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s(40-69), 2440 (62%) males, consented to participate in this study. Of these, 2166 patientswho had 1st- and 2nd-TCS, with removal of all adenomatous polyps were randomly assignedinto two groups (1087 to two-exam and 1079 to one-exam group). The results of the non-inferiority test were significant (p=0.017 in per-protocol, p=0.001 in intention-to-treat). Inper-protocol analysis (701 in two-exam vs 763 in one-exam group), the IL incidences oftwo groups were similar (1.7% vs 2.1%). The percentage of patients with adenomas in two-exam was 50.1%, versus 37.7% in one-exam group. Among all ILs, there were 6 LGD≥10mm, 5 HGD and 1 invasive cancer in two-exam, 9 LGD ≥10mm and 8 HGD in one-exam group, respectively. Morphologically, NP-CRNs were dominant (62%, 18/29) andmost of them were classified into laterally spreading tumor non-granular (LST-NG) type;(83%, 15/18). Moreover, 7 out of 15 ILs classified into LST-NG were histologically diagnosedas HGD. Conclusions: Colonoscopy performed 3 years after endoscopic removal of alladenomatous polyps detected clinically important lesions as effectively as follow-up colonos-copy after both 1 and 3 years, being such results in accordance with those of the NPS. Twocomplete colonoscopies before randomization provided us a lower incidence of ILs comparedwith NPS data (3.3%). Further investigation will be necessary to evaluate whether thedetection of NP-CRNs, especially LST-NG type determines a change in the prevention ofcolorectal cancer.

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Barriers, Misconceptions and the Lack of Physicians' RecommendationAccount for Poor Screening Uptake in Colorectal Compared With CervicalCancer: Findings of a National Population Representative SurveyReuben K. Wong, Mee Lian Wong, Yiong H. Chan, Zhu Feng, Chun Tao Wai, Khay GuanYeoh

Introduction: Colorectal (CRC) and cervical cancer are two common abdominal-pelvic malig-nancies in females which are amenable to screening, allowing for early detection and treat-ment. However the screening uptake is vastly different, with 73.4% of eligible females havingundergone cervical cancer screening versus only 27.8% for CRC screening in Singapore1.Methods: A nationwide representative population survey was conducted on 1,089 womenaged 50 years and above (to ensure respondents were age eligible for both CRC and cervicalcancer screening) in Singapore. The five domains of the Health Belief Model (HBM) pertainingto screening for both cancers were assessed in each individual by face-to-face interviews.Results are expressed as a relative risk (RR) with 95% CI in a comparison of CRC againstcervical cancer, adjusted for respondent demographics and characteristics. Results: Respond-ents felt CRC was less likely to cause suffering (RR 0.79, 0.66-0.94), lead to death (RR 0.84,0.75-0.95) and affect their family members (RR 0.82, 0.72-0.94) as compared to cervicalcancer. They also perceived CRC was less expensive to treat (RR 0.80, 0.69-0.92). However,they believed their chances of contracting CRC was higher (RR 1.72, 1.17-2.52) and theywere more worried about this possibility (RR 1.28, 1.07-1.56). Worryingly, they were morelikely to feel medical help was not needed to detect CRC (RR 1.23, 1.10-1.38) as comparedto cervical cancer, and even if they had CRC they would rather not know (RR 1.09, 1.01-1.19). Pertaining to the screening, there was a greater fear that CRC testing is potentiallydangerous (RR 1.71, 1.48-1.98), expensive (RR 1.69, 1.51-1.90), painful (RR 1.68, 1.48-1.90), and is more inconvenient (RR 1.26, 1.14 -1.40). In terms of awareness and education,respondents were more likely to have attended a talk on CRC (RR 1.24, 1.08-1.43) andknow a relative/friend with CRC (RR 1.35, 1.20-1.52). Unfortunately, physicians were alsoless likely to recommend CRC screening as compared to cervical (RR 0.78, 0.69-0.87), andthey were less likely to have had a friend encourage them to go for CRC screening (RR0.85, 0.76-0.96) versus cervical cancer. Conclusion: Significant differences in perceptionsexist between CRC and cervical cancer, which need correcting to address the big discrepancyin screening uptake. These include misconceptions on the potential morbidity and cost ofCRC as compared to cervical cancer, despite CRC being of greater concern and worry.Various perceived barriers to CRC screening, despite respondents being more aware andeducated about CRC, and a misplaced belief that professional medical attention was notneeded to make the diagnosis need addressing. Physicians should also be encouraged tomore actively recommend CRC screening. 1Singapore National Health Survey 2010

S-162AGA Abstracts

938

High Prevalence of Mismatch Repair Deficiency Among Colorectal CancersDiagnosed After ColonoscopyElena M. Stoffel, Rune Erichsen, Trine Frøslev, Mogens Vyberg, Erika S. Koeppe, StanleyR. Hamilton, John A. Baron, Henrik T. Sørensen

Background: Colonoscopy does not offer complete protection from colorectal cancer (CRC).Possible explanations for CRCs diagnosed soon after colonoscopy include missed, incom-pletely removed, and/or rapidly-growing neoplasms. Our aim was to compare characteristicsof CRC tumors diagnosed at first colonoscopy with those diagnosed during the intervalfollowing a colonoscopy. Methods: Using Danish population-based medical registries, weidentified incident CRC cases during 2007-2011 and ascertained those diagnosed in individu-als at their initial colonoscopy (DC) and those diagnosed in individuals with a history ofone or more previous colonoscopic exams predating the CRC diagnosis by >90 days (PC).PC cases were further subdivided based on time elapsed between the previous colonoscopyand CRC diagnosis. We compared tumor location (proximal to the splenic flexure vs. distal)and DNA mismatch repair (MMR) phenotypes between DC cases and PC cases diagnosedat sequential 1-2 year intervals after colonoscopy, and used spline regression analyses toexamine trends over time. For a subset of PC cases from a single hospital, we reviewedcolonoscopy reports and analyzed tumors for common somatic gene mutations, microsatellitestability and DNA methylation. Results: Of 10,365 incident CRCs, 813 (7.8%) were diagnosedin individuals with one or more previous colonoscopies (PC). Among the PC cases, 156(19%) were diagnosed within the first year after colonoscopy, 498 (61%) between 1 and10 years after colonoscopy, and 159 (20%) >10 years following colonoscopy. There wereno differences in age, sex, tumor stage or MMR phenotype between DC cases and thesubgroup of PC cases diagnosed within the first year after colonoscopy. However, PC tumorsdiagnosed up to 15 years after colonoscopy were more likely than DC tumors to be locatedin the proximal colon (Figure 1A). The prevalence of tumors with MMR-deficient phenotypeswas higher among PC cases diagnosed >1 year after colonoscopy and varied over time. Afteradjusting for sex and age, PC cases diagnosed 1 < 10 years after colonoscopy were morelikely than DC cases to exhibit MMR deficiency, regardless of tumor location (Figure1B,1C,1D). Among the 86 index colonoscopy reports reviewed, incomplete exams weremore frequent among cases diagnosed <1 year compared with 1<10 years following colonos-copy (41.1% vs 15.5%, p=0.02). Among tumors diagnosed 1<10 years after colonoscopy,16/58 (28%) exhibited MMR deficiency, 14 (24%) had BRAF mutations, and 6 (10%) hadphenotypes diagnostic of Lynch Syndrome. Conclusion: Although suboptimal exams maybe implicated in many cases of CRC diagnosed soon after colonoscopy, higher prevalenceof MMR deficiency suggests that tumor characteristics, in addition to endoscopic technique,may be a factor in the diagnosis of the subset of CRCs that evade colonoscopic surveillance.

Figure 1. Spline regression analysis of odds of proximal tumor location (A) and DNAmismatch repair (MMR) deficient phenotypes (B) among CRC tumors diagnosed after aprevious colonoscopy (PC) compared to those diagnosed at initial colonoscopy (DC), adjustedfor sex and age. (C and D display odds of MMR phenotype further stratified by proximaland distal location.) __Spline regression odds ratio (OR) with knots at 3,6,9 and 12 years---95% Confidence Interval

939

Association Between Family History of Colorectal Cancer and IncidentColorectal Cancer in the PLCO TrialAnthony Razzak, Kelly Yu, Paul Pinsky, Tom Riley, Robert E. Schoen

Background: A family history (FH) of colorectal cancer in a first degree relative (FDR) is arisk factor for incident colorectal cancer (CRC). Guidelines for screening subjects with a FHof CRC recommend earlier and more intensive screening for those with ≥ 2 FDR or a FDRdiagnosed at ≤ 60 years. The evidence base for these recommendations is limited, and lessis known about the risk of CRC for those with a FDR diagnosed at age > 60 years. Aim:Using prospective data from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancerscreening trial, we examine the relationship between FH of CRC and risk of incident CRC.Methods: PLCO enrolled 154,898 men and women, aged 55 to 74 years from 1993 to 2001.Subjects were randomized to screening flexible sigmoidoscopy or usual care and werefollowed for a median of 11.9 years. Family history and age of FDR at diagnosis wereascertained at enrollment via a baseline questionnaire. A FH was defined as having at leastone FDR (mother, father, sibling, children) with CRC. Incident CRC cases were verifiedwith medical record review. Results: Among 144,769 eligible participants, 14,961 (10.3%)had a FH of CRC. Of 2090 incident cases, 273 had a FH of CRC (13.1%) (165,057 personyears of observation (PYO)) compared with 1817 with no FH (1,423,420 PYO). Overall, aFH of CRC was associated with a significantly increased risk of incident CRC (Adj RR 1.30; 95%CI 1.10-1.50, P<0.0001). Compared to those without a FH, subjects with a FDR

diagnosed at age <60 (N=81) or between 60-70 (N=97), were at significantly increased riskfor CRC (Adj RR 1.46 ; 95%CI 1.17-1.81 and Adj RR 1.33 ; 95%CI 1.09-1.63, respectively).Subjects with a FDR diagnosed at age >70 (N=88) were not at significantly increased riskfor CRC (Adj RR 1.15; 95%CI 0.92-1.44). Subjects with ≥2 FDRs (N=35) were at significantlygreater risk of CRC (Adj RR 2.04; 95%CI 1.44-2.86). After excluding subjects with FH in≥2 FDRs, the point estimate for risk of incident CRC among subjects with a FDR ≤60 issimilar to subjects with a FDR between 60 -70 (Adj RR 1.27 and 1.33, respectively) (Table1). Conclusion: In the PLCO cohort, persons with a FH of CRC in a FDR were at a 30%increased risk for incident CRC. Those with ≥2 affected FDR were at a 2-fold higher risk.The observed risk between persons with 1 affected FDR diagnosed at age < 60 was similarto those diagnosed at age 60-70. Further investigation is needed to determine optimal CRCscreening and surveillance in those with a FH of CRC.Relationship between FH of CRC and incident CRC, stratified by FH traits

940

Prevalence and Risk Factors for Interval Colorectal Cancers: A SystematicReview and Meta-AnalysisSiddharth Singh, Preet Paul Singh, N. Jewel Samadder

Background: Despite decrease in incidence and mortality of colorectal cancer (CRC) withcolonoscopy, some patients develop interval CRCs before the recommended surveillanceperiod. We sought to estimate the prevalence and risk factors associated with intervalCRCs. Methods: Through a systematic literature search through October 2013, we identifiedobservational studies, which reported the prevalence of interval CRCs (among all CRCs).We included population-, claims-based, or multicenter studies, and excluded single-centerstudies to minimize selection bias. Interval CRCs were defined as those occurring within 6-36 months of a negative colonoscopy (i.e., no evidence of CRC, with or without polypectomy).From these included studies, we identified demographic, technical and biology-related factorsassociated with development of interval CRC, as compared to detected CRCs (i.e., thoseidentified at colonoscopy). We calculated pooled prevalence and odds ratio (of risk factors)with 95% confidence intervals (CIs), using random effects model. Results: From 2212 articles,we identified 11 studies reporting on 7900 interval CRCs. The pooled prevalence of intervalCRCs was 4.7% (95% CI, 3.5-6.1); this represents 1 in 21 (95% CI, 16-29) CRCs wereinterval CRCs. These cancers were 2.4 times more likely to arise in the proximal colon(prevalence, 7.7%; 95% CI, 5.9-10.1) as compared to distal colon (prevalence, 3.1%; 95%CI, 2.1-4.5) (OR, 2.4; 95% CI, 2.2-2.7). Compared to detected cancers, interval CRCstended to present at an earlier stage (OR, 0.83; 95% CI, 0.69-1.00). Based on time-trendanalysis, there was a declining trend in the prevalence of interval CRCs from 4.8% (95%CI, 2.9-7.8) in 1990s to 4.2% (95% CI, 2.3-7.4) between 2000-2005 and 3.7% (95% CI,2.6-5.2) beyond 2005. As compared to detected CRCs, patients with interval CRCs were4.5 times more likely to have diverticulosis (OR, 4.5; 95% CI, 3.0-6.8). There was nodifference in the sex distribution of interval CRCs. Patients with interval CRCs were lesslikely to have had their colonoscopy by a gastroenterologist, as compared to a non-gastroenter-ologists (OR, 0.84; 95% CI, 0.67-1.04), though this did not reach statistical significance.Based on 2 studies, 52-58% were attributed to missed lesions, 19-29% to inadequateexamination and/or incomplete polyp resection, and 14-24% were newly developed cancers.Based on genetic analysis in 3 studies, interval CRCs were more likely to be CpG islandmethylator phenotype-positive and have microsatellite instability. Conclusions: About 1 in21 CRCs are interval CRCs, and are more likely to arise in the proximal colon. These arisedue to an interaction of technical and biology-related factors. Measures to improve qualityof colonoscopy and better understanding of biology of interval CRCs will result in greaterbenefit from screening colonoscopy.

Pooled prevalence of proximal, distal and total interval colorectal cancers amongst all CRCs

S-163 AGA Abstracts

941

Colorectal Cancer Screening Among Insured Individuals: Is Cost a Barrier toRoutine Screening?Abhilash Perisetti, Abe E. Sahmoun

BACKGROUND: There is strong evidence to support the effectiveness of regular colorectalcancer (CRC) screening in reducing death from CRC. Data on barriers to routine CRCscreening use among insured individuals is limited. OBJECTIVES: 1) Describe the character-istics of adults who needed to see a doctor in the past 12 months but could not becauseof cost; and 2) Assess the impact of limited financial resources on the receipt of routinefecal occult blood test, sigmoidoscopy, or colonoscopy among insured patients. METHODS:We used data from 215,436 adults aged ≥ 50 and ≤ 75 years who had health insurancefrom the 2008, 2010, 2012 Behavioral Risk Factor Surveillance System [BRFSS] (excludingUS territories) to check whether the findings are consistent over time. We applied the UnitedStates Preventive Services Task Force recommendations to assess CRC screening rates amongindividuals who could and could not see a doctor because of cost. SAS v.9.3 (SAS Institute,Cary, NC) was used to analyze the data in a manner that accounts for the BRFSS's complexsample survey design. RESULTS: 16,527 (9%) of our study population needed to see adoctor in the past 12 months but could not because of cost. Comparing individuals whohad a cost constraint with individuals who did not report such a constraint, the multivariablelogistic model adjusted for age, gender, race, education attainment, general health status,having a personal doctor, length of time since last routine checkup, per capita primary carephysicians and gastroenterologists for each state showed a significant association with thereceipt of a colonoscopy within the last 12 months for 2008, 2010 and 2012 (adjusted oddsratios aOR= 0.77; 95% CI [0.69-0.85], 0.90 [0.82-0.99], 0.90 [0.80-1.00]; respectively).There was no association between cost constraint and blood stool or sigmoidoscopy testsuse. Overall, younger age 50 to 64 years old, female gender, being high school graduate orless were significantly associated with non-screening CRC regardless of the screening test.Poor or fair health, having a personal doctor, having had routine check up within last yearand the number of gastroenterologists per capita were significant predictors of CRC screeningreceipt. CONCLUSIONS: Having limited financial resources during the past 12 monthswas associated with non-screening colonoscopy. Despite health insurance, out of pocketcost of colonoscopy may prohibit adults from receiving recommended CRC screening.KEYWORDS: Epidemiology, Colorectal cancer, Screening, adherence to guidelines, HealthCare Delivery, Access to care, Ethnicity, Gender, BRFSSEffect of cost on doctor visit and CRC screening: Characteristics

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