http://www.trialregister.nl Dutch Trial Register: NTR3962.

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.

The barostat is the gold standard for measurement of proximal gastric accommodation. Ultrasonography can be used to measure gastric volume. The aim was to investigate the effects of the barostat bag on gastric accommodation and transpyloric flow. Accommodation after a liquid meal (300 ml, 450 kcal) was measured twice at random in eight healthy volunteers. Proximal accommodation was measured once using barostat and once using ultrasound (US). Antrum accommodation was measured using US. Bag volume (BV), antral area (AA), proximal gastric area, and proximal gastric diameter (PGD) data were assessed before and 1, 5, 15, 30, 40, 50, and 60 min postprandially. Transpyloric flow was measured using Doppler 1-5 min postprandially. Fasted, AA size was not affected by the barostat bag (1 mmHg > minimal distension pressure; 2.7 +/- 0.5 vs. 2.6 +/- 0.3 cm(2)). Postprandially, AAs were larger with the bag present (ANOVA, P < 0.04). Maximum AA was reached with the bag in 5 min, without the bag in 1 min postprandially (15.1 +/- 2.3 vs. 9.4 +/- 1.5 cm(2); P < 0.03). Furthermore, AAs were related to BVs (r = 0.57; P < 0.01). After bag deflation, AA decreased (11.9 +/- 1.8 to 7.0 +/- 0.9 cm(2); P = 0.02) and was comparable with the 60-min AA size without the bag (7.1 +/- 1.2 cm(2); P = 0.76) present. Proximal gastric radius calculated from the BVs and PGDs was larger with the bag present (ANOVA, P < 0.001). No effect on early gastric emptying was observed. Postprandially, the barostat bag causes dilatation of the antrum due to meal displacement without influencing early gastric emptying. This antral dilatation is likely to induce exaggerated proximal gastric relaxation observed in studies using the barostat to evaluate fundic accommodation.

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The motor mechanisms responsible for transpyloric flow of gastric contents are still poorly understood. The aim of our study was to investigate the relationship between luminal pressures and gastric wall motion and between gastroduodenal pressure gradients and pressure waves, and ante- and retro-grade transpyloric flow. In eight healthy volunteers, intraluminal pressures were recorded from the antrum and proximal duodenum. Transpyloric flow was monitored simultaneously using duplex ultrasonography, before, during and after ingestion of 300 mL meat soup. Transpyloric emptying occurred as sequences of alternating periods of emptying-reflux-emptying. Approximately one-third of the sequences were not associated with peristalsis. The antroduodenal pressure gradients were significantly lower during nonperistaltic-related emptying than during peristaltic-related emptying (0.15 (0-0.3) kPa, and 1.7 (0.2-2.0) kPa, respectively [mean plus minus (range)], P < 0.005). The duration of emptying episodes not associated with peristalsis were significantly longer than those associated with peristalsis at (6.5 (3-8.7) s and 4.4 (2-6) s, respectively, P=0.059). Manometry detected only 56% of the antral contractions seen on ultrasound. We concluded that gastric emptying of a low-calorie liquid meal occurs both during peristaltic and nonperistaltic antral activity. In spite of lower antroduodenal pressure gradients, the emptying episodes were longer for nonperistaltic emptying, which is likely to be caused by low pyloric resistance. Considerable flow seems to occur without peristalsis during gastric emptying of a low-calorie, liquid meal in humans.