Randomized Comparison of Surveillance Intervals after Colonoscopic Removal of Newly Diagnosed Adenomatous Polyps
Sidney J. Winawer, Ann G. Zauber, Michael J. O'Brien, May Nah Ho, Leonard Gottlieb, Stephen S. Sternberg, Jerome D. Waye, John Bond, Melvin Schapiro, Edward T. Stewart, Joel Panish, Fred Ackroyd, Robert C. Kurtz, Moshe Shike, for The National Polyp Study Workgroup
Background The identification and removal of adenomatous polypsand post-polypectomy surveillance are considered to be importantfor the control of colorectal cancer. In current practice, theintervals between colonoscopies after polypectomy are variable,often a year long, and not based on data from randomized clinicaltrials. We sought to determine whether follow-up colonoscopyat three years would detect important colonic lesions as wellas follow-up colonoscopy at both one and three years.
Methods Patients were eligible if they had one or more adenomas,no previous polypectomy, and a complete colonoscopy and if alltheir polyps had been removed. They were randomly assigned tohave follow-up colonoscopy at one and three years or at threeyears only. The two study end points were the detection of anyadenoma, and the detection of adenomas with advanced pathologicalfeatures (defined as those >1 cm in diameter and those withhigh-grade dysplasia or invasive cancer).
Results Of 2632 eligible patients, 1418 were randomly assignedto the two follow-up groups, 699 to the two-examination groupand 719 to the one-examination group. The percentage of patientswith adenomas in the group examined at one and three years was41.7 percent, as compared with 32.0 percent in the group examinedat three years (P = 0.006). The percentage of patients withadenomas with advanced pathological features was the same inboth groups (3.3 percent).
Conclusions Colonoscopy performed three years after colonoscopicremoval of adenomatous polyps detects important colonic lesionsas effectively as follow-up colonoscopy after both one and threeyears. An interval of at least three years is recommended beforefollow-up examination after colonoscopic removal of newly diagnosedadenomatous polyps. Adoption of this recommendation nationallyshould reduce the cost of post-polypectomy surveillance andscreening.
Adenomatous polyps have been identified with increasing frequencyin recent years as a result of the introduction of screeningwith tests of stool for occult blood and flexible-instrumentsigmoidoscopy and wider use of colonoscopy, colonoscopic polypectomy,and double-contrast barium enemas. It is widely held that adenomatouspolyps are precursors of colorectal cancer and that their removalis important because of its potential for reducing the incidenceand mortality of colorectal cancer1,2,3,4,5. These conceptshave formed the basis for the removal of adenomatous polypson detection and for the implementation of follow-up surveillanceprograms6,7,8,9,10. Periodic surveillance examinations havebeen considered necessary because of the high frequency of adenomatouspolyps detected at follow-up. The clinical relevance of mostadenomas found at follow-up, however, has not been established.In current practice, surveillance intervals after polypectomyvary, are often a year long, and have not been based on datafrom randomized clinical trials.
The National Polyp Study was organized in 1978 by a joint researchcommittee of the American Gastroenterological Association, theAmerican Society for Gastrointestinal Endoscopy, and the AmericanCollege of Gastroenterology to assess post-polypectomy surveillance11.The study was designed to be a multicenter, randomized clinicaltrial with wide geographic representation, enrolling only patientswith newly diagnosed adenomas in whom all examinations wereperformed by the investigators and incorporating a prospective,independent pathological review11. The principal goal of thistrial was to address the hypothesis that after newly diagnosedadenomatous polyps are excised by colonoscopy, follow-up colonoscopyat three years will detect important colonic lesions as effectivelyas follow-up colonoscopy at both one and three years. The resultsof this trial should be relevant to the cost effectiveness ofboth post-polypectomy surveillance and screening programs, sinceadenomatous polyps are the most frequent neoplasms found byscreening.
Methods
Enrollment
All patients referred for initial colonoscopy or polypectomyat seven participating centers who did not have a family orpersonal history of familial polyposis, inflammatory bowel disease,or a personal history of polypectomy or colorectal cancer wereidentified prospectively from November 1980 through February1990. Patients were excluded if colonoscopy revealed colorectalcancer, nonadenomatous polyps, malignant polyps (adenomas withcancer invading beyond the musculari mucosa), a sessile adenomawith a base longer than 3 cm, or the absence of polyps. Patientswere eligible if they underwent a complete colonoscopy to thelevel of the cecum, with removal of all polyps detected, andwere found to have one or more adenomas. The study protocolwas approved annually by the institutional review board of eachparticipating center. The following information was ascertainedfor all patients11: reason for referral, age and sex, and thepresence or absence of a family history of colorectal cancer,a personal history of other cancers, and polyps in first-degreerelatives.
Endoscopy and Pathological Review
All endoscopic examinations were performed by study investigators.Each polyp removed was placed in a bottle, labeled accordingto the anatomical segment involved (cecum, ascending colon,hepatic flexure, transverse colon, splenic flexure, descendingcolon, sigmoid, or rectum), and classified as sessile or pedunculated.The size of the polyp before polypectomy was estimated withuse of the open biopsy forceps, and the method of removal (i.e.,biopsy fulguration or cautery snare) was recorded. Polyps wereclassified as small ( 0.5 cm in diameter), medium (0.6 to 1.0cm), or large (>1.0 cm). Serial sections of each polyp wereobtained from the participating institutions and coded consecutivelyon an individual-case basis for simultaneous examination ata multihead microscope by the three review pathologists accordingto uniform criteria established at the beginning of the study;a consensus was reached about each polyp without knowledge ofthe clinical data or the study center from which it came12.The number of sections varied according to the size of the polyp.Additional sections were obtained if high-grade dysplasia orinvasive cancer was present. Adenomas were classified as tubularor villous. Villous adenomas were classified according to theproportion of villous component: class A, 1 to 25 percent; classB, 26 to 75 percent; class C, 76 to 99 percent; and class D,100 percent. This report is based on the classification of thepolyps after pathological review. An adenoma was defined ashaving advanced pathological features if it was large (>1.0cm) or had high-grade dysplasia or invasive cancer.
Stratification, Randomization, and Follow-up
Eligible patients consenting to enroll in the study were stratifiedaccording to the study center, the number of adenomas (singleor multiple), and the histologic type of adenoma (tubular orvillous). The patients were randomly assigned within the appropriatestratum to have a follow-up examination either one and threeyears after colonoscopy (the two-examination group) or threeyears after colonoscopy (the one-examination group). (A follow-upcolonoscopy six years after the examination at entry was alsooffered to both groups.) Blocked randomization within stratawas used to ensure balance between the two groups over time.The study coordinator contacted all patients annually to completean interval-history questionnaire and to schedule colonoscopies.
Statistical Analysis
A total enrollment of 1400 patients was planned, under the assumptionthat 975 patients would survive and undergo a follow-up colonoscopywithin the study period. The study was designed to detect adifference in the percentage of patients who had adenomas withadvanced pathological features detected at one year of 3 percent(the two-examination group), in comparison to 7 percent at threeyears (the one-examination group), with a power of 80 percentand a level of significance of 0.05 (two-sided); the differencebetween percentages was equivalent to a relative risk of 2.3or more. The relative risk that any adenomas as well as adenomaswith advanced pathological features would be detected at follow-upthree years after entry colonoscopy (the one-examination group)as compared with only one year (the two-examination group) wascalculated along with a 95 percent confidence interval. Logisticregression was used to assess the odds of detecting adenomaswith advanced pathological features at three years as comparedwith one year, with control for the stratification variablesof the histologic type of adenoma, number of adenomas, and studycenter13. In addition, logistic regression was used to assessindependent risk factors for adenomas with advanced pathologicalfeatures detected at the first follow-up examination and toexamine the effects of any interaction between study-group assignmentand characteristics at enrollment. The likelihood-ratio testwas used to determine whether a variable was an independentrisk factor for the detection of adenomas with advanced pathologicalfeatures.
Similar analyses were performed with respect to adenomas withadvanced pathological features detected at the second follow-upexamination in the two-examination group as compared with thosedetected at follow-up in the one-examination group. The percentageof patients who had adenomas with advanced pathological featuresdetected at either follow-up examination in the two-examinationgroup was compared with the percentage with such adenomas inthe one-examination group. The Wilcoxon test was used to determinewhether the number of adenomas detected at follow-up differedin the two groups14. All P values are two-sided; all analyseswere performed with SAS and BMDP software packages15,16.
Results
Enrollment
A total of 9112 patients referred for colonoscopy who had nohistory of polypectomy, inflammatory bowel disease, familialpolyposis, or colorectal cancer were identified at the sevenclinical centers. Of 3778 patients in whom polyps were detected,2632 (69.7 percent) had adenomas and were eligible for randomization;1418 (53.9 percent) of the patients with adenomas who were eligibleconsented to participate. Of these patients, 13 percent requiredmore than one colonoscopy to remove all the polyps detected.The reasons for exclusion from the study are shown in Table 1.The characteristics of the adenomas in the patients who didnot undergo randomization were similar to those of the patientswho did. Of the 1418 patients consenting to randomization, 699were assigned to the two-examination group and 719 to the one-examinationgroup. The characteristics of the two groups were comparable(Table 2).
Table 2. Characteristics of the Patients at Enrollment, According to Follow-up Group.
Overall Findings at First Follow-up Examination
Of the 660 patients in the two-examination group who were inthe study for at least one year, 545 (82.6 percent) returnedfor the first follow-up examination. Of the 547 patients inthe one-examination group who were in the study for at leastthree years, 428 (78.2 percent) returned for their follow-upexamination. The characteristics of the patients in both groupswho returned for their first follow-up examination were comparable.The median interval between enrollment and the initial follow-upexamination was 1.15 years in the two-examination group and3.15 years in the one-examination group. Follow-up clinicalstatus was determined for 97.2 percent of the patients (1379of 1418). None had severe complications resulting in seriousmorbidity or death.
The findings at the first follow-up examination at one yearin the two-examination group and at three years in the one-examinationgroup were comparable with respect to the polyps, adenomas,and types of adenomas detected (Table 3). The majority of thepatients in whom adenomas were detected at the first follow-upexamination had small adenomas that were predominantly tubular.Among those with adenomas at the first follow-up, the averagenumber of adenomas detected was 1.5 in the two-examination groupand 1.6 in the one-examination group (P = 0.20); their meansize was 0.5 cm in both groups.
Table 3. Findings at Follow-up Colonoscopy after Polypectomy.
Adenomas with Advanced Pathological Features at First Follow-up Examination
The two groups were comparable at the first follow-up examinationwith respect to the number of patients (14) and the percentageof patients who had adenomas with advanced features (two-examinationgroup vs. one-examination group, 2.6 percent vs. 3.3 percent;relative risk, 1.3; 95 percent confidence interval, 0.6 to 2.6).No invasive cancers were detected at the first follow-up examinationin the two-examination group, and two (both Dukes' stage A,or T1N0M0) in large adenomas (2.5 cm) were detected in the one-examinationgroup. The results were similar when the stratification variablesof study center, number of adenomas at enrollment, and proportionof villous component were taken into account (relative risk,1.3; 95 percent confidence interval, 0.6 to 2.7).
Risk Factors for Adenomas and Adenomas with Advanced Pathological Features
Age, the number of adenomas, and the size of the largest adenomaat enrollment were shown by multivariate analysis to be independentrisk factors for any adenoma detected at the first follow-upexamination (Table 4). However, the only factor found to besignificant in the detection of adenomas with advanced pathologicalfeatures at follow-up was the number of adenomas at enrollment(P<0.001) (Table 5).
Table 5. Multivariate Analysis of Enrollment Risk Factors for Adenomas with Advanced Pathological Features at First Follow-up Examination.
Second Follow-up Examination
Of the 431 patients in the two-examination group who completedthe first follow-up examination and were in the study for atleast three years, 338 (78.4 percent) returned for the secondexamination. The characteristics of the patients who returnedfor a second colonoscopy were similar to those of the patientswho completed the first examination. The median interval betweenenrollment and the second follow-up examination was 3.18 years.There was a marked reduction in the percentage of patients withadenomas detected (relative risk, 0.7), as well as in the percentagewho had adenomas with advanced pathological features (relativerisk, 0.3), at the second follow-up examination in the two-examinationgroup, as compared with the follow-up examination at three yearsin the one-examination group. At the second examination, 73patients (21.6 percent) were found to have adenomas, and 3 (0.9percent) had adenomas with advanced pathological features. Amongthe patients who had adenomas with advanced pathological features,one had an invasive cancer (Dukes' stage B1, or T2N0M0) in alarge adenoma (1.5 cm).
Comparison of Two Examinations with One Examination
In the two-examination group 141 patients (41.7 percent) werefound to have adenomas at either the first or second follow-upexamination. The relative risk that any adenoma would be detectedat two examinations as compared with one examination was 1.3(95 percent confidence interval, 1.1 to 1.6). However, the percentageof adenomas with advanced pathological features detected attwo examinations was the same as the percentage detected atone examination (3.3 percent) (Table 6). The average numberof follow-up colonoscopies was 2.06 in the two-examination group(both examinations combined) and 1.03 in the one-examinationgroup.
Table 6. Comparison of the Findings at Both Follow-up Examinations in the Two-Examination Group with the Findings in the One-Examination Group.
Discussion
This study demonstrates that patients who had newly diagnosedadenomas removed by colonoscopy were likely to have additionalpolyps detected at follow-up examinations. The polyps detectedat follow-up in the majority of these patients were adenomasthat contrasted with the adenomas found at enrollment in thatthey were predominantly small and tubular, with low-grade dysplasia.Only a small fraction of patients were found to have adenomaswith advanced pathological features on follow-up. The clinicalrelevance of the interval between examinations can be assessedby comparing the frequency of adenomas with advanced pathologicalfeatures detected in patients at follow-up colonoscopies. Therewere no significant overall differences between the pathologicalcharacteristics of the adenomas found at the first follow-upexamination whether it was performed at three years (one-examinationgroup) or at one year (two-examination group). Furthermore,the proportion of adenomas with advanced pathological featuresdetected in the two-examination group at one year was similarto that detected in the one-examination group at three years.In addition, the percentage of patients who had adenomas withadvanced pathological features in the two-examination groupat both one and three years was the same as in the one-examinationgroup at three years. Therefore, this study provides evidencesupporting the stated hypothesis: after newly diagnosed adenomatouspolyps have been removed by colonoscopy, follow-up colonoscopyat three years detects important colonic lesions as effectivelyas follow-up colonoscopy at both one and three years. On thebasis of these findings, an interval of at least three yearsis recommended before follow-up examination after the removalof newly diagnosed adenomatous polyps.
Studies in the pre-colonoscopy era reported that the percentageof adenomas detected after polypectomy ranged from 20 to 60percent17,18. Since the introduction of colonoscopy, severalstudies6,7,8,9,10,11,12 have reported percentages in this range.Data from the National Polyp Study on the detection of adenomasat follow-up agreed with these results. However, our study differedfrom the previous studies in that it enrolled patients at manycenters; enrolled them only if they had a newly diagnosed adenoma,which eliminated the effect of variability in the number ofprevious surveillance colonoscopies; and was a prospective randomizedtrial. One requirement for enrollment was complete colonoscopyto the level of the cecum, with removal of all identified polypsregardless of size. In addition, all polyps removed in the NationalPolyp Study were reviewed by an independent pathology committee.
It is not clear which adenomas found at follow-up are true metachronousadenomas and which are missed synchronous adenomas. Althoughall adenomas that were identified by the study investigatorswere removed, not all adenomas that are present in the colonare detected at the time of a single colonoscopy. Other studieshave estimated that half the adenomas found at follow-up aremissed synchronous adenomas and half are metachronous tumors10,20.The value of frequent examinations is questionable, since themissed adenomas are usually small and are mostly unimportantpathologically. The almost complete follow-up of the entirecohort (97.2 percent) was additional assurance that coloniclesions of clinical importance were not missed because of eitherinadequate colonoscopy or failure of a patient to return forcolonoscopy.
In this trial, the presence of multiple adenomas at enrollmentwas found to be a predictor of adenomas with advanced pathologicalfeatures at the first follow-up examination. Older age ( 60years) and large adenomas (>1.0 cm) were also notable factorsbut were not significant independent variables according tomultivariate analysis. The family histories of probands in theNational Polyp Study21 are also being studied as possible riskfactors for metachronous adenomas with advanced pathologicalfeatures. It would be desirable to increase the interval betweenfollow-up examinations in a subgroup of patients who are atlow risk for adenomas with advanced pathological features afterundergoing polypectomy. A cross-sectional analysis of the study'sdata22 supports the concept of a long natural history of colorectalcancer evolving through the adenoma stage. In addition, datarecently published23 on rigid-instrument sigmoidoscopy in personsat average risk for colorectal cancer suggest that a long intervalbetween examinations may be appropriate. The present study indicatesthat the first follow-up colonoscopy need not be performed inpatients with newly diagnosed adenomas until at least threeyears after the initial colonoscopy. Perhaps even longer intervalsare allowable, particularly if the first follow-up examinationis negative or does not reveal adenomas with advanced pathologicalfeatures.
In this study we have considered adenomas with advanced pathologicalfeatures to represent an intermediate biologic end point offuture colorectal cancer. The validity of this concept has beenexamined: according to a recently published British study,24excision of rectosigmoid adenomas of 1 cm or more, without furtherintervention, was associated with a 3.6-fold increase in thelong-term risk of colon cancer in the general population ifa single polyp was present, and with a 6.6-fold increase ifmultiple polyps were present. Spencer et al.25 found a relativerisk of colon carcinoma of only 1.2 in a Minnesota cohort thathad been treated for polyps measuring less than 1 cm. In a laterstudy from the same center,26 patients with adenomatous polypsmeasuring more than 1 cm had a significantly increased riskof colon cancer. These results support the view that adenomaswith advanced pathological features are valid indicators ofthe risk of colorectal cancer.
We conclude that the first follow-up colonoscopy can be delayedin most patients with newly diagnosed adenomas until three yearsafter all polyps identified during initial colonoscopy havebeen removed. Patients with malignant polyps or large sessileadenomas and those in whom all identified polyps have not beenremoved may require earlier follow-up colonoscopies. Widespreadadoption of this recommendation could result in large savingsnationally, better use of resources, and fewer complicationsin patients being followed after polypectomy27.
Supported by a grant (CA-26852) from the National Institutesof Health.
Source Information
From the National Polyp Study Headquarters, Memorial Sloan-Kettering Cancer Center, New York (S.J.W., A.G.Z., M.N.H., S.S.S., R.C.K., M. Shike); Mallory Institute of Pathology, Boston City Hospital, Boston (M.J.O., L.G.); Mount Sinai Hospital, New York (J.D.W.); Veterans Affairs Medical Center, Minneapolis (J.B.); Valley Presbyterian Hospital, Van Nuys, Calif. (M. Schapiro); Milwaukee County Medical Complex, Milwaukee (E.T.S.); Cedars-Sinai Medical Center, Los Angeles (J.P.); and Massachusetts General Hospital, Boston (F.A.). The following are other members of the National Polyp Study Workgroup who participated in this study: Memorial Sloan-Kettering Cancer Center, New York: C.J. Lightdale, H. Gerdes, L. Hornsby-Lewis, M. Edelman, M. Fleisher, B. Diaz, J. Lapidus, B. Flehinger, and R.A. McMahon; Strang Clinic, New York: C. Miller; Mount Sinai Hospital, New York: A. Szporn, N. Harpaz, M. Khilnani, and S. Yessayan; Veterans Affairs Medical Center, Minneapolis: H. Ansel, S. Ewing, and T. Dobson; Milwaukee County Medical Complex, Milwaukee: W. Hogan, J. Helm, R. Komorowski, and E. McLaughlin; St. Luke's Hospital, Racine, Wis.: J. Geenen, R. Venu, G.K. Johnson, and N. DeBoer; Massachusetts General Hospital, Boston: S. Hedberg, P. Shellito, D. Hall, G. Dickersin, and N. Horton; Cedars-Sinai Medical Center, Los Angeles: J. Sherman, J.A. Hamlin, S. Geller, and M. Kojimoto; Valley Presbyterian Hospital, Van Nuys, Calif.: M. Auslander, D. Kasimian, L. Kussin, and C. Scoggins; and Mallory Institute of Pathology, Boston (Pathology Review Center): C. Magrath.
Address reprint requests to Dr. Winawer at the Gastroenterology and Nutrition Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021.
References
Muto T, Bussey HJR, Morson BC. The evolution of cancer of the colon and rectum. Cancer 1975;36:2251-2270. [Medline]
Eide TJ. Risk of colorectal cancer in adenoma-bearing individuals within a defined population. Int J Cancer 1986;38:173-176. [Medline]
Winawer SJ, O'Brien MJ, Waye JD, et al. Risk and surveillance of individuals with colorectal polyps. Bull World Health Organ 1990;68:789-795. [Medline]
Winawer SJ, Schottenfeld D, Flehinger BJ. Colorectal cancer screening. J Natl Cancer Inst 1991;83:243-253. [Free Full Text]
Winawer SJ, Zauber AG, Gerdes H, et al. Reduction in colorectal cancer incidence following colonoscopic polypectomy: report from the National Polyp Study (NPS). Gastroenterology 1991;100:Suppl:A410-A410.abstract
Aubert H, Treille C, Faure H, Fournet J, Lachet B, Rachail M. Interet de la surveillance des malades polypectomises dans la prevention du cancer rectocolique: a propos de 123 cas. Gastroenterol Clin Biol 1982;6:183-187. [Medline]
Waye JD, Braunfeld SF. Surveillance intervals after colonoscopic polypectomy. Endoscopy 1982;14:79-81. [Medline]
Matek W, Guggenmoos-Holzmann I, Demling L. Follow-up of patients with colorectal adenomas. Endoscopy 1985;17:175-181. [Medline]
Kronborg O, Fenger C. Prognostic evaluation of planned follow-up in patients with colorectal adenomas: an interim report. Int J Colorectal Dis 1987;2:203-207. [CrossRef][Medline]
Winawer SJ, Zauber AG, O'Brien MJ, et al. The National Polyp Study: design, methods, and characteristics of patients with newly diagnosed polyps. Cancer 1992;70:Suppl:1236-1245. [CrossRef][Medline]
O'Brien MJ, Winawer SJ, Zauber AG, et al. The National Polyp Study: patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology 1990;98:371-379. [Medline]
Hosmer DW Jr, Lemeshow S. Applied logistic regression. New York: John Wiley, 1989.
Armitage P, Berry G. Statistical methods in medical research. 2nd ed. Oxford, England: Blackwell Scientific, 1987:411-7.
SAS/STAT user's guide, version 6. 4th ed. Vols. 1, 2. Cary, N.C.: SAS Institute, 1989.
LR stepwise logistic regression. In: BMDP statistical software manual. Vol. 2. Los Angeles: University of California Press, 1990:1013-46.
Henry LG, Condon RE, Schulte WJ, Aprahamian C, DeCosse JJ. Risk of recurrence of colon polyps. Ann Surg 1975;182:511-515. [Medline]
Kirsner JB, Rider JA, Moeller HC, Palmer WL, Gold SS. Polyps of the colon and rectum: statistical analysis of a long term follow-up study. Gastroenterology 1960;39:178-182. [Medline]
Macrae FA, Williams CB. A prospective colonoscopic follow-up study of 500 adenoma patients with multivariate analysis to predict risk of subsequent colorectal tumours. Gastrointest Endosc 1982;28:138-138.abstract
Hixson LJ, Fennerty MB, Sampliner RE, McGee D, Garewal H. Prospective study of the frequency and size distribution of polyps missed by colonoscopy. J Natl Cancer Inst 1990;82:1769-1772. [Free Full Text]
Winawer SJ, Zauber AG, Gerdes H, et al. Genetic epidemiology of colorectal cancer: relationship of familial colorectal cancer risk to adenoma proband age and adenoma characteristics. Gastroenterology 1992;102:Suppl:A409-A409.abstract
National Polyp Study Workgroup, Winawer SJ, Zauber AG, Diaz B. The National Polyp Study: temporal sequence of evolving colorectal cancer from the normal colon. Gastrointest Endosc 1987;33:167-167.abstract
Selby JV, Friedman GD, Quesenberry CP Jr, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992;326:653-657. [Abstract]
Atkin WS, Morson BC, Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas. N Engl J Med 1992;326:658-662. [Abstract]
Spencer RJ, Melton LJ III, Ready RL, Ilstrup DM. Treatment of small colorectal polyps: a population-based study of the risk of subsequent carcinoma. Mayo Clin Proc 1984;59:305-310. [Medline]
Lotfi AM, Spencer RJ, Ilstrup DM, Melton JJ III. Colorectal polyps and the risk of subsequent carcinoma. Mayo Clin Proc 1986;61:337-343. [Medline]
Ransohoff DF, Lang CA, Kuo HS. Colonoscopic surveillance after polypectomy: considerations of cost effectiveness. Ann Intern Med 1991;114:177-182.
Sidelnikov, E., Bostick, R. M., Flanders, W. D., Long, Q., Seabrook, M. E.
(2009). Colorectal Mucosal Expression of MSH2 as a Potential Biomarker of Risk for Colorectal Neoplasms. Cancer Epidemiol. Biomarkers Prev.
18: 2965-2973
[Abstract][Full Text]
Marshall, J. R.
(2009). Keeping Our Eye on the Ball: The American Society of Preventive Oncology in 2009. Cancer Epidemiol. Biomarkers Prev.
18: 2796-2802
[Full Text]
Robertson, D. J., Burke, C. A., Welch, H. G., Haile, R. W., Sandler, R. S., Greenberg, E. R., Ahnen, D. J., Bresalier, R. S., Rothstein, R. I., Cole, B., Mott, L. A., Baron, J. A.
(2009). Using the Results of a Baseline and a Surveillance Colonoscopy to Predict Recurrent Adenomas With High-Risk Characteristics. ANN INTERN MED
151: 103-109
[Abstract][Full Text]
Matsuda, T., Fujii, T., Sano, Y., Kudo, S.-e., Oda, Y., Igarashi, M., Iishi, H., Murakami, Y., Ishikawa, H., Shimoda, T., Kaneko, K., Yoshida, S.
(2009). Five-year Incidence of Advanced Neoplasia after Initial Colonoscopy in Japan: A Multicenter Retrospective Cohort Study. Jpn J Clin Oncol
39: 435-442
[Abstract][Full Text]
Park, S. H., Kim, S. Y., Lee, S. S., Bogoni, L., Kim, A. Y., Yang, S.-K., Myung, S.-J., Byeon, J.-S., Ye, B. D., Ha, H. K.
(2009). Sensitivity of CT Colonography for Nonpolypoid Colorectal Lesions Interpreted by Human Readers and With Computer-Aided Detection. Am. J. Roentgenol.
193: 70-78
[Abstract][Full Text]
Sidelnikov, E., Bostick, R. M., Flanders, W. D., Long, Q., Cohen, V. L., Dash, C., Seabrook, M. E., Fedirko, V.
(2009). MutL-Homolog 1 Expression and Risk of Incident, Sporadic Colorectal Adenoma: Search for Prospective Biomarkers of Risk for Colorectal Cancer. Cancer Epidemiol. Biomarkers Prev.
18: 1599-1609
[Abstract][Full Text]
Cafferty, F. H, Sasieni, P. D, Duffy, S. W
(2009). A deterministic model for estimating the reduction in colorectal cancer incidence due to endoscopic surveillance. Stat Methods Med Res
18: 163-182
[Abstract]
Ashbeck, E. L., Jacobs, E. T., Martinez, M. E., Gerner, E. W., Lance, P., Thompson, P. A.
(2009). Components of Metabolic Syndrome and Metachronous Colorectal Neoplasia. Cancer Epidemiol. Biomarkers Prev.
18: 1134-1143
[Abstract][Full Text]
Bertagnolli, M. M., Eagle, C. J., Zauber, A. G., Redston, M., Breazna, A., Kim, K., Tang, J., Rosenstein, R. B., Umar, A., Bagheri, D., Collins, N. T., Burn, J., Chung, D. C., Dewar, T., Foley, T. R., Hoffman, N., Macrae, F., Pruitt, R. E., Saltzman, J. R., Salzberg, B., Sylwestrowicz, T., Hawk, E. T., for the Adenoma Prevention with Celecoxib Study In,
(2009). Five-Year Efficacy and Safety Analysis of the Adenoma Prevention with Celecoxib Trial. Cancer Prevention Research
2: 310-321
[Abstract][Full Text]
Fletcher, R. H.
(2008). Colorectal Cancer Screening on Stronger Footing. NEJM
359: 1285-1287
[Full Text]
Weber, M. F, Banks, E., Ward, R., Sitas, F.
(2008). Population characteristics related to colorectal cancer testing in New South Wales, Australia: results from the 45 and Up Study cohort. J Med Screen
15: 137-142
[Abstract][Full Text]
Nnoaham, K E, Lines, C
(2008). Modelling future capacity needs and spending on colonoscopy in the English bowel cancer screening programme. Gut
57: 1238-1245
[Abstract][Full Text]
BIANCHI, L. K., BURKE, C. A.
(2008). Understanding current guidelines for colorectal cancer screening: A case-based approach. Cleveland Clinic Journal of Medicine
75: 441-448
[Abstract][Full Text]
Khuhaprema, T., Srivatanakul, P.
(2008). Colon and Rectum Cancer in Thailand: An Overview. Jpn J Clin Oncol
38: 237-243
[Abstract][Full Text]
Laiyemo, A. O., Murphy, G., Albert, P. S., Sansbury, L. B., Wang, Z., Cross, A. J., Marcus, P. M., Caan, B., Marshall, J. R., Lance, P., Paskett, E. D., Weissfeld, J., Slattery, M. L., Burt, R., Iber, F., Shike, M., Kikendall, J. W., Lanza, E., Schatzkin, A.
(2008). Postpolypectomy Colonoscopy Surveillance Guidelines: Predictive Accuracy for Advanced Adenoma at 4 Years. ANN INTERN MED
148: 419-426
[Abstract][Full Text]
Imperiale, T. F., Sox, H. C.
(2008). Guidelines for Surveillance Intervals after Polypectomy: Coping with the Evidence. ANN INTERN MED
148: 477-479
[Full Text]
Keku, T. O., Amin, A., Galanko, J., Martin, C., Schliebe, B., Sandler, R. S.
(2008). Apoptosis in Normal Rectal Mucosa, Baseline Adenoma Characteristics, and Risk of Future Adenomas. Cancer Epidemiol. Biomarkers Prev.
17: 306-310
[Abstract][Full Text]
Ngo, S. N. T., Williams, D. B., Cobiac, L., Head, R. J.
(2007). Does Garlic Reduce Risk of Colorectal Cancer? A Systematic Review. J. Nutr.
137: 2264-2269
[Abstract][Full Text]
Tappenden, P., Chilcott, J., Eggington, S., Sakai, H., Karnon, J., Patnick, J.
(2007). Option appraisal of population-based colorectal cancer screening programmes in England. Gut
56: 677-684
[Abstract][Full Text]
Levine, J. S., Ahnen, D. J.
(2006). Adenomatous Polyps of the Colon. NEJM
355: 2551-2557
[Full Text]
Boolchand, V., Olds, G., Singh, J., Singh, P., Chak, A., Cooper, G. S.
(2006). Colorectal screening after polypectomy: a national survey study of primary care physicians.. ANN INTERN MED
145: 654-659
[Abstract][Full Text]
Bertagnolli, M. M., Eagle, C. J., Zauber, A. G., Redston, M., Solomon, S. D., Kim, K., Tang, J., Rosenstein, R. B., Wittes, J., Corle, D., Hess, T. M., Woloj, G. M., Boisserie, F., Anderson, W. F., Viner, J. L., Bagheri, D., Burn, J., Chung, D. C., Dewar, T., Foley, T. R., Hoffman, N., Macrae, F., Pruitt, R. E., Saltzman, J. R., Salzberg, B., Sylwestrowicz, T., Gordon, G. B., Hawk, E. T., the APC Study Investigators,
(2006). Celecoxib for the prevention of sporadic colorectal adenomas.. NEJM
355: 873-884
[Abstract][Full Text]
Bleiberg, H., Autier, P., Huet, F., Schrauwen, A. M., Staquet, E., Delaunoit, T., Hendlisz, A., Wyns, C., Panzer, J. M., Caucheteur, B., Eisendrath, P., Grivegnee, A.
(2006). Colorectal cancer (CRC) screening using sigmoidoscopy followed by colonoscopy: a feasibility and efficacy study on a cancer institute based population. Ann Oncol
17: 1328-1332
[Abstract][Full Text]
Lanza, E., Hartman, T. J., Albert, P. S., Shields, R., Slattery, M., Caan, B., Paskett, E., Iber, F., Kikendall, J. W., Lance, P., Daston, C., Schatzkin, A.
(2006). High Dry Bean Intake and Reduced Risk of Advanced Colorectal Adenoma Recurrence among Participants in the Polyp Prevention Trial. J. Nutr.
136: 1896-1903
[Abstract][Full Text]
Paskett, E. D., Schrag, D., Kornblith, A., Lamont, E. B., Weeks, J. C., Marshall, J. R., Shapiro, C., Holland, J.
(2006). Cancer and leukemia group B cancer control and health outcomes committee: origins and accomplishments.. Clin. Cancer Res.
12: 3601s-3605s
[Abstract][Full Text]
Winawer, S. J., Zauber, A. G., Fletcher, R. H., Stillman, J. S., O'Brien, M. J., Levin, B., Smith, R. A., Lieberman, D. A., Burt, R. W., Levin, T. R., Bond, J. H., Brooks, D., Byers, T., Hyman, N., Kirk, L., Thorson, A., Simmang, C., Johnson, D., Rex, D. K.
(2006). Guidelines for Colonoscopy Surveillance after Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.. CA Cancer J Clin
56: 143-159
[Abstract][Full Text]
Sansbury, L. B., Bergen, A. W., Wanke, K. L., Yu, B., Caporaso, N. E., Chatterjee, N., Ratnasinghe, L., Schatzkin, A., Lehman, T. A., Kalidindi, A., Modali, R., Lanza, E.
(2006). Inflammatory cytokine gene polymorphisms, nonsteroidal anti-inflammatory drug use, and risk of adenoma polyp recurrence in the polyp prevention trial.. Cancer Epidemiol. Biomarkers Prev.
15: 494-501
[Abstract][Full Text]
Heitman, S. J., Manns, B. J., Hilsden, R. J., Fong, A., Dean, S., Romagnuolo, J.
(2005). Cost-effectiveness of computerized tomographic colonography versus colonoscopy for colorectal cancer screening. CMAJ
173: 877-881
[Abstract][Full Text]
Brenner, D. E., Rennert, G.
(2005). Fecal DNA Biomarkers for the Detection of Colorectal Neoplasia: Attractive, but Is It Feasible?. JNCI J Natl Cancer Inst
97: 1107-1109
[Full Text]
Eisen, G. M., Weinberg, D. S.
(2005). Narrative Review: Screening for Colorectal Cancer in Patients with a First-Degree Relative with Colonic Neoplasia. ANN INTERN MED
143: 190-198
[Abstract][Full Text]
Zalis, M. E., Barish, M. A., Choi, J. R., Dachman, A. H., Fenlon, H. M., Ferrucci, J. T., Glick, S. N., Laghi, A., Macari, M., McFarland, E. G., Morrin, M. M., Pickhardt, P. J., Soto, J., Yee, J., For the Working Group on Virtual Colonoscopy,
(2005). CT Colonography Reporting and Data System: A Consensus Proposal. Radiology
236: 3-9
[Full Text]
Bampton, P A, Sandford, J J, Cole, S R, Smith, A, Morcom, J, Cadd, B, Young, G P
(2005). Interval faecal occult blood testing in a colonoscopy based screening programme detects additional pathology. Gut
54: 803-806
[Abstract][Full Text]
Varghese, R. K., Friedman, C., Ahmed, F., Franks, A. L., Manning, M., Seeff, L. C.
(2005). Does Health Insurance Coverage of Office Visits Influence Colorectal Cancer Testing?. Cancer Epidemiol. Biomarkers Prev.
14: 744-747
[Abstract][Full Text]
Amonkar, M. M., Hunt, T. L., Zhou, Z., Jin, X.
(2005). Surveillance Patterns and Polyp Recurrence following Diagnosis and Excision of Colorectal Polyps in a Medicare Population. Cancer Epidemiol. Biomarkers Prev.
14: 417-421
[Abstract][Full Text]
Terzolo, M., Reimondo, G., Gasperi, M., Cozzi, R., Pivonello, R., Vitale, G., Scillitani, A., Attanasio, R., Cecconi, E., Daffara, F., Gaia, E., Martino, E., Lombardi, G., Angeli, A., Colao, A.
(2005). Colonoscopic Screening and Follow-Up in Patients with Acromegaly: A Multicenter Study in Italy. J. Clin. Endocrinol. Metab.
90: 84-90
[Abstract][Full Text]
Goulet, A.-C., Chigbrow, M., Frisk, P., Nelson, M. A.
(2005). Selenomethionine induces sustained ERK phosphorylation leading to cell-cycle arrest in human colon cancer cells. Carcinogenesis
26: 109-117
[Abstract][Full Text]
Mysliwiec, P. A., Brown, M. L., Klabunde, C. N., Ransohoff, D. F.
(2004). Are Physicians Doing Too Much Colonoscopy? A National Survey of Colorectal Surveillance after Polypectomy. ANN INTERN MED
141: 264-271
[Abstract][Full Text]
Pfister, D. G., Benson, A. B. III, Somerfield, M. R.
(2004). Surveillance Strategies after Curative Treatment of Colorectal Cancer. NEJM
350: 2375-2382
[Full Text]
Kelloff, G. J., Schilsky, R. L., Alberts, D. S., Day, R. W., Guyton, K. Z., Pearce, H. L., Peck, J. C., Phillips, R., Sigman, C. C.
(2004). Colorectal Adenomas: A Prototype for the Use of Surrogate End Points in the Development of Cancer Prevention Drugs. Clin. Cancer Res.
10: 3908-3918
[Full Text]
Yamaji, Y, Mitsushima, T, Ikuma, H, Watabe, H, Okamoto, M, Kawabe, T, Wada, R, Doi, H, Omata, M
(2004). Incidence and recurrence rates of colorectal adenomas estimated by annually repeated colonoscopies on asymptomatic Japanese. Gut
53: 568-572
[Abstract][Full Text]
Calabrese, P., Tavare, S., Shibata, D.
(2004). Pretumor Progression: Clonal Evolution of Human Stem Cell Populations. Am. J. Pathol.
164: 1337-1346
[Abstract][Full Text]
Hurlstone, D P, Cross, S S, Slater, R, Sanders, D S, Brown, S
(2004). Detecting diminutive colorectal lesions at colonoscopy: a randomised controlled trial of pan-colonic versus targeted chromoscopy. Gut
53: 376-380
[Abstract][Full Text]
Takahashi, P. Y., Okhravi, H. R., Lim, L. S., Kasten, M. J.
(2004). Preventive Health Care in the Elderly Population: A Guide for Practicing Physicians. Mayo Clin Proc.
79: 416-427
[Abstract]
Winawer, S. J
(2003). New colorectal cancer screening guidelines. BMJ
327: E196-197
[Full Text]
Walsh, J. M. E., Terdiman, J. P.
(2003). Colorectal Cancer Screening: Scientific Review. JAMA
289: 1288-1296
[Abstract][Full Text]
Lewis, J. D., Ng, K., Hung, K. E., Bilker, W. B., Berlin, J. A., Brensinger, C., Rustgi, A. K.
(2003). Detection of Proximal Adenomatous Polyps With Screening Sigmoidoscopy: A Systematic Review and Meta-analysis of Screening Colonoscopy. Arch Intern Med
163: 413-420
[Abstract][Full Text]
Yood, M. U., Oliveria, S., Boyer, J. G., Wells, K., Stang, P., Johnson, C. C.
(2003). Colon Polyp Recurrence in a Managed Care Population. Arch Intern Med
163: 422-426
[Abstract][Full Text]
NICOLLIER-FAHRNI, A., VADER, J.-P., FROEHLICH, F., GONVERS, J.-J., BURNAND, B.
(2003). Development of appropriateness criteria for colonoscopy: comparison between a standardized expert panel and an evidence-based medicine approach. Int J Qual Health Care
15: 15-22
[Abstract][Full Text]
Scholefield, J H, Steele, R J
(2002). Guidelines for follow up after resection of colorectal cancer. Gut
51: v3-5
[Full Text]
Atkin, W S, Saunders, B P
(2002). Surveillance guidelines after removal of colorectal adenomatous polyps. Gut
51: v6-9
[Full Text]
Nusko, G, Mansmann, U, Kirchner, T., Hahn, E G
(2002). Risk related surveillance following colorectal polypectomy. Gut
51: 424-428
[Abstract][Full Text]
Anderson, W. F., Guyton, K. Z., Hiatt, R. A., Vernon, S. W., Levin, B., Hawk, E.
(2002). Colorectal Cancer Screening for Persons at Average Risk. JNCI J Natl Cancer Inst
94: 1126-1133
[Full Text]
Green, R. J., Metlay, J. P., Propert, K., Catalano, P. J., Macdonald, J. S., Mayer, R. J., Haller, D. G.
(2002). Surveillance for Second Primary Colorectal Cancer after Adjuvant Chemotherapy: An Analysis of Intergroup 0089. ANN INTERN MED
136: 261-269
[Abstract][Full Text]
O'Shaughnessy, J. A., Kelloff, G. J., Gordon, G. B., Dannenberg, A. J., Hong, W. K., Fabian, C. J., Sigman, C. C., Bertagnolli, M. M., Stratton, S. P., Lam, S., Nelson, W. G., Meyskens, F. L., Alberts, D. S., Follen, M., Rustgi, A. K., Papadimitrakopoulou, V., Scardino, P. T., Gazdar, A. F., Wattenberg, L. W., Sporn, M. B., Sakr, W. A., Lippman, S. M., Von Hoff, D. D.
(2002). Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development : Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia. Clin. Cancer Res.
8: 314-346
[Abstract][Full Text]
Bleiberg, H.
(2002). Hemoccult should no longer be used for the screening of colorectal cancer. Ann Oncol
13: 44-46
[Full Text]
Strul, H., Arber, N.
(2002). Fecal occult blood test for colorectal cancer screening. Ann Oncol
13: 51-56
[Full Text]
Lewis, J. D., Brown, A., Localio, A. R., Schwartz, J. S.
(2002). Initial Evaluation of Rectal Bleeding in Young Persons: A Cost-Effectiveness Analysis. ANN INTERN MED
136: 99-110
[Abstract][Full Text]
BOLAND, C R, SAVIDES, T J
(2001). The changing scope of colorectal cancer. Gut
48: 449a-450
[Full Text]
Anti, M, Armuzzi, A, Morini, S, Iascone, E, Pignataro, G, Coco, C, Lorenzetti, R, Paolucci, M, Covino, M, Gasbarrini, A, Vecchio, F., Gasbarrini, G
(2001). Severe imbalance of cell proliferation and apoptosis in the left colon and in the rectosigmoid tract in subjects with a history of large adenomas. Gut
48: 238-246
[Abstract][Full Text]
Mandel, J. S., Church, T. R., Bond, J. H., Ederer, F., Geisser, M. S., Mongin, S. J., Snover, D. C., Schuman, L. M.
(2000). The Effect of Fecal Occult-Blood Screening on the Incidence of Colorectal Cancer. NEJM
343: 1603-1607
[Abstract][Full Text]
Winawer, S. J., Stewart, E. T., Zauber, A. G., Bond, J. H., Ansel, H., Waye, J. D., Hall, D., Hamlin, J. A., Schapiro, M., O'Brien, M. J., Sternberg, S. S., Gottlieb, L. S., The National Polyp Study Work Group,
(2000). A Comparison of Colonoscopy and Double-Contrast Barium Enema for Surveillance after Polypectomy. NEJM
342: 1766-1772
[Abstract][Full Text]
Loeve, F., Brown, M. L., Boer, R., van Ballegooijen, M., van Oortmarssen, G. J., Habbema, J. D. F.
(2000). Endoscopic Colorectal Cancer Screening: a Cost-Saving Analysis. JNCI J Natl Cancer Inst
92: 557-563
[Abstract][Full Text]
Stevenson, G. W.
(2000). 1998 RSNA Annual Oration in Diagnostic Radiology : Colorectal Cancer Imaging: A Challenge for Radiologists. Radiology
214: 615-621
[Full Text]
Kelloff, G. J., Sigman, C. C., Johnson, K. M., Boone, C. W., Greenwald, P., Crowell, J. A., Hawk, E. T., Doody, L. A.
(2000). Perspectives on Surrogate End Points in the Development of Drugs that Reduce the Risk of Cancer. Cancer Epidemiol. Biomarkers Prev.
9: 127-137
[Abstract][Full Text]
Holt, P. R.
(1999). Dairy Foods and Prevention of Colon Cancer: Human Studies. J. Am. Coll. Nutr.
18: 379S-391
[Abstract][Full Text]
Desch, C. E., Benson, A. B. III, Smith, T. J., Flynn, P. J., Krause, C., Loprinzi, C. L., Minsky, B. D., Petrelli, N. J., Pfister, D. G., Somerfield, M. R.
(1999). Recommended Colorectal Cancer Surveillance Guidelines by the American Society of Clinical Oncology. JCO
17: 1312-1312
[Abstract][Full Text]
Caderni, G., Palli, D., Lancioni, L., Russo, A., Luceri, C., Saieva, C., Trallori, G., Manneschi, L., Renai, F., Zacchi, S., Salvadori, M., Dolara, P.
(1999). Dietary Determinants of Colorectal Proliferation in the Normal Mucosa of Subjects with Previous Colon Adenomas. Cancer Epidemiol. Biomarkers Prev.
8: 219-225
[Abstract][Full Text]
Paillot, B, Czernichow, P, Michel, P, Merle, V, Queuniet, A-M, Duval, C, Daubert, H
(1999). Incidence of rectosigmoid adenomatous polyps in subjects without prior colorectal adenoma or cancer: a prospective cohort study. Gut
44: 372-376
[Abstract][Full Text]
LANGMAN, M, BOYLE, P
(1998). Chemoprevention of colorectal cancer. Gut
43: 578-585
[Abstract][Full Text]
Marshall, J. R., Alberts, D. S., Sampliner, R. E.
(1997). Colon Cancer Reduction: Questions About Implementation of Proven Techniques. Arch Intern Med
157: 1919-1920
[Abstract]
Winawer, S. J., Zauber, A. G., Gerdes, H., O'Brien, M. J., Gottlieb, L. S., Sternberg, S. S., Bond, J. H., Waye, J. D., Schapiro, M., Panish, J. F., Kurtz, R. C., Shike, M., Ackroyd, F. W., Stewart, E. T., Skolnick, M., Bishop, D. T., The National Polyp Study Workgroup,
(1996). Risk of Colorectal Cancer in the Families of Patients with Adenomatous Polyps. NEJM
334: 82-87
[Abstract][Full Text]
Koff, R. S.
(1995). Gastroenterology and Hepatology. JAMA
273: 1679-1680
[Abstract]
Toribara, N. W., Sleisenger, M. H.
(1995). Screening for Colorectal Cancer. NEJM
332: 861-867
[Full Text]
Winawer, S. J., Zauber, A. G., Ho, M. N., O'Brien, M. J., Gottlieb, L. S., Sternberg, S. S., Waye, J. D., Schapiro, M., Bond, J. H., Panish, J. F., Ackroyd, F., Shike, M., Kurtz, R. C., Hornsby-Lewis, L., Gerdes, H., Stewart, E. T., The National Polyp Study Workgroup,
(1993). Prevention of Colorectal Cancer by Colonoscopic Polypectomy. NEJM
329: 1977-1981
[Abstract][Full Text]
Ahlquist, D. A., Moertel, C. G., McGill, D. B., Carey, W. D., Achkar, E., Perlman, R., Budenholzer, B., Neugut, A. I., Jacobson, J. S., Allison, J. E., Brown, M. L., Mandel, J. S., Church, T. R., Ederer, F., Winawer, S. J.
(1993). Screening for Colorectal Cancer. NEJM
329: 1351-1354
[Full Text]
Bird, D. C., Spratt, J. S., Winawer, S. J., Zauber, A. G.
(1993). Post-Polypectomy Surveillance. NEJM
329: 887-888
[Full Text]
Winawer, S. J.
(1993). Colorectal Cancer Screening Comes of Age. NEJM
328: 1416-1417
[Full Text]
(1993). REPEAT COLONOSCOPY CAN WAIT UNTIL 3 YEARS AFTER POLYPECTOMY. JWatch General
1993: 3-3
[Full Text]
0.5 cm in diameter), medium (0.6 to 1.0 cm), or large (>1.0 cm). Serial sections of each polyp were obtained from the participating institutions and coded consecutively on an individual-case basis for simultaneous examination at a multihead microscope by the three review pathologists according to uniform criteria established at the beginning of the study; a consensus was reached about each polyp without knowledge of the clinical data or the study center from which it came12. The number of sections varied according to the size of the polyp. Additional sections were obtained if high-grade dysplasia or invasive cancer was present. Adenomas were classified as tubular or villous. Villous adenomas were classified according to the proportion of villous component: class A, 1 to 25 percent; class B, 26 to 75 percent; class C, 76 to 99 percent; and class D, 100 percent. This report is based on the classification of the polyps after pathological review. An adenoma was defined as having advanced pathological features if it was large (>1.0 cm) or had high-grade dysplasia or invasive cancer. 
60 years) and large adenomas (>1.0 cm) were also notable factors but were not significant independent variables according to multivariate analysis. The family histories of probands in the National Polyp Study21 are also being studied as possible risk factors for metachronous adenomas with advanced pathological features. It would be desirable to increase the interval between follow-up examinations in a subgroup of patients who are at low risk for adenomas with advanced pathological features after undergoing polypectomy. A cross-sectional analysis of the study's data22 supports the concept of a long natural history of colorectal cancer evolving through the adenoma stage. In addition, data recently published23 on rigid-instrument sigmoidoscopy in persons at average risk for colorectal cancer suggest that a long interval between examinations may be appropriate. The present study indicates that the first follow-up colonoscopy need not be performed in patients with newly diagnosed adenomas until at least three years after the initial colonoscopy. Perhaps even longer intervals are allowable, particularly if the first follow-up examination is negative or does not reveal adenomas with advanced pathological features. 
