Mo1176

Screening the Worried Well: Symptomatic Individuals Are Less Likely to HaveSignificant Neoplasia At Colonoscopy Following a Positive Colorectal CancerScreening TestDavid Mansouri, Donald C. McMillan, Emilia Crighton, Paul G. Horgan

Background: Screening for colorectal cancer using the faecal occult blood test (FOBt) reducescancer specific mortality by increasing the detection of early stage disease. However, withinnational screening programmes uptake rates are poor and it has been suggested that ratherthan detecting truly asymptomatic disease screening merely represents another way forsymptomatic individuals to present. Aim: To assess the prevalence of bowel symptoms inpatients attending for colonoscopy following a positive FOBt, and correlate these withfindings at colonoscopy. Methods: Data for patients who tested FOBt positive, underwentpre-assessment and attended for colonoscopy in the first screening round in a single geograph-ical area, was obtained from a prospectively maintained database. Symptomatic evaluationwas performed by trained nurses at pre-assessment. Results: From April 2009 to April 2011,395096 individuals were invited, 204461 (52%) responded, 6085 (3%) tested positive ofwhich 4631 (76%) attended for colonoscopy. Complete results were available for 4182(90%) individuals who were included for analysis. Of the 4182 individuals, 1772 pts (42%)had 1 or more bowel symptom(s), which were deemed significant in 1661 pts (94%).Significant symptoms were altered bowel habit (1001 pts (24%)), rectal bleeding (896 pts(21%)), abdominal pain (62 pts (2%)) or tenesmus (8 pts (0.2%)). Symptomatic patientswere more likely to be older and female (both p ,0.001). Socioeconomic deprivation wasnot related to the presence of symptoms. Of the 4182 pts attending for colonoscopy, cancerwas detected in 390 pts (9%) and significant polyps (.=3 dysplastic polyps or any dysplasticpolyp .= 1cm) were detected in 1309 pts (31%) meaning that significant neoplasia wasdetected overall in 1699 pts (41%). Patients with significant neoplasia were more likely tobe older and male (both p,0.001), however, were less likely to have significant bowelsymptoms (36% vs 42%, p,0.001). After adjustment for sex, this effect remained in malesonly (37% vs 32%, p=0.013). In those with significant neoplasia, lesions were confined tothe right side of the colon in 207 pts (12%). Those with right sided lesions were less likelyto have significant symptoms compared with those involving the left side of the colon orrectum (30% vs 37%, p=0.045). Conclusions: In patients undergoing colonoscopy followinga positive FOBt screening test, significant bowel symptoms are common and associated witha reduced likelihood of detecting significant neoplasia. This is most likely due to symptomaticindividuals being more inclined to respond to a screening invitation and suggests that furtherwork should be done to encourage participation in truly asymptomatic individuals.

Mo1177

Participation, FIT-Result and Yield in Three Rounds of Biannual FIT-BasedScreening in the NetherlandsInge Stegeman, Sascha C. van Doorn, Rosalie C. Mallant-Hent, Marco W. Mundt, PaulFockens, An K. Stroobants, Patrick M. Bossuyt, Evelien Dekker

Abstract Background Most European colorectal cancer (CRC) screening programs rely onfecal occult blood testing (FOBT), of which fecal immunochemical tests (FIT) have the bestaccuracy and adherence rates. The effectiveness of these FOBT-based programs is not onlyinfluenced by the participation and yield of the initial screening round, but also by programadherence during consecutive rounds. FIT sensitivity is relatively low and is increased byrepeated screening rounds. We aim to evaluate the participation rate, yield and progressionof FIT screening for CRC over three rounds of CRC screening . Methods A total numberof 10,050 average risk individuals were invited to participate in a third round of biennialFIT-based CRC screening, using OC-Sensor with a cut-off of 50 ng/ml buffer(or 10 ug/mgfeces). Invitees were between 50 and 75 years of age. They received an invitation, includingan information leaflet, a FIT-test, and a pre-paid return envelope. All FIT-positives wererecommended to undergo a colonoscopy unless contraindicated. Colonoscopy findings wereclassified as CRC, advanced adenoma, advanced neoplasia (CRC plus advanced adenoma)or other. Participation rates, FIT positivity rate, FIT positive predictive value and mean levelof FIT-result were calculated, and compared to the results of the first two screening rounds.Results Within this cohort, 5,671 invitees (56%) returned the FIT in this third screeninground, compared to 52% in the second round and 56% in the first round (p ,0.001).Overall, 377 (6.8%) of the third round participants had a positive FIT result, versus 7.4%in the second round and 8.1% in the first round (p ,0.01). Of the FIT positives, 316 (84%)underwent colonoscopy. 59 could not undergo colonoscopy because of medical reasons ordid not want to undergo colonoscopy. 88 participants had at least one advanced adenoma(28% of positives) and 17 had cancer (5%). The FIT positive predictive value for advancedneoplasia was 30%, compared to 44% in the second round and 55% in the first round; asignificant decline (p,0.01) The average FIT result decreased in consecutive screeningrounds from 430 ng/ml in the first round to 370 ng/ml in the second and 348 ng/ml inthe third round. This decrease was not significant (round one versus round 2 p= 0.16;round one versus round three: 0.08). Conclusion In consecutive CRC screening roundswith FIT, the participation rate stays stable, but both FIT positivity rate for advancedneoplasia and its positive predictive value decline significantly. The average concentrationof Hb in Feces decreased over several rounds of FIT based screening, though not significant.

Mo1178

Gender Differences in Fecal Immunochemical Test Performance for EarlyDetection of Colorectal NeoplasiaAtija Kapidzic, Miriam P. van der Meulen, Aafke H. van Roon, Caspar W. Looman,Anneke van Vuuren, Marjolein van Ballegooijen, Jacqueline C. Reijerink, Monique E. vanLeerdam, Ernst J. Kuipers

Background & Aims: Fecal immunochemical tests (FITs) are equally applied in men andwomen in colorectal cancer screening. However, with a higher prevalence of advancedneoplasia among men and with more proximal lesions among women, it is unclear whetherFITs perform equally well in both genders. We therefore aimed to assess FIT characteristics

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in men and women. Methods: In total, 7501 screenees (aged 50-75yrs) were approachedfor first and 6208 screenees (aged 50-75yrs) were approached for second round screeningwith a single FIT (OC-Sensor). Subjects with a FIT ≥50 ng/ml were referred for colonoscopy.The positivity rate (PR), positive predictive value (PPV), detection rate (DR) and numberneeded to screen (NNscreen) were assessed by gender for a range of FIT cut-off points (i.e.50; 75; 100; 125; 150; 175 and ≥200 ng/ml). Results: Participation rate was 63% in bothscreening rounds: 60.1% among men and 65.0% among women in the first round(p,0.0001), and 61.1% among males and 65.2% among females in the second round (p=0.000796). Around 95% of men and women with a positive FIT underwent colonoscopy.The median FIT result among positives (≥50ng/ml) was 173 ng/ml (IQR 78; 631) for menand 153 ng/ml (IQR 73; 423) for women (p=0.578). Both PR and DR were significantlyhigher in men compared to women for all cut-off levels: PR was 11.0% (CI: 9.8-12.4) inmales and 6.1% (CI: 5.7-7.1) in females in females at a cut-off level of 50 ng/ml. The DRfor advanced neoplasia was 4.4% (CI: 3.5-5.2%) in males and 2.3% (CI: 1.9-3.3%) in femalesat a cut-off level of 50 ng/ml (p ,0.0001). Likewise, males showed significantly lowernumbers needed to screen to detect one advanced neoplasia in the first round: the NNscreento find one advanced neoplasia was 23 in men and 44 in women at a cut-off level of 50ng/ml (p,0.001).The PPV for detection of advanced colorectal neoplasia was around 40%for both genders (p=0.842) at a cut-off level of 50 ng/ml. Similar patterns were seen in thesecond round. No difference in localization of advanced lesions was seen in men and women(16% vs. 18%of lesions were localized proximally, p=0.772). Conclusion: PRwas significantlyhigher in men than in women. However, FIT performs equally well in men and women interms of PPV at the full range of cut-offs used in screening practice. The detection rate ofadvanced neoplasia was significantly higher in men than in women. Likewise, the numberneeded to screen to detect one advanced neoplasia was lower in men than in women.Increasing the cut-off value in women can be considered in case of insufficient colonoscopycapacity, but at the cost of a gradual decrease in detection rate.Test characteristics of FIT at differemt cut-off levels, first screening round

FIT: fecal immunochemical test; advanced neoplasia: adenoma ≥10mm, villous component(≥ 25% villous) or high-grade dysplasia; PPV: positive predictive value; NNscreen: numberneeded to screen to detect one screenee with an advanced neoplasia *P ,0.05 Scores formen compared to scores for women in that particular FIT cut-off level

Mo1179

Potential Usefulness of Fecal Immunochemical Test Plus Fecal MicroRNAAssay As a Marker for Colorectal Cancer ScreeningShigeru Kanaoka, Shigeru Kuriyama, Moriya Iwaizumi, Takanori Yamada, MitsushigeSugimoto, Satoshi Osawa, Ken Sugimoto, Hiroaki MIyajima

Background and Aims: The fecal occult blood test (FOBT) is a noninvasive and simple testreported to reduce the morbidity and mortality of CRC. However, large-scale studies haveshown that the sensitivity of FOBT is not very high for early stage cancer and advancedadenoma, using total colonoscopy as a reference standard in all subjects. We previouslyreported that fecal microRNA (miRNA) assay is useful for the detection of colorectal advancedadenoma and early stage cancer (Gastroenterology 142(5): S-770, 2012). To further improvethe sensitivity of FOBT, we evaluated the usefulness of the combination of fecal immunochem-ical test (FIT) and fecal miRNAs assays as a marker of CRC and advanced adenoma. Methods:Stool samples from 138 subjects with CRC, 26 subjects with colorectal advanced adenoma(AA; at least 10mm in diameter), and 126 healthy subjects (HS) were obtained. Standardhistological techniques were used to classify malignancy at 0 to IV stage according to TNMclassification, yielding stage 0 (n = 15), I (n = 31), II (n = 46), III (n=32), and IV (n = 14).We purified RNA from routinely collected stool samples and analyzed expressions of miR-21 and miR-92a by quantitative real-time RT-PCR using TaqMan Assays, and did a singleFIT on same stool samples. Results: FIT had 66.7% sensitivity for CRC, 34.6% for AA and98.4% for specificity. The sensitivity for stage 0 and I was 6.7% and 45.2%, respectively,while that for among combined stage II-IV was approximately 80%. There was significantdifference in expression of two miRNAs in feces among CRC, AA and HS. When the 97.5percentile of copies of each miRNA in HS was used as cutoff value, the specificity of eachfecal miRNA assay was 96.8% for miR-21 and 97.6% for miR-92a. The sensitivity of CRCwas 39.9% for miR-21 and 44.9% for miR-92a. However, the sensitivity for AA, stage 0and I was 42.3%/ 33.3%/ 29.0% for miR-21 and 30.8%/ 26.7%/ 38.7% for miR-92a,respectively. Fecal miR-21 plus miR-92a miRNA assays detected 16 CRC subjects and 15AA subjects with negative results of FIT. The sensitivity of combination of fecal miR-21plus miR-92a assay and FIT was higher than that of FIT by itself (78.3% vs. 66.7%, P=0.04). Among subjects with AA, stage 0 and stage I who are almost cured by endoscopicor surgical resection, the sensitivity of combination of fecal miR-21 plus miR-92a assay andFIT had higher than that of FIT by itself (63.9% vs. 33.3%, P , 0.001). Conclusions: FIT

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