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Meta-Analysis: Computed Tomographic Colonography FREE

Brian P. Mulhall, MD, MPH; Ganesh R. Veerappan, MD; and Jeffrey L. Jackson, MD, MPH
[+] Article and Author Information

From Walter Reed Army Medical Center and Uniformed Services University, Washington, DC.


Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not be to be construed as reflecting the views of the Department of the Army or the Department of Defense.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Brian P. Mulhall, MD, MPH, Gastroenterology Service, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Building 2, 7F18, Washington, DC 20307; e-mail, brian.mulhall@na.amedd.army.mil.

Current Author Addresses: Dr. Mulhall: Gastroenterology Service, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Building 2, 7F18, Washington, DC 20307.

Dr. Veerappan: Department of Medicine, Walter Reed Army Medical Center, 6900 Georgia Avenue NW, Building 2, 7F18, Washington, DC 20307.

Dr. Jackson: Medicine-EDP, 4301 Jones Bridge Road, Bethesda, MD 20814.


Ann Intern Med. 2005;142(8):635-650. doi:10.7326/0003-4819-142-8-200504190-00013
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Background: Computed tomographic (CT) colonography, also called virtual colonoscopy, is an evolving technology under evaluation as a new method of screening for colorectal cancer. However, its performance as a test has varied widely across studies, and the reasons for these discrepancies are poorly defined.

Purpose: To systematically review the test performance of CT colonography compared to colonoscopy or surgery and to assess variables that may affect test performance.

Data Sources: The PubMed, MEDLINE, and EMBASE databases and the Cochrane Controlled Trials Register were searched for English-language articles published between January 1975 and February 2005.

Study Selection: Prospective studies of adults undergoing CT colonography after full bowel preparation, with colonoscopy or surgery as the gold standard, were selected. Studies had to have used state-of-the-art technology, including at least a single-detector CT scanner with supine and prone positioning, insufflation of the colon with air or carbon dioxide, collimation smaller than 5 mm, and both 2-dimensional and 3-dimensional views during scan interpretation. The evaluators of the colonogram had to be unaware of the findings from use of the gold standard test.

Data Abstraction: Data on sensitivity and specificity overall and for detection of polyps less than 6 mm, 6 to 9 mm, and greater than 9 mm in size were abstracted. Sensitivities and specificities weighted by sample size were calculated, and heterogeneity was explored by using stratified analyses and meta-regression.

Data Synthesis: 33 studies provided data on 6393 patients. The sensitivity of CT colonography was heterogeneous but improved as polyp size increased (48% [95% CI, 25% to 70%] for detection of polyps <6 mm, 70% [CI, 55% to 84%] for polyps 6 to 9 mm, and 85% [CI, 79% to 91%] for polyps >9 mm). Characteristics of the CT colonography scanner, including width of collimation, type of detector, and mode of imaging, explained some of this heterogeneity. In contrast, specificity was homogenous (92% [CI, 89% to 96%] for detection of polyps <6 mm, 93% [CI, 91% to 95%] for polyps 6 to 9 mm, and 97% [CI, 96% to 97%] for polyps >9 mm).

Limitations: The studies differed widely, and the extractable variables explained only a small amount of the heterogeneity. In addition, only a few studies examined the newest CT colonography technology.

Conclusions: Computed tomographic colonography is highly specific, but the range of reported sensitivities is wide. Patient or scanner characteristics do not fully account for this variability, but collimation, type of scanner, and mode of imaging explain some of the discrepancy. This heterogeneity raises concerns about consistency of performance and about technical variability. These issues must be resolved before CT colonography can be advocated for generalized screening for colorectal cancer.

Colorectal cancer is the second most frequent cause of cancer-related death in the United States. Nearly 150 000 new cases and 60 000 deaths occur each year from this disease (1). Because colorectal cancer develops insidiously over time as genetic mutations accumulate in clinically silent adenomatous polyps, it is most commonly diagnosed at an advanced stage (24). If the condition is diagnosed at an early stage, the prognosis is favorable, with 5-year survival rates exceeding 90% (56). Colorectal cancer, unlike many other types of cancer, can be prevented by removal of precancerous lesions. The long preclinical phase, early detectability, and improved prognosis of colorectal cancer have established the need for an accurate screening method.

Various screening tests in current use reduce the incidence and rate of death from colorectal cancer (78). Despite the proven efficacy of these tests, however, patient adherence to screening guidelines is low: Only 30% to 45% of persons eligible for screening undergo such tests. Low adherence rates are believed to be due to poor public awareness and poor public acceptance of current screening techniques (913).

An increasingly popular screening test for colorectal cancer is computed tomographic (CT) colonography, also known as CT colography or virtual colonoscopy. Computed tomographic colonography was first described in 1994 as a radiographic technique in which thin-section images of pneumocolon could be reconstructed by sophisticated software into high-resolution 2- and 3-dimensional images (14). Over time, improvements in hardware and software have allowed faster scanning, reduced exposure to radiation, and better imaging. Newer modes of imaging (called fly-through) can produce results that resemble endoscopic images and permit sophisticated characterization of detected lesions (1517). Early studies primarily used the spiral CT scanner, which has limitations in spatial resolution that can make small polyps more difficult to detect (17). The multidetector CT scanner has permitted rapid acquisition of finer images, obtained during a single breath-hold, that can greatly improve image quality and spatial resolution (1718). Many aspects of this technology are under study, including software that assists in detection of lesions, refinements in image reconstruction, and stool tagging (1921). The latter development relies on ingestion of contrast material over several days or hours, after which software digitally subtracts residual solid and fluid fecal material from the acquired images, creating a “virtually clean” mucosal surface (2223). This technique may improve sensitivity and may someday obviate the need for bowel cleansing before examination.

Although it is touted as a less invasive screening method than flexible sigmoidoscopy or colonoscopy, CT colonography typically requires full bowel cleansing and insufflation of air through the rectum (24). Studies have suggested that CT colonography may be similar, and in some cases preferable, to colonoscopy in terms of comfort and acceptability, but no convincing difference between these 2 approaches has been demonstrated (2531). If virtual colonoscopy is found to have equivalent test characteristics, improve patient adherence, and be safer or less expensive than colonoscopy, it may be more cost-effective and become the screening method of choice (3233).

Studies of the test characteristics of CT colonography have had mixed results. Pickhardt and colleagues used CT colonography in 1233 patients and found a sensitivity of 93.9% for adenomatous polyps larger than 8 mm (25). Other studies have had less favorable results, with sensitivities as low as 55% for polyps larger than 10 mm, raising concerns about the overall test performance of CT colonography when used in a broader range of settings (34). Various reasons for these discrepant results have been offered, but the source of this heterogeneity has not been fully explored (16, 3536). Such assessment is needed because patients and providers look to this technology in the hope of improving screening rates (29).

We systematically reviewed the literature to assess the test performance of CT colonography compared with colonoscopy or surgery, to define characteristics of these studies, and to attempt to explain the sources of conflicting results.

Study Identification and Selection

We searched the PubMed, EMBASE, and MEDLINE databases and the Cochrane Controlled Trials Register for all relevant articles published in the English language between 1975 and February 2005 by using the Medical Subject Headings or text words virtual colonoscopy, CT colonography, CT colography, or CT pneumocolon. The title and abstract of potentially relevant studies and review articles were screened for appropriateness before retrieval of the full articles. Two reviewers independently searched the literature. Inclusion criteria were a prospective, blinded design (in which results of CT colonography were interpreted independently of findings on colonoscopy or during surgery); enrollment of adult patients who were to undergo CT colonography after a full bowel preparation, followed by complete colonoscopy or surgery; and use of at least a single-detector CT scanner, with colon insufflation by air or carbon dioxide, scan intervals no greater than 5 mm, and use of both 2-dimensional and 3-dimensional views during scan interpretation.

Study Quality

Two observers independently extracted data on test characteristics; study setting; patients; and components of methodologic quality that may be associated with bias in test accuracy studies, including disease severity, disease prevalence, prospective design, relevant clinical sample (as opposed to a diagnostic case–control study), enrollment of a series of consecutive patients, assurance that all patients underwent reference testing, performance and interpretation of the index test without knowledge of the results of the reference test, and performance and interpretation of the reference test without knowledge of the results of the index test (33). A piloted standardized data extraction sheet was used, and disagreements were resolved by consensus.

Data Abstraction

We abstracted characteristics of the study (design, country, year, reference standard, and type of contrast used), patients (demographic and risk for colorectal cancer), scanners (manufacturer, type of viewer, type of contrast, software, and hardware), and study quality. Sensitivity and specificity were calculated per patient, per polyp, and for polyps of 3 size categories: smaller than 6 mm, 6 to 9 mm, and larger than 9 mm. When data on test performance were reported for 2 or more separate CT colonography readers, we calculated an average value. When possible, we excluded data on double readings. If a study reported data related specifically to adenomas instead of polyps, in general, we abstracted only the data for adenomas. For studies that performed retrospective analysis (for example, fly-through imaging in the study by Cotton and associates [34]), we abstracted only data on CT colonography findings before colonoscopy. If data could not be extracted or calculated from the manuscript with confidence, none were entered. Two reviewers independently abstracted data, and disagreements were resolved by consensus.

Statistical Analysis

Pooled sensitivities and specificities on a per-patient basis were combined and weighted according to sample size. Confidence intervals for each study were calculated by using exact binomial methods in a random-effects model. We focused our analysis on per-patient data because this is the most important perspective for a screening test, whereas per-polyp data emphasize the ability of CT colonography to find colonic lesions. That is, the latter analysis assesses the performance of the technology rather than its utility as a screening tool. Heterogeneity was assessed by using the I2 statistic (37). The I2 statistic provides an estimate of the amount of variance due to heterogeneity rather than chance and is based on the traditional measure of variance, the Cochrane Q statistic. Potential threshold effects were assessed by using the Spearman statistic and by creating receiver-operating characteristic curves according to the method of Moses and coworkers (38). Heterogeneity was assessed by performing stratified analyses when the potential confounding variable was dichotomous or categorical, by plotting the weighted effect size against the potential confounding variable when that variable was continuous, and by applying meta-regression methods in either case (39). Subgroup analyses were done by year of publication, imaging technique (2-dimensional imaging with 3-dimensional confirmation only when a lesion was noted, 3-dimensional imaging with 2-dimensional confirmation, 2-dimensional imaging with concomitant 3-dimensional imaging, or fly-through technology), collimation width and reconstruction interval (in millimeters), type of scanner (single-detector, multidetector, or mixed), and use of a contrast agent (yes or no). When collimation or reconstruction thickness was given in half-millimeter increments, we rounded the values up to the next whole number. The meta-regression analysis used the restricted maximum likelihood method and was performed by using indicator variables to assess differences among the strata. All analyses were performed with Stata software, version 8.2 (Stata Corp., College Station, Texas).

Our final pool of eligible studies (Appendix Figure) included 33 prospective studies involving 6393 patients that compared CT colonography to the reference standard of colonoscopy or surgery (22, 25, 34, 4069). Studies originated from 7 different countries, but most were done in the United States (64%). The average number of participants in a study was 248 (range, 20 to 1233). The mean age of participants was 61.9 years; 63.6% of participants were male, and 74% were at high risk for colorectal cancer. Sixteen studies used single-detector scanners, 13 used multidetector scanners, and 4 used both single-detector and multidetector scanners. Fifteen studies used 2-dimensional imaging, with 3-dimensional imaging on selected slices at the discretion of the radiologist; 14 studies used dedicated 2-dimensional and 3-dimensional imaging; and 2 studies used fly-through imaging with 2-dimensional reconstruction. The average collimation was 4 mm (range, 1 to 5 mm), and the average reconstruction interval was 1.86 mm (range, 1 to 5 mm). Tables 1 and 2 show detailed information from individual studies.

Table Jump PlaceholderTable 1.  Characteristics of the 33 Included Studies
Table Jump PlaceholderTable 2.  Potential Biases in the 33 Included Studies

Computed tomographic colonography was compared to various reference standards, including standard colonoscopy, segmental unblinded colonoscopy (after each colon segment is examined, the results of CT colonography are revealed to the endoscopist and discrepant segments are reexamined), optimized colonoscopy (in which videotapes of the endoscopy are reviewed in comparison with discrepant CT colonography findings), and surgical findings or results of double-contrast barium enema (when subsequent colonoscopy was not or could not be performed). Several studies used a combination of these reference standards.

Table 2 shows biases that may be present in the studies, as defined by Whiting and colleagues (70). One important source of bias was differences in disease severity or prevalence among studies. Because the baseline risk of the study participants may have been apparent to the investigators, clinical review bias was probably present in many of the studies. In addition, because the reference standards varied not only among studies but among segments from a single patient, bias could result from differential verification of findings or might be considered incorporation bias in some cases. Although most studies did not define observer variability, those that did had a range of κ values. The studies that used consensus readings may not be representative of typical CT image-reading practice and may have increased bias. In several studies, many persons interpreted the images (from CT colonography or colonoscopy), but most studies involved few readers or a single reader. The nature of these studies precluded quantitative comparisons of quality.

Sensitivity of CT Colongraphy

Per-patient sensitivity for CT colonography varied from 21% to 96% (Figure 1). The overall pooled sensitivity for CT colonography was 70% (95% CI, 53% to 87%). Sensitivity increased progressively as polyp size increased: It was 48% (CI, 25% to 70%) (range, 14% to 86%) for detection of polyps smaller than 6 mm, 70% (CI, 55% to 84%) (range, 30% to 95%) for polyps 6 to 9 mm, and 85% (CI, 79% to 91%) (range, 48% to 100%) for polyps larger than 9 mm. Each of these analyses was statistically heterogeneous (P < 0.001 for each), and most of the variance was attributable to between-study heterogeneity. The I2 statistic was 96.7% for polyps smaller than 6 mm, 93.1% for polyps 6 to 9 mm, and 85.2% for polyps larger than 9 mm. Appendix Tables 1 and 2 show data from individual studies.

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Figure 1.
Reported per-patient sensitivities in the included studies, by polyp size.

Summary statistics: For polyps <6 mm, 0.48 (95% CI, 0.25 to 0.70); for polyps 6–9 mm, 0.70 (CI, 0.55 to 0.84); for polyps >9 mm, 0.85 (CI, 0.79 to 0.91).

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Table Jump PlaceholderAppendix Table 1.  Test Performance of Computed Tomographic Colonography, by Per-Patient Analysis
Table Jump PlaceholderAppendix Table 2.  Test Performance of Computed Tomographic Colonography, by Per-Polyp Analysis

We found several potential sources for this heterogeneity. First, studies that used thinner slices for collimation appeared to have better sensitivity, and meta-regression of data from 19 studies suggested that every 1-mm increase in collimation width decreases sensitivity by 4.9% (CI, 0.8% to 7.1%). Second, the 7 studies that used multidetector scanners and that reported overall sensitivity had homogenously high sensitivity (95% [CI, 92% to 99%]; I2= 40%; P > 0.2) (Figure 2). This sensitivity was higher than that in the 9 studies reporting overall sensitivity in which a scanner with a single-detector was used (82% [CI, 76% to 92%]), although the latter results were heterogeneous (I2= 87.1%; P < 0.001). The 10 studies that used 2-dimensional imaging, with confirmation by 3-dimensional imaging only when considered necessary, yielded a sensitivity of 81.9% (CI, 71% to 91%) (I2= 87.5%; P = 0.02), whereas the 6 studies that used standard 2-dimensional imaging and concomitant 3-dimensional imaging had a pooled sensitivity of 91% (CI, 83% to 99%) (I2= 53.1%; P = 0.06) and the 2 studies that used fly-through technology had a pooled sensitivity of 99% (CI, 95% to 100%) (I2= 47.6%; P = 0.17) (Figure 3).

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Figure 2.
Reported per-patient sensitivities in the included studies, by type of scanner.
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Figure 3.
Reported per-patient sensitivities in the included studies by mode of imaging.
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Analysis of year of publication, type of scanner hardware or software, thickness of the reconstruction interval, use of contrast (bowel, intravenous, or none), and patient characteristics (age, sex, and high or average risk) yielded no other source of heterogeneity. We found no evidence of a threshold effect between sensitivity and specificity when the Spearman statistic was calculated or receiver-operating characteristic curves were constructed.

Specificity of CT Colonography

In contrast to the broad range of sensitivities reported, per-patient specificity was more consistent across polyp sizes (Figure 4). Overall, CT colonography was 86% specific (CI, 84% to 88%) (I2= 92.6%; P = 0.001) on the basis of data from 14 studies. Specificity improved as polyp size increased, and the results were homogenous within each strata. Only 4 studies reported specificity for detection of polyps smaller than 6 mm, and the pooled specificity from these studies was 91% (CI, 89% to 95%) (I2= 47.1%; P = 0.15). For polyps 6 to 9 mm in size (6 studies), specificity was 93% (CI, 91% to 95%) (I2= 50%; P = 0.07) and increased to 97% (CI, 96% to 97%) (I2= 41.8%; P > 0.2) for polyps larger than 9 mm (15 studies). Appendix Tables 1 and 2 show data from individual studies.

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Figure 4.
Reported per-patient specificities in the included studies, by polyp size.
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Appendix Figure.
Map of the literature search and selection process.

The QUORUM (Quality of Reporting of Meta-Analyses) guidelines for reporting of meta-analyses were used. CRC = colorectal cancer; CT = computed tomographic.

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We found that CT colonography is highly specific, particularly for polyps greater than 9 mm in size. However, the reported sensitivities for CT colonography vary widely, even for larger polyps. Before any screening method can be recommended for general use, it must be demonstrated to be highly and consistently sensitive in a variety of settings. The inability of our meta-analysis to clearly explain why the reported sensitivities vary so widely suggests that CT colonography needs further refinement before it can be recommended for general use in screening for colorectal cancer.

Our analysis revealed some factors that account for the wide range of sensitivities. First, scanners that used thinner collimation had higher sensitivity. Every 1-mm increase in collimation width decreased the subsequent sensitivities by almost 5%. That is, if scanners with 1-mm slices had 98% sensitivity, increasing the collimation width to 2 mm would decrease sensitivity to 93%. Second, scanners that used multiple detectors rather than single detectors were more sensitive. Finally, the mode of imaging also appeared to be important: The more recently developed fly-through technology had a sensitivity of 99%. However, this latter finding must be interpreted with caution because it is based on data from only 2 studies and considerable heterogeneity was found for the other types of imaging used. These results suggest that CT colonography is promising as a screening test for colorectal cancer. Before it is put into general use, however, it must be shown to be reliably sensitive and questions about the optimal technological characteristics of the technique must be settled. Our results are not definitive, but rather suggestive of avenues of pursuit in refinement of this method.

Our conclusions differ from those of another recent systematic review that favored use of CT colonography (71). That review included data from 14 trials and 1324 patients, compared with the 33 trials and 6393 patients in our analysis. The investigators reported a summary sensitivity of 87% for detection of polyps 6 to 9 mm and 88% for detection of polyps larger than 10 mm, and a specificity of 95% for detection of polyps larger than 10 mm. Their conclusion that “the specificity and sensitivity of CT colonography are high for polyps larger than 10 mm” does not take into account the sources of heterogeneity in the sensitivities reported among the studies that they included. Until new technology, particularly for screening tests, can be demonstrated to be consistently reliable, we believe it cannot be recommended for general use.

Other sources for the wide range in reported sensitivities may exist. Previous reports have implied that the differences in test performance among studies of CT colonography is related to the CT colonography technology used, the type of contrast medium, the mode of imaging, and the expertise of the radiologists reading the images. The available data are sufficient only to suggest that multidetector scanners, mode of imaging, and low collimation width affect test performance. Many other possible sources of false-negative results exist, including limitations in technology and technique, insufficient resolution, poor bowel distention, poor preparation, breath-hold artifacts, misinterpretation of stool or folds, sessile or flat polyps, paired lesions, software limitations, and errors in reading (perceptive errors) (4546, 55, 58, 63, 7275). Whether a study used CT colonography to detect all polyps (including hyperplastic polyps) or adenomas only may also affect test performance, because CT colonography may have a higher sensitivity for detection of adenomas (76). Delineation of these possible sources of heterogeneity requires a more sensitive technique than meta-analysis. We abstracted information on these study characteristics, but our ability to discriminate whether any of these is the source of heterogeneity is limited. In addition, we could not evaluate such factors as the expertise of the radiologists reading the CT colonography scans. Our findings cannot be taken to mean that none of these other variables are the source of heterogeneity, only that the current data do not allow us to clearly demonstrate that one of these characteristics is the explanation.

Our analysis has limitations. First, 18 of the studies used colonoscopy as the gold standard, yet colonoscopy may miss more than 10% of small polyps, up to 10% of large polyps, and up to 5% of colorectal cancers (6468). Eleven studies used segmental unblinded colonoscopy or optimized colonoscopy so that CT colonography and augmented colonoscopy could be used in tandem, to maximize overall detection of lesions. However, even these methods do not ensure that each segment of the colon is examined multiple times, so that no lesion is missed by either method. Studies that used segmental unblinded colonoscopy (in which results from CT colonography are revealed after the endoscopist has examined each colonic segment) or optimized colonoscopy (in which video images from colonoscopy are reviewed for discrepant results) demonstrated that CT colonography found polyps (and several tumors or masses) that were missed on blinded colonoscopy (25, 34, 40, 46). In addition, only 3 studies were designed to evaluate a true screening population: persons who are at average risk for colorectal cancer (Table 2) (25, 41, 64). In 1 of these studies, the rate of false-negative findings of polyps larger than 9 mm was similar to the rate of false-negative results with colonoscopy reported in studies of tandem colonoscopy, although other studies have not shown such favorable results (77).

Second, the power to elucidate sources of heterogeneity is limited by the information reported in each article and by the relatively small number of included articles. Finally, meta-regression using summary covariates for each article has limited accuracy. Finer evaluation of the source of heterogeneity would require procurement of patient-level data.

Computed tomographic colonography is very specific, particularly for detection of polyps larger than 9 mm. In studies that used a multidetector scanner, low collimation, and an optimal mode of imaging, the sensitivity of CT colonography to detect polyps larger than 9 mm was the highest and most consistent. However, results were inconsistent when other technical approaches were used and smaller polyps were present. Acceptable techniques for colorectal cancer screening should have consistently high sensitivity over specificity so that preneoplastic polyps are effectively ruled out in patients with a negative result. Although some studies have reported high sensitivities for CT colonography, the range among all studies is broad (as low as 21% overall, and as low as 48% for polyps greater than 9 mm).

Until the source of this heterogeneity is more clearly explained and CT colonography is demonstrated to be consistently and reliably sensitive, it cannot be recommended for general use. However, the technology shows much promise in this regard. Refinement of CT scanners, improved patient preparations, and evolving software for CT colonography will probably improve diagnostic accuracy. For the time being, CT colonography should be used in research protocols or when other accepted screening methods are not appropriate.

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Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B. et al.  Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. 2004; 291:1713-9. PubMed
 
Fletcher JG, Johnson CD.  Computed tomographic colonography: current and future status for colorectal cancer screening. Semin Roentgenol. 2000; 35:385-93. PubMed
 
Pickhardt PJ.  Virtual colonoscopy [Letter]. JAMA. 2004; 292:431. PubMed
 
Higgins JP, Thompson SG, Deeks JJ, Altman DG.  Measuring inconsistency in meta-analyses. BMJ. 2003; 327:557-60. PubMed
 
Moses LE, Shapiro D, Littenberg B.  Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993; 12:1293-316. PubMed
 
Thompson SG, Sharp SJ.  Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999; 18:2693-708. PubMed
 
Van Gelder RE, Nio CY, Florie J, Bartelsman JF, Snel P, De Jager SW. et al.  Computed tomographic colonography compared with colonoscopy in patients at increased risk for colorectal cancer. Gastroenterology. 2004; 127:41-8. PubMed
 
Macari M, Bini EJ, Jacobs SL, Naik S, Lui YW, Milano A. et al.  Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology. 2004; 230:629-36. PubMed
 
Macari M, Bini EJ, Jacobs SL, Lui YW, Laks S, Milano A. et al.  Significance of missed polyps at CT colonography. AJR Am J Roentgenol. 2004; 183:127-34. PubMed
 
Hoppe H, Netzer P, Spreng A, Quattropani C, Mattich J, Dinkel HP.  Prospective comparison of contrast enhanced CT colonography and conventional colonoscopy for detection of colorectal neoplasms in a single institutional study using second-look colonoscopy with discrepant results. Am J Gastroenterol. 2004; 99:1924-35. PubMed
 
Iannaccone R, Laghi A, Catalano C, Mangiapane F, Piacentini F, Passariello R.  Feasibility of ultra-low-dose multislice CT colonography for the detection of colorectal lesions: preliminary experience. Eur Radiol. 2003; 13:1297-302. PubMed
 
Johnson CD, Harmsen WS, Wilson LA, Maccarty RL, Welch TJ, Ilstrup DM. et al.  Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology. 2003; 125:311-9. PubMed
 
Pineau BC, Paskett ED, Chen GJ, Espeland MA, Phillips K, Han JP. et al.  Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps. Gastroenterology. 2003; 125:304-10. PubMed
 
Taylor SA, Halligan S, Saunders BP, Morley S, Riesewyk C, Atkin W. et al.  Use of multidetector-row CT colonography for detection of colorectal neoplasia in patients referred via the Department of Health “2-Week-wait” initiative. Clin Radiol. 2003; 58:855-61. PubMed
 
Ginnerup Pedersen B, Christiansen TE, Bjerregaard NC, Ljungmann K, Laurberg S.  Colonoscopy and multidetector-array computed-tomographic colonography: detection rates and feasibility. Endoscopy. 2003; 35:736-42. PubMed
 
Yee J, Kumar NN, Hung RK, Akerkar GA, Kumar PR, Wall SD.  Comparison of supine and prone scanning separately and in combination at CT colonography. Radiology. 2003; 226:653-61. PubMed
 
Munikrishnan V, Gillams AR, Lees WR, Vaizey CJ, Boulos PB.  Prospective study comparing multislice CT colonography with colonoscopy in the detection of colorectal cancer and polyps. Dis Colon Rectum. 2003; 46:1384-90. PubMed
 
Laghi A, Iannaccone R, Carbone I, Catalano C, DiGiulio E, Schillaci A. et al.  Detection of colorectal lesions with virtual computed tomographic colonography. Am J Surg. 2002; 183:124-31. PubMed
 
Gluecker T, Dorta G, Keller W, Jornod P, Meuli R, Schnyder P.  Performance of multidetector computed tomography colonography compared with conventional colonoscopy. Gut. 2002; 51:207-11. PubMed
 
Macari M, Bini EJ, Xue X, Milano A, Katz SS, Resnick D. et al.  Colorectal neoplasms: prospective comparison of thin-section low-dose multi-detector row CT colonography and conventional colonoscopy for detection. Radiology. 2002; 224:383-92. PubMed
 
McFarland EG, Pilgram TK, Brink JA, McDermott RA, Santillan CV, Brady PW. et al.  CT colonography: multiobserver diagnostic performance. Radiology. 2002; 225:380-90. PubMed
 
Yee J, Akerkar GA, Hung RK, Steinauer-Gebauer AM, Wall SD, McQuaid KR.  Colorectal neoplasia: performance characteristics of CT colonography for detection in 300 patients. Radiology. 2001; 219:685-92. PubMed
 
Hara AK, Johnson CD, MacCarty RL, Welch TJ, McCollough CH, Harmsen WS.  CT colonography: single- versus multi-detector row imaging. Radiology. 2001; 219:461-5. PubMed
 
Spinzi G, Belloni G, Martegani A, Sangiovanni A, Del Favero C, Minoli G.  Computed tomographic colonography and conventional colonoscopy for colon diseases: a prospective, blinded study. Am J Gastroenterol. 2001; 96:394-400. PubMed
 
Fletcher JG, Johnson CD, Welch TJ, MacCarty RL, Ahlquist DA, Reed JE. et al.  Optimization of CT colonography technique: prospective trial in 180 patients. Radiology. 2000; 216:704-11. PubMed
 
Morrin MM, Farrell RJ, Kruskal JB, Reynolds K, McGee JB, Raptopoulos V.  Utility of intravenously administered contrast material at CT colonography. Radiology. 2000; 217:765-71. PubMed
 
Mendelson RM, Foster NM, Edwards JT, Wood CJ, Rosenberg MS, Forbes GM.  Virtual colonoscopy compared with conventional colonoscopy: a developing technology. Med J Aust. 2000; 173:472-5. PubMed
 
Macari M, Milano A, Lavelle M, Berman P, Megibow AJ.  Comparison of time-efficient CT colonography with two- and three-dimensional colonic evaluation for detecting colorectal polyps. AJR Am J Roentgenol. 2000; 174:1543-9. PubMed
 
Morrin MM, Farrell RJ, Raptopoulos V, McGee JB, Bleday R, Kruskal JB.  Role of virtual computed tomographic colonography in patients with colorectal cancers and obstructing colorectal lesions. Dis Colon Rectum. 2000; 43:303-11. PubMed
 
Fenlon HM, Nunes DP, Schroy PC 3rd, Barish MA, Clarke PD, Ferrucci JT.  A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med. 1999; 341:1496-503. PubMed
 
Rex DK, Vining D, Kopecky KK.  An initial experience with screening for colon polyps using spiral CT with and without CT colography (virtual colonoscopy). Gastrointest Endosc. 1999; 50:309-13. PubMed
 
Dachman AH, Kuniyoshi JK, Boyle CM, Samara Y, Hoffmann KR, Rubin DT. et al.  CT colonography with three-dimensional problem solving for detection of colonic polyps. AJR Am J Roentgenol. 1998; 171:989-95. PubMed
 
Royster AP, Fenlon HM, Clarke PD, Nunes DP, Ferrucci JT.  CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation. AJR Am J Roentgenol. 1997; 169:1237-42. PubMed
 
Hara AK, Johnson CD, Reed JE, Ahlquist DA, Nelson H, MacCarty RL. et al.  Detection of colorectal polyps with CT colography: initial assessment of sensitivity and specificity. Radiology. 1997; 205:59-65. PubMed
 
Rockey DC, Paulson E, Niedzwiecki D, Davis W, Bosworth HB, Sanders L. et al.  Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet. 2005; 365:305-11. PubMed
 
Chung DJ, Huh KC, Choi WJ, Kim JK.  CT colonography using 16-MDCT in the evaluation of colorectal cancer. AJR Am J Roentgenol. 2005; 184:98-103. PubMed
 
Whiting P, Rutjes AW, Reitsma JB, Glas AS, Bossuyt PM, Kleijnen J.  Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med. 2004; 140:189-202. PubMed
 
Sosna J, Morrin MM, Kruskal JB, Lavin PT, Rosen MP, Raptopoulos V.  CT colonography of colorectal polyps: a metaanalysis. AJR Am J Roentgenol. 2003; 181:1593-8. PubMed
 
Taylor SA, Halligan S, Burling D, Morley S, Bassett P, Atkin W. et al.  CT colonography: effect of experience and training on reader performance. Eur Radiol. 2004; 14:1025-33. PubMed
 
Rex DK, Vining D, Kopecky KK.  An initial experience with screening for colon polyps using spiral CT with and without CT colography (virtual colonoscopy). Gastrointest Endosc. 1999; 50:309-13. PubMed
 
Pavone P, Luccichenti G, Cademartiri F.  Improving the results of virtual colonoscopy: what the future will bring. Semin Ultrasound CT MR. 2001; 22:400-2. PubMed
 
Miao YM, Amin Z, Healy J, Burn P, Murugan N, Westaby D. et al.  A prospective single centre study comparing computed tomography pneumocolon against colonoscopy in the detection of colorectal neoplasms. Gut. 2000; 47:832-7. PubMed
 
Pickhardt PJ, Choi JR, Hwang I, Schindler WR.  Nonadenomatous polyps at CT colonography: prevalence, size distribution, and detection rates. Radiology. 2004; 232:784-90. PubMed
 
Rex DK, Cutler CS, Lemmel GT, Rahmani EY, Clark DW, Helper DJ. et al.  Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology. 1997; 112:24-8. PubMed
 

Figures

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Figure 1.
Reported per-patient sensitivities in the included studies, by polyp size.

Summary statistics: For polyps <6 mm, 0.48 (95% CI, 0.25 to 0.70); for polyps 6–9 mm, 0.70 (CI, 0.55 to 0.84); for polyps >9 mm, 0.85 (CI, 0.79 to 0.91).

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Figure 2.
Reported per-patient sensitivities in the included studies, by type of scanner.
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Figure 3.
Reported per-patient sensitivities in the included studies by mode of imaging.
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Figure 4.
Reported per-patient specificities in the included studies, by polyp size.
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Appendix Figure.
Map of the literature search and selection process.

The QUORUM (Quality of Reporting of Meta-Analyses) guidelines for reporting of meta-analyses were used. CRC = colorectal cancer; CT = computed tomographic.

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Tables

Table Jump PlaceholderTable 1.  Characteristics of the 33 Included Studies
Table Jump PlaceholderTable 2.  Potential Biases in the 33 Included Studies
Table Jump PlaceholderAppendix Table 1.  Test Performance of Computed Tomographic Colonography, by Per-Patient Analysis
Table Jump PlaceholderAppendix Table 2.  Test Performance of Computed Tomographic Colonography, by Per-Polyp Analysis

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Scott RG, Edwards JT, Fritschi L, Foster NM, Mendelson RM, Forbes GM.  Community-based screening by colonoscopy or computed tomographic colonography in asymptomatic average-risk subjects. Am J Gastroenterol. 2004; 99:1145-51. PubMed
 
Taylor SA, Halligan S, Saunders BP, Bassett P, Vance M, Bartram CI.  Acceptance by patients of multidetector CT colonography compared with barium enema examinations, flexible sigmoidoscopy, and colonoscopy. AJR Am J Roentgenol. 2003; 181:913-21. PubMed
 
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Ladabaum U, Song K, Fendrick AM.  Colorectal neoplasia screening with virtual colonoscopy: when, at what cost, and with what national impact? Clin Gastroenterol Hepatol. 2004; 2:554-63. PubMed
 
Sonnenberg A, Delco F, Bauerfeind P.  Is virtual colonoscopy a cost-effective option to screen for colorectal cancer? Am J Gastroenterol. 1999; 94:2268-74. PubMed
 
Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B. et al.  Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. 2004; 291:1713-9. PubMed
 
Fletcher JG, Johnson CD.  Computed tomographic colonography: current and future status for colorectal cancer screening. Semin Roentgenol. 2000; 35:385-93. PubMed
 
Pickhardt PJ.  Virtual colonoscopy [Letter]. JAMA. 2004; 292:431. PubMed
 
Higgins JP, Thompson SG, Deeks JJ, Altman DG.  Measuring inconsistency in meta-analyses. BMJ. 2003; 327:557-60. PubMed
 
Moses LE, Shapiro D, Littenberg B.  Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993; 12:1293-316. PubMed
 
Thompson SG, Sharp SJ.  Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999; 18:2693-708. PubMed
 
Van Gelder RE, Nio CY, Florie J, Bartelsman JF, Snel P, De Jager SW. et al.  Computed tomographic colonography compared with colonoscopy in patients at increased risk for colorectal cancer. Gastroenterology. 2004; 127:41-8. PubMed
 
Macari M, Bini EJ, Jacobs SL, Naik S, Lui YW, Milano A. et al.  Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology. 2004; 230:629-36. PubMed
 
Macari M, Bini EJ, Jacobs SL, Lui YW, Laks S, Milano A. et al.  Significance of missed polyps at CT colonography. AJR Am J Roentgenol. 2004; 183:127-34. PubMed
 
Hoppe H, Netzer P, Spreng A, Quattropani C, Mattich J, Dinkel HP.  Prospective comparison of contrast enhanced CT colonography and conventional colonoscopy for detection of colorectal neoplasms in a single institutional study using second-look colonoscopy with discrepant results. Am J Gastroenterol. 2004; 99:1924-35. PubMed
 
Iannaccone R, Laghi A, Catalano C, Mangiapane F, Piacentini F, Passariello R.  Feasibility of ultra-low-dose multislice CT colonography for the detection of colorectal lesions: preliminary experience. Eur Radiol. 2003; 13:1297-302. PubMed
 
Johnson CD, Harmsen WS, Wilson LA, Maccarty RL, Welch TJ, Ilstrup DM. et al.  Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology. 2003; 125:311-9. PubMed
 
Pineau BC, Paskett ED, Chen GJ, Espeland MA, Phillips K, Han JP. et al.  Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps. Gastroenterology. 2003; 125:304-10. PubMed
 
Taylor SA, Halligan S, Saunders BP, Morley S, Riesewyk C, Atkin W. et al.  Use of multidetector-row CT colonography for detection of colorectal neoplasia in patients referred via the Department of Health “2-Week-wait” initiative. Clin Radiol. 2003; 58:855-61. PubMed
 
Ginnerup Pedersen B, Christiansen TE, Bjerregaard NC, Ljungmann K, Laurberg S.  Colonoscopy and multidetector-array computed-tomographic colonography: detection rates and feasibility. Endoscopy. 2003; 35:736-42. PubMed
 
Yee J, Kumar NN, Hung RK, Akerkar GA, Kumar PR, Wall SD.  Comparison of supine and prone scanning separately and in combination at CT colonography. Radiology. 2003; 226:653-61. PubMed
 
Munikrishnan V, Gillams AR, Lees WR, Vaizey CJ, Boulos PB.  Prospective study comparing multislice CT colonography with colonoscopy in the detection of colorectal cancer and polyps. Dis Colon Rectum. 2003; 46:1384-90. PubMed
 
Laghi A, Iannaccone R, Carbone I, Catalano C, DiGiulio E, Schillaci A. et al.  Detection of colorectal lesions with virtual computed tomographic colonography. Am J Surg. 2002; 183:124-31. PubMed
 
Gluecker T, Dorta G, Keller W, Jornod P, Meuli R, Schnyder P.  Performance of multidetector computed tomography colonography compared with conventional colonoscopy. Gut. 2002; 51:207-11. PubMed
 
Macari M, Bini EJ, Xue X, Milano A, Katz SS, Resnick D. et al.  Colorectal neoplasms: prospective comparison of thin-section low-dose multi-detector row CT colonography and conventional colonoscopy for detection. Radiology. 2002; 224:383-92. PubMed
 
McFarland EG, Pilgram TK, Brink JA, McDermott RA, Santillan CV, Brady PW. et al.  CT colonography: multiobserver diagnostic performance. Radiology. 2002; 225:380-90. PubMed
 
Yee J, Akerkar GA, Hung RK, Steinauer-Gebauer AM, Wall SD, McQuaid KR.  Colorectal neoplasia: performance characteristics of CT colonography for detection in 300 patients. Radiology. 2001; 219:685-92. PubMed
 
Hara AK, Johnson CD, MacCarty RL, Welch TJ, McCollough CH, Harmsen WS.  CT colonography: single- versus multi-detector row imaging. Radiology. 2001; 219:461-5. PubMed
 
Spinzi G, Belloni G, Martegani A, Sangiovanni A, Del Favero C, Minoli G.  Computed tomographic colonography and conventional colonoscopy for colon diseases: a prospective, blinded study. Am J Gastroenterol. 2001; 96:394-400. PubMed
 
Fletcher JG, Johnson CD, Welch TJ, MacCarty RL, Ahlquist DA, Reed JE. et al.  Optimization of CT colonography technique: prospective trial in 180 patients. Radiology. 2000; 216:704-11. PubMed
 
Morrin MM, Farrell RJ, Kruskal JB, Reynolds K, McGee JB, Raptopoulos V.  Utility of intravenously administered contrast material at CT colonography. Radiology. 2000; 217:765-71. PubMed
 
Mendelson RM, Foster NM, Edwards JT, Wood CJ, Rosenberg MS, Forbes GM.  Virtual colonoscopy compared with conventional colonoscopy: a developing technology. Med J Aust. 2000; 173:472-5. PubMed
 
Macari M, Milano A, Lavelle M, Berman P, Megibow AJ.  Comparison of time-efficient CT colonography with two- and three-dimensional colonic evaluation for detecting colorectal polyps. AJR Am J Roentgenol. 2000; 174:1543-9. PubMed
 
Morrin MM, Farrell RJ, Raptopoulos V, McGee JB, Bleday R, Kruskal JB.  Role of virtual computed tomographic colonography in patients with colorectal cancers and obstructing colorectal lesions. Dis Colon Rectum. 2000; 43:303-11. PubMed
 
Fenlon HM, Nunes DP, Schroy PC 3rd, Barish MA, Clarke PD, Ferrucci JT.  A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med. 1999; 341:1496-503. PubMed
 
Rex DK, Vining D, Kopecky KK.  An initial experience with screening for colon polyps using spiral CT with and without CT colography (virtual colonoscopy). Gastrointest Endosc. 1999; 50:309-13. PubMed
 
Dachman AH, Kuniyoshi JK, Boyle CM, Samara Y, Hoffmann KR, Rubin DT. et al.  CT colonography with three-dimensional problem solving for detection of colonic polyps. AJR Am J Roentgenol. 1998; 171:989-95. PubMed
 
Royster AP, Fenlon HM, Clarke PD, Nunes DP, Ferrucci JT.  CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation. AJR Am J Roentgenol. 1997; 169:1237-42. PubMed
 
Hara AK, Johnson CD, Reed JE, Ahlquist DA, Nelson H, MacCarty RL. et al.  Detection of colorectal polyps with CT colography: initial assessment of sensitivity and specificity. Radiology. 1997; 205:59-65. PubMed
 
Rockey DC, Paulson E, Niedzwiecki D, Davis W, Bosworth HB, Sanders L. et al.  Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Lancet. 2005; 365:305-11. PubMed
 
Chung DJ, Huh KC, Choi WJ, Kim JK.  CT colonography using 16-MDCT in the evaluation of colorectal cancer. AJR Am J Roentgenol. 2005; 184:98-103. PubMed
 
Whiting P, Rutjes AW, Reitsma JB, Glas AS, Bossuyt PM, Kleijnen J.  Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med. 2004; 140:189-202. PubMed
 
Sosna J, Morrin MM, Kruskal JB, Lavin PT, Rosen MP, Raptopoulos V.  CT colonography of colorectal polyps: a metaanalysis. AJR Am J Roentgenol. 2003; 181:1593-8. PubMed
 
Taylor SA, Halligan S, Burling D, Morley S, Bassett P, Atkin W. et al.  CT colonography: effect of experience and training on reader performance. Eur Radiol. 2004; 14:1025-33. PubMed
 
Rex DK, Vining D, Kopecky KK.  An initial experience with screening for colon polyps using spiral CT with and without CT colography (virtual colonoscopy). Gastrointest Endosc. 1999; 50:309-13. PubMed
 
Pavone P, Luccichenti G, Cademartiri F.  Improving the results of virtual colonoscopy: what the future will bring. Semin Ultrasound CT MR. 2001; 22:400-2. PubMed
 
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Computed Tomographic Colonography- Radiation Risk and Informed Consent
Posted on April 19, 2005
Eric R Frizzell
Walter Reed Army Medical Center
Conflict of Interest: None Declared

TO THE EDITOR:

We read with interest the recent meta-analysis of computed tomographic colonography (CTC) by Mulhall and colleagues. Although we agree that this novel modality holds promise, the radiation risk from potential repeated exams has not yet been well addressed.

Given that small (<5-8 mm) adenomas are common, and their risk of malignancy is low, guidelines have been proposed suggesting that 5-8 mm polyps on CTC be left in place with CTC surveillance in 1-3 year intervals to assess for stability of polyp size. (1) This poses a potential health risk, as a radiation dosage of 8 to 12 mSv, which is the estimated radiation exposure with a single CTC, has been reported to increase the risk of malignancies.(2-4) To date, there has been one publication estimating the life-time risk of malignancy from radiation exposure during CTC, as a single screening test or for surveillance with a risk of radiation related death of between 0.3% and 0.24% with a 3 or 5 year surveillance interval, respectively.(5)

Given this potential risk, it may be important for physicians to accurately inform patients of the risk of ionizing radiation with CTC. While the risk of malignancy from a single CTC is likely low, the risk from repeated surveillance with CTC may not be acceptable for many patients. These risks may be further clarified with studies of the actual growth rate and neoplastic potential of small adenomas versus the actuarial cancer risk from ultra-low dose CTC .(3, 4)

Alternatively, CTC may be envisioned as a preliminary screening tool to identify individuals with large polyps who should be referred for polyp removal and future surveillance colonoscopy. Before CTC is embraced as an accepted standard of care for colorectal cancer screening or surveillance we need to develop better guidelines on its usage, better define the risks from ionizing radiation, and adequately inform patients of the risks of ionizing radiation exposure, ideally through well designed clinical trials. Informed consent for patients undergoing elective CTC for screening, to include the potential risk of radiation related secondary malignancies should be considered.

Eric Frizzell, M.D.

Inku Hwang, M.D.

Walter Reed Army Medical Center

Washington, DC 20307-5001

Disclaimer: The opinions and assertions contained herein are the private views of the authors and are not be to be construed as reflecting the views of the Department of the Army or the Department of Defense

1. Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003;349(23):2191-200. 2. Brenner D, Elliston C, Hall E, Berdon W. Estimated risks of radiation- induced fatal cancer from pediatric CT. AJR Am J Roentgenol. 2001;176(2):289-96. 3. Macari M. Virtual colonoscopy: clinical results. Semin Ultrasound CT MR. 2001;22(5):432-42. 4. van Gelder RE, Venema HW, Florie J, et al. CT colonography: feasibility of substantial dose reduction--comparison of medium to very low doses in identical patients. Radiology. 2004;232(2):611-20. 5. Wise KN. Solid cancer risks from radiation exposure for the Australian population. Australas Phys Eng Sci Med. 2003;26(2):53-62.

Conflict of Interest:

None declared

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Summary for Patients

Accuracy of CT Colonography (Virtual Colonoscopy) for Detecting Polyps

The summary below is from the full report titled “Meta-Analysis: Computed Tomographic Colonography.” It is in the 19 April 2005 issue of Annals of Internal Medicine (volume 142, pages 635-650). The authors are B.P. Mulhall, G.R. Veerappan, and J.L. Jackson.

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