Flat adenomas in the National Polyp Study: Is there increased risk for high-grade dysplasia initially or during surveillance?

doi:10.1016/S1542-3565(04)00392-1

Clinical Gastroenterology and Hepatology

Volume 2, Issue 10, October 2004, Pages 905-911

https://doi.org/10.1016/S1542-3565(04)00392-1 Get rights and content

Background & Aims: The flat adenoma may be a more aggressive pathway in colorectal carcinogenesis. Sessile adenomas from the National Polyp Study cohort were reclassified histopathologically as flat or polypoid and compared with initial and surveillance pathology. Methods: A total of 933 sessile adenomas detected during 1980–1990 were reclassified as follows: (1) adenoma thickness (AT): ≤1.3 mm, and (2) adenoma ratio (AR): adenoma thickness <2× normal mucosa thickness. Logistic regression was used to assess whether flat adenomas had an effect on risk for high-grade dysplasia initially, and a Cox proportional hazards model assessed the risk for advanced adenomas at surveillance. Results: The analysis encompassed 8401 person-years of follow-up evaluation. AT and AR measures of adenoma flatness were 95% concordant. By the AT measure, flat adenomas (n = 474) represented 27% of all baseline adenomas. Flat adenomas were found to be no more likely to exhibit high-grade dysplasia than sessile (polypoid) or pedunculated adenomas, the odds ratio for high-grade dysplasia was 1.91 (95% confidence interval [CI], 0.66–5.47; P = 0.23) for sessile (polypoid) vs. flat adenomas and 1.78 (95% CI, 0.63–5.02; P = 0.28) for pedunculated vs. flat adenomas adjusted for size, villous component, and location, and corrected for correlation of risk within an individual patient. Patients with flat adenomas at initial colonoscopy were not at greater risk for advanced adenomas at surveillance compared with those with polypoid adenomas only, the odds ratio was 0.76 (95% CI, 0.4–1.42; P = .39), adjusted for multiplicity, age, and family history of colorectal cancer. Conclusions: Flat adenomas identified in the National Polyp Study cohort at baseline were not associated with a higher risk for high-grade dysplasia initially, or for advanced adenomas at surveillance.

Section snippets

National Polyp Study design

Patients evaluated for enrollment had been referred for colonoscopy to 1 of 7 participating clinical centers in the United States for initial colonoscopy or polypectomy between November 1980 and February 1990.1 Those patients who had a family or personal history of familial polyposis or inflammatory bowel disease, or a history of polypectomy or colorectal cancer, were excluded from the study. Randomized patients had at least one histologically documented adenoma of the colon or rectum and had

Results

There were 938 patients of the total 1418 patients randomized in the National Polyp Study who had one or more surveillance colonoscopies and are the subjects of the present analysis. These patients had a total of 1750 adenomas at the baseline colonoscopy, which were confirmed and classified histologically and by grade of dysplasia by the pathology review;10 802 (46%) of the baseline adenomas were pedunculated and slides for 15 (1%) were not available. The remaining 933 sessile adenomas were

Discussion

For the present study, we classified as flat those adenomas that had been described as sessile at a time when flat was not in the endoscopist’s lexicon but were found on review of histologic sections to be thin (≤1.3 mm) or less than twice the thickness of the contiguous mucosa. A purely histologic definition of flat adenoma without reference to endoscopic findings would not have been meaningful, as has been pointed out by Samowitz and Burt.12 The National Polyp Study endoscopy protocol

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MYC overexpression in inflammatory bowel disease-associated conventional dysplasia and association of subsequent low-grade dysplasia in follow-up biopsies
2023, Pathology Research and Practice
Diagnosis of inflammatory bowel disease (IBD)-associated dysplastic lesions can be challenging. This study aims to evaluate MYC immunohistochemistry (IHC) as a potential biomarker for IBD-associated dysplasia and compare its effectiveness with p53 IHC.
The study cohort included resections from 12 IBD patients with carcinoma and concurrent conventional low-grade dysplasia (LGD), as well as biopsies from 21 patients with visible conventional LGD, which were followed up for 2 years with subsequent endoscopic examination. MYC and p53 IHC and MYC-FISH analysis were performed.
Sensitivity for LGD detection was 67% (8/12) and 50% (6/12) for MYC and p53, respectively, but the difference was not statistically significant (p = 0.2207). MYC and p53 overexpression were not always mutually exclusive, nor were they always present simultaneously. Patients who presented dysplasia in subsequent biopsies (7/21) were found to be more likely present with multiple LGD polyps and MYC-overexpressed LGD in the initial biopsies, compared to those without subsequent dysplasia (p < 0.05). These dysplastic lesions were commonly associated with chronic colitis (p = 0.0614). The distribution of LGD sites did not show a significant difference between patients with and without subsequent LGD. In MYC overexpressed cases, homogeneously strong nuclear expression was not identified in all dysplastic epithelial cells, and no MYC amplification was found in these cases by FISH.
MYC IHC can complement p53 IHC as an adjunct biomarker for diagnosing IBD-associated conventional LGD and can be used for the prediction of subsequent LGD in the follow-up biopsies combined with endoscopic features.
Risk Factors for Metachronous Colorectal Cancer or Advanced Adenomas After Endoscopic Resection of High-risk Adenomas
2023, Clinical Gastroenterology and Hepatology
Among the characteristics of high-risk adenomas (HRAs), some may predict a higher risk of metachronous advanced lesions. Our aim was to assess which HRA characteristics are associated with high risk of metachronous colorectal cancer (CRC) or advanced adenomas (AAs).
We systematically searched Pubmed, EMBASE, and Cochrane for cohort studies and clinical trials of CRC or AA incidence at surveillance stratified by baseline lesion size, histology, and multiplicity. We calculated pooled relative risks (RRs) using a random-effects model. Heterogeneity was assessed with the I² statistic.
Fifty-five studies were included, with 936,540 patients with mean follow-up 5.4 ± 2.9 years. CRC incidence per 1000 person-years was 2.6 (2.1–3.0) for adenomas ≥20 mm, 2.7 (2.2–3.2) for high-grade dysplasia (HGD), 2.0 (1.8–2.3) for villous component, 0.8 (0.1-1.4) for ≥5 adenomas, 1.0 (0.7–1.2) for ≥3 adenomas. Metachronous CRC risk was higher in adenomas ≥20 mm vs 10 to 19 mm (RR, 2.08; 95% confidence interval [CI], 1.20–3.61), HGD vs low-grade dysplasia (RR, 2.89; 95% CI, 1.88–4.44), villous vs tubular (RR, 1.75; 95% CI, 1.33–2.31). No significant differences in CRC risk were found in ≥3 adenomas vs 1 to 2 (RR, 1.24; 95% CI, 0.84–1.83), nor in ≥5 adenomas vs 3 to 4 (RR, 0.79; 95% CI, 0.30–2.11). Compared with normal colonoscopy, RR for CRC risk was 2.61 (95% CI, 2.06–3.32) for ≥10mm, 6.62 (95% CI, 4.60–9.52) for HGD, 3.58 (95% CI, 2.24–5.73) for villous component, and 2.03 (95% CI, 1.40–2.94) for ≥3 adenomas. Similar trends were seen for metachronous AAs.
Metachronous CRC risk is highest in patients with baseline adenomas with ≥20 mm or HGD. Multiplicity does not seem to be associated with substantially higher CRC risk in the near term.
The National Polyp Study at 40: challenges then and now
2021, Gastrointestinal Endoscopy
The Natural History of Colorectal Polyps: Overview of Predictive Static and Dynamic Features
2018, Gastroenterology Clinics of North America
Prevalence of advanced histological features and synchronous neoplasia in patients with flat adenomas
2016, Gastrointestinal Endoscopy
The prevalence of advanced histology in flat adenomas is uncertain. There are limited data on the prevalence of synchronous adenomas in patients with flat adenomas. The aims of this study were to determine whether the flat adenomas harbor advanced histology more than the polypoid adenomas and whether the presence of flat adenomas is an independent predictor of synchronous adenomas.
A retrospective analysis of data from 3 prospective clinical trials conducted at 2 tertiary care referral centers that included patients undergoing screening or surveillance colonoscopy was performed. The location, size, and morphology of each polyp resected was documented and sent for histopathological examination in a unique specimen jar.
A total of 2931 polyps were removed in 1340 patients. Of the 1911 adenomas (65.2%), 293 (15.3%) were flat and 1618 (84.7%) were polypoid. The prevalence of advanced histology did not differ between flat and polypoid adenomas (1.4% vs 3.1%; P = .13). Multivariate analysis confirmed that the presence of at least 1 flat adenoma was a predictor of the presence of a large adenoma (P < .01; odds ratio [OR], 2.80; 95% CI, 1.86–4.22), advanced adenoma (P < .01; OR, 2.70; 95% CI, 1.80–4.06), and 3 or more adenomas (P < .01; OR, 2.44; 95% CI, 1.66–3.59).
Although the prevalence of advanced histology in flat adenomas is similar to that of polypoid adenomas, flat adenomas are associated with increased prevalence of synchronous large and advanced adenomas. Whether these results imply shorter surveillance intervals in patients with flat adenomas needs to be explored in future studies.
Overexpressed Claudin-1 Can Be Visualized Endoscopically in Colonic Adenomas In Vivo
2016, Cellular and Molecular Gastroenterology and Hepatology
Conventional white-light colonoscopy aims to reduce the incidence and mortality of colorectal cancer (CRC). CRC has been found to arise from missed polypoid and flat precancerous lesions. We aimed to establish proof-of-concept for real-time endoscopic imaging of colonic adenomas using a near-infrared peptide that is specific for claudin-1.
We used gene expression profiles to identify claudin-1 as a promising early CRC target, and performed phage display against the extracellular loop of claudin-1 (amino acids 53–80) to identify the peptide RTSPSSR. With a Cy5.5 label, we characterized binding parameters and showed specific binding to human CRC cells. We collected in vivo near-infrared fluorescence images endoscopically in the CPC;Apc mouse, which develops colonic adenomas spontaneously. With immunofluorescence, we validated specific peptide binding to adenomas from the proximal human colon.
We found a 2.5-fold increase in gene expression for claudin-1 in human colonic adenomas compared with normal. We showed specific binding of RTSPSSR to claudin-1 in knockdown and competition studies, and measured an affinity of 42 nmol/L and a time constant of 1.2 minutes to SW620 cells. In the mouse, we found a significantly higher target-to-background ratio for both polypoid and flat adenomas compared with normal by in vivo images. On immunofluorescence, we found significantly greater intensity for human adenomas (mean ± SD, 25.5 ± 14.0) vs normal (mean ± SD, 9.1 ± 6.0) and hyperplastic polyps (mean ± SD, 3.1 ± 3.7; P = 10^-5 and 8 × 10^-12, respectively), and for sessile serrated adenomas (mean ± SD, 20.1 ± 13.3) vs normal and hyperplastic polyps (P = .02 and 3 × 10^-7, respectively).
Claudin-1 is overexpressed in premalignant colonic lesions, and can be detected endoscopically in vivo with a near-infrared, labeled peptide.

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Supported by Department of Health and Human Services grant CA 26852 (to S.J.W., Principle Investigator), National Institutes of Health.

The following members of the National Polyp Study Workgroup also participated in the study: New York: C. J. Lightdale, M. Edelman, M. Fleisher, B. Diaz, J. Lapidus, R. A. McMahan, M. Mandelman, H. Nazario, H. Colon, P. Kadvan, C. Miller, A. Szporn, N. Harpaz, and M. Khilnani; Minneapolis: H. Ansel, S. Ewing, and T. Dobson; Milwaukee: E. Stewart, W. Hogan, J. Helm, R. Komorowski, and E. McLaughlin; Racine, Wisconsin: J. Geenen, R. Venu, G. K. Johnson, and N. DeBoer; Boston: F. Ackroyd, P. Shellito, D. Hall, G. Dickersin, and N. Horton; Los Angeles: J. Panish, J. Sherman, J. A. Hamlin, S. Geller, and M. Kojimoto; Van Nuys, California: M. Auslander, D. Kasimian, L. Kussin, and C. Scoggins; and Boston (Pathology Review Center): C. Magrath.

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Original articlesFlat adenomas in the National Polyp Study: Is there increased risk for high-grade dysplasia initially or during surveillance?

Section snippets

National Polyp Study design

Results

Discussion

Ballieres Clin Gastroenterol

Gastroenterology

Hum Pathol

Gastroenterology

Lancet

Dig Liver Dis

Gastroenterology

Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps

N Engl J Med

Prevention of colorectal cancer by colonoscopic polypectomy

N Engl J Med

Small flat adenoma of the large bowel with special reference to its clinicopathologic features

Dis Colon Rectum

Clinicopathologic features of the flat adenoma

Dis Colon Rectum

Flat adenomas exist in asymptomatic peopleimportant implications for colorectal cancer screening programmes

Gut

Original articles
Flat adenomas in the National Polyp Study: Is there increased risk for high-grade dysplasia initially or during surveillance?