Abstracts

FIT for up to 4 years, or one direct colonoscopy. Participants who had any one FITbeing positive received a colonoscopy. The incremental cost-effectiveness ratio(ICER) was assessed based on the detection rates of neoplastic lesions, and costsincluding screening compliance, polypectomy, colonoscopy complications, andstaging of CRC detected. There were 1,838,916 citizens aged between 50 to 70 yearsin the Hong Kong population in 2011. This population was assigned into our twoscreening schemes based on the proportion of the study participants choosing FITvs. colonoscopy in the programme. Results: 5,863 patients received yearly FIT and4,869 received colonoscopy. The compliance rates with yearly FIT were 97.3%,82.8%, 84.6% and 77.7%, respectively, in the first four years of follow-up. The pos-itivity rates of FIT in the first four years were 97.3%, 82.8%, 84.6% and 77.7%,respectively. Among those who chose colonoscopy, 90.7% attended for the proce-dure (nZ4,418); whereas 89.8% of participants in the FIT group who had positivefaecal test results completed colonoscopy (nZ343). Compared with FIT, colonos-copy detected significantly more neoplastic lesions (23.6% vs. 1.6%) and advancedlesions or cancer (4.2% vs. 1.2%). The cost of finding a colorectal neoplasia wasUS$16,085 by FIT and US$4,719 by colonoscopy. The cost of detecting an advancedneoplasia was US$26,712 by FIT and US$28,913 by colonoscopy. FIT (US$149,590)was more cost-effective in finding colorectal cancer than colonoscopy (US$388,268).Using FIT scheme as a control, the incremental Cost-Effectiveness Ratio (iCER) ofscreening colonoscopy was US$3,721, US$29,847 and US$984,120 to detect oneadenoma, advanced neoplasia and CRC, respectively. Conclusions: FIT is more cost-effective in screening for both advanced neoplasia and CRC than a direct colonos-copy. FIT screening is cost-effective at detecting advanced lesions, which is coherentwith the purpose of using FIT to detect malignancy.

Cost to detect one colorectal neoplasia in the Hong Kong populationaccording to screening modality

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FIT scheme1,004,618)

Colonos

opy schemeN[834,298)

Cost (US\$)

256,318,428 931,791,655 Findings N Cost per finding (US\$) N Cost per finding (US\$) adenoma 15,935 16,085 197,466 4,719 advancedneoplasia 9,596 26,712 32,227 28,913 colorectal cancer 1,713 149,590 2,400 388,268

FIT: Faecal Immunochemical Tests

228Evaluation of a 2-Gene (IKZF1 and BCAT1) DNA Blood Test forDetection of Colorectal CancerGraeme P. Young*1, Susanne K. Pedersen2, Evelien Dekker3,Stephen R. Cole4,1, Joanne M. Osborne1,4, Erin L. Symonds1,Rosalie C. Mallant-Hent5, Aidan Mcevoy2, Rohan Baker2, Snigdha Gaur2,David H. Murray2, Lawrence C. Lapointe1,21Flinders Centre for Innovation in Cancer, Flinders University, Adelaide,SA, Australia; 2Clinical Genomics P/L, Sydney, NSW, Australia;3Academic Medical Center, Amsterdam, Netherlands; 4Bowel HealthService, Repatriation General Hospital, Adelaide, SA, Australia; 5FlevoHospital, Almere, NetherlandsBackground: Two genes, BCAT1 and IKZF1, are frequently hypermethylated in colo-rectal adenoma and cancer (CRC) tissues. Since tumour-derived aberrant DNA canbe detectable in blood, and blood tests have the potential to improve screeningparticipation rates, we assessed the accuracy of a blood test comprising detection ofmethylated BCAT1 and IKZF1 across the spectrum of benign and neoplastic condi-tions encountered in the colon/rectum. Methods: Subjects comprised volunteersfrom an Australian and a Dutch hospital who were scheduled for colonoscopy forany reason, or for resection of colonic neoplasia. Circulating cell-free DNA was ex-tracted from 4mL plasma samples (phenotype blinded to process operator) andbisulphite converted. Levels of recovered DNA and methylated BCAT1 and IKZF1DNA were simultaneously determined using multiplexed qPCR. A plasma samplewas defined as positive if amplified target sequence signal above background fluo-rescence was present in any of 3 replicates in the BCAT1 or IKZF1 qPCR assay.Sensitivity and specificity for neoplasia were estimated as the primary outcomemeasures. Results: Of the 2187 volunteers (mean age 62 years, 52% male) who metenrolment criteria and provided sufficient plasma, the test was run successfully on2139 plasma specimens including 30 sample pairs taken pre- and post-surgicalremoval of neoplastic lesions. The 2-gene blood test (i.e. BCAT1 and/or IKZF1 pos-itive) successfully identified 85 of 130 CRC cases (sensitivity of 65%, 95% CI: 56-73).For UICC CRC Stages I-IV, respective positivity rates were 29% (95% CI: 14-51), 68%(54-80), 77% (60-88) and 89% (51-99). For T element of TNM staging, respectiverates were pT1 - 43%, pT2 - 58%, pT3 - 70%, pT4 - 71%. The results for the individualmarkers are shown in the Table. There was no correlation of BCAT1/IKZF1 positivitywith smoking, gender, age or family history of CRC. The twelve BCAT1/IKZF1methylation-positive CRC subjects with paired pre- and post-surgery plasma showedreduction in methylation signal after surgery, with complete disappearance of signalin 10 subjects. Sensitivity for advanced adenoma (nZ 232) was 7% (95% CI:

Vol

4.5-11.7). Specificity was 94.2% (95% CI: 92.8-95.4) in all non-neoplastic cases(nZ1283) and 94.9% (92.4-96.7) in those with a normal colon (nZ454).Conclusions: The sensitivity for cancer of this two-marker panel justifies prospectiveevaluation in a true screening population. However, if it is to be used for populationscreening, it would be advantageous to show improved participation rates relative toestablished methods and/or better sensitivity than we have observed for advancedadenoma. The presence of cancer-derived methylated DNA markers in plasmacorrelated with depth of tumour invasion. Given the high rate of marker disap-pearance after cancer resection, the panel might also be useful to monitor tumourrecurrence.

Results for the individual markers

Cases n[2109

ume 79, No. 5S : 20

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ASTROINTES

IKZF1positive

TINAL ENDO

2-gene testpositive

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Non-neoplastic

1283 67 5.2 17 1.3 74 5.8 Normal Colon 454 21 4.6 3 0.7 23 5.1 Adenoma 696 42 6.0 11 1.6 47 6.8 Advanced adenoma 232 13 5.6 6 2.6 17 7.3 Adenoma - UICC stage 0 4 0 0 0 Cancer 130 74 56.9 62 47.7 85 65.4 Cancer Stage I 24 4 16.7 4 16.7 7 29.2 Cancer Stage II 53 32 60.4 24 45.3 36 67.9 Cancer Stage III 39 28 71.8 23 59.0 30 76.9 Cancer Stage IV 9 7 77.8 8 88.9 8 88.9 Cancer Unstaged 5 3 60.0 3 60.0 4 80.0

229a Prospective, Randomized Trial of Adenoma Miss Rates AtColonoscopy Associated With 3-Minute vs. 6-Minute WithdrawalTimeSheila Kumar*, Nirav C. Thosani, Rajan Kochar, Shai Friedland,Uri Ladabaum, Ann M. Chen, Subhas BanerjeeDivision of Gastroenterology and Hepatology, Department of Medicine,Stanford University, Palo Alto, CAIntroduction: A minimum withdrawal time for screening colonoscopy of 6 minuteshas been proposed, based on an observational study. The 6-minute withdrawal timeremains controversial and has not been compared in a standardized fashion toalternate withdrawal times. Aim: To perform a prospective, randomized trial tocompare adenoma miss rates (AMR) associated with withdrawal times of 6 minutesvs. 3 minutes. Methods: Consecutive patients undergoing colonoscopy at StanfordUniversity and Palo Alto Veterans Administration Hospital were randomized to un-dergo either a 3-minute or 6-minute withdrawal (1st pass), followed immediately bya tandem 6-minute withdrawal (2nd pass). AMR was defined as the number of ad-enomas detected on the 2nd pass divided by total number of adenomas found. Achi-square statistic was used to directly compare AMR. A z-statistic was used todetermine effect of polyp size/location on AMR. A mixed-effects logistic regressionmodel was then created to compare AMR, controlling for endoscopist, size/locationof adenoma, and patient. Finally, a Cochrane-Armitage test for trend was used toevaluate the trend of adenoma detection associated with increasing withdrawal time.Results: 200 subjects were enrolled (99 in the 3-minute group, 101 in the 6-minutegroup). Demographics and indications for colonoscopy were similar between thetwo groups (Table 1). AMR was significantly higher in the 3-minute withdrawal groupcompared to the 6-minute withdrawal group (48.5% vs 21.8%; p%0.0001). Ade-nomas were significantly more likely to be missed in the 3-minute withdrawal groupin all 3 locations of the colon (right, transverse and left colon). AMR was higher inthe 3-minute withdrawal group among adenomas that were %5mm; there was nosignificant difference in AMR for adenomas that were 6-9mm or R10mm. Aftercontrolling for endoscopist, size/location of the polyp/adenoma, and the patient,AMR remained significantly higher in the 3-minute withdrawal group compared tothe 6-minute withdrawal group (OR 2.92, 95% CIZ1.54-5.55) (Table 1). Adenomadetection rate (ADR) was similar between both 3 and 6 minute withdrawal groups(38.4% vs 40.6%, pZ0.75); however, this study was not powered to detect differ-ences in ADR. There was a significant trend towards higher total number of ade-nomas detected as withdrawal time increased (52 at 3 minutes, 87 at 6 minutes, 101at 9 minutes, and 111 at 12 minutes; p!0.001) (Figure 1). Conclusions: A 3-minutewithdrawal time leads to an unacceptably high AMR. A 6-minute withdrawal time ismore appropriate for colorectal cancer screening. Location did not affect AMR;however, adenomas that were%5mm were more likely to be missed in the 3-minutewithdrawal group. Further research into the optimal withdrawal time, includingevaluation of withdrawal times longer than 6 minutes, is warranted.

AB125

Abstracts

AB126 GASTROINTESTINAL EN

3-minuteWithdrawal Group

(n[99)

DOSCOPY Vo

6-minuteWithdrawal Group

(n[101)

lume 79, No. 5

p-value

Demographics and PatientCharacteristics

Age, years- Mean (std dev)

61.0 (8.97) 61.5 (8.4) 0.94 Gender- % male 65.7% 68.3% 0.69 Indication Screening, n(%) 61 (61.6) 68 (67.3) 0.40 Surveillance- history of polyps or cancer,

n(%)

33 (33.3) 30 (29.7) 0.58

Family history of colorectal cancer, n(%)

4 (4.0) 5 (5.0) 0.73 Iron deficiency anemia, n(%) 3 (3.0) 4 (4.0) 0.70 Bright red blood per rectum, n(%) 2 (2.0) 1 (1.0) 0.56

Overall Adenoma Miss Rate

48.5% 21.8% 0.00

Adenoma Miss Rate by Location

Right 51.4% 25.0% 0.01 Transverse 43.2% 17.1% 0.01 Left 54.6% 21.7% 0.02

Adenoma Miss Rate by Size

!Z5mm 49.4% 24.7% 0.001 6-9mm 50.0% 20.0% 0.09 OZ10mm 25.0% 0.0% 0.10

230Incidence of Advanced Neoplasia in Individuals With UntreatedDiminutive Adenomas: a Longitudinal StudyYosuke Otake*1, Yasuo Kakugawa1, Minori Matsumoto1, Chihiro Tsunoda1,Taku Sakamoto1, Takeshi Nakajima1, Takahisa Matsuda1, Yutaka Saito1,Yukio Muramatsu21Endoscopy division, National Cancer Center Hospital, Tokyo, Japan;2Screening Technology and Development Division, National CancerCenter, Research Center for Cancer Prevention and Screening, Tokyo,JapanBackground and Aim: The recommendations for surveillance colonoscopy intervalsdepend not only on the number and size but also on the histopathological findingsof adenomas detected and treated. On the other hand, to reduce post-test referraland improve efficiency, computed tomographic colonography (CTC) or coloncapsule endoscopy (CCE) for screening is recommended every 5 years, irrespectiveof whether these tests are negative or only diminutive polyps have been detected.However, the long-term outcome of patients with untreated diminutive adenomas isstill unknown. This study aimed to determine the cumulative incidence of advancedneoplasia in asymptomatic patients who were found to have diminutive adenomas atinitial screening colonoscopies but were not referred for removal. We also aimed toevaluate the suitability of this non-referral strategy by comparing these results to theincidence in patients not found to have adenomas at initial screening colonoscopies.Method: Asymptomatic patients who underwent initial screening colonoscopy be-tween February 2004 and March 2008 were included in this study. Follow-up colo-noscopy within 5 years was recommended for asymptomatic patients in whomdiminutive adenomas! 5 mm were detected at the initial screening colonoscopybut who were not referred for removal and for asymptomatic patients without ad-enomas. Appropriate therapy was recommended for patients in whom adenomas R5 mm or cancer was detected. Advanced neoplasia was defined as an invasive cancer,a high-grade dysplasia, or a large adenoma R 10 mm. We retrospectively investi-gated the cumulative incidence of advanced neoplasia in patients without adenomas(Group A) and in those with adenomas! 5mm (Group B) at initial screening co-lonoscopy. To precisely differentiate non-neoplastic lesions from neoplastic onewithout biopsy, we routinely used chromoendoscopy with magnification. Results: Atotal of 2,775 patients (2,070 in Group A and 705 in Group B) were included. Themedian colonoscopy interval was 60 months in both groups, and the cumulativeincidence of advanced neoplasia was 1.7% (35/2070) in Group A and 2.8% (20/705)in Group B (p Z 0.059). Among the Group B patients, the cumulative incidence ofadvanced neoplasia was significantly higher in patients with R3 diminutive ade-nomas at the initial screening (10.7%; 7/65) than in patients with 1 or 2 diminutiveadenomas at the initial screening (2.0%; 13/640). Conclusion: The 5-year risk ofadvanced neoplasia was not increased even when diminutive adenomas detected atscreening colonoscopy had been untreated in patients with 1 or 2 diminutive ade-nomas. However, patients with R3 diminutive adenomas detected at screeningcolonoscopy that were left untreated had a significantly higher risk of neoplasiadevelopment. This approach can be applied to colorectal cancer screening usingCTC or CCE.

S : 2014

295Impact on Maximum Insertion Pain During Diagnostic andScreening Colonoscopy With on Demand Sedation: a Two CenterRandomized Controlled Trial of Air Insufflation, Water Immersionand Water ExchangeSergio Cadoni*1, Stefano Sanna2, Paolo Gallittu1, Mariangela Argiolas2,Viviana Fanari2, Laura Porcedda2, Matteo Erriu3, Felix W. Leung4,51Digestive Endoscopy Unit, S. Barbara Hospital, Iglesias, Italy; 2DigestiveEndoscopy Unit, N. S. di Bonaria Hospital, San Gavino Monreale, Italy;3Department of Surgical Sciences, University of Cagliari, Cagliari, Italy;4Gastroenterology, Sepulveda Ambulatory Care Center, Los Angeles, CA;5David Geffen School of Medicine, University of California, Los angeles,CABackground: Support for unsedated colonoscopy best exemplifies investment in pa-tient-centered care. Maximum insertion pain limits success. When separatelycompared to air insufflation (AI), water-aided colonoscopy (WAC: WI, water im-mersion; WE, water exchange) significantly reduces pain. WE (water removal duringinsertion) and WI (water removal during withdrawal) are different and comparativeeffectiveness in lowering pain is unknown. Objectives: In 2 registered two-centerRCTs (NCT01781650, 01780818) in diagnostic and screening patients we performeda head-to-head comparison of AI, WI and WE. We test the hypothesis that WEproduces significantly lower pain scores than AI and WI. Patients: Consecutivediagnostic and screening patients, on-demand sedation based on patient requestdue to pain. Methods: AI, WI and WE were implemented as previously described.Maximum pain score [visual analog scale (0Znone, 10Zmax)] reported to an un-blinded observer was used to determine if minimal sedation (midazolam 2-5 mg)was needed on patient request. Recollected maximum pain was reported similarly atdischarge to a blinded observer. Main Outcome Measurements: Maximum painscore during insertion. Results: See Tables. Demographic and baseline data (notshown) indicated even randomization. Based on similar protocol, the two data setswere combined. 576 patients were randomly allocated to AI (nZ193), WI (nZ197),or WE (nZ186). Mean maximum pain scores (95% CI) of insertion reported tounblinded observer during colonoscopy, and to blinded observer before dischargewere: AI 4.1 (4.5-4.8), 1.9 (1.5-2.2); WI 3.3 (2.9-3.7), 1.8 (1.4-2.2); and WE 2.5 (2.2-2.8), 1.3 (1.0-1.5) (P!0.0005s and 0.04s), respectively. Pearson correlation coef-ficient for these parameters was 0.6 (p!0.0005s). Correct patient guesses aboutmethod was 33%. Logistic regression shows method (WE), male gender and BMI assignificant predictors of maximum insertion pain score during procedure. Secondaryoutcomes: proportion completing without sedation, less need for abdominalcompression or loop reduction, and willingness to repeat were in favor of WACmethods. WE shows better colon preparation. Although intention-to-treat (ITT)cecal intubation rate favors AI (pZ0.038); final rates were comparable. WI had theshortest ITT cecal intubation time. Limitation: Unblinded colonoscopists.Conclusions: Patient blinding was adequate (only 33% correctly guessed method).The significant pain score correlation validated use of unblinded maximum inser-tion pain scores as primary outcome. WAC methods significantly reduce pain andsedation requirement without compromising procedural outcomes. WAC enhancesacceptance of unsedated colonoscopy by patients (higher willingness to repeatwithout sedation). Uniquely, the unblinded and blinded maximum insertion painscores of WE were significantly lower than those of AI and WI.

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