Objective Omega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22). Design A randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry. Results Both omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium , Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects. Conclusion Omega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure. Trial registration number ISRCTN18662143.
<div>Abstract<p>Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E<sub>2</sub>. We investigated whether 35 SNPs in oxylipin metabolism genes such as <i>cyclooxygenase</i> (<i>PTGS</i>) and <i>lipoxygenase</i> (A<i>LOX</i>), as well as 7 SNPs already associated with colorectal cancer risk reduction by aspirin (e.g., <i>TP53</i>; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomized 2 × 2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the <i>P</i> and <i>q</i> value. 542 (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with nonaspirin users was restricted to rs4837960 (<i>PTGS1</i>) common homozygotes [IRR, 0.69; 95% confidence interval (CI), 0.53–0.90); <i>q</i> = 0.06], rs2745557 (<i>PTGS2</i>) compound heterozygote-rare homozygotes [IRR, 0.60 (0.41–0.88); <i>q</i> = 0.06], rs7090328 (<i>ALOX5</i>) rare homozygotes [IRR 0.27 (0.11–0.64); <i>q</i> = 0.05], rs2073438 (<i>ALOX12</i>) common homozygotes [IRR, 0.57 (0.41–0.80); <i>q</i> = 0.05], and rs104522 (<i>TP53</i>) rare homozygotes [IRR, 0.37 (0.17–0.79); <i>q</i> = 0.06]. No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalized, predictive models of colorectal cancer chemoprevention by aspirin.</p>Prevention Relevance:<p>Single-nucleotide polymorphisms in genes controlling lipid mediator signaling may modify the colorectal polyp prevention activity of aspirin. Further investigation is required to determine whether testing for genetic variants can be used to target cancer chemoprevention by aspirin to those who will benefit most.</p></div>
<p>Supplementary Table 2 shows the results of Negative binomial regression analysis of total colorectal polyp number according to aspirin use stratified for each SNP</p>
Abstract The 4th meeting of the Society of Academic and Research Surgery in January 2004 was held at the Belfast Waterfront Hall, hosted by Mr Declan Carey and his colleagues from the Belfast City Hospital. The Patey prize was won by Mr Mark Duxbury et al. for a paper entitled “RNA Interference Targeting Carcinoembryonic Antigen-Related Cell Adhesion Molecule 6 (CEACAM6): A Novel Strategy For The Treatment of Pancreatic Adenocarcinoma”.
Colorectal cancer (CRC) leads to significant morbidity/mortality worldwide. Defining critical research gaps (RG), their prioritisation and resolution, could improve patient outcomes.
Abstract Background People need high-quality information to make decisions about research participation. Providing information in written format alone is conventional but may not be the most effective and acceptable approach. We developed a structure for the presentation of information using multimedia which included generic and trial-specific content. Our aim was to embed ‘Studies Within A Trial’ (SWATs) across multiple ongoing trials to test whether multimedia presentation of patient information led to better rates of recruitment. Methods Five trials included a SWAT and randomised their participants to receive a multimedia presentation alongside standard information, or standard written information alone. We collected data on trial recruitment, acceptance and retention and analysed the pooled results using random effects meta-analysis, with the primary outcome defined as the proportion of participants randomised following an invitation to take part. Results Five SWATs provided data on the primary outcome of proportion of participants randomised. Multimedia alongside written information results in little or no difference in recruitment rates (pooled odds ratio = 0.96, 95% CI: 0.79 to 1.17, p -value = 0.671, I 2 = 0%). There was no effect on any other outcomes. Conclusions Multimedia alongside written information did not improve trial recruitment rates. Trial registration ISRCTN71952900, ISRCTN 06710391, ISRCTN 17160087, ISRCTN05926847, ISRCTN62869767.
In recent years, the role of oesophageal stenting for malignant dysphagia has evolved alongside other palliative treatments for oesophageal cancer. Management has become increasingly multidisciplinary and different considerations affect decisions about the timing and appropriateness of palliative stenting. We sought to assess the current UK practice of palliative stenting in oesophageal cancer. We assessed which specialties perform the procedure, which technique is used, the use of anti-reflux stents and investigated how different clinicians involved in the care of these patients would recommend managing dysphagia in different clinical scenarios.
Method
An online survey was sent out to the professional bodies of the members of the Upper GI MDT. Opinions of health professionals including gastroenterologists, oncologists, palliative care physicians, surgeons, radiologists and nurse specialists on the benefits and discomfort associated with the procedure were evaluated. Four clinical scenarios were used to evaluate opinions on maintaining nutrition prior to stenting, stenting in end-of-life care and the role of the MDT.
Results
The survey received 239 respondents, including 92 individuals (39%) who regularly insert oesophageal stents (‘stenters’). 63% of stents are inserted via endoscopy with fluoroscopic guidance, 20% with fluoroscopic guidance alone and 17% with endoscopy alone. 74% of responders never use anti-reflux devices, irrespective of the involvement of the gastro-oesophageal junction. 92% of respondents considered that stenting improved long-term dysphagia. Among the stenters, 20% considered that patients experience significant discomfort with some distress during the procedure (compared with 43% of non-stenters) and 16% during the days post-procedure (compared with 55% of non-stenters). 92% of stenters consider that the procedure improves quality of life in the 4 weeks post-procedure, compared with 78% of non-stenters. The clinical scenarios revealed that 15% of respondents would recommend stenting in end of life care in a patient who was managing a semi-solid diet, whereas 44% would consider stenting only if swallowing deteriorated subsequently. In complete dysphagia, 40% of respondents would recommend awaiting MDT discussion prior to oesophageal stent placement.
Conclusion
Health professionals’ perceptions of patient discomfort and improvement in quality of life are associated with the individuals’ experience of performing oesophageal stent insertion. These perceptions may influence decisions about timing and indication for oesophageal stenting. Care should be taken to acknowledge this, alongside the variation in opinion among clinicians over optimal management in different scenarios.
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