Faculty Bibliography

OBJECTIVE AND IMPORTANCE: In rare cases, posterior fossa meningiomas can involve the endolymphatic sac. Such involvement can result in endolymphatic hydrops and a constellation of symptoms suggestive of Meniere's disease. The diagnosis and management of patients with these tumors is discussed. CLINICAL PRESENTATION: Three patients, each of whom presented with symptoms consistent with Meniere's disease, were found to have posterior fossa meningiomas limited to the dura overlying the endolymphatic sac. INTERVENTION: All 3 patients were diagnosed by magnetic resonance imaging and underwent complete surgical resection. In all cases, the symptoms resolved after tumor removal. CONCLUSION: Clinicians should have a degree of suspicion of posterior fossa meningioma when patients present with symptoms suggestive of Meniere's disease. Failure to do so may result in delayed diagnosis or worse outcomes for an otherwise treatable tumor

OBJECTIVES: To date, numerous studies have compared functional outcomes between stereotactic radiosurgery (SRS) and microsurgery (MS) in the treatment of vestibular schwannomas (VS). However, most of them involve tumors of difference sizes, radiation dosages, and surgical approaches. Few have systematically compared issues of dysequilibrium. By studying only patients with small tumors and no hearing, we sought to minimize confounding variables. STUDY DESIGN: A retrospective chart review and telephone questionnaire. METHODS: From 1998-2006, 31 patients with small (<1.5 cm) VS and nonserviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class C or D) were treated at our institution. Twenty-two were available for follow-up and telephone questionnaire, including the University of California Los Angeles Dizziness Questionnaire (UCLA-DQ). Twelve underwent SRS and 10 underwent MS. All MS patients underwent the translabyrinthine approach to their tumors. Outcomes measurements included tumor control, facial nerve function, tinnitus, trigeminal function, and imbalance. RESULTS: Patients undergoing SRS had comparable rates of tumor control, facial nerve function, tinnitus, and trigeminal function to MS patients. However, SRS did result in statistically significantly worse long-term imbalance when compared with MS patients. Detailed comparisons of the two modalities are made. CONCLUSIONS: In our study population, patients with small tumors and no serviceable hearing, these data suggest that MS results in comparable minimal morbidity with SRS, though posttreatment dysequilibrium is significantly decreased. While the authors recommend translabyrinthine resection of small VS with no hearing in patients able to tolerate surgery, the need for further prospective investigation is clear

OBJECTIVE: To compare quality of life (QOL) of patients with advanced laryngeal cancers treated by total laryngectomy with those who received concurrent chemoradiotherapy. STUDY DESIGN: This is a cross-sectional study of the patients treated in our institution who have completed one year of follow-up and were disease-free at the time of evaluation. SUBJECTS AND METHOD: Forty patients treated for advanced cancer of the larynx (stage III/IV), either by concurrent chemoradiation (11) or total laryngectomy and postoperative radiation (29), have been included in this study. The Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) version 4 questionnaire was used. RESULTS: Total scores for overall QOL are equal in both treatment groups (P = 0.69). Scores for individual components are similar in both treatment groups. However, dryness of mouth is significantly worse in the chemoradiotherapy group (P = 0.01) and ability to communicate with others is poorer in the laryngectomy group (P = 0.03). CONCLUSION: Long-term overall QOL remains similar in all the patients treated for advanced carcinoma of the larynx irrespective of treatment modality.

OBJECTIVE: It is unclear whether all snoring patients require polysomnography, and there are no highly sensitive clinical predictors of sleep apnea. Our objective was to develop a simple clinical screening test for OSA in snoring patients. STUDY DESIGN: Prospective, IRB-approved study at a university sleep disorders center. SUBJECTS AND METHODS: In 211 patients undergoing polysomnography, snoring severity, Epworth sleepiness scale, body mass index, demographic, and sleep study data were collected. Receiver operating characteristic (ROC) analysis and Pearson correlation were used to develop a sensitive screening test for OSA. RESULTS: Snoring severity score (SSS) and BMI were the two most accurate predictors of OSA on the ROC curve. A bipartite threshold of SSS = 4 or BMI = 26 carried sensitivity of 97.4%, specificity of 40%, positive predictive value of 82.3%, and negative predictive value of 84.2% for moderate/severe OSA. Patients at high risk were those with BMI > or =32 (89% PPV) or SSS > or =7 (92% PPV). CONCLUSIONS: The statistic most predictive of OSA was snoring severity. Combining this with BMI yielded a highly sensitive screening test for moderate/severe OSA. This clinical assessment may be useful in risk-stratifying patients for polysomnography and therapy, facilitating deferred work-up in low-risk patients and expedited therapy in high-risk patients

OBJECTIVE: Obstructive sleep apnea events are more common in REM sleep, although there is no relationship between sleep phase and pharyngeal airway status. We studied the patency of the nasal airway during REM and non-REM sleep with the use of acoustic rhinometry. METHODS: Serial acoustic rhinometric assessment of nasal cross-sectional area was performed in 10 subjects, before sleep and during REM and non-REM sleep. All measurements were standardized to a decongested baseline with mean congestion factor (MCF). RESULTS: MCF in the seated position was 10.6% (+/-3.7) and increased with supine positioning to 16.2% (+/-2.3). In REM sleep, MCF was highest, at 22.3% (+/-1.7). In non-REM sleep, MCF was lowest, at 2.3% (+/-3.1). All interstage comparisons were statistically significant on repeated measures ANOVA (P < 0.05). CONCLUSION: REM sleep is characterized by significant nasal congestion; non-REM sleep, by profound decongestion. This phenomenon may be attributable to REM-dependent variation in cerebral blood flow that affects nasal congestion via the internal carotid system. REM-induced nasal congestion, an indirect effect of augmented cerebral perfusion, may contribute to the higher frequency of obstructive events in REM sleep

BACKGROUND: Plate osteosynthesis is a widely used technique in head and neck reconstructive surgery. The objective of this study was to determine whether postoperative chemoradiotherapy, which was recently introduced for high-risk head and neck cancer, affects plate and osteosynthesis related complications. METHODS: Fifty-two consecutive patients, who had undergone plate osteosynthesis for mandibular reconstruction between October 2003 and September 2006, were included in the study. The patients were divided into 3 groups: (1) surgery alone (n = 19), (2) surgery with postoperative radiotherapy (n = 14), and (3) surgery with concurrent chemoradiotherapy (n = 19). Outcome measures included any bone or plate related complications. RESULTS: The plate and osteosynthesis related complications occurred in 10.5% of patients in surgery-alone group, 28.6% in surgery with postoperative radiation group, and 63.2% in surgery with postoperative concurrent chemoradiotherapy group. The differences in the complication rates among these 3 groups were statistically significant (p = .003). In univariate analysis, postoperative radiation (p = .007) and concurrent chemotherapy (p = .003) were found to be significantly associated with complications. In multivariate analysis, only concurrent chemotherapy was found to be statistically significant (p = .002) with odds ratio of 7.72. CONCLUSION: Postoperative concurrent chemoradiotherapy significantly increases plate and osteosynthesis related complications in oral cancer.

OBJECTIVES: This study capitalizes on the unique molecular and developmental similarities between the auditory organs of Drosophila and mammals, to investigate genes implicated in human syndromic and nonsyndromic hearing loss in a genetically tractable experimental animal model, the fruit fly Drosophila. METHODS: The Drosophila counterparts of 3 human deafness genes (DIAPH1/DFNA1, ESPN/DFNB36, and TMHS/DF-NB67) were identified by sequence similarity. An electrophysiological assay was used to record sound-evoked potentials in response to an acoustic stimulus, the Drosophila courtship song. RESULTS: Flies with mutations affecting the diaphanous,forked, and CG12026/TMHS genes displayed significant reductions in the amplitude of sound-evoked potentials compared to wild-type flies (p < 0.05 to p < 0.005). The mean responses were reduced from approximately 500 to 600 microV in wild-type flies to approximately 100 to 300 microV in most mutant flies. CONCLUSIONS: The identification of significant auditory dysfunction in Drosophila orthologs of human deafness genes will facilitate exploration of the molecular biochemistry of auditory mechanosensation. This may eventually allow for novel diagnostic and therapeutic approaches to human hereditary hearing loss

The clinical course of patients with Philadelphia chromosome negative myeloproliferative disorder is frequently complicated by thrombotic events. Post-natal vasculogenesis has been proposed to play a critical role in angiogenesis by acting through a hierarchy of endothelial progenitor cells. Some endothelial progenitor cells have been shown to share a number of features associated with monocytes while other more primitive progenitor cells produce endothelial cells in vitro exclusively. The cells which share features of monocytes and endothelial cells have been termed angiogenic monocytes. Reduced levels of angiogenic monocyte progenitor cells have been reported to be predictive of atherosclerotic disease progression. Angiogenic monocyte progenitor cells were assayed in vitro from the peripheral blood mononuclear cells of myeloproliferative disorder patients. Angiogenic monocyte colonies were plucked and analyzed for endothelial cells and hematopoietic cell markers, JAK2V617F and their ability to incorporate into vascular endothelium following their transplantation into non-obese diabetic, severe combine immunodeficient mice. Myeloproliferative disorder angiogenic monocyte colonies that were detected were uniformly JAK2V617F positive and produced cells that expressed phenotypic markers characteristic of both monocytes and endothelial cells. Reduced numbers of angiogenic monocyte colonies were present in the blood of myeloproliferative disorder patients with a high JAK2V617F burden (>50%), (p<0.01). Transplanted angiogenic monocytes were able to contribute to the vascular endothelium of non-obese diabetic, severe combine immunodeficient mice. These studies suggest that reduced numbers of circulating angiogenic monocyte progenitors contribute to the propensity to develop thrombotic complications in myeloproliferative disorder patients.

INTRODUCTION: Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has shown promise in the treatment of patients with recurrent high-grade glioma. The purpose of this study is to test the feasibility of using bevacizumab with chemoradiation in the primary management of high-grade glioma. METHODS AND MATERIALS: Fifteen patients with high-grade glioma were treated with involved field radiation therapy to a dose of 59.4 Gy at 1.8 Gy/fraction with bevacizumab 10 mg/kg on Days 14 and 28 and temozolomide 75 mg/m(2). Subsequently, bevacizumab 10 mg/kg was continued every 2 weeks with temozolomide 150 mg/m(2) for 12 months. Changes in relative cerebral blood volume, perfusion-permeability index, and tumor volume measurement were measured to assess the therapeutic response. Immunohistochemistry for phosphorylated VEGF receptor 2 (pVEGFR2) was performed. RESULTS: Thirteen patients (86.6%) completed the planned bevacizumab and chemoradiation therapy. Four Grade III/IV nonhematologic toxicities were seen. Radiographic responses were noted in 13 of 14 assessable patients (92.8%). The pVEGFR2 staining was seen in 7 of 8 patients (87.5%) at the time of initial diagnosis. Six patients have experienced relapse, 3 at the primary site and 3 as diffuse disease. One patient showed loss of pVEGFR2 expression at relapse. One-year progression-free survival and overall survival rates were 59.3% and 86.7%, respectively. CONCLUSION: Use of antiangiogenic therapy with radiation and temozolomide in the primary management of high-grade glioma is feasible. Perfusion imaging with relative cerebral blood volume, perfusion-permeability index, and pVEGFR2 expression may be used as a potential predictor of therapeutic response. Toxicities and patterns of relapse need to be monitored closely