Nonpolypoid Colon Lesions Common and Often Malignant

By Judith Groch
PALO ALTO, Calif., March 4 -- Flat and depressed nonpolypoid colorectal neoplasms are common, hard to detect, and more likely to be malignant than the more familiar colorectal polyps, researchers here reported.
Nonpolypoid neoplasms, with an overall prevalence of more than 9%, were almost 10 times (OR 9.78) more likely to be malignant than polypoid lesions, irrespective of size, Roy Soetikno, M.D., of the Veterans Affairs Palo Alto Health Care System, and colleagues reported in the March 5 issue of the Journal of the American Medical Association.
After adjusting for polyp size, the likelihood that these neoplasms harbored in situ or submucosal carcinoma was more than five times higher than the rate for standard polyps, the researchers found.
Nonpolypoid neoplasms are more difficult to detect by colonoscopy or CT colonography. They appear to be slightly elevated, completely flat, or depressed, the latter being the most difficult to detect, the researchers said.
For detection during colonoscopy, the researchers used chromoendoscopy with indigo carmine spray, to highlight neoplastic lesions.
The findings came from a cross-sectional study of 1,819 patients undergoing elective colonoscopy from July 2003 to June 2004 at a Veterans Affairs hospital in California.
The overall prevalence of the nonpolypoid lesions was 9.35% (95% CI 8.05% to 10.78%, n=170).
The prevalence of nonpolypoid neoplasms in the subpopulations
for screening, surveillance, and symptoms was 5.84% (95% CI 4.13% to 8%, n=36), 15.44% (95% CI 12.76% to 18.44%, n=101), and 6.01% (95% CI 4.17% to 8.34%, n=33), respectively.
The overall prevalence of nonpolypoid lesions with in situ or submucosal invasive carcinoma was 0.82% (95% CI 0.46% to 1.36%, n=15).
In the screening group, the prevalence was 0.32% (95% CI 0.04% to 1.17%, n=2).
Overall, nonpolypoid neoplasms were almost 10 times likelier to be cancerous (OR 9.78, 95% CI 3.93 to 24.4) than polypoid lesions, irrespective of size.
The positive, size-adjusted association of the nonpolypoid lesions with in situ or submucosal invasive carcinoma was also observed in subpopulations for screening (OR 2.01, 95% CI 0.27 to 15.3) and surveillance (OR 63.7, 95% CI 9.41 to 431).
Characterizing morphology into flat, depressed, and polypoid, the size-adjusted multivariate model of flat lesions maintained a five-fold greater association of flat lesions with carcinoma (OR 5.18, 95% CI 1.84 to 14.6).
Although nonpolypoid lesions accounted for only 15% of neoplasms overall, more than half of the in situ or submucosal invasive carcinomas (n=15) were diagnosed in nonpolypoid lesions, the researchers wrote.
The depressed type, the most difficult to detect during colonoscopy, had the highest risk (33%).
Nonpolypoid colorectal neoplasms containing carcinoma were smaller in diameter than the polypoid ones (mean diameter, 15.9 mm versus 19.2 mm, respectively).
Follow-up of colonoscopy data within three years found 13 of 393 patients to have advanced neoplasia, all of which were flat or sessile adenomas 10 mm or larger, except for one T1 carcinoma.
In this study the researchers also diagnosed flat or sessile adenomas that were likely to have been missed by the initial colonoscopy because of incomplete bowel preparation, nonpolypoid shape, or their location between folds in the rectum.
Study limitations included the lack of generalizability of the study in which most of the individuals were men and the lack of long follow-up.
Recent studies have pointed out differences in the genetic mechanisms underlying the two types of colorectal neoplasms, the investigators said.
Future studies, they added, should further evaluate whether the diagnosis and removal of these neoplasms has any effect on the prevention and mortality of colorectal cancer and particularly focus on their genetic and protein abnormalities.
"The elephant in the endoscopy suite is missed lesions," wrote David Lieberman, M.D., of the Oregon Health & Science University in Portland, in an accompanying editorial.
There is increasing recognition that even experienced endoscopists may fail to detect important pathology, he said. In fact, CT colonography studies have shown that optical colonoscopy misses 2% to 12% of polypoid lesions larger than 10 mm.
It is possible, if not likely, Dr. Lieberman wrote, that additional nonpolypoid colorectal neoplasms may be missed by both studies so that these studies underestimate the actual colonoscopic miss rate. These missed lesions may represent the most common explanation for interval cancers.
Nonpolypoid lesions may be biologically distinct from polypoid lesions and appear to be more likely to harbor malignant features. Detection and complete removal at colonoscopy may be challenging, Dr. Lieberman said.
The optimal methods for enhancing colonoscopic imaging of nonpolypoid neoplasms are uncertain and studies are needed. Chromoendoscopy with indigo carmine seems to work, but other methods might be technically easier, he said.
Moreover, additional studies are needed to determine whether imaging modalities such as CT colonography will be able to detect flat or depressed neoplasms.
Finally, longitudinal studies are needed to determine whether
patients with nonpolypoid neoplasms require more intensive colonoscopic surveillance compared with patients with polypoid lesions of similar size and histology, Dr. Lieberman concluded.
Palo Alto Institute provided funding for the study for Research and Education, a nonprofit organization.
The study authors and Dr. Lieberman, the editorialist, reported no financial conflicts.
Primary source: Journal of the American Medical AssociationSource reference:Soetikno RM, et al "Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults" JAMA 2008; 299: 1027-1035. Additional source: Journal of the American Medical AssociationSource reference: Lieberman D "Nonpolypoid colorectal neoplasia in the United States: The parachute is open" JAMA 2008; 299: 1068-1069.