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fecal occult blood; fecal immunochemical testing; fecal immunofluorescence testing, multitarget stool DNA (mt-sDNA, FOB, FIT, iFOBT, ColonCARE, Hemoccult, ICT, InSure)

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: 1) false positives: (contributions generally NOT significant) a) hemoglobin & myoglobin from meats & fish b) peroxidases from fruits & vegetables c) peroxidases in intestinal flora 2) false negatives: a) ascorbate (vitamin C) > 250 mg QD b) other antioxidants 3) iron supplement in the form of ferrous sulfate or gluconate do NOT cause a positive test 4) NSAIDs probably don't interfere with iFOBT [4,10] a) aspirin < 1250 mg/day does not interfere b) low-dose aspirin (81 mg QD) compared with no aspirin is associated with a higher sensitivity (71 vs 36%) for detecting advanced colorectal neoplasms, at the cost of a lower specificity (86 vs 91%) [12] 5) anticoagulation (warfarin) does not interfere with iFOBT [10, 21] 6) 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) 1) age < 20 years - Peutz-Jeghers syndrome 2) age 20-60 years a) Crohn's disease b) chronic radiation therapy c) NSAID-induced ulcers d) large hiatal hernia, Cameron erosion e) gastric antral vascular ectasia (watermelon stomach) f) malignancy g) von Willebrand disease 3) age > 60 years a) amyloidosis b) angiodysplasia (angiectasia) c) hereditary hemorrhagic telangiectasia d) malignancy, especially colorectal cancer 4) colorectal cancer a) 50-87% of patients with colorectal cancer yield positive results b) 16-30% reduction in mortality from colon cancer for patients that adhere to annual or biennial testing [2,3] c) 5% cumulative risk of positive fecal occult blood over period of 13 years [2] Management: 1) colonoscopy for evaluation of positive fecal occult blood 2) 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]

Related

bright red blood per rectum (BRBPR) hematochezia; bloody stool, maroon stool lower gastrointestinal hemorrhage

Specific

stool guaiac

General

hemoglobin.gastrointestinal in body fluid hemoglobin in stool point of care test

References

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