Breast Angiosarcoma Surveillance Study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall.

BACKGROUND: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort. METHODS: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres. RESULTS: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort. CONCLUSION: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study.

The Role of Positron Emission Tomography/Computed Tomography Imaging in Head and Neck Cancer after Radical Chemoradiotherapy: a Single Institution Experience.

AIMS: Positron emission tomography/computed tomography (PET/CT) is used to restage head and neck cancer 3 months after chemoradiotherapy. The purpose of this study was to determine the negative predictive value (NPV) of a scan reported as having no abnormal uptake and the positive predictive values (PPV) for different maximum standardised uptake value (SUVmax) thresholds. MATERIALS AND METHODS: Patients with squamous cell carcinoma of the oro-/hypopharynx/larynx (n = 206) were included. SUVmax and subsequent locoregional recurrence were documented. RESULTS: The median SUVmax was 11.2 (range 4-33)/4.6 (range 2-30), respectively, in patients with/without definite primary site recurrence (P = 0.004). The median SUVmax was 4.4 (range 2.6-15.6)/3.1 (range 2.1-4.6), respectively, in patients with/without definite nodal recurrence (P = 0.003). The NPV for a scan reported as having no abnormal uptake was 92%. The PPV for the SUVmax thresholds 4, 6 and 8, respectively, were 53, 65 and 92% (primary site) and 93, 100 and 100% (nodes). CONCLUSIONS: The NPV of PET/CT after chemoradiation is consistent with the literature and underlines the importance of PET/CT in restaging the primary site if salvage neck dissection is considered. The overall PPV of PET/CT remains low but is high for nodal SUVmax > 4. These data could be used to design risk-stratified follow-up schedules.

A systematic review protocol examining the effect of vitamin D supplementation on endothelial function.

INTRODUCTION: Vitamin D has potential benefits for extraskeletal health. These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction. We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function (EF), possibly through the abrogation of systemic inflammation. METHODS AND ANALYSIS: We will conduct a systematic review of all randomised controlled trials on vitamin D supplementation and EF lasting 12 weeks or more. The search will cover the period 2000-2015 and include studies that describe direct measures of EF, markers of endothelial cell (EC) activation and if concurrently reported, indicators of systemic inflammation. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis. If sufficient data are available, a meta-analysis will be conducted. The effect sizes will be generated using Hedges' g score, for both fixed and random effect models. I(2) statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources. Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger's test. Meta-regression analysis (if feasible) will be conducted with restricted maximum likelihood (REML) estimation method, controlling for potential confounders (demographics, study methods, location, etc). A backward elimination process will be applied in the regression modelling procedure. Subgroup analysis, conditional on number of studies retrieved and their sample size, will be stratified on participant disease category, total dose administered, degree of 25(OH)D change and type of supplement used. ETHICS AND DISSEMINATION: Formal ethical approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentation and the popular press. TRIAL REGISTRATION NUMBER: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42014013523.

The impact of thiamine supplementation on blood pressure, serum lipids and C-reactive protein in individuals with hyperglycemia: a randomised, double-blind cross-over trial.

BACKGROUND: The adverse effects of hyperglycemia may be potentiated when it is accompanied with hypertension and dyslipidemia. This study assessed the effects of high dose thiamine on blood pressure, serum lipids and C-reactive protein (hs-CRP) in individuals with impaired glucose metabolism. METHODS: This was a double-blind, randomised trial, where 12 hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes mellitus) received both placebo and thiamine capsules (3 × 100 mg/day) for six weeks in a cross-over manner. Anthropometric measurements, systolic and diastolic blood pressure (SBP & DBP), serum cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, hs-CRP and thiamine status were evaluated at the start, after three weeks and on the completion of each arm. RESULTS: DBP was significantly decreased in participants consuming thiamine supplements for six weeks (67.9 ± 5.8 mm Hg) relative to baseline (71.4 ± 7.4 mm Hg, p=0.005) and week 3 (70.9. ± 5.8 mm Hg, p=0.02). This was accompanied with a tendency toward a lower SBP at week six relative to baseline (116.5 ± 11.0 vs. 120.7 ± 15.3 mm Hg, p=0.06). Also, mean arterial pressure (MAP) determined in the supplement arm after six weeks was significantly lower than baseline (84.1 ± 6.5 vs. 87.8 ± 9.0, p=0.005). These variables did not change in the placebo arm. No significant change was detected in the supplement or placebo arms when lipid profile and hs-CRP were assessed. CONCLUSION/INTERPRETATION: High dose thiamine supplementation may have beneficial effects on the blood pressure of individuals with hyperglycemia at early stages, and may have a role in the prevention of further vascular complications. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12611000051943.

Vitamin D & endothelial function.

There is increasing interest in the extra-skeletal roles of vitamin D for health and well-being. Poor vitamin D status has been associated with obesity, cardiovascular disease, type 2 diabetes and mental health. Endothelial dysfunction may underscore insulin resistance and hence predispose to both cardiovascular disease (CVD) and type 2 diabetes. The objective of this review was to gain an appreciation of the recent causative evidence linking vitamin D and endothelial function. The PubMed database was searched from 2009 to date. Key words used were vitamin D, supplementation, systemic inflammation, endothelium, endothelial dysfunction and humans. Selected articles were restricted to the English language and to randomized control trials (RCTs) of vitamin D supplementation with direct measures of endothelial function. Final inclusion was based on a quality rating ≥ 3, based on the Jadad score. Ten RCTs met these criteria and were summarized for their outcomes. Only two studies showed an improvement in flow mediated dilatation with vitamin D. Three other studies reported decreases in C-reactive protein, platelet activation inhibitor-1, tissue plasminogen activator or B type natriuretic peptide. Recent evidence from good quality RCTs did not support a beneficial effect of vitamin D on vascular reactivity. Future intervention studies may need to target a higher vitamin D status and longer duration to determine whether the vitamin has a regulatory role in endothelial function.

High-dose thiamine supplementation improves glucose tolerance in hyperglycemic individuals: a randomized, double-blind cross-over trial.

PURPOSE: To assess the effect of high-dose oral thiamine supplements on glucose tolerance in patients with impaired glucose metabolism. METHODS: Twelve hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes) completed this randomized, double-blind trial, where all participants received both placebo and thiamine capsules (3 × 100 mg/day) for 6 weeks in a cross-over manner. The main endpoint was changes in 2-h plasma glucose. Fasting plasma glucose and insulin, 2-h plasma insulin, the hemostatic model assessment of insulin resistance (HOMA-IR), renal function measurement and thiamin status were also evaluated at the commencement and completion of each treatment period. RESULTS: Thiamine supplementation resulted in significant decrease in 2-h plasma glucose relative to baseline (8.78 ± 2.20 vs. 9.89 ± 2.50 mmol/l, p = 0.004), with no significant change in the placebo arm. Fasting plasma glucose and insulin, and HOMA-IR increased significantly from baseline after 6 weeks in the placebo arm (p = 0.003, p = 0.04 and p = 0.02, respectively). These variables did not change with thiamine supplementation. There were no significant changes in 2-h plasma insulin or renal function marker, within or between arms. CONCLUSION/INTERPRETATION: Supplementation with high-dose thiamine may prevent deterioration in fasting glucose and insulin, and improve glucose tolerance in patients with hyperglycemia. High-dose thiamine supplementation may prevent or slow the progression of hyperglycemia toward diabetes mellitus in individuals with impaired glucose regulation.

Patterns of relapse in glioblastoma multiforme following concomitant chemoradiotherapy with temozolomide.

OBJECTIVE: Different methods for contouring target volumes are currently in use in the UK when irradiating glioblastomas post operatively. Both one- and two-phase techniques are offered at different centres. 90% of relapses are recognised to occur locally when using radiotherapy alone. The objective of this evaluation was to determine the pattern of relapse following concomitant radiotherapy with temozolomide (RT-TMZ). METHODS: A retrospective analysis of patients receiving RT-TMZ between 2006 and 2010 was performed. Outcome data including survival were calculated from the start of radiotherapy. Analysis of available serial cross-sectional imaging was performed from diagnosis to first relapse. The site of first relapse was defined by the relationship to primary disease. Central relapse was defined as progression of the primary enhancing mass or the appearance of a new enhancing nodule within 2 cm. RESULTS: 105 patients were identified as receiving RT-TMZ. 34 patients were not eligible for relapse analysis owing to either lack of progression or unsuitable imaging. Patterns of first relapse were as follows: 55 (77%) patients relapsed centrally within 2 cm of the original gadolinium-enhanced mass on MRI, 13 (18%) patients relapsed >4 cm from the original enhancement and 3 (4%) relapsed within the contralateral hemisphere. CONCLUSION: Central relapse remains the predominant pattern of failure following RT-TMZ. Single-phase conformal radiotherapy using a 2-cm margin from the original contrast-enhanced mass is appropriate for the majority of these patients. ADVANCES IN KNOWLEDGE: Central relapse remains the predominant pattern of failure following chemoradiotherapy for glioblastomas.

Dietary fructose in relation to blood pressure and serum uric acid in adolescent boys and girls.

Evidence that fructose intake may modify blood pressure is generally limited to adult populations. This study examined cross-sectional associations between dietary intake of fructose, serum uric acid and blood pressure in 814 adolescents aged 13-15 years participating in the Western Australian Pregnancy Cohort (Raine) Study. Energy-adjusted fructose intake was derived from 3-day food records, serum uric acid concentration was assessed using fasting blood and resting blood pressure was determined using repeated oscillometric readings. In multivariate linear regression models, we did not see a significant association between fructose and blood pressure in boys or girls. In boys, fructose intake was independently associated with serum uric acid (P<0.01), and serum uric acid was independently associated with systolic blood pressure (P<0.01) and mean arterial pressure (P<0.001). Although there are independent associations, there is no direct relationship between fructose intake and blood pressure. Our data suggest that gender may influence these relationships in adolescence, with significant associations observed more frequently in boys than girls.

A clinical audit of the nutritional status and need for nutrition support amongst head and neck cancer patients treated with radiotherapy.

BACKGROUND: Radiotherapy is an effective treatment for head and neck cancers but patients often experience side effects which lead to weight loss. Nutrition intervention in the form of counselling or oral nutrition support (ONS) is frequently needed for these patients. For some patients, tube feeding is required to minimise weight loss during treatment. METHOD: Data was collected on 48 patients who received radiotherapy to the head and neck region over a nine-month period (June 2009-March 2010). Retrospective data collection was commenced in July 2010. Each patient's Diet Therapy Department record was reviewed. Main outcome measures were: 1) type of nutrition support; 2) percentage weight change during treatment; and 3) Patient-Generated Subjective Global Assessment Global (PG-SGA) rating. RESULTS: On initial assessment 28 (77.8%) patients were classified as well nourished using the PG-SGA. Mean weight loss during radiotherapy was 5.74%. Risk factors for the need for ONS and enteral nutrition support (ENS) were older age, presence of nutrition impact symptoms, high-risk tumour sites, advanced disease and chemotherapy. No significant difference was shown in weight loss between ONS and ENS groups. CONCLUSION: This study identified the need for early dietetic intervention for high nutritional risk groups of head and neck cancer patients to prevent significant weight loss. Pre-treatment nutritional status did not influence weight loss during treatment. ONS alone cannot prevent significant weight loss in patients with multiple nutrition impact symptoms. Early enteral feeding should be considered in this group of patients.

Dietary treatment of hypoglycaemia: should the Australian recommendation be increased?

Australian recommendations for treatment of hypoglycaemia are 15 g of carbohydrate repeated at 10-15 min if hypoglycaemia persists. Cited evidence is expert opinion or older studies not pertinent to current insulin regimens. This study aimed to determine the effect of increasing initial treating carbohydrate and decreasing wait-time to retreatment on resolution of hypoglycaemia in 92 free-living adults on current insulin regimens. The results support an initial treatment of 20-g carbohydrate, with a 10-min wait to repeat treatment as an optimal recommendation for the insulin-treated individual self-treating hypoglycaemia.

The role of positron emission tomography/CT imaging in head and neck cancer patients after radical chemoradiotherapy.

OBJECTIVES: Positron emission tomography with CT (PET/CT) scanning is increasingly being used in head and neck cancer to assess response after radical concomitant chemoradiotherapy. The purpose of this study was to assess the use of PET/CT following chemoradiotherapy at our institution. METHODS: All patients receiving radical chemoradiotherapy for head and neck cancer over a 9-year period were retrospectively identified. Outcome data including local control and overall survival were collected for all patients. The negative predictive value of PET/CT for local recurrence was calculated. Of those with a reported positive PET/CT scan the maximum standardised uptake values were compared with the incidence of local recurrence. RESULTS: 92 patients were identified having a post-treatment PET/CT from a total of 301 patients receiving radical concomitant chemoradiotherapy. Median time from completion of chemoradiotherapy to PET/CT scan was 3 (range 2-8) months. Median follow-up in surviving patients was 19 and 25 months in the PET/CT and non-PET/CT groups, respectively. The negative predictive value for local recurrence was 91.8%. The median maximum standardised uptake values were 10.2 (range 3.1-33) and 6.89 (range 3.1-30) in those with local recurrence and with no local recurrence, respectively. CONCLUSIONS: Post-chemoradiotherapy PET/CT may aid subsequent management decisions. Patients with a negative PET/CT scan after radical chemoradiotherapy have a 91.8% chance of remaining free of local recurrence 19 months post-treatment. A higher maximum standardised uptake value on the post-chemoradiotherapy PET/CT may predict subsequent local recurrence and warrants further investigation. Advances in knowledge Post-chemoradiotherapy PET/CT imaging aids subsequent management decisions.

Vitamin D and parathyroid hormone in insulin resistance of abdominal obesity: cause or effect?

The objective was to examine whether there were causal links between vitamin D status, parathyroid hormone, insulin resistance (IR)/insulin sensitivity (IS) and the metabolic syndrome (MS). A total of 72 Caucasian men and women, aged 55.7 ± 7.57 years, with body mass index 33.4 ± 4.02 kg/m(2) and abdominal obesity, were assessed for IR/IS based on three commonly used indices before and after 12 weeks of supervised weight loss. During weight stability, though both lower intact parathyroid hormone (iPTH) and higher vitamin D were independently associated with greater IS/lower IR, this was consistent for iPTH across the surrogate measures tested. Higher iPTH, but not lower vitamin D, increased the risk of MS after adjustment for IR/IS. Weight loss resulted in significant reductions in percent fat (-2.83 ± 2.20%), waist (-9.26 ± 5.11 cm), improvements in all IS indices, reductions in MS and iPTH (-0.28 ± 1.17 pmol/l), but no increase in vitamin D (+2.19 ± 12.17 nmol/l). Following weight loss, ΔiPTH either predicted change in IR/IS or contributed to their variance by 4.1-8.9%. On adjustment for IR/IS, higher ΔiPTH did not significantly predict MS after weight loss, though the odds ratios for the effect were sizeable. The data are suggestive of an intrinsic inverse relationship between iPTH and IS in abdominally obese individuals, independent of vitamin D. There remains the possibility of a direct relationship between iPTH and MS.

The use of herbal medicines by people with cancer: a cross-sectional survey.

BACKGROUND: A large proportion of cancer patients are estimated to use herbal medicines, but data to substantiate this are lacking. This study aimed to investigate the prevalence of herbal medicine use among cancer patients in the West Midlands, and determine the characteristics predicting herbal medicine use. METHODS: A cross-sectional survey of oncology patients (n=1498) being followed up at a hospital in Coventry was undertaken. Recipients were asked about herbal medicine use since their cancer diagnosis, and the association between sociodemographic and cancer-related characteristics and herbal medicine use was evaluated. RESULTS: A total of 1134 responses were received (75.7%). The prevalence of herbal medicine use was 19.7% (95% CI: 17.4-22.1; n=223). Users were more likely to be affluent, female, and aged under 50 years. Usage increased with time since cancer diagnosis (X(2) for trend=4.63; P=0.031). A validation data set, derived from a survey of oncology patients in Birmingham (n=541) with differing socioeconomic characteristics showed no significant difference in estimated prevalence (16.6%; 95% CI: 11.9-22.2). CONCLUSION: A substantial number of people with cancer are likely to be taking herbal medicines. Understanding the self-medication behaviours of these individuals is essential if health-care professionals are to support treatment adherence and avoid unwanted pharmacological interactions.

Radiology curriculum for medical students: clinicians' perspectives.

This study was conducted to establish clinicians' perspectives of a set of radiology curriculum topics for medical student teaching, which were held to be important by radiologists. A questionnaire was sent to clinicians in all specialties. Forty-six clinicians (51.1%) out of 90 returned the questionnaires. All curriculum topics were scored above an average of 4 (agree). The five highest ranking curriculum topics in order of importance were: developing a system for viewing chest radiographs (5.59), developing a system for viewing abdominal radiographs (5.56), developing a system for viewing bone and joint radiographs (5.33), distinguishing normal structures from abnormal in chest and abdominal radiographs (5.33) and identifying gross bone or joint abnormalities in skeletal radiographs (5.22). Correlative analysis between speciality groups showed surgical and medical specialities were significantly different in their responses of two learning outcomes: basic knowledge about the contrast media benefits and risks (P= 0.01) and ability to select the most appropriate and the most cost-effective methods of radiological investigations for clinical situations (P= 0.03). Acute specialities were not significantly different from the other two groups for these two learning outcomes. There was no statistically significant difference for other learning outcomes between the three speciality groups.

Patterns of child-bearing behaviour amongst female hospital doctors and GPs.

BACKGROUND: The number of females entering and graduating from medical school is currently increasing and, as a result, the problems they face if they wish to work as doctors and have a family are becoming more apparent. METHODS: A questionnaire study of 105 female GPs and 98 female hospital doctors was carried out in Birmingham, UK, to determine doctors' experiences and views of child-bearing whilst working as a doctor. RESULTS: Of the GP responders, 81% had children compared with 49% of hospital doctors. GPs were shown to work fewer hours than hospital doctors. Problems were identified relating to the everyday difficulties faced whilst working and raising a family. CONCLUSIONS: The results highlight the need to address the difficulties faced by females pursuing this demanding career.

Breastfeeding, body mass index, asthma and atopy in children.

The objective of this study was to determine the relationship between breastfeeding, asthma and atopy, and any influence of child body mass index (BMI). Prospective birth cohort data were used to model the association between breastfeeding duration, BMI, asthma and atopy in children at six years. After adjustment for BMI and associated covariates, breastfeeding (per additional month of feeding) was marginally associated with decreased BMI (p=0.083). BMI was significantly associated with current asthma (p=<0.0005) and atopy (p=0.055). Exclusive breastfeeding for less than four months was a risk for current asthma (p=0.033) and atopy (p=0.005). The early introduction of formula leads to an increase in child BMI and early asthma and atopy. Increased BMI is a risk factor for childhood asthma and atopy. These findings suggest that public health interventions to optimise breastfeeding duration and reduce overweight in children may help attenuate the community burden of wheezing illness early in life.

Height and weight fail to detect early signs of malnutrition in children with cystic fibrosis.

BACKGROUND: Many children with cystic fibrosis grow poorly and are malnourished. This study was undertaken to determine whether extensive anthropometry could detect early signs of malnutrition in prepubertal children with cystic fibrosis to prevent deficits in height and weight. METHODS: Height, weight, six skin folds (triceps, subscapular, supraspinale, abdominal, front thigh, and medial calf) and five girths (arm relaxed, forearm, chest, thigh, and calf) were measured in a cross-sectional study of children aged 6 to 11 years with cystic fibrosis. RESULTS: The children with cystic fibrosis were shorter and lighter for their age and gender than those in the reference groups. The mean weight and height z scores for the girls with cystic fibrosis were lower than those for the boys, significantly so for z weight ( P < 0.05). Although, the mean percent ideal body weight value of 98.6% suggested that the children with cystic fibrosis were adequately nourished, most of the measures of muscularity and adiposity of the children with cystic fibrosis were significantly lower than those of the reference group ( P < 0.05). The z scores of the anthropometric measures revealed that the deficit in muscularity of the children with cystic fibrosis was relatively much greater than the deficit in adiposity. CONCLUSIONS: The percent ideal body weight index does not seem to be an adequate measure of nutritional status in children with cystic fibrosis. Anthropometric assessments should include skin-fold and circumference measurements of numerous sites on the upper and lower body, the trunk, and the limbs to detect deterioration in nutritional status early. Early detection of deficits in nutritional status may result in the adverse effects of malnutrition on height and weight, and possibly clinical status, being prevented.