Masticator space abscess following intramuscular stimulation.

A male in his 50s presented to the hospital with preauricular tenderness, trismus and dysphagia. He had intramuscular stimulation of his left temporomandibular joint region performed 4 days prior and described worsening pain and swelling since. A CT scan revealed an abscess involving the left masticator space. Incision and drainage of the abscess was performed, and the patient was discharged home on oral antibiotics 11 days later. This is the first report of masticatory space abscess following intramuscular stimulation of the temporomandibular joint area. Acupuncture and intramuscular stimulation are common complementary medicine therapies that are generally considered safe; however, adverse events such as deep neck space infection have been reported in the literature. Current regulation of training requirements and licensure for needling therapies is highly variable. Standardisation of training and practice guidelines may help mitigate the risk of adverse events related to needling therapies in the future.

The Modified Alberta Reconstructive Technique: A prospective cohort study.

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

Utility of droplet digital polymerase chain reaction for TERT and BRAF mutational profiling of thyroid nodules.

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

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

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

Recommendations from the Canadian Association of Head and Neck Surgical Oncology for the Management of Head and Neck Cancers during the COVID-19 pandemic.

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

Development of a Patient-Centered Functional Outcomes Questionnaire in Head and Neck Cancer.

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

2b or not 2b? Shoulder function after level 2b neck dissection: A double-blind randomized controlled clinical trial.

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

Beavertail modification of the radial forearm free flap in total oral glossectomy reconstruction: Technique and functional outcomes.

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

Antitumour effects of metformin and curcumin in human papillomavirus positive and negative head and neck cancer cells.

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

The Alberta Reconstructive Technique: An Occlusion-Driven and Digitally Based Jaw Reconstruction.

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

Donor site morbidity following radial forearm free flap reconstruction with split thickness skin grafts using negative pressure wound therapy.

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

EGFR as a biomarker of smoking status and survival in oropharyngeal squamous cell carcinoma.

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

The association of Bcl-xL and p53 expression with survival outcomes in oropharyngeal cancer.

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

Long-term survival and swallowing outcomes in advanced stage oropharyngeal squamous cell carcinomas.

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

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

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

Analytic and clinical validity of thyroid nodule mutational profiling using droplet digital polymerase chain reaction.

BACKGROUND: Recent guidelines for the management of thyroid nodules incorporate mutation testing as an adjunct for surgical decision-making, however current tests are costly with limited accuracy. Droplet digital PCR (ddPCR) is an ultrasensitive method of nucleic acid detection that is particularly useful for identifying gene mutations. This study aimed to assess the analytic and clinical validity of RAS and BRAF ddPCR mutational testing as a diagnostic tool for thyroid fine needle aspirate biopsy (FNAB). METHODS: Patients with thyroid nodules meeting indication for FNAB were prospectively enrolled from March 2015 to September 2017. In addition to clinical protocol, an additional FNAB was obtained for ddPCR. Optimized ddPCR probes were used to detect mutations including HRASG12 V, HRASQ61K, HRASQ61R, NRASQ61R, NRASQ61K and BRAFV600E. The diagnostic performance of BRAF and RAS mutations was assessed individually or in combination with Bethesda classification against final surgical pathology. RESULTS: A total of 208 patients underwent FNAB and mutational testing with the following Bethesda cytologic classification: 26.9% non-diagnostic, 55.2% benign, 5.3% FLUS/AUS, 2.9% FN/SPN, 2.4% SFM and 7.2% malignant. Adequate RNA was obtained from 91.3% (190) FNABs from which mutations were identified in 21.1% of HRAS, 11.5% of NRAS and 7.4% of BRAF. Malignant cytology or BRAFV600E was 100% specific for malignancy. Combining cytology with ddPCR BRAF600E mutations testing increased the sensitivity of Bethesda classification from 41.7 to 75%. Combined BRAFV600E and Bethesda results had a positive predictive value (PPV) of 100% and negative predictive value (NPV) of 89.7% for thyroid malignancy in our cohort. CONCLUSIONS: DdPCR offers a novel and ultrasensitive method of detecting RAS and BRAF mutations from thyroid FNABs. BRAFV600E mutation testing by ddPCR may serve as a useful adjunct to increase sensitivity and specificity of thyroid FNAB.

Association of Fludeoxyglucose F 18-Labeled Positron Emission Tomography and Computed Tomography With the Detection of Oropharyngeal Cancer Recurrence.

Importance: No guidelines at present describe when fludeoxyglucose F 18-labeled positron emission tomography and computed tomography (FDG PET-CT) should be used in the initial posttreatment period for evaluation of oropharyngeal squamous cell carcinoma treatment outcome and recurrence. Objective: To compare accuracies of the initial posttreatment PET-CT between primary treatment groups and to define indicators of false-positive findings. Design, Setting, and Participants: This retrospective cohort study identified adults with a new diagnosis of oropharyngeal squamous cell carcinoma who received treatment with curative intent from October 1, 2006, through November 30, 2016, using the Alberta Cancer Registry (n = 380). Patients who underwent PET-CT within 1 year of treatment completion were included (n = 190). Of these, 103 patients (54.2%) had PET-CT findings positive for residual or recurrent disease, and 61 (32.1%) had false-positive findings. Among the 61 patients, 42 (68.9%) had received chemoradiotherapy (CRT) and 19 (31.1%) had primary surgery. Forty-two patients had true-positive findings, indicating a prevalence rate of disease of 22.1%. Data were analyzed from July through October 2017. Exposures: One of 2 primary treatment modalities (surgery with or without adjuvant therapy vs CRT). All patients had posttreatment FDG PET-CT. Main Outcomes and Measures: Primary outcome measures included the diagnostic odds ratio, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET-CT for detecting residual and/or recurrent disease. A multivariate analysis determined indicators of false-positive findings. Discriminative ability was assessed using receiver operating characteristic curve analysis of maximum standardized uptake value (SUVmax) metabolic data. Results: Of the 190 participants, 77.9% were men, with a mean (SD) age at diagnosis of 58.5 (8.5) years. The diagnostic odds ratio was 19.3 (95% CI, 5.7-65.1); pooled sensitivity, 93.3% (95% CI, 80.7%-98.3%); and pooled specificity, 57.9% (95% CI, 49.4%-66.0%). The PPV of detecting disease was 54.7% (95% CI, 38.8%-69.8%) for primary surgery and 31.1% (95% CI, 20.2%-44.4%) for CRT. The NPV was 100% (95% CI, 94.7%-100%) for primary surgery and 96.6% (95% CI, 89.5%-99.1%) for CRT. Multivariate analysis identified treatment type, p16 disease, and smoking status as indicative of false-positive findings. In the receiver operating characteristic curve analysis for primary tumors, the optimal cutoff SUVmax for indicating true- vs false-positive results was 5.1 for surgically treated patients (area under the curve, 0.729; 95% CI, 0.570-0.888) and 5.3 for patients treated with CRT (area under the curve, 0.844; 95% CI, 0.700-0.989). Conclusions and Relevance: The results indicate a higher specificity for FDG PET-CT for initial posttreatment surveillance imaging among patients treated with primary surgery compared with nonsurgical management. Both sets of patients with posttreatment FDG PET-CT findings with an SUVmax greater than 5.0 should undergo close evaluation for possible residual or recurrent disease.

Multi-dimensional analysis of oral cavity and oropharyngeal defects following cancer extirpation surgery, a cadaveric study.

BACKGROUND: Defects following resection of tumors in the head and neck region are complex; more detailed and defect-specific reconstruction would likely result in better functional and cosmetic outcomes. The objectives of our study were: 1) to improve the understanding of the two- and three-dimensional nature of oral cavity and oropharyngeal defects following oncological resection and 2) to assess the geometric dimensions and the shapes of fasciocutaneous free flaps and locoregional tissue flaps required for reconstruction of these defects. METHODS: This study was an anatomic cadaveric study which involved creating defects in the oral cavity and oropharynx in two cadaveric specimens. Specifically, partial and total glossectomies, floor of mouth excisions, and base of tongue excisions were carried out. These subsites were subsequently geometrically analyzed and their volumes measured. The two-dimensional (2D) assessment of these three-dimensional (3D) structures included measures of surface area and assessment of tissue contours and shapes. RESULTS: The resected specimens all demonstrated unique dimensional geometry for the various anatomic sites. Using 2D analysis, hemiglossectomy defects revealed right triangle geometry, whereas total glossectomy geometry was a square. Finally, the base of tongue defects exhibited a trapezoid shape. CONCLUSIONS: Customizing the geometry and dimensions of fasciocutaneous free flaps so that they are specific to the confronted head and neck defects will likely result in better functional and cosmetic outcomes.

Efficacy of EZH2 inhibitory drugs in human papillomavirus-positive and human papillomavirus-negative oropharyngeal squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with rates of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) dramatically increasing. The overexpression of enhancer of zeste homolog 2 (EZH2), a histone methyltransferase responsible for the trimethylation at lysine 27 of histone 3 (H3K27me3), is associated with a poor clinical prognosis and aggressive HPV-positive phenotypes. METHODS: We utilized three EZH2 pathway inhibitors, GSK-343, DZNeP, and EPZ-5687, and tested their efficacy in two HPV-positive and two HPV-negative OPSCC cell lines. RESULTS: Treatment with GSK-343 decreased H3K27me3 in all cell lines and treatment with DZNeP decreased H3K27me3 in only HPV-negative cell lines as determined by Western blot. Cells treated with EPZ-5687 displayed no appreciable change in H3K27me3. Epigenetic effect on gene expression was measured via ddPCR utilizing 11 target probes. Cells treated with DZNeP showed the most dramatic expressional changes, with decreased EGFR in HPV-positive cell lines and an overall increase in proliferation markers in HPV-negative cell lines. GSK-343-treated cells displayed moderate expressional changes, with CCND1 increased in HPV-positive cell lines and decreased TP53 in HPV-negative SCC-1. EPZ-5687-treated cell lines displayed few expressional changes overall. Only DZNeP-treated cells displayed anti-proliferative characteristics shown in wound-healing assays. CONCLUSIONS: Our findings suggest that EZH2 inhibitors are a viable therapeutic option for the role of epigenetic effect, potentially sensitizing tumors to current chemotherapies or limiting cell differentiation.