Faculty Bibliography

Cancer cells secrete pro-nociceptive mediators that sensitize adjacent sensory neurons and cause pain. Identification and characterization of these mediators could pinpoint novel targets for cancer pain treatment. In the present study we identified candidate genes in cancer cell lines that encode for secreted or cell surface proteins that may drive nociception. To undertake this work, we utilized an acute cancer pain mouse model, transcriptomic analysis of publicly available human tumor-derived cell line data, and a literature review. Cancer cell line supernatants were assigned a phenotype based on evoked nociceptive behavior in an acute cancer pain mouse model. We compared gene expression data from nociceptive and non-nociceptive cell lines. Our analyses revealed differentially expressed genes (DEGs) and pathways; many of the identified genes were not previously associated with cancer pain signaling. Epidermal growth factor receptor (EGFR) and disintegrin metalloprotease domain 17 (ADAM17) were identified as potential targets among the DEGs. We found that the nociceptive cell lines contained significantly more ADAM17 protein in the cell culture supernatant compared to non-nociceptive cell lines. Cytoplasmic EGFR was present in almost all (>90%) tongue primary afferent neurons in mice. Monoclonal antibody against EGFR, cetuximab, inhibited cell line supernatant-induced nociceptive behavior in an acute oral cancer pain mouse model. We infer from these data that ADAM17-EGFR signaling is involved in cancer mediator-induced nociception. The differentially expressed genes and their secreted protein products may serve as candidate therapeutic targets for oral cancer pain and warrant further evaluation.

: This combined American Neurotology Society, American Otological Society, and American Academy of Otolaryngology - Head and Neck Surgery Foundation document aims to provide guidance during the coronavirus disease of 2019 (COVID-19) on 1) "priority" of care for otologic and neurotologic patients in the office and operating room, and 2) optimal utilization of personal protective equipment. Given the paucity of evidence to inform otologic and neurotologic best practices during COVID-19, the recommendations herein are based on relevant peer-reviewed articles, the Centers for Disease Control and Prevention COVID-19 guidelines, United States and international hospital policies, and expert opinion. The suggestions presented here are not meant to be definitive, and best practices will undoubtedly change with increasing knowledge and high-quality data related to COVID-19. Interpretation of this guidance document is dependent on local factors including prevalence of COVID-19 in the surgeons' local community. This is not intended to set a standard of care, and should not supersede the clinician's best judgement when managing specific clinical concerns and/or regional conditions.Access to otologic and neurotologic care during and after the COVID-19 pandemic is dependent upon adequate protection of physicians, audiologists, and ancillary support staff. Otolaryngologists and associated staff are at high risk for COVID-19 disease transmission based on close contact with mucosal surfaces of the upper aerodigestive tract during diagnostic evaluation and therapeutic procedures. While many otologic and neurotologic conditions are not imminently life threatening, they have a major impact on communication, daily functioning, and quality of life. In addition, progression of disease and delay in treatment can result in cranial nerve deficits, intracranial and life-threatening complications, and/or irreversible consequences. In this regard, many otologic and neurotologic conditions should rightfully be considered "urgent," and almost all require timely attention to permit optimal outcomes. It is reasonable to proceed with otologic and neurotologic clinic visits and operative cases based on input from expert opinion of otologic care providers, clinic/hospital administration, infection prevention and control specialists, and local and state public health leaders. Significant regional variations in COVID-19 prevalence exist; therefore, physicians working with local municipalities are best suited to make determinations on the appropriateness and timing of otologic and neurotologic care.

The relation between pharyngeal tonsil and the bony nasopharynx determines the nasopharyngeal airway patency. Despite its importance, an anatomical study utilizing advanced imaging has not been conducted. The aim of the study was to evaluate the pharyngeal tonsil and bony nasopharynx depth and their ratio (adenoid-nasopharyngeal ratio [ANR]) with relation to sex and age in the general pediatric population. After excluding reported history of adenoidectomy, acute upper airway illness, allergy, and poor quality, 200 randomly selected head computed tomographies (CTs) of children were evaluated. CTs were divided into five age groups (0-5, 5.1-8, 8.1-11, 11.1-14, and 14.1-17 years). For each CT scan, the pharyngeal tonsil, bony nasopharynx and ANR values were calculated. A significant difference was found in the bony nasopharynx and pharyngeal tonsil depth between the five age subgroups (P < 0.001). Both bony nasopharynx and pharyngeal tonsil depth significantly increased between the age groups of 0-5 years to 5.1-8 years (4.17 mm increase, P < 0.001 and 3.47 mm increase, P < 0.009, respectively). The pharyngeal tonsil depth gradually decreases following the age of 8 years. No difference was found between age groups beyond age of eight for both the pharyngeal tonsil tissue and the bony nasopharynx. The ANR has an upward trend in the age group of 5.1-8 years. No sexual predilection was found. The bony nasopharynx and the pharyngeal tonsil tissue both grow during childhood. Different growth rates result in the narrowest airway in the age group of 5.1-8 years (ANR peak). These growth curves should be taken under consideration when treating pediatric pharyngeal tonsil hypertrophy. Clin. Anat., 2019. © 2019 Wiley Periodicals, Inc.

The purpose of this feasibility study is to develop a fully automated procedure capable of generating treatment plans with multiple fractionation schemes to improve speed, robustness, and standardization of plan quality. A fully automated script was implemented for spinal stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) plan generation using Eclipse v15.6 API. The script interface allows multiple dose/fractionation plan requests, planning target volume (PTV) expansions, as well as information regarding distance/overlap between spinal cord and targets to drive decision-making. For each requested plan, the script creates the course, plans, field arrangements, and automatically optimizes and calculates dose. The script was retrospectively applied to ten computed tomography (CT) scans of previous cervical, thoracic, and lumbar spine SBRT patients. Three plans were generated for each patient - simultaneous integrated boost (SIB) 1800/1600 cGy to gross tumor volume (GTV)/PTV in one fraction; SIB 2700/2100 cGy to GTV/PTV in three fractions; and 3000 cGy to PTV in five fractions. Plan complexity and deliverability patient-specific quality assurance (QA) was performed using ArcCHECK with an Exradin A16 chamber inserted. Dose objectives were met for all organs at risk (OARs) for each treatment plan. Median target coverage was GTV V100% = 87.3%, clinical target volume (CTV) V100% = 95.7% and PTV V100% = 88.0% for single fraction plans; GTV V100% = 95.6, CTV V100% = 99.6% and PTV V100% = 97.2% for three fraction plans; and GTV V100% = 99.6%, CTV V100% = 99.1% and PTV V100% = 97.2% for five fraction plans. All plans (n = 30) passed patient-specific QA (>90%) at 2%/2 mm global gamma. A16 chamber dose measured at isocenter agreed with planned dose within 3% for all cases. Automatic planning for spine SRS/SBRT through scripting increases efficiency, standardizes plan quality and approach, and provides a tool for target coverage comparison of different fractionation schemes without the need for additional resources.

The Surveillance, Epidemiology, and End Results program from the National Cancer Institute reports that the aggregate number of oral cavity and pharyngeal cancer cases has been increasing over the past decade and, despite an overall decline in oral cavity cancers, this increase is largely related to a dramatic increase in cancers involving oropharyngeal subsites. Early detection of oral cavity cancers is commensurate with improved survival, and opportunistic screening by trained clinicians to detect oral cavity cancer and oral potentially malignant disorders is recommended by the American Dental Association and the American Academy of Oral Medicine.

BACKGROUND:Lymph node yield (LNY) is a proposed quality indicator in neck dissection for oral cavity squamous cell carcinoma (OCSCC). METHODS:Retrospective series including 190 patients with OCSCC undergoing neck dissection between 2016 and 2018. A change in pathologic grossing protocol was initiated during the study period to assess residual adipose tissue. A generalized linear model was used to assess the impact of multiple variables on LNY. RESULTS:Mean LNY was 28.59 (SD = 17.65). The protocol identified a mean of 10.32 lymph nodes per case. Multivariable analysis identified associations between LNY and use of the pathology protocol (P = .02), number of dissected lymph node levels (P < .001), presence of pathologic lymph nodes (P = .002), body mass index (P = .02), prior neck surgery (P = .001), and prior neck radiation (P = .001). CONCLUSIONS:Assessment of residual adipose tissue within neck dissection specimens improves accuracy of LNY. LNY in neck dissection is influenced by multiple factors including methods of pathologic assessment.

BACKGROUND:One of the critical components in pain management is the assessment of pain. Multidimensional measurement tools capture multiple aspects of a patient's pain experience but can be cumbersome to administer in busy clinical settings. AIM/OBJECTIVE:We conducted a systematic review to identify brief multidimensional pain assessment tools that nurses can use in both ambulatory and acute care settings. METHODS:We searched PUBMED/MEDLINE, PsychInfo, and CINAHL databases from January 1977 through December 2019. Eligible English-language articles were systematically screened and data were extracted independently by two raters. Main outcomes included the number and types of domains captured by each instrument (e.g., sensory, impact on function, temporal components) and tool characteristics (e.g., administration time, validity) that may affect instrument uptake in practice. RESULTS:Our search identified eight multidimensional assessment tools, all of which measured sensory or affective qualities of pain and its impact on functioning. Most tools measured impact of pain on affective functioning, mood, or enjoyment of life. One tool used ecological momentary assessment via a web-based app to assess pain symptoms. Time to administer the varying tools ranged from less than 2 minutes to 10 minutes, and evidence of validity was reported for seven of the eight tools. CONCLUSIONS:Our review identified eight multidimensional pain measurement tools that nurses can use in ambulatory or acute care settings to capture patients' experience of pain. The most important element in selecting a multidimensional pain measure, though, is that one tool is selected that best fits the practice and is used consistently over time.

BACKGROUND:Virtual surgical planning has contributed to technical advancements in free fibula flap mandible reconstruction. The authors present the largest comparative study on the latest modification of this technology: the use of patient-specific, preoperatively customized reconstruction plates for fixation. METHODS:A retrospective chart review was performed on all patients undergoing mandibular reconstruction with virtually planned free fibula flaps at a single institution between 2008 and 2018. Patient demographics, perioperative characteristics, and postoperative outcomes were reviewed. Reconstructions using traditional fixation methods were compared to those using prefabricated, patient-specific reconstruction plates. RESULTS:A total of 126 patients (mean age, 48.5 ± 20.3 years; 61.1 percent male) underwent mandibular reconstruction with a free fibula flap. Mean follow-up time was 23.5 months. A customized plate was used in 43.7 percent of cases. Reconstructions with patient-specific plates had significantly shorter total operative times compared with noncustomized fixation methods (643.0 minutes versus 741.7 minutes; p = 0.001). Hardware complications occurred in 11.1 percent of patients, with a trend toward a lower rate in the customized plate group (5.5 percent versus 15.5 percent; p = 0.091). Multivariate regression showed that the use of customized plates was a significant independent predictor of fewer overall complications (p = 0.03), shorter operative time (p = 0.014), and shorter length of stay (p = 0.001). CONCLUSIONS:Compared to traditional fixation methods, patient-specific plates are associated with fewer complications, shorter operative times, and reduced length of stay. The use of customized reconstruction plates increases efficiency and represents the latest technological innovation in mandibular reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, III.

Purpose Patients receive multiple bolus trials during a videofluoroscopic swallowing study (VFSS) to assess swallow function, inclusive of narrowing within the pharyngoesophageal segment (PES). While differences in the narrowest and widest segments are visualized, the ratio of distention across boluses is not well understood. Method A retrospective review of 50 consecutive VFSSs with five boluses of varied viscosity and volume was performed. Still images at maximal PES distention were captured and scaled using a 19-mm disk. Measurements of the narrowest and widest segments were obtained, and a distention ratio was calculated. Studies were categorized by PES phenotype as normal, esophageal web, cricopharyngeal bar, or narrow PES. PES distention ratios were evaluated across bolus trials and within PES phenotypes using a mixed-methods repeated-measures analysis of variance. Results Of the 50 studies, there were 11 normal, 16 web, 10 bar, and 13 narrow PES. Quantitative differences were present for the narrowest (p = .01) and widest (p = .002) points across bolus volumes. No difference was present in distention ratio (p = .2) across volumes. Evaluating the PES phenotype, web, normal, bar, and narrow PES distention ratios differed (p = .03). Bar and PES narrow distention ratios were lower compared to that of the normal group (p = .01 for normal vs. bar and p = .02 for normal vs. PES narrow). Conclusions PES distention ratio stability across varying bolus volumes and phenotypes suggests that a reduction in trials during a VFSS may permit an equivalent PES evaluation to traditional exams. Ultimately, this could improve our understanding and accurate diagnosis of PES dysfunction.

OBJECTIVES:There are many potential advantages to combined electric and acoustic stimulation (EAS) with a cochlear implant (CI), including benefits for hearing in noise, localization, frequency selectivity, and music enjoyment. However, performance on these outcome measures is variable, and the residual acoustic hearing may not be beneficial for all patients. As such, we propose a measure of spectral resolution that might be more predictive of the usefulness of the residual hearing than the audiogram alone. In the following experiments, we measured performance on spectral resolution and speech perception tasks in individuals with normal hearing (NH) using low-pass filters to simulate steeply sloping audiograms of typical EAS candidates and compared it with performance on these tasks for individuals with sensorineural hearing loss with similar audiometric configurations. Because listeners with NH had similar levels of audibility and bandwidth to listeners with hearing loss, differences between the groups could be attributed to distortions due to hearing loss. DESIGN:Listeners with NH (n = 12) and those with hearing loss (n = 23) with steeply sloping audiograms participated in this study. The group with hearing loss consisted of 7 EAS users, 14 hearing aid users, and 3 who did not use amplification in the test ear. Spectral resolution was measured with the spectral-temporal modulated ripple test (SMRT), and speech perception was measured with AzBio sentences in quiet and noise. Listeners with NH listened to stimuli through low-pass filters and at two levels (40 and 60 dBA) to simulate low and high audibility. Listeners with hearing loss listened to SMRT stimuli unaided at their most comfortable listening level and speech stimuli at 60 dBA. RESULTS:Results suggest that performance with SMRT is significantly worse for listeners with hearing loss than for listeners with NH and is not related to audibility. Performance on the speech perception task declined with decreasing frequency information for both listeners with NH and hearing loss. Significant correlations were observed between speech perception, SMRT scores, and mid-frequency audiometric thresholds for listeners with hearing loss. CONCLUSIONS:NH simulations describe a "best case scenario" for hearing loss where audibility is the only deficit. For listeners with hearing loss, the likely broadening of auditory filters, loss of cochlear nonlinearities, and possible cochlear dead regions may have contributed to distorted spectral resolution and thus deviations from the NH simulations. Measures of spectral resolution may capture an aspect of hearing loss not evident from the audiogram and be a useful tool for assessing the contributions of residual hearing post-cochlear implantation.