Faculty Bibliography

Fibroblast growth factor (FGF) signaling is vital for many biological processes, beginning with development. The importance of FGF signaling for skeleton formation was first discovered by the analysis of genetic FGFR mutations which cause several bone morphogenetic disorders, including achondroplasia, the most common form of human dwarfism. The formation of the long bones is mediated through proliferation and differentiation of highly specialized cells - chondrocytes. Chondrocytes respond to FGF with growth inhibition, a unique response which differs from the proliferative response of the majority of cell types; however its molecular determinants are still unclear. Quantitative phosphoproteomic analysis was utilized to catalogue the proteins whose phosphorylation status is changed upon FGF1 treatment. The generated dataset consists of 756 proteins. We were able to localize the divergence between proliferative (canonical) and inhibitory (chondrocyte specific) FGF transduction pathways immediately upstream of AKT kinase. Gene Ontology (GO) analysis of the FGF1 regulated peptides revealed that many of the identified phosphorylated proteins are assigned to negative regulation clusters, in accordance with the observed inhibitory growth response. This is the first time a comprehensive subset of proteins involved in FGF inhibitory response is defined. We were able to identify a number of targets and specifically discover glycogen synthase kinase3beta (GSK3beta) as a novel key mediator of FGF inhibitory response in chondrocytes.

Although residency training offers numerous leadership opportunities, most residents are not exposed to scripted leadership instruction. To explore one program's attitudes about leadership training, a group of otolaryngology faculty (n = 14) and residents (n = 17) was polled about their attitudes. In terms of self-perception, more faculty (10 of 14, 71.4%) than residents (9 of 17, 52.9%; P = .461) considered themselves good leaders. The majority of faculty and residents (27 of 31) thought that adults could be taught leadership ability. Given attitudes about leadership ability and the potential for improvement through instruction, consideration should be given to including such training in otolaryngology residency.

TMEM16A, a Ca²⁺ -activated Cl^- channel, contributes to tumor growth in breast cancer and head and neck squamous cell carcinoma (HNSCC). Here, we investigated whether TMEM16A influences the response to EGFR/HER family-targeting biological therapies. Inhibition of TMEM16A Cl^- channel activity in breast cancer cells with HER2 amplification induced a loss of viability. Cells resistant to trastuzumab, a monoclonal antibody targeting HER2, showed an increase in TMEM16A expression and heightened sensitivity to Cl^- channel inhibition. Treatment of HNSCC cells with cetuximab, a monoclonal antibody targeting EGFR, and simultaneous TMEM16A suppression led to a pronounced loss of viability. Biochemical analyses of cells subjected to TMEM16A inhibitors or expressing chloride-deficient forms of TMEM16A provide further evidence that TMEM16A channel function may play a role in regulating EGFR/HER2 signaling. These data demonstrate that TMEM16A regulates EGFR and HER2 in growth and survival pathways. Furthermore, in the absence of TMEM16A cotargeting, tumor cells may acquire resistance to EGFR/HER inhibitors. Finally, targeting TMEM16A improves response to biological therapies targeting EGFR/HER family members.

One to two percent of ectopic parathyroid adenomas are found in the lower mediastinum and often these are best accessed via a sternotomy or thoracotomy. Video-assisted thoracoscopic surgery (VATS) is an alternative approach with less surgical trauma, decreased morbidity, shorter hospital stays, and superior cosmetic results. Ten years after the first VATS resection of an ectopic mediastinal parathyroid, a robot-assisted thoracoscopic approach was described. Here we describe a series of five robot assisted complete thymectomies in patients with primary hyperparathyroidism due to mediastinal ectopic parathyroid adenomas. A single surgeon, single institution case series of five consecutive robotic-assisted mediastinal parathyroidectomies was performed between March 2013 and September 2015. The patients' ages ranged from 31 to 65, 80 % were female, and all had primary hyperparathyroidism due to an ectopic parathyroid located in the lower mediastinum. Pre-operative imaging workup included Technetium 99-sestimibi parathyroid scan and CT scan of the chest. An ectopic parathyroid adenoma was successfully removed in all five cases, with intraoperative iOPTH decreasing ~50 % from baseline after 10 minutes. A hypercellular parathyroid was confirmed on pathologic exam in all specimens. Post-operative discharge and follow up calcium levels all returned to normal. There were no intraoperative complications, including no recurrent laryngeal nerve injuries, no postoperative morbidity, and no mortalities. This case series demonstrates that a robot-assisted complete thymectomy for mediastinal parathyroid adenomas causing primary hyperparathyroidism provides excellent visualization of the mediastinum, is effective at reducing PTH and calcium levels, and is safe with no morbidity or mortality.

Objective To evaluate the effect of anatomy-specific virtual reality (VR) surgical rehearsal on surgeon confidence and temporal bone dissection performance. Study Design Prospective pre- and poststudy of a novel virtual surgical rehearsal platform. Setting Academic otolaryngology-head and neck surgery residency training programs. Subjects and Methods Sixteen otolaryngology-head and neck surgery residents from 2 North American training institutions were recruited. Surveys were administered to assess subjects' baseline confidence in performing 12 subtasks of cortical mastoidectomy with facial recess. A cadaver temporal bone was randomly assigned to each subject. Cadaver specimens were scanned with a clinical computed tomography protocol, allowing the creation of anatomy-specific models for use in a VR surgical rehearsal platform. Subjects then rehearsed a virtual mastoidectomy on data sets derived from their specimens. Surgical confidence surveys were administered again. Subjects then dissected assigned cadaver specimens, which were blindly graded with a modified Welling scale. A final survey assessed the perceived utility of rehearsal on dissection performance. Results Of 16 subjects, 14 (87.5%) reported a significant increase in overall confidence after conducting an anatomy-specific VR rehearsal. A significant correlation existed between perceived utility of rehearsal and confidence improvement. The effect of rehearsal on confidence was dependent on trainee experience and the inherent difficulty of the surgical subtask. Postrehearsal confidence correlated strongly with graded dissection performance. Subjects rated anatomy-specific rehearsal as having a moderate to high contribution to their dissection performance. Conclusion Anatomy-specific virtual rehearsal improves surgeon confidence in performing mastoid dissection, dependent on surgeon experience and task difficulty. The subjective confidence gained through rehearsal correlates positively with subsequent objective dissection performance.

The potential for the misinterpretation of positron-emission tomography (PET) scans in the context of a possible malignancy has been confirmed in a case report showing increased 18F-fluorodeoxyglucose (FDG) uptake after unilateral vocal fold augmentation medialization. We sought to expand these findings by investigating FDG uptake in a larger cohort of patients via a retrospective chart review. We examined the records of 15 adults-8 men and 7 women-who had undergone vocal fold augmentation for unilateral vocal fold paralysis and at least one subsequent PET scan. The differences in PET standard uptake value (SUV) between the injected and noninjected vocal folds were assessed via the Wilcoxon signed-rank test. A Spearman rank correlation coefficient was then used to estimate the relationship between differences in PET uptake and the length of time between the injection and the follow-up PET scan. The mean SUV of the injected vocal folds was 3.70, and the mean in the noninjected folds was 2.97. The difference did not achieve statistical significance (p = 0.34). In addition, the rank correlation coefficient with regard to the association between the difference in PET uptake and the duration between injection and PET was -0.24, suggesting an inverse relationship. However, the correlation coefficient did not differ significantly from zero (p = 0.34). We conclude that PET uptake after vocal fold augmentation medialization is variable and that it can increase substantially. This information should be considered in the context of the diagnostic accuracy of malignancy on PET.

The existence of the adenoid first appears to have been noted by Conrad Victor Schneider in 1661. James Yearsley reported in 1842 one case in which he improved hearing by removal of a mucus membrane from behind the uvula, which indicates some appreciation of a relationship of the nasopharynx to ear disease. Hans Wilhelm Meyer, in 1868, was the first to demonstrate the relationship of the adenoid to ear disease and to develop an effective, although somewhat difficult, surgical operation to remove the adenoid. Removal of the adenoid became rapidly accepted worldwide as a treatment for many morbidities, including otitis, speech problems, cognitive problems, and sleep apnea. Until the 1920s, adenoidectomy often was performed as a staged procedure and without general anesthesia. Early tools and techniques included use of the bare fingernail, a finger ring knife, a curette, and electrical desiccation. From the mid-1930s to the early 1960s, radiation therapy of the adenoid was in extensive use, both for children and in caring for army aviators and navy submarine crews during WWII. The effectiveness of surgical adenoidectomy for hearing loss led to a belief that radiation, which had been found to ablate lymphoid tissue, would be equally effective, and led to the wide-spread use of radiation. Ultimately, 500 thousand to 2.5 million children and adults were estimated to have been treated with radiation, and follow-up studies found increased risk for cancer. Furthermore, a follow-up study by Stacey R. Guild (1890-1966), published in 1950, on a very large sample of children who previously were reported to have had their hearing loss diminished through radiation, found that irradiation had produced no effect on high-tone loss. Thus, irradiation was both useless and harmful. Acceptance of authority, which can lurk within medical culture, led to the development of a tragically misguided management of adenoid disease. Laryngoscope, 127:S13-S28, 2017.

BACKGROUND AND PURPOSE: Preoperative localization of the pituitary gland with imaging in patients with macroadenomas has been inadequately explored. The pituitary gland enhancing more avidly than a macroadenoma has been described in the literature. Taking advantage of this differential enhancement pattern, our aim was to evaluate the role of high-resolution dynamic MR imaging with golden-angle radial sparse parallel reconstruction in localizing the pituitary gland in patients undergoing trans-sphenoidal resection of a macroadenoma. MATERIALS AND METHODS: A retrospective study was performed in 17 patients who underwent trans-sphenoidal surgery for pituitary macroadenoma. Radial volumetric interpolated brain examination sequences with golden-angle radial sparse parallel technique were obtained. Using an ROI-based method to obtain signal-time curves and permeability measures, 3 separate readers identified the normal pituitary gland distinct from the macroadenoma. The readers' localizations were then compared with the intraoperative location of the gland. Statistical analyses were performed to assess the interobserver agreement and correlation with operative findings. RESULTS: The normal pituitary gland was found to have steeper enhancement-time curves as well as higher peak enhancement values compared with the macroadenoma (P < .001). Interobserver agreement was almost perfect in all 3 planes (kappa = 0.89). In the 14 cases in which the gland was clearly identified intraoperatively, the correlation between the readers' localization and the true location derived from surgery was also nearly perfect (kappa = 0.95). CONCLUSIONS: This study confirms our ability to consistently and accurately identify the normal pituitary gland in patients with macroadenomas with the golden-angle radial sparse parallel technique with quantitative permeability measurements and enhancement-time curves.

In this issue of Neuron, Chen et al. (2017) examine premotor activity representing motor planning, Allen et al. (2017) observe the global representation of goal-directed movement on the cortical network, and Makino et al. (2017) track changes in such dynamics throughout learning.