Neoplasia In Individuals Research Articles

P-436. Anal Pap Cytology for Anal Intraepithelial Neoplasia in Individuals under 45 Years of Age

Abstract Background Human Papilloma Virus (HPV)-related high-grade anal intraepithelial neoplasia (AIN) is the precursor of anal cancer. There are limited data identifying factors that influence AIN progression in adults eligible to HPV vaccines.Figure 1.Distribution of anal cytology and reference test results (n=488). (A) Anal cytology. (B) Reference testASCUS, atypical squamous cells of undetermined significance; LSIL, low grade squamous intraepithelial lesions; ASC-H, atypical squamous cells cannot exclude high-grade squamous intraepithelial lesions; HSIL, high-grade squamous intraepithelial lesions; SCCIS, squamous cell carcinoma in situ. Methods This retrospective study includes individuals followed at University of Pittsburgh Anal Dysplasia Clinic from 2020-2024. Inclusion criteria were ages 18-45 years as of 2020, all sexes/genders, people with HIV (PWH) or without, and at least one anal cytology paired with pathology (reference standard) or high-resolution anoscopy (HRA) appearance (reference standard if pathology unavailable). We used Logistic regression to evaluate factors associated with high-grade squamous intraepithelial lesion (HSIL) or squamous cell carcinoma in situ (SCCIS) on reference tests (designated as ref-HSIL here). The University of Pittsburgh IRB approved this study.Table 1.Baseline demographics. Results We included 239 individuals, with median age 37 years, 16% female, and 95 (40%) received at least one dose of HPV vaccine at initial median age of 26 years (Table 1). Of 191 PWH, 93% were virologically suppressed, with median CD4 count 748 cells/µl at initial visits (2020 or after), and median nadir CD4 count 360 cells/µl. Distribution of cytology and reference tests (149 from pathology and 339 from HRA) was shown in Figure 1. Anal cytology had low-moderate sensitivity (55%) and specificity (82%), but an acceptable negative predictive value of 96% for ref-HSIL. In full cohort, risk factors for ref-HSIL were ASC-H (atypical squamous cells, cannot exclude HSIL) or HSIL on cytology (adjusted odds ratio [aOR] 6.19, P< 0.001). In PWH, nadir CD4 count <200 cells/µl (aOR 4.08, P=0.008) was associated with ref-HSIL while viral suppression tended to be protective (Table 2). Seven individuals with initial non-ref-HSIL progressed to ref-HSIL. Nadir CD4 < 100 cells/µl (aOR 25.0, P=0.010) and current smoking (aOR 6.2, P=0.095, Table 3) showed a trend in association with progression.Table 2.Factors associated with HSIL or SCCIS on reference tests in PWH.Table 3.Factors associated with progression to HSIL/SCCIS. Conclusion In this cohort of adults ≤45 years, cytologic ASC-H or HSIL predicts ref-HSIL. In PWH, low nadir CD4 count is a risk factor for ref-HSIL, while viral suppression is protective. Low nadir CD4 count is also a risk factor for AIN progression to ref-HIL. Our study helps prioritize target individuals who need HRA the most. Disclosures All Authors: No reported disclosures

Risk of colorectal cancer among fecal immunochemical test-positive individuals by timing of previous colonoscopy: A multicenter analysis.

The risk of colorectal cancer among fecal immunochemistry test-positive individuals who had undergone previous colonoscopies remains unclear. Therefore, this study aimed to determine the differences in the risk of colorectal cancer among fecal immunochemistry test-positive individuals according to the timing of their previous colonoscopies. This multicenter, retrospective, observational study was conducted in Japan as a subgroup analysis of the J-SCOUT study (UMIN000040690), which integrated and analyzed a database comprising all colonoscopies performed at participating Japanese institutions between 2010 and 2020. This study used colonoscopy data of fecal immunochemistry test-positive individuals aged ≥20years from three facilities that entered the timing of previous colonoscopies into the endoscopy database. Histologically confirmed advanced neoplasia was the study's primary outcome. Multivariate logistic regression analysis was used to calculate the odds ratios for each variable. In total, 11,143 fecal immunochemistry test-positive patients underwent colonoscopy during the study period. Of these, 10,160 patients were included in the analysis after excluding those who met the exclusion criteria. The overall advanced neoplasia detection rate was 9.38% (953/10,160; 95% confidence interval: 8.82-9.96%). Compared with the first colonoscopy, the odds ratios for advanced neoplasia in individuals who underwent colonoscopies 1, 2, 3, 4, 5, >5, and ≥10years previously were 0.27, 0.15, 0.06, 0.10, 0.29, 0.31, and 0.31, respectively. The detection rates of advanced neoplasia were low among the fecal immunochemistry test-positive individuals who had undergone colonoscopy, particularly in the past 5years.

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

BackgroundThe 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.AimTo 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.MethodsIndividuals enrolled in an Australian surveillance program were included. Diagnostic accuracy was determined for 614 individuals completing a two-sample FIT (OC-Sensor) ≤ 3 months 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 (≥ 20 µg hemoglobin/g feces) triggered an early colonoscopy. Associations between interval FIT results and advanced neoplasia were determined using regression analysis.ResultsFIT 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 1–2 years. 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 20 months, respectively.ConclusionInterval 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.

Feasibility and Colonoscopy Yield Using the Fecal Immunochemical Test (FIT)-Based Colorectal Cancer Screening in a Latin America Country

Background and aimsOrganized colorectal cancer (CRC) is not widely practiced in Latin America and the results of regional studies may help overcome barriers for implementation of national screening programs. We aimed to describe the implementation and findings of a fecal immunochemical test (FIT)-based program in Brazil. MethodsIn a prospective population-based study, asymptomatic individuals (50 to 75 years-old) from Sao Paulo city were invited to undergo FIT for CRC screening. Participants with positive FIT (>10 μg Hb/g feces) were referred for colonoscopy. Subjects were classified into groups according to the presence of CRC, precursor lesions, and other benign findings, possibly related to bleeding. ResultsOf a total of 9,881 subjects, 7.8% had positive FIT and colonoscopy compliance was 68.9% (n=535). Boston scale was considered adequate in 99% and cecal intubation rate was 99.4%. CRC was diagnosed in 5.9% of the cases, adenoma in 63.2%, advanced adenoma (AA) in 31.4%, and advanced neoplasia (AN) in 33.0%. Age was positively associated with CRC (p=0.03). Higher FIT concentrations were associated with increased detection of CRC (p<0.008), AA (p<0.001), and AN (p<0.001). ConclusionImplementation of a FIT-based CRC screening program was feasible in a low-resource setting, and there was a high yield for neoplasia in individuals with a positive FIT. This approach could be used as a model to plan and disseminate organized CRC screening more broadly in Brazil and Latin America.

Prevalence and risk factors of colorectal neoplasia in individuals aged 40-49years: Findings from screening program in China.

The incidence of colorectal cancer (CRC) in individuals under 50 is increasing worldwide. We conducted an analysis of colonoscopy findings in high-risk individuals under 50 in the CRC screening program in Tianjin, China, to determine the detection rate and risk factors of advanced adenomas (AA), advanced colorectal neoplasia (ACN), colorectal neoplasia (CN). Our study investigated individuals aged 40-49 who underwent CRC screening and completed colonoscopy, 2012-2020, while the 50-54 age group served as a control. We compared the detection rates of AA, ACN, and CN among three age groups using univariate and multivariable logistic regression analyses, and investigated the risk factors associated with AA, ACN, and CN among individuals aged 40-49. We found a gradual increase in the detection rate of AA, ACN, and CN among individuals aged 40-54. The detection rates for AA (OR 0.58; 95% CI 0.41-0.81), ACN (OR 0.58; 95% CI 0.43-0.77), and CN (OR 0.64; 95% CI 0.56-0.74) were lower in individuals aged 40-44 compared to 45-49. The detection rates of AA (OR 1.08; 95% CI 0.87-1.34) and ACN (OR 1.12; 95% CI 0.93-1.35) in individuals aged 45-49 were comparable with 50-54. Besides, lifestyle factors, BMI, and FIT are not associated with the detection rates of AA, ACN, and CN among individuals aged 40-49. Our study reveals screening data in individuals under 50, indicating comparable detection rates of AA and ACN in individuals aged 45-49 and 50-54. These findings provide valuable data support for optimizing the optimal age to initiate screening.

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162.

Risk of recurrent advanced colorectal neoplasia in individuals with baseline non-advanced neoplasia followed up at 5 vs 7-10years.

Colorectal cancer (CRC) is one of the commonest cancers, especially among the Asian populations. We compared the recurrence rate of advanced colorectal neoplasia (ACN) at 5year vs 7-10years among individuals with non-advanced adenoma (NAA) detected and polypectomized at baseline colonoscopy in a large Chinese population. We extracted data of a large Chinese population with NAA polypectomized who received surveillance colonoscopy after 5 or 7-10years from a large database (2008-2018). The outcome variable included recurrence of ACN at surveillance colonoscopy. We examined the association between length of surveillance and the outcome variable, whilst controlling for risk factors of colorectal cancer. We include 109768 subjects who have received a baseline colonoscopy from our dataset. They were aged 67.35 (SD 9.84) years, and 60.9% of them were male subjects. The crude 5-year and 10-year recurrence rate of ACN was 1.50% and 2.42%, respectively (crude odds ratio=1.629, 95% CI 1.362 to 1.949, P<0.001). From the binary logistic regression model, individuals with surveillance colonoscopy performed at 10years had a statistically higher recurrence rate of ACN than those followed-up at 5year (adjusted odds ratio [aOR]=1.544, 95% CI 1.266 to 1.877, P<0.001), but the effect size of aOR is small. There is a small difference in recurrence of ACN between individuals who received colonoscopy workup at 5years vs 7-10years. These findings support a 7-10years surveillance period after baseline NAA was polypectomized.

Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort

Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS). Identify clinical factors associated with development of skin neoplasms in LS. Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020. Multivariable logistic regression was performed to evaluate clinical factors associated with skin neoplasia. Of 607 LS carriers, 9.2% had LS-associated skin neoplasia and 15.0% had non-LS-associated skin neoplasia; 58.2% (353/607) had documentation of prior dermatologic evaluation; 29.7% (38/128) with skin neoplasms lacked a history of visceral LS-associated malignancy. LS-associated skin neoplasms were significantly associated with male sex, age, race, MLH1 pathogenic germline variants, MSH2/EPCAM pathogenic germline variants, and personal history of non-LS skin neoplasms. Non-LS-associated skin neoplasms was significantly associated with age, number of first- and second-degree relatives with non-LS-associated skin neoplasms, and personal history of LS-associated skin neoplasms. Single-institution observational study; demographic homogeneity. Skin neoplasms are common in individuals with LS. We identified clinical factors associated with LS- and non-LS-associated skin neoplasms. Regular dermatologic surveillance should be considered for all LS carriers.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program

In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy. We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 μg hemoglobin/g feces). Incidence of advanced neoplasia (CRC or advanced adenoma) was determined at the follow-up colonoscopy. Competing-risk regression was used to assess the association between multiple negative FIT results and the risk of advanced neoplasia within 2 years. The incidence of advanced neoplasia in the cohort was 9.9% and decreased with increasing numbers of rounds of negative FIT results: 11.1% after 1 negative FIT to 5.7% after 4 negative FIT. The risk of advanced neoplasia was significantly lower in participants with 3 (subdistribution hazard ratio, 0.50; 95% confidence interval, 0.24-0.97) and 4 (subdistribution hazard ratio, 0.33; 95% confidence interval, 0.15-0.73) rounds of negative FIT compared with only 1 negative FIT. There was a low risk of advanced neoplasia after multiple rounds of negative FIT in above-average-risk people undergoing surveillance with no neoplasia or nonadvanced adenoma at prior colonoscopy. This supports the use of interval FIT to personalize surveillance by lengthening colonoscopy intervals following multiple negative FIT results.

Systematic review: non‐endoscopic surveillance for colorectal neoplasia in individuals with Lynch syndrome

SummaryBackgroundIndividuals with Lynch syndrome are at high risk for colorectal cancer (CRC). Regular colonoscopies have proven to decrease CRC incidence and mortality. However, colonoscopy is burdensome and interval CRCs still occur. Hence, an accurate, less‐invasive screening method that guides the timing of colonoscopy would be of important value.AimTo outline the performance of non‐endoscopic screening modalities for Lynch‐associated CRC and adenomas.MethodsSystematic literature search in MEDLINE and EMBASE to identify studies investigating imaging techniques and biomarkers for detection of CRC and adenomas in Lynch syndrome. The QUADAS‐2 tool was used for the quality assessment of included studies.ResultsSeven of 1332 screened articles fulfilled the inclusion criteria. Two studies evaluated either CT colonography or MR colonography; both techniques were unable to detect CRC and (advanced) adenomas <10 mm. The other five studies evaluated plasma methylated‐SEPTIN9, faecal immunochemical test (FIT), faecal tumour DNA markers (BAT‐26, hMLH1, p53, D9S171, APC, D9S162, IFNA and DCC) and faecal microbiome as screening modalities. Sensitivity for CRC varied from 33% (BAT‐26) to 70% (methylated‐SEPTIN9) to 91% (hMLH1). High specificity (94–100%) for CRC and/or adenomas was observed for methylated‐SEPTIN9, FIT and BAT‐26. Desulfovibrio was enriched in the stool of patients having adenomas. However, all these studies were characterised by small populations, high/unclear risk of bias and/or low prevalence of adenomas.ConclusionsImaging techniques are unsuitable for colon surveillance in Lynch syndrome, whereas biomarkers are understudied. Having outlined biomarker research in Lynch‐associated and sporadic CRC/adenomas, we believe that these non‐invasive markers may hold potential (whether or not combined) for this population. As they could be of great value, (pre‐)clinical studies in this field should be prioritised.

Prevalence and Predictors of Young-Onset Colorectal Neoplasia: Insights From a Nationally Representative Colonoscopy Registry

A disturbing increase in early-onset colorectal cancer (EOCRC) has prompted recent guidelines to recommend lowering the colorectal cancer (CRC) screening starting age from 50 to 45 years old for average-risk individuals. Little is known about the prevalence of colorectal neoplasia in individuals between 45 and 49 years old, or even younger, in the United States. We analyzed a large, nationally representative data set of almost 3 million outpatient colonoscopies to determine the prevalence of, and risk factors for, colorectal neoplasia among patients aged 18 to54. Findings from high-quality colonoscopies were analyzed from AMSURG ambulatory endoscopy centers (ASCs) that report their results in the GI Quality Improvement Consortium (GIQuIC) Registry. Logistic regression was used to identify risk factors for EOCRC. Increasing age, male sex, White race, family history of CRC, and examinations for bleeding or screening were all associated with higher odds of advanced premalignant lesions (APLs) and CRC. Among patients aged 45 to 49, 32% had any neoplasia, 7.5% had APLs, and 0.58% had CRC. Rates were almost as high in those aged 40 to 44. Family history of CRC portended neoplasia rates 5 years earlier. Rates of APLs were higher in American Indian/Alaskan Natives, but lower among Blacks, Asians, and Hispanics, compared with White counterparts. The prevalence of any neoplasia and APL gradually increased between 2014 and 2019, in all age groups. These data provide support for lowering the screening age to 45 for all average-risk individuals. Early messaging to patients and providers in the years leading up to age 45 is warranted, especially in those with a family history of CRC.

Increased risk of Barrett’s oesophagus and related neoplasia in individuals with a positive family history

BackgroundConsidering the poor prognosis of oesophageal adenocarcinoma (EAC), it is important to identify individuals at increased risk of developing EAC who may benefit from early detection and prevention strategies. We aimed to determine whether individuals with a positive family history of Barrett’s oesophagus (BE) and EAC are at an increased risk of oesophageal neoplasia. MethodsIn a multi-centre case–control study, BE patients with or without related oesophageal neoplasia and randomly selected population controls filled out a questionnaire to collect information on family history and other risk factors for BE and EAC. Positive family history was defined as having ≥1 first-degree relative with BE or EAC whose diagnosis was histologically confirmed in the Dutch nationwide histopathology database. FindingsWe included 480 BE patients and 420 controls without BE who had a total of 6393 first-degree relatives. A pathologically confirmed positive family history was significantly higher in BE patients compared with controls (6.5% versus 0.9; p < 0.001). Positive family history was independently associated with an increased risk of BE (OR 5.04; 95% CI 1.45–17.58; p = 0.01) after adjusting for known risk factors, such as gastroesophageal reflux disease and body mass index, and family size. InterpretationWe found that familial clustering of BE and EAC is present in 6.5% of Dutch BE patients. Subjects with ≥1 first-degree relative with BE or EAC have a 5-fold increased risk of BE and EAC. These findings emphasize the importance of a detailed family history in patients with BE or EAC to identify individuals at increased risk who may benefit from early detection strategies to prevent EAC-related mortality.

Hopes and Hypes for Artificial Intelligence in Colorectal Cancer Screening

Hopes and Hypes for Artificial Intelligence in Colorectal Cancer Screening

Risk of metachronous neoplastic lesions during post-polypectomy surveillance in individuals with advanced colorectal neoplasia at initial screening colonoscopy.

The evidence of associations between some types of advanced colorectal neoplasia (ACN) at baseline and the risk of metachronous neoplasia is inconsistent. This study aimed to elucidate the incidence of metachronous neoplasia during post-polypectomy surveillance in individuals with ACN at baseline and examine the risk factors for its high incidence. Data from individuals who underwent endoscopic resection for ACN and received surveillance colonoscopy were analyzed. Data from individuals with no neoplastic lesions at baseline were used as reference. The incidence of metachronous ACN and clinically significant neoplasia (ACN and nonadvanced adenomas sized ≥5mm) were evaluated. Risk factors for the higher incidence of these lesions were examined in individuals with ACN at baseline. During the median follow-up period of 61.8months, metachronous ACN and nonadvanced adenomas sized ≥5mm were detected in 9.6% and 32.4% of individuals with ACN at baseline (n=136), respectively. The cumulative incidence of metachronous ACN and clinically significant neoplasia in individuals with ACN at baseline (3-year incidence: 5.5% and 16.9%, respectively) was higher than that in individuals with no neoplastic lesions at baseline (P<0.01 for both). The presence of advanced histology at baseline, ≥5 neoplastic lesions at baseline, and family history of colorectal cancer were identified as risk factors for the higher incidence of clinically significant neoplasia. The relatively high incidence of metachronous neoplasia in individuals with ACN at baseline was confirmed; careful surveillance is required for these individuals, particularly in those with the risk factors.

2846 Colorectal Cancer Screening in Individuals Ages 45-49 Years: Point Sensitivity of the Multi-Target Stool DNA Test

INTRODUCTION: Colorectal cancer (CRC) incidence and mortality rates in the ≥55 year old population is decreasing, while CRC incidence and mortality is increasing in those &lt; 55 years old (SEER Cancer Stat Facts: Colorectal Cancer. NCI, Bethseda, MD). Recently, the American Cancer Society revised its CRC screening guidelines to recommend screening initiation at age 45 years for average-risk individuals (American Cancer Society, 2018). To date, most endorsed CRC screening tests have not been rigorously studied in younger age groups. In this study, we examined the point sensitivity of the multi-target stool DNA (mt-sDNA) test in patients ages 45-49 years. The mt-sDNA test is currently FDA-approved to qualitatively detect biomarkers associated with colorectal neoplasia in individuals 50 years and older and at average risk for CRC, and data do not suggest age-related changes in sensitivity of the mt-sDNA test (Imperiale et al, 2014, NEJM). METHODS: Clinical listings of Exact Sciences-sponsored studies were queried to identify archived stool samples previously collected from individuals ages 45-49 years, with confirmed diagnoses of CRC or advanced adenomas (AA; defined as ≥1 cm, or ≥25% villous morphology or high-grade dysplasia of any size). Historical information regarding CRC risk was limited. Stool samples were collected at least 7 days after the screening colonoscopy, prior to lesion excision and any pre-surgical prep or neoadjuvant treatment. Samples were analyzed per the mt-sDNA test label instructions. Mt-sDNA test sensitivity for advanced colorectal neoplasia (CRC + AA), CRC, and AA were the primary study study endpoints. RESULTS: Archived stool was available from 13 individuals with CRC and 6 with AA. Mt-sDNA test sensitivity for advanced neoplasia (CRC + AA), CRC, and AA were 89% (17/19 samples), 92% (12/13 samples), and 83% (5/6 samples), respectively. CONCLUSION: This small study using archived stool samples from individuals ages 45-49 years without complete risk status information found that mt-sDNA test sensitivity was similar to previously reported data for individuals ages 50 years and older (Imperiale et al, 2014, NEJM), providing initial demonstration of test sensitivity in this younger population. Larger studies are needed to confirm and more broadly evaluate mt-sDNA performance characteristics in an average risk screening population in this age group.

Incidence of Advanced Colorectal Neoplasia in Individuals With Untreated Diminutive Colorectal Adenomas Diagnosed by Magnifying Image-Enhanced Endoscopy.

Because of the increasing number of detected diminutive colorectal adenomas, the "diagnose-and-do-not-resect" approach has recently attracted attention as an alternative to resection. We evaluated the cumulative incidence of advanced colorectal neoplasia (ACN) in individuals with untreated diminutive adenomas and compared this incidence in individuals without adenomas. Data from 1,378 individuals who underwent first screening colonoscopy (CS) and at least one follow-up CS without polypectomy were analyzed. Patients with no adenomas or with only nonadvanced diminutive adenomas (<5 mm) diagnosed by magnifying image-enhanced endoscopy were scheduled to undergo a follow-up CS within 5 years after the initial CS without treatment. The participants were divided into 2 groups: those with untreated diminutive adenomas (group A) and those with no adenomas (group B). The cumulative incidence of ACN and the hazard ratio were assessed using Gray's test and the Fine and Gray model. During the median follow-up period of 60.9 months, 21 ACNs were detected. The 5-year cumulative incidences of ACN in group A (n = 361) and group B (n = 1,017) were 1.4% (95% confidence interval [CI]: 0.5-3.4) and 0.8% (95% CI: 0.3-1.7), respectively, without a statistically significant difference (P = 0.23). No ACNs developed from unresected adenomas. The smoking status was significantly associated with the incidence of ACN, and the hazard ratio for ACN in group A vs group B adjusted for smoking status was 1.43 (95% CI: 0.52-3.90; P = 0.48). The low 5-year cumulative incidence of ACN suggests the potential to adopt the "diagnose-and-do-not-resect" strategy as an alternative option for diminutive adenomas not requiring excessive surveillance.

Tu1012 – Low Rates of Metachronous Advanced Neoplasia in Individuals with Young-Onset Colorectal Cancer

Tu1012 – Low Rates of Metachronous Advanced Neoplasia in Individuals with Young-Onset Colorectal Cancer

Abstract 5003: Serum parathyroid hormone and risks of colorectal adenoma, adenoma recurrence and colorectal cancer, results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Abstract Background: Serum parathyroid hormone (PTH) may be related to risk of incident colorectal cancer. However, no study has prospectively examined whether serum PTH is differentially related to risks of different stages of colorectal carcinogenesis (incident adenoma and metachronous adenoma). Further, it is unclear if PTH is associated with risk of incident colorectal neoplasia in individuals receiving endoscopic screenings. To address these important scientific inquiries, we have conducted three nested case-control studies within the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial. Methods: The PLCO is a large, multicenter, population-based randomized trial designed to determine the effects of screening on cancer-related mortality with a median of 12.5 years of follow up. We evaluated the associations between serum PTH and the risks of incident colorectal adenoma (755 cases and 514 controls), metachronous adenoma (755 cases and 755 controls) and incident colorectal cancer (755 cases and 514 controls) within PLCO participants aged 55 to 74 years. Odds ratios (OR) and 95% confidence intervals (95%CIs) were estimated using unconditional logistic regression models after adjusting for potential confounding factors. Results: Compared to low serum PTH (&amp;lt;30 ng/L), higher concentrations of serum PTH were associated with significantly reduced risk of incident colorectal cancer with the ORs (95% CIs) being 0.65(0.48-0.88) and 0.52(0.35-0.76) for PTH ≥30 ng/L and PTH≥65 ng/L (p for trend, 0.001). The inverse associations appeared significant for both women and men. However, overall, serum PTH was not related to risk of incident adenoma and metachronous adenoma. Conclusion: In conclusion, compared to the lowest PTH levels, higher serum PTH were related to reduced risks of incident colorectal cancer among an US population who received endoscopy, but not incident colorectal adenoma and metachronous adenoma. Citation Format: Xiangzhu Zhu, Martha J. Shrubsole, Edward Giovannucci, Todd L. Edwards, Qi Dai. Serum parathyroid hormone and risks of colorectal adenoma, adenoma recurrence and colorectal cancer, results from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5003. doi:10.1158/1538-7445.AM2017-5003

Screening by Total Colonoscopy Following Fecal Immunochemical Tests and Determinants of Colorectal Neoplasia in Japanese Men With Alcohol Dependence.

Alcohol consumption increases the risk of colorectal adenoma and cancer. The fecal immunochemical test (FIT) is a widely used screening method for detecting colorectal neoplasia. We evaluated the results of screening and risk factors for colorectal neoplasia in individuals with alcohol dependence. Total colonoscopic screening was performed for 1006 Japanese men with alcohol dependence (462 FIT-positive and 544 FIT-negative). Advanced neoplasia was defined as neoplasia ≥10 mm, villous or tubulovillous adenoma, high-grade adenoma, or carcinoma. The detection rates for non-advanced adenoma, advanced neoplasia and intramucosal or invasive carcinoma were 38.7%, 39.4% and 9.7% for the FIT-positive group, and 33.3%, 10.8% and 2.2% for the FIT-negative group, respectively. Advanced neoplasia, especially carcinoma, was detected more frequently in the distal colon than in the proximal colon in the FIT-positive group. The respective multivariate odds ratios (ORs; 95% confidence interval) for non-advanced adenoma and advanced neoplasia were 2.83 (2.06–3.88) and 9.13 (6.19–13.5) for a positive FIT (vs. negative), 1.68 (1.39–2.02) and 1.83 (1.45–2.30) for age (per +10 years), 1.54 (1.06–2.23) and 1.88 (1.17–3.03) for current smoking (vs. non-smokers), and 1.35 (0.96–1.92) and 1.59 (1.02–2.48) for the presence of marked macrocytosis (mean corpuscular volume ≥106 fl vs. <106 fl). Genetic polymorphisms of alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 did not affect the risk of colorectal neoplasia. The detection rate for advanced colorectal neoplasia was extremely high in the FIT-positive group but remained high even in the FIT-negative group. An older age, smoking and macrocytosis were predictors of advanced colorectal neoplasia. Total colonoscopic screening was performed for 1006 Japanese alcoholic men (462 fecal immunochemical test [FIT]-positive and 544 FIT-negative). The detection rate for advanced colorectal neoplasia was extremely high in the FIT-positive group (39.4%) and high in the FIT-negative group (10.8%). Ageing, smoking and macrocytosis were predictors of advanced colorectal neoplasia.

Risk of Colorectal Neoplasia in Individuals With Self-Reported Family History: A Prospective Colonoscopy Study from 16 Asia-Pacific Regions.

We tested the hypothesis that the risk of colorectal cancer (CRC), advanced colorectal neoplasia (ACN), and colorectal adenoma among screening participants with different first-degree relatives (FDRs) affected by CRC was similar. A multi-center, prospective colonoscopy study involving 16 Asia-Pacific regions was performed from 2008 to 2015. Consecutive self-referred CRC screening participants aged 40-70 years were recruited, and each subject received one direct optical colonoscopy. The prevalence of CRC, ACN, and colorectal adenoma was compared among subjects with different FDRs affected using Pearson's χ2 tests. Binary logistic regression analyses were performed to evaluate the risk of these lesions, controlling for recognized risk factors including age, gender, smoking habits, alcohol drinking, body mass index, and the presence of diabetes mellitus. Among 11,797 asymptomatic subjects, the prevalence of CRC was 0.6% (none: 0.6%; siblings: 1.1%; mother: 0.5%; father: 1.2%; ≥2 members: 3.1%, P<0.001), that of ACN was 6.5% (none: 6.1%; siblings: 8.3%; mother: 7.7%; father: 8.7%; ≥2 members: 9.3%, P<0.001), and that of colorectal adenoma was 29.3% (none: 28.6%; siblings: 33.5%; mother: 31.8%; father: 31.1%; ≥2 members: 38.1%, P<0.001). In multivariate regression analyses, subjects with at least one FDR affected were significantly more likely to have CRC (adjusted odds ratio (AOR)=2.02-7.89), ACN (AOR=1.55-2.06), and colorectal adenoma (AOR=1.31-1.92) than those without a family history. The risk of CRC (AOR=0.90, 95% confidence interval (CI) 0.34-2.35, P=0.830), ACN (AOR=1.07, 95% CI 0.75-1.52, P=0.714), and colorectal adenoma (AOR=0.96, 95% CI 0.78-1.19, P=0.718) in subjects with either parent affected was similar to that of subjects with their siblings affected. The risk of colorectal neoplasia was similar among subjects with different FDRs affected. These findings do not support the need to discriminate proband identity in screening participants with affected FDRs when their risks of colorectal neoplasia were estimated.