Virtual colonoscopy

Author : Dr Don Rockey Duke University Medical Center Durham

2008-07-28

Polyp with virtual colonoscopy. Source: National Cancer Institute

Introduction

    Colon cancer is one of the most common cancers in the U.S. and the world; in the U.S. colon cancer accounts for approximately 150,000 new cases and 50,000 deaths/year.  Colon cancer is largely preventable, since it goes through predictable progression from early polyp to invasive cancer.  Therefore, screening is essential.  A number of screening strategies have been proposed (see the “Colon Cancer Screening” knoll).  Each of the screening strategies currently in use has advantages and disadvantages.  For example, screening stool for occult blood (“Fecal occult blood testing”) is noninvasive and inexpensive, but is not as accurate as colonoscopy, which on the other hand is more invasive and expensive. Because of these kinds of issues, there has been tremendous interest in finding alternatives methods to screen the colon.

    Among these potential alternatives, the one that has gained the most favor is computed tomographic colonography, (also CT colonography or virtual colonoscopy).  This Knol will describe the technique of virtual colonoscopy and some of the advantages and disadvantages of it.   Whatever method that patients choose for screening, the most important issue is that tens of thousands of lives are lost unnecessarily each year because people who could benefit from screening fail to receive it.

What is CT colonography (also virtual colonoscopy)?

    This technique was first proposed as a method to evaluate the colon for polyps in the 1980s, but the field remained quiet until the mid-1990s.  However, over the last decade the field has expanded remarkably.  Fundamentally, CT colonography involves performing an abdominal CT scan of the colon – with several caveats.  A typical CT scan of the abdomen (see http://www.mayoclinic.com/health/ct-scan/FL00065 for general information about CT scans) is usually performed with contrast (both oral and IV) and provides excellent detail of the abdominal organs.  In comparison, CT colonography consists of a non-contrasted  exam focused on the colon. 

    As of 2008, CT colonography requires a full bowel preparation; patients must cleanse the colon in a process that is essentially the same as that used prior to a colonoscopy.  Next, air is blown into the colon, the CT scan is performed, and then the images are reformatted so that the reading physician can interpret them.  Thus, it is not a “virtual test” at all.  Rather, the preparation is very real, (in fact, CT colonography is probably best done in the screening setting with the ability for the patient to proceed to a colonoscopy should any abnormal findings be identified by the CT colonography).

    In more detail, after the bowel preparation, the colon is filled with air, and then CT scanning of the abdomen and pelvis, typically during a single breath hold, is performed.  This is typically done in both the prone (face down) and supine (face up) positions and two-dimensional axial images are captured.  There are many variations in the way the CT is performed (variations in collimation (alignment), slice thickness, reconstruction interval, table speed, acquisition time, and radiation dose).  Regardless of the variation, captured images are then downloaded to a workstation that is equipped with software programs that allow a range of data manipulations, including multiplanar reformation, two- and three-dimensional rendering, virtual dissection, and computer aided diagnosis.  An example of the kinds of abnormalities that can be identified by CT colonography is shown in Figure 1.  Although variations in hardware, software, and general technique abound, efforts are being made to standardize the methodology.

    A major attraction of CT colonography is that it is relatively non-invasive and safe (although there are growing concerns about radiation exposure) and is relatively simple for patients to do.  Nevertheless, most patients complain about the preparation, and the filling of the colon with air.  One of the major drawbacks of CT colonography is that if a polyp or other problem is identified, then the patient will have to undergo a definitive test, namely colonoscopy, to take biopsies or to remove polyps.  Nonetheless, CT colonography is less invasive than colonoscopy and represents an important consideration when considering the large number of patients that are currently not being offered or avoid a colon cancer screening test.

    As the medical community considers incorporating CT colonography as a regular item on the menu of screening options, a variety of issues are of critical importance, including the sensitivity and specificity of the test, the patient experience, management of extracolonic lesions, and advances in colon preparation.  There are also many new issues related to training.  It is clear that CT colonography has great promise, but also that many questions about its use remain. 

How accurate is CT colonography?

    Since the introduction of CT colonography, a major endeavor in the field has been to investigate its sensitivity.  Early reports typically involved smaller populations at high risk for colorectal pathology and used comparatively slow technology (single-row scanners).  Later studies generally demonstrated improved detection sensitivity for polyps, but continued to have wide variation in results.  A number of single center studies demonstrated extremely high sensitivities that were in fact too good to be true. Subsequently, a series of large and well conducted (and well-publicized multicenter trials) reported variable results. 

    As of 2008, several facts about CT colonography have become apparent.  First, the technology has advanced considerably and could be considered “mature.”  Further refinements are expected, although these are not expected to change the general conduct of the procedure.

    Second, the ability of CT colonography to detect abnormalities appears to be proportional to their size.  A major goal of CT colonography is to detect polyps (believed to be precursors of colon cancer), and CT colonography is best at identifying large polyps (those greater than 10 mm in size).  The reported sensitivity for detecting polyps at this size is from 50% to above 90%.  Recent studies suggest that the accuracy is likely closer to the 90% figure. CT colonography is not as good as at detecting polyps that are smaller; in the 6-9 mm size range, it will likely detect approximately 70% of polyps.  At 5 mm or less, the data indicate that CT colonography is not very accurate, and the sensitivity for polyp detection is likely to be below 50%.  By comparison, colonoscopy appears to be more sensitive at detecting polyps, particularly the smaller ones. 
Third, not everyone who reads CT colonography is equal.  This is perhaps not surprising, since in essentially all walks of life, there is variability in skill with which people perform (see below under “training”).  Thus, it is essential that any practioner recommending this test or any patient having it done understand how much training and experience their physician has in reading the test.

Bowel preparation

    A major drawback of the current modalities used to examine the colon is the requirement for cathartic cleansing of the bowel.  This is true not only for CT colonography, but also for colonoscopy, and air contrast barium enema.  In several studies of CT colonography, this has been identified as one of the most poorly tolerated aspects of the test.  Thus, any test that would allow a high quality examination of the colon without this type of preparation would be highly attractive.  With CT colonography, it may be possible to use a minimal preparation that does not require full bowel catharsis.

Extracolonic lesions

    Because the entire abdomen and pelvis are scanned during a CT colonography examination, the test can readily detect lesions outside the colon, which may be a major advantage to the test.  Many studies have reported the identification of calcifications, gallstones, hernias, bone lesions, abdominal aortic aneurysms, benign, and even malignant tumors.  It has been suggested that CT colonography may be most beneficial in elderly patients who are at greatest risk for cancers or other more prominent abnormalities.  While it is clear that CT colonography is able to detect many lesions outside of the colon, further research is needed in order to understand which of these findings should be further evaluated, as well as how much cost is added to the evaluation when these are pursued. 

Patient experience and acceptability

    Several studies have examined patient experience with and preference for colon imaging procedures.  The most unpleasant aspects of all colon imaging tests include the preparation for the test, which usually involves cleansing or purging the colon, and the act of performing the test, which usually involves distension of the colon.  With CT colonography, air (or CO2) is typically blown into the colon to allow better visualization of structures.  This causes discomfort.  Some programs use CO2, which is more rapidly dissolved than air, and thus may be less uncomfortable.  One difference between CT colonography and colonoscopy is that during the latter patients typically have moderate sedation, which involves administration of sedative, amnestic, and pain-relieving medications; patients undergoing CT colonography do not require any medication (although some physicians prefer to give anti-spasmodic agents).

    In studies comparing colonoscopy and CT colonography, the data are mixed.  Some studies have demonstrated that patients have a strong preference for CT colonography, while others indicate that the majority of patients prefer colonoscopy (the preferences are usually related to the degree of discomfort caused by the test).  Interestingly, patients appear to prefer either CT colonography or colonoscopy over other examinations of the colon such as air contrast barium enema or flexible sigmoidoscopy.  Notwithstanding, how CT colonography is perceived and tolerated by patients will clearly play an important role in its use for follow-up examinations.

Safety

    It appears that CT colonography is relatively safe.  There is a small risk of perforation of the bowel (due to colon distension); the reported risk in large series of patients appears to be somewhere in the range of one in 1,000 to one in 2,000.  Importantly, perforations have typically been seen in patients with underlying colon abnormalities.  For example, patients with inflammatory bowel disease affecting the colon may have friable mucosa or ulcerations, either of which could tear if stressed.  The other situation in which perforation may be more common is after colonoscopy with polypectomy is performed, because the polypectomy may cause small defect in the colon mucosa. 

    A further important safety concern centers on the risk of radiation (see Table 1).  A routine CT scan of the abdomen delivers in the neighborhood of 10-15 millisieverts (mSv) - with an average of two CT scans per study.  Estimating risk to the individual based on this radiation dose, however, is difficult. Most of the quantitative estimates of the radiation-induced cancer risk come from analyses of atomic-bomb survivors, who are thought to have received a dose of radiation in the area of 40 mSv (the risk of cancer is clearly elevated in these subjects).  Other data about radiation risk comes from study of radiation workers in the nuclear industry.  The radiation dose in these subjects has been estimated to be approximately 20 mSv, again in the range of a routine CT scan.  Again, these radiation workers are at increased risk for developing radiation related malignancy. 

    Whether these risk scenarios are applicable to the radiation dose for CT colonography remains open given obvious differences in total dose, the timing interval over which radiation is administered, life-time accrual of radiation risk (in an adult older than 50 years old vs. in younger age), physical area of radiation exposure (abdomen only vs. full body or bone marrow, lungs), and other factors.  At this time, it is not clear that the radiation dose received with a standard CT colonography exam will be associated with an increased risk of cancer.  Moving forward, it is clear that a major area of investigation will be lowering radiation doses (and this appears to be highly feasible). 

New technology

    New technology in the CT colonography field is exploding.  CT scanners have now reached a level at which the exam can be performed rapidly and protocols are being developed that may allow relatively low radiation doses.  New image display techniques are evolving.  The addition of computer-aided diagnosis (CAD) is of particular interest, but there are many other areas of importance, including integration of differing types of data input into single reader platforms (i.e. an “all in one” platform).

Training

    It is becoming clearer that specific training is required in order for readers to accurately read CT colonography.  The exam is not necessarily easy to interpret and reading the exam appears to be more intuitive for some than others.  Data continue to emerge about how much training is required, and whether individuals with different types of backgrounds can be adequately trained to read CT colonography.  For example, while formally trained radiology experts have taken the lead in reading and training of CT colonography, it is likely that other groups will be able to adequately read the study.  Regardless of who reads the test, it will be essential that they have had adequate training.  Finally, regardless of who could or should read the exams, currently there is a general consensus that there is a lack of adequately trained readers. 

Implementation

    One of the most important areas of concern is that if it is agreed that CT colonography is a viable option for mass colon cancer screening, then how will it be implemented in clinical practice?  For example, although it represents an attractive alternative method for colon cancer screening, it is unknown whether offering CT colonography in a menu of “competing screening strategies” will truly enhance compliance. It is not known whether patients will embrace the technology and procedure, or whether concerns about radiation safety may make it unpopular.  Additionally, CT scanners are prevalent in the US, but are there enough to carry out large numbers of CT colonographic exams?

     Another major issue has to do with whether and how to report lesions identified at the time of CT colonography.  Some have advocated that small lesions (less than 5 or 6 mm) are not clinically meaningful, and that they should not be reported.  From a scientific standpoint, this may be reasonable, but there are problems with this approach.  First, it is unclear whether patients (or their physicians for that matter) will accept this approach.  We also don’t know enough about the natural history of polyps to understand whether we can really leave polyps in place and simply observe them – as would be required in a scheme in which smaller polyps might be ignored.

    Another important issue is whether there are enough skilled readers to perform enough CT colonography exams to help screen a large fraction of the population at risk (generally asymptomatic patients over the age of 50; patients with specific symptoms or those with additional risk factors should likely undergo expedited colonoscopy).  If enough readers can be trained, and CT colonography is able to incrementally increase the number of patients screened, then it would represent a very important tool in the effort to screen the population for colon cancer.  

How important are polyps?

    Since an objective of CT colonography is to detect polyps, an important consideration is: exactly how important are polyps?  Current thinking is that cancer arises through a sequential growth sequence in which a small polyp forms in the mucosa of the bowel, and this grows into a larger polyp, which ultimately grows into a cancer of the colon.  Most experts believe that the recent reduction in colon cancer deaths in the U.S. is due to an overall increase in the detection and removal of polyps (by colonoscopy) before they have had the opportunity to become cancers.

Who should have it?

    As of 2008, agreed upon indications for CT colonography are for completion of the colon exam in patients who have had a colonoscopy that failed to examine the entire colon.  This usually occurs when the colon is so difficult to move the scope through that the colonoscopist cannot examine the entire colon or when the patient is not able to tolerate the colonoscopy exam due to discomfort. CT colonography is being used to screen the colon for cancer in some patients, though as of 2008, most insurance plans do not cover the test.  It is expected that this will likely change as new data emerge about how the test is best performed.  Risks and benefits of CT colonography are summarized in Table 2.

Summary

CT colonography is a powerful new adjunct in the field of colon imaging.  It appears to be safe and reasonably well tolerated by patients.  Radiation exposure is an important consideration that must be assessed further before the test is widely implemented.   Whether CT colonography is ready for a regular place at the table in the colon cancer screening menu is unclear as of 2008, but it appears that major national societies are poised to make recommendations that take CT colonography into consideration.  For those physicians and patients willing to embrace this new and exciting technology, it is imperative to understand the multiple issues surrounding its use.  

Selected References

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2.    Vining DJ. Virtual endoscopy flies viewer through the body. Diagn Imaging (San Franc) 1996;18:127-9.
3.    Johnson CD, Hara AK, Reed JE. Computed tomographic colonography (Virtual colonoscopy): a new method for detecting colorectal neoplasms. Endoscopy 1997;29:454-61.
4.    Dachman AH, Kuniyoshi JK, Boyle CM, Samara Y, Hoffmann KR, Rubin DT, Hanan I. CT colonography with three-dimensional problem solving for detection of colonic polyps. AJR Am J Roentgenol 1998;171:989-95.
5.    Pickhardt PJ, Choi JR, Hwang I, Butler JA, Puckett ML, Hildebrandt HA, Wong RK, Nugent PA, Mysliwiec PA, Schindler WR. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003;349:2191-200.
6.    Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B, Vining DJ, Small WC, Affronti J, Rex D, Kopecky KK, Ackerman S, Burdick JS, Brewington C, Turner MA, Zfass A, Wright AR, Iyer RB, Lynch P, Sivak MV, Butler H. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. Jama 2004;291:1713-9.
7.    Hur C, Gazelle GS, Zalis ME, Podolsky DK. An analysis of the potential impact of computed tomographic colonography (virtual colonoscopy) on colonoscopy demand. Gastroenterology 2004;127:1312-21.
8.    Iannaccone R, Laghi A, Catalano C, Mangiapane F, Lamazza A, Schillaci A, et al. Computed tomographic colonography without cathartic preparation for the detection of colorectal polyps. Gastroenterology 2004;127:1300-11.
9.    Brenner DJ, Georgsson MA. Mass screening with CT colonography: should the radiation exposure be of concern? Gastroenterology 2005;129:328-37.
10.    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.
11.    Zalis ME, Perumpillichira JJ, Magee C, Kohlberg G, Hahn PF. Tagging-based, electronically cleansed CT colonography: evaluation of patient comfort and image readability. Radiology 2006;239:149-59.
12.    Burling D, Halligan S, Atchley J, Dhingsar R, Guest P, Hayward S, Higginson A, Jobling C, Kay C, Lilford R, Maskell G, McCafferty I, McGregor J, Morton D, Kumar Neelala M, Noakes M, Philips A, Riley P, Taylor A, Bassett P, Wardle J, Atkin W, Taylor SA. CT colonography: interpretative performance in a non-academic environment. Clin Radiol 2007;62:424-9; discussion 430-1.
13.    Rockey DC, Barish M, Brill JV, Cash BD, Fletcher JG, Sharma P, Wani S, Wiersema MJ, Peterson LE, Conte J. Standards for gastroenterologists for performing and interpreting diagnostic computed tomographic colonography. Gastroenterology 2007;133:1005-24.
14.    Schwartz DC, Dasher KJ, Said A, Gopal DV, Reichelderfer M, Kim DH, Pickhardt PJ, Taylor AJ, Pfau PR. Impact of a CT Colonography Screening Program on Endoscopic Colonoscopy in Clinical Practice. Am J Gastroenterol 2007.

Web sites

The American Gastroenterological Association - http://www.gastro.org
The National Institute of Diabetes and Digestive and Kidney Diseases -  http://digestive.niddk.nih.gov/ddiseases/a-z.asp
The American Cancer Society - http://www.cancer.org (Your other reference was the American Chemical Society)