ChatENT: Augmented Large Language Model for Expert Knowledge Retrieval in Otolaryngology-Head and Neck Surgery.

OBJECTIVE: The recent surge in popularity of large language models (LLMs), such as ChatGPT, has showcased their proficiency in medical examinations and potential applications in health care. However, LLMs possess inherent limitations, including inconsistent accuracy, specific prompting requirements, and the risk of generating harmful hallucinations. A domain-specific model might address these limitations effectively. STUDY DESIGN: Developmental design. SETTING: Virtual. METHODS: Otolaryngology-head and neck surgery (OHNS) relevant data were systematically gathered from open-access Internet sources and indexed into a knowledge database. We leveraged Retrieval-Augmented Language Modeling to recall this information and utilized it for pretraining, which was then integrated into ChatGPT4.0, creating an OHNS-specific knowledge question & answer platform known as ChatENT. The model is further tested on different types of questions. RESULTS: ChatENT showed enhanced performance in the analysis and interpretation of OHNS information, outperforming ChatGPT4.0 in both the Canadian Royal College OHNS sample examination questions challenge and the US board practice questions challenge, with a 58.4% and 26.0% error reduction, respectively. ChatENT generated fewer hallucinations and demonstrated greater consistency. CONCLUSION: To the best of our knowledge, ChatENT is the first specialty-specific knowledge retrieval artificial intelligence in the medical field that utilizes the latest LLM. It appears to have considerable promise in areas such as medical education, patient education, and clinical decision support. The model has demonstrated the capacity to overcome the limitations of existing LLMs, thereby signaling a future of more precise, safe, and user-friendly applications in the realm of OHNS and other medical fields.

Surgiflo® hemostatic matrix versus NasoPore® nasal packing following postassium titanyl phosphate laser surgery for hereditary hemorrhagic telangiectasia: A randomized controlled trial.

Background: To help ensure adequate hemostasis immediately following potassium titanyl phosphate (KTP) laser treatment, many centres treating hereditary hemorrhagic telangiectasia (HHT) routinely use nasal packing post-operatively. The purpose of this study was to compare hemostatic thrombin matrix with standard packing for postoperative bleeding, patient pain, and comfort. Methods: A prospective, randomized, double-blinded, non-inferiority study was conducted with participants at an HHT centre of excellence (COE) and randomized to the treatment group with reconstituted thrombin gelatin matrix (Surgiflo®) or control group with a biodegradable synthetic polyurethane foam (NasoPore®). Adult subjects with confirmed HHT and moderate to severe epistaxis (a minimum calculated epistaxis severity score [ESS] of 4.0) warranting KTP laser treatment were recruited. Data was collected 2 weeks post operatively by a blinded reviewer completing a visual outcomes evaluation and each patient completing a subjective symptoms questionnaire. Non-parametric statistical analysis was employed. Results: Twenty-eight adult patients were randomized to the treatment and control arms with comparable preoperative epistaxis severity scores. Postoperative nasal bleeding was equivalent. Significantly less pain was found in the treatment arm (p = .005). While there were trends towards less obstruction and increased satisfaction in the treatment group as well as less crusting in the control group, these findings were not statistically significant. Allocation to the treatment group was associated with an approximately $75 higher cost. Conclusions: When compared to NasoPore® for hemostasis, Surgiflo® hemostatic matrix performed equivalently while causing less discomfort in HHT patients following nasal KTP treatment. Level of evidence: 1b.

Accuracy and Reliability of 3D Imaging for Facial Movement Evaluation: Validation of the VECTRA H1.

Three-dimensional imaging can be used to obtain objective assessments of facial morphology that is useful in a variety of clinical settings. The VECTRA H1 is unique in that it is relatively inexpensive, handheld, and does not require standardized environmental conditions for image capture. Although it provides accurate measurements when imaging relaxed facial expressions, the clinical evaluation of many disorders involves the assessment of facial morphology when performing facial movements. The aim of this study was to assess the accuracy and reliability of the VECTRA H1, specifically when imaging facial movement. Methods: The accuracy, intrarater, and interrater reliability of the VECTRA H1 were assessed when imaging four facial expressions: eyebrow lift, smile, snarl, and lip pucker. Fourteen healthy adult subjects had the distances between 13 fiducial facial landmarks measured at rest and the terminal point of each of the four movements by digital caliper and by the VECTRA H1. Intraclass correlation and Bland-Altman limits of agreement were used to determine agreement between measures. The agreement between measurements obtained by five different reviewers was evaluated by intraclass correlation to determine interrater reliability. Results: Median correlation between digital caliper and VECTRA H1 measurements ranged from 0.907 (snarl) to 0.921 (smile). Median correlation was very good for both intrarater (0.960-0.975) and interrater reliability (0.997-0.999). The mean absolute error between modalities, and both within and between raters was less than 2 mm for all movements tested. Conclusion: The VECTRA H1 met acceptable standards for the assessment of facial morphology when imaging facial movements.

Development of a patient reported outcome instrument for chronic sialadenitis.

BACKGROUND: Sialendoscopy assisted treatments are a minimally invasive management modality for chronic sialadenitis. Clinicians report improved patient quality of life (QoL) following sialendoscopy assisted treatments, but there exist gaps in current literature about patient reported outcomes (PROs). PROs are outcome measures developed based on patient perceptions. OBJECTIVE: The objective of this study was to create a PRO instrument for chronic sialadenitis, to assess the efficacy of sialendoscopy assisted treatments in improve patients' QoL. DESIGN: This four-phase qualitative study employed grounded theory methodology and a modified Delphi technique. In Phase I, ten patients were interviewed to identify the QoL domains impacted by chronic sialadenitis. In Phase II, these QoL domains were presented to a focus group of different chronic sialadenitis patients, who were asked to rank them by order of importance. A conceptual framework of QoL domains impacted by chronic sialadenitis was created based on patient consensus. Itemization of the PRO questionnaire was done by a focus group of four Otolaryngologists in phase III. Lastly, the questionnaire was completed in Phase IV by cognitive interviewing of five new chronic sialadenitis patients; ensuring ease of understanding and clarity. RESULTS: Patients identified 15 domains of QoL impacted by chronic sialadenitis, divided into three sub-scales: physical symptoms, psychosocial symptoms, and activity restriction. These domains provided the basis for creation of a 22-item PRO questionnaire, with a Likert-type response scale. CONCLUSION: Clinical application of the novel questionnaire produced by this study will allow for a patient-centered assessment of the patient reported effectiveness of sialendoscopy assisted therapies for management of chronic sialadenitis. Level of evidence Level V.

Clinical diagnostic utility of ultrasound-guided fine needle aspiration biopsy in parotid masses.

BACKGROUND: Fine needle aspiration (FNA) is a common diagnostic tool used in the initial evaluation of parotid masses. In the literature, variable diagnostic accuracy of FNA is reported. Therefore, when considering clinical management of these patients, the utility of FNA is unclear. The aim of this study was to determine the capability of ultrasound-guided FNA to differentiate between benign and malignant neoplasms. Further, the way in which FNA results affect clinical decision-making was assessed. METHODS: Retrospective data were collected for all patients who underwent parotidectomy at a large Canadian tertiary care center between 2011 and 2016. Patient demographics, preoperative imaging reports, preoperative FNA results, and final pathological diagnosis were analyzed. RESULTS: Of the 199 patients who underwent parotidectomy, 184 had preoperative ultrasound-guided FNA. There were a total of 13 non-diagnostic FNAs. In diagnosing malignancy, FNA had a sensitivity and specificity of 71.4% and 98.7%, respectively. The positive predictive value (PPV) was 83.3%. The negative predictive value was 97.5%. Of the non-diagnostic FNAs, 2 out of 13 (15.4%) were deemed malignant neoplasms on final pathology. CONCLUSION: FNA is a useful adjunct in the work-up of parotid masses, but it should be used with caution. Due to limited sensitivity, it should not be relied upon as the sole determinant of a surgeon's management plan.

CSO (Canadian Society of Otolaryngology - Head & Neck Surgery) position paper on rhinologic and skull base surgery during the COVID-19 pandemic.

Healthcare services in many countries have been partially or completely disrupted by the Coronavirus (COVID-19) pandemic since its onset in the end of 2019. Amongst the most impacted are the elective medical and surgical services in order to conserve resources to care for COVID-19 patients. As the number of infected patients decrease across Canada, elective surgeries are being restarted in a staged manner. Since Otolaryngologists - Head & Neck Surgeons manage surgical diseases of the upper aerodigestive tract where the highest viral load reside, it is imperative that these surgeries resume in a safe manner. The aim of this document is to compile the current best evidence available and provide expert consensus on the safe restart of rhinologic and skull base surgeries while discussing the pre-operative, intra-operative, and post-operative care and tips. Risk assessment, patient selection, case triage, and pre-operative COVID-19 testing will be analyzed and discussed. These guidelines will also consider the optimal use of personal protective equipment for specific cases, general and specific operative room precautions, and practical tips of intra-operative maneuvers to optimize patient and provider safety. Given that the literature surrounding COVID-19 is rapidly evolving, these recommendations will serve to start our specialty back into elective rhinologic surgeries over the next months and they may change as we learn more about this disease.

The Functional & Quality of Life Outcomes of Total Glossectomy with Laryngeal Preservation.

BACKGROUND: The tongue is an essential organ for human interaction, communication and survival. To date, there is a paucity of objective functional, patient reported, or quality of life outcomes of patients undergoing a total glossectomy with preservation of the larynx (TGLP). OBJECTIVE: To examine prospectively collected objective, self-reported functional and quality of life (QOL) data in patients undergoing TGLP and free flap reconstruction. METHODS: Sixteen TGLP patients were identified in the prospective head and neck cancer and functional outcomes database between January of 2009 and December 2017. Data collection included patient age, sex, performance status, TNM staging, diagnosis and adjuvant treatment. Swallowing and speech functions were measured and prospectively recorded pre- and postoperatively. Patient reported outcomes were measured with the Speech Handicap Index (SHI) and the M.D. Anderson Dysphagia Inventory (MDADI). RESULTS: All patients had a significant reduction in their objective swallowing (P = 0.035), sentence (P = 0.001) and word intelligibility (P < .001) scores. There was no significant reduction in SHI or total MDADI scores. All patients maintained their QOL in the post-treatment time frame. There was no relationship between free-flap type and outcome. CONCLUSION: Total glossectomy with laryngeal sparing and free flap reconstruction results in significant reduction in objective functional measurements, but patients report stable functional and quality of life outcomes after treatment.

Development of the Alberta facial clinical evaluation scale: A patient-centred outcomes instrument for facial nerve paralysis.

OBJECTIVES: Facial nerve paralysis has functional, psychological and social consequences for patients. Traditionally, outcome measurements for facial nerve injuries have been clinician derived. Recent literature has shown that patient perspective is valuable and necessary in outcomes research. This study aimed to identify patient domains of concern and subsequently, develop a point-of-care questionnaire for clinical use. DESIGN: This mixed-methods prospective study was completed in three phases. In Phase I, 15 facial nerve injury patients were interviewed individually. Interviews were digitally recorded, transcribed and coded with NVivo software. Analysis led to a conceptual framework detailing the most important quality of life outcomes. During Phase II, a focus group was held with five new patients in order to prioritise the outcome themes to a top six list. A second focus group was held with Otolaryngology-Head and Neck staff surgeons to create a 25-item questionnaire based on these six themes. In Phase III, the questionnaire was administered to 10 new patients to test for comprehension. SETTING: University of Alberta Hospital, Edmonton, Alberta, Canada. PARTICIPANTS: A total of 30 patients with facial nerve injury were included in the various phases in the study. In addition, 5 staff Otolaryngology-Head and Neck surgeons participated as focus group contributors. MAIN OUTCOME MEASURES: Domains of concern and quality of life outcomes as reported by facial nerve injury patients. RESULTS: Patients identified a total of 16 themes encompassing both functional and psychological deficits related to their facial nerve injury. From these findings, a 25-item Likert-type scale, the A-FaCE scale, was developed for clinical use. CONCLUSIONS: Patients with facial nerve paralysis experience functional and psychological deficits. This study led to the creation of the first patient-reported instrument for this population that addresses functional impairment, social function, psychological well-being and self-perception of appearance.

Objective and subjective sinonasal and pulmonary outcomes in aspirin desensitization therapy: A prospective cohort study.

OBJECTIVE: Aspirin exacerbated respiratory disease (AERD) patients are challenging to manage with sinonasal and pulmonary symptoms refractory to maximal medical and surgical therapies. Our objective was to comprehensively examine objective and validated, disease-specific subjective sinonasal and pulmonary outcomes of aspirin (ASA) desensitization therapy in this patient population. METHODS: Prospective cohort study at an academic tertiary center. AERD patients with a history of chronic rhinosinusitis with nasal polyposis (CRSwNP), prior diagnosis of asthma, and a history of ASA sensitivity were eligible for inclusion. Patients underwent ASA desensitization using an established institutional protocol and continued on a 650mg twice daily maintenance dose. Baseline Sinonasal Outcome Test (SNOT-22) and Asthma Control Questionnaire (ACQ) responses, acoustic rhinometry, peak flow readings, and endoscopic scoring of nasal polyps were recorded prior to desensitization and after 6months of maintenance therapy. RESULTS: Twelve patients were recruited for participation and underwent desensitization. Eight patients continued maintenance therapy and follow up at 6months. Prior to desensitization, patients reported bothersome sinonasal symptoms with a median SNOT-22 score of 30.0±34.5 (interquartile range (IQR)). There was significant improvement after 6months of maintenance therapy to a median SNOT-22 score of 18.5±17.3 (p=0.025, Wilcoxon signed rank test). Acoustic rhinometry, endoscopic scores, ACQ and forced expiratory volume values remained stable at 6months. CONCLUSIONS: AERD patients may benefit from ASA desensitization with subjective sinonasal symptom improvement at 6months and stable asthma and objective sinonasal measures. Further discussion is needed in the otolaryngology community regarding ASA desensitization in AERD management.

Validation of a novel method for localization of parathyroid adenomas using SPECT/CT.

BACKGROUND: Accurate localization of parathyroid adenomas is of critical importance in surgical planning for minimally invasive parathyroidectomy. SPECT/CT is considered the investigation of choice but has limitations regarding localization of superior versus inferior adenomas. We proposed a novel method for localization using SPECT/CT by determining the anterior-posterior relationship of the adenoma to a horizontal line in the coronal plane through the tracheoesophageal groove. Our objective was to determine the accuracy, validity, and inter-rater reliability of this method. METHOD: This was a retrospective review of patients who underwent parathyroidectomy for a single adenoma between 2010-2017. SPECT/CT images were reviewed by two staff Otolaryngologists, a Radiologist, an Otolaryngology fellow and Otolaryngology resident. Results were compared using intra-operative report as the gold standard. Overall accuracy in determining superior/inferior and right/left adenomas was calculated, as well as Cohen's Kappa to determine agreement with operative report and inter-rater reliability. The performance was compared to that of the original radiology report. RESULTS: One hundred thirty patients met criteria and were included. Our method correctly identified the location of the adenoma in terms of both side and superior/inferior position in 80.4% [76 - 84%] of patients, which considerably outperformed the original radiology report at 48.5% [4-78%] accuracy. The agreement level between our method and operative report was high (Kappa=0.717 [0.691-0.743]), as was the inter-rater reliability (Kappa=0.706 [0.674-0.738]). CONCLUSION: We report a novel method for localization of parathyroid adenomas using SPECT/CT which outperforms standard radiology reporting. This tool can be used by surgeons and radiologists to better inform and plan for minimally invasive parathyroidectomy.

Brief electrical stimulation and synkinesis after facial nerve crush injury: a randomized prospective animal study.

BACKGROUND: Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurement in these studies has not been precise or accurate. Furthermore, no previous studies have been able to demonstrate the effect of BES on synkinesis. The objective of this study is to examine the effect of brief electrical stimulation (BES) on facial nerve function and synkinesis in a rat model. METHODS: Four groups of six rats underwent a facial nerve injury procedure. Group 1 and 2 underwent a crush injury at the main trunk of the nerve, with group 2 additionally receiving BES for 1 h. Group 3 and 4 underwent a transection injury at the main trunk, with group 4 additionally receiving BES for 1 h. A laser curtain model was used to measure amplitude of whisking at 2, 4, and 6 weeks. Fluorogold and fluororuby neurotracers were additionally injected into each facial nerve to measure synkinesis. Buccal and marginal mandibular branches of the facial nerve were each injected with different neurotracers at 3 months following injury. Based on facial nucleus motoneuron labelling of untreated rats, comparison was made to post-treatment animals to deduce whether synkinesis had taken place. All animals underwent trans-cardiac perfusion with subsequent neural tissue sectioning. RESULTS: At week two, the amplitude observed for group 1 and 2 was 14.4 and 24.0 degrees, respectively (p = 0.0004). Group 4 also demonstrated improved whisking compared to group 3. Fluorescent neuroimaging labelling appear to confirm improved pathway specific regeneration with BES following facial nerve injury. CONCLUSIONS: This is the first study to use an implantable stimulator for serial BES following a crush injury in a validated animal model. Results suggest performing BES after facial nerve injury is associated with accelerated facial nerve function and improved facial nerve specific pathway regeneration in a rat model.

Acellular Human Dermal Allograft as a Graft for Nasal Septal Perforation Reconstruction.

BACKGROUND: Nasal septal perforations pose a troubling source of morbidity for patients and a difficult problem for the otolaryngologist. Multiple surgical techniques have been tried, with inconsistent success. Prosthetic nasal buttons also have limitations, including patient intolerance and dissatisfaction. Acellular human dermal allograft (AlloDerm) has been described as an alternative material for septal perforation repair. The authors studied objective and subjective outcomes, including quantification of the patient's symptoms in septal perforation repair with AlloDerm. METHODS: The authors performed a prospective cohort study of 12 patients with 1- to 2-cm anterior septal perforations who were recruited from a tertiary care practice. Patients with admitted smoking or cocaine use in the previous 3 months or vascular or granulomatous diseases were excluded. Subjective scores on the Sino-nasal Outcome Test-22, along with objective nasal endoscopy and acoustic rhinometry measures, were collected at baseline and 2, 4, and 12 weeks postoperatively. Patients were followed for reperforation 9 to 20 months postoperatively. Data were normalized to baseline values and analyzed using analysis of variance and Bonferroni correction. RESULTS: Successful closure of the septal perforation was obtained in 10 of 12 patients and confirmed with rigid nasal endoscopy. Nasal symptom scores (Sino-nasal Outcome Test-22 ) were significantly reduced to 52.8 percent (95 percent CI, 35.1 to 70.5 percent; p < 0.01) of baseline symptoms at 4 weeks postoperatively. At 12 weeks postoperatively, symptoms were measured at 26.6 percent (95 percent CI, 10.9 to 42.1 percent; p < 0.01) of baseline symptoms. Acoustic rhinometry confirmed perforation closure, demonstrating a reduction in cross-sectional nasal area from baseline of 55.1 percent (95 percent CI, 37.7 to 66.8 percent; p < 0.01). CONCLUSION: This is the first study to use objective and subjective measurements to confirm success with acellular dermis allograft as an adjunct for septal perforation repair, demonstrating a statistically significant reduction in patient nasal symptoms following repair. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Management of Persistent Epistaxis Using Floseal Hemostatic Matrix vs. traditional nasal packing: a prospective randomized control trial.

BACKGROUND: Epistaxis is the most common emergent consultation to otolaryngology-head & neck surgery (OHNS) and with 60% of the population having experienced an episode and 1.6 in 10,000 requiring hospitalization in their lifetime. In preliminary studies Floseal® (Baxter, USA) Hemostatic Matrix has shown efficacy in up to 80% of persistent anterior epistaxis. We sought to evaluate the clinical efficacy and cost-effectiveness of Floseal® (Baxter, USA) compared to traditional nasal packing for persistent epistaxis. METHODS: A prospective, randomized controlled trial was conducted on all adult patients consulted to the OHNS service at the tertiary referral centers of the University of Alberta Hospital and Royal Alexandra Hospital for persistent epistaxis. Patients were randomized to the Floseal® (Baxter, USA) or traditional packing study arms. Our main clinical outcome measures were: 1) Hemostasis directly following treatment and at 48 h post-treatment, and 2) self-reported patient comfort at 48 h post-treatment. Further, trial data was used for a formal cost-effectiveness analysis to determine incremental cost-effectiveness ratio (ICER). Univariate sensitivity analysis and uncertainty analysis were performed. RESULTS: There were no significant differences between groups for initial hemostasis (76.9% vs. 84.6%, p = 1.000) or, hemostasis at 48 h (76.9% vs. 69.2%, p = 1.000), requirement for admission (15.4% vs. 46.1%, p = 0.2016) or 30-day re-presentation rates (15.4% vs. 46.1%, p = 0.2016). Floseal® (Baxter, USA) was superior for decreased pain during placement (2.42 vs. 7.77, p = 0.0022), treatment (0.50 vs. 4.46, p = 0.0007) and removal (0 vs. 3.85, p = 0.0021). Floseal® (Baxter, USA) provides an average $1567.61 per patient savings from the single-payer system point of view and has an ICER of - $11,891 per re-bleed prevented (95% CI: -$37,658 to +$473). Uncertainty analysis shows that Floseal® has >90% chance of not only being cost-effective, but the dominant (preferred) treatment. CONCLUSIONS: Floseal® (Baxter, USA) was demonstrated to be an effective, comfortable and cost-effective alternative treatment of persistent epistaxis when compared to traditional packing methods for patients referred to OHNS with a normal coagulation profile. TRIAL REGISTRATION: Trial registration number: NCT02488135 . Date registered: June 26, 2015.

A High-Definition Video Teaching Module for Thyroidectomy Surgery.

OBJECTIVE: With the changing landscape of postgraduate surgical education to competency-based curricula, there emerges a need for alternative forms of training. Video teaching modules have been shown to be effective tools in surgical education, complementing traditional postgraduate curricula. There is a lack of validated modules described in the literature, specifically for teaching thyroidectomy. The primary objective of this study was to develop and validate a high definition video-based teaching module instructing thyroidectomy surgery to Otolaryngology-Head and Neck Surgery trainees. DESIGN: This prospective study included intermediate to senior Otolaryngology-Head and Neck Surgery residents. Each participant first performed a thyroid lobectomy, serving as the initial assessment. After a washout period of at least 3 weeks, each participant was given the teaching module. The 15-minute module was developed using a 3-camera system and detailed a step-by-step approach to the surgery. After exposure to the module, each trainee performed the same procedure. Recordings of both procedures were deidentified and reviewed by a blinded, independent evaluator. Scoring was done using the Observational Clinical Human Reliability Assessment (OCHRA) system. SETTING: University of Alberta Hospital and Royal Alexandra Hospital, Edmonton, Alberta, Canada. PARTICIPANTS: A total of 6 intermediate to senior Otolaryngology-Head and Neck Surgery residents entered and completed the study. RESULTS: The mean error rate was 8.8 errors per procedure before module exposure and 4.5 errors per procedure after exposure, representing a 49% decrease in error occurrence (p < 0.05). The mean staff takeover event rate was 10.5 takeovers per procedure prior to module exposure and 5.0 takeovers per procedure after exposure, representing a 52% decrease in error occurrence (p < 0.05). CONCLUSION: High-definition video teaching modules are a useful complement to traditional surgical training. In a climate where new innovations for teaching thyroid surgery are needed, properly constructed and validated video teaching modules can serve as important tools in supplementing traditional surgical training.

Transoral robotic surgery with radial forearm free flap reconstruction: case control analysis.

BACKGROUND: The resection of large oropharyngeal tumors traditionally involves a lip-splitting mandibulotomy for adequate margin visualization and free flap reconstruction of the surgical defect. Transoral robotic surgery (TORS) has emerged as a technique that can resect large and complex oropharyngeal tumors, avoiding a lip-splitting approach. The aim of this study is to compare the lip-splitting mandibulotomy approach versus TORS for the management of advanced stage oropharyngeal carcinomas. METHODS: Prospectively collected data from 18 patients with advanced stage oropharyngeal squamous cell carcinoma (OPSCC) who received TORS with radial forearm free flap reconstruction (RFFF) was compared to a matched cohort of 39 patients who received a lip-splitting mandibulotomy and RFFF. Patients were matched for stage, p16 positivity, smoking, age and gender. Length of hospital stay (LOHS), tracheostomy decanulation time, operative time, surgical margin status, and post-operative complications were compared between groups. RESULTS: Patients who received TORS with RFFF had a significantly lower mean LOHS, compared to patients who were treated by lip-splitting mandibulotomy and RFFF (14.4 vs 19.7 days, p = 0.03). No significant differences were seen between groups in terms of operative time, tracheostomy decannulation time, margin positivity and post-operative complications. CONCLUSION: TORS with radial forearm free flap reconstruction is a safe, effective and cost-saving alternative to the lip-splitting mandibulotomy approach for the treatment of advanced stage OPSCC.

Ultrasensitive detection of oncogenic human papillomavirus in oropharyngeal tissue swabs.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) caused by oncogenic human papillomavirus (HPV) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV E6 and E7 oncoproteins or by p16 immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as an ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. To validate the use of a minimally invasive assay for detection of oncogenic HPV based on oropharyngeal swabs using ddPCR. Secondary objectives were to compare the accuracy of ddPCR swabs to fresh tissue p16 IHC and RT-qPCR, and to compare the cost of ddPCR with p16 IHC. METHODS: We prospectively included patients with p16+ oral cavity/oropharyngeal cancer (OC/OPSCC), and two control groups: p16- OC/OPSCC patients, and healthy controls undergoing tonsillectomy. All underwent an oropharyngeal swab with ddPCR for quantitative detection of E6 and E7 mRNA. Surgical specimens had p16 IHC performed. Agreement between ddPCR and p16 IHC was determined for patients with p16 positive and negative OC/OPSCC as well as for healthy control patients. The sensitivity and specificity of ddPCR of oropharyngeal swabs were calculated against p16 IHC for OPSCC. RESULTS: 122 patients were included: 36 patients with p16+OPSCC, 16 patients with p16-OPSCC, 4 patients with p16+OCSCC, 41 patients with p16-OCSCC, and 25 healthy controls. The sensitivity and specificity of ddPCR of oropharyngeal swabs against p16 IHC were 92 and 98% respectively, using 20-50 times less RNA than that required for conventional RT-qPCR. Overall agreement between ddPCR of tissue swabs and p16 of tumor tissue was high at ĸ = 0.826 [0.662-0.989]. CONCLUSION: Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

Investigation of EZH2 pathways for novel epigenetic treatment strategies in oropharyngeal cancer.

BACKGROUND: In recent decades, the incidence of oropharyngeal squamous cell carcinoma (OPSCC) has been rising worldwide as a result of increasing oncogenic human papillomavirus (HPV) infections in the oropharynx. EZH2 is an epigenetic regulatory protein associated with tumor aggressiveness and negative survival outcomes in several human cancers. We aimed to determine the role of EZH2 as a potential therapeutic epigenetic target in HPV-positive and negative OPSCC. METHODS: The expression of EZH2 was measured by immunohistochemistry (IHC) and droplet digital PCR (ddPCR) in 2 HPV-positive and 2 HPV-negative cell lines. The cell lines were then cultured and treated with one of 3 EZH2 epigenetic inhibitors (3-deazaneplanocin A, GSK-343 and EPZ005687) or DMSO (control). Following 2, 4 and 7 days of treatment, cells were analyzed and compared by gene expression, cell survival and proliferation assays. RESULTS: EZH2 targeting resulted in greater inhibition of growth and survival in HPV-positive compared to HPV-negative cells lines. The expression profile of genes important in OPSCC also differed according to HPV-positivity for Ki67, CCND1, MET and PTEN/PIK3CA, but remained unchanged for EGFR, CDKN2A and p53. CONCLUSION: Inhibition of EZH2 has anti-tumorigenic effects on OPSCC cells in culture that is more pronounced in HPV-positive cell lines. EZH2 is a promising epigenetic target for the treatment of OPSCC.

Detection of human papillomavirus type 16 in oropharyngeal squamous cell carcinoma using droplet digital polymerase chain reaction.

BACKGROUND: The incidence of oropharyngeal squamous cell carcinoma caused by oncogenic HPV (HPV-OPSCC) is rising worldwide. HPV-OPSCC is commonly diagnosed by RT-qPCR of HPV-16 E6 and E7 oncoproteins or by cyclin-dependent kinase inhibitor 2A, multiple tumor suppressor 1 (p16) immunohistochemistry (IHC). Droplet digital PCR (ddPCR) has been recently reported as ultra-sensitive and highly precise method of nucleic acid quantification for biomarker analysis. We aimed to validate this method for the detection of HPV-16 E6 and E7 in HPV-OPSCC. METHODS: Participants were recruited from January 2015-November 2015 at initial presentation to the University of Alberta Head and Neck Oncology Clinic. RNA was extracted, purified and quantified from prospectively collected participant tissues, and ddPCR was performed with fluorescent probes detecting HPV-16 E6 and E7. Results from ddPCR were compared with p16 IHC performed by clinical pathology as standard of care. RESULTS: Head and neck tissues were prospectively obtained from 68 participants including 29 patients with OPSCC, 29 patients with non-OPSCC and 10 patients without carcinoma. 79.2% of patients with OPSCC were p16 positive. The sensitivity and specificity of ddPCR HPV E6/E7 compared with p16 IHC in OPSCC was 91.3 and 100%, respectively. The amount of target RNA used was ≤1 ng, 20-50 times lower than reported by other for RT-qPCR HPV E6/E7. CONCLUSIONS: The ddPCR of HPV E6/E7 is a novel and highly specific method of detecting HPV-16 in OPSCC. Cancer 2016;122:1544-51. © 2016 American Cancer Society.

Brief electrical stimulation after facial nerve transection and neurorrhaphy: a randomized prospective animal study.

BACKGROUND: Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurement in these studies has not been precise or accurate. The objective of this study is to assess the effect of BES on accelerating facial nerve functional recovery from a transection injury in the rat model. METHODS: A prospective randomized animal study using a rat model was performed. Two groups of 9 rats underwent facial nerve surgery. Both group 1 and 2 underwent facial nerve transection and repair at the main trunk of the nerve, with group 2 additionally receiving BES on post-operative day 0 for 1 h using an implantable stimulation device. Primary outcome was measured using a laser curtain model, which measured amplitude of whisking at 2, 4, and 6 weeks post-operatively. RESULTS: At week 2, the average amplitude observed for group 1 was 4.4°. Showing a statistically significant improvement over group 1, the group 2 mean was 14.0° at 2 weeks post-operatively (p = 0.0004). At week 4, group 1 showed improvement having an average of 9.7°, while group 2 remained relatively unchanged with an average of 12.8°. Group 1 had an average amplitude of 13.63° at 6-weeks from surgery. Group 2 had a similar increase in amplitude with an average of 15.8°. There was no statistically significant difference between the two groups at 4 and 6 weeks after facial nerve surgery. CONCLUSIONS: This is the first study to use an implantable stimulator for serial BES following neurorrhaphy in a validated animal model. Results suggest performing BES after facial nerve transection and neurorrhaphy at the main trunk of the facial nerve is associated with accelerated whisker movement in a rat model compared with a control group.

Sanna Classification and Prognosis of Cholesteatoma of the Petrous Part of the Temporal Bone: A Retrospective Series of 81 Patients.

OBJECTIVE: To determine how classification of petrous bone cholesteatomas (PBCs) using the 5-point Sanna classification can predict major structural involvement, facial nerve outcomes, hearing outcomes, postoperative complications, and disease recurrence. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center in Bergamo, Italy. PATIENTS: Eighty-one sequential patients with radiologic and surgically confirmed diagnoses of PBC treated at a single tertiary referral center during a 20-year period. MAIN OUTCOME MEASURES: Major structural involvement, facial nerve outcomes, hearing outcomes, postoperative cerebrospinal fluid leak, and disease recurrence were evaluated on the basis of Sanna classification. RESULTS: Using the Sanna classification, 70% (57) were supralabyrinthine, 12% (10) infralabyrinthine, 7% (6) infralabyrinthine-apical, 5% (4) apical, and 5% (4) massive. Massive classification was statistically significantly associated with cochlear involvement (p = 0.009) and internal auditory canal involvement (p = 0.02). The infralabyrinthine-apical class was associated with carotid canal involvement (p = 0.03). Facial nerve interruption was observed in 35% of patients and most frequently in the apical group (75%). Neither hearing nor facial nerve outcomes were associated with Sanna classification. House-Brackmann score improved or was maintained postoperatively in 89% of patients. CONCLUSION: The Sanna classification provides anatomic detail on location of PBCs and is predictive of IAC, cochlear, and carotid artery involvement. However, classification systems for this rare condition continue to pose a challenge in being able to accurately predict facial nerve and hearing outcomes in surgical obliteration of PBC.