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The Alberta reconstructive technique (ART) is an innovative surgical procedure performed on patients undergoing primary jaw resection and reconstruction. The ART procedure was developed in collaboration with the Institute for Reconstructive Sciences in Medicine and the Division of Otolaryngology-Head and Neck Surgery, University of Alberta., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Hydrogels appear to be an attractive class of biomaterial for cartilage tissue engineering due to their high water content, excellent biocompatibility, tunable stiffness, etc. The crosslinking density of the hydrogel can affect their viscoelastic property, and therefore potentially impact the chondrogenic phenotype of re-differentiated chondrocytes in a 3D microenvironment through physical cues. To understand the effect of crosslinking densities on chondrocytes phenotype and cellular interaction with the hydrogel, this study utilized a clinical grade thiolate hyaluronic acid and thiolate gelatin (HA-Gel) hydrogel, crosslinked with poly(ethylene glycol) diacrylate to create various crosslinking densities. The HA-Gel hydrogels were then mixed with human nasal chondrocytes to generate neocartilage in vitro. The influence of the hydrogel crosslinking density and the viscoelastic property on the cell behaviours on the gene and matrix levels were evaluated using biochemistry assays, histology, quantitative polymerase chain reaction (qPCR) and next-generation sequencing (RNA seq). In general, the differences in the storage modulus of the HA-Gel hydrogel are not enough to alter the cartilaginous gene expression of chondrocytes. However, a positively correlated trend of PPAR-γ gene expression to the crosslinking density was measured by qPCR. The RNA-seq results have shown that 178 genes are significantly negatively correlated and 225 genes are positively correlated to the crosslinking density, which is worth investigating in the future studies., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The avascular nature of hyaline cartilage results in limited spontaneous self-repair and regenerative capabilities when damaged. Recent advances in three-dimensional bioprinting have enabled the precise dispensing of cell-laden biomaterials, commonly referred to as 'bioinks', which are emerging as promising solutions for tissue regeneration. An effective bioink for cartilage tissue engineering needs to create a micro-environment that promotes cell differentiation and supports neocartilage tissue formation. In this study, we introduced an innovative bioink composed of photocurable acrylated type I collagen (COLMA), thiol-modified hyaluronic acid (THA), and poly(ethylene glycol) diacrylate (PEGDA) for 3D bioprinting cartilage grafts using human nasal chondrocytes. Both collagen and hyaluronic acid, being key components of the extracellular matrix (ECM) in the human body, provide essential biological cues for tissue regeneration. We evaluated three formulations - COLMA, COLMA+THA, and COLMA+THA+PEGDA - for their printability, cell viability, structural integrity, and capabilities in forming cartilage-like ECM. The addition of THA and PEGDA significantly enhanced these properties, showcasing the potential of this bioink in advancing applications in cartilage repair and reconstructive surgery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

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., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Restoration of dental occlusion and oral rehabilitation is the ultimate goal of functional jaw reconstruction., Objective: To evaluate the prefabricated fibula flap (PFF) technique in occlusion-driven jaw reconstruction for benign or previously treated malignant disease., Design, Setting, and Participants: This cohort study was conducted from January 2000 to December 2019 at the University of Alberta Hospital and Institute of Reconstructive Sciences in Medicine in Edmonton, Alberta, Canada, among patients who underwent PFF or bone-driven and delayed osseointegrated implant installation (BDD). Patients were followed up for a minimum of 1 year after occlusal rehabilitation. Data were analyzed from July 2021 to June 2022., Exposures: Patients underwent BDD or PFF, which consists of osseointegrated dental implant installation and skin grafting of the fibular bone 3 to 6 months before jaw tumor resection or defect reconstruction. The implant osseointegration is completed at the time of jaw reconstruction, allowing for full reconstruction, loading, and restoration of the dental occlusion in the immediate postoperative period., Main Outcomes and Measure: Safety, effectiveness, accuracy, timeliness of occlusal reconstruction, and aesthetic appeal were compared between PFF and BDD. Groups were compared for the following variables: postoperative complications, number of bony segments used, number of procedures needed, total operative time, time to occlusal rehabilitation, and number of implants installed, exposed, lost, and used (ie, exposed implants - lost implants). Aesthetic appeal was assessed using standardized full-face and profile digital photographs taken before and 6 to 12 months after the operation and analyzed by 3 naive raters., Results: Among 9 patients receiving PFF (mean [SD] age, 43.3 [13.0] years; 7 men [77.8%]) and 12 patients receiving BDD (mean [SD] age, 41.9 [18.0] years; 8 men [66.7%]), the overall complication rate was similar (4 patients [44.4%] vs 3 patients [25.0%], respectively; relative risk, 1.78 [95% CI, 0.52 to 6.04]). The number of patients with implant loss was similar between PFF and BDD groups (0 patients vs 3 patients [25.0%], respectively; difference, -25.0 percentage points [95% CI, -48.4 to 9.7 percentage points]). PFF had a clinically meaningful faster mean (SD) occlusal rehabilitation compared with BDD (12.1 [1.9] months vs 60.4 [23.1] months; difference, -48.3 months [95% CI, -64.5 to -32.0 months]). The mean (SD) difference in preoperative to postoperative aesthetic score was similar between PFF and BDD groups (-0.8 [1.5] vs -0.2 [0.8]; difference, -0.6 [95% CI, -1.6 to 0.4])., Conclusions and Relevance: This study found that PFF compared with BDD was a safe, effective, and aesthetic reconstructive option for patients with benign or previously treated jaw malignant tumors. This technique may provide rapid occlusal reconstruction and oral rehabilitation.

Background: Established barriers to general exercise and physical activity among individuals with head and neck cancer include dry mouth, difficulty eating, weight loss, fear of injury, comorbidities, and treatment-related symptoms of pain and fatigue., Methods/design: A 12-week pragmatic randomized controlled trial was conducted followed by an optional supported exercise transition phase. Eligible participants were individuals with head and neck cancers who had undergone surgery and/or radiation therapy to lymph node regions in the neck. Participants were randomized to a comparison group involving a shoulder and neck physiotherapeutic exercise protocol, or to a combined experimental group comprising the shoulder and neck physiotherapeutic exercise protocol and lower-body resistance exercise training. The primary outcome of this study was fatigue-related quality of life., Results: Sixty-one participants enrolled, 59 (97%) completed the randomized trial phase, 55 (90%) completed the 24-week follow-up, and 52 (85%) completed the one-year follow-up. Statistically significant between-group differences were found in favor of the combined experimental group for the fatigue-related quality of life, fitness outcomes, and overall physical activity. Paired comparisons confirmed significant within-group improvements for both groups from baseline to one-year follow-up across most outcomes., Discussion: A group-based combined physiotherapeutic and lower-body resistance exercise program was feasible and effective. Findings are limited to individuals who had undergone a surgical neck dissection procedure. Given the complexity of head and neck cancer, further pragmatic interdisciplinary research is warranted.

Purpose: Despite the significance and complexity of tongue reconstruction surgery, a digital tool for flap design is currently lacking. This study investigates the effectiveness of employing inverse finite element method (IFEM) for meticulously designing the geometric characteristics of harvested tissue (free flap) for tongue reconstruction., Methods: In the case of an artificially simulated hemiglossectomy, IFEM algorithm was applied for algorithmic flap design. The method's effectiveness was evaluated by assessing flap deformation in a simplified virtual reconstruction, focusing on parameters such as stress, strain, and thickness., Results: The IFEM algorithm successfully generated an optimal flap design for the intended surgical removal. Analysis of the flap's overall surface area, deformation characteristics, and safety margins demonstrated the feasibility of the deformation. Notably, the stress and thickness assessments suggested that the flap's tension post-surgery would not adversely affect the mobility of the reconstructed tongue, suggesting a positive outcome for functional recovery., Conclusion: The IFEM demonstrates significant potential as a tool for precise free flap design in tongue reconstruction surgeries. Its application could lead to improved surgical accuracy and better quality of life for patients undergoing such procedures., (© 2024. CARS.)

Background: The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands., Methods: The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution., Results: In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10 years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10 years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins., Conclusions: Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins., (© 2023 American Cancer Society.)

Introduction: Resection of the mandible and temporomandibular joint (TMJ) without formal reconstruction is a devastating condition that negatively affects all aspects of the patient's life. We have approached the reconstruction of mandibular defects that include the condyle with simultaneous reconstruction with a vascularized free fibular flap (FFF) using Surgical Design and Simulation (SDS) and alloplastic TMJ prosthesis. The objective of this study is to report the functional and quality of life (QOL) outcomes in a cohort of patients that had undergone our reconstructive protocol., Methods: This was a prospective case series of adult patients that underwent mandibular reconstruction with FFF and alloplastic TMJ prosthesis at the our center. Pre-operative and post-operative maximum inter-incisal opening (MIO) measurements were collected, and patients completed a QOL questionnaire (EORTC QLQ-H&N35) during those perioperative visits., Results: Six patients were included in the study. The median patient age was 53 years. Heat map analysis of the QOL questionnaire revealed that patients reported a positive clinically significant change in the domains of pain, teeth, mouth opening, dry mouth, sticky saliva, and senses (relative change of 2.0, 3.3, 3.3, 2.0, 2.0, and 1.0 respectively). There were no negative clinically significant changes. There was a median perioperative MIO increase of 15.0 mm, and this was statistically significant (p  =  0.027)., Conclusions: This study highlights the complexities involved in mandibular reconstruction with involvement of the TMJ. Based on our findings, patients can obtain an acceptable QOL and good function following simultaneous reconstruction with FFF employing SDS and an alloplastic TMJ prosthesis., (© 2023. The Author(s).)

Background: Light-to-moderate intensity strength training (LMST) improves muscular strength, physical functioning, and some side effects in head and neck cancer survivors (HNCS). Heavy lifting strength training (HLST) may further improve these outcomes; however, it has not been studied in HNCS. The primary aim of the LIFTING trial was to examine the feasibility and safety of a HLST program in HNCS ≥1-year post-surgical neck dissection., Methods: In this single-arm feasibility study, HNCS were asked to complete a twice weekly, 12-week, supervised HLST program, gradually progressing to lifting heavy loads of 80-90% of 1 repetition maximum (1RM) for barbell squat, bench press, and deadlift. The feasibility outcomes included recruitment rate, 1RM completion rate, program adherence, barriers, and motivation. The preliminary efficacy outcomes included changes in upper and lower body strength., Results: Nine HNCS were recruited over an 8-month period during the COVID-19 pandemic. All 9 (100%) completed the 1RM tests and successfully progressed to heavy loads at approximately 5 weeks. The median attendance was 95.8% (range 71-100%), and few barriers were reported. Weight lifted increased for squat/leg press (median change: +34kg; 95% CI +25 to +47), bench press (median change: +6kg; 95% CI +2 to +10), and deadlift (median change: +12kg; 95% CI +7 to +24). No adverse events were reported and participants were motivated to continue HLST after the study., Conclusions: HLST appears feasible and safe for HNCS and may result in meaningful improvements in muscular strength. Future research should consider additional recruitment strategies and compare HLST to LMST in this understudied survivor population., Trial Registration: NCT04554667., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Insurance status has been shown to impact survival outcomes. We sought to determine whether insurance affects the choice of treatment modality among patients with advanced (T4) oral cavity squamous cell carcinoma., Methods: This is a retrospective, population-based cohort study using the Survival, Epidemiology, and End Results Program database. The population included all adult (age ≥ 18) patients with advanced (T4a or T4b) oral cavity squamous cell carcinoma diagnosed from 2007 to 2016. The main outcome was the odds of receiving definitive treatment, defined as primary surgical resection. Insurance status was categorized into uninsured, any Medicaid, and insured groups. Univariable, multivariable, and subgroup analyses were performed., Results: The study population consisted of 2628 patients, of whom 1915 (72.9%) were insured, 561 (21.3%) had Medicaid, and 152 (5.8%) were uninsured. The multivariable model showed that patients who were 80 years or older, unmarried, received treatment in the pre-Affordable Care Act (ACA) period, and who were on Medicaid or uninsured were significantly less likely to receive definitive treatment. Insured patients were significantly more likely to receive definitive treatment compared to those on Medicaid or uninsured (OR = 0.59, 95% CI 0.46-0.77, p < 0.0001 [Medicaid vs. Insured]; and OR = 0.48, 95% CI 0.31-0.73 p = 0.001 [Uninsured vs. Insured]), however these differences did not persist when considering only those patients treated following the 2014 expansion of the ACA., Conclusions: Insurance status is significantly associated with treatment modality among adults with advanced stage (T4a) oral cavity squamous cell carcinoma. These findings support the premise of expanding insurance coverage in the US., (© 2023. The Author(s).)

The ideal jaw reconstruction involves the restoration and maintenance of jaw continuity, jaw relations, joint alignment, and facial contour, and, most importantly, dental occlusal reconstruction. One of the essential requirements of achieving a consistent functional outcome is to place the bony reconstruction in the correct three-dimensional position as it relates to the other jaw segments and dentition. A protocol of occlusion-driven reconstruction of prefabricated fibular free flaps that are customized to the patient with surgical design and simulation (SDS)-planned osseointegrated implant installation was developed by our institution. This innovation introduced significant flexibility and efficiency to jaw reconstructions, but functional and cosmetic outcomes were dependent on the accuracy of the final reconstructions when compared to the SDS plan. The purpose of this study was to examine the accuracy of the SDS-planned fibular flap prefabrication in a cohort of patients undergoing jaw reconstruction. All patients that had undergone primary jaw reconstruction with prefabricated fibular free flaps were reviewed. The primary outcome of this study was the accuracy of the postoperative implant positions as compared to the SDS plan. A total of 23 implants were included in the analysis. All flaps survived, there was no implant loss postoperatively, and all the patients underwent all stages of the reconstruction. SDS planning of fibular flap prefabrication resulted in better than 2 mm accuracy of osteointegrated implant placement in a cohort of patients undergoing jaw reconstruction. This accuracy could potentially result in improved functional and cosmetic outcomes.

Introduction: Jaw defect reconstructions have been transformed by the development of free tissue transfer using vascularized bone incorporating osseointegrated dental implants. We recently developed a modification our method this procedure and termed it the Modified Alberta Reconstruction Technique (MART). The objective of this study aimed to assess the soft tissue component and outcomes of the MART as compared to the Alberta Reconstructive Technique (ART) or conventional (BDD) reconstructions., Patients and Methods: This was a prospective cohort study of adult patients who underwent jaw reconstruction with dental implant rehabilitation between 2000 and 2019 in Edmonton, Alberta. Patients were aged-matched and placed into a cohort based on the type of reconstruction they received. Outcomes were compared between the groups. Expert and aesthetic analyses were performed. Statistical analysis was conducted to determine significance., Results: A total of 46 patients (15 BDD, 15 ART and 16 MART) were included. Demographics were similar between groups. There was no difference in complications. The soft tissue component of the MART cohort was more favourable to work with as judged by the occlusal reconstructive experts. The MART was rated as more aesthetically appealing in comparison to the BDD and ART (p = 0.049)., Conclusions: The MART is a safe, effective, and aesthetically appealing procedure. It yields a good functional result and a clinically better soft tissue component for occlusal reconstructions. For a select group of patients requiring jaw reconstruction, the MART is an ideal reconstructive option as the modification provides good control of the soft tissue around the implants., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The removal of skin cancer lesions on the nose often results in the loss of nasal cartilage. The cartilage loss is either surgically replaced with autologous cartilage or synthetic grafts. However, these replacement options come with donor-site morbidity and resorption issues. 3-dimensional (3D) bioprinting technology offers the opportunity to engineer anatomical-shaped autologous nasal cartilage grafts. The 3D bioprinted cartilage grafts need to embody a mechanically competent extracellular matrix (ECM) to allow for surgical suturing and resistance to contraction during scar tissue formation. We investigated the effect of culture period on ECM formation and mechanical properties of 3D bioprinted constructs of human nasal chondrocytes (hNC)-laden type I collagen hydrogel in vitro and in vivo. Tissue-engineered nasal cartilage constructs developed from hNC culture in clinically approved collagen type I and type III semi-permeable membrane scaffold served as control. The resulting 3D bioprinted engineered nasal cartilage constructs were comparable or better than the controls both in vitro and in vivo. This study demonstrates that 3D bioprinted constructs of engineered nasal cartilage are feasible options in nasal cartilage reconstructive surgeries., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Objectives: There has been increasing interest in the management of oropharyngeal swallowing dysfunction (SwD). Its prevalence, particularly in otherwise healthy infants and toddlers (OHITs), is underappreciated. As the standard diagnostic tests are either invasive or scarce, valid parent-reported outcome (PRO) questionnaires could play a pivotal role in the understanding and managing SwD in this group. This article reviewed the literature on PRO questionnaires pertaining to SwD in OHITs., Data Source: A librarian searched Prospero, Cochrane Library, Embase, Medline, PsycINFO, HaPI, CINAHL, and SCOPUS until February 2021 using the MeSH terms for deglutition and screening methods., Review Method: Questionnaires that examined disease-specific or eating and feeding concerns or difficulties were excluded. Two reviewers independently identified PRO questionnaires for SwD that were used in OHITs and extracted the author names, publication year, questionnaire name, the studied population, and the reported psychometric assessments. A quality assessment was performed based on consensus-based standards for the selection of health measurement instruments (COSMIN) and updated criteria for good measurement properties., Results: Of the 3488 screened articles, we identified only two questionnaires, the pediatric version of the Eating Assessment Tool (PEDI-EAT-10) and the PRO questionnaire for Swallowing Dysfunction in OHITs. The PEDI-EAT-10 authors assessed the validity and reliability on children with cerebral palsy. However, concerns were identified regarding the developmental process and the internal structure validity. The PRO questionnaire for SwD in OHITs meets criteria but has not yet been validated in the population of interest nor its psychometric properties assessed., Conclusion: Two instruments were identified. The PED-EAT-10 exhibits methodological flaws, while Edmonton PRO questionnaire for SwD in OHITs awaits construct validation and could fill the current knowledge gap., (© 2021. The Author(s).)

Purpose A large knowledge gap related to dysphagia treatment adherence was identified by a recent systematic review: Few existing studies report on adherence, and current adherence tracking relies heavily on patient self-report. This study aimed to report weekly adherence and dysphagia-specific quality of life following home-based swallowing therapy in head and neck cancer (HNC). Method This was a quasi-experimental pretest-posttest design. Patients who were at least 3 months post-HNC treatment were enrolled in swallowing therapy using a mobile health (mHealth) swallowing system equipped with surface electromyography (sEMG) biofeedback. Participants completed a home dysphagia exercise program across 6 weeks, with a target of 72 swallows per day split between three different exercise types. Adherence was calculated as percent trials completed of trials prescribed. The M. D. Anderson Dysphagia Inventory (MDADI) was administered before and after therapy. Results Twenty participants (75% male), with an average age of 61.9 years ( SD = 8.5), completed the study. The majority had surgery ± adjuvant (chemo)radiation therapy for oral (10%), oropharyngeal (80%), or other (10%) cancers. Using an intention-to-treat analysis, adherence to the exercise regimen remained high from 84% in Week 1 to 72% in Week 6. Radiation therapy, time since cancer treatment, medical difficulties, and technical difficulties were all found to be predictive of poorer adherence at Week 6. A statistically significant improvement was found for composite, emotional, and physical MDADI subscales. Conclusions When using an mHealth system with sEMG biofeedback, adherence rates to home-based swallowing exercise remained at or above 72% over a 6-week treatment period. Dysphagia-specific quality of life improved following this 6-week treatment program.

Background: Mutations involving BRAF and TERT are important predictors of disease severity in thyroid cancer, but molecular testing is limited by cost and lack of adequate tissue sample. This study aimed to assess the utility of BRAFV600E and TERT testing using droplet digital PCR (ddPCR) as a diagnostic and prognostic tool for thyroid fine needle aspirate biopsy (FNAB)., Methods: Patients with thyroid nodules were prospectively enrolled from March 2015 to September 2018. Pre-operative FNAB was collected for standard cytology and molecular testing. BRAFV600E and TERT levels were analyzed by ddPCR. Cytology (Bethesda system) and ddPCR results were correlated to surgical pathology., Results: A total of 222 patients were enrolled, of which 124 received thyroid surgery. Pre-operative cytology alone with Bethesda ≥5 was 100% specific and 70% sensitive for malignancy on final surgical pathology. BRAFV600E positivity or TERT overexpression was 100% specific and 60.0% sensitive. Combining cytology (Bethesda ≥5) with BRAFV600E and TERT testing increased the sensitivity of a malignant diagnosis to 80.0%. High TERT levels and/or BRAFV600E was associated with aggressive or advanced stage pathology., Conclusions: Combining cytology with ddPCR analysis of BRAFV600E and TERT can improve the diagnostic accuracy of thyroid FNAB, and help predict aggressive pathology., (© 2021. The Author(s).)

Objectives: There is limited epidemiological information on swallowing dysfunction (SwD) in otherwise healthy infants and toddlers (OHITs). Cost, invasiveness, expertise, and resources constrain the repeatability and utility of instrumental diagnostic tests. A parent-reported outcomes (PRO) tool has the potential to mitigate these disadvantages. Hence, we set out to develop and validate a novel PRO tool to assess SwD in OHITs., Study Design: A mixed-method study., Setting: Tertiary pediatric center., Methods: We recruited parents of OHITs with SwD and excluded those with a confounding diagnosis (syndromes or neurological impairment). Interviews were conducted and thematically analyzed to extract the relevant domains and items. A similar analytical method was performed on the reports from a systematic review and literature search. Four verification sessions of parents and experts were conducted to maintain rigor. A panel of experts assessed and established the content validity of the items using a modified Delphi technique., Results: We achieved information saturation after interviewing 10 parents and generated 7 domains with 72 items. Over the course of 3 rounds of modified Delphi content validation, the domains were reduced to 3 (swallowing, breathing, and illness) containing 21 items; a content validity index of 82.1% was achieved., Conclusion: We validated the content of a new PRO instrument to assess SwD in OHITs. The instrument is composed of 3 primary domains representing 21 items. This tool has the potential to screen for swallowing dysfunction and can assess management outcomes specifically for this population at a community level.

Introduction: Current research is elucidating how the addition of depth of invasion (DOI) to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging for oral cavity squamous cell carcinoma influences its prognostic accuracy. However, there is limited research on survival in pT3N0M0 oral tongue SCC (OTSCC) patients when stratifying by DOI., Objectives: Determine 5-year overall survival (OS), and cancer-specific survival (CSS) for patients with pT3N0M0 oral OTSCC based on shallow DOI (<10 mm) and deep DOI (10-20 mm)., Methods: Retrospective review involving three tertiary care cancer centers in North America. cT3N0M0 OTSCC patients receiving primary surgical treatment from 2004 to 2018 were identified. Inclusion: age > 18 years old and confirmation of pT3N0M0 OTSCC on surgical pathology. Exclusion: patients undergoing palliative treatment or previous head and neck surgery/radiotherapy. Analysis comprised two groups: shallow pT3 (tumor diameter > 4 cm, DOI < 10 mm) and deep pT3 (DOI 10 mm-20 mm)., Results: One hundred and four patients with pT3N0M0 OTSCC were included. Mean age was 59.1 years (range: 18-80.74). Age, gender, and Charlson Comorbidity Index were similar between the two groups (p > 0.05). Recurrence, LVI, PNI, and positive margins were more common in deep T3 tumors (P < 0.05). 5-year OS (50% vs 26%, p = 0.006) and CSS (72% vs 24%, p = 0.005) were worse in deep pT3 tumors. Deep pT3 disease was an independent predictor of OS (p = 0.004) and CSS (p = 0.01) on Cox-Regression analysis., Conclusion: DOI is an independent predictor of poor survival in pT3N0M0 OTSCC patients. Consideration should be given to escalating adjuvant therapy for deep pT3N0M0 OTSCC patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Swallowing dysfunction (SwD) is under-reported in otherwise healthy infants and toddlers (OHITs). The identification of parental perceptions of factors that may hinder the diagnosis could help clinicians manage these children in a more expeditious manner. This study investigated the barriers to diagnosing SwD, as reported by the families., Design: Grounded theory study., Setting: This study was performed in a tertiary care paediatric centre in Canada., Participants: Parents of OHITs were recruited using purposeful sampling., Intervention: We used detailed, semistructured, in-person interviews and the audiotapes and transcriptions were thematically analysed. From the parental insights, we built a framework composed of three themes of barriers., Result: Ten parents of OHITs with SwD were interviewed. The children presented with recurrent coughing, choking, cold-like symptoms, recurring/consistent illnesses and feeding difficulties. They were managed with multiple rounds of antibiotics and diagnosed with allergies, asthma or recurrent viral infections before considering SwD. The three emerging themes are false beliefs about SwD among parents and some physicians, parent-related barriers and physician-related barriers. These barriers had severely impacted the parents, impairing work productivity and leading to work-related reprimands and changes in the family dynamics., Conclusion: This study suggests that there are several barriers that face the parents of OHITs when seeking a diagnosis of SwD and initiating appropriate management. These barriers likely interact with one another and amplify their effects on the family and the child. A common denominator is a lack of education regarding SwD, its clinical manifestations and the available expertise to manage this condition., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Skin cancer patients often have tumorigenic lesions on their noses. Surgical resection of the lesions often results in nasal cartilage removal. Cartilage grafts taken from other anatomical sites are used for the surgical reconstruction of the nasal cartilage, but donor-site morbidity is a common problem. Autologous tissue-engineered nasal cartilage grafts can mitigate the problem, but commercially available scaffolds define the shape and sizes of the engineered grafts during tissue fabrication. Moreover, the engineered grafts suffer from the inhomogeneous distribution of the functional matrix of cartilage. Advances in 3D bioprinting technology offer the opportunity to engineer cartilages with customizable dimensions and anatomically shaped configurations without the inhomogeneous distribution of cartilage matrix. Here, we report the fidelity of Freeform Reversible Embedding of Suspended Hydrogel (FRESH) bioprinting as a strategy to generate customizable and homogenously distributed functional cartilage matrix engineered nasal cartilage. Using FRESH and in vitro chondrogenesis, we have fabricated tissue-engineered nasal cartilage from combining bovine type I collagen hydrogel and human nasoseptal chondrocytes. The engineered nasal cartilage constructs displayed molecular, biochemical and histological characteristics akin to native human nasal cartilage., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background: Telephone consultations between physicians provide quick access to medical advice, allowing patients to be cared for by calling physicians in their local settings., Objective: As part of a quality assurance study of a physician-to-physician consultation program in Alberta, Canada, this environmental scan aims to identify the characteristics and outcomes of physician-to-physician telephone consultation programs across several countries., Methods: We searched 7 databases to identify English publications in 2007-2017 describing physician-to-physician consultations using telephones as the main technology. To identify Canadian programs, the literature search was supplemented with an additional internet search., Results: The literature search yielded 2336 citations, of which 17 publications were included. Across 7 countries, 14 telephone consultation programs provided primary care providers with access to various specialists through hotlines, paging systems, or call centers. The programs reported on the avoidance of hospitalizations, emergency department visits and specialty visits, caller satisfaction with the telephone consultation, and cost avoidance., Conclusions: Telephone consultation programs between health care providers have facilitated access to specialist care and prevented acute care use. ., (©Peter George Jaminal Tian, Jeffrey Richard Harris, Hadi Seikaly, Thane Chambers, Sara Alvarado, Dean Eurich. Originally published in JMIR Formative Research (http://formative.jmir.org), 23.02.2021.)

Objective: Human nasal septal chondrocytes (NC) are a promising minimally invasive derivable chondrogenic cell source for cartilage repair. However, the quality of NC-derived cartilage is variable between donors. Coculture of NC with mesenchymal stem cells (MSCs) mitigates the variability but with undesirable markers of chondrocyte hypertrophy, such as type X collagen, and the formation of unstable calcifying cartilage at ectopic sites. In contrast, monoculture NC forms non-calcifying stable cartilage. Formation of a stable NC-MSC coculture cartilage is crucial for clinical application. The aim of this study was to explore the utility of parathyroid hormone-related peptide (PTHrP) hormone to suppress chondrocyte hypertrophy in NC-MSC cocultures and form stable non-calcifying cartilage at ectopic sites., Methods: Human NC and bone marrow MSCs, and cocultures of NC and MSC (1:3 ratio) were aggregated in pellet form and subjected to in vitro chondrogenesis for 3 weeks in chondrogenic medium in the presence and absence of PTHrP. Following in vitro chondrogenesis, the resulting pellets were implanted in immunodeficient athymic nude mice for 3 weeks., Results: Coculture of NC and MSC resulted in synergistic cartilage matrix production. PTHrP suppressed the expression of hypertrophy marker, type X collagen ( COL10A1 ), in a dose-dependent fashion without affecting the synergism in cartilage matrix synthesis, and in vivo calcification was eradicated with PTHrP. In contrast, cocultured control (CC) pellets without PTHrP treatment expressed COL10A1 , calcified, and became vascularized in vivo ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Anderson-Baron, Liang, Kunze, Mulet-Sierra, Osswald, Ansari, Seikaly and Adesida.)

To investigate the effect of soluble factors released from human nasal chondrocytes (NCs) on cocultured human bone marrow mesenchymal stem cells (MSCs) and NC tissue-engineered constructs. Cartilage engineered from pure NCs on a three-dimensional (3D) porous collagen scaffold was cultured indirectly in a Transwell system with cartilage engineered from a direct coculture of human bone marrow-derived MSCs and NCs on a 3D porous collagen scaffold. The soluble factors were measured in the conditioned media from the different chambers of the Transwell system. Engineered cartilage from cocultures exposed to the pure NC construct exhibited reduced chondrogenic potential relative to control constructs, shown by reduced extracellular matrix deposition and increased expression of hypertrophic markers. Analysis of the soluble factors within the conditioned media showed an increase in inflammatory cytokines in the coculture chamber exposed to the pure NC construct. Principal component analysis revealed that the majority of the data variance could be explained by proinflammatory factors and hypertrophic chondrogenesis. In conclusion, our data suggest that inflammatory cytokines derived from NCs reduce the chondrogenic potential of coculture engineered cartilage through the induction of hypertrophic chondrogenesis. Impact statement The use of engineered cartilage from cocultured nasal chondrocytes (NCs) and mesenchymal stem cells for nasal cartilage reconstruction may be problematic. Our data suggest that the soluble factors from surrounding native NCs in the cartilage to be fixed can compromise the quality of the engineered cartilage if used in reconstructive surgery.

Importance: High local recurrence rates with aggressive disease remain the main concern in oral cancer survival. Use of a translational device using fluorescence visualization (FV) approved by the US Food and Drug Administration and Health Canada, has shown a marked reduction in the 3-year local recurrence rate of high-grade oral lesions in a single-center observational study., Objective: To determine whether FV- guided surgery can improve local control rates in the treatment of in situ or T1 to T2 category oral squamous cell carcinoma (OSCC)., Design, Setting, and Participants: A multicenter randomized clinical trial was conducted in a surgical setting. A total of 457 patients were enrolled between January 18, 2010, and April 30, 2015. Data analysis of the intention-to-treat population was performed from April 3, 2019, to March 20, 2020. Patients with histologically confirmed high-grade dysplasia/carcinoma in situ or T1 to T2 category OSCC were randomized to receive traditional peroral surgery or FV-guided surgery., Intervention: Fluorescence visualization during surgery., Main Outcomes and Measures: The primary outcome was local recurrence of OSCC. Secondary outcomes were failure of the first-pass margin, defined as a histologically confirmed positive margin for severe dysplasia or greater histologic change of the main specimen (ie, not the margins taken from the resection bed), regional or distant metastasis, and death due to disease., Results: Of the 457 patients enrolled in the study, 443 patients (264 [59.6%] men; mean [SD] age, 61.5 [13.3] years) completed the randomized treatment: 227 FV-guided and 216 non-FV guided surgery. The median follow-up was 52 (range, 0.29-90.8) months. In total, 45 patients (10.2%) experienced local recurrence. The 3-year local recurrence rate was 9.4% in the FV-guided group and 7.2% in the non-FV group (difference, 2.2%; 95% CI, -3.2% to 7.4%). Other similarities between the FV vs non-FV groups included failure of first-pass margin (68/227 [30.0%]) vs 65/216 [30.1%]), regional failure (39/227 [17.2%] vs 37/216 [17.1%]), disease-specific survival (23/227 [10.1%] vs 19/26 [8.8%]), and overall survival (41/227 [18.1%] vs 38/216 [17.6%]) were also similar between groups. No adverse events were judged to be related to the intervention., Conclusions and Relevance: In this randomized clinical trial, FV-guided surgery did not improve local control rates in the treatment of patients with in situ or T1 to T2 category oral cancer. Under a controlled environment, FV-guided surgery did not have an evident effect in reduction of local recurrence for localized OSCC. This result suggests that attention be directed to strategies other than improving definitions of nonapparent disease at clinical margins to identify the sources of local recurrence., Trial Registration: ClinicalTrial.gov Identifier: NCT01039298.

Importance: Conventional reconstruction techniques for superficial parotidectomy have been criticized for their ability to provide long-term volumetric correction and to prevent Frey's syndrome. Objective: To demonstrate the long-term effectiveness of a pedicled and innervated sternocleidomastoid muscle flap (PISCMMF) to reconstruct superficial parotidectomy defects. Design, Setting, and Participants: This is a retrospective cohort study of patients treated by a single surgeon in a tertiary care center from July 2012 to March 2018. Seventeen of a possible 34 eligible adults having undergone reconstruction with a PISCMMF for benign parotid disease with at least 1 year of follow-up were included through convenience sampling. Patients with revision parotid surgery, malignant parotid tumors, neck dissections, or prior spinal accessory nerve dysfunction were excluded. Intervention: A PISCMMF was used to immediately reconstruct superficial parotidectomy defects. Main Outcomes and Measures: Participants underwent three-dimensional facial imaging, starch-iodine testing for Frey's syndrome, and completed a validated satisfaction questionnaire. The surface area of the positive starch-iodine tests was calculated. An average model was generated from participant images, allowing the calculation of surface millimeter differences comparing the operative with nonoperative sides. Results: Seventeen patients [7 male (41.2%), mean age 50.82 ± 12.37 years] underwent a PISCMMF to reconstruct excision (mean specimen weight = 21.45 ± 12.22 g) of benign lesions [9 pleomorphic adenomas (52.9%), 5 Warthin's tumors (29.4%), 2 cysts (11.8%), 1 chronic parotitis (5.9%)], with a mean follow-up time of 35.41 ± 12.30 months. Rates of objective and subjective Frey's syndrome were 29.4% and 11.8%, respectively. The average surface area affected was 2.32 cm 2 [standard deviation (SD) = 1.95 cm 2 ] compared with the average surface area of 16.35 cm 2 (SD = 9.20 cm 2 ) of the excised specimens. Facial symmetry analysis revealed an average millimeter difference of -1.57 ± 2.55 mm that was not significant at a threshold of 2 mm [ t (16) = 0.69, p  = 0.50]. No participants had postoperative shoulder or neck dysfunction. Overall satisfaction was 95.4%. Age ( β  = -0.51, p  = 0.02) and case number ( β  = 0.44, p  = 0.04) were significant predictors of smaller millimeter difference ( R 2  = 0.48, F (2,14) = 6.41, p  = 0.01). The specimen mass ( β  = -0.05, p  = 0.35) did not predict millimeter difference ( R 2  = 0.11, F (1,8) = 0.10, p  = 0.35). Conclusions and Relevance: A PISCMMF immediately reconstructing parotidectomy defects successfully restores facial symmetry, prevents clinically significant Frey's syndrome, and results in high patient satisfaction in the long term without significant morbidity.

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., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Objective: To determine the rate and risk factors for osteoradionecrosis (ORN) in osseous free flaps after postoperative radiation therapy (PORT). To describe the treatment of free flap ORN., Methods: Seventy-four patients undergoing osseous free flap reconstruction were analyzed. Thirty-eight completed PORT. Patients were followed for ≥6 months., Results: The rate of ORN was 34% overall; 0% with 50 to 59.9 Gy; 8% with 60 Gy; 40% with 66 Gy; 56% with 70 to 74.4 Gy. Mean time to ORN was 13.1 months. 0/28 patients without PORT developed free flap osteonecrosis. Multivariate analysis found the only factor predicting ORN: PORT >60 Gy, which increased the risk 21-fold. Treatment included PENTACLO, hyperbaric oxygen, and surgical debridement with 75% within 2 years., Conclusion: PORT >60 Gy is significantly associated with free flap ORN. As the dose of adjuvant RT increases beyond 60 Gy, the risk of ORN in free flaps rises. Consideration should be given to lower PORT doses or delaying free flap reconstruction when feasible., (© 2020 Wiley Periodicals, Inc.)

Introduction: The SARS-CoV-2 virus (COVID19) pandemic has placed extreme pressures on the Canadian Healthcare system. Many health care regions in Canada have cancelled or limited surgical and non-surgical interventions on patients to preserve healthcare resources for a predicted increase in COVID19 related hospital admissions. Also reduced health interventions may limit the risk of possible transmission of COVID19 to other patients and health care workers during this pandemic. The majority of institutions in Canada have developed their own operational mandates regarding access to surgical resources for patients suffering from Head and Neck Cancers during this pandemic. There is a large degree of individual practitioner judgement in deciding access to care as well as resource allocation during these challenging times. The Canadian Association of Head and Neck Surgical Oncology (CAHNSO) convened a task force to develop a set of guidelines based on the best current available evidence to help Head and Neck Surgical Oncologists and all practitioners involved in the care of these patients to help guide individual practice decisions., Main Body: The majority of head and neck surgical oncology from initial diagnosis and work up to surgical treatment and then follow-up involves aerosol generating medical procedures (AGMPs) which inherently put head and neck surgeons and practitioners at high risk for transmission of COVID19. The aggressive nature of the majority of head and neck cancer negates the ability for deferring surgical treatment for a prolonged period of time. The included guidelines provide recommendations for resource allocation for patients, use of personal protective equipment for practitioners as well as recommendations for modification of practice during the current pandemic., Conclusion: 1. Enhanced triaging should be used to identify patients with aggressive malignancies. These patients should be prioritized to reduce risk of significant disease progression in the reduced resource environment of COVID19 era. 2. Enhanced triaging including aggressive pre-treatment COVID19 testing should be used to identify patients with high risk of COVID19 transmission. 3. Enhanced personal protective equipment (PPE) including N95 masks and full eye protection should be used for any AGMPs performed even in asymptomatic patients. 4. Enhanced PPE including full eye protection, N95 masks and/or powered air purifying respirators (PAPRs) should be used for any AGMPs in symptomatic or presumptive positive COVID 19 patients.

Background: RAAPID (Referral, Access, Advice, Placement, Information, and Destination) is a 24-h call center in Alberta, Canada, facilitating urgent telephone consultations between physicians and specialists. We evaluated the extent to which RAAPID calls to Otolaryngology-Head and Neck Surgery (OHNS) reduced visits to the emergency department and specialty clinics., Methods: This was a cross-sectional study evaluating all telephone consultations to OHNS from physicians in northern Alberta between 2013 and 2014 (T1) (where consultations by residents occurred) and 2015 to 2017 (T2) (where consultations were done by consultants during office hours and residents during after hours). Outcomes of the calls included medical advice, specialty clinic referrals, and emergency department (ED) referrals. Differences in the reduction of ED visits and costs, overall as well as in T1 and T2, were assessed using multivariate logistic regression., Results: Overall, 62.3% (1064/1709) of telephone consultations reduced ED visits consisting of advice being provided (n = 884; 83.1%) and referral to specialty clinics (n = 180; 16.9%). The adjusted odds ratio of calls reducing emergency visits in T2 as compared to T1 was 2.47 (95% CI 1.99 to 3.08). The adjusted odds ratio of reducing ED visits during office hours compared to after-hours 2.54 (95% CI 1.77-3.64). The estimated direct costs avoided from ED visits in T1 and T2 were $42,224.22 and $114,393.86, respectively., Conclusion: RAAPID telephone consultations to OHNS were effective in reducing ED visits and healthcare costs. This model should be considered in other areas to improve efficiencies within the health system.

Importance: Incorporation of patient perspectives, or patient-reported outcomes, in functional outcome measures has been gaining prominence in the literature on reconstructive surgery., Objective: To create and validate an instrument for measuring the main functional areas of concern for patients with head and neck cancer., Design, Setting, and Participants: This 4-phase mixed-methods qualitative study was conducted from July 1, 2013, to June 30, 2016, in a quaternary head and neck oncology center in Edmonton, Alberta, Canada. Patients were recruited from 3 Head and Neck Research Network sites: University of Alberta (Edmonton, Canada), Mount Sinai Health Network (New York, New York), and University of Turku Hospital (Turku, Finland). The inclusion criteria included 18 years of age or older, diagnosis of squamous cell carcinoma involving the subsites of the head and neck (ie, oral cavity, oropharynx, hypopharynx, and larynx), and at least 1 year since treatment completion. Those patients who were undergoing additional active treatment or with evidence of disease recurrence were excluded. Data were analyzed from July 1, 2013, to June 30, 2016., Main Outcomes and Measures: The primary outcome measures were the clinical correlation of the Edmonton-33 instrument scores with swallowing, speech, dry mouth, and chewing assessment outcomes., Results: In total, 10 patients with head and neck cancer (mean age, 59.6 years; 6 men [60%]) were included in phase 1 of the study, 5 patients (mean age, 55.2 years) were included in phase 2, 10 patients were included in phase 3, and 25 patients with head and neck cancer (mean age, 62.6 years; 14 men [56%]) participated in the phase 4 validation. The Edmonton-33 instrument scores correlated strongly with the swallowing scores of the MD Anderson Dysphagia Inventory (r = 0.77; 95% CI, 0.49-1.0), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 (EORTC QLQ-H&N35) (r = -0.73; 95% CI, -1.0 to -0.44), and the modified barium swallow test (r = -0.60; 95% CI, -0.94 to -0.25). The instrument scores were also strongly correlated with the Speech Handicap Index scores (r = -0.64; 95% CI, -0.97 to -0.31), word intelligibility scores (r = 0.61; 95% CI, 0.27-0.95), and sentence intelligibility scores (r = 0.55; 95% CI, 0.19-0.91). A moderate to strong correlation was observed between the Edmonton-33 instrument and the EORTC QLQ-H&N35 scores in the dry mouth (r = -0.54; 95% CI, -0.91 to -0.18) and chewing (r = -0.45; 95% CI, -0.84 to -0.06) domains. The factor loading values for the domains of swallowing, speech, dry mouth, and chewing were all greater than 0.3. The mean factor loading values for the items related to swallowing were 0.71 (95% CI, 0.62-0.80) and for the items related to speech were 0.76 (95% CI, 0.72-0.80). The mean factor loading values for the items related to dry mouth were 0.71 (95% CI, 0.59-0.83) and for those related to chewing were 0.77 (95% CI, 0.69-0.85)., Conclusions and Relevance: The Edmonton-33 appears to be a validated instrument that will allow patients with head and neck cancer to assess and report their own functional outcomes. It could serve as a single comprehensive measure for functional outcomes.

Objectives: Treatment for advanced head and neck cancers typically includes surgery followed by radiation therapy (RT). Radiation-induced xerostomia is a common sequela of these treatments. The modified submandibular gland transfer (M-SGT) procedure was developed to decrease xerostomia in the treatment of oral cavity cancer by sparing one submandibular gland (SMG) from radiation. This study's objectives were to: 1) elucidate the radiation-sparing capacity of the M-SGT, and 2) study the xerostomia-reducing potential of the M-SGT based on the University of Washington Quality-of-Life Questionnaire (UW-QOL)., Methods: Radiation therapy treatment plans were reviewed for all patients treated with surgery and RT who had a M-SGT at the University of Alberta Hospital during the study period. Outcomes included: 1) radiation dose received by the transferred SMG within the periparotid area compared to the submandibular triangle (ST), and 2) patient-reported saliva scores on the UW-QOL compared to historical controls without a gland transfer., Results: Twenty-two patients were included. The mean radiation dose received by the transferred SMG was 29.00 grays (Gy) (standard deviation 14.59 Gy), thus reducing the mean radiation dose to the SMG by a statistically significant 18.34 Gy (confidence interval 95% (13.37, 23.32), P < 0.01) compared to the ST and below the D50 of the SMG (34 Gy). Sixty-five percent of patients rated their saliva as normal or mildly reduced on the UW-QOL as compared to 16% of controls (P = 0.01)., Conclusion: The M-SGT technique is successful at reducing the radiation dose sustained by the SMG during adjuvant treatment and provides a significant improvement in xerostomia-related functional outcomes as compared to historical controls not receiving a gland transfer., Level of Evidence: 4 Laryngoscope, 130:925-929, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Selective neck dissection (SND) is a mainstay of head and neck cancer treatment. A common sequela is shoulder syndrome from spinal accessory nerve (SAN) trauma. Extensive dissection in neck levels 2 and 5 leads to SAN dysfunction. However, it is not known whether limited level 2 dissection reduces SAN injury. The purpose of this double-blind randomized controlled trial was to determine whether omitting level 2b dissection would improve shoulder-related quality of life and function., Methods: Patients with head and neck cancers undergoing surgery were randomized 1:1 to SND without level 2b dissection (group 1) or with it (group 2) on their dominant-hand side. Patients, caregivers, and assessors were blinded. The primary outcome was the change in the Neck Dissection Impairment Index (NDII) score after 6 months. An a priori calculation of the minimally important clinical difference in the NDII score was determined to establish a sample size of 15 patients per group (power = 0.8). Secondary outcomes included shoulder strength and range of motion (ROM) and SAN nerve conduction. The trial was registered at ClinicalTrials.gov (NCT00765791)., Results: Forty patients were enrolled, and 30 were included (15 per group). Six months after the surgery, group 2 demonstrated a significant median decrease in the NDII from the baseline (30 points) and in comparison with group 1, whose NDII dropped 17.5 points (P = .02). Shoulder ROM and SAN conduction demonstrated significant declines in group 2 (P ≤ .05). No adverse events occurred., Conclusions: Level 2b should be omitted in SND when this is oncologically safe and feasible. This allows for an optimal balance between function and cancer cure., (© 2019 American Cancer Society.)

Background: Human Papillomavirus (HPV) infection is well established in oropharyngeal squamous cell carcinoma (OPSCC) and cervical cancer (CC). However, the association between both HPV related cancers remains unclear. The purpose of this study was to investigate the association between HPV related cancers of the oropharynx and cervix., Methods: A provincial cancer registry was used to retrospectively identify all patients diagnosed with OPSCC from 1997-2015. The standardized incidence ratio (SIR) of CC history in women with p16+/-OPSCC was measured., Results: From 372 women with OPSCC included, the SIR of CC was significantly higher across all ages compared to the general population in Alberta, Canada (p < 0.0001)., Conclusions: Women with HPV/p16+ OPSCC have a significantly higher risk of CC compared to the general population., (Copyright © 2019. Published by Elsevier B.V.)

Objectives/hypothesis: The free flap reconstructive protocols of the jaws have been refined over the years and presently are based on bone-driven approaches that generally use the lower border of the mandible or the anterior surface of the maxilla as the templates for reconstruction because these contours are deemed important to the eventual cosmetic outcomes of patients. The ultimate goal of functional jaw reconstruction, however, is the reconstruction of the dental occlusion and oral rehabilitation. The purpose of the present study was to evaluate the Alberta reconstructive technique (ART), which is a new approach of occlusion-driven jaw reconstruction with digitally planned immediate osseointegrated implant installation., Study Design: Prospective cohort study., Methods: This research study considers the ART's safety, effectiveness, accuracy, timeliness of reconstruction, aesthetic appeal, and cost-effectiveness in comparison with the standard bone-driven and delayed osseointegrated implant installation (BDD) protocol., Results: The ART procedures were as safe and more effective at achieving full occlusal reconstruction and oral rehabilitation. The ART cohort of patients achieved oral rehabilitation in 21.4 month as compared to 73.1 months for the BDD cohort. There were no differences in the aesthetic appeal the two groups. The ART cost an average of $22,004 less than BDD and we calculated the quality adjusted life years gain to be between 2.14 and 4.04 in favour of ART., Conclusions: The ART is a good option for patients with jaw defects. It provides a safe, effective, accurate, aesthetic, and cost-effective reconstruction that restores form and function in a timely manner., Level of Evidence: 2b Laryngoscope, 129:S1-S14, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

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., (© 2019 John Wiley & Sons Ltd.)

The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has significantly increased in recent decades due to human papillomavirus (HPV)-mediated oncogenesis. Unfortunately, a growing number of HPV-positive (+) OPSCC survivors are living with the irreversible side effects of treatment. The novel, well-tolerated chemotherapeutics with improved side effect profiles are, therefore, in high demand. Metformin is one such drug, widely used as a first-line oral agent in the treatment of type 2 diabetes mellitus. Curcumin is another well-tolerated agent quickly gaining attention for its medicinal properties. Both metformin and curcumin have been shown to display anticancer properties. This study aimed to determine the antitumor effects of these agents, individually and combined, in HPV+​​​​ ​​​and HPV-negative (-) head and neck squamous cell carcinoma (HNSCC) cell lines. This was achieved by assessing the efficacy of varying drug concentrations on the overall cell viability, proliferation, and expression of common HNSCC biomarkers. The results from protein and RNA expression data are highly variable, as expected, with multiple pathways being affected in cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays and immunofluorescence microscopy suggest that both agents are capable of slowing proliferation and inducing apoptosis. We conclude that curcumin and metformin display effective antitumor effects in both HPV+ and HPV- HNSCC cell lines. The curcumin effects appear more pronounced in the HPV- cell lines. Metformin appears to be more effective at reducing the overall cell numbers in HPV+ cell lines. Metformin and curcumin combined did not appear to have synergistic effects on the proliferation or apoptosis of the treated cell lines., (© 2019 Wiley Periodicals, Inc.)

Objective: To determine the two-dimensional (2D) characteristics of flaps necessary to create three-dimensional (3D) tongue anatomy., Methods: Dissection of 11 fresh, nonpreserved human cadavers was performed. Six defects in each were created: total tongue, total oral tongue, hemiglossectomy, oral hemiglossectomy, total base of tongue, and hemi-base of tongue. The resections were debulked to create flat, 2D mucosal flaps. The dimensions and shapes of these flaps were determined., Results: Each specimen showed consistent dimensions and geometry between cadavers. The total tongue was pear-shaped, the total oral tongue was egg-shaped, the oral hemi-tongue was bullet-shaped, the hemi-tongue resembled a dagger, the total base of tongue was rectangular, and the hemi-base of tongue was hour-glass shaped., Conclusion: Typical dimensions and shapes of common tongue defects were determined. It is conceivable that customizing reconstructive flaps based on these data will increase the accuracy of neo-tongue reconstruction, and thus, improve functional outcomes., (© 2019 Wiley Periodicals, Inc.)

Objective: The total oral tongue (anterior 2/3 glossectomy) defect is seldom addressed in the literature. This is the first series to describe a consistent technique for its reconstruction. The aim of the study is to describe the use of the beavertail modified radial forearm free flap (BTRFFF) to reconstruct a total oral tongue defect and the functional and quality of life outcomes associated with it., Study Design: Retrospective review of prospectively collected data from 2000 to 2010., Methods: All patients at the University of Alberta undergoing head and neck free flap surgery are enrolled in a prospective functional outcomes program. Pre-operatively and at set post-operative time points patients complete videofluoroscopic swallowing studies (VFSS), speech evaluations and quality of life questionnaires (EORTC H&N-35). Peri-operative outcomes were also measured., Results: 17 consecutive patients were included. All were gastrostomy tube free at 12 months post-operatively and tolerating a full soft diet with aspiration scores of 0. Swallowing transit times increased by a mean of 0.4 s (p = 0.32). Speech intelligibility remained high with mean sentence intelligibility at 75% and single word intelligibility at 62%. Quality of life scores returned to baseline and remained satisfactory. Complications related to the BTRFFF were limited to scarring., Conclusions: The BTRFFF provides a robust reconstructive option for the total oral tongue defect with excellent long term functional outcomes and quality of life., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Active tobacco smoking is a well-known risk factor for head and neck malignancy, and strong evidence has associated tobacco as the main carcinogenic factor in squamous cell cancers of this region. Evidence supporting a carcinogenic effect of second-hand smoke (SHS) on head and neck organs in non-smokers was also demonstrated with results consistent with those for active smokers. There is little data on the effects of SHS in patients previously treated for squamous cell carcinomas of the head and neck., Objective: The purpose of this study was to prospectively evaluate the role of SHS on recurrence and survival in treated head and neck cancer patients., Methods: We conducted a prospective cohort study to examine the association between self-reported SHS exposure and the risk of recurrence and mortality in patients treated for squamous cell cancers of the head and neck in a longitudinal fashion. Patients filled out an exhaustive smoking questionnaire on presentation and abbreviated questionnaires at each follow-up visit, which occurred every 6 months. Primary outcome measures were recurrence, development of a second primary malignancy, and recurrence-free survival. Chi square analysis was used to assess the association between SHS and the primary outcomes. A multivariate binary logistic regression analysis was applied to determine the independent predictors of recurrence. Cox proportional hazards and Kaplan Meier modeling were employed to assess the possible relationships between SHS exposure and time to develop the primary outcomes., Results: Untreated new patients with a histologically confirmed diagnosis of first primary SCC of the UADT (defined as cancer of the oral cavity, the oropharynx, the hypopharynx, and the larynx) were recruited. Patients seen at The University of Texas Medical Branch (UTMB) Head and Neck oncology clinic from 1988 to 1996 were considered as cases in this study. One hundred and thirty-five patients were enrolled in the study. The median follow-up time for the sample was 54 months (3.92 years). Complete records were achieved for 92% of patients, thus 124 patients were included in the final analysis. SHS significantly correlated with recurrence and recurrence-free survival. The rate of recurrence was 46% in the group exposed to SHS and 22% in the non-exposed group. Based on multivariate binary logistic regression analysis, SHS exposure was detected as a significant independent predictor for recurrence (HR = 3.00 [95% CI 1.18-7.63]). Kaplan-Meier analysis demonstrated that patients who were not exposed to SHS had a statistically significant longer recurrence-free survival (log-rank P = 0.029). The mean survival for non SHS-exposed patients was 76 [63-89] months versus 54 [45-63] months for those exposed to SHS., Conclusions: SHS exposure is an independent predictor of recurrence and survival after head and neck cancer treatment. These results support the importance and efforts of reducing smoking at home in in the work-place.

Objective: To evaluate multilevel palate and tongue base surgery as a method of treatment of obstructive sleep apnea by comparing the pre- and postoperative apnea-hypopnea index., Methods: We conducted a systematic review. MEDLINE and Embase databases were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews. Two authors screened all articles and performed methodological quality assessment. Relevant articles where reviewed in detail. Standard inclusion criteria were applied for article selection. Relevant data were extracted and summarized, a difference of means random-effects model was performed. Our primary outcome measure was change in apnea-hypopnea index pre-/postsurgical treatment., Results: Of 1,172 studies identified from January 2006 to March 2017, 46 studies met inclusion criteria and were included in the systematic review. This included 11 surgical subgroups and 1,806 patients. Methodological quality and risk of bias assessments were completed. There was strong male predominance 86.8 (standard deviation [SD] = 10.3%), and the average age was 46.8 (SD = 4.0) years. All studies included overweight to obese patients (average body mass index = 29.1 [SD = 3.5]). The average preoperative apnea-hypopnea index was 39.0 (SD = 15.4), and the average postoperative apnea-hypopnea index decreased to 18.3 (SD = 7.5). Meta-analysis data yielded a decrease in apnea-hypopnea index of -23.67 with a 95% confidence interval of -27.27 to -20.06., Conclusions: Non-maxillomandibular advancement, multilevel surgical procedures for obstructive sleep apnea demonstrate significant improvements in reduction of apnea-hypopnea index following surgery in addition to improvement in many other sleep-specific outcomes. Future research should include larger, higher-level studies that compare surgical treatments and identify factors associated with outcomes., Level of Evidence: NA Laryngoscope, 129:1712-1721, 2019., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: There is a paucity of studies reporting long-term survival outcomes for HPV/p16 positive oropharyngeal squamous cell carcinoma (OPSCC). This study aims to compare long-term outcomes of advanced stage p16 positive and negative OPSCCs, treated by surgical and non-surgical modalities., Methods: OPSCC patients from 1998 to 2012 were identified through a prospectively collected cancer registry. P16 immunohistochemistry was used as a surrogate marker for HPV-OPSCC. Overall survival (OS) and aspiration free survival (AFS) comparisons were made between patients treated with chemoradiation (CRT) versus primary surgery and radiation/chemoradiation (S+RT/CRT) at 5, 10 and 15 years post-treatment., Results: A total of 319 patients were included. P16 positive patients and non-smokers had significantly higher long-term (5, 10 and 15-year) OS. Smokers and p16 negative patients treated with S+RT/CRT had improved long-term OS compared to patients who received CRT. Smokers and p16 negative patients had lower long-term AFS. Multivariate analysis showed improved OS was associated with p16 positivity (HR 0.42, 0.28-0.61) and surgery (HR 0.47, 0.32-0.69), whereas lower OS was associated with ECOG ≥ 2 (HR 2.46, 1.61-3.77), smoking (HR 2.37, 1.41-3.99) and higher stage (HR 1.68, 1.05-2.68)., Conclusions: In smokers and p16-negative OPSCC patients, primary surgery may be associated with improved long-term survival and dysphagia-related outcomes., (Copyright © 2018. Published by Elsevier B.V.)

Background: Donor site complications secondary to radial forearm free flap (RFFF) reconstruction can limit recovery. Optimizing hand and wrist function in the post-operative period may allow more efficient self-care and return to activities of daily living. Negative pressure wound dressings (NPD) may increase blood flow and perfusion as compared to static pressure dressings (SPD) designed to minimize shear forces during the healing period. This study aims to compare subjective and objective hand and wrist functional outcomes following RFFF reconstruction with split thickness skin grafts (STSG) in patients treated with NPD and SPD., Methods: Adult patients undergoing RFFF with STSG were identified preoperatively and randomized to receive NPD or SPD following their RFFF reconstruction. NPD involved a single-use, portable device capable of applying 80 mmHg of negative pressure to the forearm donor site. SPD involved a volar splint. Dressings were left in place for seven days with subjective and objective function assessed at seven days, one month and three months postoperatively. The primary outcome was self-reported hand function as measured with the function subscale of the Michigan Hand Questionnaire (MHQ). Secondary outcomes included hand and wrist strength, range of motion, sensation, scar aesthetics, and skin graft complications., Results: Twenty-four patients undergoing RFFF were randomized to NPD or SPD. Patients treated with NPD had improved MHQ self-reported functional scores as compared to those treated with SPD at seven days postoperatively (P = 0.016). Flexion at seven days was improved in NPD group (P = 0.031); however, all other strength and range of motion outcomes were similar between groups. There were no differences in rates of graft complications, scar aesthetics, or sensation., Conclusions: In the immediate post-operative period, NPD was associated with improved patient-reported hand and wrist function. Wound care to optimize hand and wrist function could allow for improved patient outcomes in the immediate postoperative period.

Background: This study aims to investigate EGFR as a prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC)., Methods: OPSCC patients from retrospective (1998-2009) and prospective cohorts (2014-2017) were included. Retrospectively collected tumors were used to construct tissue microarrays (TMAs), which were stained with EGFR, p16, DAPI and Pan-cytokeratin, and digitally quantified. EGFR, CDKN2A and HPV E6/7 levels from prospectively collected OPSCC was measured by droplet digital PCR (ddPCR). Biomarkers were compared to patient covariates, factors and survival outcomes., Results: A total of 249 patients were included retrospectively and 64 patients were enrolled prospectively. p16 status (p < 0.001), smoking above 10 pack years (p = 0.04), smoking above 20 pack years (p < 0.001), total EGFR tumor levels (p = 0.016), and high EGFR within high or low Ki67 tumor nuclear staining (p = 0.03) were found to be significant predictors of 5-year disease specific survival (DSS). A Cox proportional hazard model of DSS showed smoking status and eGFR expression to be dependent of each other on predicting 5-year DSS. ddPCR analysis showed a significant association between smoking status and EGFR levels., Conclusions: Total EGFR tumor levels are predictive of 5-year DSS. EGFR levels correlate with. smoking and could be an objective marker for this disease etiology.

Background: The role of molecular biomarkers in oropharyngeal squamous cell carcinoma (OPSCC) has recently been increasingly recognized. There is conflicting evidence in the literature with regards to the prognostic value of p53 and Bcl-xL., Objective: The purpose of this study was to investigate the association between p53 and Bcl-xL expression profiles and survival outcomes in OPSCC., Methods: Patients diagnosed with OPSCC and treated with curative intent between 1998 and 2009 were included in the study. Patient demographics, disease, treatment, and oncologic outcomes were collected prospectively. A tissue microarray (TMA) from patients' biopsies or surgical specimens was retrospectively constructed. The expression levels of p53, Bcl-xL, and p16 were digitally quantified and correlated to patient survival outcomes., Results: One hundred and sixty-six patients were included (mean age 56.7 years; standard deviation (SD) ± 10.0; 78% male). High expression of Bcl-xL (p= 0.04) was significantly associated with nodal disease at presentation, and decreased overall survival (OS) (p= 0.04). Combined expression of low Bcl-xL and low p53 conferred a survival advantage in non-smokers (p= 0.04). Multivariate analysis supported smoking and p16 status as independent prognosticators for OS., Conclusions: This study suggests that biomarker profiling using Bcl-xL and p53 levels may be of prognostic value in select patients with OPSCC.

Background: Xerostomia is a debilitating side effect of radiotherapy for head and neck cancer. Combining surgical submandibular-gland transfer (SMGT) with intensity-modulated radiotherapy (IMRT) may provide greater protection of salivary function., Methods: This was a single-institution, prospective phase II feasibility trial. Patients with head and neck cancer or unknown primary with neck node metastases received primary surgery with SMGT and postoperative radiotherapy with tomotherapy (60 Gy in 30 fractions). Toxicity and quality of life (QOL) were assessed before surgery, before RT, and after RT., Results: Forty patients received SMGT and IMRT. Only 1 patient experienced grade 3 salivary gland toxicity. At 12 months post-RT, the rate of absent or only mild xerostomia was 89%, and salivary flow rates were approximately 75% of pre-RT levels., Conclusions: The combination of IMRT with SMGT is feasible and with improved dose constraints may maximally spare the parotid and submandibular glands, leading to decreased xerostomia and improved patient QOL., (© 2018 Wiley Periodicals, Inc.)