Improved adenoma detection with Endocuff Vision: the ADENOMA randomised controlled trial.

OBJECTIVE: Low adenoma detection rates (ADR) are linked to increased postcolonoscopy colorectal cancer rates and reduced cancer survival. Devices to enhance mucosal visualisation such as Endocuff Vision (EV) may improve ADR. This multicentre randomised controlled trial compared ADR between EV-assisted colonoscopy (EAC) and standard colonoscopy (SC). DESIGN: Patients referred because of symptoms, surveillance or following a positive faecal occult blood test (FOBt) as part of the Bowel Cancer Screening Programme were recruited from seven hospitals. ADR, mean adenomas per procedure, size and location of adenomas, sessile serrated polyps, EV removal rate, caecal intubation rate, procedural time, patient experience, effect of EV on workload and adverse events were measured. RESULTS: 1772 patients (57% male, mean age 62 years) were recruited over 16 months with 45% recruited through screening. EAC increased ADR globally from 36.2% to 40.9% (P=0.02). The increase was driven by a 10.8% increase in FOBt-positive screening patients (50.9% SC vs 61.7% EAC, P<0.001). EV patients had higher detection of mean adenomas per procedure, sessile serrated polyps, left-sided, diminutive, small adenomas and cancers (cancer 4.1% vs 2.3%, P=0.02). EV removal rate was 4.1%. Median intubation was a minute quicker with EAC (P=0.001), with no difference in caecal intubation rate or withdrawal time. EAC was well tolerated but caused a minor increase in discomfort on anal intubation in patients undergoing colonoscopy with no or minimal sedation. There were no significant EV adverse events. CONCLUSION: EV significantly improved ADR in bowel cancer screening patients and should be used to improve colonoscopic detection. TRIAL REGISTRATION NUMBER: NCT02552017, Results; ISRCTN11821044, Results.

Eicosapentaenoic acid and aspirin, alone and in combination, for the prevention of colorectal adenomas (seAFOod Polyp Prevention trial): a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial.

BACKGROUND: The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy. METHODS: In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55-73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847. FINDINGS: Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio [RR] 0·98, 95% CI 0·87 to 1·12; risk difference -0·9%, -8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference -0·6%, -8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 [44%] of 176 had ≥1 adverse event in the placebo group compared with 82 [46%] in the EPA group, 68 [39%] in the aspirin group, and 76 [45%] in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group). INTERPRETATION: Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence. FUNDING: Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.

A randomized controlled trial of eicosapentaenoic acid and/or aspirin for colorectal adenoma prevention during colonoscopic surveillance in the NHS Bowel Cancer Screening Programme (The seAFOod Polyp Prevention Trial): study protocol for a randomized controlled trial.

BACKGROUND: The naturally-occurring omega (ω)-3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) reduces colorectal adenoma (polyp) number and size in patients with familial adenomatous polyposis. The safety profile and potential cardiovascular benefits associated with ω-3 PUFAs make EPA a strong candidate for colorectal cancer (CRC) chemoprevention, alone or in combination with aspirin, which itself has recognized anti-CRC activity. Colorectal adenoma number and size are recognized as biomarkers of future CRC risk and are established as surrogate end-points in CRC chemoprevention trials. DESIGN: The seAFOod Polyp Prevention Trial is a randomized, double-blind, placebo-controlled, 2×2 factorial 'efficacy' study, which will determine whether EPA prevents colorectal adenomas, either alone or in combination with aspirin. Participants are 55-73 year-old patients, who have been identified as 'high risk' (detection of ≥5 small adenomas or ≥3 adenomas with at least one being ≥10 mm in diameter) at screening colonoscopy in the English Bowel Cancer Screening Programme (BCSP). Exclusion criteria include the need for more than one repeat endoscopy within the three-month BCSP screening period, malignant change in an adenoma, regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs, regular use of fish oil supplements and concomitant warfarin or anti-platelet agent therapy. Patients are randomized to either EPA-free fatty acid 1 g twice daily or identical placebo AND aspirin 300 mg once daily or identical placebo, for approximately 12 months. The primary end-point is the number of participants with one or more adenomas detected at routine one-year BCSP surveillance colonoscopy. Secondary end-points include the number of adenomas (total and 'advanced') per patient, the location (left versus right colon) of colorectal adenomas and the number of participants re-classified as 'intermediate risk' for future surveillance. Exploratory end-points include levels of bioactive lipid mediators such as ω-3 PUFAs, resolvin E1 and PGE-M in plasma, urine, erythrocytes and rectal mucosa in order to gain insights into the mechanism(s) of action of EPA and aspirin, alone and in combination, as well as to discover predictive biomarkers of chemopreventive efficacy. The recruitment target is 904 patients. TRIAL REGISTRATION: Current Controlled Trials ISRCTN05926847.

Aspirin users attending for NHS bowel cancer screening have less colorectal neoplasia: chemoprevention or false-positive faecal occult blood testing?

OBJECTIVE: The NHS Bowel Cancer Screening Programme (BCSP) uses faecal occult blood (FOB) testing to select patients aged 60-69 years for colonoscopy. AIM: To examine the association between aspirin use and the detection of colorectal neoplasia in screened patients undergoing colonoscopy. METHODS: Data were collected prospectively on individuals who underwent colonoscopy following a positive FOB test in the South of Tyne area between February 2007 and 2009. The relationship between the presence of colorectal neoplasia and age, gender, body mass index (BMI) and current aspirin use were evaluated using logistic regression analysis. RESULTS: 701 individuals underwent colonoscopy. 414 (59.1%) were male and 358 (51.1%) aged over 65 years. Males had a higher incidence of colorectal neoplasia (relative risk 2.26, 95% CI 1.65-3.10, p < 0.001). Current aspirin use was associated with a lower neoplasia detection rate (relative risk 0.79, 95% CI 0.50-0.98, p = 0.039). Increased age and BMI were not significantly associated with higher neoplasia detection. CONCLUSION: Amongst individuals undergoing colonoscopy following a positive FOB test in the BCSP, current aspirin use was associated with a lower incidence of colorectal neoplasia. This may represent the chemopreventative effect of aspirin or increased false positivity of FOB testing. Further work is needed to clarify the contribution of each and could reduce the number of unnecessary colonoscopies.

High yield of colorectal neoplasia detected by colonoscopy following a positive faecal occult blood test in the NHS Bowel Cancer Screening Programme.

OBJECTIVES: The UK National Health Service Bowel Cancer Screening Programme (BCSP) is based on a strategy of biennial faecal occult blood (FOB) testing. Positive results are classified as 'abnormal' or 'weak positive' based on the number of positive windows per kit or need for repeat testing. Colonoscopy is offered to both groups. We evaluate the relationship between FOB test positivity and clinical outcome in the BCSP. SETTING: The South of Tyne and Tees (UK) Bowel Cancer Screening Centres. METHODS: Data were collected prospectively on all individuals who were offered FOB testing and colonoscopy between February 2007 and February 2009. Univariable and multivariable analyses were performed to investigate the relationship between FOB test positivity and clinical outcome. RESULTS: Following FOB testing, 1524 individuals underwent colonoscopy, 1259 (83%) after a 'weak positive' and 265 (17%) an 'abnormal' result. Cancer was detected in 180 (11.8%) and adenomas in 758 (49.7%). Individuals with an 'abnormal' result were more likely to have cancer or be 'high risk' for the development of future adenomas (110/265, 41.5%) than those with 'weak positive' results, (236/1259, 18.7%, P < 0.0001). Those with Dukes stage B, C or D cancers or cancers proximal to the splenic flexure were more likely to have an 'abnormal' result. CONCLUSIONS: The majority of colonoscopies were performed following 'weak positive' FOB results. Those with an 'abnormal' result were more likely to be diagnosed with cancer. The high yield of pathology in both the 'abnormal' and 'weak positive' groups justifies the need for colonoscopy in both.