OBSCURE GI BLEEDTalat Bessissow, MC CM, FRCPCAssistant Professor, Department of MedicineDivision of GastroenterologyMcGill University Health Center

Definition• Definition = GI bleeding of uncertain etiology after EGD, C-scope, and

small bowel radiography

• Overt OGIB = hematochezia, melena, hematemesis or CG emesis

• Occult OGIB = FOB + in abscence of visible blood, Iron deficiency Anemia

Fecal occult blood testing

• Guaiac-based tests: The pseudoperoxidase activity of hemoglobin turns the guaiac compound blue in the presence of hydrogen peroxide

Epidemiology 300,000 pts hospitalized/yr in US ... 5% of these will have

normal EGD and C-scopes

Median time for diagnosis is 2 years

Average cost $33,630 per patient

Average 7.3 tests per patient

Paradigm shift since introduction of VCE and DBE

Etiology of Obscure GI Bleeding 5% of patients presenting with GI hemorrhage have no source found by

upper endoscopy and colonoscopy.

Of these, 75% are 2ndry to small bowel lesions

Of these, 30-60% angiectasias

Am J Surg 1992;163:90–92Br Med J (Clin Res Ed)1984;288:1663–1665.

Etiology of Obscure GI BleedingUpper and lower GI

bleedingoverlooked

Mid GI bleeding

Cameron’s erosions Tumors

Fundic varices Meckel’s diverticulum

Peptic ulcer Dieulafoy’s lesion

Angiectasia Crohn’s disease

Dieulafoy’s lesion Celiac disease

GAVE Angiectasia

Neoplasms NSAID enteropathy

Erosive gastritis Hemobilia

Ischemic colitis/UC Aortoenteric fistula

Large polyps Vasculitis

Etiology

• 40% of OGIB - due to angiectasias (AVMs) Angiectasias : ectatic blood vessels made of thin wall with or

without endothelial liningo Natural history of angiectasias is not well known

o Only 10% of all patients with angioectasia will eventually bleed

o Once a lesion has bled up to 50% will not rebleed --- predictors of rebleeding: multiple bleeding episodes, transfusion requirement

o Bleeding angiectasias are associated with abnormal von Willebrand’s factor (vWF)

AVM• Conditions/diseases associated with angiodysplastic lesions:

• Elderly

• CRF

• Aortic valve disease (Heyde’s syndrome)

• Cirrhosis

• Collagen vascular disease

AVM

What is Heyde’s syndrome ?

Heyde’s syndrome: Bleeding from angiectasias in patients with AS.

o Increased consumption of high-molecular-weight multimers of VWF due to shear stress of the abnormal valve which corrects after aortic valve replacement with decreased severity of bleeding

Transfus Med Rev 2003;17:272–286.; Abdom Imaging (2009) 34:311–319

Small Bowel Bleeding• Etiology depends on the age of the patient

• Young: small intestinal tumors, Meckel’s diverticulum, Dieulafoy lesion, Crohn’s disease

• Older: (>40) vascular lesions, NSAID-induced SB disease

• Uncommon: hemobilia, hemosuccus pancreaticus, aortoenteric fistula

History and Physical Examination The nature of the exact presenting symptom is important in deciding a

practical, efficient, and cost-effective evaluation plan Hematemesis indicate upper GI bleed Melena can be anywhere from the nose to the right colon Hematochezia can be a lower GI bleed or a fast upper GI bleed

History of medications (mainly OTC)

Family history

Skin signs

Hereditary hemorrhagic telangiectasia

Blue rubber bleb nevus syndrome

Dermatitis herpetiformis

Plummer–Vinson syndrome

Tylosis

Investigation options

I. Repeat G & C

II. CTE

III. Capsule endoscopy

IV. Enteroscopy - push or SBE/DBE

V. Angiography

VI. Tagged RBC scan

Common lesions that are overlooked• EGD: Cameron’s erosions, fundic varices, PUD, angioectasias,

Dieulafoy lesion, GAVE

• C-scope: angioectasias, neoplasms

Investigation Repeat standard endoscopy, especially if anemia and overt GI

bleeding:o Overlooked lesions: fundus

o high lesser curvature antrum C loop of duodenum, posterior wall of

duodenal bulb Random SB Bx can be + for celiac disease in up to 12%

The yield of repeat colonoscopy is 6%, yield of repeat EGD is 29% (ASGE)

Am J Gastroenterol 1996;91:2099–2102

Investigation Consider side-viewing scope if pancreatobiliary

pathology is suspected Small bowel series/SBFT:

o When compared with capsule endoscopy• diagnostic yield 8% vs 67%• clinically significant finding 6% vs 42%

(NNT 3)

o Used if SB obstruction is suspected

Gastroenterology 2002;123:999–1005

Investigation CT Enterography:

o Thin sections and large volumes of enteric contrast material to better display the small bowel lumen and wall.

o Neutral enteric contrast + IV contrast

o 1.5 – 2 L of milk, PEG electrolytes or low-concentration barium

Investigation

CT Enterography:

o Advantages: displays entire wall thickness examination of deep ileal loops mesentery & perienteric fat no need for NGT

CTE

Investigation

Technetium-99m–labeled RBC scan: Limited value Blood loss of 0.1-0.4 ml/min (2U PRBCs /d) Poor localization of SB bleeding - not enough to direct operative therapy

Angiography: Useful in massive bleeding (>0.5ml/min) Diagnostic & therapeutic

Nucl Med Commun 2002;23:591–594

Investigation Endoscopic imaging:

o Intraoperative enteroscopy; Terminal ileum can be reached in 90% of cases

• diagnostic yield 58-88%• mortality up to 17%

Investigations

Push enteroscopy: Length 220-250 cm usually limited to 150 cm diagnostic yield up to 70% angioectasias in up to 60% some suggest push enteroscopy over repeat EGD as

second look

Capsule endoscopy

oSize 11x26 mmoObtains images and transmits the data via radiofrequency to a recording deviceoThe capsule is disposableoExamination takes at least 8 hours (57,600 images)oReading 60 – 120 minutes oSB obstruction is a contraindication

Capsule endoscopy Capsule endoscopy: yield 63% vs 23% for push enteroscopy Sensitivity 89 - 95% Specificity 75 – 95% +ve predictive value 97% -ve predictive value 86%

•

• Lin, GIE 2008• Rastogi et al. GIE 2004• Pennazio et al. Gastroenterol 2004• Apostolopoulos et al. Endoscopy 2006• Estevez et al. Eur J Gastro Hep 2006• Delvaux et al. Endoscopy 2004

•

Diagnostic YieldObscure/Overt GI Bleeding 36-92%Obscure/Occult GI Bleeding 41-63%Unexplained Fe-def Anemia 42-57%Yield Gain Over Push Enteroscopy

+ 30%

Yield Gain Over SB Barium Study + 36%

• Superior yield to other diagnostic modalities in both active and inactive obscure GI bleeds

Study Sens (%) Spec (%) PPV (%) NPV (%)

Pennazio 2004, Gastroenterol 88.9 95 97 82.6

Hartmann 2005, GIE 95 75 95 86

* Marmo, APT 2005, Triester, AJG 2005, Saperas AJG 2007

Double Balloon Enteroscopy

Double Balloon Enteroscopy (DBE)

o 1st described in 2001

o 200-cm enteroscope

o 140-cm overtube

Double Balloon Enteroscopy (DBE)

o Antegrade approach:

mean distance 240 +/- 100 cmmean time 72.5 +/- 23 min

• Retrograde approach:

mean distance 140 +/- 90 cm mean time 75 +/- 28 min

How Effective is DBE?

Study Diagnostic Yield (%)

Kaffes 2004, Clin Gastro Hep 76

Mehdizadeh 2006, GIE 51

Yamamoto 2006, Am J Gastro 76

Jacobs 2007, GIE 75

Tanaka 2008, GIE 54

Yadav 2010, abstract DDW 52%

How Effective is DBE?

Study Patients (n) Yield

Matsumoto 2005, Endo 13 Equivalent

May 2005, GIE 52 DBE better

Hadithi 2006, Am J Gastro 35 CE better

Mehdizadeh 2006, GIE 115 Equivalent

Ohmiya 2007, GIE 74 Equivalent

Kameda 2008, J Gastroenterol 32 Equivalent

Teshima 2010, DDW (Meta-) 1293 CE favoured although

nearly equivalent

Complications

- Perforation – 0.3-1.1%

- Bleeding (post-polypectomy) – 1.4-1.9%

- Pancreatitis – 0.2-0.3%

Melsink Endoscopy 2007, Gerson ACG 2008

Single Balloon Enteroscopy- Much more recent- Simpler to set up, works with existing Olympus

equipment- Same specifications as DBE without the second balloon

on the endoscope

Hartmann, Endoscopy 2007

Single Balloon Enteroscopy

Kawamura GIE 2008

SBE versus DBE

• Efthymiou, abstract 2010• RCT involving 79 patients recruited for mainly

OvGIB/ObGIB• About half had SBE• Depth of insertion retrograde was identical (100 cm)• Depth of insertion orally favoured DBE (250 versus 205

cm but not significant)• Therapeutic yield was 54% DBE, 37% SBE (not

significant)• Targetted biopsies or application of cautery or argon plasma

Pennazio et al. Endoscopy 2005 & AGA Technical Insitute. Gastroenterol 2007