Faecal Immunochemical Test For Haemoglobin Research Articles

Comparison and commutability study among four faecal immunochemical tests (FIT) systems.

Faecal immunochemical tests for haemoglobin (FIT) are used in colorectal cancer screening programs around the world and increasingly for triage of symptomatic patients. FIT results are currently not traceable to a common reference standard and results obtained on various FIT systems may not be equivalent. The size of the bias between the systems is difficult to quantify due to the complex pre-analytical aspects of FIT. This study aimed to quantify the bias and the correlation between four FIT systems by measuring a panel of 38 faecal samples while limiting the effect of the pre-analytical aspects. In addition, the commutability of seven candidate reference materials (RM) was assessed. Pairwise method comparisons based on faecal samples demonstrated Pearson correlation coefficients ranging between 0.944 and 0.970 and an average proportional bias of-30 to-35 % for one FIT system compared to the other three. The relative standard deviation among biases of the individual samples was around 20 %. Due to these sample specific differences, no decisive conclusions could be drawn in the commutability study. However, twocandidate RMs, prepared in the FIT system-specific storage/extraction buffers, had a better commutable profile than the other five. The use of a common threshold for all FIT systems is currently not possible due to the presence of a proportional bias. We have identified potential commutable RMs to take to further studies on the production of a common calibrator, with the aim being to reduce the analytical bias observed on different FIT systems.

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

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. 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. 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. 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.

Fecal immunochemical test for hemoglobin versus fecal calprotectin to monitor endoscopic activity in inflammatory bowel disease.

endoscopy identifies inflammatory activity, however, it is an unpleasant test and is not always accessible. The aim of the study was to compare the usefulness of quantitative fecal immunochemical test (FIT) versus fecal calprotectin (FC) to determine endoscopic activity in patients with inflammatory bowel disease (IBD). cross-sectional prospective observational study. The stool samples were collected within three days before starting the preparation for the colonoscopy. We used the Mayo index for ulcerative colitis (UC) and the simplified endoscopic index for Crohn's disease (CD). Mucosal healing (MH) was defined as the score 0 points in each of the endoscopic indices. eighty-four patients were included, 40 (47.6 %) with UC. In patients with IBD, FIT and FC showed a significant correlation with the presence of inflammatory activity/MH on endoscopy, with no statistically significant differences between the two receiver-operating characteristic (ROC) curves. Both tests improved their diagnostic performance when assessing patients with UC; the Spearman correlations between FIT and FC and endoscopic inflammatory activity were r = 0.6 (p = 0.0001) and r = 0.7 (p = 0.0001), respectively. In Crohn's disease, the diagnostic utility of both tests was lower. FIT is an alternative to monitor endoscopic activity among ulcerative colitis patients. In Crohn's disease, more studies are needed to determine the role of fecal biomarkers.

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 of the QuikRead go® point-of-care faecal immunochemical test for haemoglobin with the FOB Gold Wide® laboratory analyser to diagnose colorectal cancer in symptomatic patients.

Faecal immunochemical testing for haemoglobin (FIT) is used to triage patients for colonic investigations. Point-of-care (POC) FIT devices on the market have limited data for their diagnostic accuracy for colorectal cancer (CRC). Here, a POC FIT device is compared with a laboratory-based FIT system using patient collected samples from the urgent referral pathway for suspected CRC. A prospective, observational cohort study. Patients collected two samples from the same stool. These were measured by POC QuikRead go® (Aidian Oy, Espoo, Finland) and laboratory-based FOB Gold Wide® (Sentinel Diagnostics, Italy). Faecal haemoglobin <10μg haemoglobin/g of faeces was considered as negative. At this threshold, comparisons between the two systems were made by calculating percentage agreement and Cohen's kappa coefficient. Proportion of negative results were compared with Chi squared testing. Sensitivities for CRC were calculated. A total of 629 included patients provided paired samples for FIT to compare the QuikRead go® and FOB Gold Wide®. The agreement around the negative threshold was 83.0% and Cohen's kappa coefficient was 0.54. The QuikRead go® reported 440/629 (70.0% of samples) as negative compared to 523/629 (83.1%) for the FOB Gold Wide®, this difference was significant (p-value<0.001). Sensitivities for CRC detection by the QuikRead go® and FOB Gold Wide® were 92.9% (95% confidence interval (CI): 68.5-98.7%) and 100% (CI: 78.5-100%) respectively. Both systems were accurate in their ability to detect CRC. Whilst good agreement around the negative threshold was identified, more patients would be triaged to further colonic investigation if using the QuikRead go®.

Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions

Evaluating tests for diagnosing COVID-19 in the absence of a reliable reference standard: pitfalls and potential solutions

Detection of Circulating Tumor DNA Methylation in Diagnosis of Colorectal Cancer.

INTRODUCTION:Emerging evidence has demonstrated the potential of the circulating tumor DNA (ctDNA) methylation in the application of cancer diagnosis.METHODS:Three genes including Septin9, Syndecan-2 (SDC2), and branched-chain amino acid transaminase 1 (BCAT1), which have been well demonstrated to have aberrant expression in colorectal cancer (CRC) as tumor suppressors, were selected for detection. A total of 234 peripheral plasma samples from 104 patients with CRC and 130 patients with colorectal polyps, and 60 plasma samples from healthy controls, were collected before any treatment. A real-time polymerase chain reaction-based gene panel was used to detect the methylation of Septin9, SDC2, and BCAT1. The composite score (P) was calculated according to the cycle threshold values of the 3 methylated genes using the logistic regression equation.RESULTS:The ctDNA methylation of the 3 genes had a significantly higher level in patients with CRC, compared with patients with colorectal polyps and healthy controls. The composite score (P) showed association with tumor stages in CRC but not with the tumor location (colon or rectum). In addition, BCAT1 and Septin9 showed better performance for CRC diagnosis, by which CRC was able to distinguish from polyps with sensitivity of 83.7%, specificity of 93.9%, and area under the curve of 0.908. The diagnostic efficiency was significantly improved by combining composite score (P), carcinoembryonic antigen, and fecal immunochemical test for hemoglobin (area under the curve = 0.962).DISCUSSION:The composite score (P) derived from the ctDNA methylation levels of Septin9, SDC2, and BCAT1 can be used for CRC diagnosis with high sensitivity and high specificity. A combination of ctDNA methylation, carcinoembryonic antigen, and fecal immunochemical test for hemoglobin was proved to be the most effective approach to diagnose CRC.

Extent of disease affects the usefulness of fecal biomarkers in ulcerative colitis

BackgroundFecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC.MethodsFecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively.ResultsA total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis.ConclusionsFor the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer.

BackgroundThe faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme.AimTo determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC.Design and settingPatients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation.MethodThe diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results.ResultsIn total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively.ConclusionFIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.

Faecal immunochemical tests for haemoglobin: Analytical challenges and potential solutions

Quantitative faecal immunochemical tests for haemoglobin (FIT) are being used increasingly around the world in colorectal cancer screening programmes, and in patients presenting with lower bowel symptoms to determine who should proceed to further bowel visualisation investigations, usually colonoscopy. The clinical utility of FIT is well reported. There are a number of analytical challenges including pre-analytical variation, difficulty setting up external quality assessment schemes, access to third party internal quality control material and a lack of standardisation or harmonisation of FIT methods. Here we report the work of the International Federation of Clinical Chemistry FIT Working Group. We provide an overview of the main pre-analytical variables; discuss different approaches to external quality assurance of FIT; propose a solution to third party internal quality assurance materials and summarise the challenges of standardisation and harmonisation of FIT.

Assuring the quality of examinations using faecal immunochemical tests for haemoglobin (FIT)

Assuring the quality of examinations using faecal immunochemical tests for haemoglobin (FIT)

Assuring the quality of examinations using faecal immunochemical tests for haemoglobin (FIT).

Assuring the quality of examinations using faecal immunochemical tests for haemoglobin (FIT).

Fecal DNA Testing of TWIST1 Methylation Identifies Patients With Advanced Colorectal Adenoma Missed by Fecal Immunochemical Test for Hemoglobin.

INTRODUCTION:We have reported previously that fecal DNA testing of TWIST1 methylation in combination with the fecal immunochemical test for hemoglobin (FIT) (combination test) is useful for colorectal neoplasia screening. In this study, using larger sample sizes, we studied the clinical performance of the combination test for the detection of colorectal neoplasia and, especially, advanced colorectal adenoma.METHODS:We performed a prospective study in which FIT, fecal DNA testing of TWIST1 methylation, and colonoscopy were performed on 372 patients with colorectal neoplasia and 71 subjects without colorectal neoplasia. We assessed the individual clinical performance of each of FIT and fecal DNA testing of TWIST1 methylation and of the combination test for the detection of colorectal neoplasia including advanced adenoma based on morphologic subtypes.RESULTS:The FIT alone had a sensitivity of 7.5% (3/40) for nonadvanced adenoma, 32.3% (41/127) for advanced adenoma, and 93.7% (192/205) for colorectal cancer and a specificity of 87.3% (62/71). The combination test had a sensitivity of 35.0% (14/40) for nonadvanced adenoma, 68.5% (87/127) for advanced adenoma, and 95.6% (196/205) for colorectal cancer and a specificity of 80.3% (57/71). For morphological subtypes of advanced adenoma, the sensitivity of FIT was only 28.2% (20/71) for polypoid type and 16.1% (5/31) for nonpolypoid type, whereas the combination test increased the sensitivities to 64.8% (46/71) and 71.0% (22/31), respectively.DISCUSSION:The combination of the fecal DNA test with FIT seemed to be useful to detect colorectal neoplasia and, especially, advanced adenoma of the nonpolypoid type.

Faecal haemoglobin distributions by sex, age, deprivation and geographical region: consequences for colorectal cancer screening strategies.

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.

Elevated fecal calprotectin and lactoferrin associated with small intestinal lesions in patients with Behçet disease.

Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions. This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls. Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P=0.034 and P=0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value=119μg/g) and FL (cutoff value=17μg/g) were biomarkers for small intestinal lesions in patients with BD. The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Appraisal of the faecal haemoglobin, age and sex test (FAST) score in assessment of patients with lower bowel symptoms: an observational study

BackgroundMany 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.MethodsData 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.Results1196 (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.ConclusionsThe performance characteristics of the FAST score did not seem to enhance the utility of f-Hb alone. Locally-derived formulae might confer desired benefits.

Colorectal Cancer Screening Programme: Algarve Preliminary data

Abstract Problem The burden of disease for oncological problems is significant in Portugal. Population-based screenings, such as colorectal cancer screening (CCS) with faecal occult blood tests (FIT) is a priority program to reduce the burden of disease and a cost-effectiveness measure. Description problem Algarve CCS started in 2017,to early detect colorectal cancer reducing morbidity and mortality. Screening strategy to detect and remove cancer precursors (adenomas) and early cancer detection with less invasive treatment using a non-invasive stool test was selected. A quantitative faecal immunochemical test for haemoglobin (FIT) with higher sensitivity for adenoma and cancer, specific for human globin with no dietary restriction, with a single sample screening is considered a test with higher participation. Target population all gender from 50 to 75 are invited to participate in the CCS by letter. Screening interval is 2 years and FIT cut-off- 117 (ng Hb/mL). Software was used to manage all CCS. Health units distribute the test and a flyer. All FIT-positive were invited to do a full colonoscopy at University Hospital. Results A preliminary descriptive analysis (2017/2019) was made. After exclusions 25017 of target population participate 34,4%(n = 8594),27.5%(n = 6883) submitted it for analysis, 3.9% (n = 266) had positive FIT and were invited for a full colonoscopy with 57.5% (n = 153)participation rate. Cancer detection was 0.9‰ and adenomas detection rate was 9.9%. FIT positive with colonoscopy 3.9% (n = 6) had carcinoma and 44.4% (n = 68) had adenoma. Lessons Some operational changes were made to improve participants and professionals adherence to CCS. Pathology observed in the positive cases, reinforce the need to implement strategies to increase literacy, raise public awareness, keep the screening test and improve accessibility of health facilities. Key messages The importance of a colorectal cancer early diagnosis prevent aggressive interventions in a precancerous phase. The importance of a colorectal cancer early diagnosis improves survival and population quality of life.

Is Colorectal Cancer Screening Appropriate in Nigeria?

PURPOSEThe global burden of colorectal cancer (CRC) will continue to increase for the foreseeable future, largely driven by increasing incidence and mortality in low- and middle-income countries (LMICs) such as Nigeria.METHODSWe used the Wilson-Jungner framework (1968) to review the literature relevant to CRC screening in Nigeria and propose areas for future research and investment.RESULTSScreening is effective when the condition sought is both important and treatable within the system under evaluation. The incidence of CRC is likely increasing, although the exact burden of disease in Nigeria remains poorly understood and access to definitive diagnosis and treatment has not been systematically quantified. In high-income countries (HICs), CRC screening builds on a well-known natural history. In Nigeria, a higher proportion of CRC seems to demonstrate microsatellite instability, which is dissimilar to the molecular profile in HICs. Prospective trials, tissue banking, and next-generation sequencing should be leveraged to better understand these potential differences and the implications for screening. Fecal immunochemical test for hemoglobin (FIT) is recommended for LMICs that are considering CRC screening. However, FIT has not been validated in Nigeria, and questions about the impact of high ambient temperature, endemic parasitic infection, and feasibility remain unanswered. Prospective trials are needed to validate the efficacy of stool-based screening, and these trials should consider concomitant ova and parasite testing.CONCLUSIONUsing the Wilson-Jungner framework, additional work is needed before organized CRC screening will be effective in Nigeria. These deficits can be addressed without missing the window to mitigate the increasing burden of CRC in the medium to long term.

High-risk symptoms and quantitative faecal immunochemical test accuracy: Systematic review and meta-analysis.

BACKGROUNDThe quantitative faecal immunochemical test for haemoglobin (FIT) has been revealed to be highly accurate for colorectal cancer (CRC) detection not only in a screening setting, but also in the assessment of patients presenting lower bowel symptoms. Therefore, the National Institute for Health and Care Excellence has recommended the adoption of FIT in primary care to guide referral for suspected CRC in low-risk symptomatic patients using a 10 µg Hb/g faeces threshold. Nevertheless, it is unknown whether FIT´s accuracy remains stable throughout the broad spectrum of possible symptoms.AIMTo perform a systematic review and meta-analysis to assess FIT accuracy for CRC detection in different clinical settings.METHODSA systematic literature search was performed using MEDLINE and EMBASE databases from inception to May 2018 to conduct a meta-analysis of prospective studies including symptomatic patients that evaluated the diagnostic accuracy of quantitative FIT for CRC detection. Studies were classified on the basis of brand, threshold of faecal haemoglobin concentration for a positive test result, percentage of reported symptoms (solely symptomatic, mixed cohorts) and CRC prevalence (< 2.5%, ≥ 2.5%) to limit heterogeneity and perform subgroup analysis to assess the influence of clinical spectrum on FIT´s accuracy to detect CRC.RESULTSFifteen cohorts including 13073 patients (CRC prevalence 0.4% to 16.8%) were identified. Pooled estimates of sensitivity for studies using OC-Sensor at 10 µg Hb/g faeces threshold (n = 10400) was 89.6% [95% confidence interval (CI): 82.7% to 94.0%). However, pooled estimates of sensitivity for studies formed solely by symptomatic patients (n = 4035) and mixed cohorts (n = 6365) were 94.1% (95%CI: 90.0% to 96.6%) and 85.5% (95%CI: 76.5% to 91.4%) respectively (P < 0.01), while there were no statistically significant differences between pooled sensitivity of studies with CRC prevalence < 2.5% (84.9%, 95%CI: 73.4% to 92.0%) and ≥ 2.5% (91.7%, 95%CI: 83.3% to 96.1%) (P = 0.25). At the same threshold, OC-Sensor® sensitivity to rule out any significant colonic lesion was 78.6% (95%CI: 75.6% to 81.4%). We found substantial heterogeneity especially when assessing specificity.CONCLUSIONThe results of this meta-analysis confirm that, regardless of CRC prevalence, quantitative FIT is highly sensitive for CRC detection. However, FIT ability to rule out CRC is higher in studies solely including symptomatic patients.

Effect of a Single Aspirin Dose Prior to Fecal Immunochemical Testing on Test Sensitivity for Detecting Advanced Colorectal Neoplasms

Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men. To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling. A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017). Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test. The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-μg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma). Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-μg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-μg Hb/g stool. Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test. Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE.