Faculty Bibliography

Resection of advanced gingivo-buccal tumors results in a posterolateral mandibular and large soft tissue defect. Because of large soft tissue requirement, these defects are difficult to reconstruct using a single osteocutaneous flap. A double free flap reconstruction of such defects is recommended. However, double flap may not be feasible in certain situations. In this study, we objectively evaluated functional and cosmetic outcomes following single soft-tissue flap reconstruction in a group of patients where double flap reconstruction was not feasible. Patient and defect characteristics were obtained from charts. The speech and swallowing functions of patients were prospectively assessed by a dedicated therapist. The cosmetic outcome of reconstruction was evaluated by an independent observer. Fifty-six patients with large soft tissue and segmental posterolateral mandible defect, reconstructed with anterolateral thigh or pectoralis major flap from May 2009 till December 2010 were included. In this series, none of the flaps were lost; two patients with pectoralis major flap developed partial skin paddle loss. Most of the patients developed mandibular drift; however, majority of these patients had no postoperative trismus. All patients resumed regular or soft solid oral diet. The mean speech intelligibility was more than 70%. Majority of patients had satisfactory cosmetic outcome. The defects were classified into regions resected to develop a reconstruction algorithm for optimal reconstruction using a free or pedicle flap. In conclusion, patients with large oro-mandibular defect undergoing single soft tissue flap reconstruction have satisfactory functional and cosmetic outcome.

PURPOSE: Although the efficacy of selective neck dissection (SND) in the management of a node-negative neck is established, its utility in the management of node-positive disease remains controversial. The objective of this study was to evaluate the oncologic safety of SND in the management of N1/N2 oral cavity squamous cell carcinoma. MATERIALS AND METHODS: From a prospectively collected electronic database of patients with oral cavity cancer, a retrospective analysis was conducted of patients with nonrecurrent, clinical, and/or pathologic N1/N2 oral cavity squamous cell carcinoma who underwent SND of levels I to III/IV. The patients were stratified into 2 groups: clinical N0 but pathologic N1/N2 (cN0-pN1/N2) and clinical N1/N2 (cN1/N2). The primary outcome variable of the study was the ipsilateral regional recurrence rate. Categorical data were analyzed by the 2-sided Fisher exact test, and 3-year Kaplan-Meier ipsilateral regional control rate, regional recurrence-free survival, disease-free survival, and overall survival were estimated. RESULTS: Forty-nine patients constituted the study sample, with 37 patients in the cN1/N2 group and 12 patients in the cN0-pN1/N2 group. During the follow-up period of 3 years, 2 patients ( approximately 4%) developed ipsilateral neck recurrence, and these patients were in the cN1/N2 group. The 3-year Kaplan-Meier ipsilateral regional control rate was 95%. CONCLUSIONS: SND may produce a satisfactory ipsilateral regional control rate in patients with early-stage node-positive oral squamous cell carcinoma. A prospective, randomized clinical trial comparing SND with modified radical neck dissection may be required for a categorical conclusion of these findings.

IMPORTANCE: Neck dissection is the standard staging procedure to ascertain the pathologic status of cervical lymph nodes in patients with oral cavity squamous cell carcinoma (OSCC), but it results in multiple morbidities. OBJECTIVE: To examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB) as the sole neck staging procedure. DESIGN: Retrospective review of patients who underwent SNB during the period 2005 through 2011. SETTING: National Cancer Institute-designated comprehensive cancer center. PARTICIPANTS: Thirty-eight patients with clinically T1 or T2N0 OSCC. INTERVENTIONS: Preoperative lymphoscintigraphy with intraoperative gamma probe localization was used. Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3 levels. All patients with positive SNB results underwent neck dissection, and the patients with negative SNB results were observed clinically. MAIN OUTCOMES AND MEASURES: Sensitivity and predictive value of SNB, recurrence rates, and disease-specific survival rates. RESULTS: There were 18 T1 and 20 T2 tumors. Five patients had positive SNB results, of whom 3 had additional positive nodes on subsequent neck dissection. Two of 33 patients with negative SNB results developed a regional recurrence. The sensitivity and negative predictive value for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33), respectively. Mean follow-up was 31 months. The mean disease-free survival duration for patients with positive and negative SNB results was 30 and 65 months, respectively (P = .08). The disease-specific survival rate for patients with positive and negative SNB results was 80% and 91%, respectively. There was no significant difference in disease-specific survival between patients with true-negative and false-negative SNB results (34 vs 44 months; P = .38). CONCLUSIONS AND RELEVANCE: The majority of patients with positive results on SNB had additional positive nodes on neck dissection. A low rate of isolated neck recurrence was found in patients with negative results on SNB. Individuals with negative results on SNB exhibited better overall and disease-specific survival than those with positive results.

OBJECTIVES: We undertook to provide data regarding temporal measurements of swallow function obtained by dynamic magnetic resonance imaging in a midsagittal plane and to compare these values to normative fluoroscopy data. METHODS: Seventeen healthy female volunteers with no swallowing complaints underwent turbo-fast low-angle-shot magnetic resonance imaging with a 3-T scanner while swallowing liquid and pudding boluses delivered via syringe. Ninety sequential images were acquired with a temporal resolution of 113 ms per frame for each swallow. The imaging was performed in the midsagittal plane. The analyses focused on oral and pharyngeal transit times. RESULTS: All subjects tolerated the protocol without complaints or adverse events. The mean (+/- SD) oral transit times for liquids and pudding were measured as 0.25 +/- 0.09 second and 0.25 +/- 0.13 second, respectively. This difference was not statistically significant (p = 0.74). The mean pharyngeal transit times for liquids and pudding were measured as 0.84 +/- 0.16 second and 1.11 +/- 0.21 seconds, respectively. This difference achieved statistical significance (p < 0.0001). The intrarater and inter-rater reliabilities for the measurements were excellent. CONCLUSIONS: This sequence provided a high degree of temporal resolution of deglutition in the midsagittal plane. Furthermore, the temporal measurements acquired with dynamic magnetic resonance imaging were reliable and were relatively consistent with those of previous studies done with videofluoroscopy.

Background/Purpose: Rheumatoid arthritis (RA) patients are at increased risk of infection due to both RA itself and immunomodulating treatments. Infection rates are often difficult to compare across studies, since the rates may vary across the world, and due to methodological and demographic differences between studied populations or cohorts. We investigated rates of hospitalized infection in 5 RA registries from 4 continents, employing a standard set of analyses and standardizing rates to a common population. Methods: Participating registries were CORRONA (USA), SRR (Sweden), NOAR (UK), CORRONA International (East Europe, Latin America, India) and IORRA (Japan). The definition of hospitalized infections was harmonized as much as possible across registries. Within each registry, we analyzed a primary cohort of all RA patients from January 2000 to last available data of each registry (2010-2013), and several subcohorts for sensitivity analyses, defined by disease activity, treatment status, calendar time, duration of follow-up and prior comorbidity. Rates were standardized for age, sex and, in 1 sensitivity analysis, also for HAQ, using the distributions from a typical RA trial program population. Results: There was relatively high consistency in rates across registries, and sex/age standardization increased consistency further (Table 1). Generally, the primary cohorts provided the lowest or close to lowest rate (Table 2). In most registries, the highest rates were seen in subcohorts (either biologic naive or with prior biologic treatment) with only 18 months follow-up after treatment change (Table 2). Additional standardization for HAQ score according to a trial patient distribution led to increased rates in all registries (Table 2). Conclusion: This study constitutes the first attempt to compare the incidence of hospitalized infections internationally using existing RA cohorts. Consistent methodology, outcome definitions and analysis with standardization of rates facilitated comparison across !

OBJECTIVES/HYPOTHESIS: To characterize the anatomic distribution of lymphatic malformations of the upper airway. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care referral center specializing in the diagnosis and treatment of vascular anomalies. METHODS: A 7-year (2004-2011) retrospective chart review of patients with lymphatic malformations was performed at a tertiary care referral center. Patients with airway lymphatic malformations were identified. The anatomic distribution of lymphatic malformations within the airway was reviewed. RESULTS: A total of 141 patients with lymphatic malformations of the upper aerodigestive tract (UADT) were studied. Of these, 15 (11%) had laryngeal (supraglottic) involvement. In all of these patients, the disease was above the true vocal folds. Seventy-four (52%) patients had involvement of 1 anatomic zone (most common was the oral cavity), and 67 (48%) had involvement of multiple zones. With regard to each zone, 105 (75%) patients had involvement of the oral cavity, 50 (36%) the oropharynx, 8 (6%) the hypopharynx, 42 (30%) the parapharynx, and 12 (9%) had retropharygeal disease (some patients had multiple zones involved). No patients were identified with glottic, subglottic, or tracheal involvement. CONCLUSIONS: Based on our large series, airway involvement in head and neck lymphatic malformations may occur at multiple sites above the glottis. A high percentage of these patients have involvement of the oral cavity (75%) and oropharynx (35%). None involve the glottis, subglottis, or trachea.

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: 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.

OBJECTIVES/HYPOTHESIS: In pediatric patients with congenital malformations of the inner ear, anomalies within the anatomy may facilitate unintentional insertion of the cochlear implant electrode into the internal auditory canal. Revision procedures for removal and replacement of cochlear implant electrodes following internal auditory canal insertion are fraught with potential danger, including the theoretical risk of injury to vasculature within the internal auditory canal, repeat insertion within the internal auditory canal, and cerebrospinal fluid leak. The objective of this presentation is to describe a technique for revision cochlear implantation following internal auditory canal insertion to minimize the potential associated risks. STUDY DESIGN: Case series. METHODS: A retrospective chart review was performed on all patients at a tertiary care facility who underwent revision cochlear implantation for internal auditory canal insertion between January 1999 and July 2011. RESULTS: A total of four patients referred from outside institutions have undergone revision cochlear implantation for internal auditory canal insertion. The records from these patients were reviewed. Electrodes were safely removed in all cases without injury to the anterior inferior cerebellar artery or its branches (i.e., labyrinthine artery). Complete insertion was accomplished on reimplantation. Neural response telemetry was performed in all cases, and responses were noted. Fluoroscopy was utilized to visualize electrode progression during insertion. A detailed description of the operative technique is provided. CONCLUSIONS: This case series describes a technique for revision cochlear implantation that appears to be safe and effective in preventing potential associated complications. Laryngoscope, 2013.

Experience shapes the central nervous system throughout life. Structural and functional plasticity confers a remarkable ability on the brain, allowing neural circuits to adequately adapt to dynamic environments. This process can require selective adjustment of many excitatory and inhibitory synapses in an organized manner, in such a way as to enhance representations of behaviorally important sensory stimuli while preserving overall network excitability. The rules and mechanisms that orchestrated these changes across different synapses and throughout neuronal ensembles are beginning to be understood. Here, we review the evidence connecting synaptic plasticity to functional plasticity and perceptual learning, focusing on the roles of various neuromodulatory systems in enabling plasticity of adult neural circuits. However, the challenge remains to appropriately leverage these systems and forms of plasticity to persistently improve perceptual abilities and behavioral performance.