AGA technical review on the evaluation and management of ...



Evaluation and management of occult and obscure gastrointestinal bleeding

Occult GI bleeding: blood in the feces in amounts too small to be seen but detectable by chemical tests. No definition for obscure intestinal bleeding is offered.

Obscure GI bleeding:

• Bleeding for which no cause was discovered after “standard investigations” of the upper and lower bowel, i.e., esophagogastroduodenoscopy and colonoscopy with or without other diagnostic studies.

• Bleeding of unknown origin that persists or recurs (i.e., recurrent or persistent IDA, FOBT positivity, or visible bleeding) after a negative initial or primary endoscopy (colonoscopy and/or upper endoscopy) result.

|Bleeding definitions |

|Overt or visible bleeding |GI bleeding manifest as visible bright red or altered blood in emesis or feces |

|Occult bleeding |Initial presentation of IDA and/or positive FOBT; no visible blood in feces |

|Obscure bleeding |Recurrent or persistent IDA, positive FOBT, or visible bleeding with no bleeding source found at original endoscopy|

|Obscure-occult bleeding |Subcategory of obscure bleeding characterized by recurrent or persistent IDA and/or positive FOBT with no source |

| |found at original endoscopy; no visible blood in feces |

|Obscure-overt bleeding |Subcategory of obscure bleeding characterized by recurrent or persistent overt/visible bleeding with no source |

| |found at original endoscopy; bleeding manifest as visible blood in emesis or feces |

Clinical classification

Occult bleeding

• Positive fecal occult blood test (FOBT).

• Iron-deficiency anemia (IDA) without evidence, to the patient or physician, of visible fecal blood.

Cases of IDA or FOBT positivity represent different signs of the same disease process ( intestinal mucosal lesions that bleed slowly or intermittently.

Obscure bleeding

• Obscure-occult: manifested by recurrent IDA and/or recurrent positive FOBT.

• Obscure-overt: recurrent passage of visible blood.

Epidemiology:

• Endoscopic evaluation of patients with predominantly positive FOBT revealed a bleeding source in:

o The colon ( 22%-26%.

o Upper GI tract ( 29%-36%.

• 30%-50% of occult bleeding cases will not have a source identified at colonoscopy and upper endoscopy.

• Undiagnosed occult bleeding would only be recategorized as obscure bleeding if there were recurrence or persistence of IDA or positive FOBT results.

• Hematemesis represents an extremely rare presentation for obscure-overt bleeding.

• A small percent of cases with visible bleeding will not have a diagnosis and smaller number from that group will have recurrent obscure bleeding.

Etiology

Occult bleeding

|Causes of occult GI bleeding |

|Positive FOBT |Upper GI lesions |Colonic lesions |

| |Esophagitis |Colon polyps |

| |Peptic ulcer disease |Colon cancer |

| |Gastritis/erosions |Angiodysplasia |

| |Duodenitis/erosions |Colonic ulcers |

| |Angiodysplasia | |

| |Esophageal or gastric varices | |

| |Gastric cancer | |

| |Gastric or duodenal polyps | |

|IDA |Upper GI lesions |Colonic lesions |

| |Esophagitis |Colon polyps |

| |Peptic ulcer disease |Colon cancer |

| |Gastritis/erosions |Angiodysplasia |

| |Duodenitis |Colonic ulcers |

| |Angiodysplasia |Colitis/IBD |

| |Portal-hypertensive gastropathy |Parasitic infestation |

| |Gastric/esophageal cancer |Hemorrhoids |

| |Gastric or duodenal polyps |Recurrent diverticular bleeding |

| |Crohn's disease |Celiac sprue |

| |Gastric/duodenal lymphoma | |

| |Partial gastrectomy | |

| |GAVE | |

Obscure bleeding

|Causes of obscure GI bleeding |

|Causes within reach of an upper endoscope |Causes beyond reach of an upper endoscope |

|Erosions within hiatal hernias (Cameron's erosions) |Angiodysplasia |

|Esophagitis |Small bowel tumors |

|Angiodysplasia |Small bowel ulcers and erosions. |

|Esophageal varices |NSAID/other drug-induced lesions. |

|Peptic ulcer disease |Crohn's disease |

|Gastritis |Celiac sprue |

|Gastric polyps |Small bowel diverticulosis |

|Gastric antral vascular ectasia |Small bowel varices |

|Blue rubber bleb nevus syndrome |Lymphangioma |

|Osler–Weber–Rendu syndrome |Radiation enteritis |

|Dieulafoy's lesion |Blue rubber bleb nevus syndrome |

|Celiac sprue |Osler–Weber–Rendu syndrome |

| |Von Willebrand's disease |

| |Small bowel polyposis syndromes |

| |Gardner's syndrome |

| |Aortoenteric fistula |

| |Amyloidosis |

| |Meckel's diverticulum |

| |Hemosuccus pancreaticus, hemobilia |

Evaluation

History

• Complete medical history.

• Upper or lower intestinal symptoms can direct the initial endoscopic approach.

• May be no abdominal symptoms.

• Celiac sprue ( young patient with episodes of diarrhea and long duration of anemia who lack response to oral iron therapy.

• Consumption of medications known to cause mucosal damage

|Aspirin and other NSAIDs |Alendronate |

|Anticoagulants |Potassium chloride |

• Family history of GI blood loss:

o Hereditary hemorrhagic telangiectasia.

o Blue rubber bleb nevus syndrome.

Physical examination

• Hereditary hemorrhagic telangiectasia ( typical lesions on the upper extremities, lips, and oral mucosa.

• Blue rubber bleb nevus syndrome ( cutaneous hemangiomas.

• Celiac sprue ( dermatitis herpetiformis.

• AIDS ( Kaposi sarcoma.

• Plummer–Vinson syndrome ( brittle, spoon-shaped nails, atrophic tongue.

• Pseudoxanthoma elasticum ( chicken-skin appearance, angioid streaks in the retina.

• Ehlers–Danlos syndrome ( hyperextensible joints, ocular and dental abnormalities.

• Neurofibromatosis ( caféau lait macules, axillary freckles, cutaneous neurofibromas.

• Malignant atrophic papulosis ( discrete painless papules.

• Typical cutaneous manifestations with certain polyposis syndromes:

o Peutz–Jeghers syndrome.

o Gardner syndrome.

o Cronkhite–Canada syndrome.

o Cowden disease.

• Typical signs with neoplastic diseases:

o Sister Mary Joseph nodule of the umbilicus.

o Left supraclavicular node enlargement.

o Tylosis in esophageal cancer.

Laboratory work up

Stool analysis: parasite ova.

Complete blood picture: anemia.

Iron studies: serum iron, ferritin and TIBC.

FOBT

• Dietary modifications ( eliminating foods with a high peroxidase content before and during the collection of stool samples( reduce false-positive results:

o Certain raw vegetables and fruits.

o Red meat, poultry, fish.

o Vitamin C and aspirin.

• Stool collection ( Digital rectal evacuation or spontaneous stool passage.

• Technique:

1. Guaiac-based tests.

o Hb has pseudoperoxidase activity that turns guaiac blue due to oxidation.

o Positive results are proportional to the hemoglobin content of the stool.

o Detect small amounts of bleeding from the upper GI.

o More sensitive in lower GI lesions.

o Easily affected by diet

o Overall sensitivity poor.

2. Immunochemical tests for hemoglobin.

o Detects human Hb antigen.

o Highly sensitive.

o More specific than guaiac.

o Not affected by diet.

o Relatively insensitive in detecting bleeding from the upper GI.

3. Heme-porphyrin test:

o Extremely sensitive.

o Highly affected by nonhuman dietary heme e.g. meat.

o Not very specific

o Limited use.

Endoscopic evaluation

Colonoscopy and upper endoscopy remain the cornerstones for investigation of occult blood loss.

Bidirectional endoscopy

• Refers to an investigative technique of colonoscopy and upper endoscopy performed in sequence and in temporal relationship to the finding of occult bleeding.

Radiographic evaluation

• Double-contrast enemas have been used when results of colonoscopy are suboptimal.

• Clinical guidelines for colon cancer screening have recommended air-contrast barium enema preferably with flexible sigmoidoscopy, as an alternative to colonoscopy for the diagnostic work-up of a positive FOBT result.

• It can identify the majority of clinically significant polyps and cancers

• High sensitivity and specificity of ACBE to examine the entire colon for large polyps (>1 cm) and cancer.

• Small mucosal lesions are not detected by ACBE.

• Upper endoscopy is more sensitive than double-contrast upper GI studies for detection of upper GI tract lesions.

Other testing in occult bleeding

• Small bowel biopsy.

• Small bowel follow-through radiographs.

• Enteroclysis.

• Enteroscopy should be reserved for cases of persistent or recurrent IDA or positive FOBT results, which by definition fall into the category of obscure bleeding.

Evaluation of obscure bleeding

• Repeat upper endoscopy and colonoscopy ( source for blood loss is not apparent ( small bowel source is suspected.

• Lesions missed during upper endoscopy include:

o Erosions within large hiatal hernias (Cameron's erosions).

o Peptic ulcer disease. and

o Vascular ectasia.

• Lesions missed on initial colonoscopy include:

o Angiodysplasia.

o Neoplasia.

Diagnostic techniques

Small bowel biopsy

• Small bowel biopsy performed during upper endoscopy or enteroscopy ( celiac sprue as a cause of IDA.

• Gross findings include:

o Loss or effacement of the circular folds or rings of Kerckring.

o Scalloping of the circular folds.

o Smooth atrophic-appearing mucosa.

o Pallor and pronounced vascular pattern.

• Simple screening technique:

o Increased magnification created by viewing the small bowel mucosa while the endoscope tip is submerged under water, and then observing for the presence or absence of villi.

Enteroscopy

• Endoscopic examination of the small bowel

o Push enteroscopy ( peroral insertion of a long endoscope directly into the jejunum

o Sonde enteroscopy ( the enteroscope is usually inserted transnasally and the tip is propelled by peristalsis.

o Double balloon enteroscopy.

o Capsule endoscopy.

Push enteroscopy

• Push enteroscopy further evaluate obscure bleeding.

• Fluoroscopy has been used to assess depth of insertion of the enteroscope

• The depth of insertion past the ligament of Treitz can range from 15 to 160 cm.

• Push enteroscopy appears to be a relatively safe procedure, with a low incidence of complications which include:

o Postprocedure abdominal pain.

o Acute pancreatitis.

o Mallory–Weiss tear with bleeding requiring cauterization.

o Pharyngoesophageal tear.

Sonde enteroscopy

• The tip is dragged into the proximal small bowel with the aid of an endoscope.

• Intrinsic gut peristalsis can propel the balloon at the tip of the endoscope to the terminal ileum.

• Inspection is carried out on withdrawal of the enteroscope.

• Advantages:

o Potential for total small bowel examination.

• Disadvantages:

o Patient discomfort ( lengthy procedure (4-5 hrs).

o Mucosal visualization is limited.

o An alternate mode of intervention is necessary for therapy.

• Complications are uncommon:

o Bowel perforation.

o Epistaxis.

• Newer Sonde-type enteroscopes have been developed with video-optics, a wider field of vision, and two-way tip deflection that may improve its efficacy.

Retrograde enteroscopy

• Involves examination of the distal ileum at colonoscopy using:

o Standard colonoscope.

o Small bowel enteroscope.

o Smaller endoscope passed through the instrument channel of a specially designed therapeutic colonoscope.

• Disadvantages:

o The length of terminal ileum examined is variable.

o Diagnostic yield is low.

Double Balloon Enteroscopy

• New endoscopic technique that allows navigating the entire small bowel from either an oral or rectal approach.

• Features two balloons, one attached to the distal end of the scope and the other attached to a transparent tube sliding over the endoscope.

• When inflated with air, the balloons can grip sections of the small intestine and "shorten" the small intestine by pleating it over the endoscope.

• Sequential shortening of the small intestine over the endoscope and advancement of the endoscope enables a comprehensive examination of the entire small intestine. 

• Effective in detecting sources of obscure bleeding of small intestinal source.

o Blood vessel abnormalities.

o Large masses.

o Mucosal and submucosal polyps.

Capsule Endoscopy

• The patient swallows a small camera that records images of the intestinal tract.

• Nothing to eat or drink, including water, for approximately twelve hours before the examination.

Indications

1. Diagnosis of the site of obscure GI bleeding in adults (diagnostic yield is 50 - 70 %).

2. Diagnosis of Crohn's disease and assessment of its extent and severity.

3. Small bowel tumors.

4. Small bowel injury associated with the use of NSAIDs.

5. Delineation of whether abdominal pain is functional or organic.

6. Assessment of celiac disease.

7. Detection of rejection in small bowel transplantation.

8. Detection of graft versus host disease after bone marrow transplantation.

9. Surveillance of patients with hereditary polyposis syndromes.

Intraoperative enteroscopy (IOE)

• Indication:

o Transfusion-dependent bleeding not identified in spite of extensive diagnostic evaluation

• Route:

o Orally.

o Transnasally (using a Sonde endoscope).

o Per rectum.

o Through enterotomies.

• The lights in the operating room are lowered, and while the endoscopist examines the luminal aspect, the surgeon examines the transilluminated serosal aspect of the small bowel.

• The ability of IOE to identify potential bleeding lesions ranges from 70% to 100%.

• Disadvantages:

o Technical difficulties due to dense adhesions or infiltrating neoplasia.

o Obscured visibility caused by luminal

• Complications

o Mucosal laceration.

o Intramural hematomas.

o Mesenteric hemorrhage.

o Perforation.

o Prolonged ileus.

o Ischemia.

Small bowel x-ray series and enteroclysis

• Barium studies are often used either before enteroscopy or when push-enteroscopy has failed to reveal a source.

• Barium meal follow through.

• Enteroclysis involves instillation of contrast material through a small tube placed in the proximal intestine either directly or facilitated by endoscopy.

• Enteroclysis has higher overall diagnostic yield, higher sensitivity, and shorter procedure times than with BMFT.

• Nasal placement and pyloric intubation are the most uncomfortable aspects of enteroclysis tube placement.

Nuclear scans

• Radioisotope bleeding scans may be helpful in localizing the site of obscure-overt bleeding if bleeding rate is 0.1-0.4. ML/min ( immediate blush.

• Technetium 99m–labeled red blood cell (TRBC) scan is the most used method of radioisotope scanning.

• Advantage

o Long half-life of the label, which allows for repeat scanning if necessary over a 24-hour period.

o Readily available and safe.

• Intraoperative scintigraphy for intraoperative localization of the bleeding segment.

o The bowel is clamped every 30 cm, and a gamma camera assesses the presence of labeled blood within the clamped segment.

Angiography

• Requires active bleeding at a rate of [pic]0.5 mL/min.

• Extravasation of contrast into the bowel lumen may be found on mesenteric angiography.

• Angiographic findings:

o Typical vascular patterns seen in angiodysplasia and neoplasia.

o A slowly filling vein that persists after other mesenteric veins have emptied is the most common angiographic finding in angiodysplasia.

o Vascular tuft seen during the arterial phase and an early filling vein.

• Intraoperative angiography has helped localization of small bowel angiodysplasia and bleeding mucosal erosions so that segmental resection can be performed.

Exploratory laparotomy

• Exploratory laparotomy for obscure bleeding is seldom reported without concomitant IOE.

Other techniques

• Biphasic arterial- and venous-phase computerized tomographic (CT) scanning has been used for identification of angiodysplasia.

• Doppler ultrasonography has been reported to detect increased blood flow through angiodysplasia.

Management

• Endoscopic therapy.

• Angiographic therapy.

• Pharmacotherapy.

• Surgery.

• Nonspecific measures.

Endoscopic therapy

• Techniques:

o Thermal contact probes.

o Injection sclerotherapy.

o Argon plasma coagulation.

o Neodymium: yttrium-aluminium-garnet (Nd: YAG) laser.

o Endoscopic cauterization.

• Indications:

o Angiodysplasias.

▪ Large angiodysplasia should be initially treated around their circumference to obliterate feeder vessels.

o Gastric antral vascular ectasia.

o Vascular malformations in blue rubber bleb nevus syndrome.

o Hereditary hemorrhagic telangiectasia.

• Advantages:

o Decrease the requirement for blood transfusions.

o Significant increases in hemoglobin levels.

o Lower rates of rebleeding.

Angiotherapy

• Transcatheter vasopressin infusion or embolization for obscure-overt small bowel bleeding as well as colonic bleeding sources.

• Complications:

o Vasopressin infusion

▪ Myocardial infarction.

▪ Arrhythmias.

▪ Hypertension.

▪ Thrombosis of arteries remote from the bleeding site.

o Embolization

▪ Ileus.

▪ Intestinal infarction requiring surgical resection.

▪ Fistulization between bowel segments.

▪ Arterial thrombosis.

Pharmacotherapy

• Indications:

o Diffuse disease.

o Lesions in areas inaccessible to endoscopic therapy.

o Continued bleeding despite endoscopic therapy or surgical resection.

o Bleeding is recurrent.

o Diagnosis is unknown.

• Estrogen-progesterone combination therapy

• Ethinyl estradiol, 0.035 mg, in combination with norethisterone, 1 mg for 6-months course.

o Hereditary hemorrhagic telangiectasia and

o Von Willibrandt's disease

• Adverse effects:

o Breast tenderness.

o Vaginal bleeding in women.

o Gynecomastia and loss of libido in men.

• Octreotide

• Dose of 0.05-0.1 mg subcutaneously two to three times a day for 6 months.

• Mechanism of action:

o Reduction in splanchnic blood flow.

o Inhibiting role on angiogenesis.

• Advantages:

o Reduce blood loss from intestinal angiodysplasia.

o Rapid response

o Improvement in transfusion requirements as early as 24 hours after initiation of therapy.

• Disadvantages:

o Recurrent bleeding when therapy was discontinued.

o Mild hyperglycemia.

• Other agents with partial success

o Danazol (antigonadotrophin with weak androgenic activity).

o Desmopressin.

o Aminocaproic acid, an inhibitor of the fibrinolytic system.

Surgery

• Indications:

o Bleeding tumors.

o Obscure bleeding if nonsurgical measures are ineffective for control of bleeding.

o High transfusion requirements.

o Life threatening bleeding.

• Surgical exploration and subsequent bowel resection.

• Blind total colectomy ( massive lower intestinal bleeding.

Nonspecific measures

• These measures are beneficial when the rate of blood loss is slow.

o Iron supplementation,

o Correction of coagulation and platelet abnormalities.

o Intermittent blood transfusions.

o Discontinuation of NSAIDs.

Prognosis

• The overall prognosis in occult bleeding is generally good, with no early mortality.

• The long-term outcome will depend on diagnostic findings such as colon cancer.[pic]

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