BackgroundSpecific genes, such as BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC) tissue compared to normal colon tissue specimens. Such DNA may leak into blood and be present as cell-free circulating DNA. We have evaluated the accuracy of a novel blood test for these two markers across the spectrum of benign and neoplastic conditions encountered in the colon and rectum.MethodsCirculating DNA was extracted from plasma obtained from volunteers scheduled for colonoscopy for any reason, or for colonic surgery, at Australian and Dutch hospitals. The extracted DNA was bisulphite converted and analysed by methylation specific real-time quantitative PCR (qPCR). A specimen was deemed positive if one or more qPCR replicates were positive for either methylated BCAT1 or IKZF1 DNA. Sensitivity and specificity for CRC were estimated as the primary outcome measures.ResultsPlasma samples were collected from 2105 enrolled volunteers (mean age 62 years, 54 % male), including 26 additional samples taken after surgical removal of cancers. The two-marker blood test was run successfully on 2127 samples. The test identified 85 of 129 CRC cases (sensitivity of 66 %, 95 % CI: 57–74). For CRC stages I-IV, respective positivity rates were 38 % (95 % CI: 21–58), 69 % (95 % CI: 53–82), 73 % (95 % CI: 56–85) and 94 % (95 % CI: 70–100). A positive trend was observed between positivity rate and degree of invasiveness. The colonic location of cancer did not influence assay positivity rates. Gender, age, smoking and family history were not significant predictors of marker positivity. Twelve methylation-positive cancer cases with paired pre- and post-surgery plasma showed reduction in methylation signal after surgery, with complete disappearance of signal in 10 subjects. Sensitivity for advanced adenoma (n = 338) was 6 % (95 % CI: 4–9). Specificity was 94 % (95 % CI: 92–95) in all 838 non-neoplastic pathology cases and 95 % (95 % CI: 92–97) in those with no colonic pathology detected (n = 450).ConclusionsThe sensitivity for cancer of this two-marker blood test justifies prospective evaluation in a true screening population relative to a proven screening test. Given the high rate of marker disappearance after cancer resection, this blood test might also be useful to monitor tumour recurrence.Trial registrationACTRN12611000318987.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1674-2) contains supplementary material, which is available to authorized users.

Objectives:To compare the performance of a new blood test for colorectal cancer (CRC) to an established fecal immunochemical test (FIT) in a study population with the full range of neoplastic and non-neoplastic pathologies encountered in the colon and rectum.Methods:Volunteers were asked to complete a FIT prior to colonoscopy. Blood was collected after bowel preparation but prior to colonoscopy, and plasma was assayed for the presence of methylated BCAT1 and IKZF1 DNA using a multiplex real-time PCR assay. Sensitivity and specificity estimates for the blood test were calculated from true- and false-positive rates for neoplasia and compared with FIT at a range of fecal hemoglobin (Hb) concentration positivity thresholds.Results:In total, 1,381 volunteers (median age 64 years; 49% male) completed both tests prior to colonoscopy. Estimated sensitivity of the BCAT1/IKZF1 blood test for CRC was 62% (41/66; 95% confidence interval 49–74%) with a specificity of 92% (1207/1315; 90–93%). FIT returned the same specificity at a cutoff of 60 μg Hb/g, at which its corresponding sensitivity for cancer was 64% (42/66; 51–75%). In the range of commonly used FIT cutoffs, respective cancer sensitivity and specificity estimates with FIT were: 59% (46–71%) and 93% (92–95%) at 80 μg Hb/g, and 79% (67–88%) and 81% (78–83%) at 10 μg Hb/g. Although estimated sensitivities were not significantly different between the two tests for any stage of cancer, FIT showed a significantly higher sensitivity for advanced adenoma at the lower cutoffs. Specificity of FIT, but not of the BCAT1/IKZF1 blood test, deteriorated substantially in people with overt blood in the feces. When combining FIT (cutoff 10 μg Hb/g) with the BCAT1/IKZF1 blood test, sensitivity for cancer was 89% (79–96%) at 74% (72–77%) specificity.Conclusions:A test based on detection of methylated BCAT1/IKZF1 DNA in blood has comparable sensitivity but better specificity for CRC than FIT at the commonly used positivity threshold of 10 μg Hb/g. Further evaluation of the new test relative to FIT in the population screening context is now required to fully understand the potential advantages and disadvantages of these biomarkers in screening.

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Background and Aim Cold snare polypectomy is safe and efficacious for removing polyps <10 mm with reduced rates of delayed postpolypectomy bleeding and postpolypectomy syndrome. This technique can also be used for sessile polyps ≥10 mm; however, further evidence is required to establish its safety. The aim of this study was to compare intraprocedure and postprocedure adverse events in patients who underwent cold (CSP) versus hot snare polypectomy (HSP) of 10–20 mm sessile colonic polyps. Methods Electronic medical records and endoscopy reports of all patients who underwent polypectomy for Paris 0‐IIa, Is, or 0‐IIa + Is 10–20 mm colonic polyps between January 2015 and June 2017 at three tertiary academic hospitals and one private hospital were retrospectively reviewed. Data on patient demographics, polyp characteristics, method of polypectomy, and intraprocedural and postpolypectomy adverse events were collected. Results A total of 408 patients (median age 67, 50% male) had 604 polyps, 10–20 mm in size, removed. Of these, 258 polyps were removed by HSP, with a median size of 15 mm (interquartile range [IQR] 12–20), compared to 346 polyps that were removed by CSP, with median size of 12 mm (IQR 10–15), P < 0.001. In the HSP group, 15 patients presented with postprocedure complications, including 11 with clinically significant bleeding, 2 with postpolypectomy syndrome, and 2 with abdominal pain. This compares with no postpolypectomy complications in the CSP group, P < 0.001. Conclusion In this study, CSP was not associated with any postpolypectomy adverse events. CSP appears to be safer than HSP for removing 10–20 mm‐sized sessile polyps. A prospective multicenter study has been commenced to verify these findings and to assess the efficacy of CSP for the complete resection of polyps of this size.