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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2008;6:506–514

TATE OF THE ART

onsiderations Regarding the Present and Future Roles of Colonoscopyn Colorectal Cancer Prevention

OUGLAS K. REX and EMELY EID

epartment of Medicine, Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana

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ffective and safe colonoscopy is essential to colorectalancer prevention, regardless of the method used for colo-ectal cancer screening. The level of colorectal cancer inci-ence reduction provided by colonoscopy and polypectomyaries widely in available studies. There are several mecha-isms by which colonoscopy might fail to prevent colorec-

al cancer, and some of the mechanisms might be overcomey simple currently available measures. Further, advances

n colonoscope technology could enhance the effectivenessf colonoscopy or render it less operator-dependent. The

arge market for colorectal cancer screening in the Unitedtates has spawned innovative noncolonoscopic technolo-ies for colorectal cancer and polyp detection. Becausehese technologies are diagnosis only, their overall impactn outcomes ultimately may be determined by whether theyuccessfully increase adherence to screening (which shouldeduce colorectal cancer incidence) versus displace patientsrom colonoscopy screening (which potentially could in-rease colorectal cancer incidence), as well as their costffectiveness and the extent to which they reduce colonos-opy complications. As these strategies emerge, monitoringheir effects on adherence, cancer prevention, and proce-ural complications will be needed to optimize their roleselative to primary colonoscopy screening.

n the prevention of colorectal cancer, all roads lead tocolonoscopy (Figure 1). In most of the world, patients with

ymptoms consistent with colorectal cancer are evaluated byolonoscopy with the goal of achieving early diagnosis. Surveil-ance after removal of colorectal cancers and precancerous pol-ps also typically is performed by colonoscopy, although thentervals at which colonoscopy is recommended often varyetween countries.1– 4 The worldwide approach to colorectalancer screening is much more variable. Several countries relyn the fecal occult blood test or sigmoidoscopy for screening,5,6

ut patients with positive tests undergo colonoscopy. In suchettings, effective and safe colonoscopy remains critical to ef-

ective colorectal cancer screening (Figure 1), as has been ap-

reciated in the United Kingdom7 and in Australia.8 In thenited States and in emerging fashion in some European coun-

ries,9,10 primary colorectal cancer screening is being dominatedrogressively by colonoscopy.

The emergence of screening colonoscopy in the Unitedtates has transformed the practice of gastroenterology andubstantially has impacted general surgical practices. Demandor gastroenterologists is high, as is pursuit of gastroenterologyellowship positions by internal medicine residents. Arguably,he emergence of screening colonoscopy has impacted the prac-ice of gastroenterology more than any event of the past quarterentury, rivaling in its impact breakthroughs such as the iden-ification of Helicobacter pylori and the discovery of chronicepatitis viruses and their treatment.

By every account, millions of colonoscopies are performeder year in the United States11 at a cost of billions of dollars,nd with a nonnegligible risk of significant and occasionallyeadly complications.12–14 Any health care leader should askhether this investment and risk are associated with substantialnd optimized benefits, particularly in a system that exertsimited control over which physicians perform colonoscopy,ow well any physicians perform colonoscopy,15,16 or how oftenhysicians choose to repeat procedures in the same patients.17,18

olonoscopists should ask: are we providing for our patientshe best possible chance of colorectal cancer prevention at theowest risk? Are we serving our patients and country well byeing effective and cost effective in preventing colorectal can-er? How can we improve?

This review discusses issues pertaining to the effectiveness ofolonoscopy in colorectal cancer prevention, and discusses howesolution of these issues and the development of new alterna-ive screening and imaging technologies may alter the role ofolonoscopy in the United States.

How Well Does Colonoscopy PreventColorectal Cancer?Recent evidence on cancer risk in the United States

upports a general decline in cancer incidence, to which reduc-ions in colorectal cancer incidence are an important contrib-tor.19 In addition, the distribution of colorectal cancer stages

Abbreviations used in this paper: CT, computerized tomography;NPCC, hereditary nonpolyposis colorectal cancer.

© 2008 by the AGA Institute1542-3565/08/$34.00

doi:10.1016/j.cgh.2008.02.025

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as shifted toward earlier stages, coinciding with the emergencef screening colonoscopy.20 It is unknown to what extent theagnitude of these effects could be increased by improvements

n the effectiveness of colonoscopy or, conversely, the extent tohich the magnitude has been diminished by ineffective

olonoscopy.Evidence regarding the impact of colonoscopy on colorectal

ancer prevention is mixed. The National Polyp Study foundhat patients with adenomas who had undergone clearingolonoscopy experienced a 76% to 90% reduction in the inci-ence of colorectal cancer compared with the expected inci-ence based on reference populations.21 Long-term follow-upvaluation identified a sustained impact on colorectal cancerncidence and mortality.22 A modeling analysis found that re-uction in incidence and mortality during the first 10 years ofollow-up evaluation was almost entirely the result of the base-ine colonoscopy, and even at 20 years most of the mortalityeduction resulted from the baseline procedure.23 The impact ofhe National Polyp Study cannot be underestimated because ithaped the public’s and physicians’ views of what is achievablehrough colonoscopy and polypectomy. The National Polyptudy was the foundation of the lobbying that led to legislationroviding payment for screening colonoscopy for Medicareatients. The simple demonstration that screening colonoscopyould be performed safely and had a substantial yield24 –26 wasess important than evidence that colonoscopy and polypec-omy prevent colorectal cancer. At least 4 other studies haveeported 80% protection against colorectal cancer after colonos-opy.27–30

However, other studies examining adenoma cohorts haveocumented greater rates of incident cancer after clearingolonoscopy than were observed in the National Polyp Study.igure 2 displays incident cancer rates per thousand patientears of observation in the National Polyp Study, comparedith the Wheat Bran Fiber Trial,31 the Polyp Prevention Trial,32

he Funen Adenoma Follow-up Study,33 and 3 chemopreven-ion trials performed in the United States.34 In the chemopre-ention trials, colonoscopy and polypectomy had no measuredrotective effect against incident colorectal cancers comparedith those expected based on Surveillance, End, Epidemiologyesults.34 These results may not negate a protective effect be-

igure 1. All forms of non-olonoscopic screening rely onhe efficacy of colonoscopy toetect adenomas and cancer.OBT, fecal occult blood test;NA, deoxyribonucleic acid;CBE, double contrast bariumnema; CTC, Computed tomo-raphic colonography.

ause an adenoma cohort could have a higher incidence rate of C

ancer than the general population. Nevertheless, the protectiveevel of colonoscopy and polypectomy in these adenoma co-orts was substantially less than that described in the Nationalolyp Study. The reasons for these differences are unclear,lthough one possibility is superior baseline clearing of adeno-as in the National Polyp Study. For example, 13% of patients

ntering the National Polyp Study underwent 2 or more clear-ng baseline examinations before they were randomized. Fur-her, patients with adenomas greater than 3 cm were excludedrom the National Polyp Study, whereas all adenoma patientsere included in some trials such as the Funen Adenomaollow-up Study.33 Also, expected incidences of cancer in thearious adenoma cohorts are difficult to predict given that theize and type of adenomas may vary between studies. Similarly,istinguishing prevalent from incident cancers in the controlroups is problematic, and prevalent cancers were excludedrom the adenoma cohorts. It is impossible to determinehether unmeasured differences in the quality of colonoscopyerformance contribute to the observed differences in protec-ion.

igure 2. Incident cases of colorectal cancer per 1000 years of patientbservation. NPS, National Polyp Study21; PPT, Polyp Prevention Trial32;B, Wheat-Bran Fiber Trial31; Funen, Funen adenoma follow-up study33;

hemo, combined results of 3 U.S. chemoprevention trials.34

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508 REX AND EID CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 5

Other cohort and case-control studies have documentedeductions in risk of colorectal cancer after colonoscopy, buthe reductions were lower than observed in the National Polyptudy. For example, a case-control study found a 50% reduction

n mortality after colonoscopy in US veterans.35 A large cohortf symptomatic patients had a less than 50% reduction inancer incidence during the first 5 years after the colonoscopy.36

case-control study in the Medicaid population in Californianvolving 4458 cancer cases and 43,815 controls identified a5% reduction in colorectal cancer incidence after colonos-opy.37 In both men and women, the reduction in left-sidedancers was 84%, whereas the reduction in right-sided colonancer was 62% in men and only 18% in women.37 These stud-es19,20 confirm that colonoscopy is associated with reductionsn colorectal cancer risk, but the reductions are less than de-cribed in the National Polyp Study, although as noted previ-usly, comparisons between the studies are complicated.

In summary, evidence on the protective level of colonoscopygainst colorectal cancer is mixed. Why is colonoscopy notlways as protective against colorectal cancer as we hoped for,nd as many endoscopists and much of the public still believe?everal plausible contributors deserve investigation (Table 1).hether these contributors account for all of colonoscopy’s

ailures is uncertain, as is their relative quantitative importance.evertheless, pending definitive studies and explanations, theyeserve careful consideration by colonoscopists.

Why Is Protection Against ColorectalCancer by Colonoscopy Imperfect?What Corrective Actions Can BeTaken?Table 1 lists a priori reasons why a patient might

ndergo colonoscopy and then present in the next few yearsith colorectal cancer. Of the 5 reasons listed, at least 4 appear

o be correctable to some extent by improvements either inreparation, technique, or colonoscope technology. The relativeuantitative importance of each of the explanations is uncer-ain and the cause often is hard to identify in individual casesf interval cancers. The least correctable etiology for intervalancers would appear to be biologic causes, in which a colorec-al cancer develops rapidly from either endoscopically normal-ppearing mucosa, or from a tiny precancerous lesion. The bestnderstood mechanism for rapid growth is inactivation of aismatch repair gene. Mismatch repair gene inactivation ac-

ounts for essentially all cases of colorectal cancer arising in

able 1. A Priori Possibilities for Why ColonoscopyProtection Is Imperfect

apidly growing tumorsMost incident cancers are not poorly differentiatedThere is an increased risk of microsatellite instability in “interval”

cancers47

echnical limitations of colonoscopyHidden mucosaFlat lesions

neffective application of current colonoscopic detection technology(ie, suboptimal examination technique or time)68

neffective polypectomy63,64

neffective bowel preparation48–51

ereditary nonpolyposis colorectal cancer (HNPCC) and con- m

ributes to about 15% of sporadic colorectal cancers.38 – 40 Spo-adic cancers with microsatellite instability typically show inac-ivation of the hMLH1 gene by promoter hypermethylation.he appearance of colorectal cancers within a few years of aegative colonoscopy has been described repeatedly in HNPCCene carriers41,42 and serves as the basis for current recommen-ations to perform colonoscopy in HNPCC patients at short

ntervals.43 Hypermethylation of hMLH1, accompanied by mi-rosatellite instability and a high prevalence of BRAF muta-ions, has been associated with a hyperplastic polyp to serrateddenoma to cancer sequence that appears to occur primarily inhe proximal colon.44 This altered polyp to cancer sequence

ight be a contributor to the recent observation of lower levelsf protection against proximal colorectal cancer in femalesecause elderly women have the highest incidence of theseumors.44 However, it is possible that even interval cancersttributable to biologic mechanisms could be prevented bymprovements in colonoscopy. For example, even small adeno-

as may be important in HNPCC because the adenoma– car-inoma sequence in HNPCC can be more rapid. Techniquesuch as chromoendoscopy45 and high-definition endoscopy46

ppear capable of detecting tiny adenomas, and although thealue of these technologies in the average-risk population isncertain, they might have a useful impact in HNPCC. There

s currently no understanding of the detection rate ofolonoscopy for proximal colon hyperplastic polyps or ser-ated adenomas, or the variation between endoscopists in theetection of these lesions. That they are endoscopically aistinct group of lesions seems certain,47 but the general levelf recognition of the lesions by endoscopists, the level of aware-ess of their potential importance, and the willingness to re-ove them effectively given that they often are flat and located

n the proximal colon is entirely unknown at present. Theseuestions are important areas of investigation for colonosco-ists. Only further investigation can determine the extent tohich biologic explanations for interval cancers48 are correct-ble by improvements in colonoscopy or meticulous inspection.

The remaining explanations for interval cancers (Table 1)ach appear to be at least partly correctable. Bowel preparationas been associated with impaired detection of small49,50 and

arge adenomas50 and recently has been associated with im-aired polyp detection in prospective clinical trials.51,52 Clinicalutcomes Research Initiative investigators reported that 24% of

olonoscopies in the United States were designated as havinginadequate” bowel preparation.49 The economic impact of in-dequate bowel preparation is enormous.53

The colonoscopy community thus far has failed to identify aowel preparation that optimizes efficacy, tolerability, andafety. Bowel preparation frequently is worse in the right colonompared with the left colon, and many clinical trials noweport separate cleansing scores for the ascending colon.54 Weelieve the most consistent error in bowel preparation instruc-ions contributing to ineffective preparation is failure to useplit dosing. Split dosing refers to administration of half of thereparation on the evening before the colonoscopy and thether half on the day of the colonoscopy, preferably a few hoursefore the scheduled time for the examination. Direct testingas now established that split dosing is superior to dosing all ofhe preparation on the day before colonoscopy for both sodiumhosphate51,55 and polyethylene glycol.51,56 Anecdotally, the

ost commonly forwarded arguments against split dosing in-

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lude the inconvenience of arising during the night to ingestreparation when patients are scheduled for early morningolonoscopy and objections by some anesthesiologists who pre-er that patients ingest nothing by mouth after midnight theight before colonoscopy. In our experience, patients who un-erstand the importance of split dosing almost invariably areilling to arise during the night to take preparation doses at thereferred times, although the issue deserves formal study. In-istence by anesthesiologists that patients be nil per os after

idnight the night before colonoscopy is inconsistent withmerican Society of Anesthesiology guidelines indicating thatatients may take clear liquids until 2 hours before beingedated.57 Indeed, there is no evidence that split dosing in-reases the risk of aspiration during colonoscopy.

A second factor that is correctable and a potential cause ofnterval cancers is ineffective inspection technique. Older evi-ence that adenoma detection varies substantially between en-oscopists suggested the need for quality indicators and targetsor colonoscopy that measure the quality of mucosal inspec-ion. In 2002, the US Multisociety Task Force recommendedhat endoscopists should know their individual adenoma de-ection rates and that they should be at least 25% in men and5% in women, age 50 and older, undergoing colonoscopy.15

hese recommendations were reiterated by a joint task force ofhe American Society for Gastrointestinal Endoscopy and themerican College of Gastroenterology in 2006.16 As a secondarynd point, individual endoscopists are recommended to haveverage withdrawal times of at least 6 minutes in normalolonoscopies in which no biopsies or polypectomies are per-ormed.15,16 Despite this, few colonoscopists in the Unitedtates have yet measured their adenoma detection rates.

Recent evidence has extended the importance of measuringhese indicators by establishing that highly variable detectionxtends to large adenomas58,59 and by validating the 6-minuteithdrawal recommendation.58,60 In a prospective study of

creening colonoscopy, adenoma detection rates were found toary by more than 10-fold among 12 experienced gastroenter-logists in a private practice in Rockford, Illinois.58 There was atrong correlation between improved overall adenoma detec-ion, as well as large adenoma detection, and longer withdrawalime in patients who had normal colonoscopies. Among thoseastroenterologists with average withdrawal times greater thanminutes, the detection of adenomas 1 cm in size or greateras more than twice that (6.4% vs 2.6%) of those with averageithdrawal times of less than 6 minutes.58 Similarly, in a studyf 9 endoscopists performing more than 10,000 colonoscopiest Indiana University Hospital, there was a 4-fold differencemong endoscopists in the range of adenoma detection, andhe highest detector found 11 times more patients with 3 or

ore adenomas and 3.7 times more patients with adenomas 1m or greater compared with the lowest detector.59

The potential impact of this magnitude of variable detectionn the effectiveness of postpolypectomy surveillance guidelines

s staggering. By necessity, postpolypectomy surveillance guide-ines assume that the performance of colonoscopy is compara-le between operators,1– 4 although it is increasingly clear thathis is far from the case. Highly operator-dependent detectionf adenomas creates a scenario in which the most effectiveolonoscopists bring back more patients at short intervals,lthough these patients have had their colons cleared more

ffectively and are in less need of short-term follow-up evalua- f

ion. At the same time, the least effective adenoma detectorsring back fewer patients at short intervals, and they tell moreatients who have had both large and small adenomas gondetected to return at 10-year intervals (although the possi-ility that low adenoma detectors are the same individuals thatveruse colonoscopy for surveillance deserves investigation).he need for processes, standards, and incentives to reduce theperator dependency of adenoma detection, particularly largedenoma detection, is clear.

Although measurement of adenoma detection rates could beacilitated by electronic medical records that link pathologyeports to procedure reports, the process is relatively easy andnexpensive even when it requires chart review. There has beeno suggestion that adenoma detection rates have to be mea-ured in a continuous or ongoing fashion, or even in a repeatedashion when the rates exceed recommended thresholds. Over-ll adenoma detection as an end point is certainly a surrogateor the detection of advanced adenomas and cancer. However,he feasibility of the review process is facilitated greatly by usingverall adenoma detection (fewer charts need review to establishetection rates with narrow confidence intervals), problemsith interobserver variation in polyp size measurement areverted, and overall adenoma detection and resection correlatesith large adenoma detection and resection.58,59 Given thatdenoma detection is the purpose of most colonoscopies, iteems reasonable to establish adenoma detection rates as ariority for colonoscopists.

Although evidence that variable adenoma detection is aignificant problem among gastroenterologists is overwhelm-ng, there is also substantial evidence that on average detectiony gastroenterologists during colonoscopy is superior to that ofrimary care physicians. At least 3 large studies have docu-ented this effect with regard to cancer detection.61– 63 The

ifferences presumably reflect differences in training. There isess evidence about the relative performance of gastroenterolo-ists compared with general surgeons, although at least onetudy found that cancer detection by general surgeons wasnferior (on average) to gastroenterologists.61 There is no evi-ence regarding the comparative performance of gastroenterol-gists and colorectal surgeons. Overuse of postpolypectomyurveillance colonoscopy relative to gastroenterologists haseen described for general surgeons17 and primary care physi-ians.18 These differences underscore the importance of incor-orating quality guidelines and measurements into the prac-ices of nongastroenterologist colonoscopists.

A third potentially correctable cause of interval cancers isneffective polypectomy (Table 1). Two studies have suggestedhat ineffective polypectomy underlies more than one quarterf interval cancers, although the possibility of missed synchro-ous neoplasms cannot be excluded.64,65 How to correct inef-

ective polypectomy is uncertain. Current postpolypectomy sur-eillance guidelines recommend aggressive follow-up evaluationf patients undergoing piecemeal resection of large sessile ad-nomas1 because a piecemeal technique is associated with a 14%o 55% chance of incomplete polypectomy at the first attempt.66

he extent to which such patients are followed up closely inlinical practice is uncertain. One small randomized trial foundhat treatment of the edges of the polypectomy site with thergon plasma coagulator effectively lowered the recurrence ratefter piecemeal polypectomy.67 Beyond this, we have no data

rom randomized controlled trials to guide us in any specific

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spects of polypectomy resection technique.66 As a result,olypectomy technique in clinical practice is remarkably vari-ble,68 and based on anecdotally developed techniques that haveot been tested scientifically to compare their safety and effi-acy.

Finally, it is possible that advances in colonoscope or acces-ory technology could improve adenoma detection or reducenterobserver variability in adenoma detection (Table 2). Theseechnologies have been discussed elsewhere.69 To summarize,lthough several hold considerable promise, none of them haseen established clearly as both effective and practical in West-rn populations.69 Certainly, there has been no suggestion thatny of these technologies can substitute for an examinationhat is performed carefully using an adequate interval of time inwell-cleansed colon.In summary, although the quantitative and relative impor-

ance of a priori causes of interval cancers (Table 1) is uncertain,here is sufficient evidence to suggest corrective measures thatan be incorporated readily into all colonoscopic practicesTable 3). These measures are likely to substantially impactolorectal cancer detection and prevention everywhere whereolonoscopy is used. The extent to which corrective measuresre embraced by colonoscopists could substantially impact theffectiveness of colonoscopy relative to alternative emergingtrategies for colorectal cancer screening, which in turn couldmpact the choices of payers, guideline groups, and patientsegarding the continued use of colonoscopy for primary colo-ectal cancer screening in the United States.

Projecting the Future Role ofColonoscopyWill colonoscopy continue to dominate colorectal

ancer screening in the United States, or will its role becomeonfined to diagnostic and/or surveillance colonoscopy?

hether improvements in colonoscopy performance and tech-ology occur, as already discussed, could impact whether theole of colonoscopy in the United States changes. More effec-ive, safer, and less costly colonoscopy could prolong the dom-nation of colonoscopy in colorectal cancer screening. However,he expansion of colorectal cancer screening in the Unitedtates has created an economic market that has attracted tech-

able 2. Effectiveness and Practicality of Technologies forImproving Neoplasia Detection by Colonoscopy

Technique Effective Practical

eeing hidden mucosa betterWide angle Na YRetroflexion N NCap fitted Y IThird-eye retroscope Y (in models) I

eeing flat and depressed lesionsPan-chromoendoscopy Y NHigh definition I YNarrow band imaging Learning effect YAutofluorescence I I

OTE. A detailed review of technologies is available in reference 69., no; Y, yes; I, insufficient data available.Efficiency improved but not adenoma detection.

ology innovators, typically seeking to find a niche that fulfillsF

deficiency of colonoscopy screening. Indeed, colonoscopy hasajor deficiencies other than its failure to detect and remove all

recancerous lesions and early cancers from the colon. Thesenclude a substantial risk of perforation,12–14 the need for bowelreparation, significant numbers of patients who are unwillingo undergo the procedure for a variety of reasons,70 and theeed for sedation (which is arguably both an advantage and aisadvantage for colonoscopy). The use of current alternativeso colonoscopy such as guaiac-based fecal occult blood testing,exible sigmoidoscopy, and barium enema has decreased in thenited States whereas colonoscopy use has skyrocketed.71 New

nnovations need to overcome some or all of the problems withurrent alternative tests to substantially alter the role ofolonoscopy.

New tests to screen for colorectal cancer can be roughlyrouped into 2 categories. One category includes new stool-ased assays and potentially blood tests that compete primarilyith the guaiac-based fecal occult blood tests for detection of

olorectal cancer. The other category is alternative imagingtrategies that aim, such as colonoscopy, to detect precancerousolyps and thus prevent colorectal cancer.

In countries (and certain regions and health care systems inhe United States) with limited resources to perform screeningolonoscopy or where the wisdom of screening colonoscopy isot accepted, the role of colonoscopy is unlikely to changeiven the emergence of new tests. Colonoscopy will continue toe used in the screening process primarily to evaluate otherositive screening tests (Figure 1). In these settings, fecal im-unochemical tests and Hemoccult SENSA (Beckman Coulter,

ullerton, CA) appear promising as substitutes for older guaiac-ased fecal occult blood tests because they are more effectivend still quite affordable.72 At current performance levels fecalNA73 testing offers no clear advantage over improved fecal

ccult blood tests. The alternative imaging strategies could haven impact in these settings if the manpower to performolonoscopy is limited and there is interest in imaging theolon for the purpose of adenoma detection. Thus, both cap-ule colonoscopy74,75 and the Aer-O-Scope76 (GI View Ltd, Ra-

at Gan, Israel) are operator-independent procedures with re-ard to their technical performance (perhaps not theirnterpretation), and could be performed by nonphysician per-onnel, and thereby could increase the availability of polypmaging. Similarly, computerized tomography (CT) colonogra-

able 3. Key Measures for Improving the Effectiveness andCost Effectiveness of Colonoscopy in ColorectalCancer Prevention

se split-dosing in administration of bowel preparation forcolonoscopy

ll colonoscopists should document cecal landmarks, photographthe cecum, and document adequate cecal intubation rates15,16

ll colonoscopists should measure their adenoma detection ratesand meet standards for detection15,16

ll colonoscopists should record their withdrawal times and averageat least 6 minutes of withdrawal time in intact colons in which nobiopsies or polypectomies are performed15,16

se effective polypectomy techniques: snare techniques should beused for all polyps �5 mm in size and many smaller polyps,patients with large sessile lesions removed piecemeal needclose follow-up evaluation15,16

ollow recommended screening and surveillance intervals15,16

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hy could be used to increase the availability of imaging tech-ology and could be interpreted by nonradiologist person-el.77– 80 Because of limited availability, colonoscopy would besed in a therapeutic role when other imaging tests have de-ected polyps, particularly large polyps. In these settings theoles of colonoscopy for diagnosis in symptomatic patients andor surveillance also might be supplanted by alternative imag-ng techniques.

The projected role of colonoscopy in the United States andny other country that has adopted screening colonoscopy isore complex. For patients unwilling to undergo colonos-

opy,70 the situation is analogous to that in countries that doot use primary screening colonoscopy. The role of alternative

maging tests (Figure 3) is particularly important to considerecause these tests have polyp-detection capabilities, and thusould serve as an alternative to colonoscopy for cancer preven-ion. These tests might be used to increase adherence or toisplace colonoscopy from a primary screening role in theegment of the population that is currently willing to undergorimary screening colonoscopy. However, each of the new im-ging tests is expensive and to be competitive from a costerspective, each test must significantly limit the number ofatients with detected polyps who undergo colonoscopy. Oth-rwise, the strategy cost of using these tests will be too high.merican College of Radiology reporting recommendations forT colonography effectively reduce the proportion of patientsndergoing polypectomy because they recommend that polypsmm or smaller should not be mentioned on CT colonography

igure 3. Impact of diagnosis-only imaging tests (such as CT colonog-aphy or capsule colonoscopy) on colorectal cancer prevention mayepend on their impact on screening adherence rates. Improved ad-erence should reduce colorectal cancer incidence. Displacement ofatients from colonoscopy without improved adherence could increaseancer incidence rates.

eports, and patients with 1 or 2 polyps 6 to 9 mm in size may c

e offered a “surveillance” CT colonography in 3 years, ratherhan polypectomy.81 The medical rationale for this approach ishat the risk of conversion of large adenomas to cancer overeveral years appears small.82 Although the natural history ofmall polyps has received only limited study,83 the risk ofonversion to cancer in the short term is certainly lower thanor large polyps. Therefore, the cancer risk associated with CTCurveillance of 6- to 9-mm polyps might be minimal. In addi-ion, these strategies could reduce the complication burdenssociated with colonoscopic resection of small polyps. How-ver, in a recent decision analysis, delaying polypectomy in 6- to-mm polyps for even 3 years resulted in a 20-fold greater ratef colorectal cancers and a 10-fold greater rate of colorectalancer mortality compared with immediate polypectomy.84

hus, if a new imaging test is used primarily to displace pa-ients from colonoscopy (Figure 3), the effect potentially coulde to increase colorectal cancer compared with continued use ofolonoscopy screening. Alternatively, if new imaging tests aresed primarily to increase adherence to colorectal cancer screen-

ng, then the benefits would be clear. Increased adherence re-ults in improved cost effectiveness85 and identification of

edium- and large-sized polyps in previously nonadherent pa-ients would increase polypectomy rates and reduce colorectalancer deaths (Figure 3). Unfortunately, there is no clear evi-ence that any of the tests actually will significantly improvedherence in their current forms.86 Investigation of the impactn adherence of these tests should be a top priority for colo-ectal cancer prevention investigators.

Overall, the impact of alternative colorectal imaging strate-ies on outcomes such as colorectal cancer prevention andolonoscopy complications is uncertain and hard to predict,nd will be important to monitor as these strategies emerge.

One possible approach to noncolonoscopic imaging testshat appears to optimize their benefits and cost effectiveness iso triage their use to populations with low anticipated polyprevalence based on demographic factors such as age and sex.87

n this approach, diagnosis-only strategies are used for primarycreening in low-polyp prevalence populations, and colonos-opy is used in high-polyp prevalence populations.87 This in-ermediate approach would mitigate potential negative effectsn cancer prevention of reduced polypectomy, and at the sameime reduce complications of diagnostic colonoscopy in low-revalence populations. Further, the approach appears costffective.87

In summary, the use of alternative imaging strategies forolon polyps in countries such as the United States that cur-ently are using colonoscopy for screening and that are com-

itted to polyp detection and resection as a means of cancerrevention, will require careful monitoring. The use of theseests to increase adherence to colorectal cancer screening or tovercome manpower deficiencies in providing colonoscopyould appear to have clear benefits for cancer prevention. These of these tests on a widespread basis as an alternative toolonoscopy screening would reduce polypectomy substan-ially, which might increase colorectal cancer incidence. Re-earch into the potential of alternative imaging tests to improvedherence is as important as establishing the performance char-cteristics of the techniques. The ultimate position of colonos-opy in primary screening will depend on evidence and percep-ions regarding the issues of adherence, effectiveness, and

omplications.

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512 REX AND EID CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 6, No. 5

Plotting New Directions forColonoscopyImproved Performance and TechnologyFor the foreseeable future, colonoscopy is likely to be the

iagnostic test of choice in patients with positive screening testsnd patients with symptoms strongly predictive of colorectal can-er, particularly the bleeding symptoms: hematochezia, iron-defi-iency anemia, and melena with a negative upper endoscopy.88

herefore, every possible advance with regard to correcting causesf interval cancers is worthy of pursuit (Table 3). As noted earlier,idespread use of measures that improve colonoscopy efficacynd safety and improved colonoscope technology are likely tomprove the position of colonoscopy as a continued primarycreening tool relative to emerging imaging technologies.

In addition to advances (Table 3) that are immediatelychievable, colonoscopy is no longer a stagnant technology andew developments in imaging (Table 2) and possibly even in

nsertion platforms89,90 could enhance the effectiveness or costffectiveness of colonoscopy.

Cost ReductionsAs imaging technology advances, the detection of tiny

denomas is likely to increase,46 which could negatively impact theost effectiveness of colonoscopy by increasing the associatedolypectomy and pathology charges, perhaps without substan-ially enhancing effectiveness. One potential approach to this de-elopment is to ignore tiny adenomatous lesions, but the strengthf colonoscopy has always been its potential for simultaneousecognition and resection of precancerous lesions. An alternativepproach would be to recognize and remove tiny adenomas, ac-ompanied by expansion of the portion of the adenoma cohortonsidered at low risk, and for whom postpolypectomy surveil-ance intervals can be up to 10 years, and perhaps even longer ifxamination includes complete clearing of even the tiniest andattest lesions. The cost of pathology evaluation of very smallolyps is quite substantial and the main use of the informationbtained from pathologic resection of polyps 5 mm or less in size

s to guide postpolypectomy surveillance intervals. If reliable real-ime methods of polyp histology could be developed, small polypsould be destroyed or resected and discarded, and postpolypec-omy surveillance could be based on real-time endoscopic assess-

ent of histology. The cost savings associated with this develop-ent are obvious and the relative cost effectiveness of colonoscopy

nd polypectomy compared with alternative imaging strategiesould be enhanced by this development.

Whether involvement in colonoscopy sedation by anesthesiapecialists increases or decreases will be another key determi-ant of the relative cost effectiveness of colonoscopy comparedith alternative diagnosis-only imaging strategies.

Concluding RemarksUltimately, the role of colonoscopy in colorectal cancer

revention and in gastrointestinal practice will depend on de-elopments in technology, physician and public perceptions ofhe risks and benefits of new screening tests, and insurers’udgments about the relative costs, cost effectiveness, and costavings of different strategies. Effective and safe CT colonogra-hy without bowel preparation or development of an effective

roteomic or serum DNA assay are examples of technologies 1

hat might dramatically impact the use of screening colonos-opy. Gastroenterologists currently are involved in many as-ects of new technology development and will be uniquelyuited to direct patients to appropriate strategies based onssessment of polyp and cancer risk and procedure risk. Even ifhe role of colonoscopy becomes confined everywhere to diag-ostic examinations (Figure 1), highly effective colonoscopy wille critical to any screening approach to colorectal cancer.

The initial steps in enhancing colonoscopy’s effectiveness seemtraightforward (Table 3). Colonoscopists everywhere must be-ome experts in bowel preparation science. Investigators in bowelreparation should continue to look for an optimal combinationf efficacy, safety, and tolerability. Colonoscopy should be per-ormed everywhere in a careful and meticulous fashion, and thispproach should be documented by a record of adequate adenomaetection by individual colonoscopists.15,16 Polypectomy shouldse effective methods of resection. When methods known to bessociated with ineffective resection are used, particularly piece-eal resection of large sessile adenomas, there should be aggres-

ive follow-up evaluation. With a commitment to quality by everyolonoscopist, perhaps we may fulfill the promise of the Nationalolyp Study.

References

1. Winawer SJ, Zauber AG, Fletcher RH, et al. Guidelines for colonos-copy surveillance after polypectomy: a consensus update by theUS Multi-Society Task Force on Colorectal Cancer and the Amer-ican Cancer Society. Gastroenterology 2006;130:1872–1885.

2. Rex DK, Kahi CJ, Levin B, et al. Guidelines for colonoscopysurveillance after cancer resection: a consensus update by theAmerican Cancer Society and the US Multi-Society Task Force onColorectal Cancer. Gastroenterology 2006;130:1865–1871.

3. Atkin WS, Saunders BP. Surveillance guidelines after removal ofcolorectal adenomatous polyps. Gut 2002;51(Suppl 5):V6–V9.

4. Hoff G, Sauar J, Vatn MH, et al. Polypectomy of adenomas in theprevention of colorectal cancer: 10 years’ follow-up of theTelemark Polyp Study I. A prospective, controlled populationstudy. Scand J Gastroenterol 1996;31:1006–1010.

5. Colorectal cancer screening activities in ICSN countries. Availableat: http://appliedresearch.cancer.gov/icsn/colorectal/screening.html. Accessed: December 3, 2007.

6. Steele RJ. Fecal occult blood test screening in the United King-dom. Am J Gastroenterol 2006;101:216–218.

7. Bowles CJ, Leicester R, Romaya C, et al. A prospective study ofcolonoscopy practice in the UK today: are we adequately pre-pared for national colorectal cancer screening tomorrow? Gut2004;53:277–283.

8. The Australian bowel cancer screening pilot: outcomes for theworkforce and quality issues in colonoscopy workshop. Availableat: www.health.gov.au. Accessed: December 3, 2007.

9. Brenner H, Hoffmeister M, Stegmaier C, et al. Risk of progressionof advanced adenomas to colorectal cancer by age and sex:estimates based on 840,149 screening colonoscopies. Gut2007;56:1585–1589.

0. Regula J, Rupinski M, Kraszewska E, et al. Colonoscopy in colo-rectal-cancer screening for detection of advanced neoplasia.N Engl J Med 2006;355:1863–1872.

1. Seeff LC, Richards TB, Shapiro JA, et al. How many endoscopiesare performed for colorectal cancer screening? Results fromCDC’s survey of endoscopic capacity. Gastroenterology 2004;127:1670–1677.

2. Gatto NM, Frucht H, Sundararajan V, et al. Risk of perforationafter colonoscopy and sigmoidoscopy: a population-based study.J Natl Cancer Inst 2003;95:230–236.

3. Levin TR, Zhao W, Conell C, et al. Complications of colonoscopy

1

1

1

1

1

1

2

2

2

2

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4

4

4

4

4

4

4

5

5

May 2008 COLONOSCOPY IN COLORECTAL CANCER PREVENTION 513

in an integrated health care delivery system. Ann Intern Med2006;145:880–886.

4. Singh G, Mannalithara A, Mithal A, et al. Perforation risk followingcolonoscopy: small but significant, and on the rise. GastrointestEndosc 2007;65:AB320.

5. Rex DK, Bond JH, Winawer S, et al. Quality in the technical perfor-mance of colonoscopy and the continuous quality improvementprocess for colonoscopy: recommendations of the U.S. Multi-Soci-ety Task Force on Colorectal Cancer. Am J Gastroenterol 2002;97:1296–1308.

6. Rex DK, Petrini JL, Baron TH, et al. Quality indicators for colonos-copy. Am J Gastroenterol 2006;101:873–885.

7. Mysliwiec PA, Brown ML, Klabunde CN, et al. Are physicians doingtoo much colonoscopy? A national survey of colorectal surveillanceafter polypectomy. Ann Intern Med 2004;141:264–271.

8. Boolchand V, Olds G, Singh J, et al. Colorectal screening afterpolypectomy: a national survey study of primary care physicians.Ann Intern Med 2006;145:654–659.

9. Sedjo RL, Byers T, Barrera E Jr, et al. A midpoint assessment ofthe American Cancer Society challenge goal to decrease cancerincidence by 25% between 1992 and 2015. CA Cancer J Clin2007;57:326–340.

0. Gross CP, Andersen MS, Krumholz HM, et al. Relation betweenMedicare screening reimbursement and stage at diagnosis forolder patients with colon cancer. JAMA 2006;296:2815–2822.

1. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectalcancer by colonoscopic polypectomy. The National Polyp StudyWorkgroup. N Engl J Med 1993;329:1977–1981.

2. Zauber A, Winawer SJ, O’Brien MJ, et al. Significant long termreduction in colorectal cancer mortality with colonoscopicpolypectomy: findings of the National Polyp Study. Gastroenter-ology 2007;132:A50.

3. Zauber A, Winawer SJ, Lansdorp-Vogelaar I, et al. Effect of initialpolypectomy versus surveillance polypectomy on colorectal can-cer mortality reduction: micro-simulation modeling of the NationalPolyp Study. Am J Gastroenterol 2007;102:S558.

4. Rex D, Sledge G, Harper P, et al. Colonic neoplasia in asymp-tomatic persons with negative fecal occult blood tests: influenceof age, gender, and family history. Am J Gastroenterol 1993;88:825–831.

5. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy toscreen asymptomatic adults for colorectal cancer. Veterans AffairsCooperative Study Group 380. N Engl J Med 2000;343:162–168.

6. Imperiale T, Wagner D, Lin C, et al. Risk of advanced proximalneoplasms in asymptomatic adults according to the distal colo-rectal findings. N Engl J Med 2000;343:169–174.

7. Citarda F, Tomaselli G, Capocaccia R, et al. The Italian Multicen-tre Study Group. Efficacy in standard clinical practice of colono-scopic polypectomy in reducing colorectal cancer incidence. Gut2001;48:812–815.

8. Thiis-Evensen E, Hoff G, Sauar J, et al. Population-based surveil-lance by colonoscopy: effect on the incidence of colorectal cancer.Telemark Polyp Study I Scand. J Gastroenterol 1999;34:414–420.

9. Dove-Edwin I, Sasieni P, Adams J, et al. Prevention of colorectalcancer by colonoscopic surveillance in individuals with a familyhistory of colorectal cancer: 16 year, prospective, follow-upstudy. BMJ 2005;331:1047.

0. Brenner H, Chang-Claude J, Seiler CM, et al. Does a negativescreening colonoscopy ever need to be repeated? Gut 2006;55:1145–1150.

1. Alberts DS, Martinez ME, Roe DJ, et al. Lack of effect of ahigh-fiber cereal supplement on the recurrence of colorectal ad-enomas. Phoenix Colon Cancer Prevention Physicians’ Network.N Engl J Med 2000;342:1156–1162.

2. Schatzkin A, Lanza E, Corle D, et al. The Polyp Prevention Trial

Study Group. Lack of effect of a low-fat, high-fiber diet on the

recurrence of colorectal adenomas. N Engl J Med 2000;342:1149–1155.

3. Jorgensen OD, Kronborg O, Fenger C. The Funen Adenoma Fol-low-up Study. Incidence and death from colorectal carcinoma inan adenoma surveillance program. Scand J Gastroenterol 1993;28:869–874.

4. Robertson DJ, Greenberg ER, Beach M, et al. Colorectal cancer inpatients under close colonoscopic surveillance. Gastroenterol-ogy 2005;129:34–41.

5. Muller AD, Sonnenberg A. Prevention of colorectal cancer byflexible endoscopy and polypectomy. A case-control study of32,702 veterans. Ann Intern Med 1995;123:904–910.

6. Singh H, Turner D, Xue L, et al. Risk of developing colorectalcancer following a negative colonoscopy examination: evidencefor a 10-year interval between colonoscopies. JAMA 2006;295:2366–2373.

7. Singh G, Gerson LB, Wang H, et al. Screening colonoscopy,colorectal cancer and gender: an unfair deal for the fair sex?Gastrointest Endosc 2007;65:AB100.

8. Umar A, Boland CR, Terdiman JP, et al. Revised Bethesda Guide-lines for hereditary nonpolyposis colorectal cancer (Lynch syn-drome) and microsatellite instability. J Natl Cancer Inst 2004;96:261–268.

9. Pinol V, Castells A, Andreu M, et al. Accuracy of revised Bethesdaguidelines, microsatellite instability, and immunohistochemistryfor the identification of patients with hereditary nonpolyposiscolorectal cancer. JAMA 2005;293:1986–1994.

0. Hampel H, Frankel WL, Martin E, et al. Screening for the Lynchsyndrome (hereditary nonpolyposis colorectal cancer). N EnglJ Med 2005;352:1851–1860.

1. Dove-Edwin I, de Jong AE, Adams J, et al. Prospective results ofsurveillance colonoscopy in dominant familial colorectal cancerwith and without Lynch syndrome. Gastroenterology 2006;130:1995–2000.

2. Vasen HF, Nagengast FM, Khan PM. Interval cancers in heredi-tary non-polyposis colorectal cancer (Lynch syndrome). Lancet1995;345:1183–1184.

3. Winawer S, Fletcher R, Rex D, et al, Gastrointestinal ConsortiumP. Colorectal cancer screening and surveillance: clinical guide-lines and rationale—update based on new evidence. Gastroen-terology 2003;124:544–560.

4. Jass JR. Hyperplastic polyps and colorectal cancer: is there alink? Clin Gastroenterol Hepatol 2004;2:1–8.

5. Hurlstone DP, Karajeh M, Cross SS, et al. The role of high-magnification-chromoscopic colonoscopy in hereditary nonpol-yposis colorectal cancer screening: a prospective “back-to-back”endoscopic study. Am J Gastroenterol 2005;100:2167–2173.

6. Rex DK, Helbig CC. High yields of small and flat adenomas withhigh-definition colonoscopes using either white light or narrowband imaging. Gastroenterology 2007;133:42–47.

7. Rex DK, Ulbright TM. Step section histology of proximal colonpolyps that appear hyperplastic by endoscopy. Am J Gastroen-terol 2002;97:1530–1534.

8. Sawhney MS, Farrar WD, Gudiseva S, et al. Microsatellite instabilityin interval colon cancers. Gastroenterology 2006;131:1700–1705.

9. Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopypreparation quality on detection of suspected colonic neoplasia.Gastrointest Endosc 2003;58:76–79.

0. Froehlich F, Wietlisbach V, Gonvers JJ, et al. Impact of coloniccleansing on quality and diagnostic yield of colonoscopy: the Euro-pean Panel of Appropriateness of Gastrointestinal Endoscopy Euro-pean multicenter study. Gastrointest Endosc 2005;61:378–384.

1. Parra-Blanco A, Nicolas-Perez D, Gimeno-Garcia A, et al. The timingof bowel preparation before colonoscopy determines the quality ofcleansing, and is a significant factor contributing to the detection offlat lesions: a randomized study. World J Gastroenterol 2006;12:

6161–6166.

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2. Cohen L, Kastenberg D, Lottes SR, et al. Polyp detection rateduring colonoscopy is correlated with quality of bowel prepara-tion. Am J Gastroenterol 2006;101:S556.

3. Rex DK, Imperiale TF, Latinovich DR, et al. Impact of bowelpreparation on efficiency and cost of colonoscopy. Am J Gastro-enterol 2002;97:1696–1700.

4. Rex D, Malik P, Chasen R, et al. A randomized, single blindevaluation of oral sodium phosphate solution (OSPS) as bowelpreparation with different hydration and dosing regimens. Am JGastroenterol 2006;101:S504.

5. Rostom A, Jolicoeur E, Dube C, et al. A randomized prospective trialcomparing different regimens of oral sodium phosphate and poly-ethylene glycol-based lavage solution in the preparation of patientsfor colonoscopy. Gastrointest Endosc 2006;64:544–552.

6. Aoun E, Abdul-Baki H, Azar C, et al. A randomized single-blind trialof split-dose PEG-electrolyte solution without dietary restrictioncompared with whole dose PEG-electrolyte solution with dietaryrestriction for colonoscopy preparation. Gastrointest Endosc2005;62:213–218.

7. Practice guidelines for preoperative fasting and the use of phar-macologic agents to reduce the risk of pulmonary aspiration:application to healthy patients undergoing elective procedures: areport by the American Society of Anesthesiologist Task Force onPreoperative Fasting. Anesthesiology 1999;90:896–905.

8. Barclay RL, Vicari JJ, Doughty AS, et al. Colonoscopic withdrawaltimes and adenoma detection during screening colonoscopy.N Engl J Med 2006;355:2533–2541.

9. Chen SC, Rex DK. Endoscopist can be more powerful than ageand male gender in predicting adenoma detection at colonos-copy. Am J Gastroenterol 2007;102:856–861.

0. Simmons DT, Harewood GC, Baron TH, et al. Impact of endoscopistwithdrawal speed on polyp yield: implications for optimal colonos-copy withdrawal time. Aliment Pharmacol Ther 2006;24:965–971.

1. Rex DK, Rahmani EY, Haseman JH, et al. Relative sensitivity ofcolonoscopy and barium enema for detection of colorectal cancerin clinical practice. Gastroenterology 1997;112:17–23.

2. Bressler B, Paszat LF, Chen Z, et al. Rates of new or missedcolorectal cancers after colonoscopy and their risk factors: a popu-lation-based analysis. Gastroenterology 2007;132:96–102.

3. Singh H, Turner D, Xue L, et al. Colorectal cancers after anegative colonoscopy. Gastroenterology 2007;132:A149.

4. Pabby A, Schoen RE, Weissfeld JL, et al. Analysis of colorectalcancer occurrence during surveillance colonoscopy in the dietaryPolyp Prevention Trial. Gastrointest Endosc 2005;61:385–391.

5. Farrar WD, Sawhney MS, Nelson DB, et al. Colorectal cancersfound after a complete colonoscopy. Clin Gastroenterol Hepatol2006;4:1259–1264.

6. Rex DK. Have we defined best colonoscopic polypectomy practice inthe United States? Clin Gastroenterol Hepatol 2007;5:674–677.

7. Brooker JC, Saunders BP, Shah SG, et al. Treatment with argonplasma coagulation reduces recurrence after piecemeal resec-tion of large sessile colonic polyps: a randomized trial and rec-ommendations. Gastrointest Endosc 2002;55:371–375.

8. Singh N, Harrison M, Rex DK. A survey of colonoscopic polypec-tomy practices among clinical gastroenterologists. GastrointestEndosc 2004;99:414–418.

9. Rex DK. Maximizing detection of adenomas and cancers duringcolonoscopy. Am J Gastroenterol 2006;101:2866–2877.

0. Leard LE, Savides TJ, Ganiats TG. Patient preferences for colo-rectal cancer screening. J Fam Pract 1997;45:211–218.

1. Lieberman D, Lacey MJ, Anastassopoulos KP, et al. Medicarecolonoscopy rates among gastroenterologists between 1999 and2002: are gastroenterologists at capacity for colonoscopy inMedicare beneficiaries? Gastrointest Endosc 2005;61:AB153.

2. Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal 4

neoplasms with new fecal occult blood tests: update onperformance characteristics. J Natl Cancer Inst 2007;99:1462–1470.

3. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versusfecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704–2714.

4. Eliakim R, Fireman Z, Adler S. PillCamTM colon in comparison withstandard colonoscopy in the detection of polyps—results fromthe first prospective multi-center study. Am J Gastroenterol2006;101:S552.

5. Schoofs N, Deviere J, Van Gossum A. PillCam colon capsuleendoscopy compared with colonoscopy for colorectal tumor diag-nosis: a prospective pilot study. Endoscopy 2006;38:971–977.

6. Vucelic B, Rex D, Pulanic R, et al. The aer-o-scope: proof ofconcept of a pneumatic, skill-independent, self-propelling, self-navigating colonoscope. Gastroenterology 2006;130:672–677.

7. Ray Q, Kim C, Scott T, et al. Gastroenterologist interpretation ofCTC: pilot study demonstrating feasibility and similar accuracycompared to radiologists. Gastroenterology 2007;132:A92–A93.

8. Patrick A, Jackson L, Bell J, et al. High proficiency reading of V3Dvirtual colonoscopy by experienced optical endoscopists and en-doscopy nurses; a new era in colonoscopy? Gastrointest Endosc2007;65:AB129.

9. Bodily KD, Fletcher JG, Engelby T, et al. Nonradiologists assecond readers for intraluminal findings at CT colonography.Acad Radiol 2005;12:67–73.

0. Jensch S, van Gelder RE, Florie J, et al. Performance of radiog-raphers in the evaluation of CT colonographic images. AJR Am JRoentgenol 2007;188:W249–W255.

1. Zalis ME, Barish MA, Choi JR, et al. CT colonography reportingand data system: a consensus proposal. Radiology 2005;236:3–9.

2. Stryker SJ, Wolff BG, Culp CE, et al. Natural history of untreatedcolonic polyps. Gastroenterology 1987;93:1009–1013.

3. Hofstad B, Vatn M. Growth rate of colon polyps and cancer.Gastrointest Endosc Clin N Am 1997;7:345–363.

4. Hur C, Chung DC, Schoen RE, et al. The management of smallpolyps found by virtual colonoscopy: results of a decision analy-sis. Clin Gastroenterol Hepatol 2007;5:237–244.

5. Sonnenberg A, Delco F, Bauerfeind P. Is virtual colonoscopy acost-effective option to screen for colorectal cancer? Am J Gas-troenterol 1999;94:2268–2274.

6. Scott RG, Edwards JT, Fritschi L, et al. Community-based screen-ing by colonoscopy or computed tomographic colonography inasymptomatic average-risk subjects. Am J Gastroenterol 2004;99:1145–1151.

7. Lin OS, Kozarek RA, Schembre DB, et al. Risk stratification forcolon neoplasia: screening strategies using colonoscopy andcomputerized tomographic colonography. Gastroenterology 2006;131:1011–1019.

8. Rex DK. Colonoscopy: a review of its yield for cancers andadenomas by indication. Am J Gastroenterol 1995;90:353–365.

9. Kamal A, van Dam J. Reduced looping with a computer-assistedcolonoscope: initial experience. Am J Gastroenterol 2006;101:S523.

0. Roesch T, Adler A, Wiedenmann BH, et al. A prospective pilotstudy to assess technical performance of a new single usecolonoscope with inverted sleeve technology. Gastrointest En-dosc 2007;65:AB340.

Address requests for reprints to: Douglas K. Rex, MD, Department ofedicine, Division of Gastroenterology, Indiana University School ofedicine, 550 N. University Boulevard UH 4100, Indianapolis, Indiana

6202. e-mail: drex@iupui.edu; fax: (317) 274-5449.