A Prospective Cohort Study of Body Size and Risk of Head and Neck Cancers in the NIH-AARP Diet and Health Study

Background: The association between body size and head and neck cancers (HNCA) is unclear, partly because of the biases in case–control studies. Methods: In the prospective NIH–AARP cohort study, 218,854 participants (132,288 men and 86,566 women), aged 50 to 71 years, were cancer free at baseline (1995 and 1996), and had valid anthropometric data. Cox proportional hazards regression was used to examine the associations between body size and HNCA, adjusted for current and past smoking habits, alcohol intake, education, race, and fruit and vegetable consumption, and reported as HR and 95% confidence intervals (CI). Results: Until December 31, 2006, 779 incident HNCAs occurred: 342 in the oral cavity, 120 in the oro- and hypopharynx, 265 in the larynx, 12 in the nasopharynx, and 40 at overlapping sites. There was an inverse association between HNCA and body mass index, which was almost exclusively among current smokers (HR = 0.76 per each 5 U increase; 95% CI, 0.63–0.93), and diminished as initial years of follow-up were excluded. We observed a direct association with waist-to-hip ratio (HR = 1.16 per 0.1 U increase; 95% CI, 1.03–1.31), particularly for cancers of the oral cavity (HR, 1.40; 95% CI, 1.17–1.67). Height was also directly associated with total HNCAs (P = 0.02), and oro- and hypopharyngeal cancers (P < 0.01). Conclusions: The risk of HNCAs was associated inversely with leanness among current smokers, and directly with abdominal obesity and height. Impact: Our study provides evidence that the association between leanness and risk of HNCAs may be due to effect modification by smoking. Cancer Epidemiol Biomarkers Prev; 23(11); 2422–9. ©2014 AACR.

Carreira Alkynylations with Paraformaldehyde. A Mild and Convenient Protocol for the Hydroxymethylation of Complex Base-SensitiveTerminal Acetylenes via Alkynylzinc Triflates

A new synthetic protocol for the hydroxymethylation of terminal acetylenes is described that involves stoichiometric Carreira alkynylation with solid paraformaldehyde (HO[CH₂O]_nH) in PhMe at 60 ^oC. Significantly, the method can be successfully applied on acetylenes that possess base-sensitive ester functionality and heterocyclic rings that readily undergo metallation. While N-methylephedrine (NME) is generally the best Zn(OTf)₂-coordinating ligand for promoting hydroxymethylation, TMEDA can serve as a replacement.

Untargeted Metabolomic Analysis of Human Plasma Indicates Differentially Affected Polyamine and L-Arginine Metabolism in Mild Cognitive Impairment Subjects Converting to Alzheimer’s Disease

This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.

Plasma Clusterin Levels and the rs11136000 Genotype in Individuals with Mild Cognitive Impairment and Alzheimer's Disease

Aim: Substantial evidence links atherosclerosis and Alzheimer's disease (AD). Apolipoproteins, such as apolipoprotein E, have a causal relationship with both diseases. The rs11136000 SNP within the CLU gene, which encodes clusterin (apolipoprotein J), is also associated with increased AD risk. The aim of this study was to investigate the relationship between plasma clusterin and the rs11136000 genotype in mild cognitive impairment (MCI) and AD.

Methods: Plasma and DNA samples were collected from control, MCI and AD subjects (n=142, 111, 154, respectively). Plasma clusterin was determined by ELISA and DNA samples were genotyped for rs11136000 by TaqMan assay.

Results: Plasma clusterin levels were higher in MCI and AD subjects vs. controls (222.3 +/- 61.3 and 193.6 +/- 58.2 vs. 178.6 +/- 52.3 mu g/ml, respectively; p

Conclusion: This study examined control, MCI and AD subjects, identifying for the first time that plasma clusterin levels were influenced, not only by the presence of AD, but also the transitional stage of MCI, while rs11136000 genotype only influenced plasma clusterin levels in the control group. The increase in plasma clusterin in MCI and AD subjects may occur in response to the disease process and would be predicted to increase binding capacity for amyloid-beta peptides in plasma, enhancing their removal from the brain.

Untreated Mild Hyperglycemia During Pregnancy and Anthropometric Measures of Obesity in Offspring at Age 5-7 Years

OBJECTIVE: Obesity in the offspring of women with hyperglycemia during pregnancy has been reported, but the results are conflicting. This study examined the association of hyperglycemia during pregnancy and anthropometry in 5- to 7-year-old offspring whose mothers participated in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study at the Belfast Centre.

RESEARCH DESIGN AND METHODS: Women in the HAPO study underwent a 75-g oral glucose tolerance test (OGTT) at approximately 28 weeks of gestation. Mothers and caregivers remained blinded to the results unless the fasting plasma glucose (FPG) concentration was >5.8 mmol/L or the 2-h plasma glucose (2hPG) concentration was >11.1 mmol/L. Offspring weight, height, and skin-fold thicknesses (triceps, subscapular, and suprailiac) were measured at age 5-7 years. Overweight, obesity, and extreme obesity were defined as a BMI z score ≥85th, ≥95th, and ≥99th percentile, respectively, based on the 1990 British Growth Standard.

RESULTS: Belfast HAPO offspring (n = 1,320, 82%) aged 5-7 years attended for follow-up. Using multiple regression, maternal FPG, 1h PG, and 2hPG did not show any relation to offspring BMI z score or offspring skin-fold sum independent of maternal BMI at OGTT and offspring birth weight z score. This lack of association with maternal glycemia persisted with the offspring BMI z score expressed as ≥85th, ≥95th, or 99th percentile, and the sum of skin folds expressed as ≥90th percentile specific for sex. The initially significant relation between FPG and all offspring adiposity measures was explained by maternal BMI at the OGTT.

CONCLUSIONS: After adjustment for maternal BMI at the OGTT, higher maternal FPG concentration during pregnancy (short of diabetes) is no longer a risk factor for obesity, as reflected by BMI and the sum of skin folds in offspring aged 5-7 years.

Ultrastructure of head organs (anterior adhesive apparatus) and posterior secretory systems of Caballeria liewi Lim, 1995 (Monogenea, Ancyrocephalidae)

Caballeria liewi Lim, 1995, uses adhesive secretions from the head organs and posterior secretory systems to assist in locomotion and attachment. Ultrastructural investigations show that the head organs of C. liewi consist of three pairs of antero-lateral pit-like openings bearing microvilli and ducts leading from two types of uninucleated gland cells (located lateral to the pharynx), one type producing rod-like (S1) bodies with an electron-dense matrix containing less electron-dense vesicles and the second type producing oval (S2) bodies with a homogeneous electron-dense matrix. Interlinking band-like structures are observed between S1 bodies and between S2 bodies. S1 body is synthesised in the granular endoplasmic reticulum, transported to a Golgi complex to be packaged into vesicles and routed into ducts for exudation. The synthesis of the S2 body is unresolved. Haptoral secretions manifested externally as net-like structures are derived from dual electron-dense (DED) secretory body produced in the peduncular gland cells. The DED body consists of a less electron-dense oval core in a homogeneous electron-dense matrix. On exocytosis into the pyriform haptoral reservoir, DED bodies are transformed into a secretion with two types of inclusions (less electron-dense oval and electron-dense spherical inclusions) in an electron-dense matrix. The secretions are further transformed (as small, oval, electron-dense bodies) when transported to the superficial anchor grooves, and on exudation into the gill tissues, the secretions become an electron-dense matrix. Secretory bodies associated with uniciliated structures, anchor sleeves and marginal hooks are also observed.

Pre-Radiotherapy Dental Assessment of Head and Neck Oncology Patients: An Audit.

Objectives: Approximately 300 people are diagnosed with Head and Neck cancer annually in Northern Ireland. The management may include treatment by surgery or by chemotherapy and radiotherapy,
or a combination of modalities. Patients whose oral cavity, teeth, salivary glands and jaws that
will be affected by treatment, particularly radiotherapy should have a pre-treatment assessment. This should be done as early as possible to maximise the time available for dental management. However, this can be challenging owing to the complexities of cancer diagnosis, treatment planning and multidisciplinary management. At the Belfast Dental Hospital, a number of patients were referred post- radiotherapy with complications after not having received a pre-treatment assessment. The referrals for pre- treatment dental assessment were also late in patients’ multidisciplinary journey, limiting the time period
for dental input. The purpose of this audit was to examine the time period between dental assessment and commencement of radiotherapy and whether this was an adequate time frame for dental management. This audit will also examine the dental diseases present and the treatments required pre-radiotherapy. Methods: Data for this audit was collected over 4 months in 2012
by analysing the dental charts and referrals of new patients who were referred to and attended the dental head and neck oncology clinic. A standardised referral pro-forma was introduced from September 2013 to improve the referral process.
A re-audit was conducted over 4 months in 2014. Data was collected similarly as previous. The time period between dental assessment and commencement of radiotherapy was examined. The presence of dental disease and subsequent treatments required were also noted.
Results: 63 new patients were examined in the dental head and neck oncology clinic over 4 months in 2012. 48 (76.2%) were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 11 days. A new standardised referral pro-forma was introduced in 2013. In the re-audit, 65 new patients were seen over 4 months in 2014.
60 (92.3%) patients were examined pre-radiotherapy. The average length of time between dental assessment and radiotherapy commencement was 18 days.
Conclusion: Given the high prevalence of pre-existing dental disease amongst head and neck cancer patients, prompt dental assessment and treatment is vital. Efforts aimed at improving the care pathway are on-going through the implementation of a mandatory referral pro-forma and a dedicated assessment clinic.

Experience of Managing Head and Neck Cancer Patients Amongst Specialty Trainees in Restorative Dentistry

Background: Upon completion of Specialty Training in Restorative Dentistry, trainees (StRs) should
be proficient in maxillofacial prosthodontics to meet the restorative needs of head and neck cancer patients (HANC), and in preparation for the Intercollegiate Specialty Fellowship Examination (ISFE).1,2
Objective: The aim of this study is to collate and compare data relating to the training of Restorative Dentistry Rs in the management of HANC patients across different geographical locations within the British Isles. Methods: Current trainees were invited to complete an online questionnaire by the Specialty Registrars in Restorative Dentistry Group (SRRDG). Participants were asked to rate their confidence and experience in assessing and planning treatment for HANC patients, attending theatre and manufacturing surgical obturators, and in providing implants for appropriate cases. Respondents were also asked to appraise clinical and didactic teaching within their unit, and to rate their confidence of passing oncology- based questions in a future ISFE. Results: Responses were obtained from 21 StRs (n=21) training in all five countries within the British Isles. Most respondents were based in England (76%). A third were in their 5th year of training. Less than half reported that they were confident
of independently assessing (48%) or treatment planning (38%) HANC patients. More than half of StRs (52%) indicated that they were not confident of attending theatres alone and manufacturing a surgical obturator. One third (33%) rated their experience of treating oncology patients with implants as poor or very poor, including three in their 5th year of training. Less than one third rated didactic teaching in maxillofacial prosthodontics at their unit as good or excellent. Only 4 respondents indicated that they were confident of answering an ISFE oncology question on management of healthcare delivery. Six StRs expressed concerns over a lack of case-based exposure.
Conclusion: Experience and training in maxillofacial prosthodontics is inconsistent for StRs across the British Isles with many lacking in clinical exposure.

Prognoses and improvement for head and neck cancers diagnosed in Europe in early 2000s: The EUROCARE-5 a population-based study.

BACKGROUND: Head and neck (H&N) cancers are a heterogeneous group of malignancies, affecting various sites, with different prognoses. The aims of this study are to analyse survival for patients with H&N cancers in relation to tumour location, to assess the change in survival between European countries, and to investigate whether survival improved over time.
METHODS: We analysed about 250,000 H&N cancer cases from 86 cancer registries (CRs). Relative survival (RS) was estimated by sex, age, country and stage. We described survival time trends over 1999-2007, using the period approach. Model based survival estimates of relative excess risks (RERs) of death were also provided by country, after adjusting for sex, age and sub-site.
RESULTS: Five-year RS was the poorest for hypopharynx (25%) and the highest for larynx (59%). Outcome was significantly better in female than in male patients. In Europe, age-standardised 5-year survival remained stable from 1999-2001 to 2005-2007 for laryngeal cancer, while it increased for all the other H&N cancers. Five-year age-standardised RS was low in Eastern countries, 47% for larynx and 28% for all the other H&N cancers combined, and high in Ireland and the United Kingdom (UK), and Northern Europe (62% and 46%). Adjustment for sub-site narrowed the difference between countries. Fifty-four percent of patients was diagnosed at advanced stage (regional or metastatic). Five-year RS for localised cases ranged between 42% (hypopharynx) and 74% (larynx).
CONCLUSIONS: This study shows survival progresses during the study period. However, slightly more than half of patients were diagnosed with regional or metastatic disease at diagnosis. Early diagnosis and timely start of treatment are crucial to reduce the European gap to further improve H&N cancers outcome.