Faculty Bibliography

Since 2005, facial transplantation has emerged as a viable reconstructive option for the most severe defects not amenable to conventional reconstructive techniques, with promising aesthetic and functional outcomes to date. Key facial subunits and midface structures such as the eyelids, lips, and nose are now able to be successfully replaced rather than reconstructed, enabling adequate functional outcomes in even the most extensive defects. However, even in cases of severe facial disfigurement, the decision to proceed with transplantation versus autologous reconstruction remains a source of debate, with no current consensus regarding precise indications and inclusion/exclusion criteria. This report details the case of a candidate referred for face transplantation who ultimately underwent autologous facial reconstruction. Through this representative case, our objective is to clarify the criteria that make a patient a suitable face transplant candidate, as well as to demonstrate the outcomes achievable with a conventional autologous reconstruction, using a methodically planned, multistaged approach.

Purpose: The purpose of this study is to quantify interfractional dosimetric variations in radiotherapy of oropharyngeal cancer and investigate the application of statistical process control (SPC) to determine significantly deviated fractions for management.
Method(s): Thirteen oropharyngeal cancer patients treated by IMRT or VMAT with daily CBCT were retrospectively reviewed. CBCT images of every other fraction were imported to the software Velocity and registered to planning CT using the 6DOF couch shifts generated during patient setup. Using Velocity Adaptive Monitoring module, the setup-corrected CBCT was matched to planning CT using a deformable registration. The module also generated dose volume histograms (DVHs) at each CBCT from planning doses for the deformed plan structure sets. Volumes and dose metrics at each fraction were calculated and rated with plan values to evaluate interfractional dosimetric variations using a SPC framework. T-tests between plan and fraction volumes were performed to find statistically insignificant fractions. Average, upper and lower process capacity limits (UCL, LCL) of each dose metric were derived from these fractions using conventional SPC guidelines.
Result(s): GTV and OAR volumes in first 13 fractions had no significantly changes from the plan, subsequently reduced by 10% to treatment completion, except oral cavity. There were 3%-4% increases in parotid mean doses, but no significant differences in dose metrics of GTVand other OARs. The changes were organ and patient dependent. Control charts for various dose metrics were generated to assess the metrics for individual patient. The occurrences of one or several dose metrics out of the control limits warrant immediate investigation of the fraction.
Conclusion(s): Daily CBCT could be used to monitor dosimetric variations of targets and OARs resulting from volume changes and tissue deformation in oropharyngeal cancer radiotherapy. Treatment review with guidance of a SPC tool may enable objectively and consistently identify significantly deviated fractions

OBJECTIVES/UNASSIGNED:To examine the frequency in which angled endoscopes are necessary to visualize the true maxillary ostium (TMO) following uncinectomy and prior to maxillary antrostomy. Additionally, to identify preoperative computed tomography (CT) measures that predict need for an angled endoscope to visualize the TMO. STUDY DESIGN/UNASSIGNED:Retrospective study. SETTING/UNASSIGNED:Tertiary academic hospital. PATIENTS AND METHODS/UNASSIGNED:Patients who underwent endoscopic sinus surgery (ESS) between December of 2017 and August of 2018 were retrospectively identified. Cases were reviewed if they were primary ESS cases for chronic rhinosinusitis without polyposis and if they were at least 18 years of age. RESULTS/UNASSIGNED:Sixty-three maxillary antrostomies were reviewed (82.5% were from bilateral cases). Thirty-five cases (55.6%) required an angled endoscope in order to visualize the TMO. Of the preoperative CT measures examined, a smaller sphenoid keel-caudal septum-nasolacrimal duct (SK-CS-NL) angle was significantly associated with need for an angled endoscope intraoperatively to visualize the TMO (17.1° SD ± 3.2 vs 15.0° SD ± 2.9; P = .010). CONCLUSION/UNASSIGNED:Angled endoscopes are likely required in the majority of maxillary antrostomies to visualize the TMO. This is important to recognize in order to prevent iatrogenic recirculation. The SK-CS-NL angle may help to identify cases preoperatively which require an angled endoscope to identify the TMO during surgery.

Wind is a major navigational cue for insects, but how wind direction is decoded by central neurons in the insect brain is unknown. Here we find that walking flies combine signals from both antennae to orient to wind during olfactory search behavior. Movements of single antennae are ambiguous with respect to wind direction, but the difference between left and right antennal displacements yields a linear code for wind direction in azimuth. Second-order mechanosensory neurons share the ambiguous responses of a single antenna and receive input primarily from the ipsilateral antenna. Finally, we identify novel "wedge projection neurons" that integrate signals across the two antennae and receive input from at least three classes of second-order neurons to produce a more linear representation of wind direction. This study establishes how a feature of the sensory environment-wind direction-is decoded by neurons that compare information across two sensors.

Performance on cognitive tasks during learning is used to measure knowledge, yet it remains controversial since such testing is susceptible to contextual factors. To what extent does performance during learning depend on the testing context, rather than underlying knowledge? We trained mice, rats and ferrets on a range of tasks to examine how testing context impacts the acquisition of knowledge versus its expression. We interleaved reinforced trials with probe trials in which we omitted reinforcement. Across tasks, each animal species performed remarkably better in probe trials during learning and inter-animal variability was strikingly reduced. Reinforcement feedback is thus critical for learning-related behavioral improvements but, paradoxically masks the expression of underlying knowledge. We capture these results with a network model in which learning occurs during reinforced trials while context modulates only the read-out parameters. Probing learning by omitting reinforcement thus uncovers latent knowledge and identifies context- not "smartness"- as the major source of individual variability.

OBJECTIVE/UNASSIGNED:To evaluate rates of epiphora after transection and marsupialization of the nasolacrimal duct (NLD) during endoscopic sinus and skull base surgery. INTRODUCTION/UNASSIGNED:The nasolacrimal canal forms part of the medial wall of the maxillary sinus. Transecting the NLD is sometimes necessary for tumor resection or surgical access to maxillary sinus and infratemporal fossa pathology. There is no consensus for the endoscopic management of the NLD when only the duct is transected without involving the nasolacrimal sac. METHODS/UNASSIGNED:Medical records of 29 patients from 2 academic institutions who underwent endoscopic sinus and skull base surgery with transection of the NLD were retrospectively reviewed. Whether the duct was marsupialized or simply transected was recorded, and the postoperative rate of epiphora was calculated. RESULTS/UNASSIGNED:Mean age was 59 years (range, 14-86 years). Mean follow-up was 10.5 months (range, 1-33 months). The NLD was marsupialized in 16 (55%) and simply transected in 13 (45%) patients. Six patients underwent postoperative radiation. No patients in the marsupialization group had epiphora postoperatively, all with Munk score of 0. One patient in the transection group developed postoperative epiphora with Munk score of 1. Pathology included inverted papilloma (8), acute on chronic inflammation (6), B-cell lymphoma (3), juvenile nasopharyngeal angiofibroma (2), squamous cell carcinoma (2), Schneiderian papilloma (2), metastatic melanoma (1), HPV-related carcinoma (1), adenocarcinoma (1), benign epithelial cyst (1), adenoid cystic carcinoma (1), and erosive chronic sinusitis without nasal polyposis (1). CONCLUSION/UNASSIGNED:Management after transection of the NLD varies widely. The duct may be simply transected or marsupialized, or a formal dacryocystorhinostomy can be performed. The surgeon must also choose whether to place a stent. Based on our small series and review of the literature, marsupialization or simple transection of the NLD results in a low rate of postoperative epiphora in the setting of endoscopic sinus and skull base surgery.

OBJECTIVE:To provide recommendations to otolaryngologists and allied physicians for the comprehensive management of young infants who present with signs or symptoms of choanal atresia. METHODS:A two-iterative delphi method questionnaire was used to establish expert recommendations by the members of the International Otolaryngology Group (IPOG), on the diagnostic, intra-operative, post-operative and revision surgery considerations. RESULTS:Twenty-eight members completed the survey, in 22 tertiary-care center departments representing 8 countries. The main consensual recommendations were: nasal endoscopy or fiberscopy and CT imaging are recommended for diagnosis; unilateral choanal atresia repair should be delayed after at least age 6 months whenever possible; transnasal endoscopic repair is the preferred technique; long term follow-up is recommended (minimum one year) using nasal nasofiberscopy or rigid endoscopy, without systematic imaging. CONCLUSION/CONCLUSIONS:Choanal atresia care consensus recommendations are aimed at improving patient-centered care in neonates, infants and children with choanal atresia.

PROBLEM IDENTIFICATION/UNASSIGNED:The impact of mental health disorders (MHDs) and substance use disorders (SUDs) on healthcare utilization (HCU) in patients with cancer is an understudied phenomenon. LITERATURE SEARCH/METHODS:A literature search of studies published prior to January 2018 that examined HCU in patients with preexisting MHDs or SUDs diagnosed with cancer was conducted. DATA EVALUATION/UNASSIGNED:The research team evaluated 22 studies for scientific rigor and examined significant trends in HCU, as well as types of the MHD, SUD, and cancer studied. SYNTHESIS/RESULTS:The heterogeneity of HCU outcome measures, MHD, SUD, sample sizes, and study settings contributed to inconsistent study findings. However, study trends indicated higher rates of HCU by patients with depression and lower rates of HCU by patients with schizophrenia. In addition, the concept of HCU measures is evolving, addressing not only volume of health services, but also quality and efficacy. IMPLICATIONS FOR RESEARCH/CONCLUSIONS:Oncology nurses are essential to improving HCU in patients with MHDs and SUDs because of their close connections with patients throughout the stages of cancer care. Additional prospective studies are needed to examine specific MHDs and different types of SUDs beyond alcohol use, improving cancer care and the effectiveness of HCU in this vulnerable population.

Understanding the cellular interactions during oral carcinogenesis has the potential to identify novel prognostic and therapeutic targets. This study aimed at investigating the cancer stem cell (CSC)-fibroblast niche interactions using in-vitro dysplastic cell line models developed from different stages of 4NQO-induced oral carcinogenic mice model. The spontaneously transformed epithelial cells (DysMSCTR6, 14 and 16) were developed from three time points (mild/moderate/severe), while two fibroblast cell lines (FibroMSCTR12, 16) were developed from moderate and severe dysplastic tissue. The epithelial (Epcam+/Ck+) and the fibroblast cell lines (Vimentin+/α-SMA+/Ck-) were authenticated and assessment of cells representing progressive grades of dysplastic severity indicated a significant increase in dysplastic marker profile (P < 0.05). Evaluation of the CSC characteristics showed that an increase in expression of Cd133, Cd44, Aldh1a1, Notch1, and Sox2 was accompanied by an increase in migratory (P > 0.05) and colony formation capacity (P > 0.005). Targeting Notch1 (GSI inhibitor PZ0187; 30 μM), showed a significant reduction in cell proliferation capacity (P < 0.05) and in the dysplastic marker profile. Further, Notch1 inhibition resulted in down regulation of Cd133 and Aldh1a 1 (P < 0.05) and a complete abrogation of colony formation ability (P < 0.0001). The effect of niche interactions evaluated using FibroMSCTR12-conditioned media studies, revealed an enrichment of ALDH1A1+ cells (P < 0.05), induction of spheroid formation ability (P < 0.0001) and increased proliferation capacity (3.7 fold; P < 0.005). Although PZ0187 reduced cell viability by ∼40%, was unable to abrogate the conditioned-media induced increase in proliferation capacity completely. This study reports a Notch-1 dependent enrichment of CSC properties during dysplastic progression and a Notch-1 independent dysplastic cell-fibroblast interaction during oral carcinogenesis.