Detection Of Advanced Neoplasia Research Articles

Detection of colorectal cancer and advanced neoplasia during first surveillance interval after detection of adenomas in fecal immunochemical test cancer screening: a nationwide study.

Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines. Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines. During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37). CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.

Colorectal tumor comorbidity is common in patients with duodenal tumors: An exploratory cross-sectional study

BACKGROUND AND STUDY AIMS: The duodenum and colorectum are target organs for familial colorectal adenomatous polyposis, however, the association of duodenal epithelial tumors (DETs) and colorectal tumors is still controversial. The aim of our study was to elucidate the association between DET and colorectal tumor. PATIENTS AND METHODS: This was an exploratory cross-sectional study of patients with DETs treated by endoscopic resection at our hospital, between November 2018 and October 2022. Individuals who underwent colonoscopy as part of the health screening comprised the reference control group for comparison. In both groups, lesions suspected of being tumors were resected. The main outcome was the adenoma detection rate (ADR). Other outcomes were the detection rate of advanced neoplasia (AN) and risk factors for colorectal adenoma and AN, evaluated using univariate and multivariable analyses. RESULTS: Analyses were based on the data of 163 individuals in the DET group and 177 in the control group. ADR was higher in the DET (63.2%) than in the control (23.6%) group (p<.001). AN and invasive cancer rates were also significantly higher in the DET than in the control group (AN: 20.9% vs 3.4%, respectively, p<.001; invasive cancer: 3.1% vs 0%, respectively, p<.001). On logistic regression analysis, DET was found to be associated with a 5-fold increase in the detection rate of adenoma and 6-fold increase in AN detection. CONCLUSIONS: The study revealed significant association between DET and high ADR and a higher frequency of AN and invasive cancer. Screening colonoscopy is suggested for patients with DETs.

Histopathological comparison of colorectal neoplasia or polyps development between young adults and older adults: Our experience of 735 consecutive cases and 1269 polyps

Objective: In recent decades, there has been an increase in early-onset colorectal cancer, the need to screen individuals younger than 50 years of age, and the presence of histopathological differences remains unclear. The objective of this study was to explore the occurrence of polyps in both young adults and older individuals and to examine their potential correlation with colorectal cancer. Methods: In this retrospective study conducted between July 1, 2018, and October 5, 2022, in the Pathology Laboratory, we designed a study based on the histopathological features of colorectal polyps evaluated by an experienced gastrointestinal pathologist based on the WHO 2019 classification. Results: We evaluated 735 consecutive patients who underwent colonoscopic polypectomy between July 2018 and October 2022. The prevalence of cases under the age of 50 was 13.9%, and adults over the age of 50 was 86.1%. A total of 1269 polyps were detected, 1215 (95.7%) were epithelial polyps and 145 (11.9%) were epithelial polyps under the age of 50. One hundred four conventional adenomas and four intramucosal carcinomas were detected in cases younger than 50 years. The patients in the low-risk adenoma group was 57%, and the rate of patients in the high-risk adenoma group was 14.9%. Overall, polyps were most common in the sigmoid colon and there was a statistically significant difference between detecting tubular adenomas in the sigmoid colon (P=0.04). Conclusions: Our current results confirm the detection of sporadic colorectal adenomas and advanced neoplasia in young adults.It is important to establish professional community guidelines for surveillance colonoscopy in these age groups. doi: https://doi.org/10.12669/pjms.40.6.8475 How to cite this: Koyuncuer A. Histopathological comparison of colorectal neoplasia or polyps development between young adults and older adults: Our experience of 735 consecutive cases and 1269 polyps. Pak J Med Sci. 2024;40(6):1111-1115. doi: https://doi.org/10.12669/pjms.40.6.8475 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies. To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy. Individuals enrolled in an Australian surveillance program were included. Diagnostic accuracy was determined for 614 individuals completing a two-sample FIT (OC-Sensor) ≤ 3months preceding surveillance colonoscopy. 386 Individuals were surveyed to assess acceptability of interval FIT. Additionally, a retrospective analysis was performed on 7331 individuals offered interval FIT between colonoscopies, where a positive FIT (≥ 20µg hemoglobin/g feces) triggered an early colonoscopy. Associations between interval FIT results and advanced neoplasia were determined using regression analysis. FIT detected CRC and advanced adenoma with sensitivities of 60.0% (3/5) and 27.1% (35/129), respectively. Most (89.1%, 344/386) survey respondents preferred completing interval FIT every 1-2years. The detection rate of interval FIT for advanced neoplasia decreased with increasing FIT completion. Individuals returning a positive FIT had a higher risk of advanced neoplasia than those who did not complete FIT. Positive interval FIT reduced time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20months, respectively. Interval FIT was well accepted and enabled earlier detection of advanced neoplasia in individuals at above-average risk of CRC. Given that interval FIT predicts advanced neoplasia, it may be used to personalize surveillance colonoscopy intervals.

Polyketide synthase positive Escherichia coli one-time measurement in stool is not informative of colorectal cancer risk in a screening setting.

Environmental factors like the pathogenicity island polyketide synthase positive (pks+) Escherichia coli (E. coli) could have potential for risk stratification in colorectal cancer (CRC) screening. The association between pks+ E. coli measured in fecal immunochemical test (FIT) samples and the detection of advanced neoplasia (AN) at colonoscopy was investigated. Biobanked FIT samples were analyzed for both presence of E. coli and pks+ E. coli and correlated with colonoscopy findings; 5020 CRC screening participants were included. Controls were participants in which no relevant lesion was detected because of FIT-negative results (cut-off ≥15 μg Hb/g feces), a negative colonoscopy, or a colonoscopy during which only a nonadvanced polyp was detected. Cases were participants with AN [CRC, advanced adenoma (AA), or advanced serrated polyp (ASP)]. Existing DNA isolation and quantitative polymerase chain reaction (qPCR) procedures were used for the detection of E. coli and pks+ E. coli in stool. A total of 4542 (90.2%) individuals were E. coli positive, and 1322 (26.2%) were pks+ E. coli positive. The prevalence of E. coli in FIT samples from individuals with AN was 92.9% compared to 89.7% in FIT samples of controls (p = 0.010). The prevalence of pks+ E. coli in FIT samples from individuals with AN (28.6%) and controls (25.9%) was not significantly different (p = 0.13). The prevalences of pks+ E. coli in FIT samples from individuals with CRC, AA, or ASP were 29.6%, 28.3%, and 32.1%, respectively. In conclusion, the prevalence of pks+ E. coli in a screening population was 26.2% and did not differ significantly between individuals with AN and controls. These findings disqualify the straightforward option of using a snapshot measurement of pks+ E. coli in FIT samples as a stratification biomarker for CRC risk. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

The diagnostic yield of colonoscopic surveillance following resection of early age onset colorectal cancer.

The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia. A retrospective cohort study of prospectively collected data was conducted at St Mark's hospital, London, United Kingdom, for patients diagnosed with EOCRC who underwent at least one episode of post-CRC colonoscopic surveillance between 1978 and 2022. We collected clinicopathological data including tumour molecular status and neoplasia detection rates. In total, 908 colonoscopic surveillance procedures were performed in 195 patients over 2581.3 person-years of follow-up. The diagnostic yields of metachronous CRC, advanced adenomas and non-advanced adenomas were 1.76%, 3.41% and 22.69% respectively. Sixteen patients (8.21%) developed metachronous CRC, and the majority (87.5%) were detected more than 3years post index EOCRC diagnosis. Detection of advanced neoplasia was significantly higher in EOCRC patients with Lynch syndrome (26.15%) compared with those in whom Lynch syndrome was excluded (13.13%) (OR, 2.343; 95% CI, 1.014-5.256; p=0.0349). During colonoscopic surveillance post-EOCRC resection, the long-term risk of developing metachronous advanced neoplasia remains high in the context of Lynch syndrome, but this trend is not as clearly evident when Lynch syndrome has been excluded.

Clinical performance study of a fecal bacterial signature test for colorectal cancer screening.

The fecal immunochemical test (FIT) is the most widely used test for colorectal cancer (CRC) screening. RAID-CRC Screen is a new non-invasive test based on fecal bacterial markers, developed to complement FIT by increasing its specificity. The test was previously clinically evaluated in FIT-positive patients (>20 μg of hemoglobin/g of feces, "FIT20"), in which it reduced the proportion of false positive results by 16.3% while maintaining most of FIT20's sensitivity. The aim of this study was to compare the sensitivity and specificity of a CRC screening program using RAID-CRC Screen in addition to FIT20 as a triage test in a European screening population undergoing screening colonoscopy with a CRC screening program with FIT20 alone in the same cohort. A cohort of 2481 subjects aged > 55 years from the German screening colonoscopy program was included. The colonoscopy findings were used as the gold standard in calculating the diagnostic capacity of the tests and included 15 CRC and 257 advanced neoplasia cases. RAID-CRC Screen added to FIT20 provided the same sensitivity as FIT20 alone (66.7%) in detecting CRC and a significantly higher specificity (97.0% vs. 96.1%, p<0.0001). The positive predictive value was 11.9% when using RAID-CRC Screen and 9.5% with FIT20 alone, and the negative predictive value was 99.8% in the two scenarios. For advanced neoplasia detection, the use of RAID-CRC Screen yielded significantly lower sensitivity than with FIT20 alone (17.5% vs. 21.8%, p = 0.0009), and the overall specificity was significantly higher when using RAID-CRC Screen compared with FIT20 alone (98.2% vs. 97.8%, p = 0.0039). Our findings confirm the results obtained in previous clinical studies in a CRC screening setting, showing the potential of RAID-CRC Screen to increase the overall specificity of FIT-based screening.

Screening uptake of colonoscopy versus fecal immunochemical testing in first-degree relatives of patients with non-syndromic colorectal cancer: A multicenter, open-label, parallel-group, randomized trial (ParCoFit study).

Colonoscopy screening is underused by first-degree relatives (FDRs) of patients with non-syndromic colorectal cancer (CRC) with screening completion rates below 50%. Studies conducted in FDR referred for screening suggest that fecal immunochemical testing (FIT) was not inferior to colonoscopy in terms of diagnostic yield and tumor staging, but screening uptake of FIT has not yet been tested in this population. In this study, we investigated whether the uptake of FIT screening is superior to the uptake of colonoscopy screening in the familial-risk population, with an equivalent effect on CRC detection. This open-label, parallel-group, randomized trial was conducted in 12 Spanish centers between February 2016 and December 2021. Eligible individuals included asymptomatic FDR of index cases <60 years, siblings or ≥2 FDR with CRC. The primary outcome was to compare screening uptake between colonoscopy and FIT. The secondary outcome was to determine the efficacy of each strategy to detect advanced colorectal neoplasia (adenoma or serrated polyps ≥10 mm, polyps with tubulovillous architecture, high-grade dysplasia, and/or CRC). Screening-naïve FDR were randomized (1:1) to one-time colonoscopy versus annual FIT during 3 consecutive years followed by a work-up colonoscopy in the case of a positive test. Randomization was performed before signing the informed consent using computer-generated allocation algorithm based on stratified block randomization. Multivariable regression analysis was performed by intention-to-screen. On December 31, 2019, when 81% of the estimated sample size was reached, the trial was terminated prematurely after an interim analysis for futility. Study outcomes were further analyzed through 2-year follow-up. The main limitation of this study was the impossibility of collecting information on eligible individuals who declined to participate. A total of 1,790 FDR of 460 index cases were evaluated for inclusion, of whom 870 were assigned to undergo one-time colonoscopy (n = 431) or FIT (n = 439). Of them, 383 (44.0%) attended the appointment and signed the informed consent: 147/431 (34.1%) FDR received colonoscopy-based screening and 158/439 (35.9%) underwent FIT-based screening (odds ratio [OR] 1.08; 95% confidence intervals [CI] [0.82, 1.44], p = 0.564). The detection rate of advanced colorectal neoplasia was significantly higher in the colonoscopy group than in the FIT group (OR 3.64, 95% CI [1.55, 8.53], p = 0.003). Study outcomes did not change throughout follow-up. In this study, compared to colonoscopy, FIT screening did not improve screening uptake by individuals at high risk of CRC, resulting in less detection of advanced colorectal neoplasia. Further studies are needed to assess how screening uptake could be improved in this high-risk group, including by inclusion in population-based screening programs. This trial was registered with ClinicalTrials.gov (NCT02567045).

Serum methylation of GALNT9, UPF3A, WARS, and LDB2 as noninvasive biomarkers for the early detection of colorectal cancer and advanced adenomas

BackgroundEarly detection has proven to be the most effective strategy to reduce the incidence and mortality of colorectal cancer (CRC). Nevertheless, most current screening programs suffer from low participation rates. A blood test may improve both the adherence to screening and the selection to colonoscopy. In this study, we conducted a serum-based discovery and validation of cfDNA methylation biomarkers for CRC screening in a multicenter cohort of 433 serum samples including healthy controls, benign pathologies, advanced adenomas (AA), and CRC.ResultsFirst, we performed an epigenome-wide methylation analysis with the MethylationEPIC array using a sample pooling approach, followed by a robust prioritization of candidate biomarkers for the detection of advanced neoplasia (AN: AA and CRC). Then, candidate biomarkers were validated by pyrosequencing in independent individual cfDNA samples. We report GALNT9, UPF3A, WARS, and LDB2 as new noninvasive biomarkers for the early detection of AN. The combination of GALNT9/UPF3A by logistic regression discriminated AN with 78.8% sensitivity and 100% specificity, outperforming the commonly used fecal immunochemical test and the methylated SEPT9 blood test.ConclusionsOverall, this study highlights the utility of cfDNA methylation for CRC screening. Our results suggest that the combination methylated GALNT9/UPF3A has the potential to serve as a highly specific and sensitive blood-based test for screening and early detection of CRC.

The Diagnostic Performance of Fecal Immunochemical Tests for Detecting Advanced Neoplasia at Surveillance Colonoscopy

An increasing burden on health care resources has resulted in a backlog of individuals requiring colonoscopy, with delays in surveillance possibly detrimental for individuals at increased risk of colorectal cancer (CRC). This study investigated the use of a 2-sample fecal immunochemical test (FIT) to establish those most likely to have advanced neoplasia (AN) and in need of prioritized surveillance colonoscopy. This was a prospective study conducted in the tertiary care setting. Participants completed a 2-sample FIT (OC-Sensor, Eiken Chemical Company) within 90 days of surveillance colonoscopy. The sensitivity of FIT for detection of AN (CRC or advanced adenoma) in moderate- and high-risk individuals was determined at fecal hemoglobin thresholds between 2 and 80 μg/g feces. A total of 766 patients were included (median age, 66.1 years [interquartile range, 58.1-72.9]; 49.9% male), with AN detected in 8.6% (66/766, including 5 CRC). For moderate-risk individuals (with prior history of adenoma or a significant family history of CRC), sensitivity of FIT for AN ranged from 73.5% at 2 μg/g feces, to 10.2% at 80 μg/g feces. For high-risk conditions (confirmed/suspected genetic syndromes or prior CRC), sensitivity of FIT was similar, ranging from 70.6% at the lowest positivity threshold of 2 μg/g feces, to 11.8% at 80 μg/g feces. Independent variables in the whole cohort for association with detection of AN at surveillance colonoscopy were age (odds ratio, 1.03; 95% confidence interval, 1.00-1.06) and FIT hemoglobin result ≥10 μg/g feces (odds ratio, 1.81; 95% confidence interval, 1.04-3.16). The use of FIT before surveillance colonoscopy provides clinicians with insights into the risk of AN. This raises the possibility of a method to triage individuals, facilitating the more efficient management of endoscopic resources.

Role of Artificial Intelligence in Colonoscopy Detection of Advanced Neoplasias : A Randomized Trial.

The role of computer-aided detection in identifying advanced colorectal neoplasia is unknown. To evaluate the contribution of computer-aided detection to colonoscopic detection of advanced colorectal neoplasias as well as adenomas, serrated polyps, and nonpolypoid and right-sided lesions. Multicenter, parallel, randomized controlled trial. (ClinicalTrials.gov: NCT04673136). Spanish colorectal cancer screening program. 3213 persons with a positive fecal immunochemical test. Enrollees were randomly assigned to colonoscopy with or without computer-aided detection. Advanced colorectal neoplasia was defined as advanced adenoma and/or advanced serrated polyp. The 2 comparison groups showed no significant difference in advanced colorectal neoplasia detection rate (34.8% with intervention vs. 34.6% for controls; adjusted risk ratio [aRR], 1.01 [95% CI, 0.92 to 1.10]) or the mean number of advanced colorectal neoplasias detected per colonoscopy (0.54 [SD, 0.95] with intervention vs. 0.52 [SD, 0.95] for controls; adjusted rate ratio, 1.04 [99.9% CI, 0.88 to 1.22]). Adenoma detection rate also did not differ (64.2% with intervention vs. 62.0% for controls; aRR, 1.06 [99.9% CI, 0.91 to 1.23]). Computer-aided detection increased the mean number of nonpolypoid lesions (0.56 [SD, 1.25] vs. 0.47 [SD, 1.18] for controls; adjusted rate ratio, 1.19 [99.9% CI, 1.01 to 1.41]), proximal adenomas (0.94 [SD, 1.62] vs. 0.81 [SD, 1.52] for controls; adjusted rate ratio, 1.17 [99.9% CI, 1.03 to 1.33]), and lesions of 5 mm or smaller (polyps in general and adenomas and serrated lesions in particular) detected per colonoscopy. The high adenoma detection rate in the control group may limit the generalizability of the findings to endoscopists with low detection rates. Computer-aided detection did not improve colonoscopic identification of advanced colorectal neoplasias. Medtronic.

Antithrombotic drug use does not affect the fecal immunochemical test PPV for colorectal cancer, but warfarin may have an impact in a Japanese cohort

The fecal immunochemical test (FIT) is used for colorectal cancer (CRC) screening. Patients on antithrombotic drugs (ATs) are often screened for CRC, but the effect of ATs on FIT results is controversial. We divided individuals with FIT-positive results into two groups, patients treated with and without ATs, and retrospectively compared invasive CRC rates, advanced neoplasia detection rates (ANDRs), adenoma detection rates (ADRs), and polyp detection rates (PDRs) between the two groups. We evaluated the factors influencing the FIT positive predictive value (PPV) using propensity matching, adjusting for age, sex, and bowel preparation. We enrolled 2327 individuals (54.9% male; mean age, 66.7 ± 12.7 years). We grouped 463 individuals into the AT user group and 1864 into the nonuser group. Patients in the AT user group were significantly older and more likely to be male. After propensity score matching for age, sex, and Boston bowel preparation scale, the ADR and PDR in the AT user group were significantly lower than those in the nonuser group. Univariate logistic analysis revealed that multiple AT use (odds ratio [OR]: .39, p<0.001) had the lowest OR for FIT PPV, followed by age- and sex-adjusted factors for the ADR and any AT use (OR: .67, p=0.0007). No significant factors related to AT use were observed among age-adjusted predictive factors for invasive CRC, but warfarin use was a borderline significant positive predictive factor (OR: 2.23, p=0.059). AT use may not affect the PPV for detecting invasive CRC in patients with positive FIT results, but warfarin may have an impact.

Frequency of Use and Outcomes of Colonoscopy in Individuals Older Than 75 Years

The benefits from colorectal cancer (CRC) screening may take 10 to 15 years to accrue. Therefore, screening is recommended for older adults who are in good health. To determine the number of screening colonoscopies done in patients older than 75 years with a life expectancy of fewer than 10 years, diagnostic yield, and associated adverse events within 10 days and 30 days of the procedure. This cross-sectional study with a nested cohort between January 2009 and January 2022 in an integrated health system assessed asymptomatic patients older than 75 years who underwent screening colonoscopy in the outpatient setting. Reports with incomplete data, any indication other than screening, patients who had a colonoscopy within the previous 5 years, and patients with a personal history of inflammatory bowel disease or CRC were excluded. Life expectancy based on a prediction model from previous literature. The primary outcome was the percentage of screened patients who had limited (<10 years) life expectancy. Other outcomes included colonoscopy findings and adverse events that developed within 10 days and 30 days of the procedure. A total of 7067 patients older than 75 years were included. The median (IQR) age was 78 (77-79) years, 3967 (56%) were women, and 5431 (77%) were White with an average of 2 comorbidities (taken from a select group of comorbidities). The proportion of colonoscopies performed on patients with a life expectancy of fewer than 10 years aged 76 to 80 years was 30% in both sexes and increased with age-82% of men and 61% of women aged 81 to 85 years (71% total), and 100% of patients beyond the age of 85 years. Adverse events requiring hospitalizations were common at 10 days (13.58 per 1000) and increased with age, particularly among patients older than 85 years. The detection of advanced neoplasia varied from 5.4% among patients aged 76 to 80 years to 6.2% in those aged 81 to 85 years and 9.5% among patients older than 85 years (P = .02). Of the total population, 15 patients (0.2%) had invasive adenocarcinoma; among patients with a life expectancy of fewer than 10 years, 1 of 9 was treated, whereas 4 of 6 patients with a life expectancy of greater than or equal to 10 years were treated. In this cross-sectional study with a nested cohort, most screening colonoscopies performed in patients older than 75 years were in patients with limited life expectancy and associated with increased risk of complications. Colorectal cancer was exceedingly rare.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test

Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n= 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n= 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n= 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. gov, Number: NCT00102011.

Risk prediction for advanced neoplasia using longitudinal adherence measures to fecal immunochemical test-based colorectal cancer screening programs

BackgroundPatterns of longitudinal adherence may predict advanced neoplasia (AN) detection in subsequent rounds of colorectal cancer (CRC) screening. However, after more than five rounds, it is important to obtain a simplified measure. The aim was to determine the best simplified measure of longitudinal adherence to predict AN detection in CRC screening. MethodsIndividuals with four invitations from a Dutch Fecal immunochemical testing (FIT-)based pilot study and two Italian FIT-based CRC screening programs were included. We calculated AN detection in the fourth round, stratified by prior adherence. Five simplified measures were compared to full information (permutations) using chi-squared goodness-of-fit: adherence previous invitation, consistency, frequency, frequency + adherence previous invitation, and proportion of invitations covered. ResultsAN detection in the fourth round was highly dependent on prior adherence behavior. For inconsistent adherence, detection in the fourth round was strongly dependent on frequency and time since last participation. The performance of the simplified measures to capture this variation differed considerably. ‘Adherence previous invitation’ scored worst in predicting AN detection. ‘Frequency+adherence previous invitation’ had lowest chi-squared goodness-of-fit. DiscussionThe simplified measure ‘frequency+adherence previous invitation’ is the best measure to reflect patterns of longitudinal adherence and could be used to emphasize to individuals the importance of CRC screening.

Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT)

BackgroundIn 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 µg Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT.MethodsThis mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals’ perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening.DiscussionThe aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality.Trial registration: ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886

Fundic Gland Polyps Lack DNA Content Abnormality Characteristic of Other Adenomatous Precursor Lesions in the Gastrointestinal Tract

Fundic gland polyps (FGPs) develop sporadically (frequently after proton pump inhibitor therapy) or in the setting of a hereditary polyposis syndrome, such as familial adenomatous polyposis (FAP). FAP-related FGPs often demonstrate low-grade dysplasia (LGD) and are frequently associated with APC mutations, even in the absence of dysplasia. Sporadic FGPs with dysplasia are molecularly similar to FAP-related FGPs and demonstrate frequent mutations in APC gene. Despite having similar molecular alterations with colorectal and other adenomatous precursor lesions in the gastrointestinal (GI) tract, FGPs rarely progress to advanced gastric neoplasia (high-grade dysplasia [HGD] or adenocarcinoma), and their role in gastric tumorigenesis remains unclear but likely limited. The clinicopathologic features of 192 patients diagnosed with FGPs, including 86 with FAP-related FGPs (33 with dysplastic FGPs and 53 with nondysplastic FGPs) and 106 with sporadic FGPs (12 with dysplastic FGPs and 94 with nondysplastic FGPs), were analyzed. DNA flow cytometry was performed on 111 FAP-related FGP biopsies, including 32 FGPs with LGD and 79 nondysplastic FGPs, to assess the presence of abnormal DNA content (ie, aneuploidy or elevated 4N fraction). Moreover, 40 sporadic FGP biopsies, including 14 dysplastic (13 LGD and 1 HGD) and 26 nondysplastic FGPs, were examined for DNA content abnormality. Patients with FAP and nondysplastic FGPs were more likely to be younger (mean age, 32 years) and present with multiple FGPs (92%, defined as having ≥2 FGPs) than those with sporadic nondysplastic FGPs (61 years and 65%, respectively; P < .001). They also recorded higher rates of previous or concurrent gastric epithelial dysplasia not occurring in a FGP (8%, P = .016), nongastric GI dysplasia (96%, P < .001), and nongastric GI malignancy (17%, P = .001) compared with those with sporadic nondysplastic FGPs (0%, 52%, and 2%, respectively). The sporadic group was more frequently associated with proton pump inhibitor therapy (78%, P < .001), gastric intestinal metaplasia (24%, P = .004), and a family history of gastric cancer (10%, P = .027) than the FAP group (19%, 6%, and 0%, respectively). Almost all FAP-related FGPs had a polypoid endoscopic appearance (98% vs 84% for sporadic FGPs; P = .009). The mean size of the largest FAP-related FGPs (0.5 cm) was similar to that of sporadic FGPs (0.7 cm) (P = .069). None of the 147 patients with FAP-related or sporadic nondysplastic FGPs were associated with subsequent detection of advanced gastric neoplasia within a mean follow-up time of 54 months (range, <1 to 277 months). However, 2 (4%) of the 45 patients with FAP-related or sporadic dysplastic FGPs developed advanced gastric neoplasia within a mean follow-up time of 59 months (range, <1 to 236 months). One (3%) of the 33 patients with FAP and dysplastic FGPs developed signet ring cell adenocarcinoma, whereas 1 (8%) of the 12 patients with sporadic dysplastic FGPs developed HGD (P = .445). However, none of the FAP-related and sporadic FGP biopsies, regardless of the presence or absence of dysplasia, demonstrated DNA content abnormality. In conclusion, FGPs lack large-scale chromosomal changes that are characteristic of the typical adenoma-carcinoma sequence involved in the development of other GI malignancies. Progression to advanced gastric neoplasia is rare in FGPs, which may be partly explained by the apparent lack of the chromosomal instability phenotype in these lesions.

Comparison of adenoma detection rate between high-definition colonoscopes with different fields of view: 170 degrees versus 140 degrees

In newer generation colonoscopes, the field of view (FOV) varies approximately between 170° and 140°, depending on the type of colonoscopy. To the best of our knowledge, no study has investigated whether the visual field difference of the colonoscope affects quality indicators, such as the adenoma detection rate (ADR), without using additional devices to expand the FOV in colonoscopes with the same resolution. This study aimed to investigate the difference in quality indicators, such as ADR, between 170° and 140° FOV in colonoscopes with the same high-definition resolution. We retrospectively analyzed the medical records of patients who underwent screening or surveillance colonoscopy at the Dong-A University Hospital in Busan, South Korea, between March 2021 and February 2022. We calculated the overall ADR ratios for patients who underwent colonoscopy with 140° and 170° FOV. Polyp detection rate (PDR), sessile serrated PDR, and advanced neoplasia detection rate were calculated for each group. Factors associated with adenoma detection were identified using a logistical regression analysis. A total of 1711 patients were included in the study (838 patients in the 170° group and 873 patients in the 140° group). ADR (43.79 vs 41.92%, P = .434) did not significantly differ between the 2 groups. The generational differences were not statistically significant either for PDR (56.44 vs 53.49%, P = .220), sessile serrated PDR (1.19 vs 0.92%, P = .575), or advanced neoplasia detection rate (5.00 vs 4.58%, P = .735). Multivariate regression analysis revealed that, age, male sex, and long withdrawal time were the most significant factors affecting adenoma detection. This study revealed that there were no differences in ADR while employing high definition colonoscopes with a 170° FOV and a 140° FOV.

Potential Modifiers and Different Cut-offs in Diagnostic Accuracy of Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia: A Diagnostic Test Accuracy Meta-analysis.

Background: Fecal immunoglobulin test (FIT) has been advocated as the first line of screening for colorectal cancer (CRC) in several jurisdictions. Most studies have focused on CRC as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different thresholds of FIT as compared with colonoscopy for detection of advanced colonic neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as the reference standard to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy (DTA) meta-analysis. Diagnostic accuracy of different cut-offs of FIT, including 25, 50, 75, 100, 150, and 200 ng/mL, were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers, including age, location of the tumor, and time from FIT to colonoscopy. Results: Twenty-four studies were included with no evidence of publication bias. The sensitivity of FIT did not decrease with lowering the cut-off, although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL, and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. Diagnostic accuracy of FIT did not significantly differ in proximal versus distal lesions or in individuals below or over the age of 50 years. The results remained robust in a meta-regression of the location of the study, time from FIT to colonoscopy, and methodological quality. Conclusion: The sensitivity of FIT might have been overestimated in previous studies focusing on CRC, and it seems to be independent of age, location of neoplasia, or cut-offs, contrary to some previous studies. Lowering the cut-off will reduce the diagnostic odds ratio (DOR) by increasing specificity but without any effect on sensitivity.

S252 Screening With FIT-DNA: Impact on Colonoscopy Withdrawal Time, Adenoma Detection and Endoscopist’s Recommendation for Follow-Up

Introduction: Limited data exist on colonoscopy after abnormal fecal immunochemical test (FIT)-DNA (a.k.a. multitarget stool DNA test). We hypothesized that endoscopists perform a more careful exam (e.g., longer withdrawal time (WT)) and recommend early re-screening after FIT-DNA+/negative colonoscopy due to expectations about test performance. We aimed to A) determine adenoma detection rate (ADR) and other lesion detection rates and B) assess endoscopist behavior regarding WT and recommendations after negative colonoscopy for 3 indications: 1) FIT-DNA+, 2) average-risk screening (SCR) and 3) abnormal fecal occult blood test (FOBT+, guaiac or FIT). Methods: Using GIQuIC data (2019-2022) from 727 endoscopy units, we identified patients aged 50-75 years undergoing colonoscopy for FIT-DNA+, SCR or FOBT+. We excluded colonoscopy with any other indications (e.g., family history), inadequate bowel preparation or incomplete exam. If pathology was obtained but results were not available, the record was excluded from pathology-related outcomes. Generalized estimating equations clustered by endoscopist were used to assess the association between indication and outcomes while adjusting for patient characteristics and endoscopist's screening ADR. Results: >1.8 million colonoscopies were included; demographics varied by indication (Table). FIT-DNA+ was associated with higher ADR (59.6%) than SCR (39.3%, p< 0.0001) and FOBT+ (53.8%, p< .0001) and greater detection of advanced neoplasia and sessile serrated lesions (Table). Among those with no pathology obtained on colonoscopy, WT was longer for FIT-DNA+ than for SCR and FOBT+. Among patients aged 50-65 years with no pathology and ASA < IV, a 10-year colonoscopy was recommended in only 80.1% of FIT-DNA+ patients vs. 87.2% of SCR and 86.5% of FOBT+. In multivariable models, compared to FIT-DNA+, SCR and FOBT+ are associated with shorter WT (p< 0.0001 for both), and lower odds of adenoma detection (OR 0.48 (95% CI 0.47-0.50) and 0.71 (0.68-0.74), respectively) and recommendations for re-screening in < 10 years (OR 0.64 (0.57-0.72) and 0.84 (0.74-0.96), respectively). Conclusion: FIT-DNA+ is associated with greater neoplasia detection than FOBT+ and SCR, but also with longer WT and more recommendations for early re-screening after a negative colonoscopy. Despite lower specificity of FIT-DNA vs. FOBT, endoscopists seem to have greater concern for missed pathology in FIT-DNA+/negative colonoscopies, leading to downstream impacts on healthcare utilization. Table 1. - Colonoscopy for Abnormal FIT-DNA vs. Average Risk Screening vs. Abnormal FOBT:Patient Characteristics, Findings and Follow-Up Recommendations After a Negative Exam FIT-DNA+(n=23,046) Average Risk Screening(n=1,760,840) FOBT+(n=26,455) Age, mean (sd) 64.2 (7.1) 58.7 (7.2) 63.8 (7.2) Male (%)Female (%) 9,939 (43.1)13,107 (56.9) 816,630 (46.4)944,210 (53.6) 12,698 (48.0)13,757 (52.0) White (%)Black of African American (%)Asian (%)Other (%)Unknown/Declined (%) 15,777 (68.5)1085 (4.7)211 (0.9)514 (2.2)5459 (23.7) 1,022,859 (58.1)171,348 (9.7)56,644 (3.2)68,966 (3.9)441,033 (25.1) 16,387 (61.9)2112 (8.0)959 (3.6)1224 (4.6)5773 (21.8) Non-Hispanic (%)Hispanic/Latino (%)Unknown/Decline 14,234 (61.8)560 (2.4)8252 (35.8) 1,018,724 (57.9)107,147 (6.1)634,969 (36.1) 16,691 (63.1)2407 (9.1)7357 (27.8) Total endoscopists contributing colonoscopies 2650 4845 3223 Endoscopist mean ADR‡(sd) with minimum 50 colonoscopies 39.1% (10.2)(Endoscopist n=2467) 39.2% (10.9)(Endoscopist n=3878) 39.5% (10.6)(Endoscopist n=3006) Colonoscopy Findings Adenoma Detection Rate (ADR) 59.6% *,§ 39.3% § 53.8% ADR for Males 67.6% *,§ 46.4% § 61.0% ADR for Females 53.6% *,§ 33.2% § 47.2% Advanced Neoplasia Detection± 22.2% *,§ 7.6% § 17.4% Sessile Serrated Lesion Detection 16.2% *,§ 8.2% † 8.8% Adenocarcinoma Detection 1.5% * 0.3% § 1.4% Analysis of Subgroup with No Polyps on Colonoscopy (i.e., No Pathology Obtained) Median Withdrawal Time, Minutes (interquartile range) (n=4211)8.5 (6.9-11.0) *,§ (n=673,519)7.8 (6.4-9.9) (n=7455)7.8 (6.3-10.1) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)< 10 Years (%)10 Years (%) (n=2125)422 (19.9)1703 (80.1) (n=567,568)72,403 (12.8)495,165 (87.2) (n=4301)579 (13.5)3722 (86.5) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)≤3 Years (%)4 or 5 Years (%)6-9 Years (%)10 Years (%)Excluded intervals n:OtherNone (n=2125)*,§ 76 (3.6)333 (15.7)13 (0.6)1703 (80.1) 1518 (n=567,568)§ 3840 (0.7)65,289 (11.5)3274 (0.6)495,165 (87.2) 2335974 (n=4301)65 (1.5)478 (11.1)36 (0.8)3722 (86.5) 2919 ‡ADR includes average risk screening only, ages 50-75, photodocumentation of the cecum, adequate bowel preparation.*p<0.0001 compared with average risk screening.§p<0.0001 compared with FOBT+.†p=0.0002 compared with FOBT+. ± Includes either 1) adenoma≥10 mm, with high grade dysplasia, or with villous component; OR 2) sessile serrated polyp (SSP)≥10 mm, SSP with dysplasia, or traditional serrated adenoma; OR 3) adenocarcinoma.