A zebra's hoofbeats: An uncommon cause of overt

obscure gastrointestinal bleedingDr. Sean O’Loghlen PGY-2

Queen’s UniversityTed Giles Clinical Vignettes2015 CSIM Annual MeetingCharlottetown, PEI, Canada

•“When you hear hoofbeats, think of horses not zebras”

• Attributed to Dr. Theodore Woodward, circa 1940

Case Report

• A 61 year old man presents with a two week history of melena and fatigue. He denies any syncope or pre-syncope, abdominal pain, or chest pain. He is otherwise asymptomatic.

• Past medical history:• Hemorrhoids• Atrial fibrillation• Coronary artery disease with prior coronary artery bypass surgery (2011)• Dyslipidemia• Chronic back pain

• Medications:• ASA 81 mg PO once daily• Naproxen 500 mg PO BID PRN

Case Report

• Social history:• Retired mechanical engineer.• No Alcohol intake• Ex-smoker, 14-pack year history in total

• On examination:• Vitals:

• Supine: blood pressure 147/84 heart rate 69• Standing: blood pressure 129/84 heart rate 78• Asymptomatic with change in position

• Abdomen was obese, soft and non-tender. No appreciable masses or adenopathy. DRE demonstrated melena.

• Normal cardiac, respiratory and neurological examinations

Case Report

89 215

6.5

MCV: 88.8

140

3.9

107

28

Cr: 79

Urea: 4.5

INR: 1.1 Troponin: <0.010PTT: 23 CK: 85

AST: 22ALT: 16 Lactate: 1.2ALP: 57 VBG: 7.37 / 49 / 28

Case Report

• The patient is admitted to hospital for further assessment and management. Aspirin and Naproxen are stopped. Gastroenterology is consulted for consideration of endoscopy to identify the source of bleeding.

• Esophagogastroduodenoscopy:• Normal esophageal mucosa, no evidence of esophagitis, no varices• Normal stomach with a very small erosion, no coffee grounds or blood• “The patient’s anemia is not explained by upper endoscopy”

• Colonoscopy• Prep was excellent. Advanced successfully to cecum.• Mild internal hemorrhoids, no polyps, no cause of hemorrhage is identified

Case Report

• The patient’s bleeding resolves spontaneously. He is discharged home in stable condition.

• He is seen in outpatient follow-up with gastroenterology, and capsule endoscopy is arranged.

• The small bowel is well visualized on the study and no obvious source of bleeding is identified.

Case Report

• Six months pass and the patient presents again to hospital. He reports four days of melena followed by one day of bright red blood per rectum. He has also had two syncopal episodes at this point.

• On examination:• Blood pressure 95/62, heart rate 93• Appears pale and weak. Dizzy and symptomatic when sitting upright.• Dry mucous membranes, dry axilla, decreased capillary refill• Significant diffuse abdominal pain to light touch, mild voluntary guarding but

no rigidity or rebound tenderness

• The patient is re-admitted to hospital for further work-up and management

Case Report

89 364

18.3

MCV: 86.8

136

3.8

102

28

Cr: 86

Urea: 5.9

INR: 1.3 Troponin: <0.010PTT: 17 CK: 19

AST: 23ALT: 29 Lactate: 3.8

VBG: 7.37 / 44 / 25

Case Report

• In summary: A 61 year old man presents with recurrent gastrointestinal bleeding in the setting of previously negative upper and lower endoscopy as well as a negative video capsule endoscopy.

• What next?

Defining the Problem

• Overt obscure gastrointestinal bleeding:• Visible bleeding i.e. hematochezia or melena

(as opposed to occult gastrointestinal bleeding)

• Persists or recurs despite a negative upper and lower endoscopy

• Challenging to diagnose and manage effectively

• Source of significant morbidity and mortality• Differential diagnosis:

• Source may be Upper GI, small bowel, or Lower GI

Differential Diagnosis of Obscure GI BleedUpper Gastrointestinal Small Bowel Lower Gastrointestinal

Cameron lesion (5-15%) Angioectasia (20-55%) Angioectasia (2%)

Angioectasia (5-10%) Small bowel tumour (10-20%) Neoplasm (1%)

Varices (1-5%) Crohn’s disease (2-10%) Dieulafoy leson (<1%)

Dieulafoy lesion (2-3%) Celiac disease (2-5%)

Gastric antral vascular ectasia (GAVE) (1-2%)

Meckel’s diverticulum (2-5%)

Portal hypertensive gastropathy (1-2%)

NSAID enteropathy (5%)

Dieulafoy lesion (1-2%)

Ectopic varices (1-2%)

Portal hypertensive enteropathy (1-2%)

Radiation enteritis (<1%)

Modalities to Identify Source of Bleeding

• Repeat upper or lower endoscopy• Miss rates for upper and lower endoscopy respectively are up to 26% and

29% respectively

• Videocapsule endoscopy (diagnostic yield: 56-72%)• Double balloon enteroscopy, single balloon enteroscopy, spiral

enteroscopy (diagnostic yield: 43-81%)• Push enteroscopy (diagnostic yield: 24-56%)• CT enterography, CT angiography (diagnostic yield: 45-89%)• Angiography (diagnostic yield 27-77%)• Labelled RBC scan (diagnostic yield 15-25%)

Approach to Overt Obscure GI Bleeding

American society for Gastrointestinal Endoscopy

Case Report• Given our patients worsening abdominal pain

and recent negative endoscopic investigations, an urgent CT angiography was arranged.

Case Report

• CT report:• “Within the center of the mesentery, there is a lobulated

homogeneously enhancing mass that measures 8.8 x 5.9 cm… The mass appears to be pulling over a loop of jejunum into the right lower quadrant. There is some soft tissue attenuation within the mesentery of this pulled loop…This may represent local extension of the mass or local edema. There is no evidence of calcification within the mass. There is no evidence of bowel obstruction.”

• “Large mass in the mesentery is directly in contact with a loop of jejunum. Consideration is mainly GIST, with lymphoma being a secondary option. Periportal adenopathy.”

Case Report• After the CT scan, the patient was brought to the OR emergently

given his active bleeding and large intrabdominal mass for an exploratory laparotomy. The mass and an adjacent segment of small bowel was resected and a primary anastomosis was made.

• Pathology:• Gastrointestinal Stromal Tumour

• Gross ulceration of tumour into small bowel mucosa• 8 x 7.5 x 5.5 cm• Completely resected; margins negative – closest margin is 3.5 cm• Mitotic rate 5/50 per high powered field • Immunohistochemistry: HIT CD117 +ve, DOG1 & CD34 –ve, S100 & SMA –ve, Ki-67

proliferation index <1% (very low)• “Intermediate risk”

Gastrointestinal Stromal Tumours

• Unusual cause of gastrointestinal bleeding. Incidence is 10 cases / million people.

• Represent 0.3-0.5% of GI malignancies and is most common sarcoma of the GI tract.

• Usually occurs in the setting of gain-of-function mutation in C-kit proto-oncogene which is a tyrosine kinase (similar mutations involved in AML, melanoma, testicular seminoma)

• Typically thought to arise from interstitial cells of cajal

Gastrointestinal Stromal Tumours

• Presentation:• Abdominal fullness or pain• Anemia• Occult obscure gastrointestinal

bleeding• Overt obscure gastrointestinal

bleeding is an unusual presentation…

Gastrointestinal Stromal Tumours

• Management:• Surgical resection is the treatment of choice. Lesions >2cm should be

resected. Lesions <2cm can be monitored with serial imaging.• Medical management involves treatment with Imatinib, which interferes with

tumour proliferation by disrupting signalling via the C-kit oncogene• Imatinib is used in the following situations:

• Unresectable or metastatic disease• Neoadjuvant therapy for disease where surgical resection would carry high morbidity

and mortality (given for 2-6 months before surgery)• Adjuvant therapy for disease that is at a moderate to high risk of recurrence

Learning Objectives

• 1. Diagnose the cause of an overt obscure gastrointestinal bleed using a rational approach

• 2. Recognize the indications and limitations of capsule endoscopy in identifying sources of obscure gastrointestinal bleeds

• 3. Recognize the historical and physical examination findings compatible with gastrointestinal stromal tumours

Learning Objectives

• 1. Diagnose the cause of an overt obscure gastrointestinal bleed using a rational approach

• Upper and lower endoscopy have appreciable miss rates and repeat endoscopy may be a reasonable option

• The most frequent source of bleeding in obscure gastrointestinal bleeds is from the small bowel

• Choice of diagnostic test is predicated on the acuity and severity of bleeding• Capsule endoscopy and deep enterography (double balloon, single balloon

and spiral) are complimentary procedures with the highest diagnostic yields. Enterography offers the opportunity for therapeutic intervention

• In patients with recurrent GI bleeds despite negative upper, lower and capsule endoscopy, the optimal approach is unclear

Learning Objectives

• 2. Recognize the indications and limitations of capsule endoscopy in identifying sources of obscure gastrointestinal bleeds

• Capsule endoscopy is most commonly used to detect an occult source of blood loss in the GI tract after negative upper and lower endoscopy

• It is a safe, minimally invasive test allowing for full visualization of the GI tract• It does not offer the opportunity for therapeutic intervention – if a significant

lesion is found, another modality needs to be pursued to ameliorate it• It is not an ideal modality to assess the esophagus, stomach or colon• There is the risk of capsule retention in patients with Crohn’s, prior abdominal

surgery or radiation

Learning Objectives

• 3. Recognize the historical and physical examination findings compatible with gastrointestinal stromal tumours

• GIST typically presents with abdominal fullness or discomfort, and anemia secondary to occult obscure gastrointestinal bleeding

• Overt obscure gastrointestinal bleeding is an unusual presentation• Often the tumours are large and palpable on physical examination• Intra-abdominal metastasis is present in 30-40% of patients on presentation• Many are found incidentally

References

• American Gastroenterological Association (AGA) Institute Technical Review on Obscure Gastrointestinal Bleeding. Gastroenterology 2007;133:1697–1717

• Joensuu H, Hohenberger P, Corless C. Gastrointestinal stromal tumour. Lancet 2013;382(9896):973-983

• Leung W, Ho S, Suen B, Lai L, Yu S, Ng E, Ng S, Chiu P, Sung J, Chan F, Lau J. Capsule Endoscopy or Angiography in Patients With Acute Overt Obscure Gastrointestinal Bleeding: A Prospective Randomized Study With Long-Term Follow-Up. Am J Gastroenterol. 2012;107(9):1370-6

• Liao Z, Gao R, Xu C, Li Z. Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. GastrointestEndosc. 2010;71(2):280-6

• Miettinen M, Lasota J. Gastrointestinal stromal tumours: Pathology and prognosisat different sites. Semin Diagn Pathol. 2006 May;23(2):70-83

References (continued)

• Triester SL, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, Shiff AD, Sharma VK. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol. 2005;100(11):2407-18.

• Liu K, Kaffes AJ. Review article: the diagnosis and investigation of obscure gastrointestinal bleeding. Aliment Pharmacol Ther. 2011;34(4):416-23.

• Yuval JB, Almogy G, Doviner V, Bala M. Diagnostic and therapeutic approach to obscure gastrointestinal bleeding in a patient with a jejunal gastrointestinal stromal tumor: a case report. BMC Res Notes. 2014 Oct 7;7:695.

• ASGE Standards of Practice Committee, Fisher L, Lee Krinsky M, Anderson MA, Appalaneni V, Banerjee S, Ben-Menachem T, Cash BD, Decker GA, Fanelli RD, FriisC, Fukami N, Harrison ME, Ikenberry SO, Jain R, Jue T, Khan K, Maple JT, Strohmeyer L, Sharaf R, Dominitz JA. The role of endoscopy in the management of obscure GI bleeding. Gastrointest Endosc. 2010 Sep;72(3):471-9.

Approach to Obscure GI Bleeding

American Gastroenterological Association Algorithm

Gastrointestinal Stromal Tumours

Miettinen et al. Gastrointestinal stromal tumors: Pathology and prognosis at different sites. Sem Diag Path. 2006.