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Developmental Biology Sep 2021Trachea-esophageal defects (TEDs), including esophageal atresia (EA), tracheoesophageal fistula (TEF), and laryngeal-tracheoesophageal clefts (LTEC), are a spectrum of... (Review)
Review
Trachea-esophageal defects (TEDs), including esophageal atresia (EA), tracheoesophageal fistula (TEF), and laryngeal-tracheoesophageal clefts (LTEC), are a spectrum of life-threatening congenital anomalies in which the trachea and esophagus do not form properly. Up until recently, the developmental basis of these conditions and how the trachea and esophagus arise from a common fetal foregut was poorly understood. However, with significant advances in human genetics, organoids, and animal models, and integrating single cell genomics with high resolution imaging, we are revealing the molecular and cellular mechanisms that orchestrate tracheoesophageal morphogenesis and how disruption in these processes leads to birth defects. Here we review the current understanding of the genetic and developmental basis of TEDs. We suggest future opportunities for integrating developmental mechanisms elucidated from animals and organoids with human genetics and clinical data to gain insight into the genotype-phenotype basis of these heterogeneous birth defects. Finally, we envision how this will enhance diagnosis, improve treatment, and perhaps one day, lead to new tissue replacement therapy.
Topics: Animals; Digestive System Abnormalities; Disease Models, Animal; Esophagus; Humans; Organoids; Trachea
PubMed: 34023332
DOI: 10.1016/j.ydbio.2021.05.015 -
Annals of Translational Medicine Jun 2018Benign tracheoesophageal fistula (TEF) results from an abnormal communication between the posterior wall of the trachea or bronchi and the adjacent anterior wall of the... (Review)
Review
Benign tracheoesophageal fistula (TEF) results from an abnormal communication between the posterior wall of the trachea or bronchi and the adjacent anterior wall of the esophagus. It can be acquired or congenital. The onset of the TEF has a negative impact on the patient's health status and quality of life because of swallowing difficulties, recurrent aspiration pneumonia, and severe weight loss. Several acquired conditions may cause TEF. The most frequent is prolonged orotracheal intubation (75% of the cases). Usually, there is an erosion of the tracheal and esophageal wall by the continuous pressure between the endotracheal tube and the esophageal wall; particularly in the presence of a nasogastric or feeding tube within the esophageal lumen. Furthermore, tracheal stenosis is often associated, and adds complexity to the disease. Preparation for the surgical procedure may take weeks or even months. It includes definitive weaning from mechanical ventilation, treatment of respiratory infection, physiotherapy, and correction of malnutrition through enteral feeding. Surgical repair of a TEF is an elective procedure. It consists of division of the fistula, suture of the esophagus and trachea and protection of the suture lines with a buttressed muscle flap. TEF repair is a complex and challenging procedure, thus, high morbidity and mortality are expected. Nonetheless, surgical management yields excellent long-term results, and it should be considered the first-line treatment for this condition. Definitive fistula closure occurs in about 90-95% of the cases.
PubMed: 30023373
DOI: 10.21037/atm.2018.05.25 -
Acta Biomaterialia Sep 2021Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges...
Pleural and tracheal injuries remain significant problems, and an easy to use, effective pleural or tracheal sealant would be a significant advance. The major challenges are requirements for adherence, high strength and elasticity, dynamic durability, appropriate biodegradability, and lack of cell or systemic toxicity. We designed and evaluated two sealant materials comprised respectively of alginate methacrylate and of gelatin methacryloyl, each functionalized by conjugation with dopamine HCl. Both compounds are cross-linked into easily applied as pre-formed hydrogel patches or as in situ hydrogels formed at the wound site utilizing FDA-approved photo-initiators and oxidants. Material testing demonstrates appropriate adhesiveness, tensile strength, burst pressure, and elasticity with no significant cell toxicity in vitro assessments. Air-leak was absent after sealant application to experimentally-induced injuries in ex-vivo rat lung and tracheal models and in ex vivo pig lungs. Sustained repair of experimentally-induced pleural injury was observed for up to one month in vivo rat models and for up to 2 weeks in vivo rat tracheal injury models without obvious air leak or obvious toxicities. The alginate-based sealant worked best in a pre-formed hydrogel patch whereas the gelatin-based sealant worked best in an in situ formed hydrogel at the wound site thus providing two potential approaches. These studies provide a platform for further pre-clinical and potential clinical investigations. STATEMENT OF SIGNIFICANCE: Pneumothorax and pleural effusions resulting from trauma and a range of lung diseases and critical illnesses can result in lung collapse that can be immediately life-threatening or result in chronic leaking (bronchopleural fistula) that is currently difficult to manage. This leads to significantly increased morbidity, mortality, hospital stays, health care costs, and other complications. We have developed sealants originating from alginate and gelatin biomaterials, each functionalized by methacryloylation and by dopamine conjugation to have desired mechanical characteristics for use in pleural and tracheal injuries. The sealants are easily applied, non-cytotoxic, and perform well in vitro and in vivo model systems of lung and tracheal injuries. These initial proof of concept investigations provide a platform for further studies.
Topics: Alginates; Animals; Biocompatible Materials; Gelatin; Hydrogels; Rats; Swine; Tissue Adhesives
PubMed: 34245891
DOI: 10.1016/j.actbio.2021.06.048 -
Orphanet Journal of Rare Diseases Dec 2011A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx,... (Review)
Review
A laryngo-tracheo-esophageal cleft (LC) is a congenital malformation characterized by an abnormal, posterior, sagittal communication between the larynx and the pharynx, possibly extending downward between the trachea and the esophagus. The estimated annual incidence of LC is 1/10,000 to 1/20,000 live births, accounting for 0.2% to 1.5% of congenital malformations of the larynx. These incidence rates may however be underestimated due to difficulty in diagnosing minor forms and a high mortality rate in severe forms. A slightly higher incidence has been reported in boys than in girls. No specific geographic distribution has been found. Depending on the severity of the malformation, patients may present with stridor, hoarse cry, swallowing difficulties, aspirations, cough, dyspnea and cyanosis through to early respiratory distress. Five types of laryngo-tracheo-esophageal cleft have been described based on the downward extension of the cleft, which typically correlates with the severity of symptoms: Type 0 laryngo-tracheo-esophageal cleft to Type 4 laryngo-tracheo-esophageal cleft. LC is often associated with other congenital abnormalities/anomalies (16% to 68%), mainly involving the gastro-intestinal tract, which include laryngomalacia, tracheo-bronchial dyskinesia, tracheo-bronchomalacia (mostly in types 3 and 4), and gastro-esophageal reflux disease (GERD). The syndromes most frequently associated with an LC are Opitz/BBB syndrome, Pallister Hall syndrome, VACTERL/VATER association, and CHARGE syndrome. Laryngeal clefts result from failure of fusion of the posterior cricoid lamina and abnormal development of the tracheo-esophageal septum. The causes of the embryological developmental anomalies leading to LC are not known but are thought to be multifactorial. LC appears to be mostly sporadic although some familial cases with suspected autosomal dominant transmission have been reported. The age of diagnosis depends mainly on the severity of the clinical symptoms and therefore on the extent of the LC. Diagnosis is made either based on clinical manifestations or on investigations, such as endoscopy, X-ray, CT scan, performed for other conditions. Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal reflux disease and neurological swallowing disorders, as well as laryngomalacia and laryngeal palsy. Prenatal diagnosis of LC has never been reported, although associated anomalies may be detected on fetal ultrasonography. Once the cleft is diagnosed, it is essential to determine its length to orient the management and treatment approach. Management involves maintenance of satisfactory ventilation, prevention of secondary pulmonary complications as a result of repeated aspirations, and adequate feeding. Endotracheal intubation may be required for respiratory distress in severe cases. Treatment requires endoscopic or external surgery to close the cleft. Surgery should be performed as early as possible to avoid complications related to aspiration and gastric reflux, except in type 0 and type 1 cases in which conservative measures must first be attempted. The prognosis is variable depending on the severity of the LC and associated malformations. Early diagnosis and appropriate treatment and management help to reduce mortality and morbidity.
Topics: Abnormalities, Multiple; Animals; Child; Child, Preschool; Congenital Abnormalities; Endoscopy; Esophagus; Female; Humans; Infant; Infant, Newborn; Larynx; Male; Prognosis; Rats; Trachea
PubMed: 22151899
DOI: 10.1186/1750-1172-6-81 -
Seminars in Pediatric Surgery Dec 2022Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without...
Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without trachea-esophageal fistula (EA+/-TEF) to esophageal web, duplication, stricture, tracheomalacia and tracheal agenesis. Despite the relative frequency of EA, however, the underlying etiology remains unknown and is likely due to a combination of genetic, epigenetic and environmental factors. In recent years, animal models have dramatically increased our understanding of the molecular and morphological processes involved in normal esophageal development during the key stages of anterior-posterior regionalization, dorsal-ventral patterning and morphogenic separation. Moreover, the use of animal models in conjunction with increasingly advanced techniques such as genomic sequencing, sophisticated live imaging studies and organoid models have more recently cast light on potential mechanisms involved in EA pathogenesis. This article aims to unravel some of the mysteries behind the anatomy and embryology of EA whilst providing insights into future directions for research.
Topics: Animals; Humans; Tracheoesophageal Fistula; Esophageal Atresia; Trachea; Tracheomalacia
PubMed: 36459913
DOI: 10.1016/j.sempedsurg.2022.151231 -
Anaesthesia Sep 1994Agenesis of the trachea is a rare anomaly. The main signs are respiratory distress and cyanosis, inability to vocalize and impossible tracheal intubation. In most cases...
Agenesis of the trachea is a rare anomaly. The main signs are respiratory distress and cyanosis, inability to vocalize and impossible tracheal intubation. In most cases concomitant congenital anomalies of the heart, digestive tract or genitourinary tract are present. Endoscopy and X ray studies will confirm the diagnosis. There is no long-term surgical solution because no suitable material for a tracheal prosthesis is available at present, therefore the condition is ultimately fatal. We report a case of tracheal agenesis. After the diagnosis was established the baby's lungs were ventilated for several hours via an oesophageal tube and two broncho-oesophageal fistulae, but she finally died from untreatable respiratory acidosis. Autopsy revealed a Floyd's type III tracheal agenesis and a laryngeal cleft.
Topics: Acidosis, Respiratory; Bronchial Fistula; Esophageal Fistula; Female; Humans; Infant, Newborn; Respiratory Distress Syndrome, Newborn; Trachea
PubMed: 7978136
DOI: 10.1111/j.1365-2044.1994.tb04453.x -
Respiratory Care Apr 2005Tracheostomy may be associated with numerous acute, perioperative complications, some of which continue to be relevant well after the placement of the tracheostomy. A... (Review)
Review
Tracheostomy may be associated with numerous acute, perioperative complications, some of which continue to be relevant well after the placement of the tracheostomy. A number of clinically important unique late complications have been recognized as well, including the formation of granulation tissue, tracheal stenosis, tracheomalacia, tracheoinnominate-artery fistula, tracheoesophageal fistula, ventilator-associated pneumonia, and aspiration. The clinical relevance of these complications is considerable, as their manifestations range from minimally symptomatic to failure to wean from the ventilator (tracheal stenosis) to life-threatening hemorrhage (tracheoinnominate fistula). Treatment modalities vary depending upon the nature of the complication. For the most frequent complication, tracheal stenosis, a multidisciplinary approach utilizing bronchoscopy, laser, airway stents, and tracheal surgery is most effective.
Topics: Arterio-Arterial Fistula; Humans; Ischemia; Pneumonia; Pneumonia, Aspiration; Trachea; Tracheal Stenosis; Tracheoesophageal Fistula; Tracheostomy
PubMed: 15807919
DOI: No ID Found -
Journal of Clinical Medicine Nov 2023Recurrent tracheoesophageal fistula (RTEF) is usually a consequence of leakage or other complications after esophageal atresia repair performed through right-sided...
BACKGROUND
Recurrent tracheoesophageal fistula (RTEF) is usually a consequence of leakage or other complications after esophageal atresia repair performed through right-sided access. This results in extensive intrapleural adhesions, and open redo surgery poses a challenge. Alternatively, endoscopic endotracheal fistula obliteration usually requires repetitive procedures, and its success rate varies significantly between centers. We present a novel approach to recurrent fistulas. The innovation is in reaching the fistula through the virgin field via left-sided three-port thoracoscopy instead of classical right-sided thoracotomy.
METHODS
This is a presentation of a new operative technique based on a retrospective case series of patients operated on at our department between 2016 and 2023.
RESULTS
Eight patients after esophageal atresia repair (six with RTEF and two with post-fistula tracheal diverticula) were successfully treated with left-sided thoracoscopy. There were no conversions. One patient required rethoracoscopy for chylothorax. Another one, after RTEF closure, underwent multiple endoscopic obliterations of subsequent tracheal diverticulum. No other major complications nor re-recurrences were noted.
CONCLUSIONS
Left-sided thoracoscopy in redo esophageal atresia has the advantage of a "virgin" operative field and grants feasible access to the RTEF or tracheal diverticulum. We believe that this approach is worth further exploration because it combines minimal invasiveness with high effectiveness without all the consequences of a thoracotomy.
PubMed: 38068303
DOI: 10.3390/jcm12237251 -
Orphanet Journal of Rare Diseases May 2007Oesophageal atresia (OA) encompasses a group of congenital anomalies comprising of an interruption of the continuity of the oesophagus with or without a persistent... (Review)
Review
Oesophageal atresia (OA) encompasses a group of congenital anomalies comprising of an interruption of the continuity of the oesophagus with or without a persistent communication with the trachea. In 86% of cases there is a distal tracheooesophageal fistula, in 7% there is no fistulous connection, while in 4% there is a tracheooesophageal fistula without atresia. OA occurs in 1 in 2500 live births. Infants with OA are unable to swallow saliva and are noted to have excessive salivation requiring repeated suctioning. Associated anomalies occur in 50% of cases, the majority involving one or more of the VACTERL association (vertebral, anorectal, cardiac, tracheooesophageal, renal and limb defects). The aetiology is largely unknown and is likely to be multifactorial, however, various clues have been uncovered in animal experiments particularly defects in the expression of the gene Sonic hedgehog (Shh). The vast majority of cases are sporadic and the recurrence risk for siblings is 1%. The diagnosis may be suspected prenatally by a small or absent stomach bubble on antenatal ultrasound scan at around 18 weeks gestation. The likelihood of an atresia is increased by the presence of polyhydramnios. A nasogastric tube should be passed at birth in all infants born to a mother with polyhydramnios as well as to infants who are excessively mucusy soon after delivery to establish or refute the diagnosis. In OA the tube will not progress beyond 10 cm from the mouth (confirmation is by plain X-ray of the chest and abdomen). Definitive management comprises disconnection of the tracheooesophageal fistula, closure of the tracheal defect and primary anastomosis of the oesophagus. Where there is a "long gap" between the ends of the oesophagus, delayed primary repair should be attempted. Only very rarely will an oesophageal replacement be required. Survival is directly related to birth weight and to the presence of a major cardiac defect. Infants weighing over 1500 g and having no major cardiac problem should have a near 100% survival, while the presence of one of the risk factors reduces survival to 80% and further to 30-50% in the presence of both risk factors.
Topics: Abnormalities, Multiple; Animals; Digestive System Surgical Procedures; Esophageal Atresia; Genetic Testing; Humans; Infant, Newborn; Patient Selection; Preoperative Care; Prognosis; Risk Assessment; Tracheoesophageal Fistula
PubMed: 17498283
DOI: 10.1186/1750-1172-2-24 -
Annals of Medicine and Surgery (2012) Aug 2022Critically ill COVID-19 patients have to undergo positive pressure ventilation, a non-physiological and invasive intervention that can be lifesaving in severe ARDS.... (Review)
Review
Critically ill COVID-19 patients have to undergo positive pressure ventilation, a non-physiological and invasive intervention that can be lifesaving in severe ARDS. Similar to any other intervention, it has its pros and cons. Despite following Lung Protective Ventilation (LPV), some of the complications are frequently reported in these critically ill patients and significantly impact overall mortality. The complications related to invasive mechanical ventilation (IMV) in critically ill COVID-19 patients can be broadly divided into pulmonary and non-pulmonary. Among pulmonary complications, the most frequent is ventilator-associated pneumonia. Others are barotrauma, including subcutaneous emphysema, pneumomediastinum, pneumothorax, bullous lesions, cardiopulmonary effects of right ventricular dysfunction, and pulmonary complications mimicking cardiac failure, including pulmonary edema. Tracheal complications, including full-thickness tracheal lesions (FTTLs) and tracheoesophageal fistulas (TEFs) are serious but rare complications. Non-Pulmonary complications include neurological, nephrological, ocular, and oral complications.
PubMed: 35874936
DOI: 10.1016/j.amsu.2022.104201