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Purpose: Recent reports have suggested that fluid restriction as part of Enhanced Recovery after Surgery (ERAS) pathways may increase the risk of AKI in radical cystectomy (RC) patients. We sought to evaluate the impact of ERAS initiation on AKI incidence at a high-volume tertiary care center., Materials and Methods: We performed a retrospective review of our IRB approved database to identify patients receiving RC from 2010 to 2019. ERAS was initiated at our institution in October 2016. Acute kidney injuries were graded according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria and must have occurred within 7 days of indexed RC. Estimated glomerular filtration rate (eGFR) was captured at baseline, 1, 3, 6, and 12 months respectively. Categorical variables were compared with the Pearson-Chi square test. Quantitative variables were analyzed with the Wilcoxon-Rank sum test. Multivariable binary logistic regression and interaction analysis was used to identify predictors of AKI., Results: Twelve hundred patients were included. Twenty-two percent of patients experienced an AKI within 7 days. Patients in the ERAS cohort experienced less AKIs after RC (18% vs. 25%, P = 0.003). When adjusting for year of surgery, ERAS was not a significant predictor for AKI on multivariable analysis (OR: 0.87, P = 0.73). On interaction analysis, during the ERAS era, intracorporeal robot-assisted radical cystectomy (iRARC) was associated with decreased odds of AKI (OR: 0.39, P = 0.034). There were no significant differences in eGFR at 12 months postoperatively (P = 0.16)., Conclusion: Unlike previous reports, ERAS initiation was not associated with increased risk of AKI at a tertiary care high-volume center., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To describe the successes and challenges associated with developing an otolaryngology-head and neck surgery (OHNS) medical education app and website., Design: From 2010 to 2018, OHNS faculty across Canada contributed to the development of a smartphone app, LearnENT. LearnENT 1.0, was initially launched in 2012 using the Apple iOS 6 platform. The app utilized a novel user interface and interactive features to help learners develop approaches to OHNS clinical problems, review relevant anatomy, history, and physical examination skills. However, the release of iOS 7 necessitated a redesign and relaunch of LearnENT which occurred from 2015 to 2018 to produce the final version of the app, LearnENT 2.0. Through the relaunching process, the LearnENT team redesigned the app's interface, produced a web version of the app, and created a new content management system., Setting: OHNS departments across Canada., Participants: OHNS faculty members, residents, and medical students., Results: Through this approach, a sustainable, widely accessible, open access OHNS e-Learning resource was developed. Since the relaunch, the LearnENT app has 2728 user accounts and has been widely used across the globe with users in 36 countries outside of North America. LearnENT is currently the official learning app of the Canadian Society of OHNS, has been featured on several different medical education platforms and incorporated into medical school curricula at various institutions., Conclusions: The authors successfully created a novel e-Learning resource with the goal of improving OHNS medical education both nationally and internationally., (Copyright © 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Head and neck squamous cell carcinoma (HNSCC) affects various anatomical sites, which often dictates whether the cancer is managed with primary surgery or radiation. This study aimed to assess differences in single nucleotide variation (SNV), copy number, mRNA abundance, methylation, and tumor microenvironment (TME) between HPV-negative oral cavity (OC), oropharyngeal (OPC), hypopharyngeal (HPC), and laryngeal (LC) cancers within The Cancer Genome Atlas (TCGA)., Methods: We downloaded the clinical information and molecular data for the TCGA HNSCC cohort from the data portal and published literature. The TME was estimated using mRNA abundance data. We conducted our analyses within the Bioconductor statistical framework in the R environment. CNA and mRNA abundance results were correlated and grouped with SNV results for downstream pathway analysis., Results: LC had a higher mutational burden than OC and OPC (p <10 -4 ). LC tumors were enriched in CSMD3, NSD1, DCHS2 and ANK2 SNVs, while OC tumors were enriched in CASP8 SNVs (FDR < 0.1). LCs were enriched for neuronal and glycosylation pathways, while OCs were enriched for extracellular matrix pathways. B cells and endothelial cells were more abundant in LC while monocytes were more abundant in OC (FDR < 0.1). OPC was the most hypoxic, followed by OC then LC (FDR < 0.05). OC had greater methylation of Hox genes than LC. Subsite analysis revealed that oral tongue cancers had fewer CASP8 and FBN2 mutations and higher dendritic cell abundance than other oral cavity cancers., Conclusions: We identified significant genomic, transcriptional, and microenvironmental differences between HPV-negative HNSCC. Further study is warranted to determine if these findings portend differential response to specific treatment modalities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Survival in head and neck squamous cell carcinoma (HNSCC) has been associated with patient sex, typically with males experiencing poorer outcomes. It is unclear if this disparity is based in divergent tumor biology. We analyzed the TCGA HNSCC cohort to uncover disparities in the somatic single nucleotide variation (SNV), copy number alteration (CNA) and mRNA abundance profiles between males and females. Critically, we stratified our results by tumor HPV status to control for this significant confounder., Methods: SNV, CNA and mRNA abundance differences between males and females were compared separately for the HPV-positive (n = 67) and negative (n = 431) TCGA HNSCC cohorts. Overall survival outcomes were compared in males and females in both HPV-positive and HPV-negative subsets of patients., Results: Females were found to have poorer overall survival than males (p = 0.048), largely due to higher rates of HPV-positive disease among men. SNV analysis revealed that in HPV-positive disease, there were no differences by sex after accounting for the false discovery rate (FDR). In HPV-negative tumors, BRWD3 mutations occurred more frequently in the tumors of female patients compared to males after adjusting for the FDR (p = 0.02). Further, HPV-negative BRWD3 mutant tumors were found to have significantly worse 5-year overall survival compared to wildtype on multivariate analysis (p = 0.02). There were 88 heterozygous deletions and 14 amplifications that were differentially altered between male and female HPV-negative tumors and associated with expression changes. Pathway analysis of these genes revealed that tumors from males were enriched in five pathways including chemokine and phosphophatidylinositol signaling., Conclusions: Reanalysis of the TCGA HNSCC dataset stratified by sex revealed that males in this cohort had a significant survival advantage, due to a higher proportion of HPV-positive disease. Mutations in BRWD3 were more frequent in HPV-negative tumors of females and were associated with poorer overall survival. BRWD3 may represent a novel biomarker of patient outcomes, but will require additional validation., 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 © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Spleen tyrosine kinase (SYK) is a promoter of cell survival in a variety of cell types, including normal and cancerous epithelial cells. We hypothesized that SYK would an important therapeutic target to inhibit for the treatment of HNSCC., Materials and Methods: SYK protein abundance in patient tumours was evaluated. SYK protein and mRNA abundance was used to examine patient survival and human papillomavirus (HPV) status. Small-interfering RNAs and gene editing with CRISPR/Cas9 were used to evaluate SYK expression on proliferation in HNSCC cell lines. The potency of SYK inhibitor ER27319 maleate on cellular proliferation was tested using a panel of 28 HNSCC cell lines and in vivo in HNSCC patient-derived xenograft (PDX) models., Results: Moderate to high protein expression of SYK was observed in 24% of patient tumors and high SYK expression was exclusively observed in HPV-positive samples (p < 0.001). SYK inhibition with RNA interference, gene editing or a SYK inhibitor (ER27319) decreased cell proliferation and migration. Treatment of PDXs with ER27319 maleate was observed to reduce tumour burden in vivo in two of three models., Conclusions: HPV-positive HNSCC harbours high SYK protein levels. We demonstrate that proliferation, migration and overall burden of these tumours can be reduced by genetic or pharmacologic inhibition of SYK. Taken together, these data establish SYK as a therapeutic target for HNSCC., 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 © 2019. Published by Elsevier Ltd.)

Objectives: The PI3K/AKT/mTOR pathway is frequently altered in head and neck squamous cell cancer (HNSCC), making this pathway a logical therapeutic target. However, PI3K targeting is not universally effective. Biomarkers of response are needed to stratify patients likely to derive benefit and exclude those unlikely to respond., Materials and Methods: We examined the sensitivity of cell lines with constitutively-active (G12V mutant) HRAS and wild-type HRAS to PI3K inhibition using flow cytometry and cell viability assays. We then overexpressed and silenced HRAS and measured sensitivity to the PI3K inhibitor BYL719. Immunoblotting was used to determine activation of the PI3K pathway. MEK and mTOR inhibitors were then tested in HRAS mutant cells to determine their efficacy., Results: HRAS mutant cell lines were non-responsive to PI3K inhibition. Overexpression of HRAS led to reduced susceptibility to PI3K inhibition, while knockdown improved sensitivity. Immunoblotting revealed suppressed AKT phosphorylation upon PI3K inhibition in both wild-type and HRAS mutant cell lines, however mutant lines maintained phosphorylation of S6, downstream of mTOR. Targeting mTOR effectively reduced viability of HRAS mutant cells and we subsequently examined the ERK-TSC2-mTOR cascade as a mediator of resistance to PI3K inhibition., Conclusions: HRAS mutant cells are resistant to PI3K inhibition and our findings suggest the involvement of a signalling intersection of the MAPK and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity. mTOR inhibition alone or in combination with MAPK pathway inhibition may be a promising therapeutic strategy for this subset of HNSCC tumors., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Both early and advanced stage laryngeal cancers are treated with organ-preserving strategies including radiation alone or concurrent chemoradiotherapy. While organ-preserving modalities have proven effective in eradicating cancer while also preserving laryngeal function, there remains a proportion of cases where residual or recurrent cancer prevails, or conversely, where radiotherapy renders a larynx dysfunctional. In these circumstances, salvage total laryngectomy is often the surgical treatment. The effects of radiotherapy to the neck, amplified by chemotherapy, can create an inhospitable surgical environment, making the salvage laryngectomy an operation fraught with the potential for major complications such as the dreaded pharyngocutaneous fistula. The introduction of vascularized tissue from outside the irradiated field decreases the risk of major wound complications. Free tissue transfer, with a variety of donor sites available, is commonly employed to reconstruct either a patch or a circumferential segment of the pharynx. When there is enough pharyngeal mucosa for primary closure, a vascularized onlay graft or a pharyngeal interposition graft can be used to reinforce the closure. This has been demonstrated to both reduce the severity of pharyngocutaneous fistula and decrease the risk of developing a pharyngocutaneous fistula compared to primary closure alone. Beyond mitigating the risk for perioperative complications, flap selection may have implications on the long-term outcomes after salvage total laryngectomy and these must be considered preoperatively. The purpose of this review is to examine the various options for reconstruction after salvage total laryngectomy and to examine some of their advantages and disadvantages in the short and long-term., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: The temporoparietal fascia flap (TPFF) is a versatile tool in head and neck reconstruction. This article aims to describe the spectrum of TPFF applications through a series of case studies and related review of the literature., Methods: Medical records were reviewed to identify cases that represent major TPFF application categories. A literature review was performed to support the presentation and discussion of each case category., Results: Seven cases were identified each representing a distinct application category. These included auricular reconstruction, hair-bearing tissue transfer, facial soft tissue augmentation, cutaneous and mucosal oncologic defect repair, reconstruction after salvage laryngectomy, skull base reconstruction, and orbital reconstruction., Conclusion: The TPFF is a uniquely versatile tool in head and neck reconstructive surgery. Outstanding in its pliable, ultra-thin yet hardy and highly vascular form, the temporoparietal fascia flap is a workhorse for the creative head and neck reconstructive surgeon., (Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Tracheal suction catheters (TSCs) are used to clear mucus from an endotracheal tube (ETT). The clearance rate is critical because airway mucus stasis leads to obstruction, but prolonged catheter suctioning can lead to hypoxemia. The rate of mucus clearance from an ETT is thought to be influenced by the properties of the mucus, the pressure used to suction the mucus, and the diameter of the catheter. In this study, different adult TSCs were evaluated for their ability to suction mucus simulants that had properties similar to airway mucus., Methods: Six different 14F TSC designs were evaluated. All catheters had the same end hole size, but the two side holes were sized at 3 mm, 4 mm, or 5 mm. A coagulant (Polyox Water Soluble Resin Coagulant NF; Dow Chemical Company; Cary, NC) was mixed with water at concentrations of 0.5%, 1.5%, and 3.0% to simulate mucus or sputum. Suction effectiveness was evaluated by the mass percentage of the coagulant suctioned over 10 s at 100 mm Hg from an 8.0 ETT., Measurements and Results: The 1.5% and 3.0% simulants had properties comparable to human airway mucus and sputum. Suction effectiveness was less with the 3.0% coagulant simulant compared with the 1.5% and 0.5% simulants. Suction effectiveness was greater (p < 0.01) with TSCs that had nonparallel holes and a side hole diameter of 5 mm when tested with the 1.5% and 3.0% simulants. However, no best catheter could be identified among TSCs when tested with the more liquid-like 0.5% simulant., Conclusions: Greater TSC side hole diameter and nonparallel positioning was important for suctioning mucus simulants that are similar to mucus or sputum. The distance between side holes, end hole size, suction force, and duration of suctioning were not tested but could also have an effect on TSC performance.