Detection of Upper Gastrointestinal Disorders in Patients with Positive Fecal Immunochemical Test (FIT) and Normal Colonoscopy: A Cross-Sectional Study

Abstract Introduction Colorectal cancer (CRC) is the second most prevalent cancer in the world, and the fecal immunochemical test (FIT) can be mentioned among the CRC screening methods based on the detection of occult blood in the feces, which may indicate upper gastrointestinal (UGI) malignancies; therefore, patients with a positive FIT but normal colonoscopy may be considered for a UGI endoscopy. Materials and Methods The present study was conducted on patients with a positive FIT who were submitted to colonoscopy with normal results. They subsequently underwent endoscopy for the detection of UGI disorders. Results We included 121 patients (64.5% of women and 35.5% of men; average age: 58.85 ± 12.93 years), 72.7% of whom were positive for Helicobacter pylori. The predominant result of the UGI endoscopy was normal, followed by erythema of the gastric mucosa, and anemia and dyspepsia were the most common clinical findings. The most common pathological result was chronic gastritis, followed by acute gastritis. Only one patient presented stomach cancer (adenocarcinoma). Conclusion Considering the small prevalence of cancer in the UGI endoscopies of patients with positive FIT and normal colonoscopy, to the performance of UGI endoscopy in these patients may not be necessary.

Implementation of an organized colorectal cancer screening program through quantitative fecal immunochemical test followed by colonoscopy in an urban low-income community: Guidance and strategies

Abstract Fecal Immunochemical Test (FIT) followed by a colonoscopy is an efficacious strategy to improve the adenoma detection rate and Colorectal Cancer (CRC). There is no organized national screening program for CRC in Brazil. The aim of this research was to describe the implementation of an organized screening program for CRC through FIT followed by colonoscopy, in an urban low-income community of São Paulo city. The endpoints of the study were: FIT participation rate, FIT positivity rate, colonoscopy compliance rate, Positive Predictive Values (PPV) for adenoma and CRC, and the rate of complications. From May 2016 to October 2019, asymptomatic individuals, 50-75 years old, received a free kit to perform the FIT. Positive FIT (≥ 50 ng/mL) individuals were referred to colonoscopy. 10,057 individuals returned the stool sample for analysis, of which (98.2%) 9,881 were valid. Women represented 64.8% of the participants. 55.3% of individuals did not complete elementary school. Positive FIT was 7.8% (776/9881). The colonoscopy compliance rate was 68.9% (535/776). There were no major colonoscopy complications. Adenoma were detected in 63.2% (332/525) of individuals. Advanced adenomatous lesions were found in 31.4% (165/525). CRC was diagnosed in 5.9% (31/525), characterized as adenocarcinoma: in situ in 3.2% (1/31), intramucosal in 29% (9/31), and invasive in 67.7% (21/31). Endoscopic treatment with curative intent for CRC was performed in 45.2% (14/31) of the cases. Therefore, in an urban low-income community, an organized CRC screening using FIT followed by colonoscopy ensued a high participation rate, and high predictive positive value for both, adenoma and CRC.

Evaluation of quantitative stool occult blood test in opportunistic screening for colorectal cancer / 中华健康管理学杂志

Objective:To evaluate the efficacy of quantitative fecal immunochemical test (fecal immunochemical test, FIT) in the screening of colorectal cancer and precancerous lesions.Methods:47 243 patients who underwent quantitative FIT screening for colorectal cancer in the Health Management Department of Shenzhen People′s Hospital from January 2019 to October 2020 were enrolled as subjects. Colonoscopy was recommended for patients with positive quantitative FIT. A follow-up was done after one year to compare the results of the quantitative FIT positive group and the negative group after colonoscopy. Data were adjusted by propensity score matching method and a receiver operating characteristic curve ( ROC) was established to evaluate the diagnostic effect of quantitative FIT combined with colonoscopy on colorectal cancer and precancerous lesions. Results:A hemoglobin concentration>100 μg/L was set as a positive threshold. There were 2 472 positive cases of quantitative FIT, and the positive rate was 5.23%. After one-year follow-up, 284 patients had completed colonoscopy; the colonoscopy compliance was 11.49%. Of the negative population, 1 493 patients selected colonoscopy within one year. Compared with the results of gold standard colonoscopy, the sensitivity and specificity of quantitative FIT for screening for advanced adenoma and cancer were 26.53% and 86.54%, respectively. The sensitivity for colorectal cancer screening was 94.44% and screening for advanced adenoma was 22.77%. After propensity score matching, there were 256 FIT positive patients and 705 FIT negative patients. Colorectal cancer was the outcome variable, while FIT combined with colonoscopy, age combined with colonoscopy, and FIT combined with age combined with colonoscopy were the diagnostic indicators. The areas under the curve were 0.841(95% CI:0.778-0.904), 0.677(95% CI: 0.535-0.820), and 0.882(95% CI:0.807-0.958), respectively. Conclusion:Quantitative FIT has a high susceptibility to opportunistic screening for colorectal cancer, and a low sensitivity to advanced adenoma. At the same time, quantitative FIT combined with colonoscopy has a good diagnostic accuracy for colorectal cancer, which is better than the effect of using age as a cut-off point for colonoscopy. Quantitative FIT combined with age and colonoscopy has the best effect on screening for colorectal cancer. Quantitative FIT has a high sensitivity to colorectal cancer and a low sensitivity to advanced adenoma.

Colorectal Cancer Screening: Current Status and Progress / 胃肠病学

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In recent years, the overall incidence of CRC in China has shown an upward trend. According to the national estimates of cancer in China, CRC was the second most commonly diagnosed cancer of the digestive system. Screening of CRC can significantly reduce its morbidity and mortality. The screening methods are diverse. At present, a two-step screening program based on fecal immuno-chemical test (FIT) and colonoscopy is recommended by authoritative guidelines or consensus in many countries. Other screening methods can be used as individualized options and supplements. Multigene germline mutation detection should be performed for extremely high-risk population with multiple colorectal polyps (>10 polyps) and CRC personal or family history; or with more than 20 polyps.

Application and prospect of fecal DNA test in colorectal cancer screening / 中华胃肠外科杂志

Effective early screening and primary prevention is one of the major initiatives to decrease the morbidity and mortality of colorectal cancer in China. As a new non-invasive screening method for colorectal cancer in recent years, fecal DNA test detects colorectal cancer by analyzing gene mutations from intestinal tumor cells in the feces. The most widely used method among fecal DNA test is multi-target stoolDNA test (MT-sDNA). Many studies abroad on this emerging technique have been carried out to verify its high sensitivity, and it is gradually used in the clinic with continuous improvement and development of technology. Meanwhile, domestic MT-sDNA is still in the prototype stage, and more researches from Chinese population are needed. Compared with traditional screening methods, MT-sDNA technology has the advantages of non-invasiveness, painlessness and convenience. But its defects exist, such as high cost and low specificity. MT-sDNAis in accordance with precision medicine, and can largely make up for the shortcomings of traditional screening methods for colorectal cancer. It also holds a great promise for promoting the screening for colorectal cancer. This paper is aimed to discuss the application value of fecal DNA test by introducing its related researches at home and abroad,and summarizing its merits and demerits.

The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces

BACKGROUND/AIMS: Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. METHODS: Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. RESULTS: The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. CONCLUSIONS: The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC.

Usefulness of fecal immunochemical test and fecal calprotectin for detection of active ulcerative colitis

BACKGROUND/AIMS: Ulcerative colitis undergoes periods of exacerbation and remission. Fecal calprotectin levels increase with gut inflammation and correlate with endoscopic disease activity in ulcerative colitis. Intestinal blood loss and fecal immunochemical test levels also correlate with endoscopic disease activity. This study statistically evaluated the usefulness of fecal calprotectin, fecal immunochemical test, and C-reactive protein (CRP) as markers of disease activity. METHODS: A total 106 ulcerative colitis patients who underwent endoscopy and fecal calprotectin, fecal immunochemical test, and CRP testing, from March 2015 to August 2016, were retrospectively reviewed. Disease activity was assessed using a partial Mayo score and Mayo endoscopic score. The ability of fecal and serologic tests to reflect endoscopic disease severity was statistically evaluated. RESULTS: Among 106 patients, 68 underwent endoscopy and stool study within 2 weeks. In patients with mild to severe activity, fecal immunochemical test and fecal calprotectin were superior to CRP at Mayo endoscopic score detection rate. The area under the curves of fecal immunochemical test and fecal calprotectin for the detection of Mayo endoscopic score ≥1 were 0.956 and 0.942, respectively, and were superior to that of CRP (0.756). At Mayo endoscopic score, the effects of combination of fecal immunochemical test and CRP or fecal calprotectin and CRP were found to be higher than those of the independent fecal immunochemical test or fecal calprotectin. CONCLUSIONS: Fecal immunochemical test and fecal calprotectin can effectively detect active ulcerative colitis better than remission. As these markers reflect the status of mucosal inflammation, they may reduce the requirement for invasive endoscopic examination.

Budget Impact of the Accreditation Program for Clinical Laboratories on Colorectal Cancer Screening via Fecal Immunochemical Testing: Results from the National Cancer Screening Program in Korea

BACKGROUND: False-positive fecal immunochemical test (FIT) results in the National Cancer Screening Program (NCSP) for colorectal cancer may lead to unnecessary procedures, such as colonoscopies, increasing the medical costs. We estimated reductions in the cost of National Health Insurance according to the accreditation status of screening facilities participating in the NCSP for colorectal cancer. METHODS: We used data collected between 2007 and 2010 from NCSP and the Korea Central Cancer Registry to identify patients with colorectal cancer. We also ascertained the history of the accreditation of each facility by the Korean Laboratory Accreditation Program (KLAP). Budget impact was defined as a reduction in medical costs achieved when the false-positive rate of the non-accredited facilities decreased relative to that of the accredited facilities. RESULTS: A total of 3,285 screening facilities participated in the NCSP. Of these, 196 were accredited by the KLAP. The false-positive rate of the accredited facilities was 2.47%, and that of the non-accredited facilities was 6.83%. Medical costs were estimated to be reduced by approximately 19 million US dollars (USD), and the cost of detecting one case of colorectal cancer was estimated to decrease from 9,212 USD to 7,332 USD if the false-positive rate of non-accredited facilities were decreased to that of the accredited facilities. Clinics were estimated to have the largest associated cost reduction. CONCLUSIONS: Quality assurance in clinical laboratories could lower false-positive rates and prevent the use of unnecessary procedures, ensuring patient safety and increasing the cost-effectiveness of FIT screening in the NCSP for colorectal cancer.

Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis

BACKGROUND/AIMS: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. METHODS: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. RESULTS: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p<0.0001 vs r=0.30, p=0.054). CONCLUSIONS: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.

Is It Necessary to Repeat Fecal Occult Blood Tests with Borderline Results for Colorectal Cancer Screening?

The fecal immunochemical test (FIT) is the initial non-invasive investigation of choice for population-based colorectal cancer (CRC) screening. We evaluated the positivity rate in repeated tests using the same fecal specimen that showed borderline results in the FIT. A total of 6,465 patients were tested with the FIT in a tertiary-care hospital from July to December 2016. FIT was done using OC-Sensor PLEDIA (Eiken Chemical Co., Tokyo, Japan). Among 6,465 patients, 364 (5.6%) patients showed a positive FIT result of over 20 µg Hb/g feces. A total of 112 (1.7%) patients showed borderline scores of 10.2–20 µg Hb/g feces, and 5,989 (92.6%) patients showed negative results of less than 10 µg Hb/g feces. Among the 101 repeat-tested patients, 19 (18.8%) of the patients' scores converted to levels above the positive cut-off threshold. Repeated results of 19 patients showed score elevations from 20.2 to 68 µg Hb/g feces. These results suggest that it is most important to analyze properly prepared samples, even if only once. Therefore, the laboratory staff should ensure the proper preparation of stool specimens for FIT. Laboratory directors should choose the best cut-off value for detecting CRC at their respective institutions.

Fecal immunochemical test followed by colonoscopy in opportunistic screening for colorectal neoplasm / 中华全科医师杂志

Objective To assess the fecal immunochemical test (FIT) followed by colonoscopy in opportunistic screenings for colorectal neoplasm.Methods Total 6 193 patients, who underwent opportunistic colorectal cancer (CRC) screening, were classified into four groups: 3 812 patients underwent direct colonoscopy (group 1), 1 244 patients received one FIT followed by colonoscopy (group 2), 341 patients received two FITs followed by colonoscopy (group 3), and 796 patients received three FITs followed by colonoscopy (group 4).Results Total 97 (1.6%) patients with CRC and 1 038 (16.8%) with colorectal adenoma were detected.The positive predictive value of 1, 2 and 3 positive tests out of three FITs for CRC were 4.53%, 5.62% and 8.94%, respectively, which was higher than that of direct colonoscopy (1.52%).One or more positive tests out of three FIT had the largest area under receiver operating characteristic curve (0.743).For colorectal adenoma, detection rate of direct colonoscopy (17 581.25/105) was higher than all FIT strategies (3 732.30/105-13 127.41/105).Conclusions Single or repeated FIT and colonoscopy have different screening utility.One or more positive tests out of three FIT followed by colonoscopy is preferred to screen CRC, and direct colonoscopy is better for detection of colorectal adenoma.

A Combination of Fecal Immunochemical Test Results and Iron Deficiency Anemia for Detection of Advanced Colorectal Neoplasia in Asymptomatic Men

PURPOSE: A substantial proportion of patients with colorectal cancer (CRC) present with iron deficiency anemia (IDA), and fecal immunochemical test (FIT) has proven to be an effective method for detecting the majority of CRC cases. A combination strategy of FIT results and IDA may be useful for risk stratification for detecting advanced colorectal neoplasia (ACRN). We compared the prevalence of ACRN among four groups stratified by FIT results and the presence of IDA. MATERIALS AND METHODS: A cross-sectional study was performed on asymptomatic male participants who underwent both FIT and colonoscopy between 2010 and 2014 as part of a comprehensive health screening program in Korea. RESULTS: Of 17236 participants, 522 (3.0%) showed positive FIT results and 26 (0.2%) had IDA. The mean age of the study participants was 40.8 years. The participants were classified into four groups: positive FIT result/IDA (G1, n=7), positive FIT result/no IDA (G2, n=515), negative FIT result/IDA (G3, n=19), and negative FIT result/no IDA (G4, n=16695). The prevalences of ACRN in G1, G2, G3, and G4 were 28.6, 13.4, 5.3, and 1.5%, respectively (p<0.001) and those of CRC were 28.6, 1.6, 0.0, and 0.01%, respectively (p<0.001). Subjects with positive FIT results and IDA had an increased risk of ACRN and CRC in both group aged <50 and ≥50 years. CONCLUSION: Subjects with positive FIT results and IDA had an increased risk of ACRN. Our results suggest that a combination strategy of FIT and IDA may be helpful in selecting and prioritizing asymptomatic men for colonoscopy.

Cost-effectiveness comparison in colorectal cancer screening with fecal immunochemical test and colonoscopy between ages and genders / 中华消化内镜杂志

Objective To investigate the rational program of colorectal cancer(CRC)screening between ages and genders by using single or repeated fecal immunochemical test(FIT)and colonoscopy. Methods Data of 6 193 patients who underwent opportunistic CRC screening at Peking Union Medical College Hospital were retrospectively analyzed.Patients were divided into four groups:(1)direct colonoscopy;(2)one FIT followed by colonoscopy;(3)two FITs followed by colonoscopy;(4)three FITs followed by colonoscopy.Cost-effectiveness of the four screening procedures was compared between different age groups and genders.Results Ninety-seven(1.6%)patients with CRC and 1 038(16.8%)with colorectal adenoma were detected. In patients younger than 40 years old,1-3 positive FIT strategies were superior to direct colonoscopy. In men aged 40 to 60,one or two positive FITs out of three was more cost-effective than direct colonoscopy,so was one positive FIT out of three in women aged 40 to 60. Direct colonoscopy was the most cost-effective strategy in men older than 60,while one positive FIT out of two was the best screening choice in women older than 60. Conclusion Age and gender are two influential factors for cost-effectiveness of CRC screening. Direct colonoscopy is the most cost-effective screening strategy for men older than 60,but one or more positive FIT followed by colonoscopy is preferred in other age and gender groups.

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

PURPOSE: False-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 METHODS: A 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. RESULTS: Among 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). CONCLUSION: Hemorrhoids 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.

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin?

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

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.

The Significance of Fecal Immunochemical Test to Screen for Colorectal Cancer in National Cancer Screening Program

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the major causes of death and poses a major public health concern. The National CRC Screening Programme (NCSP) provides annual CRC screening using a fecal occult blood test for individuals >50 years of age since 2004. The purpose of the current study was to determine the outcomes and efficacy of a fecal immunochemical test (FIT) based on the NCSP in a quality-controlled university hospital setting. METHODS: We retrospectively reviewed the medical records and a standardized questionnaire from the NCSP of 3,852 individuals who underwent a FIT between March and December 2009. All of the subjects submitted a stool specimen for a FIT, while a double-contrast barium enema or colonoscopy was performed as a confirmatory examination for FIT-positive individuals. The CRC screening rate and rate of detection colorectal adenomas, advanced adenomas, and colorectal cancers by FIT were evaluated. RESULTS: The CRC screening rate with FIT was very high (72.3%), but the positive rate of detection by FIT was only 1.3%. The rate of detection for colorectal cancers, adenomas, and advanced adenomas by FIT was 0.08%, 0.39%, and 0.13%, respectively. The quantitative values of FIT in individuals with colorectal adenomas and cancers were significantly higher than other colorectal diseases. Men (P=0.001) and elderly individuals (P=0.039) were significantly more common in the FIT-positive group than the FIT-negative group. Approximately 28% of the subjects with FIT-positive tests did not receive a confirmatory examination. CONCLUSIONS: Although the FIT had a low rate of detection, the FIT was a useful screening tool for detection of CRC in the NCSP. It will be important to increase CRC screening rates and confirmatory examination rates.