A lower gastrointestinal (GI) bleed (LGIB) is defined as acute or chronic bleeding from the colon or anorectum (distal portion of digestive tract including the anal canal and distal few centimetres of the rectum.1 LGIB accounts for 20% to 25% of all cases of GI bleeding.1,2 Causes for LGIB are numerous and can be anatomic (e.g., diverticular disease, Meckel's diverticulum), vascular (e.g., ischemia), traumatic, inflammatory (e.g., colitis, Crohn's disease), or neoplastic (e.g., small-bowel tumours).1 Factors contributing to development of LGIB include advanced age and use of non-steroidal anti-inflammatory agents.3 Acute bleeding stops spontaneously in 85% of patients with LGIB.1,3
Colonoscopy is the diagnostic procedure of choice for acute and chronic bleeding; angiography is used if colonoscopy fails or cannot be performed.1,4 Nuclear imaging is used for cases of unexplained intermittent (i.e., slow) bleeding, when colonoscopy or angiography fail to detect the source of bleeding.1 Technetium-99m(99mTc)–labelled erythrocytes can detect bleeding at a rate of 0.1 to 5 mL/minute, thus showing blood flow and localizing the area of the bleeding.4 The detection of bleeding sites might be difficult due to the intermittent nature of bleeding.5,6 This may lead to a delay in treatment and result in morbidity and mortality.2
Population: Patients with suspected lower gastrointestinal bleeding.
Intervention: 99mTc active bleeding scintigraphy (scan).
Radionuclide scans have been used for localization of LGIB since the 1970s.7 This test uses serial images following an intravenous bolus injection of radiopharmaceuticals.8 Two radiopharmaceuticals are used for this purpose: 99mTc-sulfur colloid (SC) and 99mTc-labelled red blood cells (RBCs).7,9-11
In 99mTc-SC technique, the radiotracer is used in early phase vascular imaging. The theoretical consideration behind this technique is that 99mTc-SC is rapidly cleared from the circulation by the liver, spleen, and bone marrow (half-life 2.5 minutes to 3.5 minutes), whereas extravasated radio-labelled blood in the GI tract will not be cleared as rapidly and will stay in the GI tract. Therefore, a higher contrast can be seen between the location of extravasated blood and the diminishing background activity.9,10 The main limitation of this technique is that the radiopharmaceutical remains in circulation for 10 to 15 minutes only, so that detection of the bleeding site is not possible after this time period.9
99mTc-labelled RBCs remain in circulation for a longer period of time and are the most commonly used radiopharmaceutical for detection of GI bleeding.9-11 This technique allows for the detection and localization of intermittent bleeding.9 In addition, small amounts of bleeding can be detected by 99mTc-labelled RBCs, because this method is sensitive to low rates of bleeding (0.1 mL/minute to 0.5 mL/minute).12 Acquisition of single-photon emission computed tomography (SPECT) or hybrid SPECT/ computed tomography (CT) images with 99mTc-labelled RBC scan is shown to be helpful in the detection of bleeding sites.8,13
Other 99mTc-based radiopharmaceuticals such as 99mTc-labelled albumin and 99mTc–heat-damaged RBCs have also been studied for scintigraphic diagnosis of LGIB.14
Comparators: For this report, abdominal angiography is considered an alternative to 99mTc scintigraphy (scan).
Other new techniques, such as CT-angiography (helical CT after injection of a contrast agent) or magnetic resonance (MR) angiography (magnetic resonance imaging [MRI] with an intravascular contrast agent) have also been used for detecting LGIB.5,17
Outcomes: Eleven outcomes (referred to as criteria) are considered in this report:
Definitions of the criteria are in Appendix 1.
The literature search was performed by an information specialist using a peer-reviewed search strategy.
Published literature was identified by searching the following bibliographic databases: MEDLINE with In-Process records via Ovid; The Cochrane Library (2011, Issue 1) via Wiley; PubMed; and University of York Centre for Reviews and Dissemination (CRD) databases. The search strategy was comprised of both controlled vocabulary, such as the National Library of Medicine's MeSH (Medical Subject Headings), and keywords. The main search concepts were radionuclide imaging and gastrointestinal hemorrhage.
Methodological filters were applied to limit retrieval to health technology assessments, systematic reviews, meta-analyses (HTA/SR/MA), randomized controlled trials, and non-randomized studies, including diagnostic accuracy studies. No date or human limits were applied to the HTA/SR/MA search. For primary studies, the retrieval was limited to documents published between January 1, 1996 and March 1, 2011, and the human population. Both searches were also limited to English language documents. Regular alerts were established to update the search until October 2011. Detailed search strategies are located in Appendix 2.
Grey literature (literature that is not commercially published) was identified by searching relevant sections of the CADTH Grey Matters checklist. Google was used to search for additional web-based materials. The searches were supplemented by reviewing the bibliographies of key papers. See Appendix 2 for more information on the grey literature search strategy.
Targeted searches were done as required for the criteria, using the aforementioned databases and Internet search engines. When no literature was identified addressing specific criteria, experts were consulted.
There were eight potential clinical articles identified through the MA/SR/HTA filtered search and two were subjected to full-text review. Two hundred and thirty one potential primary studies were identified with the primary studies search. Additional studies were identified in searches for grey literature, targeted searches, and alerts.
No relevant systematic reviews and meta-analyses were included through this search. One systematic review, identified through the grey literature search, was included and used to abstract data on the diagnostic accuracy of 99mTc scintigraphy.18
No randomized controlled trials reporting on the accuracy of diagnostic tests of interest, patient outcomes, or quality of life were found. Nine observational studies reported on the diagnostic accuracy of the alternative tests of interest.15,19-26 Of these, two studies were excluded due to lack of comparison to a confirmatory or gold standard test,15,26 and the remaining seven studies were retained. Two of the included primary studies,24,25 along with two additional qualitative review articles found by the search,27,28 summarized the results of older observational studies on diagnostic accuracy of either 99mTc scintigraphy or abdominal angiography (Appendix 4).
The remaining articles from the database searches, along with other articles found through searching the grey literature, articles from the targeted searches, or articles from the reference lists of the identified potential articles, were used to abstract information regarding the rest of the criteria. When no literature was identified addressing specific criteria, experts were consulted.
|Domain 1: Criteria Related to the Underlying Health Condition|
|1||Size of the affected population||The annual incidence of hospitalization (considered an estimation of incidence) for LGIB has been estimated to be 20 to 30 per 100,000 persons in the US.1,7,8,12,13,29
Assuming the incidence rate in Canada is similar to that of the US, this corresponds to more than 1 in 10,000 (0.01%) and less than or equal to 1 in 1,000 (0.1%).
|Timeliness and urgency of test results in planning patient management||The timely detection and accurate localization of bleeding sites are essential for the guidance of treatment in high-risk patients.2,9,11,19
According to the Saskatchewan hospital guidelines, radionuclide scans for detection of acute GI bleeding should be performed within 24 hours of the request (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). Test results have a significant impact on the management of the condition or the effective use of heath care resources.
|3||Impact of not performing a diagnostic imaging test on mortality related to the underlying condition||Mortality is reported in 2% to 4% of patients with LGIB.1,3,13 Early diagnosis of patients with severe bleeding, and early therapeutic interventions, lead to lower mortality rates.13
Diagnostic imaging results can have minimal impact on mortality.
|4||Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition||No studies investigating the impact of scintigraphy or angiography on health outcomes or quality of life in patients with LGIB were identified, although between 5% and 50% of patients with persistent LGIB require surgical interventions.7 Failure to diagnose and treat chronic LGIB results in chronic anemia, which does affect quality of life and also can cause anxiety (MIIMAC expert opinion).
Diagnostic imaging results can have moderate impact on morbidity or quality of life.
|Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses|
|5||Relative impact on health disparities||To be scored locally.
|6||Relative acceptability of the test to patients||GI Scintigraphy: Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent.
Abdominal angiography: Patients undergoing X-ray angiography may have concerns over radiation exposure and injection of contrast material.
99mTc-GI scintigraphy is significantly more acceptable to patients than abdominal angiography.
|7||Relative diagnostic accuracy of the test||
No studies comparing the diagnostic accuracy of scintigraphy to CT-angiography or MR-angiography were identified. The included systematic review reported a pooled sensitivity rate of 62% for scintigraphy.18
There was a noticeable heterogeneity between the seven included primary studies,19-25 regarding patient population, scintigraphy techniques, and reference standard. No studies comparing the diagnostic accuracy of scintigraphy to CT-angiography or MR-angiography were identified.
NA = not available; Obs = observational studies; SR = systematic review; 99mTc = technetium-99m.
Nuclear medicine tests can be performed over a longer observation period, thus increasing the likelihood that bleeding will be present at the time of testing (MIIMAC expert opinion).
Overall, the diagnostic accuracy of 99mTc-based scintigraphy is significantly better than abdominal angiography.
|8||Relative risks associated with the test||
99mTc-scintigraphy for GI bleeding: 99mTc-scintigraphy is non-invasive and associated with no morbidities or mortalities.2,22 On rare occasions, allergic reactions to radiopharmaceuticals used for scintigraphy may occur.12,32
Abdominal Angiography: This is an invasive procedure, with a potential for major complications, particularly in the elderly and in patients with comorbid illness.12,28 AEs are reported in 0% to 26% of patients undergoing angiography.2,7,28 The most common complication is hematoma or bleeding at the catheter site.7 Other potential AEs include arterial dissection, catheter site infection, loss of pulses in the lower extremity, and allergic reactions to the contrast agent.2,7,12,28 More contrast is needed for the imaging of LGIB than for many other tests (MIIMAC expert opinion).
Both abdominal scintigraphy and angiography expose the patient to ionizing radiation. The average radiation exposure is higher for angiography than for GI bleeding scintigraphy.33
GI = gastrointestinal; mSv = millisievert.
|9||Relative availability of personnel with expertise and experience required for the test||
As of 2006 in Canada, there were 2,034 diagnostic radiologists, 221 nuclear medicine physicians, 12,255 radiological technologists, and 1,781 nuclear medicine technologists. Yukon, Northwest Territories, and Nunavut did not have the available personnel to perform and interpret tests to image lower GI bleeding. Other jurisdictions (e.g., Prince Edward Island) may offer limited nuclear medicine services.
Overall, the availability of health professionals to evaluate LGIB is good; however, a specialized centre to perform abdominal angiography may be required.
Assuming the equipment is available, if GI scintigraphy using 99mTc-radiolabelled isotopes is not available, it is estimated that 25% to 74% of the procedures can be performed in a timely manner using abdominal angiography.
|10||Accessibility of alternative tests (equipment and wait times)||
Equipment: As of January 1, 2007, there was an average of 18.4 nuclear medicine cameras per million people, with none available in the Yukon, Northwest Territories, or Nunavut.32 There were 179 angiography suites for an average of 5.5 suites per million people.37
Wait times: In 2007, the latest year for which data are available, the average time for nuclear medicine examinations at MUHC hospitals was five days. However, the wait times were reported to be less than one day for emergency cases.38 In the same year, wait times of angiography procedures at MUHC hospitals were 21 days in general, and less than 12 hours for emergency and urgent cases.38
A specialized centre may be required to perform abdominal angiography.
Assuming the necessary expertise is available, it is estimated that between 25% to 74% of procedures can be performed in a timely manner using abdominal angiography.
|11||Relative cost of the test||
According to our estimates, the cost of 99mTc-labelled RBC scintigraphy is $239.80. Abdominal angiography is a significantly more costly alternative.
AE = adverse event; CT = computed tomography; GI = gastrointestinal; LGIB = lower gastrointestinal bleed; MIIMAC = Medical Isotopes and Imaging Modalities Advisory Committee; MR = magnetic resonance; MUHC = McGill University Health Centre; RBC = red blood cells; 99mTc = technetium-99m; US = United States.
Criterion 1: Size of affected population (link to definition)
The reviewed literature consistently considered acute bleeding requiring hospitalization in the estimation of LGIB incidence.
The annual incidence of hospitalization for LGIB has been estimated to be 20 to 30 per 100,000 persons in the United States.1,7,8,12,13,29 The corresponding rate was not available for Canada.
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Criterion 2: Timeliness and urgency of test results in planning patient management (link to definition)
Although approximately 85% of LGIB cases are self-limited, improving without treatment, timely detection and accurate localization of bleeding sites to prevent the development of serious complications is essential for the treatment of the remaining 15% of patients.2,9 Additionally, localization of LGIB site can be helpful in the selection of the initial catheter placement at angiography and guidance of a surgical resection, if necessary.11,19 The time of diagnosis has been reported to be an important determinant of outcome in acute LGIB.2
Compared with angiography or colonoscopy, 99mTc-labelled RBC scans are easier to perform and need no patient preparation.5 The use of scintigraphy can minimize the potential delays in the diagnosis of LGIB.2 However, patients with massive LGIB usually undergo emergency angiography to localize and control the bleeding through appropriate therapeutic interventions during angiography.5
According to the Saskatchewan hospital guidelines, radionuclide scans for the detection of acute GI bleeding should be performed within the first 24 hours after the test is requested (Patrick Au, Acute and Emergency Services Branch, Saskatchewan Ministry of Health: unpublished data, 2011). No Canadian benchmarks were found for abdominal angiography wait times. Based on an American guideline, an urgent angiography should be performed within one hour of a positive scintigraphy, regardless of time of the day.39
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Criterion 3: Impact of not performing a diagnostic imaging test on mortality related to the underlying condition (link to definition)
Although acute LGIB stops without any intervention in 85% of patients, mortality is reported in 2% to 4% of patients.1,3,13 Higher mortality rates (greater than 5%) have been reported in studies published in the 1980s.7 Early diagnosis of patients with severe bleeding, and early therapeutic interventions, may lead to lower mortality rates.13
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Criterion 4 Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition (link to definition)
Recurrence can be problematic for patients with LGIB, particularly for ones with chronic GI bleeding, e.g. from diverticulosis or angiodysplasia.40 Between 5% and 50% of patients with persistent bleeding require surgical interventions.7 However, advances in diagnostic imaging techniques including nuclear scanning and angiography have changed the management of GI bleeding and resulted in declining rates of recurrence and surgery.7,40 Our search found no studies investigating the impact of scintigraphic evaluations or visceral angiography on health outcomes or quality of life in patients with LGIB. Chronic LGIB, however, is a significant problem, and failure to diagnose and treat it results in chronic anemia, which does affect quality of life and also can cause anxiety (Medical Isotopes and Imaging Modalities Advisory Committee [MIIMAC] expert opinion). Two studies were identified by the targeted search that evaluated health-related outcomes following push enteroscopy (endoscopic evaluation of small intestine) in patients with GI bleeding.41,42 Although push enteroscopy was not a comparator of interest in this review, these two studies were included for review, as it was deemed that push enteroscopy in detection of GI bleeding and guidance of treatment may be similar to that of other modern imaging modalities, including scintigraphy and angiography.
In the study by Vakil et al.,41 29 patients with unexplained GI bleeding underwent push enteroscopy. The total number of patients requiring blood transfusion declined significantly in the year following enteroscopy due to appropriate therapeutic interventions, compared with one year preceding the procedure (P = 0.03). Furthermore, in patients who underwent therapeutic interventions at the time of enteroscopy, functional status improved from a Karnofsky performance score of 60 to 90 (P = 0.005).
Hayat et al.42 studied 21 patients with suspected small intestinal bleeding in the United Kingdom (age range 25 to 87 years) who underwent push enteroscopy to determine the impact of the procedure on the management of GI bleeding and prevention of unnecessary diagnostic testing. Following the test, the certainty of diagnosis increased in 35% of patients, and the mean value of certainty of diagnosis, as perceived by the requesting physicians, increased from 1.35 (prior to the test) to 2.40 (following test, P = 0.01). In 40% of patients, the management and treatment plans changed, based on the results of the test. In addition, the requesting physicians assigned a median "usefulness score" of 3 to the test (on a scale of 1 for "not helpful" to 5 for "very helpful").
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Criterion 5: Relative impact on health disparities (link to definition)
To be scored locally.
LGIB is more common in men than in women. Its incidence is also age-dependent, and the annual rate of hospitalization increases from 1 per 100,000 patients in the third decade of life to over 200 per 100,000 patients in the ninth decade. Non-steroidal anti-inflammatory drugs and aspirin are shown to increase the risk of LGIB.
Health disparity might be present if disadvantaged social groups systematically experience poorer health or more health risks than do more advantaged social groups.43 Disadvantaged groups can be defined based on gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs. Our targeted search found disparity concerns in the following disadvantage groups:
Ethnic and racial groups
GI infections with the bacterium Helicobacter pylori are described in Inuit and Alaskan natives; these infections can result in higher rates of iron deficiency anemia due to gastritis or GI bleeding in the Arctic population.
In its 2010 report on health care disparities, the Agency for Healthcare Research and Quality reported the death rates from complications of care, such as sepsis, renal failure, GI bleeding, cardiac arrest and shock, in adult patients admitted to community hospitals in the United States. The indicator is called "failure to rescue." Based on this report, in 2007, the death rates following complications of care — including GI bleeding — were significantly higher in Asians than Whites (130.2 per 1000 compared with 111.3 per 1000).30 According to the 2009 version of the same report, Hispanics had a higher rate of death due to in-hospital GI bleeding and other complications of care (listed previously) compared to non-Hispanic whites (122.1 per 1,000 compared with 117.1 per 1000).31
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Criterion 6: Relative acceptability of the test to patients (link to definition)
Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent.
Angiography uses one of three imaging technologies: X-ray, CT, MRI and contrast material to image blood vessels. Patients may have concerns about the injection of contrast media.
Other new techniques, such as CT-angiography (helical CT following injection of a contrast agent) or MR-angiography (MR imaging with an intravascular contrast agent) have also been used to for detection of LGIB.5,17
Angiography using CT
Patients undergoing CT scan may have concerns about radiation exposure and may also feel claustrophobic while in the scanner. This is less of a problem with new CT scanners (MIIMAC expert opinion). Patients may be required to hold their breaths for a substantial period of time, which is seen as "uncomfortable" and "difficult," particularly for patients with severe abdominal pain.44
Angiography using MRI
Because of the closed space of an MRI, patients may experience feelings of claustrophobia, as well as being bothered by the noise; however, this may be less of a problem with new MRI machines, if available (MIIMAC expert opinion). It has been reported that up to 30% of patients experience apprehension, and 5% to 10% endure some severe psychological distress, panic, or claustrophobia.45,46 Some patients may have difficulty remaining still during the scan. Patients are not exposed to radiation during an MRI scan, which may be more acceptable to some.
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Criterion 7: Relative diagnostic accuracy of the test (link to definition)
Overall, one systematic review18 and seven observational studies,19-25 reported on the diagnostic accuracy of 99mTc-scintigraphy and angiography. Two qualitative reviews27,28 were also considered for this review (Appendix 4).
Because our search strategy was designed to identify only studies comparing 99mTc-scintigraphy to other potential alternatives, the identified studies were mainly focused on the diagnostic accuracy of 99mTc-scintigraphy (Appendix 4). Angiography was used as the reference of standard in two of the studies.22,23 The remaining studies used surgical results or a combination of diagnostic procedures (including angiography) and clinical findings as the gold standard. Our search did not capture studies evaluating the diagnostic accuracy of angiography compared to surgery or other references of standards that were used by 99mTc-scintigraphy studies. Therefore, indirect comparison of 99mTc-scintigraphy to angiography was not possible. One of the included qualitative reviews summarized the diagnostic accuracy of angiography from nine studies published between 1974 and 1997.27No studies comparing the diagnostic accuracy of scintigraphy to CT-angiography or MR-angiography were identified.
A systematic review was undertaken by the Center for Evidence-based Practice of the University of Pennsylvania Health System to inform development of a practice guideline on the management of acute LGIB.18 This review, published in 2009, included 13 studies measuring the ability of 99mTc-labelled RBC scintigraphy to localize LGIB compared with other imaging techniques. No details were provided about the methodological quality of the included studies. Reported pooled sensitivity rate was 62% for scintigraphy. The overall percentage of positive test results ranged across the studies from 28% to 65% (pooled rate = 49%). However, according to the authors, the assessment of the diagnostic accuracy of 99mTc scintigraphy was difficult due to lack of a definitive gold standard in most of the included studies, especially for the patients who had a negative test result. The percentage of the positive scintigraphy results that were confirmed by further diagnostic procedures (e.g., angiography or colonoscopy) or by surgery was reported to range between 41% and 82% (pooled rate = 62%).
No randomized controlled trials evaluating the diagnostic accuracy of the alternative tests of interest were found by the literature search. Seven observational studies,19-25 including two head-to-head studies of 99mTc-scintigraphy versus angiography,22,23 were identified. Six of the eight studies of the included studies compared the accuracy of 99mTc-scintigraphy with surgery19,20,24 or a combination of other diagnostic tests (including angiography) and clinical findings20,21,25 (Appendix 4). The scintigraphic techniques varied across the included studies.
Peynircioglu et al.23 retrospectively studied 45 patients with massive GI bleeding (requiring more than four units of blood in 24 hours and systolic blood pressure less than 90 mmHg) who were referred to receive transcatheter mesenteric angiography. All of the patients had previous endoscopy, scintigraphy, or CT angiography (CTA). Sensitivity and specificity of scintigraphy was calculated for the patients who underwent scintigraphy prior to angiography (18 patients with LGIB and four patients with lower and upper GI bleeding). The results are shown in Appendix 4. In this study, the diagnostic accuracy of endoscopy and CTA was also compared with angiography. Based on their study findings, the authors concluded that scintigraphy should be performed to detect LGIB prior to angiography. They also stressed that CTA should be considered as an alternative to scintigraphy in emergency settings, due to its ability to provide broader insight into the underlying causes of LGIB.
Brunnler et al.22 retrospectively evaluated the results of scintigraphy in 92 patients with suspected obscure GI bleeding. However, the diagnostic accuracy of scintigraphy was reported based on the results of the test in 33 patients who underwent angiography, as well. Compared with angiography, as the gold standard, scintigraphy had an overall sensitivity of 79% and a specificity of 30% in the detection of LGIB. The safety outcomes were also recorded in this study. The authors concluded that scintigraphy studies were safe and superior to angiography. They concluded that scintigraphy could be a helpful procedure, particularly for older patients in whom invasive procedures are of concern.
Howarth et al.21 reported the diagnostic ability of scintigraphic studies in correct localization of obscure GI bleeding in a series of 137 hospitalized patients. All of the patients underwent 99mTc-labelled RBC scintigraphy. Some patients underwent additional diagnostic tests, such as colonoscopy or angiography. However, the final diagnoses were made using hospital discharge diagnosis or clinical confirmation of definite GI bleeding (e.g., rectal blood loss and/or hypovolemic shock). In this study, scintigraphy showed a sensitivity of 87% in the detection of active bleeding and 54% in the localization of GI bleeding. The results of the study also showed that the diagnostic ability of 99mTc-labelled RBC scintigraphy in localizing active bleeding is significantly lower in the small intestine than in the colon. The authors concluded that, in most cases, detection and localization of GI bleeding may require more than one diagnostic test, and that the diagnostic accuracy of endoscopic and angiographic investigations are lower than scintigraphy in cases of intermittent GI bleeding.
Wu et al.20 evaluated the clinical value of two 99mTc-labelled scintigraphy techniques in 90 patients referred with clinical evidence of GI bleeding: conventional non-subtraction scintigraphy (CNS), and sequential subtraction scintigraphy (SSS). All patients underwent 12 CNS imaging every five minutes, up to 60 minutes. Then, 11 SSS images were obtained with "t+5" minutes subtracted from each other (using a computer), up to 60 minutes. Delayed images were obtained until 24 hours if the early images were non-diagnostic. The results of each scintigraphy technique were compared to the final diagnoses made by endoscopy, angiography, surgery, and clinical findings. The sensitivity of scintigraphic images taken at 30 minutes was 56.4% and 87% for CNS and SSS, respectively. Images taken at 60 minutes yielded a sensitivity of 85.4 % and 91.9% for CNS and SSS, respectively. In 62 patients who underwent surgical operation, the sensitivity of scintigraphic techniques in localization of the bleeding site was also compared to the surgical findings (92.8% and 73.8% for CNS and SSS, respectively) (Appendix 4). The authors concluded that SSS can be considered as a suitable technique in pediatrics, the elderly, and critically ill patients due to its higher sensitivity and shorter examination time.
O'Neill et al.24 performed a retrospective chart review of a series or 26 patients with upper and lower GI bleeding who underwent cinematic 99mTc-labelled RBC scintigraphy. Twenty-five of 26 patients also underwent surgical operation, and the results of surgery were considered as the gold standard. The site of bleeding was correctly localized by scintigraphy in 88% of patients. Eleven patients (42%) also underwent angiography, in which four examinations were documented as negative. Three of four patients with negative angiograms had a positive scintigraphy. However, the final diagnoses of these cases, made following surgery, were not mentioned in the article. The authors concluded that cinematic 99mTc-labelled RBC scintigraphy is a sensitive and non-invasive alternative to angiography in localizing the site of GI bleedings.
Emslie et al.25 reviewed the medical records of 80 patients who underwent 99mTc-labelled RBC scintigraphy for diagnosis of GI bleeding in a single centre. The results were compared with confirmatory studies, such as angiography, colonoscopy, surgery, or combinations of them. Overall, the results of scintigraphy were concordant with the final diagnosis in 60 of 75 patients (accuracy = 80%). Scintigraphy was reported to have a sensitivity of 88%. Based on their results, the authors recommended 99mTc-labelled RBC scintigraphy as a non-invasive, quick, and easily performed test that can be considered as an initial test for the diagnosis of GI bleeding.
Gutierrez et al.19 retrospectively studied the medical records of 105 patients who had a 99mTc-labelled RBC scintigraphy for the diagnosis of LGIB. Ninety per cent of the patients had additional diagnostic procedures. Twenty-five of 105 patients underwent surgical operations. Surgical evidence was used as the reference standard in this group to show that scintigraphy correctly identified the site of bleeding in 22 patients (accuracy = 88%). The authors concluded that 99mTc-labelled RBC scintigraphy should be used as the primary diagnostic test, early in the hospital course. They emphasized that scintigraphy can improve patient outcomes by guiding the surgeon in segmental resection of the affected site.
Qualitative literature reviews
Two of the primary studies24,25 provided a qualitative summary of the results of other observational studies on the accuracy of scintigraphy in the diagnosis of GI bleeding, as background information in their articles. Two additional qualitative reviews27,28 summarized the results of case-series and observational studies to demonstrate the ability of scintigraphy detection and localization of LGIB. One of these reviews27 also included the findings of nine studies evaluating the accuracy of abdominal angiography in the diagnosis of LGIB. The results are shown in Appendix 4.
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Criterion 8: Relative risks associated with the test (link to definition)
99mTc-scintigraphy for GI bleeding
99mTc-scintigraphy is non-invasive and associated with no morbidities2 or mortalities.22 On rare occasions, allergic reactions to radiopharmaceuticals used for scintigraphy may occur.12,32
Angiography is an invasive procedure with a potential for major complications, particularly in the elderly and in patients with comorbid illness.12,28 Adverse events (AEs) are reported in 0% to 26% of patients undergoing angiography.2,7,28 The most common complication is hematoma or bleeding at the catheter site.7 Other potential AEs include arterial dissection, catheter site infection, loss of pulses in lower extremity, and contrast reaction.2,7,12,28
Other new techniques, such as CT-angiography (helical CT following injection of contrast agent) or MR-angiography (MRI with an intravascular contrast agent), have also been used to detect LGIB.5,17
Angiography using CT
Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.47 In addition, patients may experience mild side effects from the contrast agent such as nausea, vomiting, or hives. A 2009 retrospective review of all intravascular doses of low-osmolar iodinated and gadolinium (Gd) contrast materials administered at the Mayo Clinic between 2002 and 2006 (456,930 doses) found that 0.15% of patients given CT contrast material experienced side effects, most of which were mild. A serious side effect was experienced by 0.005% of patients.48 CT is contraindicated in patients with elevated heart rate, hypercalcemia, and impaired renal function. According to the American College of Radiology Manual on Contrast Media,49 the frequency of severe, life-threatening reactions with Gd are extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.49
Angiography using MRI
MRI is contraindicated in patients with metallic implants including pacemakers.50 MRI is often used in conjunction with the contrast agent Gd. Some patients may experience an allergic reaction to the contrast agent (if required), which may worsen with repeated exposure.47 Side effects of Gd include headaches, nausea, and metallic taste. Gd is contraindicated in patients with renal failure or end-stage renal disease, as they are at risk of nephrogenic systemic fibrosis. According to the American College of Radiology Manual on Contrast Media,49 the frequency of severe, life-threatening reactions with Gd are extremely rare (0.001% to 0.01%). Moderate reactions resembling an allergic response (i.e., rash, hives, urticaria) are also very unusual and range in frequency from 0.004% to 0.7%.49
Among the modalities to diagnose lower gastrointestinal bleeding, both GI bleeding scintigraphy and angiography expose the patient to ionizing radiation. The average effective dose of radiation delivered can be found in Table 2. As the table shows, abdominal angiography delivers larger doses of radiation than GI scintigraphy. A precise comparison of radiation doses used by the two diagnostic tests is difficult because a part of radiation exposure from angiography is related to the therapeutic component of this procedure.2
|Procedure||Average Effective Dose (mSv)|
|Average background dose of radiation per year||1 to 3.034-36|
GI = gastrointestinal; mSv = millisevert.
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Criterion 9: Relative availability of personnel with expertise and experience required for the test (link to definition)
The personnel required for the performance of the imaging tests to diagnose lower GI bleeding are presented by imaging modality. A summary of the availability of personnel required for the conduct of methods to diagnose lower GI bleeding, by GI scintigraphy or any of the alternative imaging modalities, is provided in Tables 3 and 4.
In Canada, physicians involved in the performance, supervision, and interpretation of GI scintigraphy should be nuclear medicine physicians or diagnostic radiologists with training and expertise in nuclear imaging.51 Physicians should have a Fellowship of Certification in Nuclear Medicine or Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Nuclear medicine technologists are required to conduct GI scintigraphy. Technologists must be certified by the Canadian Association of Medical Radiation Technologists (CAMRT) or an equivalent licensing body.
To perform abdominal angiography, diagnostic radiologists should be qualified in vascular/interventional radiology32 and must have a Fellowship or Certification in Diagnostic Radiology with the Royal College of Physicians and Surgeons of Canada and/or the Collège des médecins du Québec. Foreign-trained radiologists are also qualified if they are certified by a recognized certifying body and hold a valid provincial licence.51
|Professional||Total Number of Professionals in Canada||Provinces and Territories with no professionals available|
|Diagnostic radiology physicians||2,034||YT, NT, NU|
|Nuclear medicine physicians||221||PEI, YT, NT, NU|
|Medical physicists||322||PEI, YT, NT, NU|
|Radiological technologists||12,255||Available in all jurisdictions|
|Nuclear medicine technologists||1,781||1 technologist for all territories|
NA = not available; NT = Northwest Territories; NU = Nunavut; PEI = Prince Edward Island; YT = Yukon.
|Jurisdiction||Diagnostic Radiology Physicians||Nuclear Medicine Physicians||Medical Radiation Technologists||Nuclear Medicine Technologists||Sonographers||Medical Physicists|
AB = Alberta; BC = British Columbia; MB = Manitoba; ON = Ontario; NB = New Brunswick; NL = Newfoundland and Labrador; NR = not reported by jusrisdiction; NS = Nova Scotia; NT= Northwest Territories; NU = Nunavut; PEI= Prince Edward Island; QC = Quebec; YT = Yukon.
* This represents a total for all of the jurisdictions.
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Criterion 10: Accessibility of alternative tests (equipment and wait times) (link to definition)
There are notable variations in the availability of medical imaging technologies across Canada. Table 5 provides an overview of the availability of equipment required to diagnose lower GI bleeding.
|Nuclear Medicine Cameras||Angiography Suites||SPECT/CT Scanners|
|Number of devices||60332||17932||9654|
|Average number of hours of operation per week (2006–2007)32||39||40||n/a|
|Provinces and territories with no devices available||YT, NT, NU||YT, NT, NU||PEI, YT, NT, NU|
CAR = Canadian Association of Radiologists; NT= Northwest Territories; NU = Nunavut; PEI= Prince Edward Island; SPECT/CT = single-photon emission computed tomography/computed tomography;YT = Yukon.
To perform GI scintigraphy, nuclear medicine facilities with gamma cameras are required. As of January 1, 2007, there was an average of 18.4 nuclear medicine cameras per million people, with none available in the Yukon, Northwest Territories, or Nunavut.3299mTc-labelled RBC scintigraphy is usually used for detection and localization of intermittent bleeding, in which episodes of bleeding may only occur for short periods of time. Thus, the likelihood of a positive diagnosis depends on repeated, and sometimes continuous, image acquisition. Therefore, limitations of equipment and imaging time may affect the sensitivity of this technique in the diagnosis of LGIB.9
In 2007, the latest year for which data are available, the average time for nuclear medicine examinations at McGill University Health Centre hospitals was five days. However, the wait times were reported to be less than one day for emergency cases.38 In the same year, wait times of angiography procedures at McGill University Health Centre hospitals were 21 days in general, and less than 12 hours for emergency and urgent cases.38
Abdominal angiography should be performed in an angiography suite equipped to a minimum of a high-resolution image intensifier, and television chain with standard angiographic filming capabilities and adequate angiographic supplies. Digital angiographic systems are also recommended. Appropriate emergency equipment and medications must be immediately available to treat AEs associated with administered medications. The equipment, medications, and other emergency support must also be appropriate for the range of ages and sizes in the patient population.37
Return to Summary Table.
Criterion 11: Relative cost of the test (link to definition)
Fee codes from the Ontario Schedule of Benefits were used to estimate the relative costs of 99mTc-labelled RBC scintigraphy and its alternatives. Technical fees are intended to cover costs incurred by the hospital (i.e., radiopharmaceutical costs, medical/surgical supplies, and non-physician salaries). Maintenance fees are not billed to OHIP — estimates here were provided by St. Michael's Hospital in Toronto. Certain procedures (i.e., PET scan, CT scan, MRI scan) are paid for, in part, out of the hospital's global budget; these estimates were provided by The Ottawa Hospital. It is understood that the relative costs of imaging will vary from one institution to the next.
According to our estimates (Table 6), the cost of 99mTc-labelled RBC scintigraphy is $239.80. Abdominal angiography is a significantly more costly alternative.
|Fee Code||Description||Tech. Fees ($)||Prof. Fees ($)||Total Costs ($)|
|99mTc-labelled RBC scintigraphy|
|J878||Abdominal scintigraphy — for gastrointestinal bleed-labelled RBCs||146.85||50.95||197.80|
|Maintenance fees — from global budget||42.00||42.00|
|Abdominal, thoracic, cervical, or cranial angiogram by catheterization using film changer, cine, or multiformat camera — non-selective||61.20||32.50||93.70|
|Abdominal, thoracic, cervical, or cranial angiogram by catheterization using film changer, cine, or multiformat camera — selective (per vessel, to a maximum of 4)||81.35 (×3) = 244.05||39.40 (×3) = 118.20||362.25|
|J021||Insertion of catheter (including cut-down, if necessary) and injection, if given||121.40 (Spec)
|J022 (×3)||Selective catheterization — add to catheter insertion fee (per vessel, to maximum of 4), each 60.15||60.15 (×3) = 180.45||180.45|
|Maintenance fees — from global budget||51.00||51.00|
Prof. = professional; RBC = red blood cells; 99mTc = technetium-99m; Tech. =technical.
Return to Summary Table.
|Domain 1: Criteria Related to the Underlying Health Condition|
|1. Size of the affected population||The estimated size of the patient population that is affected by the underlying health condition and which may potentially undergo the test. The ideal measure is point prevalence, or information on how rare or common the health condition is.|
|2. Timeliness and urgency of test results in planning patient management||The timeliness and urgency of obtaining the test results in terms of their impact on the management of the condition and the effective use of health care resources.|
|3. Impact of not performing a diagnostic imaging test on mortality related to the underlying condition||Impact of not performing the test, in whatever way, on the expected mortality of the underlying condition. Measures could include survival curves showing survival over time, and/or survival at specific time intervals with and without the test.|
|4. Impact of not performing a diagnostic imaging test on morbidity or quality of life related to the underlying condition||Impact of not performing the test, in whatever way, on the expected morbidity or on the quality of life reduction of the underlying condition. Measures of impact may include natural morbidity outcome measures such as events or disease severity, or might be expressed using generic or disease-specific quality of life rating scales with and without the test.|
|Domain 2: Criteria Comparing 99mTc with an Alternative, or Comparing between Clinical Uses|
|5. Relative impact on health disparities||Health disparities are defined as situations where there is a disproportionate burden (e.g., incidence, prevalence, morbidity, or mortality) amongst particular population groups (e.g., gender, age, ethnicity, geography, disability, sexual orientation, socioeconomic status, and special health care needs).
Impact on health disparities is assessed by estimating the proportion of current clients of the 99mTc-based test that are in population groups with disproportionate burdens.
(Explanatory note: The implication of this definition is that, everything else being the same, it is preferable to prioritize those clinical uses that have the greatest proportion of clients in groups with disproportionate burdens.)
|6. Relative acceptability of the test to patients||Acceptability of the 99mTc-based test from the patient's perspective compared with alternatives. Patient acceptability considerations include discomfort associated with the administration of the test, out-of-pocket expenses or travel costs, factors that may cause great inconvenience to patients, as well as other burdens. This criterion does not include risks of adverse events but is about everything related to the experience of undergoing the test.|
|7. Relative diagnostic accuracy of the test||Ability of the test to correctly diagnose the patients who have the condition (sensitivity) and patients who do not have the condition (specificity) compared with alternatives.|
|8. Relative risks associated with the test||Risks associated with the test (e.g., radiation exposure, side effects, adverse events) compared with alternatives. Risks could include immediate safety concerns from a specific test or long-term cumulative safety concerns from repeat testing or exposure.|
|9. Relative availability of personnel with expertise and experience required for the test||Availability of personnel with the appropriate expertise and experience required to proficiently conduct the test and/or interpret the test findings compared with alternatives.|
|10. Accessibility of alternatives (equipment and wait times)||Availability (supply) of equipment and wait times for alternative tests within the geographic area. Includes consideration of the capacity of the system to accommodate increased demand for the alternatives. Excludes any limitation on accessibility related to human resources considerations.|
|11. Relative cost of the test||Operating cost of test (e.g., consumables, heath care professional reimbursement) compared with alternatives.|
|Databases:||Ovid MEDLINE In-Process & Other Non-Indexed Citations and Ovid MEDLINE <1948 to March 1, 2011>|
|Date of Search:||March 2, 2011|
|Alerts:||Monthly search updates began March 1, 2011 and ran until October 2011.|
|Study Types:||Health technology assessments, systematic reviews, meta-analyses, randomized controlled trials, non-randomized studies, and diagnostic accuracy studies.|
No date limit for systematic reviews; publication years 1996 – March 2011 for primary studies
Human limit for primary studies
|/||At the end of a phrase, searches the phrase as a subject heading|
|MeSH||Medical subject heading|
|exp||Explode a subject heading|
|*||Before a word, indicates that the marked subject heading is a primary topic;
or, after a word, a truncation symbol (wildcard) to retrieve plurals or varying endings
|?||Truncation symbol for one or no characters only|
|ADJ||Requires words are adjacent to each other (in any order)|
|ADJ#||Adjacency within # number of words (in any order)|
|.hw||Heading word: usually includes subject headings and controlled vocabulary|
|.tw||Text word: searches title, abstract, captions, and full text|
|.mp||Keyword search: includes title, abstract, name of substance word, subject heading word and other text fields|
|.nm||Name of substance word: used to search portions of chemical names and includes words from the CAS Registry/EC Number/Name (RN) fields|
|.jw||Journal words: searches words from journal names|
|Ovid MEDLINE Strategy|
|Line #||Search Strategy|
|2||exp Technetium Compounds/|
|3||exp Organotechnetium Compounds/|
|6||(technetium* or TC-99* or TC99* or TC-99m* or TC99m* or 99mTC* or 99m-TC* or 99mtechnetium* or 99m-technetium* or TC-rhenium-sulfur aerosol or TCReS colloid).tw,nm.|
|7||Radionuclide Imaging/ or Perfusion Imaging/|
|8||Tomography, Emission-Computed, Single-Photon/|
|10||(((radionucl* or nuclear or radiotracer*) adj2 (imag* or scan* or test* or diagnos*)) or scintigraph* or scintigram* or scintiphotograph*).tw.|
|11||(single-photon adj2 emission*).tw.|
|12||(RBC adj5 (imaging or scan*)).tw.|
|13||(red adj2 cell* adj5 (imaging or scan*)).tw.|
|14||(sulfur colloid* adj5 (imaging or scan*)).tw.|
|17||((GI or gastric or gastrointestin* or gastro-intestin* or nonvariceal* or non-variceal*) adj5 (bleed* or blood or hemorrhage* or haemorrhage* or lesion or rebleed*)).tw.|
|18||(hematochezia* or LGIB).tw.|
|21||Meta-Analysis/ or Systematic Review/ or Meta-Analysis as Topic/ or exp Technology Assessment, Biomedical/|
|22||((systematic* adj3 (review* or overview*)) or (methodologic* adj3 (review* or overview*))).tw.|
|23||((quantitative adj3 (review* or overview* or synthes*)) or (research adj3 (integrati* or overview*))).tw.|
|24||((integrative adj3 (review* or overview*)) or (collaborative adj3 (review* or overview*)) or (pool* adj3 analy*)).tw.|
|25||(data synthes* or data extraction* or data abstraction*).tw.|
|26||(handsearch* or hand search*).tw.|
|27||(mantel haenszel or peto or der simonian or dersimonian or fixed effect* or latin square*).tw.|
|28||(met analy* or metanaly* or health technology assessment* or HTA or HTAs).tw.|
|29||(meta regression* or metaregression* or mega regression*).tw.|
|30||(meta-analy* or metaanaly* or systematic review* or biomedical technology assessment* or bio-medical technology assessment*).mp,hw.|
|31||(medline or Cochrane or pubmed or medlars).tw,hw.|
|32||(cochrane or health technology assessment or evidence report).jw.|
|34||exp "Sensitivity and Specificity"/|
|35||False Positive Reactions/|
|36||False Negative Reactions/|
|39||(predictive adj4 value*).tw.|
|49||(Validation Studies or Evaluation Studies).pt.|
|50||Randomized Controlled Trial.pt.|
|51||Controlled Clinical Trial.pt.|
|52||(Clinical Trial or Clinical Trial, Phase II or Clinical Trial, Phase III or Clinical Trial, Phase IV).pt.|
|54||(random* or sham or placebo*).ti.|
|55||((singl* or doubl*) adj (blind* or dumm* or mask*)).ti.|
|56||((tripl* or trebl*) adj (blind* or dumm* or mask*)).ti.|
|57||(control* adj3 (study or studies or trial*)).ti.|
|58||(non-random* or nonrandom* or quasi-random* or quasirandom*).ti.|
|59||(allocated adj "to").ti.|
|67||(observational adj3 (study or studies or design or analysis or analyses)).ti.|
|69||(prospective adj7 (study or studies or design or analysis or analyses or cohort)).ti.|
|70||((follow up or followup) adj7 (study or studies or design or analysis or analyses)).ti.|
|71||((longitudinal or longterm or (long adj term)) adj7 (study or studies or design or analysis or analyses or data or cohort)).ti.|
|72||(retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti.|
|73||((case adj control) or (case adj comparison) or (case adj controlled)).ti.|
|74||(case-referent adj3 (study or studies or design or analysis or analyses)).ti.|
|75||(population adj3 (study or studies or analysis or analyses)).ti.|
|76||(cross adj sectional adj7 (study or studies or design or research or analysis or analyses or survey or findings)).ti.|
|79||77 not 78|
|80||15 and 19 and 33|
|81||limit 80 to english language|
|82||15 and 19 and 79|
|83||limit 82 to (english language and humans and yr="1996 -Current")|
|PubMed||Same MeSH, keywords, limits, and study types used as per MEDLINE search, with appropriate syntax used.|
Issue 1, 2011
|Same MeSH, keywords, and date limits used as per MEDLINE search, excluding study types and Human restrictions. Syntax adjusted for Cochrane Library databases.|
|GREY LITERATURE SEARCHING|
|Dates for Search:||March 2011|
|Keywords:||Included terms for radionuclide imaging and gastrointestinal hemorrhage.|
The following sections of the CADTH grey literature checklist, "Grey matters: a practical tool for evidence-based medicine" were searched:
Angiodysplasia: A small vascular malformation of the intestine. It is a common cause of unexplained gastrointestinal bleeding and anemia.
Meckel's diverticulum: A Meckel's diverticulum is a pouch on the wall of the lower part of the intestine that is present at birth and may contain tissue that is identical to tissue of the stomach or pancreas.
Millisievert (mSv): The sievert, named after Rolf Sievert, a Swedish medical physicist, is a unit of dose equivalent. It shows the biological effects of radiation as opposed to the physical aspects, which are characterized by the absorbed dose (milligray). mSv is one-thousandth of sievert.
The Karnofsky Performance Status: An instrument that was originally designed as a measure of functional performance to be used in evaluating the efficacy of cancer chemotherapy trials. It is currently used as a measure given by a patient's physician to assess the patient's ability to perform certain ordinary tasks. The lower the Karnofsky score, the worse the survival for most serious illnesses. The general categories are as follows: score 80 to100 — able to carry out normal activity, no special care needed, may need assistance to care for needs; score 40 to 70 — unable to work, able to live at home and care for most personal needs; score 10 to 40 — unable to care for self, requires institutional care or equivalent.
Visual Analog Scale (VAS): A VAS usually consists of a single horizontal line on a page, with verbal and numerical descriptors at each end. Vertical lines and sometimes numbers are added to make scale units. One end point of the line (usually denoted as 10 or 100) is labelled as "the best health state possible" and the opposite end point (denoted as 0) is labelled as "the worst health state possible.
(data collection period)
(no. of patients)
|Standard of Reference||Test||Diagnostic Accuracy|
|Sensitivity %||Specificity %||Other|
|Peynircioglu et al., 201123||Turkey||Retrospective case series
|Massive GI bleeding
|Angiography||99mTc scan||50||66.7||PPV: 42.9%
|Brunnler et al., 200822||Germany||Retrospective medical record review
|Obscure GI bleeding
|Angiography||99mTc scan||79||30||PPV: 77%
|Howarth et al., 200221||Australia||Retrospective case series
|Obscure GI bleeding (47)||Clinical discharge diagnosis or clinical confirmation of GI bleeding||99mTc-RBC scan||87 (detection)
|Wu & Seto, 200120||China||Retrospective case series
|Endoscopy, angiography, and clinical findings||Non-subtraction 99mTc-RBC scan||56.4 (30-min. image)
85.4 (60-min. image)
|sequential subtraction 99mTc-RBC scan||87 (30-min. image)
91.9 (60-min. image)
|Non-subtraction 99mTc-RBC scan||92.8||–||–|
|Sequential subtraction 99mTc-RBC scan||73.8||–||–|
|O'Neill et al., 200024||USA||Retrospective medical record review
|Upper and lower GI bleeding who underwent cinematic TC-99m RBC scans and required surgical intervention (26)||Surgery (intraoperative findings, surgical pathology, post-operative clinical course)||99mTc-RBC scan||88||–||–|
|Emslie et al., 199625||USA||Retrospective case series
|Lower GI bleeding
|Confirmatory studies (angiography, colonoscopy, surgery)||99mTc-RBC scan||88*||85*||Accuracy 80%*|
|Gutierrez et al., 199819||USA||Retrospective medical record review
|Lower GI bleeding (105)||Surgery||99mTc-RBC scan||88||–||–|
GI = gastrointestinal; 99mTc = technetium-99m; RBC = red blood cell; min. = minute; PPV = positive predictive value; NPV = negative predictive value; NA = not available.
*Calculated using data from article.
|Review||Test||No of included studies
(total number of tested patients)
|Correct localization of LGIB %|
|Range (reported by included studies)||Summary estimate|
|Hoedema, 200527||99mTc scan||8 (380)||52 to 95||NA|
|Angiography||9 (436)||40 to 86||NA|
|Strate, 201028||99mTc scan||7 (447)||44 to 100||68|
LGIB = lower gastrointestinal bleeding; NA = not available; 99mTc= technetium 99m