Faculty Bibliography

High-frequency ripple oscillations, observed most prominently in the hippocampal CA1 pyramidal layer, are associated with memory consolidation. The cellular and network mechanisms underlying the generation of the rhythm and the recruitment of spikes from pyramidal neurons are still poorly understood. Using intracellular, sharp electrode recordings in freely moving, drug-free mice, we observed consistent large depolarizations in CA1 pyramidal cells during sharp wave ripples, which are associated with ripple frequency fluctuation of the membrane potential ("intracellular ripple"). Despite consistent depolarization, often exceeding pre-ripple spike threshold values, current pulse-induced spikes were strongly suppressed, indicating that spiking was under the control of concurrent shunting inhibition. Ripple events were followed by a prominent afterhyperpolarization and spike suppression. Action potentials during and outside ripples were orthodromic, arguing against ectopic spike generation, which has been postulated by computational models of ripple generation. These findings indicate that dendritic excitation of pyramidal neurons during ripples is countered by shunting of the membrane and postripple silence is mediated by hyperpolarizing inhibition.

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.

Primary mucosal melanoma of the head and neck (MMHN) comprises approximately 1% of all malignant melanomas. It presents more commonly in an elderly population and has no significant gender predominance. Given its rarity, most evidence of the causes, behavior, and treatment approaches for MMHN originates from isolated case reports and retrospective series. Between 1945 and 2011, at least 1951 cases of MMHN have been reported in the literature. Despite numerous technological developments in surgery and radiation therapy, as well as advances in systemic modalities, MMHN is an aggressive malignancy with a very poor prognosis. Complete surgical excision with clear margins remains the primary treatment modality. Adjuvant postoperative radiation therapy may improve locoregional control but does not appear to affect survival. Definitive particle radiation therapy promises to provide high rates of local control for nonoperable patients. Recent molecular evidence suggests that proto-oncogene KIT aberrations in a subset of mucosal melanomas may represent a potential diagnostic value and serve as a therapeutic target for tyrosine kinase inhibitors in an adjuvant setting for patients with advanced MMHN.

BACKGROUND:Pharyngeal stenosis is a complication of head and neck cancer and sleep apnea treatment that results in functional impairment. Due to the location of the stenosis and tendency to recur, surgical management is challenging. Robotic surgery may allow these areas to be treated with surgical technique that would be difficult using traditional approaches. METHODS:A retrospective chart review was performed to identify patients who underwent transoral robotic surgery (TORS) for pharyngeal stenosis at a tertiary hospital system. RESULTS:Five patients were identified, ages 8-75 years. Length of follow-up ranged from 1-12 months. There was one failure, a 74 year old male with a history of chemoradiation to the area who has required additional procedures. CONCLUSION/CONCLUSIONS:TORS may offer improved surgical access to the pharynx in patients who require complex reconstruction that would otherwise be very difficult. Appropriate patient selection is necessary and long-term follow-up is warranted for the selected cases.

The human vocal fold is a complex structure made up of distinct layers that vary in cellular and extracellular matrix composition. Elucidating the mechanical properties of vocal fold tissues is critical for the study of both acoustics and biomechanics of voice production, and essential in the context of vocal fold injury and repair. Both quasistatic and dynamic behavior in the 10-300Hz range was explored in this preliminary investigation. The resultant properties of the lamina propria were compared to that of the nearby thyroarytenoid muscle. Er, quantified via quasistatic testing of the lamina propria, was 609+/-138MPa and 758+/-142MPa in the muscle (p=0.001). E' of the lamina propria as determined by dynamic testing was 790+/-526MPa compared to 1061+/-928MPa in the muscle. Differences in E' did not achieve statistical significance via linear mixed effect modeling between the tissue types (p=0.95). In addition, frequency dependence was not significant (p=0.18).

Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction. PERSPECTIVE: Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.

UNLABELLED: As financial pressures drive health care to be more cost-effective and efficient, performing procedures outside the main operating room (MOR) is becoming more common. Pediatric sedation units (PSU) have proven both effective and safe at providing anesthesia for children. However, there is limited data available regarding the PSU and its potential application in pediatric otolaryngology. OBJECTIVE: To evaluate the experience of performing pediatric outpatient procedures in a PSU through a parental satisfaction survey. METHODS: Pediatric otolaryngology procedures performed in the PSU were prospectively recorded in a database. A prospective survey analysis was performed that measured parental satisfaction with scheduling/registration for surgery, nursing care, surgeon care, facility environment, timing/duration, and overall satisfaction. Parents completed this survey for outpatient procedures performed in either the PSU or in the MOR. The same attending surgeon was involved in all cases, with the only independent variable being the location of the surgery. Fifty surveys were collected for each group, and the surveys scores were statistically compared using nonparametric statistical analysis. RESULTS: Parental satisfaction was high in both the PSU and OR, with mean overall satisfaction scores of 4.8 and 4.9 (respectively) on an ordinal scale from 1 to 5. Parents reported greater clarity in preoperative information in the MOR (mean 4.8) compared to the PSU (mean 4.6) (p<0.006). Also, parents reported that MOR procedures started on time more often than those in the PSU (90-64%, p<0.002). There were no significant differences between locations in any other survey metrics, with mean satisfaction scores ranging from 4.5 to 5.0. CONCLUSIONS: The PSU is a satisfactory patient experience for outpatient procedures in pediatric otolaryngology at our institution. However, this parent survey has identified education prior to surgery and timeliness of surgery as two areas to improve to meet the satisfaction standard provided by the OR.

BACKGROUND:Cosmesis is of increasing importance to the otolaryngology patient population. This is the first report of clinical outcomes of robot-assisted neck dissection by North American groups. METHODS:This is a retrospective case-control study. Cases included three patients who underwent isolated, ipsilateral robot-assisted neck dissection. Operative time, estimated blood loss, lymph node retrieval, total drainage, hospital stay and complications from this group were compared against the outcomes of six consecutive patients who underwent conventional neck dissection. RESULTS:Operative times were longer in robot-assisted neck dissection (mean 234 min) compared with the conventional neck dissection (mean 110 min). There were no significant differences between the two groups in other outcomes. CONCLUSIONS:Robot-assisted selective neck dissection of levels II-IV is feasible through a modified facelift incision. Our initial data suggest that this procedure is surgically sound. It should be applied by experienced surgeons who wish to avoid a cervical incision.