Immunological Stool Test

The immunological stool test (fecal immunochemical test, FIT) is primarily used for early detection and thus prevention of colorectal cancer. The test is based on the immunological detection of occult blood (synonym: fecal occult blood test – FOBT; more precise immunological FOBT = iFOBT). Since April 1, 2017, the immunological fecal occult blood test (quantitative iFOBT) has replaced the previously common hemoccult fecal occult blood test (gujac-based test; gFOBT) paid for by the statutory health insurance. As part of colorectal cancer screening, iFOBT is recommended once a year from the age of 50. From the age of 55, colonoscopy (colonoscopy) is additionally offered as a screening examination. Confounding factors

  • Proton pump inhibitors (proton pump inhibitors, acid blockers):
    • Sensitivity (percentage of diseased patients in whom disease is detected by use of the test, i.e., a positive test result occurs) at 43.0% (PPI) and 65.6% (non-PPI), respectively
    • Specificity (probability that actually healthy people who do not suffer from the disease in question are also detected as healthy in the test) at 86.9% (PPI) and 92.3% (non-PPI), respectively
    • PPI users also had a 63% increased odds ratio for a false positive stool test result (possibly due to gastric acid-related dysbiosis of the small intestinal mucosa, more undigested hemoglobin from upper sections of the gastrointestinal tract, or NSAID-related small intestinal lesions)

The procedure

The detection of fecal occult blood is very valuable for the diagnosis of colon cancer (colorectal cancer) or colorectal polyps. 70-80% of all colorectal polyps are adenomas, which are neoplasms (new formations) that carry malignant potency, meaning they can degenerate malignantly. The rich vascularization (blood supply) of these neoplasms quickly leads to small blood inclusions in the stool, which are not visible to the naked eye. In the past, the so-called hemoccult stool test was used for detection in addition to the immunological stool test. This test detects minute amounts of blood through the peroxidase activity (enzymatic activity) of hemoglobin (red blood pigment). (Sensitivity (percentage of diseased patients in whom the disease is detected through the use of the test, i.e. The predictive value is 40-65%, i.e. in 40-65% of patients colorectal cancer – confirmed by colonoscopy – was correctly detected by the hemoccult test. The patient is given test pads and samples of his stool are taken. The test can give false positive results, as it also reacts to animal blood and plant substances from food. For this reason, the patient must avoid raw or semi-raw meat products (e.g. blood sausage) beforehand. The immunological stool test is more specific because it detects only human hemoglobin (the patient no longer has to follow a special diet). The immunological test for human hemoglobin (iFOBT) contains specific antibodies (substances that react with specific surface features of hemoglobin) and is therefore a more sensitive procedure (hemoccult vs. immunological stool test: increase in sensitivity of 90% with simultaneous improvement in specificity of about 40% for carcinomas and advanced adenomas. A population-based longitudinal study provides preliminary evidence that the immunologic stool test with a cutoff of 20 μg (per g of feces) cannot reliably detect advanced neoplasms in the proximal colon i.e., the right-sided section between the caecum and transverse colon. The PICR (proportional interval cancer rate = proportion of clinically significant cancers that were either missed at screening or redeveloped before the next screening appointment) averaged 25.2 percent for the proximal colon, 6 percent for the distal colon, and 9.9 percent for the rectum. The cut-off point of 20 ng/ml hemoglobin in stool leads to a higher sensitivity (50% higher detection rate for colon cancer/colon cancer and 256% higher rate for high-risk adenomas) and at the same time a decrease in specificity (probability that actually healthy persons who do not suffer from the disease in question are also detected as healthy in the test) .A positive test result only indicates blood in the stool and for this reason must be investigated further. Among other things, the blood may originate from the upper gastrointestinal tract (gastrointestinal tract) as a result of a ventriculi ulcer. Hemorrhoids (nodular dilatations of small arteries in the area of the bowel outlet that bleed easily) can also cause a positive test result. Transport/Storage: transport within 24 h, intermediate storage in refrigerator (4 – 8 °C) up to 1 day possible.When using special collection systems, the material is stable for 5 days after sample collection at room temperature.

Indications (areas of application)

  • Early diagnosis in patients aged 50 years and older.
  • Patients with genetic (familial) predisposition to colorectal carcinoma (colorectal cancer):
    • In HNPCC (hereditary non-polyposis colorectal cancer; hereditary colorectal cancer without polyposis, also known as “Lynch syndrome“) colorectal cancer screening including colonoscopy begins at the age of 25.
    • In FAP (familial adenomatous polyposis; obligate precancerous disease / later cancer significantly likely; degeneration begins from the fifteenth year of life!) colorectal cancer screening incl. colonoscopy begins already from the 10.year of age
    • In patients with “frequent occurrence of colorectal cancer in the family”, the colorectal cancer screening incl. colonoscopy is already performed for the first time if the patient is 10 years younger than the sick family member was when he became ill

Interpretation

For the quantitative immunological stool test, which is paid by the statutory health insurance, the detection threshold (“cut-off” value for sufficient sensitivity and specificity) was set at 50 ng Hb/ml. The immunological stool test is a reliable method for detecting occult blood in stool. A negative quantitative immunologic stool test excludes underlying colorectal carcinoma 100% and high-risk adenoma 97.8%. Among participants screened by colonoscopy, a single positive immunologic stool test (cutpoint ≥ 50 ng /ml) had 35% sensitivity and 93% specificity for detecting advanced adenoma and 38% sensitivity* and 93% specificity* * for detecting advanced neoplasia (advanced adenoma and/or colorectal carcinoma). In a meta-analysis of twelve studies in high-risk patients (relatives of colorectal cancer patients), the immunological stool test achieved a sensitivity* of 93% and a specificity* of 91% for colorectal carcinoma. In advanced neoplasms, sensitivity was 48% and specificity was 93%. According to these data, the immunological stool test has a high diagnostic accuracy for colorectal carcinoma in patients at increased risk. But it detects only half of the cases with advanced neoplasms. * Percentage of diseased patients in whom the disease is detected by use of the test, i.e., a positive test result occurs. * * Probability that actually healthy persons who do not suffer from the disease in question are also recognized as healthy in the test. A positive test result requires endoscopic examination of the entire colon (colonoscopy). According to a European quality guideline, colonoscopic clarification should be performed within 31 days. Evaluations by Kaiser Permanente’s Research Institute of patients with a positive test result showed that the risk of colon cancer (colon cancer) being detected during colonoscopy increased by 3% with each month. However, a significantly increased tumor rate (compared to patients who had a colonoscopy appointment in the first month) was only seen after a 10-month delay in colonoscopy. Additional notes

  • The positive predictive value of an immunologic stool test is not significantly altered by oral anticoagulants (OACs) or acetylsalicylic acid (ASA)/nonsteroidal anti-inflammatory drugs (NSAIDs). CONCLUSION: Thus, there is no reason to suspend treatment with the above agents because of an immunological stool test.
  • In an intervention study, the sensitivity of the immunologic stool test for advanced neoplasms (neoplasms) at the threshold of 10.2 µg Hb/g stool after ASA administration of 300 mg for 2 days before the stool sample was 40.2% after placebo 30.4%.However, the difference of 9, 8% was not significant: P = 0.14.Note: It is possible that a higher ASA dose or ASA administration for several days before the test may improve the sensitivity of the immunological stool test.
  • In patients with unexplained bowel symptoms, a negative result in an immunologic stool test (FIT test) can rule out colorectal cancer 99.8% of the time.

Benefit

Timely detection and removal of intestinal polyps or early diagnosis of tumor disease can reduce the risk of mortality.