Magnetic resonance colonography versus colonoscopy as a diagnostic investigation for colorectal cancer: a meta-analysis

Clinical Radiology (2005) 60, 980–989

Magnetic resonance colonography versus colonoscopy as a diagnostic investigation for colorectal cancer: a meta-analysis S. Purkayasthaa, P.P. Tekkisa,*, T. Athanasioua, O. Aziza, R. Negusb, W. Gedroycc, A.W. Darzia Departments of aSurgical Oncology and Technology, Imperial College of Science, Technology and Medicine, b Gastroenterology, and cInterventional MRI, St Mary’s Hospital, London, UK Received 9 December 2004; received in revised form 30 March 2005; accepted 14 April 2005

KEYWORDS Meta-analysis; Colonoscopy; Virtual colonography; Magnetic resonance imaging; Colorectal cancer

AIMS: Magnetic resonance colonography (MRC) is emerging as a potential complementary investigation for the diagnosis of colorectal cancer (CRC) and also for benign pathology such as diverticular disease. A meta-analysis reporting the use of MRC is yet to be performed. The aim of this study was to evaluate the diagnostic accuracy of MRC compared with the gold-standard investigation, conventional colonoscopy (CC). METHODS: A literature search was carried out to identify studies containing comparative data between MRC findings and CC findings. Quantitative meta-analysis for diagnostic tests was performed, which included the calculation of independent sensitivities, specificities, diagnostic odds ratios, the construction of summary receiver operating characteristic (SROC) curves, pooled analysis and sensitivity analysis. The study heterogeneity was evaluated by the Q-test using a random-effect model to accommodate the cluster of outcomes between individual studies. RESULTS: In all, 8 comparative studies were identified, involving 563 patients. The calculated pooled sensitivity for all lesions was 75% (95% CI: 47% to 91%), the specificity was 96% (95% CI: 86% to 98%) and the area under the ROC curve was 90% (weighted). On sensitivity analysis, MRC had a better diagnostic accuracy for CRC than for polyps, with a sensitivity of 91% (95% CI: 97% to 91%), a specificity of 98% (95% CI: 66% to 99%) and an area under the ROC curve of 92%. There was no significant heterogeneity between the studies with regard to the diagnostic accuracy of MRC for CRC. CONCLUSION: This meta-analysis suggests that MRC is an imaging technique with high discrimination for cases presenting with colorectal cancer. The exact diagnostic role of MRC needs to be clarified (e.g. suitable for an elderly person with suspected CRC). Further evaluation is necessary to refine its applicability and diagnostic accuracy in comparison with other imaging methods such as computed tomography colonography. Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Introduction

* Guarantor and correspondent: P.P. Tekkis, Department of Surgical Oncology and Technology, St Mary’s Hospital, Praed Street, London N2 1NY, UK. Tel.: C44 207 886 1110; fax: C44 207 886 1810. E-mail address: [email protected] (P.P. Tekkis).

Colorectal cancer (CRC) is a leading cause of cancer death, in both men and women. The majority of diagnoses are among the elderly population (aged 75 years and over), but mortality rates appear to be on the decline.1 The significant morbidity associated with CRC has pertinent social implications for

0009-9260/$ - see front matter Q 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.crad.2005.04.015

Magnetic resonance colonography versus colonoscopy as a diagnostic investigation

individuals and for populations, and thus poses a challenge to provide acceptable screening methods, earlier diagnosis and efficient treatment. Conventional colonoscopy (CC) is the gold standard investigation for the diagnosis of CRC, and has been shown to be more accurate than double-contrast barium enema in the detection of colonic neoplasia.2,3 It is an invasive procedure which often requires sedation and full bowel preparation, but allows biopsies of lesions to be taken. However, rarely it can be associated with potentially life-threatening complications.4 Less invasive diagnostic and screening tools such as faecal occult blood (FOB) testing, although effective, have been shown by some to be less specific and sensitive for colorectal polyps and cancer.5 Virtual colonoscopy (VC), including computed tomography colonography (CTC), has been studied as a possible alternative for the diagnosis of CRC and other colonic pathologies. It has been reported to be feasible, safe and well tolerated.6–10 However, its diagnostic accuracy for smaller lesions is still contentious, some studies suggesting a good accuracy for lesions as small as 6 mm,6 whereas others cast doubts as to whether this technique may not miss these and even larger carcinomas.10 A recent meta-analysis11 of over 1000 patients compared CTC with CC across 14 studies, and reported high overall sensitivity and specificity for lesions larger than 10 mm, but much lower accuracy for smaller lesions.11 This, together with the radiation dose involved in CTC, has led investigators to evaluate the role of magnetic resonance colonography (MRC). MRC is based on the acquisition of data sets of cross-sectional images which are subsequently segmented and rendered so as to produce reconstructed two-dimensional and three-dimensional (3D) images. MRC relies on ultra-fast, T1-weighted, 3D gradient-echo data acquisitions collected during a single breath hold.12 For MRC, the colon is filled with water combined with a paramagnetic contrast agent such as gadolinium. The lumen of the colon thus appears bright and the walls dark. Lesions within the wall protrude into the bright lumen, appearing as filling defects. The difficulty in differentiating masses from faeces can be avoided by imaging the patient prone and supine, and more recently by using techniques to render the lumen and faeces dark while enhancing the colonic walls.13 This faecal tagging (FT), or dark-lumen colonography method, is facilitated by the administration of barium sulphate orally and as an enema,13,14 which then renders the lumen and faeces dark. Subsequent intravenous administration of gadolinium causes the colonic wall to

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appear bright. FT has also been evaluated for use without bowel preparation and shown to be useful, producing readily interpretable images.15 To our knowledge, there is no meta-analytical work on the accuracy of MRC, nor any randomized trials comparing MRC with CTC. However, a number of prospective, comparative studies of MRC versus CC have been reported, which assess the accuracy of MRC as a diagnostic tool for CRC and polyps. The present study uses meta-analytical techniques to calculate an overall estimation of the diagnostic accuracy of MRC for the diagnosis of CRC, and to evaluate the diagnostic accuracy that depends on study design (sample size), type of lesion and technical modifications of technique (use of contrast agents, bowel preparation and FT).

Methods Study selection A literature search (Embase, Ovid, Medline, using Pubmed as the search engine and the Cochrane database) was performed of all studies of the use of MRC published between 1990 and 2004 (last search 26 September 2004). The following keywords and Mesh headings were used: “comparative studies”; “virtual colonography”; “colonoscopy/methods AND comparative studies”; and “magnetic resonance colonography” limited to “human subjects”. The “related articles” function in Pubmed was involved to broaden the search, and all abstracts, studies, and citations scanned were reviewed. No language restrictions were imposed. References of the articles obtained were also searched by hand.

Inclusion and exclusion criteria We considered all studies that reported a direct comparison of MRC findings with CC for healthy volunteers and for patients presenting with symptoms suggestive of CRC and benign polyps. Individuals with lesions of all sizes were included. Studies that reported results on the same patient population were excluded, and studies in which the outcomes of interest were not reported for the two techniques or where it was impossible to calculate these from the published results were excluded. Subjects with diagnoses other than benign or malignant (neoplastic) colorectal lesions were also excluded from the final analysis (e.g. those with colonic diverticulosis, inflammatory bowel disease or extracolonic pathologies), and studies that reported only on MRC without comparison to CC

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were excluded. Authors were not contacted for direct confirmation of exact patient cohorts.

Outcomes and definitions The primary endpoint was “correct patient diagnosis” on MRC compared with CC for all lesions. A secondary endpoint was the diagnostic accuracy of MRC compared with CC for malignant lesions confirmed by histopathological examination. Studies that did not involve FT or intravenous (IV) contrast were evaluated separately. Studies which used a scout film for radiological conformation for adequate distension of the bowel lumen were also evaluated separately.

Data extraction Two reviewers (S. P. and P. T.), independently extracted the data from each study, and in the case of discrepancy a decision was made by consensus. Extracted information included first author, year of publication, study population characteristics (age, gender, symptomatic or asymptomatic patients, any other risks for CRC such as previous treated cancers), study design including number of subjects and type of study, technical parameters (MRI coil calibration in Teslas, number of coils used, the use of IV contrast, bowel preparation, enema pressure, optimal filling position, field of view, flip angle, matrix, section width, use of FT, use of antispasmolytics, number of radiologists involved, and examination time), endpoints (determination of benign and malignant pathologies per patient), diagnostic confirmation (biopsy, surgery, no confirmation) and verification bias which refers to nonconfirmation of the negative test results by the reference standard, occurring when the reference standard is invasive or otherwise undesirable. In the present study, this represented the failure to compare MRC with CC, or to confirm with histology the diagnosis of malignant or benign colorectal polyps.

Statistical analysis For all study subgroups that recorded comparative MRC and CC data, the true-positive (TP), falsepositive (FP), true-negative (TN) and false-negative (FN) results were calculated. The individual study sensitivities and specificities were extracted or calculated using two-by-two contingency tables for each endpoint of correct per-patient diagnosis. Cells with a “zero” value create computational errors in the regression estimates and standard

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errors; this was resolved by adding the value 0.5 in each cell of the two-by-two table for the study in question. The overall pooled sensitivity and specificity, with 95% confidence intervals (CI), were estimated by the DerSimonian Laird method (random effects model) to incorporate the variation of outcomes among the studies.16 In addition, summary receiver operator characteristic (SROC) analysis was performed to examine the interaction between sensitivity and specificity, and to quantify test performance using the area under the curve (AUC), diagnostic odds ratio (DOR) and Q value.

Sensitivity analysis Two strategies were employed to quantitatively assess heterogeneity. In the first, data were reanalyzed using both weighted and unweighted regression in order to accommodate the variation in sample size between the various study populations. In the second, sensitivity analysis was undertaken using subgroup analysis with the following variables: All studies for all lesion sizes; study size (more than 50 patients in total); studies in which no IV contrast was used; studies in which no agent was involved for FT; and studies that received radiological confirmation of adequate filling of the colon before the MRC. The analysis was conducted using SPSS Version 11.0 for Windows (SPSS, Chicago, IL, USA) and MetaTest Software Version 0.9 (developed by Joseph Lau, Division of Clinical Care Research, New England Medical Centre, 750 Washington Street, Box 63, Boston, MA 02111, USA).

Results Eligible studies Initial searching with the keyword “virtual colonoscopy” revealed 485 studies; “virtual colonoscopy AND comparative study” obtained 113 studies; “magnetic resonance colonography”, 91 studies; and “magnetic resonance colonography AND comparative study”, 18 studies. Initial evaluation of the abstracts and subsequently the complete texts of the papers that fulfilled our inclusion criteria identified 12 articles comparing MRC with CC for colonic lesion detection,14,17–27 whereas 4 studies were excluded.24–27 In the first study, the cases proceeding to MRC were not validated colonoscopically,24 and in the other studies there was an apparent overlap of the patient cohort with more

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recent studies by the same authors.25–27 The most recent studies with the largest sample size were included in the meta-analysis. On three occasions, 2 studies by the same institution investigated different patient groups, and thus all 6 studies were included in the final analysis.14,17–19,22,23 This left 8 prospective comparative studies,14,17–23 comprising a total of 588 patients, of whom 563 had complete colonoscopic examinations (96%). All 8 studies included cohorts of patients who were due to undergo clinically indicated colonoscopy, and thus the subjects had a greater than normal risk for being diagnosed with colorectal cancer. There were totals of 131 TP, 70 FN, 15 FP and 347 TN findings. On review of the data extraction, there was 100% agreement between the two reviewers. The comparisons of these studies, patient characteristics, inclusion and exclusion criteria are shown in Table 1. The age of subjects ranged from 17 to 90 years.

based, with or without contrast, 1 study using air and 1 study using air and water); how optimal colon filling was assessed (7 studies assessing this radiologically with a scout image and 1 clinically by the patient’s perception of fullness); the position in which the patient rested during the data acquisition (3 studies in the prone position, 3 in both prone and supine positions and 2 not reporting on this parameter); the field of view (ranging from 34 to 42 cm); the flip angle (ranging from 158 to 458 for the 3D data sets); the matrix; section sizes; whether FT was involved (2 studies); spasmolytic dose used (all used IV buscopan, ranging from 5 mg to 40 mg, 1 study also using 1 mg glucagon IV); the numbers of radiologists who interpreted the images (6 studies reported by two, 1 study by three and 1 study not commenting on this aspect of the methodology); and the examination time, which approximated to 20 min (2 studies).

Verification bias

Statistical data synthesis and false-positive and false-negative findings

Each patient underwent both the test (MRC) and the gold standard (CC) for purposes of comparison, and thus the primary endpoint verification bias was zero. Of the 7 studies that allowed extrapolation of data for the analysis of detection of CRC, all used histology for confirmation,14,18–23 and thus the verification bias for this subgroup was also zero.

Technical parameters The technical parameters extracted from 8 studies are shown in Table 2. These included the types and numbers of body coils; the use of IV contrast media for image augmentation (4 studies); the use of mechanical bowel preparation (6 studies); the type of enema and its pressure (6 studies using water Table 1

The sensitivity, specificity and DORs for each study are shown in Table 3; 3 studies reported FP results17,20,21 and only 1 stated the cause of the FP finding (a prominent colonic fold or faecal matter).20 All but 1 study (sample size of 6 patients)22 documented FN findings. Among the remainder, Luboldt et al.17 found 29 FNs, of which 18 lesions were less than 5 mm in diameter and 11 were between 5 and 10 mm. Lauenstein et al.14 recorded FNs in 2 cases (1 patient had two polyps sized 6 mm and 8 mm, respectively, and 1 patient had a flat adenoma for which the size was not reported). Ajaj et al.19 identified 1 FN finding only, which was a 4-mm polyp in the sigmoid colon. Pappalardo et al.20 detailed 2 cases with FN

Study characteristics

Author

No. of patients

No. of examinations

Age in years (range)

Inclusion criteria

Exclusion criteria

Study design

Luboldt17 Lauenstein14 Ajaj19 Pappalardo20 Leung21 Ajaj18 Lauenstein22 Luboldt23

132 24 55 70 156 122 12 17

115 24 55 70 156 120 6 17

60 (18–86) 57.4 (33–78) 60.6 (44–77) 59 (19–85) 55.2 (9.1a) 60.2 (17–90)

1 1 2–4 1,2,5,6 1 1,2,5–8 1,9 1

1,2 1 1 1,3 7–11 1 1 2,4–6

Prospective Prospective Prospective Prospective Prospective Prospective Prospective Prospective

66 (48–86)

Inclusion criteria: 1, suspected colorectal cancer; 2, positive faecal occult blood; 3, family history of colorectal cancer; 4, diarrhoea; 5, change of bowel habit; 6, overt bleeding per rectum; 7, abdominal pain; 8, deranged liver function tests; healthy volunteer subjects. Exclusion criteria: 1, contraindications to MR; 2, acute abdomen; 3, large bowel obstruction; 4, claustrophobia; 5, pregnancy; 6, PPM (permanent pacemeker); 7, barium enema or colonoscopy performed in last 5years; 8, known diverticular disease or IBD (inflammatory bowel disease); 9, severe medical co-morbidity; 10, metal prosthesis; 11, anticoagulation. a Standard deviation.

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20 No Prone only Radiological 80

Radiological –

Radiological 100–150

No 1 1.5 Luboldt

1,4 1.5 Lauenstein22

23

Yes

2.0 l H2O (yes) 2.0–2.5 l H20 (yes) 3.0 l H20 (no) Yes 1,3 1.5 Ajaj

18

Leung21

Pappalardo

Ajaj19

Sensitivity analysis, logit functions and SROC curve

Radiol, radiologists; 1, body coil; 2, dual surface coil; 3, build in spinal array; 4, large flex. a Plus 1 mg glucagon IV.

384K25! 192K160 458 34–42

2–3/0

230!256 158 45

1.57/3.14

Yes

20

3

2 40 No 4/0 128 45

Supine/prone Clinical – No 1,3,4 1.5

No 1 1

Yes 2,3 1.5

20

Yes 2 1.5 Lauenstein

findings, which were polyps less than 5 mm in diameter. Leung et al.,21 however, extracted 32 FN results, the majority of which were polyps less than 10 mm in diameter; 1/4 cancers was missed. This study21 was the only one that judged the optimal filling of the colon clinically, rather than radiologically, was one of 2 studies that used solely air as the medium for the enema, and was one of 3 studies that did not use IV contrast (one of the other studies that did not use IV contrast also had a high number of FN findings.17) Ajaj et al.18 reported 2 FN results, one of which was a 10-mm intraluminal lipoma and the other was described as “a very small polyp”. Finally, Luboldt et al.23 identified 2 FN results, one a 5-mm polyp in 1 patient and the other comprising innumerable polyps less than 10 mm in diameter in another patient with polyposis coli. The only study that did not report any FN results did record that MRC diagnosed 1 cancer in the transverse colon, just proximal to the splenic flexure, which was not picked up on CC but was confirmed at surgery.22

20G2.7 2 20a

256!134/ 256!165 168!256 1508/58 34–40

2.5/4

No

2 5 No 2.2–2.6/0 256!160 408 34–35 –

Radiological

Supine/prone

128 Prone only Radiological –

100–150

Radiological

Prone only

45

158

45

1.54/0

No

40

2

!20 2 20 Yes 1.57/3.14

2 20 No 2–3/6

256!160/ 384!192 460!512/ 256!230 168!256 908/408 34–42 1.5

Table 2

14

Luboldt17

1

No

3 l H20 (yes) 1.0–1.5 l H2O (no) 2.0 l H20 (yes) 1.5–2.0 l H20 (yes) Air (yes)

100

Radiological

Supine/prone

Matrix 2D/3D Flip angle 2D/3D Enema pressure (cm H2O) Enema (bowel prep) IV contrast Coils TMR Author

Technical parameters used in the individual studies

Optimal filling

Position

Field of view (cm)

2D/3D section thickness (mm)

Tagging

Buscopan (mg)

Radiol (number)

Exam time (min)

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The pooled sensitivity over the 8 studies was 75% (95% CI: 47% to 91%) and a specificity of 96% (95% CI: 86% to 98%). This is shown graphically in the forest plot in Fig. 1. The plot of the logit of TPR minus the logit of FPR, against the logit of TPR plus the logit of FPR, for each study, is shown in Fig. 2. A weighted regression line is superimposed on the data points, with the intercept (a) and a slope (b) shown in Table 4. These parameters were then used to construct the area under the SROC curve, which measured 96% and 90% for unweighted and weighted results, respectively (Fig. 3). The overall DOR for all the studies diagnosing any size of lesion was 52.82 (95% CI: 9.38 to 297.25) with a Q value of 31.18, denoting significant heterogeneity between the studies (p!0.001). For the detection of malignant lesions 7 studies were used,14,18–23 which included a total of 440 patients and provided a sensitivity of 91% (95% CI: 79% to 97%) and a specificity of 98% (95% CI: 96% to 99%). The DOR for the detection of cancerous lesions was 576.41 (95% CI: 135 to 2448.56). The Q value was 3.66 (no significant heterogeneity between the studies, pZ0.818), and the AUC from the SROC was 97.7% and 98.4% for unweighted and weighted results, respectively. Further sensitivity analysis was performed using IV contrast (weighted AUC 86.4%), FT (weighted AUC 88.9%), scout films for optimized colon filling (weighted AUC 87.9%)

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Table 3 Individual study results for diagnosis of all colonic lesions in patients undergoing MR colonography compared with conventional colonoscopy Author

No. of patients

True Cve/false Kve

False Cve/true Kve

Sensitivity

Specificity

DOR

Luboldt17 Lauenstein14 Ajaj19 Pappalardo20 Leung21 Ajaj18 Lauenstein22 Luboldt23

115 24 55 70 156 120 6 17

27/29 13/2 8/1 53/2 3/32 11/2 4/0 12/2

11/48 0/9 0/46 1/14 3/118 0/107 0/2 0/3

0.482 0.867 0.889 0.964 0.086 0.846 1.000 0.857

0.814 1.000 1.000 0.933 0.975 1.000 1.000 1.000

4.063 102.60 527.00 371.00 3.688 989.00 45.00 35.00

DOR, diagnostic odds ratio.

and studies with greater than 50 patients included as subgroups (weighted AUC 88.5%). Because of lack of comparative group data on the different sizes of lesions, we were not able to evaluate the accuracy of MRC based on various thresholds of sizes of polyps or cancers. Analysis was also carried out excluding data from studies that included healthy volunteers, which might raise the negative predictive value of MRC because of a low incidence of pathology. This revealed an AUC of 0.96, pooled sensitivity and specificity of 0.63, (95%CI: 0.56 to 0.70) and 0.95 (95%CI: 0.92 to 0.97), respectively, a DOR of 39.158 (95%CI: 5.72 to 267.89) with a Q value of 25.66 (p! 0.001), thus demonstrating significant heterogeneity. Therefore, excluding the studies with volunteers did not have much impact on the overall results. (Table 4).

Extracolonic findings on MRC Extracolonic findings were described by 3/8 studies. The first17 reported 5 liver metastases,

1 hepatocellular carcinoma, 5 ovarian cancers and 1 prostate cancer. The second14 found liver metastases (no numbers given) and 1 abdominal aortic aneurysm. The third21 demonstrated liver cysts in 21.2% of patients, renal cysts in 23.7% of patients and fibroids in 5.1% of patients. It also diagnosed 1 case as renal cell carcinoma and 1 as gastrointestinal stromal tumour.

Discussion Our study evaluated several single-centre trials that compared MRC and CC; these investigations have different diagnostic thresholds and different technical parameters. Meta-analysis of the results was necessary to assess the accuracy of MRC with respect to polyp and CRC diagnosis. Diagnostic accuracy relating to specific cancer sizes was not estimable as these data were not available. All studies showed a good specificity, but there was a great range of sensitivities (Table 3), probably due to technical differences between the studies (see

Figure 1 Heterogeneity of sensitivity and specificity results across the studies. A random effects model (DerSimonian Laird method) was used for pooling the results (REM).

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Figure 2 Scatter plot with weighted regression line demonstrating the relationship between the Logit (TPR)KLogit (FPR) plotted against the Logit (TPR)CLogit (FPR) for each individual study. TPR, true-positive rate; FP, false-positive rate. Logit(x)ZK1/(1KLn).

below). Despite the observed heterogeneity of the studies, the overall diagnostic accuracy of MRC was adequate, with a sensitivity of 75% (95% CI: 47% to 91%) and a specificity of 96% (95% CI: 86% to 98%). MRC was more useful in the detection of malignant lesions, with a sensitivity of 91% (95% CI: 79% to 97%) and specificity of 98% (95% CI: 96% to 99%). Heterogeneity may be either methodological (differences between the studies, e.g. type of study, institution, clinicians involved, blinding, radiological settings), clinical (differences between the patients) or may be due to differences in diagnostic thresholds between different studies. Although it was not feasible to analyze the diagnostic accuracy of MRC based on lesion size, on reviewing the literature, MRC seemed effective for demonstrating lesions of 10 mm or larger.14,17,20 This result is comparable to CTC,11 which has been shown by some investigators to be more helpful than double-contrast barium enema.28 Only 1 study reported a good diagnostic rate for smaller lesions with MRC,18 but this needs to be evaluated further. The 1 study in our analysis that reported high FN rates used clinical criteria for optimal colon filling, and air as the contrast medium for the enema.21 It is intuitive that diagnostic MRC relies heavily on good bowel distension and sufficient contrast between the bowel lumen and the colonic wall to highlight small lesions, and thus we can hypothesize that the methodological aspects of this study led to the higher FN rate. The studies included for this meta-analysis

incorporated a very wide range of techniques, e.g. bright lumen, dark lumen, prepared, not prepared, tagged, not tagged, air filling, water filling, etc. It is clear that in radiological terms these are fundamental differences that further increase heterogeneity and will have an impact on results, and this limits the potential conclusions from this analysis. Reader experience was not stratified within the studies, and therefore this could not be extracted as a subgroup for individual analysis; it would also account for heterogeneity between the studies included. Furthermore, the centres involved in the individual studies were specialist centres with an interest in MRC. Their interpretation was potentially very different from centres where MRC might be a new addition to radiological techniques. The potential advantages of MRC over CC are that it is less invasive, with less potential serious complications, requires less time for the investigation and has been reported to have good patient acceptability. Extracolonic pathologies related to the disease can also be evaluated, e.g. lymph node and distant metastasis, which can be used in the staging process; incidental, yet clinically relevant extracolonic disease can also be diagnosed. In contrast to CC, if a stenosing lesion is found, the proximal colon can still be evaluated by MRC for synchronous lesions and other intraluminal disease. Potential disadvantages of MRC include lack of universal availability, unsuitability for biopsies, susceptibility to motion artefact, need for breath

(0.900) (0.984) (0.864) (0.889) (0.879) (0.885) 0.959 0.977 0.924 0.964 0.932 0.973 0.150 (0.102) 0.005 (0.005) 0.111 (0.069) 0.153 (0.97) 0.160 (0.114) 0.159 (0.096) 31.18 (!0.001) 3.66 (0.818) 12.96 (0.073) 29.18 (!0.001) 28.66 (!0.001) 28.30 (!0.001) 52.82 (9.38, 297.25) 576.41 (135.0, 2448.56) 15.49 (2.33, 103.01) 91.13 (10.87, 763.9) 50.66 (6.61, 388.29) 55.82 (5.52, 564.03) (3.269) (5.985) (2.861) (3.083) (2.901) (3.025) 8 7 4 6 7 5 Overall data Cancer only No IV contrast No faecal tagging Scout film (OFC) Studies O50 patients

OFC, radiological assessment for optimal filling of colon using a scout film.

4.542 5.714 4.070 4.794 4.097 5.326 0.175 (0.254) K0.438 (K0.292) 0.563 (0.396) 0.246 (0.221) K0.443 (K0.069) 0.356 (0.207) 0.96 (0.86, 0.98) 0.98 (0.96, 0.99) 0.92 (0.75, 0.98) 0.96 (0.85, 0.99) 0.94 (0.82, 0.98) 0.96 (0.85, 0.99) 0.75 (0.47, 0.91) 0.91 (0.79, 0.97) 0.64 (0.20, 0.93) 0.71 (0.36, 0.91) 0.83 (0.63, 0.94) 0.68 (0.28, 0.92)

No. of studies Variable

563 440 358 533 407 516

Sensitivity analysis Table 4

No. of patients

Sensitivity (95% CI)

Specificity (95% CI)

Slope (weighted)

Intercept (weighted)

DOR (95% CI)

Q value (p value)

AUC partial

AUC (weighted)

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holding, clinical contraindications in some cases and longer interpretation times. Cost also is an issue; 1 study reported MRC examination costs of approximately $550, whereas a subsequent CC indicated by positive findings on the MRC cost $380.20 Cost-effectiveness has not yet been formally investigated. However, the financial benefit will be apparent once the FN rate is minimized and the cost of MRC reduces with time. At a population level, if MRC were to be validated for screening purposes the implications might be substantial; this requires further evaluation. As with all new technology, the diagnostic accuracy of MRC is expected to improve as the techniques are refined, clinicians become more proficient in interpreting the images and the use of the investigation increases with more clinical practice and clinical trials. New technology and techniques are often accompanied by initial enthusiasm, which settles with progression into everyday clinical practice. This is evident from the fact that 8 studies fulfilled the inclusion criteria for the present meta-analysis. It remains to be seen how research in this field progresses as MRC is used more regularly. MRC accuracy may also improve with the use of dark-lumen colonography, in conjunction with FT.14,18 The technique can be performed without bowel preparation, which may increase patient acceptance, particularly for elderly patients who are not able to tolerate full bowel preparation or who require IV hydration in preparation for CC. The tagging substance used is barium sulphate, which is cheap, easily available and has a favourable side-effect profile. 22 Interpretation can be facilitated with the use of IV contrast agents in order to enhance lesions within the wall. This is further aided by applying a “flythrough” of the colon to double-check for small lesions. Specialized software may enable the viewer to digitally straighten the colon in areas where folds may mask potential pathologies. The diagnostic accuracy of any test is only as good as the gold standard that measures it. CC remains the best diagnostic method but has its limitations, including FN rates, operator dependency and small but clinically significant noncompletion rates.29 One of the included studies reported that MRC detected 1 cancer in the transverse colon, just proximal to the splenic flexure, which was not detected by CC but was confirmed at surgery. However, how this malignancy was diagnosed as warranting surgery in the first place, or whether this was a synchronous tumour, was not mentioned. CC may be improved further in terms of visualization, invasiveness and reproducibility. The role of MRC may also be

988

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Figure 3 Summary receiver operating characteristic curves for all 8 studies. Numerals on the graph represent the individual sensitivities and specificities for the studies used in the analysis. The weighted and unweighted curves are displayed.

extended for preoperative staging, evaluation of circumferential margin involvement and planning operative approach. Such data sets may be used in the future for image overlay during surgery. The ideal candidates for MRC include patients with symptoms suspicious of CRC or possibly those with a higher risk of having a failed CC, e.g. with a rigid colon following multiple laparotomies. Individuals with chronic diarrhoea may be better served by CC because of the need for biopsies, even if a normal endoscopic examination excludes microscopic causes of the symptoms. MRC may also be useful in further evaluation of possibly inoperable lesions before stenting.

techniques would help to illustrate which method might provide better sensitivities and specificities for CRC. Currently, further refinements are necessary in the acquisition of imaging data sets in order to be able to detect smaller premalignant and malignant lesions as well as other benign conditions such as inflammatory bowel disease and diverticular disease. The lack of radiation and the prospect that the technique may not require bowel preparation may render MRC preferable to CTC for the purposes of screening and diagnosis of CRC.

References Conclusion Our study highlights the need for further evaluation of MRC compared with CC and CTC. This may be facilitated by multicentred, prospective clinical trials, to determine usefulness for identifying small luminal lesions, preoperative staging, evaluating extracolonic pathologies and even screening in the future. A comparison of dark- and light-lumen

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