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The right test for colon cancer screening?
EDITORIAL
The right test for colon cancer screening? For individuals at increased risk for colon cancer, colonoscopy is typically recommended to evaluate the entire colon, but for individuals at average risk, several available screening options are felt to be effective, including fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy.1 High-risk groups include individuals with a personal history of an adenoma, cancer, inflammatory bowel disease, or a family member with colorectal neoplasia. Older individuals are also at higher risk for colon cancer and they too might be candidates for colonoscopy screening rather than one of the alternatives. Age has long been recognized as a powerful factor in the risk for colon cancer. Although recent evidence has suggested that age might influence the risk for adenomas, information on the distribution of colorectal adenomas is more limited than information on cancer. In this issue of Gastrointestinal Endoscopy, Yamaji et al2 note a rightward shift in adenomas with aging. The investigators report the results of a prospective study of the location of adenomas found during annual colonoscopy screening in Japan. The investigators limited the study cohort to patients who had two recent negative colonoscopies to ensure that adenomas detected on follow-up were truly incident. During a mean total follow-up time of 4.6 years, 6304 patients underwent follow-up colonoscopy. The ratio of right-sided (defined as proximal to the splenic flexure) to left-sided adenomas in patients with a single adenoma detected on follow-up increased with age (p Z 0.04). The proportion of cases with multiple adenomas on the right side of the colon also increased with age (p Z 0.02). As expected, the incidence rates for both right-sided and left-sided adenomas increased with age, but the increase in incidence rate with age was observed to be greater for right-sided adenomas. Due in part to the short follow-up time (mean of 1.4 years between colonoscopies), the number of large adenomas (O10 mm) was inadequate for statistical analysis. For the analysis, subjects were classified into the following age groups: !40, 40-49, 50-59, and 60-69 years (the number of patients older than 69 was too small for stable statistics). The incidence rates for the age groups were: right-sided adenomas 1.8%, 2.9%, 3.9%, and 5.6%,
respectively; left-sided adenomas 1.9%, 2.4%, 3.4%, and 3.5%, respectively. Clearly there is an increase in the incidence of adenoma with age and a greater rate of increase for right-sided lesions. What does this study add to our current knowledge? Several prior studies, including an analysis by these same investigators, found an increased proportion of right-sided colon cancers with age,3-6 an increase that does not seem to be entirely explained by prior endoscopic screening. Crosssectional studies have also reported an increasing proportion of right-sided adenomas with age, consistent with the trends observed for colon cancer.7,8 The novelty of the current study, according to the investigators, is the
In addition to differences in the frequency of right-sided lesions by age, the epidemiology and biology of colon cancer point to distinguishable differences between right- and left-sided cancers.
Copyright ª 2006 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2005.10.008
requirement for two negative examinations, which allows them to more accurately calculate the incidence of rightand left-sided adenomas according to age. Restricting their cohort to patients who had two recent negative colonoscopies increased the likelihood that the adenomas detected on follow-up were, indeed, incident adenomas, rather than missed lesions. This allowed the investigators to estimate the rate of incident adenomas, but also selected a population that is at low risk for colon cancer. Therefore, while the proportion of right-sided adenomas in their study population does appear to increase with age, the clinical consequences of these small incident adenomas in a low-risk population are not clear and may not necessarily reflect incident colon cancer risk. In some respects, a design that included patients having their first examination might better reflect the overall natural history of adenomas, because it would represent the full spectrum of lesions at a given age, rather than the generally small adenomas that develop in the first year or so after a negative examination. In addition to differences in the frequency of right-sided lesions by age, the epidemiology and biology of colon cancer point to distinguishable differences between right- and
www.giejournal.org
Volume 63, No. 3 : 2006 GASTROINTESTINAL ENDOSCOPY 459
Editorial
Wei & Sandler
1. Pignone M, Rich M, Teutsch SM, Berg AO, Lohr KN. Screening for colorectal cancer in adults at average risk: a summary of the evidence
for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 137:132-41. Yamaji Y, Mitsushima T, Ikuma H, et al. Right-side shift of colorectal adenomas with aging. Gastrointest Endosc 2006;63:453-8. Okamoto M, Shiratori Y, Yamaji Y, et al. Relationship between age and site of colorectal cancer based on colonoscopy findings. Gastrointest Endosc 2002;55:548-51. Cooper GS, Yuan Z, Landefeld CS, Johanson JF, Rimm AA. A national population-based study of incidence of colorectal cancer and age. Implications for screening in older Americans. Cancer 1995;75: 775-81. Slater G, Papatestas AE, Tartter PI, Mulvihill M, Aufses AH Jr. Age distribution of right- and left-sided colorectal cancers. Am J Gastroenterol 1982;77:63-6. Gonzalez EC, Roetzheim RG, Ferrante JM, Campbell R. Predictors of proximal vs. distal colorectal cancers. Dis Colon Rectum 2001;44: 251-8. Patel K, Hoffman NE. The anatomical distribution of colorectal polyps at colonoscopy. J Clin Gastroenterol 2001;33:222-5. Gerharz CD, Gabbert H, Krummel F. Age-dependent shift-to-the-right in the localization of colorectal adenomas. Virchows Arch A Pathol Anat Histopathol 1987;411:591-8. Haenszel W, Correa P. Cancer of the large intestine: epidemiologic findings. Dis Colon Rectum 1973;16:371-7. Risio M, Reato G, di Celle PF, et al. Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer. Cancer Res 1996;56:5470-4. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993;260:816-9. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812-6. Lynch HT, Smyrk TC, Watson P, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104:1535-49.
460 GASTROINTESTINAL ENDOSCOPY Volume 63, No. 3 : 2006
www.giejournal.org
left-sided cancers. There are geographic differences in the incidence rates of colon cancer, with a predominance of right-sided cancers in low-incidence regions.9 Colon cancers characterized by microsatellite instability, either related to hereditary non-polyposis colorectal cancer or due to an acquired defect, tend to be right-sided10 and are associated with a better prognosis.11-13 So is colonoscopy the right test for our older patients? We already know that the risk for colon adenomas and colon cancers, both right-sided and left-sided, increases with age. This increase in risk with age, which is more dramatic than the relative differences in risk between right- versus left-sided lesions, remains the most compelling argument for a complete colon evaluation for older patients (of course, weighing the risks of the procedure and the shorter life expectancy of older individuals). These data for an increased proportion of right-sided cancers tilt the balance just a bit further in favor of colonoscopy.
2. 3.
4.
5.
6.
7. 8.
9.
Jeffrey T. Wei, MD, MPH Robert S. Sandler, MD, MPH Division of Gastroenterology and Hepatology University of North Carolina School of Medicine Chapel Hill, North Carolina, USA
10.
11. 12.
REFERENCES 13.
The right test for colon cancer screening? For individuals at increased risk for colon cancer, colonoscopy is typically recommended to evaluate the entire colon, but for individuals at average risk, several available screening options are felt to be effective, including fecal occult blood tests, flexible sigmoidoscopy, and colonoscopy.1 High-risk groups include individuals with a personal history of an adenoma, cancer, inflammatory bowel disease, or a family member with colorectal neoplasia. Older individuals are also at higher risk for colon cancer and they too might be candidates for colonoscopy screening rather than one of the alternatives. Age has long been recognized as a powerful factor in the risk for colon cancer. Although recent evidence has suggested that age might influence the risk for adenomas, information on the distribution of colorectal adenomas is more limited than information on cancer. In this issue of Gastrointestinal Endoscopy, Yamaji et al2 note a rightward shift in adenomas with aging. The investigators report the results of a prospective study of the location of adenomas found during annual colonoscopy screening in Japan. The investigators limited the study cohort to patients who had two recent negative colonoscopies to ensure that adenomas detected on follow-up were truly incident. During a mean total follow-up time of 4.6 years, 6304 patients underwent follow-up colonoscopy. The ratio of right-sided (defined as proximal to the splenic flexure) to left-sided adenomas in patients with a single adenoma detected on follow-up increased with age (p Z 0.04). The proportion of cases with multiple adenomas on the right side of the colon also increased with age (p Z 0.02). As expected, the incidence rates for both right-sided and left-sided adenomas increased with age, but the increase in incidence rate with age was observed to be greater for right-sided adenomas. Due in part to the short follow-up time (mean of 1.4 years between colonoscopies), the number of large adenomas (O10 mm) was inadequate for statistical analysis. For the analysis, subjects were classified into the following age groups: !40, 40-49, 50-59, and 60-69 years (the number of patients older than 69 was too small for stable statistics). The incidence rates for the age groups were: right-sided adenomas 1.8%, 2.9%, 3.9%, and 5.6%,
respectively; left-sided adenomas 1.9%, 2.4%, 3.4%, and 3.5%, respectively. Clearly there is an increase in the incidence of adenoma with age and a greater rate of increase for right-sided lesions. What does this study add to our current knowledge? Several prior studies, including an analysis by these same investigators, found an increased proportion of right-sided colon cancers with age,3-6 an increase that does not seem to be entirely explained by prior endoscopic screening. Crosssectional studies have also reported an increasing proportion of right-sided adenomas with age, consistent with the trends observed for colon cancer.7,8 The novelty of the current study, according to the investigators, is the
In addition to differences in the frequency of right-sided lesions by age, the epidemiology and biology of colon cancer point to distinguishable differences between right- and left-sided cancers.
Copyright ª 2006 by the American Society for Gastrointestinal Endoscopy 0016-5107/$32.00 doi:10.1016/j.gie.2005.10.008
requirement for two negative examinations, which allows them to more accurately calculate the incidence of rightand left-sided adenomas according to age. Restricting their cohort to patients who had two recent negative colonoscopies increased the likelihood that the adenomas detected on follow-up were, indeed, incident adenomas, rather than missed lesions. This allowed the investigators to estimate the rate of incident adenomas, but also selected a population that is at low risk for colon cancer. Therefore, while the proportion of right-sided adenomas in their study population does appear to increase with age, the clinical consequences of these small incident adenomas in a low-risk population are not clear and may not necessarily reflect incident colon cancer risk. In some respects, a design that included patients having their first examination might better reflect the overall natural history of adenomas, because it would represent the full spectrum of lesions at a given age, rather than the generally small adenomas that develop in the first year or so after a negative examination. In addition to differences in the frequency of right-sided lesions by age, the epidemiology and biology of colon cancer point to distinguishable differences between right- and
www.giejournal.org
Volume 63, No. 3 : 2006 GASTROINTESTINAL ENDOSCOPY 459
Editorial
Wei & Sandler
1. Pignone M, Rich M, Teutsch SM, Berg AO, Lohr KN. Screening for colorectal cancer in adults at average risk: a summary of the evidence
for the U.S. Preventive Services Task Force. Ann Intern Med 2002; 137:132-41. Yamaji Y, Mitsushima T, Ikuma H, et al. Right-side shift of colorectal adenomas with aging. Gastrointest Endosc 2006;63:453-8. Okamoto M, Shiratori Y, Yamaji Y, et al. Relationship between age and site of colorectal cancer based on colonoscopy findings. Gastrointest Endosc 2002;55:548-51. Cooper GS, Yuan Z, Landefeld CS, Johanson JF, Rimm AA. A national population-based study of incidence of colorectal cancer and age. Implications for screening in older Americans. Cancer 1995;75: 775-81. Slater G, Papatestas AE, Tartter PI, Mulvihill M, Aufses AH Jr. Age distribution of right- and left-sided colorectal cancers. Am J Gastroenterol 1982;77:63-6. Gonzalez EC, Roetzheim RG, Ferrante JM, Campbell R. Predictors of proximal vs. distal colorectal cancers. Dis Colon Rectum 2001;44: 251-8. Patel K, Hoffman NE. The anatomical distribution of colorectal polyps at colonoscopy. J Clin Gastroenterol 2001;33:222-5. Gerharz CD, Gabbert H, Krummel F. Age-dependent shift-to-the-right in the localization of colorectal adenomas. Virchows Arch A Pathol Anat Histopathol 1987;411:591-8. Haenszel W, Correa P. Cancer of the large intestine: epidemiologic findings. Dis Colon Rectum 1973;16:371-7. Risio M, Reato G, di Celle PF, et al. Microsatellite instability is associated with the histological features of the tumor in nonfamilial colorectal cancer. Cancer Res 1996;56:5470-4. Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993;260:816-9. Aaltonen LA, Peltomaki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993;260:812-6. Lynch HT, Smyrk TC, Watson P, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104:1535-49.
460 GASTROINTESTINAL ENDOSCOPY Volume 63, No. 3 : 2006
www.giejournal.org
left-sided cancers. There are geographic differences in the incidence rates of colon cancer, with a predominance of right-sided cancers in low-incidence regions.9 Colon cancers characterized by microsatellite instability, either related to hereditary non-polyposis colorectal cancer or due to an acquired defect, tend to be right-sided10 and are associated with a better prognosis.11-13 So is colonoscopy the right test for our older patients? We already know that the risk for colon adenomas and colon cancers, both right-sided and left-sided, increases with age. This increase in risk with age, which is more dramatic than the relative differences in risk between right- versus left-sided lesions, remains the most compelling argument for a complete colon evaluation for older patients (of course, weighing the risks of the procedure and the shorter life expectancy of older individuals). These data for an increased proportion of right-sided cancers tilt the balance just a bit further in favor of colonoscopy.
2. 3.
4.
5.
6.
7. 8.
9.
Jeffrey T. Wei, MD, MPH Robert S. Sandler, MD, MPH Division of Gastroenterology and Hepatology University of North Carolina School of Medicine Chapel Hill, North Carolina, USA
10.
11. 12.
REFERENCES 13.