Search

BACKGROUND: Screening for colorectal cancer by use of guaiac-based faecal occult blood tests (FOBT) reduces disease-specific mortality. However, due to imperfect specificity, about half of individuals positive for guaiac FOBT are negative for neoplasia on colonoscopy. We aimed to assess whether the testing of individuals positive for guaiac FOBT in a screening programme for colorectal cancer by use of a sensitive immunochemical FOBT could select more appropriately those who should receive colonoscopy. METHODS: We invited individuals who were guaiac FOBT positive in the second screening round of a pilot study in Scotland, UK, to give two samples, each from separate stools, for immunochemical FOBT while awaiting colonoscopy. Results were classed as: both samples negative (N/N), one sample negative and one positive (N/P), and both samples positive (P/P); data were assessed for sampling bias. We compared immunochemical findings with those from colonoscopy using odds ratios of positive samples (P/P) versus negative (N/N and N/P). Sensitivity, specificity, and positive and negative likelihood ratios for cancer, and for cancer and high-risk adenomatous polyps were also calculated. FINDINGS: 1486 participants were invited and 801 (54%) sets of duplicate samples were returned. We found no evidence of sampling bias with regard to sex, age, or degree of positivity on guaiac FOBT. Of 800 sets returned with consent and analysed, 173 (22%) were N/N, 129 (16%) were N/P, and 498 (62%) were P/P. Chi2 test showed a highly significant positive correlation between degree of positivity on guaiac FOBT and on immunochemical FOBT (p<0.003). 795 individuals had data for colonoscopy: one (<1%) of 171 N/N participants and one (<1%) of 127 N/P participants had colorectal cancer, compared with 38 (8%) of 497 P/P participants; adenomatous polyps were found in 28 (16%) N/N individuals, 24 (19%) N/P individuals, and 193 (39%) P/P individuals. Normal colonoscopy was less common in the P/P group (85 [17%]) than in the N/N (67 [39%]) and N/P (49 [39%]) groups. The odds ratio for P/P being associated with cancer was 7.57 (95% CI 1.84-31.4) and with high-risk adenomatous polyps was 3.11 (1.86-5.18). Sensitivity of a P/P result for cancer was 95.0% (81.8-99.1), and for cancer and high-risk adenomatous polyps was 90.1% (84.4-94.0); specificity was 39.5% (36.0-43.1) and 47.8% (43.9-51.8), respectively. INTERPRETATION: Immunochemical FOBT for individuals with positive guaiac FOBT could decrease substantially the number of false positives in a screening programme for colorectal cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of the UK colorectal cancer guaiac faecal occult blood test screening pilot studies on incidence trends, stage distribution and mortality trends. Design: Ecological study. Setting: Scotland and the West Midlands. Data: We extracted anonymised colorectal cancer (ICD-10 C18-C20) registration (1982-2006) and death records (1982-2007), along with corresponding mid-year population estimates. Intervention: Residents of the screening pilot areas, in the age group 50-69 years, were offered biennial guaiac faecal occult blood test screening from 2000 onwards. Screening was not offered routinely in non-pilot areas until the start of the roll-out of the national screening programmes in England and in Scotland in 2006 and 2007, respectively. Main Outcome Measures: We analysed trends in age-specific incidence and mortality rates, and Dukes' stage distribution. Within each country/region, we compared the screening pilot areas to non-screening pilot ('control') areas using Chi square tests and Poisson regression modelling. Results: Following the start of the screening pilots, as expected in the prevalent round of a new screening programme, in the pilot areas there was a short-lived increase in incidence of colorectal cancer among 50-69 year olds except for females in the West Midlands. A trend towards earlier stage and less advanced disease was also observed, with males showing significant increases in Dukes' A and corresponding decreases in Dukes' C in the screening pilot areas (all P < 0.03). With the exception of females in the West Midlands, mortality rates for colorectal cancer decreased significantly and at a faster rate in the populations invited for screening. Conclusion: The existence of a natural control population not yet invited for screening provided a unique opportunity to assess whether the benefits of colorectal cancer screening, beyond the setting of a randomised controlled trial, could be detected using routinely collected statistics. Our analysis suggests that screening will fulfil its aim of reducing mortality from colorectal cancer. [ABSTRACT FROM AUTHOR]

Aim: Faecal immunochemical tests (FIT) are highly sensitive for colorectal cancer (CRC) detection. Little evidence exists regarding repeat FIT. The repeat FIT (RFIT) study aimed to determine whether second and third FIT provide reassurance and improve CRC or significant bowel disease (SBD) identification., Methods: This was a prospective observational study. Patients recruited from urgent referrals returned three FIT and underwent colonoscopy. Chi-square tests compared categorical data. Diagnostic accuracy variables (sensitivity/specificity/positive predictive value [PPV]/negative predictive value [NPV]) were calculated for one, two and three FIT (95% CI). Three negative FIT (<10 μg Hb/g of faeces [μg/g]) groups (one, two, three) were compared with positive groups (one or more FIT ≥10 μg/g). CRC and SBD detection rates were compared by strategy., Results: A total of 460 patients (mean age: 66.8 years, 233 males and 227 females, 23 CRC, 80 SBD) were included in the study. For one, two and three negative FIT, CRC sensitivity remained static (95.7%); specificity (44.6%, 40.7% and 38.4%) and NPV decreased (99.5%, 99.4% and 99.4%). For SBD, sensitivity increased (78.8%, 83.8% and 86.3%), specificity decreased (47.4%, 43.7% and 41.6%) and NPV increased (91.4%, 92.7% and 93.5%). In one, two and three positive FIT groups, CRC detection was 8.3%,16.1% and 20.9%. CRC mean FIT was 150 μg/g, <6 μg/g for benign pathology., Conclusions: One or more negative FIT increases the sensitivity for CRC/SBD. Repeating FIT provides greater differentiation of patients with and without CRC/SBD compared to single FIT but is associated with decreased specificity and PPV. Multiple negative FIT may offer reassurance; however, application of repeating FIT may be restricted given the associated increase in investigations., (© 2024 The Author(s). Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Aim: Faecal immunochemical testing (FIT) is used in the detection of colorectal cancer (CRC). FIT is invariably used at a single faecal haemoglobin (f-Hb) concentration threshold. The aim of this observational study was to explore risk scoring models (RSMs) with f-Hb and other risk factors for CRC in symptomatic patients attending primary care, potentially speeding diagnosis and saving endoscopy resources., Method: Records of patients completing FIT were linked with The Scottish Cancer Registry and with other databases with symptoms, full blood count and demographic variables, and randomized into derivation and validation cohorts. Stepwise multivariable logistic regression created RSMs assessed in the validation cohort., Results: Of 18 805 unique patients, 9374 and 9431 were in the derivation and validation cohorts, respectively: f-Hb, male sex, increasing age, iron deficiency anaemia and raised systemic immune inflammation index created the final RSM. A risk score threshold of ≥2.363, generating the same number of colonoscopies as a f-Hb threshold of ≥10 μg Hb/g gave improved sensitivity for CRC in both cohorts. A RSM which excluded f-Hb was used to investigate the effect of raising the f-Hb threshold from ≥10 to ≥20 μg Hb/g in those with a low risk score. This approach would have generated 234 fewer colonoscopies but missed four CRCs., Conclusion: The RSM conferred no significant benefit to patients with very low f-Hb and CRC. Alternative strategies combining FIT with other variables may be more appropriate for safety-netting of symptomatic patients. Further work to develop and investigate the value of RSM for significant bowel disease other than CRC may also be beneficial., (© 2024 Association of Coloproctology of Great Britain and Ireland.)

Objective: To compare interval cancer proportions (ICP) in the faecal immunochemical test (FIT)-based Scottish Bowel Screening Programme (SBoSP) with the former guaiac faecal occult blood test (gFOBT)-based SBoSP and investigate associations between interval cancer (IC) and faecal haemoglobin concentration (f-Hb) threshold, sex, age, deprivation, site, and stage., Methods: The ICP data from first year of the FIT-based SBoSP and the penultimate year of the gFOBT-based SBoSP were compared in a prospective cohort design., Results: With FIT, 801 colorectal cancers (CRCs) were screen detected (SDC), 802 were in non-participants, 548 were ICs, 39 were colonoscopy missed and 72 were diagnosed after incomplete screening; with gFOBT: 540, 904, 556, 45, and 13, respectively. FIT had a significantly higher proportion of SDC compared to IC than gFOBT. For FIT and gFOBT, ICP was significantly higher in women than men. As f-Hb threshold increased, ICP increased and, for any f-Hb threshold for men, a lower threshold was required for comparable ICP in women. In Scotland, the current threshold of ≥80 µg Hb/g faeces would have to be lowered to ≥40 µg Hb/g faeces for women to achieve sex equality for ICP. In the FIT-based SBoSP, there were four times as many stage I SDC than IC. This was reversed in advanced stages, with twice as many stage IV CRC diagnosed as IC versus SDC., Conclusions: Reducing the numbers of IC requires lowering the f-Hb threshold. Using different f-Hb thresholds for women and men could eliminate the sex disparity, but with additional colonoscopy., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aimed to develop a risk-scoring model in the Scottish Bowel Screening Programme incorporating faecal haemoglobin concentration with other risk factors for colorectal cancer., Methods: Data were collected for all individuals invited to participate in the Scottish Bowel Screening Programme between November 2017 and March 2018 including faecal haemoglobin concentration, age, sex, National Health Service Board, socioeconomic status, and screening history. Linkage with The Scottish Cancer Registry identified all screening participants diagnosed with colorectal cancer. Logistic regression was performed to identify which factors demonstrated significant association with colorectal cancer and could be used in the development of a risk-scoring model., Results: Of 232,076 screening participants, 427 had colorectal cancer: 286 diagnosed following a screening colonoscopy and 141 arising after a negative screening test result giving an interval cancer proportion of 33.0%. Only faecal haemoglobin concentration and age showed a statistically significant association with colorectal cancer. Interval cancer proportion increased with age and was higher in women (38.1%) than men (27.5%). If positivity in women were mirrored in men at each age quintile interval cancer proportion would still have remained higher in women (33.2%). Moreover, an additional 1201 colonoscopies would be required to detect 11 colorectal cancers., Conclusions: Development of a risk scoring model using early data from the Scottish Bowel Screening Programme was not feasible due to most variables showing insignificant association with colorectal cancer. Tailoring the faecal haemoglobin concentration threshold according to age could help to diminish some of the disparity in interval cancer proportion between women and men. Strategies to achieve sex equality using faecal haemoglobin concentration thresholds depend considerably on which variable is selected for equivalency and this requires further exploration., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers., Design: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles., Results: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states ( phase I ), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations ( phase II ). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence., Conclusion: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact., Competing Interests: Competing interests: Board membership: TRL, RES, LG, FM, CS, RS, H-MC, ED, AK, HS, GAM, SI. Consultancy: LG, UL, GPY, FM, JM, SG, ED, AK, HS, SI. Expert testimony: FM. Grants or contract research: RSB, TRL, RES, FM, RS, FM, ED, ML, GAM, LC. Lectures/Other education events: LG, FM, H-MC, ED, AK. Patents: GPY, RSB, BC, AK, GAM. Receipt of equipment or supplies: LG, RES, ED, ML, GAM. Stock/Stock options: GPY, UL, JM, SG, ED, AK, GAM. Other professional relationships: GPY, SG., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Faecal hemoglobin concentrations (f-Hb) can be quantitated using faecal immunochemical test for haemoglobin (FIT) analytical systems. FIT are of proven value and widely used in colorectal cancer (CRC) screening. Several factors affect f-Hb including sex, age, deprivation, geographical region, and FIT system. Thus, FIT data may not be transferable. Women are disadvantaged in programmes using a single f-Hb threshold for all participants, but risk scoring or sex stratified thresholds could be used to minimise this problem. In addition, low but detectable f-Hb, below the threshold, implies future risk of CRC. In several countries, where colonoscopy resources are constrained, FIT are now accepted as of added value in assessment of patients presenting in primary or secondary care with symptoms, although some serious colorectal disease is missed. Elevated f-Hb in the absence of any discernible colorectal lesions is common and has been found in several diseases with a systemic inflammatory component, including circulatory, respiratory, digestive, neuropsychological, blood and endocrine diseases, and others. There is growing evidence for the value of f-Hb in post-polypectomy surveillance, potentially saving costs and colonoscopy. There may be a role for FIT systems which have lower limits of detection than currently available methods. The faecal material remaining in FIT specimen collection devices could be used for further studies, including assessment of the microbiome. The estimation of f-Hb is now a mature investigative tool but further research will undoubtedly expand applications of value., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Author. Published by Elsevier Ltd.. All rights reserved.)

Background: Colorectal cancer (CRC) screening using faecal tests reduces disease-specific mortality. To investigate mortality and its association with sex, rates in women and men, and in different age ranges, were examined, before and after screening began in Scotland., Methods: From 1990-99, no structured screening existed. Three pilots ran from 2000 to 2007 and subsequent full roll-out completed in 2009. Crude mortality rates for 1990-2020 were calculated relative to Scottish population estimates, and age-sex standardized rates calculated for all, pre-screening (<50 years), screening (5-74 years) and post-screening (>74 years) age ranges., Results: CRC mortality declined from 1990 to 2020, but not linearly, and differed between sexes. In women, 1990-99 showed a steady decline [average annual percentage change (AAPC): -2.1%, 95% confidence interval (CI): -2.8% to -1.4%], but a less marked decline after 2000 (AAPC: -0.7%, 95% CI: -0.9% to -0.4%). In men, no clear decline was seen from 1990 to 1999 (AAPC: -0.4%, 95% CI: -1.1% to 0.4%), but mortality declined from 2000 to 2020 (AAPC: -1.7%, 95% CI: -1.9% to -1.5%). This pattern was exaggerated in the screening age ranges. For 2000-20, the overall reduction in mortality was less in women and in the screening age range. In the post-screening age range, reductions were smaller, but an increase was seen in the pre-screening age range, greater in women., Conclusions: CRC mortality fell during 1990-2020, but the decline differed markedly between sexes, indicating a larger beneficial effect of screening on CRC mortality in men compared to women: use of different thresholds for the sexes might lead to equality., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

Objectives: The exploration of the metabolites in the degradation pathways of vitamin D (VTD) has gained importance in recent years and simultaneous quantitation of twenty-five-hydroxy vitamin D (25(OH)D) mass concentration together with 24,25-dihydroxyvitamin D (24,25(OH)2D) has been proposed as a newer approach to define VTD deficiency. Yet, no data are available on 24,25(OH)2D biological variation (BV). In this study, we evaluated 24,25(OH)2D's BV on the European Biological Variation Study (EuBIVAS) cohort samples to determine if analytical performance specifications (APS) for 24,25(OH)2D could be generated., Methods: Six European laboratories recruited 91 healthy participants. 25(OH)D and 24,25(OH)2D concentrations in K 3 -EDTA plasma were examined weekly for up to 10 weeks in duplicate with a validated LC-MS/MS method. The Vitamin D Metabolite Ratio (24,25(OH)2D divided by 25(OH)D × 100) was also calculated at each time point., Results: Linear regression of the mean 24,25(OH)2D concentrations at each blood collection showed participants were not in steady state. Variations of 24,25(OH)2D over time were significantly positively associated with the slopes of 25(OH)D concentrations over time and the concentration of 25(OH)D of the participant at inclusion, and negatively associated with body mass index (BMI), but not with age, gender, or location of the participant. The variation of the 24,25(OH)2D concentration in participants over a 10 weeks period was 34.6%. Methods that would detect a significant change linked to the natural production of 24,25(OH)2D over this period at p<0.05 would need a relative measurement uncertainty ( u %)<14.9% while at p<0.01, relative measurement uncertainty should be <10.5%., Conclusions: We have defined for the first time APS for 24,25(OH)2D examinations. According to the growing interest in this metabolite, several laboratories and manufacturers might aim to develop specific methods for its determination. The results presented in this paper are thus necessary prerequisites for the validation of such methods., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Background: Faecal Immunochemical tests (FITs) in the assessment of patients presenting with symptoms have generally used a single sample. Little evidence pertains to the use of replicate, where a number of tests are done prior to decision-making or repeat FIT, where additional FIT are performed following clinical decision-making. Overwhelmingly, research has focussed on FIT to help identify colorectal cancer (CRC). The aim of this review is to assess the available literature concerning replicate and repeat FIT in symptomatic patients to help generate consensus and guide future research., Methods: The terms 'faecal immunochemical test' or 'FIT' were combined with 'multiple' or 'repeat'. EMBASE, Medline and PubMed database and other searches were conducted. All papers published in English were included with no exclusion date limits until November 2021., Results: Of the 161 initial papers screened, seven were included for review. Qualitative and quantitative FIT outcomes were assessed in the studies. The primary aims of most related to whether replicate FIT increased diagnostic yield of CRC, with colonoscopy used as the reference standard. One publication assessed the impact of a new COVID-adapted pathway on CRC detection. No consensus on replicate FIT was apparent. Some concluded that FITs may help minimise missed CRC diagnoses: others showed no increase in diagnostic yield of CRC., Conclusions: Current evidence on replicate and repeat FIT is both minimal and conflicting. FIT is a superb clinical tool, but significant gaps surrounding application remain. Further studies relating to replicate and repeat FIT are required.

Objective: Roll-out of population-based colorectal cancer (CRC) screening with faecal immunochemical test (FIT) is limited by availability of further investigations, particularly colonoscopy and examination of excised lesions. Our objective was to assess whether variation in number of faecal samples and threshold adjustment can optimise resource utilisation and CRC detection rate., Methods: Three different screening strategies were compared for the same FIT threshold using a quantitative FIT system: one FIT, positive when > 20 µg Hb/g faeces; two FIT, positive when either was > 20 µg Hb/g faeces; and two FIT, positive when the mean was > 20 µg Hb/g faeces. We calculated changes in the size of population the provider could invite to screening for an equal number of screening positive results, and CRC and adenoma detected., Results: In our setting, Region of Murcia, south of Spain (not fully rolled out screening programme), changing the usual strategy of two FIT, positive when either to positive when the mean was > 20 µg Hb/g faeces, would increase population invited by 37.81% with the same number of positive results (which would generate a CRC detection rate of 19.2%). In a fully rolled out programme, changing the strategy from one to two FIT (positive when the mean is > 20 µg Hb/g faeces), would increase CRC detection rate by 4.64% with an increase of only 13.34% in positive FIT., Conclusions: In a population-based CRC screening programme, smart use of number of FITs and positivity threshold can increase population invited and CRC detection without increasing the number of colonoscopies and pathological examinations needed.

Objective: How faecal haemoglobin concentrations (f-Hb) vary from one round to the next in a colorectal cancer (CRC) screening programme, and relate to colonoscopy findings, are unknown. Our aim was to use data from the first two rounds of the faecal immunochemical test (FIT) based Scottish Bowel Screening Programme (SBoSP) to explore these issues., Methods: Faecal haemoglobin concentration (f-Hb) percentiles in the second round were compared with those in the first when the first round yielded a negative FIT result (<80 µg Hb/g faeces), a positive FIT but no colonoscopy, CRC, all adenoma, and a negative colonoscopy. In addition, the outcomes in the first and second rounds were compared., Results: The profiles of f-Hb in the first and second rounds differed in (a) those who had had a negative FIT result in the first round and (b) those in whom neoplastic pathology had been found. In contrast, the pattern of difference between profiles in those who had had a negative colonoscopy was very similar to that in those in whom an adenoma had been found. In addition, the risk of CRC being diagnosed in the second round after a negative colonoscopy in the first was 3.0%, not very different to that after a negative test result (4.9%)., Conclusions: Adenomas may be rarely the cause of a positive FIT result. An alternative explanation as to why these are detected using FIT is required. In addition, a negative colonoscopy for a positive FIT result does not rule out the finding of significant neoplastic pathology in the next round.

Objective: Guidelines on colorectal cancer (CRC) screening with guaiac faecal occult blood tests (gFOBTs) and faecal immunochemical tests (FITs) include the need for a pilot before a programme is introduced. Interval cancers (ICs), cancers arising after a negative screening test result but before the next scheduled invite, are important indicators of programme quality. Our aim was to compare IC in the gFOBT-based Scottish Bowel Screening Programme (SBoSP), a FIT-based pilot, and the FIT-based SBoSP, to assess if the pilot provided data that was reflected in the subsequent programme., Design: The IC proportions (ICPs) data ([IC/(IC + screen detected CRC)] x 100) from the penultimate year of the gFOBT-based SBoSP, the 6-month pilot and the first year of the FIT-based SBoSP were compared. To ensure appropriate comparison, these data were only from the two pilot NHS Boards., Results: For all participants, and females and males, the ICPs were very similar in the gFOBT-based SBoSP and the pilot. The faecal haemoglobin concentration (f-Hb) threshold for the pilot was set at ≥80 μg Hb/g faeces. However, in marked contrast, in the FIT-based SBoSP, at the same threshold, the ICPs were lower. In all three groups, the ICPs were higher in females than in males., Conclusions: Data on variables in pilots, including ICP, can be informative, but only if variables such as FIT system are held consistent between pilot and programme. Lowering the f-Hb threshold for females to give the same ICP as males might be a strategy to minimise sex inequality.

Currently, women are disadvantaged compared to men in colorectal cancer (CRC) screening, particularly in programmes that use faecal immunochemical tests for haemoglobin (FIT) followed by colonoscopy. Although there is no single cause for all the known disadvantages, many can be attributed to the ubiquitous finding that women have lower faecal haemoglobin concentrations (f-Hb) than men; there are many plausible reasons for this. Generally, a single f-Hb threshold is used in CRC screening programmes, leading to lower positivity for women than men, which causes poorer outcomes for women, including lower CRC detection rate, higher interval cancer (IC) proportion, and higher CRC mortality. Many of the now widely advocated risk scoring strategies do include factors taking account of sex, but these have not been extensively piloted or introduced. Using different f-Hb thresholds for the sexes seems advantageous, but there are difficulties, including deciding which characteristic should be selected to achieve equivalency, for example, positivity, IC proportions, or specificity. Moreover, additional colonoscopy resources, often constrained, would be required. Governments and their agencies should be encouraged to prioritise the allocation of resources to put simple strategies into practice, such as different f-Hb thresholds to create equal positivity in both sexes., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Polypectomy may be performed at colonoscopy and then subsequent surveillance undertaken. It is thought that faecal haemoglobin concentration (f-Hb), estimated by quantitative faecal immunochemical tests (FIT), might be a useful tumour marker., Methods: Consecutive patients enrolled in colonoscopy surveillance were approached at two hospitals. A specimen for FIT was provided before colonoscopy and, ideally after 3 weeks, a second FIT sample from those who had polypectomy. A single FIT system (OC-Sensor io, Eiken Chemical Co., Ltd) was used to generate f-Hb., Results: 1103 Patients were invited; 643 returned a FIT device (uptake: 58.3%). Four patients had known inflammatory bowel disease (IBD) and were excluded, leaving 639 (57.9%) with an age range of 25-90 years (median 64 years), 54.6% male. Of 593 patients who had a f-Hb result and completed colonoscopy, advanced neoplasia was found in 41 (6.9%); four colorectal cancer (CRC): 0.7% and 37 advanced adenoma (AA): 6.3%, and a further 127 (21.4%) had non-advanced adenoma (NAA). The median f-Hb was significantly greater in AA as compared to NAA; 6.0 versus 1.0 μg Hb/g faeces, p < 0.0001.134/164 (81.7%) of invited patients returned a second FIT device: 28 were patients with AA in whom median pre-polypectomy f-Hb was 19.2, falling to 3.5 μg Hb/g faeces post-polypectomy, p = 0.01, and 106 with NAA had median pre-polypectomy f-Hb 0.8 compared to 1.0 μg Hb/g faeces post-polypectomy, p = 0.96., Conclusions: Quantitative FIT could provide a good tumour marker in post-polypectomy surveillance, reduce colonoscopy requirements and minimise potential risk to patients.

Objectives: Faecal immunochemical tests for haemoglobin (FIT) are used in colorectal cancer (CRC) screening programmes and to triage patients presenting with symptoms suggestive of CRC for further bowel investigations. There are a number of quantitative FIT analytical systems available. Currently, there is no harmonisation or standardisation of FIT methods. The aim of the study was to assess the comparability of numerical faecal haemoglobin concentrations (f-Hb) obtained with four quantitative FIT systems and the diagnostic accuracy at different f-Hb thresholds., Methods: A subgroup of the National Institute for Health and Care Excellence (NICE) FIT study, a multicentre, prospective diagnostic accuracy study were sent four FIT specimen collection devices from four different FIT systems or two FIT devices for one FIT system. Faecal samples were examined and analysis of results carried out to assess difference between methods at thresholds of limit of detection (LoD), 10 µg haemoglobin/g faeces (µg/g) and 100 μg/g., Results: 233 patients returned specimen collection devices for examination on four different systems; 189 patients returned two FIT kits for one system. At a threshold of 100 μg/g the sensitivity is the same for all methods. At lower thresholds of LoD and 10 μg/g differences were observed between systems in terms of patients who would be referred and diagnostic accuracies., Conclusions: The lack of standardisation or harmonisation of FIT means that differences are observed in f-Hb generated on different systems. Further work is required to understand the clinical impact of these differences and to minimise them., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: There is evidence that colorectal cancer screening using faecal haemoglobin is less effective in women than men. The faecal haemoglobin concentrations were therefore examined in women and men with screen-detected colorectal cancer., Setting: Scottish Bowel Screening Programme, following the introduction of a faecal immunochemical test from November 2017, to March 2020 ., Methods: Data were collated on faecal haemoglobin concentrations, pathological stage and anatomical site of the main lesion in participants who had colorectal cancer detected. The data in women and men were compared., Results: For the faecal haemoglobin concentrations studied ( > 80 µg Hb/g faeces), the distributions indicated lower concentrations in women. Marked differences were found between women and men diagnosed with colorectal cancer. The median faecal haemoglobin concentration for women ( n  = 720) was 408 µg Hb/g faeces compared to 473 µg Hb/g faeces for men ( n  = 959) ( p  = 0.004) and 50.6% of the results were > 400 µg Hb/g faeces in women; in men, this was 57.8%. The difference in faecal haemoglobin concentrations in women and men became less statistically significant as stage advanced from stages I-IV. For right-sided, left-sided and rectal colorectal cancer, a similar gender difference persisted in all sites. Differences in faecal haemoglobin between the genders were significant for left-sided cancers and stage I and approached significance for rectal cancers and stage II, but all sites and stages showed lower median faecal haemoglobin concentrations for women., Conclusions: To minimise gender inequalities, faecal immunochemical test-based colorectal cancer screening programmes should evaluate a strategy of using different faecal haemoglobin concentration thresholds in women and men.

Multimorbidity is the major cause of ill-health and premature death in developed countries. The ability to identify individuals at risk of developing chronic disease, particularly multimorbidity, reliably, and simply, and to identify undiagnosed disorders, is vital to reducing the global burden of disease. This narrative review, the first of recent studies, demonstrates that raised faecal haemoglobin concentration (f-Hb) is associated with increased all-cause and cause-specific mortality and with longer-term conditions including diabetes, hypertension, cardiovascular disease, and psoriasis, and with probable intake of particulate matter. We and others have hypothesized that elevated f-Hb (measured using a faecal immunochemical test) has considerable potential to identify individuals at risk of, or who already have, early stage, undiagnosed chronic disease. If f-Hb does prove to be an effective biomarker for chronic disease and multimorbidity, individuals with detectable f-Hb, but without an obvious source of gastrointestinal blood loss, could benefit from further assessment and early intervention. To test this hypothesis rigorously, longitudinal data-linkage methodology is required linking colorectal cancer screening data, and data on patients presenting with lower gastrointestinal symptoms, with routinely collected health information.

Aims: The presence of detectable faecal haemoglobin (f-Hb) has been shown to be associated with all-cause mortality and with death from a number of chronic diseases not known to cause gastrointestinal blood loss. This effect is independent of taking medicines that increase the risk of bleeding. To further investigate the association of f-Hb with chronic disease, the relationship between f-Hb and prescription of medicines for a variety of conditions was studied., Methods: All subjects (134 192) who participated in guaiac faecal occult blood test (gFOBT) screening in Tayside, Scotland, between March 2000 and March 2016, were studied in a cross-sectional manner by linking their gFOBT result (abnormal or normal) with prescribing data at the time of the test., Results: The screening participants with an abnormal gFOBT result were more likely to have been being prescribed medicines for heart disease, hypertension, diabetes and depression than those with a normal test result. This association persisted after adjustment for sex, age and deprivation (OR 1.35 (95%CI 1.23 to 1.48), 1.39 (1.27 to 1.52), 1.35 (1.15 to 1.58), 1.36 (1.16 to 1.59), all p<0.0001, for the four medicine categories, respectively)., Conclusions: The results of this study confer further substantial weight to the concept that detectable f-Hb is associated with a range of common chronic conditions that have a systemic inflammatory component; we speculate that f-Hb might have potential in identifying individuals who are high risk of developing chronic conditions or are at an early stage of disease., Competing Interests: Competing interests: CGF undertook consultancy with Immunostics Inc., Ocean, New Jersey, USA, the manufacturer of the gFOBT kits used in the Pilot and Programme., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Lower gastrointestinal (GI) symptoms are poor predictors of colorectal cancer (CRC). The aim of this study was to examine the diagnostic yield of colonoscopy by faecal haemoglobin (f-Hb) concentration in symptomatic patients assessed in primary care by faecal immunochemical testing (FIT)., Method: In three Scottish NHS Boards, FIT kits (HM-JACKarc, Hitachi Chemical Diagnostics Systems Co., Ltd, Tokyo, Japan) were used by general practitioners to guide referrals for patients with lower GI symptoms (laboratory data studied for 12 months from December 2015 onwards in Tayside, 18 months from June 2018 onwards in Fife and 5 months from September 2018 onwards in Greater Glasgow and Clyde). Cases of CRC diagnosed at colonoscopy were ascertained from colonoscopy and pathology records., Results: Four thousand eight hundred and forty one symptomatic patients who underwent colonoscopy after FIT submission were included. Of the 2166 patients (44.7%) with f-Hb <10 µg Hb/g faeces (µg/g), 14 (0.6%) were diagnosed with CRC, with a number needed to scope (NNS) of 155. Of the 2675 patients (55.3%) with f-Hb ≥10 µg/g, 252 were diagnosed with CRC (9.4%) with a NNS of 11. Of the 705 patients with f-Hb ≥400 µg/g, 158 (22.4%) were diagnosed with CRC with a NNS of 5. Over half of those diagnosed with CRC with f-Hb <10 µg/g had coexisting anaemia., Conclusion: Symptomatic patients with f-Hb ≥10 µg/g should undergo further investigation for CRC, while higher f-Hb concentrations could be used to triage for urgency during the COVID-19 recovery phase. Patients with f-Hb <10 µg/g and without anaemia are very unlikely to be diagnosed with CRC and the majority need no further investigation., (© 2020 The Association of Coloproctology of Great Britain and Ireland.)

Background: Faecal haemoglobin concentration (f-Hb), estimated using a faecal immunochemical test, can be safely implemented in primary care to assess risk of colorectal cancer (CRC). Clinical outcomes of patients presenting with symptoms of lower gastrointestinal disease were examined using an extensive range of f-Hb thresholds to decide on reassurance or referral for further investigation., Methods: All patients who attended primary care and submitted a single faecal specimen faecal immunochemical test in the first year of the routine service had f-Hb estimated using HM-JACKarc: f-Hb thresholds from <2 to ≥ 400 µg Hb/g faeces (µg/g) were examined., Results: Low f-Hb thresholds of <2, <7, <10 and <20 µg/g gave respective CRC risks of 0.1, 0.3, 0.3 and 0.4%, numbers needed to scope for one CRC of 871, 335, 300 and 249, and 'false negative' rates of 2.9, 11.4, 13.3 and 17.1%. With thresholds of <2, <7, <10 and <20 µg/g, 48.6, 74.6, 78.1 and 83.2% respectively of symptomatic patients could be managed without further investigation. With reassurance thresholds of <2 µg/g, <7 µg/g and <10 µg/g, the thresholds for referral for urgent investigation would be >400 µg/g, ≥200 µg/g and ≥100 µg/g. However, patients with a f-Hb concentration of <10 or <20 µg/g with iron deficiency anaemia, or with severe or persistent symptoms, should not be denied further investigation., Conclusions: In primary care, f-Hb, in conjunction with clinical assessment, can safely and objectively determine individual risk of CRC and decide on simple reassurance or urgent, or routine referral.

Currently the 25-hydroxy vitamin D (25(OH)D) concentration is thought to be the best estimate of the vitamin D status of an individual. Unfortunately, its measurement remains complex, despite recent technological advances. We evaluated the biological variation (BV) of 25(OH)D in order to set analytical performance specifications (APS) for measurement uncertainty (MU). Six European laboratories recruited 91 healthy participants. The 25(OH)D concentrations in K 3 -EDTA plasma were examined weekly for up to 10 weeks in duplicate on a Lumipulse G1200 (Fujirebio, Tokyo, Japan). The linear regression of the mean 25(OH)D concentrations at each blood collection showed that participants were not in a steady state. The dissection of the 10-sample collection into two subsets, namely collections 1-5 and 6-10, did not allow for correction of the lack of homogeneity: estimates of the within-subject BV ranged from 5.8% to 7.1% and the between-subject BV ranged from 25.0% to 39.2%. Methods that would differentiate a difference induced by 25(OH)D supplementation at p < 0.05 should have MU < 13.6%, while at p < 0.01, the MU should be <9.6%. The development of APS using BV assumes a steady state of patients. The findings in this study suggest that patients are not in steady state. Therefore, APS that are based on MU appear to be more appropriate.

Objective: Faecal immunochemical tests (FIT) are replacing guaiac faecal occult blood tests (FOBT) in colorectal cancer (CRC) screening. Data from the first year of FIT screening were compared with those from FOBT screening and assumptions based on a pilot evaluation of FIT., Design: Data on uptake, positivity, positive predictive value (PPV) for CRC and higher-risk adenoma from participants in the first year of the FIT-based Scottish Bowel Screening Programme (n=919 665), with a threshold of 80 µg Hb/g faeces, were compared with those from the penultimate year of the FOBT-based programme (n=862 165) and those from the FIT evaluation (n=66 225)., Results: Overall, uptake of FIT was 63.9% compared with 56.4% for FOBT. Positivity was 3.1% and 2.2% with FIT and FOBT; increases were seen in both sexes, and across age range and deprivation. More CRC and adenomas were detected by FIT, but the PPV for CRC was less (5.2% with FIT and 6.4% with FOBT). However, for higher-risk adenoma, PPV was greater with FIT (24.3% with FIT and 19.3% with FOBT). In the previous FIT evaluation, uptake was 58.5% with FIT compared with 54.0% with FOBT; positivity was 2.5% with FIT and 2.0% with FOBT., Conclusion: Transition to FIT from FOBT produced higher uptake and positivity with lower PPV for CRC and higher PPV for adenoma. The FIT pilot evaluation underestimated uptake and positivity. Introducing FIT at the same threshold as the evaluation caused a 67.2% increase in colonoscopy demand instead of a predicted 10%., Competing Interests: Competing interests: CGF undertook consultancy with Immunostics Inc, Ocean, New Jersey, USA, and Hitachi Chemical Diagnostic Systems Co, Ltd, Tokyo, Japan., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Fecal immunochemical test (FIT) performance can be affected by post-collection variables. Collection technique might also affect fecal hemoglobin concentration (f-Hb). Variation in quantity of feces collected in samples returned in a colorectal cancer detection program, and the effects of under-sampling, were assessed., Methods: Collection devices obtained from patients undergoing FIT were assessed for the color (in five classes) of the feces in buffer, mass, and f-Hb. Associations between these were examined in an in vitro study on Hb-spiked feces. Variables possibly associated with under-sampling were investigated using multivariable logistic regression. The effect of low sample mass on clinical performance (false-negative results) was determined., Results: Of 6,898 samples collected by 3,449 individuals (46.9% male, median age: 65.3 years), the buffer was lightest in color in 362 (5.2%), and darkest in 420 (6.1%). Samples with the lightest color had a significantly lower f-Hb compared with all darker classes ( P < 0.001). Mass was recorded for 650 devices: The lightest colored samples had significantly lower mass ( P < 0.05). The correlation between mass and f-Hb was confirmed in vitro ( r = 0.897, P < 0.001). Low mass was not associated with age, sex, or technical factors ( P > 0.05). Under-sampling related to the lightest color was not associated with false-negative results for colorectal cancer and advanced adenoma, but was for all neoplasia and inflammatory bowel disease., Conclusions: Wide variation existed in the amount of feces collected. Under-sampling results in lower measured f-Hb and may increase false-negative results., Impact: Color of sample buffer could be used to identify inadequate sampling., (©2020 American Association for Cancer Research.)

Objectives Faecal immunochemical tests for haemoglobin (FIT) are becoming widely used in colorectal cancer (CRC) screening and assessment of symptomatic patients. Faecal haemoglobin concentration (f-Hb) thresholds are used to guide subsequent investigation. We established the distributions of f-Hb in a large screening population by sex, age, deprivation and geography. Methods Single estimates of f-Hb were documented for all individuals participating in the first 18 months of the Scottish Bowel Screening Programme (SBoSP). The distributions of f-Hb were generated for all participants, all men and women, and men and women by age quintile and deprivation quintile. Distributions were also generated by geographical region for all participants, men and women, and by deprivation. Comparisons of f-Hb distributions with those found in a pilot evaluation of FIT and three other countries were performed. Results f-Hb was documented for 887,248 screening participants, 422,385 men and 464,863 women. f-Hb varied by sex, age, deprivation quintile and geographical region. The f-Hb distributions by sex and age differed between the SBoSP and the pilot evaluation and the three other countries. Conclusions f-Hb is higher in men than in women and increases with age and deprivation in both sexes. f-Hb also varies by geographical region, independently of deprivation, and by country. The f-Hb distribution estimated by pilot evaluation may not represent the population distribution. Decision limits have advantages over reference intervals. Use of partitioned f-Hb thresholds for further investigation, based on the data generated, has advantages and disadvantages, as do risk scores based on a spectrum of influencing variables.

Background: Current guidelines document persistent rectal bleeding as an alarm symptom in patients presenting to primary care. We studied whether a faecal immunochemical test could assist in their assessment., Methods: From December 2015, faecal immunochemical tests were routinely available to primary care when assessing patients with new-onset bowel symptoms: general practitioners were encouraged to include faecal haemoglobin concentration (f-Hb) within any referral to secondary care. Results with f-Hb ≥10  μ g Hb/g faeces were defined as positive. The incidence of significant bowel disease (SBD: colorectal cancer [CRC], higher-risk adenoma [HRA: any ≥1 cm, or three or more] and inflammatory bowel disease [IBD]) at subsequent colonoscopy, referred symptoms and f-Hb were recorded., Results: Of 1447 patients with a faecal immunochemical test result and colonoscopy outcome, SBD was diagnosed in 296 patients (20.5%; 95 with CRC, 133 with HRA, and 68 with IBD). Four hundred and sixty-two patients (31.9%) reported rectal bleeding: 294 had f-Hb ≥10  μ g Hb/g faeces. At colonoscopy, 105/294 had SBD versus 14/168 with rectal bleeding and f-Hb <10  μ g Hb/g faeces ( P  < 0.0001), comprising one case of CRC (0.6%), 12 HRA (7.1%) and one new case of IBD (0.6%); further, the single cancer and 8 of the 12 HRA were located in the descending colon., Conclusion: Patients with rectal bleeding and f-Hb <10  μ g Hb/g faeces are unlikely to have SBD and could be investigated by sigmoidoscopy alone. Using the faecal immunochemical test to guide investigation of patients with rectal bleeding is a rational and practical way forward.

Background: Quantitative faecal immunochemical tests measure faecal haemoglobin concentration (f-Hb), which increases in the presence of colorectal neoplasia., Objective: We examined the diagnostic accuracy of faecal immunochemical test (FIT)in patients at increased risk of colorectal cancer (CRC) attending for surveillance colonoscopy as per national guidelines., Methods: A total of 1103 consecutive patients were prospectively invited to complete a FIT before their scheduled colonoscopy in two university hospitals in 2014- 2016. F-Hb was analysed on an OC-Sensor io automated analyser (Eiken Chemical Co., Ltd, Tokyo, Japan) with a limit of detection of 2 µg Hb/g faeces. The diagnostic accuracy of f-Hb for CRC and higher-risk adenoma was examined., Results: A total of 643 patients returned a faecal test. After excluding 4 patients with known inflammatory bowel disease, 639 (57.9%) remained in the study: age range: 25-90 years (median: 64 years, interquartile range (IQR): 55-71): 54.6% male. Of 593 patients who also completed colonoscopy, 41 (6.9%) had advanced neoplasia (4 CRC, 37 higher-risk adenoma). Of the 238 patients (40.1%) who had detectable f-Hb, 31 (13.0%) had advanced neoplasia (2 CRC, 29 higher-risk adenoma) compared with 10 (2.8%) in those with undetectable f-Hb (2 CRC, 8 higher-risk adenoma). Detectable f-Hb gave negative predictive values of 99.4% for CRC and 97.2% for CRC plus higher-risk adenoma., Conclusion: In patients at increased risk of CRC under colonoscopy surveillance, a test measuring faecal haemoglobin can provide an objective estimate of the risk of advanced neoplasia, and could enable tailored scheduling of colonoscopy.

Objectives: Flexible sigmoidoscopy screening at around age 60 can reduce colorectal cancer incidence. Insufficient evidence exists on flexible sigmoidoscopy at age 60 in a population being offered biennial faecal occult blood test screening from age 50. This randomized controlled trial assessed if flexible sigmoidoscopy would be an effective adjunct to faecal occult blood test., Methods: In the Scottish Bowel Screening Programme between June 2014 and December 2015, 51,769 individuals were randomized to be offered flexible sigmoidoscopy instead of faecal occult blood test at age 60 or to continue faecal occult blood test. Those not accepting flexible sigmoidoscopy and those with normal flexible sigmoidoscopy were offered faecal occult blood test. All with flexible sigmoidoscopy-detected neoplasia or a positive faecal occult blood test result were offered colonoscopy., Results: Overall flexible sigmoidoscopy uptake was 17.8%, higher in men than women, and decreased with increasing deprivation (25.7% in the least to 9.2% in the most deprived quintile). In those who underwent flexible sigmoidoscopy, detection rate for colorectal cancer was 0.13%, for adenoma 7.27%, and for total neoplasia 7.40%. In those who underwent colonoscopy after a positive flexible sigmoidoscopy, detection rate for colorectal cancer was 0.28%, adenoma 8.66%, and total neoplasia 8.83%. On an intention to screen basis, there was no difference in colorectal cancer detection rate between the study and control groups. Adenoma and total neoplasia detection rate were significantly higher in the study group, with odds ratios of 5.95 (95%CI: 4.69-7.56) and 5.10 (95%CI: 4.09-6.35), respectively., Conclusions: In a single screening round at age 60, there was low uptake and neoplasia detection rate. Flexible sigmoidoscopy detected significantly more neoplasia than faecal occult blood test alone.

Background Monthly medians of patient results are useful in assessment of analytical quality in medical laboratories. Separate medians by gender makes it possible to generate two independent estimates of contemporaneous errors. However, for plasma creatinine, reference intervals (RIs) are different by gender and also higher over 70 years of age. Methods Daily, weekly and monthly patient medians were calculated from the raw data of plasma creatinine concentrations for males between 18 and 70 years, males >70 years, females between 18 and 70 years and females >70 years. Results The medians of the four groups were all closely associated, with similar patterns. The mean of percentage bias from each group defined the best estimate of bias. The maximum half-range (%) of the bias evaluations provided an estimate of the uncertainty comparable to the analytical performance specifications: thus, bias estimates could be classified as optimum, desirable or minimum quality. Conclusions Medians by gender and age are useful in assessment of analytical stability for plasma creatinine concentration ranging from 60 to 90 μmol/L. The daily medians are valuable in rapid detection of large systematic errors, the weekly medians in detecting minor systematic errors and monthly medians in assessment of long-term analytical stability.

Background: Many patients present in primary care with lower bowel symptoms, but significant bowel disease (SBD), comprising colorectal cancer (CRC), advanced adenoma (AA), or inflammatory bowel disease (IBD), is uncommon. Quantitative faecal immunochemical tests for haemoglobin (FIT), which examine faecal haemoglobin concentrations (f-Hb), assist in deciding who would benefit from colonoscopy. Incorporation of additional variables in an individual risk-score might improve this approach. We investigated if the published f-Hb, age and sex test score (FAST score) added value., Methods: Data from the first year of routine use of FIT in primary care in one NHS Board in Scotland were examined: f-Hb was estimated using one HM-JACKarc FIT system (Kyowa Medex Co., Ltd., Tokyo, Japan) with a cut-off for positivity ≥10 μg Hb/g faeces. 5660 specimens were received for analysis in the first year. 4072 patients were referred to secondary care: 2881 (70.6%) of these had returned a FIT specimen. Of those referred, 1447 had colonoscopy data as well as the f-Hb result (group A): 2521 patients, also with f-Hb, were not immediately referred (group B). The FAST score was assessed in both groups., Results: 1196 (41.7%) of patients who returned a specimen for FIT analysis had f-Hb ≥10 μg Hb/g faeces. In group A, 252 of 296 (85.1%) with SBD had f-Hb > 10 μg Hb/g faeces, as did 528 of 1151 (45.8%) without SBD. Using a FAST score > 2.12, which gives high clinical sensitivity for CRC, only 1143 would have been referred for colonoscopy (21.0% reduction in demand): 286 of 296 (96.6%) with SBD had a positive FAST score, as did 857 of 1151 (74.5%) without SBD. However, one CRC, five AA and four IBD would have been missed. In group B, although 95.2% had f-Hb < 10 μg Hb/g faeces, 1371 (53.7%) had FAST score ≥ 2.12: clinical rationale led to only 122 of group B completing subsequent bowel investigations: a FAST score > 2.12 was found in 13 of 15 (86.7%) with SBD., Conclusions: The performance characteristics of the FAST score did not seem to enhance the utility of f-Hb alone. Locally-derived formulae might confer desired benefits.