Faecal Immunochemical Test For Haemoglobin Research Articles

PWE-019 An Evaluation Of Quantitative Faecal Immunochemical Tests For Haemoglobin

IntroductionThe NHS Bowel Cancer Screening Programme (BCSP) in England provides biennial screening using a guaiac-based faecal occult blood test (gFOBT) for people aged 60–74 years. The European guidelines1 recommend use...

Tests and investigations for colorectal cancer screening

Worldwide, colorectal (CRC) is the third most common form of cancer, after lung and breast cancer, and the fourth most common cause of cancer death, although in developed countries CRC incidence is higher and it accounts for an even higher proportion of cancer deaths. Successful treatment of early-stage CRC confers substantial survival advantage, and there is now overwhelming evidence that screening average-risk individuals for CRC reduces the incidence and disease-specific mortality. In spite of considerable research for new biomarkers for CRC, the detection of blood in faeces remains the most effective screening tool. The best evidence to date for population-based CRC screening comes from randomised-controlled trials that used a guaiac-based faecal occult blood test (gFOBt) as the first-line screening modality, whereby test-positive individuals are referred for follow-up investigations, usually colonoscopy. A major innovation in the last ten years or so has been the development of other more analytically sensitive and specific screening techniques for blood in faeces. The faecal immunochemical test for haemoglobin (FIT) confers substantial benefits over gFOBt in terms of analytical sensitivity, specificity and practicality and FIT are now recommended for CRC screening by the European guidelines for quality assurance in colorectal cancer screening and diagnosis. The challenge internationally is to develop high quality CRC screening programmes for which uptake is high. This is especially important for developing countries witnessing an increase in the incidence of CRC as populations adopt more westernised lifestyles.This review describes the tests available for CRC screening and how they are being used worldwide. The reader will gain an understanding of developments in CRC screening and issues that arise in choosing the most appropriate screening test (or tests) for organised population-based screening internationally and optimising the performance of the chosen test (or tests). Whilst a wide range of literature has been cited, this is not a systematic review. The authors provide FOBT CRC screening for a population of 14.6 million in the south of England and the senior author (SPH) was the lead author of the European guidelines for quality assurance in colorectal cancer screening and diagnosis and leads the World Endoscopy Organization Colorectal Cancer Committee’s Expert Working Group on ‘FIT for Screening’.

Population Screening for Colorectal Cancer Means Getting FIT: The Past, Present, and Future of Colorectal Cancer Screening Using the Fecal Immunochemical Test for Hemoglobin (FIT)

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

Darmkrebsfrüherkennung

Colorectal cancer (CRC) is the second most common cancer among both men and women in Germany. Owing to its relatively slow growth, perspectives for effective early detection are much better than for other forms of cancer. To summarize the evidence on effectiveness and cost-effectiveness of CRC screening, and to provide an overview on the current state and perspectives for effective CRC screening. Summary and critical review of evidence from randomized trials and observational epidemiological studies. A reduction in CRC mortality by offering annual fecal occult blood tests or once-only flexible sigmoidoscopy has been demonstrated in randomized trials. Novel fecal immunochemical tests for hemoglobin in stool have been shown to be more sensitive than traditional fecal occult blood tests and could substantially improve noninvasive CRC screening. Epidemiological studies suggest that the majority of CRC cases and deaths could be prevented by colonoscopy and removal of colorectal adenomas. However, adherence to screening offered outside organized screening programs is low. The National Cancer Plan recommends an organized CRC screening program in Germany. The law on the early detection of cancer from April 2013 has paved the way for its implementation. The great potential for CRC prevention by early detection has so far only been realized to a very limited extent in Germany. Introduction of an organized screening program and the offer of enhanced noninvasive screening tests could strongly enhance the utilization and effectiveness of CRC screening in Germany. The political frame has been set, and timely quality-assured implementation is required.

Predictive power of quantitative and qualitative fecal immunochemical tests for hemoglobin in population screening for colorectal neoplasm

The aim of this study was to evaluate the performance of qualitative and quantitative fecal immunochemical tests (FITs) in population screening for colorectal neoplasm. A total of 9000 participants aged between 40 and 74 years were enrolled in this study. Each participant received two stool sampling tubes and was asked to simultaneously submit two stool samples from the same bowel movement. The stool samples of each participant were tested using an immunogold labeling FIT dipstick (qualitative FIT) and an automated fecal blood analyzer (quantitative FIT). Colonoscopy was performed for those who test positive in either FIT. The positive predictive values and population detection rates of the FITs for predicting colorectal neoplasm were compared. A total of 6494 (72.16%) participants simultaneously submitted two stool samples. The diagnostic consistency for a positive result between quantitative and qualitative FITs was poor (κ=0.278, 95% confidence interval=0.223-0.333). The positive predictive values of the quantitative FIT were significantly higher than those of the qualitative FIT for predicting large (≥1 cm) adenomas (23 cases, 14.29% and 16 cases, 6.72%, P=0.013) and colorectal cancer (10 cases, 6.21% and 5 cases, 2.10%, P=0.034); however, the population detection rate for advanced neoplasm of the quantitative FIT was not significantly different from that of the qualitative FIT. Quantitative FIT is superior to qualitative FIT in predicting advanced colorectal neoplasm during colorectal cancer screening. Further studies are needed to elucidate the causes of the predictive superiority.

Patient attitudes towards faecal immunochemical testing for haemoglobin as an alternative to colonoscopic surveillance of groups at increased risk of colorectal cancer

To examine attitudes towards an annual faecal immunochemical test for haemoglobin (FIT) versus three-yearly colonoscopic surveillance of individuals at intermediate risk of colorectal cancer (CRC). A London hospital. Five semi-structured discussion groups were conducted with 28 adults (aged 60-74, 61% female) with different levels of CRC risk and experience of colonoscopy or colonoscopic surveillance. Information was presented sequentially using a step-by-step discussion guide. Results were analyzed using thematic analysis. When evaluating FIT in the context of a surveillance programme, all respondents readily made comparisons with related tests that they had been exposed to previously. Those with no experience of surveillance were enthusiastic about an annual FIT to replace three-yearly colonoscopy, because they felt that the higher testing frequency could improve detection of advanced lesions. Those with experience of colonoscopic surveillance did not perceive FIT to be as accurate as colonoscopy, and therefore either preferred colonoscopy on its own or wanted an annual FIT in addition to three-yearly colonoscopy. FIT may be well-received as an additional method of surveillance for new patients at intermediate risk of CRC. More research is required to better understand potential barriers associated with FIT surveillance for patients with experience of colonoscopic surveillance.

Screening and Primary prevention of Colorectal Cancer: a Review of sex-specific and site-specific differences

Colorectal cancer (CRC) is the second commonest cancer in England. Incidence rates for colorectal adenomas and advanced colorectal neoplasia are higher in men than in women of all age groups. The male-to-female ratio for CRC incidence rates differs for different parts of the large bowel. To summarize the current evidence on colorectal screening and prevention, focussing on potential differences in benefits between sexes and colorectal sites. , We reviewed the evidence from randomized controlled trials (RCTs) of the impact of different screening approaches on CRC incidence and mortality, overall, for each sex separately, and for subsites of the large bowel. (ii) We reviewed studies comparing detection parameters for faecal immunochemical tests for haemoglobin (FIT) with guaiac FOBt (gFOBt). (iii) The role of aspirin in CRC prevention in the general population was reviewed using evidence from RCTs, with specific emphasis on the differences observed between sexes and lesion site. (i) Our intention-to-treat random-effects meta-analysis showed that once-only flexible sigmoidoscopy (FS) screening performed on average-risk individuals aged 55 + decreased CRC incidence by 18% and mortality by 28%, but sex-specific results were lacking. (ii) Modern quantitative FIT were superior to qualitative gFOBt in average-risk population screening in their ability to discriminate between individuals with and without colorectal neoplasia. Some recent FIT studies suggest varying operating characteristics in men and women. (iii) Evidence of an effect of aspirin on the incidence of CRC (in particular, proximal disease) in both sexes aged 40 and over at average-risk of CRC is emerging. We encourage researchers of CRC screening and prevention to publish their results by sex where possible. Pilot studies should be undertaken before implementation of quantitative FIT in a national screening programme to establish the appropriate threshold. Finally, individual risk assessment for CRC and non-CRC events, will be necessary to make an informed decision on whether a patient should receive aspirin chemoprevention.

Making colorectal cancer screening FITTER for purpose with quantitative faecal immunochemical tests for haemoglobin (FIT)

Making colorectal cancer screening FITTER for purpose with quantitative faecal immunochemical tests for haemoglobin (FIT)

Diagnostic inconsistency of faecal immunochemical tests for haemoglobin in population screening of colorectal cancer

There is currently very little data available on the consistency of quantitative and qualitative faecal immunochemical test (FIT) for colorectal cancer screening. A representative random population (n=1889, 40-74 year olds) in Jiashan, China was invited for FIT screening in 2012. Faecal samples were collected by a single specimen collection device and simultaneously tested by a quantitative FIT (OC-SENSOR, OC) and two qualitative FITs (FIT A and FIT B with intrinsic positive haemoglobin cut-off concentrations of 20 μg Hb/g faeces and 40 μg Hb/g faeces, respectively). The observational criteria for a positive result of the qualitative FIT were set according to the density of the colour appearing in the test strip. The results produced by the quantitative and qualitative FIT for each sample were compared. κ coefficient was used to measure consistency. A total of 1368 (72.4%) individuals returned faecal samples. Both FIT A and FIT B precisely identified all faecal samples with haemoglobin concentration above 100 μg Hb/g faeces, but the overall consistency was poor for OC & FIT A (κ=0.32, 95% CI 0.20-0.44) and was moderate for OC & FIT B (κ=0.74, 95% CI 0.64-0.85). A more favourable consistency (κ=0.64, 95% CI 0.57-0.72) was achieved when a different positive criterion was employed for FIT A. The diagnostic inconsistency between quantitative and qualitative FITs mainly exists in the faecal samples with low haemoglobin concentrations. Refining the criterion for a positive result may be a feasible way to improve the accuracy of qualitative FIT.

Clinical outcomes using a faecal immunochemical test for haemoglobin as a first-line test in a national programme constrained by colonoscopy capacity.

Because of their many advantages, faecal immunochemical tests (FIT) are superseding traditional guaiac-based faecal occult blood tests in bowel screening programmes. A quantitative FIT was adopted for use in two evaluation National Health Service (NHS) Boards in Scotland using a cut-off faecal haemoglobin concentration chosen to give a positivity rate equivalent to that achieved in the Scottish Bowel Screening Programme. Uptake and clinical outcomes were compared with results obtained contemporaneously in two other similar NHS Boards and before and after the evaluation in the two evaluation NHS Boards. During the evaluation, uptake was 58.5%. This was higher than in the same NHS Boards both before and after the evaluation, higher than in the other two NHS Boards and higher than the 53.7% achieved overall in Scotland. The overall positivity rate was higher in men than in women and increased with age in both genders. Positive predictive values for cancer (4.8%), high-risk adenoma (23.3%), all adenoma (38.2%) and all neoplasia (43.0%) in the two test NHS Boards were similar in all groups. In summary, this evaluation of the FIT supports the introduction of FIT as a first-line test, even when colonoscopy capacity is limited.

Use of a faecal immunochemical test narrows current gaps in uptake for sex, age and deprivation in a bowel cancer screening programme

To investigate the characteristics of participants screened for bowel cancer using a faecal immunochemical test for haemoglobin (FIT). Scottish Bowel Screening Programme. 65909 men and women in two NHS Boards, aged 50 to 74, were invited to participate in an evaluation of FIT as a first-line test. Uptake was calculated by sex, age in quintiles, and deprivation in quintiles, and compared with a group who had completed a guaiac faecal occult blood test (gFOBT) and for whom details of sex, age and deprivation were well documented. FIT kits from 38672 participants were tested. The overall uptake of 58.7% was significantly higher than the 53.9% for gFOBT (p < 0.0001). Uptakes in the two NHS Boards were 57.6% and 54.4% for men and 63.2% and 59.1% for women, higher than the 49.5% and 58.1% completing gFOBT. Uptake was higher for FIT than gFOBT in all age and deprivation quintiles for both men and women in both NHS Boards. The difference in uptake fell with age for men but rose for women; the increase in uptake was greater for men than women. Uptake fell as deprivation decreased for both sexes, and was similar in both NHS Boards. Use of FIT increases uptake over gFOBT, and the greatest increases are seen in men, younger participants, and more deprived individuals, groups for which an increase in uptake is likely to be beneficial. The results support a move to FIT as a first-line screening test for those countries still using gFOBT.

PWE-023 Could Faecal Immunochemical Tests for Haemoglobin (FIT) Change Surveillance of People with Intermediate Risk Adenomas?

IntroductionThe NHS Bowel Cancer Screening Programme (BCSP) in England uses a biennial guaiac faecal occult blood test and identifies intermediate risk (IR) adenomas in approximately 5,000 people a year who...

Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy

There is increasing evidence that faecal immunochemical tests (FITs) for haemoglobin offer a number of advantages over traditional guaiac based faecal occult blood tests (gFOBTs). However, evidence on diagnostic performance from direct comparisons with colonoscopy findings in all participants in the average risk population is still sparse. We aimed for a head-to-head comparison of three quantitative FITs with a gFOBT among participants of the German screening colonoscopy programme. Pre-colonoscopy stool samples and colonoscopy reports were obtained from 2235 participants of screening colonoscopy in 2005–2009. To enhance comparability of diagnostic performance of the various tests, we assessed sensitivity, specificity, predictive values and likelihood ratios of FITs after adjusting the FIT cut-off haemoglobin (Hb) concentrations in such a way that FIT positivity rates equalled the positivity rate of the gFOBT. Colorectal cancer, advanced adenomas and other adenomas were found in 15 (0.7%), 207 (9.3%) and 398 (17.8%) participants. The gFOBT was positive in 111 (5.0%) participants, with sensitivities (specificities) for detecting colorectal cancer, any advanced neoplasm or any neoplasm of 33.3% (95.2%), 8.6% (95.4%) and 5.5% (95.2%). At the same positivity rate, all three FITs outperformed the gFOBT in all indicators. In particular, all sensitivities of FITs were approximately two to three times higher at increased levels of specificity. All differences were statistically significant, except for some of the performance indicators for colorectal cancer. In conclusion, FITs can detect much larger proportions of colorectal neoplasms even if their cut-offs are set to levels that ensure equally low positivity rates as gFOBT.

Critical considerations of fecal occult blood tests for colorectal cancer

1University of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UK *Author for correspondence: r.j.c.steele@dundee.ac.uk The most commonly used strategy in colo­ rectal cancer (CRC) screening pro grams involves the use of stool tests to detect occult blood, and guaiac fecal occult blood tests (gFOBTs) are, to date, the only fecal tests shown to reduce CRC mortality in population­based randomized trials [1]. However, gFOBTs also carry disadvantages. A major concern is that interval cancers account for around 50% of cancers detected in gFOBT screened populations [2] and recent data show that gFOBTs are less sensitive in women than in men, and in both rectal and right­sided cancers when compared with left­sided disease [2,3]. In addition, the test is associated with a high false­positive rate with no neoplasia detected in around half of colonoscopies performed following a positive gFOBT [2,3]. This may be, in part, explained by the fact that gFOBTs are not specific for human hemoglobin (Hb) and are subject to possible dietary interference from, for example, red meat and high­peroxidase fruits and vegetables. As a result, it has been common practice to instruct participants to adhere to dietary restrictions ahead of sample collection, although this may act as a barrier to screening and affect participation rates [4]. However, data from a meta­analysis did not support dietary restrictions with gFOBTs, leading to recommendations that restrictions are abandoned to improve adherence rates [5]. Fecal immunochemical tests (FITs) are now available and are increasingly being used in screening programs. Unlike gFOBTs, FITs are specific for the detection of human Hb, eliminating any potential for dietary interference, and are also more specific than gFOBT for lower gastrointestinal bleeding. In addition, modern FITs generally allow a more convenient method of sample collection, and are associated with better participation rates [6]. Another major advantage of FIT is that automated versions not only eliminate interobserver variability, but also the quantitative nature of these tests allow provision of a measured fecal Hb concentration. Screening program “...the adoption of fecal immunochemical tests in colorectal cancer screening programs has potential to address participation, appropriate positivity rates and the problem of false‐negative results.” EDITORIAL

Newer Fecal Tests: Opportunities for Professionals in Laboratory Medicine

There are differences in practice between the US, Europe, and other countries in screening for colorectal neoplasia (1) and investigation of other common lower gastrointestinal tract problems. Colonoscopy is often considered the gold standard for detection of colorectal neoplasia, and deaths from colorectal cancer can undoubtedly be reduced through removal of adenomatous polyps (2, 3). Colonoscopy is a scarce resource in many countries, however, and it may be limited to those with comprehensive health insurance. Consequently, there is much interest in using fecal tests to decide who will truly benefit from colonoscopy, particularly because the symptoms reported for colorectal diseases overlap considerably, making clinical decision-making about whom to refer difficult. In this issue of the Journal, Kok and colleagues (4) report a study on the diagnostic accuracy of point-of-care tests (POCTs)6 for fecal calprotectin and occult blood in primary care and assessing what they term “organic bowel disease.” A qualitative immunochemical fecal occult blood test was used. We have recommended (5) that tests that use antibodies to detect fecal hemoglobin be termed “fecal immunochemical tests for hemoglobin” and that the abbreviation “FIT” be used, because guaiac-based fecal occult blood tests (gFOBTs) and FITs are very different tests. As the authors mention, FITs are rapidly superseding traditional gFOBTs because of their many advantages, including that only a single sample is generally collected, the available collection devices encourage adoption of the test, the test is more specific for lower gastrointestinal bleeding, and dietary restriction is definitely not required. Indeed, the many disadvantages of gFOBTs with respect to sample collection and handling, analysis, and interpretation of results (6) have led to the general consensus that their use is obsolete because of the much better performance characteristics of FITs. We strongly advocate that professionals in laboratory medicine (PLMs) encourage current users of …

A Proposal to Standardize Reporting Units for Fecal Immunochemical Tests for Hemoglobin

Fecal immunochemical tests for hemoglobin are replacing traditional guaiac fecal occult blood tests in population screening programs for many reasons. However, the many available fecal immunochemical test devices use a range of sampling methods, differ with regard to hemoglobin stability, and report hemoglobin concentrations in different ways. The methods for sampling, the mass of feces collected, and the volume and characteristics of the buffer used in the sampling device also vary among fecal immunochemical tests, making comparisons of test performance characteristics difficult. Fecal immunochemical test results may be expressed as the hemoglobin concentration in the sampling device buffer and, sometimes, albeit rarely, as the hemoglobin concentration per mass of feces. The current lack of consistency in units for reporting hemoglobin concentration is particularly problematic because apparently similar hemoglobin concentrations obtained with different devices can lead to very different clinical interpretations. Consistent adoption of an internationally accepted method for reporting results would facilitate comparisons of outcomes from these tests. We propose a simple strategy for reporting fecal hemoglobin concentration that will facilitate the comparison of results between fecal immunochemical test devices and across clinical studies. Such reporting is readily achieved by defining the mass of feces sampled and the volume of sample buffer (with confidence intervals) and expressing results as micrograms of hemoglobin per gram of feces. We propose that manufacturers of fecal immunochemical tests provide this information and that the authors of research articles, guidelines, and policy articles, as well as pathology services and regulatory bodies, adopt this metric when reporting fecal immunochemical test results.

The diagnostic and prognostic role of cytokines in colon cancer

The diagnostic and prognostic role of cytokines in colon cancer Tiha M Long, Jean-Pierre RaufmanDepartment of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: In the United States, colorectal cancer (CRC) is the third most common cancer diagnosis in both men and women. Many patients are diagnosed with advanced stage CRC which has a high rate of mortality compared to localized CRC. Developing novel diagnostic tools is important for early detection to decrease both morbidity and mortality. Currently, colonoscopy is the most common screening test, though its effectiveness in reducing mortality remains uncertain and it is costly, invasive and carries risk. Stool-based tests such as fecal occult blood test and fecal immunochemical test for hemoglobin are relatively inexpensive, cause no discomfort and have no risk but lack sufficient specificity or sensitivity. Stool DNA tests may be more sensitive, but are not cost-effective and have not been sufficiently evaluated in population-based studies. To improve diagnostic efficacy, it is necessary to develop tests that limit patient discomfort and are cost-effective while providing adequate sensitivity and specificity. Elucidating serum biomarker profiles for various stages of CRC would provide a platform from which to develop enzyme-linked immunosorbent and multiplex bead array assays for clinical use. Both inflammation-induced and sporadic CRC trigger immune responses that are mediated by cytokine production. Many inflammatory serum proteins have been analyzed for their ability to predict cancer. Patient cohort studies have detected differential expression of inflammatory serum biomarkers in healthy controls compared to persons with various stages of CRC. Moreover, proteomics and animal research have uncovered additional serum factors implicated in CRC. Analysis of known differentially-expressed biomarkers along with further study of potential biomarkers may lead to clinically useful serum biomarker profiles for CRC.Keywords: cytokine, multiplex bead array, inflammatory bowel disease, colitis-associated cancer

Fecal Tests: From Blood to Molecular Markers

Detection of molecular markers for colorectal neoplasia in feces has the potential to improve performance of simple noninvasive screening tests for colorectal cancer. Most research has explored the value of DNA-based, RNA-based, and protein-based markers. In all cases there has been a trend to move from a single marker to a panel of markers to improve sensitivity. Unfortunately, no type of molecular marker has proved specific for neoplasia. DNA tests have been improved by combining mutation detection with assessment of DNA integrity plus epigenetic markers of neoplasia. RNA-based approaches are just beginning to explore the full power of transcriptomics. So far, no protein-based fecal test has proved better than fecal immunochemical tests for hemoglobin. Finally, no marker or panel of markers has yet been developed to the point where it has been evaluated in large unbiased population studies to assess performance across all stages of neoplasia and in all practical environments.

Population‐based screening for colorectal cancer: Australian research and implementation

Australia is one of the first countries in the world to implement an organized whole-of-population screening program for colorectal cancer (CRC). Australians have made broad contributions to CRC in general ranging from primary prevention through genetics, secondary prevention and treatment, to palliation. This overview focuses on some of the contributions of direct relevance to population-based screening, stretching from technology development to population-based controlled studies and health services research. In terms of simple screening tests in a two-step screening strategy, the evidence is overwhelming that fecal immunochemical tests for hemoglobin (FITs) improve detection and are more acceptable. FIT-based screening is clearly acceptable to Australians and it has been demonstrated that a national organized screening program is feasible. In terms of benefit for Australians, with full roll out and high uptake by the population we could see the number of cases dying from CRC halved by this strategy. To this will be added the extra-screening benefits of improved diagnosis, improved treatment and improved public awareness, all benefits of other screening programs. CRC screening has progressed from a matter of irrelevance and distaste, to commonwealth government policy in the context of an organized program for all Australians.

T2019 A Fecal Immunochemical Test for Hemoglobin Using a Single Stool Sample Is Effective for Detecting Significant Colorectal Neoplasia

T2019 A Fecal Immunochemical Test for Hemoglobin Using a Single Stool Sample Is Effective for Detecting Significant Colorectal Neoplasia