Faculty Bibliography

PURPOSE OF REVIEW: To describe the efficacy of mitomycin C in combating airway stenosis. RECENT FINDINGS: Recent publications discussing mitomycin C utility have not altered the mixed results previously established by prospective trials. SUMMARY: Mitomycin C has been used for the past 16 years to inhibit pediatric airway fibroblast proliferation. Its benefit remains more hypothetical than proven and its future role remains uncertain.

OBJECTIVE: The preferential delayed enhancement of the perilymphatic space enables detection of the non-enhancing endolymphatic hydrops present in patients with Meniere's disease. The aim of this study was to evaluate the diagnostic utility of delayed postcontrast 3D FLAIR images and a color map of fused postcontrast FLAIR and constructive interference steady state (CISS) images in the identification of endolymphatic hydrops in patients with clinically diagnosed Meniere's disease. STUDY DESIGN: Case control, blinded study. SETTING: Tertiary referral center. PATIENTS: Ten patients with Meniere's disease and five volunteer controls. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Two neuroradiologists blinded to the clinical history independently evaluated for the presence of endolymphatic hydrops on the images of both inner ears for test and control subjects. Both the standard gray-scale FLAIR images and the fused color map images were independently reviewed. RESULTS: The gray-scale 3D FLAIR images demonstrated 68.2% sensitivity and 97.4% specificity, and the fused color map images demonstrated 85.0% sensitivity and 88.9% specificity in the identification of endolymphatic hydrops in Meniere's disease. There was significant correlation between the gray-scale 3D FLAIR images and fused color map images with the categorization of involvement (p = 0.002). Inter-evaluator reliability was excellent (kappa = 0.83 for gray-scale images, kappa = 0.81 for fused color map). CONCLUSION: Delayed 3D FLAIR and fused 3D FLAIR-CISS color map images of the inner ears after intravenous contrast administration are potentially useful diagnostic tools in the evaluation of patients with suspected Meniere's disease.

BACKGROUND: Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. METHODS: The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. RESULTS: In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor gamma (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). CONCLUSIONS: The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients. Cancer 2014. (c) 2014 American Cancer Society.

BACKGROUND: We present a case report of a trachea-colonic fistula and demonstrate our unique approach to repair, which was efficient and effective. METHODS: The patient was a 50-year-old man who had a congenital tracheoesophageal fistula repair with colonic interposition as a child who now developed a fistula between his colon and trachea. RESULTS: We performed a transtracheal approach, with primary closure of redundant colon mucosa as well as direct repair of the trachea. An inferiorly based sternocleidomastoid muscle flap was interposed between these 2 layers to augment the repair. The patient had an uneventful recovery with an effective reconstitution of the alimentary tract and the airway. CONCLUSION: Tracheo-colonic fistula is an extremely rare pathology, and the scarring that develops after a prior esophagectomy makes a traditional lateral approach very difficult. The transtracheal approach is an effective method to obtain needed exposure in order to carry out the repair. (c) 2013 Wiley Periodicals, Inc. Head Neck, 2014.

PURPOSE: To retrospectively review our single institution experience of patients with tonsillar squamous cell carcinoma. MATERIAL AND METHODS: Between 1999 and 2005, a total of 79 patients were identified. Stage distribution was as follows: stages I-II, III, IVA, and IVB were in 6, 14, 43, and 16 patients, respectively. Sixty-three patients (80%) were male. Median age was 55.5 years. Treatment generally consisted of external beam radiation therapy (RT) (median dose, 70 Gy), concomitant chemotherapy (CCRT) (cisplatin 100 mg/m on days 1, 22, and 43), and neck dissection (ND), and was administered as follows: stages I/II, 6 patients received RT alone; stages III/IVA, 20, 5, and 32 patients received RT alone, CCRT, and CCRT followed by ND, respectively; stage IVB, 9 and 7 patients received CCRT and CCRT plus ND, respectively. RESULTS: After a median follow-up of 56 months (range, 12 to 122 mo), the 5-year local control (LC), regional control (RC), distant control (DC), and overall survival (OS) by stage were as follows: stage I-II 100%, 100%, 100%, 100%; stage III-IVA 98%, 96%, 95%, and 88%; stage IVB 100%, 100%, 69%, and 66%, respectively. Among stage IVB patients, DC was significantly lower (P=0.01) and a trend toward lower OS was noted (P=0.08). Long-term percutaneous endoscopic gastrostomy dependence was noted in 3% of them who had received CCRT. The effect of both chemotherapy and ND on treatment outcomes was analyzed; in stage III/IVA patients treated with or without chemotherapy, LC was 97% and 100% (P=0.43); RC was 92% and 100%(P=0.27); and DC was 91% and 94% (P=0.92), respectively. In stage III/IVA, patients treated with CCRT with or without ND, RC was 100% and 88%, respectively (P=0.087). CONCLUSIONS: Primary radiotherapy with or without CCRT followed by ND provides excellent tumor control with acceptable toxicity in treating squamous cell carcinoma of the tonsil.

The purpose of this study was to investigate the reliability of tongue and handgrip strength and endurance measurements in healthy adults using the Iowa Oral Performance Instrument. Fifty-one healthy participants (21 males, 30 females; age range = 19-57 years) were tested on four occasions 1 week apart to determine test-retest reliability. The primary outcome measures were isometric tongue and handgrip strength (best of three trials) and sustained isometric endurance. Small increases (changes in group mean) in both anterior (1.7 %) and posterior (2.5 %) tongue strength and handgrip strength (5 %) between weeks 1 and 2 were observed with no change in subsequent weeks, suggesting that 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 initial variation for anterior (CV 10.8 %) and posterior (CV 11.8 %) tongue strength and handgrip strength (CV 15.2 %) but this was reduced in weeks 2-4. Intraclass correlation coefficients (ICC) indicated acceptable and improved reliability for both anterior (ICC 0.77-0.90) and posterior (ICC 0.79-0.86) tongue strength and handgrip strength (ICC 0.69-0.91) after week 1. Additional exploratory analyses were conducted with a subset of data to determine whether two values within 5 kPa (tongue) or 15 kPa (handgrip) provide superior strength reliability. Neither tongue nor hand endurance measurements were sufficiently reliable. These findings suggest that tongue and handgrip strength values demonstrate acceptable reliability, especially if familiarization is provided. Further investigation is needed to reduce sources of variability in tongue endurance measurements.

BACKGROUND: Prophylactic central neck dissection (PCND) for papillary thyroid cancer (PTC) is controversial. Recent publications suggest that the number and size of nodes and the presence of extranodal extension (ENE) are important features for risk stratification of lymph node metastases. We analyzed these features in clinically unapparent nodes that would not otherwise be removed. We also investigated the impact of surgeon experience on the ability to detect metastatic lymph nodes intraoperatively. METHODS: Forty-seven patients with well-differentiated PTC, with no preoperative evidence of central metastases, were included in this study. Intraoperatively, clinically apparent disease was determined by inspection and palpation by the senior surgeon and a fellow/senior resident, and recorded in a blinded fashion. Rate of occult metastases based on intraoperative evaluation were tabulated for each group of surgeons. Histopathologic features of occult nodes were analyzed to determine what clinicians would be missing by foregoing a PCND, and how that would have impacted the patient management. RESULTS: The rate of occult metastases, based on senior surgeon assessment, was 26%, and did not differ significantly from fellow/senior resident assessment. The level of agreement between these two surgeon groups was moderate (k=0.665). Analysis of the false negative cases revealed that the size of the largest undetected node ranged from 0.1 to 1.3 cm; 36% of patients with occult metastases demonstrated five or more positive nodes, and 27% showed ENE. DISCUSSION: Clinical assessment based on intraoperative inspection and palpation had poor sensitivity and specificity in identifying metastatic central nodes, regardless of the level of experience of the surgeon. There was moderate agreement between surgeons of different experience levels. Sensitivity improved significantly with larger size of positive nodes, but not with the presence of multiple positive nodes or presence of ENE. In foregoing PCND in this patient population, our results suggest that treating clinicians miss potentially virulent disease with a large number of occult positive central nodes and occult nodes with ENE. This is the first report to address the pathologic features of clinically nonevident central nodes showing a high incidence of clinically relevant, adverse histologic features, as well as the impact of surgeon experience in performing the important intraoperative determination of whether there are clinically evident nodes that require removal.

Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits.

Behavioral and neural findings demonstrate that animals can locate low-frequency sounds along the azimuth by detecting microsecond interaural time differences (ITDs). Information about ITDs is also available in the amplitude modulations (i.e., envelope) of high-frequency sounds. Since medial superior olivary (MSO) neurons encode low-frequency ITDs, we asked whether they employ a similar mechanism to process envelope ITDs with high-frequency carriers, and the effectiveness of this mechanism compared with the process of low-frequency sound. We developed a novel hybrid in vitro dynamic-clamp approach, which enabled us to mimic synaptic input to brain-slice neurons in response to virtual sound and to create conditions that cannot be achieved naturally but are useful for testing our hypotheses. For each simulated ear, a virtual sound, computer generated, was used as input to a computational auditory-nerve model. Model spike times were converted into synaptic input for MSO neurons, and ITD tuning curves were derived for several virtual-sound conditions: low-frequency pure tones, high-frequency tones modulated with two types of envelope, and speech sequences. Computational models were used to verify the physiological findings and explain the biophysical mechanism underlying the observed ITD coding. Both recordings and simulations indicate that MSO neurons are sensitive to ITDs carried by spectrotemporally complex virtual sounds, including speech tokens. Our findings strongly suggest that MSO neurons can encode ITDs across a broad-frequency spectrum using an input-slope-based coincidence-detection mechanism. Our data also provide an explanation at the cellular level for human localization performance involving high-frequency sound described by previous investigators.