False-positive Fecal Immunochemical Test Research Articles

Role of demographics in noninvasive testing for colorectal cancer screening: do targeted cut-off values improve detection?

Fecal immunochemical test (FIT) is a yearly alternative colorectal screening modality for average risk individuals unwilling or unable to undergo invasive colorectal cancer (CRC) screening due to cost and accessibility. This study aimed to determine whether FIT should be interpreted within the context of patient demographics and medical history. Patients >50 years old who had a FIT followed by colonoscopy within 1 year were analyzed based on age, race, BMI, social and medical comorbidities. False positive (FP) and false negative (FN) FIT results within each patient demographic and medical history variable were determined by comparing with the gold standard of colonoscopy using χ2 analysis. One thousand twenty-five patients were reviewed. 21.8% of FIT results were positive. Factors which differed in positive FIT rates were age (P=0.003), smoking (P<0.001), alcohol (P=0.001), and hypertension (P<0.001). The difference in rates of FP and FN FIT outcomes among each variable underwent further subanalysis. The FP was 66.8% and the FN rate was 12.8%. Higher FN outcomes were noted in those above 70, males and smokers, though the result was only statistically significant for males (P=0.009). Females were observed to have higher FP rates (P=0.019). Females had higher FP FIT rates compared to males, indicating that sex may influence FIT outcomes and should be accounted for when interpreting FIT results. This information can be utilized to identify populations at higher risk of FP or FN FIT results to target CRC screening. Additionally, recalculating the FP and FN rates for each variable may help determine new FIT targets.

S263 Role of Demographics in Non-Invasive Testing for Colorectal Cancer Screening: Do Targeted Cut-Off Values Improve Detection?

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. For those unable or unwilling to undergo invasive screening, fecal immunochemical test (FIT) is a yearly alternative due to its cost and accessibility compared to the Cologuard. Few studies have examined how patient factors influence FIT outcomes. This study aims to determine whether FIT should be interpreted within the context of patient demographics and medical history. Methods: A retrospective review of patients >50 years old who had a FIT followed by a colonoscopy within 1 year from 2016-2019 was performed. Patients were analyzed based on age, race, body mass index (BMI), comorbidities, smoking, and alcohol use. FIT values above 100 ng/mL were positive based on manufacturer recommendations (Polymedco, NY). Chi-square test was used to compare positive FIT rates within each of the patient demographics and medical history. Fisher’s exact test was used when sparse cells were encountered in contingency tables. False positive (FP) and negative (FN) FIT results were determined by comparing with the gold standard of colonoscopy. Results: 1025 patients were reviewed. 21.8% of FIT results were positive. Factors which differed in positive FIT rates were age (P = 0.003), smoking (P < 0.001), alcohol (P = 0.001), and hypertension (P < 0.001). A significant trend was noted with increasing positive findings with older age (Cochran-Armitage test, P = 0.001). The difference in rates of FP and FN FIT outcomes among each variable underwent further sub-analysis. The FP rate was 66.8% and the FN rate was 12.8%. Higher FN outcomes were noted in those above the age of 70, males and smokers, though the result was only statistically significant for males (P = 0.009). Females were observed to have higher FP rates than males (P = 0.019). African Americans had the highest rates of a positive FIT overall, and the FN rates were the lowest; neither result was statistically significant. Patients on aspirin and with a history of alcohol use had higher FP rates but did not meet statistical significance. Conclusion: Females were found to have higher FP FIT rates compared to males indicating that patient demographics may influence the FIT outcome. We can use this information to identify populations at higher risk of FP or FN FIT outcomes to target CRC screening. Additionally, recalculating the FP and FN rates for each variable by adjusting FIT cutoff may help determine new FIT targets to better improve sensitivity and specificity.Table 1.: Patient characteristics and fecal immunochemical test (FIT) positive rates.

Predictive Modeling of Colonoscopic Findings in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program

BackgroundThe fecal immunochemical test (FIT) is the primary modality used by the Los Angeles County Department of Health Services (LADHS) for colorectal cancer (CRC) screening in average-risk patients. Some patients referred for FIT-positive diagnostic colonoscopy have neither adenomas nor more advanced pathology. We aimed to identify predictors of false-positive FIT (FP-FIT) results in our largely disenfranchised, low socioeconomic status population.MethodsWe conducted a retrospective study of 596 patients who underwent diagnostic colonoscopy following a positive screening FIT. Colonoscopies showing adenomas (or more advanced pathology) were considered positive. We employed multiple logistic and linear regression as well as machine learning models (MLMs) to identify clinical predictors of FP-FIT (primary outcome) and the presence of advanced adenomas (secondary outcome).ResultsOverall, 268 patients (45.0%) had a FP-FIT. Female sex and hemorrhoids (odds ratios [ORs] 1.59 and 1.89, respectively) were associated with increased odds of FP-FIT and fewer advanced adenomas (β = − 0.658 and − 0.516, respectively). Conversely, increasing age and BMI (ORs 0.94 and 0.96, respectively) were associated with decreased odds of FP-FIT and a greater number of advanced adenomas (β = 0.073 and 0.041, respectively). MLMs predicted FP-FIT with high specificity (93.8%) and presence of advanced adenoma with high sensitivity (94.4%).ConclusionIncreasing age and BMI are associated with lower odds of FP-FIT and greater number of advanced adenomas, while female sex and hemorrhoids are associated with higher odds of FP-FIT and fewer advanced adenomas. The presence of the aforementioned predictors may inform the decision to proceed with diagnostic colonoscopy in FIT-positive patients.

False-positive fecal immunochemical test results in colorectal cancer screening and gastrointestinal drug use.

The study aimed to determine the influence of drug treatments (proton pump inhibitors [PPIs] combined with other drugs) on the false-positive (FP) rate in the fecal immunochemical test (FIT). Patients undergoing colonoscopy in the setting of a CRC screening program due to a positive FIT result were included prospectively. Demographic data and drug intake of PPIs, antiplatelet therapy (APA), anticoagulants, selective serotonin reuptake inhibitors (SSRIs), and nonsteroidal anti-inflammatory drugs (NSAIDs) were collected. An FP FIT result was considered normal colonoscopy or with nonneoplastic pathology (NNP). Logistic regression models were used to evaluate the effect of these drugs on the rate of FP FIT results. We included 515 patients, and 59% (304/515) were males. The rate of FP FIT results was 48% (249/515). Study drug use was higher in patients > 60 years old and females than in those < 60 years old and males (p < 0.001 and p = 0.049, respectively). Multivariate logistic regression revealed that female sex (OR = 2.7 95% CI 1.9-3.9), NNP (OR = 1.5 95% CI 1.1-2.2), and the use of any of the study drugs (OR = 1.4 95% CI 0.9-2.0) were independent risk factors for FP FIT results. The risk of FP FIT results was significantly higher in PPI users than in nonusers (OR = 1.8 95% CI 1.1-2.9), specifically when PPIs were combined with other drugs (OR = 2.01 95% CI 1.1-3.6) only in men. Female sex, NNP, and PPIs combined with other drugs in males were identified as independent risk factors for FP FIT results.

Impact of antithrombotics on the fecal immunochemical test for colorectal cancer screening : a multi-center Belgian experience.

Impact of antithrombotics on the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening remains unclear. Patients undergoing colonoscopy for positive FIT in 2015 were assessed at 3 Belgian centers. Significant findings were advanced polyps (AP) (sessile serrated, tubular or villous adenomas >1cm or high-grade dysplasia) and CRC. False positive FIT and detection of AP/CRC with antithrombotics were calculated. 510 patients (64% male, median (IQR) age 63.2 (60.2 - 66.4) years) were included. Colorectal pathology in 371/510 (73%) was associated with male gender (70% vs. 48% ; p= .0001) and family history (16% vs. 8% ; p= .02). Antithrombotics in 125/510 (25%) were associated with male gender (78% vs. 59% ; p= .0001), older age (65.2 (62.2-70.3) vs. 62.3 (58.7-66.3) years ; p= .0001) and GI-symptoms (18% vs. 11% ; p= .04). False positive FIT (25% vs. 28% ; p= .52) and detection of AP (42% vs. 36% ; p=.27) or CRC (6% vs. 5% ; p= .69) were similar in patients with vs. no antithrombotics. Use of antithrombotics did not predict a higher chance of colorectal pathology after adjusting for confounders. Although antithrombotics were prescribed more frequently in male and older patients, detection of AP/CRC was similar. Despite increased GI symptoms, false positive FIT was similar with antithrombotics.

Proton-pump inhibitors are associated with a high false-positivity rate in faecal immunochemical testing.

False-positivity rates in faecal immunochemical test (FIT) can be affected by drug exposure. We aimed to assess the association between proton pump inhibitors (PPI) consumption and false positive (FP) results in a colorectal cancer (CRC) screening programme using electronic prescription records. A retrospective cohort study within a population-based screening program for CRC from 2010 to 2016 was performed. Participants with a conclusive FIT result and with prescription electronic data were included. An FP result was defined as having a positive FIT (≥ 20µg haemoglobin/g faeces) and a follow-up colonoscopy without intermediate or high-risk lesions or CRC. Screening data were anonymously linked to the public data analysis program for health research and innovation (PADRIS) database that recorded patient diseases history and reimbursed medication. PPI exposure was defined as having retrieved at least one dispensation of PPI three months prior to the FIT. A total of 89,199 tests (of 46,783 participants) were analysed, 4824 (5.4%) tested positive and the proportion of FP was 53.5%. Overall, 17,544 participants (19.7%) were PPI users prior to FIT performance. PPI exposure increased the probability of obtaining an FP FIT result from 50.4 to 63.3% (adjusted OR 1.39; 95% CI 1.18-1.65). Nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, antibiotics, and laxatives were also associated with an FP result. The effect of PPI was independent and showed a synergistic interaction with nonsteroidal anti-inflammatory drugs. PPIs increase FIT positivity at the expense of FP results. The recommendation to avoid their use before FIT performance could reduce up to 3% of colonoscopies and 9% of FP results.

Enhancing bowel screening: Preventing colorectal cancer by flexible sigmoidoscopy in New Zealand

ObjectivesThe prevention of colorectal cancer (CRC) attainable from introducing once-in-a-lifetime flexible sigmoidoscopy (FSIG) screening was assessed. Study designThis is a review of relevant available information for the assessment of the impact and resource demands of FSIG in New Zealand. MethodsThe reduction in bowel cancer incidence achievable by one-off FSIG screening from 50 to 59 years of age, an age group for which bowel screening is not currently offered, was reviewed. The prevention of CRC attainable from an offer of screening at 55 years of age in New Zealand was also estimated. The number and cost of the FSIG screening procedures required and referrals for colonoscopies and the savings in treatment were calculated. ResultsAnnually, about 27,500 FSIG screening procedures would be required if 50% of those turning 55 years of age accepted an offer of once-in-a-lifetime FSIG screening. This would result in three–four-fold fewer people being referred for colonoscopy than in the national 2-yearly faecal immunochemical test (FIT) screening programme and subsequently reduce demand for colonoscopy from a false-positive FIT. The number of CRC cases prevented would increase over 17 years to more than 300 per year by 2033. After 10–15 years of screening, the annual savings in health service costs, primarily from CRC prevented, were sufficient to completely fund the FSIG screening. ConclusionsInclusion of FSIG screening in the national bowel screening programme would significantly reduce both the incidence and mortality of CRC in New Zealand, reduce the colonoscopy demand of current bowel screening and reduce long-term health service costs.

Return to bowel screening after a false-positive faecal immunochemical test in BowelScreen (the National Bowel Screening Programme in Ireland).

Objective Little research exists on what predicts individual return to screening after a false-positive faecal immunochemical test in a population bowel screening programme. We aimed to quantify the impact of false-positive faecal immunochemical test in the first round of screening on re-attendance in BowelScreen, the National Bowel Screening Programme in Ireland. Methods A retrospective cohort study was conducted. False-positivity was defined as a positive faecal immunochemical test with subsequent colonoscopy showing no evidence of malignancy or surveillance requirement. In those with a false-positive faecal immunochemical test, logistic regression was used to predict repeat participation in the second round. Results Of 196,149 individuals who attended the first screening round, 108,075 were eligible and re-invited in the second round, and 93,971 accepted the invitation (86.9%). Second round uptake was higher in faecal immunochemical test-negative individuals compared with those having false-positive results (87.5% vs. 73.1%; p &lt; 0.001). Older age (odds ratio (OR) 0.75; 95% confidence interval (CI) 0.60–0.94), computed tomography colonography (unsuitability/failed colonoscopy) (OR 0.40; 95% CI 0.21–0.73), and longer duration from screening invitation to faecal immunochemical test result (OR 0.991; 95% CI 0.9872–0.995) were predictors of non-re-attendance in the next screening round. Conclusion There is a significant reduction in re-attendance rates for individuals with false-positive faecal immunochemical test results. The letter sent following a negative colonoscopy is being reviewed to ensure that it provides adequate encouragement to re-attend. There are roles for screening promotion and for Gastroenterologists and Advanced Nurse Practitioners to emphasize the importance of regular faecal immunochemical tests after a negative colonoscopy.

GPs' perspectives on colorectal cancer screening and their potential influence on FIT-positive patients: an exploratory qualitative study from a Dutch context.

BackgroundIn the Dutch colorectal cancer (CRC) screening programme, individuals receive a faecal immunochemical test (FIT) to do at home. After a positive FIT result, a follow-up colonoscopy is recommended to identify CRC or advanced adenomas (AA). GPs may influence their patients’ decisions on adherence to follow-up by colonoscopy.AimTo explore GPs’ perspectives on the CRC screening programme and their potential influence on FIT-positive patients to follow up with the recommended colonoscopy.Design & settingSemi-structured interviews among GPs in Amsterdam, the Netherlands.MethodGPs were approached using purposive sampling. Analysis was performed on 11 interviews using open coding and constant comparison.ResultsAll interviewed GPs would recommend FIT-positive patients without obvious contraindications to adhere to a follow-up colonoscopy. If patients were likely to be distressed by a positive FIT result, most GPs described using reassurance strategies emphasising a low cancer probability. Most GPs stressed the probability of false-positive FIT results. Some described taking a positive screening result in CRC screening less seriously than one in breast cancer screening. Most GPs underestimated CRC and AA probabilities after a positive FIT result. When told the actual probabilities, some stated that this knowledge might change the way they would inform patients.ConclusionThese results imply that some of the interviewed GPs have too low a perception of the risk associated with a positive FIT result, which might influence their patients’ decision-making. Simply informing GPs about the actual rates of CRC and AA found in the screening programme might improve this risk perception.

Are Hemorrhoids Associated with False-Positive Fecal Immunochemical Test Results?

PurposeFalse-positive (FP) results of fecal immunochemical tests (FITs) conducted in colorectal cancer (CRC) screening could lead to performing unnecessary colonoscopies. Hemorrhoids are a possible cause of FP FIT results; however, studies on this topic are extremely rare. We investigated whether hemorrhoids are associated with FP FIT results.Materials and MethodsA retrospective study was conducted at a university hospital in Korea from June 2013 to May 2015. Of the 34547 individuals who underwent FITs, 3946 aged ≥50 years who underwent colonoscopies were analyzed. Logistic regression analysis was performed to determine factors associated with FP FIT results.ResultsAmong 3946 participants, 704 (17.8%) showed positive FIT results and 1303 (33.0%) had hemorrhoids. Of the 704 participants with positive FIT results, 165 had advanced colorectal neoplasia (ACRN) and 539 had no ACRN (FP results). Of the 1303 participants with hemorrhoids, 291 showed FP results, of whom 81 showed FP results because of hemorrhoids only. Participants with hemorrhoids had a higher rate of FP results than those without hemorrhoids (291/1176, 24.7% vs. 248/2361, 10.5%; p<0.001). Additionally, the participants with hemorrhoids as the only abnormality had a higher rate of FP results than those experiencing no such abnormalities (81/531, 15.3% vs. 38/1173, 3.2%; p<0.001). In multivariate analysis, the presence of hemorrhoids was identified as an independent predictor of FP results (adjusted odds ratio, 2.76; 95% confidence interval, 2.24–3.40; p<0.001).ConclusionHemorrhoids are significantly associated with FP FIT results. Their presence seemed to be a non-negligible contributor of FP results in FIT-based CRC screening programs.

Prescription drugs associated with false-positive results when using faecal immunochemical tests for colorectal cancer screening

BackgroundThe most common side effect in population screening programmes is a false-positive result which leads to unnecessary risks and costs. AimsTo identify factors associated with false-positive results in a colorectal cancer screening programme with the faecal immunochemical test (FIT). MethodsCross-sectional study of 472 participants with a positive FIT who underwent colonoscopy for confirmation of diagnosis between 2013 and 2014. A false-positive result was defined as having a positive FIT (≥20μg haemoglobin per gram of faeces) and follow-up colonoscopy without intermediate/high-risk lesions or cancer. ResultsWomen showed a two-fold increased likelihood of a false-positive result compared with men (adjusted OR, 2.3; 95%CI, 1.5–3.4), but no female-specific factor was identified. The other variables associated with a false-positive result were successive screening (adjusted OR, 1.5; 95%CI, 1.0–2.2), anal disorders (adjusted OR, 3.1; 95%CI, 2.1–4.5) and the use of proton pump inhibitors (adjusted OR, 1.8; 95%CI, 1.1–2.9). Successive screening and proton pump inhibitor use were associated with FP in men. None of the other drugs were related to a false-positive FIT. ConclusionConcurrent use of proton pump inhibitors at the time of FIT might increase the likelihood of a false-positive result. Further investigation is needed to determine whether discontinuing them could decrease the false-positive rate.

Risk factors for false positive and for false negative test results in screening with fecal occult blood testing

Differences in the risk of a false negative or a false positive fecal immunochemical test (FIT) across subgroups may affect optimal screening strategies. We evaluate whether subgroups are at increased risk of a false positive or a false negative FIT result, whether such variability in risk is related to differences in FIT sensitivity and specificity or to differences in prior CRC risk. Randomly selected, asymptomatic individuals were invited to undergo colonoscopy. Participants were asked to undergo one sample FIT and to complete a risk questionnaire. We identified patient characteristics associated with a false negative and false positive FIT results using logistic regression. We focused on statistically significant differences as well as on variables influencing the false positive or negative risk for which the odds ratio exceeded 1.25. Of the 1,426 screening participants, 1,112 (78%) completed FIT and the questionnaire; 101 (9.1%) had advanced neoplasia. 102 Individuals were FIT positive, 65 (64%) had a false negative FIT result and 66 (65%) a false positive FIT result. Participants at higher age and smokers had a significantly higher risk of a false negative FIT result. Males were at increased risk of a false positive result, so were smokers and regular NSAID users. FIT sensitivity was lower in females. Specificity was lower for males, smokers and regular NSAID users. FIT sensitivity was lower in women. FIT specificity was lower in males, smokers and regular NSAID users. Our results can be used for further evidence based individualization of screening strategies.

Hemorrhoids detected at colonoscopy: an infrequent cause of false-positive fecal immunochemical test results

Colorectal cancer screening by fecal immunochemical tests (FITs) is hampered by frequent false-positive (FP) results and thereby the risk of complications and strain on colonoscopy capacity. Hemorrhoids might be a plausible cause of FP results. To determine the contribution of hemorrhoids to the frequency of FP FIT results. Retrospective analysis from prospective cohort study. Five large teaching hospitals, including 1 academic hospital. All subjects scheduled for elective colonoscopy. FIT before bowel preparation. Frequency of FP FIT results in subjects with hemorrhoids as the only relevant abnormality compared with FP FIT results in subjects with no relevant abnormalities. Logistic regression analysis to determine colonic abnormalities influencing FP results. In 2855 patients, 434 had positive FIT results: 213 had advanced neoplasia and 221 had FP results. In 9 individuals (4.1%; 95% CI, 1.4-6.8) with an FP FIT result, hemorrhoids were the only abnormality. In univariate unadjusted analysis, subjects with hemorrhoids as the only abnormality did not have more positive results (9/134; 6.7%) compared with subjects without any abnormalities (43/886; 4.9%; P = .396). Logistic regression identified hemorrhoids, nonadvanced polyps, and a group of miscellaneous abnormalities, all significantly influencing false positivity. Of 1000 subjects with hemorrhoids, 67 would have FP results, of whom 18 would have FP results because of hemorrhoids only. Potential underreporting of hemorrhoids; high-risk individuals. Hemorrhoids in individuals participating in colorectal cancer screening will probably not lead to a substantial number of false-positive test results.

Small Bowel Evaluation in Asymptomatic Fecal Immunochemical Test-Positive Patients with a Negative Colonoscopy: Is It Necessary?

Screening for colorectal cancer (CRC) and its precursors by fecal occult blood test (FOBT) is widely recommended and is being applied more than ever [1–3]. Although annual or biennial guaiac fecal occult blood test (gFOBT) screening has been proved to reduce the mortality of CRC [4], the gFOBT has been faulted for its low sensitivity [5, 6]. More recently, the fecal immunochemical test (FIT) has been introduced as an alternative to the gFOBT. The FIT is currently preferred over the gFOBT due to its higher sensitivity and improved detection rate for advanced neoplasia [5, 7–10]. Besides its diagnostic performance, the FIT has several advantages over the gFOBT including no need for dietary restriction, easier stool collection method, and automated analysis [11]. Furthermore, quantitative FIT allows for the adjustment of the cutoff value for an abnormal result based on population characteristics and available colonoscopy resources. Due to these characteristics, quantitative FIT is more favored as a screening tool than qualitative FIT [11]. The FIT selectively reacts with the globin moiety of human hemoglobin [12]. Because globin is rapidly degraded by proteases in the upper gastrointestinal (GI) tract, the FIT dose not detect small amounts of blood in the upper GI tract and selectively recognizes occult bleeding of colorectal origin [12]. With regard to small bowel lesions, although there is a possibility that some small bowel occult bleeding could be identified by FIT, no data are currently available regarding this issue. In the current issue of Digestive Diseases and Sciences, Chiba et al. [13] present the results of their prospective study on small bowel evaluation in asymptomatic FIT-positive subjects with a negative colonoscopy. In this, the first study to evaluate the small bowel with capsule endoscopy (CE) in asymptomatic FIT-positive patients with a negative colonoscopy, 53 asymptomatic patients with FIT-positivity and a negative total colonoscopy and esophagogastroduodenoscopy underwent CE. The CE findings were classified into three categories: P0, no abnormalities or findings without potential for bleeding; P1, findings with uncertain potential for bleeding; and P2, findings with high potential for bleeding. The cecal completion rate was 92.5%. There were no cases of P2, 19 cases of P1, and 34 cases of P0. Moreover, no abnormalities were identified in five patients who underwent additional diagnostic evaluations that were considered necessary based on the individual clinical results. No clinically significant small bowel lesions were found in the asymptomatic FIT-positive patients with negative bidirectional endoscopy. Although FIT has been widely accepted as a CRC screening tool, 40–60% of subjects with a positive FIT are found to have no lesions in their colon or rectum to explain their positive status [5, 14, 15]. How then do we explain the discrepancy between the results of FIT and colonoscopy? There are several possible explanations for this discrepancy. First, this may reflect true false-positive results of FIT for advanced neoplasia. Quantitative FIT results are subjected to predetermined cut-off values for fecal hemoglobin; this methodology could inevitably yield some true false positives. Additionally, medications that can increase the likelihood of GI bleeding may cause false-positive FIT J. J. Park Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University, Seoul, Korea

Hemorrhoids Are an Infrequent Cause of False Positive Fecal Immunochemical Test Results

Hemorrhoids Are an Infrequent Cause of False Positive Fecal Immunochemical Test Results