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Background and AimsVariation in colorectal neoplasia detection limits the effectiveness of screening colonoscopy. By evaluating neoplasia detection rates of individual colonoscopists, we aimed to quantify the effects of pre-procedural knowledge of a positive (+) multi-target stool DNA (mt-sDNA) on colonoscopy quality metrics.MethodsWe retrospectively identified physicians who performed a high volume of + mt-sDNA colonoscopies; colorectal neoplasia at post-mt-sDNA colonoscopy was recorded. These colonoscopists were stratified into quartiles based on baseline adenoma detection rates. Baseline colonoscopy adenoma detection rates and sessile serrated lesion detection rates were compared to post-mt-sDNA colonoscopy neoplasia diagnosis rates among each quartile. Withdrawal times were measured from negative exams.ResultsDuring the study period (2014–17) the highest quartile of physicians by volume of post-mt-sDNA colonoscopies were evaluated. Among thirty-five gastroenterologists, their median screening colonoscopy adenoma detection rate was 32% (IQR, 28–39%) and serrated lesion detection rate was 13% (8–15%). After + mt-sDNA, adenoma diagnosis increased to 47% (36–56%) and serrated lesion diagnosis increased to 31% (17–42%) (both p < 0.0001). Median withdrawal time increased from 10 (7–13) to 12 (10–17) minutes (p < 0.0001) and was proportionate across quartiles. After + mt-sDNA, lower baseline detectors had disproportionately higher rates of adenoma diagnosis in female versus male patients (p = 0.048) and higher serrated neoplasia diagnosis rates among all patients (p = 0.0092).ConclusionsKnowledge of + mt-sDNA enriches neoplasia diagnosis compared to average risk screening exams. Adenomatous and serrated lesion diagnosis was magnified among those with lower adenoma detection rates. Awareness of the mt-sDNA result may increase physician attention during colonoscopy.Pre-procedure knowledge of a positive mt-sDNA test improves neoplasia diagnosis rates among colonoscopists with lower baseline adenoma detection rates, independent of withdrawal time.

Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy. We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated. Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia. MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.

BackgroundAtopy patch testing (APT) has shown potential for predicting dietary food triggers in studies of children and adolescents with eosinophilic esophagitis (EoE).AimsTo assess the efficacy of APT in adults with EoE.MethodsWe conducted a prospective open-label pilot study of patients ≥ 18 years old with diagnosis of EoE at Mayo Clinic in Rochester, Minnesota, from November 2014 to January 2016. All patients underwent patch testing using intact food products, followed by a six food elimination diet and stepwise food reintroduction. Response to elimination diet was assessed with serial endoscopy with biopsies as well as clinical symptoms. APT results were directly compared to elimination diet results for assessment of efficacy. Correlation between clinical symptoms, endoscopic score, and histology was also qualitatively evaluated.ResultsFifty percent of the patients had a positive APT, while only 16% had an APT result confirmed histologically during food reintroduction. Sensitivity of APT was calculated to be 5.9%, with specificity of 92.0%. Furthermore, we found significant qualitative inter-patient heterogeneity in the correlation between clinical symptoms, EREFS score, and histology.ConclusionsAPT does not reliably predict food triggers identified by food elimination diet in adult patients with EoE. As a result, APT does not have a clear role in the evaluation of patients with EoE.

Introduction: The multi-target stool DNA test (MT-sDNA) is FDA-approved for average-risk colorectal cancer (CRC) screening. Because radiation therapy (RT) to the pelvis or abdomen may cause bleeding, false positive MT-sDNA tests might be increased. However colonoscopy is more technically difficult after RT, increasing interest in MT-sDNA for CRC screening in this population. Among patients (pts) previously treated with RT along or away from the aerodigestive track, we aimed to measure the positive predictive value of MT-sDNA screening in routine clinical practice and compare results to those screened by colonoscopy alone. Methods: A search strategy was designed to identify all pts with a history of RT. Diagnostic codes and free text searches were trialed and with detailed chart review the search string revised to exclude insensitive terms. Then the revised search string was applied to all pts having MT-sDNA testing during the study period. These results were also compared to a radiation oncology and cancer center registries. Pts with RT exposure after the time of MT-sDNA collection were excluded. Pts were stratified by RT applied along versus outside of the aerodigestive tract. Neoplastic findings were recorded in MT-sDNA positive pts who underwent subsequent diagnostic colonoscopy. Controls were those with RT followed by screening colonoscopy alone. Two-tailed Fisher exact probability testing compared pre-cancer rates between groups. Results: The search identified 220 pts who had RT prior to MT-sDNA testing at our multi-site academic and community practice from 09/2014-12/2016. Radiation was delivered along the aerodigestive tract in 108 pts. MT-sDNA was positive in 45/220 (20%) and colonoscopy findings these 40, 30 (75%) had polypoid lesions (21 adenomatous and 9 sessile serrated). Positive predictive value by MT-sDNA was similar when stratified by site of prior RT (Figure). MT-sDNA enriched the yield for colorectal neoplasm at diagnostic colonoscopy, compared to screening colonoscopy alone (Table). Advanced lesions were >3 times more common in MT-sDNA positive pts compared to colonoscopy alone (p=0.003); overall, 30/40 (75%) of positive MT-sDNA pts were found to have any adenomatous or serrated polyps versus 30/70 (43%) who had colonoscopy alone (p=0.001). Conclusion: This study suggests that MT-sDNA remains a reliable CRC screening tool among patients with a history of radiation therapy, irrespective of treatment site.

Introduction: Colorectal cancer (CRC) has been reported in 6-9% of individuals within 3-5 years of reportedly negative screening colonoscopy. Approximately one quarter of patients with prior screening colonoscopy are found to have advanced colorectal neoplasia (CRN) detected by multi-target stool DNA (MT-sDNA) testing. However, the use of MT-sDNA as an interval test to identify CRN between screening colonoscopies has not been studied. Therefore, we aimed to investigate the positive predictive value (PPV) of MT-sDNA ordered in routine clinical practice stratified by time since most recent colonoscopy. Methods: In a large multi-setting practice, we identified all patients with positive MT-sDNA testing between 10/1/2014 and 12/31/2016. From the medical record, we abstracted patients exposure to prior CRC screening by colonoscopy, date of prior colonoscopy, date of positive MT-sDNA, and presence of factors that increase CRN risk above average. Diagnostic colonoscopy and pathology reports were reviewed to enumerate CRN findings. Positive predictive values were calculated for each endpoint, stratified by time since prior colonoscopy (0-5 years, 6-9 years, 10 years or >11 years), and compared using Mantel-Haenszel Chi-Square and Fisher exact tests. Results: Of the 1035 patients identified with positive MT-sDNA testing, 444 had both confirmed prior screening colonoscopy and post MT-sDNA diagnostic colonoscopy. 395 (89%) were found to be at average risk for CRC, while 49 (11%) were at increased risk. Median age was 71 (IQR 66-77) years. Time between prior colonoscopy and MT-sDNA was 0-5 years in 50/444 (11%), 6-9 years in 74 (17%), 10 years in 55 (12%), and >11 years in 265 (60%). PPV of MT-sDNA for any CRN was 62% at 0-5 years, 65% at 6-9 years, 62% at 10 years and 64% at >11 years (p=0.91 for trend). Overall, any CRN was found in 282/444 patients (64%), advanced CRN in 107 patients (24%), and any SSP in 106 patients (24%). CRC was identified in 4 patients (1%), 6-17 years since colonoscopy. In the 437 patients in whom lesion location was documented, right sided CRN was identified in 235 (54%). PPV stratified by time for any endpoint was not significant either for the overall cohort (Figure) or when only average-risk patients were analyzed. Conclusion: MT-sDNA has high PPV for CRN even when used <5 years since prior colonoscopy. Prospective studies investigating the use of MT-sDNA as an interval test between screening colonoscopies are justified.

Introduction: Multi-target stool DNA (MT-sDNA) testing was approved by the FDA for average-risk colorectal cancer (CRC) screening in 2014, and its use has increased exponentially. MT-sDNA performance was demonstrated in cross-sectional screen-setting studies, and post-approval clinical-use data are now emerging. We aimed to measure compliance to diagnostic colonoscopy and positive predictive value of MT-sDNA in average risk patients, with and without prior screening by colonoscopy. Methods: In a large multi-setting practice, we identified all patients with positive MT-sDNA test results between 10/1/2014 and 12/31/2016. From the medical record, we abstracted patients exposure to prior CRC screening by colonoscopy, date of colonoscopy, personal and family history of colorectal neoplasia (CRN), and presence or absence of high risk conditions. Those at increased CRN risk were excluded. Diagnostic colonoscopy and pathology reports were reviewed to enumerate findings of any CRN and advanced CRN. Positive predictive values were calculated for each endpoint and stratified by prior screening colonoscopy exposure. Results: Among the 1035 patients identified with a positive MTsDNA test, 926 (89%) met average risk screening criteria. Of the 926, 410 (44%) did not have prior screening colonoscopy; 238/410 (58%) were >60 years old. Of the 516/926 (56%) that had previous colonoscopy, median time between colonoscopy and MT-sDNA testing was 10.3 (IQR 9.3-11.3) years. Of the 926 with positive MT-sDNA, 821 (89%) had a documented subsequent diagnostic colonoscopy. Diagnostic colonoscopy was completed at a median of 42 (IQR, 25-66) days after positive MT-sDNA. Of these 821, 569 (69%) had CRN identified by colonoscopy, with 247 (30%) of patients harboring advanced CRN; CRC was found in 7 (1%). In previously screened patients (n=473), CRN was identified on diagnostic colonoscopy in 310 (positive predictive value [PPV]=66%)(Table). Among patients without prior screening (n=348), yield was higher with 259 found to have CRN (PPV=74%, p=0.007). Advanced CRN was found in 26% of patients with and 36% of those without prior screening colonoscopy, respectively (p=0.0001). Conclusion: Compliance to diagnostic colonoscopy after a positive MT-sDNA test was high. CRN was identified in more than 2 out of every 3 patients with positive MT-sDNA. Yield of diagnostic colonoscopy was higher in the 44% of patients with positive MT-sDNA who had not received prior CRC screening by colonoscopy.

Introduction: While colonoscopy is recommended for patients in whom symptoms or history suggest increased risk of colorectal neoplasia (CRN), an invasive structural exam is not always feasible. Noninvasive multi-target stool DNA (MT-sDNA) testing is approved by the FDA for average-risk colorectal cancer (CRC) screening, but has not been evaluated in persons at increased risk. Therefore, we aimed to estimate the positive predictive value (PPV) of MT-sDNA ordered in increased-risk individuals compared to those at average risk. Methods: In a large multi-setting practice, we identified all patients with positive MT-sDNA tests from 10/1/2014 to 12/31/2016. To identify patients at increased risk, we reviewed the medical record to assess for personal history of CRN, family history of CRC, aerodigestive cancer history, evidence of unexplained iron deficiency anemia or gastrointestinal bleeding, and presence of inflammatory bowel disease (IBD). Diagnostic colonoscopy and pathology reports were reviewed to enumerate neoplastic findings. PPVs for endpoints of any CRN, advanced CRN, CRC, right-sided CRN and sessile serrated polyps (SSP) for individuals at both average- and increased-risk were compared using 2-tailed Fisher exact tests. Results: 1035 patients with positive MT-sDNA testing were identified, 109 (11%) of whom were at increased risk. Median age was 74 years (interquartile range [IQR] 68-80) in the increased-risk group, compared to 68 years (IQR 61-74) in the average-risk group (p<0.0001). Sex distribution was similar between groups (43% male, p=0.92). Increased-risk conditions included iron deficiency anemia (42%), history of advanced CRN (17%), first degree relative with CRC at age <60 (17%), and rectal bleeding (13%). 84 of the 109 patients (77%) underwent diagnostic colonoscopy, compared to 821/926 (89%) average-risk patients (p=0.001). Of the 84, 52 (62%) had CRN, with 21 (25%) harboring advanced CRN. Two (2%) cases of CRC were identified. The PPV for any CRN was not significantly different between the increased- and average-risk populations (62% vs 69%, p=0.18). While SSP was more common in the average risk group, PPV for all other endpoints were similar (Figure). Conclusion: The PPV of MT-sDNA is similar across average- and increased-risk patient populations. Prospective studies are justified to evaluate MT-sDNA in increased-risk populations, particularly in those for whom colonoscopy is logistically or medically complicated.

Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose. In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy. Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy. The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.