The acid test: Proton pump inhibitors in persistent throat symptoms: A systematic review of systematic reviews.

INTRODUCTION: Proton pump inhibitors (PPIs) have evolved to become a frequent treatment option for patients with persistent throat symptoms. The evidence for their use in this context is, however, conflicting. This review assesses the quality of the published systematic reviews and meta-analyses evaluating PPIs in persistent throat symptoms. METHODS: Following a literature search, systematic review were evaluated using the Reporting of Bias in Systematic Reviews (ROBIS) tool and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Outcome measures were analysed using the "checklist to operationalize measurement characteristics of patient-reported outcome measures." RESULTS: 10 systematic reviews were assessed. All but one were at high risk of bias. No review met the PRISMA checklist criteria. No identified PROM met the checklist requirements for validation. Significant methodological concerns include inappropriate selection of studies for inclusion, poor selection of outcome measures, a lack of appropriate bias assessments and inconsistent reporting of reviews. CONCLUSION: The quality of evidence concerning the role of PPIs in persistent throat symptoms gives serious cause for concern. Collectively, nine studies at high risk of bias have been cited 714 times. Systematic reviews typically attract these high numbers of citations and, if their premises and conclusions do not withstand scrutiny, they are open to widespread misinterpretation, perpetuation of misunderstanding and negative clinical impact.

Sporadic medullary thyroid cancer: a systematic review and meta-analysis of clinico-pathological and mutational characteristics predicting recurrence.

INTRODUCTION: Sporadic medullary thyroid cancer accounts for 75% of all medullary thyroid cancers and presents at a more advanced disease stage than its hereditary counterparts. Yet there is little evidence to support risk stratification of patients according to risk of recurrence. METHODS: A systematic review and meta-analysis was performed investigating clinical and pathological factors that are associated with recurrent disease in patients with medullary thyroid cancer. RESULTS: 10 studies totalling 458 patients were included in the meta-analyses. T3 and T4 disease (OR 9.33 (95% CI 2.5 - 34.82) p = 0.0009.), AJCC stage III and IV disease (OR 13.34 (95% CI 2.9 - 60.3) p = 0.0008) and the presence of nodal disease (OR 7.28 (95% CI 7.2-43.3) p = 0.03) were all associated with recurrent disease. RET mutations (OR 0.08 (95% CI -0.03-0.19) p = 0.17) and RET 918 T mutations (OR 1.77 (95% CI 0.804.0) P = 0.17) were not associated with disease recurrence. It was not possible to pool data with respect to extrathyroidal extension, extracapsular extension, peri-neural and lymphovascular invasion and RAS mutations. CONCLUSION: T3 and T4 disease, AJCC stage III and IV disease and the presence of nodal disease are associated with recurrent disease. The heterogeneous reporting of recurrence and the lack of individual patient data precludes larger scale meta-analyses. Future research in this area should involve collaboration to establish standardised definitions of disease recurrence.

HPV sensitizes OPSCC cells to cisplatin-induced apoptosis by inhibiting autophagy through E7-mediated degradation of AMBRA1.

Oropharyngeal squamous cell carcinoma (OPSCC) is an increasing world health problem with a more favorable prognosis for patients with human papillomavirus (HPV)-positive tumors compared to those with HPV-negative OPSCC. How HPV confers a less aggressive phenotype, however, remains undefined. We demonstrated that HPV-positive OPSCC cells display reduced macroautophagy/autophagy activity, mediated by the ability of HPV-E7 to interact with AMBRA1, to compete with its binding to BECN1 and to trigger its calpain-dependent degradation. Moreover, we have shown that AMBRA1 downregulation and pharmacological inhibition of autophagy sensitized HPV-negative OPSCC cells to the cytotoxic effects of cisplatin. Importantly, semi-quantitative immunohistochemical analysis in primary OPSCCs confirmed that AMBRA1 expression is reduced in HPV-positive compared to HPV-negative tumors. Collectively, these data identify AMBRA1 as a key target of HPV to impair autophagy and propose the targeting of autophagy as a viable therapeutic strategy to improve treatment response of HPV-negative OPSCC.Abbreviations: AMBRA1: autophagy and beclin 1 regulator 1; CDDP: cisplatin (CDDP); FFPE: formalin-fixed paraffin-embedded (FFPE); HNC: head and neck cancers (HNC); HPV: human papillomavirus (HPV); hrHPV: high risk human papillomavirus (hrHPV); OCSCC: oral cavity squamous carcinomas (OCSSC); OPSCC: oropharyngeal squamous cell carcinoma (OPSCC); OS: overall survival (OS); qPCR: quantitative polymerase chain reaction; RB1: RB transcriptional corepressor 1; ROC: receiver operating characteristic curve (ROC).

The role of autophagy in squamous cell carcinoma of the head and neck.

Half a million new head and neck cancers are diagnosed each year worldwide. Although traditionally thought to be triggered by alcohol and smoking abuse, there is a growing subset of oropharyngeal cancers driven by the oncogenic human papilloma virus (HPV). Despite advances in both surgical and non-surgical treatment strategies, survival rates have remained relatively static emphasising the need for novel therapeutic approaches. Autophagy, the principal catabolic process for the lysosomal--mediated breakdown of cellular products is a hot topic in cancer medicine. Increasing evidence points towards the prognostic significance of autophagy biomarkers in solid tumours as well as strategies through which to harness autophagy modulation to promote tumour cell death. However, the role of autophagy in head and neck cancers is less well defined. In the present review, we summarise the current understanding of autophagy in head and neck cancers, revealing key areas for future translational research.

Narrow band imaging for the diagnosis of head and neck squamous cell carcinoma: A systematic review.

Narrow band imaging (NBI) is reported to improve the diagnostic accuracy of head and neck cancers. The purpose of this review was to evaluate the diagnostic accuracy of NBI in the literature. A systematic review was performed in PubMed, Web of Knowledge, and the Cochrane Library until March 2015. Two reviewers independently assessed articles and extracted data. Meta-analyses were performed in MetaDisc 1.6. Five hundred seventeen studies were identified and 17 were included in this study. Combined use of NBI and white light imaging (WLI) showed high diagnostic accuracies for primary, recurrent, and nasopharyngeal lesions. Methodological heterogeneity exists and meta-analyses were only appropriate for cancers of unknown primary (CUP) in which NBI performed on 115 patients across 4 studies demonstrated high sensitivity (74.1%; 95% confidence interval [CI] = 52.5% to 100%) and specificity (94.1%; 95% CI = 23.7% to 100%). NBI may further help identify lesions in CUP not seen by positron emission tomography (PET)-CT. NBI offers a high level of diagnostic accuracy for head and neck cancers. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2358-E2367, 2016.

Transoral laser microsurgery ± adjuvant therapy versus chemoradiotherapy for stage III and IVA oropharyngeal squamous cell carcinoma: Preliminary comparison of early swallowing outcomes.

BACKGROUND: Observational data suggests transoral surgery may offer benefit in swallowing over chemoradiotherapy. METHODS: In this preliminary, non-randomized study, patients with stage III and IVA oropharyngeal carcinoma treated with transoral laser microsurgery (TLM) were assessed pretreatment and 3 months after treatment using the MD Anderson Dysphagia Inventory (MDADI), the Performance Status Scale (PSS), and a timed Water Swallow Test (WST). Comparisons were made with a historical chemoradiotherapy (CRT) cohort. RESULTS: Based on patients with measurements at both times, the decrease in score between baseline and 3 months was greater for CRT patients (n = 26-28) than for TLM (n = 20-21) patients for each of MDADI, PSS, and WST. A repeated measures analysis that looked at all 3 scores simultaneously and allowed for missing values gave mostly similar results (except for MDADI). CONCLUSION: TLM was associated with good early swallowing outcomes at 3 months and may offer a benefit over CRT. The results should be viewed as preliminary data, providing useful reference for any proposed controlled trial.

Clinical leadership: a role for students?

Since the publication of the 'To Err is Human' report, patient safety and quality improvement has been an increasingly important agenda in health care. This article explores the role that students can play in leading change in health-care systems.