Faculty Bibliography

OBJECTIVE:Analysis of the efficacy of sphenopalatine artery (SPA) and internal maxillary artery (IMAX) ligation within the pterygopalatine fossa to control posterior epistaxis. METHODS:Demographic and clinical data were collected in sixty-two consecutive patients who had SPA/IMAX ligation surgery. Clinical outcomes such as re-bleed rates and complications were acquired. RESULTS:A total of 62 patients were studied. Thirty-eight percent of patients had previously undergone silver nitrate nasal cautery for epistaxis. Nine patients had undergone previous attempt of SPA procedure or embolization in other services. Two patients returned to the operating room for anterior ethmoid ligation. There was one mortality within 30 days of surgery. Follow up ranged from 3 months to 56 months (median= 28 months). CONCLUSIONS:Dual SPA and IMAX ligation is effective in the control of difficult epistaxis cases, even in those patients with prior surgical intervention.

Program cell death ligand-1 (PD-L1) membranous expression on >5% tumor cells (PD-L1 positive tumors) is an unfavorable prognostic marker in many solid tumors. We previously showed that approximately 40% of neurofibromatosis type 2 (NF2) meningiomas are PD-L1 positive tumors. However, due to the invasive nature of biopsies, collection of tumor tissue is not always feasible. Thus, a non-invasive alternative is needed to evaluate the status of tumor growth and confirm PD-L1 positive tumors before the consideration of immunotherapy. It has recently been revealed that expression of PD-L1 on tumor associated macrophages is also a strong prognostic indicator. We retrieved formalin-fixed paraffin-embedded (FFPE) tissue from 10 NF2 meningioma cases to identify PD-L1 expression on macrophages and/or monocytes. We found that 3 out of 4 PD-L1 positive tumors were associated with expression of PDL-1 on CD68 (-) monocyte-like cells located in the peri-and intravascular lumens. These cells were only observed in 1 out of 6 PD-L1 negative tumors. Compared to others, tumors with PD-L1 expression on monocyte-like cells presented a higher Ki-67 proliferative index that was above 10%. Our results suggest that PD-L1 positive circulating CD68 (-) monocyte-like cells are correlated with tumor cell PD-L1 expression and progression in NF2 meningiomas

OBJECTIVES/OBJECTIVE:To compare the diagnostic performance of the Hum Test against the Weber Test using pure tone audiometry (PTA) as the "gold standard" comparator. METHODS:29 participants with normal hearing of ages 18 to 35 without any history of hearing abnormalities or otologic conditions were enrolled. Subjects underwent three tests (Hum Test, Weber Test, and PTA) across two conditions: with an ear plug in one ear (side randomized) and without ear plugs. RESULTS:When examining the ability of the Hum Test to detect simulated conductive hearing loss (CHL), the test had a sensitivity of 89.7% and specificity of 100% with high pitched humming and 93.1% and 100%, respectively, with low pitched humming. The Weber Test had a sensitivity and specificity of 96.6% and 100%, respectively. McNemar's test demonstrated agreement between the Hum Test, performed with either high pitched ( P = .32) or low pitched ( P = .56) humming, and the Weber Test. Receiver operating characteristic (ROC) curves for the Hum Test (both high and low pitched) and Weber test were compared and demonstrated no statistically significant difference. CONCLUSION/CONCLUSIONS:The Hum Test is comparable to the Weber Test with regards to its sensitivity, specificity, and diagnostic accuracy in assessing new onset unilateral CHL in previously normal hearing subjects.

OBJECTIVE:Technological change is leading to an evolution in medical education. The objective of our study was to assess the impact of a medical knowledge app, called PulseQD, on resident education within our otolaryngology-head and neck surgery department at Montefiore Medical Center, Albert Einstein College of Medicine (Bronx, NY). METHODS:A prospective cohort study was conducted within the Department of Otolaryngology-Head and Neck Surgery from July 2016 to June 2017. All faculty attendings and residents were asked to participate in the study and were included. A Web and mobile-based app, PulseQD, that allowed for collaborative learning was implemented. Questionnaires were given at the beginning and end of the academic year. Otolaryngology Training Exam (OTE) scores were collected RESULTS: A total of 20 residents and 13 faculty members participated in the study. Residents used online sources of medical information significantly more often than faculty (90% and 54%, respectively, P = 0.0179). Residents and faculty felt that PulseQD offered a valuable perspective on clinically relevant medical information (P = 0.0003), was a great way to test clinical and medical knowledge (P = 0.0001), and improved the sharing and discussing of medical knowledge (P < 0.0001). There was a statistically significant 5.8% improvement in OTE scores (P = 0.0008) at the end of the academic year. CONCLUSION/CONCLUSIONS:The implementation of a novel mobile app, PulseQD, was well received by residents and faculty in the Department of Otolaryngology-Head and Neck Surgery. Preliminary data suggest that app-based learning may lead to improved performance on knowledge-based assessments. LEVEL OF EVIDENCE/METHODS:NA. Laryngoscope, 2017.

Objectives To investigate the clinical predictors and survival implications of perineural invasion (PNI) in parotid gland malignancies. Study Design Case series with chart review. Setting Tertiary care medical center. Subjects and Methods Patients with parotid gland malignancies treated surgically from 2000 to 2015 were retrospectively identified in the Head and Neck Cancer Registry at a single institution. Data points were extracted from the medical record and original pathology reports. Results In total, 186 patients with parotid gland malignancies were identified with a mean follow-up of 5.2 years. Salivary duct carcinoma (45), mucoepidermoid carcinoma (44), and acinic cell carcinoma (26) were the most common histologic types. A total of 46.2% of tumors were found to have PNI. At the time of presentation, facial nerve paresis (odds ratio [OR], 64.7; P < .001) and facial pain (OR, 3.7; P = .002) but not facial paresthesia or anesthesia (OR, 2.8, P = .085) were predictive of PNI. Malignancies with PNI were significantly more likely to be of advanced T and N classification, be high-risk pathologic types, and have positive margins and angiolymphatic invasion. PNI positivity was associated with worse overall (hazard ratio, 2.62; P = .001) and disease-free survival (4.18; P < .001) on univariate Cox regression analysis. However, when controlling for other negative prognosticators, age, and adjuvant therapy, PNI did not have a statistically significant effect on disease-free or overall survival. Conclusions PNI is strongly correlated with more aggressive parotid gland malignancies but is not an independent predictor of worse survival. Facial paresis and pain were predictive of PNI positivity, and facial paresis correlated with worse overall and disease-free survival.

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.

In contrast to adulthood, meningiomas are rare among children and adolescents. Although recent papers have characterized the genomics of adult meningiomas, the molecular profiles of childhood meningiomas have not been elucidated in detail. We analyzed 41 tumor samples from 37 pediatric meningioma patients (female: 17, male: 20; age range: 1-21 years). Atypical meningioma WHO grade II was the most frequent histological subtype (N=14, 38%). Most tumors were located at the convexity (N=18) or the skull base (N=15). Lack of SMO, AKT, KLF4/TRAF7 mutations by Sanger sequencing (n=22) prompted whole genome sequencing of a subset (n=7). All seven cases exhibited bi-allelic inactivation of NF2 (combined large deletion and germline (5/7) or somatic (2/7) base exchanges/frameshifts). Subsequently, tumor samples from all 37 patients were subjected to 450K DNA methylation profiling and targeted DNA sequencing using brain tumor specific gene panel. Loss of chromosome 22 was frequent (N=28, 76%), followed by loss of chromosome 1 (N=12, 32%) and chromosome 18 (N=7, 19%). Moreover, separation into three groups was evident: One encompassing all clear-cell meningiomas with enrichment for SMARCE1 mutations, a second dominated by atypical meningiomas, and a third group composed of benign meningiomas, as well as rare subtypes such as rhabdoid meningiomas. When analyzed with 105 adult tumors, most of pediatric meningiomas (28/37) clustered into a separate methylation group both by unsupervised hierarchical clustering and t-stochastic nearest neighbor embedding (t-SNE). Four recurrences were similar to the primary tumor. These data suggest that pediatric meningiomas are genetically distinct from adult counterparts