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Year in Review: New Research

Program Leadership

Joseph Curry, MD
Vice Chairman, Research, Department of Otolaryngology - Head & Neck Surgery

Contact

Beth Kangas, RN, BSN, CCRC, ACRP-PM
Clinical Research Nurse
Sidney Kimmel Medical College Alumni
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The Department of Otolaryngology – Head and Neck Surgery at Thomas Jefferson University Hospital, which is ranked among the nation’s Best Hospitals by U.S. News & World Report, includes many physicians trained in subspecialty areas such as advanced head and neck oncology surgery, rhinology and skull base surgery, otology, laryngology, sleep surgery and facial plastic and reconstructive surgery. 

Otolaryngologists at Thomas Jefferson University Hospital continue to advance medicine to make these procedures and others better and safer for patients.

Below is our department's important Otolaryngology – Head & Neck Surgery recent research, as we take a look back at the outstanding research our team has accomplished.

Immunostimulatory Cancer-Associated Fibroblast Subpopulations Can Predict Immunotherapy Response in Head & Neck Cancer

Cancer-associated fibroblasts (CAF) have been implicated as potential mediators of checkpoint immunotherapy response. However, the extensive heterogeneity of these cells has precluded rigorous understanding of their immunoregulatory role in the tumor microenvironment.

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We performed high-dimensional single-cell RNA sequencing (scRNA-seq) on four patient tumors pretreatment and posttreatment from a neoadjuvant trial of patients with advanced-stage head and neck squamous cell carcinoma that were treated with the αPD-1 therapy, nivolumab. The head and neck CAF (HNCAF) protein activity profiles, derived from this cohort of paired scRNA-seq, were used to perform protein activity enrichment analysis on the 28-patient parental cohort of clinically annotated bulk transcriptomic profiles. Ex vivo coculture assays were used to test functional relevance of HNCAF subtypes.

Our findings demonstrate the functional importance of distinct HNCAF subsets in modulating the immunoregulatory milieu of human HNSCC. In addition, we have identified clinically actionable HNCAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.

Retrograde Cricopharyngeus Dysfunction: The Jefferson Experience

To describe our center's experience with the identification and treatment of retrograde cricopharyngeus dysfunction (R-CPD), a syndrome involving the inability to belch previously described by only one institution. Additionally, because all patients initially learned of their condition and sought treatment as a result of social media posts, we queried their source and comfort with this form of medical referral.

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Retrospective chart review of patients who underwent botulism toxin injection into the cricopharyngeus muscle for treatment of R-CPD from 2019 to 2022. Demographic data, most common symptoms at presentation, and response to treatment and complications were documented. Post-treatment questionnaires were reviewed.

 The majority of patients in our cohort were young and female. The inability to burp and bloating were the most common presenting symptoms. Social media was the primary source of referral. Our institution favors 80-100 units for an effective response.

Gender Gap Among Rhinology & Skull Base Surgeons

Since 2017, the number of women matriculating into medical school each year has outnumbered men, most recently at rates of 53.6% versus 46.2% in 2020.1, 2 Similarly, the proportion of female otolaryngology residents has increased from 27.5% in 2008 to 38% in 2019. Despite this, the percentage of actively practicing female otolaryngologists has remained relatively stable, comprising 11.2% of the workforce in 2008 and 12.3% in 2019.3, four women were found to make up 18% of practicing rhinologists.5 This study examines the rhinology workforce and aims to evaluate trends in the rhinology fellowship match, fellow job placement on graduation, and career trends between men and women..

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Since 2017, the number of women matriculating into medical school each year has outnumbered men, most recently at rates of 53.6% versus 46.2% in 2020.1, 2 Similarly, the proportion of female otolaryngology residents has increased from 27.5% in 2008 to 38% in 2019. Despite this, the percentage of actively practicing female otolaryngologists has remained relatively stable, comprising 11.2% of the workforce in 2008 and 12.3% in 2019.3, 4 Women were found to make up 18% of practicing rhinologists.5 This study examines the rhinology workforce and aims to evaluate trends in the rhinology fellowship match, fellow job placement on graduation, and career trends between men and women.

Data were collected on all rhinology fellows from 1992 to 2020 using the American Rhinologic Society (ARS) website and program websites. Fellowship program websites were explored and gender differences in the faculty were noted.

Of the 36 ARS sanctioned programs, 33 had matriculation data available. Between 1992 and 2020, 397 physicians graduated from ARS fellowship programs in the United States, Canada, and Australia; 78 (19.6%) were women and 319 (80.4%) were men. A total of 198 (51.8%) entered academic positions (43 women [21.7%]). Graduation year was available for 378 graduates. Over the past two decades (2000–2010 vs 2011–2020), although an increase in the number of female fellows from 18 (18.8%) to 56 (20.8%) and male fellows from 78 (81.2%) to 213 (79.2%) was observed, the proportion of men and women completing fellowship remained stable (odds ratio [OR], 1.13; 95% confidence interval [CI], 0.63 – 2.05 [p = 0.66]). Of the 36 rhinology fellowship program directors, only two (5.5%) were women. 

Trial in Progress: Preliminary Data on Impact of a Virtual Reality 3D Modeling Protocol on Surgeon Task Load Burden

Surgical margins are the single most important predictor of locoregional recurrence in head and neck squamous cell carcinoma and one of the most important prognosticating factors. VR may potentially improve conceptualization of complex 3-dimensional intraoperative wounds as well as intraoperative communication between surgeon and pathologist at no risk to patients. This trial aimed to determine the feasibility of implementing a novel VR/3D CEP and measure its impact on surgeon task load burden. 

Poster (PDF)

Results from post-VR surveys (N=10) showed 100% of HNC surgeons found the VR planning to be useful and felt the protocol would be easily integrated into normal workflow. 80% of post-VR survey respondents were able to clearly visualize the tumor on Medical Holodeck. 30% of post-VR survey respondents indicated the VR protocol led to a change in surgical plan.

Reduced gastroesophageal reflux disease symptom severity following upper airway surgery for comorbid obstructive sleep apnea

To evaluate patient-reported quality of life pertaining to gastroesophageal reflux disease symptoms in patients undergoing upper airway surgery for comorbid obstructive sleep apnea.

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A prospective survey-based study was conducted on patients with gastroesophageal reflux disease and comorbid obstructive sleep apnea receiving surgery from July 2020–December 2020. Patients completed the Gastroesophageal Reflux Disease-Health Related Quality of Life Questionnaire at two time-points: one week before surgery and at 6 months following surgery. Disease-related symptoms were rated from 0 (no symptoms) to 5 (incapacitating symptoms). Patient survey scores, demographics, medications, and sleep study parameters were collected for analysis. A p-value <0.05 indicated statistical significance.

Our results suggest that upper airway surgery to treat obstructive sleep apnea may have a positive impact on patient-reported symptoms of gastroesophageal reflux disease, and further investigation into the role of surgery in this setting for improvement of both quality of life and true clinical disease severity is merited.

Unique volatile metabolite signature of sinonasal inverted papilloma detectable in plasma and nasal secretions

Sinonasal inverted papilloma (SNIP) is a benign neoplasm with aggressive features, including a high recurrence rate and a propensity for malignant transformation. Accurate diagnosis with complete resection and the need for close long-term surveillance is widely accepted as standard management. In this study, we investigate whether SNIP produces a unique volatile metabolite signature, which may ultimately lead to a novel approach to diagnose and monitor SNIP.

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Whole blood and nasal secretions from patients with SNIP and healthy age-, sex-, and smoking-status-matched controls, were collected. There were 56 blood samples and 42 nasal secretion samples collected. The volatile metabolite signature of SNIP plasma and nasal secretion samples were compared with those of healthy controls using chromatography.

This study suggests that SNIP produces a unique, detectable volatile metabolite signature. With further investigation, this can have dramatic clinical implications for diagnosis and monitoring. Although most volatile metabolite studies have investigated solid-organ malignancy, this novel study addresses a benign sinonasal neoplasm by using nasal secretions and plasma as an analysis medium, representing the first such study.

Rate of Fat Graft Volume Loss After Parotidectomy

Reconstruction after parotidectomy can include fat grafting, which allows for symmetry, but grafts have demonstrated volume loss over time.

This study aims to provide quantitative evidence for the rate of volume loss of fat grafts.

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Patients who received parotidectomy with fat graft reconstruction at a single institution from August 2016 to October 2020 were identified. Relationships between clinical factors and the logarithmic rate of fat graft volume loss were analyzed.

Twelve patients received parotidectomy, fat graft reconstruction, and underwent a postoperative magnetic resonance imaging (MRI) scan. Rate of fat graft volume loss was a mean of 1.8% per month (standard deviation [SD]: 2.1% per month). Total parotid fat graft volume loss was a mean of 57.4% (SD: 67.5%).

Fat grafts have the potential of 60% volume loss at approximately 1 year. If there is clinical suspicion that patients will require adjuvant radiation or have clinical factors such as a smoking or alcohol-use history, volume requirements may be even greater to maintain adequate parotid volume for aesthetic purposes.

Recurrence of premalignant oral cavity and oropharynx lesions after pulsed diode laser treatment

Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser.

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Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment.

Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate.

Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Impact of Head & Neck Cancer Diagnosis & Treatment on Patient-Partner Intimacy

To determine the effects of head and neck squamous cell carcinoma diagnosis and treatment on patient- and partner-perceived intimacy and to understand if a diagnosis of HPV-related head and neck squamous cell carcinoma influences patient-partner intimacy.

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An investigator-developed questionnaire was used to prospectively survey patients and partners in 2 groups based on human papillomavirus (HPV) status: HPV+ and HPV- at diagnosis (visit 1) and after treatment (visit 2). Surveys were scored on a 60-point scale, and results were categorized as follows: loss of intimacy (0-30), stable relationship (31-41), or improvement in intimacy (42-60). Responses of couples who participated together were assessed for concordance. Responses were considered discordant if patient and partner scores equated to different levels of perceived intimacy.

Patients and partners reported stable or improved intimacy at both time points, and most couples tended to agree on their levels of perceived intimacy. A diagnosis of HPV did not appear to significantly affect intimacy scores.

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