Occult and Obscure Gastrointestinal Bleeding

Advantages of FIT Test

• Specific for human hemoglobin, does not recognize cow or other mammalian hemoglobin.

• There are no false positive results with cabbage, cauliflower, or broccoli (pseudoperoxidase).

• Hemoglobin released from UGI tract bleeding is digested, and is not immune reactive to FIT.

• 6.

  Is testing a nasogastric (NG) aspirate for fecal occult blood clinically useful?

  No. This test is frequently falsely positive because of incidental microscopic bleeding from nasopharyngeal or esophageal trauma during NG tube insertion.

• 7.

  What is fecal genetic testing and can this test be used to replace the standard guaiac test for occult blood to screen for colon cancer?

  Passage of stool through the colon leads to shedding of microscopic amounts of colonic cellular DNA that remain viable in stool for many days. Genetic mutations present in microscopic amounts in this tissue can be detected by polymerase chain reaction of stool samples. An array of genetic tests is performed to detect genetic mutations associated with colon cancer, such as APC mutation (a molecular marker for adenomatous polyps), and BAT mutation (a marker for mismatch repair gene mutations). This test is currently investigational as a screening test for colon cancer and is not commercially available. The sensitivity of a single fecal DNA test is reportedly approximately 80% for colon cancer but is much lower for advanced adenomas, a characteristic that currently limits its clinical applicability. Even so, it has a higher sensitivity than guaiac testing for detecting advanced adenomas. It is hoped that future identification of novel genetic mutations in colonic carcinogenesis will yield additional genetic tests to place in the genetic array to increase test sensitivity, especially for detecting adenomas.

• 8.

  What is the sensitivity and specificity of guaiac testing for fecal blood?

  The sensitivity of guaiac testing depends on the specific brand used. Several guaiac reagents are marketed. The most sensitive brand is the Hemoccult II-SENSA test. The sensitivity also depends on the lesion to be detected. It is not a good test for detecting colonic adenomas because adenomas infrequently bleed. It is moderately (up to 80%) sensitive at detecting colon cancer when performed on 3 consecutive days to account for intermittent bleeding from colon cancer.

  The specificity of guaiac testing is only approximately 20% to 30% for detecting significant colonic lesions. The yield of colonoscopy performed for a guaiac-positive test is colon cancer in 3% to 4% of patients and colonic adenomas in 15% to 20% of patients (or higher in older adult patients).

• 9.

  How is a patient with a positive fecal occult blood test (FOBT) evaluated?

  The evaluation of a positive FOBT depends somewhat on the clinical situation.

  Asymptomatic persons with positive FOBT and iron-deficient anemia require colonoscopy. If colonoscopy is negative for a source of FOBT or anemia, then esophagogastroduodenoscopy (EGD) should be performed.

• 10.

  How do patients with iron-deficiency anemia present clinically in terms of symptoms, signs, and laboratory abnormalities?

  • Pica

  • Pallor

  • Weakness

  • Palpitations

  • Koilonychia

  • High-output congestive heart failure

  • Dyspnea on exertion

  • Orthostatic symptoms

  • Microcytic, hypochromic indices for erythrocytes

  • Percent iron saturation <16%

• 11.

  How should young menstruating women with iron-deficiency anemia be evaluated?

  The evaluation of iron-deficiency anemia in pregnant or relatively young menstruating females is individualized according to clinical presentation and menstrual and obstetric history. Iron deficiency during pregnancy is common. In a series of 186 menstruating women, 12% had a clinically important lesion detected by endoscopy. The most common cause of bleeding was peptic ulcer disease in 3%, and gastric cancer in 3%. On multivariate analysis, independent predictors of a significant lesion at endoscopy included a positive FOBT, hemoglobin less than 10 g/dL, and abdominal symptoms. Menstruating females presenting with iron-deficiency anemia who have a positive FOBT, anemia out of proportion to menstrual blood loss, abdominal symptoms, are 40 years old or older, or have a family history of GI malignancy should be strongly considered for GI endoscopy.

• 12.

  How often is iron-deficiency anemia caused by underlying chronic GI blood loss?

  Approximately 60% of persons with iron deficiency will have an identifiable cause detected by EGD and colonoscopy:

  • EGD demonstrates 36% (11% duodenal ulcer, 5% gastric ulcer, 3% anastomotic ulcer).

  • Colonoscopy demonstrates 25% (cancer was most common cause).

  • Diagnostic investigations should always be directed by symptoms and signs.

  Non-GI causes should be considered as a potential cause of iron deficiency:

  • Pregnancy

  • Hematuria

  • Celiac disease

  • Menstrual bleeding

  • Nutritional deficiencies

• 13.

  What do the terms upper GI bleeding (UGIB), lower GI bleeding (LGIB), and middle GI bleeding (MGIB) mean?

  See Table 52-1 . Although this categorization is appealingly simplistic, sometimes clinically suspected MGIB, based on one negative EGD and one negative colonoscopy, turns out to be UGIB that was missed on an initial EGD or LGIB that was missed on an initial colonoscopy. This initial misdiagnosis can occur in up to 20% of cases of suspected MGIB.

  Table 52-1

  Categorization of Gastrointestinal Bleeding Terms

  Location	Definition	Method of Evaluation
  UGIB	Esophagus, stomach, duodenum to the ligament of Treitz	EGD
  LGIB	Colon from the ileocecal valve to the anus	Colonoscopy (usually) Nuclear medicine studies or arteriography (special situations)
  MGIB	Small bowel from ligament of Treitz to the ileocecal valve	Capsule endoscopy, enteroscopy (push-type, single balloon, or double balloon) Radiologic (contrast enterography)

  EGD, Esophagogastroduodenoscopy; LGIB, lower gastrointestinal bleeding; MGIB, middle gastrointestinal bleeding; UGIB, upper gastrointestinal bleeding.

• 14.

  What is meant by obscure GI bleeding ?

  Obscure GI bleeding, sometimes referred to as GI bleeding of obscure origin (GIBOO) , is defined as recurrent or persistent GI bleeding without identifiable source despite EGD, colonoscopy, and a radiologic examination of the small bowel. The obscure bleeding may be acute and gross or occult and microscopic. Obscure GI bleeding constitutes approximately 5% of all GI bleeding.

  This definition of GIBOO is becoming outdated because of improved detection by capsule endoscopy and a variety of small bowel endoscopic techniques.

• 15.

  What radiologic tests are available for patients with GIBOO and what is their yield?

  • Small bowel series: Yield is only approximately 10%. Disadvantages: misses angiodysplasia, and contrast in the gut obscures and precludes angiography.

  • Enteroclysis: Yield is approximately 15%. Disadvantages: misses angiodysplasia, and contrast in the gut obscures and precludes angiography.

  • Computed tomography enterography: Method is good for Crohn’s disease and small bowel tumors. Disadvantages: misses angiodysplasia, and contrast in the gut obscures and precludes angiography.

  • Nuclear medicine bleeding scan: 99 m technetium is attached to autologous erythrocytes ex-vivo and then reintroduced intravenously. Extravasated blood in the bowel lumen confirms active bleeding. GI bleeding low as 0.1 to 0.5 mL per minute can be detected, but localization is generalized to abdominal regions.

  • Mesenteric angiography: Yield is approximately 20%. A bleeding scan is often performed first to confirm that bleeding is active, followed via mesenteric angiography. Angiography may be therapeutic. Actively bleeding lesions can be arrested by embolization with gelfoam or metal coils delivered by the angiographic catheter. The major risk of therapeutic embolization is mesenteric ischemia, which has decreased to 1% or less with super-selective cannulation.

• 16.

  When a patient is referred to a tertiary center for GIBOO, is it worthwhile for the specialized gastroenterologist at this center to repeat another EGD or colonoscopy before performing specialized small bowel examinations?

  Patients referred to a tertiary center for GIBOO usually undergo repeat EGD and colonoscopy. The yield on repeat EGD is approximately 10%. Commonly identified lesions include Cameron ulcers or erosions within a hiatal hernia, peptic ulcers, vascular angiodyplasia, gastric antral vascular ectasia, and Dieulafoy lesions. Esophageal varices that were thought to be incidental findings on the first EGD may be recognized as the bleeding source on repeat EGD by finding stigmata of recent hemorrhage on the varices, such as wale bites or red streaks. When a cause of iron-deficiency anemia is not identified, normal-appearing duodenal mucosa should be biopsied to exclude possible celiac disease.

  Repeat colonoscopy is especially important when the initial procedure was hampered by incomplete or poor bowel preparation. Commonly identified lesions at repeat colonoscopy include colon cancer, angiodysplasia, diverticular bleeding, and Crohn’s colitis.

• 17.

  How is small bowel capsule used for endoscopy of the small bowel in patients with GIBOO?

  The most widely available and most commonly performed endoscopic test to evaluate the small bowel for GIBOO is small bowel capsule endoscopy. This capsule primarily supplies images of the small bowel, but can also supply limited images of the esophagus, stomach, and cecum. The capsule contains a light source to illuminate the gut, one or more cameras for color photography, a wireless transmitter to transmit the images electronically, and a battery to power these electronic operations. A recorder is usually worn by the patient to receive the transmitted images. The capsule battery generally permits transmission of endoscopic images for approximately 8 hours. The capsule is swallowed with water and passively traverses the alimentary tract by peristalsis. Patients fast overnight before the procedure and should receive a liquid polyethylene glycol–3350 bowel preparation shortly before the procedure to evacuate luminal debris and provide a clear fluid interface.

  Three small bowel capsule brands are commercially available. The PillCam is the latest model produced by Given Imaging (Yoqneam, Israel), which developed the first device. It has a variable frame rate, ranging from two frames per second when stationary up to six frames per second when moving quickly. Other brands include the EndoCapsule by Olympus Corporation (Allentown, PA), and the MiRoCam capsule marketed by Medivators, Inc. (Minneapolis, MN), which was recently approved for use in America.

• 18.

  What other endoscopic tests are available to evaluate the small bowel in patients with obscure GI bleeding?

  Various “long endoscope” endoscopy tests permit diagnosis and potential treatment.

  • Push enteroscopy uses an enteroscope that is similar, but substantially longer than a standard UGI endoscope. The longer enteroscope allows intubation more distally, typically into the proximal jejunum, approximately 50 cm beyond the ligament of Treitz.

  • Spiral enteroscopy uses a 118-cm long overtube with a soft, raised, spiral helix at its distal end (Spirus Medical Inc., Stoughton, MA) that is placed over a long enteroscope. The overtube is affixed to the enteroscope via a coupling device that permits rotation of the overtube. The spiral ridge of the overtube engages the small bowel plicae circulares (folds) during clockwise rotation like a screw into wood. The enteroscope is advanced by rotating the overtube clockwise, which pleats the small bowel onto the overtube. The most common complication is self-limited mucosal trauma from spiraling over mucosal folds. There is a low rate of major complications of 0.4%, including a 0.3% rate of GI perforations. Spiral enteroscopy is not widely available.

  • Double-balloon enteroscopy consists of a 200-cm long enteroscope with a latex balloon at its tip, and a 145-cm long soft overtube with another latex balloon at its tip, and pumps to inflate both balloons. The enteroscope is advanced during repetitive cycles of inflation and deflation of the individual balloons coupled with alternating advancement of the enteroscope or overtube. The diagnostic yield for the indication of obscure bleeding ranges from 40% to 80%. The rate of major complications is approximately 0.7%, with a 0.4% rate of GI perforation.

  • Single-balloon enteroscopy uses a 140-cm long overtube and a 200-cm long enteroscope. The overtube is equipped with an inflatable balloon at its tip to aid in endoscope advancement through the small bowel by pleating of small bowel on the overtube. The average depth of small bowel insertion ranges from 150 to 250 cm. Single-balloon enteroscopy has a yield somewhat lower than double-balloon enteroscopy, with a diagnostic yield of 40% to 65%. Complications include abdominal pain, pyrexia, mucosal tears, aspiration pneumonia, cardiovascular events, and perforation. The rate of GI perforation is approximately 0.4%.

• 19.

  What are the common causes of GIBOO as determined by capsule endoscopy?

  Capsule endoscopy identifies a source for GIBOO in 56% of cases:

  • Small bowel angiodysplasia in 22%

  • Small bowel ulcers in 10%

  • Small bowel tumors in 7%

  • Small bowel varices in 3%

  • Luminal blood without identifiable lesion approximately 8%

  • Esophageal or gastric source approximately 8%

  • Colonic angiodsyplasia 2%

• 20.

  What are the advantages, disadvantages, and contraindications of capsule enteroscopy?