Surgical Navigation in the Anterior Skull Base Using 3-Dimensional Endoscopy and Surface Reconstruction.

Importance: Image guidance is an important adjunct for endoscopic sinus and skull base surgery. However, current systems require bulky external tracking equipment, and their use can interrupt efficient surgical workflow. Objective: To evaluate a trackerless surgical navigation system using 3-dimensional (3D) endoscopy and simultaneous localization and mapping (SLAM) algorithms in the anterior skull base. Design, Setting, and Participants: This interventional deceased donor cohort study and retrospective clinical case study was conducted at a tertiary academic medical center with human deceased donor specimens and a patient with anterior skull base pathology. Exposures: Participants underwent endoscopic endonasal transsphenoidal dissection and surface model reconstruction from stereoscopic video with registration to volumetric models segmented from computed tomography (CT) and magnetic resonance imaging. Main Outcomes and Measures: To assess the fidelity of surface model reconstruction and accuracy of surgical navigation and surface-CT model coregistration, 3 metrics were calculated: reconstruction error, registration error, and localization error. Results: In deceased donor models (n = 9), high-fidelity surface models of the posterior wall of the sphenoid sinus were reconstructed from stereoscopic video and coregistered to corresponding volumetric CT models. The mean (SD; range) reconstruction, registration, and localization errors were 0.60 (0.24; 0.36-0.93), 1.11 (0.49; 0.71-1.56) and 1.01 (0.17; 0.78-1.25) mm, respectively. In a clinical case study of a patient who underwent a 3D endoscopic endonasal transsphenoidal resection of a tubercular meningioma, a high-fidelity surface model of the posterior wall of the sphenoid was reconstructed from intraoperative stereoscopic video and coregistered to a volumetric preoperative fused CT magnetic resonance imaging model with a root-mean-square error of 1.38 mm. Conclusions and Relevance: The results of this study suggest that SLAM algorithm-based endoscopic endonasal surgery navigation is a novel, accurate, and trackerless approach to surgical navigation that uses 3D endoscopy and SLAM-based algorithms in lieu of conventional optical or electromagnetic tracking. While multiple challenges remain before clinical readiness, a SLAM algorithm-based endoscopic endonasal surgery navigation system has the potential to improve surgical efficiency, economy of motion, and safety.

Predictors of non-primary auditory and vestibular symptom persistence following surgical repair of superior canal dehiscence syndrome.

Objective: Patients with superior canal dehiscence syndrome (SCDS) can present with a plethora of auditory and/or vestibular symptoms associated with a bony defect of the superior semicircular canal. While surgical repair is a reasonable option for patients with significant localizing symptoms, the degree of clinical improvement will vary among patients and poses challenges in outcome prediction. This study aims to assess the relationship between preoperative and postoperative symptoms and identify predictors of symptom persistence following repair. Study design: Retrospective chart review. Setting: Tertiary neurotology single-institution care center. Main outcome measures: The primary outcome was to determine the proportion of resolved and persistent primary (most bothersome) and non-primary audiologic and vestibular symptoms following SCD repair. Secondary outcomes included comparison of patient, operative and radiologic characteristics between patients with resolved vs. persistent symptoms. Standardized patient questionnaires including 11 auditory and 8 vestibular symptoms were administered to patients at their preoperative and follow-up visits. Patient pre- vs. postoperative survey results, demographic and clinical characteristics, operative characteristics, audiometric data and cervical vestibular evoked myogenic potential (cVEMP) thresholds were compared via univariate χ2 and multivariate binary logistic regression analyses between those patients reporting full postoperative resolution of symptoms and persistence of one or more symptoms. Radiologic computed tomography (CT) measurements of superior canal dehiscence (SCD) defect size, location, and laterality were also compared between these two groups. Results: Of 126 patients (132 ears) included in our study, 119 patients (90.2%) reported postoperative resolution (n = 82, 62.1%) or improvement (n = 37, 28.0%) of primary (most bothersome) symptoms, while 13 patients (9.8%) reported persistence of primary symptoms. The median (interquartile range) and range between surgery and questionnaire completion were 9 (4-28), 1-124 months, respectively. Analyzing all symptoms (primary and non-primary) 69 (52.3%) and 68 (51.1%) patients reported complete postoperative auditory and vestibular symptom resolution, respectively. The most likely persistent symptoms included imbalance (33/65/67, 50.8%), positional dizziness (7/20, 35.0%) and oscillopsia (44/15, 26.7%). Factors associated with persistent auditory symptoms included history of seizures (0% vs. 7.6%, p = 0.023), auditory chief complaint (50.0% vs. 70.5%), higher PTA (mean 19.6 vs. 25.1 dB, p = 0.043) and higher cervical vestibular evoked myogenic potential (cVEMP) thresholds at 1000 Hz (mean 66.5 vs. 71.4, p = 0.033). A migraine diagnosis (14.0% vs. 41.9% p < 0.010), bilateral radiologic SCD (17.5% vs. 38.1%, p = 0.034) and revision cases (0.0% vs. 14.0%, p = 0.002) were associated with persistent vestibular symptoms. Neither SCD defect size nor location were significantly associated with symptom persistence (P > 0.05). Conclusions: Surgical repair for SCDS offers meaningful reduction in the majority of auditory and vestibular symptoms. However, the persistence of certain, mostly non-primary, symptoms and the identification of potential associated factors including migraines, PTA thresholds, cVEMP threshold, bilateral SCD, and revision cases emphasize the importance of individualized patient counseling and management strategies.

An External Validation Study for Automated Segmentation of Vestibular Schwannoma.

OBJECTIVE: To validate how an automated model for vestibular schwannoma (VS) segmentation developed on an external homogeneous dataset performs when applied to internal heterogeneous data. PATIENTS: The external dataset comprised 242 patients with previously untreated, sporadic unilateral VS undergoing Gamma Knife radiosurgery, with homogeneous magnetic resonance imaging (MRI) scans. The internal dataset comprised 10 patients from our institution, with heterogeneous MRI scans. INTERVENTIONS: An automated VS segmentation model was developed on the external dataset. The model was tested on the internal dataset. MAIN OUTCOME MEASURE: Dice score, which measures agreement between ground truth and predicted segmentations. RESULTS: When applied to the internal patient scans, the automated model achieved a mean Dice score of 61% across all 10 images. There were three tumors that were not detected. These tumors were 0.01 ml on average (SD = 0.00 ml). The mean Dice score for the seven tumors that were detected was 87% (SD = 14%). There was one outlier with Dice of 55%-on further review of this scan, it was discovered that hyperintense petrous bone had been included in the tumor segmentation. CONCLUSIONS: We show that an automated segmentation model developed using a restrictive set of siloed institutional data can be successfully adapted for data from different imaging systems and patient populations. This is an important step toward the validation of automated VS segmentation. However, there are significant shortcomings that likely reflect limitations of the data used to train the model. Further validation is needed to make automated segmentation for VS generalizable.

A Proof-of-Concept Computer Vision Approach for Measurement of Tympanic Membrane Perforations.

OBJECTIVE: Size, an important characteristic of a tympanic membrane perforation (TMP), is commonly assessed with gross estimation via visual inspection, a practice which is prone to inaccuracy. Herein, we demonstrate feasibility of a proof-of-concept computer vision model for estimating TMP size in a small set of perforations. METHODS: An open-source deep learning architecture was used to train a model to segment and calculate the area of a perforation and the visualized tympanic membrane (TM) in a set of endoscopic images of mostly anterior and relatively small TMPs. The model then computed relative TMP size by calculating the ratio of perforation area to TM area. Model performance on the test dataset was compared to ground-truth manual annotations. In a validation survey, otolaryngologists were tasked with estimating the size of TMPs from the test dataset. The primary outcome was the average absolute error of model size predictions and clinician estimates compared to sizes determined by ground-truth manual annotations. RESULTS: The model's average absolute error for size predictions was a 0.8% overestimation for all test perforations. Conversely, among the 38 survey respondents, the average clinician error was a 11.0% overestimation (95% CI, 5.2-16.7%, p = 0.003). CONCLUSIONS: In a small sample of TMPs, we demonstrated a computer vision approach for estimating TMP size is feasible. Further validation studies must be done with significantly larger and more heterogenous datasets. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:2906-2911, 2024.

Proof-of-Concept Computer Vision Model for Instrument and Anatomy Detection During Transcanal Endoscopic Ear Surgery.

High-definition video captured during transcanal endoscopic ear surgery (TEES) can serve as imaging data for computer vision algorithms. This report describes a proof-of-concept model for automated anatomy and instrument detection during TEES.

AI Model Versus Clinician Otoscopy in the Operative Setting for Otitis Media Diagnosis.

Prior work has demonstrated improved accuracy in otitis media diagnosis based on otoscopy using artificial intelligence (AI)-based approaches compared to clinician evaluation. However, this difference in accuracy has not been shown in a setting resembling the point-of-care. In this study, we compare the diagnostic accuracy of a machine-learning model to that of pediatricians using standard handheld otoscopes. We find that the model is more accurate than clinicians (90.6% vs 59.4%, P = .01). This is a step towards validation of AI-based diagnosis under more real-world conditions. With further validation, for example on different patient populations and in deployment, this technology could be a useful addition to the clinician's toolbox in accurately diagnosing otitis media.

Auditory and Vestibular Symptom Improvement With Surgery for Superior Canal Dehiscence Syndrome.

OBJECTIVE: (1) To measure the change in auditory and vestibular symptoms following superior canal dehiscence (SCD) surgery, and (2) to determine differences in clinical features and surgical outcomes between superior canal dehiscence syndrome (SCDS) patients with primarily auditory or vestibular complaints. STUDY DESIGN: Retrospective cohort study. SETTING: Single surgeon series at the tertiary academic medical center from 2002 to 2021. METHODS: Retrospective review of SCDS patients who underwent surgical repair. (1) Patients were administered a standardized symptom questionnaire at preoperative and follow-up visits, and results were compared with paired statistical testing. (2) Patients were divided into 2 cohorts based on either auditory or vestibular chief complaint and differences in demographic, clinical, and outcome variables were examined. RESULTS: Our study included 113 patients with 118 operated ears. Twenty-seven patients (24%) had radiographic bilateral dehiscence. 10/11 auditory symptoms (91%) and 5/8 vestibular symptoms (63%) solicited on the questionnaire improved significantly with surgery, except for nonpulsatile tinnitus, sense of imbalance, positional dizziness, and oscillopsia. Analyses stratified by chief complaint (auditory vs vestibular) revealed overall similar characteristics and surgical outcomes. Patients with chief vestibular complaints underwent surgery at an earlier age (45.5 vs 53.9 years, p < 0.05). CONCLUSION: SCD surgery alleviates a wide range of auditory and vestibular symptoms. Overall, we did not find significant differences between patients with chief auditory versus vestibular complaints, and both groups benefited from surgery. Symptoms are not directly linked to third-window physiology and certain vestibular symptoms may be more likely to persist. Bilateral dehiscence may play an important role in persistent symptoms as well.

Development of a Predictive Model for Persistent Dizziness Following Vestibular Schwannoma Surgery.

OBJECTIVE: In an era of vestibular schwannoma (VS) surgery where functional preservation is increasingly emphasized, persistent postoperative dizziness is a relatively understudied functional outcome. The primary objective was to develop a predictive model to identify patients at risk for developing persistent postoperative dizziness after VS resection. METHODS: Retrospective review of patients who underwent VS surgery at our institution with a minimum of 12 months of postoperative follow-up. Demographic, tumor-specific, preoperative, and immediate postoperative features were collected as predictors. The primary outcome was self-reported dizziness at 3-, 6-, and 12-month follow-up. Binary and multiclass machine learning classification models were developed using these features. RESULTS: A total of 1,137 cases were used for modeling. The median age was 67 years, and 54% were female. Median tumor size was 2 cm, and the most common approach was suboccipital (85%). Overall, 63% of patients did not report postoperative dizziness at any timepoint; 11% at 3-month follow-up; 9% at 6-months; and 17% at 12-months. Both binary and multiclass models achieved high performance with AUCs of 0.89 and 0.86 respectively. Features important to model predictions were preoperative headache, need for physical therapy on discharge, vitamin D deficiency, and systemic comorbidities. CONCLUSION: We demonstrate the feasibility of a machine learning approach to predict persistent dizziness following vestibular schwannoma surgery with high accuracy. These models could be used to provide quantitative estimates of risk, helping counsel patients on what to expect after surgery and manage patients proactively in the postoperative setting. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3534-3539, 2023.

Making Use of Artificial Intelligence-Generated Synthetic Tympanic Membrane Images.

This diagnostic study examines the application of generative artificial intelligence in clinical tool research and development.

Hospital-Negotiated Pricing of Cochlear Implants.

Access to cochlear implantation can be restricted by financial burden, and little is known about the extent to which cochlear implant (CI) devices prices may vary between hospitals or manufacturers. We performed a cross-sectional analysis of private payer-negotiated prices for CI devices. In total, 161 hospitals were analyzed. Prices varied widely across hospitals and between payers. Despite clinical equipoise between manufacturers with regards to CI user outcomes, significant differences in prices were identified, with higher prices for MED-EL ($38,478 ± 2633) than for Cochlear Ltd. ($34,150 ± 2418, p < .001). Markup analysis for Cochlear Ltd. devices revealed a mean 58.5% ± 7.4% markup in excess of the company's average sales price ($24,649). Negotiated prices were also at least $5000 lower when all 3 brands were offered at the same center (p < .05). Further research examining the influence of patient outcomes and hospital volume on prices are needed.

Generation of synthetic tympanic membrane images: Development, human validation, and clinical implications of synthetic data.

Synthetic clinical images could augment real medical image datasets, a novel approach in otolaryngology-head and neck surgery (OHNS). Our objective was to develop a generative adversarial network (GAN) for tympanic membrane images and to validate the quality of synthetic images with human reviewers. Our model was developed using a state-of-the-art GAN architecture, StyleGAN2-ADA. The network was trained on intraoperative high-definition (HD) endoscopic images of tympanic membranes collected from pediatric patients undergoing myringotomy with possible tympanostomy tube placement. A human validation survey was administered to a cohort of OHNS and pediatrics trainees at our institution. The primary measure of model quality was the Frechet Inception Distance (FID), a metric comparing the distribution of generated images with the distribution of real images. The measures used for human reviewer validation were the sensitivity, specificity, and area under the curve (AUC) for humans' ability to discern synthetic from real images. Our dataset comprised 202 images. The best GAN was trained at 512x512 image resolution with a FID of 47.0. The progression of images through training showed stepwise "learning" of the anatomic features of a tympanic membrane. The validation survey was taken by 65 persons who reviewed 925 images. Human reviewers demonstrated a sensitivity of 66%, specificity of 73%, and AUC of 0.69 for the detection of synthetic images. In summary, we successfully developed a GAN to produce synthetic tympanic membrane images and validated this with human reviewers. These images could be used to bolster real datasets with various pathologies and develop more robust deep learning models such as those used for diagnostic predictions from otoscopic images. However, caution should be exercised with the use of synthetic data given issues regarding data diversity and performance validation. Any model trained using synthetic data will require robust external validation to ensure validity and generalizability.

Roid Rage: Historical Perspective on the Emergence of Oral Steroids as a Treatment of Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVES: To review the historical circumstances that led to the emergence of corticosteroid therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) and to discuss how this history has influenced current perspectives on the condition. METHODS: PubMed and Google scholar were used to identify articles of ISSNHL and oral corticoid steroid use. Historical articles accessed through our institutional medical library were also reviewed. RESULTS: The use oral corticosteroids as a treatment for ISSNHL was seemingly influenced by three key historical circumstances that, together, provided the substrate for the treatment's use in ISSNHL. First, ISSNHL was a frustrating condition with uncertainty regarding its etiology and few reliable treatment options. Second, the discovery of corticosteroids was awarded the Nobel Prize in 1950, which led to widespread application of this therapy. Third historical circumstance was the evolution and emergence of more rigorous methodological study designs in clinical research. In 1980, these events culminated in a double-blind study evaluating the effectiveness of oral steroids for treatment of ISSNHL. Interestingly, this study is often misrepresented as a randomized controlled trial, which ultimately contributed to adoption of a new standard for treatment in ISSNHL. Research subsequent to these historical events has challenged the notion of corticosteroids as a gold standard but has not altered the historically established paradigm of corticosteroid treatment. CONCLUSIONS: The use of steroids as a treatment for ISSNHL evolved from our specialty's need to address a complex condition, a novel therapeutic discovery, and a landmark study that met emerging methodological standards. Despite these strong historical foundations, ISSNHL remains a condition with an unknown etiology and the therapeutic value of corticosteroids remains unpredictable despite their gold standard label.

Pediatric Endoscopic Endonasal Skull Base Surgery: A Retrospective Review Over 11 Years.

OBJECTIVE: To show the safety and efficacy of the endoscopic endonasal approach (EEA) for skull base surgery in pediatric patients through descriptive analysis of cases over an 11-year period. METHODS: The study comprised 94 patients undergoing EEA for skull base surgery, between January 2007 and June 2018, at 2 tertiary pediatric hospitals. Descriptive statistics are presented regarding the presentation, intraoperative details, and complications. RESULTS: Over the study period, 130 surgeries were performed in 94 patients: 94 primary surgeries and 36 reoperations. The mean patient age was 13.8 years and 48.9% of patients were female. Presenting signs/symptoms included endocrinopathies (56.4%), vision abnormalities (37.2%), and cranial nerve deficits (20.2%). EEA alone was used in 95.7% of primary surgeries and 91.7% of reoperations. Diseases treated included craniopharyngioma (18.1%), pituitary adenoma (17.0%), Rathke cleft cyst (13.8%), chordoma (9.6%), osteosarcoma (5.3%), juvenile nasopharyngeal angiofibroma (4.3%), skull base fracture (4.3%), and encephalocele (3.2%). A lumbar drain was used in 20.2% of primary surgeries and 25% of reoperations. A nasoseptal flap was used in 36.2% of primary surgeries and 25% of reoperations. Postoperative complications included cerebrospinal fluid leak (12.8%), sinusitis (7.4%), bacterial meningitis (3.2%), and carotid artery injury in 1 reoperation. CONCLUSIONS: EEA for anterior cranial base disease is safe and efficacious in pediatric patients and can be used to treat many of the rare and heterogenous diseases that arise in this anatomic location. Management strategies and rates of sinonasal and intracranial complications including cerebrospinal fluid leak rate are similar to those reported in adult cohorts.

Development of a Predictive Model for Individualized Hearing Aid Benefit.

OBJECTIVES: To develop a model to predict individualized hearing aid benefit. To provide interpretations of model predictions on global and individual levels. METHODS: We compiled a data set of patients with hearing loss who trialed hearing aids and completed the Client Oriented Scale of Improvement (COSI) questionnaire, a validated patient-reported outcome measure of hearing aid benefit. Features included demographic, medical, and audiological measures. The outcome was the COSI score for change in listening ability with hearing aids, scaled from 1 to 5. Model development was performed using fivefold cross-validation repeated three times with hyperparameter tuning. Model performance was assessed using the root mean squared error (RMSE) of the COSI scores. Model interpretation was performed using Shapley Additive Explanations. RESULTS: The data set comprised 1,286 patients across 3,523 listening situations. The best performing model was random forest with an RMSE of 0.80, found to be significantly better than the next best model (eXtreme gradient boosting with RMSE of 0.85, p < 0.01). The most important features in predicting hearing aid benefit were shorter duration of hearing aid use, higher pure-tone average in the better hearing ear, and younger age. CONCLUSION: We have developed a predictive model for hearing aid benefit that can also provide individualized explanations of model predictions. Predictive modeling could be a useful tool in assessing a patient's candidacy and predicted benefit from hearing aids.

"Human vs Machine" Validation of a Deep Learning Algorithm for Pediatric Middle Ear Infection Diagnosis.

OBJECTIVE: We compared the diagnostic performance of human clinicians with that of a neural network algorithm developed using a library of tympanic membrane images derived from children taken to the operating room with the intent of performing myringotomy and possible tube placement for recurrent acute otitis media (AOM) or otitis media with effusion (OME). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center from 2018 to 2021. METHODS: A training set of 639 images of tympanic membranes representing normal, OME, and AOM was used to train a neural network as well as a proprietary commercial image classifier from Google. Model diagnostic prediction performance in differentiating normal vs nonpurulent vs purulent effusion was scored based on classification accuracy. A web-based survey was developed to test human clinicians' diagnostic accuracy on a novel image set, and this was compared head to head against our model. RESULTS: Our model achieved a mean prediction accuracy of 80.8% (95% CI, 77.0%-84.6%). The Google model achieved a prediction accuracy of 85.4%. In a validation survey of 39 clinicians analyzing a sample of 22 endoscopic ear images, the average diagnostic accuracy was 65.0%. On the same data set, our model achieved an accuracy of 95.5%. CONCLUSION: Our model outperformed certain groups of human clinicians in assessing images of tympanic membranes for effusions in children. Reduced diagnostic error rates using machine learning models may have implications in reducing rates of misdiagnosis, potentially leading to fewer missed diagnoses, unnecessary antibiotic prescriptions, and surgical procedures.

A Rare Complication of Chronic Otitis Media: Central Skull Base Osteomyelitis Managed With Combined Endoscopic Transmastoid and Transsphenoidal Debridement.

OBJECTIVE: This report describes a case of otogenic central skull base osteomyelitis (CSBO) requiring complex surgical intervention and reviews the literature on management of this entity. PATIENT: A 76-year-old man presented with a nearly 20-year history of chronic otomastoiditis and cholesteatoma with ultimate progression to severe CSBO with involvement of the petrous apex, clivus, and craniocervical junction. INTERVENTIONS: CSBO was managed with culture-directed antibiotic therapy, hyperbaric oxygen, and surgical intervention including serial combined endoscopic transmastoid and transsphenoidal debridements. MAIN OUTCOME MEASURES: Symptom resolution, antibiotic holiday, and stable disease on surveillance imaging. RESULTS: With antibiotic treatment and surgical debridement including creation of a drainage pathway from the skull base to the sphenoid sinus, intermittent stretches of disease quiescence were realized over the course of nearly a decade. Despite extensive debridement and skull base reconstruction, the patient ultimately succumbed to the disease process. CONCLUSIONS: CSBO poses significant management challenges to the otologist. Herein, we present a rare case of CSBO managed over a prolonged period of time with antibiotics and combined anterior and lateral skull base debridement.

Feeding Tube Placement Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To identify factors that may predict the need for feeding tubes in patients undergoing transoral robotic surgery (TORS) in the perioperative setting. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary center. METHODS: A retrospective series of patients undergoing TORS for oropharyngeal squamous cell carcinoma (OPSCC) was identified between October 2016 and November 2019 at a single tertiary academic center. Patient data were gathered, such as frailty information, tumor characteristics, and treatment, including need for adjuvant therapy. Multiple logistic regression was performed to identify factors associated with feeding tube placement following TORS. RESULTS: A total of 138 patients were included in the study. The mean age was 60.2 years (range, 37-88 years) and 81.9% were male. Overall 82.9% of patients had human papilloma virus-associated tumors, while 28.3% were current or former smokers with a smoking history ≥10 pack-years. Eleven patients (8.0%) had a nasogastric or gastrostomy tube placed at some point during their treatment. Five patients (3.6%) had feeding tubes placed perioperatively (<4 weeks after TORS), of which 3 were nasogastric tubes. Six patients (4.3%) had feeding tubes placed in the periadjuvant treatment setting for multifactorial reasons; 5 of which were gastrostomy tubes. Only 1 patient (0.7%) was gastrostomy dependent 1 year after surgery. Multiple logistic regression did not demonstrate any significant predictive variables affecting perioperative feeding tube placement following TORS for OPSCC. CONCLUSIONS: Feeding tubes are seldom required after TORS for early-stage OPSCC. With appropriate multidisciplinary planning and care, patients may reliably avoid the need for feeding tube placement following TORS for OPSCC.

Impact of surgical margins on local control in patients undergoing single-modality transoral robotic surgery for HPV-related oropharyngeal squamous cell carcinoma.

BACKGROUND: The impact of close surgical margins on oncologic outcomes in HPV-related oropharyngeal squamous cell carcinoma (HPV + OPSCC) is unclear. METHODS: Retrospective case series including patients undergoing single modality transoral robotic surgery (TORS) for HPV + OPSCC at three academic medical centers from 2010 to 2019. Outcomes were compared between patients with close surgical margins (<1 mm or requiring re-resection) and clear margins using the Kaplan-Meier method. RESULTS: Ninety-nine patients were included (median follow-up 21 months, range 6-121). Final margins were close in 22 (22.2%) patients, clear in 75 (75.8%), and positive in two (2.0%). Eight patients (8.1%) recurred, including two local recurrences (2.0%). Four patients died during the study period (4.0%). Local control (p = 0.470), disease-free survival (p = 0.513), and overall survival (p = 0.064) did not differ between patients with close and clear margins. CONCLUSIONS: Patients with close surgical margins after TORS for HPV + OPSCC without concurrent indications for adjuvant therapy may be considered for observation alone.

Opioid Usage and Prescribing Predictors Following Transoral Robotic Surgery for Oropharyngeal Cancer.

OBJECTIVE/HYPOTHESIS: Pain management following transoral robotic surgery (TORS) varies widely. We aim to quantify opioid usage following TORS for oropharyngeal squamous cell carcinoma (OPSCC) and identify prescribing predictors. STUDY DESIGN: Retrospective cohort study. METHODS: A consecutive series of 138 patients undergoing TORS for OPSCC were reviewed from 2016 to 2019. Opioid usage (standardized to morphine milligram equivalents [MME]) was gathered for 12 months post-surgery via prescribing record cross-check with the Massachusetts Prescription Awareness Tool. RESULTS: Of 138 OPSCC TORS patients, 92.8% were human papillomavirus (HPV) positive. Adjuvant therapy included radiation (XRT;67.4%) and chemoradiation (cXRT;6.5%). Total MME usage from start of treatment averaged 1395.7 MMEs with 76.4% receiving three prescriptions or less. Categorical analysis showed age <65, male sex, overweight BMI, lower frailty, former smokers, HPV+, higher T stage, and BOT subsite to be associated with increased MMEs. Adjuvant therapy significantly increased MMEs (TORS+XRT:1646.2; TORS+cXRT:2385.0; TORS alone:554.7 [P < .001]) and 12-month opioid prescription totals (TORS+XRT:3.2; TORS+cXRT:5.5; TORS alone:1.6 [P < .001]). Adjuvant therapy increased time to taper (total MME in TORS alone versus TORS+XRT/cXRT: 0 to 3 months:428.2 versus 845.5, 4 to 6 months:46.8 versus 541.8, 7 to 9 months:12.4 versus 178.6, 10 to 12 months:11.0 versus 4.4,[P < .001]). Positive predictors of opioid prescribing at the 4- to 6-month and 4- to 12-month intervals included adjuvant therapy (odds ratio [OR]:5.56 and 4.51) and mFI-5 score ≥3 (OR:36.67 and 31.94). Following TORS at 6-, 9-, and 12-month, 15.7%, 6.6%, and 4.1% were still using opioids. CONCLUSIONS: In OPSCC treated with TORS, opioid use tapers faster for surgery alone versus with adjuvant therapy. Opioid prescribing risks include adjuvant therapy and higher frailty index. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1888-E1894, 2021.

In situ hybridization for high risk HPV E6/E7 mRNA in oropharyngeal squamous cell carcinoma.

OBJECTIVES: To report a single institution's experience using human papillomavirus (HPV) E6/E7 mRNA in-situ hybridization (mRNA ISH) for HPV detection in oropharyngeal squamous cell carcinoma (OPSCC). To review the literature on HPV detection methods. STUDY DESIGN: Retrospective chart review, literature review. SETTING: Tertiary care academic hospital. SUBJECTS AND METHODS: We conducted a retrospective chart review of 122 OPSCC biopsy specimens. mRNA ISH was performed on formalin-fixed paraffin-embedded (FFPE) tissue with a pool of 18 high risk HPV probes using an automated stainer; p16 immunohistochemistry (IHC) was also performed. We conducted a literature review on HPV detection methods including p16 IHC, mRNA ISH, DNA ISH, and PCR. RESULTS: In our cohort, mRNA ISH had a sensitivity and specificity of 100% and 100% with reference to p16 (100% concordance). 2-year OS was 87.5% vs. 94.5% for p16/HPV-negative vs. positive patients. 2-year DFS was 60.0% vs. 84.2%. On literature review, mRNA ISH demonstrated consistently high sensitivity and specificity ranging from 88-98% and 90-100% respectively. In comparison, the specificity of p16 was 85-95%. CONCLUSIONS: Our report supports the use of mRNA ISH for HPV detection in OPSCC and validates its feasibility using automated tissue staining methods on FFPE tissue. Our findings and literature review support that mRNA ISH may have superior specificity and be easier to interpret than p16. Further study on the prognostic value and cost-effectiveness of mRNA ISH is warranted and may establish this HPV detection method as the "gold standard."