The mechanisms of action of metformin on head and neck cancer in the pre-clinical setting: a scoping review.

This scoping review identifies the mechanistic pathways of metformin when used to treat head and neck cancer cells, in the pre-clinical setting. Understanding the underlying mechanisms will inform future experimental designs exploring metformin as a potential adjuvant for head and neck cancer. This scoping review was conducted according to the Joanna-Briggs Institute framework. A structured search identified 1288 studies, of which 52 studies fulfilled the eligibility screen. The studies are presented in themes addressing hallmarks of cancer. Most of the studies demonstrated encouraging anti-proliferative effects in vitro and reduced tumor weight and volume in animal models. However, a few studies have cautioned the use of metformin which supported cancer cell growth under certain conditions.

Development of a non-invasive exhaled breath test for the diagnosis of head and neck cancer.

BACKGROUND: Improving the ability to identify early-stage head and neck squamous cell carcinoma (HNSCC) can improve treatment outcomes and patient morbidity. We sought to determine the diagnostic accuracy of breath analysis as a non-invasive test for detecting HNSCC. METHODS: Standardised breath samples were collected from 181 patients suspected of HNSCC prior to any treatment. A selected ion flow-tube mass spectrometer was used to analyse breath for volatile organic compounds. Diagnosis was confirmed by histopathology. A binomial logistic regression model was used to differentiate breath profiles between cancer and control (benign disease) patients based on mass spectrometry derived variables. RESULTS: In all, 66% of participants had early-stage primary tumours (T1 and T2) and 58% had regional node metastasis. The optimised logistic regression model using three variables had a sensitivity and specificity of 80% and 86%, respectively, with an AUC for ROC curve of 0.821 (95%CI 0.625-1.0) in the testing cohort. CONCLUSIONS: Breath analysis for non-invasive diagnosis of HNSCC appears to be practical and accurate. Future studies should be conducted in a primary care setting to determine the applicability of breath analysis for early identification of HNSCC.

Breath methane to hydrogen ratio as a surrogate marker of intestinal dysbiosis in head and neck cancer.

Exhaled breath compounds can non-invasively detect head and neck squamous cell carcinoma (HNSCC). Here we investigated exhaled compounds related to intestinal bacterial carbohydrate fermentation. Fasting breath samples were collected into 3 litre FlexFoil PLUS bags from patients awaiting a biopsy procedure for suspected HNSCC. Samples were analysed using a Syft selected ion flow-tube mass spectrometer and a Quintron BreathTracker. Two tailed non-parametric significance testing was conducted with corrections for multiple imputations. 74 patients were diagnosed (histological) with HNSCC and 61 patients were benign (controls). The methane to hydrogen ratio was significantly different between cancer and non-cancer controls (p = 0.0440). This ratio increased with tumour stage with a significant difference between T1 and T4 tumours (p = 0.0259). Hydrogen levels were significantly higher in controls who were smokers (p = 0.0129), with no smoking dependent methane changes. There were no differences in short chain fatty acids between groups. Exhaled compounds of intestinal carbohydrate fermentation can detect HNSCC patients. These findings suggest a modified carbohydrate fermentation profile in HNSCC patients that is tumour stage and smoking status dependent.

A review of breath analysis techniques in head and neck cancer.

Cancers of the head and neck region are a severely disabling group of diseases with no method for early detection. Analysis of exhaled breath volatile organic compounds shows promise as biomarkers for early detection and disease monitoring. This article reviews breath analysis in the setting of head and neck cancer, with a practical focus on breath sampling techniques, detection technologies and valid data analysis methods. Title and abstract keyword searches were conducted on PubMed and Embase databases to identify English language studies without a time-period limitation. The main inclusion criteria were human studies comparing head and neck cancer patients to healthy controls using exhaled breath analysis. Multiple breath collection techniques, three major detection technologies and multiple data analysis methods were identified. However, the variability in techniques and lack of methodological standardization does not allow for adequate study replication or data pooling. Twenty-two volatile organic compounds identified in five studies have been reported to discriminate head and neck cancer patients from healthy controls. Breath analysis for detection of head and neck cancer shows promise as a non-invasive detection tool. However, methodological standardization is paramount for future research study design to provide the potential for translating these techniques into routine clinical use.

A review of the use of transnasal humidified rapid insufflation ventilatory exchange for patients undergoing surgery in the shared airway setting.

Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) is a recent technique that delivers warm humidified high flow oxygen to patients, allowing for prolonged apneic oxygenation. A review of current literature was performed to determine the use of THRIVE in apneic patients undergoing surgery in a shared airway setting. An initial free hand search was done to identify keywords followed by a systematic search of major databases with no date or language restrictions. Inclusion criteria include all apneic patients who receive THRIVE for any operative procedure. Fifteen studies fulfilled the inclusion criteria. There were ten case series, two case reports, two review articles and one randomized controlled trial. All of the studies discussed the use of THRIVE during laryngopharyngeal surgeries. The median apnea time reported ranged between 13 and 27 min. There were no significant complications reported as a result of using THRIVE. Most studies identified in this review were observational in nature involving laryngopharyngeal procedures. They have demonstrated THRIVE to be effective in providing apneic oxygenation during short procedures in adult patients. Further studies are required to determine the limitations of safe use in specific populations and when THRIVE is combined with diathermy or laser use.

Circulating microRNAs in head and neck cancer: a scoping review of methods.

Circulating microRNAs have been described as head and neck cancer biomarkers in multiple anatomical subsites including the oral cavity, nasopharynx, larynx, salivary glands and the skin. While there is an expanding volume of published literature showing the significance of individual or panels of microRNAs, the clinical validation of candidate biomarkers is lacking. The various methods used to collect, store, process and interpret these microRNAs are likely introducing bias and contributing to the inconsistent results. A systematic scoping review was conducted using PRISMA standards to identify published English literature between 2007 and 2018. Pubmed and EMBASE databases were searched using specific keyword combinations related to head and neck cancer, circulating samples (whole blood, plasma or serum) and microRNA. Following the title and abstract review, two primary authors appraised the articles for their suitability to include in the review based on the detail of methodological descriptions. Thirty suitable articles were identified relating to nasopharyngeal carcinoma, oral cavity, oropharyngeal and laryngeal squamous cell carcinoma as well as primary salivary gland malignancies. Comprehensive methodological analysis identified poor reporting of detailed methodology, variations in collection, storage, pre-processing, RNA isolation and relative quantification including normalisation method. We recommend standardising the pre-processing, RNA isolation, normalisation and relative quantitation steps at biomarker discovery phase. Such standardisation would allow for bias minimisation and effective progression into clinical validation phases.

Effectiveness of primary surgery versus primary radiotherapy on unknown primary head and neck squamous cell carcinoma: a systematic review protocol.

REVIEW QUESTION: The review question is: what is the effectiveness of primary surgery versus primary radiotherapy on disease-free survival and quality of life in adults with an unknown primary, head and neck squamous cell carcinoma?

Scoping review of pediatric tonsillectomy quality of life assessment instruments.

OBJECTIVES/HYPOTHESIS: Sleep-disordered breathing or recurrent tonsillitis have detrimental effects on the child's physical health and quality of life. Tonsillectomy is commonly performed to treat these common conditions and improve the child's quality of life. This scoping review aims to present a comprehensive and descriptive analysis of quality of life questionnaires as a resource for clinicians and researchers when deciding which tool to use when assessing the quality of life effects after tonsillectomy. STUDY DESIGN: A comprehensive search strategy was undertaken across MEDLINE (PubMed), CINAHL, Embase, and Cochrane CENTRAL. METHODS: Quality of life questionnaires utilized in studies investigating pediatric patients undergoing tonsillectomy for chronic tonsillitis or sleep-disordered breathing were included. Methodological quality and data extraction were conducted as per Joanna Briggs Institute methodology. RESULTS: Ten questionnaires were identified, consisting of six generic and four disease-specific instruments. The Pediatric Quality of Life Inventory was the most commonly utilized generic questionnaire. The Obstructive Sleep Apnea-18 was the most commonly utilized disease-specific questionnaire. CONCLUSIONS: This review identified a range of generic and disease-specific quality of life questionnaires utilized in pediatric patients who have undergone tonsillectomy with or without adenoidectomy for sleep-disordered breathing or chronic tonsillitis. Important aspects of each questionnaire have been summarized to aid researchers and clinicians in choosing the appropriate questionnaire when evaluating the quality of life effects of tonsillectomy. LEVEL OF EVIDENCE: NA Laryngoscope, 127:2399-2406, 2017.

Comparing surgical experience with performance on a sinus surgery simulator.

BACKGROUND: This study evaluates whether surgical experience influences technical competence using the Flinders sinus surgery simulator, a virtual environment designed to teach nasal endoscopic surgical skills. METHODS: Ten experienced sinus surgeons (five consultants and five registrars) and 14 novices (seven resident medical officers and seven interns/medical students) completed three simulation tasks using haptic controllers. Task 1 required navigation of the sinuses and identification of six anatomical landmarks, Task 2 required removal of unhealthy tissue while preserving healthy tissue and Task 3 entailed backbiting within pre-set lines on the uncinate process and microdebriding tissue between the cuts. RESULTS: Novices were compared with experts on a range of measures, using Mann-Whitney U -tests. Novices took longer on all tasks (Task 1: 278%, P < 0.005; Task 2: 112%, P < 0.005; Task 3: 72%, P < 0.005). In Task 1, novices' instruments travelled further than experts' (379%, P < 0.005), and provided greater maximum force (12%, P < 0.05). In Tasks 2 and 3 novices performed more cutting movements to remove the tissue (Task 2: 1500%, P < 0.005; Task 3: 72%, P < 0.005). Experts also completed more of Task 3 (66%, P < 0.05). CONCLUSIONS: The study demonstrated the Flinders sinus simulator's construct validity, differentiating between experts and novices with respect to procedure time, instrument distance travelled and number of cutting motions to complete the task.

Role of adenosine kinase in cochlear development and response to noise.

Adenosine signalling has an important role in cochlear protection from oxidative stress. In most tissues, intracellular adenosine kinase (ADK) is the primary route of adenosine metabolism and the key regulator of intracellular and extracellular adenosine levels. The present study provides the first evidence for ADK distribution in the adult and developing rat cochlea. In the adult cochlea, ADK was localized to the nuclear or perinuclear region of spiral ganglion neurons, lateral wall tissues, and epithelial cells lining scala media. In the developing cochlea, ADK was strongly expressed in multiple cell types at birth and reached its peak level of expression at postnatal day 21 (P21). Ontogenetic changes in ADK expression were evident in the spiral ganglion, organ of Corti, and stria vascularis. In the spiral ganglion, ADK showed a shift from predominantly satellite cell immunolabelling at P1 to neuronal expression from P14 onward. In contrast to the role of ADK in various aspects of cochlear development, the ADK contribution to the cochlear response to noise stress was less obvious. Transcript and protein levels of ADK were unaltered in the cochlea exposed to broadband noise (90-110 dBSPL, 24 hr), and the selective inhibition of ADK in the cochlea with ABT-702 failed to restore hearing thresholds after exposure to traumatic noise. This study indicates that ADK is involved in purine salvage pathways for nucleotide synthesis in the adult cochlea, but its role in the regulation of adenosine signalling under physiological and pathological conditions has yet to be established.