The n e w e ng l a n d j o u r na l of m e dic i n e

clinical practice

Adenomatous Polyps of the Colon

Joel S. Levine, M.D., and Dennis J. Ahnen, M.D.

This Journal feature begins with a case vignette highlighting a common clinical problem.
Evidence supporting various strategies is then presented, followed by a review of formal guidelines,
when they exist. The article ends with the authors’ clinical recommendations.

A 52-year-old man with no personal or family history of colon cancer, colonic polyps,
or inflammatory bowel disease underwent a screening colonoscopy that showed no
abnormalities except for a 1.5-cm pedunculated polyp at the hepatic flexure that was
removed by means of a snare with cautery. The polyp was a tubulovillous adenoma
without high-grade dysplasia. How should his care be managed?

The Cl inic a l Probl e m

In 2006, it is estimated that there will be more than 145,500 new cases of colorectal From the University of Colorado School
cancer and 55,000 deaths from this disease in the United States, making colorectal of Medicine ( J.S.L., D.J.A.) and the Den-
ver Department of Veterans Affairs Medi-
cancer the second most common cause of death from cancer.1 Colonic adenomas, cal Center (D.J.A.) — both in Denver. Ad-
the precursors of almost all sporadic colorectal cancers, are found in up to 40% of dress reprint requests to Dr. Ahnen at the
persons by 60 years of age. The adenoma–carcinoma sequence — the progression Gastroenterology Section (111E), Denver
Department of Veterans Affairs Medical
from normal colonic mucosa to small tubular adenomas to larger adenomas and Center, 1055 Clermont St., Denver, CO
those with more advanced histologic features (villous features, high-grade dysplasia, 80220, or at dennis.ahnen@uchsc.edu.
or both) to cancer — is a central tenet of our understanding and management of
N Engl J Med 2006;355:2551-7.
colonic adenomas. Although not all colonic polyps (Fig. 1) are adenomas (hyper- Copyright © 2006 Massachusetts Medical Society.
plastic polyps account for about half of small, rectosigmoid polyps) and more than
90% of adenomas do not progress to cancer, it is currently not possible to reliably
identify those that will progress. Thus, colonic polyps identified at colonoscopy
should be removed if it is technically feasible to do so. Complete removal of a colonic
adenoma eliminates the risk of cancer from that adenoma, but the finding of a
colonic adenoma may indicate an increased risk of metachronous adenomas and
colorectal cancer for both the patient and his or her first-degree relatives (i.e., parents,
siblings, and children).
Colonic adenomas are typically asymptomatic and are most commonly found by
means of endoscopic or radiologic imaging studies performed because of unrelated
symptoms or for colorectal cancer screening. Since at least 25% of men and 15%
of women who undergo colonoscopic screening by experienced endoscopists are
found to have one or more adenomas, the cumulative burden of subsequent sur-
veillance colonoscopy on the health care system is substantial. In 1999, it was esti-
mated that one quarter of the 4.4 million colonoscopies performed in the United
States were for polyp surveillance, and there has been a marked increase in endo-
scopic screening since that time.2

S t r ategie s a nd E v idence

Colonoscopic Polypectomy and Surveillance

Colonoscopic surveillance is recommended for patients with adenomas because the
risks of new (metachronous) adenomas and colorectal cancer among these patients

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 The n e w e ng l a n d j o u r na l of m e dic i n e

factor of 2 to 3.4 Advanced adenomas are also

A predictive of an increased risk of colorectal cancer.
B have also been reported in some studies to be pre-
Figure 1. Removal of a Pedunculated Polyp.
A pedunculated polyp (Panel A) being removed with a
snare around its short stalk (Panel B). Reproduced with
permission from Hans Bjorknas (www.gastrolab.net).
are greater — by a factor of 2 to 4 — than they
are among persons without adenomas.3-5 How-
ever, these risks vary considerably according to the
characteristics of the index adenoma. The recog-
nition that a larger size and more advanced his-
tologic features are independent risk factors for
the presence of invasive cancer within an adeno-
ma has led to the use of the term “advanced ad-
enoma” for adenomas that are 1 cm or larger in
diameter or that have any advanced histologic fea-
tures (tubulovillous or villous histologic features
or high-grade dysplasia).
The overall risk of the development of metach-
ronous adenomas after the removal of an adeno-
ma is about 5 to 10% per year,4 but this risk varies
according to the initial findings on colonoscopy.
As compared with the presence of one or two
small tubular adenomas, the presence of three
or more such adenomas or of one or more ad-
vanced adenomas is associated with a risk of
metachronous adenomas that is increased by a
In one study, the finding of one or more advanced
adenomas at rigid sigmoidoscopy was associated
with a rate of metachronous proximal colon can-
cer (i.e., above the reach of the sigmoidoscope)
that was about 5 times higher than that in the
general population6; in contrast, the finding of
only small, rectosigmoid tubular adenomas was
not associated with an increased future risk of co-
lon cancer.6 Other characteristics of the baseline
adenoma (e.g., a location proximal to the splenic
flexure) or of the patient (e.g., male sex, older age,
or a first-degree relative with colorectal cancer)
dictive of metachronous adenomas or colorectal
cancer.4
Limited observational data suggest that ade-
nomas that are smaller than 1 cm do not grow
much during a 2-to-3-year period, whereas larger
polyps have a greater tendency to grow and prog-
ress to cancer.7-9 In one study, polyps 1 cm or
larger that were detected by means of a barium
enema progressed to cancer at a rate of about 1%
per year.9 Small adenomas can, however, have
advanced histologic features, including foci of in-
vasive cancer. Thus, the usual practice is to re-
move all polyps endoscopically if it is technically
possible to do so. The current recommendations
regarding intervals between colonoscopies are
stratified on the basis of the number, size, and
histologic features of the adenomas found at colo-
noscopy (Table 1).
The success of colonoscopic polypectomy and
surveillance depends on the identification and
complete removal of the adenoma or adenomas
(see video, available with the full text of this ar-
ticle at www.nejm.org). It is thought that most
colorectal cancers that occur within 5 years after
colonoscopic polypectomy develop because of fail-
ure to identify or completely remove high-risk
neoplasms (advanced adenomas or cancers) at the
time of the initial colonoscopy.4 The adequacy of
a polypectomy is assessed according to the endo-
scopic appearance of the polypectomy site and by
a review of the pathological specimen to deter-
mine whether its margins are free of neoplastic
tissue. This determination is sometimes difficult,
particularly with large, sessile lesions that were
removed in pieces. Endoscopy repeated within a
few months is warranted if there is doubt about
the adequacy of the initial polypectomy.
The adenoma “miss rate,” which can vary by

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Copyright © 2006 Massachusetts Medical Society. All rights reserved.
 clinical pr actice
a factor of 2 to 3 among examiners, is about 6 to
12% for adenomas that are 1 cm or larger and up
to 25% for smaller adenomas.11-13 Thus, missed
adenomas or cancers may contribute to the occur-
rence of colorectal cancer despite colonoscopic
surveillance and may underlie many instances of
“metachronous” neoplasia reported during sur-
veillance. In this issue of the Journal, Barclay and
colleagues14 note an important relationship be-
tween adenoma detection rates and the with-
drawal time of the colonoscope. They report that
endoscopists with an average withdrawal time
that was longer than 6 minutes had significantly
higher rates of adenoma detection than those
with a shorter average withdrawal time. To be
most effective, colonoscopy should be performed
by well-trained, certified endoscopists who me-
ticulously examine the entire colon during with-
drawal of the instrument.
Recommendations regarding the appropriate
interval for colonoscopic surveillance are based
on the estimated 5 to 15 years required for the
minority of adenomas that progress to cancer to
do so,15 the results of limited data from con-
trolled trials of surveillance intervals, and the
recognized associations between certain findings
at the initial colonoscopy and the subsequent risk
of the development of advanced adenomas and
cancer. Until the mid-1990s, patients with colonic
adenomas were routinely advised to undergo
colonoscopic surveillance every year. The National
Polyp Study,16 a randomized trial that compared
the findings of follow-up colonoscopic surveil-
lance at 1 and 3 years with those of follow-up
colonoscopy at 3 years alone, showed that the
detection of advanced adenomas was low (3.3%)
and was the same in the two groups. This study
indicates that surveillance intervals that are short-
er than 3 years are not required for most patients
with adenomas. A smaller trial in Denmark17
comparing surveillance intervals of 2 and 4 years
showed a nonsignificant difference in the rate of
detection of advanced adenomas or colorectal
cancer between groups at 4 years (5.2% and 8.6%,
respectively). Patients with more than 10 adeno-
mas, those with a large, sessile adenoma that was
removed piecemeal, and those suspected of hav-
ing a familial colon cancer syndrome are generally
excluded from these controlled trials and require
earlier follow-up.
Although controlled trials have not compared
surveillance intervals that are longer than 3 to
4 years, the low rate of colorectal cancer (<0.5%)
n engl j med 355;24
The New England Journal of Medicine
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Table 1. U.S. Consensus Guidelines for Colonoscopic Surveillance
after Polypectomy.*
Recommended Interval
Colonoscopic Findings between Colonoscopies
Small, rectal, hyperplastic polyps 10 yr or other average-risk screening option†
1 or 2 Low-risk adenomas‡ 5–10 yr
3–10 Low-risk adenomas or any 3 yr
high-risk adenoma§
>10 Adenomas <3 yr
Inadequately removed adenomas 2–6 mo
* More intensive surveillance is indicated when the patient’s family history is
suggestive of hereditary nonpolyposis colorectal cancer, an adenomatous syn-
drome, or a hyperplastic polyposis syndrome.4,10
† Other screening options include fecal occult-blood testing every year, sigmoid-
oscopy every 5 years, both, or barium enema every 5 years.
‡ Low-risk adenomas are tubular adenomas that are smaller than 1 cm.
§ High-risk adenomas are large (≥1 cm) or histologically advanced adenomas
(tubulovillous or villous adenomas and those with high-grade dysplasia).
after 5 to 6 years of follow-up in patients with
only one or two small, tubular adenomas on initial
colonoscopy3-6,18-20 suggests that a follow-up inter-
val of 5 or more years is safe for these patients.
Nutritional Management and Chemoprevention
The mortality from colon cancer varies by a factor
of more than 20 among countries,21 and the rate
of colon cancer increases substantially among per-
sons who emigrate from low-risk to high-risk
countries within only one to two generations. These
observations strongly suggest a role of environ-
mental factors in the pathogenesis of colorectal
adenomas and cancer. Case–control and cohort
studies suggest that obesity, physical inactivity,
excessive alcohol intake, smoking, and a diet that
is high in fat or low in fruits, vegetables, or fiber
are associated with an increased risk of adenomas
and colorectal cancer.22 Although avoiding obe-
sity, engaging in regular exercise, and consuming
a healthful diet are prudent, randomized interven-
tion trials suggest that modest dietary changes
(10% lower fat, 25 to 75% higher fiber, and 50%
more fruits and vegetables) in adults over a pe-
riod of 3 to 8 years do not significantly reduce the
risk of adenoma or colorectal cancer.23-25
Trials of calcium and nonsteroidal antiinflam-
matory drugs (NSAIDs) in patients with previous
adenomas have shown that these agents appear to
have modest efficacy in reducing the risk of me-
tachronous adenomas. One trial26 showed that
supplemental calcium carbonate (1200 mg of ele-
mental calcium per day) reduced the rate of me-
www.nejm.org december 14, 2006 2553
 The n e w e ng l a n d j o u r na l
tachronous adenomas by 20%. Enthusiasm for
calcium chemoprevention was tempered, howev-
er, by the report on the Women’s Health Initiative
trial.27 This trial assessed the effects of supple-
mental calcium (1000 mg of elemental calcium)
and vitamin D (400 IU) on the risk of colon cancer
in more than 36,000 women at average risk for this
disease. Although this trial was limited by a rela-
tively low adherence rate (only about 70% of sub-
jects took 50% or more of the study medication
through the end of the study) and a high rate of
use of nonstudy calcium supplements (almost 70%
of all subjects took supplemental calcium), it did
not show a protective effect of calcium and vita-
min D supplementation on the incidence of colo-
rectal cancer.
Data on NSAIDs are also mixed. Two recent
articles28,29 reported that metachronous adenoma
rates decreased by 35 to 45% among patients who
received the selective cyclooxygenase 2 (COX-2)
inhibitor celecoxib, but this benefit was out-
weighed by a rate of serious cardiovascular events
that was 1.3 to 3.4 times that among patients who
did not receive this drug.30 Aspirin also prevents
metachronous adenomas, but concerns remain
about the risks of bleeding and ulcers associated
with aspirin, and there is uncertainty about the
optimal dose. One trial31 showed that among pa-
tients who received aspirin at a dose of 325 mg
per day, there was a 35% reduction in the rate of
metachronous adenomas after 13 months, where-
as another trial32 showed significant reductions
in the rate of metachronous adenomas (20% for
any adenoma and 40% for advanced adenomas)
after 3 years at a dose of 80 mg per day but no
effect at a dose of 325 mg per day. Chemopreven-
tion of colorectal adenomas or cancer with the
use of calcium or aspirin is not routinely recom-
mended, but it may be considered in selected
populations (e.g., patients at low risk for compli-
cations of these agents and those who would
benefit from these agents for other reasons such
as a cardiovascular benefit with aspirin and osteo-
porosis prevention with calcium).
Guidel ine s
Winawer et al.4 recently reported consensus rec-
ommendations for colonoscopic surveillance that
have been endorsed by the American Cancer So-
ciety and the professional gastroenterology socie-
ties in the United States. The recommendations
2554 n engl j med 355;24
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of m e dic i n e
(Table 1) are based on the colonoscopic findings,
with an interval between colonoscopies that rang-
es from 5 to 10 years among patients with low-
risk adenomas and an interval of 3 years among
those with high-risk adenomas. More intensive
surveillance is advised if a strong family history
of multiple adenomas or colorectal cancer sug-
gests a familial cancer syndrome.
The consensus guidelines emphasize the crit-
ical importance of adequate bowel cleansing and
of high-quality colonoscopy and polypectomy, and
they acknowledge that discontinuing surveillance
but continuing average-risk screening may be ap-
propriate for subgroups of patients with low-risk
adenomas. In practice, colonoscopic surveillance
is often performed at intervals that are shorter
than those recommended. More than 50% of
gastroenterologists and colorectal surgeons sur-
veyed from 1999 to 2000 reported that they rou-
tinely recommend colonoscopy at more frequent
intervals than those suggested by the published
guidelines.33 Excessive colonoscopic surveillance
is expensive and diverts substantial endoscopic
capacity away from screening efforts that could
have a greater effect in preventing colorectal
cancer.
A r e a s of Uncer ta in t y
Controversies regarding Surveillance
after Polypectomy
If adenomas are the major precursors of colorec-
tal cancer, colonoscopic removal of adenomas
should substantially decrease the risk of this can-
cer. Only indirect evidence is available, however, to
provide support for this idea. The National Polyp
Study34 and the Italian Multicenter Study Group35
reported marked reductions in the incidence of
colorectal cancer among patients who underwent
colonoscopic surveillance after the removal of co-
lonic adenomas; the rates among these patients
were 66 to 76% lower than registry-based estimates
of rates in the general population and 88 to 90%
lower than those among historical controls with
adenomas. However, in other cohorts of patients
who have undergone colonoscopic surveillance
after polypectomy,23,24,35-39 the rates of colorectal
cancer have been two to four times higher than
those in the National Polyp Study and the Italian
Multicenter Study Group cohorts. These higher
rates, which are closer to those in the general
population, translate into substantially lower es-
www.nejm.org december 14, 2006
 clinical pr actice

timates of the reduction in the risk of colorectal crease in the risk of colorectal cancer (by a factor
cancer. All of these estimates are flawed, however, of 1.5 to 2), but data on which subgroups are at
because of the lack of adequate control groups. highest risk are limited and inconsistent. The
Regardless of the precise magnitude of the bene- National Polyp Study43 showed that the detection
fit, it is clear that colonoscopic polypectomy and of any adenoma in patients younger than 60 years
surveillance cannot entirely prevent colorectal can- of age conferred an increased risk of colorectal
cer, and patients should be informed of the limi- cancer (by a factor of 2.6) in their relatives as
tations as well as the benefits of this approach. compared with the risk among relatives of older
Data from controlled trials to guide decisions patients. Other studies found that the increased
about when surveillance should be discontinued risk was limited to relatives of patients with large
are also lacking. Since the risks associated with or histologically advanced adenomas, independent
cathartics, sedation, and colonoscopy are increased of the patient’s age.44,45 Some have recommended
among the elderly and patients with coexisting that the first-degree relatives of patients with
disease, it would seem reasonable to discontinue colonic adenomas that were detected before 60
surveillance in patients with an estimated life ex- years of age should begin colonoscopic screening
pectancy of less than 10 years. Similarly, the at 40 years of age or 10 years younger than the
benefit of continued surveillance after one or age at diagnosis of the youngest person in the fam-
more negative colonoscopies in patients who ini- ily with an adenoma,46-48 but this recommenda-
tially had an adenoma is uncertain. tion has not been validated in controlled trials.
Although the prevalence of adenomas and Clinicians should encourage patients with colonic
colorectal cancer is higher among men than adenomas to tell their first-degree relatives about
among women40 and is higher among blacks than their adenoma diagnosis and to advise their rela-
among whites or Hispanic persons,1 the recom- tives to talk with their own clinicians about
mended surveillance intervals do not vary accord- screening.
ing to sex, race, or ethnic group. It is not known
whether other forms of imaging, such as com- Sum m a r y a nd R ec om mendat ions
puted tomography, could replace surveillance
colonoscopy or whether stool analyses for blood Colonic adenomas are the precursor lesions of
or mutations could complement it. almost all colorectal cancers, but most adenomas
Although small, distal hyperplastic polyps are
never progress to cancer; for those that do, pro-
not thought to progress to cancer, it has been gression is thought to take many years. In a pa-
suggested that some large hyperplastic polyps tient found to have one or more adenomas on
and related lesions (serrated adenomas) may do colonoscopy, the usual practice is to remove all
so.41 These adenomas have a serrated luminal adenomas completely, with confirmation based on
border that is similar to that of hyperplastic both endoscopic and pathological assessment.
polyps, but they are also characterized by altered
Colonoscopic surveillance is recommended at in-
patterns of proliferation and maturation. Recent tervals that vary according to the number and types
clinical and molecular analyses suggest that these
of adenomas found and the presence or absence
serrated polyps may be the precursors of a type of a family history of colorectal polyps and can-
of sporadic colorectal cancer characterized by DNA
cer, although some of these recommendations are
microsatellite instability.42 The natural history of
based on limited data. For the patient described in
these large, hyperplastic polyps and serrated the vignette, who had a large (greater than 1 cm),
adenomas is not well defined, and appropriate histologically advanced (tubulovillous) adenoma,
surveillance intervals for patients with these le-
initial colonoscopic surveillance would be recom-
sions have not been established. Currently, follow-
mended in 3 years. He should be advised that
up for such patients is often similar to that forcolonoscopic surveillance by an expert endosco-
patients with nonserrated adenomas. pist, although not perfect, is the best way to de-
crease his subsequent risk of colon cancer. He
Surveillance for Relatives of Patients should encourage his first-degree relatives to dis-
with Adenomas cuss their family history and screening with their
First-degree relatives of patients with sporadic clinicians. Chemoprevention with calcium or low-
colonic adenomas appear to have a modest in- dose aspirin could be considered for this patient,

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The New England Journal of Medicine

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Copyright © 2006 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l
but their use would not alter the colonoscopic
surveillance intervals.
Dr. Levine reports receiving grant support from Berlex and
Wyeth. Dr. Ahnen reports having received honoraria for consulting
References
1. Jemal A, Siegel R, Ward E, et al. Can-
cer statistics, 2006. CA Cancer J Clin 2006;
56:106-30.
2. Increased use of colorectal cancer tests
— United States, 2002 and 2004. MMWR
Morb Mortal Wkly Rep 2006;55:308-11.
3. Avidan B, Sonnenberg A, Schnell TG,
Leya J, Metz A, Sontag S. New occurrence
and recurrence of neoplasms within 5 years
of a screening colonoscopy. Am J Gastro-
enterol 2002;97:1524-9.
4. Winawer SJ, Zauber AG, Fletcher RH,
et al. Guidelines for colonoscopy surveil-
lance after polypectomy: a consensus up-
date by the US Multi-Society Task Force
on Colorectal Cancer and the American
Cancer Society. Gastroenterology 2006;130:
1872-85.
5. Lotfi AM, Spencer RJ, Ilstrup DM,
Melton LJ III. Colorectal polyps and the
risk of subsequent carcinoma. Mayo Clin
Proc 1986;61:337-43.
6. Atkin WS, Morson BC, Cuzick J. Long-
term risk of colorectal cancer after exci-
sion of rectosigmoid adenomas. N Engl J
Med 1992;326:658-62.
7. Hoff G, Foerster A, Vatn MH, Sauar J,
Larsen S. Epidemiology of polyps in the
rectum and colon: recovery and evalua-
tion of unresected polyps 2 years after de-
tection. Scand J Gastroenterol 1986;21:
853-62.
8. Hofstad B, Vatn MH, Andersen SN, et
al. Growth of colorectal polyps: redetec-
tion and evaluation of unresected polyps
for a period of three years. Gut 1996;39:
449-56.
9. Stryker SJ, Wolff BG, Culp CE, Libbe
SD, Ilstrup DM, MacCarty RL. Natural his-
tory of untreated colonic polyps. Gastro-
enterology 1987;93:1009-13.
10. Chow E, Lipton L, Lynch E, et al. Hyper-
plastic polyposis syndrome: phenotypic
presentations and the role of MBD4 and
MYH. Gastroenterology 2006;131:30-9.
11. Rex DK, Cutler CS, Lemmel GT, et al.
Colonoscopic miss rates of adenomas de-
termined by back-to-back colonoscopies.
Gastroenterology 1997;112:24-8.
12. Pickhardt PJ, Choi JR, Hwang I, et al.
Computed tomographic virtual colonos-
copy to screen for colorectal neoplasia in
asymptomatic adults. N Engl J Med 2003;
349:2191-200.
13. Atkin W, Rogers P, Cardwell C, et al.
Wide variation in adenoma detection rates
at screening flexible sigmoidoscopy. Gas-
troenterology 2004;126:1247-56.
14. Barclay RL, Vicari JJ, Doughty AS, Jo-
hanson JF, Greenlaw RL. Colonoscopic
withdrawal times and adenoma detection
during screening colonoscopy. N Engl
J Med 2006;355:2533-41.
2556 n engl j med 355;24
The New England Journal of Medicine
Downloaded from nejm.org at Arizona Health Sciences Center and UMC on December 13, 2012. For personal use only. No other uses without permission.
Copyright © 2006 Massachusetts Medical Society. All rights reserved.
of m e dic i n e
from Exact Sciences and for lecturing from AstraZeneca. No other
potential conflict of interest relevant to this article was reported.
We thank Dr. Finlay Macrae for his thoughtful review of the
manuscript.
15. Kelloff GJ, Schilsky RL, Alberts DS, et
al. Colorectal adenomas: a prototype for
the use of surrogate end points in the de-
velopment of cancer prevention drugs.
Clin Cancer Res 2004;10:3908-18.
16. Winawer SJ, Zauber AG, O’Brien MJ,
et al. Randomized comparison of surveil-
lance intervals after colonoscopic removal
of newly diagnosed adenomatous polyps.
N Engl J Med 1993;328:901-6.
17. Jorgensen OD, Gronborg O, Fenger C.
A randomized surveillance study of patients
with pedunculated and small sessile tubu-
lar and tubulovillous adenomas. Scand J
Gastroenterol 1995;30:686-92.
18. van Stolk RU, Beck GJ, Baron JA, Haile
R, Summers R. Adenoma characteristics
at first colonoscopy as predictors of ade-
noma recurrence and characteristics at
follow-up. Gastroenterology 1998;115:13-8.
19. Martinez ME, Sampliner R, Marshall
JR, Bhattacharyya AK, Reid ME, Alberts
DS. Adenoma characteristics as risk fac-
tors for recurrence of advanced adenomas.
Gastroenterology 2001;120:1077-83.
20. Noshirwani KC, van Stolk RU, Rybicki
LA, Beck GJ. Adenoma size and number
are predictive of adenoma recurrence: im-
plications for surveillance colonoscopy.
Gastrointest Endosc 2000;51:433-7.
21. Parkin DM, Bray F, Ferlay J, et al.
Global cancer statistics, 2000. CA Cancer
J Clin 2005;55:74-108.
22. Gatof D, Ahnen D. Primary preven-
tion of colorectal cancer: diet and drugs.
Gastroenterol Clin North Am 2002;31:587-
623.
23. Schatzkin A, Lanza E, Corle D, et al.
Lack of effect of a low-fat, high-fiber diet
on the recurrence of colorectal adenomas.
N Engl J Med 2000;342:1149-55.
24. Alberts DS, Martinez ME, Roe DJ, et al.
Lack of effect of a high-fiber cereal sup-
plement on the recurrence of colorectal ad-
enomas. N Engl J Med 2000;342:1156-62.
25. Beresford SA, Johnson KC, Ritenbaugh
C, et al. Low-fat dietary pattern and risk
of colorectal cancer: the Women’s Health
Initiative Randomized Controlled Dietary
Modification Trial. JAMA 2006;295:643-54.
26. Baron JA, Beach M, Mandel JS, et al.
Calcium supplements for the prevention
of colorectal adenomas. N Engl J Med
1999;340:101-7.
27. Wactawski-Wende J, Kotchen JM, An-
derson GL, et al. Calcium plus vitamin D
supplementation and the risk of colorec-
tal cancer. N Engl J Med 2006;354:684-96.
[Erratum, N Engl J Med 2006;354:1102.]
28. Bertagnolli MM, Eagle CJ, Zauber AG,
et al. Celecoxib for the prevention of spo-
radic colorectal adenomas. N Engl J Med
2006;355:873-84.
www.nejm.org december 14, 2006
29. Arber N, Eagle CJ, Spicak J, et al. Cele-
coxib for the prevention of colorectal ad-
enomatous polyps. N Engl J Med 2006;
355:885-95.
30. Psaty BM, Potter JD. Risks and bene-
fits of celecoxib to prevent recurrent ade-
nomas. N Engl J Med 2006;355:950-2.
31. Sandler RS, Halabi S, Baron JA, et al.
A randomized trial of aspirin to prevent
colorectal adenomas in patients with pre-
vious colorectal cancer. N Engl J Med
2003;348:883-90. [Erratum, N Engl J Med
2003;348:1939.]
32. Baron JA, Cole BF, Sandler RS, et al.
A randomized trial of aspirin to prevent
colorectal adenomas. N Engl J Med 2003;
348:891-9.
33. Mysliwiec PA, Brown ML, Klabunde
CN, Ransohoff DF. Are physicians doing
too much colonoscopy? A national survey
of colorectal surveillance after polypec-
tomy. Ann Intern Med 2004;141:264-71.
34. Winawer SJ, Zauber AG, Ho MN, et al.
Prevention of colorectal cancer by colono-
scopic polypectomy. N Engl J Med 1993;
329:1977-81.
35. Citarda F, Tomaselli G, Capocaccia R,
Barcherini S, Crespi M, Italian Muticenter
Study Group. Efficacy in standard clinical
practice of colonoscopic polypectomy in
reducing colorectal cancer incidence. Gut
2001;48:812-5.
36. Robertson DJ, Greenberg ER, Beach
M, et al. Colorectal cancer in patients un-
der close colonoscopic surveillance. Gas-
troenterology 2005;129:34-41.
37. Meagher AP, Stuart M. Does colono-
scopic polypectomy reduce the incidence
of colorectal carcinoma? Aust N Z J Surg
1994;64:400-4.
38. Loeve F, van Ballegooijen M, Boer R,
Kuipers EJ, Habbema JDF. Colorectal can-
cer risk in adenoma patients: a nation-wide
study. Int J Cancer 2004;111:147-51.
39. Williams CB, Macrae FA. The St. Mark’s
neoplastic polyp follow up study. In: Rozen
P, ed. Secondary prevention of colorectal
cancer: an international perspective. Basel,
Switzerland: Karger, 1986:226.
40. Murakami R, Tsukuma H, Kanamori S,
et al. Natural history of colorectal polyps
and the effect of polypectomy on occur-
rence of subsequent cancer. Int J Cancer
1990;46:159-64.
41. Regula J, Rupinski M, Kraszewska E,
et al. Colonoscopy in colorectal-cancer
screening for detection of advanced neo-
plasia. N Engl J Med 2006;355:1863-72.
42. Snover DC, Jass JR, Fenoglio-Preiser C,
Batts KP. Serrated polyps of the large in-
testine: a morphologic and molecular re-
view of an evolving concept. Am J Clin
Pathol 2005;124:380-91.
 clinical pr actice

43. Winawer SJ, Zauber AG, Gerdes H, et
al. Risk of colorectal cancer in the fami-
lies of patients with adenomatous polyps.
N Engl J Med 1996;334:82-7.
44. Lynch KL, Ahnen DJ, Byers T, Weiss
DG, Lieberman DA. First-degree relatives
of patients with advanced colorectal ade-
nomas have an increased prevalence of
colorectal cancer. Clin Gastroenterol Hep-
atol 2003;1:96-102.
45. Bazzoli F, Fossi S, Sottili S, et al. The
risk of adenomatous polyps in asymptom-
atic first-degree relatives of persons with
colon cancer. Gastroenterology 1995;109:
783-8.
46. Smith RA, Cokkinides V, Eyre HJ.
American Cancer Society guidelines for
the early detection of cancer, 2006. CA
Cancer J Clin 2006;56:11-25.
47. Winawer S, Fletcher R, Rex D, et al.
Colorectal cancer screening and surveil-
lance: clinical guidelines and rationale —
update based on new evidence. Gastroen-
terology 2003;124:544-60.
48. Rex DK, Johnson DA, Lieberman DA,
Burt RW, Sonnenberg A. Colorectal cancer
prevention 2000: screening recommenda-
tions of the American College of Gastro-
enterology. Am J Gastroenterol 2000;95:
868-77.
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