Gastrointestinal Bleeding (Obscure)

other

Role of Other Investigations

Computed Tomography Angiography (CTA)

• With the development of MDCT, a non-invasive method of establishing a cause for OGIB has been developed. However, trials comparing capsule endoscopy and MDCT have clearly demonstrated the higher diagnostic yield with CE. 23 In a recent prospective cohort study CTA identified a source of OGIB in 24% of patients compared to 68% when CE was utilised in the same cohort but it was unclear whether the bleeding was inactive or active in these patients 24
• CTA is only likely to be useful in patients with active bleeding
• Hence at this stage, MDCT should be considered after CE and DBE in the assessment of OGIB

Mesenteric Angiography

• The role of mesenteric angiography in the assessment of OGIB is hampered by a paucity of studies in this sub-group of gastrointestinal bleeders 1
• Diagnostic yields of 40-44% 25,26 have been quoted in the literature, although yields as high as 74% have been reported. 27 The diagnosis can be made based on extravasation of contrast into the bowel lumen or typical angiographic appearances of vascular lesions. The rate of active bleeding has to be at least >0.5mL/min, for contrast to be seen in the bowel lumen 1
• Provocative angiography (the use of anti-coagulants) has also been trialed in OGIB with mixed success. Although a higher yield of diagnosis was found, this came at the expense of more adverse effects (groin hematoma) 1
• Significant morbidity is associated with angiography, including renal failure, arterial dissection, ischemic colitis and death
• Given the high sensitivity and safety of other techniques (capsule endoscopy and double balloon enteroscopy), angiography should be reserved for truly occult OGIB.

Small Bowel Follow-Through / Enteroclysis

• Oral ingestion of a barium suspension is required for a Small Bowel Follow-Through (SBFT) series. In a large retrospective series of greater than 1000 patients for a range of indications, SBFT had a diagnostic yield of 5.6% (12/215 patients) for the detection of OGIB. 28 A more recent retrospective series found comparable results (3% of barium studies for OGIB) 23
• Enteroclysis requires the placement of a tube in the proximal small bowel. A contrast solution is then instilled through the tube and sequential fluoroscopy is undertaken to identify an abnormality. This technique has been shown to have a diagnostic yield in OGIB of 21%. 29 However this is at this expense of patient discomfort
• Small bowel barium studies have low diagnostic yield in suspected OGIB and have been replaced by cross-sectional imaging (CT / MRI) where needed

Intra-Operative Enteroscopy / Exploratory Laparotomy

• Intra-operative Enteroscopy (IOE) at laparotomy involves the passage of an endoscope per oral, transnasally, per rectum or via enterotomies at the time of exploratory laparotomy
• It requires considerable resources including an endoscopist and surgeon and rarely done these days
• IOE has been shown to have excellent diagnostic yields in the assessment of OGIB 1
• It is however associated with significant morbidity and mortality 1

Bleeding

Active Versus Inactive Bleeding

• Choice of investigation following initial endoscopies for OGIB mainly depends on bleeding being active or inactive at the time of presentation and on the patient demographics
• For inactive bleeding, assuming all investigative modalities are available, a reasonable strategy in older patients (>50 years) is to perform CE initially to detect lesions followed by targeted DBE for biopsy or intervention. 31,32 A negative CE however, should be followed by CT enterography or enteroclysis
• For inactive bleeding in younger patients, it is reasonable to perform CT enteroclysis in view of higher likelihood of finding tumors rather than angiodysplasia in this group
• In patients presenting with active bleeding, radiological investigations are the mainstay given their high sensitivity and non-invasiveness. CT Angiography can detect bleeding rates of 0.5 ml/min and above. If CTA is negative, this usually signifies that catheter angiography is not indicated since the latter is less sensitive than the former and has been shown to detect bleeding rates greater than 0.5 ml/min only
• If bleeding persists following a negative CTA, technetium 99m – labeled RBC nuclear scan is used as the second line of investigation at some institutions while others may use this as the first line of investigation for active bleeding. Among the available modalities, RBC nuclear scan is the most sensitive for active GI bleeding and can detect bleeding rates as low as 0.1 mL/min 11
• Life-threatening hemorrhage should indicate catheter angiography as the first line of management

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Capsule Endoscopy (CE)

• Has been shown to have higher diagnostic yield for obscure GI bleeding when prospectively compared with other imaging modalities. Compared to intra-operative enteroscopy at laparotomy (reference gold standard), CE has a sensitivity, specificity, positive predictive value & negative predictive value of 95%, 75%, 95% and 86% respectively 4
• Two meta-analyses examining CE compared to other conventional diagnostic modalities in patients with OGIB have supported the findings of initial small cohort studies 5,6
• Studies that have examined the long-term results following CE for the investigation of OGIB, have proved the clinical utility of this diagnostic modality in altering patient outcome 7
• Despite lack of studies on accuracy and strong RCTs, a weight of evidence and consensus points to CE being most useful in inactive OGIB 8,9 and has similar diagnostic yield as DBE for the evaluation of OGIB 10
• American Society for Gastrointestinal Endoscopy (ASGE) guidelines for management of OGIB named CE as the primary procedure of choice after excluding upper GI and colorectal lesions with endoscopy 11
• Contraindications for its use include a history of GI motility disorder, a history of known strictures or fistulae, a history of extensive abdominal surgery, an active swallowing disorder and the presence of a cardiac pacemaker/implantable cardiac defibrillator (relative contraindication as some groups have safely performed CE in this group)
• Advantages of CE include
• Non-invasive
• Accepted and well tolerated by patients
• Ability to visualise the entire small bowel
• Disadvantages of CE include
• Technical malfunction of the capsule and Slow GI transit time may result in part of the small bowel being not visualised
• Difficulty in localising lesions due to lack of anatomical details
• Inability to perform diagnostic or therapeutic maneuvers, requiring further invasive investigations
• Strictures may result in capsule retention needing further intervention for their retrieval
• May not detect mass lesions and extra-mucosal abnormalities

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Double Balloon Enteroscopy (DBE)

• Enteroscopy was first introduced in 1973; small bowel ‘push enteroscopy’ is an important tool for the investigation of small bowel
• Initial endoscopes permitted examination of a variable length of the small bowel (proximal jejunum). The diagnostic yield for the evaluation of a cause of OGIB has been reported to be between 38-75% with push enteroscopy 1
• In 2001, a Japanese group developed a method of examining the entire small bowel. DBE either per oral, per anal or a combination of both (total enteroscopy) has increased the diagnostic yield of OGIB 3
• Most researchers and specialists propose a CE-guided DBE where targeted DBE is performed for biopsy and intervention in patients with a positive CE examination 12
• Can visualize the entire small bowel using retrograde and antegrade intubation but a recent systematic review concluded that complete enteroscopy was possible in only 44% of cases even with combined antegrade and retrograde approaches 13
• In two large case series that examined the utility of DBE in a range of small bowel diseases, the yield of DBE in establishing a cause of occult gastrointestinal bleeding was 73-75% 14,15
• Initial studies comparing capsule endoscopy (CE) to DBE have demonstrated a clear diagnostic benefit for CE. Access to the entire small intestine was 90.2% for CE, significantly higher than DBE (62.5%) 16 but, a recent meta-analysis comparing CE and DBE suggested similar diagnostic yields for evaluation of OGIB 10
• Retrograde DBE can be of use if Meckel’s diverticula are considered as the cause for OGIB 17
• Advantages of enteroscopy include
• Ability for diagnostic and therapeutic intervention
• Improved visualization of the small bowel as a result of insufflation of air
• Focused examination of any abnormality visualized
• Disadvantages/adverse effects of enteroscopy include
• Technically demanding and time-consuming
• Limited availability
• Visceral perforation
• Mucosal bleeding as a result of contact by the enteroscope
• Pancreatitis
• Abdominal pain a result of the insufflation of air into the bowel
• Given the non-invasive nature of CE, there is a strong move towards using this modality as a first line investigation prior to enteroscopy 4,16

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Computed Tomography (CT) Enteroclysis / Enterography

• CT enterography and enteroclysis are CT techniques used to provide better images of the small bowel lumen and wall
• CT enterography involves rapid oral ingestion of 2L of contrast media before CT scanning
• The contrast used is usually neutral (water density) or diluted positive contrast. Neutral intra-luminal contrast is essential for obscure GI bleeding. CT may be performed in several phases (e.g. non-contrast, post-contrast arterial, portal venous phase or delayed phase), or combined with CT angiography when investigating active bleeding. Limitations include inability of some patients to consume a large amount of fluid in a short period of time, achieving appropriate timing of the scan to obtain good bowel distension and radiation dose
• CT enteroclysis involves passing a naso-jejunal catheter under fluoroscopic guidance. Neutral or dilute positive contrast is instilled through the tube allowing rapid filling and distension of the intestine. Images are obtained as for CT enterography. Limitations of this technique include more invasive nature (compared to enterography), achieving correct timing of scan (less problematic than enterography) and radiation dose. Enteroclysis has been shown to provide superior bowel distension than enterography 18, however it is uncertain whether this translates into better diagnostic outcomes. There are few comparisons in the literature. Two studies found similar accuracy between the two techniques 18,19
• CT techniques are unable to detect angiodysplastic lesions in the bowel, which are usually small and flat and are better visualized with endoscopic techniques like CE or DBE. However, cross-sectional imaging can detect non-mucosal lesions such as tumours. One study found multiphase CT enterography to have a higher diagnostic yield than capsule endoscopy, but there was a high prevalence of tumours in the study population 20
• CT is more likely to be of importance for patients below 50 years as the most common cause for OGIB in this group is tumours 21
• A recent study comparing CE and uniphasic multidetector CT suggest that the techniques are complimentary, since CE may miss extra-mucosal lesions best seen on a CT 22

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Nuclear Scintigraphy

• Nuclear scintigraphy techniques have been validated in acute GI bleeding, where there is active blood loss into the bowel lumen. However there is a lack of studies utilising this investigation for OGIB 1
• The diagnostic yield of technetium 99m labeled red cells in a series was reported as 33% 30
• Meckel’s diverticula may also present with bleeding and/or pain. No studies have been performed comparing various modalities in their detection, but since the occurrence of bleeding suggests the presence of ectopic gastric mucosa, scintigraphy with technetium labeled sodium pertechnetate is a useful procedure 17
• There are several limitations of nuclear scintigraphy in OGIB
• Nuclear scanning localises active bleeding to a region of the abdomen, not a particular site
• The rate of active bleeding has to be at least 0.1-0.4mL/min for a positive result
• Scanning is not therapeutic, thus requiring further invasive procedures

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