Faculty Bibliography
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school:SOM
Department/Unit:Otolaryngology
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7772
Intraoperative Transcranial Motor-Evoked Potential Monitoring of the Facial Nerve during Cerebellopontine Angle Tumor Resection
Objective To determine whether transcranial motor-evoked potential (TCMEP) monitoring of the facial nerve (FN) during cerebellopontine angle (CPA) tumor resection can predict both immediate and long-term postoperative FN function. Design Retrospective review. Setting Tertiary referral center. Main Outcome Measures DeltaTCMEP (final-initial) and immediate and long-term facial nerve function using House Brackmann (HB) rating scale. Results Intraoperative TCMEP data and immediate and follow-up FN outcome are reported for 52 patients undergoing CPA tumor resection. Patients with unsatisfactory facial outcome (HB >2) at follow-up had an average deltaTCMEP of 57 V, whereas those with HB I or II had a mean deltaTCMEP of 0.04 V (t = -2.6, p < 0.05.) Intraoperative deltaTCMEP did not differ significantly between groups with satisfactory (HB I, II) and unsatisfactory (HB > 2) facial function in the immediate postoperative period. Conclusion Intraoperative TCMEP of the facial nerve can be a valuable adjunct to conventional facial nerve electromyography during resection of tumors at the CPA. Intraoperative deltaTCMEP >57 V may be worrisome for long-term recovery of satisfactory facial nerve function.
PMCID:3578638
PMID: 24083121
ISSN: 2193-634x
CID: 563692
Selective Neck Dissection in Node-Positive Squamous Cell Carcinoma of the Head and Neck
Objective. The optimal type of neck dissection in head and neck squamous cell carcinoma (SCC) with clinical cervical metastases has not been determined. The following study was performed to determine the rate of regional control with selective neck dissection (SND) in these patients.Study Design. Case series with planned data collection.Settings. Single institution, cancer center.Methods and Subjects. Patients with cervical lymph node metastases from mucosal cancers of the head and neck who were treated with SND from 2000 to 2010 were selected. Demographics, tumor characteristics, extent of neck dissection, adjuvant treatments, locoregional control, and survival were recorded. Recurrence in the neck and disease-specific survival (DSS) were primary and secondary end points.Results. One hundred eight patients underwent SND. Sixty-nine (64%) were male. Median age was 62 (20-89) years. The most common primary site was the oral cavity (71.3%). Ninety-five (88%) received adjuvant treatment. Median follow-up was 21 months. Six patients (5.5%) had isolated recurrence in the dissected neck. Patients with N2C disease had poorer neck recurrence-free survival. At the end of study, 64 (59.3%) patients had no evidence of disease, and 23 (21.3%) had died of disease. Two-year DSS was 76.9%. Number of positive nodes (P = .026) and positive surgical margins (P = .001), among others, were predictors of poorer DSS.Conclusion. In a highly selected group of patients with cervical lymph node metastases from head and neck SCC, selective neck dissection is effective in controlling the disease in the neck when performed in the setting of a multimodality treatment, including adjuvant radiotherapy or radiochemotherapy.
PMCID:5787853
PMID: 22517013
ISSN: 0194-5998
CID: 177313
Safety and Efficacy of Anakinra in Patients with Deficiency of Interleukin-1 Receptor Antagonist [Meeting Abstract]
ISI:000309748304308
ISSN: 0004-3591
CID: 1529112
Image-guided surgical navigation in otology
OBJECTIVES/HYPOTHESIS: To evaluate the efficacy of image-guided surgical navigation (IGSN) in otologic surgery and establish practice guidelines. STUDY DESIGN: Prospective study. METHODS: Between January 2003 and January 2010, all patients requiring complicated surgery for chronic otitis media, glomus jugulare, atresia, cerebrospinal fluid leak with or without encephalocele, and cholesterol granuloma of the petrous apex were offered IGSN. The accuracy of IGSN relative to pertinent pathology and 11 anatomic landmarks was established. Additionally IGSN-related operative time, complications, and surgical outcome were recorded. RESULTS: In the study period there were 820 otologic procedures, among 94 patients (96 ears) with disease meeting proposed criteria. Thirteen patients (15 procedures) consented to the use of IGSN. All patients had a minimum 6 months of follow-up. The average additional operative time required was 36.7 minutes. The mean accuracy error was 1.1 mm laterally at the tragus but decreased to 0.8 mm medially at the level of the oval window. The mean accuracy of IGSN was within 1 mm in 10 of the 11 targeted surgical anatomic landmarks. CONCLUSIONS: Interactive image-guided surgical navigation during complex otologic surgery may improve surgical outcome and decrease morbidity by providing an accurate real-time display of surgical instrumentation relative to patient anatomy and pathology. In select cases, the extra cost of imaging immediately prior to surgery and extra operating room time may be compensated by enhancing the ability to distinguish distorted anatomy relative to disease, potentially improving surgical outcome. IGSN, although useful, does not replace surgical expertise and experience.
PMID: 22961537
ISSN: 0023-852x
CID: 178842
A single supratherapeutic dose of ridaforolimus does not prolong the QTc interval in patients with advanced cancer
PURPOSE: This dedicated QTc study was designed to evaluate the effect of the mammalian target of rapamycin inhibitor, ridaforolimus, on the QTc interval in patients with advanced malignancies. METHODS: We conducted a fixed-sequence, single-blind, placebo-controlled study. Patients (n = 23) received placebo on day 1 and a single 100-mg oral dose of ridaforolimus on day 2 in the fasted state. Holter electrocardiogram (ECG) monitoring was performed for 24 h after each treatment, and blood ridaforolimus concentrations were measured for 24 h after dosing. The ECGs were interpreted in a blinded fashion, and the QT interval was corrected using Fridericia's formula (QTcF). After a washout of at least 5 days, 22 patients went on to receive a therapeutic regimen of ridaforolimus (40 mg orally once daily for 5 days per week). RESULTS: The upper limit of the two-sided 90 % confidence interval for the placebo-adjusted mean change from baseline in QTcF was <10 ms at each time point. No patient had a QTcF change from baseline >30 ms or QTcF interval >480 ms. Geometric mean exposure to ridaforolimus after the single 100-mg dose was comparable to previous experience with the therapeutic regimen. There appeared to be no clear relationship between individual QTcF change from baseline and ridaforolimus blood concentrations. Ridaforolimus was generally well tolerated, with adverse events consistent with prior studies. CONCLUSIONS: Administration of the single 100-mg dose of ridaforolimus did not cause a clinically meaningful prolongation of QTcF, suggesting that patients treated with ridaforolimus have a low likelihood of delayed ventricular repolarization.
PMCID:3456920
PMID: 22878520
ISSN: 1432-0843
CID: 2166332
Spontaneous intracranial hypotension presenting with severe sensorineural hearing loss and headache
PMCID:3600858
PMID: 22722142
ISSN: 1531-7129
CID: 178049
Prevalence of jugular bulb abnormalities and resultant inner ear dehiscence: a histopathologic and radiologic study
Objective Jugular bulb abnormalities (JBA), including high-riding jugular bulb (HRJB) and jugular bulb diverticulum (JBD), can erode into the inner ear. In this study, the authors investigate the prevalence and consequences of JBA and their erosion into inner ear structures using temporal bone histopathology and computed tomography (CT). Study Design Cross-sectional study of temporal bone histopathology and radiology. Setting Academic medical center. Subjects and Methods In total, 1579 temporal bone specimens and 100 CT of the temporal bones (200 ears) were examined for JBA and any associated dehiscence of inner ear structures. Temporal bone specimens were examined for histological consequences of inner ear erosion. Jugular bulb dimensions were measured on axial CT scans and compared across groups. Accompanying demographic and clinical information were reviewed. Results High jugular bulbs were noted in 8.2% (130/1579) of temporal bone specimens and in 8.5% (17/200) of temporal bone CT. The prevalence of JBA increases during the first 4 decades of life and stabilizes thereafter. High-riding jugular bulbs eroded inner ear structures such as the vestibular aqueduct, vertical facial nerve, or posterior semicircular canal in 2.8% (44/1579) of cases histologically and 1.5% (3/200) radiologically. In most, jugular bulb-mediated inner ear dehiscence was clinically and radiologically silent. Conclusion Jugular bulb abnormalities are common. They are present in 10% to 15% individuals and are primarily acquired by the fourth decade of life. In 1% to 3% of cases, the HRJB erodes into the inner ear and most frequently involves the vestibular aqueduct.
PMID: 22619257
ISSN: 0194-5998
CID: 178829
Sialoendoscopy for the treatment of pediatric salivary gland disorders
OBJECTIVE:To show that sialoendoscopy is both a safe and effective alternative to traditional treatments for juvenile recurrent parotitis and sialolithiasis. DESIGN/METHODS:Retrospective medical chart review. SETTING/METHODS:Two major pediatric tertiary care centers. PATIENTS/METHODS:Eighteen pediatric patients. INTERVENTIONS/METHODS:A total of 33 sialendoscopic procedures on 27 glands. MAIN OUTCOME MEASURES/METHODS:Indications for surgery, age at onset of symptoms, age at procedure, sex, intraoperative findings, complications, recurrences, need for additional procedures, and follow-up interval. RESULTS:Juvenile recurrent parotitis was the most common indication for sialendoscopy (12 of 18) followed by sialolithiasis (4 of 18). Ten of 12 patients with juvenile recurrent parotitis were asymptomatic after 1 or 2 sialendoscopies (8 patients and 2 patients, respectively). There were 6 minor complications. Three patients ultimately required gland excision for disease management. CONCLUSION/CONCLUSIONS:Sialoendscopy is safe and effective as a treatment for pediatric salivary gland disorders.
PMID: 23069821
ISSN: 1538-361x
CID: 5481092
Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis
BACKGROUND:BG-12 (dimethyl fumarate) is in development as an oral treatment for relapsing-remitting multiple sclerosis, which is commonly treated with parenteral agents (interferon or glatiramer acetate). METHODS:In this phase 3, randomized study, we investigated the efficacy and safety of oral BG-12, at a dose of 240 mg two or three times daily, as compared with placebo in patients with relapsing-remitting multiple sclerosis. An active agent, glatiramer acetate, was also included as a reference comparator. The primary end point was the annualized relapse rate over a period of 2 years. The study was not designed to test the superiority or noninferiority of BG-12 versus glatiramer acetate. RESULTS:At 2 years, the annualized relapse rate was significantly lower with twice-daily BG-12 (0.22), thrice-daily BG-12 (0.20), and glatiramer acetate (0.29) than with placebo (0.40) (relative reductions: twice-daily BG-12, 44%, P<0.001; thrice-daily BG-12, 51%, P<0.001; glatiramer acetate, 29%, P=0.01). Reductions in disability progression with twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate versus placebo (21%, 24%, and 7%, respectively) were not significant. As compared with placebo, twice-daily BG-12, thrice-daily BG-12, and glatiramer acetate significantly reduced the numbers of new or enlarging T(2)-weighted hyperintense lesions (all P<0.001) and new T(1)-weighted hypointense lesions (P<0.001, P<0.001, and P=0.002, respectively). In post hoc comparisons of BG-12 versus glatiramer acetate, differences were not significant except for the annualized relapse rate (thrice-daily BG-12), new or enlarging T(2)-weighted hyperintense lesions (both BG-12 doses), and new T(1)-weighted hypointense lesions (thrice-daily BG-12) (nominal P<0.05 for each comparison). Adverse events occurring at a higher incidence with an active treatment than with placebo included flushing and gastrointestinal events (with BG-12) and injection-related events (with glatiramer acetate). There were no malignant neoplasms or opportunistic infections reported with BG-12. Lymphocyte counts decreased with BG-12. CONCLUSIONS:In patients with relapsing-remitting multiple sclerosis, BG-12 (at both doses) and glatiramer acetate significantly reduced relapse rates and improved neuroradiologic outcomes relative to placebo. (Funded by Biogen Idec; CONFIRM ClinicalTrials.gov number, NCT00451451.).
PMID: 22992072
ISSN: 1533-4406
CID: 5347972
Transforming fusions of FGFR and TACC genes in human glioblastoma
The brain tumor glioblastoma multiforme (GBM) is among the most lethal forms of human cancer. Here, we report that a small subset of GBMs (3.1%; 3 of 97 tumors examined) harbors oncogenic chromosomal translocations that fuse in-frame the tyrosine kinase coding domains of fibroblast growth factor receptor (FGFR) genes (FGFR1 or FGFR3) to the transforming acidic coiled-coil (TACC) coding domains of TACC1 or TACC3, respectively. The FGFR-TACC fusion protein displays oncogenic activity when introduced into astrocytes or stereotactically transduced in the mouse brain. The fusion protein, which localizes to mitotic spindle poles, has constitutive kinase activity and induces mitotic and chromosomal segregation defects and triggers aneuploidy. Inhibition of FGFR kinase corrects the aneuploidy, and oral administration of an FGFR inhibitor prolongs survival of mice harboring intracranial FGFR3-TACC3-initiated glioma. FGFR-TACC fusions could potentially identify a subset of GBM patients who would benefit from targeted FGFR kinase inhibition.
PMCID:3677224
PMID: 22837387
ISSN: 0036-8075
CID: 178308
