Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines. IntroductionAccording to recent estimates by the International Agency for Research on Cancer [1], colorectal cancer (CRC) is the most common cancer in Europe with 432 000 new cases reported annually in men and women combined. It is the second most common cause of cancer deaths in Europe with 212 000 deaths reported in 2008.Worldwide, CRC ranks third in incidence and fourth in mortality with an estimated 1.2 million cases and 0.6 million deaths annually. In the 27 Member States of the European Union (EU), CRC ranks first in incidence and second in mortality, with approximately 334000 new cases and 149000 deaths estimated in 2008.Even in those Member States in the lower range for age-standardized rates of CRC, the burden of disease is significantly greater when compared with many other HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript regions of the world (see reference [1]). CRC is therefore an important health problem across the EU.Screening can be effective in cancer control in populations with a significant burden of CRC, provided the services are of high quality [2]. The aim of CRC screening is to lower the burden of cancer in the population by discovering disease in its early, latent stages [3]. Evidence-based methods permit treatment that is more effective than if disease is diagnosed later when symptoms have occurred. Early treatment of invasive lesions, for example by endoscopic resection of early CRC, can also be less detrimental for quality of life. The endoscopic removal of pre-malignant lesions also reduces the incidence of CRC by avoiding the progression to cancer. Randomized trials in people of average risk invite...

Markedly improved participation rates were achieved in a mature gFOBt-based national screening programme and disparities between men and women were reduced. High positivity rates, particularly in men and previous non-respondents, challenge the available colonoscopy resource, but improvements in neoplasia detection are still achievable within this limited resource.

SummaryBackgroundUptake in the national colorectal cancer screening programme in England varies by socioeconomic status. We assessed four interventions aimed at reducing this gradient, with the intention of improving the health benefits of screening.MethodsAll people eligible for screening (men and women aged 60–74 years) across England were included in four cluster-randomised trials. Randomisation was based on day of invitation. Each trial compared the standard information with the standard information plus the following supplementary interventions: trial 1 (November, 2012), a supplementary leaflet summarising the gist of the key information; trial 2 (March, 2012), a supplementary narrative leaflet describing people's stories; trial 3 (June, 2013), general practice endorsement of the programme on the invitation letter; and trial 4 (July–August, 2013) an enhanced reminder letter with a banner that reiterated the screening offer. Socioeconomic status was defined by the Index of Multiple Deprivation score for each home address. The primary outcome was the socioeconomic status gradient in uptake across deprivation quintiles. This study is registered, number ISRCTN74121020.FindingsAs all four trials were embedded in the screening programme, loss to follow-up was minimal (less than 0·5%). Trials 1 (n=163 525) and 2 (n=150 417) showed no effects on the socioeconomic gradient of uptake or overall uptake. Trial 3 (n=265 434) showed no effect on the socioeconomic gradient but was associated with increased overall uptake (adjusted odds ratio [OR] 1·07, 95% CI 1·04–1·10, p<0·0001). In trial 4 (n=168 480) a significant interaction was seen with socioeconomic status gradient (p=0·005), with a stronger effect in the most deprived quintile (adjusted OR 1·11, 95% CI 1·04–1·20, p=0·003) than in the least deprived (1·00, 0·94–1·06, p=0·98). Overall uptake was also increased (1·07, 1·03–1·11, p=0·001).InterpretationOf four evidence-based interventions, the enhanced reminder letter reduced the socioeconomic gradient in screening uptake, but further reducing inequalities in screening uptake through written materials alone will be challenging.FundingNational Institute for Health Research.

A randomly selected sample of physicians in three large cities was asked to read one of four vignettes describing a patient. They then completed a set of objective attitude measures eliciting their reactions to the patient described in the vignette. The vignettes were identical except that the patient's illness was identified as either acquired immunodeficiency syndrome (AIDS) or leukemia and the patient's sexual preference as either heterosexual or homosexual. Harsh attitude judgments were associated with the IntroductionNearly 28,000 cases of acquired immunodeficiency syn-

Objective To determine the accuracy of guaiac and immunochemical faecal occult blood tests (FOBTs) for the detection of colorectal cancer in an average-risk screening population. Methods Fifteen electronic databases, the internet, key journals and reference lists of included studies were searched. We included diagnostic accuracy studies that compared guaiac or immunochemical FOBTs with any reference standard, for the detection of colorectal cancer in an average-risk adult population, with sufficient data to construct a 2 Â 2 table.Results Fifty-nine studies were included. Thirty-three evaluated guaiac FOBTs, 35 immunochemical FOBTs and one evaluated sequential FOBTs. Sensitivities for the detection of all neoplasms ranged from 6.2% (specificity 98.0%) to 83.3% (specificity 98.4%) for guaiac FOBTs, and 5.4% (specificity 98.5%) to 62.6% (specificity 94.3%) for immunochemical FOBTs. Specificity ranged from 65.0% (sensitivity 44.1%) to 99.0% (sensitivity 19.3%) for guaiac FOBTs, and 89.4% (sensitivity 30.3%) to 98.5% (sensitivity 5.4%) for immunochemical FOBTs. Diagnostic case-control studies generally reported higher sensitivities. Sensitivities were higher for the detection of CRC, and lower for adenomas, in both the diagnostic cohort and diagnostic case-control studies for both guaiac and immunochemical FOBTs. Conclusions Immudia HemSp appeared to be the most accurate immunochemical FOBT, however, there was no clear evidence to suggest whether guaiac or immunochemical FOBTs performed better, either from direct or indirect comparisons. Poor reporting of data limited the scope of this review, and the use the Standards for Reporting of Diagnostic Accuracy guidelines is recommended for reporting future diagnostic accuracy studies.

SUMMARY BackgroundThe diagnosis of colorectal cancer (CRC) can be difficult as symptoms are variable with poor specificity. Thus, there is a quest for simple, non-invasive testing that can help streamline those with significant colonic pathology.

BackgroundFaecal calprotectin (FC), a cytosolic protein released by neutrophils (S100 family) in response to inflammation, is a simple, non-invasive test that can be used to differentiate irritable bowel syndrome (IBS) with inflammatory bowel disease (IBD), where there can be considerable symptom overlap.Aims and methodsThe aims of the study were (1) to be able to predict the ability of FC to exclude IBD and determine cut-offs when in remission, (2) to investigate the effects of time and temperature on stability of FC and (3) compare three ELISA kits to measure FC: Buhlmann, PhiCal v1 and PhiCal v2. A total of 311 patients with altered bowel habit were tested for FC; 144 with IBS, 148 with IBD and 19 with other organic causes.ResultsSensitivity and specificity of FC (with PhiCal v2 kit) to distinguish between functional disorder (IBS) and IBD using cut-off 50 μg/g were 88% and 78%, respectively, with a negative predictive value of 87%. Area under the receiver operating curve was 0.84 (CI 0.78 to 0.90). For those with IBD, FC values below 250 μg/g corresponded with remission of disease with a sensitivity and specificity of 90% and 76%, respectively. Area under the receiver operating curve was 0.93 (CI 0.89 to 0.97). FC was stable once extracted and frozen for up to 2.5 months. Pearson correlation was good between Buhlmann assay and PhiCal v2 (r2 = 0.95).ConclusionsFC has up to 87% negative predictive value to exclude IBD, and cut-offs less than 250 μg/g had 90% sensitivity to determine remission in IBD. Once frozen, FC is stable and the ELISA monoclonal plates were broadly comparable.

Aim Faecal markers, such as the faecal immunochemical test for haemoglobin (FIT) and faecal calprotectin (FCP), have been increasingly used to exclude colorectal cancer (CRC) and colonic inflammation. However, in those with lower gastrointestinal symptoms there are considerable numbers who have cancer but have a negative FIT test (i.e. false negative), which has impeded its use in clinical practice. We undertook a study of diagnostic accuracy CRC using FIT, FCP and urinary volatile organic compounds (VOCs) in patients with lower gastrointestinal symptoms. Method One thousand and sixteen symptomatic patients with suspected CRC referred by family physicians were recruited prospectively in accordance with national referring protocol. A total of 562 patients who completed colonic investigations, in addition to providing stool for FIT and FCP as well as urine samples for urinary VOC measurements, were included in the final outcome measures. Results The sensitivity and specificity for CRC using FIT was 0.80 [95% confidence interval (CI) 0.66–0.93] and 0.93 (CI 0.91–0.95), respectively. For urinary VOCs, the sensitivity and specificity for CRC was 0.63 (CI 0.46–0.79) and 0.63 (CI 0.59–0.67), respectively. However, for those who were FIT‐negative CRC (i.e. false negatives), the addition of urinary VOCs resulted in a sensitivity of 0.97 (CI 0.90–1.0) and specificity of 0.72 (CI 0.68–0.76). Conclusions When applied to the FIT‐negative group, urinary VOCs improve CRC detection (sensitivity rises from 0.80 to 0.97), thus showing promise as a second‐stage test to complement FIT in the detection of CRC.