***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Analysis of prospect i ve follow-up data usually includes a Cox regression model . When a hazard rate ratio , obtained as the exponential of an estimated regression coefficient from the Cox model , is greater than 1.0 , it consistently exceeds relative risk , and is exceeded by the odds ratio . The divergence of these distinct epidemiologic measures increases with the product of three factors : ( 1 ) the length of follow-up , ( 2 ) the average rate of the end point occurence over the follow-up period , and ( 3 ) the magnitude of risk , either above or below 1 . Cornfield 's rare disease assumption is basically the product of the first two of these factors . However , risks in excess of 2.5 have a powerful effect on the divergence of these measures , and this point has received less emphasis . Conversely , and as seen frequently in applications , relative risk , hazard rate ratio , and odds ratio numerically approximate one another with shorter follow-up , rarer end points , and risks closer to 1 . Although the hazard rate ratio is not always distinguished from relative risk , it is commonly close to , and is always between , relative risk and the odds ratio . Consistent and accurate terminology would have us use hazard rate ratio with Cox regression and odds ratio with logistic regression . The term " relative risk " seems to be a default choice , regardless of the model being used . However , when relative risk is the object of the model chosen , as in a Poisson regression approximation of two binomial proportions or an equivalent weighted least squares , then for us , relative risk is the accurate terminology Background : Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma and therefore need to be kept under surveillance . It is essential to avoid unnecessary examinations by tailoring the frequency of follow up examinations to individual risk . Methods : A total of 3134 patients undergoing endoscopic removal of colorectal adenomas were prospect ively recorded on the Erlangen Registry of Colorectal Polyps between 1978 and 1996 . A multivariate analysis of 1159 patients on long term follow up was performed to identify risk factors determining surveillance intervals for patients with metachronous adenomas of advanced pathology — that is , adenomas > 10 mm or with high grade dysplasia or invasive carcinoma . Results : Univariate analysis revealed that sex , parental history of colorectal carcinoma , and characteristics of the initial findings —that is , size , multiplicity , and amount of villous structure — were significant predictors of metachronous adenomas of advanced pathology . On the basis of multivariate analysis , two risk groups were identified : ( 1 ) patients with no parental history of colorectal carcinoma with only small ( ≤10 mm ) tubular adenomas at the initial clearing examination have a very low risk , and we estimated that 10 % will develop advanced metachronous adenomas after 10 years ; ( 2 ) the high risk group contained all other patients , 10 % of whom will show metachronous adenomas of advanced pathology at follow up after only three years . Conclusions : The risk of developing metachronous adenomas with advanced pathology can be stratified for various patient and adenoma characteristics . Surveillance intervals can be scheduled for low risk ( 10 years ) and high risk ( three years ) patients . Risk related follow up thus helps to avoid unnecessary examinations PURPOSE : The value of routine colonoscopy in the prevention or early detection of metachronous carcinoma of the colon and rectum remains unproven . This study attempts to clarify this issue . METHODS : An analysis of a personal series of 460 patients with primary colorectal carcinoma treated by the second author between 1972 and 1990 was review ed . After various exclusions , there remained 231 patients who had been prospect ively followed by colonoscopy with a mean follow-up period of 56 years . RESULTS : In 48 ( 21 percent ) patients , there were synchronous adenomas present at the time of the initial resection for carcinoma and 35 ( 73 percent ) of these patients subsequently developed metachronous adenomas , being recurrent in 22 . Ninety-five ( 52 percent ) of the 183 patients without synchronous adenomas eventually developed metachronous adenomas , so that overall 130 ( 56 percent ) patients developed metachronous adenomas . Four patients developed a metachronous carcinoma that was either Dukes A or B , and all remain well at the time of final follow-up . These metachronous carcinomas were found after a mean interval of seven and three-quarter years . All four patients had synchronous adenomas and all developed metachronous adenomas on multiple occasions before the metachronous carcinoma was detected . Thus , a subset consisting of only 22 patients produced all four metachronous malignancies — a rate of 18 percent . CONCLUSION : It would appear that the presence of synchronous adenomas with the subsequent development of recurring metachronous adenomas is significant and warrants a more intensive follow-up program to ensure the early diagnosis and more likely cure of any metachronous carcinoma BACKGROUND & AIMS Limited data exist regarding the actual risk of developing advanced adenomas and cancer after  polypectomy  or the factors that determine risk . METHODS We pooled individual data from 8 prospect i ve studies comprising 9167 men and women aged 22 to 80 with previously resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with the development of advanced colorectal neoplasms during surveillance . RESULTS During a median follow-up period of 47.2 months , advanced colorectal neoplasia was diagnosed in 1082 ( 11.8 % ) of the patients , 58 of whom ( 0.6 % ) had invasive cancer . Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas ( 24.1 % ; st and ard error , 2.2 ) and those with an adenoma 20 mm in size or greater ( 19.3 % ; st and ard error , 1.5 ) . Risk factor patterns were similar for advanced adenomas and invasive cancer . In multivariate analyses , older age ( P < .0001 for trend ) and male sex ( odds ratio [ OR ] , 1.40 ; 95 % confidence interval [ CI ] , 1.19 - 1.65 ) were associated significantly with an increased risk for metachronous advanced neoplasia , as were the number and size of prior adenomas ( P < .0001 for trend ) , the presence of villous features ( OR , 1.28 ; 95 % CI , 1.07 - 1.52 ) , and proximal location ( OR , 1.68 ; 95 % CI , 1.43 - 1.98 ) . High- grade dysplasia was not associated independently with metachronous advanced neoplasia after adjustment for other adenoma characteristics . CONCLUSIONS Occurrence of advanced colorectal neoplasia is common after polypectomy . Factors that are associated most strongly with risk of advanced neoplasia are patient age and the number and size of prior adenomas Acquired or inherited mutations in the adenomatous polyposis coli ( APC ) tumor suppressor gene are causally linked to colorectal cancer . Given the significance of APC in colorectal cancer , we investigated the association between common single-nucleotide polymorphisms ( SNP ) in the APC gene and the odds of developing metachronous colorectal adenomas as a surrogate measure of colorectal cancer risk . Coding SNPs at codons 486 , 1678 , 1822 , 1960 , and 2502 were analyzed in a total of 1,399 subjects who participated in two r and omized clinical trials for the prevention of colorectal adenomas . No association was found for any single SNP and the odds of metachronous adenoma . In contrast , a TA haplotype ( codons 486 and 1822 ) was associated with a statistically significant 27 % and 26 % reduction in the odds of any and nonadvanced metachronous adenoma after adjustment for baseline adenoma characteristics [ odds ratio ( OR ) , 0.73 ; 95 % confidence interval ( 95 % CI ) , 0.59 - 0.91 and OR , 0.74 ; 95 % CI , 0.57 - 0.94 ] , respectively . No significant reduction in odds was observed for advanced metachronous lesions . Diplotype analysis revealed a strong gene dose effect with carriers of two alleles containing TT-AA ( codons 486 and 1822 , respectively ) having an 89 % lower odds for advanced metachronous adenomas ( OR , 0.11 ; 95 % CI , 0.01 - 0.80 ) when compared with the common CC-AA diplotype ( codons 486 and 1822 , respectively ) . Our findings support an important role for germ-line allele sequence in the APC gene and individual risk of metachronous adenomatous polyps PURPOSE : The aim of this study was to identify the high-risk groups for metachronous colorectal carcinoma among patients who undergo colorectal cancer surgery . METHODS : Three hundred forty-one patients undergoing colorectal cancer surgery who had undergone surveillance colonoscopy at least twice during a period of more than three years were analyzed . A metachronous colorectal carcinoma was defined as a new colorectal carcinoma detected by surveillance colonoscopy after surgery . RESULTS : Surveillance colonoscopy was performed 4.6 times per patient during an average of 6.2 years . Twenty-two metachronous colorectal carcinomas in 19 patients were detected , and 14 ( 64 percent ) of 22 were detected within five years of surgery . The cumulative incidence of developing colorectal carcinomas during a five-year period was 5.3 percent . Seventeen ( 77 percent ) of 22 carcinomas were 10 mm or less in size . Ten ( 71 percent ) of the 14 carcinomas in early stages showed a flat appearance . Univariate analysis showed that extracolonic malignancy , coexistence of adenoma , and synchronous multiple colorectal carcinoma were significant predictive factors for detecting colorectal carcinomas in surveillance colonoscopy and that family history of colorectal carcinoma was a possible predictive factor . Multivariate analysis performed with Cox proportional hazards regression model showed that extracolonic malignancy and the coexistence of adenoma were significant predictive factors . CONCLUSION : We recommend that patients with the above predictive factors receive surveillance colonoscopy meticulously and regularly BACKGROUND : Compared with the general population , patients with a previous colorectal cancer are at higher risk for a second colorectal cancer , but detailed risk analysis by subsite is scarce . OBJECTIVE : Our goal was to investigate the risk of a second cancer in relation to subsite as a basis for planning surveillance strategies , . DESIGN , SETTING , AND PATIENTS : This was a retrospective analysis of a prospect ively design ed , population -based cancer registry ( The Netherl and s Cancer Registry ) . Patients with a stage I , II , or III colorectal cancer diagnosed between 1989 and 2008 were included . MAIN OUTCOME MEASURES : Cumulative incidence , st and ardized incidence ratio , and absolute excess risk for second primary cancers in subsites of the colon and rectum were estimated for follow-up periods of 2 to 5 , 6 to 10 , and more than 10 years after the index cancer in patients older than 50 years and in those aged 50 years or younger . RESULTS : A total of 123,347 patients had a first invasive colorectal cancer diagnosed between 1989 and 2008 . Of these , 1849 patients ( 1.5 % ) had a second colorectal lesion that was found more than 1 year after the initial cancer and diagnosed as a second primary colorectal cancer . In patients older than 50 years , the 20-year cumulative incidence for second cancers was 3.4 % in the proximal colon , 1.2 % in the distal colon , and 1.2 % in the rectum . More than 60 % of second cancers occurred within 5 years after the index cancer . The st and ardized incidence ratio was highest in the proximal-colon ( 1.9 ; 95 % CI , 1.8–2.0 ) , followed by the distal-colon ( 1.0 , 95 % CI , 0.9–1.1 ) , and the rectum ( 0.9 , 95 % CI , 0.8–1.0 ) . The corresponding absolute excess risks per 10 000 person years were 9 in the proximal colon , 0.1 in the distal colon , and 1 in the rectum . After 5 years of follow-up , elevated risk was observed only in the proximal colon . A similar risk pattern was observed in patients younger than 50 years . The absolute excess risk for a second cancer in the proximal colon increased over time . The proportion of stage III and stage IV second cancers increased from 31 % during the first 5 years of follow-up to 38 % after 10 years of follow-up . LIMITATIONS : Limitations of this study included lack of data regarding polypectomy rates and interval of surveillance colonoscopies . CONCLUSIONS : Compared with the general population , individuals with previous colorectal cancer have a higher risk for a second cancer in all subsites of the colon and rectum . Among long-term survivors older than 50 years , risk remains elevated only in the proximal colon . Further studies should be encouraged to develop a suitable surveillance method for aging , high-risk , long-term colorectal cancer survivors 
    Output:
    
Meta‐regression showed duration of follow‐up was not a source of heterogeneity for most associations .
There was no evidence that lifestyle factors were associated with metachronous CRC or polyp risk .
Conclusion : A comprehensive list of risk factors identified for metachronous CRC or polyp may have important clinical implication