophagus
with a water-soluble isotonic medium may be performed on day 6 or 7 to assess for leaks and to
view the caliber of the repair (see the image below). If the esophagus is patent and reasonably
sized, the baby may be orally fed; starting with expressed breast milk is ideal. Then, the chest
tube is removed. As soon as the baby is feeding well, the intravenous line is discontinued, and
the baby can be discharged. Oral ranitidine is prescribed for 6 months because of the propensity
for gastroesophageal reflux in this group of patients and because of the risk of stricture as a
secondary effect.
This postoperative contrast-enhanced radiograph reveals esophageal gastric tube
replacement. The anastomosis to the upper pouch is in the chest. The linear staple line of the tube
can be observed.
Follow-up
If all is well with the patient and if the parents have been briefed on what to look for, a
reasonable follow-up regimen may include the following steps:
Make contact with the community physician who is responsible for the general medical care of
the child and ensure that he or she is briefed on the baby's history, condition, and expected
outcome.
The nurse on the surgical team should follow up by telephone in one week.
The surgeon should follow up in one month to interview the parents and generally assess the
child's condition, growth, and healing at the surgical site.
The patient should return at 3 months for a similar assessment.
At a 1-year follow-up and general assessment, swallowing function, respiratory issues, and
other factors should be addressed.
Radiologic assessment of the esophagus is required only if a significant history of choking,
cyanosis, regurgitation, dysphagia, growth failure, coughing, or wheezing is noted. Subsequent
endoscopic evaluation can be performed as indicated.
Follow-up care when the child is older can be performed as needed. Specific reassessment with
esophageal endoscopy and biopsy when the patient is aged approximately 12 years has been
advised by some who also advise follow-up with periodic endoscopy every few years until the
patient is an adult. Although Barrett esophagus and subsequent malignant change has been
described in this condition, presumably because of gastroesophageal reflux, whether endoscopic
surveillance is necessary in patients with repaired esophageal atresia remains unclear.
[29, 30]

Complications
Early complications
Early complications may include an anastomotic leak,
[31]
recurrent tracheoesophageal fistula
(TEF), and anastomotic stricture.
An anastomotic leak tends to occur 3-4 days after surgery. This leak has been reported in
approximately 15% of cases. Pain and distress are often evident. Signs of sepsis may be present.
The chest tube drains saliva. Treatment is supportive; appropriate antibiotics should be used, and
the child should be given nothing by mouth. Surgery is not indicated, even with huge leaks. If the
leak persists, esophagography may be performed with water-soluble contrast material to assess
its magnitude. The usual protocol is to wait and let the leak close. If an extrapleural approach
was used, the child is usually less ill than with other approaches, and the resultant
esophagocutaneous fistula closes within days. If a transpleural approach was used, then the child
is more ill and has an empyema that may require further treatment and drainage. No absolute
evidence indicates that postoperative leaks lead to anastomotic stenoses.
Recurrent TEF may occur within days; most often, it occurs weeks later. Its incidence has been
variously reported as 3-14%. Its first manifestation may be pneumonia, although the child may
cough and have respiratory distress with feeding. The diagnosis is made by means of an
esophagography performed with water-soluble contrast material under fluoroscopic guidance
with the child prone. The contrast material is slowly injected through a catheter in the esophagus
as the tube is slowly withdrawn, and lateral views are obtained by means of videofluoroscopy.
The recurrent fistula is observed as a wisp of contrast material that suddenly crosses over to the
trachea. This so-called pull-back esophagraphy is the most accurate method for diagnosing a
recurrent fistula. Bronchoscopy and esophagoscopy may provide supplementary information.
One endoscopic technique is to inject 0.5 mL of methylene blue into the endotracheal tube and
through the esophagoscope while watching for it to come through the fistula. Historically, these
fistulae were believed to require surgical repair by means of repeat right-sided thoracotomy;
however, the authors have been successful in a minority of cases of fistulae by allowing them to
close spontaneously while maintaining the nothing by mouth restriction and while administering
antibiotics for one week. Endoscopic cautery and fibrin glue have also been reported to be
occasionally successful.
Anastomotic stricture has been reported in as many as 50% of cases, but the rate partially
depends on the definition of stricture. Essentially, 100% of babies have a waist at the
anastomotic site, but this may not be functionally significant. In cases in which the stricture
appears to be functionally significant on oral contrast-enhanced studies, esophageal dilation is
best and is most safely performed by means of a Grntzig balloon technique under fluoroscopic
control (in the authors' opinion). This procedure should be performed by an experienced
radiologist who can monitor the balloon pressure, position, and inflation diameter. In newborns,
this technique of dilatation would best be deferred until the child is aged at least 6 weeks, and at
least 4 weeks after anastomosis.
Other methods involve the passage of tapered dilators of various sorts (eg, Tucker and Maloney
dilators). Certainly, the methods can be effective but are performed in essentially a blind manner
unless done under fluoroscopic control. They also involve longitudinal and radial force vectors,
as opposed to the pure radial force vectors of the Grntzig technique. Repeat dilations are often
necessary. Histamine 2 (H2)receptor blockade should be started because acid reflux can be both
an aggravating and a causative factor in stricture formation.
Other factors to consider include the surgical technique; the type of suture used; the length of the
atretic gap; ischemia of the distal portion; and, possibly, whether an anastomotic leak has
occurred. Strictures resistant to a few dilations need more aggressive treatment, which may
include an antireflux operation, stricture resection, or both; rarely, they require esophageal
replacement. Stents have been used but are still investigational. Surprisingly, parents can be
taught to perform regular Maloney dilations at home in selected cases.
Late complications
Late complications may include gastroesophageal reflux, esophageal dysmotility, and
tracheomalacia. Some of these complications may appear early.
Gastroesophageal reflux is particularly problematic in patients with esophageal atresia because
of congenital distal dysmotility of the esophagus, dysfunction of the physiologic antireflux
barrier, possible partial vagotomy during surgery, or essential vagal dysfunction that can lead to
delayed gastric emptying. Essentially all babies with esophageal atresia have detectable
gastroesophageal reflux. Patients who require treatment must be carefully identified.
All babies with esophageal atresia should be prophylactically treated with ranitidine until they
are aged 6 months. Failure to thrive, coughing, choking spells, wheezing and asthma, recurrent
pneumonias, vomiting, cyanosis, dying spells, excessive drooling, and apparent dysphagia are all
indications to investigate the degree of gastroesophageal reflux. Oral contrast material should be
administered, and endoscopy should be performed. Strictures should be dilated. A pH probe
study may help if the probe is placed below any present stricture. A gastric emptying scan should
be obtained. All factors should be carefully considered.
Surgical approaches to helping the child may include an antireflux operation. A partial-wrap
fundoplication is usually preferred because of the dysmotility of the repaired esophagus.
Dysphagia after even a very loose wrap is not uncommon. If the stomach has delayed emptying,
balloon pyloroplasty or surgical pyloroplasty may be considered to speed emptying. The authors
have used a surgically conservative approach in children with this condition; the authors prefer to
treat the reflux medically, with H2-receptor blockade or proton pump inhibition when possible.
However, certainly some patients require a surgical approach for later complications.
Esophageal dysmotility is an ongoing problem.
[32]
It has various dysphagic manifestations. The
children eventually learn that they must masticate thoroughly and drink fluids when eating. Food
bolus obstructions, even without a significant stricture, are not uncommon in toddlers. Parents
must be mindful of this possibility and choose their child's foods accordingly. The use of motility
agents such as domperidone may help.
Tracheomalacia is the manifestation of disordered embryogenesis. In its severe form, which
occurs in approximately 10% of patients, dramatic signs include an inability to wean the patient
from a ventilator and the classic dying spells in which the patient becomes pale and limp and,
usually, apneic and cyanotic for a short time. Children with this condition require examination
and treatment. Milder cases of tracheomalacia may cause recurrent pneumonias or asthma
attacks, and in general respiratory ailments are common in these children.
Bronchoscopy performed while the patient is spontaneously breathing reveals a trachea that
significantly collapses, flattens, or closes upon expiration. Treatment consists of
aortopexy,
[33]
which suspends the aortic arch to the underside of the sternum and, thus,
secondarily suspends the anterior tracheal wall anteriorly, preventing its collapse. If this is
unsuccessful, stent placement may help, but this option is controversial. Tracheostomy is the
final management option. Fortunately, tracheomalacia tends to improve with time, growth, and
maturation.
Outcome and Prognosis
Statistics regarding mortality rates in esophageal atresia are constantly changing and
improving.
[34, 35, 36, 37]
One must consider the classification system used in reporting such
statistics.
Montreal classification
[16]

o Class I - Mortality rate of 7.3%
o Class II - Mortality rate of 69.2%
Spitz grouping
[15]

o Group I - Mortality rate of 3%
o Group II - Mortality rate of 41%
o Group III - Mortality rate of 78%
Waterston categorization
[38]

o Category A - Mortality rate of 0%
o Category B - Mortality rate of 4%
o Category C - Mortality rate of 11%
Fetuses with prenatal diagnoses of esophageal atresia seem to have a worse prognosis.
[39]
The
cohort of babies in whom esophageal atresia is detected prenatally has a 75% mortality rate,
whereas the cohort of babies in whom esophageal atresia is not detected prenatally has a 21%
mortality rate. Babies who survive have varied morbidities related to any of the associated
anomalies and complications. However, most children who undergo a successful repair of
esophageal atresia are relatively healthy.
Future and Controversies
The future is bright, with the following considerations: More accurate prenatal diagnosis and
prenatal treatment may be possible. Minimally invasive techniques for repair with thoracoscopic
surgery are now used in some centers, with good results.
[40]
A better understanding of the
pathoembryologic processes of this condition may reveal its causative agents or genetic factors.
This knowledge, in turn, may lead to specific prenatal treatments or preventive techniques.
Recently, the incidence of this disorder has decreased, perhaps because of increased usage of
prenatal folic acid supplements.
Debates continue about the best operative technique (eg, right-sided or left-sided thoracotomy)
for patients with right-sided aortic arches, suture type and technique, esophageal lengthening
strategies, and procedures for mobilizing the distal esophagus.
[41]
Other discussions include when
to use cervical esophagostomy and the choice of esophageal replacement.
[42]
The advent of
esophageal atresia repairs that combine both minimally invasive and radiologic interventional
techniques may be near.
The management of gastroesophageal reflux in esophageal atresia is particularly challenging;
some advocate aggressive fundoplication, and others prefer more conservative medical
treatment. In addition, the true incidence and treatment of tracheomalacia continues to be the
subject of debate. Lastly, the proper evidence-based guidelines for long-term follow-up are still
elusive.
Tissue engineering of the esophagus may offer solutions for replacement of lost esophageal
tissue.
[43]
Experimental studies have shown promising results in the culture of esophageal
epithelial cells and esophageal smooth muscle cells.
[44]
Viability of these cell on biodegradable
scaffolds in vitro may provide the necessary replacement esophageal tissue in future.











DAFTAR PUSTAKA
1. O'Neil JA, Rowe MI, Grosfeld JL. Pediatric Surgery. 5
th
ed. St Louis, Mo: Mosby-Year
Book; 1998:941-67.
2. Ashcraft KW, Holder TM. Pediatric Esophageal Surgery. Orlando, FL: Grune and
Stratton; 1996.
3. Moore KL, Persaud TV. The Developing Human: Clinically Oriented Embryology. 5
th
ed.
Philadelphia, Pa: WB Saunders; 1993.
4. O'Rahilly R, Muller F. Chevalier Jackson lecture. Respiratory and alimentary relations in
staged human embryos. New embryological data and congenital anomalies. Ann Otol
Rhinol Laryngol. Sep-Oct 1984;93(5 Pt 1):421-9.
5. Kluth D, Steding G, Seidl W. The embryology of foregut malformations. J Pediatr Surg.
May 1987;22(5):389-93.
6. Spilde TL, Bhatia AM, Marosky JK, et al. Fibroblast growth factor signaling in the
developing tracheoesophageal fistula. J Pediatr Surg. Mar 2003;38(3):474-7.
7. Crisera CA, Maldonado TS, Longaker MT, Gittes GK. Defective fibroblast growth factor
signaling allows for nonbranching growth of the respiratory-derived fistula tract in
esophageal atresia with tracheoesophageal fistula. J Pediatr Surg. Oct 2000;35(10):1421-
5.
8. Orford J, Manglick P, Cass DT, Tam PP. Mechanisms for the development of esophageal
atresia. J Pediatr Surg. Jul 2001;36(7):985-94.
9. Gross RE. The Surgery of Infancy and Childhood. Philadelphia, PA: WB Saunders;
1953:76.
10. Beasley SW, Hutson JM, Auldist AW. Essential Paediatric Surgery. Oxford, England:
Oxford University Press; 1996.
11. Cotran RS, Kumar V, Robbins T. Robbins Pathological Basis of Disease. 5
th
ed.
Philadelphia, PA: WB Saunders; 1994.
12. Greenfield LJ, Mulholland M, Oldham KT. Surgery: Scientific Principles and Practice.
2
nd
ed. Philadelphia, Pa: Lippincott-Raven; 1997:2011-6.
13. Shaw-Smith C. Oesophageal atresia, tracheo-oesophageal fistula, and the VACTERL
association: review of genetics and epidemiology. J Med Genet. Jul 2006;43(7):545-54.
14. Dunn JC, Fonkalsrud EW, Atkinson JB. Simplifying the Waterston's stratification of
infants with tracheoesophageal fistula. Am Surg. Oct 1999;65(10):908-10.
15. Spitz L, Kiely EM, Morecroft JA, Drake DP. Oesophageal atresia: at-risk groups for the
1990s. J Pediatr Surg. Jun 1994;29(6):723-5.
16. Poenaru D, Laberge JM, Neilson IR, Guttman FM. A new prognostic classification for
esophageal atresia. Surgery. Apr 1993;113(4):426-32.
17. Randolph JG, Newman KD, Anderson KD. Current results in repair of esophageal atresia
with tracheoesophageal fistula using physiologic status as a guide to therapy. Ann Surg.
May 1989;209(5):526-30; discussion 530-1.
18. Konkin DE, O'hali WA, Webber EM, Blair GK. Outcomes in esophageal atresia and
tracheoesophageal fistula. J Pediatr Surg. Dec 2003;38(12):1726-9.
19. Diaz LK, Akpek EA, Dinavahi R, Andropoulos DB. Tracheoesophageal fistula and
associated congenital heart disease: implications for anesthetic management and
survival. Paediatr Anaesth. Oct 2005;15(10):862-9.
20. Way LW, ed. Current Surgical Diagnosis and Treatment. 10
th
ed. New York, NY:
Appleton & Lange; 1994.
21. McCollum MO, Rangel SJ, Blair GK, et al. Primary reversed gastric tube reconstruction
in long gap esophageal atresia. J Pediatr Surg. Jun 2003;38(6):957-62.
22. Skarsgard ED. Dynamic esophageal lengthening for long gap esophageal atresia:
experience with two cases. J Pediatr Surg. Nov 2004;39(11):1712-4.
23. Foker JE, Linden BC, Boyle EM, Marquardt C. Development of a true primary repair for
the full spectrum of esophageal atresia. Ann Surg. Oct 1997;226(4):533-41; discussion
541-3.
24. Foker JE, Kendall TC, Catton K, Khan KM. A flexible approach to achieve a true
primary repair for all infants with esophagealatresia.Semin Pediatr Surg. Feb
2005;14(1):8-15.
25. Allal H, Kalfa N, Lopez M, et al. Benefits of the thoracoscopic approach for short- or
long-gap esophageal atresia. J Laparoendosc Adv Surg Tech A. Dec 2005;15(6):673-7.
26. Bax KM, van Der Zee DC. Feasibility of thoracoscopic repair of esophageal atresia with
distal fistula. J Pediatr Surg. Feb 2002;37(2):192-6.
27. Holcomb GW 3rd, Rothenberg SS, Bax KM, et al. Thoracoscopic repair of esophageal
atresia and tracheoesophageal fistula: a multi-institutional analysis. Ann Surg. Sep
2005;242(3):422-8; discussion 428-30.
28. Rothenberg SS. Thoracoscopic repair of tracheoesophageal fistula in newborns. J Pediatr
Surg. Jun 2002;37(6):869-72.
29. Deurloo JA, Ekkelkamp S, Taminiau JA, et al. Esophagitis and Barrett esophagus after
correction of esophageal atresia. J Pediatr Surg. Aug 2005;40(8):1227-31.
30. Deurloo JA, Ekkelkamp S, Hartman EE, et al. Quality of life in adult survivors of
correction of esophageal atresia. Arch Surg. Oct 2005;140(10):976-80.
31. Chittmittrapap S, Spitz L, Kiely EM, Brereton RJ. Anastomotic leakage following
surgery for esophageal atresia. J Pediatr Surg. Jan 1992;27(1):29-32.
32. Pederiva F, Burgos E, Francica I, Zuccarello B, Martinez L, Tovar JA. Intrinsic
esophageal innervation in esophageal atresia without fistula. Pediatr Surg Int. Jan
2008;24(1):95-100.
33. Blair GK, Cohen R, Filler RM. Treatment of tracheomalacia: eight years' experience. J
Pediatr Surg. Sep 1986;21(9):781-5.
34. Clark DC. Esophageal atresia and tracheoesophageal fistula. Am Fam Physician. Feb 15
1999;59(4):910-6, 919-20.
35. Encinas JL, Luis AL, Avila LF, Martinez L, et al. Impact of preoperative diagnosis of
congenital heart disease on the treatment of esophageal atresia. Pediatr Surg Int. Feb
2006;22(2):150-3.
36. Jolley SG. A longitudinal study of children treated with the most common form of
esophageal atresia and tracheoesophageal fistula. J Pediatr Surg. Sep 2007;42(9):1632-3;
author reply 1633.
37. Lopes MF, Botelho MF. Midterm follow-up of esophageal anastomosis for esophageal
atresia repair: long-gap versus non-long-gap. Dis Esophagus. 2007;20(5):428-35.
38. Engum SA, Grosfeld JL, West KW, et al. Analysis of morbidity and mortality in 227
cases of esophageal atresia and/or tracheoesophageal fistula over two decades. Arch Surg.
May 1995;130(5):502-8; discussion 508-9.
39. Stringer MD, McKenna KM, Goldstein RB, et al. Prenatal diagnosis of esophageal
atresia. J Pediatr Surg. Sep 1995;30(9):1258-63.
40. van der Zee DC, Vieirra-Travassos D, Kramer WL, Tytgat SH. Thoracoscopic elongation
of the esophagus in long gap esophageal atresia. J Pediatr Surg. Oct 2007;42(10):1785-8.
41. Spitz L, Kiely E, Brereton RJ. Esophageal atresia: five year experience with 148 cases. J
Pediatr Surg. Feb 1987;22(2):103-8.
42. Spitz L. Esophageal atresia: past, present, and future. J Pediatr Surg. Jan 1996;31(1):19-
25.
43. Saxena AK, Ainoedhofer H, Hllwarth ME. Culture of ovine esophageal epithelial cells
and in vitro esophagus tissue engineering.Tissue Eng Part C Methods. Feb
2010;16(1):109-14.
44. Saxena AK, Kofler K, Aindhofer H, Hllwarth ME. Esophagus tissue engineering:
hybrid approach with esophageal epithelium and unidirectional smooth muscle tissue
component generation in vitro. J Gastrointest Surg. Jun 2009;13(6):1037-43.
45. Saxena AK, Ainoedhofer H, Hllwarth ME. Esophagus tissue engineering: in vitro
generation of esophageal epithelial cell sheets and viability on scaffold. J Pediatr Surg.
May 2009;44(5):896-901.