screening at 3 or 5 years to a usual-care control group.31 Flexible sigmoidoscopy reduced CRC incidence

by 21% with a benefit observed in both the proximal and distal colon, and reduced overall mortality by

26% (intention-to-treat analyses). Mortality from distal CRC (distal to the splenic flexure) was reduced

by 50%, while mortality from proximal CRC was unaffected. The Italian Randomized Controlled Trial

(SCORE) demonstrated that once-only sigmoidoscopy significantly reduced CRC incidence by 18% and

mortality by 22% (not significant) in intention-to-treat analyses, and by 31% and 38%, respectively in

per-protocol analyses (both significant).32 These results have resulted in once in a lifetime flexible

sigmoidoscopy being included as an option in the UK National Health Service Bowel Cancer Screening

Programme; FOBT is the other option.

Colonoscopy, Barium Enema, Computed Tomography Colonography, and Stool DNA

Testing

Colonoscopy may be the most effective tool to screen for colorectal neoplasia (and especially

adenomas), but data from prospective randomized trials are lacking. The NPS of polypectomy and

surveillance strongly suggested a reduction in colorectal cancer mortality as a result of removing

adenomatous polyps compared to historic reference populations. A Canadian population-based study

compared the risk of developing colorectal cancer after a negative colonoscopy in all Ontario residents

with a history of a complete negative colonoscopy with controls consisting of the Ontario population

without a history of colonoscopy.33 In the negative colonoscopy cohort, the relative risk of distal

colorectal cancer was significantly lower than the control group in each of the 14 years of follow-up,

while the relative risk for proximal colorectal cancer was significantly lower mainly during the last 7

years of follow-up. A second Canadian case-control study demonstrated that complete colonoscopy was

also associated with fewer deaths from left-sided colorectal cancer, but not from right-sided cancer.

Several other population-based analyses and analyses of individual screening programs in the United

States, Canada, and Europe also suggest that increased use of colonoscopy is associated with mortality

reduction from CRC, but this reduction varies by the site of the cancer.34–38 A large case-control study

using SEER-Medicare data demonstrated that colonoscopy was associated with a 60% decreased risk of

CRC-related death, but the association was stronger for distal (OR 0.24; 95% CI: 0.21 to 0.27) than

proximal (OR 0.58; 95% CI: 0.53 to 0.64) CRC, consistent with European and Canadian studies.38 These

reports suggest that either proximal lesions are not detected as reliably as distal ones at colonoscopy,

that the lesions grow at different rates based upon location in the colon, or both.

These findings are of interest in light of arguments that colonoscopy is preferable to sigmoidoscopy,

because there may be a substantial incidence of proximal colonic cancers and advanced adenomas

beyond the reach of the sigmoidoscope. Some of these individuals may not have distal findings on

sigmoidoscopy that would trigger a subsequent colonoscopy. Two trials

39,40 suggested that

approximately 50% of individuals with advanced proximal neoplasms (adenoma >1 cm; adenoma with

villous features or dysplasia; cancer) have no distal neoplasms. Fewer than 2% of those who did not

have distal neoplasms, however, had an advanced proximal lesion. A decision analysis commissioned by

the USPSTF supports colonoscopy every 10 years as a screening option measured in life-years gained,

and the joint guidelines authored by the ACS, USMTF, and ACR recommend colonoscopy as a means of

preventing colorectal cancer through adenoma detection and removal.

High-contrast endoscopy using dye or stain solutions combined with colonoscopy (chromoendoscopy)

or high-resolution optical methods (e.g., narrow-band imaging and laser confocal endoscopy) have been

suggested as a means of identifying lesions in high-risk groups, or as an adjunct to colonoscopy where

flat lesions (so-called “flat adenomas”) are suspected. Recent evidence suggests that flat or depressed

neoplasms are more common than previously appreciated and carry a high relative risk of containing in

situ or invasive carcinoma.41

Air-contrast barium enema (ACBE) has been included as an option in a variety of screening guidelines,

but has for the most part been supplanted by other methods due to its poor sensitivity for detecting

small polyps. CT colonography, or “virtual” colonoscopy, involves the use of helical CT to generate

high-resolution images of the abdomen and pelvis. CT colonography has the potential advantage of

being a rapid and safe method of providing full structural evaluation of the entire colon. Two trials

provide evidence that CT colonography may be a valid alternative for primary colon cancer screening.

The National CT Colonography Trial42 directed by the American College of Radiology Imaging Network

(ACRIN) was a multicenter study that employed CT colonography and same-day colonoscopy using a

standard matching protocol in 2,600 asymptomatic individuals. Per patient sensitivity of CT

colonography for adenomas greater than 10 mm was 90% with a negative predictive value of 99%. A

1737

second trial43 compared CT colonography and optical colonoscopy in parallel screening cohorts and

demonstrated similar rates of detection of advanced neoplasia in both groups. Several key issues need to

be addressed as the use of CT colonography becomes more widespread, principal among which is

determination of the acceptable size cut-off of a lesion detected by CT colonography that will

necessitate a follow-up colonoscopy.

A great deal of knowledge has been accumulated recently about genetic alterations that occur during

colon carcinogenesis, as discussed earlier. A molecular approach to colorectal cancer screening is

therefore attractive since it targets biologic changes that are fundamental to the neoplastic process.

Fecal DNA testing relies on the detection of genetic alterations in DNA shed into the stool from

neoplastic lesions. Recent prospective data using a multimarker panel which includes both stool DNA

testing and FIT showed >90% sensitivity for detecting colorectal cancer, but suboptimal performance

for detecting high-risk adenomas. The sensitivity for detection of advanced adenoma with the combined

stool DNA marker/FIT panel was 42.4%. FIT alone detected only 23.8% of advanced adenomas.29 Based

on these data, the FDA has approved the combined panel for screening for colorectal neoplasia.

Management of Adenomas

Index Polypectomy

Once detected, adenomas should be completely removed, preferably by endoscopic snare polypectomy

(Fig. 67-8). Polypectomy is relatively safe and easily performed when adenomas are small or

pedunculated. Newer techniques such as EMR and ESD have made it possible to remove even large

sessile lesions (Fig. 67-9). Large sessile villous adenomas (>2 cm), especially those with high-grade

dysplasia have a great potential for malignant degeneration. If such lesions cannot be completely

removed by snare polypectomy or EMR, and when there is uncertainty about the polypectomy margin

in the case of pathologically advanced lesions, segmental surgical resection may be necessary.

Diminutive polyps, on the other hand, carry little malignant potential. If they are too small for snare

polypectomy, ablation with a hot biopsy forceps is a reasonable approach. Because 30% to 50% of

patients with one adenoma have a synchronous adenoma elsewhere in the colon, the entire colon should

be “cleared” by colonoscopy in polyp-bearing patients.

Figure 67-8. Endoscopic snare polypectomy. A: A small colonic polyp. B: The polypectomy snare is placed around the polyp. C:

The snare is closed around the base of the polyp, and the head of the polyp is gently pulled away from the wall and into the

lumen. Current is applied to cut the stalk and cauterize the site. D: The site after completion of polypectomy.

Quality Measures

As the number of colonoscopies (and colonoscopists) increases, quality assurance measures will need to

be adopted. One measure of quality assurance relates to adequate visualization of the colonic mucosa.

ADR is defined by the percentage of screening or surveillance colonoscopies of average risk with at least

one adenoma and is the most commonly used quality measure in practice. Benchmarks for adequate

ADRs have been suggested as at least 15% for women and 25% for men (20% overall). The ADR is

1738

considered by the ASGE/ACG Task Force on Quality in Endoscopy to be the best neoplasia-related

indicator of quality performance for screening colonoscopy. The ADR has been demonstrated to be an

independent predictor of the risk of interval colorectal cancer after screening colonoscopy.44–46

Endoscopist characteristics derived from administrative data are associated with the development of

postcolonoscopy colorectal cancer, and have potential use as quality indicators. Other quality measures

include the quality of bowel preparation and completeness of polyp resection. The incomplete resection

rate in the Complete Adenoma Resection (CARE) study was 10.1% overall, and varied broadly among

endoscopists.

Figure 67-9. Endomucosal resection (EMR) of a large sessile polyp. A: Large sessile adenoma seen at colonoscopy. B: Salinecontaining indigo carmine dye is injected into the mucosa to lift the polyp. C: The polyp is resected piecemeal using a

polypectomy snare. D: Completed EMR.

Follow-Up

Much of our current practice has come from information gained through the NPS, first organized in

1978. Additional metachronous adenomas are likely to develop in patients who have had adenomas

removed. Colonoscopic surveillance studies have provided estimates of the frequency and time course of

recurrence in these patients. Data from the NPS suggested a recurrence rate of 32% to 42% by 3 years

after index polypectomy. A prospective colonoscopic analysis also demonstrated a cumulative

recurrence rate at 3 years of 42%. Most adenomas detected at this 3-year interval were small tubular

adenomas. Age above 60 years, multiple adenomas at index polypectomy and large size of the index

adenoma predicted polyp recurrence in the NPS, but only multiplicity predicted recurrence of polyps

with advanced pathologic features (i.e., >1 cm, high-grade dysplasia, or invasive cancer) at follow-up.

The 3-year recurrence rate in patients with a known history of adenoma (42%) was higher than the

incidence rate of adenoma appearance de novo during this period in patients who had no adenomas

detected on index colonoscopy (16%).22

The high recurrence rate of adenomas after index polypectomy supports the use of postpolypectomy

surveillance in patients with known histories of adenoma. Colonoscopy is the preferred means of followup in these patients. ACBEs are inadequate for surveillance examinations; they miss a substantial

1739

number of large lesions and most small polyps. Barium enema has been supplanted by the use of CT

colonography, as discussed earlier. Colonoscopy is the most accurate means of evaluating the colonic

mucosa, and most importantly, allows biopsy and removal of polyps.

Several studies, including data from the NPS, indicate that surveillance intervals for colonoscopy

should be tailored to risk of recurrence. One recent study examined the relative risk for advanced

neoplasia within 5.5 years of a baseline colonoscopy.47 There was a strong association between the

results of baseline-screening colonoscopy and the rate of serious incident lesions during surveillance.

This study confirmed that patients with one or two small tubular adenomas represent a low-risk group

compared with other patients with colorectal neoplasia.

Table 67-3 lists the 2012 updated Multi-Society Task Force on Colorectal Cancer guidelines for

screening, surveillance, and early detection of colorectal adenomas and cancer for individuals at

increased risk or at high risk of disease. This group represents the American Gastroenterological

Association Institute, the American Society for Gastrointestinal Endoscopy, and the American College of

Gastroenterology. A clinical decision tool based on these guidelines was also published in 2014.48 These

guidelines suggest that those whose index lesion consists of one or two small tubular adenomas with

low-grade dysplasia should have a follow-up colonoscopy no sooner than 5 to 10 years after the initial

polypectomy. The precise timing within this interval should be based on clinical factors (prior findings,

family history, patient and physician preferences). In those with a large (>1 cm) adenoma, multiple (3

to 10) adenomas, or adenomas with high-grade dysplasia or villous change, colonoscopy should be

repeated within 3 years after the initial polypectomy. Although the risk for recurrence of advanced

adenomas at this follow-up interval is greater in patients with high-risk adenomas than those with lowrisk adenomas, the incremental risk is small.49 If the examination is normal or shows only one or two

small tubular adenomas with low-grade dysplasia, then the interval for the subsequent examination

should be 5 years. Patients with more than 10 adenomas on a single examination should have a followup colonoscopy less than 3 years after the initial polypectomy and the presence of an underlying

familial polyposis syndrome should be considered. Patients with sessile adenomas that are removed

piecemeal should have follow-up colonoscopy in 2 to 6 months to verify complete removal. Guidelines

for follow-up of serrated polyps are currently similar to those of conventional adenomas (3 years for

lesions ≥10 mm, or with dysplasia for TSAs; 5 years for lesions in the proximal colon and without

dysplasia; and 1 year for serrated polyposis syndrome).

Table 67-3 Guidelines for the Surveillance of Adenomas in People at Increased or

High Risk for Colorectal Cancer

1740

Management of Malignant Polyps

Endoscopic polypectomy is adequate treatment for an adenomatous polyp–containing cancer if it can be

demonstrated that the cancer is confined to the head of the polyp (i.e., carcinoma in situ or

intramucosal carcinoma; Fig. 67-10). The adequacy of simple polypectomy has been controversial in

cases in which malignant cells have invaded the polyp stalk (Fig. 67-11), but most studies indicate that

polypectomy is adequate treatment provided that a margin of more than 2 mm is present, the cancer is

not poorly differentiated, and no vascular or lymphatic invasion is noted. The presence of cancer at or

near the margin is significantly associated with an adverse outcome, even in the absence of other

unfavorable parameters. On the other hand, in the absence of unfavorable histology and with a negative

margin, the incidence of residual cancer is low (<1%). These criteria are more difficult to assess in

sessile polyps. If an adequate margin cannot be demonstrated or negative histologic parameters are

present, surgery is recommended to treat the possibility of residual neoplasia or regional lymph node

metastases.

1741