Faculty Bibliography

BACKGROUND: Previous studies support a role for mitogen-activated protein kinase pathway signaling, and more recently Akt/mammalian target of rapamycin (mTOR), in pediatric low-grade glioma (PLGG), including pilocytic astrocytoma (PA). Here we further evaluate the role of the mTORC1/mTORC2 pathway in order to better direct pharmacologic blockade in these common childhood tumors. METHODS: We studied 177 PLGGs and PAs using immunohistochemistry and tested the effect of mTOR blockade on 2 PLGG cell lines (Res186 and Res259) in vitro. RESULTS: Moderate (2+) to strong (3+) immunostaining was observed for pS6 in 107/177 (59%) PAs and other PLGGs, while p4EBP1 was observed in 35/115 (30%), pElF4G in 66/112 (59%), mTOR (total) in 53/113 (47%), RAPTOR (mTORC1 component) in 64/102 (63%), RICTOR (mTORC2 component) in 48/101 (48%), and pAkt (S473) in 63/103 (61%). Complete phosphatase and tensin homolog protein loss was identified in only 7/101 (7%) of cases. In PA of the optic pathways, compared with other anatomic sites, there was increased immunoreactivity for pS6, pElF4G, mTOR (total), RICTOR, and pAkt (P < .05). We also observed increased pS6 (P = .01), p4EBP1 (P = .029), and RICTOR (P = .05) in neurofibromatosis type 1 compared with sporadic tumors. Treatment of the PLGG cell lines Res186 (PA derived) and Res259 (diffuse astrocytoma derived) with the rapalog MK8669 (ridaforolimus) led to decreased mTOR pathway activation and growth. CONCLUSIONS: These findings suggest that the mTOR pathway is active in PLGG but varies by clinicopathologic subtype. Additionally, our data suggest that mTORC2 is differentially active in optic pathway and neurofibromatosis type 1-associated gliomas. MTOR represents a potential therapeutic target in PLGG that merits further investigation.

OBJECTIVE: To measure early audiometric changes after primary stapedotomy. STUDY DESIGN: Case series with chart review. SETTING: Academic inner-city hospitals. SUBJECTS AND METHODS: Consecutive patients operated on by the first author were included (only 1 ear in cases of bilateral surgery), and their audiometric results were reviewed. Data were analyzed from 45 ears. Air and bone audiometric measures were analyzed from 5 days post operation and 6 months post operation. Threshold shifts were quantified at 5 days and 6 months post operation. RESULTS: Overall results for the group were good, with 91% of patients achieving an air-bone gap less than or equal to 10 dB by 6 months post operation. Threshold shifts in at least 1 frequency were common at 5 days (62% of patients), but less so at 6 months (36%). Patients with shifts did not have worse overall outcomes at 6 months than those with no shifts. No difference in results was observed for the 2 prostheses used in this series. CONCLUSION: Early audiometric results after stapedectomy commonly reveal worsened bone conduction (postoperative threshold shifts), which may reflect cochlear trauma, but do not lead to poorer outcomes as measured by conventional methods.

Purpose: This study investigated the reliability of tongue strength and endurance measurements in healthy adults using the Iowa Oral Performance Instrument (IOPI). Method(s): 51 healthy participants (21 males, 30 females) aged 19-57 years were tested on four occasions 1 week apart to determine test-retest reliability. The outcome measures were isometric tongue strength (best of three trials) and tongue endurance time at 50 % of maximal strength. Result(s): Small increases (changes in group mean) in both anterior (1.7 %) and posterior (2.5 %) tongue strength between weeks 1 and 2 were observed with no change in subsequent weeks suggesting there is only a small learning effect for these measurements. The within subject variation (mean-typical error expressed as a coefficient of variation, CV) indicated higher than desirable variation for anterior (CV 8.2 %) and posterior (CV 10.5 %) tongue strength but this was reduced in weeks 2-4. Intra-class correlations (ICC) indicated acceptable and improved reliability for both anterior (ICC 0.77-0.90) and posterior (ICC 0.79-0.86) tongue strength after week 1. In contrast, tongue endurance values were found to be extremely variable. For example, reliability measures of anterior tongue endurance for weeks 1-2 were 15.5 % (change in mean), 64 % (CV) and 0.49 (ICC), with only modest improvements in subsequent weeks. Conclusion: These findings suggest that tongue strength values demonstrate acceptable reliability, especially if familiarization is provided. Further investigation is being conducted to determine whether two values within 5 kPa provides superior tongue strength measurement reliability. Additional investigation is also needed to reduce sources of variability in tongue endurance measurements

BACKGROUND: BRAF V600E mutation is the most common genetic alteration in papillary thyroid cancer (PTC). We used a mutation-specific antibody for immunohistochemical (IHC) detection of the BRAF V600E mutation and correlated expression with clinicopathologic features. The study was designed to validate the accuracy and determine the clinical importance of IHC detection of the BRAF V600E mutation in PTC. METHODS: Direct sequencing and IHC for BRAF V600E mutation was performed in 37 consecutive patients with PTCs. IHC was scored on an intensity proportion scale. IHC positive tumors were stratified into intensity categories. The categories were assessed for clinicopathologic variables, including age, extrathyroidal extension, lymphovascular invasion, and lymph node metastases. RESULTS: A total of 25 PTCs were BRAF V600E-positive and 12 were BRAF mutation-negative on IHC. The BRAF V600E mutation-specific antibody had a sensitivity of 89% and specificity of 100% for detecting the mutation. Tumors with high-intensity staining were more likely to have extrathyroidal extension. CONCLUSION: IHC is an accurate method for the detection of the BRAF V600E mutation in PTC, and its ability to quantify the mutation expression may serve as a better predictor of tumor behavior than molecular sequencing. It provides a potentially rapid, easily applicable, and economic alternative to current techniques.

BACKGROUND: A 270-degree partially tubed pectoralis major myocutaneous flap (PMMF) is an excellent option for total circumferential pharyngoesophageal defects in patients who are not candidates for more complex reconstructions. METHODS: Patients undergoing circumferential pharyngoesophageal reconstruction with partially tubed PMMF were reviewed. End points were stricture, fistula, resumption of oral intake, perioperative death, and recurrence. RESULTS: Eleven patients underwent 270-degree PMMF for reconstruction: 6 (55%) were men and 5 (45%) were women (mean, 62 years; range, 42-78 years). Three patients (27%) developed fistulas and 2 (18%) developed stenosis. Ten patients (91%) were able to resume adequate nutrition via oral intake. There were no perioperative deaths. CONCLUSIONS: Patients with severe comorbidities, metastatic disease, a lack of donor vessels, or a potentially hostile abdomen may not be ideal candidates for free tissue transfer. For these patients, partially tubed PMMF using the prevertebral fascia provides a reliable alternative for reconstruction with excellent functional results.

Head and neck cancer is a unique cause of dysphagia. Altered swallow function can be secondary to the mechanical effects of a tumor invading normal anatomy needed for deglutition, or as a direct sequela of cancer treatment (surgery and/or radiation +/- chemotherapy). This article outlines the incidence of head and neck cancer, effects of anatomic changes associated with common surgical intervention, and the consequences of treatment-induced dysphagia. Assessment and rehabilitation techniques applicable for this population are discussed.

This study investigated the perceptual relationship between acoustic and electric stimuli presented to CI users with functional contralateral hearing. Fourteen subjects with unilateral profound deafness implanted with a MED-EL CI scaled the perceptual differences between pure tones presented to the acoustic hearing ear and electric biphasic pulse trains presented to the implanted ear. The differences were analyzed with a multidimensional scaling (MDS) analysis. Additionally, speech performance in noise was tested using sentence material presented in different spatial configurations while patients listened with both their acoustic hearing and implanted ears. Results of alternating least squares scaling (ALSCAL) analysis consistently demonstrate that a change in place of stimulation is in the same perceptual dimension as a change in acoustic frequency. However, the relative perceptual differences between the acoustic and the electric stimuli varied greatly across subjects. A degree of perceptual separation between acoustic and electric stimulation (quantified by relative dimensional weightings from an INDSCAL analysis) was hypothesized that would indicate a change in perceptual quality, but also be predictive of performance with combined acoustic and electric hearing. Perceptual separation between acoustic and electric stimuli was observed for some subjects. However, no relationship between the degree of perceptual separation and performance was found.

OBJECTIVES/HYPOTHESIS/OBJECTIVE:To evaluate the transoral anatomy of the tonsillar fossa and lateral pharyngeal wall and to correlate these findings with radiographic measurements and transoral robotic surgery (TORS) of patients with early tonsillar tumor. STUDY DESIGN/METHODS:Preclinical cadaveric study and patient cohort. METHODS:Six complete cadaveric dissections were performed to identify key anatomic landmarks, and these landmarks were validated in two consecutive patients with T1 human papillomavirus-positive squamous cell carcinoma of the tonsil treated by TORS. For radiographic landmark analysis, 25 patients who underwent contrast-enhanced computed tomography (CT) of the neck for a variety of endoscopic skull base procedures were selected. Measurements were taken from the lateral pharyngeal wall at C2-C3 interspace and greater horn of hyoid (C6) to the external carotid artery (ECA). RESULTS:The glossopharyngeal (IX) nerve was consistently identified deep to the superior constrictor musculature and at the intersection of the posterior tonsillar pillar with the base of tongue. The styloglossus muscle forms the deep plane medial to the ECA. The mean measurements for left C2-C3 interspace to the ECA and right C2-C3 interspace to ECA were 17.6 ± 0.8 mm and 18.4 ± 0.8 mm, respectively. Similarly, the mean measurements for left hyoid to ECA and right hyoid to ECA were 3.4 ± 0.8 mm and 4.3 ± 0.6 mm, respectively. CONCLUSIONS:A systematic approach to dissect the tonsillar fossa and lateral pharyngeal wall can be performed using key anatomic landmarks. CT measurements taken at the C2-C3 interspace and greater horn of hyoid bone (C6 level) to the ECA are consistently and reliably achieved.