Faculty Bibliography

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

PURPOSE OF REVIEW: This article reviews the significant recent literature on the constantly evolving approach to surgical rejuvenation of the forehead and brow. RECENT FINDINGS: Recent literature describes a variety of modifications to traditional endoscopic approaches, particularly regarding new permanent and temporary fixation techniques. There is continued effort to deepen our understanding of upper facial anatomy and its relationship to the aging process. As interest and research in this area continue to grow, improved quantification of surgical results becomes important. SUMMARY: There has been significant development and refinement of endoscopic approaches to foreheadplasty. Nonetheless, debate regarding the durability, quality of results, and complications of endoscopic versus open approaches continues. Ultimately, optimal results may be achieved through a variety of surgical techniques, but require a thorough understanding of the anatomic basis of aging, attention to detail, and adequate brow fixation

OBJECTIVES/HYPOTHESIS: Although the diagnostic accuracy of paradoxical vocal fold movement disorder and chronic cough has improved, the underlying pathophysiology remains relatively unknown. We hypothesize that one potential etiological factor in these patients is an aberrant laryngeal sensory response and sought to determine if respiratory retraining in addition to antireflux therapy alters this aberrant response. STUDY DESIGN: Retrospective, outcomes. METHODS: Sixteen patients who had been on at least 3 months of twice-daily proton pump inhibitors with no subjective improvement in their primary complaint of cough, self-reported symptoms of gastroesophageal and laryngopharyngeal reflux, and concurrent paradoxical vocal fold movement (PVFM) were included in the current study. In addition to continuing twice daily pharmacological therapy, subjects underwent a course of respiratory retraining. Outcome measures including the Reflux Symptom Index (RSI), transnasal flexible laryngoscopy, and laryngopharyngeal sensory discrimination thresholds were obtained prior to and following a course of respiratory retraining. RESULTS: Mean bilateral laryngeal sensory response improved significantly after combined respiratory retraining and aggressive proton pump inhibitor therapy (P = .01). In addition, mean RSI score decreased significantly following treatment (P = .02). Specifically, 13 of 16 patients experienced improved sensory response, corresponding with patient reports of improved PVFM symptoms following treatment. CONCLUSIONS: Aberrant laryngeal sensation was identified in patients with PVFM and chronic cough. This response, however, normalized following a limited course of respiratory retraining, corresponding with improved patient symptoms

OBJECTIVES: To investigate the influence of age, and age-at-implantation, on speech production intelligibility in prelingually deaf pediatric cochlear implant recipients. METHODS: Forty prelingually, profoundly deaf children who received cochlear implants between 8 and 40 months of age. Their age at testing ranged between 2.5 and 18 years. Children were recorded repeating the 10 sentences in the Beginner's Intelligibility Test. These recordings were played back to normal-hearing listeners who were unfamiliar with deaf speech and who were instructed to write down what they heard. They also rated each subject for the intelligibility of their speech production on a 5-point rating-scale. The main outcome measures were the percentage of target words correctly transcribed, and the intelligibility ratings, in both cases averaged across 3 normal-hearing listeners. RESULTS: The data showed a strong effect of age at testing, with older children being more intelligible. This effect was particularly pronounced for children implanted in the first 24 months of life, all of whom had speech production intelligibility scores of 80% or higher when they were tested at age 5.5 years or older. This was true for only 5 out of 9 children implanted at age 25-36 months. CONCLUSIONS: Profoundly deaf children who receive cochlear implants in the first 2 years of life produce highly intelligible speech before the age of 6. This is also true for most, but not all children implanted in their third year

Vestibular schwannomas (VS) arising sporadically or in patients with neurofibromatosis type 2 (NF2) consistently lack expression of Merlin, a tumor suppressor. Conventional treatment options include surgery and radiotherapy but there is no validated medical option. Recent evidence suggests that Merlin deficiency may result in abnormal activation of receptor tyrosine kinases (RTKs) and downstream signaling, promoting tumor growth. Although small-molecule RTK inhibitors are widely available for clinical use, no such therapy has been validated in patients with VS. To screen for RTK activation, surgical VS specimens from patients with and without NF2 were analyzed by phospho-RTK profiling arrays. Downstream signaling pathway activation was analyzed by phospho-MAPK arrays. Activated RTKs and downstream kinases were validated immunohistochemically in corresponding formalin-fixed, paraffin-embedded tissues. Phospho-RTK arrays and immunohistochemistry showed consistent overexpression and activation of EGFR family receptors and evidence of ERK1/2 downstream signaling was observed in all samples analyzed (n = 11). Based on the findings, the small-molecule EGFR/ErbB2 kinase inhibitor lapatinib was selected for evaluation of target inhibition and treatment efficacy in our in vitro human schwannoma model. EGFR/ErbB2 targeted therapy with lapatinib inhibited ErbB2 phosphorylation and survivin upregulation, as well as downstream ERK1/2 and AKT activation, resulting in decreased proliferation. We conclude that EGFR family receptor activation is a consistent feature of both sporadic and NF2-related VS. Molecular targeted therapy with lapatinib downregulates survivin and has antiproliferative activity in a preclinical VS model. Based on these findings, a clinical trial with lapatinib for the treatment of VS is currently underway

The review considers management strategies for malignant melanoma metastatic to the larynx. This rare clinical entity lacks clear treatment recommendations because extirpative surgery can often result in severe functional debilitation in patients with limited life expectancy. Here, we report a case of melanoma metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma. The patient was treated with partial laryngectomy and local radiation therapy. The rationale for treatment decisions and for surgical and radiotherapeutic techniques and the associated literature are discussed

In humans, auditory perception reaches maturity over a broad age range, extending through adolescence. Despite this slow maturation, children are considered to be outstanding learners, suggesting that immature perceptual skills might actually be advantageous to improvement on an acoustic task as a result of training (perceptual learning). Previous non-human studies have not employed an identical task when comparing perceptual performance of young and mature subjects, making it difficult to assess learning. Here, we used an identical procedure on juvenile and adult gerbils to examine the perception of amplitude modulation (AM), a stimulus feature that is an important component of most natural sounds. On average, Adult animals could detect smaller fluctuations in amplitude (i.e., smaller modulation depths) than Juveniles, indicating immature perceptual skills in Juveniles. However, the population variance was much greater for Juveniles, a few animals displaying adult-like AM detection. To determine whether immature perceptual skills facilitated learning, we compared naive performance on the AM detection task with the amount of improvement following additional training. The amount of improvement in Adults correlated with naive performance: those with the poorest naive performance improved the most. In contrast, the naive performance of Juveniles did not predict the amount of learning. Those Juveniles with immature AM detection thresholds did not display greater learning than Adults. Furthermore, for several of the Juveniles with adult-like thresholds, AM detection deteriorated with repeated testing. Thus, immature perceptual skills in young animals were not associated with greater learning