Bolstered by recent data showing the excellent clinical performance, safety profile, and cost-effectiveness of CT colonography (CTC) for colorectal cancer screening [1-6], the American Cancer Society officially endorsed this tool as a recommended screening test in 2008 [7]. Beyond pure clinical validation and the progressive acceptance by key medical societies and technology assessment groups, the next logical step leading to widespread implementation of CTC screening will be broader coverage by national third-party payers. With broader coverage and implementation for CTC screening on the horizon, involved physicians must be well versed in a number of key concepts regarding colorectal polyps, including the expected screening prevalence, histologic characteristics, morphologic features, and existing evidence on natural history. These topics will generally not be covered adequately in CTC-specific reviews on technique or interpretation.

Furthermore, although some of these concepts may have been inculcated during residency or fellowship training, much of the classic data that has been passed down was based on high-risk or symptomatic cohorts. Unfortunately, these often-quoted statistics do not apply to asymptomatic screening and may lead to inappropriate patient management. Newer and more applicable data based on actual screening cohorts now exist and should replace this older teaching. The purpose of this article is to provide a timely update on a variety of key polyp topics to construct a proper framework for physicians who are interested in providing CTC screening as a clinical service.

The need for rational evidence-based screening algorithms and surveillance guidelines based on polyp size is an important challenge facing large-scale implementation of CTC screening. Most experts would agree that large polyps detected at CTC screening will generally warrant polypectomy, whereas immediate colonoscopy is not necessary for isolated diminutive polyps (≤ 5 mm) [2, 4, 5, 8-13]. Specifically regarding diminutive lesions detected at CTC, an American Gastroenterological Association (AGA) future trends report from 2004 noted that “polyps ≤ 5 mm in size do not appear to be a compelling reason for colonoscopy and polypectomy” [13]. Ransohoff [11] added that “few clinicians would likely argue that colonoscopy is justified” for diminutive lesions, adding that “the overwhelming majority cannot possibly represent an important near-term health threat.” In an insightful editorial from 2001, Bond [8] remarked that “a large volume of scientific data indicates that clinicians need to shift their attention away from simply finding and harvesting all diminutive colorectal adenomas toward strategies that allow the reliable detection of the much less common, but much more dangerous, advanced adenoma.”

Although a small number of gastroenterologists have suggested that colonoscopy referral might be considered for isolated CTC-detected diminutive lesions [14], the real controversy regarding the clinical management of polyps detected at CTC clearly relates to the handling of small (6-9 mm) colorectal polyps [4, 7, 12, 13, 15, 16]. To critically and objectively analyze this issue, we must rise above the potential traps of protectionist turf battles and focus more on our current knowledge of the histology and, more importantly, our understanding of the behavior and natural history of small colorectal polyps in a screening population.

Because most polyps detected at primary optical colonoscopy screening are generally removed, polyp histology according to lesion size has been well established. However, one must keep in mind that the histology of resected polyps represents a static cross-sectional end point that does not provide any longitudinal information regarding clinical behavior or significance. Therefore, polyp histology alone does not describe the prior growth rate, and it does not reliably predict what the future risk would have been if the polyp had been left in place. Furthermore, it is absolutely critical to ascertain whether the data are derived from asymptomatic screening populations or symptomatic high-risk cohorts because the rates of clinically important histology will greatly differ between these two groups. Lesion size is widely accepted as undoubtedly the single most important determinant of clinical significance. Larger lesions are more often neoplastic; more frequently show advanced histology; and, of course, represent the vast majority of life-threatening cancers.

The ideal target for screening and prevention of colorectal cancer is the “advanced adenoma,” which is defined as an adenoma that is large (≥ 10 mm) or contains histologic findings of either high-grade dysplasia or a prominent villous component [17]. The serrated polyp pathway, which is distinct from the classic adenoma-carcinoma sequence, may account for about 15% of colorectal cancer cases [18]. For this particular pathway, sessile serrated adenomas less than 10 mm in size without dysplasia should not be considered as histologically advanced lesions, but serrated adenomas that are large or exhibit dysplasia should be categorized as advanced (O'Brien MJ, personal communication).

In terms of prevalence data for colorectal polyps according to both size and relevant histology, a common pitfall is to quote the older classic literature that is largely based on symptomatic, high-risk series [19-21]. Instead, one should realize the wealth of more recent data derived from a number of endoscopic screening trials [2, 4, 22-29] involving predominately healthy, asymptomatic cohorts including both men and women (Table 1). These modern studies, which are predominately optical colonoscopy trials but also include some combined CTC-optical colonoscopy studies, comprise well over 100,000 subjects and show some remarkably similar findings that should serve as our new reference point for screening in terms of expected polyp prevalence and histology according to lesion size. Several other trials that either did not include a good sex mix or reported findings only in terms of proximal and distal disease [30-32] were excluded from consideration but largely parallel the larger representative series.

Although 35-50% of adults over the age of 50 years may harbor at least one colorectal polyp [2, 4, 6, 25, 27, 29], the largest lesion will be diminutive in size in the majority of individuals. In fact, recent screening studies have shown a remarkably narrow 13-16% prevalence range for polyps 6 mm and larger (Table 1), with a representative value of about 14% as an approximate average. The polyp prevalence at the 6-mm size threshold is more reproducible than the prevalence for all polyps (i.e., including diminutive lesions) and is much more clinically relevant to CTC screening. The prevalence for large polyps is about 5-6%, whereas about 8% will have a polyp in the 6- to 9-mm range (Table 1). As a general rule, approximately one third of diminutive lesions are adenomatous (almost exclusively tubular adenomas) and two thirds are nonadenomatous, predominately consisting of nonneoplastic mucosal tags and hyperplastic polyps [4, 33]. Above the 6-mm size threshold, the ratio of adenomatous to nonadenomatous polyps reverses, with neoplastic lesions representing approximately two thirds of nondiminutive lesions [4, 6, 33]. It has been well established in the gastrointestinal literature that finding three or more adenomas at optical colonoscopy increases a patient's future risk for additional adenomas at surveillance [34], but the risk related to multiple diminutive-only tubular adenomas is probably much lower. Therefore, CTC detection of at least one nondiminutive adenoma would presumably identify most patients at increased risk.

Because of the central importance of advanced adenomas for colorectal cancer prevention [2, 4, 8, 17, 23], the overall and size-specific prevalence data for these lesions are critical considerations in determining appropriate screening strategies. The presence of high-grade dysplasia, previously termed “carcinoma in situ,” is of particular interest because it is believed to be more clinically relevant than villous histology in terms of more imminent cancer transformation [35, 36]. Of course, the prevalence of invasive cancer according to polyp size is also an important consideration. When recent data are analyzed in terms of important histology, it is again remarkable how closely the results agree with each other and also how much they differ from the classic teaching. The overall prevalence of advanced adenomas in modern screening cohorts has ranged from 3.3% to 6.9% in most recent trials (Table 1), which is considerably lower than the prevalence values for groups at increased risk.

Although large adenomas (≥ 10 mm) compose about 90-95% of all advanced neoplasia [23], approximately 4% of 6- to 9-mm adenomas will show advanced histology, with a reported range of 2.7-5.3% (Table 1). By comparison, 10% of 5- to 10-mm adenomas were found to be advanced in a higher-risk cohort [37]. Given the screening prevalence of 6- to 9-mm polyps of about 8% and a frequency of advanced histology in small adenomas of 4%, the overall screening prevalence of small advanced adenomas is approximately 0.3%, with a reported range of 0.17-0.56% (Table 1). Fortunately, the presence of high-grade dysplasia in 6- to 9-mm adenomas is even more uncommon, with an overall prevalence of about 0.05% (Table 1). Although the overall prevalence of diminutive polyps is many times higher than small 6- to 9-mm polyps, the prevalence of diminutive advanced neoplasia is even lower than that for small polyps [29].

A commonly quoted historical figure for the cancer rate among small 6- to 9-mm adenomas is 0.9% [13, 19-21]. However, this figure is based on higher-risk or symptomatic cohorts and not on true screening populations. When the recent large screening studies are tallied, the frequency of cancer dips to 0.1% or lower, ranging from 0% to 0.5% (Table 1), with most reported cancers concentrated within one Korean series [27]. The percentage is even lower if all 6- to 9-mm polyps rather than just small adenomas are considered in the denominator. We have yet to encounter a subcentimeter invasive cancer in our combined CTC and optical colonoscopy experience, including more than 1,000 6- to 9-mm polyps. Even for large 1- to 2-cm adenomas, the cancer rate appears to be only about 1% or less (Table 1), which is considerably lower than the commonly quoted historical range of 5-10%, which again is based on high-risk cohorts and not on screening populations [19, 21]. Given that about 30-40% of large polyps are nonadenomatous [4, 6, 33] and that some large lesions detected at CTC may be false-positive findings [6, 38], the actual cancer risk for a 1- to 2-cm lesion detected at CTC is actually well under 1%, which is lower than the 1-2% frequency for significant complications at optical colonoscopy referral for therapeutic polypectomy [39-42]. This risk is also lower than the accepted 2% cancer rate for BI-RADS category 3 breast lesions at mammography, for which follow-up is recommended. The natural history data on 1- to 2-cm polyps from Stryker et al. [43] (discussed later) provide further evidence that even these relatively large lesions are predominately benign findings.

Polyps are generally divided into three major morphologic categories: sessile, pedunculated, and flat. Sessile polyps have a relatively broad base of attachment, classically creating a bowler hat appearance, whereas pedunculated polyps have a defined head and stalk that connects the lesion to the adjacent colonic surface. The term “polypoid lesions” refers to both sessile and pedunculated polyps. These polyps account for the vast majority of cases, including most advanced adenomas and cancers [2, 23]. Flat lesions represent a subset of sessile polyps that, as the name implies, have a nonpolypoid or plaquelike morphology. A polyp height that is less than half of the width has been commonly used as a morphologic descriptor [44, 45], but this definition is generally too forgiving and could include lesions that would be better labeled as sessile. For smaller flat polyps less than 2-3 cm in size, lesion elevation above the surrounding mucosal surface is typically 3 mm or less [10]. Categorization of large, superficially elevated lesions that are clearly flat in morphology but may exceed a maximal height of 3 mm is less uniform. The term “carpet lesion,” also referred to as a laterally or superficially spreading tumor, best applies to this important subset of flat lesions that tend to be quite large in cross-sectional area but not bulky [46].

Both the prevalence and clinical significance of flat (nonpolypoid) lesions have been the source of recent debate. Endoscopic detection of nonpolypoid lesions may be increased by the use of advanced endoscopic techniques, such as chromoendoscopy and narrow-band imaging. However, unlike the case for East Asia [47], there is little evidence to suggest that small, flat, aggressive lesions represent a major problem in the U.S. screening population. Although a single-center Veterans Administration study by Soetikno et al. [45] suggested that important nonpolypoid lesions may be more common in the United States than previously thought, closer inspection of this work reveals that the conclusions are not supported by the findings [48]. First, a clear distinction must be made between the relatively flat lesions primarily described in this study (defined as elevated lesions with a height less than half the diameter) and completely flat or depressed lesions. What has been widely overlooked is that the authors remarked that “completely flat lesions are exceedingly rare” and presumably were completely absent in this study. Furthermore, depressed lesions comprised less than 1% of all colorectal lesions (18 of 2,770), only four of which were seen at screening. Therefore, nearly all nonpolypoid lesions from this study were elevated from the surrounding mucosa, which is a critical distinction that favors detection at both standard colonoscopy and CTC. In addition, the authors combined carcinoma in situ, which is more appropriately termed “high-grade dysplasia,” with invasive cancer [35]. This is an unfortunate and misleading way to report histology, especially because the majority of nonpolypoid “cancers” in this study (11 of 15) were actually noninvasive advanced adenomas. The average size of advanced nonpolypoid lesions was relatively large (1.6 cm) and similar in size to their polypoid counterparts (1.9 cm), which also bodes well for detection at CTC.

In contradistinction to the Veterans Administration study [45], data from the National Polyp Study showed that flat adenomas were actually less likely to harbor high-grade dysplasia compared with sessile or pedunculated adenomas [49]. In addition, patients with flat adenomas were not found to be at greater risk for advanced adenomas at subsequent surveillance colonoscopy. If aggressive flat lesions in this trial had somehow been missed, more incident cancers presumably would have developed over the course of longitudinal evaluation [48, 50]. In fact, the relative frequency of flat adenomas in the National Polyp Study was similar to that reported when chromoendoscopic techniques are used.

Our own experience with 125 flat lesions measuring 6 mm or greater detected at CTC screening has also shown a nonaggressive picture [51]. Of 92 flat lesions less than 3 cm in size evaluated at subsequent optical colonoscopy, 23 (25.0%) were neoplastic, five (5.4%) were histologically advanced, and none was malignant. In comparison, polypoid lesions measuring less than 3 cm were much more likely to be neoplastic (60.3%; 363 of 602), histologically advanced (12.1%, 73 of 602), and malignant (0.5%, 3 of 602). None of the nine flat lesions seen only at colonoscopy (i.e., CTC false-negative findings) was histologically advanced and only two were neoplastic (tubular adenomas). All 10 carpet lesions (defined as flat, laterally spreading tumors ≥ 3 cm) were neoplastic and nine were histologically advanced. These findings suggest that flat lesions less than 3 cm are not a major concern compared with polypoid lesions of similar size and that large carpet lesions represent the subset of polyps with flat morphology of most interest.

Because flat lesions are generally less conspicuous than polypoid lesions, they can be more challenging to detect initially at both CTC and optical colonoscopy. However, good sensitivity can nonetheless be achieved with combined 3D-2D polyp detection at CTC, as shown in the United States Department of Defense screening trial [44]. Both phantom and clinical studies have shown that 3D endoluminal display improves the sensitivity for detecting flat lesions [44, 47, 52]. Of course, the 2D images remain critical for lesion confirmation. In our recent clinical experience, more large flat advanced adenomas were detected at primary CTC screening compared with primary optical colonoscopy screening, albeit uncommon with either approach [2]. Interestingly, histologically advanced or depressed small flat lesions appear to be exceedingly rare in our screening population. In fact, most flat lesions detected (or missed) at CTC are hyperplastic polyps, which are generally distinct from serrated polyps and probably of no clinical significance [33, 53]. This is likely due in part to the tendency of hyperplastic polyps to flatten when the colonic lumen is distended [54]. In comparison, large serrated polyps tend to be more conspicuous at CTC in our experience. In the Mayo Clinic experience, the great majority of occult polyps at CTC (i.e., missed lesions that could not be identified even retrospectively) were flat hyperplastic polyps ranging in size from 6 to 2.1 cm [55]. This mirrors our own clinical experience with occult lesions at CTC [33, 56]. Given these collective findings, we believe that flat lesions remain a diagnostic challenge but do not represent a major drawback to widespread CTC screening.

Carpet lesions are an important subset of flat lesions that, despite their large surface area, can be relatively subtle at CTC because of the relative paucity of raised tissue. These lesions have a strong predilection for the rectum and cecum [57]. Despite their large linear size, they have a relatively low rate of malignancy but frequently show villous features, with or without high-grade dysplasia [46, 57]. Although classic carpet lesions are less conspicuous than sessile or pedunculated polyps, they are nonetheless detectable at CTC in our experience because of fixed-fold distortion or edges with a rolled-up or polypoid appearance. Optimal preparation and distention, as well as a hybrid 3D-2D detection strategy, allow confident detection of carpet lesions. In some cases, endoscopic mucosal resection can serve as the definitive treatment, whereas others will require more aggressive surgery [46].

The natural history of small colorectal polyps has become a central issue of critical importance. One reason is that CTC is undoubtedly a highly efficacious and cost-effective approach to population screening when only large polyps (≥ 10 mm) necessitate referral for polypectomy [9]. If small (6-9 mm) CTC-detected polyps were to be referred to invasive optical colonoscopy for polypectomy in all cases, the utility of CTC as an intermediate filter would be decreased somewhat, although it would likely still remain quite useful [2, 4, 5]. To underscore the importance of this topic, the AGA issued a statement that “The need to define the natural history and biological significance of polyps smaller than a centimeter is central to refining colorectal cancer screening, irrespective of modality.” Although our ongoing natural history study (discussed later) is the first, to our knowledge, to follow a substantial cohort of small 6- to 9-mm polyps using CTC as the surveillance tool, a number of older studies have followed small unresected polyps using other colorectal examinations, including endoscopy and barium enema. In fact, contrary to the prevailing general perception, a fair amount of data on polyp natural history already exists from these older longitudinal trials, which have somehow been forgotten over time. When considered together as a group, all of these longitudinal studies have repeatedly shown the benign, indolent nature of unresected subcentimeter colorectal polyps. No study to date has ever shown that leaving 6- to 9-mm polyps in place is a harmful practice. It is instructive to briefly review these early trials, some of which are well over 40 years old.

In Norway, Hofstad et al. [58] performed serial colonoscopy on unresected subcentimeter polyps and found that only one (0.5%) of 189 lesions eclipsed the 10-mm threshold after a 1-year time interval. At the 3-year follow-up mark, most polyps in this study remained stable or regressed in size, and there was an overall tendency to net regression among the medium-sized (5-9 mm) polyps [59]. The authors of this endoscopic trial concluded that following unresected 5- to 9-mm polyps for 3 years was a safe practice.

Longitudinal studies using flexible sigmoidoscopy have also shown the stability of smaller polyps over time [60-62]. In one study that used serial sigmoidoscopy to follow polyps measuring up to 15 mm in size over a 3- to 5-year period, Knoernschild [60] reported a significant increase in polyp size in only 4% of patients. In a longitudinal study using barium enemas to follow colorectal polyps, Welin et al. [63] showed exceedingly slow growth rates by studying 375 unresected polyps over a mean interval of 30 months. The high observed adenoma detection rates at surveillance in the National Polyp Study, in conjunction with the low observed colorectal cancer incidence, was thought to be explainable only by regression of adenomas [64]. Finally, in a classic barium enema study by Stryker et al. [43], the cumulative 5-year and 10-year risks of cancer related to large colorectal polyps (≥ 1 cm) left in place were less than 3% and 10%, respectively. Although the authors concluded that their findings supported the practice of routine polypectomy for large lesions, it may come as a surprise to some how benign the behavior is for the great majority of these polyps for which there is no debate on management.

These longitudinal studies that used endoscopic or barium enema techniques to follow unresected polyps are very reassuring, but they have done surprisingly little to quell the current debate over the clinical management of small polyps detected at CTC screening [14]. Part of the problem may simply be a lack of awareness that these studies even exist. However, there are issues beyond this simple fact that further reinforce the need for repeating a natural history trial using CTC as the instrument. For one, CTC provides superior polyp measurement capabilities, including improved accuracy and reproducibility for linear size assessment, compared with the other colorectal imaging examinations [65, 66]. Furthermore, CTC allows polyp volume assessment, which greatly amplifies interval changes in polyp size compared with linear measurement [67]. A secondary limitation of the prior polyp surveillance studies was that the sample sizes of some studies were generally underpowered to influence a change in practice. However, even without such largescale proof, the CT Colonography Reporting and Data System C-RADS consensus opinion from the Working Group on Virtual Colonoscopy stated that 3-year CTC surveillance for patients with one or two 6- to 9-mm polyps represented a reasonable clinical approach [10].

To provide further evidence on the safety of short-term CTC surveillance for patients with one or two 6- to 9-mm polyps and hopefully to eventually influence screening practice and policy, we undertook a prospective natural history study. This trial represents a collaborative effort between the University of Wisconsin (UW) School of Medicine and Public Health in Madison, WI, and the National Naval Medical Center (NNMC) in Bethesda, MD. The precise protocol used at each center for polyp follow-up differs in a relatively small but meaningful way that provides even more complementary data. At UW, enrolled patients with 6- to 9-mm polyps that did not show a measurable increase in size at 1- to 2-year CTC follow-up are eligible for continued CTC surveillance (with an expanded interval out to 3-5 years). At NNMC, all patients undergo optical colonoscopy for polypectomy follow-up after CTC surveillance performed at 1 year. Therefore, the UW arm is relatively rich is polyp-years but lacks histologic data for most polyps that are stable or regressed, whereas the NNMC arm provides needed histologic data but loses the opportunity for continued longitudinal follow-up.

We presented the interim results of CTC surveillance for 128 small colorectal polyps from our initial 100 patients combined at the 2008 annual meeting of the Society of Gastrointestinal Radiologists [68]. The mean patient age was 60.0 years. A measurable change in linear polyp size was defined as an increase in diameter of 1.0 mm or greater. The average CTC follow-up interval was 1.4 years (range, 362-1,126 days), corresponding to more than 184 cumulative polyp-years of data. Of the 128 small polyps, 12 (9.4%) showed interval growth, including 11 proven adenomas (one polyp was removed but could not be retrieved at optical colonoscopy). Importantly, there were no cancers among the histologically proven lesions. Five of the adenomas that grew represented advanced lesions, which represent 4% of the 128 total polyps. Because this is the expected percentage of advanced lesions for the entire group of 6- to 9-mm polyps (Table 1), it suggests that all advanced lesions in this cohort were detectable by interval growth and removed. The remaining 116 polyps (90.6%) did not increase in size, including 73 polyps that were stable, nine that were measurably smaller, and 34 that were not seen at follow-up, which had either completely regressed or represented a false-positive finding at the initial examination. Given that our positive predictive value for CTC-detected polyps 6 mm or greater sent to optical colonoscopy is more than 90% [69], it is likely that most of these lesions had truly regressed. None of the 128 6- to 9-mm polyps surpassed the 10-mm threshold at CTC follow-up.

The mean growth rate for the entire polyp group was -1.41 mm/y—a negative value given the large fraction of lesions that regressed. The mean growth rate for proven adenomas and advanced adenomas was 0.40 and 1.43 mm/y, respectively. From these initial results, we concluded that short-term CTC surveillance appears to be a very safe practice and can noninvasively identify the small subset of polyps (∼ 10%) that are of potential clinical relevance, particularly the histologically advanced lesions. For the remaining 90% of cases, it is possible that unnecessary optical colonoscopy could be avoided. We are encouraged by these preliminary results and will continue our work to confirm these findings on a larger scale. We are also assessing the role of volume measurement for polyp surveillance at CTC.

In addition to our ongoing longitudinal surveillance trial, we have also looked at the theoretical cost-effectiveness of immediate polypectomy versus 3-year CTC surveillance for small (6- to 9-mm) polyps detected at CTC screening [16]. Without any intervention, we estimated that the 5-year colorectal cancer death rate for patients with unresected 6- to 9-mm polyps was 0.08%, which already represents a sevenfold decrease from the 0.56% 5-year colorectal cancer death rate in the general screening population, the majority of whom do not harbor polyps. Therefore, for patients with 6- to 9-mm polyps detected at CTC screening, the exclusion of large polyps (≥ 10 mm) already confers a very low colorectal cancer risk. For the concentrated cohort with a small polyp, the death rate was further reduced to 0.03% with the CTC surveillance strategy and 0.02% with immediate colonoscopy referral. However, for each additional cancer-related death prevented with immediate polypectomy versus CTC follow-up, 10,000 additional colonoscopy referrals would be needed, resulting in 10 perforations and an exorbitant incremental cost-effectiveness ratio of $372,853. We concluded that the high costs, additional complications, and relatively low incremental yield associated with immediate polypectomy of 6- to 9-mm polyps support the practice of 3-year CTC surveillance, which allows selective noninvasive identification of small polyps at risk. We would emphasize that CTC surveillance of small unresected polyps should only be undertaken in the context of a dedicated CTC program in which a reliable mechanism for follow-up is in place. In addition to the management of small polyps, we have explored other economic aspects of CTC screening [1, 5, 70], but these are beyond the scope of this article.

As the medical community evaluates the increasing role of CTC screening, we believe it is prudent to review and, more importantly, update several key concepts regarding colorectal polyps, which are generally not covered in articles focusing on CTC technique and interpretation. With the advent of less-invasive colorectal screening tests such as CTC, strict adherence to a “leave no polyp behind” approach would seem inappropriate on either clinical or economic grounds, let alone from a patient safety standpoint. At the very least, we must be open to novel approaches to colorectal screening in addition to optical colonoscopy that can safely and effectively increase compliance rates. Simply because all cancers presumably arise from smaller benign polyps does not imply that all small lesions are therefore dangerous and in need of resection. Although the mindset of universal polypectomy may apply in the case of primary optical colonoscopy screening, where the invasive barrier has already been breached, this represents an ineffective strategy for the safer noninvasive tests that provide a filter between polyp detection and invasive therapy. Furthermore, it is important to move beyond the ingrained literature regarding polyp prevalence and histology that was derived from high-risk or symptomatic cohorts and does not apply to screening. A bevy of data from modern screening cohorts can now replace this older information. It is also important to understand the current concepts and existing data surrounding nonpolypoid lesions and the natural history of small colorectal polyps. The ongoing longitudinal evaluation of small polyps with CTC will continue to add to our knowledge of the natural history. It is our hope that this overview of key polyp concepts can provide a solid foundation for those interested in providing CTC screening as a clinical service.

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

P. J. Pickhardt is a consultant for Medicsight, Viatronix, Fleet, and Covidien and a cofounder of VirtuoCTC.

D. H. Kim is a consultant for Medicsight and Viatronix and a cofounder of VirtuoCTC.

Address correspondence to P. J. Pickhardt ([email protected]).