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(1) Background: To compare oncologic outcomes of South Asian (SA) patients treated for oral squamous cell carcinoma (OSCC) to the general population. (2) Methods: Adult patients who underwent surgical resection of OSCC +/- adjuvant treatment between 2009 and 2022 (N = 697) at a regional cancer centre in Canada were included. SA patients, identified using a validated method, were compared to non-SA patients. Kaplan-Meier methods were used to compare the primary outcomes, disease-specific survival (DSS) and recurrence-free survival (RFS) across baseline univariate characteristics, including betel nut consumption. Median follow-up time was 36.4 months. Cox proportional hazard models were used to identify independent predictors of survival with significance set at p < 0.05. (3) Results: SA patients (9% of cohort, N = 64) were significantly younger and had lower rates of smoking and alcohol consumption compared to non-SA patients ( p < 0.05). SA patients had a two-fold higher risk of recurrence and significantly worse disease-specific survival, even after adjusting for stage and high-risk features [RFS: HR 2.01 (1.28-3.14), DSS: HR 1.79 (1.12-2.88)]. The consumption of betel nut was not associated with outcomes. (4) Conclusions: SA patients had significantly worse oncologic outcomes, even after controlling for known predictors of poor prognosis. These findings are novel and can inform personalized treatment decisions and influence public health policies when managing patients with different ethnic backgrounds., Competing Interests: The authors declare no conflicts of interest.

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.)

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: 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.)

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.

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.

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.

Background: The extent of initial surgical resection for low-risk papillary thyroid cancer (PTC) remains debatable. Since the 2015 American Thyroid Association (ATA) guidelines, several retrospective studies have reported that 40-60% of patients initially treated with lobectomy would require a completion thyroidectomy (CTx) due to high-risk pathological features (HRFs). These studies are limited by variable preoperative stratification and inability to quantify the value of intraoperative assessment. The study objectives were to determine whether diligent preoperative and intraoperative assessment improves the appropriateness of initial surgery for low-risk PTCs and whether varying the criteria for lobectomy reduces the need for CTx. Methods: A prospectively collected province-wide database was analyzed over a 10-year period (2008-2017) for patients who underwent a total thyroidectomy (TT) for PTC without preoperative HRFs. All patients had preoperative ultrasound and fine-needle aspirates. Unique to this database are mandatory synoptic operative fields that identify intraoperative risk factors such as positive lymph nodes and local invasion. Results: In total, 74% of patients (709/959) were deemed eligible for lobectomy. Of those eligible, 149 (21%) had intraoperative risk factors that would necessitate conversion to TT at the initial operation. A further 209 (30%) would require CTx due to HRFs on final pathology. Varying the preoperative criteria for lobectomy did not significantly affect intraoperative conversion or CTx rates. Conclusions: Although intraoperative assessment reduced the need for CTx in 21%, up to 30% of patients would still require a second operation. Altering the preoperative criteria does not influence this outcome. Patients deemed eligible for lobectomy should be informed that despite careful pre- and intraoperative assessment, there is up to a 30% risk of requiring CTx.

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: 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.

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.

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.

Background: Long operating time and high blood loss contribute to post-surgical morbidity. Therefore, strategies to reduce these factors should to be tested using robust methods. The purpose of this study was to evaluate the impact of using the harmonic scalpel on operating time and blood loss in patients undergoing resection for advanced oral cancer (OSCC)., Methods: Thirty-six adult head and neck cancer patients with advanced OSCC requiring primary tumor resection with uni- or bi- lateral selective neck dissection from July 2012 to September 2014 were randomized to either the control group (traditional surgery) or the experimental group (harmonic surgery). Patients older than 18 years who were able to provide informed consent were eligible. Primary outcomes of interest were: intraoperative blood loss (mL) and operative time (minutes) for the ablative part of the surgery., Results: Mean blood loss in the experimental group was 260 mL versus 403 mL in the control group (p = 0.08). Mean operative time was 140 min in the experimental group and 159 min in the control group (p = 0.2)., Conclusions: In this randomized controlled trial, use of the harmonic scalpel did not effect intraoperative blood loss or OR time in patients undergoing surgery for advanced OSCC., Trial Registration: ClinicalTrials.gov, NCT02017834 .

Background: Indications for performing a prophylactic central neck dissection (pCND) in papillary thyroid cancer (PTC) remain controversial. It is unclear how identification of lymph node (LN) metastases should impact the decision to treat with radioactive iodine (RAI). The goals of this study were to identify indications for performing pCND and identify factors that predict the use of adjuvant RAI., Methods: This was a population based cross-sectional analysis. A prospectively collected database identified 594 patients who underwent total thyroidectomy +/- CND. A multivariate model was constructed to identify indications for pCND and predictors of the use of RAI., Results: 425 CNDs were performed of which 224 were prophylactic. Conventional risk factors (age, tumor size, extra-thyroidal extension) were not associated with performing a pCND. The presence of clinically suspicious lymphadenopathy was the only factor associated with performing CND, thus rendering the CND therapeutic. Positive LNs were retrieved in 39 % of pCND's, upstaging 87 patients. Among all peri-operative predictors of receiving RAI, presence of LN metastases was the strongest predictor [OR = 5.9 (3.7-9.5)], while tumor size was a modest predictor [OR = 1.8 (1.5-2.1)]. Other conventional risk factors did not predict use of adjuvant RAI., Conclusions: Conventional risk factors were not indications for performing a pCND, implying that the decision was based on individual surgeon preference. Performing pCND upstaged 39 % of patients from cN0 to pN1a, increasing the likelihood of receiving RAI 6-fold. Conventional risk factors were not predictors of receiving adjuvant RAI. This highlights the need for a unified approach to performing a pCND and administering RAI.

Background: In 2014, Alberta Health Services released guidelines for treating oral squamous cell carcinoma (OSCC)., Methods: A retrospective analysis was performed to assess the historical selection of patients with OSCC for postoperative radiotherapy (PORT) in a prospectively collected cohort of patients being treated with primary surgery. The primary outcome was compliance with the 2014 Alberta Health Services (AHS) guideline recommendations for PORT. The secondary outcome was the selection of PORT according to published pathological indications of high, intermediate, and low risk of recurrence. Reasons for discordance were analyzed., Result: Noncompliance with the new AHS guidelines and published indications for PORT was observed in 17% and 30% of cases, respectively. The reasons for discordance with published indications included: clinician decision (n = 41) and unmodifiable factors (n = 17)., Conclusion: The impact of noncompliance on patient outcomes is being studied. The effect of the publication of the guidelines on selection for PORT going forward will be monitored. © 2016 Wiley Periodicals, Inc. Head Neck 38: First-1529, 2016., (© 2016 Wiley Periodicals, Inc.)

Background: The purposes of this study were to explore the association of a postoperative clinical care pathway for patients undergoing major head and neck surgery with microvascular reconstruction on postdischarge health care utilization and cost and to compares a nonpathway group (n = 60) to a prospective, pathway-managed group (n = 54). Our primary purpose was to understand whether pathway-managed patients used postdischarge health care resources differently than patients managed without a care pathway., Methods: Health care utilization data (counts and costs) were collected for the 3 months after discharge. Differences in utilization were compared using Poisson regression. The null hypothesis was that there were no differences in utilization between the pathway and nonpathway groups., Results: Pathway patients had fewer postdischarge encounters in 2 of 4 sectors. Readmission costs were significantly less in the pathway group only., Conclusion: A postoperative inpatient clinical care pathway in patients with head and neck cancer is associated with decreased health care utilization and inpatient costs in the 3 months after discharge. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1216-E1220, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is a growing problem that presents a significant challenge to Otolaryngologist-Head and Neck Surgeons. Knowledge of HPV status yields critical prognostic information, with potential for treatment selection based on tumour HPV status. The current gold standard of diagnosis, PCR, is expensive, demanding and time consuming. Alternatives such as p16 immunohistochemistry are subjective and potentially inaccurate. Loop-mediated isothermal amplification (LAMP) is a rapid, robust and inexpensive molecular diagnostic technique., Objectives: Our aim was to verify LAMP as a potential bedside diagnostic assay for subtyping of HPV in OPSCC., Study Design: DNA from 72 formalin-fixed paraffin embedded (FFPE) OPSCC patient samples was tested. PCR and LAMP were then performed to specifically identify HPV 16, 18, 31, 33 and 35., Results and Conclusions: For these high-risk subtypes, LAMP had an overall sensitivity of 99.4% and specificity of 93.2% relative to PCR. LAMP is a promising technology that can accurately diagnose high-risk HPV infection., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: The lack of prognostic biomarkers in oral squamous cell carcinoma (OSCC) has hampered treatment decision making and survival in OSCC remains poor. Histopathological features are used for prognostication in OSCC and, although useful for predicting risk, manual assessment of histopathology is subjective and labour intensive. In this study, we propose a method that integrates multiple histopathological features of the tumor microenvironment into a single, digital pathology-based biomarker using nuclear fractal dimension (nFD) analysis., Methods: One hundred and seven consecutive OSCC patients diagnosed between 1998 and 2006 in Calgary, Canada were included in the study. nFD scores were generated from DAPI-stained images of tissue microarray (TMA) cores. Ki67 protein expression was measured in the tumor using fluorescence immunohistochemistry (IHC) and automated quantitative analysis (AQUA®). Lymphocytic infiltration (LI) was measured in the stroma from haematoxylin-eosin (H&E)-stained TMA slides by a pathologist., Results: Twenty-five (23.4%) and 82 (76.6%) patients were classified as high and low nFD, respectively. nFD was significantly associated with pathological tumor-stage (pT-stage; P = 0.01) and radiation treatment (RT; P = 0.01). High nFD of the total tumor microenvironment (stroma plus tumor) was significantly associated with improved disease-specific survival (DSS; P = 0.002). No association with DSS was observed when nFD of either the tumor or the stroma was measured separately. pT-stage (P = 0.01), pathological node status (pN-status; P = 0.02) and RT (P = 0.03) were also significantly associated with DSS. In multivariate analysis, nFD remained significantly associated with DSS [HR 0.12 (95% CI 0.02-0.89, P = 0.04)] in a model adjusted for pT-stage, pN-status and RT. We also found that high nFD was significantly associated with high tumor proliferation (P < 0.0001) and high LI (P < 0.0001), factors that we and others have shown to be associated with improved survival in OSCC., Conclusions: We provide evidence that nFD analysis integrates known prognostic factors from the tumor microenvironment, such as proliferation and immune infiltration, into a single digital pathology-based biomarker. Prospective validation of our results could establish nFD as a valuable tool for clinical decision making in OSCC.

Background: Oral cavity squamous cell carcinoma (SCC) represents the most common SCC affecting the head and neck region. Long-term survival of patients with oral cavity SCC is adversely affected by lymph node metastasis and further decreased by the presence of lymph node extracapsular spread (ECS)., Methods: Using a case-control design, preoperative CT scans from patients with oral cavity SCC and metastatic lymphadenopathy were evaluated by 2 independent neuroradiologists, blinded to the study, for a number of radiologic parameters, including central node necrosis. Multivariate logistic regression was used to identify parameters independently predicting pathologic ECS., Results: For both neuroradiologists, central node necrosis was a significant predictor of ECS, with high interrater agreement (kappa = 0.71). On multivariate analysis, only central node necrosis independently predicted ECS (odds ratio [OR] = 12.1; 95% confidence interval [CI] = 1.24-119). Central node necrosis predicted ECS with 91% sensitivity and 88% negative predictive values., Conclusion: Our findings suggest that central node necrosis on preoperative CT scans is strongly associated with the presence of ECS., (© 2014 Wiley Periodicals, Inc.)

Background: Pulmonary complications are common after major head and neck oncologic surgery with microsurgical reconstruction and are associated with increased mortality and morbidity. Clinical care pathways are evidence-based tools that reduce unnecessary practice variation and ultimately improve patient outcomes. In this study, the authors evaluate the effectiveness of a comprehensive care pathway on reducing postoperative pulmonary complications and hospital length of stay in patients undergoing major head and neck carcinoma resection with free flap reconstruction., Methods: Fifty-five consecutive patients treated according to a prescribed postoperative clinical care pathway were compared to a historical cohort of patients treated before the implementation of the pathway. The incidence of pulmonary complications, hospital length of stay, and free flap survival were compared between the control and intervention groups., Results: Patients on the clinical care pathway had 32.5 percent fewer pulmonary complications (p < 0.0001) and 7.4 days' shorter hospital length of stay (p = 0.0007) than patients not on the postoperative pathway. There was no significant difference in the rate of flap reoperation., Conclusions: A multidisciplinary, comprehensive, clinical care pathway for patients undergoing major head and neck surgery with microsurgical reconstruction is effective in reducing postoperative pulmonary complications and hospital length of stay. The postoperative pathway is safe in this patient population and should be considered for adoption into clinical practice., Clinical Question/level of Evidence: Therapeutic, III.

The ING1 epigenetic regulator and tumor suppressor plays a central role in apoptosis. The Ing1 gene is functionally inactivated in many cancer types but is rarely mutated. Although most studies have implicated the major ING1 isoform, p33ING1b, in nuclear apoptotic signalling, we recently discovered a novel and potent apoptosis-inducing effect of p33ING1b translocation to the mitochondria in response to DNA damage. In the present study, we examined the impact of cytoplasmic/mitochondrial localization of p33ING1b in oral squamous cell carcinoma (OSCC) patient samples and explored the therapeutic potential of adenovirally-overexpressed p33ING1b in OSCC cell lines in combination with ionizing radiation (IR) treatment. In contrast with previous reports, we found that p33ING1b protein and mRNA levels are higher in OSCC compared to normal epithelial cells. In OSCC patient samples, higher levels of intra-tumoral cytoplasmic p33ING1b correlated with increased apoptotic markers and significantly better patient survival. This association was strongest in patients who received post-operative radiotherapy. IR treatment induced p33ING1b translocation to the mitochondria and adenoviral-p33ING1b synergized with IR to kill OSCC cells. Our results identify a novel functional relationship between cytoplasmic p33ING1b and patient survival and highlight the potential for the use of p33ING1b as a therapeutic agent in combination with adjuvant radiotherapy in OSCC.

Background: The objective of this study is to evaluate the cost-effectiveness of a postoperative clinical care pathway for patients undergoing major head and neck oncologic surgery with microvascular reconstruction., Methods: This is a comparative trial of a prospective treatment group managed on a postoperative clinical care pathway and a historical group managed prior to pathway implementation. Effectiveness outcomes evaluated were total hospital days, return to OR, readmission to ICU and rate of pulmonary complications. Costing perspective was from the government payer., Results: 118 patients were included in the study. All outcomes demonstrated that the postoperative pathway group was both more effective and less costly, and is therefore a dominant clinical intervention. The overall mean pre- and post-pathway costs are $22,733 and $16,564 per patient, respectively. The incremental cost reduction associated with the postoperative pathway was $6,169 per patient., Conclusion: Implementing the postoperative clinical care pathway in patients undergoing head and neck oncologic surgery with reconstruction resulted in improved clinical outcomes and reduced costs.

Objective: Patients with head and neck cancer frequently present to academic tertiary referral centers with imaging studies that have been performed and interpreted elsewhere. At our institution, these outside head and neck imaging studies undergo formal second opinion reporting by a fellowship-trained academic neuroradiologist with expertise in head and neck imaging. The purpose of this study was to determine the impact of this practice on cancer staging and patient management., Methods: Our institutional review board approved the retrospective review of randomized original and second opinion reports for 94 consecutive cases of biopsy proven or clinically suspected head and neck cancer in calendar year 2010. Discrepancy rates for staging and recommended patient management were calculated and, for the 32% (30/94) of cases that subsequently went to surgery, the accuracies of the reports were determined relative to the pathologic staging gold standard., Results: Following neuroradiologist second opinion review, the cancer stage changed in 56% (53/94) of cases and the recommended management changed in 38% (36/94) of patients with head and neck cancer. When compared to the pathologic staging gold standard, the second opinion was correct 93% (28/30) of the time., Conclusion: In a majority of patients with head and neck cancer, neuroradiologist second opinion review of their outside imaging studies resulted in an accurate change in their cancer stage and this frequently led to a change in their management plan.

Aim: The prognostic significance of Ki67 expression in cancers, including oral squamous cell carcinoma (OSCC), is unclear. This may be partly attributed to the lack of consensus surrounding the optimal approach for measuring tumour Ki67 expression. The aim of this study was to evaluate the association between different measures of Ki67 expression and disease-specific survival (DSS) in OSCC., Methods: Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded (FFPE) pre-treatment tumour tissue obtained from 121 OSCC patients diagnosed between 1998 and 2006. Ki67 expression was quantified using fluorescence immunohistochemistry (IHC) and AQUAnalysis® in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Intensity and percentage-based approaches for Ki67 scoring were tested for their association with survival., Results: Ki67 scores obtained from intensity and percentage-based approaches had similar associations with prognosis. We also found that high basal (lowest observed in triplicate cores) Ki67 expression was more strongly associated with improved 5-year disease-specific survival than hot-spot and average Ki67 measurements. The association of high basal Ki67 expression with improved prognosis was most pronounced in patients who received postoperative radiation. Cox proportional hazards analysis showed that the basal Ki67 expression is an independent prognostic marker in our OSCC cohort when adjusted for pathological T-stage, nodal status and treatment., Conclusions: Our study provides a framework for reaching a consensus on the optimal approach for measuring Ki67 expression in cancers. Our results suggest that rigorous comparisons of measurement approaches should be applied in a tumour-type and treatment-specific manner to enhance the clinical application of Ki67 assessment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Prolonged procedure time in head and neck cancer ablation and free flap reconstruction cases has been shown to significantly increase perioperative complications. The authors' objective was to evaluate the effectiveness of a standardized surgical nursing team for head and neck cancer ablation and free flap reconstruction operations for reducing procedure time., Methods: A retrospective cohort analysis of consecutive patients presenting for head and neck cancer ablation and free flap reconstruction between January 1, 2007, and September 1, 2010, was performed. A standardized head and neck surgical nursing team was introduced on May 1, 2009, at our center. Procedure time and case time were measured before and after the introduction of the team. Univariable analyses were performed to evaluate the difference in procedure and case time between the two cohorts. A multivariable linear regression model was developed to control for confounding variables., Results: There were 52 cases before the team was introduced and 49 cases after. Mean procedure time was reduced by 47.1 minutes (p = 0.04) and mean case time was reduced by 68.9 minutes (p = 0.01) after team introduction. The multivariable linear regression analysis demonstrated a significant reduction in operative time after team introduction, controlling for confounding variables., Conclusions: The introduction of a standardized surgical nursing team led to a significant reduction in procedure and case time. A standardized team approach improves operating room efficiency in complex cases such as free flap reconstruction following tumor ablation., Clinical Question/level of Evidence: Therapeutic, III.

Every year, approximately 25,000 patients are diagnosed with oral cavity squamous cell carcinoma (OCSCC) in the USA. The 5-year survival rate for OCSCC is approximately 40%. Intratumoral hypoxia confers poor prognosis and treatment failure but direct tumor oxygen measurement is challenging. Carbonic anhydrase IX (CAIX) is a marker of tissue hypoxia and we have recently shown that stromal CAIX is associated with reduced survival in patients with HPV-negative head and neck cancer. We examined the importance of this observation in OCSCC patients. We identified patients diagnosed and treated with OCSCC in Calgary (Alberta, Canada) between 1998 and 2005. Clinical and pathologic data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of archived tumor tissue. Stromal CAIX expression was assessed by quantitative immunohistochemistry (AQUA-HistoRx). The primary endpoint was disease-specific survival. We identified 102 patients with OCSCC; 87 patients had surgery as their primary treatment and adequate tumor tissue for TMA construction was available for all patients. CAIX expression was evaluable for 61 patients. High (top quartile) stromal CAIX expression was associated with significantly reduced 5-year disease-specific survival compared to low stromal CAIX expression (p<0.006). This study confirms our previously reported association between high stromal CAIX expression and significantly reduced overall survival in an independent, predominantly p16-negative, cohort of surgically treated OCSCC. Assessment of stromal CAIX expression could identify patients with the least favorable prognosis and inform therapeutic strategies in OCSCC., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: To determine the impact of the harmonic scalpel on intraoperative blood loss and operative time in selective neck dissection (SND) (levels I-IV) for head and neck squamous cell carcinoma (HNSCC)., Study Design: Prospective randomized controlled trial., Setting: A single, tertiary care institution (Foothills Medical Centre) in Calgary, Alberta, Canada., Subjects: A total of 31 patients (36 neck dissections) were prospectively enrolled between January 2009 and March 2010., Methods: Patients were randomized to receive a neck dissection with either the harmonic scalpel or the traditional technique of using electrocautery and sharp dissection. The study included adult patients older than age 18 years diagnosed with HNSCC and who required an SND (levels I-IV). Study exclusion criteria included previous treatment for head and neck cancer and all patients unwilling or unable to provide informed consent. Primary clinical outcomes were intraoperative blood loss and operative time. Secondary outcomes included intraoperative complications and surgical drain output., Results: Intraoperative blood loss was significantly lower in the harmonic scalpel group compared to the traditional group (158 vs 61 mL, P = .02). There was no difference in operative time (81 minutes harmonic vs 85 minutes traditional) or total drain output (at both 48 hours and 1 week) between the groups. There were no intraoperative complications reported in either group., Conclusions: Results from this study suggest that the harmonic scalpel can reduce blood loss during SND for HNSCC. The harmonic scalpel had no impact on operative time, postoperative drain output, or complication rate.