Faculty Bibliography

UNLABELLED:Achieving stable and desirable changes in tip rotation (TR) and tip projection (TP) is among the primary goals of modern day rhinoplasty. The tongue-in-groove (TIG) technique is one technique in rhinoplasty used to improve TR and/or TP. Performing TIG endonasally using a permanent suture can be quite cumbersome as the suture needs to be buried under the skin. We describe a variation of TIG technique for endonasal rhinoplasty using a permanent suture buried in small columellar skin incisions. The technique details are described and the postoperative changes in TR and TP are analyzed for the degree of change and longevity. A retrospective review of the preoperative and postoperative photographs of 12 patients treated with the endonasal TIG technique were analyzed for changes in TR and TP. Out of 12 patients, there were seven females (58.3%) and five males (41.7%), with age ranging from 17 to 49 years. The follow-up ranged from 6 months to 53 months, with mean follow-up of 12.1 months. All patients were treated by the senior author in a major New York City hospital. Postoperative changes in TR and TP were compared by measuring the nasolabial angle as well as the Goode ratio using a photo editing software. Using a t-test and a p-value criteria of 0.05, the difference between the preoperative and postoperative TR (p = 0.0069) and TP (p = 0.026) was found to be statistically significant. None of the study patients developed any complications related to the use of a permanent suture material during the follow-up period. Our modified TIG technique is a quick, reliable, and safe option in the surgical armamentarium to achieve desired changes in TR and/or TP. LEVEL OF EVIDENCE/METHODS: 4.

OBJECTIVE:It has been postulated that treatment outcomes are similar between transoral robotic surgery (TORS) and definitive chemoradiation (CRT) for oropharyngeal squamous cell carcinomas (OPSCC). We compared oncologic and quality of life (QOL) outcomes between definitive CRT and definitive TORS. MATERIALS AND METHODS:An observational comparison study was performed on 92 patients treated with TORS±adjuvant therapy and 46 patients treated with definitive CRT between July 2005 and January 2016. The Kaplan Meier method was used for survival analyses, and the Mann-Whitney test was used to compare QOL scores between groups. RESULTS:All patients had T0-T2 and N0-N2 disease, although CRT patients had higher clinical staging (p<0.001). HPV+ disease was present in 79% (n=73) of TORS patients and 91% (n=19) of tested CRT patients. Median follow-up was 22.1months (range: 0.33-83.4). There were no significant differences in locoregional control or overall survival between CRT and TORS groups. Definitive TORS resulted in better saliva-related QOL than definitive CRT at 1, 6, 12, and 24months (p<0.001, p=0.025, p=0.017, p=0.011). Among TORS patients, adjuvant therapy was associated with worse QOL in the saliva domain at 6, 12, and 24months (p<0.001, p<0.001, p=0.007), and taste domain at 6 and 12months (p=0.067, p=0.008). CONCLUSION:Definitive CRT and definitive TORS offer similar rates of locoregional control, overall survival, and disease-free survival in patients with early stage OPSCC. TORS resulted in significantly better short and long-term saliva-related QOL, whereas adjuvant therapy was associated with worse saliva and taste-related QOL compared to TORS alone.

We report an evidence-based management algorithm for benign lymphoepithelial cysts (BLEC) of the parotid glands in HIV patients based on long-term outcomes after radiation therapy. From 1987 to 2013, 72 HIV-positive patients with BLEC of the parotid glands treated at our institutions were identified and their medical records were reviewed and analyzed. The primary endpoint of our study was to determine a dose response in HIV patients with BLEC. In group A (≤18 Gy), which received a median dose of 10 Gy (8-18), overall response (OvR), complete response (CR), partial response (PR), and local failure (LF) was experienced by 7, 7, 0, and 93 %, respectively. In group B (≥22.5 Gy), which received a median dose of 24 Gy (22.5-30), OvR, CR, PR, and LF was experienced by 88, 65, 23, and 12 %. Logistic regression revealed that higher dose (≥22.5 Gy) predicted for cosmetic control (p = 0.0003). Multiple regression analysis revealed higher dose predicted for cosmetic control (p = 0.0001) after adjusting for confounding variables (age, gender, race, HAART use, BLEC duration, and fractionation size). No patients in either group experienced RTOG grade ≥3 toxicities. A radiation dose of 24 Gy delivered in 12-16 fractions of 1.5-2 Gy per fraction provides long-term cosmetic control in HIV-positive patients with BLEC of the parotid glands.

OBJECTIVE: Optic gliomas are characterized as pilocytic astrocytoma (PA) or pilomyxoid astrocytoma (PMXA). Prominent chondroid myxoid matrix is typical of PMXA but not PA. We investigated the composition of myxoid matrix and its role in vasculariztion of optic gliomas. MATERIAL-METHODS: We reviewed clinicopathological data of 120 patients with optic glioma diagnosed at NYU Langone Medical Center from 1996 to 2014.We analyzed microvascular density (MVD), perfusion, hypoxia and proliferation by immunohistochemistry and ultrastructural features by electron microscopy. Liquid chromatography-mass spectrometry (LC-MS) was performed to identify components of the myxoid matrix in PMXA. RESULTS: PMXA showed significantly lowerMVD by CD34 (8.1 vs 14.5, pvalue < 0.002) and Erg (7 vs. 13.6, p-value 0.003) than PA, however GLUT-1 showed equal distribution. Electron microscopy showed that PMXA contains both regular blood vessels with endothelial lining and channels completely lacking endothelia and smooth muscle. LC-MS stratified optic gliomas into three distinct groups. We identified 5389 proteins of which 188 were differentially expressed in the three groups (p < 0.05, Benjamini-Hochberg adjustment). Between PAand PMXA,most of differentially expressed proteins (146/188) displayed a positive fold change (increasing in PMXA relative to PA), and a minority (42/188) showed a negative fold change. Abundant extracellular matrix proteins were a chondroitin sulfate proteoglycan versican (VCAN 3.7-fold increase Q=0.000463) and its paralog vertebrate Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1, 22-fold increase from the PA to the PMXA group Q=4.60x10-7). CONCLUSIONS: Optic gliomas develop endothelium-independent channels evocative invertebrate blood supply. The myxoid matrix is composed of VCAN and linking paralog HAPLN1. Targeting the myxoid matrix may provide novel avenues for therapy of optic gliomas and PMA

BACKGROUND:The purpose of this study was to characterize oncologic outcomes in early (T1-T2, N0) and intermediate (T1-T2, N1) oropharyngeal squamous cell carcinoma (SCC) after surgery. METHODS:Patients with oropharyngeal SCC treated with surgery were identified from 2 academic institutions. RESULTS:Of 188 patients, 143 met the inclusion criteria. Eighty-six (60%) had T1 to T2 N0 and 57 (40%) had T1 to T2 N1 disease. Sixty-five patients (45%) underwent a robotic-assisted resection, whereas the remaining had transoral (n = 60; 42%), mandible-splitting (n = 11; 8%), or transhyoid approaches (n = 7; 5%). Human papillomavirus (HPV) status was known for 97 patients (68%), and 54 (55%) were HPV positive. Three-year recurrence-free survival (RFS) was 82% (95% confidence interval [CI] = 0.75-0.89). Since 2008, HPV infection was protective of recurrence (log-rank p = .0334). A single node did not increase the risk of recurrence (p = .467) or chance of a second primary (p = .175). CONCLUSION:Complete surgical resection is effective therapy for early and intermediate oropharyngeal SCC. HPV-negative patients were at increased risk for locoregional recurrence or second primary disease. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1471, 2016.

OBJECTIVES/HYPOTHESIS:To establish the prevalence of abnormal vestibular test findings in children with enlarged vestibular aqueduct (EVA) and determine if these findings correlate with clinical symptoms, radiographic findings (EVA size and laterality), audiometric findings, and genetic testing in these patients. STUDY DESIGN:Prospective cohort. METHODS:Patients 3 to 12 years of age with hearing loss and imaging findings consistent with EVA treated at our tertiary care institution were sequentially enrolled from 2009 to 2011. The following six outcome measurements were analyzed: audiometric findings, EVA laterality, temporal bone measurements, genetic testing, vestibular testing (cervical-evoked myogenic potentials, posturography, rotational chair, and calorics), and vestibular symptoms. RESULTS:Twenty-seven patients with EVA (mean age 9.2 years, 48% female) were enrolled in and completed the study. Vertigo was reported in six patients. Twenty-four of 27 (89%) had at least one abnormal vestibular test result. Midpoint and operculum size correlated with directional preponderance (P = .042 and P = .032, respectively). Also, high-frequency pure tone average (HFPTA) correlated with unilateral weakness (P = .002). Walking at a later age correlated with abnormal posturography results. There was no correlation between EVA laterality and vestibular test findings. CONCLUSION:We found a high rate of vestibular pathology in children with EVA; however, the prevalence of abnormal vestibular test findings in this patient population was not correlated with vestibular symptoms. Enlarged vestibular aqueduct size, HFPTA, and walking at a later age were correlated with abnormal vestibular test findings. In view of these results, it may be prudent to consider vestibular testing in children with these clinical characteristics. LEVEL OF EVIDENCE:2b. Laryngoscope, 126:2344-2350, 2016.

For bilateral cochlear implant (CI) patients, electrodes that receive the same frequency allocation often stimulate locations in the left and right ear that do not yield the same perceived pitch, resulting in a pitch mismatch. This pitch mismatch may be related to degraded binaural abilities. Pitch mismatches have been found for some bilateral CI users and the goal of this study was to determine whether pitch mismatches are prevalent in bilateral CI patients, including those with extensive experience with bilateral CIs. To investigate this possibility, pitch matching was conducted with 16 bilateral CI patients. For 14 of the 16 participants, there was a significant difference between those electrodes in the left and right ear that yielded the same pitch and those that received the same frequency allocation in the participant's clinical map. The results suggest that pitch mismatches are prevalent with bilateral CI users. The results also indicated that pitch mismatches persist even with extended bilateral CI experience. Such mismatches may reduce the benefits patients receive from bilateral CIs.

Comparison of tumors from The Cancer Genome Atlas (TCGA) reveals that head and neck squamous cell carcinomas (HNSCC) harbor the most frequent genomic amplifications of Fas-associated death domain (FADD), with or without Baculovirus inhibitor of apoptosis repeat containing BIRC2 (cIAP1), affecting about 30% of patients in association with worse prognosis. Here, we identified HNSCC cell lines harboring FADD/BIRC2 amplifications and overexpression by exome sequencing, RT-PCR, and Western blotting. In vitro, FADD or BIRC2 siRNA knockdown inhibited HNSCC displaying amplification and increased expression of these genes, supporting their functional importance in promoting proliferation. Birinapant, a novel SMAC mimetic, sensitized multiple HNSCC lines to cell death by agonists TNFα or TRAIL and inhibited cIAP1>XIAP>IAP2. Combination of birinapant and TNFα induced sub-G0 DNA fragmentation in sensitive lines and birinapant alone also induced significant G2-M cell-cycle arrest and cell death in UM-SCC-46 cells. Gene transfer and expression of FADD sensitized resistant UM-SCC-38 cells lacking FADD amplification to birinapant and TNFα, supporting a role for FADD in sensitization to IAP inhibitor and death ligands. HNSCC varied in mechanisms of cell death, as indicated by reversal by inhibitors or protein markers of caspase-dependent apoptosis and/or RIPK1/MLKL-mediated necroptosis. In vivo, birinapant inhibited tumor growth and enhanced radiation-induced TNFα, tumor responses, and host survival in UM-SCC-46 and -11B xenograft models displaying amplification and overexpression of FADD+/- BIRC2 These findings suggest that combination of SMAC mimetics such as birinapant plus radiation may be particularly active in HNSCC, which harbor frequent FADD/BIRC2 genomic alterations. Cancer Res; 76(18); 5442-54. ©2016 AACR.

IMPORTANCE:The elective management of no clinical or radiologic evidence of lymph node metastasis in the neck (cN0) in early stage T1-T2 oral tongue squamous cell carcinoma (OTSCC) has been the subject of much debate during the past 3 decades and continues to be controversial. OBJECTIVE:To systematically review the literature and carry out a meta-analysis of studies that compared elective neck dissection (END) with observation in patients with early-stage T1-T2 OTSCC and cN0 neck. DATA SOURCES:The MEDLINE, Scopus, Google scholar, and Cochrane databases were systematically searched for articles published between January 1, 1970, and June 1, 2015. Search terms used were squamous cell carcinoma, oral tongue, mobile tongue, T1, T2, early stage, elective neck dissection, no neck treatment, observation, wait and watch, node-negative neck, and N0 neck. STUDY SELECTION:Controlled clinical trials, prospective and retrospective cohorts, case-control studies, and case series that compared END with observation in patients with early-stage T1-T2 OTSCC who had no clinical or radiologic evidence of lymph node metastasis to the neck were eligible for inclusion in this meta-analysis. All patients included had a histopathologic diagnosis of SCC and at least 6 months of follow-up. Regional (neck) nodal recurrence, overall survival (OS), and disease-specific survival (DSS) were tested. DATA EXTRACTION AND SYNTHESIS:Four researchers independently extracted information on population characteristics, outcomes of interest, and study design. Discrepancies were resolved by consensus. Fixed effects were used to determine hazard ratios (HRs) and odds ratio (ORs) were used for studies including samples without substantial heterogeneity; random effects were evaluated for samples with significant heterogeneity. RESULTS:A total of 20 retrospective and 3 prospective randomized studies that met the inclusion criteria, with a total of 3244 patients, were included in the meta-analysis The results showed that END significantly reduced risk of regional recurrence (random-effects model: OR, 0.32; 95% CI, 0.22-0.46; P < .001) and improved DSS (fixed-effects model: HR, 0.49; 95% CI, 0.33-0.72; P < .001) compared with management by observation. However, END did not significantly improve OS (random-effects model: HR, 0.71; 95% CI, 0.41-1.22; P = .21). CONCLUSIONS AND RELEVANCE:The findings of this systematic review and meta-analysis indicate that END can significantly reduce the rate of regional nodal recurrence and improve DSS in patients with cT1T2N0 OTSCC.