Importance of Adenomas 5 mm or Less in Diameter That Are Detected by Sigmoidoscopy

doi:10.1056/NEJM199701023360102

Volume 336:8-12		January 2, 1997		Number 1

Importance of Adenomas 5 mm or Less in Diameter That Are Detected by Sigmoidoscopy

Thomas E. Read, M.D., Julie D. Read, R.N., and Lynn F. Butterly, M.D.

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ABSTRACT

Background The need for colonoscopy in patients with adenomas5 mm or less in diameter that are detected by sigmoidoscopyis controversial.

Methods We prospectively determined the prevalence of proximalcolonic neoplasms in asymptomatic patients at average risk forcolorectal cancer, each of whose index lesion on screening fiberopticsigmoidoscopy was a benign adenoma. Polyps found on sigmoidoscopyunderwent biopsy, and colonoscopy was recommended to all patientswith neoplastic polyps. Rectosigmoid adenomas were classifiedas diminutive (<5 mm in diameter), small (6 to 10 mm in diameter),or large (>11 mm in diameter).

Results Of 3496 consecutive patients referred for sigmoidoscopy,311 had neoplastic rectosigmoid polyps; 108 of these patientswere excluded from the analysis because of a history of colonicneoplasia, symptoms, prior colonic evaluation, or incompletefollow-up data. The remaining 203 patients made up the studygroup, and all underwent colonoscopy. Neoplasms were found inthe proximal colon in 40 of 137 patients (29 percent) with diminutiveindex polyps, 15 of 52 patients (29 percent) with small indexpolyps, and 8 of 14 patients (57 percent) with large index polyps.Advanced neoplasms (adenomas >10 mm in diameter, adenomaswith a villous component or moderate-to-severe dysplasia, carcinomain situ, or frank carcinoma) were found in 8 patients (6 percent),5 patients (10 percent), and 4 patients (29 percent), respectively.Two patients with diminutive index polyps had proximal carcinomain situ, and two had proximal stage I carcinomas; one patientwith a large index polyp had proximal stage III carcinoma.

Conclusions The substantial prevalence of proximal colonic neoplasms,including advanced lesions, in asymptomatic average-risk patientswith rectosigmoid adenomas <5 mm in diameter warrants colonoscopyin these patients.

Increased use of flexible sigmoidoscopy as a screening examinationfor colorectal carcinoma has led to increased detection of benignadenomatous polyps <5 mm in diameter (referred to as diminutive)in the rectosigmoid of asymptomatic patients.¹^,² Although adenomasare neoplastic lesions that are considered to be the precursorsof most colorectal cancers,³^,⁴ the clinical importance of diminutiveadenomas that are found on screening sigmoidoscopy has beenthe subject of considerable debate.²^,³^,⁵^,⁶^,⁷^,⁸^,⁹^,¹⁰^,¹¹^,¹²^,¹³^,¹⁴^,¹⁵^,¹⁶^,¹⁷^,¹⁸^,¹⁹^,²⁰^,²¹^,²²Some believe that adenomas of the rectosigmoid, no matter whattheir size, are markers of neoplastic change throughout thecolon and thus recommend colonoscopy for patients with suchadenomas.²^,⁸^,⁹^,¹¹^,¹²^,¹⁴^,¹⁵^,²⁰^,²¹^,²² Others believe that theprobability of discovering an advanced proximal neoplasm islow (1 to 4 percent), and therefore, colonoscopy is not indicated.⁵^,⁶^,⁷^,¹⁰^,¹⁶^,¹⁷^,¹⁹No consensus has been reached.³ Studies in which it was concludedthat colonoscopy is unnecessary have been retrospective,¹⁷^,¹⁹have relied on follow-up of patients by means of national cancerregistries⁶ or autopsy records,¹⁷ or have based their conclusionson the low prevalence of advanced proximal neoplasms, despitefinding a substantial prevalence of smaller proximal neoplasticpolyps.⁵^,¹⁰^,¹⁹ Studies advocating colonoscopy could be criticizedfor including symptomatic patients or patients at risk for colorectalneoplasms⁹^,¹²^,¹⁵ or for having only a small group of patientsavailable for analysis.⁸^,¹¹^,¹²^,²¹

We prospectively determined the prevalence of proximal colonicneoplasms in a large group of asymptomatic patients at averagerisk for colorectal cancer who were found to have diminutivebenign adenomatous polyps on screening flexible sigmoidoscopy.Because the definition of diminutive polyps in the literaturehas ranged from <5 mm to <10 mm in diameter, we classifiedpolyps <5 mm as diminutive and those 6 to 10 mm as small.We also compared patients with diminutive or small polyps witha group of patients whose index rectosigmoid polyps were large(>11 mm).

Methods

Data were collected prospectively on 3496 consecutive patientsreferred for screening flexible sigmoidoscopy at the Lahey–HitchcockMedical Center between May 1992 and April 1995. In preparationfor sigmoidoscopy, patients were instructed to take 10 oz (300ml) of magnesium citrate (Cumberland–Swan, Smyrna, Tenn.),3 bisacodyl tablets (Dulcolax, Ciba, Woodbridge, N.J.), andonly clear liquids on the day before examination and to usea Fleet enema (C.B. Fleet, Lynchburg, Va.) on the day of theexamination. Sigmoidoscopy was performed with a 60-cm flexiblefiberoptic instrument (Pentax, Orangeburg, N.Y.). All polypsidentified by sigmoidoscopy underwent biopsy. Colonoscopy wasrecommended to all patients in whom adenomatous polyps werefound. All colonoscopies were performed within one year of sigmoidoscopy(usually within three months). In preparation for colonoscopy,patients underwent whole-gut lavage with polyethylene glycol–electrolytesolution (Colyte, Reed and Carnrick, Jersey City, N.J.). Colonoscopywas performed with a video colonoscope (Pentax). All polypsfound at colonoscopy were removed. Patients who had an incompletecolonoscopic examination were referred for air–contrastbarium enema. The size and location of the lesions were obtainedfrom the endoscopy report. The examiner used biopsy forcepsas a visual guide to estimate the size of the polyps. The histologiccharacteristics of the polyps were obtained from the pathologyreport. Advanced neoplasms were defined as adenomas >10 mmin diameter, adenomas with a villous component or moderate-to-severedysplasia, carcinoma in situ, or frank carcinoma.

To obtain an asymptomatic, average-risk study population, weexcluded patients from the analysis if they had a history ofcolon cancer, neoplastic polyps, or inflammatory bowel disease;had a positive fecal occult-blood test (Hemoccult); had a first-degreerelative with colon cancer; had rectal bleeding; had anemia;had a recent change in bowel habits; or had undergone colonoscopyor enema with contrast medium within five years before flexiblesigmoidoscopy. Patients were also excluded if they did not undergocolonoscopy at our institution, declined to undergo colonoscopy,or had an incomplete colonoscopy and then did not have a subsequentair–contrast barium enema.

Statistical comparisons between groups were calculated withFisher's exact test (two-tailed).

Results

Polypoid lesions were found on 768 of the 3496 screening flexible-sigmoidoscopicexaminations (22 percent). The histologic characteristics ofthe most advanced (index) lesion identified are shown in Table 1.Ninety of the 311 patients with neoplastic rectosigmoid polypswere excluded from the analysis because of a history of colonicneoplasia, symptoms, or prior colonic evaluation. Eighteen additionalpatients were excluded from the analysis because of incompletefollow-up data: seven had undergone colonoscopy elsewhere; fivedeclined to undergo colonoscopy; one had not yet undergone colonoscopy;two had had incomplete colonoscopy and had not subsequentlyhad an air–contrast enema; and three had had an air–contrastenema that was not preceded by colonoscopy.

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Table 1. Histologic Characteristics of Index Lesions Found at Flexible Sigmoidoscopy.

The study population was thus composed of 203 asymptomatic,average-risk patients in whom benign neoplastic polyps wereidentified by screening flexible sigmoidoscopy, and who thenunderwent colonoscopy at our institution. Colonoscopy to thececum was achieved in 189 of the 203 patients (93 percent).The 14 patients in whom cecal intubation was not confirmed underwentair–contrast barium enema examinations, all of which showedno mass lesions. Patients were divided into three groups onthe basis of the size of their index rectosigmoid neoplasms:137 patients had diminutive index polyps (<5 mm in diameter),52 patients had small index polyps (6–10 mm in diameter),and 14 patients had large index polyps (>11 mm in diameter).The histologic characteristics of the index rectosigmoid neoplasmsare shown in Table 2.

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Table 2. Histologic Characteristics of Index Neoplastic Lesions Found at Flexible Sigmoidoscopy in 203 Asymptomatic Average-Risk Patients.

Among the 137 patients with diminutive index lesions (mean [±SD]age, 60.7 ± 6.7 years), the mean size of the rectosigmoidpolyps was 3.4 ± 1.7 mm and the index neoplasm was solitaryin 128 (93 percent). Proximal neoplasms were found in 29 percentat colonoscopy (Table 3), and advanced proximal neoplasms werefound in 6 percent, including three tubular adenomas >10mm in diameter, one tubulovillous adenoma, two adenomas withcarcinoma in situ, and two frank carcinomas. The two patientswith frank carcinoma had stage I lesions (T2N0M0 according tothe tumor–node–metastasis system of staging), andboth underwent colectomy. As of October 1996, both were freeof disease. The presence of multiple diminutive rectosigmoidadenomas was not predictive of advanced proximal neoplasia:four of the nine patients with more than one adenoma at flexiblesigmoidoscopy had proximal neoplasms, but none had advancedproximal neoplasms.

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Table 3. Histologic Characteristics and Size of the Most Advanced Proximal Neoplasm Found at Colonoscopy in 203 Asymptomatic Average-Risk Patients with Benign Rectosigmoid Adenomas, According to the Size of the Index Lesions.

Among the 52 patients with small index lesions (age, 61.7 ±7.2 years), the mean size of the rectosigmoid polyps was 6.3± 2.4 mm and the index lesion was solitary in 44 (85percent). The prevalence of proximal neoplastic lesions (29percent) and advanced proximal neoplasms (10 percent) was similarto the prevalence in patients with diminutive rectosigmoid adenomas(Table 3). Advanced proximal neoplasms included three tubularadenomas >10 mm in diameter and two tubulovillous adenomas(35 mm and 15 mm in diameter). As in the group with diminutiveindex lesions, the presence of multiple small rectosigmoid adenomaswas not predictive of advanced proximal neoplasia: three ofthe eight patients with more than one adenoma at flexible sigmoidoscopyhad proximal neoplasms, but none had advanced proximal neoplasms.

Among the 14 patients with large index lesions (age, 63.7 ±5.2 years), the mean size of the rectosigmoid polyps was 13.3± 6.5 mm and the index lesion was solitary in 10 (71percent). Proximal neoplasms were discovered on colonoscopyin 8 of the 14 patients (57 percent): four tubular adenomas6 to 10 mm in diameter and four neoplasms >11 mm, includingone tubulovillous adenoma and one stage III carcinoma (T3N1M0)(Table 3). Thus, 4 of 14 patients (29 percent) had advancedproximal neoplasms in this group.

Increased size of the index rectosigmoid neoplasm did not correlatewith the prevalence of proximal neoplasia (P = 0.11), but itdid correlate with the prevalence of advanced proximal neoplasia(P = 0.02). Age was not a significant variable. Of the 203 patientsin the study population, 29 percent of the 143 patients under65 years of age had proximal neoplasms, as compared with 35percent of the 60 patients over 65. Advanced neoplasms werefound in 7 percent of those under 65, as compared with 12 percentof those over 65.

Discussion

We found that asymptomatic, average-risk patients with diminutiveor small rectosigmoid adenomas on screening flexible sigmoidoscopyhave a 29 percent prevalence of proximal neoplasms at colonoscopy.Our data are consistent with those of prior studies that usedsimilar methods, which demonstrated a 26 to 42 percent prevalenceof proximal neoplasms in patients with diminutive rectosigmoidadenomas.⁸^,¹⁰^,¹¹^,¹²^,¹⁵^,¹⁹^,²¹ However, some of these studiesincluded symptomatic patients or patients with established riskfactors for the development of colorectal carcinoma.⁹^,¹²^,¹⁵We used strict exclusion criteria to avoid such biases.

We also found that patients with diminutive or small rectosigmoidadenomas have a substantial prevalence of advanced proximalneoplasms — 6 percent and 10 percent, respectively. Moststriking were the four patients whose diminutive rectosigmoidadenomas prompted the discovery of early-stage proximal carcinomas.Although the prevalence of advanced neoplasms in prior studieshas varied somewhat (1 to 13 percent),⁵^,¹⁰^,¹⁵^,²¹ our valuesare within this range and are higher than those expected inthe general population (3 percent), as estimated by Grossmanet al. in their age-adjusted analysis of autopsy data.¹⁰

The substantial prevalence of proximal colonic neoplasms inour patients with diminutive rectosigmoid adenomas suggeststhat neoplastic change in the distal colon may be a marker forneoplastic change in the proximal colon. Since we did not performcolonoscopy in a control group of patients who had no neoplasmsat sigmoidoscopy, this association remains unproved. The prevalenceof proximal neoplasia in asymptomatic, average-risk patientswithout neoplastic polyps in the rectosigmoid has ranged from13 to 28 percent in the literature,⁸^,¹⁴^,²¹^,²³ although the largestof these studies, by Rex et al. (422 patients), had only a 15percent prevalence of proximal neoplasia.¹⁴

Some have argued that diminutive rectosigmoid adenomas are notmarkers for proximal neoplasia¹⁰^,¹⁹ because of autopsy datademonstrating adenomatous colorectal polyps in 23 to 46 percentof American and Western European adults.²⁴^,²⁵^,²⁶^,²⁷ However,the average age of patients in autopsy studies is about 10 yearsolder²⁴^,²⁵^,²⁶^,²⁷ than in our series, and the prevalence of adenomatouspolyps has been shown to increase with age, by about 7.5 percentper decade.²⁴^,²⁵^,²⁸^,²⁹ Autopsy series do not exclude symptomaticpatients or patients at high risk for colon carcinoma, whichmay result in a higher prevalence of colonic neoplasia thanis seen in asymptomatic patients at average risk.

Some studies of patients with diminutive rectosigmoid adenomashave demonstrated a low prevalence (1 to 3 percent) of advancedproximal neoplasms.⁵^,¹⁰ However, our study and others¹⁵^,²¹ havefound a substantially higher prevalence (6 to 13 percent). Furthermore,a paucity of advanced proximal neoplasms should not be reassuring,since a small, benign adenoma will not necessarily remain smalland benign. Untreated polyps have been shown to grow and undergomalignant change,¹⁸ and autopsy studies have shown that polypsize increases with increasing age,²⁸ suggesting that polypsgrow over time. Carcinoma can exist in small polyps; 15 percentof malignant polyps removed in a study of colonoscopic polypectomieswere less than 10 mm in diameter.²² Data from the National PolypStudy suggest that the removal of even diminutive colorectaladenomas may prevent the development of colorectal carcinoma.⁴

The decision to proceed with colonoscopy in patients with rectosigmoidadenomas should ideally be based on the reduction in the riskof colorectal carcinoma afforded by colonoscopic polypectomyof proximal lesions. It is difficult to estimate this risk becausecolorectal cancers grow slowly and are relatively uncommon ascompared with benign polyps. Atkin et al. found a low incidenceof subsequent colon cancer in patients who had had small (<10mm) rectosigmoid adenomas removed by rigid sigmoidoscopy andwere not subsequently monitored by colonoscopy.⁶ Spencer etal. found no increase in the risk of subsequent colon carcinomain patients who had small (<10 mm) rectosigmoid polyps observedor fulgurated without biopsy.¹⁷ It is difficult to draw firmconclusions from their data, however. Follow-up of patientsthrough the National Health Service Central Register,⁶ medicalrecords, or autopsy¹⁷ may be inaccurate. Many patients in thestudy by Atkin et al. did in fact undergo colonic evaluation,resulting in polypectomies, which may have reduced the riskof colon carcinoma.⁶ The study by Spencer et al. was retrospective,and selection bias was introduced by the exclusion of 227 patientswho did undergo biopsy of their polyps and had unfavorable histologiccharacteristics, and by the inclusion of the 68 percent of patientswho underwent barium enema before entering the study.¹⁷ In addition,since no biopsies were performed, many of these polyps may havebeen non-neoplastic polyps, which are not associated with anincreased risk of proximal neoplasia.¹⁴^,²¹

Given the difficulties of evaluating the subsequent risk ofcarcinoma, we believe that the prognostic value of neoplasticrectosigmoid polyps is best estimated by their association withproximal colonic neoplasia. Advanced rectosigmoid neoplasmsare clearly associated with advanced proximal neoplasms. Inaddition, our data show that patients with diminutive or smalladenomas on screening sigmoidoscopy have a substantial riskof having proximal colonic neoplasms, many of which are advancedlesions. It may ultimately be more cost effective to decreasethe frequency of subsequent colonoscopies than to abandon evaluationof the proximal colon.

Our study did not address the issue of proximal neoplasms inasymptomatic patients with negative fecal occult-blood testswho do not have rectosigmoid neoplasms and who would thus bemissed with the current screening strategy. Screening colonoscopyhas been advocated by some because of its ability to detectproximal neoplasms in the absence of distal neoplasms.²³^,³⁰However, the great cost has deterred most centers from adoptingsuch a program.¹³ Since flexible sigmoidoscopy remains the recommendedendoscopic screening procedure for colorectal cancer in asymptomatic,average-risk patients,³¹^,³² findings at sigmoidoscopy will thusdictate the need for subsequent colonoscopy. We believe thesubstantial prevalence of proximal neoplasms and advanced proximalneoplasms in patients with diminutive and small rectosigmoidadenomas clearly warrants colonoscopy.

Supported in part by a grant from Hoechst-Marion-Roussel andby the Robert E. Crozier Research Endowment Fund.

We are indebted to Barbara Kodner for editorial assistance;to Jack D. Baty, Department of Biostatistics, Washington UniversitySchool of Medicine, for statistical advice; and to Dr. RichardMacDermott and Dr. Pat Roberts, Lahey–Hitchcock MedicalCenter, for their helpful suggestions.

Source Information

From the Departments of Colon and Rectal Surgery (T.E.R., J.D.R.) and the Section of Gastroenterology (L.F.B.), Lahey–Hitchcock Medical Center, Burlington, Mass.

Address reprint requests to Dr. Butterly at the Section of Gastroenterology, Lahey–Hitchcock Medical Center, 41 Mall Rd., Burlington, MA 01805.

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