Population screening for colorectal cancer means getting FIT:the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT)

Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening

New insights into the lymphovascular microanatomy of the colon and the risk of metastases in pT1 colorectal cancer obtained with quantitative methods and three-dimensional digital reconstruction

Aims: UK faecal occult blood test screening has tripled the proportion of pT1 colorectal cancers. The risk of metastasis is predicted by depth of invasion, suggesting that access to deep lymphovascular vessels is important. The aim of this study was to quantify the distribution and size of the submucosal vasculature, and generate a novel three-dimensional (3D) model to validate the findings. Methods and results: Thirty samples of normal large bowel wall were immunostained with CD31, a vascular endothelium marker, to identify blood vessels, which were quantified and digitally analysed for their number, circumference, area and diameter in the deep mucosa and submucosa (Sm1, Sm2, and Sm3). The model required serial sections, a double immunostain (using CD31 and D2-40), and 3D reconstruction. Significant differences were shown between submucosal layers in the number, circumference and area of vessels (P < 0.001). Blood vessels were most numerous in the mucosa (11.79 vessels/0.2 mm2) but smaller [median area of 247 μm2, interquartile range (IQR) 162–373 μm2] than in Sm2, where they were fewer in number (6.92 vessels/0.2 mm2) but considerably larger (2086 μm2, IQR 1007–4784 μm2). The 3D model generated novel observations on lymphovascular structures. Conclusions: The number and size of blood vessels do not increase with depth of submucosa, as hypothesized. The distribution of vessels suggests that we should investigate the area or volume of submucosal invasion rather than the depth

Killing spinors and hypersurfaces

We consider spin manifolds with an Einstein metric, either Riemannian or indefinite, for which there exists a Killing spinor. We describe the intrinsic geometry of nondegenerate hypersurfaces in terms of a PDE satisfied by a pair of induced spinors, akin to the generalized Killing spinor equation. Conversely, we prove an embedding result for real analytic pseudo-Riemannian manifolds carrying a pair of spinors satisfying this condition.Comment: 26 page

Interventions to increase uptake of faecal tests for colorectal cancer screening: a systematic review

International guidelines promote screening by faecal tests in asymptomatic individuals at average risk of colorectal cancer (CRC), but uptake does not reach recommended levels in most countries. The aim of this study was to synthetize evidence on (a) interventions aiming to increase uptake of faecal tests for CRC screening, in asymptomatic individuals at average risk of CRC, (b) interventions that targeted general practitioner (GP) involvement and (c) interventions that targeted nonresponders or disadvantaged groups. A systematic review of randomized-controlled trials, searching PubMed, Embase and the Cochrane Library database, based on the Cochrane’s Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 guidelines was performed. The risk of bias of included trials was assessed. From 24 included RCTs, the following interventions increase uptake of faecal tests: advance notification letter (OR 1.20–1.51), postal mailing (OR 1.31–7.70), telephone contacts with an advisor (OR 1.36–7.72). Three interventions showed positive effects of GP involvement such as a GP-signed invitation letter [odds ratio (OR)=1.26], GP communication training (OR=1.22) or mailing reminders to GPs (OR=14.8). Inconclusive results were found for studies comparing different types of faecal tests and those testing the effectiveness of providing various types of written information. Advance notification letters, postal mailing of the faecal tests, written reminders and telephone contacts with an advisor increase patient uptake of faecal tests. There was only limited evidence on the effect of GP involvement on screening test uptake and a lack of studies focusing on nonresponders or disadvantaged groups

A comparative effectiveness trial of two faecal immunochemical tests for haemoglobin (FIT). Assessment of test performance and adherence in a single round of a population-based screening programme for colorectal cancer

Aim: To compare acceptability and diagnostic accuracy of a recently available faecal immunochemical test (FIT) system (HM-JACKarc) with the FIT routinely used in an established screening programme (OC-Sensor).Design: Randomised controlled trial (ISRCTN20086618) within a population-based colorectal cancer (CRC) screening programme. Subjects eligible for invitation in the Umbria Region (Italy) programme were randomised (ratio 1:1) to be screened using one of the FIT systems.Results: Screening uptake among the 48 888 invitees was the same for both systems among subjects invited in the first round and higher with OC-Sensor than with HM-JACKarc (relative risk (RR): 1.03; 95% CI 1.02 to 1.04) among those invited in subsequent rounds. Positivity rate (PR) was similar with OC-Sensor (6.5%) as with HM-JACKarc (6.2%) among subjects performing their first FIT screening and higher with OC-Sensor (5.6%, RR: 1.25, 95% CI 1.12 to 1.40) than with HM-JACKarc (4.4%) among those screened in previous rounds. Positive predictive value (PPV) (OC-Sensor: 25.9%, HM-JACKarc: 25.6%) and detection rate (DR) (OC-Sensor: 1.40%; HM-JACKarc: 1.42%) for advanced neoplasia (AN: CRC + advanced adenoma) were similar among subjects performing their first FIT screening. The differences in the AN PPV (OC-Sensor: 20.3%, HM-JACKarc: 22.6%) and DR (OC-Sensor: 0.96%, HM-JACKarc: 0.83%) among those screened in previous rounds were not statistically significant. The number needed to scope to detect one AN was 3.9 (95% CI 5.8 to 2.9) and 3.9 (95% CI 5.5 to 2.9) at first and 4.9 (95% CI 5.8 to 4.2) and 4.4 (95% CI 5.3 to 3.7) at subsequent screening, with OC-Sensor and HM-JACKarc, respectively.Conclusions: Our results suggest that acceptability and diagnostic performance of HM-JACKarc and of OC-Sensor systems are similar in a screening setting.Trial registration number: ISRCTN20086618; Results.</p

Effect of second timed appointments for non-attenders of breast cancer screening in England : a randomised controlled trial

BACKGROUND: In England, participation in breast cancer screening has been decreasing in the past 10 years, approaching the national minimum standard of 70%. Interventions aimed at improving participation need to be investigated and put into practice to stop this downward trend. We assessed the effect on participation of sending invitations for breast screening with a timed appointment to women who did not attend their first offered appointment within the NHS Breast Screening Programme (NHSBSP). METHODS: In this open, randomised controlled trial, women in six centres in the NHSBSP in England who were invited for routine breast cancer screening were randomly assigned (1:1) to receive an invitation to a second appointment with fixed date and time (intervention) or an invitation letter with a telephone number to call to book their new screening appointment (control) in the event of non-attendance at the first offered appointment. Randomisation was by SX number, a sequential unique identifier of each woman within the NHSBSP, and at the beginning of the study a coin toss decided whether women with odd or even SX numbers would be allocated to the intervention group. Women aged 50-70 years who did not attend their first offered appointment were eligible for the analysis. The primary endpoint was participation (ie, attendance at breast cancer screening) within 90 days of the date of the first offered appointment; we used Poisson regression to compare the proportion of women who participated in screening in the study groups. All analyses were by intention to treat. This trial is registered with Barts Health, number 009304QM. FINDINGS: We obtained 33 146 records of women invited for breast cancer screening at the six centres between June 2, 2014, and Sept 30, 2015, who did not attend their first offered appointment. 26 054 women were eligible for this analysis (12 807 in the intervention group and 13 247 in the control group). Participation within 90 days of the first offered appointment was significantly higher in the intervention group (2861 [22%] of 12 807) than in the control group (1632 [12%] of 13 247); relative risk of participation 1·81 (95% CI 1·70-1·93; p<0·0001). INTERPRETATION: These findings show that a policy of second appointments with fixed date and time for non-attenders of breast screening is effective in improving participation. This strategy can be easily implemented by the screening sites and, if combined with simple interventions, could further increase participation and ensure an upward shift in the participation trend nationally. Whether the policy should vary by time since last attended screen will have to be considered. FUNDING: National Health Service Cancer Screening Programmes and Department of Health Policy Research Programme