evaluating occult bleeding… it’s all about...

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Occult GI Bleeding: Which Tests, How Many, In

What Sequence?

David Greenwald, MD

Montefiore Medical Center

Albert Einstein College of Medicine

Evaluating Occult Bleeding…It’s All About Choices...

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Another choice…

Nomenclature

• Occult GI bleeding– No visible evidence of blood loss apparentNo visible evidence of blood loss apparent

to health care provider or patient

– Initial presentation of positive fecal blood test or iron deficiency anemia

• Obscure GI bleedingBl di f th GI t t th t i t– Bleeding from the GI tract that persists or recurs without an obvious etiology

• Divided into overt and occult

Raju GS, Gerson L, Das A, Lewis B, Gastroenterology. 2007

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Occult GI Bleeding:Causes

• Colon cancer

• Vascular ectasias

• Small bowel sources

• HemosuccusVascular ectasias

• IBD

• Diverticular disease

• Peptic ulcer disease

• Esophagitis

Hemosuccuspancreaticus

• Hemobilia

• Aortoenteric fistula

• EndometriosisEsophagitis

• Gastritis

• PHG, GAVE

• Non-GI sources– Epistaxis

– Hemoptysis

Testing for Occult BloodGuaiac based testing

– Hemoglobin identified by pseudoperoxidasereaction

• Turns guaiac impregnated paper blue

– Needed for test to be positive 50% of time• Fecal blood loss 10 cc per day (10 mg per gram/stool)

– False positives• Red meat, dietary peroxidases (turnips, radishes)

– False negatives• Vitamin C

– Screening studies: 1-16% positive in healthy, many false positives Heitson P, et al. AJG 2008

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Immunochemical Tests

• Immunologic assays for intact human hemoglobin

• Detects 0.3 mg/gram of stool

• Does not detect UGI bleeding sources– Hemoglobin is degraded in small bowel

• Compared to guaiac based testing– More specific

– Equal or more sensitive when used for colorectal cancer screening

van Rossum LG, van Rijn AF, Laheij RJ, et al, Gastroenterology 2008

Evaluation of a Positive Fecal Occult Blood Test

Positive fecal occult blood testPositive fecal occult blood test– With anemia or UGI symptoms

• Upper endoscopy and colonoscopy

• If both negative, small bowel studies

– Without anemia or UGI symptomsC l• Colonoscopy

• If colonoscopy negative, further testing unnecessary

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• History and physical guide evaluation– Colorectal cancer increases after age 50Colorectal cancer increases after age 50

– Renal failure associated with vascular GI lesions

– Oral telangiectasias may suggest HHT

• Likelihood that test is a true positive matters• Many lesions bleed in an occult manner rarely

– Esophageal varices, colonic diverticulaEsophageal varices, colonic diverticula

• Others bleed in an occult manner often – Colon cancer

• Co-existent disease– Diverticula and colon cancer may occur together


• Colonoscopy– Detects polyps, cancer, vascular lesions

• Endoscopy– Patients with anemia

• Prevalence of lesions in upper tract greater than or equal that of colonic lesions

– UGI bleeding sources • Patients with iron deficiency 36%-56%

• Patients without iron deficiency 13%-28%

• Both colonoscopy and endoscopy – Lesions in 5%-17%

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Small bowel examination– UGI series/SBFT

– CT enterography

– MR enterography

– Wireless capsule endoscopy


– UGI series/SBFT• Misses erosions, ulcers, vascular lesions

Yi ld 0 6%– Yield 0-6%

• Enteroclysis– Yield < 20%

– Patient discomfort, tedious

– CT enterography• Neutral contrast agentg

• Better evaluation of small bowel wall

• Yield up to 45%

– MR enterography– No ionizing radiation

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Evaluation of a Positive Fecal Occult Blood TestSmall Bowel evaluation

Wireless capsule endoscopyWireless capsule endoscopy• First line test

• Equal or more sensitive than other

small bowel imaging modalities

• Results– 60% of studies yield a diagnosis

– Changed management plans 74% as a result of capsule finding

Ahmad NA, Iqbal N, Joyce A Clin Gastroenterol Hepatol. 2008


Wireless capsule endoscopy• Meta-analysis of 14 observational studies

• Overall yield for any small bowel findings– Capsule endoscopy 63%

– Push enteroscopy 26%

– Barium studies 8%

• Capsule retention p– Established Crohn’s Disease

– History of small bowel obstruction due to adhesions

– Radiation related enteritis

Triester SL, Leighton JA, Leontiadis G, et al , Am J Gastroenterol. 2005

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Situations

FOBT positi e on aspirin antiplateletFOBT positive on aspirin, antiplatelet agents or anticoagulants– May provoke bleeding lesion to bleed

– Neither warfarin nor low dose aspirin alone cause FOBT to be positive

– Positive FOBT merits evaluation

Greenberg PD, Cello JP, Rockey DC Am J Med. 1996;100(6):598


Situations

Alcohol ab seAlcohol abuse– 1000 patients, 2.2% positive for occult bleeding

• All had UGI mucosal inflammation

• PUD 24%

• Premalignant colonic neoplasia 32%

Fecal occult blood should not be attributed to• Fecal occult blood should not be attributed to alcohol use

Zwas FR, Lyon DT Am J Gastroenterol. 1996

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SituationsPremenopausal woman with iron

deficiency anemia– When to evaluate

• Anemia out of proportion to menstrual blood loss

• Abdominal symptoms

• Family history of GI malignancy

– Yield 12-35% • For possible GI cause of iron deficiency anemia

Vannella L, Aloe Spiriti MA, et al, Aliment Pharmacol Ther, 2008

Occult GI BleedingAlgorithm

Rockey DC, Nature Reviews Gastroenterology & Hepatology 2010

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Evaluation of Obscure GI Bleeding

Obscure Bleeding– 5% of patients with GI bleeding

– Source• Small bowel 75%

• Missed lesions in UGI or LGI tract 25%

Szold A, Katz LB, Lewis BS Am J Surg. 1992;163(1):90

Obscure GI Bleeding Often Overlooked Lesions

• Upper GI

Cameron’s erosions– Cameron s erosions

– Fundic varices

– Peptic ulcer

– Vascular ectasia

– Dieulafoy lesions

– GAVEGAVE

• Lower GI

– Vascular ectasia

– Neoplasms

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Obscure GI Bleeding

Younger than 40 years– Tumors (GIST lymphoma carcinoid adenocarcinoma)– Tumors (GIST, lymphoma, carcinoid, adenocarcinoma)

– Meckel’s diverticulum

– Dieulafoy’s lesion

– Crohn’s disease

– Celiac disease

Obscure GI Bleeding

Older than 40 years– Vascular ectasias

– NSAID enteropathy

– Celiac disease

– Uncommon• Hemobilia

• Hemosuccus pancreaticus

• Aortoenteric fistula• Aortoenteric fistula

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Obscure Bleeding:Other Conditions

• Kaposi’s sarcoma • Neurofibromatosis

• Puetz-jeghers

• Tylosis

• Ehlers-Danlos

• Blue rubber bleb

• Malignant atrophic papulosis

• Klippel-Trenaunay-Weber syndrome

nevus syndrome

• Henoch-Schonleinpurpura

Evaluation of Patients with Obscure GI Bleeding

History and physical clues– Recurrent hematemesis UGI

– Recurrent hematochezia LGI

– Melena Little localization value

– Review OTC meds NSAID use

– Review family history Colorectal or endometrial cancer may be clue HNPCC• Colorectal or endometrial cancer may be clue- HNPCC

– Skin, nail, mucosal changes• Telangiectasias of lips or mouth HHT

• Dermatitis herpetaformis Celiac disease

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Evaluation of Obscure Bleeding

• Repeat upper endoscopy or colonoscopy??– Best yields with overt bleedingBest yields with overt bleeding

• Melena

• Red blood per rectum

– Frequently missed lesions• Cameron’s ulcer, Peptic ulcers

• Vascular ectasiaVascular ectasia– Medial aspect of second part of duodenum

– Use side viewing endoscope

• Hemobilia

• Aortoenteric fistula Zaman A, Katon RM Gastrointest Endosc, 1998

Evaluation of Obscure Bleeding

• Repeat colonoscopy• Repeat colonoscopy– May be reasonable if initial exam limited

• Poor preparation

• High quality initial exam is key

– Consider hemorrhoidsSi id d f bl di• Sigmoidoscopy on day of bleeding

Ibrahim AM, Hackford AW, Lee YM, Cave DR Dis Colon Rectum, 2008

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Wireless Capsule Endoscopy

• Non-invasive, physiologic, relatively safe

• Lacks therapeutic capability

• Yields additional findings in 25-55% after push enteroscopy

• Capsule endoscopy as first strategySi ifi tl d d d f dditi l– Significantly reduced need for additional studies vs. push enteroscopy (25% vs. 79%)

de Leusse A, Vahedi K, Edery J, et al. Gastroenterology, 2007

Wireless Capsule Endoscopy

AGA Technical Review (2007) – Cause of bleeding in younger patients

should be investigated aggressively

– Small bowel tumors are the most common cause of obscure bleeding in people under age 50

– Capsule endoscopy can diagnose such tumors early and lead to improved outcomes

Raju GS, Gerson L, Das A, Lewis B Gastroenterology, 2007

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Repeat Capsule Study??

Initial capsule study negative

• Occult bleeding evaluation– Yield on 2nd capsule study generally low

• 6%-11%

– May be considered • When obscure bleeding changes from occult to g g

overt

• When hemoglobin concentration drops by more than 4g/dl

Svarta S, Segal B, Law J, et al Can J Gastroenterol. 2010

Push Enteroscopy

• Instrument is 220-250 cm long, therapy possible

– Insertion to approx 150 cm, better with overtube

– Readily available, safe, allows therapy

• Yield for obscure bleeding– 24%

– Angiodysplasia most common finding

M l i ithi th h f– Many lesions within the reach of a

standard endoscope

Lin S, Rockey DC, Gastroenterol Clin North Am, 2005

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Deep Enteroscopy

• Double balloonDouble balloon

• Single balloon

• Spiral enteroscopy

• Generally yields complementary information along with capsule study

Small bowel carcinoid

information along with capsule study– Diagnostic yield of deep enteroscopy 43%-81%

– Treatment success 43%-84%

Deep Enteroscopy

• 200 patients with obscure GI bleeding– Deep enteroscopy identified 155 bleeding p py g

sources

– Most common• Small bowel erosions and ulcers

– Improved yield when…• Deep enteroscopy within one month of overtDeep enteroscopy within one month of overt

bleeding

• 84% vs. 57%

– Overall control of bleeding in 64%Shinozaki S, Yamamoto H, Yano T, et al, Clin Gastroenterol Hepatol, 2010

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Capsule vs. Deep Enteroscopy

• Diagnostic yield – Controlled, prospective trial

• Deep enteroscopy 63%

• Capsule endoscopy 44%

– Meta Analysis• Deep enteroscopy 57%

• Capsule endoscopy 60%

May A, Nachbar L, Schneider M, AJG, 2006Pasha s, Leighton J, Das A, et al, Clin Gastreenterol Hepatol, 2008

Capsule vs. Deep Enteroscopy

Obscure overt bleedingCost effectiveness analysis– Cost effectiveness analysis

• Initial deep enteroscopy cost-effective

– But…• Capsule directed deep enteroscopy was

associated with better long-term outcomes because of…

– Fewer complications

– Decreased utilization of endoscopic resources

Gerson L, Kamal A Gastrointest Endosc. 2008

Capsule and deep enteroscopy are complementary studies

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Radionuclide Scanning

• Bleeding scan – Detects bleeding at rate of 0.1-0.5 ml/minute

• Uses 99mTc pertechnitate autologous RBCs

• Localizes bleeding in obscure, overt bleeding– Early blush more accurate than delayed positive

• Limitations– Localizes to a general location in abdomen only

– Accuracy rates 24-91%

– Study is purely diagnostic• May need follow up angiography

Radionuclide Scanning

Colonic ectasia

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Angiography

• Useful in evaluation of overt obsureGIB– Bleeding rate > 0.5 ml/min

– Localizes bleeding site better than nuclear scans

– Diagnostic yield• 27%-77% in LGI bleeding• 27%-77% in LGI bleeding

• Directed therapy possible– Superselective mesenteric embolization

Angiography

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Intraoperative Enteroscopy• Endoscope insertion during surgery or

through an enterotomy– Diagnostic yield 60-88 %Diagnostic yield 60 88 %

– Recurrent bleeding rates 13-60%

– Complications• Serosal tears

• Avulsion of SMV

• CHF, azotemia, prolonged ileus

G ll d f f il f ll th• Generally reserved for failure of all other modalities– Often directed by capsule findings

Douard R, Wind P, Panis, et al. Am J Surgery 2010

Provocative Testing

• Agents– Vasodilators (tolazoline, nitroglycerin)

– Anticoagulants (heparin)

– Fibrinolytics (urokinase, streptokinase)

– May induce bleeding during nuclear scans, angiography, endoscopy

• Mixed results• Mixed results– Safety and cost effectiveness questioned

• Insufficient evidence to support or refuteASGE Standards of Practice Guidelines, Gastrointest Endosc, 2010

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Approach to Patient With Obscure Overt Bleeding

ASGE Standards of Practice Guidelines, Gastrointest Endosc, 2010

Approach to Patient with Obscure Occult Bleeding

ASGE Standards of Practice Guidelines, Gastrointest Endosc, 2010

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Occult GI Bleeding

• Which Tests?– Many choices

• How Many?– As many as it takes

– Guided by evidence

• In What Sequence?• In What Sequence?– Most effective first

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evaluating occult bleeding… it’s all about...

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