OBSCURE GI BLEED Talat Bessissow, MC CM, FRCPC Assistant Professor, Department of Medicine Division of Gastroenterology McGill 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;163:90–92 Br Med J (Clin Res Ed)1984;288:1663–1665.

Etiology of Obscure GI Bleeding Upper and lower GI bleeding overlooked Mid GI bleeding Cameron’s erosions Tumors Fundic varices Meckel’s diverticulum Peptic ulcer Dieulafoy’s lesion Angiectasia Crohn’s disease Celiac disease GAVE 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 lining Natural history of angiectasias is not well known Only 10% of all patients with angioectasia will eventually bleed Once a lesion has bled up to 50% will not rebleed --- predictors of rebleeding: multiple bleeding episodes, transfusion requirement 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. 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 Repeat G & C CTE Capsule endoscopy Enteroscopy - push or SBE/DBE Angiography 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: Overlooked lesions: fundus 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 Gastroenterology 2002;123:999–1005 Consider side-viewing scope if pancreatobiliary pathology is suspected Small bowel series/SBFT: When compared with capsule endoscopy diagnostic yield 8% vs 67% clinically significant finding 6% vs 42% (NNT 3) Used if SB obstruction is suspected Gastroenterology 2002;123:999–1005

Investigation CT Enterography: Thin sections and large volumes of enteric contrast material to better display the small bowel lumen and wall. Neutral enteric contrast + IV contrast 1.5 – 2 L of milk, PEG electrolytes or low-concentration barium

Investigation CT Enterography: 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: 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 Size 11x26 mm Obtains images and transmits the data via radiofrequency to a recording device The capsule is disposable Examination takes at least 8 hours (57,600 images) Reading 60 – 120 minutes SB 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%

36-92% 41-63% 42-57% + 30% + 36% Diagnostic Yield Obscure/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% 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

Pennazio 2004, Gastroenterol 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 75 86 * Marmo, APT 2005, Triester, AJG 2005, Saperas AJG 2007

Double Balloon Enteroscopy Double Balloon Enteroscopy (DBE) 1st described in 2001 200-cm enteroscope 140-cm overtube

Double Balloon Enteroscopy (DBE) Antegrade approach: mean distance  240 +/- 100 cm mean 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 Jacobs 2007, GIE 75 Tanaka 2008, GIE 54 Yadav 2010, abstract DDW 52%

CE favoured although nearly equivalent 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 Ohmiya 2007, GIE 74 Kameda 2008, J Gastroenterol 32 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 Pennazio et al. Endoscopy 2005 & AGA Technical Insitute. Gastroenterol 2007