High-dose sublesional bevacizumab (avastin) for pediatric recurrent respiratory papillomatosis.

OBJECTIVES: We review and report the use of high-dose bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP) in pediatric patients. METHODS: We included all patients with pediatric-onset RRP who underwent bevacizumab (25 mg/mL) injections by a single practitioner. A series of 5 consecutive subepithelial injections were administered at 4- to 6-week intervals with concomitant 532 nm KTP laser ablation. The lesions were staged according to the Derkay staging system. The outcomes included pretreatment and posttreatment Derkay scores, the time interval between procedures, and voice outcomes. The demographic data extracted included sex, age at diagnosis, and current age. RESULTS: Nine patients were included in this study, with 1 patient lost to follow-up; their median age was 8 years (range, 3 to 21 years). The mean bevacizumab dose was 14.25 mg (range, 5 to 45 mg). There was a median Derkay score of 11.5 (range, 4 to 23) at the time of diagnosis and a median 58% improvement following therapy. All patients demonstrated an increased time interval between injections, for a median improvement of 2.05× (range, 1.6× to 3.25×). CONCLUSIONS: Evidence exists in support of vascular endothelial growth factor as an important factor in the development of RRP. Although some variability in response is demonstrated by this study, high-dose bevacizumab appears to yield promising results for pediatric patients with RRP.

Systemic Bevacizumab for Treatment of Respiratory Papillomatosis: International Consensus Statement.

OBJECTIVES/HYPOTHESIS: The purpose of this study is to develop consensus on key points that would support the use of systemic bevacizumab for the treatment of recurrent respiratory papillomatosis (RRP), and to provide preliminary guidance surrounding the use of this treatment modality. STUDY DESIGN: Delphi method-based survey series. METHODS: A multidisciplinary, multi-institutional panel of physicians with experience using systemic bevacizumab for the treatment of RRP was established. The Delphi method was used to identify and obtain consensus on characteristics associated with systemic bevacizumab use across five domains: 1) patient characteristics; 2) disease characteristics; 3) treating center characteristics; 4) prior treatment characteristics; and 5) prior work-up. RESULTS: The international panel was composed of 70 experts from 12 countries, representing pediatric and adult otolaryngology, hematology/oncology, infectious diseases, pediatric surgery, family medicine, and epidemiology. A total of 189 items were identified, of which consensus was achieved on Patient Characteristics (9), Disease Characteristics (10), Treatment Center Characteristics (22), and Prior Workup Characteristics (18). CONCLUSION: This consensus statement provides a useful starting point for clinicians and centers hoping to offer systemic bevacizumab for RRP and may serve as a framework to assess the components of practices and centers currently using this therapy. We hope to provide a strategy to offer the treatment and also to provide a springboard for bevacizumab's use in combination with other RRP treatment protocols. Standardized delivery systems may facilitate research efforts and provide dosing regimens to help shape best-practice applications of systemic bevacizumab for patients with early-onset or less-severe disease phenotypes. LEVEL OF EVIDENCE: 5 Laryngoscope, 131:E1941-E1949, 2021.

Competency-Based Assessment Tool for Pediatric Esophagoscopy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric esophagoscopy with foreign body removal. STUDY DESIGN: Blinded modified Delphi consensus process. SETTING: Tertiary care center. METHODS: A list of 25 potential items was sent via the Research Electronic Data Capture database to 66 expert surgeons who perform pediatric esophagoscopy. In the first round, items were rated as "keep" or "remove" and comments were incorporated. In the second round, experts rated the importance of each item on a seven-point Likert scale. Consensus was determined with a goal of 7 to 25 final items. RESULTS: The response rate was 38/64 (59.4%) in the first round and returned questionnaires were 100% complete. Experts wanted to "keep" all items and 172 comments were incorporated. Twenty-four task-specific and 7 previously-validated global rating items were distributed in the second round, and the response rate was 53/64 (82.8%) with questionnaires returned 97.5% complete. Of the task-specific items, 9 reached consensus, 7 were near consensus, and 8 did not achieve consensus. For global rating items that were previously validated, 6 reached consensus and 1 was near consensus. CONCLUSIONS: It is possible to reach consensus about the important steps involved in rigid esophagoscopy with foreign body removal using a modified Delphi consensus technique. These items can now be considered when evaluating trainees during this procedure. This tool may allow trainees to focus on important steps of the procedure and help training programs standardize how trainees are evaluated. LEVEL OF EVIDENCE: 5. Laryngoscope, 131:1168-1174, 2021.

Competency-Based Assessment Tool for Pediatric Tracheotomy: International Modified Delphi Consensus.

OBJECTIVES/HYPOTHESIS: Create a competency-based assessment tool for pediatric tracheotomy. STUDY DESIGN: Blinded, modified, Delphi consensus process. METHODS: Using the REDCap database, a list of 31 potential items was circulated to 65 expert surgeons who perform pediatric tracheotomy. In the first round, items were rated as "keep" or "remove," and comments were incorporated. In the second round, experts were asked to rate the importance of each item on a seven-point Likert scale. Consensus criteria were determined a priori with a goal of 7 to 25 final items. RESULTS: The first round achieved a response rate of 39/65 (60.0%), and returned questionnaires were 99.5% complete. All items were rated as "keep," and 137 comments were incorporated. In the second round, 30 task-specific and seven previously validated global rating items were distributed, and the response rate was 44/65 (67.7%), with returned questionnaires being 99.3% complete. Of the Task-Specific Items, 13 reached consensus, 10 were near consensus, and 7 did not achieve consensus. For the 7 previously validated global rating items, 5 reached consensus and two were near consensus. CONCLUSIONS: It is feasible to reach consensus on the important steps involved in pediatric tracheotomy using a modified Delphi consensus process. These items can now be considered to create a competency-based assessment tool for pediatric tracheotomy. Such a tool will hopefully allow trainees to focus on the important aspects of this procedure and help teaching programs standardize how they evaluate trainees during this procedure. LEVEL OF EVIDENCE: 5 Laryngoscope, 130:2700-2707, 2020.

Arytenoid prolapse: a source of obstruction following laryngotracheoplasty.

OBJECTIVE: Arytenoid prolapse is a potential source of upper airway obstruction following laryngotracheoplasty, and may be difficult to identify. We explored the incidence, clinical features, etiology, and surgical approach to patients with arytenoid prolapse following laryngotracheoplasty. STUDY DESIGN: Case series with chart review. SUBJECTS AND METHODS: The charts of 93 patients diagnosed with arytenoid prolapse following laryngotracheoplasty from 1981 to 2007 were reviewed. RESULTS: The incidence was 5.7 percent (93/1634). Forty-nine patients had unilateral prolapse; 44 had bilateral prolapse. Average time from laryngotracheoplasty to presentation was 36.8 months. Common symptoms were dyspnea on exertion, tracheostomy dependence, and sleep-disordered breathing. Fifty-four patients (58%) required surgical intervention, with arytenoid reduction performed in 45 patients. Nine underwent reduction during revision laryngotracheoplasty or cricotracheal resection. Fourteen patients required a second procedure for persistent prolapse. Thirty-nine (42%) required no intervention. Symptom resolution or decannulation was achieved in all patients in whom prolapse was the source of obstruction. Statistically significant differences were found when anterior vs posterior graft utilization was compared. CONCLUSIONS: Arytenoid prolapse is a cause of airway obstruction following laryngotracheoplasty. Subtle airway complaints and decannulation failures are common features. Both endoscopic and open procedures can successfully treat arytenoid prolapse. Potential etiologies are discussed.

Outcome measures for pediatric laryngotracheal reconstruction: International consensus statement.

OBJECTIVES: Develop multidisciplinary and international consensus on patient, disease, procedural, and perioperative factors, as well as key outcome measures and complications, to be reported for pediatric airway reconstruction studies. METHODS: Standard Delphi methods were applied. Participants proposed items in three categories: 1) patient/disease characteristics, 2) procedural/intraoperative/perioperative factors, and 3) outcome measures and complications. Both general and anatomic site-specific measures were elicited. Participants also suggested specific operations to be encompassed by this project. We then used iterative ranking and review to develop consensus lists via a priori Delphi consensus criteria. RESULTS: Thirty-three pediatric airway experts from eight countries in North and South America, Europe, and Australia participated, representing otolaryngology (including International Pediatric Otolaryngology Group members), pulmonology, general surgery, and cardiothoracic surgery. Consensus led to inclusion of 19 operations comprising open expansion, resection, and slide procedures of the larynx, trachea, and bronchi as well as three endoscopic procedures. Consensus was achieved on multiple patient/comorbidity (10), disease/stenosis (7), perioperative-/intraoperative-/procedure-related (16) factors. Consensus was reached on multiple outcome and complication measures, both general and site-specific (8 general, 13 supraglottic, 15 glottic, 17 subglottic, 8 cervical tracheal, 12 thoracic tracheal). The group was able to clarify how each outcome should be measured, with specific instruments defined where applicable. CONCLUSION: This consensus statement provides a framework to communicate results consistently and reproducibly, facilitating meta-analyses, quality improvement, transfer of information, and surgeon self-assessment. It also clarifies expert opinion on which patient, disease, procedural, and outcome measures may be important to consider in any pediatric airway reconstruction patient. LEVEL OF EVIDENCE: 5 Laryngoscope, 129:244-255, 2019.

History of pediatric laryngotracheal reconstruction.

In the early twentieth century, John Winslow wrote that there was no more difficulty in laryngology than treating chronic stenosis of the larynx and trachea. Winslow described cases as "excessively rebellious to treatment" and treatment requiring "patience, persistence, self-sacrifice and skill on the part of the surgeon" and "discomfort or even suffering by the patient." Three decades later, Chevalier Jackson wrote that curing patients required perseverance over a period of time rarely as short as 3 months and as long as 7 years. Significant strides in surgical technique have been made; this article chronicles the development of laryngotracheal reconstruction in children.

Diagnosis and management of laryngotracheal stenosis.

INTRODUCTION: Laryngotracheal stenosis comprises a broad spectrum of congenital and acquired conditions that commonly cause pediatric airway obstruction. Although the majority of these conditions were historically managed with endoscopic dilations, the introduction of operative procedures such as laryngotracheoplasty, cricotracheal resection, and slide tracheoplasty changed the treatment paradigm. The gradual evolution of endoscopic technology enabled surgeons to perform certain procedures endoscopically that were previously only able to be performed in an open fashion. Areas covered: This review highlights the important aspects of the diagnosis, workup, and surgical treatment of pediatric laryngotracheal stenosis. Important articles describing research and techniques within pediatric airway reconstruction are summarized and included in the review. Expert commentary: The importance of the multidisciplinary concept of treating laryngotracheal stenosis is evidenced by the establishment of aerodigestive centers internationally. In order to continue successfully treating complex cases of laryngotracheal stenosis, further airway research is needed. The application and feasibility of tracheal transplantation and replacement is likely the next frontier in the treatment of laryngotracheal stenosis.

Short- versus Long-term Stenting in Children with Subglottic Stenosis Undergoing Laryngotracheal Reconstruction.

Objectives Suprastomal stents are routinely used in laryngotracheal reconstruction (LTR) to stabilize grafts and provide framework to sites of repair. However, the duration of stenting varies according to patient history and physician preference. We examined outcomes of short- versus long-term stenting in children with subglottic stenosis (SGS) undergoing LTR. Study Design Case series with chart review. Setting Tertiary care pediatric hospital. Subjects and Methods Thirty-six children <18 years old who underwent double-stage LTR for SGS from January 2012 to January 2015 were included. Demographic data, stenosis grade, and decannulation rates were compared between children with short-term stenting (≤21 days; n = 14) and those with long-term stenting (>21 days; n = 22). Results No significant difference between groups was seen for sex, age, race, or previous repair. Children in the short-term group were stented for 10.9 ± 4.9 days, compared with 44.0 ± 10.6 for those long-term ( P < .0001). A similar number of children with short- versus long-term stents had grade 3/4 stenosis preoperatively (71.4% vs 77.2%). Although time to decannulation was not significantly different, 72.7% of children with long-term stents were decannulated, as opposed to 35.7% with short-term stents ( P = .03). After adjusting for grade at surgery and age, children with long-term stents had 4.3 greater odds (95% CI, 1.0-18.3) of decannulation than children with short-term stents. Conclusions Children with long-term stenting were more likely to be successfully decannulated. Although long-term stenting improved outcomes for children with SGS, additional research is needed to better define ideal candidates for short- versus long-term stenting.

Structure and Functions of Pediatric Aerodigestive Programs: A Consensus Statement.

Aerodigestive programs provide coordinated interdisciplinary care to pediatric patients with complex congenital or acquired conditions affecting breathing, swallowing, and growth. Although there has been a proliferation of programs, as well as national meetings, interest groups and early research activity, there is, as of yet, no consensus definition of an aerodigestive patient, standardized structure, and functions of an aerodigestive program or a blueprint for research prioritization. The Delphi method was used by a multidisciplinary and multi-institutional panel of aerodigestive providers to obtain consensus on 4 broad content areas related to aerodigestive care: (1) definition of an aerodigestive patient, (2) essential construct and functions of an aerodigestive program, (3) identification of aerodigestive research priorities, and (4) evaluation and recognition of aerodigestive programs and future directions. After 3 iterations of survey, consensus was obtained by either a supermajority of 75% or stability in median ranking on 33 of 36 items. This included a standard definition of an aerodigestive patient, level of participation of specific pediatric disciplines in a program, essential components of the care cycle and functions of the program, feeding and swallowing assessment and therapy, procedural scope and volume, research priorities and outcome measures, certification, coding, and funding. We propose the first consensus definition of the aerodigestive care model with specific recommendations regarding associated personnel, infrastructure, research, and outcome measures. We hope that this may provide an initial framework to further standardize care, develop clinical guidelines, and improve outcomes for aerodigestive patients.

Upper airway volume segmentation analysis using cine MRI findings in children with tracheostomy tubes.

OBJECTIVE: The purpose of this study is to evaluate the airway dynamics of the upper airway as depicted on cine MRI in children with tracheotomy tubes during two states of airflow through the upper airway. MATERIALS AND METHODS: Sagittal fast gradient echo cine MR images of the supra-glottic airway were obtained with a 1.5T MRI scanner on seven children with tracheotomy tubes. Two sets of images were obtained with either the tubes capped or uncapped. The findings of the cine MRI were retrospectively reviewed. Volume segmentation of the cine images to compare the airway volume change over time (mean volume, standard deviation, normalized range, and coefficient of variance) was performed for the capped and uncapped tubes in both the nasopharynx and hypopharynx (Signed Rank Test). RESULTS: Graphical representation of the airway volume over time demonstrates a qualitative increased fluctuation in patients with the tracheotomy tube capped as compared to uncapped in both the nasopharyngeal and hypopharyngeal regions of interest. In the nasopharynx, the mean airway volume (capped 2.72 mL, uncapped 2.09 mL, p = 0.0313), the airway volume standard deviation (capped 0.42 mL, uncapped 0.20 mL, p = 0.0156), and the airway volume range (capped 2.10 mL, uncapped 1.09 mL, p = 0.0156) were significantly larger in the capped group of patients. In the hypopharynx, the airway volume standard deviation (capped 1.54 mL, uncapped 0.67 mL, p = 0.0156), and the airway volume range (capped 6.44 mL, uncapped 2.93 mL, p = 0.0156) were significantly larger in the capped tubes. The coefficient of variance (capped 0.37, uncapped 0.26, p = 0.0469) and the normalized range (capped 1.52, uncapped 1.09, p = 0.0313) were significantly larger in the capped tubes. CONCLUSION: There is a statistically significant change in airway dynamics in children with tracheotomy tubes when breathing via the airway as compared to breathing via the tracheotomy tube.

Immunocompetency in children with recurrent respiratory papillomatosis: prospective study.

OBJECTIVES: We sought to investigate the immunologic status of children with recurrent respiratory papillomatosis and to evaluate possible correlations between the patients' immunocompetency and the clinical course of the disease. METHODS: Twenty children with recurrent respiratory papillomatosis underwent immunologic evaluation every 6 months for determination of complete blood count, serum immunoglobulin levels, lymphocyte subpopulations, lymphocyte response to mitogen stimulation, and natural killer cell function. The patients were observed prospectively (42 to 56 months), and their clinical course was recorded. The findings were compared with those in healthy age-matched controls. RESULTS: The CD4/CD8 ratio and the lymphocyte response to mitogen stimulation were significantly reduced in the study children compared to normal controls. A reduction in lymphocyte response to mitogen stimulation was significantly correlated to a high number of papilloma sites and more frequent recurrences. Abnormal natural killer cell function was significantly correlated to more frequent recurrences. CONCLUSIONS: A compromised cell-mediated immune response may be associated with repeated or persistent human papillomavirus infections, leading to the development of recurrent respiratory papillomatosis. Patients with an aggressive clinical course may have underlying cell-mediated immunodeficiency. Long-term prospective investigations are needed to establish the role of the host immune system in the pathogenesis of recurrent respiratory papillomatosis in children.

Management of symptomatic tracheal pouches.

OBJECTIVE: Acquired tracheal pouches arise following tracheoesophageal fistula (TEF) repair, but are usually asymptomatic. Symptomatic tracheal pouches are rare, and the optimal management strategy debated. The evolution of our management to this challenging problem is presented. DESIGN: A case series over a 5-year period. SETTING: A tertiary care pediatric hospital. PATIENTS: Children with a past history of TEF repair in whom severity of pouch-related respiratory symptomatology warranted surgical intervention. MAIN OUTCOME MEASURES: Symptomatology, bronchoscopic findings, number and type of surgical interventions required, complications, and outcomes. RESULTS: Eleven patients required surgical intervention for a symptomatic tracheal pouch. Symptoms were due to stasis of secretions with associated pulmonary soiling in three children, severe tracheomalacia in six children, and respiratory obstruction related to the tip of a tracheotomy tube or endotracheal tube being displaced intermittently into the pouch in six children. Surgical management of the pouch included one fulguration with the CO(2) laser, one with microlaryngeal instruments, Bugbee cautery in two, open resection in one, and transcervical division in another. The final five children had endoscopic pouch division with Clickline biopsy forceps. All children have had resolution of their pouch-related symptoms, although two remain tracheotomy-dependent. CONCLUSIONS: Symptomatic tracheal pouches are rare. Surgical intervention to divide the common party wall between the trachea and the pouch may alleviate associated respiratory symptomatology. The Clickline biopsy forceps is a safe, rapid, and effective method of dividing a tracheal pouch.

The clinical relevance of the submucosal cricoid cleft.

PURPOSE: Although fairly uncommon and sometimes difficult to diagnose, laryngeal clefts have been well-defined in the literature. The submucosal cleft variant has been described anatomically, but not clinically. We describe a series of patients with a submucosal cricoid cleft variant and its clinical relevance. METHODS: This is a case series of patients presenting with submucosal cricoid. A submucosal cricoid cleft is defined as a dehiscent posterior cricoid plate with an intact mucosal bridge. RESULTS: Eight patients presented during a 4 year period from October 2002 to September 2006. Patient ages ranged from 6 days to 15 years, with a mean age of 40 months. Four patients (50%) had a submucosal cricoid cleft only while four children presented with a laryngotracheal cleft in addition to the submucosal cricoid cleft. Six patients were diagnosed with subglottic stenosis and had tracheotomies. Four patients (50%) failed laryngotracheal reconstruction (LTR) prior to submucosal cricoid cleft diagnosis. Two patients had their submucosal cricoid cleft diagnosed during initial airway reconstruction surgery. Two patients were diagnosed after feeding difficulties. The submucosal cricoid cleft was felt to be an important factor contributing to the failure of previous laryngotracheal reconstruction. Almost all of the patients (7/8) had co-morbidities. Two patients needed revision airway surgery, both successful. Four of the six patients with a tracheostomy have been decannulated. CONCLUSION: Because of the subtle nature of its clinical presentation, submucosal cricoid cleft can be a challenging diagnostic entity, and the results of surgical reconstruction may be compromised if the cleft is undiagnosed.

The Management of Cyanotic Spells in Children with Oesophageal Atresia.

Cyanotic spells, also known as blue spells, dying spells, or apparent life-threatening events, refer to a bluish tone visible in the mucosal membranes and skin caused by an oxygen decrease in the peripheral circulation. Although this decrease may be transient and benign, it may also be indicative of a severe underlying problem that requires immediate intervention. Children with oesophageal atresia (OA) are at risk for a number of coexisting conditions that may trigger cyanotic spells. This current article will focus on the management of cyanotic spells both in children with innominate artery compression and those with tracheomalacia.

Inverting suprastomal granulomas.

Although suprastomal granulomas are a common complication of tracheotomy, they usually are an incidental finding and do not always require treatment. However, large granulomas may require removal, either to assist with speech production or to make the airway safer in the event of an accidental decannulation. Very large suprastomal granulomas extending up to or even through the vocal cords have been described. However, inverting suprastomal granulomas extending distally down the length of a tracheotomy tube have not been previously described. We present two cases of large suprastomal granulomas that extended distally down the trachea. Both extended beyond the tip of the tracheotomy tube, causing partial airway obstruction, and therefore required excision. Laryngoscope, 127:2883-2885, 2017.

Open excision of subglottic hemangiomas to avoid tracheostomy.

OBJECTIVE: To assess the efficacy of open excision as an alternative to tracheostomy in the management of subglottic hemangioma. DESIGN: A retrospective review of patients undergoing open surgical excision of subglottic hemangiomas over a 10-year period. SETTING: A tertiary pediatric center. PATIENTS: The study included 22 children ranging in age from 2 to 42 months (median age, 5 months) who underwent open excision of subglottic hemangioma over a 10-year period. RESULTS: Twenty-one patients were treated with single-stage procedures, with postoperative endotracheal intubation for an average of 5 days. One patient who had a preexisting tracheostomy was treated with a 2-stage procedure and underwent decannulation 2 months after excision. Seven other patients were tracheostomy dependent at the time of excision and underwent decannulation at the time of the procedure. Cartilage grafts were inserted in 10 patients. There were no problems with subglottic stenosis. Twenty-one patients reported good voice and no airway symptoms after a mean follow-up period of 42 months. Five patients had significant postoperative problems. Three patients required further endoscopic procedures for removal of granulation tissue, and 1 patient, who remains minimally symptomatic, developed an anterior glottic web. One patient required a 6-month course of steroids after surgery to treat residual glottic hemangioma. CONCLUSIONS: Open surgical excision of subglottic hemangiomas can be performed as a single procedure, avoiding a tracheostomy, when modern surgical techniques developed for laryngotracheal reconstruction are incorporated. This approach can avoid repeated endoscopic procedures, prolonged treatment with corticosteroids, and years spent with a tracheostomy waiting for spontaneous involution of the hemangioma.

Management of incidental thyroglossal duct cysts during laryngotracheal reconstruction.

Thyroglossal duct cysts originate from trapped elements of the thyroglossal duct tract during embryological descent of the thyroid gland. The incidental finding of a thyroglossal duct cyst during cervical surgery has not been described previously. We present four cases of small asymptomatic thyroglossal duct cysts discovered as an incidental finding during laryngotracheal reconstruction. In each case, the cyst was removed using a Sistrunk procedure. In all four cases the patient was successfully decannulated, and there were no cases of cyst recurrence. We also consider the implications that these four cases may have on the perceived incidence of the thyroglossal duct cysts and their management.

Airway reconstruction in children with recurrent respiratory papillomatosis.

OBJECTIVE: To determine if children with recurrent respiratory papillomatosis were at increased risk of complications due to their disease following major airway reconstruction. METHODS: We retrospectively reviewed our airway surgery database and the medical records of all children diagnosed with recurrent respiratory papillomatosis who were evaluated at Cincinnati Children's Hospital Medical Center between January 1998 and August 2003. All patients with active airway papillomas or a history of recurrent respiratory papillomatosis who underwent open airway reconstruction at our institution were included in the study. RESULTS: Seven children with recurrent respiratory papillomatosis underwent major airway reconstruction. Six children had tracheotomies and five are now decannulated following their airway reconstruction. Five children had active papillomas at the time of surgery and none had significant worsening of their papillomas following their procedures. Two patients in remission underwent airway reconstruction without recurrence of their papillomas. CONCLUSIONS: Major airway reconstruction can be safely performed in children with recurrent respiratory papillomatosis.