Fecal occult blood (FOB) refers to
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
in the
feces that is not visibly apparent (unlike other types of
blood in stool such as
melena or
hematochezia). A fecal occult blood test (FOBT) checks for hidden (occult) blood in the stool (feces).
The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the
fecal immunochemical test (FIT). The newer and recommended tests look for
globin
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myogl ...
,
DNA, or other blood factors including
transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
, while conventional
stool guaiac tests look for
heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
.
Medical uses
Fecal occult blood testing (FOBT), as its name implies, aims to detect subtle blood loss in the
gastrointestinal tract, anywhere from the
mouth to the
colon. Positive tests ("positive stool") may result from either
upper gastrointestinal bleeding
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit or in altered form as black stool. D ...
or
lower gastrointestinal bleeding and warrant further investigation for
peptic ulcer
Peptic ulcer disease (PUD) is a break in the inner lining of the stomach, the first part of the small intestine, or sometimes the lower esophagus. An ulcer in the stomach is called a gastric ulcer, while one in the first part of the intestines ...
s or a
malignancy
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
(such as
colorectal cancer or
gastric cancer
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
). The test does not directly detect
colon cancer but is often used in clinical
screening for that disease. It can also be used to look for active occult blood loss in
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
or when there are gastrointestinal symptoms.
Colorectal cancer screening
An estimated 1–5% of large tested populations have a positive fecal occult blood test. Of those, about 2–10% have cancer, while 20–30% have
adenomas.
Screening methods for colon cancer depend on detecting either precancerous changes such as certain kinds of polyps or on finding early and thus more treatable cancer. The extent to which screening procedures reduce the risk of gastrointestinal cancer or deaths depends on the rate of precancerous and cancerous disease in that population. gFOBT (guaiac fecal occult blood test) and flexible sigmoidoscopy screening have each shown benefit. Other colon cancer screening tools such as iFOBT (immunochemical fecal occult blood test) or colonoscopy are also included in guidelines.
In 2009 the
American College of Gastroenterology
The American College of Gastroenterology (ACG) is a Bethesda, Maryland–based medical association of gastroenterologists.
The association was founded in 1932 and holds annual meetings and regional postgraduate continuing education courses, es ...
(ACG) suggested that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a
colonoscopy every ten years in average-risk individuals, beginning at age 50.
The ACG suggests that cancer detection tests such as any type of FOB are an alternative that is less preferred, and if a colonoscopy is declined, the FIT (fecal immunochemical test, or iFOBT) should be offered instead. The 2017 US Multi-Society Task Force (MSTF)'s recommended first-tier tests are a colonoscopy every 10 years or annual FIT test. If FIT is utilized, proper steps must be taken to ensure appropriate use and follow-up of abnormal FIT results. FIT tests however are not that useful in picking up adenomas, even when advanced.
The
United States Preventive Services Task Force
The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...
(USPSTF)'s 2016 recommendation, instead of emphasizing specific screening approaches, has instead chosen to highlight that there is convincing evidence that colorectal cancer screening substantially reduces deaths from the disease among adults aged 50 to 75 years and that not enough adults are using this effective preventive intervention. The ACG and MSTF also included CT colonography every five years, and fecal DNA testing as considerations. All three recommendation panels recommended replacing any older low-sensitivity, guaiac-based fecal occult blood testing (gFOBT) with either newer high-sensitivity guaiac-based fecal occult blood testing (hs gFOBT) or fecal immunochemical testing (FIT). MSTF looked at six studies that compared high-sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there was no clear difference in overall performance between these methods.
The English
National Health Service
The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...
(NHS) introduced a Bowel Cancer Screening Program in 2006. It is now offered to patients aged 60–74 years. In 2019 FIT was introduced as the primary screening test in England and Wales, replacing gFOBt. However, research carried out in the UK has suggested that the FIT threshold for further investigation is set at a point that may miss more than half of bowel cancer cases and only identifies one in four high-risk polyps.
The American College of Gastroenterology has recommended the abandoning of gFOBT testing as a colorectal cancer screening tool, in favor of the fecal immunochemical test.
Though the FIT test is preferred, even the guaiac FOB testing of average risk populations may have been sufficient to reduce the mortality associated with
colon cancer by about 25%.
With this lower efficacy, it was not always cost-effective to screen a large population with gFOBT.
If colon cancer is suspected in an individual (such as in someone with an unexplained
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
), fecal occult blood tests may not be clinically helpful. If a doctor suspects colon cancer, more rigorous investigation is necessary, whether or not the test is positive.
In 2006, the Australian Government introduced the National Bowel Cancer Program which has been updated several times since; targeted screening will be done of all Australians aged from 50 to 74 by 2020. Cancer Council Australia recommended that FOBT should be done every two years. People over 50 not yet eligible for the national program can arrange with their doctor for an FOBT.
The
Canadian Cancer Society
The Canadian Cancer Society (french: Société canadienne du cancer) is Canada's largest national cancer charity and the largest national charitable funder of cancer research in Canada.
History
The idea to form the Canadian Cancer Society origin ...
recommends that men and women aged 50 and over have an FOBT at least every two years.
In colon cancer screening, using only one sample of feces collected by a doctor performing a
digital rectal examination is discouraged.
The use of the
M2-PK Test is encouraged over gFOBT for routine screening, as it may pick up tumors whether or not they are bleeding.
[ It is able to detect 80 percent of colorectal cancers and 44 percent for adenoma > 1 centimeter, while gFOBT picks up 13 to 50 percent of colorectal cancers.]
Other sources of bleeding
Gastrointestinal bleeding
Gastrointestinal bleeding (GI bleed), also called gastrointestinal hemorrhage (GIB), is all forms of bleeding in the gastrointestinal tract, from the mouth to the rectum. When there is significant blood loss over a short time, symptoms may include ...
has many potential sources, and positive results usually result in further testing for the bleeding site, usually looking for lower gastrointestinal bleeding before upper gastrointestinal bleeding
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit or in altered form as black stool. D ...
causes unless there are other clues. Colonoscopy is usually preferred to computerized tomographic colonography.
A positive test can result from upper gastrointestinal bleeding
Upper gastrointestinal bleeding is gastrointestinal bleeding in the upper gastrointestinal tract, commonly defined as bleeding arising from the esophagus, stomach, or duodenum. Blood may be observed in vomit or in altered form as black stool. D ...
or lower gastrointestinal bleeding. The common causes are:
* 2–10%: cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
( colorectal cancer, gastric cancer
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
)
* 20–30% adenoma or polyps
* Diverticular disease
Diverticular disease is when problems occur due to diverticulosis, a condition defined by the presence of pouches in the wall of the large intestine (diverticula). This includes diverticula becoming inflamed (diverticulitis) or bleeding. Colonic p ...
* Hemorrhoid
Hemorrhoids (or haemorrhoids), also known as piles, are vascular structures in the anal canal. In their normal state, they are cushions that help with stool control. They become a disease when swollen or inflamed; the unqualified term ''he ...
s
* Inflammatory bowel disease
* Angiodysplasia of the colon
* Sickle cell anemia
Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...
In the event of a positive fecal occult blood test, the next step in the workup is a form of visualization of the gastrointestinal tract by one of several means:
# Sigmoidoscopy
Sigmoidoscopy (from the Greek term for letter " s/Ï‚" + "eidos" + "scopy": namely, to look inside an "s"/"Ï‚"-like object) is the minimally invasive medical examination of the large intestine from the rectum through to the nearest part of the co ...
, an examination of the rectum and lower colon with a lighted instrument to look for abnormalities, such as polyps.
# Colonoscopy, a more thorough examination of the rectum and entire colon.
# Virtual colonoscopy
Virtual colonoscopy (VC, also called CT colonography or CT pneumocolon) is the use of CT scanning or magnetic resonance imaging (MRI) to produce two- and three-dimensional images of the colon (large intestine), from the lowest part, the rectum, ...
# Upper gastrointestinal endoscopy
An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are inse ...
. It is sometimes performed with chromoendoscopy, a method that assists the endoscopist by enhancing the visual difference between cancerous and normal tissue, by either marking the abnormally increased DNA content (toluidine blue) or failing to stain the tumor, possibly due to decreased surface glycogen on tumor cells(Lugol). Infrared fluorescent endoscopy and ultrasonic endoscopy can interrogate vascular abnormalities such as esophageal varices.
# Double-contrast barium enema
A lower gastrointestinal series is a medical procedure used to examine and diagnose problems with the human colon of the large intestine. Radiographs (X-ray pictures) are taken while barium sulfate, a radiocontrast agent, fills the colon via an ...
: a series of x-rays of the colon and rectum.
Testing secretions for blood
The use of an FOBT for bleeding from the mouth, nose, esophagus, lungs, stomach and the initial portion of the small intestine, while the same as fecal testing, is discouraged, due to technical considerations including poorly characterized test performance characteristics such as sensitivity, specificity, and analytical interference. However, chemical confirmation that coloration is due to blood rather than coffee, beets, medications, or food additives can be of significant clinical assistance.
Marathon runners
Gastrointestinal (GI) complaints and low-intensity GI bleeding frequently occur in marathon runners. Strenuous exercise, particularly in elite athlete runners and less frequently in other exercise activities, can cause acute incapacitating gastrointestinal symptoms including heartburn, nausea, vomiting, abdominal pain, diarrhea and gastrointestinal bleeding. Approximately one third of endurance runners experience transient but exercise-limiting symptoms, and repetitive gastrointestinal bleeding occasionally causes iron deficiency and anaemia. Runners can sometimes experience significant symptoms including hematemesis
Hematemesis is the vomiting of blood. It is always an important sign. It can be confused with hemoptysis (coughing up blood) or epistaxis (nosebleed), which are more common. The source is generally the upper gastrointestinal tract, typically abo ...
. Exercise is associated with extensive changes in gastrointestinal (GI) tract physiology, including diversion of blood flow from the GI tract to muscles and lungs, decreased GI absorption and small intestinal motility, increased colonic transit, neuroimmunoendocrine changes in hormones and peptides such as vasoactive intestinal peptide
Vasoactive intestinal peptide, also known as vasoactive intestinal polypeptide or VIP, is a peptide hormone that is vasoactive in the intestine. VIP is a peptide of 28 amino acid residues that belongs to a glucagon/secretin superfamily, the lig ...
, secretin and peptide-histidine-methionine. Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various leucocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multi ...
, and in immunoglobulin levels and major histocompatibility complex expression. Symptoms can be exacerbated by dehydration or by pre-exercise ingestion of certain foods and hypertonic
In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane- ...
liquids, and lessened by adequate training.
Ingestion of 800mg of cimetidine two hours before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding. Conversely, 800mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and post-race guaiac test positivity but did not affect race performance.
Methodology
There are four methods in clinical use to test for occult blood in feces. These look at different properties, such as antibodies, heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
, globin
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myogl ...
, or porphyrin
Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...
s in blood, or at DNA from cellular material such as from lesions of the intestinal mucosa.
* Fecal immunochemical testing (FIT), and immunochemical fecal occult blood test (iFOBT). FIT products utilize specific antibodies to detect globin
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myogl ...
. FIT screening is more effective in terms of health outcomes and cost compared with guaiac FOBT. According to the guidelines of the American College of Gastroenterology, "Annual fecal immunochemical testing is the preferred colorectal cancer detection test."[Colorectal Cancer http://patients.gi.org/topics/colorectal-cancer] A FIT test detects globin levels in feces at or above 50 nanograms per mL, the established cutoff by the World Health Organization for Colorectal Cancer Screening. FIT testing has replaced most gFOBT tests as the colon cancer screening test of choice. This methodology can be adapted for automated test reading and to report quantitative results, which are potential factors in design of a widescale screening strategy. The number of fecal samples submitted for FIT may affect the clinical sensitivity and specificity of the methodology. High-sensitivity gFOBT tests such as Hemoccult SENSA remain an accepted option and may retain a role in monitoring gastrointestinal conditions such as ulcerative colitis; however, the FIT test is preferred in recent guidelines. FIT is widely used outside of the US, and generally cost less than US$20 per test in 2020, compared to US$1,000 or more for a colonoscopy.
* Stool guaiac test for fecal occult blood (gFOBT): – The stool guaiac test involves smearing some feces onto some absorbent paper that has been treated with a chemical. Hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3%â ...
is then dropped onto the paper; if trace amounts of blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the cir ...
are present, the paper will change color in one or two seconds. This method works as the heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consis ...
component in hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...
has a peroxidase
Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides.
Functionality
Peroxidases typically ca ...
-like effect, rapidly breaking down hydrogen peroxide. In some settings such as gastric or proximal upper intestinal bleeding, the guaiac method may be more sensitive than tests detecting globin because globin is broken down in the upper intestine to a greater extent than is heme. There are various commercially available gFOBT tests which have been categorized as being of low or high sensitivity, and only high-sensitivity tests remain an acceptable alternative to FIT testing, which is now the best-practices recommendation in colon cancer screening. Optimal clinical performance of the stool guaiac test depends on preparatory dietary adjustment. The stool guaiac test for hidden (occult) blood in the stool should be used at home following the test kit's directions with spontaneously passed stool or on samples submitted to a clinical laboratory. Testing kits are available at pharmacies in some countries without a prescription, or a health professional may order a testing kit for use at home. If a home fecal occult blood test detects blood in the stool it is recommended to see a health professional to arrange further testing.
* Stool DNA screening test
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
s look for DNA alterations that have been associated with cancer.
Additional methods of looking for occult blood are being explored, including transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
dipstick and stool cytology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living an ...
.
Test performance
Reference standards
The estimates for test performance characteristics are based on comparison with a variety of reference methods including 51-chromium studies, analytical recovery studies in spiked stool samples, analytical recovery after ingestion of autologous blood, rarer studies of carefully quantified blood instilled at bowel surgery , as well as other research approaches. Additionally, clinical studies look at a variety of additional factors.
Gastrointestinal blood loss
In healthy people about 0.5 to 1.5ml of blood escapes blood vessels into the stool each day. Significant amounts of blood can be lost without producing visible blood in the stool, estimated as 200ml in the stomach, 100ml in the duodenum, and lesser amounts in the lower intestine. Tests for occult blood identify lesser blood loss.
Clinical sensitivity and specificity
Fecal immunochemical testing (FIT) can identify as little as 0.3ml of daily blood in the stool; yet this test threshold doesn't cause undue false positives from normal upper intestinal blood leakage because it does not detect occult blood from the stomach and upper small intestine. Thus, the FIT test is much more specific for bleeding from the colon or lower gastrointestinal tract than alternatives. The detection rate of the test decreases if the time from sample collection to laboratory processing is delayed; processing the sample in under five days from collection is recommended. It does not appear to be affected by aspirin, anticoagulants, or nonsteroidal anti-inflammatory drugs.
Stool guaiac test for fecal occult blood (gFOBT) sensitivity varies depending on the site of bleeding. Moderately sensitive gFOBT can pick up a daily blood loss of about 10ml (about two teaspoonfuls), and higher sensitivity gFOBT can pick up lesser amounts, requires at least 2ml to become positive. The sensitivity of a single-stool guaiac test to pick up bleeding has been quoted at 10 to 30%, but if a standard three tests are done as recommended the sensitivity rises to 92%. Reduced patient compliance with the collection of three samples hampers the usefulness of this test. Further discussion of sensitivity and specificity issues that relate particularly to the guaiac method is found in the stool guaiac test article.
Fecal porphyrin
Porphyrins ( ) are a group of heterocyclic macrocycle organic compounds, composed of four modified pyrrole subunits interconnected at their α carbon atoms via methine bridges (=CH−). The parent of porphyrin is porphine, a rare chemical com ...
quantification by HemoQuant can yield a false positive
A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test resul ...
result due to exogenous blood and various porphyrins. HemoQuant is the most sensitive test for upper gastrointestinal bleeding and therefore may be most appropriate fecal occult blood test to use in the evaluation of iron deficiency. It is advisable to stop ingesting red meat and aspirin for three days prior to specimen collection. False positives can occur with myoglobin, catalase, or protohemes and in certain types of porphyria.
Fecal DNA tests as of 2008 had not been studied enough to support widespread use.
Regulation
Safety regulations from US accreditor the Joint Commission
The Joint Commission is a United States-based nonprofit tax-exempt 501(c) organization that accredits more than 22,000 US health care organizations and programs. The international branch accredits medical services from around the world. A majorit ...
may have unintentionally decreased digital rectal examination and FOBT in hospital settings such as Emergency Departments.
References
External links
FOBT Overview
at Mayo Clinic
Overview
at Cleveland Clinic
Cleveland Clinic is a nonprofit American academic medical center based in Cleveland, Ohio. Owned and operated by the Cleveland Clinic Foundation, an Ohio nonprofit corporation established in 1921, it runs a 170-acre (69 ha) campus in Cleveland, ...
ColonCancerCheck
including fact sheets in 24 languages at Ontario Ministry of Health and Long-Term Care
*
{{DEFAULTSORT:Fecal Occult Blood
Blood tests
Diagnostic gastroenterology
Feces
Stool tests
de:Guajak-Test