Fecal occult blood
Encyclopedia
Fecal occult blood refers to blood
in the feces
that is not visibly apparent. A fecal occult blood test (FOBT) checks for hidden (occult) blood
in the stool (feces
). Newer tests look for globin
, DNA
, or other blood factors including transferrin
, while conventional stool guaiac test
s look for heme
.
, anywhere from the mouth
to the colon
. Positive tests ("positive stool") may result from either upper gastrointestinal bleeding
or lower gastrointestinal bleeding
and warrant further investigation for peptic ulcer
s or a malignancy (such as colorectal cancer
or gastric cancer). The test does not directly detect colon cancer but is often used in clinical screening
for that disease, but it can also be used to look for active occult blood loss in anemia or when there are gastrointestinal symptoms.
The different methods of testing for "fecal occult blood" as broadly considered actually test for particular components of blood or for aberrantly expressed cellular markers from the intestinal mucosa.
in feces
. These look at different properties, such as heme
, globin
, and porphyrin
s in blood or at DNA
from cellular material such as from lesions of the intestinal mucosa.
Additional methods of looking for occult blood are being explored, including transferrin dipstick and stool cytology.
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 variety of additional factors.
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 10 ml (about two teaspoonfuls), and higher sensitivity gFOBT can pick up lesser amounts, sometimes becoming positive at about 2 ml. 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%. Further discussion of sensitivity and sensitivity issues that relate particularly to the guaiac method is found in the stool guaiac test
article.
Fecal Immunochemical Testing (FIT) picks up as little as 0.3 ml but because it does not detect occult blood from the stomach and upper small intestine the test threshold doesn't cause undue false positives from normal upper intestinal blood leakage and it is much more specific for bleeding from the colon or lower gastrointestinal tract. The detection rate of the test decreases if the time from sample collection to laboratory processing is delayed.
Fecal porphyrin
quantification by HemoQuant can be false positive
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 Advised to stop red meat and aspirin for 3 days prior to specimen collection False positives can occur with myoglobin, catalase, or protohemes and in certain types of porphyria
The DNA based PreGen-Plus was four times more sensitive than fecal blood testing, including detection of early stage disease, when treatment is most effective. Sensitivity increased to 51.6% compared to 12.9%.
Additional clinical trials of the PreGen-Plus method are underway to more fully characterize its clinical performance. Expanding the range of DNA testing by looking at additional known genetic markers, such as CTNNB1
, or by analyzing epigenetically
methylated genes
such as MLH1
which is very common in hyperplastic polyps
(HP) with microsatellite instability
(MSI) and in proximal colon tumours that have poorer differentiation, does not appear to appreciably increase the sensitivity of the method because CTNNB1 mutations are infrequent in sporadic colorectal cancer, and because BAT26 alterations and lack of MLH1 expression show a high degree of overlap.
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
causes unless there are other clinical clues. Colonoscopy is usually preferred to computerized tomographic colonography.
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 adenoma
s.
A positive test can result from upper gastrointestinal bleeding
or lower gastrointestinal bleeding
. The common causes are:
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:
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 incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials.
Evidence
for other colon cancer screening tools such as iFOBT or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.
Guaiac FOB testing of average risk populations may reduce the mortality associated with colon cancer
by about 25%. It is not always cost effective to screen a large population.
If colon cancer is suspected in an individual (such as in someone with an unexplained anemia
) 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.
The 2009 recommendations of the American College of Gastroenterology (ACG) suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 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 which should be offered to patients who decline colonoscopy or another cancer prevention test. However, two other recent guidelines, from the US Multisociety Task Force (MSTF) and the US Preventive Services Task Force (USPSTF) while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every 5 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 (gFOBT) or fecal immunochemical testing (FIT). MSTF looked at 6 studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there were no clear difference in overall performance between these methods.
In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is strongly discouraged.
A related concept to colon cancer screening by FOBT, based on most neoplasms affecting the surface epithelium and losing small amounts of blood but no visible blood loss, is screening in populations at high risk for esophageal or gastric cancers by testing for blood by swallowing a small capsule that is recovered after 3 to 5 minutes by gentle retrieval by means of an attached nylon thread.
, secretin
and peptide-histidine-methionine. Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various leucocytes
, 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
liquids, and lessened by adequate training.
Ingestion of 800 mg of cimetidine 2 hr before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding. Conversely, 800 mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and postrace guaiac test positivity but did not affect race performance.
Additional studies have reviewed the effect of cimetidine and of PPI
Role of endoscopy in marathon runners with positive FOBT
This is a different process than march hemoglobinuria.
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
in the feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
that is not visibly apparent. A fecal occult blood test (FOBT) checks for hidden (occult) blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
in the stool (feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
). Newer tests look for globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
, DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, or other blood factors including transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
, while conventional stool guaiac test
Stool guaiac test
The stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
s look for heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
.
Purpose
Fecal occult blood testing (FOBT), as its name implies, aims to detect subtle blood loss in the gastrointestinal tractGastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, anywhere from the mouth
Mouth
The mouth is the first portion of the alimentary canal that receives food andsaliva. The oral mucosa is the mucous membrane epithelium lining the inside of the mouth....
to the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
. Positive tests ("positive stool") may result from either upper gastrointestinal bleeding
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding refers to hemorrhage in the upper gastrointestinal tract. The anatomic cut-off for upper GI bleeding is the ligament of Treitz, which connects the fourth portion of the duodenum to the diaphragm near the splenic flexure of the colon.Upper GI bleeds are considered...
or lower gastrointestinal bleeding
Lower gastrointestinal bleeding
Lower gastrointestinal bleeding, commonly abbreviated LGIB, refers to any form of bleeding in the lower gastrointestinal tract. LGIB is a common ailment seen at emergency departments. It presents less commonly than upper gastrointestinal bleeding . It is estimated that UGIB accounts for 100-200 per...
and warrant further investigation for peptic ulcer
Peptic ulcer
A peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
s or a malignancy (such as colorectal cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
or gastric cancer). The test does not directly detect colon cancer but is often used in clinical screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
for that disease, but it can also be used to look for active occult blood loss in anemia or when there are gastrointestinal symptoms.
Nomenclature
In 2007 the nomenclature of overt, obscure and occult bleeding was clarified.The different methods of testing for "fecal occult blood" as broadly considered actually test for particular components of blood or for aberrantly expressed cellular markers from the intestinal mucosa.
Methodology
There are four methods in clinical use for testing for occult bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
in feces
Feces
Feces, faeces, or fæces is a waste product from an animal's digestive tract expelled through the anus or cloaca during defecation.-Etymology:...
. These look at different properties, such as heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
, globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
, and porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
s in blood or at DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
from cellular material such as from lesions of the intestinal mucosa.
- Fecal Immunochemical Testing (FIT), and immunochemical fecal occult blood test (iFOBT): – Many commercial products rely on these methods, which chemically depend on specific antibodiesAntibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
to detect globinGlobinGlobins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
. For colorectal cancer screening, the FIT tests are superior to low sensitivity gFOBT. Although FIT may be a consideration to replace gFOBT in colon cancer screening, high sensitivity gFOBT, such as Hemoccult SENSA, remains an accepted option alongside FIT in recent guidelines, being assessed as having similar overall performance characteristics to FIT. The number of fecal samples submitted for FIT may affect the clinical sensitivity and specificity of the methodology. 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. FOBT may have a role in monitoring gastrointestinal conditions such as ulcerative colitis.
- Stool guaiac testStool guaiac testThe stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
for fecal occult blood (gFOBT): – The stool guaiac testStool guaiac testThe stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
involves smearing some feces on to some absorbent paper that has been treated with a chemical. Hydrogen peroxideHydrogen peroxideHydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
is then dropped on to the paper; if trace amounts of bloodBloodBlood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
are present, the paper will change color in one or two seconds. This method works as the hemeHemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
component in hemoglobinHemoglobinHemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
has a peroxidasePeroxidasePeroxidases are a large family of enzymes that typically catalyze a reaction of the form:For many of these enzymes the optimal substrate is hydrogen peroxide, but others are more active with organic hydroperoxides such as lipid peroxides...
-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 are now recommended in colon cancer screening. Optimal clinical performance of the stool guaiac testStool guaiac testThe stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
depends on preparatory dietary adjustment.
- Fecal porphyrinPorphyrinPorphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
quantification: – HemoQuant, unlike gFOBT and FIT, permits precise quantification of hemoglobin, and is analytically validatedVerification and ValidationIn software project management, software testing, and software engineering, verification and validation is the process of checking that a software system meets specifications and that it fulfills its intended purpose...
with gastric juice and urine, as well as stool samples. The heme moiety of intact hemoglobin is chemically convertedRedoxRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
by oxalic acid and ferrous oxalate or ferrous sulfate to protoporphyrin, and the porphyrin content of both the original sample and of the sample after hemoglobin conversion to porphyrin is quantified by comparative fluorescence against a reference standardReference standardA drug reference standard is a standardized substance which is used as a measurement base for similar substances. Where the exact active substances of a new drug are not known, a reference standard provides a calibrated level of biological effects against which new preparations of the drug can be...
; the specificity for hemoglobin is increased by subtracting the fluorescence of a sample blank prepared with citric acid to correct for the potential confounding effect of existing non-specific substances. Precise quantification measurement has been very useful in many clinical research applications.
- Fecal DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
testhttp://www.cancerquest.org/fecal-dna-test: – The PreGen-Plus test extracts human DNA from the stool sample and tests it for alterations that have been associated with cancer. The test looks at 23 individual DNA alterations, including 21 specific point alterations in the APC, KRASKRASGTPase KRas also known as V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog and KRAS, is a protein that in humans is encoded by the KRAS gene. Like other members of the Ras family, the KRAS protein is a GTPase and is an early player in many signal transduction pathways...
and p53P53p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
genes, as well as testing BAT26, a gene involved in microsatellite instabilityMicrosatellite instabilityMicrosatellites are repeated sequences of DNA. Although the length of these microsatellites is highly variable from person to person, each individual has microsatellites of a set length. These repeated sequences are common, and normal...
(MSI). and a proprietary DNA Integrity Assay (DIA).
Additional methods of looking for occult blood are being explored, including transferrin dipstick and stool cytology.
Reference standards
The estimates for test performance characteristics are based on comparison with a variety of reference methodsReference standard
A drug reference standard is a standardized substance which is used as a measurement base for similar substances. Where the exact active substances of a new drug are not known, a reference standard provides a calibrated level of biological effects against which new preparations of the drug can be...
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 variety of additional factors.
Gastrointestinal blood loss in health
In healthy people about 0.5 to 1.5 ml 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 200 ml in the stomach, 100 ml in the duodenum, and lesser amounts in the lower intestine. Tests for occult blood identify lesser blood loss.Clinical sensitivity and specificity
Stool guaiac testStool guaiac test
The stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
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 10 ml (about two teaspoonfuls), and higher sensitivity gFOBT can pick up lesser amounts, sometimes becoming positive at about 2 ml. 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%. Further discussion of sensitivity and sensitivity issues that relate particularly to the guaiac method is found in the stool guaiac test
Stool guaiac test
The stool guaiac test or guaiac fecal occult blood test is one of several methods that detect the presence of fecal occult blood...
article.
Fecal Immunochemical Testing (FIT) picks up as little as 0.3 ml but because it does not detect occult blood from the stomach and upper small intestine the test threshold doesn't cause undue false positives from normal upper intestinal blood leakage and it is much more specific for bleeding from the colon or lower gastrointestinal tract. The detection rate of the test decreases if the time from sample collection to laboratory processing is delayed.
Fecal porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
quantification by HemoQuant can be false positive
Type I and type II errors
In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...
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 Advised to stop red meat and aspirin for 3 days prior to specimen collection False positives can occur with myoglobin, catalase, or protohemes and in certain types of porphyria
The DNA based PreGen-Plus was four times more sensitive than fecal blood testing, including detection of early stage disease, when treatment is most effective. Sensitivity increased to 51.6% compared to 12.9%.
Additional clinical trials of the PreGen-Plus method are underway to more fully characterize its clinical performance. Expanding the range of DNA testing by looking at additional known genetic markers, such as CTNNB1
Beta-catenin
Beta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
, or by analyzing epigenetically
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
methylated genes
DNA methylation
DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring...
such as MLH1
MLH1
MutL homolog 1, colon cancer, nonpolyposis type 2 , also known as MLH1, is a human gene located on Chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer.It can also be associated with Turcot syndrome....
which is very common in hyperplastic polyps
Colorectal polyp
A colorectal polyp is a polyp occurring on the lining of the colon or rectum. Untreated colorectal polyps can develop into colorectal cancer....
(HP) with microsatellite instability
Microsatellite instability
Microsatellites are repeated sequences of DNA. Although the length of these microsatellites is highly variable from person to person, each individual has microsatellites of a set length. These repeated sequences are common, and normal...
(MSI) and in proximal colon tumours that have poorer differentiation, does not appear to appreciably increase the sensitivity of the method because CTNNB1 mutations are infrequent in sporadic colorectal cancer, and because BAT26 alterations and lack of MLH1 expression show a high degree of overlap.
Clinical application
The stool guaiac test for hidden (occult) blood in the stool can be done at home or in the doctor's office, or can be performed 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.Sources of gastrointestinal bleeding
Gastrointestinal bleedingGastrointestinal bleeding
Gastrointestinal bleeding or gastrointestinal hemorrhage describes every form of hemorrhage in the gastrointestinal tract, from the pharynx to the rectum. It has diverse causes, and a medical history, as well as physical examination, generally distinguishes between the main forms...
has many potential sources, and positive results usually result in further testing for the bleeding site, usually looking for lower gastrointestinal bleeding
Lower gastrointestinal bleeding
Lower gastrointestinal bleeding, commonly abbreviated LGIB, refers to any form of bleeding in the lower gastrointestinal tract. LGIB is a common ailment seen at emergency departments. It presents less commonly than upper gastrointestinal bleeding . It is estimated that UGIB accounts for 100-200 per...
before upper gastrointestinal bleeding
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding refers to hemorrhage in the upper gastrointestinal tract. The anatomic cut-off for upper GI bleeding is the ligament of Treitz, which connects the fourth portion of the duodenum to the diaphragm near the splenic flexure of the colon.Upper GI bleeds are considered...
causes unless there are other clinical clues. Colonoscopy is usually preferred to computerized tomographic colonography.
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 adenoma
Adenoma
An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
s.
A positive test can result from upper gastrointestinal bleeding
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding refers to hemorrhage in the upper gastrointestinal tract. The anatomic cut-off for upper GI bleeding is the ligament of Treitz, which connects the fourth portion of the duodenum to the diaphragm near the splenic flexure of the colon.Upper GI bleeds are considered...
or lower gastrointestinal bleeding
Lower gastrointestinal bleeding
Lower gastrointestinal bleeding, commonly abbreviated LGIB, refers to any form of bleeding in the lower gastrointestinal tract. LGIB is a common ailment seen at emergency departments. It presents less commonly than upper gastrointestinal bleeding . It is estimated that UGIB accounts for 100-200 per...
. The common causes are:
- 2–10%: cancerCancerCancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
(colorectal cancerColorectal cancerColorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
, gastric cancer) - 20–30% adenoma or polypPolyp (medicine)A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...
s - Bleeding peptic ulcerPeptic ulcerA peptic ulcer, also known as PUD or peptic ulcer disease, is the most common ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful. It is defined as mucosal erosions equal to or greater than 0.5 cm...
- AngiodysplasiaAngiodysplasiaIn medicine , angiodysplasia is a small vascular malformation of the gut. It is a common cause of otherwise unexplained gastrointestinal bleeding and anemia. Lesions are often multiple, and frequently involve the cecum or ascending colon, although they can occur at other places...
of the colon - Sickle cell anemia
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:
- SigmoidoscopySigmoidoscopySigmoidoscopy From Greek Sigma - eidos - scopy, to look inside an s-like object, is the minimally invasive medical examination of the large intestine from the rectum through the last part of the colon. There are two types of sigmoidoscopy, flexible sigmoidoscopy, which uses a flexible endoscope,...
, an examination of the rectum and lower colon with a lighted instrument to look for abnormalities, such as polyps. - ColonoscopyColonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
, a more thorough examination of the rectum and entire colon. - Virtual colonoscopyVirtual colonoscopyVirtual colonoscopy is a medical imaging procedure which uses x-rays and computers to produce two- and three-dimensional images of the colon from the lowest part, the rectum, all the way to the lower end of the small intestine and display them on a screen...
- EndoscopyEndoscopyEndoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
refers to upper gastrointestinal endoscopy. It is sometimes performed with chromoendoscopy, a method that assists the endoscopist by enhancing the visual difference between cancerous and normal tissue, either by 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 enemaBarium enemaA lower gastrointestinal series, also called a barium enema, is a medical procedure used to examine and diagnose problems with the human colon . X-ray pictures are taken while barium sulfate fills the colon via the rectum.-Procedure:...
: a series of x-rays of the colon and rectum.
Stool color
Although red or black stools can be an indication of bleeding, a dark or black color can be due to black licorice, blueberries, iron supplements, lead, Pepto-bismol, and a red color can come from natural or artificial coloring such as red gelatin, popsicles, Kool-Aid, and large amounts of beets.Colorectal cancer screening
ScreeningScreening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
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 incidence of gastrointestinal cancer or mortality depends on the rate of precancerous and cancerous disease in that population. gFOBT and flexible sigmoidoscopy screening have each shown benefit in randomized clinical trials.
Randomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
Evidence
Evidence-based medicine
Evidence-based medicine or evidence-based practice aims to apply the best available evidence gained from the scientific method to clinical decision making. It seeks to assess the strength of evidence of the risks and benefits of treatments and diagnostic tests...
for other colon cancer screening tools such as iFOBT or colonoscopy is substantial and guidelines have been issued by several advisory groups but does not include randomized studies.
Guaiac FOB testing of average risk populations may reduce the mortality associated with colon cancer
Colorectal cancer
Colorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
by about 25%. It is not always cost effective to screen a large population.
If colon cancer is suspected in an individual (such as in someone with an unexplained anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
) 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.
The 2009 recommendations of the American College of Gastroenterology (ACG) suggest that colon cancer screening modalities that are also directly preventive by removing precursor lesions should be given precedence, and prefer a colonoscopy every 10 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 which should be offered to patients who decline colonoscopy or another cancer prevention test. However, two other recent guidelines, from the US Multisociety Task Force (MSTF) and the US Preventive Services Task Force (USPSTF) while permitting immediate colonoscopy as an option, did not categorize it as preferred. The ACG and MSTF also included CT colonography every 5 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 (gFOBT) or fecal immunochemical testing (FIT). MSTF looked at 6 studies that compared high sensitivity gFOBT (Hemoccult SENSA) to FIT, and concluded that there were no clear difference in overall performance between these methods.
In colon cancer screening, using only one sample of feces collected by a doctor performing a digital rectal examination is strongly discouraged.
Iron deficiency anemia
An extensive literature has examined the clinical value of FOBT in iron deficiency anemia.Gastrointestinal disease and medications
Conditions such as ulcerative colitis or certain types of relapsing infectious diarrhea can vary in severity over time, and FOBT may assist in assessing the severity of the disease. Medications associated with gastrointestinal bleeding such as Bortezomib are sometimes monitored by FOBT.Outpatient clinics
Several studies have reported clinical benefit from gFOBT testing including urology and gynecology clinics.Inpatient guaiac testing
Several studies have questioned the traditional Admission Screening Guaiac (ASG). The utility of following stool guaiac in ICU settings is also questioned.Testing of upper gastrointestinal or aerodigestive tract secretions for occult blood
The use of tests for occult blood in disorders of the mouth, nasal passages, esophagus, lungs and stomach, while analogous to fecal testing, is often 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.A related concept to colon cancer screening by FOBT, based on most neoplasms affecting the surface epithelium and losing small amounts of blood but no visible blood loss, is screening in populations at high risk for esophageal or gastric cancers by testing for blood by swallowing a small capsule that is recovered after 3 to 5 minutes by gentle retrieval by means of an attached nylon thread.
Regulatory impact
Regulations from the Joint Commission may have unintentionally decreased digital rectal examination and FOBT in hospital settings such as Emergency Departments.Fecal occult blood in 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. Exercise is associated with extensive changes in gastrointestinal (GI) tract physiology, including diversion of blood flow from the GI tract to muscle and lungs, decreased GI absorption and small intestinal motility, increased colonic transit, neuroimmunoendocrine changes in hormones and peptides such as vasoactive intestinal peptideVasoactive intestinal peptide
Vasoactive intestinal peptide also known as the vasoactive intestinal polypeptide or VIP is a peptide hormone containing 29 amino acid residues that is produced in many tissues of vertebrates including the gut, pancreas and suprachiasmatic nuclei of the hypothalamus in the brain...
, secretin
Secretin
Secretin is a hormone that controls the secretions into the duodenum, and also separately, water homeostasis throughout the body. It is produced in the S cells of the duodenum in the crypts of Lieberkühn...
and peptide-histidine-methionine. Substantial changes occur in stress hormones including cortisol, in circulating concentrations and metabolic behavior of various leucocytes
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
, and in immunoglobulin levels and major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
expression. Symptoms can be exacerbated by dehydration or by pre-exercise ingestion of certain foods and hypertonic
Tonicity
Tonicity is a measure of the osmotic pressure gradient of two solutions separated by a semipermeable membrane. It is commonly used when describing the response of cells immersed in an external solution...
liquids, and lessened by adequate training.
Ingestion of 800 mg of cimetidine 2 hr before running a marathon did not significantly affect the frequency of gastrointestinal symptoms or occult gastrointestinal bleeding. Conversely, 800 mg of cimetidine 1 hr before the start and again at 50 miles of a 100-mile running race substantially decreased GI symptoms and postrace guaiac test positivity but did not affect race performance.
Additional studies have reviewed the effect of cimetidine and of PPI
Role of endoscopy in marathon runners with positive FOBT
This is a different process than march hemoglobinuria.
External links
- FOBT Overview at Mayo ClinicMayo ClinicMayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
- Overview at Cleveland ClinicCleveland ClinicThe Cleveland Clinic is a multispecialty academic medical center located in Cleveland, Ohio, United States. The Cleveland Clinic is currently regarded as one of the top 4 hospitals in the United States as rated by U.S. News & World Report...
- ColonCancerCheck including fact sheets in 24 languages at Ontario Ministry of Health and Long-Term Care