Efficacy of Systemic Bevacizumab for Recurrent Respiratory Papillomatosis with Pulmonary Involvement.

OBJECTIVES: Pulmonary papillomatosis is a rare but severe manifestation of recurrent respiratory papillomatosis (RRP). Efficacy data of systemic bevacizumab for pulmonary RRP are limited. This study's objective was to characterize disease response of pulmonary RRP to systemic bevacizumab. METHODS: A retrospective review was performed to identify patients with pulmonary RRP seen at three medical institutions. Clinical symptoms, CT findings, and disease response were compared before and after initiation of systemic bevacizumab therapy. Disease response was categorized as complete response, partial response, stabilization, or progression for each subsite involved by papilloma. RESULTS: Of the 12 pulmonary RRP patients treated with systemic bevacizumab, 4 (33.3%) were male, and 11 (91.7%) were juvenile-onset RRP patients. All presented with laryngeal, tracheal, and pulmonary RRP. The median (range) age at first bevacizumab infusion was 48.1 (19.5-70.2) years. Progression to pulmonary malignancy was identified in 3 (25.0%) patients, 2 before initiation of and 1 after complete cessation of bevacizumab therapy. Clinical symptoms such as dyspnea (75.0% vs. 25.0%; p = 0.01) and dysphagia and/or odynophagia (33.3 vs. 0.0%; p = 0.03) were significantly decreased following bevacizumab therapy. Compared with pre-treatment baseline, 9 (75.0%) patients experienced a stable-to-partial response in the lungs to systemic bevacizumab, and 10 (83.3%) experienced partial-to-complete responses in the larynx and trachea. CONCLUSION: Systemic bevacizumab is effective in stabilizing progression in even the most severe cases of RRP, with both a dramatic reduction in laryngeal and tracheal disease as well as a stable-to-partial response of pulmonary involvement in a majority of patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:577-581, 2024.

Long-Term Follow-up of Parenteral Bevacizumab In Patients with Recurrent Respiratory Papillomatosis.

OBJECTIVE: The clinical course of recurrent respiratory papillomatosis (RRP) varies from spontaneous remission to severe airway obstruction with wide variability in recurrence. Standard treatment involves debulking to improve voice and/or breathing. Non-surgical therapies are emerging in hopes of non-operative disease control. This retrospective review analyzes long-term safety, efficacy, and durability of clinical control in the largest reported series of parenteral bevacizumab in adults with RRP. METHODS: Twenty-three patients with known RRP who have been receiving off-label systemic bevacizumab were included. Dosage, infusion interval, number of cycles, debulking requirements, subjective outcomes, adverse events, and reasons for treatment termination were investigated. RESULTS: Patients have been followed for an average of 791.43 (21-1468) days. The most common starting dosing regimen was 15 mg/kg at 3 weeks in 11 followed by 10 mg/kg at 6 weeks intervals in 6 individuals. Long-term maintenance dosage varied with the least intensive regimen being 10 mg/kg at 14-week intervals. Subjective improvement of voice and/or breathing was reported in 18/23 subjects. The median time for patients that needed a procedure after treatment was 634 days. Procedures after infusions decreased from 3.08 ± 2.48 procedures in the year prior to 0.52 ± 1.12 during systemic Bevacizumab, and to 0.86 ± 2.05 after stopping bevacizumab. Therapy termination occurred in 8 subjects where only 3 were due to adverse events. CONCLUSION: Parenteral bevacizumab remains a well-tolerated treatment for patients with recalcitrant RRP. There appears to be a durable reduction in the frequency of debulking surgery requirements although on a maintenance regimen. Laryngoscope, 133:2725-2733, 2023.

A Novel Device for Placement of a Secondary Tracheoesophageal Voice Prosthesis: A Preliminary Feasibility Study.

BACKGROUND: Tracheoesophageal puncture (TEP) for post-laryngectomy speech rehabilitation can be performed at the time of laryngectomy (primary) or at a subsequent time (secondary). Traditionally, the secondary procedure is performed using a rigid esophagoscope. Diseases like esophageal stricture, limited neck extension, and soft-tissue fibrosis can make this procedure technically challenging or impossible. We developed a novel device to perform a secondary tracheoesophageal puncture using a flexible esophagoscope. OBJECTIVE: To test the feasibility of a novel device used to create a secondary TEP in post-laryngectomy cadavers. METHODS: In this study, we performed a total laryngectomy on 3 fresh cadavers to establish the feasibility of our prototype. In each cadaver, a flexible esophagoscope was passed into the pharynx with the prototype. The prototype was passed through a working port and deployed to distend the esophagus. The puncture was visualized and a wire was passed via the newly established fistula. The device was activated, securing the wire, and then the esophagoscope and device were removed. RESULTS: There was 100% successful deployment of the prototype device, allowing rapid creation of the puncture and security of the guide wire in each cadaver. There was no evidence of collateral mucosal injury or esophageal perforation. CONCLUSIONS: The prototype device offers an alternative method to safely and efficiently perform a secondary TEP without the requirement of rigid esophagoscopy which can sometimes be technically impossible in this patient population.

Cystic Lesions of the Jaw in Children: A 15-Year Experience.

IMPORTANCE: Pediatric jaw cysts represent a rarely symptomatic clinical entity and are not well addressed in the otolaryngology literature. It is important that otolaryngologists should be familiar with these lesions, which can manifest as jaw swelling or as paranasal sinus abnormalities. OBJECTIVE: To review the clinical presentation, radiologic features, management, and outcomes of jaw cysts in children treated at a single academic institution. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review at a tertiary care children's hospital among patients 16 years and younger who were seen with a cystic jaw lesion. MAIN OUTCOMES AND MEASURES: Medical records were reviewed for data on symptoms, physical examination findings, imaging, pathology, interventions, and outcomes among children who were seen at the Department of Oral and Maxillofacial Surgery or the Department of Otorhinolaryngology-Head and Neck Surgery at the University of Maryland Medical Center between January 1997 and December 2012 and were diagnosed as having a jaw cyst. RESULTS: Fifty-seven patients were identified who were diagnosed as having a true cystic jaw lesion and whose complete medical records were available for review. The most common cystic lesions were keratocystic odontogenic tumors (n = 19) and dentigerous cysts (n = 17). Fifty-six percent (32 of 57) of all cystic lesions were asymptomatic on presentation and were identified by imaging. The second most common presentation was local swelling (n = 15), followed by dental irregularities (n = 6). All patients, except for 1 with an eruption cyst, required surgical intervention, including biopsy, enucleation, curettage, or ostectomy, with reconstruction as indicated. Keratocystic odontogenic tumors tended to require more treatment (median, 2 procedures) for metachronous lesions or recurrence. CONCLUSIONS AND RELEVANCE: Pediatric jaw cysts are unusual, and data are scarce regarding their presentation and management. Many of these cysts are asymptomatic and are identified incidentally on orthopantomography. Keratocystic odontogenic tumors were the most common lesion seen in our series, followed by dentigerous cysts. Surgical intervention is required in most patients with a cystic lesion of the jaw.

Tumors of the pediatric maxillofacial skeleton: a 20-year clinical study.

IMPORTANCE: Pediatric jaw tumors are a rare clinical entity and are not well addressed in the otolaryngology literature. It is important that otolaryngologists be familiar with the clinical features, management, and outcomes associated with these lesions. OBJECTIVE: To review the clinical presentation, management, and outcomes of jaw tumors in children treated at a tertiary care academic center. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of children 16 years or younger who presented to the departments of Oral-Maxillofacial Surgery and Otorhinolaryngology at the University of Maryland Medical Center between 1992 and 2012 and were diagnosed as having a jaw tumor. A PubMed review of literature from 1992 to 2013 on jaw tumors in children was also conducted. MAIN OUTCOMES AND MEASURES: Medical records were reviewed for data on symptoms, physical findings, pathologic diagnosis, intervention, and outcomes. RESULTS: The medical records of 76 patients evaluated for a jaw mass were reviewed, and 20 were found to have a diagnosis of a jaw tumor. The 2 most common pathologic diagnoses were ameloblastoma (n = 5) and juvenile ossifying fibroma (n = 4). Two tumors were malignant, a rhabdomyosarcoma and a teratoma. Thirteen patients presented with evidence of a mass or swelling, 5 patients were asymptomatic with a lesion found on surveillance panoramic radiography, and 1 patient presented with epistaxis and 1 with facial weakness and pain. All tumors excluding a lymphangioma and a rhabdomyosarcoma were managed surgically. Eight patients underwent more than 1 procedure including secondary reconstruction prior to a satisfactory outcome. CONCLUSIONS AND RELEVANCE: Pediatric jaw tumors are rare lesions most commonly presenting with a swelling or mass. Patients can be asymptomatic with the lesion identified on routine imaging. Certain clinical features such as age, location of tumor, and presence or absence of bone and soft tissue can narrow the differential diagnosis and identify tumors that may be malignant. Incisional biopsy is an important first step. A majority of jaw tumors are benign but require surgical intervention for eradication of disease. Multiple procedures, including reconstruction, may be required for certain lesions prior to cure.

Physical activity, change in biomarkers of myocardial stress and injury, and subsequent heart failure risk in older adults.

OBJECTIVES: The aim of this study was to evaluate the association between physical activity and changes in levels of highly sensitive troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the subsequent risk of the development of heart failure (HF) in community-dwelling older adults. BACKGROUND: Higher baseline levels of cTnT and NT-proBNP and increases over time correlate with the risk of HF in older adults. Factors modifying these levels have not been identified. METHODS: NT-proBNP and cTnT were measured at baseline and 2 to 3 years later in adults 65 years of age and older free of HF participating in the Cardiovascular Health Study. Self-reported physical activity and walking pace were combined into a composite score. An increase was prespecified for NT-proBNP as a >25% increment from baseline to ≥190 pg/ml and for cTnT as a >50% increment from baseline in participants with detectable levels (≥3 pg/ml). RESULTS: A total of 2,933 participants free of HF had NT-proBNP and cTnT measured at both time points. The probability of an increase in biomarker concentrations between baseline and follow-up visits was inversely related to the physical activity score. Compared with participants with the lowest score, those with the highest score had an odds ratio of 0.50 (95% confidence interval: 0.33 to 0.77) for an increase in NT-proBNP and an odds ratio of 0.30 (95% confidence interval: 0.16 to 0.55) for an increase in cTnT, after adjusting for comorbidities and baseline levels. A higher activity score associated with a lower long-term incidence of HF. Moreover, at each level of activity, an increase in either biomarker still identified those at higher risk. CONCLUSIONS: These findings suggest that moderate physical activity has protective effects on early heart failure phenotypes, preventing cardiac injury and neurohormonal activation.