Virginia Mullooly

Voice Restoration following Laryngectomy: The Role of Primary versus Secondary Tracheoesophageal Puncture

A protocol was established at our institution to compare a series of primary and secondary tracheoesophageal punctures using the Singer-Blom voice prosthesis. Over a 24-month period, 20 primary and 18 secondary punctures were performed. Voice production, fluency of voice, and functional use were graded. Our data support the use of both primary and secondary voice restoration following laryngectomy.

Early efficacy trial of anakinra in corticosteroid-resistant autoimmune inner ear disease

BACKGROUND Autoimmune inner ear disease (AIED) is a rare disease that results in progressive sensorineural hearing loss. Patients with AIED initially respond to corticosteroids; however, many patients become unresponsive to this treatment over time, and there is no effective alternative therapy for these individuals. METHODS We performed a phase I/II open-label, single-arm clinical trial of the IL-1 receptor antagonist anakinra in corticosteroid-resistant AIED patients. Given that the etiology of corticosteroid resistance is likely heterogeneous, we used a Simon 2-stage design to distinguish between an unacceptable (≤10%) and an acceptable (≥30%) response rate to anakinra therapy. Subjects received 100 mg anakinra by subcutaneous injection for 84 days, followed by a 180-day observational period. RESULTS Based on patient responses, the Simon 2-stage rule permitted premature termination of the trial after 10 subjects completed the 84-day drug period, as the target efficacy for the entire trial had been achieved. Of these 10 patients, 7 demonstrated audiometric improvement, as assessed by pure tone average (PTA) and word recognition score (WRS). In these 7 responders, reduced IL-1β plasma levels correlated with clinical response. Upon discontinuation of treatment, 3 subjects relapsed, which correlated with increased IL-1β plasma levels. CONCLUSION We demonstrated that IL-1β inhibition in corticosteroid-resistant AIED patients was effective in a small cohort of patients and that IL-1β plasma levels associated with both clinical hearing response and disease relapse. These results suggest that a larger phase II randomized clinical trial of IL-1β inhibition is warranted. TRIAL REGISTRATION ClinicalTrials.gov NCT01267994. FUNDING NIH, Merrill & Phoebe Goodman Otology Research Center, and Long Island Hearing & Speech Society.

Voice restoration after laryngopharyngoesophagectomy

Although various methods of alaryngeal communication after laryngectomy have been described, little attention has been given to voice restoration after laryngopharyngoesophagectomy. This article deals with our experience reconstructing the hypopharynx and cervical esophagus in five patients by the use of microvascular free tissue grafts. Voice restoration procedures with use of a Blom-Singer prostheses were used uniformly and resulted in the attainment of functional voice in each patient, it is our feeling that this method should be used equally in patients undergoing both traditional laryngectomy and laryngopharyngoesophagectomy.

Polymorphism of Transporter Associated with Antigen Presentation 1 as a Potential Determinant for Severity of Disease in Recurrent Respiratory Papillomatosis Caused by Human Papillomavirus Types 6 and 11

Recurrent respiratory papillomatosis (RRP) is a rare disease caused by human papillomaviruses (HPVs). It is characterized by multiple recurrences of benign neoplasms and has a variable clinical course, ranging from infrequent recurrence to acute airway obstruction. One way in which HPV subverts the immune system in RRP is by interfering with TAP1 (transporter associated with antigen presentation 1). We examined whether a known TAP1 polymorphism in the ATPase domain altered the severity of disease in patients with RRP. The presence of this polymorphism was significantly correlated with severity of disease (P=.015). Because of the proximity of the TAP1 gene to human leukocyte antigen (HLA) class II genes on chromosome 6, we postulated that a linkage disequilibrium may exist. Of the patients with polymorphic TAP1, 36% were positive for HLA-DRB1*0102 (P=.021; P=.147 with Bonferronis correction). However, this association appeared to mitigate the severity of disease (P=.04). Therefore, severity of disease in a patient with RRP might be determined by sequencing TAP1, in conjunction with HLA class II genes.

Clinical effects of alpha‐interferon dose variation on laryngeal papillomas

Achieving optimal clinical control of recurrent respiratory papillomatosis with prolonged treatment with human leukocyte (alpha) interferon appears to be dose‐related and often requires individualized dosage elevation. Six of eight patients in this study needed a maximum dose of 18 × 106 IU/week for part of the therapy period to achieve better disease control. The strong correlation found between dosage and response suggests that it is the interferon causing the effect on disease expression, not just the unpredictable nature of the disease.