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The aim of this study was to determine whether implementing ERAS (Enhanced Recovery After Surgery) elements/protocols improves outcomes in orthognathic surgery (OGS) compared to conventional care. To achieve this, ERAS-specific perioperative elements were identified and literature on ERAS for OGS was systematically reviewed. Using PRISMA methodology and GRADE approach, 44 studies with 49 perioperative care elements (13 pre-, 15 intra-, 21 postoperative) were analyzed. While 39 studies focused on single elements, only five presented multimodal protocols, with three related to ERAS. Preoperative elements included antimicrobial and steroid prophylaxis and prevention of postoperative nausea and vomiting. Intraoperative aspects, especially anesthesiological, showed high evidence. Outcome parameters were heterogeneous: complications and postoperative pain were well-investigated with high evidence, while length of stay (LOS) and patient satisfaction received low to medium evidence. ICU LOS, healthcare costs, and readmission rates were underreported. The meta-analysis revealed significant results for pain reduction and trends towards fewer complications and shorter LOS in the ERAS group. Overall, ERAS protocols are not established in OMFS, particularly OGS. Further research is needed in pre- and postoperative care and standardized multimodal analgesia. The next step should be developing a comprehensive OGS protocol through a consensus conference and implementing it in clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Head and neck cancer (HNC) treatment often consists of major surgery followed by adjuvant therapy, which can result in treatment-related side effects, decreased physical function, and diminished quality of life. Perioperative nutrition interventions and early mobilization improve recovery after HNC treatment. However, there are few studies on prehabilitation that include exercise within the HNC surgical care pathway. We have designed a multiphasic exercise prehabilitation intervention for HNC patients undergoing surgical resection with free flap reconstruction. We will use a hybrid effectiveness-implementation study design guided by the RE-AIM framework to address the following objectives: (1) to evaluate intervention benefits through physical function and patient-reported outcome assessments; (2) to determine the safety and feasibility of the prehabilitation intervention; (3) to evaluate the implementation of exercise within the HNC surgical care pathway; and (4) to establish a post-operative screening and referral pathway to exercise oncology resources. The results of this study will provide evidence for the benefits and costs of a multiphasic exercise prehabilitation intervention embedded within the HNC surgical care pathway. This paper describes the study protocol design, multiphasic exercise prehabilitation intervention, planned analyses, and dissemination of findings. Trial registration: https://clinicaltrials.gov/NCT04598087., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Head and neck oncological resection and reconstruction is a complex process that requires multidisciplinary collaboration and prolonged operative time. Numerous factors are associated with operative time, including a surgeon's experience, team familiarity, and the use of new technologies. It is paramount to evaluate the contribution of these factors and modalities on operative time to facilitate broad adoption of the most effective modalities and reduce complications associated with prolonged operative time., Objective: To examine the association of head and neck cancer resection and reconstruction interventions with operative time., Design, Setting, and Participants: This large cohort study included all patients who underwent head and neck oncologic resection and free flap-based reconstruction in Calgary (Alberta, Canada) between January 1, 2007, and March 31, 2020. Data were analyzed between November 2021 and May2022., Interventions: The interventions that were implemented in the program were classified into team-based strategies and the introduction of new technology. Team-based strategies included introducing a standardized operative team, treatment centralization in a single institution, and introducing a microsurgery fellowship program. New technologies included use of venous coupler anastomosis and virtual surgical planning., Main Outcomes and Measures: The primary outcome was mean operative time difference before and after the implementation of each modality. Secondary outcomes included returns to the operating room within 30 days, reasons for reoperation, returns to the emergency department or readmissions to hospital within 30 days, and 2-year and 5-year disease-specific survival. Multivariate regression analyses were performed to examine the association of each modality with operative time., Results: A total of 578 patients (179 women [30.9%]; mean [SD] age, 60.8 [12.9] years) undergoing 590 procedures met inclusion criteria. During the study period, operative time progressively decreased and reached a 32% reduction during the final years of the study. A significant reduction was observed in mean operative time following the introduction of each intervention. However, a multivariate analysis revealed that team-based strategies, including the use of a standardized nursing team, treatment centralization, and a fellowship program, were significantly associated with a reduction in operative time., Conclusions: The results of this cohort study suggest that among patients with head and neck cancer, use of team-based strategies was associated with significant decreases in operative time without an increase in complications.

The spatial organization of the tumor microenvironment has a profound impact on biology and therapy response. Here, we perform an integrative single-cell and spatial transcriptomic analysis on HPV-negative oral squamous cell carcinoma (OSCC) to comprehensively characterize malignant cells in tumor core (TC) and leading edge (LE) transcriptional architectures. We show that the TC and LE are characterized by unique transcriptional profiles, neighboring cellular compositions, and ligand-receptor interactions. We demonstrate that the gene expression profile associated with the LE is conserved across different cancers while the TC is tissue specific, highlighting common mechanisms underlying tumor progression and invasion. Additionally, we find our LE gene signature is associated with worse clinical outcomes while TC gene signature is associated with improved prognosis across multiple cancer types. Finally, using an in silico modeling approach, we describe spatially-regulated patterns of cell development in OSCC that are predictably associated with drug response. Our work provides pan-cancer insights into TC and LE biology and interactive spatial atlases ( http://www.pboselab.ca/spatial_OSCC/ ; http://www.pboselab.ca/dynamo_OSCC/ ) that can be foundational for developing novel targeted therapies., (© 2023. Springer Nature Limited.)

There are few prognostic biomarkers and targeted therapeutics currently in use for the clinical management of oral squamous cell carcinoma (OSCC) and patient outcomes remain poor in this disease. A majority of mutations in OSCC are loss-of-function events in tumour suppressor genes that are refractory to conventional modes of targeting. Interestingly, the chromosomal segment 3q22-3q29 is amplified in many epithelial cancers, including OSCC. We hypothesized that some of the 468 genes located on 3q22-3q29 might be drivers of oral carcinogenesis and could be exploited as potential prognostic biomarkers and therapeutic targets. Our integrative analysis of copy number variation (CNV), gene expression and clinical data from The Cancer Genome Atlas (TCGA), identified two candidate genes: NCBP2, TFRC, whose expression positively correlates with worse overall survival (OS) in HPV-negative OSCC patients. Expression of NCBP2 and TFRC is significantly higher in tumour cells compared to most normal human tissues. High NCBP2 and TFRC protein abundance is associated with worse overall, disease-specific survival, and progression-free interval in an in-house cohort of HPV-negative OSCC patients. Finally, due to a lack of evidence for the role of NCBP2 in carcinogenesis, we tested if modulating NCBP2 levels in human OSCC cell lines affected their carcinogenic behaviour. We found that NCBP2 depletion reduced OSCC cell proliferation, migration, and invasion. Differential expression analysis revealed the upregulation of several tumour-promoting genes in patients with high NCBP2 expression. We thus propose both NCBP2 and TFRC as novel prognostic and potentially therapeutic biomarkers for HPV-negative OSCC., (© 2023. The Author(s).)

Background: Otolaryngology-head and neck surgical (OHNS) trainees' operating exposure is supplemented by a combination of didactic teaching, textbook reading, and cadaveric dissections. Conventional teaching, however, may not adequately equip trainees with an understanding of complex visuospatial relationships of the middle ear. Both face and content validation were assessed of a novel three-dimensional (3D) photorealistic virtual ear simulation tool underwent face and content validation as an educational tool for OHNS trainees., Methods: A three-dimensional mesh reconstruction of open access imaging was generated using geometric modeling, which underwent global illumination, subsurface scattering, and texturing to create photorealistic virtual reality (VR) ear models were created from open access imaging and comiled into a educational platform. This was compiled into an educational VR platform which was explored to validate the face and content validity questionnaires in a prospective manner. OHNS post-graduate trainees were recruited from University of Toronto and University of Calgary OHNS programs. Participation was on a voluntary basis., Results: Total of 23 OHNS post-graduate trainees from the two universities were included in this study. The mean comfort level of otologic anatomy was rated 4.8 (± 2.2) out of 10. Senior residents possessed more otologic surgical experience (P < 0.001) and higher average comfort when compared to junior residents [6.7 (± 0.7) vs. 3.6 (± 1.9); P = 0.001]. Face and content validities were achieved in all respective domains with no significant difference between the two groups. Overall, respondents believed OtoVIS was a useful tool to learn otologic anatomy with a median score of 10.0 (8.3-10.0) and strongly agreed that OtoVIS should be added to OHNS training with a score of 10.0 (9.3-10.0)., Conclusions: OtoVIS achieved both face and content validity as a photorealistic VR otologic simulator for teaching otologic anatomy in the postgraduate setting. As an immersive learning tool, it may supplement trainees' understanding and residents endorsed its use., (© 2023. The Author(s).)

Background: There is a growing concern with inappropriate, excessive perioperative blood transfusions. Understanding the influence of low preoperative hemoglobin (Hgb) on perioperative blood transfusion (PBT) in head and neck cancer (HNC) surgery with free flap reconstruction may help guide clinical practice to reduce inappropriate treatment among these patients. The objective is to synthesize evidence regarding the association between preoperative Hgb and PBT among major HNC free flap surgeries., Methods: Terms and synonyms for HNC surgical procedures, Hgb and PBT were used to search MEDLINE, Embase, CINAHL, Cochrane Central Register of Controlled Trials and Cochrane Database of Reviews from inception to February 2020. Reference lists of included full texts and studies reporting the preoperative Hgb, anemia or hematocrit (exposure) and the PBT (outcome) in major HNC surgery with free flap reconstruction were eligible. Studies examining esophageal, thyroid and parathyroid neoplasms were excluded; as were case reports, case series (n < 20), editorials, reviews, perspectives, viewpoints and responses. Two independent, blinded reviewers screened titles, abstracts and full texts in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. A random-effects model was used to pool reported data. The primary outcome was the proportion of patients who had a PBT. Subgroup analysis examined sources of heterogeneity for perioperative predictors of PBT (age, sex, flap type, flap site and preoperative Hgb). We also examined mean preoperative Hgb in the PBT and no PBT groups., Results: Patients with low preoperative Hgb were transfused more than those with normal Hgb (47.62%, 95% CI = 41.19-54.06, I 2  = 0.00% and 13.92%, 95% CI = 10.19-17.65, I 2  = 20.69%, respectively). None of the predictor variables explained PBT. The overall pooled mean preoperative Hgb was 12.96 g/dL (95% CI = 11.33-14.59, I 2  = 0.00%) and was 13.58 g/dL (95% CI = 11.95-15.21, I 2  = 0.00%) in the no PBT group and 12.05 g/dL (95% CI = 10.01 to 14.09, I 2  = 0.00%) in the PBT group., Conclusions: The heterogeneity between studies, especially around the trigger for PBT, highlights the need for additional research to guide clinical practice of preoperative Hgb related to PBT to enhance patient outcomes and improve healthcare stewardship., (© 2023. The Author(s).)

Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15-30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV + OPSCC patients., Methods: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes., Findings: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2-25.5, P = 3.6 × 10 -5 ) and mixed (HR = 6.4, 95% CI: 2.2-18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation., Interpretation: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV + OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned., Funding: CIHR, European Union, and the NIH., Competing Interests: Declaration of interests PYFZ, JWB, PCB, JSM and ACN have a US patent pending for the UWO3 score. All other authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Head and neck cancer (HNC) surgical patients experience a high symptom burden. Multiphasic exercise prehabilitation has the potential to improve patient outcomes, and to implement it into the care pathway, the perspectives of patients and healthcare providers (HCPs) must be considered. The purpose of this study was thus to gather feedback from HNC surgical patients and HCPs on building exercise into the standard HNC surgical care pathway. Methods: Semi-structured interviews were conducted with patients and HCPs as part of a feasibility study assessing patient-reported outcomes, physical function, and in-hospital mobilization. Interview questions included satisfaction with study recruitment, assessment completion, impact on clinical workflow (HCPs), and perceptions of a future multiphasic exercise prehabilitation program. This study followed an interpretive description methodology. Results: Ten patients and ten HCPs participated in this study. Four themes were identified: (1) acceptability and necessity of assessments, (2) the value of exercise, (3) the components of an ideal exercise program, and (4) factors to support implementation. Conclusion: These findings highlight the value of exercise across the HNC surgical timeline from both the patient and the HCP perspective. Results have informed the implementation of a multiphasic exercise prehabilitation trial in HNC surgical patients.

Background: Understanding occurrence and timing of second events (recurrence and second primary cancer) is essential for cancer specific survival analysis. However, this information is not readily available in administrative data., Methods: Alberta Cancer Registry, physician claims, and other administrative data were used. Timing of second event was estimated based on our developed algorithm. For validation, the difference, in days between the algorithm estimated and the chart-reviewed timing of second event. Further, the result of Cox-regression modeling cancer-free survival was compared to chart review data., Results: Majority (74.3%) of the patients had a difference between the chart-reviewed and algorithm-estimated timing of second event falling within the 0-60 days window. Kaplan-Meier curves generated from the estimated data and chart review data were comparable with a 5-year second-event-free survival rate of 75.4% versus 72.5%., Conclusion: The algorithm provided an estimated timing of second event similar to that of the chart review., (© 2022 Wiley Periodicals LLC.)

Background: Head and neck cancer (HNC) patients are an understudied population whose treatment often includes surgery, causing a wide range of side effects. Exercise prehabilitation is a promising tool to optimize patient outcomes and may confer additional benefits as a prehabilitation tool. The primary objective of this study was to assess the feasibility of measuring patient-reported outcomes (PROs), physical function, and in-hospital mobilization across the HNC surgical timeline in advance of a future prehabilitation trial. The secondary objective was to examine potential changes in these outcomes across the surgical timeline., Methods: HNC patients scheduled to undergo oncologic resection with free-flap reconstruction completed assessments of PROs and physical function at three timepoints across the surgical timeline (baseline, in-hospital, and postsurgical/outpatient). Mobilization was measured during the in-hospital period. The feasibility of recruitment and measurement completion was tracked, as were changes in both PROs and physical function., Results: Of 48 eligible patients, 16 enrolled (recruitment rate of 33%). The baseline and in-hospital PROs were completed by 88% of participants, while the outpatient assessments were completed by 81% of participants. The baseline and in-hospital assessment of physical function were completed by 56% of participants, and 38% completed the outpatient assessment. Measuring in-hospital mobilization was completed for 63% of participants., Conclusion: Measuring PROs and in-hospital mobilization is feasible across the surgical timeline in HNC; however, the in-person assessment of physical function prior to surgery was not feasible. A multidisciplinary collaboration between exercise specialists and clinicians supported the development of new clinical workflows in HNC surgical care that will aid in the implementation of a future prehabilitation trial for this patient population., (© 2022. The Author(s).)

Objective: This study aimed to evaluate the association between prescribers' opioid prescribing history and persistent postoperative opioid use in cancer patients undergoing curative-intent surgery., Background: Study has shown that patients may be over-prescribed analgesics after surgery. However, whether and how the prescriber's opioid prescribing behavior impacts persistent opioid use is unclear., Methods: All adults with a diagnosis of solid cancers who underwent surgery during the study period (2009-2015) in Alberta, Canada and were opioid-naïve were included. The key exposure was the historical opioid-prescribing pattern of a patient's most responsible prescriber. The primary outcome was "new persistent postoperative opioid user," was defined as a patient who was opioid-naïve before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery., Results: We identified 24,500 patients. Of these, 2106 (8.6%) patients became a new persistent opioid user after surgery. Multivariate analysis demonstrated that patients with most responsible prescribers that historically prescribed higher daily doses of opioids (≥50 vs <50 mg oral morphine equivalent) had an increased risk of new persistent opioid use after surgery (odds ratio = 2.41, P < 0.0001). In addition to the provider's prescribing pattern, other factors including younger age, comorbidities, presurgical opioid use, chemotherapy, type of tumor/surgical procedure were also found to be independently associated with new persistent postoperative opioid use., Conclusions: Our results suggest that prescriber with a history of prescribing a higher opioid dose is an important predictor of persistent postoperative opioid use among cancer patients undergoing curative-intent surgery., Competing Interests: All the authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Summary: Patient-reported outcomes regarding donor-site morbidity and quality of life for the fibula free flap in head and neck reconstruction patients have not been studied. The authors reviewed and identified patients who had undergone head and neck reconstruction using a fibula free flap (2011 to 2016). Patients were assessed via physical examination and two patient-reported outcomes questionnaires: the Foot and Ankle Outcome Score (score range, 0 to 100) and the Pain Disability Questionnaire (score range, 0 to 100). Quantitative data were analyzed with appropriate statistical tests. Semistructured interviews exploring donor-site challenges were performed and analyzed using thematic analysis. Seventeen patients agreed to participate. Their mean age was 62 years (range, 41 to 81 years). Mean follow-up was 38 months (range, 12 to 65 years). Mean perceived level of function compared to baseline was 67 percent. Mean scores for the Foot and Ankle Outcome Score subscales were 84.6 (pain), 80.5 (symptoms), 86.7 (activities of daily living), 67.7 (sport), and 65.6 (quality of life). The mean Pain Disability Questionnaire score was 26.3 (mild/moderate perceived disability). Higher perceived level of function was associated with higher Foot and Ankle Outcome Score values (pain, symptoms, and activities of daily living, p < 0.05). Donor limbs had decreased range of motion and manual muscle testing scores compared with their contralateral limbs (p < 0.05). Lack of ankle support and balance, resulting in limitations and aversions to daily and sporting activities, were the most common themes regarding donor-site challenges. In conclusion, patients who have undergone fibula free flap harvest struggle with ankle support and balance and face functional difficulties that have an impact on their quality of life. Multidisciplinary approaches for targeted rehabilitation after fibula free flap harvest should be explored to determine the impact on patients' quality of life., (Copyright © 2021 by the American Society of Plastic Surgeons.)

One of the foundational elements of enhanced recovery after surgery (ERAS) guidelines is early postoperative mobilization. For patients undergoing head and neck cancer (HNC) surgery with free flap reconstruction, the ERAS guideline recommends patients be mobilized within 24 h postoperatively. The objective of this study was to evaluate compliance with the ERAS recommendation for early postoperative mobilization in 445 consecutive patients who underwent HNC surgery in the Calgary Head and Neck Enhanced Recovery Program. This retrospective analysis found that recommendation compliance increased by 10% despite a more aggressive target for mobilization (from 48 to 24 h). This resulted in a decrease in postoperative mobilization time and a stark increase in the proportion of patients mobilized within 24 h (from 10% to 64%). There was a significant relationship between compliance with recommended care and time to postoperative mobilization (Spearman's rho = -0.80; p < 0.001). Hospital length of stay was reduced by a median of 2 days, from 12 (1QR = 9-16) to 10 (1QR = 8-14) days ( z = 3.82; p < 0.001) in patients who received guideline-concordant care. Engaging the clinical team and changing the order set to support clinical decision-making resulted in increased adherence to guideline-recommended care for patients undergoing major HNC surgery with free flap reconstruction.

Surgery with free flap reconstruction is a standard treatment for head and neck cancer (HNC). Because of the complexity of HNC surgery, recovery can be challenging, and complications are common. One of the foundations of enhanced recovery after surgery (ERAS) is early postoperative mobilization. The ERAS guidelines for HNC surgery with free flap reconstruction recommend mobilization within 24 h. This is based mainly on evidence from other surgical disciplines, and the extent to which mobilization within 24 h improves recovery after HNC surgery has not been explored. This retrospective analysis included 445 patients from the Calgary Head and Neck Enhanced Recovery Program. Mobilization after 24 h was associated with more complications of any type (OR = 1.73, 95% CI [confidence interval] = 1.16-2.57) and more major complications (OR = 1.76; 95% CI = 1.00-3.16). When accounting for patient and clinical factors, mobilization after 48 h was a significant predictor of major complications (OR = 2.61; 95% CI = 1.10-6.21) and prolonged length of stay (>10 days; OR = 2.85, 95% CI = 1.41-5.76). This comprehensive analysis of the impact of early mobilization on postoperative complications and length of stay in a large HNC cohort provides novel evidence supporting adherence to the ERAS early mobilization recommendations. Early mobilization should be a priority for patients undergoing HNC surgery with free flap reconstruction.

Background: Physician opioid-prescribing patterns have significant impacts on the current opioid crisis. Patients who use opioids in the postoperative period are at risk of developing chronic postoperative opioid use. This study determined the rate of chronic postoperative opioid use among head and neck cancer patients undergoing primary surgery with free-flap reconstruction. Additionally, this study identified major risk factors associated with the development of chronic postoperative opioid use., Methods: A retrospective chart review was performed for all adults (age ≥ 18 years) undergoing primary head and neck surgical resection with free-flap reconstruction between January 2008 and December 2015. Patients were identified from a prospectively collected database, Otobase™. Data from the provincial drug insurance program were used to capture drug dispensing information to determine chronic opioid use at 3- and 12-months postoperatively. Data extracted from Otobase™ included patient demographics, social habits, clinical stage, pathological stage, type of surgery, and adjuvant treatment., Results: The total cohort was comprised of 212 patients. Chronic opioid use at 3- and 12- months postoperatively was observed in 136 (64%) and 116 (55%) patients, respectively. Of the 212 patients, 85 patients (40%) were identified as preoperative opioid users and 127 were opioid naïve (60%). Of the 85 patients who were preoperative opioid users, 70 (82%) and 63 (77%) patients continued to use opioids 3- and 12-months postoperatively, respectively. The proportion of opioid-naïve patients who were using opioids at 3- and 12-months postoperatively was 52% (66 patients) and 42% (53 patients), respectively. Identified risk factors included preoperative opioid use, prior tobacco use, advanced pathologic T-stage, and adjuvant treatment., Conclusions: Among head and neck cancer patients that have undergone major resection with free-flap reconstruction, the prevalence of chronic postoperative opioid users was considerable. Identified risk factors included preoperative opioid use, prior tobacco use, tumor stage, and adjuvant treatment.

Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore the association between MMA and postoperative opioid use and pain control in patients undergoing major head and neck surgery. We performed a retrospective study in adult (age ≥ 18 years) patients undergoing primary head and neck cancer resection with free-flap reconstruction. All patients were treated using an established care pathway. The baseline group was treated between January 2015-December 2015 ( n = 41), prior to the implementation of MMA, and were compared to an MMA-treated cohort treated between December 2017-June 2019 ( n = 97). The primary outcome was the proportion of opioids prescribed and oral morphine equivalents (OMEs) consumed during the hospitalization. The secondary outcome was pain control. We found that the post-MMA group consumed fewer opioids in the postoperative period compared to the pre-MMA group. Prior to post-operative day (POD) 6, pain control was better in the post-MMA group; however, the pain control lines intersect on POD 6 and the pre-MMA group appeared to have better pain control from PODs 7-10. In conclusion, our data suggest MMA is an effective method of pain control and opioid reduction in patients undergoing surgery for head and neck cancer with free flap reconstruction. MMA use was associated with a significant decrease in the quantity of opioids consumed postoperatively. The MMA protocol was associated with improved pain management early in the postoperative course. Finally, the MMA protocol is a feasible method of pain control and may reduce the adverse side effects associated with opioid use.

Background: Close margins influence treatment and outcome in patients with oral squamous cell carcinoma (OSCC). This study evaluates 187 cases of surgically treated OSCC regarding the impact of close margins on recurrence-free survival (RFS) and disease-specific survival (DSS)., Methods: Predictors of worsened outcome were identified using Kaplan-Meier analysis and multivariate Cox regression analysis., Results: Tumour size [HR:1.70(0.95-3.08)], nodal status [HR:2.15(1.00-4.64)], presence of extracapsular spread (ECS) [HR:6.36(2.41-16.74)] and smoking history [HR:2.87(1.19-6.86)] were associated with worsened RFS. Similar factors were associated with worsened DSS. Close margins did not influence RFS or DSS., Conclusions: While most conventional risk factors for OSCC conferred a worsened outcome, close margins did not. One explanation for this would be that close margins (< 5 mm) are equivalent to clear margins and the cutoff definition for a close margin should be re-evaluated. Lack of standardized pathology could also reduce accuracy of reporting of close surgical margins.

Few studies have evaluated vascularized nerve grafts (VNGs) for facial nerve (CNVII) reconstruction. We sought to evaluate long-term outcomes for CNVII recovery following reconstruction with VNGs. A retrospective review of all patients at a tertiary centre who underwent radical parotidectomy and immediate CNVII reconstruction with VNGs was performed (January 2009-December 2019). Preoperative demographics, perioperative factors (flap type, source of VNGs), and postoperative factors [complications, adjuvant therapy, revisionary procedures, length of follow-up, and CNVII function via the House-Brackmann scale (HB)] were collected. Data were summarized qualitatively. Twelve patients (M age = 53 ± 18 years) with a mean follow-up of 33 (± 23) months were included. Six patients underwent reconstruction with a radial forearm flap and dorsal sensory branches of the radial nerve. Six patients underwent reconstruction with an anterolateral thigh flap and only deep motor branches of the femoral nerve to the vastus lateralis (n = 4) or combined with the lateral femoral cutaneous nerve (n = 2). Two patients regained nearly normal function (HB = 2). Eight patients regained at least resting symmetry (HB = 3 for n = 7; HB = 4 for n = 1). One patient regained a flicker of movement (HB = 5). One patient did not regain function (HB = 6). Six patients had static revision procedures to improve symmetry. Five patients had disease recurrence; 3 died from their disease. VNGs offer a practical and viable addition to the CNVII reconstruction strategy, and result in good functional recovery with acceptable donor site deficits. The associated adipofascial component of these flaps can also augment the soft tissue defect left after tumor ablation., (Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

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.

Few, scalable, evidence-based psychosocial interventions exist for adolescent and young adult cancer survivors (AYAs, 18-39 years old). Using an existing, facilitated, online synchronous chat group-plus-education model (OSG+E), we replaced their educational workbook with an AYA-created film to stimulate an age-specific, emotion-focused group discussion (OSG+V). This randomized proof-of-concept trial compared the two models' content suitability, group processes, and feasibility over 9 months in 34 male and female AYAs with a range of cancers. AYAs rated the OSG + V model more suitable, cohesive, and as having higher levels of important group processes than the OSG+E. A larger randomized trial is feasible for this AYA-appropriate, emotion-focused OSG + V model.

Background: Care pathways (CPs) are helpful in reducing unwanted variation in clinical care. Most studies of CPs show they improve clinical outcomes but there is little known about the long-term impact of CPs as part of a sustained quality management program. Head and neck (HN) surgery with free flap reconstruction is complex, time-consuming and expensive. Complications are common and therefore CPs applied to this patient population are the focus of this paper. In this paper we report outcomes from a 9 year experience designing and using CPs in the management of patients undergoing major head and neck resection with free flap reconstruction., Methods: The Calgary quality management program and CP design is described the accompanying article. Data from CP managed patients undergoing major HN surgery were prospectively collected and compared to a baseline cohort of patients managed with standard care. Data were retrospectively analyzed and intergroup comparisons were made., Results: Mobilization, decannulation time and hospital length of stay were significantly improved in pathway-managed patients (p = 0.001). Trend analysis showed sustained improvement in key performance indicators including complications. Return to the OR, primarily to assess a compromised flap, is increasing., Conclusions: Care pathways when deployed as part of an ongoing quality management program are associated with improved clinical outcomes in this complex group of patients.

Background: Care pathways (CPs) offer a proven method of systematically improving patient care. CPs are particularly helpful in complex clinical conditions where variation in care is a problem such as patients undergoing major head and neck resection with free flap reconstruction. Although CPs have been used to manage this patient group, most CPs are implemented as part of relatively short-term quality improvement projects. This paper outlines a detailed methodology for designing and delivering a quality management program sustained for 9 years., Methods: We describe a change management approach informed by Kotter's "8 Step Process" that provided a useful framework to guide program development and implementation. We then provide a detailed, step by step description of how such a program can be implemented as well as a detailed summary of time and costs for design, implementation and sustainability phases. An approach to design and delivery of a measurement, audit and feedback system is also provided., Results: We present a summary of resources needed to design and implement a head and neck surgery quality management program. The primary result of this study is a design for a sustainable quality management program that can be used to guide and improve care for patients undergoing major head and neck resection with free flap reconstruction., Conclusions: A change management approach to design and delivery of a head and neck quality management program is practical and feasible.

Following publication of the original article [1], the authors identified incorrect ordering and incorrect files being used for Figs. 1, 2 and 3.

Background: Trainees in Otolaryngology-Head and Neck Surgery must gain proficiency in a variety of challenging temporal bone surgical techniques. Traditional teaching has relied on the use of cadavers; however, this method is resource-intensive and does not allow for repeated practice. Virtual reality surgical training is a growing field that is increasingly being adopted in Otolaryngology. CardinalSim is a virtual reality temporal bone surgical simulator that offers a high-quality, inexpensive adjunct to traditional teaching methods. The objective of this study was to establish the face and content validity of CardinalSim through a national study., Methods: Otolaryngologists and resident trainees from across Canada were recruited to evaluate CardinalSim. Ethics approval and informed consent was obtained. A face and content validity questionnaire with questions categorized into 13 domains was distributed to participants following simulator use. Descriptive statistics were used to describe questionnaire results, and either Chi-square or Fishers exact tests were used to compare responses between junior residents, senior residents, and practising surgeons., Results: Sixty-two participants from thirteen different Otolaryngology-Head and Neck Surgery programs were included in the study (32 practicing surgeons; 30 resident trainees). Face validity was achieved for 5 out of 7 domains, while content validity was achieved for 5 out of 6 domains. Significant differences between groups (p-value of < 0.05) were found for one face validity domain (realistic ergonomics, p = 0.002) and two content validity domains (teaching drilling technique, p = 0.011 and overall teaching utility, p = 0.006). The assessment scores, global rating scores, and overall attitudes towards CardinalSim, were universally positive. Open-ended questions identified limitations of the simulator., Conclusion: CardinalSim met acceptable criteria for face and content validity. This temporal bone virtual reality surgical simulation platform may enhance surgical training and be suitable for patient-specific surgical rehearsal for practicing Otolaryngologists.

Objectives/hypothesis: To examine if there has been a reduction in premature mortality due to head and neck cancers and their subtypes in the Canadian population between 1980 and 2010., Study Design: Retrospective database review., Methods: Mortality data for head and neck cancers were obtained from the World Health Organization's mortality database. Years of life lost (YLL) was calculated according to Canadian life tables. A new measure, average lifespan shortened (ALSS), was calculated as a ratio of YLL over the expected lifespan., Results: During the period of interest, decreases in age standardized rates of death adjusted to the World Standard Population were observed mainly among men. The adjusted YLL rates remained unchanged with respect to oral cancers in women, but slightly decreased for oral cancers in men and for laryngeal cancers in both sexes. Our new measure of ALSS showed that in 1980, patients with oral cancers lost an average of 20% of their lifespan, whereas in 2010, men and women still lost approximately 20% and 18%, respectively. Patients with laryngeal cancers lost 18% of their lifespan in both sexes in 1980 and 17% in 2010. The ALSS subanalysis showed that the largest gain of lifespan was observed for cancers of the hypopharynx in men and for cancers of the floor of mouth and nasopharynx in women., Conclusions: There appears to be modest improvements in premature mortality due to head and neck cancers in Canada over a 30-year period, with the exception of oral cancers in men. Changes in premature mortality varied slightly by cancer subtypes., Level of Evidence: NA Laryngoscope, 130:911-917, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To test the performance of an oral cancer prognostic 13-gene signature for the prediction of survival of patients diagnosed with HPV-negative and p16-negative oral cavity cancer., Materials and Methods: Diagnostic formalin-fixed paraffin-embedded oral cavity cancer tumor samples were obtained from the Fred Hutchinson Cancer Research Center/University of Washington, University of Calgary, University of Michigan, University of Utah, and seven ARCAGE study centers coordinated by the International Agency of Research on Cancer. RNA from 638 Human Papillomavirus (HPV)-negative and p16-negative samples was analyzed for the 13 genes using a NanoString assay. Ridge-penalized Cox regressions were applied to samples randomly split into discovery and validation sets to build models and evaluate the performance of the 13-gene signature in predicting 2-year oral cavity cancer-specific survival overall and separately for patients with early and late stage disease., Results: Among AJCC stage I/II patients, including the 13-gene signature in the model resulted in substantial improvement in the prediction of 2-year oral cavity cancer-specific survival. For models containing age and sex with and without the 13-gene signature score, the areas under the Receiver Operating Characteristic Curve (AUC) and partial AUC were 0.700 vs. 0.537 (p < 0.001), and 0.046 vs. 0.018 (p < 0.001), respectively. Improvement in predicting prognosis for AJCC stage III/IV disease also was observed, but to a lesser extent., Conclusions: If confirmed using tumor samples from a larger number of early stage oral cavity cancer patients, the 13-gene signature may inform personalized treatment of early stage HPV-negative and p16-negative oral cavity cancer patients., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Same-day surgery (SDS) following mastectomy is safe and well accepted. Overnight admission in patients fit for discharge is an inefficient use of health resources. In response to a national review highlighting SDS following mastectomy at 1.4% in Alberta, a perioperative pathway was conceived., Methods: The pathway was implemented across Alberta at 13 hospitals beginning in 2016. A steering committee was assembled, and clinical and administrative leads at each site were identified. Opportunities along the patient care experience whereby action could be taken to promote uptake of SDS were identified. Provincially branded support materials including presentations, order sets, and standard operating procedures were developed. Nurse educators provided in-service teaching such as standardized drain care and discharge teaching. Educational booklets, group classes, and online resources were developed for patients and families. An audit of SDS rates, unscheduled return to the emergency department (ED), and readmission rates was reported to teams quarterly, allowing for iterative modifications. Patient-reported experience measures (PREMs) were collected., Results: SDS following mastectomy increased from 1.7 to 47.8%, releasing an estimated 831 bed days per year. No differences in unexpected return to the ED or readmission to hospital existed between SDS patients and those admitted overnight. A total of 102 patients completed the PREM survey, of whom 90% felt "excellent or good" with the plan to go home, how to care for themselves once home, and who to contact should issues arise., Conclusions: Implementation of a provincial perioperative pathway improved uptake of SDS following mastectomy and demonstrated favorable PREMs.

Background: There are a number of studies in the literature that describe the prevalence, causes, and factors associated with chronic postoperative opioid use, but there is a lack of synthesis of the literature to guide clinicians in optimally managing postoperative pain while avoiding opioid dependence. Thus, the goal of this study was to perform a systematic review of the literature to investigate the prevalence of chronic postoperative opioid use and the associated risk factors., Materials and Methods: A systematic search was performed using Ovid Medline and Embase according to PRISMA guidelines. Data were collected on the following outcomes of interest: prevalence of opioid use at 3, 6, and 12 months postoperatively, and risk factors associated with chronic postoperative opioid use., Results: Forty-three articles were included in the final analysis. The mean prevalence of chronic postoperative opioid use in all populations at 3, 6, and 12 months postoperatively was 30.5%, 25.6%, and 25.2%, respectively. The prevalence of patients who developed chronic opioid use at 3, 6, and 12 months postoperatively was 10.4%, 8.5%, and 9.8%, respectively. Forty of the articles analyzed risk factors associated with chronic postoperative opioid use. The most common associated risk factor identified was preoperative opioid use with 27 articles demonstrating a significant association with chronic postoperative opioid use., Discussion: The current opioid crisis is in part secondary to the prevalence of chronic opioid use following surgery. This study identified associated risk factors with chronic postoperative opioid use, which may help identify patients at risk for developing chronic postoperative opioid use.

Background: Second event (recurrence or second primary cancer)-free survival is an important indicator for assessing treatment efficacy. However, second events are not explicitly documented in administrative data such as cancer registries. Thus, validated algorithms using administrative data are needed to identify second events of oropharyngeal cancers., Methods: The algorithms were developed using classification and regression tree models. Data from chart review served as the reference standard. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated., Results: The high-sensitivity algorithm achieved 87.9% (95% confidence interval: 82.2%-93.6%) sensitivity, 84.5% (81.1%-87.8%) specificity, 61.2% (54.1%-68.4%) PPV, 96.2% (94.2%-98.1%) NPV, and 85.2% (82.3%-88.1%) accuracy. The high-PPV algorithm obtained 52.4% (43.6%-61.2%) sensitivity, 99.1% (98.2%-100.0%) specificity, 94.2% (88.7%-99.7%) PPV, 88.2% (85.3%-91.0%) NPV, and 88.9% (86.3%-91.5%) accuracy., Conclusion: The validity of the algorithms for identifying second events following primary treatment of oropharyngeal cancers was acceptable., (© 2019 Wiley Periodicals, Inc.)

Background: Recurrence is not explicitly documented in cancer registry data that are widely used for research. Patterns of events after initial treatment such as oncology visits, re-operation, and receipt of subsequent chemotherapy or radiation may indicate recurrence. This study aimed to develop and validate algorithms for identifying breast cancer recurrence using routinely collected administrative data., Methods: The study cohort included all young (≤ 40 years) breast cancer patients (2007-2010), and all patients receiving neoadjuvant chemotherapy (2012-2014) in Alberta, Canada. Health events (including mastectomy, chemotherapy, radiation, biopsy and specialist visits) were obtained from provincial administrative data. The algorithms were developed using classification and regression tree (CART) models and validated against primary chart review., Results: Among 598 patients, 121 (20.2%) had recurrence after a median follow-up of 4 years. The high sensitivity algorithm achieved 94.2% (95% CI: 90.1-98.4%) sensitivity, 93.7% (91.5-95.9%) specificity, 79.2% (72.5-85.8%) positive predictive value (PPV), and 98.5% (97.3-99.6%) negative predictive value (NPV). The high PPV algorithm had 75.2% (67.5-82.9%) sensitivity, 98.3% (97.2-99.5%) specificity, 91.9% (86.6-97.3%) PPV, and 94% (91.9-96.1%) NPV. Combining high PPV and high sensitivity algorithms with additional (7.5%) chart review to resolve discordant cases resulted in 94.2% (90.1-98.4%) sensitivity, 98.3% (97.2-99.5%) specificity, 93.4% (89.1-97.8%) PPV, and 98.5% (97.4-99.6%) NPV., Conclusion: The proposed algorithms based on routinely collected administrative data achieved favorably high validity for identifying breast cancer recurrences in a universal healthcare system in Canada.

Background: Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer., Method: Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups., Results: Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7-69.9%) to 80.7% (95% CI 79.5-81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3-57.1%) to 45.3% (95% CI 44.1-46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center., Conclusions: Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.

Objective: This study compares the volume of on-call otolaryngology consultations in a tertiary care center over a 5-year period. The objective of this study was to identify changes in the volume of consultations in an inpatient setting., Methods: A cross-sectional retrospective study was performed to determine the volume of consultations. The years 2010 and 2015 were the timepoints for the cross-sectional analysis. A review of electronic medical records was performed to identify all patients associated with the otolaryngology service from the emergency department, inpatient wards, and intensive care units. The primary outcome was the number of otolaryngology consultations per year., Results: The number of on-call consultations in 2010 was 992. In 2015, the number of on-call consultations was 2174. This represents a 120% increase in the number of consultations over a 5-year period ( P < .001)., Conclusion: There has been a significant increase in the volume of on-call otolaryngology consultations at our tertiary care center. This increase has the potential to adversely affect patient care. A better understanding of the cause of this increase may allow policymakers and health care practitioners to improve patient access, physician workloads, and resource allocation.

Background: Operative endoscopy and flexible fiber-optic in-office tissue biopsy are common techniques to assess suspicious laryngopharyngeal lesions., Methods: The primary outcome was the delay to the initiation of treatment. Secondary outcomes were delay to biopsy, histopathological diagnosis, and assessment at a multidisciplinary oncology clinic. A retrospective analysis was performed to assess the relative delays between these approaches to biopsy of laryngopharyngeal lesions., Results: There were 114 patients in the study cohort; 44 in-office and 70 operative endoscopic biopsies). The mean delay from consultation to biopsy was 17.4 days for the operative endoscopy group and 1.3 days for the in-office group. The mean delay from initial otolaryngology consultation to initiation of treatment was 51.7 days and 44.6 days for the operative endoscopy and in-office groups, respectively., Conclusion: In-office biopsy reduced the time from initial consultation to biopsy. The temporal gains via in-office biopsy did not translate into faster access to treatment. This outcome highlights the opportunity to improve access to treatment for patients with early diagnosis.

Background: Our study quantifies the effectiveness of perioperative pain control in a cohort of patients undergoing major head and neck surgery with free flap reconstruction. Our long-term goal is to improve pain control and thereby increase mobility, decrease postoperative complications and decrease hospital stay., Methods: A retrospective analysis was performed at a tertiary, academic head and neck surgical oncology program in Calgary, Alberta, Canada from January 1, 2015 - December 31, 2015. Pain scores were recorded prospectively. Primary outcomes were frequency of postoperative pain assessments and pain intensity using the numeric rating scale., Results: The cohort included 41 patients. Analysis was limited to pain scores recorded from postoperative days 1-14. There was an average of 7.3 pain measurements per day (SD 4.6, range 1-24) with the most frequent monitoring on postoperative days 1-4. Median pain scores ranged from 0 to 4.5 with the highest median score on postoperative day 6. The daily maximum pain scores recorded ranged from 8 to 10 with scores of 10 recorded on postoperative days 1, 2, 3, 5, 7, 8, and 10. Patients most frequently had inadequate pain control on postoperative days 1, 2, 4, and 5 with the majority occurring on postoperative day 1., Conclusions: Postoperative pain control could be improved at our centre. The frequency of pain assessments is also highly variable. Ongoing measurement, audit, and feedback of analgesic protocol effectiveness is an excellent first step in improving perioperative pain management in patients undergoing major head and neck cancer surgery with free flap reconstruction.

Purpose of Review: To review the development and the benefits of enhanced recovery after surgery (ERAS) protocols in non-head and neck disciplines and to describe early implementation efforts in major head and neck surgeries., Recent Findings: Several groups have adopted ERAS protocols for major head and neck surgery and demonstrated its feasibility and effectiveness., Summary: There is growing evidence that clinical and financial outcomes for patients undergoing major head and neck surgery rehabilitation can be significantly improved by standardizing preoperative, intraoperative, and postoperative treatment protocols. Current experience is limited to single centers. A future goal is to broaden the adoption of ERAS in head and neck surgical oncology to include national and international collaboration, data sharing, and learning.

Background: Oropharyngeal Squamous Cell Carcinoma (OPSCC) is increasing in incidence despite a decline in traditional risk factors. Human Papilloma Virus (HPV), specifically subtypes 16, 18, 31 and 35, has been implicated as the high-risk etiologic agent. HPV positive cancers have a significantly better prognosis than HPV negative cancers of comparable stage, and may benefit from different treatment regimens. Currently, HPV related carcinogenesis is established indirectly through Immunohistochemistry (IHC) staining for p16, a tumour suppressor gene, or polymerase chain reaction (PCR) that directly tests for HPV DNA in biopsied tissue. Loop mediated isothermal amplification (LAMP) is more accurate than IHC, more rapid than PCR and is significantly less costly. In previous work we showed that a subtype specific HPV LAMP assay performed similar to PCR on purified DNA. In this study we examined the performance of this LAMP assay without DNA purification., Methods: We used LAMP assays using established primers for HPV 16 and 18, and new primers for HPV 31 and 35. LAMP reaction conditions were tested on serial dilutions of plasmid HPV DNA to confirm minimum viral copy number detection thresholds. LAMP was then performed directly on different human cell line samples without DNA purification., Results: Our LAMP assays could detect 10 5 , 10 3 , 10 4 , and 10 5 copies of plasmid DNA for HPV 16, 18, 31, and 35, respectively. All primer sets were subtype specific, with no cross-amplification. Our LAMP assays also reliably amplified subtype specific HPV DNA from samples without requiring DNA isolation and purification., Conclusions: The high risk OPSCC HPV subtype specific LAMP primer sets demonstrated, excellent clinically relevant, minimum copy number detection thresholds with an easy readout system. Amplification directly from samples without purification illustrated the robust nature of the assay, and the primers used. This lends further support HPV type specific LAMP assays, and these specific primer sets and assays can be further developed to test for HPV in OPSCC in resource and lab limited settings, or even bedside testing.

Background: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is increasing and has better survival than non-HPV related oropharyngeal SCC. This study compared surgical to nonsurgical treatments and demographic, clinical, and survival differences in patients with oropharyngeal SCC, stratified by p16 status., Methods: We assembled a cohort of adult patients with oropharyngeal SCC diagnosed between 2000 and 2008 in Alberta. The tumor p16 biomarker was measured using fluorescent immunohistochemistry., Results: In this cohort, p16 data were available for 115 of 357 patients; and 66% (n = 76) were p16-positive. Patients with p16 data had comparable outcomes to those without. Surgically treated p16-negative patients had improved 5-year disease-specific survival (DSS) and overall survival (OS) compared with nonsurgical patients. There were no differences in survival outcomes between surgical and nonsurgical treatment for patients with p16-positive disease., Conclusion: Patients with p16-positive oropharyngeal SCC had similar outcomes regardless of treatment. Patients with p16-negative tumors may benefit from primary surgery with postoperative adjuvant therapy., (© 2017 Wiley Periodicals, Inc.)

Oral squamous cell carcinoma (OSCC) is the most commonly diagnosed type of head and neck cancer, accounting for ~300,000 new cases worldwide annually. Carbonic anhydrase IX (CAIX) and Ki-67 have been associated with reduced disease-specific survival (DSS) in patients with OSCC. We previously proposed a combined CAIX and Ki-67 signature of 'functional hypoxia' and sought to replicate this association in a larger independent cohort of patients with OSCC at the Fred Hutchinson Cancer Research Center (FHCRC) in Seattle. The study population included patients with incident primary OSCC treated at the University of Washington Medical Center and the Harborview Medical Center in Seattle between December 2003 and February 2012. Archived tumor blocks were obtained with tissue samples from 189 patients, and triplicate 0.6 mm cores were assembled into tissue microarrays (TMAs). Fluorescence immunohistochemistry and AQUAnalysis ® were used to quantify the expression of tumoral CAIX (tCAIX) and stromal CAIX (sCAIX) and tumoral Ki-67 for each TMA core. Hazard ratios for DSS were calculated using Cox proportional hazards analysis. High tCAIX and sCAIX expression levels were associated with reduced DSS (aHR=1.003, 95% CI:1.00-1.01 and aHR=1.010, 95% CI:1.001-1.019, per AQUA score unit, respectively). Ki-67 expression was not associated with survival (aHR=1.01, 95% CI:0.99-1.02) in the FHCRC cohort. DSS for patients with high sCAIX and low Ki-67 did not differ from that of other patient groups. Elevated tCAIX was associated with reduced DSS as a continuous and as a dichotomized (75%) variable. sCAIX was associated with DSS as a continuous variable but not when dichotomized (75%). However, the previously proposed 'functional hypoxia' signature was not replicated in the current FHCRC study. The failure to replicate our prior observation of poorer survival in patients with combined high sCAIX and low tumoral Ki-67 was likely due to the absence of an association between tumoral Ki-67 and DSS in this cohort. However, the association between DSS and tCAIX and sCAIX supports a role for CAIX in OSCC clinical outcomes.

The majority of head and neck cancers arise from the oral cavity and oropharynx. Many of these lesions will be amenable to surgical resection using transoral approaches including transoral robotic surgery (TORS). To develop and control TORS tools, precise dimensions of the oral cavity and pharynx are desirable. CT angiograms of 76 patients were analyzed. For the oral cavity, only the maximum length and width were measured, while for the pharynx, the width, length, and areas of the airway were all measured and the volume calculated. A prototype TORS tool was developed and tested based on the findings and dimensions. The design modification of the tool is in progress. The mean male oral cavity width and length were 93.3 ± 4.3 and 77.0 ± 7.2 mm, respectively, and the mean male pharyngeal width, length, area, and volume were 26.5 ± 7.2 mm, 16.2 ± 8.8 mm, 325 ± 149 mm 2 , and 28,440 ± 14,100 mm 3 , respectively, while the mean female oral cavity width and length were 84.5 ± 12.9 and 71.0 ± 6.3 mm, respectively, and the mean female pharyngeal width, length, area, and volume were 24.8 ± 5.6 mm, 13.7 ± 3.2 mm, 258 ± 98 mm 2 , and 17,660 ± 7700 mm 3 , respectively. The developed TORS tool was tested inside the oral cavity of an intubation mannequin. These data will also be used to develop an electronic no-go cone-shape tunnel to improve the safety of the surgical field. Reporting the oral cavity and pharyngeal dimensions is important for design of TORS tools and creating control zones for the workspace of the tool inside the oral cavity.

Objective To evaluate the effect of anatomy-specific virtual reality (VR) surgical rehearsal on surgeon confidence and temporal bone dissection performance. Study Design Prospective pre- and poststudy of a novel virtual surgical rehearsal platform. Setting Academic otolaryngology-head and neck surgery residency training programs. Subjects and Methods Sixteen otolaryngology-head and neck surgery residents from 2 North American training institutions were recruited. Surveys were administered to assess subjects' baseline confidence in performing 12 subtasks of cortical mastoidectomy with facial recess. A cadaver temporal bone was randomly assigned to each subject. Cadaver specimens were scanned with a clinical computed tomography protocol, allowing the creation of anatomy-specific models for use in a VR surgical rehearsal platform. Subjects then rehearsed a virtual mastoidectomy on data sets derived from their specimens. Surgical confidence surveys were administered again. Subjects then dissected assigned cadaver specimens, which were blindly graded with a modified Welling scale. A final survey assessed the perceived utility of rehearsal on dissection performance. Results Of 16 subjects, 14 (87.5%) reported a significant increase in overall confidence after conducting an anatomy-specific VR rehearsal. A significant correlation existed between perceived utility of rehearsal and confidence improvement. The effect of rehearsal on confidence was dependent on trainee experience and the inherent difficulty of the surgical subtask. Postrehearsal confidence correlated strongly with graded dissection performance. Subjects rated anatomy-specific rehearsal as having a moderate to high contribution to their dissection performance. Conclusion Anatomy-specific virtual rehearsal improves surgeon confidence in performing mastoid dissection, dependent on surgeon experience and task difficulty. The subjective confidence gained through rehearsal correlates positively with subsequent objective dissection performance.

Importance: Head and neck cancers often require complex, labor-intensive surgeries, especially when free flap reconstruction is required. Enhanced recovery is important in this patient population but evidence-based protocols on perioperative care for this population are lacking., Objective: To provide a consensus-based protocol for optimal perioperative care of patients undergoing head and neck cancer surgery with free flap reconstruction., Evidence Review: Following endorsement by the Enhanced Recovery After Surgery (ERAS) Society to develop this protocol, a systematic review was conducted for each topic. The PubMed and Cochrane databases were initially searched to identify relevant publications on head and neck cancer surgery from 1965 through April 2015. Consistent key words for each topic included "head and neck surgery," "pharyngectomy," "laryngectomy," "laryngopharyngectomy," "neck dissection," "parotid lymphadenectomy," "thyroidectomy," "oral cavity resection," "glossectomy," and "head and neck." The final selection of literature included meta-analyses and systematic reviews as well as randomized controlled trials where available. In the absence of high-level data, case series and nonrandomized studies in head and neck cancer surgery patients or randomized controlled trials and systematic reviews in non-head and neck cancer surgery patients, were considered. An international panel of experts in major head and neck cancer surgery and enhanced recovery after surgery reviewed and assessed the literature for quality and developed recommendations for each topic based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. All recommendations were graded following a consensus discussion among the expert panel., Findings: The literature search, including a hand search of reference lists, identified 215 relevant publications that were considered to be the best evidence for the topic areas. A total of 17 topic areas were identified for inclusion in the protocol for the perioperative care of patients undergoing major head and neck cancer surgery with free flap reconstruction. Best practice includes several elements of perioperative care. Among these elements are the provision of preoperative carbohydrate treatment, pharmacologic thromboprophylaxis, perioperative antibiotics in clean-contaminated procedures, corticosteroid and antiemetic medications, short acting anxiolytics, goal-directed fluid management, opioid-sparing multimodal analgesia, frequent flap monitoring, early mobilization, and the avoidance of preoperative fasting., Conclusions and Relevance: The evidence base for specific perioperative care elements in head and neck cancer surgery is variable and in many cases information from different surgerical procedures form the basis for these recommendations. Clinical evaluation of these recommendations is a logical next step and further research in this patient population is warranted.

Objectives: This article presents a quantitative technique to assess motion quality and smoothness during the performance of micromanipulation tasks common to surgical maneuvers. The objective is to investigate the effectiveness of the jerk index, a derivative of acceleration with respect to time, as a kinetostatic measure for assessment of surgical performance., Design: A surgical forceps was instrumented with a position tracker and accelerometer that allowed measurement of position and acceleration relative to tool motion. Participants were asked to perform peg-in-hole tasks on a modified O'Connor Dexterity board and a Tweezer Dexterity pegboard (placed inside a skull). Normalized jerk index was calculated for each individual task to compare smoothness of each group., Setting: This study was conducted at Project neuroArm, Cumming School of Medicine, the University of Calgary., Participants: Four groups of participants (surgeons, surgery residents, engineers, and gamers) participated in the tests., Results: Results showed that the surgeons exhibited better jerk index performance in all tasks. Moreover, the residents experienced motions closer to the surgeons compared to the engineers and gamers. One-way analysis of variance test indicated a significant difference between the mean values of normalized jerk indices among 4 groups during the performance of all tasks. Moreover, the mean value of the normalized jerk index significantly varied for each group from one task to another., Conclusions: Normalized jerk index as an independent parameter with respect to time and amplitude is an indicator of motion smoothness and can be used to assess hand motion dexterity of surgeons. Furthermore, the method provides a quantifiable metrics for trainee assessment and proficiency, particularly relevant as surgical training shifts toward a competency-based paradigm., (Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)