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Background: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss., Objective: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally., Methodology: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited., Results: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months., Conclusions: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants., Level of Evidence: 4 Laryngoscope, 134:4313-4320, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives : Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods : CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results : The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions : Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.

Importance: Late effects of head and neck cancer (HNC) treatment include profound dysphagia, chronic aspiration, and death. Functional laryngectomy (FL) can improve patient survival and quality of life (QoL); however, removing a failing larynx for a noncancer reason is a difficult decision. Data regarding the ability of FL to improve self-perceptions of voice, swallowing, and QOL in survivors of HNC with intractable aspiration are inconclusive., Objective: To investigate the association of FL with changes in self-reported perceptions of voice, swallowing, oral intake, QoL, and mood in survivors of HNC experiencing profound dysphagia and intractable aspiration., Design, Settings, and Participants: This cohort study was conducted at a single academic institution and included survivors of HNC with profound swallowing dysfunction and intractable aspiration who underwent FL from July 2016 through March 2022. Of the initial 22 patients enrolled, 2 patients (15%) died of aspiration pneumonia before receiving FL. Data analyses were performed from July 2016 through March 2023., Main Outcomes and Measures: Self-reported measures of voice using the VHI (30-item Voice Handicap Index), swallowing using the EAT-10 (10-item Eating Assessment Tool), functional oral intake scale using the FOIS (Functional Oral Intake Scale), and quality of life using the FACT-H&N (Functional Assessment of Cancer Therapy-Head & Neck) were assessed before FL and at 1, 3, and 6 months after FL. Mood states were evaluated using the POMS (Profile of Mood States, second edition), before FL and at 6 months after FL., Results: The study analyses included 20 patients (mean [SD] age, 72.4 (7.0) years; 19 [95%] males and 1 [5%] female) who underwent FL and had complete data across all time points. Among these, 12 patients (60%) had received chemoradiation for oropharyngeal, 7 (35%) for laryngeal, or 1 (5%) for nasopharyngeal cancer. The mean (SD) time from completion of oncologic treatment to FL was 15.5 (5.5) years. Mean (SD) score on the EAT-10 improved from 33.2 (7.4) to 23.1 (10.8) at 1 month; 12.1 (9.1) at 3 months; and 8.3 (7.4) at 6 months, with a large effect size (η2 = 0.72; 95% CI, 0.54-0.80). Mean (SD) score on the FOIS improved from 2.0 (1.5) to 2.9 (1.7) at 1 month; 4.8 (2.5) at 3 months; and 5.2 (1.7) at 6 months, with a large effect size (η2 = 0.6; 95% CI, 0.38-0.71). Improvement in oral intake was achieved in 19 patients (95%), and feeding tubes were removed in 10 of 16 patients (63%) who were feeding tube-dependent; 6 patients (27%) continued to require supplemental tube feedings. Mean (SD) score on the VHI improved from 63.6 (34.0) to 86.9 (33.7) at 1 month; 71.3 (36.1) at 3 months; and 39.7 (26.9) at 6 months, with a large effect size (η2 = 0.42; 95% CI, 0.19-0.56). Seventeen patients (85%) were able to use a tracheoesophageal voice prosthesis for alaryngeal communication. Mean (SD) score on the FACT-H&N improved from 86.2 (17.8) to 93.6 (18.4) at 1 month; 109.0 (18.4) at 3 months; and 121.0 (16.8) at 6 months, with a large effect size (η2 = 0.64; 95% CI, 0.42-0.74). Mean (SD) score on the POMS improved from 58.9 (13.2) at baseline to 44.5 (9.9) at 6 months, with a large effect size (Cohen d = 1.04; 95% CI, 0.48-1.57). None of the patients experienced major complications of FL; 1 patient (5%) had a postoperative pharyngocutaneous fistula., Conclusions and Relevance: The findings of this cohort study indicate that FL was associated with marked improvements in self-perception of voice and swallowing, functional oral intake, QoL, and mood state among survivors of HNC. These findings can serve as a framework for FL counseling among HNC survivors experiencing profound dysphagia and intractable aspiration.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Purpose: The purpose of this study is to examine the use of the Patient Health Questionnaire-2 (PHQ-2) to screen for depression in patients undergoing treatment for head and neck cancer and to evaluate potential patient-specific risk factors that may contribute to depression., Materials and Methods: This is a retrospective study at a tertiary-level hospital of outpatient adult patients with head and neck cancer who completed the PHQ-2/9 from 2019 to 2020. Patients were given a PHQ-2 during a surveillance visit. A positive PHQ-2 screen (score ≥ 3) prompted further evaluation with a PHQ-9. Patients were stratified into either low risk (PHQ-2 score < 3) or high risk (PHQ-2 score ≥ 3) for depression. Univariate regression was performed on all variables, and a multivariate logistic regression was performed on statistically significant variables (P < 0.05)., Results: In total, 110 patients were included in this study. Fifteen (14 %) patients had a positive PHQ-2 screen with a score ≥ 3 and underwent evaluation with a PHQ-9. The median PHQ-9 score was 15 (6-26). The PHQ-2 ≥ 3 group were significantly younger (59 years vs. 67 years; P = 0.03) and had a greater number of patients with a psychiatric history (33 % vs. 8 %; P < 0.01)., Conclusions: There is a strong association between a PHQ-2 score ≥ 3 and detection of depressive symptoms among patients with head and neck cancer. Younger age and pretreatment mental illness are significant risk factors for developing depression following treatment. Early screening and treatment should be considered for all patients to mitigate the burden of depression and suicide in this patient population. Further research is warranted to investigate utilization of the PHQ-2/9 to detect depression and barriers that exist for timely screening and interventions., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Head and neck cancer surgeons frequently interact with dying patients with advanced disease and their families, but little is known about their bereavement practices after a patient's death. The aim of this study is to elucidate the frequency of common bereavement practices, cited barriers to bereavement, and predictive physician factors that lead to an increase in bereavement practices among head and neck cancer surgeons., Methods: A 20-item survey was sent to 827 active surgeons of the American Head and Neck Society. Approval was obtained and the survey was distributed through the American Head and Neck Society. Demographics, frequency of common bereavement practices, empathy, and barriers were assessed. Multiple linear regression was performed to determine physician factors associated with more frequent bereavement follow-up., Results: There were 156 respondents (18.9% response rate). Overall, surgeons were more likely to usually/always call (48.5%) or send a letter (42.4%) compared with other practices such as attending funerals (0%), offering family meetings (18.6%), or referring family members to counseling (7.7%). Many barriers were cited as being at least somewhat important: being unaware about a patient's death (67.3%) was the most cited, whereas 51.3% cited a lack of mentorship/training in this area. Scoring higher on empathy questions (P ≤ .001) was associated with more frequent surgeon bereavement follow-up with the family of deceased patients., Conclusion: There is substantial practice variation among surgeons suggesting a lack of consensus on their roles in bereavement follow-up. Having higher empathy was predictive of higher engagement., Level of Evidence: NA Laryngoscope, 132:1971-1975, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: This study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP)., Methods: FLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology., Results: Among the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%., Conclusions: FLIm may be a useful diagnostic adjunct for detecting HNSCCUP., (© 2022 Wiley Periodicals LLC.)

Introduction: Radiofrequency ablation (RFA) has gained significant recent global interest in the treatment of benign thyroid nodules and thyroid cancer. It is a relatively new, minimally invasive, thermal ablation technique that is an alternative to surgery. Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the use of RFA in the treatment of benign thyroid nodules and thyroid cancers. These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised., Objective: To identify and perform a quality appraisal of clinical practice guidelines for RFA in the treatment of benign thyroid nodules and thyroid cancer using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool., Methods: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases from inception to November 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICCs) were calculated to determine level of agreement between reviewers., Results: Seven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Two guidelines were classified "high" quality, one "average" quality, and the rest "low" quality. The "Clarity and Presentation" (65.68 ± 26.1) and "Editorial Independence" (61.32 ± 25.8) domains received the highest mean scores, while the "Applicability" (32.14 ± 22.8) and "Rigor of Development" (45.02 ± 29.8) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.722-0.944)., Conclusion: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of RFA guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies amongst guidelines in the indications and use of RFA., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate a possible link between breast and thyroid cancer., Methods: A multicenter retrospective review of patients in the electronic medical records of six Accrual to Clinical Trial (ACT) institutions with both breast cancer and thyroid carcinoma. Each center queried its data using a predefined data dictionary. Information on thyroid and breast cancer included dates of diagnosis, histology, and patient demographics., Results: A random-effects model was used. There were 4.24 million women's records screened, 44 605 with breast cancer and 11 846 with thyroid cancer. The relative risks observed at each institution ranged from 0.49 to 13.47. The combined risk ratio (RR) estimate was 1.77 (95% confidence interval: 0.50-5.18)., Conclusion: There was no association between the risk of developing thyroid cancer and being a breast cancer survivor compared to no history of breast cancer, but the range of relative risks among the participating institutions was wide. Our findings warrant further study of more institutions with larger sample size. Additionally, further analysis of the significance of regional RR differences may be enlightening., (© 2022 Wiley Periodicals LLC.)

Background : Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N 1 -acetylspermine (ASP), N 8 -acetylspermidine (ASD) and N 1 ,N 12 -diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.

Objectives/hypothesis: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer., Study Design: Prospective, phase I, open label, clinical trial., Methods: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 × 10 6 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes., Results: Ten individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (±8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (±11.1) to 31.8 (±9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (±2.1) to 6.8 (±1.8), and the mean FOIS did not significantly change from 5.4 (±0.5) to 4.6 (±0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (±5.57) to 21.3 (±6.3) (P = .12)., Conclusion: Results of this phase I clinical trial demonstrate that injection of 150 × 10 6 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted., Level of Evidence: 3 Laryngoscope, 132:523-527, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: To describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center., Study Design: Retrospective cohort study., Setting: Academic institution., Methods: We performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre-COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed., Results: There were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre-COVID-19 period (40.3%) ( P = .024), as well as a larger median tumor size during the COVID-19 period ( P = .0002). There were no differences between nodal disease burden ( P = .48) and distant metastases ( P = .42)., Conclusion: Despite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic., (© The Authors 2021.)

Objectives: To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship., Methods: Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence., Results: Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho-oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and described the role of key clinicians in survivorship including surgical, medical and radiation oncologists; dentists; primary care physicians; psychotherapists; as well as physical, occupational, speech, and respiratory therapists., Conclusion: Head and neck cancer survivorship is complex and requires a multidisciplinary approach centered around patients and their caregivers. As survival related to head and neck cancer treatment improves, addressing post-treatment concerns appropriately is critically important to our patient's quality of life. There continues to be a need to define effective and efficient programs that can coordinate this multidisciplinary effort toward survivorship., Competing Interests: None of the authors have any conflicts of interest., (© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Purpose: We sought to enumerate secondary medical conditions from hospitalization records in adolescent and young adult (AYA) differentiated thyroid cancer (DTC) survivors and identify characteristics of patients with increased likelihood of subsequent medical diagnoses. Methods: Using data from the California Cancer Registry and statewide hospitalization data, we examined incident oncologic, endocrine, pulmonary, hematologic, and cardiovascular diagnoses in 12,312 AYA (aged 15-39) patients diagnosed with DTC in 1996-2012 and surviving >2 years after diagnosis with follow-up through 2014. We calculated the cumulative incidence of each condition accounting for the competing risk of death and used multivariable Cox proportional hazards regression to evaluate sociodemographic and clinical characteristics associated with each incident condition. Results: The 10-year cumulative incidences of multiple medical conditions were particularly high in blacks and Hispanics. Asian/Pacific Islander survivors were most likely to develop subsequent cancers. Men had higher rates of cardiovascular and diabetes diagnoses than women, but lower rates of asthma and cytopenias. Low socioeconomic status and/or public or no insurance were associated with a higher risk of several diagnoses. More extensive disease stage and thyroid surgery increased the risk of calcium and phosphorus metabolism disorders. Neck reoperation associated with the risk of cytopenias, as well as subsequent endocrine, cardiovascular, and respiratory diagnoses. Conclusion: The incidence of medical conditions after thyroid cancer diagnosis and treatment differ among racial/ethnic groups and sexes. Those residing in lower socioeconomic neighborhoods, those with public or no insurance, and those who require further neck surgery have substantially higher burdens of subsequent medical diagnoses.

Background: Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications., Methods: Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment., Main Outcome: wound complications., Results: Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not., Conclusions: Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy., (© 2021 Wiley Periodicals LLC.)

Objective: To demonstrate the diagnostic ability of label-free, point-scanning, fiber-based Fluorescence Lifetime Imaging (FLIm) as a means of intraoperative guidance during oral and oropharyngeal cancer removal surgery., Methods: FLIm point-measurements acquired from 53 patients (n = 67893 pre-resection in vivo, n = 89695 post-resection ex vivo) undergoing oral or oropharyngeal cancer removal surgery were used for analysis. Discrimination of healthy tissue and cancer was investigated using various FLIm-derived parameter sets and classifiers (Support Vector Machine, Random Forests, CNN). Classifier output for the acquired set of point-measurements was visualized through an interpolation-based approach to generate a probabilistic heatmap of cancer within the surgical field. Classifier output for dysplasia at the resection margins was also investigated., Results: Statistically significant change (P 0.01) between healthy and cancer was observed in vivo for the acquired FLIm signal parameters (e.g., average lifetime) linked with metabolic activity. Superior classification was achieved at the tissue region level using the Random Forests method (ROC-AUC: 0.88). Classifier output for dysplasia (% probability of cancer) was observed to lie between that of cancer and healthy tissue, highlighting FLIm's ability to distinguish various conditions., Conclusion: The developed approach demonstrates the potential of FLIm for fast, reliable intraoperative margin assessment without the need for contrast agents., Significance: Fiber-based FLIm has the potential to be used as a diagnostic tool during cancer resection surgery, including Transoral Robotic Surgery (TORS), helping ensure complete resections and improve the survival rate of oral and oropharyngeal cancer patients.

We report the case of a myopericytoma of the neck. A 23-year-old female noticed a small, nontender mass in her left supraclavicular fossa. The mass grew over a period of 5 months, prompting the patient to seek evaluation. There were no motor or sensory deficits. Imaging suggested a mass originating from the middle scalene muscle. Computed tomography-guided core needle biopsy demonstrated a spindle cell neoplasm with smooth muscle differentiation. Complete surgical excision was performed. Histopathological and immunohistochemical evaluation of the tissue sample suggested myopericytoma. Myopericytoma is an extremely rare tumor of the head and neck. To our knowledge, this is the first reported case of a myopericytoma originating from a scalene muscle.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Objective: Although basal cell carcinoma (BCC) is the most common skin cancer, locally aggressive BCC of the head and neck is rare and not well studied., Study Design: Retrospective review of patients who underwent primary surgical resection of locally aggressive head and neck BCC at a single tertiary academic center., Results: Eighty-seven patients with 98 tumors demonstrated a 5-year Kaplan-Meier estimated recurrence-free survival of 64.5%, overall survival of 83.3%, and disease-specific survival of 98.3%. Intraoperative positive frozen section margin was a strong independent predictor of local recurrence (hazard ratio 6.88, P = 0.038) and was more likely to occur in tumors previously treated with radiation (odds ratio 6.47 = 0.05)., Conclusion: Locally aggressive BCCs of the head and neck have high rates of local recurrence but low disease-specific mortality when treated with primary surgery and selected use of adjuvant therapy. Intraoperative positive frozen section margin is a strong independent predictor of local recurrence and is more likely in tumors that were previously treated with radiation therapy., Level of Evidence: 4 Laryngoscope, 130:115-119, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Laryngeal transplantation offers the hope of replacing voice and laryngeal function in patients with debilitating laryngeal injuries or loss of the larynx from trauma or oncologic reasons. Our group at UC Davis performed a laryngotracheal transplantation, and our experience is reviewed in this chapter. The indications, challenges, and limitations of this procedure are highlighted, and the world's other published cases are reviewed., (© 2020 S. Karger AG, Basel.)

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation., (©2019 The Authors. Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press 2019.)

This study evaluates the potential for fluorescence lifetime imaging (FLIm) to enhance intraoperative decisionmaking during robotic-assisted surgery of oropharyngeal cancer. Using a custom built FLIm instrument integrated with the da Vinci robotic surgical platform, we first demonstrate that cancer in epithelial tissue diagnosed by histopathology can be differentiated from surrounding healthy epithelial tissue imaged in vivo prior to cancer resection and ex vivo on the excised specimen. Second, we study the fluorescence properties of tissue imaged in vivo at surgical resection margins (tumor bed). Fluorescence lifetimes and spectral intensity ratios were calculated for three spectral channels, producing a set of six FLIm parameters. Current results from 10 patients undergoing TORS procedures demonstrate that healthy epithelium can be resolved from cancer ( P < .001) for at least one FLIm parameter. We also showed that a multiparameter linear discriminant analysis approach provides superior discrimination to individual FLIm parameters for tissue imaged both in vivo and ex vivo . Overall, this study highlights the potential for FLIm to be developed into a diagnostic tool for clinical cancer applications of the oropharynx. This technique could help to circumvent the issues posed by the lack of tactile feedback associated with robotic surgical platforms to better enable cancer delineation., Competing Interests: CONFLICT OF INTEREST The authors declare no potential conflict of interests.

Objectives: Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively., Materials and Methods: A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared., Results: 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs., Conclusion: In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Physician practice patterns regarding diagnosis and management of malnutrition in the head and neck cancer patient population are not well studied., Methods: A 17-question survey was distributed to 1392 members of the American Head and Neck Society (AHNS). The impact of hospital type, fellowship training, experience, and specialty was assessed., Results: Among AHNS members, there were 124 total respondents (9% response rate), including both otolaryngologists and radiation oncologists. Respondents strongly agreed (90%) that malnutrition negatively impacts patient outcomes. The majority (63%) felt comfortable screening for malnutrition, but 13% reported no routine assessment of malnutrition; 57% were unfamiliar with relevant guidelines. Barriers to screening included lack of familiarity with screening tools/guidelines, lack of time, and lack of access to dietitian., Conclusion: Although there was a strong consensus among respondents that the identification and management of malnutrition among head and neck cancer patients is critical, familiarity with relevant guidelines was poor., (© 2019 Wiley Periodicals, Inc.)

Objective: The recommended treatment for cutaneous squamous cell cancer (CuSCC) of the head and neck is Mohs surgical excision or wide local excision. Excision is recommended to a gross surgical margin of 4-6 mm however this is based on limited evidence and specify a goal histologic margin. The objective of this study was therefore to examine the reported histological margin distance following WLE of advanced CuSCC and its association with recurrence and survival., Study Design: Retrospective database review., Setting: All patients included received treatment at UC Davis Department of Otolaryngology-Head and Neck Surgery and/or Radiation Oncology in Sacramento, California., Subjects and Methods: The patients included were treated for advanced CuSCC with primary surgery with or without adjuvant therapy. Kaplan Meier survival curves with log rank analysis were then performed to compare 5-year recurrence free survival, and disease-specific survival for patients with different margin distances., Results: Total number of subjects was 92. The overall 5-year DSS and RFS was 68.8 and 51.0% respectively. When the pathological margin distance was ≥5 mm, 5-year disease specific survival was improved when compared to margin distance less than 5 mm (94.7 vs 60.7 p = 0.034)., Conclusion: The findings of this study suggest that a histologic margin of at least 5 mm may increase survival in advanced head and neck CuSCC patients.

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum-refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer-related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET-mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Background: There is currently a lack of evidence-based guidelines regarding postoperative opioids after thyroid and parathyroid surgery. This study aimed to objectively characterize contemporary postoperative pain management practices via a national survey of head and neck endocrine surgeons., Methods: A standardized electronic survey was distributed to the membership of the American Head and Neck Society's Endocrine section., Results: A total of 102 surgeons completed the survey representing a 34% response rate. In all, 65.7% of respondents utilize opioids with wide variations in the total morphine equivalents prescribed. Practice environment (χ 2 = 10.0; P = 0.04) and performing preoperative pain counseling (χ 2 = 9.7; P = 0.002) were significantly associated with a decreased likelihood of prescribing postoperative opioids. Utilization of non-opioid pain management strategies was common and significantly associated with performing outpatient surgery (χ 2 = 6.2; P = 0.013) and preoperative pain counseling (χ 2  = 4.5; P = 0.034)., Conclusions: Pain management practice patterns vary significantly among head and neck endocrine surgeons which further emphasize the need for evidence-based guidelines., (© 2019 Wiley Periodicals, Inc.)

Mesenchymal stem cells (MSCs) facilitate functional recovery in numerous animal models of inflammatory and ischemic tissue-related diseases with a growing body of research suggesting that exosomes mediate many of these therapeutic effects. It remains unclear, however, which types of proteins are packaged into exosomes compared with the cells from which they are derived. In this study, using comprehensive proteomic analysis, we demonstrated that human primed MSCs secrete exosomes (pMEX) that are packaged with markedly higher fractions of specific protein subclasses compared with their cells of origin, indicating regulation of their contents. Notably, we found that pMEX are also packaged with substantially elevated levels of extracellular-associated proteins. Fibronectin was the most abundant protein detected, and data established that fibronectin mediates the mitogenic properties of pMEX. In addition, treatment of SHSY5Y cells with pMEX induced the secretion of growth factors known to possess mitogenic and neurotrophic properties. Taken together, our comprehensive analysis indicates that pMEX are packaged with specific protein subtypes, which may provide a molecular basis for their distinct functional properties.

Due to loss of tactile feedback the assessment of tumor margins during robotic surgery is based only on visual inspection, which is neither significantly sensitive nor specific. Here we demonstrate time-resolved fluorescence spectroscopy (TRFS) as a novel technique to complement the visual inspection of oral cancers during transoral robotic surgery (TORS) in real-time and without the need for exogenous contrast agents. TRFS enables identification of cancerous tissue by its distinct autofluorescence signature that is associated with the alteration of tissue structure and biochemical profile. A prototype TRFS instrument was integrated synergistically with the da Vinci Surgical robot and the combined system was validated in swine and human patients. Label-free and real-time assessment and visualization of tissue biochemical features during robotic surgery procedure, as demonstrated here, not only has the potential to improve the intraoperative decision making during TORS but also other robotic procedures without modification of conventional clinical protocols.

Importance: Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignant tumors worldwide. There is conflicting evidence regarding the indications for and benefits of adjuvant radiation therapy for advanced CSCC tumors of the head and neck., Objective: To assess indications for adjuvant radiation therapy in patients with CSCC., Design, Setting, and Participants: Retrospective analysis of 349 patients with head and neck CSCC treated with primary resection with or without adjuvant radiation therapy at 2 tertiary referral centers from January 1, 2008, to June 30, 2016., Main Outcomes and Measures: Data were compared between treatment groups with a χ2 analysis. Disease-free survival (DFS) and overall survival (OS) were analyzed using a Kaplan-Meier survival analysis with log-rank test and a Cox proportional hazards multivariate regression., Results: A total of 349 patients had tumors that met the inclusion criteria (mean [SD] age, 70 [12] years; age range, 32-94 years; 302 [86.5%] male), and 191 (54.7%) received adjuvant radiation therapy. The 5-year Kaplan-Meier estimates were 59.4% for DFS and 47.4% for OS. Patients with larger, regionally metastatic, poorly differentiated tumors with perineural invasion (PNI) and younger immunosuppressed patients were more likely to receive adjuvant radiation therapy. On Cox proportional hazards multivariate regression, patients with periorbital tumors (hazard ratio [HR], 2.48; 95% CI, 1.00-6.16), PNI (HR, 1.90; 95% CI, 1.12-3.19), or N2 or greater nodal disease (HR, 2.16; 95% CI, 1.13-4.16) had lower DFS. Immunosuppressed patients (HR, 2.17; 95% CI, 1.12-4.17) and those with N2 or greater nodal disease (HR, 2.43; 95% CI, 1.42-4.17) had lower OS. Adjuvant radiation therapy was associated with improved OS for the entire cohort (HR, 0.59; 95% CI, 0.38-0.90). In a subset analysis of tumors with PNI, adjuvant radiation therapy was associated with improved DFS (HR, 0.47; 95% CI, 0.23-0.93) and OS (HR, 0.44; 95% CI, 0.24-0.86). Adjuvant radiation therapy was also associated with improved DFS (HR, 0.36; 95% CI, 0.15-0.84) and OS (HR, 0.30; 95% CI, 0.15-0.61) in patients with regional disease., Conclusions and Relevance: Among patients with advanced CSCC, receipt of adjuvant radiation therapy was associated with improved survival in those with PNI and regional disease.

The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors present differently than traditional mucosal head and neck cancers, and those affected often lack classic risk factors such as tobacco and alcohol use. Currently, there are no approved approaches for prevention and early detection of disease, thus leading many patients to present with advanced cancers requiring intense surgical or nonsurgical therapies resulting in significant side effects and cost to the health-care system. In this review, we outline the evolving epidemiology of HPV-related OPC. We also summarize the available evidence corresponding to HPV-related OPC prevention, including efficacy and safety of the HPV vaccine in preventing oral HPV infections. Finally, we describe emerging techniques for identifying and screening those who may be at high risk for developing these tumors.

Syphilis may present with a myriad of oral manifestations in the primary, secondary, and tertiary stages, and may be confused with malignancy. Despite a rise in the incidence of syphilis, tertiary syphilis is exceedingly rare. Tertiary syphilis gummas usually affect the hard palate, while tongue involvement is very rare. A 55-year-old male with extensive smoking and alcohol use was referred for malignancy evaluation with an ulcerative mass creating a tongue cleft, and a positron emission tomography scan suggestive for malignancy. Biopsy results demonstrated no carcinoma but histology demonstrated granulomatous inflammation. Further laboratory results demonstrated elevated rapid plasma reagin titers with Treponema pallidum immunoglobulin G antibodies present. The patient was diagnosed with tertiary syphilis, received appropriate antibiotic therapy, and had healing of the tongue with a persistent cleft. Syphilis may mimic many disease processes. As such, it is important to include this disease in the differential of an unusual tongue lesion. An oral lesion may be the first sign of infection., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recovery after major head and neck cancer surgery is a complex process. In addition to perioperative sequelae such as pain, wound infections, venous thromboembolism (VTE), and pneumonia, these patients frequently suffer from malnutrition. We provide a contemporary evidence-based approach to common aspects of perioperative care to guide the clinician in the optimal management of patients. Particular emphasis is placed on the preoperative education of patients and the identification and management of malnutrition around the time of surgery. This article discusses recommendations for perioperative antibiotics, pain management, and prophylaxis against VTE and pneumonia in this patient population., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In an era of rising differentiated thyroid cancer incidence, the rate and impact of neck reoperation may inform the intensity of earlier interventions and surveillance. This study sought to define predictors of neck reoperation and to assess its impact on survival., Methods: Using the California Cancer Registry linked to the California Office of Statewide Health Planning and Development records, a retrospective cohort study was performed of 24,230 patients with total or near-total thyroidectomy for papillary or follicular thyroid cancer between 1991 and 2008 and follow-up through 2013. The primary outcome was neck reoperation 91 days to 5 years after the initial thyroid surgery. Using logistic and Cox proportional hazards regression, the impact of sociodemographics, tumor staging, and hospital thyroid cancer surgery volume on neck reoperation and survival was determined., Results: Neck reoperation was identified in 1231 (5.1%) patients in increasing odds from 1991 to 2008. In multivariable models, male sex, papillary thyroid cancer, and advancing tumor stage were associated with neck reoperation. Among men, neck reoperation was associated with Asian/Pacific Islander (odds ratio [OR] = 1.44 [confidence interval (CI) 1.07-1.94]) race/ethnicity. Among women, neck reoperation was associated with younger age (15-34 years; OR = 1.50 [CI 1.17-1.92] versus ≥55 years), and Asian/Pacific Islander (OR = 1.24 [CI 1.02-1.51]) or Hispanic (OR = 1.20 [CI 1.00-1.44]) race/ethnicity. After controlling for baseline characteristics, neck reoperation predicted worse thyroid cancer-specific survival (hazard ratio = 4.26 [CI 3.50-5.19]). The effect differed between men and women, and was most pronounced among women who received radioiodine in initial treatment (hazard ratio = 8.32 [CI 6.14-11.27])., Conclusions: Neck reoperation is becoming increasingly frequent and is strongly predictive of mortality. Advancing tumor stage, Asian/Pacific Islander race/ethnicity, male sex, as well as younger age and Hispanic ethnicity among women predict a higher risk for neck reoperation and subsequent mortality, reflecting a higher risk of persistent or more biologically aggressive disease.

Background: Lichen planus (LP) is a T-cell mediated autoimmune disorder of unknown aetiology that affects the skin, nails, oral and genital mucous membranes. Conventionally, oral LP (OLP) is diagnosed through clinical assessment and histopathological confirmation by oral biopsy., Aim: To explore the use of time-resolved fluorescence spectroscopy (TRFS) to detect fluorescence lifetime changes between lesional OLP and perilesional normal mucosa., Methods: In this pilot study, measurements of lesional and perilesional buccal and mouth floor mucosa were conducted in vivo with a TRFS system. Histopathological findings were consistent with OLP in 8 out of 10 patients biopsied. Two patients with histopathological diagnoses of frictional hyperkeratosis and oral candidiasis, respectively, were excluded from the study., Results: Our preliminary data show that lifetime values in the 360-560 nm spectral range indicate a significant differentiation between normal and diseased tissue. In contrast to the standard oral biopsy procedure, this technique is noninvasive, painless, time-efficient and safe., Conclusions: Future studies are needed to better elucidate the diagnostic capability of TRFS and to further explore the sources of fluorescence contrast. This pilot study suggests that, based on fluorescence lifetime parameters, TRFS is a very promising technology for the development of a novel OLP diagnostic technique., (© 2018 British Association of Dermatologists.)

Objective: Total laryngectomy is a well-established treatment for locally advanced laryngeal cancer. Evidence for the benefit of post-operative radiotherapy after laryngectomy in patients with locally advanced primaries and N0 or N1 nodal disease is limited. This study aimed to determine whether total laryngectomy alone is adequate therapy for certain patient subgroups with locally advanced laryngeal cancer., Design: We performed a retrospective survival analysis of patients in the surveillance epidemiology and end results (SEER) database with locally advanced laryngeal cancer between 2004 and 2012., Outcome Measures: Primary outcome measure was overall survival., Results: For all patients with T3-4aN0-1 tumours, overall survival was worse for those treated with laryngectomy only when compared using the Kaplan-Meier with a log-rank test and when accounting for demographic and tumour data using a Cox multivariate regression. Other independent predictors of poor survival included age >65 years old, Medicaid or uninsured payor status, supraglottic primary and N1 nodal disease. Stage- and subsite-specific analysis revealed that patients with T4a primary tumours, N1 nodal disease and supraglottic subsite had worse overall survival when treated with laryngectomy alone. Alternatively, patients with T3 primary tumours, N0 nodal disease, glottic subsite had equivalent overall survival and disease-specific survival when treated with laryngectomy alone vs laryngectomy with post-operative radiotherapy., Conclusion: Locally advanced laryngeal cancer patients with T3 primaries, no nodal disease or primaries of the glottis may not benefit from post-operative radiotherapy when treated with primary total laryngectomy., (© 2017 John Wiley & Sons Ltd.)

We report a case of myopericytoma of the neck. A 23-year-old woman noticed a small, nontender mass in her left supraclavicular fossa. The mass had grown over a period of 5 months, prompting her to seek evaluation. On examination, no motor or sensory deficits were present. Imaging suggested that a mass had originated in the middle scalene muscle. Computed-tomography-guided core needle biopsy demonstrated a spindle-cell neoplasm with smooth-muscle differentiation. Complete surgical excision was performed. Histopathologic and immunohistochemical evaluations of the tissue sample suggested a myopericytoma. Myopericytoma is an extremely rare tumor of the head and neck. To the best of our knowledge, this is the first reported case of a myopericytoma originating in a scalene muscle.

Oral leukoplakia is defined as a white oral lesion not related to another disease process. These lesions are largely asymptomatic, and the clinical relevance of oral leukoplakia is primarily tied to its association with oral cavity squamous cell carcinoma. Timely workup and effective management of these lesions can reduce the risk of malignant transformation and promote early diagnosis of invasive tumors. A biopsy should be performed promptly of any persistent or suspicious leukoplakia with subsequent management dictated by histologic findings. Benign lesions can be observed or treated with topical therapy, and dysplastic lesions should be excised. Some risk of malignant transformation remains even after treatment, and close follow-up is required. Oral cavity squamous cell carcinoma is an aggressive malignancy that can result from malignant conversion of oral leukoplakia or occur de novo. These tumors are primarily treated with surgical resection and adjuvant radiation or chemoradiation as dictated by histopathologic findings., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignancies worldwide. With advanced CSCC of the head and neck, there is conflicting evidence on what constitutes high-risk disease. Our objective is to evaluate which factors are predictive of recurrence and nodal spread and survival. Study Design Case series with chart review. Setting Tertiary academic institution. Subjects and Methods Patients with advanced head and neck CSCC treated with primary resection identified by chart review. Results A total of 212 patients met inclusion criteria, with a mean age of 70.4 years; 87.3% were men. Mean tumor diameter was 3.65 cm, with an average depth of invasion of 1.38 cm. The mean follow-up time was 35 months (median, 21.5), and over that period 67 recurrences were recorded, 49 of which were local. The 5-year Kaplan-Meier estimate of disease-free survival for the cohort was 53.2%. On Cox multivariate analysis, recurrent disease, perineural invasion (PNI), and poorly differentiated histology were independent predictors of recurrence. On multinomial logistic regression, patients with primary tumors on the ear, cheek, temple, or lip, as well as those with PNI, were more likely to present with nodal metastasis. Conclusion For advanced CSCCs of the head and neck, patients with recurrent disease, PNI, and poorly differentiated tumors are at highest risk for local recurrence. Patients with tumors or the ear, cheek, temple, or lip, as well as those with PNI, are at increased risk of harboring nodal disease.

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.

Background: Treatment recommendations for advanced-stage laryngeal squamous cell carcinoma (SCC) have evolved significantly over the last 2 decades., Methods: We retrospectively analyzed patients in the Surveillance, Epidemiology, and End Results (SEER) database with advanced-stage laryngeal SCC treated between 2004 and 2012., Results: A total of 6797 patients were identified in the SEER database who met inclusion criteria, with 2051 patients undergoing primary surgery and 4746 patients undergoing primary radiotherapy (RT) or chemoradiotherapy (CRT). Disease-specific survival (DSS) and overall survival (OS) were significantly better for patients treated with primary surgery when compared using Kaplan-Meier curves and a Cox multivariate regression. When survival analysis was repeated for patients stratified by T classification, N classification, and subsite, OS and DSS benefits from primary surgery were observed for patients with T3 and T4a tumors, N0 neck disease, or supraglottic primaries., Conclusion: Patients with advanced-stage laryngeal SCC with T3 and T4a tumors, N0 neck disease, or supraglottic primaries have the greatest chance of survival when treated with primary surgery. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1380-1386, 2016., (© 2016 Wiley Periodicals, Inc.)

Purpose of Review: The management of orbital tumours has evolved significantly over the last two decades, as the body of knowledge about these tumours grows and new techniques are introduced that reduce surgical morbidity. The purpose of this review is to highlight and evaluate the most recent advancements in the management of these tumours., Recent Findings: Several recent retrospective series emphasize the broad range of pathologic processes that can arise within the orbit. In addition, there have been a number of recent studies describing advances in endonasal endoscopic techniques for resection of orbital tumours., Summary: This articles summarizes the current opinion regarding the management of orbital tumours. Recent studies reviewing the range of diseases that affect the orbit and technical advances are summarized.