Regular Health Checks: Cross-Sectional Survey

Objective: To investigate whether Danish providers of general health checks present a balanced account of possible benefits and harms on their websites and whether the health checks are evidence-based. Methods and Design: Cross-sectional study. The search engines Google and Jubii (Danish) were in July and August 2009 used to identify 56 websites using Danish search terms for ‘‘health check’ ’ and ‘‘health examination’’. The content of the websites were evaluated using a checklist with 15 officially recommended information items. All tests offered through the websites were registered. The evidence for tests offered through at least 10 % of the websites was identified in structured searches using PubMed and The Cochrane Library. Results: We found 36 different tests on 56 websites offering health checks. Twenty one tests were offered on at least 10 % of the websites. Seventeen (81%) of these tests were unsupported by evidence, or there was evidence against them for screening purposes. We found evidence supporting screening using body-mass-index, blood pressure, cholesterol, and faecal occult blood testing. None of the websites mentioned possible risks or harms. The websites presented a median of 1 of the 15 information items; the highest number from any provider was 2. Conclusions: Information from Danish providers of health checks was sparse and tests were often offered against existing evidence or despite lack of evidence. None of the included websites mentioned potential risks or harms

Association between Hashimoto's Thyroiditis and Thyroid Cancer in 64,628 Patients

BACKGROUND: The incidence of thyroid cancer (TC) is increasing although explanatory causes are lacking. A link between cancer and inflammation is well documented but unclear for autoimmune thyroid diseases and TC. We aimed to systematically review the association between Hashimoto’s thyroiditis (HT) and papillary, follicular, medullary, anaplastic thyroid carcinoma, and thyroid lymphoma (TL). METHODS: PubMed, OVID Medline, Google Scholar, and the Cochrane Library were searched from 1955 to 2016. The inclusion criteria were age >18 years, ≥20 cases of HT or TC. We collectively examined the incidence of HT in TC and of TC in HT. RESULTS: We identified 36 studies (64,628 subjects) published between 1955 and 2016 from 13 countries. We found a relative risk (RR) of HT among papillary thyroid cancer (PTC) of 2.36 [95% confidence intervals (CIs) 1.55–3.29, p < 0.001], an RR of PTC among HT of 1.40 (95% CI 1.07–1.85, p = 0.016), and an RR of TL among HT of 9.74 (95% CI 3.93–24.13, p < 0.001). CONCLUSION: We report an association between HT and PTC and between HT and TL. No association was found between HT and follicular, medullary, or anaplastic thyroid cancer

Novel nomograms for survival and progression in HPV+ and HPV- oropharyngeal cancer:a population-based study of 1,542 consecutive patients

BACKGROUND: No study has combined tumour and clinical covariates for survival to construct an individual risk-profile for overall survival (OS), time to progression (TTP), and survival after progression (SAP) in patients with HPV+ and HPV– oropharyngeal squamous cell carcinoma (OPSCC). Based on the largest-to-date, unselected, population-based cohort of patients diagnosed with OPSCC, we performed a comprehensive analysis of long-term OS, TTP, and SAP and constructed novel nomograms to evaluate patients' prognoses. RESULTS: At a median follow-up of 4.0 years (range: 0.8–15.8 yrs.), 690 deaths were recorded. The 5-year OS, TTP, and SAP for the HPV+/p16+ subgroup were 77%, 82%, and 33, vs. 30%, 66%, and 6% for the HPV–/p16– group (P < 0.01). 376 patients failed to maintain disease control with a median TTP of 13 months in the HPV+/p16+ subgroup vs. 8.5 months in the HPV–/p16– subgroup (P < 0.05). HPV combined with p16 status remained one of the most informative covariates in the final Cox regression model for OS, TTP, and SAP. METHODS: We included all patients diagnosed with OPSCC (n = 1,542) between 2000–2014 in Eastern Denmark. Survival rates were estimated by the Kaplan-Meier method. A multivariate Cox regression model was used to construct predictive, internally validated nomograms. CONCLUSION: The HPV+/p16+ subgroup had improved OS, TTP, and SAP compared with other combinations of HPV and p16 after adjusting for covariates. Nomograms were constructed for 1-, 5- and 10-year survival probability. Models may aid patients and clinicians in their clinical decision making as well as in counselling, research, and trial design

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX):study protocol for a randomized controlled trial.

BACKGROUND: Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. METHODS: This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. DISCUSSION: The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. TRIAL REGISTRATION: EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238. First received on 2 July 2015. The trial is prospectively registered. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-017-1856-0) contains supplementary material, which is available to authorized users

Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis

Background: p16INK4a (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. Methods: In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Findings: Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74·7%) of 7654 patients were male and 1940 (25·3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10·9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=–0·744, p=0·0035). The proportion of patients with p16+/HPV– oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29·7% vs 9·0%, p<0·0001). 5-year overall survival was 81·1% (95% CI 79·5–82·7) for p16+/HPV+, 40·4% (38·6–42·4) for p16–/HPV–, 53·2% (46·6–60·8) for p16–/HPV+, and 54·7% (49·2–60·9) for p16+/HPV–. 5-year disease-free survival was 84·3% (95% CI 82·9–85·7) for p16+/HPV+, 60·8% (58·8–62·9) for p16–/HPV–; 71·1% (64·7–78·2) for p16–/HPV+, and 67·9% (62·5–73·7) for p16+/HPV–. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Interpretation: Patients with discordant oropharyngeal cancer (p16–/HPV+ or p16+/HPV–) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16–/HPV– oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions

Prognostic implications of p16 and HPV discordance in oropharyngeal cancer (HNCIG-EPIC-OPC): a multicentre, multinational, individual patient data analysis

Background p16(INK4a) (p16) immunohistochemistry is the most widely used biomarker assay for inferring HPV causation in oropharyngeal cancer in clinical and trial settings. However, discordance exists between p16 and HPV DNA or RNA status in some patients with oropharyngeal cancer. We aimed to clearly quantify the extent of discordance, and its prognostic implications. Methods In this multicentre, multinational individual patient data analysis, we did a literature search in PubMed and Cochrane database for systematic reviews and original studies published in English between Jan 1, 1970, and Sept 30, 2022. We included retrospective series and prospective cohorts of consecutively recruited patients previously analysed in individual studies with minimum cohort size of 100 patients with primary squamous cell carcinoma of the oropharynx. Patient inclusion criteria were diagnosis with a primary squamous cell carcinoma of oropharyngeal cancer; data on p16 immunohistochemistry and on HPV testing; information on age, sex, tobacco, and alcohol use; staging by TNM 7th edition; information on treatments received; and data on clinical outcomes and follow-up (date of last follow-up if alive, date of recurrence or metastasis, and date and cause of death). There were no limits on age or performance status. The primary outcomes were the proportion of patients of the overall cohort who showed the different p16 and HPV result combinations, as well as 5-year overall survival and 5-year disease-free survival. Patients with recurrent or metastatic disease or who were treated palliatively were excluded from overall survival and disease-free survival analyses. Multivariable analysis models were used to calculate adjusted hazard ratios (aHR) for different p16 and HPV testing methods for overall survival, adjusted for prespecified confounding factors. Findings Our search returned 13 eligible studies that provided individual data for 13 cohorts of patients with oropharyngeal cancer from the UK, Canada, Denmark, Sweden, France, Germany, the Netherlands, Switzerland, and Spain. 7895 patients with oropharyngeal cancer were assessed for eligibility. 241 were excluded before analysis, and 7654 were eligible for p16 and HPV analysis. 5714 (74middot7%) of 7654 patients were male and 1940 (25middot3%) were female. Ethnicity data were not reported. 3805 patients were p16-positive, 415 (10middot9%) of whom were HPV-negative. This proportion differed significantly by geographical region and was highest in the areas with lowest HPV-attributable fractions (r=-0middot744, p=0middot0035). The proportion of patients with p16+/HPV- oropharyngeal cancer was highest in subsites outside the tonsil and base of tongue (29middot7% vs 9middot0%, p<0middot0001). 5-year overall survival was 81middot1% (95% CI 79middot5-82middot7) for p16+/HPV+, 40middot4% (38middot6-42middot4) for p16-/HPV-, 53middot2% (46middot6-60middot8) for p16-/HPV+, and 54middot7% (49middot2-60middot9) for p16+/HPV-. 5-year disease-free survival was 84middot3% (95% CI 82middot9-85middot7) for p16+/HPV+, 60middot8% (58middot8-62middot9) for p16-/HPV-; 71middot1% (64middot7-78middot2) for p16-/HPV+, and 67middot9% (62middot5-73middot7) for p16+/HPV-. Results were similar across all European sub-regions, but there were insufficient numbers of discordant patients from North America to draw conclusions in this cohort. Interpretation Patients with discordant oropharyngeal cancer (p16-/HPV+ or p16+/HPV-) had a significantly worse prognosis than patients with p16+/HPV+ oropharyngeal cancer, and a significantly better prognosis than patients with p16-/HPV- oropharyngeal cancer. Along with routine p16 immunohistochemistry, HPV testing should be mandated for clinical trials for all patients (or at least following a positive p16 test), and is recommended where HPV status might influence patient care, especially in areas with low HPV-attributable fractions. Copyright (c) 2023 The Author(s). Published by Elsevier Ltd

Developmentally Delayed Male with Mincer Blade Obstructing the Oesophagus for a Period of Time Suspected to Be 6 Months

Introduction. Sharp, retained foreign bodies in the oesophagus are associated with severe complications. Developmentally delayed patients are especially subject to foreign objects. We describe a 37-year-old, developmentally delayed male with a mincer blade obstructing the oesophagus. Six months prior to surgical intervention, the patient was hospitalized in a condition of sepsis and pneumonia where the thoracic X-ray reveals a foreign body in the proximal oesophagus. When rehospitalized 6 months later, a mincer blade of the type used in immersion blenders was surgically removed. During these 6 months the patient’s main symptoms were dysphagia, weight loss, and diarrhoea. When developmentally delayed patients present with dysphagia, we strongly encourage the awareness of the possible presence of foreign bodies. To our knowledge this is the first reported case of a mincer blade in the oesophagus