Safety Recommendations for Evaluation and Surgery of the Head and Neck During the COVID-19 Pandemic

Importance The rapidly expanding novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has challenged the medical community to an unprecedented degree. Physicians and health care workers are at added risk of exposure and infection during the course of patient care. Because of the rapid spread of this disease through respiratory droplets, health care workers who come in close contact with the upper aerodigestive tract during diagnostic and therapeutic procedures, such as otolaryngologists–head and neck surgeons, are particularly at risk. A set of safety recommendations was created based on a review of the literature and communications with physicians with firsthand knowledge of safety procedures during the COVID-19 pandemic. Observations A high number of health care workers were infected during the first phase of the pandemic in the city of Wuhan, China. Subsequently, by adopting strict safety precautions, other regions were able to achieve high levels of safety for health care workers without jeopardizing the care of patients. The most common procedures related to the examination and treatment of upper aerodigestive tract diseases were reviewed. Each category was reviewed based on the potential risk imposed to health care workers. Specific recommendations were made based on the literature, when available, or consensus best practices. Specific safety recommendations were made for performing tracheostomy in patients with COVID-19. Conclusions and Relevance Preserving a highly skilled health care workforce is a top priority for any community and health care system. Based on the experience of health care systems in Asia and Europe, by following strict safety guidelines, the risk of exposure and infection of health care workers could be greatly reduced while providing high levels of care. The provided recommendations, which may evolve over time, could be used as broad guidance for all health care workers who are involved in the care of patients with COVID-19

Cancer stem cells: Mediators of tumorigenesis and metastasis in head and neck squamous cell carcinoma

BackgroundCancer stem cells (CSCs) represent a subpopulation of cells responsible for tumor growth. Their role in head and neck squamous cell carcinoma (HNSCC) tumorigenesis and metastasis remains uncertain.MethodsWound healing and an orthotopic animal model were used to study cells expressing the CSC phenotype (CD44high and aldehyde dehydrogenase [ALDH]+) and assess mobility, tumorigenesis, and metastasis. A prospective collection of 40 patient‐derived primary HNSCC specimens were analyzed for CSC‐proportion compared to clinical variables.ResultsCSCs exhibited significantly faster wound closure and greater tumorigenesis and regional metastasis in vivo than non‐CSCs. In primary patient tumors, size and advanced stage were correlated with elevated proportion of CSCs, however, not with survival.ConclusionHNSCC stem cells mediate tumorigenesis and regional metastasis in vivo. In primary patient tumors, CSC‐proportion was associated with tumor size and stage, but not with metastatic spread or survival. CSC burden alone may only represent a minor variable in understanding CSCs and metastasis. © 2014 Wiley Periodicals, Inc. Head Neck 37: 317–326, 2015Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110728/1/hed23600.pd

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma

BackgroundTotal laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.MethodsA prospectively maintained single‐institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan‐Meier survival curves and hazard ratios (HRs) were calculated.ResultsFive‐year overall survival (OS) was 49%. Five‐year disease‐free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation‐27 [ACE‐27] scale; HR 3.76; 95% confidence interval [CI] 1.56‐9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74‐4.88).ConclusionSevere comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/1/hed24918.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139972/2/hed24918_am.pd

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/1/cncr30802.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138837/2/cncr30802_am.pd

Comprehensive review of genetic factors contributing to head and neck squamous cell carcinoma development in low‐risk, nontraditional patients

BackgroundThe past 2 decades have seen an increased incidence of head and neck squamous cell carcinoma (HNSCC) in a nontraditional, low‐risk patient population (ie, ≤45 years of age, no substance use history), owing to a combination of human papillomavirus (HPV) infection and individual genetic variation.MethodsArticles positing genetic variants as contributing factors in HNSCC incidence in low‐risk, nontraditional patients were identified using a PubMed search, reviewed in detail, and concisely summarized herein.ResultsRecent data suggest that common polymorphisms in DNA repair enzymes, cell‐cycle control proteins, apoptotic pathway members, and Fanconi anemia‐associated genes likely modulate susceptibility to HNSCC development in low‐risk, nontraditional patients.ConclusionAt present, there is a lack of robust, comprehensive data on genetic drivers of oncogenesis in low‐risk patients and a clear need for further research on genetic alterations underlying the rising incidence of HNSCC in low‐risk, nontraditional patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143606/1/hed25057_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143606/2/hed25057.pd

Saturated Fatty Acids Dampen the Immunogenicity of Cancer by Suppressing STING

Oncogenes destabilize STING in epithelial cell-derived cancer cells, such as head and neck squamous cell carcinomas (HNSCCs), to promote immune escape. Despite the abundance of tumor-infiltrating myeloid cells, HNSCC presents notable resistance to STING stimulation. Here, we show how saturated fatty acids in the microenvironment dampen tumor response to STING stimulation. Using single-cell analysis, we found that obesity creates an IFN-I-deprived tumor microenvironment with a massive expansion of suppressive myeloid cell clusters and contraction of effector T cells. Saturated fatty acids, but not unsaturated fatty acids, potently inhibit the STING-IFN-I pathway in HNSCC cells. Myeloid cells from obese mice show dampened responses to STING stimulation and are more suppressive of T cell activation. In agreement, obese hosts exhibited increased tumor burden and lower responsiveness to STING agonist. As a mechanism, saturated fatty acids induce the expression of NLRC3, depletion of which results in a T cell inflamed tumor microenvironment and IFN-I-dependent tumor control

Paired phase II trials evaluating cetuximab and radiotherapy for low risk HPV associated oropharyngeal cancer and locoregionally advanced squamous cell carcinoma of the head and neck in patients not eligible for cisplatin

BackgroundAlternative therapeutic strategies are needed for localized oropharyngeal carcinoma. Cetuximab represents a potential option for those ineligible for cisplatin or, until recently, an agent for de‐escalation in low risk HPV+ oropharyngeal carcinoma (OPSCC). Our objective was to define the toxicity and efficacy of cetuximab‐radiotherapy.MethodsWe conducted paired phase II trials evaluating cetuximab‐radiotherapy in two cohorts (a) low risk HPV+ OPSCC and (b) cisplatin ineligible. The mean follow‐up was 48 months.ResultsForty‐two patients were enrolled in cohort A with a 2‐year disease free survival (DFS) of 81%. Twenty‐one patients were enrolled in cohort B prior to closure due to adverse outcomes with a 2‐year DFS of 37%. Severe toxicities were seen in 60% of patients, 30% required enteral nutrition.ConclusionAmong cisplatin ineligible patients, cetuximab treatment engendered poor outcomes. Rates of severe toxicities were on par with platinum‐based regimens suggesting that cetuximab is not a benign treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/2/hed26085.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156234/1/hed26085_am.pd

Mutational profiles of persistent/recurrent laryngeal squamous cell carcinoma

BackgroundWe sought to describe targeted DNA sequencing data of persistent/recurrent laryngeal squamous cell carcinoma (LSCC) and to compare gene‐specific alteration frequencies with that of primary, untreated LSCC specimens from The Cancer Genome Atlas (TCGA).MethodsThe tumors of 21 patients with persistent/recurrent LSCC were subjected to targeted DNA sequencing using the Ion AmpliSeq Comprehensive Cancer Panel. Gene‐specific alteration frequencies were compared (Chi‐Square test) to primary, untreated LSCC sequencing data from TCGA using the cBioPortal platform.ResultsPersistent/recurrent LSCC was characterized by a high rate of inactivating alterations in TP53 (38.1%) and CDKN2A (33%), amplification events of CCND1 (19.1%), and ERBB2 (14.3%), and NOTCH1 (19.1%) mutations. Comparison of primary vs persistent/recurrent LSCC revealed significant differences in alteration frequencies of eight critical genes: BAP1, CDKN2A, DCUN1D1, MSH2, MTOR, PIK3CA, TET2, and TP53.ConclusionsOur results provide preliminary support for a distinct mutational profile of persistent/recurrent LSCC that requires validation in larger cohorts.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/1/hed25444.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147873/2/hed25444_am.pd

High temperature corrosion research at the Albany Research Center

The Severe Environment Corrosion and Erosion Research Facility (SECERF) at the Albany Research Center is operational. SECERF consists of 6 modules that share the availability of up to 10 different gases to produce environments for high temperature corrosion and erosion research. Projects to be conducted in the modules include: corrosion sensors for fossil energy systems, thermal gradient effects on high temperature corrosion, the development of sulfidation resistant alloys, determination of the effects of ash on the corrosion of metals and alloys in coal and waste combustion and coal gasification environments, high temperature erosion-corrosion of metals, and molten slag effects on refractories. Results from two areas, the effect of ash deposits on alloy corrosion and thermal gradient effects on the corrosion of metals, will be highlighted. Ash produced in coal gasifiers, coal combustors, and waste combustors, when deposited on metal surfaces, provides sites for corrosion attack and contributes chemical species that participate in the corrosion reaction. Results are presented for the corrosion of 304L stainless steel, that was either uncoated or coated with ash or with ash containing NaCl or Na2SO4, in air-water vapor mixtures at 600 C. The presence of high heat fluxes and temperature gradients in many fossil energy systems creates the need for an understanding of their effects on corrosion and oxidation. Such information would be useful for both improved alloy design and for better translation of isothermal laboratory results to field use. Temperature gradients in a solid oxide result in two changes that modify diffusion within the oxide. The first is when a gradient in point defect concentration is created within the oxide, for example, where more vacancies are expected at a higher temperature. The second change is when the presence of a temperature gradient biases the diffusion jump of an atom. Results of tests are presented for cobalt with metal surface temperatures of approximately 920-950 C in N2 plus 1-10 vol% O2 environments with a heat flux of about 40 kW/m2. Non-equilibrium thermodynamics were used to develop oxidation rate equations in temperature gradients that were combined with point defect information of CoO to predict oxidation rates