Tracheo-oesophageal fistula (TOF) is a common congenital malformation involving a communication (fistula) between the trachea and oesophagus. It typically occurs with oesophageal atresia (OA),with the upper end of the oesophagus ending in a blind pouch. TOF/ OA is a relatively common congenital anomaly occurring in approximately 1:3000-4500 live births.
Around 30% of TOF/ OA infants are born prematurely.
How do the trachea and oesophagus develop?
The oesophagus and trachea share a common embryologic origin: the foregut.
Around four weeks gestation, the respiratory diverticulum buds off the anterior aspect of the foregut tube in the region of the primitive pharynx and extends caudally to create a separate trachea and oesophagus. Successful formation of these structures is mediated by an intricate interplay of growth and transcription factors; hence, disruption to this results in these pathological anatomical variations. Genetic mutations in N-myc, Sox2 and CHD7 have been implicated as possible underlying mutations in syndromic TOF/OA with associated anomalies.
How do you classify tracheo-oesophageal fistulas?
There are five main types of TOF/ OA classified according to their anatomical configuration.
● Type C (proximal OA with distal TOF) is the most common type accounting for 85% of cases.
● Type A (isolated OA without TOF) accounts for 8-10% of cases.
● Type E (H-type TOF without OA) accounts for 8% of cases.
● Type D (OA with proximal and distal TOF) account for 2% of cases.
● Type B (distal OA with proximal TOF) accounts for 1% of cases.
What syndromes are associated with TOFs?
Approximately 50% of cases of TOF and OA are associated with other anomalies. They may be part of syndromes such as:
- VACTERL – Vertebral anomalies (absent vertebrae or hemivertebrae), Anorectal anomalies (imperforate anus), Cardiac defects, TracheoEsophageal fistula, Renal anomalies (renal agenesis, renal anomalies), and radial Limb hyperplasia
- CHARGE – Coloboma, Heart defects, Atresia choanae, Growth retardation, Genital abnormalities, and Ear abnormalities
Around 20% of infants born with oesophageal atresia will have some sort of congenital heart disease.
How do TOFs and oesophageal atresia present?
Clinical presentation varies depending on the type of TOF and the presence (or absence) of oesophageal atresia.
Suppose OA is present (types A-D). In that case, infants are usually symptomatic immediately after birth with excessive secretions. This manifests as drooling, choking or coughing post-feeds, poor tolerance of feeds, and respiratory distress.
If a fistula exists between the trachea and distal oesophagus (types C-E), they may have prominent abdominal distension as large volumes of air may enter the trachea, fistula and stomach during infant crying. This distension reduces the ability of the lungs to expand, leading to atelectasis and respiratory compromise. Additionally, reflux of gastric contents through the fistula may cause chemical pneumonitis and aspiration pneumonia, further compromising respiratory function.
Infants with H-type TOF may present at different ages depending on the size of the defect. If the fistula is large, infants will show signs of choking and coughing with feeds as milk is aspirated through the fistula into the trachea. If the fistula is small, they may be asymptomatic until after the newborn period. They typically have a prolonged history of mild respiratory distress associated with feeding, recurrent chest infections and failure to thrive.
How do you work up a child with a possible TOF?
Oesophageal atresia is usually diagnosed when a nasogastric tube (NGT) cannot be passed further than approximately 9-11cm or a coiled NGT is seen in the upper pouch on a chest x-ray. Suspect a distal TOF if you see a gas-filled stomach and distal GI tract on the x-ray or if you hear a tympanic sound on percussion. Conversely, a gasless stomach may suggest a pure OA or OA with proximal TOF.
If you suspect a proximal TOF, or are unsure, you can order an upper GI tract contrast study (using a water-soluble contrast). Polyhydramnios and a non-visualised or small stomach on a second or third-trimester obstetric ultrasound raise should raise suspicion.
An upper GI contrast series using a thickened water-soluble contrast material confirms the diagnosis of an H-type TOF. A prone withdrawal oesophagogram used to be the radiological investigation of choice; this involved injecting contrast material into the distal oesophagus and withdrawing the catheter slowly while the patient lies on their front, looking for contrast flow through a fistula into the trachea. A contrast swallow study, or even more invasive methods like endoscopy and bronchoscopy, are equally efficacious.
Given the high incidence of syndromes like CHARGE or VACTERL in infants with TOF/OA, it is essential to look for other anomalies. An echocardiogram, renal tract ultrasound, and spinal X-rays or ultrasound can help look for heart, renal and vertebral anomalies.
Consider if there could have been an oesophageal perforation from the traumatic insertion of a nasogastric or orogastric tube. This often occurs at the level of the piriform sinus.
What is the initial management for a child with a TOF/OA?
The initial priorities include respiratory stabilization, decompressing the upper pouch to prevent aspiration, and planning surgical intervention. Fluid resuscitation should be commenced if the neonate is hemodynamically unstable, although ideally, you should avoid placing an endotracheal tube as this can cause gastric distension and subsequent perforation.
Once stable, they should be put in an infant warmer with the head elevated to 30 degrees and have a Replogle/sump catheter inserted into the upper pouch on continuous suction. They should be kept nil by mouth prior to operative intervention. A preoperative echocardiogram is usually performed to rule out a significant congenital cardiac disease that might influence the timing of surgery. It also identifies the position of the aortic arch.
Most infants with TOF/OA undergo a single operation. This involves a primary anastomosis of the oesophageal ends and ligating the tracheo-oesphageal fistula. Ideally, it happens within a day or two of birth.
There are two possible approaches: an open thoracotomy or via thoracoscopy. A minimally invasive thoracoscopic approach is associated with less postoperative pain. Surgeons usually take a right-sided approach unless a right-sided aortic arch is identified on the pre-op echo. In theatre, the TOF is ligated, and the tracheal opening is closed. Each end of the oesophagus is then mobilised to permit anastomosis. A trans-anastomotic feeding tube is placed to facilitate feeding in the early postoperative period. The surgeons also place a retropleural drain. This is monitored closely in the postoperative period. The presence of saliva indicates an anastomotic leak.
5% cases (usually an isolated OA) have a ‘long gap OA’ – the two oesophageal ends are spaced too far apart (over 4cm) to achieve a successful primary anastomosis. Ideally, the native oesophagus is preserved, and patients undergo delayed primary anastomosis or lengthening procedures. These include a circular myotomy, oesophageal flap, Foker technique (tension sutures for oesophageal lengthening) or Kimura technique (extra-thoracic oesophageal lengthening). If these attempts appear futile, the oesophagus can be replaced by using conduits (i.e. stomach, bowel).
During this time, patients get a gastrostomy tube for gastric feeding and cervical oesophagostomy for ‘sham’ oral feeds to help develop oromotor skills. A Replogle tube in the upper pouch allows saliva drainage and reduces aspiration and pneumonia risk. Infants are managed in NICU, post-operatively for optimisation of analgesia, respiratory support, close monitoring of fluid balance, establishing feeds, managing sepsis risk, and observation for any complications.
Challenges in the premature infant
Ventilated, preterm infants with TOF/OA and associated respiratory distress syndrome present a unique challenge due to their fragile pulmonary status and risk of developing progressive cardiopulmonary dysfunction. Elevated airway pressures required for ventilation in premature infants, with a pre-existing background of poor lung compliance, can lead to gastric inflation and significant abdominal distension (as air preferentially travels down the low resistance fistula rather than the lungs), hence further compromising lung expansion. Furthermore, recurrent aspirations through the TOF causing chemical pneumonitis and soiling lead to worsening respiratory status. In order to counteract these issues, one should first consider minimizing airway pressures for ventilation by instead adopting HFOV (high-frequency oscillating ventilation). Furthermore, one should consider measures to reduce gastric distension if it compromises ventilation. Traditionally, an emergency gastrostomy would be performed. However this may paradoxically worsen respiratory status as ventilated gas preferentially passes through the fistula (path of least resistance) rather than into the lungs. Currently, emergency transpleural ligation of TOF (but not division) is recommended, with the aim to re-operate in 8-10 days to divide the fistula and repair the atresia. The aim of these interventions is to buy time to allow the infant’s respiratory distress syndrome to improve, clear pulmonary secretions and reach a level of clinical stability suitable for definitive repair.
What are the complications of a TOF repair?
Anastomotic leak (10-15% of cases) can occur in the immediate postoperative period or after several days. An early leak (within 48 hours) is suspected through a new pleural effusion, pneumothorax and sepsis and requires immediate exploration in the operating theatre. A delayed leak (after several days) can usually heal without surgical intervention and instead be managed conservatively with antibiotics, pulmonary toilet and optimisation of nutrition. Repeat an oesophagram in one week to assess for resolution of the leak.
Anastomotic stricture formation (10-20% cases) can occur at any time, from early postoperative to months or even years later. Clinical symptoms include choking, gagging or failure to thrive, most noticeable during the transition to solid foods. A contrast swallow or oesophagoscopy can confirm this and subsequently be corrected by endoscopic balloon dilatation(s) until a stable diameter permits normal eating and symptoms’ dissipation. Recurrent stricture formation is defined as the reappearance of symptoms ≥3 times at more than 30 days post dilatation, in which fundoplication, steroid stricture injection, topical application of mitomycin C or stent insertion should then be considered.
Gastroesophageal reflux (GOR) can manifest due to impaired oesophageal motility and anatomical changes of the gastroesophageal junction following TOF/OA surgery. Clinical symptoms can include choking, coughing or wheezing with feeds, crying or arching back during feeds, refusal to feed, poor weight gain or weight loss. 24-hour oesophageal pH-metry remains the gold standard for the diagnosis of GOR. Routinely these infants are prophylactically treated with anti-reflux medication for at least one year postoperatively. A Nissen fundoplication can help correct this in failed medical management or recurrent anastomotic stenosis, although ongoing feeding issues can persist.
Dysmotility can result from surgical repair and abnormal innervation, mainly affecting the distal oesophageal segment at birth. An upper GI contrast study can evaluate for evidence of dysmotility and differentiate the degree of severity. There are no specific medication options to treat dysmotility, as pro-kinetics is not recommended.
Dysphagia and feeding difficulty are some of the leading causes of nutritional problems, which can result from GOR, oesophagitis, dysmotility, anastomotic stricture, aspiration or food aversion related to a history of food impaction. This can be distressing for parents. However, it should not hinder the proper introduction to solids and a wide range of foods. Solids should still be introduced around 4-6 months but may require a slower introduction to solids and transition through different textures and varieties of foods. Involving a speech pathologist to assist with swallowing difficulties and exercises to aid chewing/ swallowing, as well as a dietician for optimisation of nutritional intake, can be beneficial.
Tracheomalacia (15% cases), a floppy trachea, can present due to lack of cartilage development and cause stridulous noises, a harsh brassy barking ‘TOF’ cough, reduced sputum clearance and breathing difficulties. TOF/OA children have a greater predisposition to suffering prolonged respiratory illnesses in their first few years of life secondary to inadequate clearance of secretions from tracheomalacia. Adopting chest physiotherapy input and mucus clearance exercises will help reduce the incidence, and these children are encouraged to have annual influenza vaccines. Other long-term complications include Barrett’s oesophagus and oesophageal cancer, resulting from chronic reflux.
What are the outcomes for a child with a TOF?
The survival rate for stable infants with TOF/OA nowadays exceeds 90% owing to earlier diagnosis, advances in neonatal anaesthesia and perioperative care, advanced ICU management, and early treatment of surgery. Unstable infants have an increased mortality rate owing to potentially fatal associated congenital and cardiac anomalies, prematurity, and/or pre-operative respiratory compromise with ventilatory requirements. The Spitz Prognostic classification system is the most widely accepted prognostic tool for TOF/ OA infants to predict survival outcomes based on two main criteria: birth weight (BW) and the presence of significant cardiac disease. Group 1 (BW >1500g without primary cardiac disease) had a 97-98% survival rate, group 2 (BW <1500g or significant cardiac disease) had a 59-82% survival rate, and group 3 (BW <1500g and major cardiac disease) had a 22-50% survival rate.
How should children with a TOF repair be followed up?
Motility, digestive and nutritional problems are frequent issues in the long-term follow-up of these patients; thus, focusing on early detection and management is essential in preserving quality of life. Clinicians should routinely monitor for any symptoms or signs of GOR, dysphagia, aspiration or nutritional decline and investigate and manage thoroughly as indicated. Long-term endoscopic surveillance of these patients is also recommended.
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