Faculty Bibliography

OBJECTIVES: We assessed the safety and efficacy of balloon dilation as treatment for recurrent stenosis after pediatric laryngotracheoplasty. METHODS: We studied a retrospective case series at an academic tertiary care children's hospital. We included all patients under the age of 18 years with subglottic or tracheal stenosis treated at our institution with balloon dilation between June 2007 and April 2009. The records were analyzed for patient demographics, presenting symptoms, surgical technique, and airway description. The outcome measures were airway diameter, postoperative symptoms, tracheotomy status, and complications. RESULTS: Ten patients (9 with subglottic stenosis and 1 with tracheal stenosis) underwent 20 balloon dilation procedures without complication. The average age at the time of the procedure was 17 months (range, 3 months to 9 years). The patient presenting symptoms were stridor in 7 cases and tracheotomy in 3 cases. Vascular balloons (diameter range, 6 to 12 mm; length, 20 mm) were inflated to 10 to 12 cm H2O pressure for an average of 40 seconds (range, 10 to 120 seconds). Each procedure consisted of 1 to 3 dilation cycles. The immediate postdilation airway area increased by an average factor of 4.9 (range, 1.9 to 9). Six patients had repeat procedures with an average interval between dilations of 67 days (range, 6 to 337 days). Stridor was eliminated or greatly improved in all patients on the first postoperative day; 7 patients sustained this benefit, with an average follow-up time of 10 months (range, 4 to 23 months). Six of the 10 patients had undergone previous laryngeal reconstruction (age range, 3 months to 4 years). Of these 6, 3 have no tracheotomy, with a mean follow-up of 12.5 months. The 3 children who benefited the least from dilation were noted to have more diffuse and chronic inflammation of the larynx in comparison to the responders. CONCLUSIONS: This case series suggests that balloon dilation is a relatively safe and effective procedure. It may be particularly well suited to recent stenosis after laryngotracheal reconstruction.

This study investigated cochlear implant (CI) users' ability to perceive pitch cues from time-varying virtual channels (VCs) to identify pitch contours. Seven CI users were tested on apical, medial, and basal electrode pairs with stimulus durations from 100 to 1000 ms. In one stimulus set, 9 pitch contours were created by steering current between the component electrodes and the VC halfway between the electrodes. Another stimulus set only contained 3 pitch contours (flat, falling, and rising). VC discrimination was also tested on the same electrodes. The total current level of dual-electrode stimuli was linearly interpolated between those of single-electrode stimuli to minimize loudness changes. The results showed that pitch contour identification (PCI) scores were similar across electrode locations, and significantly improved at longer durations. For durations longer than 300 ms, 2 subjects had nearly perfect 9-contour identification, and 5 subjects perfectly identified the 3 basic contours. Both PCI and VC discrimination varied greatly across subjects. Cumulative d(') values for VC discrimination were significantly correlated with 100-, 200-, and 500-ms PCI scores. These results verify the feasibility of encoding pitch contours using current steering, and suggest that identification of such pitch contours strongly relies on CI users' sensitivity to VCs.

Completion of the human genome project approximately 15 years ago was followed closely by advancements in array technology. Investigators quickly applied this new powerful tool to the genomic and proteomic study of oral squamous cell carcinoma (OSCC). Resultant publications documented chromosome, gene, mRNA, and protein alterations that characterize oral cancer. In this review, we summarize how the genomic, proteomic, and epigenetic array studies have provided insight into the process of oral carcinogenesis. We discuss the significant limitations and requirement for validation of these array studies. We also review the manner in which state-of-the-art, high-throughput approaches are being used to search for salivary and serum oral cancer biomarkers

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, has shown promise in treating recurrent adult high-grade glioma (HGG). However, there is very little data on recurrent or progressive pediatric HGG treated with bevacizumab. We report the results of a single institution experience using bevacizumab and irinotecan in children who relapsed or progressed following standard therapy. Twelve pediatric patients with recurrent or progressive HGG received bevacizumab at 10 mg/kg every 2 weeks with irinotecan at 125 mg/m(2). Magnetic resonance imaging (MRI) was performed prior to therapy and every 8 weeks subsequently. Ten patients had supratentorial HGG; 2 had DIPG. Radiological responses were defined according to MacDonald's criteria. Progression-free survival (PFS), overall survival (OS), and toxicities were analyzed. Ten (83.3%) patients tolerated bevacizumab without serious toxicity. Therapy was discontinued in 1 patient because of anaphylaxis. Another patient developed grade III delayed wound healing and deep vein thrombosis. Two patients (16.7%) experienced a partial response after the first MRI. No complete radiographic responses were seen. Stable disease was noted in 4 (33.3%) patients. The median PFS and OS were 2.25 and 6.25 months, respectively. A diffuse invasive recurrence pattern was noted in 5 (45.5%) patients. Treatment tolerance, toxicity, and recurrence profiles were comparable to adult HGG patients treated with bevacizumab. However, the radiological response rate, response duration, and survival appeared inferior in pediatric patients. Genetic differences in pediatric gliomas might account for this difference

OBJECTIVES/HYPOTHESIS: Inflammation and its role in a coordinated fibroplastic response, which disrupts the structure of the vocal folds following injury, is critical. Cyclooxygenase-2 (COX-2) is an important enzyme involved in both inflammation and fibrosis; in addition, it is a prime target for therapeutic intervention. We sought to study this pathway in vocal fold fibroblasts to provide a foundation for future interventional studies. STUDY DESIGN: In vitro. METHODS: Human vocal fold fibroblasts were incubated with IL-1 beta to determine the effects on COX-2 signaling, along with upstream regulatory mechanisms and downstream mediators of wound healing. In vitro methods to assess mRNA expression, as well as intracellular and secreted protein (sodium dodecyl sulfate polyacrylamide gel electrophoresis and enzyme-linked immunosorbent assay) were employed. RESULTS: IL-1 beta regulation of COX-2 mRNA and protein levels was dose and time dependent and IL-1 beta altered PGE(2) metabolism, via regulation of both synthetic and degradative enzymes. IL-1 beta increased nuclear factor (NF)-kappaB activation and nuclear translocation. Inhibition of the p50 and p65 subunits of NF-kappaB decreased IL-1 beta-induced COX-2 transcription. IL-1 beta also altered mRNA expression of four cell-surface prostaglandin receptors. CONCLUSIONS: Inflammation and fibrosis are important in the vocal fold pathophysiologic response to injury. Our data suggest that COX-2 and PGE(2) are inducible in human vocal fold fibroblasts, and this response appears to be NF-kappaB-dependent. We purport this fundamental investigation will lead to increased insight regarding injury and repair in the vocal folds, with the ultimate goal of developing novel clinical care paradigms

OBJECTIVE:: To determine whether intraoperative neural response telemetry (tNRT) is predictive of postoperative speech perception. STUDY DESIGN:: Retrospective review. SETTING:: Tertiary referral center. PATIENTS:: Children (n = 24) aged between 5 and 17 years and adults 18 years and older (n = 73) with severe-to-profound hearing loss and implanted with the Nucleus Freedom device between 2005 and 2008 and observed at least 1 year were included. INTERVENTION:: Intraoperative neural response telemetry after insertion of the electrode array. MAIN OUTCOME MEASURE:: Measures included 1) intraoperative tNRT measurements and 2) preoperative and 1-year postoperative open-set word recognition scores using age-appropriate open-set tests for children and adults. Intraoperative neural response telemetry levels for electrodes E20, E15, E10, and E5 in each patient were correlated to performance at the 1-year evaluation interval. RESULTS:: No correlation existed between tNRT responses and open-set speech performance at the 1-year evaluation. Several patients had absent tNRT in the OR but developed speech recognition abilities, whereas the remaining patients had intraoperative responses with levels of postoperative performance ranging from 0% to 100%. CONCLUSION:: This study suggests that there is no significant correlation between intraoperative tNRT and speech perception performance at 1 year. At the time of surgery, tNRT provides valuable information regarding the electrical output of the implant and the response of the auditory system to electrical stimulation and preliminary device programming data; however, it is not a valuable predictor of postoperative performance. Furthermore, the absence of tNRT does not necessarily indicate a lack of stimulation

Hemangioblastomas frequently develop in patients with von Hippel-Lindau (VHL) disease, an autosomal dominant genetic disorder. The tumors are characterized by a dense network of blood capillaries, often in association with cysts. Although activation of receptor tyrosine kinase (RTK) signaling, including epidermal growth factor receptor (EGFR) has been implicated in the development of malignant brain tumors such as high-grade gliomas, little is known about the role of RTK signaling in hemangioblastomas. To address this issue, we examined hemangioblastoma tumor specimens using receptor tyrosine kinase (RTK) activation profiling and immunohistochemistry. Six human hemangioblastomas were analyzed with a phospho-RTK antibody array, revealing EGFR phosphorylation in all tumors. EGFR expression was confirmed by immunohistochemistry in all tumors analyzed and downstream effector pathway activation was demonstrated by positive staining for phospho-AKT. Our findings suggest that, in primary hemangioblastomas, RTK upregulation and signaling predominantly involves EGFR, providing an attractive molecular target for therapeutic intervention

We report an unusual manifestation of penetrating facial trauma. It was suffered by a recreational fly fisherman who was hiking away from a casting spot when he fell and was impaled by a section of his graphite flyrod. The circumstances of his injury, its clinical manifestations, and its imaging findings are discussed. Emergency physicians and radiologists should be aware of the computed tomography appearance of impaled foreign bodies and their capability to penetrate deeply to reach critical vascular and neurologic structures. The role of imaging in penetrating trauma to the face and skull base for guiding appropriate intervention is emphasized.

PURPOSE: To examine the acute morbidity of high dose head and neck RT and CRT in patients with infected with HIV. METHODS AND MATERIALS: All HIV-positive patients who underwent radiation therapy for head and neck cancer in our department between 2004 and 2008 were reviewed. Treatment related data were examined. All treatments were delivered with megavoltage photon beams or electron beams. Patients were evaluated by an attending radiation oncologist for toxicity and response on a weekly basis during therapy and monthly after treatment in a multidisciplinary clinic. Acute toxicities were recorded using the Radiation Therapy and Oncology Group (RTOG) common toxicity criteria. Response to treatment was based on both physical exam as well as post-treatment imaging as indicated. RESULTS: Thirteen patients who underwent RT with a diagnosis of HIV were identified. Median age was 53 years and median follow-up was 22 months. Twelve had squamous cell carcinoma and one had lymphoproliferative parotiditis. Median radiation dose was 66.4 Gy and median duration of treatment was 51 days. The median number of scheduled radiotherapy days missed was zero (range 0 to 7). One patient (8%) developed Grade 4 confluent moist desquamation. Eight patients (61%) developed Grade 3 toxicity. CONCLUSION: Based on our results, HIV-positive individuals appear to tolerate treatment for head and neck cancer, with toxicity similar to that in HIV-negative individuals