**1. Introduction**

Oesophageal atresia (OA), a congenital anomaly characterised by absence or loss of a segment of the oesophagus, commonly affects the thoracic portion of the oesophagus, leaving upper and lower oesophageal segments. Loss of the oesophageal luminal continuity leads to impaired in utero swallowing of amniotic fluid as well as postnatal swallowing of saliva and food. Besides the loss of oesophageal continuity, most of the patients tend to have a connection between the trachea and the lower oesophageal segment and a few between the trachea and the upper oesophageal segment, a condition called tracheo-oesophageal fistula (TOF). In view of these, the main principles guiding the definitive surgical management of oesophageal atresia are (1) to disconnect any tracheo-oesophageal fistula and (2) to establish a conduit for swallowing, preferably using the native oesophageal segments.

During the early years, the surgical management of oesophageal atresia was associated with lots of challenges and high mortality [1–4]. Over the past two to three decades, however, the surgical outcome has improved significantly in most centres in the developed countries. This improvement is attributed to advances

#### **Figure 1.**

*Flow chart showing various topics to be discussed under oesophageal atresia.*

in neonatal anaesthesia, well-established neonatal intensive care units (NICU), availability of total parental nutrition (TPN) and refined surgical skills [1, 5–8]. Conversely, the surgical outcome of oesophageal atresia in developing countries still remains very poor due to lack of the aforementioned facilities, in addition to late presentation [9–11].

This chapter seeks to discuss OA by focusing on the topics shown in **Figure 1**.

## **2. Embryology of the oesophagus**

The oesophagus develops from the primitive foregut as a continuation of the pharynx. It is said to be present by the fifth week of gestation, and it attains its final foetal length (8–10 cm) during the 7th week of gestation [12]. Thus, the length of the oesophagus at birth is 8–10 cm, and this doubles during the first few years of life [12].

The normal embryology of the foregut, as found in most reports and textbooks of embryology, is divided into five developmental steps [13]:

1.During the first step, the endoderm (epithelium) of the primitive foregut differentiates into a ventral area called the *lung field* and a dorsal area called *oesophageal area*. The epithelium of the ventral area (lung field) of the primitive foregut consists of 3–4 cell layers, while that of the dorsal area (oesophageal area) has only one cell layer. This phase occurs when the embryo is about 22–23 days old.

**49**

*Oesophageal Atresia: Drowning a Child in His/Her Own Saliva*

2.Lung (tracheal) bud develops at the caudal end of the lung field.

3.During the third step, beginning caudally at the area of the lung bud, the

lateral walls of the foregut start to approximate, developing longitudinal ridges inside the lumen of the foregut. This clearly separates the ventral lung field

4.Epithelial tracheo-oesophageal septum develops during the fourth step; and it is assumed that this process also starts caudally and ends cranially close to the laryngeal primordium. This process is described by most investigators in four steps: (i) the epithelium of the longitudinal ridges starts to proliferate; (ii) the ridges, therefore, fuse in the midline of the primitive foregut and form an epithelial septum; (iii) cell death takes place in the central areas of the septum, noticeable by the appearance of nuclei pyknosis and (iv) as a result, mesenchymal tissue

then expands into the area between the trachea and the oesophagus.

a mesenchymal septum called tracheo-oesophageal septum.

Other developmental features of the oesophagus include [12]:

5.Separation of the respiratory tract from the oesophagus becomes definitive between the sixth and the seventh weeks of gestation through the formation of

It should be noted that most steps in this schematic description of the foregut

Mesenchymal circular coat (muscle) develops early in the sixth week of gesta-

Blood vessels enter the oesophageal wall during the seventh month of gestation and lymph capillaries between the third and fourth months of life [12]. The most important embryologic structure for blood supply to the oesophagus is the fourth branchial arch. The arch produces the subclavian artery and its branches, including the inferior thyroid artery which supplies the cervical oesophagus. The fourth branchial arch also produces the aorta, from which vessels spring to supply the

The formation of the oesophageal epithelium is peculiar; it "changes face" four times. The epithelium is stratified columnar at the start of embryonic life, becoming cuboidal later. In foetal life, it is ciliated columnar, and, finally, it becomes stratified squamous soon after birth. Innervation of the oesophageal wall is received from sympathetic nerve fibres from the thoracic trunk and celiac plexus and parasympa-

The oesophageal wall is formed from endoderm and mesoderm (**Figure 2**). The endoderm produces the oesophageal epithelium and glands, whereas the mesoderm produces the connective tissue, muscular coat, and angioblasts. Splanchnic mesenchyme surrounds the oesophagus and trachea. The splanchnic mesenchyme forms

The causal branchial arches (4 and 6) are responsible for the formation of the striated musculature of the upper oesophagus and pharynx. They are innervated by the vagus nerve (nerve to the fourth arch) and the recurrent laryngeal nerve branch

The oesophageal lumen is almost filled with vacuolated cells from proliferation of oesophageal epithelium during the seven–eighth weeks of gestation. The filling is never complete, and hence the so-called solid stage does not exist. At 10 weeks' gestation, the lumen of the oesophagus is restored as the vacuolated cells disappear.

tion. The longitudinal muscle forms between the ninth and twelfth weeks of gestation, and the muscularis mucosa develops at approximately the fourth month

*DOI: http://dx.doi.org/10.5772/intechopen.84525*

and the dorsal oesophageal area.

embryology lack clear evidence [13].

thetic innervation from the vagus nerve.

the smooth muscle of the lower oesophagus.

of the vagus nerve (nerve to the sixth arch) [12].

of gestation [12].

thoracic oesophagus.

*Pediatric Surgery, Flowcharts and Clinical Algorithms*

in neonatal anaesthesia, well-established neonatal intensive care units (NICU), availability of total parental nutrition (TPN) and refined surgical skills [1, 5–8]. Conversely, the surgical outcome of oesophageal atresia in developing countries still remains very poor due to lack of the aforementioned facilities, in addition to late

This chapter seeks to discuss OA by focusing on the topics shown in **Figure 1**.

The oesophagus develops from the primitive foregut as a continuation of the pharynx. It is said to be present by the fifth week of gestation, and it attains its final foetal length (8–10 cm) during the 7th week of gestation [12]. Thus, the length of the oesophagus at birth is 8–10 cm, and this doubles during the first few years of life [12]. The normal embryology of the foregut, as found in most reports and textbooks

1.During the first step, the endoderm (epithelium) of the primitive foregut differentiates into a ventral area called the *lung field* and a dorsal area called *oesophageal area*. The epithelium of the ventral area (lung field) of the primitive foregut consists of 3–4 cell layers, while that of the dorsal area (oesophageal area) has only one cell layer. This phase occurs when the embryo is about

of embryology, is divided into five developmental steps [13]:

*Flow chart showing various topics to be discussed under oesophageal atresia.*

**48**

presentation [9–11].

**Figure 1.**

22–23 days old.

**2. Embryology of the oesophagus**

2.Lung (tracheal) bud develops at the caudal end of the lung field.


It should be noted that most steps in this schematic description of the foregut embryology lack clear evidence [13].

Other developmental features of the oesophagus include [12]:

Mesenchymal circular coat (muscle) develops early in the sixth week of gestation. The longitudinal muscle forms between the ninth and twelfth weeks of gestation, and the muscularis mucosa develops at approximately the fourth month of gestation [12].

Blood vessels enter the oesophageal wall during the seventh month of gestation and lymph capillaries between the third and fourth months of life [12]. The most important embryologic structure for blood supply to the oesophagus is the fourth branchial arch. The arch produces the subclavian artery and its branches, including the inferior thyroid artery which supplies the cervical oesophagus. The fourth branchial arch also produces the aorta, from which vessels spring to supply the thoracic oesophagus.

The formation of the oesophageal epithelium is peculiar; it "changes face" four times. The epithelium is stratified columnar at the start of embryonic life, becoming cuboidal later. In foetal life, it is ciliated columnar, and, finally, it becomes stratified squamous soon after birth. Innervation of the oesophageal wall is received from sympathetic nerve fibres from the thoracic trunk and celiac plexus and parasympathetic innervation from the vagus nerve.

The oesophageal wall is formed from endoderm and mesoderm (**Figure 2**). The endoderm produces the oesophageal epithelium and glands, whereas the mesoderm produces the connective tissue, muscular coat, and angioblasts. Splanchnic mesenchyme surrounds the oesophagus and trachea. The splanchnic mesenchyme forms the smooth muscle of the lower oesophagus.

The causal branchial arches (4 and 6) are responsible for the formation of the striated musculature of the upper oesophagus and pharynx. They are innervated by the vagus nerve (nerve to the fourth arch) and the recurrent laryngeal nerve branch of the vagus nerve (nerve to the sixth arch) [12].

The oesophageal lumen is almost filled with vacuolated cells from proliferation of oesophageal epithelium during the seven–eighth weeks of gestation. The filling is never complete, and hence the so-called solid stage does not exist. At 10 weeks' gestation, the lumen of the oesophagus is restored as the vacuolated cells disappear.

**Figure 2.**

*Embryologic duo responsible for genesis of the oesophagus.*

#### **2.1 Anatomy of the oesophagus**

The oesophagus is a muscular tube connecting the pharynx to the stomach. At birth, the length of the oesophagus is about 8–10 cm, and this doubles in the first few years of life. The length of the oesophagus in the adult is about 25 cm. It extends from the lower border of the cricoid cartilage (at the level of the C6 vertebra) to the cardiac orifice of the stomach at the level of T11 vertebra. The upper limit in the newborn is found at the level of the fourth or fifth cervical vertebra and ends higher at the level of the T9 vertebra [14, 15].

The oesophageal wall is composed of mucosa, submucosa, muscularis propria and adventitia, lacking a distinct serosa. The mucosa is the strongest layer of the oesophageal wall. Hence, meticulous approximation of the oesophageal mucosa is essential for a technically sound anastomosis.

The oesophagus is divided into three segments—*cervical, thoracic and abdominal segments*. The cervical portion is somewhat curved, with its convex side to the left, thereby projecting to the left of the trachea. Incisions for approaching the cervical oesophagus are commonly made on this side. Anteriorly, the cervical oesophagus is covered by the trachea.

The arterial blood supply to the oesophagus is generally considered with regard to the cervical, thoracic and abdominal segments of the oesophagus. The arterial blood supply to the pharyngo-oesophageal junction and the cervical oesophagus is derived from branches of the inferior thyroid artery. In addition, the pharyngo-oesophageal junctional area of the oesophagus is supplied by small arterial branches of the subclavian (artery of Luschka), common carotid, vertebral, superior thyroid and costocervical trunk vessels [12, 16]. The thoracic oesophagus is supplied from oesophageal branches of the aorta, the bronchial arteries and the right intercostal arteries. Accessory oesophageal branches are also present directly from the internal mammary, common carotid and superior intercostal arteries [12, 17]. The left gastric artery provides oesophageal blood supply to the abdominal segment of the oesophagus in most individuals. Rarely, oesophageal arteries will arise from an accessory left hepatic artery. In less than one-half of individuals, the oesophagus receives arterial blood via the left inferior phrenic artery and rarely from the right inferior phrenic artery [16]. A welldeveloped subepithelial network of capillaries is present in the oesophageal mucosa and submucosa [18, 19]. The excellent submucosa plexus of the proximal oesophagus allows for extensive mobilization without compromise to the blood supply, whereas caution should be taken distally because of the segmental lower oesophageal blood supply.

Venous drainage from the oesophagus includes intrinsic and extrinsic vessels. The intrinsic system includes subepithelial and submucosal veins that join gastric veins and perforating veins that join with the extrinsic system of veins. The extrinsic veins include larger longitudinal vessels that run on the outer surface of the oesophagus and are close to the vagus nerves. These vessels connect the left gastric vein to the azygous or hemiazygous veins either directly or indirectly via the posterior bronchial veins. Extrinsic veins drain into the inferior thyroid, vertebral and deep cervical veins in the cervical region. Oesophageal veins at the level of the

**51**

vagotomy.

**2.2 Physiology of the oesophagus**

lial tracheo-oesophageal septum [13].

*Oesophageal Atresia: Drowning a Child in His/Her Own Saliva*

cardia join the phrenic and abdominal oesophageal veins to drain primarily into the left gastric vein, as well as the gastroepiploic and splenic veins [20]. This may be a point of importance when dealing with a patient with portal hypertension.

The oesophageal lymphatics form plexuses in the mucosa (lamina propria), submucosa, muscularis, and adventitia with interconnectivity [12]. Collecting trunks

In the oesophageal wall are two plexuses of nerves for intrinsic nerve supply: (i) Meissner's plexus in the submucosa and (ii) Auerbach's plexus in the connective tissue between the circular and longitudinal muscularis externa [12]. These plexuses form networks of multipolar ganglion cells, the processes of which are in contact with one another and receive axons from the vagus. The oesophagus receives extrinsic nerve supply from three sources: the (a) cerebrospinal, (b) sympathetic and (c) parasympathetic (vagal) nervous systems [12].

The cricopharyngeal (CP) muscle, which is located at the pharyngo-oesophageal junction, attaches to the cricoid cartilage and forms a C-shaped muscular band. It is innervated by the pharyngeal plexus of the vagus nerve and the recurrent laryngeal nerve [21]. The main function of the CP muscle is to control luminal flow between the pharynx and oesophagus. The CP sphincter muscle is tonically contracted at rest and relaxes during swallowing. The major component of the upper oesophageal sphincter (UES) is the CP muscle, although the inferior pharyngeal constrictor and

The function of the lower oesophageal sphincter is abolished by total truncal

The main function of the oesophagus is for swallowing, and this is achieved through peristalsis. Functionally, the oesophagus is divided into three areas: (i) the upper oesophageal sphincter (UOS), (ii) the oesophageal body and (iii) the lower oesophageal sphincter (LOS). The coordinated activity of these three parts is essential to ensure propulsion of bolus from the pharynx to the stomach. The UOS plays a key role in controlling regurgitation of oesophageal content into the pharynx and the airways, while the LOS prevents reflux of gastric content into the oesophagus.

Various theories were developed in the past to explain the embryology of foregut

anomalies. These theories are grouped into four [13]: (i) oesophageal occlusion theory, (ii) theories of spontaneous deviation of the tracheo-oesophageal septum,

Tandler postulated the theory of foregut occlusion in 1902 as a physiological occlusion during duodenal development [13]. Such physiological occlusion is also postulated to occur during oesophageal development; and that failure of recanalisation leads to oesophageal atresia [13]. Tracheo-oesophageal septal deviation is found to be another theory that explains the development of OA [13]. Various mechanisms have been used to explain the mechanical theory [13]. These include ventral pressure on the developing oesophagus by a very big anlage of the heart and aberrant vessels. The NOS theories include the development of a very large tracheal field that uses too much tissue to form the trachea, resulting in a shortage of dorsal tissue. Abnormal septation, combined with a disturbance in the organ inducing field, is believed to account for OA with TOF. Isolated TOF is speculated to result from a loss of epithelial proliferation or through an excessive necrosis in the area of the epithe-

(iii) mechanical theories and (iv) not otherwise specified (NOS) theories.

originate in the submucosa and empty into the nearest lymph nodes.

striated muscles of the proximal oesophagus also contribute [22].

**2.3 Aetiology and pathogenesis of oesophageal atresia**

*DOI: http://dx.doi.org/10.5772/intechopen.84525*

#### *Oesophageal Atresia: Drowning a Child in His/Her Own Saliva DOI: http://dx.doi.org/10.5772/intechopen.84525*

*Pediatric Surgery, Flowcharts and Clinical Algorithms*

*Embryologic duo responsible for genesis of the oesophagus.*

**2.1 Anatomy of the oesophagus**

**Figure 2.**

at the level of the T9 vertebra [14, 15].

covered by the trachea.

essential for a technically sound anastomosis.

The oesophagus is a muscular tube connecting the pharynx to the stomach. At birth, the length of the oesophagus is about 8–10 cm, and this doubles in the first few years of life. The length of the oesophagus in the adult is about 25 cm. It extends from the lower border of the cricoid cartilage (at the level of the C6 vertebra) to the cardiac orifice of the stomach at the level of T11 vertebra. The upper limit in the newborn is found at the level of the fourth or fifth cervical vertebra and ends higher

The oesophageal wall is composed of mucosa, submucosa, muscularis propria and adventitia, lacking a distinct serosa. The mucosa is the strongest layer of the oesophageal wall. Hence, meticulous approximation of the oesophageal mucosa is

The oesophagus is divided into three segments—*cervical, thoracic and abdominal segments*. The cervical portion is somewhat curved, with its convex side to the left, thereby projecting to the left of the trachea. Incisions for approaching the cervical oesophagus are commonly made on this side. Anteriorly, the cervical oesophagus is

The arterial blood supply to the oesophagus is generally considered with regard to the cervical, thoracic and abdominal segments of the oesophagus. The arterial blood supply to the pharyngo-oesophageal junction and the cervical oesophagus is derived from branches of the inferior thyroid artery. In addition, the pharyngo-oesophageal junctional area of the oesophagus is supplied by small arterial branches of the subclavian (artery of Luschka), common carotid, vertebral, superior thyroid and costocervical trunk vessels [12, 16]. The thoracic oesophagus is supplied from oesophageal branches of the aorta, the bronchial arteries and the right intercostal arteries. Accessory oesophageal branches are also present directly from the internal mammary, common carotid and superior intercostal arteries [12, 17]. The left gastric artery provides oesophageal blood supply to the abdominal segment of the oesophagus in most

individuals. Rarely, oesophageal arteries will arise from an accessory left hepatic artery. In less than one-half of individuals, the oesophagus receives arterial blood via the left inferior phrenic artery and rarely from the right inferior phrenic artery [16]. A welldeveloped subepithelial network of capillaries is present in the oesophageal mucosa and submucosa [18, 19]. The excellent submucosa plexus of the proximal oesophagus allows for extensive mobilization without compromise to the blood supply, whereas caution should be taken distally because of the segmental lower oesophageal blood supply. Venous drainage from the oesophagus includes intrinsic and extrinsic vessels. The intrinsic system includes subepithelial and submucosal veins that join gastric veins and perforating veins that join with the extrinsic system of veins. The extrinsic veins include larger longitudinal vessels that run on the outer surface of the oesophagus and are close to the vagus nerves. These vessels connect the left gastric vein to the azygous or hemiazygous veins either directly or indirectly via the posterior bronchial veins. Extrinsic veins drain into the inferior thyroid, vertebral and deep cervical veins in the cervical region. Oesophageal veins at the level of the

**50**

cardia join the phrenic and abdominal oesophageal veins to drain primarily into the left gastric vein, as well as the gastroepiploic and splenic veins [20]. This may be a point of importance when dealing with a patient with portal hypertension.

The oesophageal lymphatics form plexuses in the mucosa (lamina propria), submucosa, muscularis, and adventitia with interconnectivity [12]. Collecting trunks originate in the submucosa and empty into the nearest lymph nodes.

In the oesophageal wall are two plexuses of nerves for intrinsic nerve supply: (i) Meissner's plexus in the submucosa and (ii) Auerbach's plexus in the connective tissue between the circular and longitudinal muscularis externa [12]. These plexuses form networks of multipolar ganglion cells, the processes of which are in contact with one another and receive axons from the vagus. The oesophagus receives extrinsic nerve supply from three sources: the (a) cerebrospinal, (b) sympathetic and (c) parasympathetic (vagal) nervous systems [12].

The cricopharyngeal (CP) muscle, which is located at the pharyngo-oesophageal junction, attaches to the cricoid cartilage and forms a C-shaped muscular band. It is innervated by the pharyngeal plexus of the vagus nerve and the recurrent laryngeal nerve [21]. The main function of the CP muscle is to control luminal flow between the pharynx and oesophagus. The CP sphincter muscle is tonically contracted at rest and relaxes during swallowing. The major component of the upper oesophageal sphincter (UES) is the CP muscle, although the inferior pharyngeal constrictor and striated muscles of the proximal oesophagus also contribute [22].

The function of the lower oesophageal sphincter is abolished by total truncal vagotomy.

#### **2.2 Physiology of the oesophagus**

The main function of the oesophagus is for swallowing, and this is achieved through peristalsis. Functionally, the oesophagus is divided into three areas: (i) the upper oesophageal sphincter (UOS), (ii) the oesophageal body and (iii) the lower oesophageal sphincter (LOS). The coordinated activity of these three parts is essential to ensure propulsion of bolus from the pharynx to the stomach. The UOS plays a key role in controlling regurgitation of oesophageal content into the pharynx and the airways, while the LOS prevents reflux of gastric content into the oesophagus.

#### **2.3 Aetiology and pathogenesis of oesophageal atresia**

Various theories were developed in the past to explain the embryology of foregut anomalies. These theories are grouped into four [13]: (i) oesophageal occlusion theory, (ii) theories of spontaneous deviation of the tracheo-oesophageal septum, (iii) mechanical theories and (iv) not otherwise specified (NOS) theories.

Tandler postulated the theory of foregut occlusion in 1902 as a physiological occlusion during duodenal development [13]. Such physiological occlusion is also postulated to occur during oesophageal development; and that failure of recanalisation leads to oesophageal atresia [13]. Tracheo-oesophageal septal deviation is found to be another theory that explains the development of OA [13]. Various mechanisms have been used to explain the mechanical theory [13]. These include ventral pressure on the developing oesophagus by a very big anlage of the heart and aberrant vessels. The NOS theories include the development of a very large tracheal field that uses too much tissue to form the trachea, resulting in a shortage of dorsal tissue. Abnormal septation, combined with a disturbance in the organ inducing field, is believed to account for OA with TOF. Isolated TOF is speculated to result from a loss of epithelial proliferation or through an excessive necrosis in the area of the epithelial tracheo-oesophageal septum [13].

Aetiologically, various genetic defects have been found to be associated with oesophageal atresia. Important genes related to the pathogenesis of OA, and mostly involved in developmental pathways, include vitamin A effectors, retinoic acid receptors a and b (Rara and Rarb), sonic hedgehog pathway effectors (Shh, Gli2, Gli3 and Foxf1) and other homeobox containing transcription factors (Hoxc4, Ttf-1 and Pcsk5) [23]. Various environmental teratogens have also been implicated in the pathogenesis of OA-TOF [23]. Infants born to mothers with prolonged exposure to contraceptive pills (exposure to progesterone and oestrogen) during pregnancy have high risk. Oesophageal atresia has also been reported in some infants of hyperthyroid and uncontrolled diabetic mothers. Intrauterine exposure to thalidomide and diethylstilbestrol are also found to be associated with OA.
