Recruitment strategies and consent rates in a national prospective colorectal cancer screening cohort: results from year 1 of the Voyage Study.

OBJECTIVE: To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial. DESIGN: Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported. RESULTS: During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals. CONCLUSIONS: Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data. TRIAL REGISTRATION NUMBER: NCT04124406.

Interval colorectal cancers after negative faecal immunochemical test in the New Zealand Bowel Screening Pilot.

OBJECTIVE: Evaluate the diagnostic performance of faecal immunochemical test (FIT), identify risk factors for FIT-interval colorectal cancers (FIT-IC) and describe long-term outcomes of participants with colorectal cancers (CRC) in the New Zealand Bowel Screening Pilot (BSP). DESIGN: From 2012 to 2017, the BSP offered eligible individuals, aged 50-74 years, biennial screening using a quantitative FIT with positivity threshold of 15 µg haemoglobin (Hb)/g faeces. Retrospective review of prospectively maintained data extracted from the BSP Register and New Zealand Cancer Registry identified any CRC reported in participants who returned a definitive FIT result. Further details were obtained from hospital records. FIT-ICs were primary CRC diagnosed within 24 months of a negative FIT. Factors associated with FIT-ICs were identified using logistic regression. RESULTS: Of 387 215 individuals invited, 57.4% participated with 6.1% returning positive FIT results. Final analysis included 520 CRC, of which 111 (21.3%) met FIT-IC definition. Overall FIT sensitivity for CRC was 78.7% (95% CI=74.9% to 82.1%), specificity was 94.1% (95% CI=94.0% to 94.2%). In 78 (70.3%) participants with FIT-IC, faecal Hb was reported as undetectable. There were no significant associations between FIT-IC and age, sex, ethnicity and deprivation. FIT-ICs were significantly associated with proximal tumour location, late stage at diagnosis, high-grade tumour differentiation and subsequent round screens. Median follow-up time was 74 (2-124) months. FIT-IC had significantly poorer overall survival. CONCLUSION: FIT sensitivity in BSP compared favourably to published data. FIT-ICs were more likely to be proximal tumours with poor long-term outcomes. Further lowering of FIT threshold would have minimal impact on FIT-IC.

Faecal metabolome and its determinants in inflammatory bowel disease.

OBJECTIVE: Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD. DESIGN: We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels. RESULTS: We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of Ruminococcus gnavus was positively associated with tryptamine levels. In addition, we found 158 associations between metabolites and dietary patterns, and polymorphisms near NAT2 strongly associated with coffee metabolism. CONCLUSION: In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

Faecal occult blood loss accurately predicts future detection of colorectal cancer. A prognostic model.

OBJECTIVES: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). DESIGN: Prognostic model. SETTING: Dutch biennial FIT-based screening programme during 2014-2018. PARTICIPANTS: 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 µg Hb/g faeces) in rounds 1 and 2. INTERVENTIONS: Colonoscopy follow-up in participants with a positive FIT (F-Hb ≥47 µg Hb/g faeces). MAIN OUTCOMES: We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. RESULTS: Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). CONCLUSION: Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information.

Development of a new version of the Bristol Stool Form Scale: translation, content validity, face validity, and reliability of the Persian version.

OBJECTIVES: The Bristol Stool Form Scale (BSFS) is the most widely used scale for stool form assessment. This study aimed to translate the BSFS into the Persian version and determine its content validity, face validity, and reliability. DESIGN: Following permission, a forward-backward translation procedure was applied to translate the scale from English into Persian. A cross-sectional study was conducted on a sample of 210 participants from the general and gastrointestinal clinics of a teaching hospital affiliated with the Tehran University of Medical Sciences, Tehran, Iran, from January 2020 to August 2020. The samples were selected using convenience sampling. A group of 10 experts and 10 adults assessed content and face validity, respectively. The kappa index evaluated the reliability of the instruments. RESULTS: Participants' mean (±SD) age was 37.62 (±8.87) years. Most of the participants (65.7%) were women. The highest percentage of concordance was 100% for stool type 7, and stool type 5 had the lowest concordance percentage (78.1%). The overall kappa index was 0.79. CONCLUSION: The Persian version of the BSFS is a valid and reliable measure for assessing stool form, and now it can be used in research and clinical practice.

Role of the faecal immunochemical test in patients with risk-stratified suspected colorectal cancer symptoms: A systematic review and meta-analysis to inform the ACPGBI/BSG guidelines.

Background: The UK National Institute for Health and Care Excellence (NICE), recommended in 2017 the use of the faecal immunochemical test (FIT) to guide investigations in patients presenting with NICE-defined low-risk symptoms suspicious for colorectal cancer (CRC). At that time, NICE did not recommend FIT use for high-risk symptoms. This is the first systematic review to evaluate the diagnostic accuracy of FIT in NICE-defined high and low-risk symptoms and was designed to inform the joint ACPGBI/BSG guidelines. Methods: We performed a systematic literature review and meta-analysis. PROSPERO registration number CRD42021224674. Medline and EMBASE databases were searched from inception to 31st March 2022. We included studies recruiting adult patients presenting with suspected CRC symptoms in whom FIT was performed and diagnostic accuracy data for CRC detection could be derived at a limit of detection (LoD) and/or 10 µg haemoglobin/gram faeces threshold in four commonly used analysers. FIT performance was assessed for high-risk, low-risk and individual symptoms where possible. Bivariate meta-analysis was performed where study numbers allowed. Findings: Thirty-one studies (79566 patients) met inclusion criteria. At 10 µg/g, for "all symptoms" (n = 35,945) sensitivity and specificity were 91.0% (95% CI: 88.9, 92.7) and 75.2% (95% CI: 69.6, 80.1); for "high-risk" symptoms (n = 18,264), 88.7% (95% CI: 84.4, 92.0) and 78.5% (95% CI: 73.0, 83.2); and for "low-risk" symptoms (n = 2161), 88.7% (95% CI: 78.1, 95.3) and 88.5% (95% CI: 87.1, 89.9), respectively. At LoD, for "all symptoms" (n = 26,056) sensitivity and specificity were 94.7% (95% CI: 90.5, 97.1) and 66.5% (95% CI: 58.7, 73.6); for "high-risk" symptoms (n = 16,768), 92.8% (95% CI: 86.4, 96.3) and 70.3% (95% CI: 66.5, 73.8); and for "low-risk" symptoms (n = 2082), 94.7% (95% CI: 85.4, 98.9) and 71.9% (95% CI: 69.9, 73.9), respectively. Summary estimates were similar across different analysers. Interpretation: FIT sensitivity for CRC detection is maximised at the LoD; its performance is similar in high and low-risk symptoms, and across different analysers where a common threshold is used. FIT performance for CRC detection is adequate and transferrable to clinical diagnostic pathways. Funding: This review was part-funded by NHS England awarded to RM Partners. RB and RC were funded by research fellowships awarded by Croydon University Hospital.

Faecal immunochemical testing (FIT) in patients with signs or symptoms of suspected colorectal cancer (CRC): a joint guideline from the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG).

Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management.

Faecal immunochemical tests safely enhance rational use of resources during the assessment of suspected symptomatic colorectal cancer in primary care: systematic review and meta-analysis.

OBJECTIVE: Implementation of faecal immunochemical tests (FIT) as a triage test in primary healthcare may improve the efficiency of referrals without missing cases of colorectal cancer (CRC). We aim to summarise the performance characteristics of FITs for CRC in symptomatic patients presenting to primary healthcare. DESIGN: We performed a systematic literature review of Medline and EMBASE databases from May 2018 to November 2020. Previous related systematic searches were also adapted to this aim and completed with reference screening. We identified studies performed on adult patients consulting for abdominal symptoms in primary care which reported data such that the FIT diagnostic performance parameters for CRC could be obtained. Bivariate models were used to synthesise available evidence. Meta-regression analysis was performed to evaluate the causes of heterogeneity. RESULTS: Twenty-three studies (69 536 participants) were included (CRC prevalence 0.3%-6.2%). Six studies (n=34 691) assessed FIT as rule in test (threshold of ≥150 µg Hb/g faeces) showing a sensitivity of 64.1% (95% CI 57.8% to 69.9%) and a specificity of 95.0% (95% CI 91.2% to 97.2%). A threshold of 10 µg/g (15 studies; n=48 872) resulted in a sensitivity of 87.2% (95% CI 81.0% to 91.6%) and a specificity of 84.4% (95% CI 79.4% to 88.3%) for CRC. At a 20 µg Hb/g faeces threshold (five studies; n=24 187) less than one additional CRC would be missed per 1000 patients investigated compared with 10 µg Hb/g faeces threshold (CRC prevalence 2%). CONCLUSION: FIT is the test of choice to evaluate patients with new-onset lower gastrointestinal symptoms in primary healthcare.

Calprotectin: from biomarker to biological function.

The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn's disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.

Point-of-care faecal calprotectin testing in patients with paediatric inflammatory bowel disease during the COVID-19 pandemic.

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.

Faecal immunochemical test is superior to symptoms in predicting pathology in patients with suspected colorectal cancer symptoms referred on a 2WW pathway: a diagnostic accuracy study.

OBJECTIVE: To assess whether a faecal immunochemical test (FIT) could be used to select patients with suspected colorectal cancer (CRC) symptoms for urgent investigation. DESIGN: Multicentre, double-blinded diagnostic accuracy study in 50 National Health Service (NHS) hospitals across England between October 2017 and December 2019. Patients referred to secondary care with suspected CRC symptoms meeting NHS England criteria for urgent 2 weeks wait referral and triaged to investigation with colonoscopy were invited to perform a quantitative FIT. The sensitivity of FIT for CRC, and effect of relevant variables on its diagnostic accuracy was assessed. RESULTS: 9822 patients were included in the final analysis. The prevalence of CRC at colonoscopy was 3.3%. The FIT positivity decreased from 37.2% to 19.0% and 7.6%, respectively, at cut-offs of 2, 10 and 150 µg haemoglobin/g faeces (µg/g). The positive predictive values of FIT for CRC at these cut-offs were 8.7% (95% CI, 7.8% to 9.7%), 16.1% (95% CI 14.4% to 17.8%) and 31.1% (95% CI 27.8% to 34.6%), respectively, and the negative predictive values were 99.8% (95% CI 99.7% to 99.9%), 99.6% (95% CI 99.5% to 99.7%) and 98.9% (95% CI 98.7% to 99.1%), respectively. The sensitivity of FIT for CRC decreased at the same cut-offs from 97.0% (95% CI 94.5% to 98.5%) to 90.9% (95% CI 87.2% to 93.8%) and 70.8% (95% CI 65.6% to 75.7%), respectively, while the specificity increased from 64.9% (95% CI 63.9% to 65.8%) to 83.5% (95% CI 82.8% to 84.3%) and 94.6% (95% CI 94.1% to 95.0%), respectively. The area under the receiver operating characteristic curve was 0.93 (95% CI 0.92 to 0.95). CONCLUSION: FIT sensitivity is maximised to 97.0% at the lowest cut-off (2 µg/g); a negative FIT result at this cut-off can effectively rule out CRC and a positive FIT result is better than symptoms to select patients for urgent investigations. TRIAL REGISTRATION NUMBER: ISRCTN49676259.

Gut microbiome composition and risk factors in a large cross-sectional IBS cohort.

Objective: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is difficult to diagnose and treat due to its inherent heterogeneity and unclear aetiology. Although there is evidence suggesting the importance of the microbiome in IBS, this association remains poorly defined. In the current study, we aimed to characterise a large cross-sectional cohort of patients with self-reported IBS in terms of microbiome composition, demographics, and risk factors. Design: Individuals who had previously submitted a stool sample for 16S microbiome sequencing were sent a comprehensive survey regarding IBS diagnosis, demographics, health history, comorbidities, family history, and symptoms. Log ratio-transformed abundances of microbial taxa were compared between individuals reporting a diagnosis of IBS without any comorbidities and individuals reporting no health conditions. Univariable testing was followed by a multivariable logistic regression model controlling for relevant confounders. Results: Out of 6386 respondents, 1692 reported a diagnosis of IBS without comorbidities and 1124 reported no health conditions. We identified 3 phyla, 15 genera, and 19 species as significantly associated with IBS after adjustment for confounding factors. Demographic risk factors include a family history of gut disorders and reported use of antibiotics in the last year. Conclusion: The results of this study confirm important IBS risk factors in a large cohort and support a connection for microbiome compositional changes in IBS pathogenesis. The results also suggest clinical relevance in monitoring and investigating the microbiome in patients with IBS. Further, the exploratory models described here provide a foundation for future studies.

Audit of the impact of the York faecal calprotectin care pathway on colonoscopy activity.

BACKGROUND: The York faecal calprotectin care pathway (YFCCP) was developed to optimise effective primary care differentiation between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We undertook an audit of colonoscopy activity at York Teaching Hospitals after the introduction of the YFCCP, to assess its impact. METHODS: Faecal calprotectin (FC) results were reconciled with colonoscopy activity in patients 18-60 years after the implementation of the YFCCP. This permitted individual patient tracking of their FC values, the timing of those requests by primary care, the date of subsequent referral and investigation and the end clinical diagnoses. RESULTS: Primary care uptake of FC increased fourfold with the introduction of the YFCCP. Following implementation, FC-related referrals for colonoscopy fell from 24% to 13%. The number of patients needed to colonoscope to diagnose organic colonic disease (IBD, significant adenomatous polyps or colorectal cancer) fell from 6.8 to 3.8 when the YFCCP was applied. This represents a cost saving of £41 015 per thousand patients tested in primary care. We estimate that outpatient time to diagnosis fell from a median of 41 to 29 days. CONCLUSION: This audit of FC activity and colonoscopy outcomes provides substantial supportive evidence for the effectiveness of the YFCCP. Popular in primary care, it has led to a reduction in referrals. The diagnostic accuracy determined in this audit is in line with earlier evaluations. Accepting the weaknesses of audit we conclude that this evaluation likely underestimates the benefits of the YFCCP in terms of resource use saving and time to diagnosis.

Experience of adopting faecal immunochemical testing to meet the NICE colorectal cancer referral criteria for low-risk symptomatic primary care patients in Oxfordshire, UK.

OBJECTIVE: To compare the diagnostic performance of guaiac faecal occult blood (gFOB) testing with faecal immunochemical test (FIT) in a low-risk symptomatic primary care population to provide objective data on which to base local referral guidelines. DESIGN: Stool samples from routine primary care practice sent for faecal occult blood testing were analysed by a standard gFOB method and the HM-JACKarc FIT between January and March 2016. Symptoms described on the test request were recorded. Patients were followed up over 21 months for evidence of serious gastrointestinal pathology including colorectal adenocarcinoma. RESULTS: In 238 patients, the sensitivity and specificity for colorectal adenocarcinoma detection using gFOB were 85.7% and 65.8%, respectively, compared with 85.7% and 89.2% for FIT. The positive predictive value (PPV) for gFOB was 7.1% and negative predictive value (NPV) was 99.3%. Comparatively, the PPV for FIT was 19.4% and NPV 99.5%. The improved performance of FIT over gFOB was due to a lower false positive rate (10.8 vs 34.2, p≤0.01) with no increase in the false negatives rate. For any significant colorectal disease, the PPV for FIT increased to 35.5% with a reduction in NPV to 95.7%. CONCLUSION: In this low-risk symptomatic patient group, the proportion of samples considered positive by FIT was considerably lower than gFOB with the same rate of colorectal adenocarcinoma detection. One in three of those with positive FIT had a significant colorectal disease. This supports National Institute of Health and Care Excellence recommendation that FIT can be reliably used as a triage test in primary care without overburdening endoscopy resources.

Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.

Faecal immunochemical tests (FIT) versus colonoscopy for surveillance after screening and polypectomy: a diagnostic accuracy and cost-effectiveness study.

OBJECTIVE: The English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or one ≥10 mm). We investigated whether faecal immunochemical tests (FITs) could reduce surveillance burden on patients and endoscopy services. DESIGN: Intermediate-risk patients (60-72 years) recommended 3 yearly surveillance were recruited within the BCSP (January 2012-December 2013). FITs were offered at 1, 2 and 3 years postpolypectomy. Invitees consenting and returning a year 1 FIT were included. Participants testing positive (haemoglobin ≥40 µg/g) at years one or two were offered colonoscopy early; all others were offered colonoscopy at 3 years. Diagnostic accuracy for CRC and advanced adenomas (AAs) was estimated considering multiple tests and thresholds. We calculated incremental costs per additional AA and CRC detected by colonoscopy versus FIT surveillance. RESULTS: 74% (5938/8009) of invitees were included in our study having participated at year 1. Of these, 97% returned FITs at years 2 and 3. Three-year cumulative positivity was 13% at the 40 µg/g haemoglobin threshold and 29% at 10 µg/g. 29 participants were diagnosed with CRC and 446 with AAs. Three-year programme sensitivities for CRC and AAs were, respectively, 59% and 33% at 40 µg/g, and 72% and 57% at 10 µg/g. Incremental costs per additional AA and CRC detected by colonoscopy versus FIT (40 µg/g) surveillance were £7354 and £180 778, respectively. CONCLUSIONS: Replacing 3 yearly colonoscopy surveillance in intermediate-risk patients with annual FIT could reduce colonoscopies by 71%, significantly cut costs but could miss 30%-40% of CRCs and 40%-70% of AAs. TRIAL REGISTRATION NUMBER: ISRCTN18040196; Results.

Practical guidance on the use of faecal calprotectin.

Differentiation between inflammatory bowel disease (IBD) and functional gut disorders, and the determination of mucosal disease activity in established cases of IBD remain the cornerstones of disease diagnosis and management. Non-invasive, accurate biomarkers of gut inflammation are needed due to the variability of symptoms, the inaccuracies of currently available blood markers and the cost and invasive nature of endoscopy. Numerous biomarkers have been used and/or considered with some in current use. This article reviews the current evidence base around the indications for using biomarkers and their limitations, with a particular focus on faecal calprotectin.

Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms.

OBJECTIVE: In primary care, assessing which patients with bowel symptoms harbour significant disease (cancer, higher-risk adenoma or IBD) is difficult. We studied the diagnostic accuracies of faecal haemoglobin (FHb) and faecal calprotectin (FC) in a cohort of symptomatic patients. DESIGN: From October 2013 to March 2014, general practitioners were prompted to request FHb and FC when referring patients with bowel symptoms to secondary care. Faecal samples were analysed for haemoglobin (EIKEN OC-Sensor io) and calprotectin (BÜHLMANN Calprotectin ELISA). Patients triaged to endoscopy were investigated within 6 weeks. All clinicians and endoscopists were blind to the faecal test results. The diagnostic accuracies of FHb and FC for identification of significant bowel disease were assessed. RESULTS: 1043 patients returned samples. FHb was detectable in 57.6% (median 0.4 µg/g, 95% CI 0.4 to 0.8; range 0-200). FC at 50 µg/g or above was present in 60.0%. 755 patients (54.6% women, median age 64 years (range 16-90, IQR 52-73)) returned samples and completed colonic investigations. 103 patients had significant bowel disease; the negative predictive values of FHb for colorectal cancer, higher-risk adenoma and IBD were 100%, 97.8% and 98.4%, respectively. Using cut-offs of detectable FHb and/or 200 µg/g FC detected two further cases of IBD, one higher-risk adenoma and no additional cancers. CONCLUSIONS: In primary care, undetectable FHb is a good 'rule-out' test for significant bowel disease and could guide who requires investigation.