The intratumor microbiome varies by geographical location and anatomical site in head and neck squamous cell carcinoma.

Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly heterogeneous cancer that is characterized by distinct phenotypes based on anatomical site and etiological agents. Recently, the intratumor microbiome has been implicated in cancer pathogenesis and progression. Although it is well established that the gut microbiome varies with geographical location and is highly influenced by factors such as diet, environment, and genetics, the intratumor microbiome is not very well characterized. In this review, we aim to characterize the HNSCC intratumor microbiome by geographical location and anatomical site. We conducted a review of primary literature from PubMed and assessed studies based on relevancy and recency. To the best of our knowledge, we are the first to comprehensively examine the tumor microenvironment of HNSCC with respect to these two primary factors on a large scale. Our results suggest that there are unique bacterial and fungal biomarkers for HNSCC for each of the following geographical locations: North America, Asia, Europe, Australia, and Africa. We also identified a panel of microbial biomarkers that are unique to two primary HNSCC anatomic sites, as well as microbial biomarkers associated with various etiological agents of HNSCC. Future study of these microbes may improve HNSCC diagnostic and therapeutic modalities by accounting for differences based on geographic regions and anatomical sites.

The Intratumor Bacterial and Fungal Microbiome Is Characterized by HPV, Smoking, and Alcohol Consumption in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) tumor phenotypes and clinical outcomes are significantly influenced by etiological agents, such as HPV infection, smoking, and alcohol consumption. Accordingly, the intratumor microbiome has been increasingly implicated in cancer progression and metastasis. However, few studies characterize the intratumor microbial landscape of HNSCC with respect to these etiological agents. In this study, we aimed to investigate the bacterial and fungal landscape of HNSCC in association with HPV infection, smoking, and alcohol consumption. RNA-sequencing data were extracted from The Cancer Genome Atlas (TCGA) regarding 449 tissue samples and 44 normal samples. Pathoscope 2.0 was used to extract the microbial reads. Microbe abundance was compared to clinical variables, oncogenic signatures, and immune-associated pathways. Our results demonstrated that a similar number of dysregulated microbes was overabundant in smokers and nonsmokers, while heavy drinkers were characterized by an underabundance of dysregulated microbes. Conversely, the majority of dysregulated microbes were overabundant in HPV+ tumor samples when compared to HPV- tumor samples. Moreover, we observed that many dysregulated microbes were associated with oncogenic and metastatic pathways, suggesting their roles in influencing carcinogenesis. These microbes provide insights regarding potential mechanisms for tumor pathogenesis and progression with respect to the three etiological agents.

Orbital floor reconstruction via autologous radial forearm free flap with palmaris longus tendon.

We describe reconstruction of the orbital floor following suprastructure maxillectomy for resection of maxillary squamous cell carcinoma utilizing an osteocutaneous radial forearm free flap and palmaris longus tendon.

Radiofrequency ablation and related ultrasound-guided ablation technologies for treatment of benign and malignant thyroid disease: An international multidisciplinary consensus statement of the American Head and Neck Society Endocrine Surgery Section with the Asia Pacific Society of Thyroid Surgery, Associazione Medici Endocrinologi, British Association of Endocrine and Thyroid Surgeons, European Thyroid Association, Italian Society of Endocrine Surgery Units, Korean Society of Thyroid Radiology, Latin American Thyroid Society, and Thyroid Nodules Therapies Association.

BACKGROUND: The use of ultrasound-guided ablation procedures to treat both benign and malignant thyroid conditions is gaining increasing interest. This document has been developed as an international interdisciplinary evidence-based statement with a primary focus on radiofrequency ablation and is intended to serve as a manual for best practice application of ablation technologies. METHODS: A comprehensive literature review was conducted to guide statement development and generation of best practice recommendations. Modified Delphi method was applied to assess whether statements met consensus among the entire author panel. RESULTS: A review of the current state of ultrasound-guided ablation procedures for the treatment of benign and malignant thyroid conditions is presented. Eighteen best practice recommendations in topic areas of preprocedural evaluation, technique, postprocedural management, efficacy, potential complications, and implementation are provided. CONCLUSIONS: As ultrasound-guided ablation procedures are increasingly utilized in benign and malignant thyroid disease, evidence-based and thoughtful application of best practices is warranted.

Enhancer RNA Profiling in Smoking and HPV Associated HNSCC Reveals Associations to Key Oncogenes.

Smoking and HPV infection are known causes for the vast majority of head and neck squamous cell carcinomas (HNSCC) due to their likelihood of causing gene dysregulation and genomic alterations. Enhancer RNAs (eRNAs) are non-coding RNAs that are known to increase nearby and target gene expression, and activity that has been suggested to be affected by genetic and epigenetic alterations. Here we sought to identify the effects of smoking and HPV status on eRNA expression in HNSCC tumors. We focused on four patient cohorts including smoking/HPV+, smoking/HPV-, non-smoking/HPV+, and non-smoking/HPV- patients. We used TCGA RNA-seq data from cancer tumors and adjacent normal tissue, extracted eRNA read counts, and correlated these to survival, clinical variables, immune infiltration, cancer pathways, and genomic alterations. We found a large number of differentially expressed eRNA in each patient cohort. We also found several dysregulated eRNA correlated to patient survival, clinical variables, immune pathways, and genomic alterations. Additionally, we were able to find dysregulated eRNA nearby seven key HNSCC-related oncogenes. For example, we found eRNA chr14:103272042-103272430 (eRNA-24036), which is located close to the TRAF3 gene to be differentially expressed and correlated with the pathologic N stage and immune cell populations. Using a separate validation dataset, we performed differential expression and immune infiltration analysis to validate our results from the TCGA data. Our findings may explain the association between eRNA expression, enhancer activity, and nearby gene dysregulation.

Inappropriate requesting of parathyroid scintigraphy at an academic medical center.

BACKGROUND: Primary hyperparathyroidism is a biochemical, not radiologic diagnosis. Parathyroid scintigraphy should only be requested for surgical planning, not to confirm diagnosis. Here we determined reasons for inappropriately ordered parathyroid scintigraphy. METHODS: We generated a database of patients undergoing parathyroid scintigraphy over 5 years, who did not undergo parathyroidectomy. RESULTS: Over 5 years 129 parathyroid scintigraphies (of 308 total scans) were performed in patients who did not undergo parathyroidectomy. We determined that only 58 (45%) had true primary hyperparathyroidism. The most common reason for the scan was to "confirm the diagnosis." Only 20% were ordered for adenoma localization, although surgery was not performed. Physicians requesting parathyroid scintigraphies specialized in a variety of disciplines. CONCLUSION: Forty-two percent of parathyroid scintigraphies were requested inappropriately to "confirm" a diagnosis of primary hyperparathyroidism. We propose to change the ordering system to clarify that parathyroid scintigraphy is a functional tool to optimize surgery when the diagnosis is secure.

Robotic surgery may improve overall survival for T1 and T2 tumors of the hypopharynx: An NCDB cohort study.

BACKGROUND: Hypopharyngeal cancer is associated with poor survival. Robotic surgery is emerging as a treatment for hypopharyngeal tumors, but no rigorous data are available to assess its effect on survival. METHODS: The National Cancer Database (NCDB) was used to identify patients with T1 and T2 hypopharyngeal tumors undergoing robotic surgery, laser surgery, and primary radiation with or without chemotherapy from 2010 to 2016. All adult patients with available staging and no distant metastasis were included. RESULTS: We compared 57 patients undergoing robotic surgery, 236 undergoing laser surgery, and 5,742 undergoing primary radiation. Compared to laser surgery, patients undergoing robotic surgery were significantly more likely to have negative margins, neck dissection, lower incomes, and care at an academic center. Rates of robotic surgery also significantly increased from 2010 to 2015. After multivariate regression, robotic surgery was associated with significantly improved overall survival compared to laser surgery and primary radiation. CONCLUSION: Robotic surgery improves overall survival for T1 and T2 hypopharyngeal tumors compared to laser surgery and primary radiation in this NCDB cohort. This effect may be mediated by decreased positive margin rates relative to laser surgery. Rates of hypopharyngeal robotic surgery are expected to increase with wider adoption of robotic platforms and may improve overall survival rates for hypopharyngeal cancer.

Characterizing Posterior Neck Masses: A Single-Institution Retrospective and Systematic Review.

OBJECTIVE: Posterior neck masses are a relatively poorly characterized entity. The authors attempt to further characterize the anatomy and pathology of the posterior neck by way of a combined single-institution retrospective chart review and systematic review of the literature. METHODS: A single-institution retrospective chart review was undertaken for all patients undergoing excision of a posterior neck mass between January 1, 2012, and January 1, 2017. A systematic review of the Medline, Embase, Web of Science, and Cochrane database was undertaken in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in search of case reports and series describing posterior neck masses. RESULTS: A total of 28 patients who underwent excision of a posterior neck mass were encountered during the retrospective chart review. All pathologies were benign, the most prevalent of which was lipoma (22/28, 79%). A total of 19 articles describing a collective 36 posterior neck masses were encountered during the systematic review. Lipomas were the most common pathology (15/36, 42%). All but one of the masses reported were benign (35/36, 97%). CONCLUSIONS: Patients presenting with posterior neck masses can be reassured of a low risk of malignancy. The majority of posterior neck masses can be appropriately evaluated via physical examination and ultrasound.

Meta-analysis of risk of occult lymph node metastasis in the irradiated, clinically N0 neck.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) after radiation is associated with poor survival, and management of the clinically negative (N0) neck during salvage surgery is controversial. METHODS: Studies were selected according to preferred reporting items for systematic reviews and meta-analyses guidelines. Inclusion criteria were patients with HNSCC, prior radiation to the lateral neck nodal basin, undergoing salvage surgery for local recurrence, persistence or second primary, and N0 at time of salvage. Eleven studies with a total of 382 patients met inclusion criteria. RESULTS: The rate of occult metastasis was 15.4%. The pooled rate of occult nodal metastasis was 16.2% for oral cavity, 12.9% for oropharynx, 23.7% for hypopharynx, and 27.3% for supraglottic or transglottic tumors. There was a significantly higher relative risk of occult metastasis for locally advanced tumors. CONCLUSION: Elective neck dissection at time of salvage surgery should be considered based on subsite, T classification, and prior history of nodal metastasis.

Facial Paralysis Following Core Needle Biopsy of a Deep Lobe Parotid Tumor: A Case Report.

OBJECTIVES:: To report a case of total facial paralysis as the result of a core needle biopsy. METHODS:: Case report and literature review. RESULTS:: A 70-year-old man was diagnosed with a deep lobe parotid tumor on computed tomography. During a core needle biopsy, he developed complete facial paralysis. The cause was discovered to be a direct stab injury to the main trunk of the facial nerve. CONCLUSIONS:: When biopsying parotid lesions adjacent to the main trunk of the facial nerve, the use of smaller-gauge needles and additional patient counseling should be considered.

Association of Preoperative Anemia With 30-Day Morbidity and Mortality Among Patients With Thyroid Cancer Who Undergo Thyroidectomy.

Importance: Despite the ease of preoperative anemia diagnosis and the availability of treatment options, the morbidity and mortality associated with this condition remain unacceptably high, and the literature describing the association of preoperative anemia with postoperative outcomes following thyroid surgery in patients with thyroid cancer remain sparse. Reporting outcomes in this patient population may help to facilitate preoperative optimization. Objective: To assess whether an association exists between preoperative anemia and outcomes following thyroid surgery in patients with thyroid cancer. Design, Setting, and Participants: This retrospective, cross-sectional, cohort study used the American College of Surgeons National Surgical Quality Improvement Program database to identify 32 166 patients between 2007 and 2016 with Current Procedural Terminology codes for thyroid surgery and with the International Classification of Diseases, Ninth Revision code of malignant thyroid cancer. Exposures: Preoperative anemia as defined using the World Health Organization criteria of hematocrit less than 36% in nonpregnant females and less than 39% in males. Main Outcomes and Measures: Multivariable logistic regression analysis was conducted to assess the association of preoperative anemia with the following 30-day postoperative outcomes: pulmonary, infectious, and cardiac complications, overall and serious morbidity (surgical site infection and medical complications), prolonged hospital length of stay (≥75th percentile for the cohort), and mortality. Results: Among the 24 912 patients with thyroid cancer who underwent thyroidectomy included in the final analysis, the median (interquartile range) age was 51 (40-62) years and the majority were women (18 705 [75.1%]). The prevalence of preoperative anemia was 12.5% (n = 3108). Within the overall study population, hypertension (9242 patients [37.1%]) followed by active smoking (2992 patients [12.0%]) were the most prevalent comorbidities. The unadjusted odds of anemia vs no anemia were significantly higher for every 10-year increase in age (odds ratio [OR], 1.10; 95% CI, 1.08-1.13) and for black vs white patients (OR, 2.82; 95% CI, 2.51-3.17). The adjusted odds of postoperative overall morbidity (OR, 1.68; 95% CI, 1.29-2.17), mortality (OR, 3.36; 95% CI, 1.37-8.28), and pulmonary (OR, 2.36; 95% CI, 1.65-3.34) and infectious (OR, 1.62; 95% CI, 1.12-2.29) complications were higher in patients with preoperative anemia than in those without preoperative anemia. Conclusions and Relevance: The findings from this study suggest that preoperative anemia may not only be associated with racial differences and a higher comorbidity burden but may also increase the likelihood of postoperative morbidity and mortality. These results may provide a basis for further risk reduction strategies and preoperative optimization.

Opioid prescribing practices in patients undergoing surgery for oral cavity cancer.

OBJECTIVES: Opioids have been overprescribed after general and orthopedic surgeries, but prescribing patterns have not been reported for head and neck surgery. The objectives of this retrospective review are to describe postoperative opioid prescriptions after oral cancer surgery and determine which patients receive higher amounts. METHODS: A single institution retrospective review was performed for 81 adults with oral cavity tumors undergoing surgery. Opioid prescriptions upon discharge were reported in daily oral morphine equivalents (OME). High opioids were defined as > 90 mg daily and > 200 mg total, commensurate with U.S. Center for Disease Control and Prevention and state guidelines. Multivariable logistic regression was performed to investigate factors associated with high opioids. RESULTS: The median number of doses dispensed was 30 (interquartile range [IQR] 30-45; range 3-120). The median daily dose was 30 mg (IQR 20-45 mg; range 15-240 mg). Five patients (6%) received higher than the recommended daily dose. The median total dispensed amount was 225 mg (IQR 150-250 mg; range 15-1200 mg). Fifty-one (63%) received greater than the recommended total dose. On multivariable logistic regression, advanced tumor stage (odds ratio [OR] 11.5; 95% confidence interval [CI] 1.2-109.4; P = 0.034) and inpatient pain scores (OR 1.3 per 1-unit increase; 95% CI 1.0-1.7; P = 0.039) were associated with receiving high total opioids after surgery. CONCLUSION: The majority of patients received greater than the recommended 200 mg total OME. Advanced stage and higher inpatient pain scores were associated with receiving more opioids for discharge. Consensus-driven analgesic plans are needed to reduce excess opioids after discharge following head and neck surgery. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2361-2366, 2018.

Needle Biopsy of Routine Thyroid Nodules Should Be Performed Using a Capillary Action Technique with 24- to 27-Gauge Needles: A Systematic Review and Meta-Analysis.

BACKGROUND: Fine-needle biopsy is the international standard for diagnostic evaluation of thyroid nodules. There is a lack of consensus regarding the optimal needle biopsy technique. The implementation of capillary action versus aspiration and the optimal needle gauge remain topics of debate. METHODS: A systematic review of the Medline, Embase, and Cochrane databases was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles evaluating the effects of capillary action versus aspiration and needle gauge on success rates of fine-needle biopsy of the thyroid were assessed for inclusion. The primary outcome of interest was the rate of non-diagnostic cytopathology. RESULTS: Twenty-four articles with a collective 4428 nodules were ultimately included in the review. Twenty articles evaluated capillary action versus aspiration, and six evaluated needle gauge. All but two studies were prospective, most of which were blinded trials with or without randomization. Using a random-effects model, capillary action was associated with a statistically significant reduction in the relative risk of non-diagnostic cytopathology (relative risk = 0.57 [confidence interval 0.34-0.92]; p = 0.02). There was a nonsignificant trend in favor of smaller needle gauges. CONCLUSION: Given the statistically significant deceased rate of non-diagnostic cytopathology with capillary action and the potential for increased pain and complications with larger needles without a proven benefit, needle biopsy of routine thyroid nodules should be performed without aspiration and with smaller needle gauges (24-27G).

Indocyanine green fluorescence-guided parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: Our aim was to evaluate the ease and utility of using indocyanine green fluorescence angiography for intraoperative localization of the parathyroid glands. METHODS: Indocyanine green fluorescence angiography was performed during 60 parathyroidectomies for primary hyperparathyroidism during a 22-month period. Indocyanine green was administered intravenously to guide operative navigation using a commercially available fluorescence imaging system. Video files were graded by 3 independent surgeons for strength of enhancement using an adapted numeric scoring system. RESULTS: There were 46 (77%) female patients and 14 (23%) male patients whose ages ranged from 17 to 87 (average 60) years old. Of the 60 patients, 43 (71.6%) showed strong enhancement, 13 (21.7%) demonstrated mild to moderate vascular enhancement, and 4 (6.7%) exhibited little or no vascular enhancement. Of the 54 patients who had a preoperative sestamibi scan, a parathyroid adenoma was identified in 36, while 18 failed to localize. Of the 18 patients who failed to localize, all 18 patients (100%) had an adenoma that fluoresced on indocyanine green imaging. The operations were performed safely with minimal blood loss and short operative times. CONCLUSION: Indocyanine green angiography has the potential to assist surgeons in identifying parathyroid glands rapidly with minimal risk.

Esophageal dilation in head and neck cancer patients: A systematic review and meta-analysis.

OBJECTIVE: To characterize the safety profile and effectiveness of esophageal dilation in head and neck cancer patients. METHODS: A systematic review was undertaken for articles reporting outcomes of esophageal dilation in head and neck cancer patients. The Medline, Scopus, Web of Science, and Cochrane databases were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Complications related to esophageal dilation in head and neck cancer patients was the primary outcome of interest. Success rates, demographic data, cancer staging, and treatment data were assessed secondarily. Statistical analyses included both qualitative and quantitative assessments. A limited meta-analysis and pooling of the data was performed using a random effects model. RESULTS: Of the collective 8,243 initial candidate articles, 15 retrospective studies containing data for a collective 449 patients were ultimately included in the analysis. There was significant heterogeneity in the outcomes data. With an overall complication rate of 10.6% (95% confidence interval [CI]: 4.1%,17%) and a pooled success rate of 72.9% (95% CI: 65.7%,80.1%) per patient, the articles generally supported the use of dilation. CONCLUSION: Head and neck cancer patients experience a higher rate of complications following dilation compared to patients with other causes of benign stricture. Esophageal dilation is effective in improving dysphagia, but these benefits are often transient and thus necessitate repeat interventions. Laryngoscope, 128:111-117, 2018.

Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma.

Purpose: Preclinical models have shown that the effectiveness of GL-ONC1, a modified oncolytic vaccinia virus, is enhanced by radiation and chemotherapy. The purpose of this study was to determine the safety of GL-ONC1 when delivered intravenously with chemoradiotherapy to patients with primary, nonmetastatic head and neck cancer.Experimental Design: Patients with locoregionally advanced unresected, nonmetastatic carcinoma of the head/neck, excluding stage III-IVA p16-positive oropharyngeal cancers, were treated with escalating doses and cycles of intravenous GL-ONC1, along with radiotherapy and chemotherapy. The primary aims were to define the MTD and dose-limiting toxicities, and to recommend a dose for phase II trials.Results: Between May 2012 and December 2014, 19 patients were enrolled. The most frequent adverse reactions included grade 1-2 rigors, fever, fatigue, and rash. Grade 3 adverse reactions included hypotension, mucositis, nausea, and vomiting. In 2 patients, the rash was confirmed as viral in origin by fluorescence imaging and viral plaque assay. In 4 patients, viral presence in tumor was confirmed on midtreatment biopsy by quantitative PCR. In 1 patient, live virus was confirmed in a tongue tumor 7 days after receiving the first dose of virus. The MTD was not reached. With median follow-up of 30 months, 1-year (2-year) progression-free survival and overall survival were 74.4% (64.1%) and 84.6% (69.2%), respectively.Conclusions: Delivery of GL-ONC1 is safe and feasible in patients with locoregionally advanced head/neck cancer undergoing standard chemoradiotherapy. A phase II study is warranted to further investigate this novel treatment strategy. Clin Cancer Res; 23(19); 5696-702. ©2017 AACR.

Electronic cigarettes induce DNA strand breaks and cell death independently of nicotine in cell lines.

OBJECTIVES: Evaluate the cytotoxicity and genotoxicity of short- and long-term e-cigarette vapor exposure on a panel of normal epithelial and head and neck squamous cell carcinoma (HNSCC) cell lines. MATERIALS AND METHODS: HaCaT, UMSCC10B, and HN30 were treated with nicotine-containing and nicotine-free vapor extract from two popular e-cigarette brands for periods ranging from 48 h to 8 weeks. Cytotoxicity was assessed using Annexin V flow cytometric analysis, trypan blue exclusion, and clonogenic assays. Genotoxicity in the form of DNA strand breaks was quantified using the neutral comet assay and γ-H2AX immunostaining. RESULTS: E-cigarette-exposed cells showed significantly reduced cell viability and clonogenic survival, along with increased rates of apoptosis and necrosis, regardless of e-cigarette vapor nicotine content. They also exhibited significantly increased comet tail length and accumulation of γ-H2AX foci, demonstrating increased DNA strand breaks. CONCLUSION: E-cigarette vapor, both with and without nicotine, is cytotoxic to epithelial cell lines and is a DNA strand break-inducing agent. Further assessment of the potential carcinogenic effects of e-cigarette vapor is urgently needed.