Do risk scores improve use of faecal immunochemical testing for haemoglobin in symptomatic patients in primary care?

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.

Interval cancers in a national colorectal screening programme based on faecal immunochemical testing: Implications for faecal haemoglobin concentration threshold and sex inequality.

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.

Faecal haemoglobin: Measurement, applications, and future potential.

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.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

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.

Improved use of faecal immunochemical tests for haemoglobin in the Scottish bowel screening programme.

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.

Analytical performance specifications for the measurement uncertainty of 24,25-dihydroxyvitamin D examinations.

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 K3-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.

Sex variation in colorectal cancer mortality: trends and implications for screening.

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.

Replicate and repeat faecal immunochemical tests in symptomatic patients: A systematic review.

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.

Heterochromatin in the fungal plant pathogen, Zymoseptoria tritici: Control of transposable elements, genome plasticity and virulence.

Heterochromatin is a repressive chromatin state that plays key roles in the functional organisation of eukaryotic genomes. In fungal plant pathogens, effector genes that are required for host colonization tend to be associated with heterochromatic regions of the genome that are enriched with transposable elements. It has been proposed that the heterochromatin environment silences effector genes in the absence of host and dynamic chromatin remodelling facilitates their expression during infection. Here we discuss this model in the context of the key wheat pathogen, Zymoseptoria tritici. We cover progress in understanding the deposition and recognition of heterochromatic histone post translational modifications in Z. tritici and the role that heterochromatin plays in control of genome plasticity and virulence.

Up-regulation of the PI3K/AKT and RHO/RAC/PAK signalling pathways in CHK1 inhibitor resistant Eµ-Myc lymphoma cells.

The development of resistance and the activation of bypass pathway signalling represents a major problem for the clinical application of protein kinase inhibitors. While investigating the effect of either a c-Rel deletion or RelAT505A phosphosite knockin on the Eµ-Myc mouse model of B-cell lymphoma, we discovered that both NF-κB subunit mutations resulted in CHK1 inhibitor resistance, arising from either loss or alteration of CHK1 activity, respectively. However, since Eµ-Myc lymphomas depend on CHK1 activity to cope with high levels of DNA replication stress and consequent genomic instability, it was not clear how these mutant NF-κB subunit lymphomas were able to survive. To understand these survival mechanisms and to identify potential compensatory bypass signalling pathways in these lymphomas, we applied a multi-omics strategy. With c-Rel-/- Eµ-Myc lymphomas we observed high levels of Phosphatidyl-inositol 3-kinase (PI3K) and AKT pathway activation. Moreover, treatment with the PI3K inhibitor Pictilisib (GDC-0941) selectively inhibited the growth of reimplanted c-Rel-/- and RelAT505A, but not wild type (WT) Eµ-Myc lymphomas. We also observed up-regulation of a RHO/RAC pathway gene expression signature in both Eµ-Myc NF-κB subunit mutation models. Further investigation demonstrated activation of the RHO/RAC effector p21-activated kinase (PAK) 2. Here, the PAK inhibitor, PF-3758309 successfully overcame resistance of RelAT505A but not WT lymphomas. These findings demonstrate that up-regulation of multiple bypass pathways occurs in CHK1 inhibitor resistant Eµ-Myc lymphomas. Consequently, drugs targeting these pathways could potentially be used as either second line or combinatorial therapies to aid the successful clinical application of CHK1 inhibitors.

Do faecal test-based colorectal cancer screening pilots provide data that are reflected in subsequent programmes? Evidence from interval cancer proportions.

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.

Strategies to minimise the current disadvantages experienced by women in faecal immunochemical test-based colorectal cancer screening.

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.

Comparison with first round findings of faecal haemoglobin concentrations and clinical outcomes in the second round of a biennial faecal immunochemical test based colorectal cancer screening programme.

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.

A comparison of the faecal haemoglobin concentrations and diagnostic accuracy in patients suspected with colorectal cancer and serious bowel disease as reported on four different faecal immunochemical test systems.

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.

One or two faecal immunochemical tests in an organised population-based colorectal cancer screening programme in Murcia (Spain).

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.

Faecal haemoglobin concentration in adenoma, before and after polypectomy, approaches the ideal tumour marker.

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.

Faecal haemoglobin concentrations in women and men diagnosed with colorectal cancer in a national screening programme.

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.

Faecal Haemoglobin Estimated by Faecal Immunochemical Tests-An Indicator of Systemic Inflammation with Real Clinical Potential.

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.

[In current practice, what is the best test to detect blood in the stool ?] / En pratique courante, quel est le meilleur test pour rechercher du sang dans les selles ?

"In current practice, what is the best test to detect the presence of blood in faeces? Testing for the presence of blood in faeces is still widely performed in France, although the uptake in the national colorectal cancer screening programme is less than desirable, as is use in routine practice to guide diagnosis when patients present with gastrointestinal or general symptoms. Guaiac-based tests (Hemoccult) are obsolete and have been replaced by faecal immunochemical tests (FITs), both quantitative (OC-Sensor), currently reserved for the screening programme, and qualitative, performed by all medical laboratories. However, qualitative FITs should be abandoned: their visual reading is subjective, their positivity rate is highly variable, around 50%, and their diagnostic sensitivity for colorectal cancer has not been well determined. In contrast, quantitative FITs are reliable and their performance has been well evaluated. Several neighbouring countries use these tests in general practice to assess the risk of colorectal cancer in symptomatic patients and to determine the indication for colonoscopy. In this context, the decision thresholds are very different from those of organised screening: a faecal haemoglobin concentration below 4-10 µg/g is associated with a very low risk of cancer, a concentration above 4-10 µg/g should be investigated by colonoscopy, and a concentration above 150 µg/g requires an urgent colonoscopy."

"En pratique courante, quel est le meilleur test pour rechercher du sang dans les selles ? La recherche de sang dans les selles, malgré son caractère quelque peu désuet, est, à juste titre, encore très prescrite en France, insuffisamment dans le programme national de dépistage organisé du cancer colorectal et en pratique courante pour guider une conduite diagnostique en cas de symptômes digestifs ou généraux. Les tests au gaïac (Hemoccult), obsolètes, ont été remplacés par des tests immunochimiques, quantitatifs (OC-Sensor) réservés au programme de dépistage, et qualitatifs réalisés par tous les laboratoires de biologie médicale. Pourtant les tests qualitatifs sont obsolètes et devraient être abandonnés : leur lecture est subjective, leur taux de positivité très variable, proche de 50 %, et leur sensibilité diagnostique pour le cancer colorectal non évaluée. Au contraire, les tests quantitatifs sont fiables et leurs performances parfaitement évaluées. Plusieurs pays voisins utilisent ces tests en médecine générale pour évaluer le risque de cancer colorectal chez les patients symptomatiques et poser l'indication d'une coloscopie. Dans ce contexte, les seuils décisionnels sont très différents de ceux du dépistage organisé : un taux d'hémoglobine fécale inférieur à 4-10 µg/g de selles est associé à un risque infime de cancer, un taux supérieur à 4-10 µg/g doit être exploré par coloscopie, et un taux supérieur à 150 µg/g relève d'une coloscopie urgente."