International Journal of Pediatric Otorhinolaryngology 78 (2014) 905–911
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Review Article
Laryngeal cleft: Evaluation and management Douglas R. Johnston a,*, Karen Watters b,c, Lynne R. Ferrari d, Reza Rahbar b,c a
Division of Otolaryngology, Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE, United States Department of Pediatric Otolaryngology and Communication Enhancement, Boston Children’s Hospital, Boston, MA, United States c Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States d Department of Anesthesiology, Boston Children’s Hospital, Boston, MA, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 13 December 2013 Received in revised form 14 March 2014 Accepted 15 March 2014 Available online 27 March 2014
Objectives: Review the latest diagnostic and treatment modalities for laryngeal and laryngotracheoesophageal clefts as they can be a major cause of respiratory and feeding morbidity in the infant and pediatric population. Methods: Literature review of published reports. Results: The presentation of laryngeal cleft usually involves respiratory symptoms, such as stridor, chronic cough, aspiration, and recurrent respiratory infections. Clefts of the larynx and trachea/ esophagus can occur in isolation, as part of a syndrome (Opitz-Frias, VATER/VACTERL, Pallister Hall, CHARGE), or with other associated malformations (gastrointestinal, genitourinary, cardiac, craniofacial). This publication reviews the presenting signs/symptoms, diagnostic options, prognosis, and treatment considerations based on over a decade of experience of the senior author with laryngeal clefts. Conclusions: Type I laryngeal clefts can be managed medically or surgically depending on the degree of morbidity. Types II, III, and IV require endoscopic or open surgery to avoid chronic respiratory and feeding complications. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Laryngeal cleft Laryngotracheoesophageal cleft Stridor Aspiration Cough
Contents 1. 2. 3.
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Modified barium swallow (MBS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing. 3.4. Operative endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Medical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Surgical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Postoperative care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Abbreviations: MBS, modified barium swallow; FEES, functional endoscopic evaluation of swallowing. * Corresponding author at: Division of Otolaryngology, Nemours A.I. DuPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, United States. Tel.: +1 6107011116; fax: +1 3026515835. E-mail address: [email protected] (D.R. Johnston). http://dx.doi.org/10.1016/j.ijporl.2014.03.015 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Laryngeal and laryngotracheoesophageal clefts (hereafter referred to as laryngeal cleft) represent a spectrum of clinical symptoms and presentations based on the depth of the cleft and the overall health of the child. Type I and II laryngeal clefts often have delays in diagnosis, whereas types III and IV are likely to
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present within the first days of life. Likewise, a type I cleft in an otherwise healthy child may have minimal clinical impact, whereas the same cleft in a child with cardiac disease can cause significant morbidity. Therefore, clinicians who treat laryngeal clefts must treat the patient in the context of his or her overall clinical picture and recognize that laryngeal clefts represent a spectrum of disease. Initially described by Richter in 1792, laryngeal clefts have been underdiagnosed for centuries. The first successful repair of a laryngeal cleft was performed by Petterson in 1955 [1]. A series of over 20 patients did not appear until the 1990s [2–5]. Although it has been suggested that inheritance may be autosomal dominant, it is now clear that no such associations exist [6]. A slight male preponderance is observed [2,3,5]. Estimates of the incidence of laryngeal clefts are challenging because type I clefts often go misdiagnosed for long periods and usually surface at tertiary care institutions. Nonetheless, amongst patients who have direct laryngoscopy for recurrent respiratory symptoms, the incidence ranges from 0.2 to 7.6% [3,7–12]. Embryologically, a posterior laryngeal cleft is believed to result from incomplete formation of the interarytenoid muscle with or without absence of the interarytenoid mucosa. The former is known as a submucous laryngeal cleft and the latter a type I laryngeal cleft, which does not extend beyond the level of the vocal cords. Incomplete formation of the posterior cricoid cartilage alone forms a type II cleft, and incomplete formation of the tracheoesophageal septum distal to the cricoid cartilage forms either a type III or IV cleft. Extension beyond the cricoid cartilage into the tracheoesophageal septum is a type III, and extension into the thorax is a type IV. This Benjamin and Inglis classification is the most widely used and functional of those proposed to date [13] (Fig. 1). The interarytenoid muscle (along with all intrinsic laryngeal muscles) and the cricoid cartilage are [(Fig._1)TD$IG]
derivatives of the sixth branchial arch [14]. The above spectrum of developmental insults occurs between the fifth and sixth embryologic weeks. Diagnosis and management of laryngeal clefts are far from uniform and can inspire controversy. Specifically, there is a lack of standardized evaluation and diagnosis; modified barium swallow (MBS) and functional endoscopic evaluation of swallowing (FEES) have an unclear role in diagnosis; the role, efficacy, and duration of feeding therapy are debated; and, lastly, the timing and type of surgical intervention is quite variable. Our diagnostic and treatment recommendations are presented herein. 2. Presentation Presenting signs of a posterior laryngeal cleft are most often respiratory in nature. Chronic cough is common, especially with feeding, as is a variable degree of respiratory distress, depending on cleft depth. In a child with significant medical morbidities, cough may be prominent and associated with frank cyanosis. Conversely, a child with a type I cleft may have minimal disease manifestations, such as mild feeding difficulties. In our first published series of 22 patients, roughly 90% (20/22) with type I-III clefts had respiratory symptoms, including aspiration, recurrent pneumonia, stridor, and cyanosis [4]. Our second series of 74 type I and II patients demonstrated a 50–60% rate of wheezing and chronic cough, whereas hospital respiratory admissions ranged from 15% for type I clefts to 25% for type II [5]. Other authors have reported variable rates of respiratory presenting signs in type I and II clefts, most commonly stridor, recurrent respiratory infections, and chronic cough [2,3,15]. Type III and IV clefts invariably are associated with greater respiratory symptoms with recurrent pneumonia and often excessive pulmonary mucous. They usually present within the first few days of life.
Fig. 1. Posterior view (top row), superior view (middle row), and endoscopic intraoperative view (bottom row) of Benjamin and Inglis classification of laryngeal and laryngotracheoesophageal clefts: column A, normal larynx; column B, type I extends to the level of vocal cords; column C, type II extends below vocal cords into cricoid cartilage; column D, type III extends through cricoid cartilage to cervical trachea/esophagus; column E, type IV extends to level of thoracic trachea/esophagus. Note: it is difficult in endoscopic view to show depth of type IV cleft as there frequently is redundant mucosa [13].
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Table 1 Syndromes with possible laryngeal and laryngo-tracheoesophageal clefts. Syndrome
Features
Opitz Frias Pallister Hall VACTERL CHARGE
Hypertelorism, hypospadias, cleft lip and palate Abnormalities of hypothalamus/pituitary gland; poly- and syndactyly; imperforate anus; cardiac, pulmonary, and renal abnormalities Vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistulas, ear anomalies, renal abnormalities, Limb malformation Coloboma of the eyes, heart anomalies, choanal atresia, growth and mental retardation, genital anomalies, ear abnormalities
Type I clefts usually do not have considerable symptomatology until at least several months of age and diagnosis is commonly established between two and five years of age [3,5,15]. When laryngeal cleft is not included in the differential diagnosis for patients with recurrent respiratory symptoms, diagnosis can be delayed into adulthood. Establishing a comprehensive differential diagnosis is essential in light of the fact that most children with these symptoms will not have a laryngeal cleft. Clinically significant laryngomalacia, gastroesophageal reflux disease, neuromuscular swallowing disorders, and reactive airway disease are much more common than laryngeal clefts. Congenital defects in association with laryngeal clefting are seen in over half of this population (58–68%) [2,3,5,16]. These defects can include other anatomic malformations or coincident pathology. Of the associated malformations, gastrointestinal are the most common, including esophageal atresia, microgastria, tracheoesophageal fistula, imperforate anus, and intestinal malrotation, among others. Genitourinary defects are less common and include hypospadias and kidney malformations. Cardiac abnormalities cannot be ignored, such as aortic coarctation, transposition of the great vessels, patent ductus arteriosus, and septal defects. Less common are craniofacial abnormalities, including cleft lip and palate, micrognathia, and choanal atresia. Lastly, respiratory defects comprise a small percentage and are comprised largely of tracheal and bronchial size and shape irregularities. Coincident pathologies seen commonly with laryngeal clefts are laryngomalacia, which was present in up to 90% of type I clefts in one series [15], tracheo-bronchomalacia in over half of patients, and gastroesophageal reflux disease. The abnormal configuration of the posterior larynx, and possibly trachea, can result in redundant arytenoid, posterior laryngeal, and esophageal mucosa, which results in prolapse during inspiration and associated airway narrowing. The presence of clinically significant gastroesophageal disease is likely quite high, given the greater chance of aspiration of gastric contents, but pH probe proven disease is usually not established. Syndromic associations with laryngeal clefts are Opitz Frias syndrome (hypertelorism, hypospadias, cleft lip and palate), Pallister Hall syndrome (hypothalamic/pituitary abnormalities, poly- and syndactyly, imperforate anus, cardiac, pulmonary, renal abnormalities), VACTERL syndrome (Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracheoesophageal fistulas (TEF), Ear anomalies, Renal anomalies, Limb anomalies), and CHARGE syndrome (Coloboma, Heart anomalies, choanal Atresia, growth and mental Retardation, Genital anomalies, and Ear anomalies) [17] (Table 1). Due to the above syndromes and other less common ones, a genetic evaluation is warranted in many laryngeal cleft patients. 3. Diagnosis The cornerstone of diagnosis of a laryngeal cleft is direct laryngoscopy with palpation of the interarytenoid area, but the most important factor in the diagnosis is including this rare anomaly in the differential diagnosis. Patients with type III and IV clefts often require early bronchoscopy for hypoxic and apneic episodes, at which time
the astute clinician can diagnose the condition. The more difficult task is to identify the patient who requires direct laryngoscopy due to persistent respiratory symptoms that could be ascribed to other disorders, such as laryngomalacia, GERD, or vocal cord paralysis; or persistent feeding difficulty that might be related to hypoxia, birth trauma, congenital infections, or maternal drug use. A posterior laryngeal cleft should be ruled out in any pediatric patient with a history of recurrent pneumonia, feeding difficulty with coughing and choking, or post-feeding stridor. Type I and II laryngeal clefts often have symptom overlap with reactive airway disease and the asthma-like symptoms of recurrent aspiration can show some response to the same bronchodilators. Radiologic features of lower respiratory tract infections and asthma are also often similar. Wheezing and chronic cough are usually managed by pediatricians and, next, referred to a pulmonologist when refractory to treatment. Thus, the delay in referral to an otolaryngologist can continue for some time. The clue for referral to an otolaryngologist lies in the persistence of symptoms despite aggressive treatment for asthma. Similarly, treatment of suspected GERD or bronchiolitis should affect a measurable and durable benefit, especially as these conditions should improve over the first 2 years of life. 3.1. Chest X-ray All children with the above respiratory symptoms usually come to obtain a chest X-ray, which is a minor, albeit important, part of the diagnostic algorithm. Persistent, chronic aspiration will be identified as pneumonia or peribronchial cuffing. The chest X-ray can, also, be normal in 25% of type I and 13% of type II clefts [5]. 3.2. Modified barium swallow (MBS) The MBS is a critical part of the evaluation of cleft patients, but it must be emphasized that it can be normal in those who aspirate intermittently. Most patients will have undergone multiple MBS studies prior to presenting to an otolaryngologist and the cumulative radiation dose can be considerable, so repeating this test must be done cautiously. The technique of a MBS is for a speech/swallowing pathologist to administer a patient various consistencies of food containing a radio-labeled tracer that can be identified under fluoroscopy. Anterior–posterior and lateral views are obtained to study the oral, pharyngeal, esophageal, and gastric phases of swallowing. Importantly, the MBS can identify patients who have a discoordinated swallow. Those patients with global neurodevelopmental delay will often have poor coordination in the complex pharyngeal phase of swallowing, pointing to other diagnostic considerations. A positive swallow study for aspiration in an otherwise healthy child has a strong correlation with an anatomic abnormality. Overall, over 75% of patients with type I and II clefts will, in our experience, display aspiration on MBS. 3.3. Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing (FEES) assist in diagnosis because they
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provide a dynamic view of laryngeal function. The flexible exam, as well as FEES, is possible in certain age groups and can alert the clinician to anatomic abnormalities, especially the presence of a vocal cord palsy or paralysis, which can lead to decreased laryngeal sensation and aspiration [12]. The FEES technique involves an otolaryngologist, often with a speech/swallow pathologist, administering various consistencies of food dyed for easy identification. A flexible fiberoptic endoscope is passed transnasally and positioned in the nasopharynx or posterior oropharynx to visualize after the swallow if food pooling or penetration/aspiration has occurred. The advantages of FEES are superior anatomic evaluation relative to MBS, including vocal cord motion; location of aspiration, penetration, and secretion pooling; and possible visualization of changes after swallowing maneuvers are employed. Disadvantages include a foreign object in the airway, which has an unknown effect on swallowing, and the inability to evaluate the global swallowing coordination, which is better assessed on MBS. Like MBS, FEES can be normal in children who intermittently aspirate. 3.4. Operative endoscopy The hallmark to diagnosis is palpation of the interarytenoid area during direct laryngoscopy. Due to the usual constellation of feeding and respiratory symptoms in laryngeal cleft patients, many patients undergo otolaryngologic, gastroenterologic, and pulmonologic examinations under the same general anesthetic (triple scope). In association with our anesthesia colleagues, we typically perform direct laryngoscopy under spontaneous ventilation to achieve a dynamic view of the airway. After laryngoscopic and tracheobronchoscopic views are obtained under spontaneous ventilation to rule out edema, cobblestoning, rigid or malacic stenosis, tracheoesophageal fistulae, or other anatomic abnormalities, we then palpate the interarytenoid area. A blunt laryngeal probe is used to palpate the depth of the interarytenoid groove with particular attention paid to not applying excessive pressure that would distort or deepen the interarytenoid mucosa. If the cleft extends below the vocal cords, the cricoid is palpated for evidence of dehiscence. If the cricoid cartilage is not palpable with the probe, the cleft is at least a type III and extends into the cervical or thoracic trachea. In review of the literature, most authors agree that determining the presence of a type I laryngeal cleft versus a deep interarytenoid groove can be a challenge regardless of the method of examination, which is why a patient’s symptoms and other comorbidities must be considered when planning treatment in these patients. Parsons and colleagues employ the use of a right angle probe that is inserted to the depth of the interarytenoid area. The probe is then rotated such that the right angle extension is parallel to the plane of one of the vocal cords. Thus, the depth of the cleft can be accurately measured with respect to the vocal cords [3]. Within the tracheobronchial tree, it is common to find diffuse mucosal edema with blunting of the tracheal rings and carina. Mucosal cobblestoning is also commonly identified. At the time of flexible bronchoscopy by the pulmonary team, aspirates of tracheal/bronchial secretions are measured for the lipid-laden macrophage index (LLMI) and neutrophil percentage. LLMI is a non-specific marker indicating an inflammatory process in the tracheobronchial tree. In our series, both the type I and II patients displayed significant elevations in lipid-laden macrophage index and neutrophil percentage [5]. 4. Treatment 4.1. Medical management Goals of medical management are to maintain optimal respiration, prevent pulmonary complications of recurrent pneumonia,
and to ensure adequate nutrition [18]. Medical management as a treatment is primarily for type I clefts, or those with deep interarytenoid grooves, but can be suitable for patients with type II clefts in certain situations. This approach includes feeding therapy involving the thickening of liquids and food consistency, or designating a patient nil per os (NPO) depending on how the patient performs on MBS or swallowing evaluation. One fascinating report details the case of a young teen with a type III laryngeal cleft that had been medically managed since his diagnosis at 7 years of age [19]. Patients with type II clefts awaiting surgery, or who have significant medical morbidity that precludes surgery, begin with medical management, as well. A second component in medical management is treating comorbid medical conditions that overlap with or contribute to swallowing dysfunction. Specifically, maximizing treatment for GERD with proton pump inhibitor therapy, treatment for reactive airway disease, and treatment of food allergy can improve aerodigestive edema and irritation and, consequently, swallow function. Many authors agree that a trial of medical management in type I clefts can avoid the need for surgical repair [3,5,12,15]. In our experience, we usually allow for at least a 6 month period of feeding and medical therapy before re-evaluating the swallowing competence via MBS. Improvement in swallow function and coordination is often a result of patient growth and conditioning, which is facilitated by proper patient nutrition. If continued pulmonary aspiration and/or infection are occurring, the patient is scheduled for endoscopic repair. A literature review helps to detail the rate of medical management (Table 2). As the table shows, the ‘‘success’’ of medical management is quite variable. 4.2. Surgical management For those type I clefts that fail medical treatment strategies, surgery should be considered. Cleft types II, III, and IV will almost all go on to surgical therapy because aspiration is usually a foregone conclusion. Endoscopic repair should be considered for type I, II and selective type III clefts. Most type III and all type IV clefts are treated with open thoracotomy procedures [4,20,21]. Electing to perform type III cleft repair endoscopically should be done with the expectation that revision attempts are much more likely than for types I and II. Endoscopic repair of type I and II posterior laryngeal clefts has become the gold standard (Fig. 2) [4–5,12,17–18,20–23]. Lidocaine (4%) via topical application is used for local anesthesia. We advocate the use of the Lindholm suspension laryngoscope (Karl Storz Co., Tuttlingen, Germany) seated in the vallecula. Direct communication with an experienced anesthetist facilitates obtaining the proper anesthetic level. We prefer ‘‘tubeless’’ anesthesia, where the patient is induced with inhalational agent and is maintained with intravenous agents, such as propofol or remifentanyl. We do not typically use jet ventilation, but do deliver oxygen to the oropharynx throughout the procedure using the jet needle or a cut-off, modified endotracheal tube at the side of the laryngoscope. To prepare the edges of the cleft for closure, a CO2
Table 2 Rate of medical management of type I laryngeal clefts. Author
# of pts
# Treated conservatively
Chien et al. Evans et al. van der Doef et al. Parsons et al. Rahbar et al.
20 25 31 41 53
4/20 (20%) 13/25 (52%) 28/31 (91%) 41/41 (100%) 25/53 (47%)
[(Fig._2)TD$IG]
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Fig. 2. Schematic drawing (top row) and intraoperative photos (bottom row) of endoscopic repair of type 2 laryngeal cleft: (A) laser-denuded cleft mucosa; (B) first suture in one side; (C) first suture through both sides; (D) inferior suture tied to approximate inferior cleft; (E) superior suture tied to approximate superior cleft.
micromanipulator laser in pulse mode with 20 ms pulses denudes the mucosa on both sides of the cleft. CO2 laser with flexible fiber delivery is also efficacious. The wattage delivered to the tissue should be between 3 and 5 W. Our suture technique involves specifically designed endoscopic instruments that permit closure of the full depth of the cleft. Although many authors advocate a two-layer closure [2,12,21], we recommend a single layer closure with deep absorbable 5-0 or 6-0 Vicryl suture with a short half curve needle (Ethicon, Sommerville, NJ). Rarely is tracheotomy needed in type I or II for pulmonary toilet. Gastrostomy tubes are not uncommon for patients who cannot feed safely by mouth. Outcomes for endoscopic repair of type I clefts are largely favorable for cleft closure and cessation of aspiration, whereas significant medical comorbidities can be associated with persistent aspiration. Our experience with 24 patients with type I clefting who obtained a postoperative MBS resulted in a normal study 17 pts (71%), and persistent aspiration in 7. These 7 patients all had significant comorbidities, including hypotonia, gastrostomy tube dependence, TEF, and syndromes. Our experience with type II patients showed that 14 of 17 (82%) patients who had a postoperative MBS had resolution of aspiration. The remaining 3 patients had gastrostomy dependence with TEF, Optiz G syndrome, and Waardenburg syndrome with Hirschsprung’s disease requiring multiple transplants [5]. In Evans’ series including the early era of endoscopic repair, 13/16 (81%) patients (15 type I and 1 type II) had successful endoscopic repair on the first attempt, and 15/16 (94%) if revision endoscopic surgery cases are included [2]. Success was not evaluated by a normal MBS. Similarly, Chien and colleagues had success in 15/16 (94%) type I clefts after endoscopic repair, although MBS was not used postoperatively and follow up was limited to 3 months [12]. The 1 patient with failure of endoscopic repair had a history of TEF and resulting tracheal stenosis and chronic pulmonary disease. Garabedian had success in 4/4 type I and II patients with endoscopic management without the use of MBS for postoperative surveillance [21]. Surgical management of type III and IV clefts is mostly via open approaches, but Garabedian and colleagues have demonstrated in 4 patients with type III clefts that endoscopic repair is also possible (2 required revision procedures) [21]. As these more severe clefting defects are associated with more severe coincident anatomic abnormalities, surgical management may include additional procedures not covered in this article, such as repair of esophageal atresia or microgastria with gastric transection and temporary diversion of gastric contents until repair sites heal and continuity can be reestablished. Likewise, tracheotomy and gastrostomy (or duodenal or jejunal) tubes are often needed for pulmonary toilet and enteral nutrition, respectively. Distal food diversion permits
less stress at the suture lines. We would not hesitate to perform tracheotomy and/or gastrostomy in type III and IV patients as prolonged treatment courses should be expected and these interventions offer life sustaining airway and nutritional support. Because tracheo- and broncho-malacia are common in type III and IV clefts, a tracheotomy tube, or a customized bifurcated tube, can stent the airway and limit the need for positive pressure ventilation. Coincident gastric abnormalities can significantly alter gastric emptying and can result in continued aspiration from refractory esophageal reflux, along with pressure and inflammation at the anastomotic sites, which may, amongst other things, contribute to the lower success of closure in type III and IV clefts. The crux of surgical therapy for type III and IV clefts is to recreate separate, functional tracheal and esophageal lumens. This dual repair results in two suture lines and a greater chance for anastomotic leak compared with a single suture line. Anterior approaches with cervical and/or thoracic incisions are employed for the best exposure, but lateral approaches to the pharynx and cervical and thoracic trachea are advantageous in some instances. A right posterolateral thoracotomy has been described in combination with a right cervical approach to access the thoracic and cervical portions separately [26,27]. Anterior approaches have the advantage of lower risk to the recurrent laryngeal nerves, but may have increased risk for postoperative tracheomalacia. Some surgical and anesthesia teams will perform the repair of a type III or IV cleft under extra corporeal membrane oxygenation (ECMO) or cardiopulmonary bypass, which prevents an obstructed view of the repair site by the endotracheal tube, especially in type IV clefts [23,24]. Various tissues have been used as interposition grafts to allow for a more robust tension-free closure, including pericardium, sternocleidomastoid muscle flaps, pleura, strap muscle, jejunum, and tibial periosteum, to name a few [23,25–30] (Fig. 3). Techniques for cleft closure include a two layer closure with either symmetric or asymmetric flaps and, also, complete separation of the tracheal and esophageal lumens. Asymmetric flaps have the advantage of avoiding overlapping suture lines. Common complications include tracheoesophageal fistula, which has been improved with the use of vascularized, thick interposition grafts, such as the sternal head of the sternocleidomastoid that can be detached at the mastoid and rotated inferiorly. Kawaguchi and colleagues report tracheoesophageal fistula in 6 of 9 postoperative patients with type III and IV clefts [26]. These fistulas can result in recurrent aspiration, chronic lung disease, and the need for multiple revision procedures. Tracheotomy dependence is common, largely due to significant tracheomalacia, but possibly to chronic lung disease, as well. In the 5 survivors in Kawaguchi’s series, 2 remain tracheotomy dependent at 9 and 11
[(Fig._3)TD$IG]
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Fig. 3. Operative photos of open repair of type III laryngeal cleft. (A) Chin at top edge of photo and endotracheal tube sewn into tracheotomy incision at bottom edge of photo. Exposure of strap muscles in midline approach; (B) cleft seen in middle of photo deep to divided anterior tracheal wall with retracting sutures in place; (C) retractors hold open anterior tracheal wall and forceps grasp tibial periosteum to be used for repair of cleft; (D) retractors hold open anterior tracheal wall with repaired cleft and tied sutures in deep portion of photo.
years of follow up. Current mortality rates for type III and IV clefts can reach 50–75% in the literature due to coincident congenital anomalies and the complex operative and perioperative care of these children. Insightful modifications to surgical and supportive care have resulted in improved morbidity and mortality within institutions [17,24,26,28]. 4.3. Postoperative care Postoperative management after endoscopic repairs consists of normal respiration without an endotracheal tube. Diet is resumed immediately with the same pre-surgical dietary restrictions. Diet advancement occurs slowly and with reassessment for aspiration. Anti-reflux therapy and antibiotics are also employed while the child remains hospitalized, which is 48 h at our institution. Following open repairs of type III or IV clefts, care consists of a variable period of endotracheal intubation (either transnasal or transoral) to allow the repair to heal with a stent in place. Some authors prefer a tracheotomy tube. If ECMO has been used, patients can remain free from intubation for approximately 7 days. Enteral feeding with a nasogastric/nasoduodenal tube or pre-existing gastric/duodenal/jejunal tube is maintained for at least a few weeks to avoid anastomotic breakdown due to exposure to gastric refluxate. Diet advancement is conservative, yet complicated due to frequent gastric abnormalities, feeding diversion, and medical complexities. If symptoms persist despite repair and maximum consistency management, or a repeat MBS demonstrates continued aspiration or deep penetration, persistence of a laryngeal cleft should be ruled out. Revision surgery is rare (less than 1%) in our series, but should be attempted endoscopically in the same fashion for type I and II clefts. Revision surgery due to tracheoesophageal fistulas in type III and IV clefts is almost always performed in an open fashion. 5. Conclusions In conclusion, laryngeal clefts have variable presentations based on their depth and the overall health of the child. Type I and, sometimes, type II clefts can have an insidious presentation with persistent vague respiratory and feeding difficulty. Endoscopic repair is commonly preferred in types I and II. Conversely, type III and IV laryngeal clefts present quickly in the newborn period with significant respiratory distress and coincident congenital anomalies. They mandate airway protection and, usually, open surgical repair.
Authors’ contributions Dr. Johnston conceptualized and designed the manuscript, drafted the initial manuscript, and approved the final manuscript as submitted. Karen Watters, Lynne R. Ferrari and Reza Rahbar reviewed and revised the manuscript, and approved the final manuscript as submitted. Reza Rahbar also aided in the creation of the manuscript figures. Funding None. Conflict of interest None declared. References [1] G. Petterson, Inhibited separation of larynx and the upper part of the trachea from oesophagus in a newborn: report of a case successfully operated upon, Acta Chir. Scand. 110 (3) (1955) 250–254. [2] K.L. Evans, R. Courteney-Harris, C.M. Bailey, J.N. Evans, D.S. Parsons, et al., Management of posterior laryngeal and laryngotracheoesophageal clefts, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 1380–1385. [3] D.S. Parsons, F.E. Stivers, D.R. Giovanetto, S.E. Phillips, Type I posterior laryngeal clefts, Laryngoscope 108 (1998) 403–410. [4] R. Rahbar, I. Rouillon, G. Roger, A. Lin, R.C. Nuss, F. Denoyelle, et al., The presentation and management of laryngeal cleft: a 10-year experience, Arch. Otolaryngol. Head Neck Surg. 132 (2006) 1335–1341. [5] R. Rahbar, J.L. Chen, R.L. Rosen, K.C. Lowry, J.M. Simon, D.A. Perez, et al., Endoscopic repair of laryngeal cleft type I and type II: when and why? Laryngoscope 119 (2009) 1797–1802. [6] P.D. Phelan, J.G. Stocks, H.E. Williams, D.M. Danks, Familial occurrence of congenital laryngeal clefts, Arch. Dis. Child. 48 (1973) 275–278. [7] I.R. McIntosh, K.K. Merritt, M.R. Richards, M.H. Samuels, M.T. Bellows, The incidence of congenital malformations: a study of 5,964 pregnancies, Pediatrics 14 (5) (1954) 505–522. [8] P. Narcy, S. Bobin, P. Contencin, C. Le Pajolec, Y. Manac’h, Laryngeal anomalies in newborn infants: apropos of 687 cases, Ann. Otolaryngol. Chir. Cervicofac. 101 (5) (1984) 363–373 (in French). [9] G. Moungthong, L.D. Holinger, Laryngotracheoesophageal clefts, Ann. Otol. Rhinol. Laryngol. 106 (12) (1997) 1002–1011. [10] B. Fearon, D. Ellis, The management of long term airway problems in infants and children, Ann. Otol. Rhinol. Laryngol. 80 (5) (1971) 669–677. [11] C. Eriksen, D. Zwillenberg, N. Robinson, Diagnosis and management of cleft larynx: literature review and case report, Ann. Otol. Rhinol. Laryngol. 99 (9 Pt 1) (1990) 703–708. [12] W. Chien, J. Ashland, K. Haver, S.C. Hardy, P. Curren, C.J. Hartnick, Type I laryngeal cleft: establishing a functional diagnostic and management algorithm, Int. J. Pediatr. Otorhinolaryngol. 70 (12) (2006) 2073–2079. [13] B. Benjamin, A. Inglis, Minor congenital laryngeal clefts: diagnosis and classification, Ann. Otol. Rhinol. Laryngol. 98 (6) (1989) 417–420.
D.R. Johnston et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 905–911 [14] M.H. Hast, The developmental anatomy of the larynx, Otolaryngol. Clin. North Am. 3 (3) (1970) 413–438. [15] H.P. van der Doef, J.B. Yntema, F.J. van den Hoogen, H.A. Marres, Clinical aspects of type 1 posterior laryngeal clefts: literature review and a report of 31 patients, Laryngoscope 117 (2007) 859–863. [16] B. Roth, K.G. Rose, G. Benz-Bohm, H. Guenther, Laryngo-tracheo-oesophageal cleft: clinical features, diagnosis and therapy, Eur. J. Pediatr. 140 (1) (1983) 41–46. [17] S.M. Pezzettigotta, N. Leboulanger, G. Roger, F. Denoyelle, E.N. Garabedian, Laryngeal cleft, Otolaryngol. Clin. North Am. 41 (2008) 913–933. [18] N. Leboulanger, E.N. Garabedian, Laryngo-tracheo-oesophageal clefts, Orphanet J. Rare Dis. 6 (2011) 81. [19] D.S. Parsons, T. Herr, Delayed diagnosis of a laryngotracheoesophageal cleft, Int. J. Pediatr. Otorhinolaryngol. 39 (1997) 169–173. [20] K. Sandu, P. Monnier, Endoscopic laryngotracheal cleft repair without tracheotomy or intubation, Laryngoscope 116 (4) (2006) 630–634. [21] E.N. Garabedian, S. Pezzettigotta, N. Leboulander, R. Harris, J. Nevoux, F. Denoyelle, et al., Endoscopic surgical treatment of laryngotracheal clefts, Arch. Otolaryngol. Head Neck Surg. 136 (1) (2010) 70–74. [22] P.J. Koltai, D. Morgan, J.N. Evans, Endoscopic repair of supraglottic laryngeal clefts, Arch. Otolaryngol. Head Neck Surg. 117 (3) (1991) 273–278. [23] L.R. Ferrari, D. Zurakowski, J. Solari, R. Rahbar, Laryngeal cleft repair: the anesthetic perspective, Pediatr. Anesthesia 23 (2013) 334–341.
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[24] N.N. Mathur, G.J. Peek, C.M. Bailey, M.J. Elliot, Strategies for managing type IV laryngotracheoesophageal clefts at Great Ormond Street Hospital for children, Int. J. Pediatr. Otorhinolaryngol. 70 (11) (2006) 1901–1910. [25] B.B. Simpson, D.P. Ryan, P.K. Donahoe, J.J. Schnitzer, S.H. Kim, D.P. Doody, Type IV laryngotracheoesophageal clefts: surgical management for long-term survival, J. Pediatr. Surg. 31 (8) (1996) 1128–1133. [26] A.L. Kawaguchi, P.K. Donahoe, D.P. Ryan, Management and long-term follow up of patients with types III and IV laryngotracheoesophageal clefts, J. Pediatr. Surg. 40 (2005) 158–165. [27] D.P. Ryan, D.D. Muehrcke, D.P. Doody, S.H. Kim, P.K. Donahoe, Laryngotracheoesophageal cleft (type IV): management and repair of lesions beyond the carina, J. Pediatr. Surg. 26 (8) (1991) 962–970. [28] K. Geller, Y. Kim, J. Koempel, K.D. Anderson, Surgical management of type III and IV laryngotracheoesophageal clefts: the three-layered approach, Int. J. Pediatr. Otorhinolaryngol. 74 (2010) 652–657. [29] K. Hashizume, Y. Kanamori, M. Sugiyama, M. Ito, Y. Kamii, Successful repair of the esophagus in type-IV laryngo-tracheo-esophageal cleft using interposed jejunum, Pediatr. Surg. Int. 19 (2003) 211–213. [30] E.N. Garabedian, V. Ducroz, G. Roger, F. Denoyelle, Posterior laryngeal clefts: preliminary report of a new surgical procedure using tibial periosteum as an interposition graft, Laryngoscope 108 (1998) 899–902.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Review Article
Laryngeal cleft: Evaluation and management Douglas R. Johnston a,*, Karen Watters b,c, Lynne R. Ferrari d, Reza Rahbar b,c a
Division of Otolaryngology, Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE, United States Department of Pediatric Otolaryngology and Communication Enhancement, Boston Children’s Hospital, Boston, MA, United States c Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States d Department of Anesthesiology, Boston Children’s Hospital, Boston, MA, United States b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 13 December 2013 Received in revised form 14 March 2014 Accepted 15 March 2014 Available online 27 March 2014
Objectives: Review the latest diagnostic and treatment modalities for laryngeal and laryngotracheoesophageal clefts as they can be a major cause of respiratory and feeding morbidity in the infant and pediatric population. Methods: Literature review of published reports. Results: The presentation of laryngeal cleft usually involves respiratory symptoms, such as stridor, chronic cough, aspiration, and recurrent respiratory infections. Clefts of the larynx and trachea/ esophagus can occur in isolation, as part of a syndrome (Opitz-Frias, VATER/VACTERL, Pallister Hall, CHARGE), or with other associated malformations (gastrointestinal, genitourinary, cardiac, craniofacial). This publication reviews the presenting signs/symptoms, diagnostic options, prognosis, and treatment considerations based on over a decade of experience of the senior author with laryngeal clefts. Conclusions: Type I laryngeal clefts can be managed medically or surgically depending on the degree of morbidity. Types II, III, and IV require endoscopic or open surgery to avoid chronic respiratory and feeding complications. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Laryngeal cleft Laryngotracheoesophageal cleft Stridor Aspiration Cough
Contents 1. 2. 3.
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Chest X-ray . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Modified barium swallow (MBS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing. 3.4. Operative endoscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1. Medical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2. Surgical management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3. Postoperative care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
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1. Introduction Abbreviations: MBS, modified barium swallow; FEES, functional endoscopic evaluation of swallowing. * Corresponding author at: Division of Otolaryngology, Nemours A.I. DuPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, United States. Tel.: +1 6107011116; fax: +1 3026515835. E-mail address: [email protected] (D.R. Johnston). http://dx.doi.org/10.1016/j.ijporl.2014.03.015 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
Laryngeal and laryngotracheoesophageal clefts (hereafter referred to as laryngeal cleft) represent a spectrum of clinical symptoms and presentations based on the depth of the cleft and the overall health of the child. Type I and II laryngeal clefts often have delays in diagnosis, whereas types III and IV are likely to
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present within the first days of life. Likewise, a type I cleft in an otherwise healthy child may have minimal clinical impact, whereas the same cleft in a child with cardiac disease can cause significant morbidity. Therefore, clinicians who treat laryngeal clefts must treat the patient in the context of his or her overall clinical picture and recognize that laryngeal clefts represent a spectrum of disease. Initially described by Richter in 1792, laryngeal clefts have been underdiagnosed for centuries. The first successful repair of a laryngeal cleft was performed by Petterson in 1955 [1]. A series of over 20 patients did not appear until the 1990s [2–5]. Although it has been suggested that inheritance may be autosomal dominant, it is now clear that no such associations exist [6]. A slight male preponderance is observed [2,3,5]. Estimates of the incidence of laryngeal clefts are challenging because type I clefts often go misdiagnosed for long periods and usually surface at tertiary care institutions. Nonetheless, amongst patients who have direct laryngoscopy for recurrent respiratory symptoms, the incidence ranges from 0.2 to 7.6% [3,7–12]. Embryologically, a posterior laryngeal cleft is believed to result from incomplete formation of the interarytenoid muscle with or without absence of the interarytenoid mucosa. The former is known as a submucous laryngeal cleft and the latter a type I laryngeal cleft, which does not extend beyond the level of the vocal cords. Incomplete formation of the posterior cricoid cartilage alone forms a type II cleft, and incomplete formation of the tracheoesophageal septum distal to the cricoid cartilage forms either a type III or IV cleft. Extension beyond the cricoid cartilage into the tracheoesophageal septum is a type III, and extension into the thorax is a type IV. This Benjamin and Inglis classification is the most widely used and functional of those proposed to date [13] (Fig. 1). The interarytenoid muscle (along with all intrinsic laryngeal muscles) and the cricoid cartilage are [(Fig._1)TD$IG]
derivatives of the sixth branchial arch [14]. The above spectrum of developmental insults occurs between the fifth and sixth embryologic weeks. Diagnosis and management of laryngeal clefts are far from uniform and can inspire controversy. Specifically, there is a lack of standardized evaluation and diagnosis; modified barium swallow (MBS) and functional endoscopic evaluation of swallowing (FEES) have an unclear role in diagnosis; the role, efficacy, and duration of feeding therapy are debated; and, lastly, the timing and type of surgical intervention is quite variable. Our diagnostic and treatment recommendations are presented herein. 2. Presentation Presenting signs of a posterior laryngeal cleft are most often respiratory in nature. Chronic cough is common, especially with feeding, as is a variable degree of respiratory distress, depending on cleft depth. In a child with significant medical morbidities, cough may be prominent and associated with frank cyanosis. Conversely, a child with a type I cleft may have minimal disease manifestations, such as mild feeding difficulties. In our first published series of 22 patients, roughly 90% (20/22) with type I-III clefts had respiratory symptoms, including aspiration, recurrent pneumonia, stridor, and cyanosis [4]. Our second series of 74 type I and II patients demonstrated a 50–60% rate of wheezing and chronic cough, whereas hospital respiratory admissions ranged from 15% for type I clefts to 25% for type II [5]. Other authors have reported variable rates of respiratory presenting signs in type I and II clefts, most commonly stridor, recurrent respiratory infections, and chronic cough [2,3,15]. Type III and IV clefts invariably are associated with greater respiratory symptoms with recurrent pneumonia and often excessive pulmonary mucous. They usually present within the first few days of life.
Fig. 1. Posterior view (top row), superior view (middle row), and endoscopic intraoperative view (bottom row) of Benjamin and Inglis classification of laryngeal and laryngotracheoesophageal clefts: column A, normal larynx; column B, type I extends to the level of vocal cords; column C, type II extends below vocal cords into cricoid cartilage; column D, type III extends through cricoid cartilage to cervical trachea/esophagus; column E, type IV extends to level of thoracic trachea/esophagus. Note: it is difficult in endoscopic view to show depth of type IV cleft as there frequently is redundant mucosa [13].
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Table 1 Syndromes with possible laryngeal and laryngo-tracheoesophageal clefts. Syndrome
Features
Opitz Frias Pallister Hall VACTERL CHARGE
Hypertelorism, hypospadias, cleft lip and palate Abnormalities of hypothalamus/pituitary gland; poly- and syndactyly; imperforate anus; cardiac, pulmonary, and renal abnormalities Vertebral anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistulas, ear anomalies, renal abnormalities, Limb malformation Coloboma of the eyes, heart anomalies, choanal atresia, growth and mental retardation, genital anomalies, ear abnormalities
Type I clefts usually do not have considerable symptomatology until at least several months of age and diagnosis is commonly established between two and five years of age [3,5,15]. When laryngeal cleft is not included in the differential diagnosis for patients with recurrent respiratory symptoms, diagnosis can be delayed into adulthood. Establishing a comprehensive differential diagnosis is essential in light of the fact that most children with these symptoms will not have a laryngeal cleft. Clinically significant laryngomalacia, gastroesophageal reflux disease, neuromuscular swallowing disorders, and reactive airway disease are much more common than laryngeal clefts. Congenital defects in association with laryngeal clefting are seen in over half of this population (58–68%) [2,3,5,16]. These defects can include other anatomic malformations or coincident pathology. Of the associated malformations, gastrointestinal are the most common, including esophageal atresia, microgastria, tracheoesophageal fistula, imperforate anus, and intestinal malrotation, among others. Genitourinary defects are less common and include hypospadias and kidney malformations. Cardiac abnormalities cannot be ignored, such as aortic coarctation, transposition of the great vessels, patent ductus arteriosus, and septal defects. Less common are craniofacial abnormalities, including cleft lip and palate, micrognathia, and choanal atresia. Lastly, respiratory defects comprise a small percentage and are comprised largely of tracheal and bronchial size and shape irregularities. Coincident pathologies seen commonly with laryngeal clefts are laryngomalacia, which was present in up to 90% of type I clefts in one series [15], tracheo-bronchomalacia in over half of patients, and gastroesophageal reflux disease. The abnormal configuration of the posterior larynx, and possibly trachea, can result in redundant arytenoid, posterior laryngeal, and esophageal mucosa, which results in prolapse during inspiration and associated airway narrowing. The presence of clinically significant gastroesophageal disease is likely quite high, given the greater chance of aspiration of gastric contents, but pH probe proven disease is usually not established. Syndromic associations with laryngeal clefts are Opitz Frias syndrome (hypertelorism, hypospadias, cleft lip and palate), Pallister Hall syndrome (hypothalamic/pituitary abnormalities, poly- and syndactyly, imperforate anus, cardiac, pulmonary, renal abnormalities), VACTERL syndrome (Vertebral anomalies, Anal atresia, Cardiac anomalies, Tracheoesophageal fistulas (TEF), Ear anomalies, Renal anomalies, Limb anomalies), and CHARGE syndrome (Coloboma, Heart anomalies, choanal Atresia, growth and mental Retardation, Genital anomalies, and Ear anomalies) [17] (Table 1). Due to the above syndromes and other less common ones, a genetic evaluation is warranted in many laryngeal cleft patients. 3. Diagnosis The cornerstone of diagnosis of a laryngeal cleft is direct laryngoscopy with palpation of the interarytenoid area, but the most important factor in the diagnosis is including this rare anomaly in the differential diagnosis. Patients with type III and IV clefts often require early bronchoscopy for hypoxic and apneic episodes, at which time
the astute clinician can diagnose the condition. The more difficult task is to identify the patient who requires direct laryngoscopy due to persistent respiratory symptoms that could be ascribed to other disorders, such as laryngomalacia, GERD, or vocal cord paralysis; or persistent feeding difficulty that might be related to hypoxia, birth trauma, congenital infections, or maternal drug use. A posterior laryngeal cleft should be ruled out in any pediatric patient with a history of recurrent pneumonia, feeding difficulty with coughing and choking, or post-feeding stridor. Type I and II laryngeal clefts often have symptom overlap with reactive airway disease and the asthma-like symptoms of recurrent aspiration can show some response to the same bronchodilators. Radiologic features of lower respiratory tract infections and asthma are also often similar. Wheezing and chronic cough are usually managed by pediatricians and, next, referred to a pulmonologist when refractory to treatment. Thus, the delay in referral to an otolaryngologist can continue for some time. The clue for referral to an otolaryngologist lies in the persistence of symptoms despite aggressive treatment for asthma. Similarly, treatment of suspected GERD or bronchiolitis should affect a measurable and durable benefit, especially as these conditions should improve over the first 2 years of life. 3.1. Chest X-ray All children with the above respiratory symptoms usually come to obtain a chest X-ray, which is a minor, albeit important, part of the diagnostic algorithm. Persistent, chronic aspiration will be identified as pneumonia or peribronchial cuffing. The chest X-ray can, also, be normal in 25% of type I and 13% of type II clefts [5]. 3.2. Modified barium swallow (MBS) The MBS is a critical part of the evaluation of cleft patients, but it must be emphasized that it can be normal in those who aspirate intermittently. Most patients will have undergone multiple MBS studies prior to presenting to an otolaryngologist and the cumulative radiation dose can be considerable, so repeating this test must be done cautiously. The technique of a MBS is for a speech/swallowing pathologist to administer a patient various consistencies of food containing a radio-labeled tracer that can be identified under fluoroscopy. Anterior–posterior and lateral views are obtained to study the oral, pharyngeal, esophageal, and gastric phases of swallowing. Importantly, the MBS can identify patients who have a discoordinated swallow. Those patients with global neurodevelopmental delay will often have poor coordination in the complex pharyngeal phase of swallowing, pointing to other diagnostic considerations. A positive swallow study for aspiration in an otherwise healthy child has a strong correlation with an anatomic abnormality. Overall, over 75% of patients with type I and II clefts will, in our experience, display aspiration on MBS. 3.3. Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing Flexible fiberoptic laryngoscopy and functional endoscopic evaluation of swallowing (FEES) assist in diagnosis because they
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provide a dynamic view of laryngeal function. The flexible exam, as well as FEES, is possible in certain age groups and can alert the clinician to anatomic abnormalities, especially the presence of a vocal cord palsy or paralysis, which can lead to decreased laryngeal sensation and aspiration [12]. The FEES technique involves an otolaryngologist, often with a speech/swallow pathologist, administering various consistencies of food dyed for easy identification. A flexible fiberoptic endoscope is passed transnasally and positioned in the nasopharynx or posterior oropharynx to visualize after the swallow if food pooling or penetration/aspiration has occurred. The advantages of FEES are superior anatomic evaluation relative to MBS, including vocal cord motion; location of aspiration, penetration, and secretion pooling; and possible visualization of changes after swallowing maneuvers are employed. Disadvantages include a foreign object in the airway, which has an unknown effect on swallowing, and the inability to evaluate the global swallowing coordination, which is better assessed on MBS. Like MBS, FEES can be normal in children who intermittently aspirate. 3.4. Operative endoscopy The hallmark to diagnosis is palpation of the interarytenoid area during direct laryngoscopy. Due to the usual constellation of feeding and respiratory symptoms in laryngeal cleft patients, many patients undergo otolaryngologic, gastroenterologic, and pulmonologic examinations under the same general anesthetic (triple scope). In association with our anesthesia colleagues, we typically perform direct laryngoscopy under spontaneous ventilation to achieve a dynamic view of the airway. After laryngoscopic and tracheobronchoscopic views are obtained under spontaneous ventilation to rule out edema, cobblestoning, rigid or malacic stenosis, tracheoesophageal fistulae, or other anatomic abnormalities, we then palpate the interarytenoid area. A blunt laryngeal probe is used to palpate the depth of the interarytenoid groove with particular attention paid to not applying excessive pressure that would distort or deepen the interarytenoid mucosa. If the cleft extends below the vocal cords, the cricoid is palpated for evidence of dehiscence. If the cricoid cartilage is not palpable with the probe, the cleft is at least a type III and extends into the cervical or thoracic trachea. In review of the literature, most authors agree that determining the presence of a type I laryngeal cleft versus a deep interarytenoid groove can be a challenge regardless of the method of examination, which is why a patient’s symptoms and other comorbidities must be considered when planning treatment in these patients. Parsons and colleagues employ the use of a right angle probe that is inserted to the depth of the interarytenoid area. The probe is then rotated such that the right angle extension is parallel to the plane of one of the vocal cords. Thus, the depth of the cleft can be accurately measured with respect to the vocal cords [3]. Within the tracheobronchial tree, it is common to find diffuse mucosal edema with blunting of the tracheal rings and carina. Mucosal cobblestoning is also commonly identified. At the time of flexible bronchoscopy by the pulmonary team, aspirates of tracheal/bronchial secretions are measured for the lipid-laden macrophage index (LLMI) and neutrophil percentage. LLMI is a non-specific marker indicating an inflammatory process in the tracheobronchial tree. In our series, both the type I and II patients displayed significant elevations in lipid-laden macrophage index and neutrophil percentage [5]. 4. Treatment 4.1. Medical management Goals of medical management are to maintain optimal respiration, prevent pulmonary complications of recurrent pneumonia,
and to ensure adequate nutrition [18]. Medical management as a treatment is primarily for type I clefts, or those with deep interarytenoid grooves, but can be suitable for patients with type II clefts in certain situations. This approach includes feeding therapy involving the thickening of liquids and food consistency, or designating a patient nil per os (NPO) depending on how the patient performs on MBS or swallowing evaluation. One fascinating report details the case of a young teen with a type III laryngeal cleft that had been medically managed since his diagnosis at 7 years of age [19]. Patients with type II clefts awaiting surgery, or who have significant medical morbidity that precludes surgery, begin with medical management, as well. A second component in medical management is treating comorbid medical conditions that overlap with or contribute to swallowing dysfunction. Specifically, maximizing treatment for GERD with proton pump inhibitor therapy, treatment for reactive airway disease, and treatment of food allergy can improve aerodigestive edema and irritation and, consequently, swallow function. Many authors agree that a trial of medical management in type I clefts can avoid the need for surgical repair [3,5,12,15]. In our experience, we usually allow for at least a 6 month period of feeding and medical therapy before re-evaluating the swallowing competence via MBS. Improvement in swallow function and coordination is often a result of patient growth and conditioning, which is facilitated by proper patient nutrition. If continued pulmonary aspiration and/or infection are occurring, the patient is scheduled for endoscopic repair. A literature review helps to detail the rate of medical management (Table 2). As the table shows, the ‘‘success’’ of medical management is quite variable. 4.2. Surgical management For those type I clefts that fail medical treatment strategies, surgery should be considered. Cleft types II, III, and IV will almost all go on to surgical therapy because aspiration is usually a foregone conclusion. Endoscopic repair should be considered for type I, II and selective type III clefts. Most type III and all type IV clefts are treated with open thoracotomy procedures [4,20,21]. Electing to perform type III cleft repair endoscopically should be done with the expectation that revision attempts are much more likely than for types I and II. Endoscopic repair of type I and II posterior laryngeal clefts has become the gold standard (Fig. 2) [4–5,12,17–18,20–23]. Lidocaine (4%) via topical application is used for local anesthesia. We advocate the use of the Lindholm suspension laryngoscope (Karl Storz Co., Tuttlingen, Germany) seated in the vallecula. Direct communication with an experienced anesthetist facilitates obtaining the proper anesthetic level. We prefer ‘‘tubeless’’ anesthesia, where the patient is induced with inhalational agent and is maintained with intravenous agents, such as propofol or remifentanyl. We do not typically use jet ventilation, but do deliver oxygen to the oropharynx throughout the procedure using the jet needle or a cut-off, modified endotracheal tube at the side of the laryngoscope. To prepare the edges of the cleft for closure, a CO2
Table 2 Rate of medical management of type I laryngeal clefts. Author
# of pts
# Treated conservatively
Chien et al. Evans et al. van der Doef et al. Parsons et al. Rahbar et al.
20 25 31 41 53
4/20 (20%) 13/25 (52%) 28/31 (91%) 41/41 (100%) 25/53 (47%)
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Fig. 2. Schematic drawing (top row) and intraoperative photos (bottom row) of endoscopic repair of type 2 laryngeal cleft: (A) laser-denuded cleft mucosa; (B) first suture in one side; (C) first suture through both sides; (D) inferior suture tied to approximate inferior cleft; (E) superior suture tied to approximate superior cleft.
micromanipulator laser in pulse mode with 20 ms pulses denudes the mucosa on both sides of the cleft. CO2 laser with flexible fiber delivery is also efficacious. The wattage delivered to the tissue should be between 3 and 5 W. Our suture technique involves specifically designed endoscopic instruments that permit closure of the full depth of the cleft. Although many authors advocate a two-layer closure [2,12,21], we recommend a single layer closure with deep absorbable 5-0 or 6-0 Vicryl suture with a short half curve needle (Ethicon, Sommerville, NJ). Rarely is tracheotomy needed in type I or II for pulmonary toilet. Gastrostomy tubes are not uncommon for patients who cannot feed safely by mouth. Outcomes for endoscopic repair of type I clefts are largely favorable for cleft closure and cessation of aspiration, whereas significant medical comorbidities can be associated with persistent aspiration. Our experience with 24 patients with type I clefting who obtained a postoperative MBS resulted in a normal study 17 pts (71%), and persistent aspiration in 7. These 7 patients all had significant comorbidities, including hypotonia, gastrostomy tube dependence, TEF, and syndromes. Our experience with type II patients showed that 14 of 17 (82%) patients who had a postoperative MBS had resolution of aspiration. The remaining 3 patients had gastrostomy dependence with TEF, Optiz G syndrome, and Waardenburg syndrome with Hirschsprung’s disease requiring multiple transplants [5]. In Evans’ series including the early era of endoscopic repair, 13/16 (81%) patients (15 type I and 1 type II) had successful endoscopic repair on the first attempt, and 15/16 (94%) if revision endoscopic surgery cases are included [2]. Success was not evaluated by a normal MBS. Similarly, Chien and colleagues had success in 15/16 (94%) type I clefts after endoscopic repair, although MBS was not used postoperatively and follow up was limited to 3 months [12]. The 1 patient with failure of endoscopic repair had a history of TEF and resulting tracheal stenosis and chronic pulmonary disease. Garabedian had success in 4/4 type I and II patients with endoscopic management without the use of MBS for postoperative surveillance [21]. Surgical management of type III and IV clefts is mostly via open approaches, but Garabedian and colleagues have demonstrated in 4 patients with type III clefts that endoscopic repair is also possible (2 required revision procedures) [21]. As these more severe clefting defects are associated with more severe coincident anatomic abnormalities, surgical management may include additional procedures not covered in this article, such as repair of esophageal atresia or microgastria with gastric transection and temporary diversion of gastric contents until repair sites heal and continuity can be reestablished. Likewise, tracheotomy and gastrostomy (or duodenal or jejunal) tubes are often needed for pulmonary toilet and enteral nutrition, respectively. Distal food diversion permits
less stress at the suture lines. We would not hesitate to perform tracheotomy and/or gastrostomy in type III and IV patients as prolonged treatment courses should be expected and these interventions offer life sustaining airway and nutritional support. Because tracheo- and broncho-malacia are common in type III and IV clefts, a tracheotomy tube, or a customized bifurcated tube, can stent the airway and limit the need for positive pressure ventilation. Coincident gastric abnormalities can significantly alter gastric emptying and can result in continued aspiration from refractory esophageal reflux, along with pressure and inflammation at the anastomotic sites, which may, amongst other things, contribute to the lower success of closure in type III and IV clefts. The crux of surgical therapy for type III and IV clefts is to recreate separate, functional tracheal and esophageal lumens. This dual repair results in two suture lines and a greater chance for anastomotic leak compared with a single suture line. Anterior approaches with cervical and/or thoracic incisions are employed for the best exposure, but lateral approaches to the pharynx and cervical and thoracic trachea are advantageous in some instances. A right posterolateral thoracotomy has been described in combination with a right cervical approach to access the thoracic and cervical portions separately [26,27]. Anterior approaches have the advantage of lower risk to the recurrent laryngeal nerves, but may have increased risk for postoperative tracheomalacia. Some surgical and anesthesia teams will perform the repair of a type III or IV cleft under extra corporeal membrane oxygenation (ECMO) or cardiopulmonary bypass, which prevents an obstructed view of the repair site by the endotracheal tube, especially in type IV clefts [23,24]. Various tissues have been used as interposition grafts to allow for a more robust tension-free closure, including pericardium, sternocleidomastoid muscle flaps, pleura, strap muscle, jejunum, and tibial periosteum, to name a few [23,25–30] (Fig. 3). Techniques for cleft closure include a two layer closure with either symmetric or asymmetric flaps and, also, complete separation of the tracheal and esophageal lumens. Asymmetric flaps have the advantage of avoiding overlapping suture lines. Common complications include tracheoesophageal fistula, which has been improved with the use of vascularized, thick interposition grafts, such as the sternal head of the sternocleidomastoid that can be detached at the mastoid and rotated inferiorly. Kawaguchi and colleagues report tracheoesophageal fistula in 6 of 9 postoperative patients with type III and IV clefts [26]. These fistulas can result in recurrent aspiration, chronic lung disease, and the need for multiple revision procedures. Tracheotomy dependence is common, largely due to significant tracheomalacia, but possibly to chronic lung disease, as well. In the 5 survivors in Kawaguchi’s series, 2 remain tracheotomy dependent at 9 and 11
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Fig. 3. Operative photos of open repair of type III laryngeal cleft. (A) Chin at top edge of photo and endotracheal tube sewn into tracheotomy incision at bottom edge of photo. Exposure of strap muscles in midline approach; (B) cleft seen in middle of photo deep to divided anterior tracheal wall with retracting sutures in place; (C) retractors hold open anterior tracheal wall and forceps grasp tibial periosteum to be used for repair of cleft; (D) retractors hold open anterior tracheal wall with repaired cleft and tied sutures in deep portion of photo.
years of follow up. Current mortality rates for type III and IV clefts can reach 50–75% in the literature due to coincident congenital anomalies and the complex operative and perioperative care of these children. Insightful modifications to surgical and supportive care have resulted in improved morbidity and mortality within institutions [17,24,26,28]. 4.3. Postoperative care Postoperative management after endoscopic repairs consists of normal respiration without an endotracheal tube. Diet is resumed immediately with the same pre-surgical dietary restrictions. Diet advancement occurs slowly and with reassessment for aspiration. Anti-reflux therapy and antibiotics are also employed while the child remains hospitalized, which is 48 h at our institution. Following open repairs of type III or IV clefts, care consists of a variable period of endotracheal intubation (either transnasal or transoral) to allow the repair to heal with a stent in place. Some authors prefer a tracheotomy tube. If ECMO has been used, patients can remain free from intubation for approximately 7 days. Enteral feeding with a nasogastric/nasoduodenal tube or pre-existing gastric/duodenal/jejunal tube is maintained for at least a few weeks to avoid anastomotic breakdown due to exposure to gastric refluxate. Diet advancement is conservative, yet complicated due to frequent gastric abnormalities, feeding diversion, and medical complexities. If symptoms persist despite repair and maximum consistency management, or a repeat MBS demonstrates continued aspiration or deep penetration, persistence of a laryngeal cleft should be ruled out. Revision surgery is rare (less than 1%) in our series, but should be attempted endoscopically in the same fashion for type I and II clefts. Revision surgery due to tracheoesophageal fistulas in type III and IV clefts is almost always performed in an open fashion. 5. Conclusions In conclusion, laryngeal clefts have variable presentations based on their depth and the overall health of the child. Type I and, sometimes, type II clefts can have an insidious presentation with persistent vague respiratory and feeding difficulty. Endoscopic repair is commonly preferred in types I and II. Conversely, type III and IV laryngeal clefts present quickly in the newborn period with significant respiratory distress and coincident congenital anomalies. They mandate airway protection and, usually, open surgical repair.
Authors’ contributions Dr. Johnston conceptualized and designed the manuscript, drafted the initial manuscript, and approved the final manuscript as submitted. Karen Watters, Lynne R. Ferrari and Reza Rahbar reviewed and revised the manuscript, and approved the final manuscript as submitted. Reza Rahbar also aided in the creation of the manuscript figures. Funding None. Conflict of interest None declared. References [1] G. Petterson, Inhibited separation of larynx and the upper part of the trachea from oesophagus in a newborn: report of a case successfully operated upon, Acta Chir. Scand. 110 (3) (1955) 250–254. [2] K.L. Evans, R. Courteney-Harris, C.M. Bailey, J.N. Evans, D.S. Parsons, et al., Management of posterior laryngeal and laryngotracheoesophageal clefts, Arch. Otolaryngol. Head Neck Surg. 121 (1995) 1380–1385. [3] D.S. Parsons, F.E. Stivers, D.R. Giovanetto, S.E. Phillips, Type I posterior laryngeal clefts, Laryngoscope 108 (1998) 403–410. [4] R. Rahbar, I. Rouillon, G. Roger, A. Lin, R.C. Nuss, F. Denoyelle, et al., The presentation and management of laryngeal cleft: a 10-year experience, Arch. Otolaryngol. Head Neck Surg. 132 (2006) 1335–1341. [5] R. Rahbar, J.L. Chen, R.L. Rosen, K.C. Lowry, J.M. Simon, D.A. Perez, et al., Endoscopic repair of laryngeal cleft type I and type II: when and why? Laryngoscope 119 (2009) 1797–1802. [6] P.D. Phelan, J.G. Stocks, H.E. Williams, D.M. Danks, Familial occurrence of congenital laryngeal clefts, Arch. Dis. Child. 48 (1973) 275–278. [7] I.R. McIntosh, K.K. Merritt, M.R. Richards, M.H. Samuels, M.T. Bellows, The incidence of congenital malformations: a study of 5,964 pregnancies, Pediatrics 14 (5) (1954) 505–522. [8] P. Narcy, S. Bobin, P. Contencin, C. Le Pajolec, Y. Manac’h, Laryngeal anomalies in newborn infants: apropos of 687 cases, Ann. Otolaryngol. Chir. Cervicofac. 101 (5) (1984) 363–373 (in French). [9] G. Moungthong, L.D. Holinger, Laryngotracheoesophageal clefts, Ann. Otol. Rhinol. Laryngol. 106 (12) (1997) 1002–1011. [10] B. Fearon, D. Ellis, The management of long term airway problems in infants and children, Ann. Otol. Rhinol. Laryngol. 80 (5) (1971) 669–677. [11] C. Eriksen, D. Zwillenberg, N. Robinson, Diagnosis and management of cleft larynx: literature review and case report, Ann. Otol. Rhinol. Laryngol. 99 (9 Pt 1) (1990) 703–708. [12] W. Chien, J. Ashland, K. Haver, S.C. Hardy, P. Curren, C.J. Hartnick, Type I laryngeal cleft: establishing a functional diagnostic and management algorithm, Int. J. Pediatr. Otorhinolaryngol. 70 (12) (2006) 2073–2079. [13] B. Benjamin, A. Inglis, Minor congenital laryngeal clefts: diagnosis and classification, Ann. Otol. Rhinol. Laryngol. 98 (6) (1989) 417–420.
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