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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

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Diagnostic Yield of Dual-phase Computed Tomography Enterography in Patients With Obscure Gastrointestinal Bleeding and a Non-diagnostic Capsule Endoscopy
Jaya R Agrawal; Anne C Travis; Koenraad J Mortele; Stuart G Silverman; Rie Maurer; Sarathchandra I Reddy; John R Saltzman Posted: 04/18/2012; J Gastroenterol Hepatol. 2012;27(4):751-759. 2012 Blackwell Publishing

Abstract and Introduction

Abstract

Background and Aim: In patients with obscure gastrointestinal (GI) bleeding, capsule endoscopy is widely used to determine the source of bleeding. However, there is currently no consensus on how to further evaluate patients with obscure GI bleeding with a non-diagnostic capsule endoscopy examination. This study aims to determine the diagnostic yield of dual-phase computed tomographic enterography (CTE) in patients with obscure GI bleeding and a non-diagnostic capsule endoscopy. Methods: Patients with obscure GI bleeding who were referred for capsule endoscopy were prospectively enrolled. Obscure GI bleeding was defined as overt if there was obvious GI bleeding; otherwise it was defined as occult. Patients with a nondiagnostic capsule endoscopy and no contraindications underwent a CTE. Results: Capsule endoscopy was performed in 52 patients; 26 patients (50%) had occult GI bleeding and 26 patients (50%) had overt GI bleeding. CTE was then performed in 25 of the 48 patients without a definitive source of bleeding seen on capsule endoscopy. The diagnostic yield of CTE was 0% (0/11) in patients with occult bleeding versus 50% (7/14) in patients with overt bleeding (P < 0.01). Using clinical follow up as the gold standard, for the 25 patients with a non-diagnostic capsule, CTE had a sensitivity of 33% (95% confidence interval 0.15, 0.56) and a specificity of 75% (95% confidence interval 0.22, 0.99). Conclusions: In patients with a non-diagnostic capsule endoscopy examination, CTE is useful for detecting a source of GI bleeding in patients with overt, but not occult, obscure GI bleeding.
Introduction

Obscure gastrointestinal (GI) bleeding refers to GI bleeding without a source diagnosed by upper endoscopy or colonoscopy. In 4070% of cases of obscure gastrointestinal bleeding, a bleeding lesion is localizable to the small bowel.[1] In obscure gastrointestinal bleeding, capsule endoscopy has a diagnostic yield of 4080%, and has demonstrated diagnostic superiority to push enteroscopy, barium studies, angiography, computed tomographic (CT) angiography, and routine abdominal CT scan.[2
19]

However, capsule endoscopy has some limitations. First, there are concerns that the high sensitivity of capsule endoscopy in occult GI bleeding comes at the cost of reduced specificity. Haghighi et al. reported 160 patients with obscure GI bleeding.[20] Angioectasias were found in 68% of patients, ulcers in 29% of patients and erosions in 21% of patients. However, the same authors also studied 40 healthy volunteers and found similar results in non-bleeding patients: 78% of the volunteers had angioectasias, 19% had ulcers and 41% had erosions. In practice, a clinician evaluating a patient for obscure GI bleeding often has trouble distinguishing between a "true source" of bleeding, warranting a potentially invasive procedure versus an incidental finding. A second limitation of capsule endoscopy is the tendency of images to be obscured by blood in the setting of active bleeding. This conceals the location and nature of the underlying lesion and often requires the clinician to perform additional diagnostic testing before making a decision on an appropriate therapeutic intervention. In situations where the capsule is non-diagnostic, inconclusive or insufficient, the subsequent diagnostic algorithm is not welldefined. Cross-sectional imaging currently does not have an established role in this setting. CT enterography (CTE) combines the spatial and temporal resolution of CT with an orally administered neutral enteric contrast material that permits detailed visualization of the small bowel. Unlike nuclear medicine techniques and catheter angiography, CT is less labor-intensive, more readily available, provides precise anatomic localization, and in the case of angiography, is less invasive. The obscure gastrointestinal bleeding CTE protocol at our institution utilizes a dual-phase technique that obtains images at two time-points to better identify active bleeding. We prospectively studied a diagnostic algorithm that employed capsule endoscopy followed by CTE if capsule endoscopy was non-diagnostic to investigate the effectiveness of CTE in the evaluation of obscure gastrointestinal bleeding. Methods
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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

Subject Selection and Study Protocol

Patients with obscure gastrointestinal bleeding who were referred to Brigham and Women's Hospital for capsule endoscopy in 2007 and 2008 for the problem of obscure GI bleeding were prospectively enrolled (http://www.clinicaltrials.gov NCT00593021). Patients were eligible if they were older than age 17 years, had had prior non-diagnostic upper endoscopy and colonoscopy and were diagnosed by an attending gastroenterologist with obscure GI bleeding. The patients' bleeding patterns were categorized as: occult-obscure GI bleeding (defined as anemia without overt bleeding), prior overt-obscure GI bleeding (defined as hematochezia, melena, or hematemesis, noted in the past in a patient who was asymptomatic at the time of evaluation), or active overt-obscure GI bleeding (defined as passage of melena or hematochezia within 12 h before enrollment and ongoing transfusion requirement in a hospitalized patient). Patients who were unable to give consent were excluded. This study was approved by our institutional review board (approved 1 October 2007). After written informed consent was obtained, a detailed medical history was recorded from patient interview and chart review. All patients underwent capsule endoscopy. The capsule endoscopy was read as "positive" if active bleeding was seen or a definitive source was identified; "possibly positive" if a lesion with the potential to bleed was seen, and "negative" if no lesion with the potential to bleed was seen. Patients with definitive findings were offered therapeutic endoscopy and did not undergo CTE. Patients with a non-diagnostic capsule endoscopy (possible or negative capsule endoscopy), or a positive capsule endoscopy in which the underlying lesion was obscured by blood, were offered a CTE. Inpatients with active bleeding underwent CTE within 48 h of a non-diagnostic capsule endoscopy. For outpatients, the CTE was scheduled electively. Patients with renal insufficiency (blood creatinine > 1.5 mg/dL or estimated glomerular filtration rate < 60 mL/min/1.73 m2) or an allergy to iodinated contrast media were not offered a CTE, but remained in the study for the follow-up period. Further testing was conducted at the discretion of the referring physician. Patients were followed by chart review for a minimum of 120 days. If no follow-up visit was recorded after the 4-month period, the patient's referring gastroenterologist was contacted for patient information. Patients were followed until the conclusion of the study; the range of the follow-up period was 415 months (mean follow up 11.2 months). All laboratory results, diagnostic, therapeutic and medical interventions were recorded during the study follow-up period. The presence or absence of persistent symptoms, anemia and the need for continued iron replacement, hospitalization, transfusion or erythropoietin therapy was also recorded. The final diagnosis recorded used as the reference or gold standard for this study was the referring gastroenterologists' impression based on the final results of all of the study procedures, further testing (endoscopy and surgery) and clinical course.
Capsule Endoscopy

Beginning 24 h prior to the capsule endoscopy, patients were placed on a clear liquid diet and then underwent an overnight fast. On the morning of the test, patients swallowed a capsule endoscope (PillCam SB2; Given Imaging Limited, Yoqneam, Israel) with water. Images were reviewed by one of two study gastroenterologists (A.C.T., S.I.R.) experienced in the interpretation of capsule endoscopy using Rapid Reader version 5 software (Given Imaging Limited, Yoqneam, Israel). Both readers had access to the patients' clinical information and determined whether the capsule was positive, possibly positive or negative based on whether or not findings on the capsule seemed responsible for the patient's clinical presentation. All capsule readings were done prior to CTE and patients with a negative or non-diagnostic capsule study were subsequently referred for CTE.
Dual-phase CTE

Prior to undergoing CTE, patients drank 1350 mL of a neutral oral-enteric contrast material containing 0.1% barium suspension (Volumen; GE Healthcare, Waukesha, WI, USA). Multidetector-row CT scanners (40320 row) from two manufacturers (Siemens Medical Solutions; Forcheim, Germany and Toshiba America Medical Systems, Tustin, CA, USA) were used with the following scanning parameters: kVp 120, tube current modulated with a quality reference mAs of 200, and 0.6-mm collimation. Images were reconstructed axially with 3-mm sections, and 1.5-mm increments. Coronal and sagittal images were reconstructed with 3-mm sections and 3-mm increments. Images were obtained at 40 s and 70 s after the administration of 150 cc intravenous contrast medium (Ultravist 300, Bayer Healthcare, NJ, USA). Images were reviewed by a single radiologist (K.J.M.) experienced in the interpretation of dual-phase CTE who had access to the patients' clinical information, but was blinded to the results of the capsule endoscopy. CTE results were read as "positive" if findings believed to explain the source of bleeding were seen and "negative" if no source of bleeding was seen.
Analysis
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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

To calculate a diagnostic yield for capsule endoscopy, the number of patients with a positive or possibly positive capsule endoscopy was divided by the total number of patients who underwent capsule endoscopy. Similarly, for the patients who underwent CTE, the diagnostic yield was calculated by dividing the number of patients with positive findings that could explain the bleeding, divided by the total number of patients who underwent CTE. 2 or Fisher's exact tests were used to compare categorical data. Due to multiple testing, a reduced alpha of P < 0.01 was considered significant. Results
Patient Population and Study Schema

There were 57 patients who met the inclusion criteria (Fig. 1), of whom 52 were enrolled in the study (three refused and two were unable to give consent). There was a female predominance of 63% (33/52). The majority of patients were over the age of 40 years (49/52). The bleeding was occult in 26/52 patients (50%) and overt in 26/52 patients (50%). Of the patients with occult bleeding, 14/26 (54%) were both heme-positive and iron-deficient, 10/26 (38%) were either heme-positive or iron-deficient but not both, and 2/26 (8%) had unexplained normocytic anemia, without documented evidence of heme-positivity or iron deficiency. Of the patients with overt bleeding, 16/26 (62%) presented with prior bleeding and 10/26 (38%) presented with active bleeding (all hospitalized patients).

Figure 1. Study schema. Fifty-two patients were enrolled in the study. Four patients had capsule findings interpreted as a definitive source of bleeding. Forty-eight patients were considered for dual-phase computed tomography enterography
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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

(CTE); 25 underwent CTE. CTE identified lesions believed to be the source of bleeding in seven patients.
Diagnostic Yield of Capsule Endoscopy

The overall diagnostic yield of capsule endoscopy was 48% (25/52 patients). Positive sources of bleeding were found in 10/52 patients (19%). Definitive sources of GI bleeding were found in four patients; two of these patients had large jejunal angioectasias and two had ulcers (jejunal and gastric). In the remaining six patients, blood obscured the underlying lesion (and thus these patients were eligible for CTE). Possible sources of bleeding were seen in 15/52 patients (29%). Small bowel angioectasias (some with concurrent gastric antral vascular ectasia) were found in 12 patients, and three showed erosive gastropathies. No identifiable source of bleeding was found in 27/52 patients (52%). Overall, 48/52 patients were eligible for a CTE due to a negative capsule (n = 27), a capsule with a "possible" but not definitive source of bleeding (n = 15), or a capsule with active bleeding where the underlying lesion was obscured by blood (n = 6). The diagnostic yields of capsule endoscopy were 38% (10/26 patients), 50% (6/16 patients), and 70% (7/10 patients), for patients with occult, prior overt, or active obscure bleeding, respectively (P = 0.21). Of note, in patients with occult bleeding who were both heme-positive and iron-deficient, the diagnostic yield of capsule endoscopy was 71% (10/14), whereas it was 0% (0/12) in those who did not meet both criteria (P < 0.0001).
Diagnostic Yield of CTE

Of the 48 patients eligible for CTE based upon their capsule endoscopy results, 25 underwent the examination (13 were excluded for renal insufficiency, three were excluded for contrast allergy, four refused CTE testing, two had their symptoms resolve spontaneously, and one patient was lost to follow up). The overall diagnostic yield for CTE in all patients who underwent CTE for a non-diagnostic capsule was 28% (7/25 patients). Using clinical follow up as the gold standard, for the 25 patients with a non-diagnostic capsule, CTE had a sensitivity of 33% (95% confidence interval [CI] 0.15, 0.56) and a specificity of 75% (95%CI 0.22, 0.99). Analyzing the results by clinical presentation, CTE yielded a diagnosis in 0/11 patients (0%) with occult bleeding and in 7/14 patients (50%) with overt (prior and active) bleeding (P < 0.01). The yield of CTE was 3/9 (33%) in patients with prior bleeding and 4/5 (80%) in patients with active bleeding (Fig. 2). Four of six patients with active bleeding seen on capsule endoscopy, where the underlying lesion was obscured by blood, underwent CTE; the CTE was positive in two (50%).

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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

Figure 2. Diagnostic yield of computed tomography enterography (CTE) in patients with a non-diagnostic capsule endoscopy. Diagnostic yield of dual-phase CTE in patients presenting with occult, prior overt, and active overt bleeding, respectively. The differences in diagnostic yield among the three categories were statistically significant (P < 0.01). , Occult bleeding; , Prior overt bleeding; , Active overt bleeding. The true positive CTE findings included an ulcer in the terminal ileum (one patient with no findings on capsule, Fig. 3), jejunal angioectasias (one patient with a positive capsule endoscopy but the lesion was obscured by blood, Fig. 4), a Meckel's diverticulum (one patient with a positive capsule endoscopy but the lesion was obscured by blood), portal hypertension (three patients with previously undiagnosed cirrhosis, including one with esophageal varices, one with gastric varices, and one with portal hypertensive gastropathy, two of whom had "possible" findings of gastric erosions and small bowel angioectasia and the third had no findings), and an enhancing mass and layering of blood in the terminal ileum, later documented to be metastatic melanoma (one patient with no findings on capsule endoscopy). All lesions were seen in both the arterial and enteric phases. In the case of the jejunal angioectasias, one lesion appeared to expand on the 70-s delayed enteric phase, suggesting active bleeding.

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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

Figure 3. Terminal ileum ulcer on computed tomography enterography (CTE). Dual-phase CTE shows hyperenhancement of a soft tissue lesion in the terminal ileum (arrow) in a patient presenting with intermittent melena and no findings on capsule endoscopy. This lesion was found to be a terminal ileum ulcer on repeat colonoscopy with ileal intubation to 10 cm; symptoms resolved after endoscopic treatment.

Figure 4. Jejunal angioectasias on computed tomography enterography (CTE). Dual-phase CTE showing hyperenhancing lesions (arrows) in the mucosa of the jejunum, suggesting angioectasias. The diagnostic evaluation in patients with a positive CTE examination is summarized in Table 1. Of note, in three of the seven patients with diagnostic (true positive) CTE (ileal ulcer, ileal mass, gastric varices), the capsule endoscopy yielded no findings. In two of these patients, the CTE identified the underlying bleeding lesion where the capsule endoscopy visualized only blood (Meckel's, small bowel angioectasias [AVM]). In a third patient, the CTE confirmed the source suggested by capsule endoscopy (portal hypertensive gastropathy). In another patient, the CTE showed cirrhosis and esophageal varices in a patient in whom the presumed source of bleeding based on capsule endoscopy was jejunal AVM. In this case, the final diagnosis was that of the CTE (varices). In one additional patient, the CTE showed diffuse, left-sided colonic enhancement, more pronounced during the enteric phase. Repeat colonoscopy with biopsy was negative, and therefore this result was felt to be a false positive CTE.
Table 1. Diagnostic evaluation of patients with positive CTE examinations
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CT Enterography in Patients With Obscure GI Bleeding (printer-friendly)

Type of bleeding Occult

Capsule result Negative

CTE result Colonic enhancement Cirrhosis Bleeding AVM duodenal bulb Bleeding ileal mucosa Meckel's

Follow-up testing Repeat CLS normal Repeat EGD Varix Upper DBE AVM treated CLS-Ileal Ulcer treated None

Final diagnosis Unknown Varices treated

CTE findings Symptoms on interpretation follow up False positive True positive Persistent Resolved Persistent anemia Resolved Resolved Persistent anemia Resolution of bleeding; hospice Persistent anemia

Overt Jejunal AVM intermittent (possible source) Overt Jejunal blood intermittent (probable source) Overt Negative intermittent Overt acute Overt acute Overt acute Overt acute Jejunal blood (probable source)

Small True positive bowel AVM Ileal Ulcer treated Meckel's resected True positive True positive

Portal HTN gastropathy (possible Cirrhosis source) Negative

Enteroscopy portal HTN Portal HTN True positive gastropathy gastropathy Metastatic cancer Ulcer, varices

Bleeding mass None terminal ileum Gastric varices Repeat EGD, capsule varices, duodenal ulcer

True positive

Negative

True positive

AVM, small bowel angioectasias; CLS, colonoscopy; CTE, computed tomography enterography; EGD, upper endoscopy; DBE, double balloon enteroscopy; HTN, hypertensive.

The diagnostic evaluation in patients with a non-diagnostic CTE examination is summarized in Table 2. Of the 17 negative examinations (Table 2), three had spontaneous resolution of symptoms on follow up. The clinician following the patients determined that most likely these results represent true negative CTE, where no bleeding lesions were present at the time of the examination. The remaining 14 patients had false negative examinations. In five patients, the final diagnosis recorded by the physician after follow-up testing was the result of prior capsule endoscopy which was initially read as a possible source. These included a jejunal AVM, a gastric ulcer, two ileal AVM, and enteritis. In the remaining nine patients, both the capsule endoscopy and CTE yielded no findings suggestive of a bleeding source. In five of these patients no source was ever found, though symptoms persisted or chronic iron replacement was required to treat recurrent anemia. In the other four patients, follow-up testing yielded final diagnoses of AVM (n = 2), celiac disease (n = 1), and Meckel's diverticulum (n = 1).
Table 2. Diagnostic evaluation of patients with negative CT enterography examinations

Type of bleeding Occult Occult Overt intermittent Occult Occult

Capsule result AVM (possible source) Negative Gastric erosion (possible source)

CTE result Negative

Follow-up testing DBE showed no AVM

CTE findings interpretation True negative True negative True negative False negative

Final diagnosis ? AVM, unknown Unknown Unknown AVM AVM

Symptoms on follow up Resolved Resolved Resolved Persistent Chronic iron therapy

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Negative None Negative None

Jejunal AVM (possible Negative None source) Negative Negative

Repeat EGD: AVM, False negative gastric

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Occult Occult Occult Occult Occult Occult Overt intermittent Overt intermittent Overt intermittent Overt intermittent Overt intermittent Overt acute

Gastric ulcer (possible Negative None source) Ileal AVM (possible source) Negative Negative Negative Negative Negative Negative Ileal AVM (possible source) Negative Focal enteritis (probable source) Jejunal blood (probable source) Negative None Negative None Negative None Negative None Negative None Negative CLS, RBC scan: colonic AVM

False negative False negative False negative False negative False negative False negative False negative False negative False negative False negative False negative False negative

Ulcer AVM

Persistent Chronic iron therapy

Celiac disease Resolved Unknown Unknown Unknown Colonic AVM treated Unknown AVM Unknown Radiation Enteritis Meckel's resected Persistent Chronic iron therapy Persistent Resolved Persistent Chronic iron therapy Persistent Persistent Resolved

Negative None Negative None Negative None Negative None Negative Meckel's scan: Meckel's

AVM, small bowel angioectasias; CLS, colonoscopy; EGD, upper endoscopy; DBE, double balloon enteroscopy; RBC, red blood cell.

Table 2. Diagnostic evaluation of patients with negative CT enterography examinations

Type of bleeding Occult Occult Overt intermittent Occult Occult Occult Occult Occult Occult

Capsule result AVM (possible source) Negative Gastric erosion (possible source)

CTE result Negative

Follow-up testing DBE showed no AVM

CTE findings interpretation True negative True negative True negative False negative

Final diagnosis ? AVM, unknown Unknown Unknown AVM AVM Ulcer AVM

Symptoms on follow up Resolved Resolved Resolved Persistent Chronic iron therapy Persistent Chronic iron therapy

Negative None Negative None

Jejunal AVM (possible Negative None source) Negative Negative

Repeat EGD: AVM, False negative gastric False negative False negative False negative False negative

Gastric ulcer (possible Negative None source) Ileal AVM (possible source) Negative Negative Negative None Negative None Negative None

Celiac disease Resolved Unknown Persistent

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Occult Occult Overt intermittent Overt intermittent Overt intermittent Overt intermittent Overt intermittent Overt acute

Negative Negative Negative Negative Ileal AVM (possible source) Negative Focal enteritis (probable source) Jejunal blood (probable source)

Negative None Negative None Negative CLS, RBC scan: colonic AVM

False negative False negative False negative False negative False negative False negative False negative False negative

Unknown Unknown Colonic AVM treated Unknown AVM Unknown Radiation Enteritis Meckel's resected

Chronic iron therapy Persistent Resolved Persistent Chronic iron therapy Persistent Persistent Resolved

Negative None Negative None Negative None Negative None Negative Meckel's scan: Meckel's

AVM, small bowel angioectasias; CLS, colonoscopy; EGD, upper endoscopy; DBE, double balloon enteroscopy; RBC, red blood cell.

Of the seven diagnostic CT enterographies, three showed findings related to portal hypertension and the patients were treated with beta blockers; in one, anemia resolved completely. The remaining four patients proceeded to therapeutic procedures based upon the CTE results. The patient with a Meckel's diverticulum underwent surgery with cessation of bleeding. The patient with a terminal ileum ulcer underwent colonoscopy with successful endoscopic control of bleeding and no persistent symptoms. The patient with a mass bleeding into the terminal ileum underwent selective right colic artery embolization with control of bleeding. This patient was discharged to hospice so persistence of anemia could not be evaluated. The final patient with jejunal angioectasias underwent double balloon enteroscopy; however, overt bleeding had resolved prior to this procedure and the jejunal lesions were not visualized during the examination (though smaller AVM of upper small bowel were treated); anemia persisted in this patient. Incidental findings on CTE that required follow-up testing were found in 5/25 patients (20%) who underwent CTE. The findings included an adrenal mass requiring follow-up CT, an ovarian cyst requiring follow-up ultrasound, fatty liver requiring liver blood tests and clinical follow up, enlarged lymph nodes requiring follow-up CT, and bony sclerosis requiring follow-up bone scan. The results of the subsequent testing were all either normal or benign. Discussion Capsule endoscopy is a good initial test to evaluate patients with obscure gastrointestinal bleeding. In our study, the diagnostic yield of capsule endoscopy for all types of bleeding was 48%, within the range (4080%) that has been reported in prior studies.[21] Our study also confirms that evaluation of the small bowel in patients who are not both iron deficient and hemepositive may have limited utility.[2224] We did not find CTE to be useful in the evaluation of patients with occult-obscure GI bleeding. However, our study suggests that CTE may have an important role in the evaluation of patients with overt-obscure GI bleeding. There is no consensus on a course of action when capsule endoscopy results are non-diagnostic or difficult to interpret. There has been a role suggested for repeat upper and lower endoscopy, repeat capsule endoscopy, and deep enteroscopy. In our study, nearly 20% of the patients had obscure GI bleeding attributed to lesions that were within reach of a standard upper endoscope or colonoscope; a phenomenon that has been reported in other studies of obscure GI bleeding.[22] An underlying diagnosis of cirrhosis and portal hypertension accounted for 12% of bleeding. This finding suggests that repeat upper endoscopy should be considered as part of the evaluation for patients with possible chronic liver disease and obscure GI bleeding. A role for repeat capsule endoscopy has also been suggested, with recent studies showing diagnostic yield of 2075%,
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depending on the reason for the repeat exam.[25,26] In addition, endoscopic techniques of visualizing the deep small bowel have improved over recent years; most notably, double-balloon enteroscopy allows the potential for endoscopic visualization of the entire small bowel. The diagnostic yield of double-balloon enteroscopy is comparable to that of wireless capsule endoscopy, and in some studies exceeds the sensitivity of wireless capsule endoscopy.[19,2736] Double-balloon enteroscopy is an invasive modality, however, often requiring general anesthesia for several hours, and equipment and expertise that is not widely available. In our study, double-balloon enteroscopy was typically used only after capsule endoscopy was performed, and most frequently employed with the goal of confirming and treating a source of GI bleeding diagnosed on capsule endoscopy. Similar to other studies,[29] enteroscopy (both push and double balloon) could not always be used to identify the lesions seen on capsule endoscopy, and was therapeutic in only a few cases in our study. We suspect other technologies used for deep enteroscopy, such as spiral and single-balloon, might have had similar results. Furthermore, as in other studies,[37] many patients continue to bleed even after therapeutic interventions. CTE detected seven lesions not found using other modalities. The patients diagnosed with cirrhosis and portal hypertension could have been effectively evaluated using routine abdominal CT or ultrasound. In the remaining four patients, however, we believe that the visualized lesions would not have been identified without the small bowel distension and high-dose IV contrast used in this CTE technique. IV contrast materials display the enhancement of the lesions and are therefore the key feature of the technique. In the subset of patients with active overt bleeding, the diagnostic yield for dual-phase CTE was 80%. While prior studies using CT for the evaluation of obscure gastrointestinal bleeding demonstrated only limited utility of CT, those studies may have lower yield because they did not utilize large volumes of a neutral enteric contrast to distend and visualize the small bowel and were frequently only single-phase.[3844] In 2008, Huprich et al. described 22 patients with obscure GI bleeding who were examined with CTE using a triple-phase acquisition technique, rather than a dual-phase protocol.[45] The bleeding was overt in nine and occult in 13. Overall, the diagnostic yield in overt bleeding was 6/9 (67%), and in occult bleeding it was 2/13 (15%), again demonstrating a higher diagnostic yield of CTE in patients with overt compared with occult bleeding. A subsequent study using triphasic CTE also, like this study, showed poor detection of mucosal lesions, such as ulcers and AVM.[46] Lee et al. also used a triphasic technique and reported an overall diagnostic yield of 24.6%, with higher yield in large-volume bleeding, results that were very similar to our study.[47] We utilized a dual-phase rather than a triphasic technique that was used to reduce radiation exposure. The effective dose estimate for the CTE scans during this study was 10 mSv per phase resulting in a 20-mSv effective dose for a dual-phase examination. It is possible that the dual-phase technique did not detect lesions that a triphasic technique may have detected, especially the lesions seen only on a delayed phase. However, our results suggest that a dual-phase approach is satisfactory and exposure to additional radiation for additional phases may not be necessary; however, determining this with certainty would require prospective trials with direct comparison of the dual-phase and triple-phase techniques. We did not find CTE to be useful in the evaluation of patients with occult-obscure GI bleeding. Capsule endoscopy appears to be a more sensitive test in such patients, in part due to its ability to detect flat mucosal lesions (particularly angioectasias), even when they are not actively bleeding. Furthermore Shin et al. reports that a negative CTE for obscure gastrointestinal bleeding does not confer protection against re-bleeding and these patients should continue to be evaluated and followed due to low sensitivity, particularly in the subset of patients with occult bleeding.[48] On the other hand, our study suggests that CTE may have an important role in the evaluation of overt-obscure GI bleeding. Although capsule endoscopy had a high diagnostic yield in patients with overt bleeding, in many of the studies, the underlying lesion was obscured by blood and more precise characterization was obtained by CTE. There are several limitations to our study. Although our diagnostic yield for CTE was similar to other studies evaluating bleeding,[47,48] in our study very few patients were under the age of 40 years, likely leading to the underrepresentation of small bowel tumors, the most likely cause of obscure gastrointestinal bleeding in younger patients.[49] A higher prevalence of small bowel tumors might have increased the overall yield of CTE as demonstrated in other studies.[50,51] Additionally, renal insufficiency prevented the use of CTE in many patients. It should be noted, however, that renal insufficiency is common in this population, as it is associated with anemia, iron deficiency, and small bowel angioectasias. Therefore, our study did reflect potential "real-world" limitations of this diagnostic modality in this population. Another limitation is that the CTE images were reviewed by a single expert radiologist, which may limit the study's generalizability. Similar to other reports, we used as a reference or gold standard results of tests (surgery or endoscopy) and clinical follow up. However, a limitation is that pathologic confirmation was available in only a few cases. Therefore, even though up to 15 months of clinical follow up was available, capsule endoscopy and CTE could not be compared with a true gold standard. Because a true gold standard is lacking, in some cases it is not possible to be sure that all of the bleeding sources identified were actually responsible for the patients'
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bleeding. This can be a particular problem with capsule endoscopy where mucosal lesions in the bowel are often multiple and may or may not contribute to bleeding. As in other studies of obscure GI bleeding, many patients remained symptomatic without a diagnosis, despite extensive testing. Our results suggest a complimentary role for dual-phase CTE and capsule endoscopy in the evaluation of patients with obscure GI bleeding. We advocate further study of dual-phase CTE in patients with overt-obscure gastrointestinal bleeding, with direct comparisons with capsule endoscopy, angiography, scintigraphy, and newer enteroscopy techniques, such as double-balloon, single-balloon, and spiral enteroscopy. If the value of CTE in patients with overt-obscure GI bleeding is confirmed in future studies, the current diagnostic algorithm should be revised to include cross-sectional imaging in the evaluation of patients with overt-obscure GI bleeding.
References

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Acknowledgments There are no acknowledgments or potential conflicts of interests. Participation All authors participated in study design, data acquisition, analysis, interpretation, manuscript drafting and revision. J Gastroenterol Hepatol. 2012;27(4):751-759. 2012 Blackwell Publishing

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