Automated immunochemical quantitation of haemoglobin in faeces collected on cards for screening for colorectal cancer
ABSTRACT Simple card collection systems are becoming available for faecal immunochemical tests (FITs) as well as guaiac faecal occult blood tests (gFOBTs). FITs are now obtainable that allow quantitation of haemoglobin, so that the analytical detection limit can be set to give a positivity rate that is manageable in terms of the available colonoscopy. A combination of a card collection device and an automated FIT analytical system could be advantageous.
The quantitation of haemoglobin in samples collected on cards with a new analytical system and the relationship between faecal haemoglobin concentration and pathology were investigated in a cohort of gFOBT-positive individuals.
All groups had large ranges of haemoglobin concentration and there was overlap between the groups. Median haemoglobin concentrations in participants with normal findings on colonoscopy (167), diverticular disease (43), hyperplastic polyps (41), low risk adenoma (63), higher risk adenoma (35) and cancer (27) were 13.5, 15.6, 16.8, 15.2, 65.6 and 168.9 ng/ml haemoglobin, respectively. Those with diverticular disease, hyperplastic polyps and low risk adenoma were not significantly different from the normal group (p>0.2), but those with higher risk adenoma had significantly higher concentrations (p<0.001), as did those with cancer (p<0.001). Receiver operating characteristic analysis demonstrates that the cut-off concentration can be set to give appropriate clinical characteristics; optimum sensitivity and specificity are achieved at 26.7 ng/ml.
The haemoglobin in faeces on simple FIT card collection devices can be immunoturbidimetrically analysed quantitatively, and the concentration relates to the presence or absence of significant neoplastic disease.
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ABSTRACT: To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors. We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ≥ 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations. The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (β = 0.088, P < 0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R(2) > 0.95, P < 0.001). Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.World Journal of Gastroenterology 12/2013; 19(45):8366-72. DOI:10.3748/wjg.v19.i45.8366 · 2.43 Impact Factor
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ABSTRACT: Background & Aims The latest generation of fecal immunochemical tests (FIT) allows for quantitation of hemoglobin in feces, allowing for selection of an optimal cut-off concentrations. We investigated whether individuals with positive results from quantitative FITs, in combination with other factors, could be identified as being at greatest risk for advanced colorectal neoplasia. Methods In a retrospective study, we analyzed data from a consecutive series of 3109 participants with positive results from FITs (≥20 μg/g of feces) included in the 1st round of the Barcelona colorectal cancer screening program, from December 2009 through February 2012. All participants underwent colonoscopy and were assigned groups with any advanced colorectal neoplasia or with non-advanced colorectal neoplasia (but other diagnosis or normal examination findings). Results Median fecal hemoglobin concentrations were significantly higher in participants with advanced colorectal neoplasia (105 μg/g; interquartile range [IQR], 38–288 μg/g) compared to participants with non-advanced colorectal neoplasia (47 μg/g; IQR, 23–119 μg/g) (P<.001). Positive predictive values for advanced colorectal neoplasia, determined using arbitrary fecal hemoglobin concentrations, differed with sex and age. Multivariate logistic regression analysis identified sex (men: odds ratio [OR], 2.07; 95% confidence interval [CI], 1.78–2.41), age (60–69 years old: OR, 1.24; 95% CI, 1.07–1.44), and fecal hemoglobin concentration (>177 μg/g: OR, 3.80; 95% CI, 3.07–4.71) as independent predictive factors for advanced colorectal neoplasia. Combining these factors, we identified 16 risk categories associated with different probabilities of identifying advanced colorectal neoplasia. Risk for advanced colorectal neoplasia increased 11.46-fold among individuals in the highest category compared with the lowest; positive predictive values ranged from 21.3% to 75.6%. Conclusions Fecal hemoglobin concentration, in addition to sex and age, in individuals with positive results from FITs can be used to stratify probability for detection of advanced colorectal neoplasia. These factors should be used to prioritize individuals for colonoscopy examination.Gastroenterology 09/2014; 147(3). DOI:10.1053/j.gastro.2014.06.008 · 13.93 Impact Factor
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ABSTRACT: 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'.Clinical biochemistry 04/2014; DOI:10.1016/j.clinbiochem.2014.04.019 · 2.23 Impact Factor