Italian multicentre randomised controlled trial of ‘once-only sigmoidoscopy’
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer Screening
PROVIDER: 2414886 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:BackgroundColorectal cancer is the third most common cancer worldwide. Previous analyses have only reported follow-up after flexible sigmoidoscopy for a maximum of 12 years. We aimed to examine colorectal cancer incidence and mortality after a single flexible sigmoidoscopy screening and 17 years of follow-up.MethodsIn this multicentre randomised trial (UK Flexible Sigmoidoscopy Screening Trial), done between Nov 14, 1994, and March 30, 1999, 170 432 eligible men and women, who had indicated on a previous questionnaire that they would probably attend screening if invited, were randomly assigned (1:2) to an intervention group (offered flexible sigmoidoscopy screening) or a control group (not contacted). Randomisation was done centrally in blocks of 12, and stratified by trial centre, general practice, and household type. The nature of the intervention did not allow the staff to be masked to arm of the trial; however, randomisation was done in batches so that the control group and participants not yet randomised were unaware of their allocation status. The primary outcomes were incidence and mortality of colorectal cancer. Hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality were estimated for intention-to-treat and per-protocol analyses. The trial is registered with ISRCTN, number 28352761.FindingsOur cohort analysis included 170 034 people: 112 936 in the control group and 57 098 in the intervention group, 40 621 (71%) of whom were screened and 16 477 (29%) were not screened. During screening and a median of 17·1 years' follow-up, colorectal cancer was diagnosed in 1230 individuals in the intervention group and 3253 in the control group, and 353 individuals in the intervention group versus 996 individuals in the control group died from colorectal cancer. In intention-to-treat analyses, colorectal cancer incidence was reduced by 26% (HR 0·74 [95% CI 0·70-0·80]; p<0·0001) in the intervention group versus the control group and colorectal cancer mortality was reduced by 30% (0·70 [0·62-0·79]; p<0·0001) in the intervention group versus the control group. In per-protocol analyses, adjusted for non-compliance, colorectal cancer incidence and mortality were 35% (HR 0·65 [95% CI 0·59-0·71]) and 41% (0·59 [0·49-0·70]) lower in the screened group.InterpretationA single flexible sigmoidoscopy continues to provide substantial protection from colorectal cancer diagnosis and death, with protection lasting at least 17 years.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation.
| S-EPMC6168937 | biostudies-literature
Project description:Colorectal adenomas are benign precursor lesions of colorectal cancer (CRC) that arise from normal epithelium1. The prevalence of adenomas in the large intestine is much higher than the incidence of cancer implying that the majority of adenomas will never progress to CRC4. In clinical practice, adenomas detected during colonoscopy are completely removed, and consequently the natural history of disease disrupted. Based on the prevalence of focal cancer in endoscopically removed adenomas, it is estimated that only 5% of adenomas will eventually progress to CRC. The aim of the present study was to characterize adenomas at low and high risk of progressing to cancer by extensive molecular profiling at DNA, RNA, and protein level, allowing to examine the biological processes in which they differ and to discover putative drivers of early colorectal tumor development.
2019-08-22 | PXD012254 | Pride
Project description:ObjectiveTo investigate the outcomes of biennial guaiac faecal occult blood test (gFOBT) screening after once-only flexible sigmoidoscopy (FS) screening.MethodsBetween 1994 and 1999, as part of the UK FS Screening Trial (UKFSST), adults aged 55-64 were randomly allocated to an intervention group (offered FS screening) or a control group (not contacted). From 2006, a subset of UKFSST participants (20,895/44,041 intervention group; 41,497/87,149 control group) were invited to biennial gFOBT screening by the English Bowel Cancer Screening Programme. We analysed gFOBT uptake, test positivity, yield of colorectal cancer (CRC), and positive predictive value (PPV) for CRC, advanced adenomas (AAs), and advanced colorectal neoplasia (ACN: AA/CRC).ResultsUptake of gFOBT at first invitation was 1.9% lower (65.7% vs. 67.6%, p?<?0.01) among intervention versus control group participants. Positivity was 0.4% lower (2.0% vs. 2.4%, p?<?0.01) and CRC yield was 0.08% lower (0.19% vs. 0.27%, p?=?0.14). PPVs were also lower in the intervention versus control group, at 10.3% vs. 12.3% ( p?=?0.44) for CRC, 22.7% vs. 31.4% ( p?<?0.01) for AA, and 33.0% vs. 43.7% ( p?<?0.01) for ACN. Among those who refused FS ( n?=?5532), gFOBT uptake at first invitation was 47.7%, CRC yield was 0.25%, and PPV for ACN was 46.2%. Among FS attenders ( n?=?15,363), uptake was 72.2%, CRC yield was 0.18%, and PPV for ACN was 27.9%.ConclusionsUptake, positivity and PPV of gFOBT screening were reduced following prior offer of FS screening. However, a quarter of FS screened participants receiving a diagnostic examination after positive gFOBT were diagnosed with ACN.
| S-EPMC6376653 | biostudies-literature
Project description:Colonoscopy is the gold standard for colorectal cancer prevention by allowing the resection of superficial colorectal adenomas or adenocarcinomas. This protection, more effective in the left colon than in the right colon, is imperfect and there are some adenomas and cancers omitted during colonoscopy. The G-EYE colonoscope equipped with an integrated distal balloon would better unfold the haustrations and stabilize the endoscope. Thus, the detection rate of adenomas would be improved by this better vision. The main objective of this study is to confirm that the use of the G-EYE colonoscope allows better detection of adenomatous polyps, decrease the rate of omitted adenomes and then is more effective.
| 2306473 | ecrin-mdr-crc
Project description:Guaiac faecal occult blood testing (gFOBT) consistently demonstrates reductions in deaths from colorectal cancer of around 16% and gFOBT screening is now routine in all four countries of the United Kingdom. However, gFOBT has significant limitations and is associated with a substantial interval cancer rate in the region of 50 %, indicating a severe deficiency in sensitivity for cancer. Additionally, as the majority of colorectal cancers arise from pre-existing adenomas, it is important for colorectal screening programmes to detect adenomas in order to reduce the incidence of the disease as well as the associated mortality. Although gFOBT does detect some adenomas, most randomised trials have not demonstrated a reduction in colorectal cancer incidence. Also, FOBT screening tends to under-detect cancers in women and it is relatively insensitive for rectal cancer when compared with colon cancer.
Single flexible sigmoidoscopy (FS), between the ages of 55 and 65 years, has been shown to bring about a significant reduction in colorectal cancer mortality. In addition, and most importantly, after a period of four years a significant reduction in colorectal cancer incidence was observed. FS does not suffer from low specificity since false positives do not occur, and there is independent evidence that it is more sensitive than a single gFOBT. In addition, FS is ideally suited to detecting rectal cancers and adenomas, and it is unlikely that there would be a gender difference in the sensitivity.
Single FS has not been compared with biennial FOBT and there is no information regarding the utility of FS in a population that has already been exposed to FOBT screening. It is hypothesised that offering a combination of gFOBT and FS would provide an enhanced screening algorithm that would be associated with better outcomes than gFOBT alone. In order to test this hypothesis a randomised evaluation pilot study of FS screening integrated into the current gFOBT Screening Programme, will be carried out in those around age 60, as this appears to be the age at which adenoma prevalence peaks.
| 2198905 | ecrin-mdr-crc
Project description:To study the dynamics of RNA interactomes, RIC-seq was performed on several biological replicates of colorectal cancer patients, each including colorectal adenomas, cancerous tissues, and tissues distal to cancer
2023-03-23 | GSE221551 | GEO
Project description:A major challenge in reducing the death rate of colorectal cancer is to screen patients using low-invasive testing. Blood test shows a high compliance rate with reduced invasiveness. In this work, a multiplex isobaric tag labeling strategy coupled with mass spectrometry is adopted to relatively quantify primary and secondary amine-containing metabolites in serum for the discovery of metabolite biomarkers of colorectal cancer. Serum samples from patients at different risk statuses and colorectal cancer growth statuses are studied. Metabolite identification is based on accurate mass matching and/or retention time of labeled metabolite standards. We quantify 40 metabolites across all the serum samples, including 18 metabolites validated with standards. We find significantly decreased levels of threonine and asparagine in the patients with growing adenomas or high-risk adenomas (p < 0.05). Glutamine levels decrease in patients with adenomas of unknown growth status or high-risk adenomas. In contrast, arginine levels are elevated in patients with low-risk adenoma. Receiver operating characteristic analysis shows high sensitivity and specificity of these metabolites for detecting growing adenomas. Based on these results, we conclude that potential metabolite biomarkers identified here contribute to distinguishing colorectal patients with growing adenomas from normal individuals and patients with unknown growth status of adenomas.
2022-12-28 | ST002420 | MetabolomicsWorkbench
Project description:Background and study aims
Bowel cancer is the fourth most commonly diagnosed cancer in the UK. Bowel cancers develop slowly from common bowel growths or polyps, so removing them can help prevent cancer. Screening with flexible sigmoidoscopy (also called ‘bowel scope’ or Flexi-scope) involves insertion of a thin flexible tube with a light and camera on the end into the bowel to examine the inner surface. Small bowel polyps can be removed during screening. The aim of the UK Flexible Sigmoidoscopy Screening Trial (UKFSST) was to determine whether having just one flexible sigmoidoscopy screen at around 60 years of age could prevent bowel cancer from developing and reduce the number of deaths from bowel cancer. The trial also aimed to determine how long any benefit lasts, and what is the best age to do the screening examination.
Who can participate?
Men and women who were aged 55–64 years and registered at a participating GP practice between November 1994 and March 1999.
What does the study involve?
The UKFSST was a randomised controlled trial. People who participated in the trial were randomly assigned to receive either flexible sigmoidoscopy screening or no screening (which was the usual care offered at the time of the trial).
| 2414980 | ecrin-mdr-crc
Project description:We report a novel high-throughput method to empirically quantify individual-specific regulatory element activity at the population scale. The approach combines targeted DNA capture with a high-throughput reporter-gene expression assay. As demonstration, we have measured the activity of more than 100 putative regulatory elements from 95 individuals in a single experiment. We found that, in agreement with previous reports, most genetic variants have weak effects on distal regulatory element activity. Because haplotypes are typically maintained within but not between assayed regulatory elements, the approach can be used to identify likely causal regulatory haplotypes that contribute to human phenotypes. Finally, we demonstrate the utility of the method to functionally fine map causal regulatory variants in regions of high linkage disequilibrium identified by expression quantitative trait loci (eQTL) analyses. 104 candidate regulatory elements from 95 individuals were resequenced using Illumina custom amplicon sequencing. We then cloned the resulting DNA fragments into a massively parallel reporter assay to quantify allele-specific regulatory activity from that population. SNP-fdr.txt contains output of significance evaluation haplotype.fasta.gz contains the reference used to generate alignment files
2015-06-15 | E-GEOD-68331 | biostudies-arrayexpress
Project description:In children and younger adults up to 39 years of age, SARS-CoV-2 usually elicits mild symptoms that resemble the common cold. Disease severity increases with age starting at 30 and reaches astounding mortality rates that are ~330 fold higher in persons above 85 years of age compared to those 18-39 years old. To understand age-specific immune pathobiology of COVID-19 we have analyzed soluble mediators, cellular phenotypes, and transcriptome from over 80 COVID-19 patients of varying ages and disease severity, carefully controlling for age as a variable. We found that reticulocyte numbers and peripheral blood transcriptional signatures robustly correlated with disease severity. By contrast, decreased numbers and proportion of naïve T cells, reported previously as a COVID-19 severity risk factor, were found to be general features of aging and not of COVID-19 severity, as they readily occurred in older participants experiencing only mild or no disease at all. Single-cell transcriptional signatures across age and severity groups showed that severe but not moderate/mild COVID-19 causes cell stress response in different T cell populations, and some of that stress was unique to old severe participants, suggesting that in severe disease of older adults, these defenders of the organism may be disabled from performing immune protection. These findings shed new light on interactions between age and disease severity in COVID-19.
2023-01-11 | GSE212584 | GEO