Faculty Bibliography

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.

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.

Rapidly progressive Alzheimer's disease (rpAD) is a particularly aggressive form of Alzheimer's disease, with a median survival time of 7-10 months after diagnosis. Why these patients have such a rapid progression of Alzheimer's disease is currently unknown. To further understand pathological differences between rpAD and typical sporadic Alzheimer's disease (sAD) we used localized proteomics to analyze the protein differences in amyloid plaques in rpAD and sAD. Label-free quantitative LC-MS/MS was performed on amyloid plaques microdissected from rpAD and sAD patients (n = 22 for each patient group) and protein expression differences were quantified. On average, 913 +/- 30 (mean +/- SEM) proteins were quantified in plaques from each patient and 279 of these proteins were consistently found in plaques from every patient. We found significant differences in protein composition between rpAD and sAD plaques. We found that rpAD plaques contained significantly higher levels of neuronal proteins (p = 0.0017) and significantly lower levels of astrocytic proteins (p = 1.08 x 10-6). Unexpectedly, cumulative protein differences in rpAD plaques did not suggest accelerated typical sAD. Plaques from patients with rpAD were particularly abundant in synaptic proteins, especially those involved in synaptic vesicle release, highlighting the potential importance of synaptic dysfunction in the accelerated development of plaque pathology in rpAD. Combined, our data provide new direct evidence that amyloid plaques do not all have the same protein composition and that the proteomic differences in plaques could provide important insight into the factors that contribute to plaque development. The cumulative protein differences in rpAD plaques suggest rpAD may be a novel subtype of Alzheimer's disease.

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.

BACKGROUND: Noninvasive encapsulated follicular variant of papillary thyroid carcinoma, a diagnosis implying malignancy as a variant of papillary thyroid carcinoma (PTC), has recently been reclassified to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical pathology. Due to the effects of such a recategorization on rate of malignancy and clinical management algorithms, it is imperative that we explore whether presurgical fine-needle aspiration can differentiate NIFTP from PTC and follicular adenoma (FA). METHODS: Cytology slides from subjects with final surgical pathology resection diagnoses of NIFTP/encapsulated follicular variant of papillary thyroid carcinoma, classic PTC, and FA made between January 2013 and August 2016 were assessed. The Bethesda System diagnoses were tabulated and cytomorphologic features were analyzed for an association with surgical pathology diagnoses. RESULTS: A total of 56 NIFTP, 67 classic PTC, and 30 FA cases were included. The presurgical NIFTP diagnosis according to The Bethesda System was most often atypia of undetermined significance (37.5%) followed by suspicious for follicular neoplasm/follicular neoplasm (26.8%), suspicious for malignancy (17.9%), benign (10.7%), and positive for malignancy (7.1%). The most common NIFTP cytomorphologic features were nuclear enlargement (83.9%), nuclear crowding (82.1%), nuclear clearing (69.6%), and microfollicles (73.2%). All cytomorphologic features demonstrated statistically significant associations (P value range, <.001-.002) between NIFTP and PTC, whereas select cytomorphologic features demonstrated significant associations between NIFTP and FA. CONCLUSIONS: Several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC, and FA on fine-needle aspiration. Although diagnostic confirmation of NIFTP must occur at the time of excision, similar to follicular neoplasms, the possibility of NIFTP may be raised preoperatively on cytology. Cancer Cytopathol 2017;125:378-88. (c) 2017 American Cancer Society.

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.

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.

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.