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Background
Virtual endoscopy combines the features of endoscopic viewing and computerized tomography (CT) data to create a virtual image that is artificially generated by a computer. In the evaluation of gastrointestinal cancers, virtual endoscopy has been most commonly used in colorectal carcinomas and to a much lesser extent in gastric carcinomas. The clinical application of virtual endoscopic techniques is also being used with other procedures such as bronchoscopy, gastroscopy, cystoscopy, sinus imaging, virtual angioscopy, and cerebral ventriculography (Oto, 2002; Dykes, 2001).
Virtual Colonoscopy:
Three-dimensional CT colography, or "virtual colonoscopy" combines the use of rapid helical CT with computer software capable of rendering images of the whole colon. Using a conventional workstation and a dynamic display of images, a radiologist conducts virtual examinations of the bowel, simulating the way endoscopists view the colon. Virtual colonoscopy provides a method for processing data that can display computer images of the colon in a more anatomic life-like format and is being promoted by some as a non-invasive screening test for colorectal neoplasia.
Pickhardt et al (2003) reported that CT virtual colonoscopy with the use of a three-dimensional (3-D) approach is an accurate screening method for the detection of colorectal neoplasia in asymptomatic average-risk adults and compares favorably with optical colonoscopy in terms of the detection of clinically relevant lesions. However, in an editorial that accompanied the study by Pickhardt et al, Morrin and LaMont (2003) stated that “if the results of this well-designed study are reproducible on a wider scale, and if the important questions regarding the appropriate size threshold and surveillance of smaller polyps can be resolved, then screening virtual colonoscopy is ready for prime time”.
A study by Cotton et al (2004) reported that the accuracy of CT colonography (virtual colonoscopy) for the detection of colorectal cancer is less reliable than previously thought. CT colonography involves the examination of computer-generated images of the colon constructed from data obtained from an abdominal computed tomographic examination. Several studies have suggested a high degree of sensitivity for CT colonography; however, those results were obtained at single, specialized centers. Cotton reported on a new study that was designed to evaluate the accuracy of CT colonography in routine practice at 9 major hospital centers.
In this study, researchers assessed the accuracy of CT colonography in 615 patients aged 50 years or older who were referred for routine, clinically indicated colonoscopy (Cotton et al, 2004). Colonoscopy was performed within 2 hours of the colonography and results were compared. The sensitivity of CT colonography for detecting 1 or more lesions sized at least 6 mm was 39 % and for lesions sized at least 10 mm, it was 55 %. These results were significantly lower than those for conventional colonoscopy, with sensitivities of 99 % and 100 %, respectively. CT colonography missed 2 of 8 cancers. The accuracy of CT colonography varied considerably between centers. At the 1 center that had "substantial" prior experience with CT colonography, the sensitivity was 82 % for lesions of 6 mm or more. Sensitivity at all of the other centers combined was 24 %, with no improvement in accuracy as the number of cases at each center was increased. Preference questionnaires after both procedures were performed showed that 46 % of the patients preferred CT colonography versus 41 % who preferred conventional colonoscopy.
The authors stated that "even if the results of CT colonography continue to be good in the hands of experts, it has yet to be proven that this expertise can be taught and disseminated reliably into daily practice". The authors concluded that CT colonography is not yet ready for widespread clinical application; techniques and training need to be improved.
This is in agreement with the update of the clinical guidelines on colorectal cancer screening and surveillance that were prepared by a panel convened by the U.S. Agency for Health Care Policy and Research and published in 1997 under the sponsorship of a consortium of gastroenterology societies (Winawer et al, 2003). It stated that promising new screening tests (virtual colonoscopy and tests for altered DNA in stool) are in development but are not yet ready for use outside of research studies.
In addition, the American College of Gastroenterology does not recommend virtual colonoscopy for screening colorectal cancers. It states that more research is needed to verify the validity and generalizeability of the 3-D approach to polyp detection. It will also be necessary to develop recommendations for training in CT colonography as well as requirements of hardware and software systems and specification of methods for technical performance. Systems that allow same-day polypectomy on patients with positive CT colonography studies are not yet widely available (Rex, 2004)
An assessment prepared for the Ontario Ministry of Health and Long-Term Care (2003) found that, "[a]lthough [CT colonography] offers the potential advantage of being less invasive than colonoscopy and has the ability to image the entire colon, it lacks the necessary sensitivity required for screening." The assessment noted that, in addition, unlike standard colonoscopy, CT colonography (CTC) "offers no therapy that can be applied once an abnormality is detected"; standard colonoscopy is necessary to resect lesions detected by CT colonography. The assessment concluded that "[w]ith the limited sensitivity and specificity of CTC relative to colonoscopy, together with the lack of therapeutic intervention, this method of screening may result in inconvenience, cost, and complications of both tests" and that "[b]ased on the current evidence, CTC cannot be proposed for population-based colorectal cancer screening." The assessment explained that "[p]atients with colonic symptoms or a personal/family history of polyps will benefit more in several ways if they undergo colonoscopy including excision of premalignant polyps."
The assessment concluded, however, that CT colonography can be considered for diagnostic purposes in patients in whom performing colonoscopy is clinically contraindicated or for those patients who had incomplete colonoscopy because of stenosis or obstruction of the colon (Ontario Ministry of Health and Long-Term Care, 2003). In support of this conclusion, the assessment reasoned that that CT colonography is able to visualize the entire colon in most patients with occlusive tumors or stenosing lesions, and that CT colonography may be preferable to barium enema in terms of the extent of the proximal colon that can be visualized and in terms of detecting extracolonic lesions.
An American Gastroenterological Association (AGA) Task Force Report (Van Dam et al, 2004) concluded that, although virtual colonoscopy has significant promise, the technology is still evolving and results of virtual colonoscopy for screening are highly variable.
According to the University of Michigan Health System’s guidelines on adult preventive health care (2004), recommended methods for colon cancer screening include fecal occult-blood testing, flexible sigmoidoscopy or colonoscopy. Winawer (2005) noted that “several options are now available for screening of colorectal cancer, and the emerging technology of stool DNA testing and virtual colonoscopy shows promise …There are quality-control issues at every step.” van Gelder et al (2005) stated that “despite a growing body of evidence, it remains uncertain to what extent patient acceptance, radiation issues, flat lesions, and extracolonic findings will be a stumbling block to using CT colonography for colorectal cancer screening.”
An assessment by the Danish Centre for Health Technology Assessment (DACEHTA, 2005) concluded that "[d]espite the potential economic benefits, CT colonography should not replace colonoscopy as the primary diagnostic method in a Danish outpatient colonoscopy population. Such a strategy requires further research at a few centres before widespread use in routine clinical practice."
Some reports of virtual colonoscopy demonstrate sensitivity similar to that of conventional colonoscopy for polyps 5 mm or larger (Pineau et al, 2003; Paonessa et al, 2005). However, in a meta-analysis on CT colonography, Mulhall et al (2005) concluded that “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”. In an editorial that accompanied the article by Mulhall et al, Imperiale (2005) stated that “until we understand more about the factors -- both within and among institutions -- that are responsible for the varying sensitivity of CT colonography, we should not recommend it as a screening test.” There are also concerns that virtual colonoscopy can not reliably detect flat lesions, and that flat lesions are more common than previously thought (Soetikno et al, 2008).
An assessment prepared for the Swedish Council on Health Technology Assessment (SBU, 2004) summarized current evidence for CT colonography: “Most studies have shown that CT colonography offers high diagnostic reliability for malignant tumors and polyps 10 mm or larger, inconsistent diagnostic reliability for changes of 5 to 9 mm, and insufficient diagnostic reliability for changes smaller than 5 mm. Some studies, however, have shown unacceptable diagnostic reliability even for malignant tumors and polyps larger than 10 mm.” The assessment stated that CT colonography may compare favorably to barium enema. The assessment explained: “The extent to which CT colonography can replace double-contrast barium enema in patients with disease symptoms has not been completely studied since CT colonography almost exclusively has been compared to colonoscopy. However, the diagnostic reliability of CT colonography compared to colonoscopy appears to be at least equal to the diagnostic reliability of double contrast barium enema compared to colonoscopy.” The assessment explained that one advantage of CT colonography is that, in findings of colon tumors, CT colonography can, in the same examination, also provide information on changes in adjacent tissues and metastases in the lymph nodes and liver. The assessment stated that another advantage of CT colonography is that patients usually experience less discomfort and pain with CT colonography than with conventional colonoscopy and double-contrast barium enema. The assessment noted, however, that it generally is not the examination per se that causes the most discomfort for the patient, but the pre-examination procedure, i.e., the use of laxatives, that is similar in all of the methods of examining the colon.
On the other hand, the National Institute for Health and Clinical Excellence (2005) stated that "Current evidence on the safety and efficacy of computed tomographic colonoscopy (virtual colonoscopy) appears adequate to support the use of this procedure provided that the normal arrangements are in place for consent, audit and clinical governance."
Guidelines on evaluation of patients with lower gastrointestinal bleeding from the American Society for Gastrointestinal Endoscopy (2005) state that "[v]irtual colonoscopy or computed tomographic (CT) colonography also can be used to rule out a proximal colonic lesion in patients who have had an incomplete colonoscopy."
Virtual colonoscopies should only be performed at centers with an appropriate generation of CT scan -- a minimum 4 detector CT scanner; collimation of 3 mm or less, overlapping sections at an interval that is 2/3 or less of the collimation, and scan times should be 30 seconds or less in order to minimize respiratory motion.
Scholmerich (2003) stated that virtual colonoscopy using CT or MRI does not appear to offer much help in the diagnosis of inflammatory bowel disease (Crohn’s disease).
The American Cancer Society guidelines on colorectal cancer screening recommend several methods of screening, including virtual colonoscopy, based in part upon the presumption that the availability of multiple methods of screening will improve compliance (Levin et al, 2008). Colorectal cancer screening guidelines from the American Cancer Society recommend CT colonography (virtual colonoscopy) performed every 5 years as an acceptable alternative to optical colonoscopy performed every 10 years for screening of average-risk persons. However, there are no studies demonstrating that virtual colonoscopy does, in fact, increase compliance. Virtual colonoscopy is similar to optical colonoscoppy in that it requires completion of a pre-procedure cathartic regimen. If a lesion in found on virtual colonoscopy, the patient must return another day and complete another cathartic regimen for an optical colonoscopy to remove the lesion. By contrast, optical colonoscopy allows for identification and removal of a lesion in 1 procedure.
An assessment of CT colonography prepared by the Institute for Clinical and Economic Review (ICER) for the Washington State Health Care Authority (Scherer et al, 2008) found that, in direct comparison to optical colonoscopy, CT colonography every 10 years is substantially more expensive and marginally less effective in preventing cases of cancer (47 versus 52 in a lifetime cohort of 1,000 individuals) and cancer deaths (24 versus 26). The investigators reported that only 1 CT colonography screening strategy is as effective as optical colonoscopy every 10 years, and that strategy is to perform CT colonography every 5 years with colonoscopy referral for polyps greater than 6 mm. For this strategy, the cost per life-year gained for CT colonography versus optical colonoscopy was $630,700. The assessment noted that the preponderance of the data suggests that, among patients who experienced both CTC and colonoscopy, a small majority preferred CT colonoscopy. The assessment stated that it is unclear whether preferences elicited among some patients for CTC would result in a larger number of unscreened individuals in a population being screened. The review found no studies examining whether the availability of CT colonography results in increased numbers of individuals being screened within a population.
ICER (2008) prepared an update to their assessment after publication of the National CT Colonography Trial, conducted by the American College of Radiology Imaging Network (ACRIN) (citing Johnson, et al., 2008). In the ACRIN study, the largest multicenter study of CTC published to date, over 2,500 asymptomatic patients were scheduled for optical colonoscopy at 15 clinical sites across the U.S. Patients first received CTC, followed by same-day colonoscopy in most cases. CTC sensitivity and specificity for detecting polyps ≥ 10 mm in size were 90% and 86%. Sensitivity and specificity for polyps ≥ 6 mm were somewhat lower (78%, 88%). The range of sensitivity across individual radiologist interpreters was 67%-100%. Extracolonic findings were reported in 66% of the participants; 16% were deemed to require either additional evaluation or urgent care. No data on the subsequent outcomes or costs due to incidental findings were reported. The ICER update noted that a key new piece of evidence given in this study is the relatively broad range of performance across radiologists, all of whom received special training in CTC evaluation and/or had performed more than 500 interpretations. The ICER updated stated that decision-makers should consider whether the variability in performance demonstrated in the ACRIN study suggests that the actual performance in the general community is likely to be lower than that reported in this study. The ICER assessment stated that other questions remain unanswered, such as the effects of a cumulative radiation dose from CTC tests every 5-10 years as well as the impact of extracolonic findings from CTC on net health benefits and cost-effectiveness within the population.
Rex and colleagues (2009) updated the American College of Gastroenterology (ACG)'s recommendation on colorectal cancer (CRC) screening. The CRC screening tests are now grouped into cancer prevention tests and cancer detection tests. Colonoscopy every 10 years, beginning at age 50, remains the preferred CRC screening strategy. It is recognized that colonoscopy is not available in every clinical setting because of economic limitations. It is also realized that not all eligible persons are willing to undergo colonoscopy for screening purposes. In these cases, patients should be offered an alternative CRC prevention test (flexible sigmoidoscopy every 5 to10 years, or a CT colonography every 5 years) or a cancer detection test (fecal immunochemical test for blood, FIT).
The U.S. Preventive Services Task Force (2008) provided the following statements on screening for CRC: (i) it recommends screening for CRC using fecal occult blood testing, sigmoidoscopy, or colonoscopy in adults, beginning at age 50 years and continuing until age 75 years. The risks and benefits of these screening methods vary (A recommendation), (ii) it recommends against routine screening for CRC in adults 76 to 85 years of age. There may be considerations that support CRC screening in an individual patient (C recommendation), (iii) it recommends against screening for CRC in adults older than age 85 years (D recommendation); and (iv) it concludes that the evidence is insufficient to assess the benefits and harms of CT colonography and fecal DNA testing as screening modalities for CRC.
The Canadian Agency for Drugs and Technologies in Health's technology assesssment on CTC for CRC screening in an average risk screening population (Ho et al, 2008) concluded that (i) CTC and colonoscopy have comparable sensitivity and specificity for detecting polyps that are 10 mm or greater and for detecting CRC, and CTC has lower sensitivity and specificity than colonoscopy for detecting polyps that are smaller than 10 mm, and (ii) colonoscopy is more cost-effective than CTC. Colonoscopy leads to reduced disease burden at less cost than CTC. Compared with no screening, colonoscopy is likely to reduce disease burden at additional cost and may be perceived as cost-effective. However, increased screening with colonoscopy requires additional infra-structure. If colonoscopy is not available, CTC is the next most cost-effective strategy for detecting CRC.
An assessment by the Ontario Ministry of Health and Long-Term Care (2009) concluded that magnetic resonance colonography (MRC) and CTC with 16-slice or 64-slice scanners have equal sensitivity for the detection of colorectal cancer, as well as for the detection of large and medium sized polyps; however, MRC does not carry the associated risks of ionizing radiation. The assessment found that MRC and CTC with 16-slice or 64-slice scanners can reliably detect most colorectal cancers and large colorectal polyps; however, about 20 % of medium-sized colorectal polyps will be missed by both techniques. The report found, however, that none of the techniques can reliably detect small polyps and MRC has a much lower sensitivity for the detection of small polyps compared with CTC.
An assessment by the French National Authority for Health (Tessier-Vetzel, et al., 2010) concluded that colonoscopy should be the first line screening test for colorectal cancer. They concluded that CT colonography does not meet the requirements for a first-line screening test for persons at average or high risk for colorectal cancer, but suggested that it may be indicated in cases where comorbidities jeopardize the safety of colonoscopy. They stated that colonoscopy is the only acceptable method for screening persons at very high risk for colorectal cancer.
Graser et al (2013) examined if MRC can be used to screen for colorectal adenomas and cancers. These investigators analyzed data from 286 asymptomatic adults (40 to 82 years old) who underwent 3 Tesla MRC and colonoscopic examinations on the same day. Fecal occult-blood testing (FOBT) was performed before bowel preparation. Colonoscopists were initially blinded to the findings on MRC and unblinded after withdrawal from the respective segments. Sensitivities for adenoma and per-patient sensitivities and specificities were calculated based on the unblinded results of colonoscopy. These researchers detected 133 adenomas and 2 cancers in 86 patients; 37 adenomas were greater than or equal to 6 mm, and 20 adenomas were advanced. Sensitivities of MRC and colonoscopy for adenomas greater than or equal to 6 mm were 78.4 % (95 % confidence interval [CI]: 61.8 to 90.2) and 97.3 % (95 % CI: 85.8 to 99.9); for advanced adenomas these values were 75 % (95 % CI: 50.9 to 91.3) and 100 % (95 % CI: 83.2 to 100.0), respectively. Magnetic resonance colonography identified 87.1 % (95 % CI: 70.2 to 96.4), colonoscopy 96.8 % (95 % CI: 83.3 to 99.9), and FOBT 10.0 % (95 % CI: 2.1 to 26.5) of individuals with adenomas greater than or equal to 6 mm and 83.8 % (95 % CI: 58.6 to 96.4), 100 % (95 % CI: 81.5 to 100.0), and 17.6 % (95 % CI: 3.8 to 43.4) of individuals with advanced neoplasia. Specificities of MRC, colonoscopy, and FOBT for individuals with adenomas greater than or equal to 6 mm were 95.3 % (95 % CI: 91.9 to 97.5), 96.9 % (95 % CI: 93.9 to 98.6), and 91.8 % (95 % CI: 87.6 to 94.9), respectively. The authors concluded that 3 Tesla MRC detects colorectal adenomas greater than or equal to 6 mm and advanced neoplasia with high levels of sensitivity and specificity. Although MRC detects colorectal neoplasia with lower levels of sensitivity than colonoscopy, it strongly outperforms one-time FOBT.
The California Technology Assessment Forum (CTAF) concluded that virtual colonoscopy for colorectal cancer screening does not meet CTAF criteria (Walsh, 2009). The CTAF assessment found that the recent results of the ACRIN [American College of Radiology Imaging Network] trial [citing Johnson et al, 2008] have shown that virtual colonoscopy has diagnostic accuracy comparable to that of optical colonoscopy and importantly that this level of diagnostic accuracy can be achieved in the “real world.” The CTAF assessment explained that the ACRIN study was done in multiple institutions, using multiple bowel preparations and colonoscopy procedures in place at the participating institutions, thereby increasing its generalizability. The CTAF assessment noted, however, that the radiologists were highly trained in how to interpret virtual colonoscopy results. The CTAF assessment stated that, despite the exciting results of the ACRIN trial, several important questions remain before virtual colonoscopy screening can be recommended for widespread use. One unanswered question is how well would virtual colonoscopy screening perform in a setting where the radiologists were not so highly trained. A second unanswered question is what is the clinical impact of the possible harms of the procedure, including radiation risk (especially with virtual colonoscopy repeated periodically) and the high incidence of extra-colonic findings. The CTAF assessment concluded that, despite its diagnostic accuracy, because the impact of the potential harms is not currently known, virtual colonoscopy "is not currently recommended for screening asymptomatic individuals for CRC."
On May 12, 2009, the Centers for Medicare & Medicaid Services (CMS) issued a final coverage determination that refused coverage of CTC for colorectal screening. It stated that the evidence is inadequate to conclude that CTC is an appropriate colorectal cancer screening test.
A number of studies have reported on individuals expressed preferences for colorectal cancer screening with CTC versus optical colonoscopy (see, e.g., Hawley et a., 2008; Moawad, et al, 2010). It is unclear whether preferences elicited among some patients for CTC would result in a larger number of unscreened individuals in a population being screened.
A randomized controlled trial from the Netherlands (Stoop, et al., 2012) found that the diagnostic yield for advanced neoplasia was similar for CT colonography and colonoscopy. Participation in colorectal cancer screening with CT colonography was significantly better than with colonoscopy, but colonoscopy identified significantly more advanced neoplasia per 100 participants than did CT colonography.The randomized controlled clinical trial (de Wijkerslooth, et al., 2012) also found that people invited to screening via CT colonography perceived the procedure (ahead of it) as less burdensome than colonoscopy. After actually having undergone the procedure, CT colonography screenees perceived it as having been more burdensome than colonoscopy screenees. Intended participation in a future round of screening was comparable. Rex (2012) commented on these studies, noting that the generalizability of these results to the U.S. population is uncertain because the use of screening colonoscopy is much more widespread in the U.S. than Europe. Nevertheless, these findings suggest that, over time, the reputation of CT colonography from the standpoint of patient burden and acceptability, even using the noncathartic approach, would likely diminish relative to colonoscopy (Rex, 2012). In addition, these results do not take into account that patients had no knowledge of test performance, which was substantially better for colonoscopy than CT colonography. Rex stated that understanding test performance characteristics is bound to influence the relative acceptability of the two tests.
Several studies have compared the results of CTC in the elderly, finding performance similar to CTC in the nonelderly population (Johnson et al, 2012; Cash et al, 2012; Macari et al, 2011; Kim et al, 2010).
Keegan et al (2010) evaluated the ability of CTC to perform at high levels of sensitivity and specificity for CRC screening in an asymptomatic population. Searches were done in PubMed, Cochrane Library, TRIP Database, and UpToDate, utilizing the terms CT colonography, colonoscopy, virtual colonoscopy, screening, and colon cancer. In PubMed the following limits and terms were used: published in the last 5 years, humans, meta-analysis, randomized controlled trial, and English. A meta-analysis by Mulhall et al revealed 2 studies meeting inclusion/exclusion criteria: Pickhardt et al and Macari et al. Searching Pickhardt et al through "related articles" in PubMed yielded the Wessling et al study. The authors concluded that CTC can achieve high accuracy, but only under specific conditions using multi-detector CT scanners, primary 3-D data interpretation, well-prepared patients, collimation of less than or equal to 1.25 mm, and data interpretation by an experienced radiologist. They stated that cost-effectiveness and compliance in the general population, as well as radiation exposure and follow-up requirements with colonography for CRC screening, need further study.
Rockey (2010) stated that CTC has received considerable attention in the last decade as a colon-imaging tool. The technique has also been proposed as a potential primary colon cancer-screening method in the United States. The accuracy of the technique for the detection of large lesions seems to be high, perhaps in the range of colonoscopy. Overall, the field is rapidly evolving. Available data suggest that CTC, although a viable colon cancer screening modality in the United States, is not ready for widespread implementation, largely because of the lack of standards for training and reading and the limited number of skilled readers.
Hanly et al (2012) systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening. PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered. A total of 16 studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or micro-simulation (n = 2) models were used. Eleven considered direct medical costs only; 5 included indirect costs. Fourteen compared CTC with no screening; 14 compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; and 7 considered complications. Computed tomography colonography appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings. The authors concluded that evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. They stated that future studies should (i) compare CTC with currently favored tests, especially fecal immunochemical tests; (ii) consider extra-colonic findings; and (iii) conduct comprehensive sensitivity analyses.
Kolligs (2012) stated that the highest evidence for all screening tests has been demonstrated for guaiac-based fecal occult blood testing. Colonoscopy is a diagnostic and therapeutic tool and it serves as the reference standard for other tests in clinical studies. Fecal immunochemical tests have a higher sensitivity than guaiac-based tests. Several novel techniques are under development and could be adopted by screening programs in the future. Next to colonoscopy, CTC and colon capsule endoscopy have the highest sensitivity for colorectal neoplasia. Molecular tests that are based on the detection of genetic and epigenetic changes of DNA released by the tumor into feces or blood have a high potential and could potentially replace occult blood tests in the future. The author concluded that colonoscopy is the primary instrument for screening for colorectal neoplasia. Fecal occult blood testing should only be performed if colonoscopy is denied and CTC has not yet been approved for screening in Germany.
An assessment by the Ludwig Boltzmann Institut (Patera, et al., 2012) of colorectal cancer screening concluded that "[l]arge prospective multi-center trials are warranted to collect data on CTcolonography as a candidate for first-line screening test in the average risk population."
The American College of Physicians’ clinical guidelines on “Screening for colorectal cancer” (Qaseem et al, 2012) stated that “Computed tomography colonography is an option for screening in average-risk patients older than 50 years and is supported by some guidelines. However, the U.S. Preventive Services Task Force (USPSTF) found that the evidence is insufficient to assess the benefits and harms of CTC”.
Members of an advisory panel convened by the U.S. Food and Drug Administration (FDA, 2013) were in agreement that radiation patients receive in CT colonography is not likely to be significant. Some FDA panelists expressed concern that CT colonography is less sensitive in smaller polyps less than 6 millimeters. Others noted that CT colonography was not able to reliably detect “flat” or serrated polyps, which may contribute to 30% of all colon cancers. Panelists also expressed concern that untrained professionals would be reading the CTC and missing possible lesions that need follow-up. The benefits and harms of detection of extracolonic findings were also discussed. Panelists suggested that CT colonography may provide a useful option for patients who have contraindications to sedation or those on anticoagulants.
Virtual Upper Endoscopy:
Virtual upper gastrointestinal (GI) endoscopy is a minimally invasive test that utilizes 3-D CT to simulate conventional upper endoscopy images. Potential clinical applications include the evaluation of early gastric carcinoma, advanced gastric carcinoma, leiomyoma, lymphoma, and benign ulcer. For dedicated imaging of the stomach, an oral contrast agent (e.g., water) is administered to opacify and distend the stomach and GI tract and an intravenous contrast agent is used (e.g., Omnipaque 350) for complete evaluation.
Virtual upper GI endoscopy has not been studied as extensively as virtual colonoscopy. A limited number of studies have been published and most of these studies have been conducted outside the United States involving small numbers of patients. Early reports of 3-D imaging of the stomach by spiral CT were limited to shaded-surface display (Ogata et al, 1999). However, the development of multidetector row scanners has improved the visualization of subtle tumors by allowing thinner collimation. The detection rate of gastric lesions using virtual GI endoscopy has been reported to be between 73 % to 96.7 % in early gastric cancer and between 90 % to 100 % in advanced gastric cancer (Kim et al, 2001; Bhandari et al, 2004). The overall accuracy, sensitivity, and specificity for endoscopic ultrasound and 3-D multi-detector row CT in the pre-operative determination of depth of invasion of gastric cancer (T stage) have been reported to be 87.5 %, 82.4 %, and 96 %; and 83.3 %, 69.1 %, and 94.4 %, respectively. The accuracy, sensitivity, and specificity of endoscopic ultrasound and 3-D multi-detector row CT for lymph node staging were reported to be 79.1 %, 57 %, and 89.5 %; and 75 %, 57.4 %, and 89.3 %, respectively (Bhandari et al, 2004).
In a prospective study, Kim et al (2005) evaluated the accuracy of multi-detector row CT gastrography for the pre-operative staging of gastric cancer, with pathologic and surgical results as the reference standard. A total of 106 patients with endoscopically proved gastric cancer underwent unenhanced and contrast material-enhanced multi-detector row CT gastrography, with effervescent granules used as oral contrast material. Gastric cancer was detected in 92 (87 %) of 106 patients with transverse CT imaging and in 104 (98 %) with volumetric CT imaging. The overall accuracy of the tumor staging was 77 % with transverse CT imaging and 84 % with volumetric CT imaging (p < 0.001). The overall accuracy for lymph node staging was 62 % with transverse CT imaging and 64 % with volumetric CT imaging (p = 0.057). For staging of metastases, there was no difference between transverse and volumetric CT imaging (86 % for both) (p > 0.99). The authors concluded that multi-detector row CT gastrography with multi-planar reformation and virtual endoscopy, compared with transverse CT imaging, can improve the accuracy of preoperative staging of gastric cancer. This difference was significant for tumor staging but not for the staging of lymph nodes and metastases.
A prospective study of the pre-operative assessment of gastric cancer tumors using 32-multi-detector row CT was carried out by Kikuchi et al (2006) on patients (n = 74) with adenocarcinoma of the stomach (T1 tumors, n = 38; T2 and T3 tumors, n = 36). In 35 (47 %) out of the 74 patients, the primary lesions could be detected on 2-D images obtained by CT. In these patients, virtual endoscopic images of these tumors could be created. A total of 27 advanced cancer tumors (75 %) were assessed based on 2-D CT images and 27 larger tumors (greater than 40 mm) (69 %) were assessed based on 2-D CT images. Significant differences were found with respect to depth of tumor (p < 0.0001) and tumor size (p < 0.0001) between tumors that could or could not be assessed on multi-detector CT. The authors concluded that future studies are required to fully explore the ability of multi-detector CT to assess tumor volume in advanced gastric cancer cases and to determine the optimum application of this approach.
In a prospective study, Mazzeo et al (2004) assessed the diagnostic capabilities of multi-detector CT in various esophageal pathologic conditions. A total of 33 patients underwent a multi-detector CT study after esophageal distention by means of effervescent powder administered after induction of pharmacologic esophageal hypotonia. All acquired images were post-processed with 2-D and 3-D software tools. The CT data were compared with the results of conventional radiology (n = 33), endoscopy (n = 28), endoscopy ultrasonography (n = 14), or surgery (n = 14). Follow-up ranged between 4 and 15 months. Final diagnoses were leiomyoma (n = 6), squamous cell carcinoma (n = 6), adenocarcinoma (n = 4), esophageal infiltration by thyroid cancer (n = 1), benign polyposis (n = 2), chronic esophagitis (n = 5), post-sclerotherapy stenosis (n = 1), and no abnormalities (n = 7). Pathologic wall thickening was observed in 25 of 33 cases (76 %), with values ranging between 3.6 and 36 mm (mean, 9.6 mm). Spiral CT demonstrated 21 true-positive cases, and 7 true-negative cases. There were 4 false-negative cases and 1 false-positive case. Sensitivity was 84 %, specificity was 87 %, diagnostic accuracy was 85 %, positive-predictive value was 95 %, and negative-predictive value was 64 %. The authors concluded that evaluation of the esophagus with multi-detector CT is a promising technique and easy to use, allowing panoramic exploration, virtual endoluminal visualization, accurate longitudinal and axial evaluations, and simultaneous evaluation of T (tumor penetration) and N (lymph node involvement) parameters.
The first virtual gastroscopy study in North American patients assessed the feasibility of performing virtual gastroscopy on 10 patients with no reported GI abnormalities. The authors stated that the anatomy of the stomach including the lumen, the cardia, the pylorus, gastric folds and the incisura angularis were well-visualized using 3-D spiral CT. It was not possible to visualize the esophagus by virtual endoscopy because of difficulties keeping the lumen patent long enough to provide accurate imaging. The authors concluded that further development is needed before virtual gastroscopy can be considered for clinical application (Ezzeddine et al, 2006).
Virtual gastroscopy is also being evaluated to assess the gastric mucosa in patients who have undergone laparoscopic Roux-en-Y gastric bypass. One small case series reported promising results (Alva et al, 2008).
Conventional upper GI endoscopy provides direct visualization of the mucosa, permits evaluation of color changes that may be indicative of pathology, and suspicious lesions can be biopsied and the tissue sample evaluated histologically. While virtual upper GI endoscopy using CT is a promising method for the detection and evaluation of upper GI lesions, randomized controlled studies comparing it to conventional upper GI endoscopy are needed to determine its clinical value.
Appendix
Virtual colonoscopies should only be performed at centers with an appropriate generation of multi-detector CT scan -- a minimum 4 detector CT scanner; collimation of 3 mm or less, overlapping sections at an interval that is 2/3 or less of the collimation, and scan times should be 30 seconds or less in order to minimize respiratory motion (Taskar et al, 1995; Scherer et al, 2008). In addition, scans should be read by trained readers by virtue of having read least 30 CT scans (Halligan et al, 2005; ACR, 2006).
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