Table 1. Summary of Criterion Evidence

SUMMARY TABLE

Table 1: Summary of Criterion Evidence Domain 1: Criteria Related to the Underlying Health Condition Criterion Synthesized Information 1 Size of the affected No estimates of point prevalence of acute cholecystitis were found in the literature. An Ontario population hospital-based study29 estimated the annual incidence of acute cholecystitis from 1992 to 2000 to be 0.88 people per 1,000 population. The size of affected population is more than 1 in 10,000 (0.01%) and less than or equal 1 in 1,000

(0.1%) 2 Timeliness and Saskatchewan hospital guidelines indicate that cholescintigraphy for diagnosis of suspected acute urgency of test cholecystitis should be conducted within 24 hours (Patrick Au, Acute and Emergency Services results in planning Branch, Saskatchewan Ministry of Health: unpublished data, 2011) patient management The target time frame for performing the test is in 24 hours or less and obtaining the 99mTc-based test results in the appropriate timely manner for the underlying condition has significant impact on

the management of the condition or the effective use of health care resources. 3 Impact of not If a test for diagnosing acute cholecystitis is not available, treatment might be delayed and performing a complications associated with high mortality rates might be more likely to develop. Complications diagnostic imaging from acute cholecystitis occur in around 20% of patients and complicated acute cholecystitis is test on mortality associated with a mortality rate of around 25%.33 Perforation of the gallbladder, which occurs in related to the 3% to 15% of patients with cholecystitis, has a 60% mortality rate.34 Acute acalculous cholecystitis underlying condition has a mortality rate of around 30%.35

Diagnostic imaging test results can have minimal impact on mortality. 4 Impact of not If a test for diagnosing acute cholecystitis is not available, treatment might be delayed and performing a patients may have to suffer symptoms of acute cholecystitis longer than necessary. Delayed diagnostic imaging treatment will make patients more susceptible to complications that could increase the global test on morbidity or hospitalization length and have an impact on their survival or quality of life. quality of life related Diagnostic imaging test results can have moderate impact on morbidity or quality of life. to the underlying condition

Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information

5 Relative impact on To be scored locally. Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information health disparities 6 Relative acceptability Cholescintigraphy of the test to patients Patients may have concerns about radiation exposure and the intravenous injection of a radiopharmaceutical agent. 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 breath for a substantial period of time, which is seen as “uncomfortable” and “difficult,” particularly for patients with severe abdominal pain.36 MRCP MRCP is an MRI-based imaging test. Because of the closed space of an MRI, patients may experience feelings of claustrophobia as well as be bothered by the noise. 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.37,38 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. U/S Some discomforts associated with U/S include cold, unspecified pain, and tenderness. In a study comparing U/S with MRI in undiagnosed shoulder pain, 100% of the patients participating said that they would be willing to undergo the U/S exam again.39 This test may be preferred in pediatric patients as there is no exposure to ionizing radiation, and the test does not require sedation. Overall, acceptability to patients of cholescintigraphy using 99mTc-radiolabelled isotopes is:  minimally more acceptable than CT  minimally less acceptable than MRCP,  minimally less acceptable than U/S.

7 Relative diagnostic Cholescintigraphy versus U/S accuracy of the test The table presents the sensitivity and specificity reported in one systematic review15 and three primary studies25,27,28 that compared the diagnostic accuracy of cholescintigraphy and U/S for acute cholecystitis. Diagnosis of acute cholecystitis was confirmed with pathological or surgical Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information findings (gold standard).

Diagnostic Accuracy Author, Cholescintigraphy U/S Year N Sensitivity Specificity N Sensitivity Specificity Shea et al. 199415 2466 0.97 0.90 532 0.88 0.80

Chatziioannou et 107 0.88 0.93 107 0.50 0.88 al. 200027

Kalimi et al. 28 0.86 NR 50 0.48 NR 200128

Alobaidi et al. 22 0.91 NR 100 0.62 NR 200425

N = number of patients; U/S = ultrasound. Cholescintigraphy versus CT No studies comparing the diagnostic accuracy of cholescintigraphy and CT for acute cholecystitis were identified. Cholescintigraphy versus MRCP No studies comparing the diagnostic accuracy of cholescintigraphy and MRCP for acute cholecystitis were identified. Based on limited evidence and expert opinion, the diagnostic accuracy of cholescintigraphy using 99mTc-radiolabelled isotopes is:  moderately better than CT  similar to MRCP,  minimally better than U/S.

8 Relative risks Non–radiation-related Risks associated with the Cholescintigraphy test Risks associated with a cholescintigraphy include allergy to HIDA and pain during CCK injection (causes gallbladder contraction), chills, nausea, and rash.40 CT Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information Some patients may experience an allergic reaction to the contrast agent (if required).41 In addition, patients may experience mild side effects from the contrast agent, such as nausea, vomiting, or hives. A 2009 retrospective review of 456,930 intravascular doses of low-osmolar iodinated and Gd contrast materials administered between 2002 and 2006 found 0.15% of patients experienced side effects, most of which were mild. According to the American College of Radiology Manual on Contrast Media,42 the frequency of severe, life-threatening reactions with Gd is extremely rare (0.001% to 0.01%). MRCP MRCP is an MRI-based test and is contraindicated in patients with metallic implants, including pacemakers.43 MRI is often used in conjunction with the contrast agent Gd. Some patients may experience an allergic reaction to the contrast agent (if required).41 Gd is contraindicated in patients with renal failure or end-stage renal disease, as they are at risk of nephrogenic systemic fibrosis. The frequency of severe, life-threatening reactions with Gd is extremely rare (0.001% to 0.01%).42 U/S There are no reported risks associated with U/S in the literature that was reviewed. Radiation-related Risks Some tests expose patients to radiation. The following table presents the effective radiation dose to which patients are exposed during the various diagnostic tests.

Radiation doses Test Effective Radiation Dose (mSv)

Cholescintigraphy 3.144 Abdominal CT 8.044 MRCP (MRI) 030 Abdominal U/S 030 Annual natural radiation exposure 1 to 3.044-46

Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information Overall, the risks associated with cholescintigraphy using 99mTc-radiolabelled isotopes is:  minimally safer than CT  minimally less safe than MRCP,  minimally less safe than U/S. 9 Relative availability of As of 2006 in Canada, there were 2,034 diagnostic radiologists, 221 nuclear medicine physicians, personnel with 12,255 radiological technologists, 1,781 nuclear medicine technologists, and 2,900 sonographers expertise and available across Canada. Yukon, Northwest Territories, and Nunavut do not have the available experience required personnel to perform and interpret tests to detect bile leak. Other jurisdictions (e.g., Prince Edward for the test Island) may offer limited nuclear medicine services. Assuming the necessary equipment is available, if cholescintigraphy using 99mTc-radiolabelled isotopes is not available, it is estimated that:  more than 95% of the procedures can be performed in a timely manner using CT  25-74% of the procedures can be performed in a timely manner using MRCP  more than 95% of the procedures can be performed in a timely manner using U/S. 10 Accessibility of Cholescintigraphy alternative tests For the diagnosis of acute cholecystitis, nuclear medicine facilities with gamma cameras (including (equipment and wait SPECT) are required. As of January 1, 2007, there was an average of 18.4 nuclear medicine times) cameras per million people, with none available in the Yukon, Northwest Territories, or Nunavut.47 MRCP No MRI scanners are available in the Yukon, Northwest Territories, or Nunavut.48 According to CIHI’s National Survey of Selected Medical Imaging Equipment database, the average number of hours of operation per week for MRI scanners in 2006-2007 ranged from 40 hours in Prince Edward Island to 99 hours in Ontario with a national average of 71 hours.47 In 2010, the average wait time for MR imaging in Canada was 9.8 weeks.49 CT No CT scanners are available in Nunavut.48 For CT scanners, the average weekly use ranged from 40 hours in Prince Edward Island to 69 hours in Ontario, with a national average of 60 hours.47

U/S Domain 2: Criteria Comparing 99mTc with an Alternative or Comparing Between Clinical Uses Criterion Synthesized Information The median wait time for a U/S in Canada was estimated to be 4.5 weeks in 2010.49 No information was found on the number of U/S machines available in Canada. Assuming the necessary expertise is available, if cholescintigraphy using 99mTc-radiolabelled isotopes is not available, it is estimated that:  more than 95% of the procedures can be performed in a timely manner using CT  25-74% of the procedure can be performed in a timely manner using MRCP,  more than 95% of the procedures can be performed in a timely manner using U/S.

11 Relative cost of the According to our estimates, the cost of cholescintigraphy with 99mTc-based radioisotopes is test $298.38. CT is minimally more costly and MRCP is moderately more costly. U/S is minimally less costly.

Relative costs Test Total costs ($) Cost of test relative to 99mTc-based test ($) Cholescintigraphy 298.38 Reference CT 383.85 +85.47 MRCP 595.15 +296.77 U/S 88.25 -210.13

CCK = cholecystokinin; CIHI = Canadian Institute for Health Information; CT = computed tomography; Gd = Gadolinium; HIDA = hepatobiliary iminodiacetic acid; MRCP = magnetic resonance cholangiopancreatography; MRI = magnetic resonance imaging; mSv = millisievert; NR = not reported; SPECT = single-photon emission computed tomography; 99mTc = technetium-99m; U/S = ultrasound.