Pathologic Features of Initial Adenomas as Predictors for Metachronous Adenomas of the Rectum
04 Nov 1998-Journal of the National Cancer Institute (Oxford University Press)-Vol. 90, Iss: 21, pp 1661-1665
TL;DR: The risk of metachronous adenomas is closely related to the pathology of initial adenomatous polyps, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.
Abstract: Background Colorectal cancer is the third most common cancer in the world, arising mostly from pre-existing adenomatous polyps (adenomas) of the large bowel. Patients with colorectal adenomas are at increased risk of colorectal cancer because of a high recurrence rate for adenomas. We followed a cohort of 1490 patients with rectal adenomas to determine whether recurrence might be related to pathologic characteristics of the initial adenomas. Methods The patients were identified in Haining County, China, from 1977 through 1978 by means of examination with a 15-cm rigid sigmoidoscope. They were followed by endoscopic examination at years 2, 4, 6, 11, and 16 after their initial polypectomy. New adenomas in the rectum were identified in 280 patients in these follow-up examinations. Results Statistically significant twofold to threefold elevated risks of metachronous (recurrent) adenomas were observed for patients who had more than two initial adenomas or whose most advanced initial adenoma was more than 1.0 cm in size, was of villous/tubulovillous type, or showed moderate to severe dysplasia. Much stronger associations were observed for advanced metachronous neoplasms, which are defined as cancers or adenomas with severe dysplasia, with multivariate adjusted relative risks (95% confidence interval) of 4.2 (1.8-9.9) for a large initial adenoma (>1.0 cm), 8.1 (4.2-15.6) for villous/tubulovillous architecture, and 14.4 (5.0-41.3) for severe dysplasia. In particular, patients who had a large (>1.0 cm) adenoma with severe dysplasia at baseline had a relative risk of 37 (7.8-174.7) of developing advanced metachronous neoplasms compared with patients who had small adenoma(s) with mild dysplasia. Conclusions The risk of metachronous adenomas is closely related to the pathology of initial adenomas, thus allowing identification of a high-risk group of adenoma patients for close surveillance after their initial polypectomy.
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Memorial Sloan Kettering Cancer Center1, Harvard University2, Boston University3, University of Texas MD Anderson Cancer Center4, American Cancer Society5, Oregon Health & Science University6, University of Utah7, Kaiser Permanente8, University of Minnesota9, University of Colorado Denver10, University of Vermont11, University of Texas Southwestern Medical Center12, Creighton University13, Eastern Virginia Medical School14, Indiana University15
TL;DR: In this article, a careful analytic approach was designed to address all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be stratified more definitely at their baseline colonoscopy into those at lower risk or increased risk for a subsequent advanced neoplasia.
677 citations
Memorial Sloan Kettering Cancer Center1, Harvard University2, Boston University3, University of Texas MD Anderson Cancer Center4, American Cancer Society5, Oregon Health & Science University6, University of Utah7, Kaiser Permanente8, University of Minnesota9, University of Colorado Denver10, University of Vermont11, University of Texas Southwestern Medical Center12, Creighton University13, Eastern Virginia Medical School14, Indiana University15
TL;DR: A careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia.
Abstract: Adenomatous polyps are the most common neoplastic findings uncovered in people who undergo colorectal screening or have a diagnostic workup for symptoms. It was common practice in the 1970s for these patients to have annual follow-up surveillance examinations to detect additional new adenomas as well as missed synchronous adenomas. As a result of the National Polyp Study report in 1993, which demonstrated clearly in a randomized design that the first postpolypectomy examination could be deferred for 3 years, guidelines published by a gastrointestinal consortium in 1997 recommended that the first follow-up surveillance be 3 years after polypectomy for most patients. In 2003, these guidelines were updated, colonoscopy was recommended as the only follow-up examination, and stratification at baseline into lower and higher risk for subsequent adenomas was suggested. The 1997 and 2003 guidelines dealt with both screening and surveillance. However, it has become increasingly clear that postpolypectomy surveillance is now a large part of endoscopic practice, draining resources from screening and diagnosis. In addition, surveys have demonstrated that a large proportion of endoscopists are conducting surveillance examinations at shorter intervals than recommended in the guidelines. In the present paper, a careful analytic approach was designed addressing all evidence available in the literature to delineate predictors of advanced pathology, both cancer and advanced adenomas, so that patients can be more definitely stratified at their baseline colonoscopy into those at lower or increased risk for a subsequent advanced neoplasia. People at increased risk have either three or more adenomas, or high-grade dysplasia, or villous features, or an adenoma ≥1 cm in size. It is recommended that they have a 3-year follow-up colonoscopy. People at lower risk who have one or two small (<1 cm) tubular adenomas with no high-grade dysplasia can have a follow up in 5 to 10 years, whereas people with hyperplastic polyps only should have a 10-year follow up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.
597 citations
Cites background from "Pathologic Features of Initial Aden..."
...Most of the studies that assessed risk factors for advanced adenomas at surveillance were either randomized controlled trials of surveillance,(25) chemoprevention trials, prospective surveillance studies,(24) or registry-based observational cohort studies of patients returning for surveillance with less structured follow up outside the context of a clinical trial.(7,12,21,30,31,33,35) The most consistent evidence for predicting subsequent advanced adenomas indicates that multiplicity, size, villous histology, and high-grade dysplasia are the important factors at baseline....
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...0 cm at baseline.(30) Noshirwani, et al....
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...4), respectively, for the development of subsequent advanced neoplasia (rectal cancer or severe dysplasia) in patients with moderate and severe dysplasia at baseline.(30) Lieberman, et al....
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...High-grade dysplasia is related to larger adenoma size and villous component at baseline and is an important predictor for subsequent advanced neoplasia in three of the observational cohort studies.(7,24,30) By definition, all adenomas have some level of dysplasia....
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...0) for the detection of advanced neoplasms (rectal cancer, or adenoma with severe dysplasia) at follow up.(30) Loeve reported a significant trend for increasing risk of colorectal cancer at surveillance in relationship to increasing villous component or carcinoma in situ compared with tubular histology....
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University of Arizona1, Dartmouth College2, Portland VA Medical Center3, National Institutes of Health4, Memorial Sloan Kettering Cancer Center5, Veterans Health Administration6, University of Minnesota7, United States Department of Veterans Affairs8, Harvard University9, Fred Hutchinson Cancer Research Center10
TL;DR: Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas.
507 citations
TL;DR: There is a strong association between results of baseline screening colonoscopy and rate of serious incident lesions during 5.5 years of surveillance and patients with 1 or 2 tubular adenomas less than 10 mm represent a low-risk group compared with other patients with colon neoplasia.
402 citations
TL;DR: Large or proximally located adenomas are important indicators of recurrence of advanced lesions and careful surveillance of this area is warranted.
255 citations
References
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TL;DR: The size, histological type, and grade of dysplasia of a large series of colorectal adenomas removed by colonoscopic polypectomy were matched against other variables such as anatomical site, age, sex, and number ofAdenomas per patients to show the possible significance of severe Dysplasia as a selective marker for increased coloreCTal cancer risk.
Abstract: The size, histological type, and grade of dysplasia of a large series of colorectal adenomas removed by colonoscopic polypectomy were matched against other variables such as anatomical site, age, sex, and number of adenomas per patients. Special emphasis was placed on the criteria for grading dysplasia in adenomas and the possible significance of severe dysplasia as a selective marker for increased colorectal cancer risk. The results showed that small adenomas (mostly with mild dysplasia) were evenly distributed throughout the colorectum but that adenomas showing severe dysplasia (mostly the larger tumours, greater than 10 mm diameter) were concentrated in the left colon and rectum, particularly the sigmoid part which is also the segment with the highest risk of colorectal carcinoma in high risk populations. Severe dysplasia in adenomas appears to be a selective histopathological marker for increased colorectal cancer risk. It is closely linked with increasing age and numbers of adenomas per patient, with the large adenomas and particularly those with a villous component in their histology. Severe dysplasia and multiple adenomas could be valuable markers for selecting from the total adenoma population those most deserving of close surveillance in follow-up cancer prevention programmes. Conceptually it would appear advantageous to think in term of the dysplasia-carcinoma sequence in the colorectum rather than the polyp-cancer or adenoma-carcinoma sequence. The implications of these results in the study of the aetiology of colorectal cancer are discussed.
361 citations
TL;DR: The number of adenoma‐bearing individuals in the living population of northern Norway was estimated in each cohort for the period 1974–76 by determining the prevalence of colorectal adenomas in an autopsy population of 271 consecutive cases, representative of the population of the area with regard to underlying causes of death.
Abstract: Assuming that all colorectal cancers develop from preexisting adenomas, the annual conversion rate, defined as the number of cancers occurring each year as a percentage of all adenoma-bearing individuals, was determined. The number of adenoma-bearing individuals in the living population of northern Norway was estimated in each cohort for the period 1974–76 by determining the prevalence of colorectal adenomas in an autopsy population of 271 consecutive cases, representative of the population of the area with regard to underlying causes of death. During the 10-year period 1974–1983 a total of 656 colorectal cancers were recorded among an estimated number of 26,419 adenoma-bearing individuals aged over 35 years. The annual conversion rate was found to be 0.25%, indicating that an average adenoma-bearing individual is only at a moderate risk of colorectal cancer. The annual conversion rates for individuals having large adenomas, or adenomas with villous structures, or severe dyspla- sia were roughly estimated to be 3%, 17% and 37% respectively, assuming that colorectal cancer develops from one of these sub-groups of adenomas only.
218 citations
211 citations
Journal Article•
TL;DR: The data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma.
Abstract: Mutation and loss of heterozygosity (LOH) in the p53 gene were analyzed in 274 colorectal tumors of 4 histopathological grades. Among 160 tumors from 40 familial adenomatous polyposis patients, none of 58 adenomas with moderate dysplasia had p53 mutations, whereas 8% (3 of 37) of severe adenomas, 15% (6 of 40) of intramucosal carcinomas, and 40% (10 of 25) of invasive carcinomas had p53 mutations. Only 3% (1 of 33) of severe adenomas showed both mutation and LOH, while 25% (6 of 24) of intramucosal carcinomas and 40% (10 of 25) of invasive carcinomas had both mutation and LOH. All intramucosal and invasive carcinomas that had mutations lost the other allele of the p53 gene. In 114 tumors from 86 non-familial adenomatous polyposis patients, similar results were obtained; no adenoma showed both mutation and LOH, but both alterations occurred in intramucosal and invasive carcinoma. As regards specificity in 56 mutations detected in the present study, the frequently affected codons were codons 175, 238, 245, 248, 273, and 282, 4 of these amino acids being arginine, and 72% (39 of 54) of all mutations were GC to AT transition. Although expression into p53 polyadenylated RNA was high in every invasive carcinoma irrespective of the presence of mutation or LOH, there was a correlation between mutation and protein level; immunostaining of p53 protein was negative in almost all adenomas, but it was positive in 86% of invasive carcinomas exhibiting p53 mutation. These data suggest that genetic changes on both alleles of the p53 gene through mutation and LOH, which result in abnormal protein accumulation, are involved in the conversion of adenoma to early carcinoma. Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.
186 citations
TL;DR: There are roughly two types of colorectal cancers, one of the infiltrating or ulcero‐infiltrating type, which usually would arise de novo and account for approximately 40% of all coloreCTal cancer cases, and the exophytictype, which would mainly follow an adenoma‐carcinoma sequence, although some might be de noovo cancers, in particular in the right colon.
Abstract: Although it is well known that colorectal cancers can arise on a preexisting adenoma or de novo, the relative importance of these two pathways is still highly controversial. The authors studied the proportion of cancers with adenomatous remnants in a nonselected population-based series of 1630 resected colorectal cancers, so that they could estimate by subsite the importance of the adenoma-carcinoma sequence. Four factors appeared to be related independently to the presence of adenomatous tissue within cancers in a multiple logistic model: tumor extension, growth pattern, location, and size. It appeared that infiltrating and ulcero-infiltrating tumors, which represented 39.8% of all resected colorectal cancers, very rarely displayed adenomatous tissue (0.5%), whereas it was more common in fungating and ulcero-fungating cancers (25.8%; P less than 0.001). In these exophytic cancers, the presence of adenomatous tissue was related very closely to the tumor size and extension, and it was seen in as many as 83% of small cancers (less than 2 cm) limited to the mucosa or submucosa. Right colon cancer showed consistently fewer adenomatous remnants than left colon or rectal cancer. These figures suggest that there are roughly two types of colorectal cancers, one of the infiltrating or ulcero-infiltrating type, which usually would arise de novo and account for approximately 40% of all colorectal cancer cases, and the exophytic type, which would mainly follow an adenoma-carcinoma sequence, although some might be de novo cancers, in particular in the right colon.
184 citations