fecal occult blood; fecal immunochemical testing; fecal immunofluorescence testing, multitarget stool DNA (mt-sDNA, FOB, FIT, iFOBT, ColonCARE, Hemoccult, ICT, InSure)
Introduction
Detection of traces of blood in the feces too small to be seen.
Indications
- screening for colon cancer
- specificity of mt-sDNA decreases with advancing age, thus best in patients 50-65 years old[24]
- evaluation of anemia
- evaluation of gastrointestinal hemorrhage
- abdominal pain
- changes in bowel movements
- weight loss
- melena
Procedure
The stool Guaiac test assesses peroxidase activity by addition of hydrogen peroxide to guaiac, orthotoluidine, orthodinisidine or benzidine. Guaiac is the most commonly used, & the least sensitive reagent resulting in formation of a blue color with peroxidase activity. Peroxidase activity results most commonly from the presence of hemoglobin.
Newer tests, iFOBT, ColonCARE, Hemoccult, ICT, InSure, use antibody to hemoglobin (immnunochemical FOBT, iFOBT)
Sensitivity of iFOBT for detecting colorectal carcinoma is 88%, equally sensitive for right & left sided carcinomas[15]
Sensitivity of iFOBT for detecting advanced adenomas is 38-44% vs 17% for Guaiac based methods[11][15]
Aspirin 300 mg before FIT does not improve sensitivity[23]
Specificities of iFOBT & Guaiac based methods are similar (92% vs. 93%)[17], thus > 50% will have false positive within 10 years if done annually
Fewer colonoscopies are necessary to detect colon cancer with iFOBT than with Guaiac based methods[11]
Quantitative immunochemical testing holds promise[7][8]
Fecal immunochemical testing (FIT) detects human globulin.[22]
Various FIT tests had a sensitivity of 0.91 at a threshold of 10 ug/g & 0.71 at a threshold of greater than 20 ug/g for colorectal cancer.
Sensitivity of FIT is lower for advanced adenomatous polyps 0.25-0.40 (0.10-0.40)[26]
Specificity of FIT ranged from 0.90 to 0.95.[22] (85-97%)[26]
At a specificity of 0.9, if done every 2 years, cumulative specificity is 0.59 over a 10 year period; if done every year 0.35.
Normal individuals lose 2.0-2.5 mL of blood into the gastrointestinal tract daily. Guaiac test kits detect > 5-10 mL of blood in the feces/day (5-10 mg of hemoglobin/gram of stool) assuming a blood hemoglobin of 15 g/dL with an average stool passage of 150 g/day.
Peroxidase activity from hemoglobin is diminished with passage through the GI tract, thus bleeding from the upper GI tract is less likely to produce a positive test than bleeding from the lower GI tract. Similarly, hemoglobin is more likely to be digested in the upper GI tract, thus less likely to be detected when a GI bleed originates from the upper GI tract.
Interferences
- false positives: (contributions generally NOT significant)
- hemoglobin & myoglobin from meats & fish
- peroxidases from fruits & vegetables
- peroxidases in intestinal flora
- false negatives:
- ascorbate (vitamin C) > 250 mg QD
- other antioxidants
- iron supplement in the form of ferrous sulfate or gluconate do NOT cause a positive test
- NSAIDs probably don't interfere with iFOBT[4][10]
- anticoagulation (warfarin) does not interfere with iFOBT [10, 21]
- aspirin or direct-acting oral anticoagulants associated with lower positive predictive value of FIT for cancer & advanced adenomas[21]
- for aspirin positive predictive value for colorectal cancer is 3.8% vs 6.4% non users, & 27.2% vs 32.6% for advanced adenomas
- for direct-acting oral anticoagulants positive predictive value for colorectal cancer is 0.9% vs 6.8%, & 20.5% vs 32.4% for advanced adenomas[21]
Differential diagnosis
(of positive test)
- age < 20 years
- age 20-60 years
- Crohn's disease
- chronic radiation therapy
- NSAID-induced ulcers
- large hiatal hernia, Cameron erosion
- gastric antral vascular ectasia (watermelon stomach)
- malignancy
- von Willebrand disease
- age > 60 years
- colorectal cancer
- 50-87% of patients with colorectal cancer yield positive results
- 16-30% reduction in mortality from colon cancer for patients that adhere to annual or biennial testing[2][3]
- 5% cumulative risk of positive fecal occult blood over period of 13 years[2]
Management
- colonoscopy for evaluation of positive fecal occult blood
- insufficient evidence to recommend routine upper endoscopy (EGD) following negative colonoscopy (fecal occult blood +)[11]
- risk of cancer proximal to the colon within 3 years < 1% [27]
Notes
- annual fecal immunochemical testing by mail[18]
- cumulative positive FIT rate over 5 consecutive screenings for persons aged 50-64 years was 18% for women & 25% for men
- colorectal cancer detection rate: 0.3% in 1st round, 0.2% in 2nd round, < 0.1% therafter
- advanced adenoma detection: 1.3% in 1st round, 0.9% in 2nd round
- positive FOBT associated with increased all-cause mortality[20]
- biennial screening with fecal immunochemical testing is associated with 34% fewer advanced colorectal cancers & 40% fewer colorectal cancer- related deaths[25]
More general terms
More specific terms
Additional terms
- bright red blood per rectum (BRBPR)
- hematochezia; bloody stool, maroon stool
- lower gastrointestinal hemorrhage
References
- ↑ Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 539
- ↑ 2.0 2.1 2.2 Journal Watch 22(5):38, 2002 Traverso G et al, N Engl J Med 346:311, 2002
- ↑ 3.0 3.1 Journal Watch 24(14):112, 2004 Faivre J, Dancourt V, Lejeune C, Tazi MA, Lamour J, Gerard D, Dassonville F, Bonithon-Kopp C. Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study. Gastroenterology. 2004 Jun;126(7):1674-80. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15188160
- ↑ 4.0 4.1 Prescriber's Letter 12(3): 2005 Aspirin and Nonsteroidal Anti-inflammatory Agents and their Effect on Fecal Occult Blood Tests Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210310&pb=PRL (subscription needed) http://www.prescribersletter.com
Journal Watch 25(3):29, 2005 Kahi CJ, Imperiale TF. Do aspirin and nonsteroidal anti-inflammatory drugs cause false-positive fecal occult blood test results? A prospective study in a cohort of veterans. Am J Med. 2004 Dec 1;117(11):837-41. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15589487 - ↑ Prescriber's Letter 12(9): 2005 New Take-Home Screening Tests for Colon Cancer Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211007&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Fraser CG, Matthew CM, Mowat NA, Wilson JA, Carey FA, Steele RJ. Immunochemical testing of individuals positive for guaiac faecal occult blood test in a screening programme for colorectal cancer: an observational study. Lancet Oncol. 2006 Feb;7(2):127-31. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16455476
- ↑ 7.0 7.1 Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, Birkenfeld S, Leshno M, Niv Y. A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med. 2007 Feb 20;146(4):244-55. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17310048
Imperiale TF. Quantitative immunochemical fecal occult blood tests: is it time to go back to the future? Ann Intern Med. 2007 Feb 20;146(4):309-11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17310056 - ↑ 8.0 8.1 Guittet L et al, Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population Gut 2007, 56:210 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16891354
- ↑ van Rossum LG et al. Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology 2008 Jul; 135:82. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18482589
- ↑ 10.0 10.1 Levi Z et al Sensitivity, but not specificity, of a quantitative immunochemical fecal occult blood test for neoplasia is slightly increased by the use of low-dose aspirin, NSAIDs, and anticoagulants. Am J Gastroenterol 2009 Apr; 104:933. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19293792
Iles-Shih L et al. Prevalence of significant neoplasia in FOBT-positive patients on warfarin compared with those not on warfarin. Am J Gastroenterol 2010 Sep; 105:2030 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20683445 - ↑ 11.0 11.1 11.2 11.3 Park DI et al. Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening. Am J Gastroenterol 2010 Sep; 105:2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20502450 <Internet> http://dx.doi.org/10.1038/ajg.2010.179
Allison JE. FIT: A valuable but underutilized screening test for colorectal cancer - It's time for a change. Am J Gastroenterol 2010 Sep; 105:2026 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20818351 <Internet> http://dx.doi.org/10.1038/ajg.2010.181 - ↑ 12.0 12.1 Physician's First Watch, Dec 8, 2010 Massachusetts Medical Society http://www.jwatch.org
Brenner H et al Low-Dose Aspirin Use and Performance of Immunochemical Fecal Occult Blood Tests JAMA. 2010 Dec 8;304(22):2513-20. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21139112 <Internet> http://jama.ama-assn.org/content/304/22/2513.short - ↑ Occult Blood, Fecal Laboratory Test Directory ARUP: http://www.aruplab.com/guides/ug/tests/0020374.jsp
- ↑ de Wijkerslooth TR et al. Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol 2012 Oct; 107:1570. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22850431
- ↑ 15.0 15.1 15.2 Lee JK, Liles EG, Bent S et al Accuracy of Fecal Immunochemical Tests for Colorectal Cancer: Systematic Review and Meta-analysis. Ann Intern Med. 2014;160(3):171-181 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24658694 <Internet> http://annals.org/article.aspx?articleid=1819122
- ↑ Hernandez V, Cubiella J, Gonzalez-Mao MC et al Fecal immunochemical test accuracy in average-risk colorectal cancer screening. World J Gastroenterol. 2014 Jan 28;20(4):1038-47 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24574776
- ↑ 17.0 17.1 Kapidzic A et al. Attendance and yield over three rounds of population-based fecal immunochemical test screening. Am J Gastroenterol 2014 Aug; 109:1257 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24980879
- ↑ 18.0 18.1 Jensen CD et al Fecal Immunochemical Test Program Performance Over 4 Rounds of Annual Screening: A Retrospective Cohort Study. Ann Intern Med 2016 Apr 5; 164:456 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26811150 <Internet> http://annals.org/article.aspx?articleid=2484289
- ↑ Zorzi M, Hassan C, Capodaglio G et al. Long-term performance of colorectal cancer screening programmes based on the faecal immunochemical test. Gut 2017 Nov 3; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29101260
- ↑ 20.0 20.1 Orciari Herman A, Fairchild DG Positive FOBT Results Associated with Increased Mortality Risk. Physician's First Watch, July 17, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org Reference to Gut article, Link broken
- ↑ 21.0 21.1 21.2 Randel KR, Botteri E, Romstad KMK et al Effects of Oral Anticoagulants and Aspirin on Performance of Fecal Immunochemical Tests in Colorectal Cancer Screening. Gastroenterology. 2019 Jan 25. PMID: https://www.ncbi.nlm.nih.gov/pubmed/30689972
- ↑ 22.0 22.1 22.2 Imperiale TF, Gruberv RN, Stump TE et al Performance Characteristics of Fecal Immunochemical Tests for Colorectal Cancer and Advanced Adenomatous Polyps: A Systematic Review and Meta-analysis. Ann Intern Med. 2019. Feb 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30802902 https://annals.org/aim/article-abstract/2726664/performance-characteristics-fecal-immunochemical-tests-colorectal-cancer-advanced-adenomatous-polyps
Allison J. Why What You May Not Know About Fecal Immunochemical Testing Matters. Ann Intern Med. 2019. Feb 26 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30802903 https://annals.org/aim/article-abstract/2726665/why-what-you-may-know-about-fecal-immunochemical-testing-matters - ↑ 23.0 23.1 Brenner H et al. Effect of a single aspirin dose prior to fecal immunochemical testing on test sensitivity for detecting advanced colorectal neoplasms: A randomized clinical trial. JAMA 2019 May 7; 321:1686 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31063574 https://jamanetwork.com/journals/jama/fullarticle/2732573
- ↑ 24.0 24.1 Berger BM, Kisiel JB, Imperiale TF et al. Low incidence of aerodigestive cancers in patients with negative results from colonoscopies, regardless of findings from multi-target stool DNA tests. Clin Gastroenterol Hepatol 2019 Aug 5; PMID: https://www.ncbi.nlm.nih.gov/pubmed/31394289 Free Article
- ↑ 25.0 25.1 Chiu HM, Jen GH, Wang YW et al Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers. Gut. 2021 Jan 25 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33495268 Free article.
- ↑ 26.0 26.1 26.2 Levy BT, Xu Y, Daly JM et al Comparative Performance of Common Fecal Immunochemical Tests: A Cross-Sectional Study. Ann Intern Med. 2024 Sep 3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/39222513 https://www.acpjournals.org/doi/10.7326/M24-0080
- ↑ 27.0 27.1 de Klaver W et al. Risk of cancers proximal to the colon in fecal immunochemical test positive screenes in a colorectal cancer screening program. Gastroenterology 2024 Sep; 167:788. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38697486 https://www.gastrojournal.org/article/S0016-5085(24)00493-1/fulltext