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Objectives: To determine if the assessment of CD8+ tumor-infiltrating lymphocytes (TILs) adds prognostic information to the PD-L1 combined positive score (CPS) in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)., Methods: A retrospective case series was performed of 77 patients with R/M HNSCC between 2003 and 2019. From pre-treatment biopsies, CD8+ TILs and PD-L1 CPS were quantified on a tissue microarray. Associations of biomarkers with overall survival and immune checkpoint inhibition (ICI) response were assessed., Results: Neither CD8+ TIL counts nor PD-L1 CPS alone were associated with overall survival; however, combined high TILs and CPS ≥ 1 were associated with improved survival compared to low TILS and CPS < 1 (18.5 vs. 10.0 months, p = 0.058). For patients treated with ICI (n = 28), PD-L1 CPS predicted ICI response more strongly than CD8+ TILs., Conclusions: In R/M HNSCC, the combination of PD-L1 CPS and CD8+ TILs is a stronger prognostic biomarker for overall survival compared with either biomarker alone., (© 2025 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: Induction chemotherapy (IC) followed by chemoradiation (CRT) is one treatment approach for patients with locoregionally advanced oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV). This pilot study aimed to assess whether a circulating tumor (ct) DNA assay outperforms PET-CT in assessing treatment response in patients with HPV + OPSCC treated with induction chemotherapy (IC) followed by chemoradiation (CRT)., Materials and Methods: Patients treated with IC and definitive CRT for HPV + OPSCC were included. HPV ctDNA and PET-CT were performed pre-treatment, 2-3 weeks after IC and 3 months after CRT. CtDNA levels were correlated with tumor volumes. Post-IC and post- CRT ctDNA levels were correlated post-induction and post-treatment imaging responses., Results: Seventeen patients were included. Baseline ctDNA levels correlated with volume of primary tumor (R2 = 0.33, p = 0.02), but did not correlate with nodal volumes (R2 = 0.01, p = 0.7) or total disease burden (R2 = 0.02, p = 0.6). After IC, 5.9 % (1/17) of patients had complete response by PET- CT, whereas 52.9 % (9/17) had complete molecular response by ctDNA testing. After completion of CRT, 76.5 % (13/17) patients had complete clinical response to treatment. Of patients who had ctDNA clearance after IC, 88.9 % (8/9) remained disease free after definitive CRT, whereas one had progressive disease diagnosed by both imaging and ctDNA. HPV ctDNA clearance after IC predicted disease control after CRT more strongly than PET-CT IC response (61.5 % (8/13) vs 7.7 % (1/13), p = 0.01)., Conclusions: HPV ctDNA clearance following IC outperforms standard imaging in assessing response and may help identify patients with favorable prognosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Purpose: We examined operative efficiency, rate of facial nerve paresis, and post-operative outcomes in patients undergoing retrograde (RGD) vs anterograde dissection (AGD) of the facial nerve controlling for tumor location., Methods: Single-institution, retrospective analysis of patients with benign parotid tumors undergoing superficial parotidectomy with facial nerve dissection over a six-year period. Operative and pathology reports were reviewed to classify tumor size, location in relation to facial nerve branches, and technique for facial nerve dissection. Chi-square and Student's t-test were used to compare operative time, rates of facial nerve paresis, and post-operative outcomes between groups., Results: Our cohort included 35 patients who underwent RGD and 70 who underwent AGD of the facial nerve. Pleomorphic adenoma was most common in both the RGD (n = 25, 71.4 %) and AGD (n = 69, 98.6 %) groups. Both groups were balanced for demographics, tumor size and location in relation to facial nerve branches. Operative times, rate of surgical drain use, and frequency of post-operative admission were significantly reduced in the RGD group. The rate of temporary facial nerve paresis was significantly reduced (n = 3, 8.6 % vs n = 30, 42.9 % in the RGD vs AGD groups, respectively, p < 0.001) and more frequently limited to single nerve distributions in the RGD group., Conclusion: RGD of the facial nerve during superficial parotidectomy for benign parotid tumors is associated with reduced operative times, post-operative admission rates, and rates of facial nerve paresis compared to AGD even when controlling for tumor location., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The osteocutaneous radial forearm (OCRFF) is a versatile free flap option for bony defects of the head and neck, given the thinness and pliability of the forearm cutaneous paddle, pedicle length, reliability, lack of atherosclerosis, and functional concerns common to other osseous donor sites. The OCRFF was once associated with a high risk of radial fracture, in addition to concerns about the quality and durability of bone stock for osseous reconstruction, particularly for the mandible. Following the introduction of prophylactic plating of the radius, the incidence of symptomatic radial fracture has drastically decreased. Furthermore, modifications of the bony osteotomies and other evolutions of this flap harvest have increased the use of the OCRFF throughout the head and neck. Despite these advantages, the OCRFF is not widely utilized by microvascular reconstructive surgeons due to perceived limitations and risks. Herein, we present a multidisciplinary, contemporary review of the harvest technique, outcomes, and perioperative management for the OCRFF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Large full-thickness lip defects present a reconstructive challenge., Objective: To describe the impact on clinical outcomes and institutional cost of the depressor anguli oris myocutaneous (DAOM) flap as an axial pattern transposition flap for reconstruction of large, full-thickness lip defects., Methods: A multicenter retrospective cohort study of adults with large full-thickness lip defects who underwent DAOM flap reconstruction from 2011 to 2018 was conducted. DAOM flap anatomy and surgical technique were reviewed. The primary outcome of flap viability as well as additional clinical outcomes of postoperative complications and functional results were documented with follow-up ranging up to 11 years. Median length of stay and average institutional cost of care were analyzed., Results: A total of 12 patients underwent DAOM flap reconstruction for large full-thickness lip defects. There was 100% flap survival with no episodes of reoperation or readmission. All patients reported maintenance of distinct oral commissures, wide oral opening and full gingivolabial sulcus, excellent oral competence, and intelligible speech. Mean case length was 144 ± 11.5 min with a mean length of stay of 1.6 ± 0.5 days and estimated mean institutional cost of $3766.67 ± $1167.06., Conclusions: The DAOM flap is an excellent reconstructive option for large full-thickness lip defects with strong functional results and limited donor site morbidity and institutional cost of care., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: Large language model (LLM)-based chatbots such as ChatGPT have been publicly available and increasingly utilized by the general public since late 2022. This study sought to investigate ChatGPT responses to common patient questions regarding Human Papilloma Virus (HPV) positive oropharyngeal cancer (OPC)., Methods: This was a prospective, multi-institutional study, with data collected from high volume institutions that perform >50 transoral robotic surgery cases per year. The 100 most recent discussion threads including the term "HPV" on the American Cancer Society's Cancer Survivors Network's Head and Neck Cancer public discussion board were reviewed. The 11 most common questions were serially queried to ChatGPT 3.5; answers were recorded. A survey was distributed to fellowship trained head and neck oncologic surgeons at 3 institutions to evaluate the responses., Results: A total of 8 surgeons participated in the study. For questions regarding HPV contraction and transmission, ChatGPT answers were scored as clinically accurate and aligned with consensus in the head and neck surgical oncology community 84.4% and 90.6% of the time, respectively. For questions involving treatment of HPV+ OPC, ChatGPT was clinically accurate and aligned with consensus 87.5% and 91.7% of the time, respectively. For questions regarding the HPV vaccine, ChatGPT was clinically accurate and aligned with consensus 62.5% and 75% of the time, respectively. When asked about circulating tumor DNA testing, only 12.5% of surgeons thought responses were accurate or consistent with consensus., Conclusion: ChatGPT 3.5 performed poorly with questions involving evolving therapies and diagnostics-thus, caution should be used when using a platform like ChatGPT 3.5 to assess use of advanced technology. Patients should be counseled on the importance of consulting their surgeons to receive accurate and up to date recommendations, and use LLM's to augment their understanding of these important health-related topics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Patients undergoing head and neck cancer surgery after prior radiation or chemoradiation are at high risk for wound complications. Hypothyroidism is a known risk factor for wound complications, especially fistulae after salvage total laryngectomy. The purpose of this phase II clinical trial is to investigate the effect of perioperative intravenous levothyroxine supplementation on wound complications in patients undergoing salvage total laryngectomy., Patients and Methods: Euthyroid patients previously treated with radiation/chemoradiation undergoing total laryngectomy were prospectively recruited (n = 72). Postoperatively, intravenous levothyroxine was administered at a weight-based dose (1.3 mcg/kg/d) and transitioned to enteral dosing on day 7. Free T3, T4, and thyroid-stimulating hormones were collected, and dosing was adjusted accordingly. The primary endpoints were rates of fistula formation and fistula requiring reoperation, compared with matched historic controls. All patients were monitored for adverse effects., Results: The rate of postoperative hypothyroidism was 21% compared with 49% in a matched historic cohort. The rate of fistula formation was 18.1%, whereas the rate of fistula requiring reoperation was 4.2%, significantly lower than rates in our historic cohort (34.6% and 14.8%, respectively; P = 0.02 and 0.01). Postoperative hypothyroidism and recurrent clinical stage predicted fistula requiring reoperation in multivariate analysis; other acute phase reactants were not predictive. There were no observed adverse events related to levothyroxine supplementation., Conclusions: Postoperative intravenous levothyroxine supplementation reduced rates of acute hypothyroidism, fistula formation, and fistula requiring reoperation in patients undergoing salvage total laryngectomy without adverse effects. Intravenous levothyroxine is a viable strategy to reduce wound complications in this high-risk patient population., (©2024 American Association for Cancer Research.)

The osteocutaneous radial forearm free flap (OCRFFF) is a versatile flap with the ability to reconstruct complex defects. We detail the techniques necessary to harvest an OCRFFF, including an outline on making 90-degree osteotomies to maximize bone harvest. In this pictorial essay, we provide illustrations of the anatomy and surgical techniques necessary for OCRFFF harvest. Detailed discussion is provided on how to protect the perforators to the bone and the approach to making osteotomies in a 90-degree fashion. The approach for prophylactic plating of the radius to prevent radius fractures is outlined. A case presentation on the real-life utilization of this flap is included. The OCRFFF is an excellent head and neck reconstructive option. While there are limitations to its use for patients requiring dental rehabilitation or long/anterior mandibular defects, for the right patient and indication it has shown great success in reconstructive efforts., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objective: To determine the association between preoperative thyroid hormone replacement and complications following major abdominal surgery., Methods: A retrospective case series was performed of patients enrolled in the Michigan Surgical Quality Collaborative (MSQC) who underwent major abdominal surgery at an academic institution over a 10-year period. The principal explanatory variable was preoperative thyroid hormone replacement. Primary outcomes were morbidity, mortality and length of stay., Results: 2700 patients were identified. On multivariate analysis correcting for established predictors of operative morbidity, patients on preoperative thyroid replacement had a 1.5- fold increased risk of serious morbidity(p ​= ​0.01), and a 1.7- fold greater risk for serious sepsis(p ​= ​0.04). Thyroid replacement was associated with longer length of stay(p ​< ​0.001). While there was a high degree of missing data for surgical approach (31.1 ​% missing data), results suggest that patients on thyroid hormone replacement were more likely to undergo an open rather than minimally invasive surgery(p ​< ​0.01). Open surgery was associated with greater risk of serious morbidity(p ​= ​0.003) and longer length of stay(p ​< ​0.001)., Conclusions: Preoperative thyroid hormone replacement independently predicts operative morbidity and length of stay following major abdominal surgery., Competing Interests: Declaration of competing interest We have no conflicts of interest to disclose. This manuscript has not been published elsewhere and is not under consideration by another journal., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity., Methods: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS)., Results: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively., Conclusion: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes., Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC., Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023., Exposure: TORS for OPSCC., Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined., Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%])., Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.

Objectives: To define the role of hypothyroidism and other risk factors for unplanned readmissions after surgery for head and neck cancer., Study Design: Retrospective cohort study., Methods: The Nationwide Readmission Database (NRD) was used to identify patients who underwent surgery for mucosal head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx) between 2010 and 2017. Univariate and multivariate logistic regression were performed to determine patient, tumor, and hospital related risk factors for 30-day readmission. Readmitted patients were stratified by preoperative diagnosis of hypothyroidism to compare readmission characteristics., Results: For the 131,013 patients who met inclusion criteria, the readmission rate was 15.9%. Overall, 11.91% of patients had a preoperative diagnosis of hypothyroidism. After controlling for other variables, patients with a preoperative diagnosis of hypothyroidism had 12.2% higher odds of readmission compared to those without hypothyroidism (OR: 1.12, 1.03-1.22, p = 0.008). Patients with hypothyroidism had different reasons for readmission, including higher rates of wound dehiscence, fistula, infection, and electrolyte imbalance. Among readmitted patients, the length of stay for index admission (mean 10.5 days vs. 9.2 days, p < 0.001), readmission (mean 7.0 vs. 6.6 days, p = 0.05), and total hospital charge were higher for hypothyroid patients ($137,742 vs. $119,831, p < 0.001)., Conclusion: Hypothyroidism is an independent risk factor for 30-day readmission following head and neck cancer resection. Furthermore, hypothyroid patients are more likely to be readmitted for wound complications, infection, and electrolyte imbalance. Targeted interventions should be considered for hypothyroid patients to decrease readmission rates and associated patient morbidity, potentially leading to earlier initiation of adjuvant treatment., Level of Evidence: 3 Laryngoscope, 133:2988-2998, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Historical data reveal that, compared with women, men are more likely to pursue a head and neck surgical oncology fellowship, but little is known about possible gender differences in academic productivity., Objective: To assess demographic trends and academic productivity among American Head & Neck Society (AHNS) fellowship graduates., Design, Setting, and Participants: This cross-sectional study used electronically published data from the AHNS on fellowship graduates in the US and Canada from July 1, 1997, to June 30, 2022. Scopus was used to extract h-indices for each graduate., Exposure: Scholarly activity., Main Outcomes and Measures: Main outcomes were changes in demographic characteristics and academic productivity among AHNS graduates over time. Data analysis included effect size, η2, and 95% CIs., Results: A total of 691 AHNS fellowship graduates (525 men [76%] and 166 women [24%]) were included. Over the study period, there was an increase in the number of programs offering a fellowship (η2, 0.84; 95% CI, 0.68-0.89) and an increase in the absolute number of women who completed training (η2, 0.66; 95% CI, 0.38-0.78). Among early-career graduates pursuing an academic career, there was a small difference in the median h-index scores between men and women (median difference, 1.0; 95% CI, -1.1 to 3.1); however, among midcareer and late-career graduates, there was a large difference in the median h-index scores (midcareer graduates: median difference, 4.0; 95% CI, 1.2-6.8; late-career graduates: median difference, 6.0; 95% CI, 1.0-10.9). A higher percentage of women pursued academic positions compared with men (106 of 162 [65.4%] vs 293 of 525 [55.8%]; difference, 9.6%; 95% CI, -5.3% to 12.3%)., Conclusions and Relevance: This cross-sectional study suggests that women in head and neck surgery begin their careers with high levels of academic productivity. However, over time, a divergence in academic productivity between men and women begins to develop. These data argue for research to identify possible reasons for this observed divergence in academic productivity and, where possible, develop enhanced early faculty development opportunities for women to promote their academic productivity, promotion, and advancement into leadership positions.

Background: Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread., Methods: A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998- 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival., Results: Median overall survival (mOS) improved over time (6.7 months in 1998-2007 to 11.8 months in 2008-2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2-2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4-3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02-2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1-3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4-4.0]), DFI >6 months (OR, 2.4 [1.5-4.0]), and body mass index ≥30 (OR, 2.3 [1.1-4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24-0.55)., Conclusion: These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials., Plain Language Summary: After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body. This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns. Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients. These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests., (© 2023 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Objectives: To develop a high-performance droplet digital PCR (ddPCR) assay capable of enhancing the detection of human papillomavirus (HPV) circulating tumor DNA (ctDNA) in plasma from patients with HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC)., Materials and Methods: Plasma samples from subjects with HPV+ OPSCC were collected. We developed a high-performance ddPCR assay designed to simultaneously target nine regions of the HPV16 genome., Results: The new assay termed 'ctDNA HPV16 Assessment using Multiple Probes' (CHAMP- 16) yielded significantly higher HPV16 counts compared to our previously validated 'Single-Probe' (SP) assay and a commercially available NavDx® assay. Analytical validation demonstrated that the CHAMP-16 assay had a limit of detection (LoD) of 4.1 copies per reaction, corresponding to < 1 genome equivalent (GE) of HPV16. When tested on plasma ctDNA from 21 patients with early-stage HPV+ OPSCC and known HPV16 ctDNA using the SP assay, all patients were positive for HPV16 ctDNA in both assays and the CHAMP-16 assay displayed 6.6-fold higher HPV16 signal on average. Finally, in a longitudinal analysis of samples from a patient with recurrent disease, the CHAMP-16 assay detected HPV16 ctDNA signal ∼ 20 months prior to the conventional SP assay., Conclusion: Increased HPV16 signal detection using the CHAMP-16 assay suggests the potential for detection of recurrences significantly earlier than with conventional ddPCR assays in patients with HPV16+ OPSCC. Critically, this multi-probe approach maintains the cost-benefit advantage of ddPCR over next generation sequencing (NGS) approaches, supporting the cost-effectiveness of this assay for both large population screening and routine post-treatment surveillance., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Some of the authors are inventors of HPV ctDNA assay technology, for which the University of Michigan is pursuing patent protection., (Published by Elsevier Ltd.)

Abstract: Circulating tumor DNA (ctDNA) has become an area of intense study in many solid malignancies including head and neck cancer. This is of particular interest for human papillomavirus-mediated oropharyngeal squamous cell carcinoma as this cohort of patients has excellent survival and is undergoing current clinical trials aimed at treatment de-escalation. Recent studies have demonstrated the prognostic implications of pretreatment ctDNA and the utility of monitoring ctDNA during and posttreatment; however, there is a need for a more critical understanding of ctDNA as it is beginning to be incorporated into clinical trials. This review discusses the current state of ctDNA in oropharynx cancer focusing on ctDNA kinetics and minimal residual disease detection and ends with a discussion of future applications., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer., Materials and Methods: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3)., Results: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %., Conclusion: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Examine the relationship between hospital volume and overall mortality in a surgical cohort of head and neck squamous cell carcinoma (HNSCC) patients., Materials & Methods: A retrospective review of the NCDB was completed for adults with previously untreated HNSCC diagnosed between 2004 and 2016. Mean annual hospital volume was calculated using the number of head and neck cancer cases treated at a given facility divided by the number of years the facility reported to the NCDB. Facilities were separated into three categories based on their volume percentile, informed by inflection points from a natural cubic spline: Hospital Group 1 (<50%); Hospital Group 2 (50-90%); Hospital Group 3 (90%+). Cox proportional hazard models were used to examine the association between volume percentiles (continuous or categorical) with patient overall survival, adjusting for important patient and facility variables known to impact survival., Results: Risk of death decreased by 2.97% for every 10% increase in facility percentile after adjusting for other risk factors. Patients treated at facilities in Hospital Group 1 had a 23.1% increase in risk of mortality (HR 1.231 [95% CI 1.12-1.35]) relative those at facilities in Hospital Group 3. No significant difference in mortality risk was found between Hospital Group 2 versus Hospital Group 3 (HR 1.031 [95% CI 0.97-1.10])., Conclusions: Survival of HNSCC patients is significantly improved when treated at facilities >50th percentile in annual hospital volume. This may support the regionalization of care to high volume head and neck centers with comprehensive facilities and supportive services to maximize patient outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Oral cavity cancer (OCC) is traditionally associated with smoking, but there is an increasing prevalence of the disease among non-smokers. This review investigates possible modifiable risk factors in the development of OCC in non-smokers (OCCNS)., Methods: PubMed, EMBASE, Web of Science, and Scopus were searched for publications prior to June 2021. Comparative studies investigating modifiable OCCNS risk factors were identified following PRISMA guidelines. Publication date, population size, and results were indexed. Study quality was assessed using MINORS (Methodological Index for Non-Randomized Studies). Factors examined by multiple studies were analyzed using random-effect meta-analysis framework., Results: Literature search resulted in 1,625 unique publications. 52 records met inclusion criterion, investigating alcohol (n = 22), chewing products (n = 18), diet (n = 7), dental health (n = 11), and medical comorbidities (n = 6)., Conclusion: This review demonstrates the paucity of large studies investigating OCCNS risk factors. Further investigation is warranted to help clinicians risk-stratify patients without traditional risk factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Fibula free flaps (FFF) are often considered the first choice for mandibular reconstruction, but scapular system free flaps (SFF) have increased in popularity due to versatility, donor site advantages, and patient factors., Methods: Retrospective chart review of patients undergoing mandibulectomy with FFF or SFF reconstruction from 2016 to 2021., Results: Hundred and seventy-six patients (FFF n = 145, SFF n = 31) underwent the aforementioned procedures. Mean FFF operative time was 9.47 h versus 9.88 for SFF (p = 0.40). Two-flap reconstructions required 12.65 h versus 10.09 for SFF with soft tissue (p = 0.002). Donor site complications were identified in 65.6% of FFF with skin grafting., Conclusions: These findings suggest that SFF requires similar operative time and results in reduced donor site morbidity as compared to FFF. Supine, concurrent harvesting of SFF allows for single-flap harvest with significantly shorter operative time. SFF could be considered a primary option for mandible reconstruction for complex defects and in select patients., (© 2022 Wiley Periodicals LLC.)

Objective: Surgical procedures that render patients acutely aphonic can cause them to experience significant anxiety and distress. We queried patient perceptions after tracheostomy or laryngectomy and investigated whether introducing augmentative technology was associated with improvement in patient-reported outcomes., Methods: Participants included hospitalized patients who acutely lost the ability to speak due to tracheostomy or total laryngectomy from April 2018 to December 2019. We distributed questions regarding the patient communication experience and relevant questions from the validated V-RQOL questionnaire (Voice-Related Quality of Life). Patients were offered a tablet with the electronic communication application Verbally. Pre- and postintervention groups were compared with chi-square analyses., Results: Surveys were completed by 35 patients (n = 18, preintervention; n = 17, postintervention). Prior to using augmentative technology, 89% of patients who were aphonic reported difficulty communicating, specifically noting breathing or suctioning (56%), treatment and discharge plans (78%), or immediate needs, such as pain and using the bathroom (39%). Communication difficulties caused anxiety (55%), depression (44%), or frustration (62%), and 92% of patients were interested in using an electronic communication device. Patients reported less trouble communicating after the intervention versus before (53% vs 89%, P = .03), including less difficulty communicating about treatment or discharge plans (35% vs 78%, P < .01). V-RQOL scores were unchanged., Discussion: Acute loss of phonation arising from surgery can be highly distressing for patients, and use of augmentative technology may alleviate some of these challenges by improving communication. Further studies are needed to identify what additional strategies may improve overall well-being., Implications for Practice: Electronic communication devices may benefit patients with acute aphonia.

Objectives: Phosphaturic mesenchymal tumor (PMT) is a rare, polymorphous neoplasm with a highly variable presentation and natural history and unpredictable clinical course. The primary objective was to describe our clinical experience with and management of 4 markedly different cases of sinonasal and skull base PMT., Methods: A retrospective case series with chart review, and relevant literature review, was performed at a tertiary academic medical center between 1998 and 2020. Adult patients treated for PMTs of the sinonasal area and skull base were included. Our main outcome measures included postoperative laboratory findings and radiological evidence of disease remission., Results: Four patients (2 Males, 2 Females; Mean Age: 63.5 years) with PMTs of the skull base have been managed at our institution since 1998. Patient presentations varied, ranging from severe phosphorus wasting and osteoporosis to symptoms secondary to mass effect, including nasal obstruction and rhinorrhea. All 4 patients were eventually found to have elevated levels of fibroblast growth factor 23. Tumors were located in the sinonasal area (right frontal sinus, right ethmoid sinus, and right nasal cavity, respectively) in 3 patients and in the lateral skull base (right jugular foramen) in 1 patient. All 4 patients underwent complete surgical resection of their tumors. PMT tissue pathology was confirmed in all cases. Gross total resection was achieved in all patients. There was no chemical or radiological evidence of disease recurrence in any patients at follow-up., Conclusions: The presentation of skull base PMT is variable, and it may mimic other mass pathologies of the head and neck. Complete surgical resection with negative margins is potentially curative.

Human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved outcomes compared to non-virally mediated disease. Clinical trials are actively investigating de-escalation strategies to maintain excellent survival outcomes while minimizing toxicity. Delivery of effective precision medicine-based therapeutic approaches are strengthened by the identification of biomarkers to predict treatment response. Plasma circulating tumor (ct) DNA is the most studied liquid biomarker in head and neck cancer and has shown great promise in the ability to determine treatment response and monitor for disease recurrence. In this review, we examine the emerging evidence for ctDNA as a biomarker in HPV related OPSCC and discuss opportunities for future investigation and integration into clinical practice., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm., Study Design: Retrospective study., Setting: Tertiary care hospital., Methods: Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM)., Results: After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response ( P = .012)., Conclusion: These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.

Objective: To create a longitudinal near-peer mentorship program for medical students applying to otolaryngology., Methods: A program for longitudinal near-peer mentorship was designed based on a needs analysis of senior medical students. Program objectives were to (1) provide didactic education on common otolaryngology consults, (2) facilitate resident-student networking, and (3) enable applicants to meet other students. Senior otolaryngology residents were matched with medical students from across the United States applying to otolaryngology for a series of online small group meetings. Sessions included resident-designed didactics covering high-yield clinical scenarios and a mentorship component focused on transition to residency topics. Program evaluation included anonymized pre- and post-tests for each didactic session and an anonymous post-program participant survey., Results: There were 40 student participants from across the United States, with an average attendance of 73% of sessions per participant. Performance on didactic testing improved for 2 of the 3 sessions. Participants stated they would be very likely to recommend each session to another student in the future (4.96/5.00, obs = 155). Participants stated the most valuable part of the program was interacting with residents (82% of responses), transition to residency advice (28%), and learning about otolaryngology consults (28%). Suggestions for improvement included expanding content, increasing the number of sessions, and involving additional faculty and residents., Conclusion: A longitudinal virtual experience can be valuable for near-peer mentorship for medical students applying to otolaryngology., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: In locally advanced p16+ oropharyngeal squamous cell carcinoma (OPSCC), (i) to investigate kinetics of human papillomavirus (HPV) circulating tumor DNA (ctDNA) and association with tumor progression after chemoradiation, and (ii) to compare the predictive value of ctDNA to imaging biomarkers of MRI and FDG-PET., Experimental Design: Serial blood samples were collected from patients with AJCC8 stage III OPSCC ( n = 34) enrolled on a randomized trial: pretreatment; during chemoradiation at weeks 2, 4, and 7; and posttreatment. All patients also had dynamic-contrast-enhanced and diffusion-weighted MRI, as well as FDG-PET scans pre-chemoradiation and week 2 during chemoradiation. ctDNA values were analyzed for prediction of freedom from progression (FFP), and correlations with aggressive tumor subvolumes with low blood volume (TV LBV ) and low apparent diffusion coefficient (TV LADC ), and metabolic tumor volume (MTV) using Cox proportional hazards model and Spearman rank correlation., Results: Low pretreatment ctDNA and an early increase in ctDNA at week 2 compared with baseline were significantly associated with superior FFP ( P < 0.02 and P < 0.05, respectively). At week 4 or 7, neither ctDNA counts nor clearance were significantly predictive of progression ( P = 0.8). Pretreatment ctDNA values were significantly correlated with nodal TV LBV , TV LADC , and MTV pre-chemoradiation ( P < 0.03), while the ctDNA values at week 2 were correlated with these imaging metrics in primary tumor. Multivariate analysis showed that ctDNA and the imaging metrics performed comparably to predict FFP., Conclusions: Early ctDNA kinetics during definitive chemoradiation may predict therapy response in stage III OPSCC., (©2021 American Association for Cancer Research.)

Background: During the last two decades, significant advancements in the treatment of laryngeal cancer have occurred. Although survival of head and neck cancer patients has improved over time, the temporal trend of laryngeal cancer survival is an area of controversy., Methods: From 2004 to 2016, 77,527 patients who had laryngeal cancer treated with curative intent in the United States were identified in the National Cancer Database. Relative and observed survival rates were assessed for temporal trends. Multinomial logistic regression investigated the relationship between American Joint Committee on Cancer (AJCC) stage and increasing calendar year., Results: No significant improvement in 2- or 5-year observed survival (OS) or relative survival (RS) was observed. The 5-year RS ranged from 61.72 to 63.97%, and the 5-year OS ranged from 54.26 to 56.52%. With each increasing year, the proportion of stage 4 disease increased, with risk for stage 4 disease at the time of diagnosis increasing 2.2% annually (adjusted odds ratio [aOR], 1.022; 95% confidence interval [CI], 1.017-1.028; p < 0.001). This increase was driven by a 4.7% yearly increase in N2 disease (aOR, 1.047; 95% CI, 1.041-1.053; p < 0.001), with an annual 1.2% increase in T3 disease (aOR, 1.012; 95% CI, 1.007-1.018; p < 0.001) and a 1.2% increase in T4 disease (aOR, 1.012; 95% CI, 1.005-1.018; p < 0.001)., Conclusion: Despite advances in the field, laryngeal cancer survival in the United States is not improving over time. This may be due to an increase in the proportion of stage 4 disease, driven primarily by increasing nodal disease. To achieve survival improvement commensurate with scientific and technologic advances, efforts should be made to diagnose and treat laryngeal cancer at earlier stages to prevent further stage migration., (© 2021. Society of Surgical Oncology.)

Despite the rising incidence of human papillomavirus related (HPV+) oropharyngeal squamous cell carcinoma (OPSCC), treatment of metastatic disease remains palliative. Even with new treatments such as immunotherapy, response rates are low and can be delayed, while even mild tumor progression in the face of an ineffective therapy can lead to rapid death. Real-time biomarkers of response to therapy could improve outcomes by guiding early change of therapy in the metastatic setting. Herein, we developed and analytically validated a new droplet digital PCR (ddPCR)-based assay for HPV16 circulating tumor DNA (ctDNA) and evaluated plasma HPV16 ctDNA for predicting treatment response in metastatic HPV+ OPSCC. We found that longitudinal changes HPV16 ctDNA correlate with treatment response and that ctDNA responses are observed earlier than conventional imaging (average 70 days, range: 35-166). With additional validation in multi-site studies, this assay may enable early identification of treatment failure, allowing patients to be directed promptly toward clinical trials or alternative therapies., Competing Interests: CONFLICTS OF INTEREST The study team has filed an invention disclosure on the HPV16 ctDNA assay and the University of Michigan intends to file a patent on the assay technology., (Copyright: © 2021 Haring et al.)

Opinion Statement: Human papilloma virus (HPV) related head and neck cancer is rising in prevalence, preferentially affecting young patients and imparting long term toxicities. Despite this, there are no screening tests or clinical biomarkers for treatment monitoring. HPV circulating tumor DNA (HPV ctDNA) represents a novel circulating biomarker which may provide real-time assessment of tumor response to therapy and recurrence. Early work suggests the promise of this assay as a predictive biomarker in numerous clinical settings, namely risk of recurrence after chemoradiation in locally advanced disease. Advancement of these findings to the clinic will require a collaborative effort in the field, including technical harmonization of assay testing characteristics, understanding of the normal kinetics in patients being treated with standard of care therapies, and appropriately designed phase III trials prior to implementation in the clinic. If successful, HPV ctDNA has the potential to revolutionize clinical trial treatment paradigms and transform patient care.

Aim: To describe a novel technique for the reconstruction of geometrically complex defects of the midface using an osteotomized folded scapular tip-free flap., Methods: Five patients underwent maxillectomy with defects disrupting two or more of the following facial axes: orbital, nasofacial, and palatal axes. Patients underwent primary reconstruction using an angular artery-based scapular tip-free flap with an osteotomy to fold the flap. Harvest techniques, including placement of osteotomies, folding and plating, surgical esthetic, and functional outcomes, are presented., Results: Osteotomies placed in the scapular tip-free flap allowed folding of the osseous flap and improved restoration of all three facial axes with a single flap. In one patient, the tip of the scapula was used to reconstruct the nasofacial axis, while the body and lateral border were used to reconstruct the palate. In four patients, the tip of the scapula was used to reconstruct the orbital axis, while the body and lateral border were used to reconstruct the nasofacial axis. Patients had successful oronasal separation, healed wounds withstanding adjuvant therapy, satisfactory orbital positioning and facial projection, preserved masticatory surfaces and opportunity for dental implants., Conclusion: The midface is geometrically complex and is one of the most challenging head and neck sites to reconstruct. Ablative defects in this area can disrupt facial axes resulting in poor esthetic and functional outcomes. This study demonstrates the reconstructive advantages of a novel osteotomized folded scapular tip-free flap., Competing Interests: Conflicts of interest All authors declared that there are no conflicts of interest.

Background: Current limitations in the supply of ventilators during the Covid19 pandemic have limited respiratory support for patients with respiratory failure. Split ventilation allows a single ventilator to be used for more than one patient but is not practicable due to requirements for matched patient settings, risks of cross-contamination, harmful interference between patients and the inability to individualize ventilator support parameters. We hypothesized that a system could be developed to circumvent these limitations., Methods and Findings: A novel delivery system was developed to allow individualized peak inspiratory pressure settings and PEEP using a pressure regulatory valve, developed de novo, and an inline PEEP 'booster'. One-way valves, filters, monitoring ports and wye splitters were assembled in-line to complete the system and achieve the design targets. This system was then tested to see if previously described limitations could be addressed. The system was investigated in mechanical and animal trials (ultimately with a pig and sheep concurrently ventilated from the same ventilator). The system demonstrated the ability to provide ventilation across clinically relevant scenarios including circuit occlusion, unmatched physiology, and a surgical procedure, while allowing significantly different pressures to be safely delivered to each animal for individualized support., Conclusions: In settings of limited ventilator availability, systems can be developed to allow increased delivery of ventilator support to patients. This enables more rapid deployment of ventilator capacity under constraints of time, space and financial cost. These systems can be smaller, lighter, more readily stored and more rapidly deployable than ventilators. However, optimizing ventilator support for patients with individualized ventilation parameters will still be dependent upon ease of use and the availability of medical personnel., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: KVK, GEG and DAZ are founders of MakeMedical LLC, which is the legal manufacturer of this device (provided at cost). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery., Methods: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998-2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS)., Results: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04- < 0.001) and DSS (p = 0.04-0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04)., Conclusion: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery.

Cutaneous squamous cell carcinoma (cSCC) and melanoma encompass the majority of all malignant skin cancers. There has been an increase in their incidence globally in recent decades. In cases of high-risk, unresectable, or metastatic disease; or when patient factors or preferences limit the availability of conventional surgery or radiotherapy; or a systemic therapy is often warranted. Our improved understanding of the molecular and immune pathogenesis underlying tumor growth and development has been critical in advancing cancer therapeutics. Over the past several years, several new systemic agents have been approved for both diseases. The role of cytotoxic chemotherapy is gradually waning with the introduction of targeted therapy and immunotherapy. In this article, we review the current and relevant literature and evidence of cytotoxic chemotherapy, targeted therapy, and immune checkpoint inhibitors in the adjuvant and neoadjuvant settings for cSCC and melanoma. Additionally, we describe their role in the unresectable or metastatic disease setting., Competing Interests: P.S. has received an honorarium from Regeneron Pharmaceuticals for participation in a research advisory board. All the other authors report no conflict of interest., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: Despite the clinical importance of chronic and severe irritability, there is a paucity of controlled trials for its pharmacological treatment. Here, we examine the effects of adding citalopram (CTP) to methylphenidate (MPH) in the treatment of chronic severe irritability in youth using a double-blind randomized placebo-controlled design., Method: After a lead-in phase of open treatment with stimulant, 53 youth meeting criteria for severe mood dysregulation (SMD) were randomly assigned to receive CTP or placebo (PBO) for 8 weeks. A total of 49 participants, 48 of them (98%) meeting disruptive mood dysregulation disorder (DMDD) criteria, were included in the intent-to-treat analysis. The primary outcome measure was the proportion of response based on improvements of irritability at the week 8 of the trial., Results: At the end of the trial, a significantly higher proportion of response was seen in those participants randomly assigned to CTP+MPH compared to PBO+MPH (35% CTP+MPH versus 6% PBO+MPH; odds ratio = 11.70, 95% CI = 2.00-68.16, p = 0.006). However, there were no differences in functional impairment between groups at the end of the trial. No differences were found in any adverse effect between treatment groups, and no trial participant exhibited hypomanic or manic symptoms., Conclusion: Adjunctive CTP might be efficacious in the treatment of chronic severe irritability in youth resistant to stimulant treatment alone., Clinical Trial Registration Information: A Controlled Trial of Serotonin Reuptake Inhibitors Added to Stimulant Medication in Youth With Severe Mood Dysregulation; https://clinicaltrials.gov; NCT00794040., (Published by Elsevier Inc.)

Importance: Prior studies suggest that the use of facial nerve monitoring decreases the rate of immediate postoperative facial nerve weakness in parotid surgery, but published data are lacking on normative values for these parameters or cutoff values to prognosticate facial nerve outcomes., Objective: To identify intraoperative facial nerve monitoring parameters associated with postoperative weakness and to evaluate cutoff values for these parameters under which normal nerve function is more likely., Design, Setting, and Participants: This retrospective case series of 222 adult patients undergoing parotid surgery for benign disease performed with intraoperative nerve monitoring was conducted at an academic medical institution from September 13, 2004, to October 30, 2014. The data analysis was conducted from May 2018 to January 2019., Main Outcomes and Measures: The main outcome measure was facial nerve weakness. Receiver operating characteristic curves were generated to define optimal cut point to maximize the sensitivity and specificity of the stimulation threshold, mechanical events, and spasm events associated with facial nerve weakness., Results: Of 222 participants, 121 were women and 101 were men, with a mean (SD) age of 51 (16) years. The rate of temporary facial nerve paresis of any nerve branch was 45%, and the rate of permanent paralysis was 1.3%. The mean predissection threshold was 0.22 milliamperes (mA) (range, 0.1-0.6 mA) and the mean postdissection threshold was 0.24 mA (range, 0.08-1.0 mA). The average number of mechanical events was 9 (range, 0-66), and mean number of spontaneous spasm events was 1 (range, 0-12). Both the postdissection threshold (area under the curve [AUC], 0.69; 95% CI, 0.62-0.77) and the number of mechanical events (AUC, 0.58; 95% CI, 0.50-0.66) were associated with early postoperative facial nerve outcome. The number of spasm events was not associated with facial nerve outcome. The optimal cutoff value for the threshold was 0.25 mA, and the optimal cutoff for number of mechanical events was 8. If a threshold of greater than 0.25 mA was paired with more than 8 mechanical events, there was a 77% chance of postoperative nerve weakness. Conversely, if a threshold was 0.25 mA or less and there were 8 mechanical events or less, there was 69% chance of normal postoperative nerve function. No parameters were associated with permanent facial nerve injury., Conclusions and Relevance: Postdissection threshold and the number of mechanical events are associated with immediate postoperative facial nerve function. Accurate prediction of facial nerve function may provide anticipatory guidance to patients and may provide surgeons with intraoperative feedback allowing adjustment in operative techniques and perioperative management.

Background: Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined., Methods: A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed., Results: PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up)., Conclusions: PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.

Unresectable recurrent or metastatic head and neck cancer is an incurable disease with survival of approximately 12 months. Head and neck tumors exhibit numerous derangements in the tumor microenvironment that aid in immune evasion and may serve as targets for future therapies. Pembrolizumab is now approved as a first line therapy. Despite the promise of currently approved immunotherapies there continues to be low response rates and additional strategies are needed. Here, alterations in the immune microenvironment and current therapeutic strategies are reviewed with a focus on novel immunologic approaches.

Head and neck cancers consist of a heterogeneous group of cancers that are difficult to treat successfully. Limited screening options result in patients being diagnosed at advanced stages at presentation, and difficulty with treatment options and post-treatment surveillance can lead to poor outcomes. In this setting, tools for early and precise detection of disease will be highly valuable. Liquid biopsies, or use of analytes in blood, saliva, and other body fluid samples, provide new avenues for cancer screening with the potential for early detection, treatment modification, and surveillance of head and neck cancers. Early studies of liquid biopsies in specific head and neck cancers have had encouraging results. Nevertheless, various challenges remain before its routine adoption into clinical use is feasible. With continued advancement in the field of liquid biopsies, there is great promise for clinical implementation and significant improvement in head and neck cancer care.

Objective: After recurrent laryngeal nerve injury (RLN), spontaneous reinnervation of the larynx occurs with input from multiple sources. The purpose of this study was to determine the timing and efficiency of reinnervation across a resected RLN segment in a rat model of RLN injury., Study Design: Animal study., Methods: Twelve male 60-day-old Sprague Dawley rats underwent resection of a 5-mm segment of the right RLN. Rats were sacrificed at 1, 2, 4, and 12 weeks after nerve injury to harvest the larynx and trachea for immunohistologic analysis. The distal RLN segment was stained with neurofilament, and axons were counted and compared to the nonoperated side. Thyroarytenoid (TA) muscles were stained with alpha-bungarotoxin, synaptophysin, and neurofilament to identify intact neuromuscular junctions (NMJ). The number of intact NMJs from the denervated side was compared to the nonoperated side., Results: Nerve fibers regenerated across the resected RLN gap into the distal recurrent laryngeal nerve to innervate the TA muscle. The number of nerve fibers in the distal nerve segment increased over time and reached the normal number by 12 weeks postdenervation. Axons formed intact neuromuscular junctions in the TA, with 48.8% ± 16.7% of the normal number of intact NMJs at 4 weeks and 88.3% ± 30.1% of the normal number by 12 weeks., Conclusion: Following resection of an RLN segment in a rat model, nerve fibers spontaneously regenerate through the distal segment of the transected nerve and form intact NMJs in order to reinnervate the TA muscle., Level of Evidence: NA. Laryngoscope, 128:E117-E122, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Severe, chronic irritability is receiving increased research attention, and is the cardinal symptom of a new diagnostic category, disruptive mood dysregulation disorder (DMDD). Although data from epidemiological community samples suggest that childhood chronic irritability predicts unipolar depression and anxiety in adulthood, whether these symptoms are stable and cause ongoing clinical impairment is unknown. The present study presents 4-year prospective and longitudinal diagnostic and impairment data on a clinical sample of children selected for symptoms of severe irritability (operationalized as severe mood dysregulation [SMD])., Methods: Youth meeting criteria for SMD (n = 200) were evaluated at baseline using standard diagnostic methods. Two-year (n = 78) and 4-year (n = 46) follow-up diagnostic and clinical impairment ratings collected at 6-month intervals were completed with those youths enrolled in the study for a sufficient time., Results: Although the number of youth meeting strict categorical SMD criteria declined over time (49 and 40% at 2 and 4 years, respectively), many individuals not meeting full criteria continued to display clinically significant irritability symptoms (2 years: 42%; 4 years: 37%). Impairment due to these irritability symptoms remained consistently in the moderate range on the Clinical Global Impressions Scale., Conclusions: By the 4-year follow-up, only 40% of youths meet strict SMD criteria; however, most continue to display clinically impairing symptoms and significant impairment warranting psychiatric treatment. These findings provide evidence for the course of irritability, with implications for DMDD. Future research with populations meeting DMDD criteria and followed through the ages of high risk for psychiatric diagnoses is necessary., (Published 2014. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Children with bipolar disorder (BD) or severe mood dysregulation (SMD) show behavioural and neural deficits during facial emotion processing. In those with other psychiatric disorders, such deficits have been associated with reduced attention to eye regions while looking at faces., Methods: We examined gaze fixation patterns during a facial emotion labelling task among children with pediatric BD and SMD and among healthy controls. Participants viewed facial expressions with varying emotions (anger, fear, sadness, happiness, neutral) and emotional levels (60%, 80%, 100%) and labelled emotional expressions., Results: Our study included 22 children with BD, 28 with SMD and 22 controls. Across all facial emotions, children with BD and SMD made more labelling errors than controls. Compared with controls, children with BD spent less time looking at eyes and made fewer eye fixations across emotional expressions. Gaze patterns in children with SMD tended to fall between those of children with BD and controls, although they did not differ significantly from either of these groups on most measures. Decreased fixations to eyes correlated with lower labelling accuracy in children with BD, but not in those with SMD or in controls., Limitations: Most children with BD were medicated, which precluded our ability to evaluate medication effects on gaze patterns., Conclusion: Facial emotion labelling deficits in children with BD are associated with impaired attention to eyes. Future research should examine whether impaired attention to eyes is associated with neural dysfunction. Eye gaze deficits in children with BD during facial emotion labelling may also have treatment implications. Finally, children with SMD exhibited decreased attention to eyes to a lesser extent than those with BD, and these equivocal findings are worthy of further study.

Objective: Irritability is common in children and adolescents and is the cardinal symptom of disruptive mood dysregulation disorder, a new DSM-5 disorder, yet its neural correlates remain largely unexplored. The authors conducted a functional MRI study to examine neural responses to frustration in children with severe mood dysregulation., Method: The authors compared emotional responses, behavior, and neural activity between 19 severely irritable children (operationalized using criteria for severe mood dysregulation) and 23 healthy comparison children during a cued-attention task completed under nonfrustrating and frustrating conditions., Results: Children in both the severe mood dysregulation and the healthy comparison groups reported increased frustration and exhibited decreased ability to shift spatial attention during the frustration condition relative to the nonfrustration condition. However, these effects of frustration were more marked in the severe mood dysregulation group than in the comparison group. During the frustration condition, participants in the severe mood dysregulation group exhibited deactivation of the left amygdala, the left and right striatum, the parietal cortex, and the posterior cingulate on negative feedback trials, relative to the comparison group (i.e., between-group effect) and to the severe mood dysregulation group's responses on positive feedback trials (i.e., within-group effect). In contrast, neural response to positive feedback during the frustration condition did not differ between groups., Conclusions: In response to negative feedback received in the context of frustration, children with severe, chronic irritability showed abnormally reduced activation in regions implicated in emotion, attention, and reward processing. Frustration appears to reduce attention flexibility, particularly in severely irritable children, which may contribute to emotion regulation deficits in this population. Further research is needed to relate these findings to irritability specifically, rather than to other clinical features of severe mood dysregulation.

Research from the adaptive memory framework shows that thinking about words in terms of their survival value in an incidental learning task enhances their free recall relative to other semantic encoding strategies and intentional learning (Nairne, Pandeirada, & Thompson, 2008). We found similar results. When participants used incidental survival encoding for a list of words (e.g., "Will this object enhance my survival if I were stranded in the grasslands of a foreign land?"), they produced better free recall on a surprise test than did participants who intentionally tried to remember those words (Experiment 1). We also found this survival processing advantage when the words were presented within the context of a survival or neutral story (Experiment 2). However, this advantage did not extent to memory for a story's factual content, regardless of whether the participants were tested by cued recall (Experiment 3) or free recall (Experiments 4-5). Listening to a story for understanding under intentional or incidental learning conditions was just as good as survival processing for remembering story content. The functionalist approach to thinking about memory as an evolutionary adaptation designed to solve reproductive fitness problems provides a different theoretical framework for research, but it is not yet clear if survival processing has general applicability or is effective only for processing discrete stimuli in terms of fitness-relevant scenarios from our past., (2012 APA, all rights reserved)