Otolaryngology Commons^™

Examination Of Care Processes And Treatment Optimization For Head And Neck Cancer Patients In A Community Setting “Hub And Hub” Model, Harleen K. Sethi, Elijah Walker, Travis Weinsheim, Matthew J. Brennan, Christopher E. Fundakowski

Otolaryngology (ENT) Resident Research

Objective

To examine referral pattern, the timing of diagnostic/staging processes, and treatment initiation for new head and neck cancer patients in a community setting.

Methods

Patients with a newly diagnosed previously untreated diagnosis of head neck cancer managed at Asplundh Cancer Pavilion/Abington Memorial Hospital from October 2018 to March 2020. Source of referral and preceding workup were examined as well as intervals between initial head and neck consult and various timepoints of treatment initiation.

Results

One hundred and five patients were included in the study. The primary referral sources were external general otolaryngology (56.3%). Oral surgery and dermatology obtained tissue …

Tadalafil Enhances Immune Signatures In Response To Neoadjuvant Nivolumab In Resectable Head And Neck Squamous Cell Carcinoma, Adam J. Luginbuhl, Jennifer Johnson, Larry Harshyne,, Alban J Linnenbach, Sanket Kumar Shukla, Angela Alnemri, Gaurav Kumar, David Cognetti, Joseph Curry, Nikita Kotlov, Zoya Antysheva, Sandrine Degryse, Kyle Mannion, Michael K Gibson, James Netterville, Brandee Brown, Rita S. Axelrod, Ralph G. Zinner, Madalina Tuluc, Stacey Gargano, Benjamin E Leiby, Ayako Shimada, M G Mahoney, Ubaldo E. Martinez-Outshoorn, Ulrich Rodeck, Young J Kim, Andrew P. South, Athanassios Argiris

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: We hypothesize that the addition of the phosphodiesterase-5 inhibitor tadalafil to the PD-1 inhibitor nivolumab, is safe and will augment immune-mediated antitumor responses in previously untreated squamous cell carcinoma of the head and neck (HNSCC).

Patients and methods: We conducted a two-arm multi-institutional neoadjuvant randomized trial in any-stage resectable HNSCC (NCT03238365). Patients were stratified at randomization by human papillomavirus (HPV) status. Patients in both arms received nivolumab 240 mg intravenously on days 1 and 15 followed by surgery on day 28. Those in the combination therapy arm also received tadalafil 10 mg orally once daily for 4 weeks. Imaging, …

P16 Represses Dna Damage Repair Via A /Novel Ubiquitin-Dependent Signaling Cascade, David P Molkentine, Jessica M Molkentine, Kathleen A Bridges, David R Valdecanas, Annika Dhawan, Reshub Bahri, Andrew J Hefner, Manish Kumar, Liangpeng Yang, Mohamed Abdelhakiem, Phillip M Pifer, Vlad Sandulache, Aakash Sheth, Beth M Beadle, Howard D Thames, Kathryn A Mason, Curtis R Pickering, Raymond E Meyn, Heath D Skinner

Faculty, Staff and Students Publications

Squamous cell carcinoma driven by human papillomavirus (HPV) is more sensitive to DNA-damaging therapies than its HPV-negative counterpart. Here, we show that p16, the clinically used surrogate for HPV positivity, renders cells more sensitive to radiotherapy via a ubiquitin-dependent signaling pathway, linking high levels of this protein to increased activity of the transcription factor SP1, increased HUWE1 transcription, and degradation of ubiquitin-specific protease 7 (USP7) and TRIP12. Activation of this pathway in HPV-positive disease led to decreased homologous recombination and improved response to radiotherapy, a phenomenon that can be recapitulated in HPV-negative disease using USP7 inhibitors in clinical development. This …

Otosyphilis: A Rare Cause Of Reversible Hearing Loss In A Teenage Male, Shan He, Anna H Messner, Gayatri Mirani

Faculty, Staff and Students Publications

A high index of suspicion and a thorough neurotologic examination at the onset of presentation are imperative to generate the diagnosis of otosyphilis. Complete audiologic recovery is rare but possible in approximately 20%-25% of patients after appropriate treatment. We present a case of reversible hearing loss secondary to otosyphilis in a teenage male patient with a new diagnosis of human immunodeficiency virus (HIV). Audiology findings were consistent with mixed hearing loss. Lumbar puncture results were consistent with neurosyphilis. Prompt treatment with a 14-day course of intravenous penicillin led to the complete recovery of hearing. In this case report, the pathophysiology, …

Stat6 Blockade Abrogates Aspergillus-Induced Eosinophilic Chronic Rhinosinusitis And Asthma, A Model Of Unified Airway Disease, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Clinical Symptoms Contributing To Zenker's Diverticulum Repair: A Retrospective Review, Jhon F. Martinez Paredes, Razan Al Fakir, Amy L. Rutt

School of Medicine Publications

Objective: Zenker's diverticulum (ZD) is usually associated with dysphagia and other symptoms due to the interrelated functions of several systems. Surgical management of ZD is effective for all sizes of diverticula, but not all patients decide to undergo surgery. The purpose of this study was to determine the relationship between clinical presentation and patients' decision to undergo surgical repair.

Subjects and methods: This is a retrospective study including 165 patients with ZD treated over the last 11 years. Data collection includes patients' chief complaints and symptoms, medical history, findings on radiologic swallow evaluations, and patients' decision to undergo surgery. Pearson …

Head And Neck Cancer Survivorship Consensus Statement From The American Head And Neck Society, Neerav Goyal, Andrew Day, Joel Epstein, Joseph Goodman, Evan Graboyes, Scharukh Jalisi, Ana P Kiess, Jamie A Ku, Matthew C Miller, Aru Panwar, Vijay A Patel, Assuntina Sacco, Vlad Sandulache, Amy M Williams, Daniel Deschler, D Gregory Farwell, Cherie-Ann Nathan, Carole Fakhry, Nishant Agrawal

Faculty, Staff and Students Publications

OBJECTIVES: To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship.

METHODS: Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence.

RESULTS: Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho-oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and …

Evaluation Of Programmed Death Ligand 1 Expression In Cytology To Determine Eligibility For Immune Checkpoint Inhibitor Therapy In Patients With Head And Neck Squamous Cell Carcinoma, Zhonghua Liu, Michelle Williams, John Stewart, Bonnie S Glisson, Clifton Fuller, Sinchita Roy-Chowdhuri

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have recently emerged as a frontline treatment for head and neck squamous cell carcinoma (HNSCC). The evaluation of PD-L1 expression by immunohistochemistry in histologic samples is used to determine the eligibility of patients with HNSCC for immunotherapy. Patients with newly diagnosed HNSCC are frequently diagnosed by fine-needle aspiration (FNA) of lymph nodes with metastatic disease. However, the evaluation of PD-L1 expression with the proposed combined positive score (CPS) has not been well established in cytology specimens.

Methods: This study retrospectively identified 21 …

A Rare Case Of A Middle Ear Glomangioma., Margaret E. Wieser, David R. Gilley, Jason G. May, Arnaldo L. Rivera

Manuscripts, Articles, Book Chapters and Other Papers

Glomus tumors are benign hyperplasia of glomus bodies, and they are rarely found in the head and neck. The middle ear is an exceptionally rare site for a true glomus tumor, and there are only three previously reported cases in this location. Glomus tumors are etiologically different than glomus tympanicum, which are paragangliomas of the middle ear that are often mistakenly referred to as "glomus tumors." This is a common misconception due to the "glomus" misnomer. We report a case of a patient diagnosed with a middle ear glomangioma after initially presenting to our clinic with tinnitus and hearing loss. …

Otitis Media Practice During The Covid-19 Pandemic., Tal Marom, Jacob Pitaro, Udayan Shah, Sara Torretta, Paola Marchisio, Ayan Kumar, Patrick Barth, Sharon Ovnat Tamir

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome …

Management Of Oral Cavity Mucormycosis In A Ketoacidotic Patient With Targeted Debridement And A Palate Obturator, Jennifer Adams, Adam Bender-Heine

School of Medicine Publications

Mucormycosis is an opportunistic mycosis common in poorly-controlled insulin dependent diabetic patients particularly with ketoacidosis. It often begins as a nasal and paranasal sinus infection with inhalation of spores into the paranasal sinuses of a susceptible host. In this case report we review the clinical symptoms, relevant imaging, and management of a diabetic patient with mucormycosis threatening his better seeing eye. This case report offers the clinician a review of important clinical and diagnostic findings that can help direct the need for orbital exenteration. In addition, various reconstruction options are considered to help guide informed management.

Eagle Syndrome: Efficacies Of Medical And Surgical Treatments, Kirklin Mitchell

Capstone Showcase

Eagle Syndrome is a rare syndrome caused by elongation of the styloid process of the temporal bone or calcification of the stylohyoid ligament occurring in a very small percentage of the population that can cause a wide range of common symptoms, leading to it being often misdiagnosed. While there are no set standards for treating Eagle Syndrome, both pharmaceutical and surgical options exist. Pharmaceutical options are often ineffective in long term treatment so surgery is usually required for full symptom resolution. Transoral and Transcervical surgeries have similar efficacies but each come with important drawbacks when considering which type of surgery …

Integrated Microtia And Aural Atresia Management, Mai Thy Truong, Yi-Chun Carol Liu, Jocelyn Kohn, Sivakumar Chinnadurai, David A Zopf, Melissa Tribble, Paul B Tanner, Kathleen Sie, Kay W Chang

Faculty, Staff and Students Publications

OBJECTIVES: To present recommendations for the coordinated evaluation and management of the hearing and reconstructive needs of patients with microtia and aural atresia.

METHODS: A national working group of 9 experts on microtia and atresia evaluated a working document on the evaluation and treatment of patients. Treatment options for auricular reconstruction and hearing habilitation were reviewed and integrated into a coordinated care timeline.

RESULTS: Recommendations were created for children with microtia and atresia, including diagnostic considerations, surgical and non-surgical options for hearing management and auricular reconstruction, and the treatment timeline for each option. These recommendations are based on the collective …

Screening For Balance In Children And Adults In A Community Science Education Setting: Normative Data, Influence Of Age, Sex, And Body Mass Index, And Feasibility, Phyllis Friello, Nathan Silver, Haleh Sangi-Haghpeykar, Helen S Cohen

Faculty, Staff and Students Publications

BACKGROUND: Screening standing and walking balance is useful for people suspected of having vestibular disorders, a variety of neurologic and musculoskeletal disorders, and for screening astronauts returning after exposure to microgravity. Visitors to a community science education center children and adults, aged 4 to 85, were tested on tandem walking with eyes closed and the modified Romberg test on compliant foam. They were then asked about their experience participating in research, many people for the first time.

METHODS: Subjects performed 10 steps of tandem walking with eyes closed, and three trials of the modified Romberg, or Clinical Test of Sensory …

Metabolic Targeting, Immunotherapy And Radiation In Locally Advanced Non-Small Cell Lung Cancer: Where Do We Go From Here?, Annika Dhawan, Phillip M Pifer, Vlad C Sandulache, Heath D Skinner

Faculty, Staff and Students Publications

In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with …

Proton Image-Guided Radiation Assignment For Therapeutic Escalation Via Selection Of Locally Advanced Head And Neck Cancer Patients [Pirates]: A Phase I Safety And Feasibility Trial Of Mri-Guided Adaptive Particle Radiotherapy, Lisanne V Van Dijk, Steven J Frank, Ying Yuan, Brandon Gunn, Amy C Moreno, Abdallah S R Mohamed, Kathryn E Preston, Yun Qing, Michael T Spiotto, William H Morrison, Anna Lee, Jack Phan, Adam S Garden, David I Rosenthal, Johannes A Langendijk, Clifton D Fuller

Faculty, Staff and Student Publications

Introduction: Radiation dose-escalation for head and neck cancer (HNC) patients aiming to improve cure rates is challenging due to the increased risk of unacceptable treatment-induced toxicities. With "Proton Image-guided Radiation Assignment for Therapeutic Escalation via Selection of locally advanced head and neck cancer patients" (PIRATES), we present a novel treatment approach that is designed to facilitate dose-escalation while minimizing the risk of dose-limiting toxicities for locally advanced HPV-negative HNC patients. The aim of this Phase I trial is to assess the safety & feasibility of PIRATES approach.

Methods: The PIRATES protocol employs a multi-faceted dose-escalation approach to minimize the risk …

Stat6 Suppression Prevents Bleomycin-Induced Dermal Fibrosis, Hua Sun, Ashish Damania, Megan L Mair, Eniola Otukoya, Yi-Dong Li, Katherine Polsky, Yuying Zeng, Jeremiah A Alt, Martin J Citardi, David B Corry, Amber U Luong, John Morgan Knight

Faculty, Staff and Student Publications

Unified airway disease, including concurrent asthma and chronic rhinosinusitis (CRS), is a common, but poorly understood disorder with no curative treatment options. To establish a murine model of chronic unified eosinophilic airway inflammation, mice were challenged with Aspergillus niger, and sinonasal mucosa and lung tissue were evaluated by immunohistochemistry, flow cytometry, and gene expression. Inhalation of A niger conidia resulted in a Th2-biased lung and sinus inflammation that typifies allergic asthma and CRS. Gene network and pathway analysis correlated with human disease with upregulation of not only the JAK-STAT and helper T-cell pathways, but also less expected pathways governing …

Three-Dimensional (3d) Anatomic Location, Extension, And Timing Of Severe Osteoradionecrosis Of The Mandible, Lucas G Sapienza, Justin J Thomas, Weiyuan Mai, Alexander N Hanania, Sandeep Hunjan, Vlad C Sandulache, Albert C Chen

Faculty, Staff and Students Publications

BACKGROUND: The purpose of this study was to describe the topography, extension (volume), and timing of severe osteoradionecrosis (ORN) that required mandible resection in patients previously treated for head and neck cancer at a high-volume Veterans Affairs Medical Center.

MATERIALS AND METHODS: The records from a reference hyperbaric oxygen clinic were retrospectively analyzed (n = 50, 2018-2021). Inclusion criteria were: I) severe ORN defined as progressive ORN that required resection; II) pathologic confirmation of ORN; and III) availability of pre-operative CT-imaging. Using a radiotherapy (RT) imaging software, we performed a detailed volumetric (3D) analysis of the bone involvement by ORN. …

Extended Effects Of A Wearable Sensory Prosthesis On Gait, Balance Function And Falls After 26 Weeks Of Use In Persons With Peripheral Neuropathy And High Fall Risk–The Walk2wellness Trial, Lars I E Oddsson, Teresa Bisson, Helen S Cohen, Ikechukwu Iloputaife, Laura Jacobs, Doris Kung, Lewis A Lipsitz, Brad Manor, Patricia Mccracken, Yvonne Rumsey, Diane M Wrisley, Sara R Koehler-Mcnicholas

Faculty, Staff and Students Publications

BACKGROUND: We recently reported that individuals with impaired plantar sensation and high fall risk due to sensory peripheral neuropathy (PN) improved gait and balance function following 10 weeks of use of Walkasins

MATERIALS AND METHODS: Participants had clinically diagnosed PN with impaired plantar sensation, high fall risk (Functional Gait Assessment, FGA score < 23) and ability to sense tactile stimuli above the ankle at the location of the device. Additional outcomes included 10 m Gait Speed, Timed Up and Go (TUG), Four-Stage Balance Test, and self-reported outcomes, including Activities-Specific Balance Confidence scale and Vestibular Disorders Activities of Daily Living Scale. Participants tracked falls using a calendar.

RESULTS: We assessed falls and self-reported outcomes from 44 individuals after 26 weeks of device use; 30 of them conducted in-person testing of clinical outcomes. Overall, improvements in clinical outcomes seen at 10 weeks of use remained sustained at 26 weeks with statistically significant increases compared to baseline …

Subjective Versus Objective Tests Of Dizziness And Vestibular Function In Epidemiologic Screening Research, Helen S Cohen, Haleh Sangi-Haghpeykar, Michael W Plankey

Faculty, Staff and Students Publications

BACKGROUND: Many epidemiologic studies of vestibular disorders are based on responses to questionnaires which have not been tested against objective tests of the vestibular system.

OBJECTIVE: The goal was to determine if the dizziness and balance questions used in the National Health Interview Survey (NHIS) are valid and predict performance on objective tests of the vestibular system (VNG).

METHODS: Data from 367 participants recruited from the community, aged 21.4 to 87.6 years, were collected in the Otolaryngology department at a tertiary care center. They were asked the eight NHIS questions twice, at least 30 minutes apart and were tested on …